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Maternal mental health: New consensus on optimal care
A new consensus bundle of recommendations calls on ob.gyns. to integrate mental health care into their care of pregnant and postpartum women.
The interdisciplinary Council on Patient Safety in Women’s Health Care issued a consensus document summarizing existing recommendations on maternal mental health and pairing them with appropriate screening and other resources. The bundle of recommendations was jointly issued by the American College of Obstetricians and Gynecologists, the National Association of Nurse Practitioners in Women’s Health, and other groups (Obstet Gynecol. 2017 Mar;129(3):422-430)*.
While no novel information is included in the bundle, the goal is to provide a streamlined document that pairs previous recommendations with resources and tools.
“Embedding a mental health professional with the women’s health care provider would seem to be the ideal, [but] in reality, this may not be available in every setting or geographic location,” Susan Kendig, JD, MSN, WHNP-BC, FAANP, policy director for the National Association of Nurse Practitioners in Women’s Health, and one of the authors of the document, said in an interview. “The purpose of the consensus bundle is to provide a framework for women’s health care providers to use in developing a system of care that includes standardized risk assessment for existing or emerging mental health issues, strategies for brief interventions, identification of community resources available to the woman, and/or resources to support the provider in addressing the woman’s needs and facilitating appropriate referrals, and addressing emergencies to prevent harm.”
The framework is grouped in four domains: readiness, recognition and prevention, response, and reporting and systems learning.
Readiness is focused largely on setting up clinical and administrative protocols, including mental health screening that is seamlessly integrated into the patient visit, established algorithms that are triggered according to screening results, and designated staff to both educate colleagues on the protocols and to drive their implementation.
The goal for physicians in all settings, according to the authors, is to balance cost, availability of tools, ease of use, and the validity of the tools against the need to capture often unrecognized signs and symptoms of mood and anxiety disorders, including changes in sleep patterns, appetite, or anxiety levels that often are attributed to the physiologic and neuroendocrinologic changes inherent in childbirth. More than 80% of women know something is “off” but do not bring up their symptoms to their clinician, according to the recommendation document.
“Coordination and team cohesiveness is not necessarily dependent on co-location,” Ms. Kendig said. “Virtual teams, where care is coordinated among providers at different locations, can also achieve positive outcomes.”
The follow-on to this – recognition and prevention – views every patient visit as an opportunity to draw a thorough picture of mental and physical health by taking a complete family and patient history, maintaining routine screening, and offering psychoeducation to patients and their families or others on whom they rely for emotional support.
When a woman does screen positive for perinatal mood or anxiety disorders, the next bundle offers a rough outline of a stage-based response for intervention and follow-up.
“Screening alone does not appear to improve pregnancy or maternal-child outcomes,” the authors wrote.
Several possible algorithms are included in the document, including for emergent mental health concerns such as suicidal or homicidal ideation.
The final domain relies on data capture, taking a systems approach to not only delivering care, but also improving it. This includes scheduling regular staff debriefings after severe maternal mental health crises, troubleshooting why some patients become lost to follow-up, and examining data to see patterns.
On Twitter @whitneymcknight
CORRECTION, 3/20/17: An earlier version of this article misstated the citation.
A new consensus bundle of recommendations calls on ob.gyns. to integrate mental health care into their care of pregnant and postpartum women.
The interdisciplinary Council on Patient Safety in Women’s Health Care issued a consensus document summarizing existing recommendations on maternal mental health and pairing them with appropriate screening and other resources. The bundle of recommendations was jointly issued by the American College of Obstetricians and Gynecologists, the National Association of Nurse Practitioners in Women’s Health, and other groups (Obstet Gynecol. 2017 Mar;129(3):422-430)*.
While no novel information is included in the bundle, the goal is to provide a streamlined document that pairs previous recommendations with resources and tools.
“Embedding a mental health professional with the women’s health care provider would seem to be the ideal, [but] in reality, this may not be available in every setting or geographic location,” Susan Kendig, JD, MSN, WHNP-BC, FAANP, policy director for the National Association of Nurse Practitioners in Women’s Health, and one of the authors of the document, said in an interview. “The purpose of the consensus bundle is to provide a framework for women’s health care providers to use in developing a system of care that includes standardized risk assessment for existing or emerging mental health issues, strategies for brief interventions, identification of community resources available to the woman, and/or resources to support the provider in addressing the woman’s needs and facilitating appropriate referrals, and addressing emergencies to prevent harm.”
The framework is grouped in four domains: readiness, recognition and prevention, response, and reporting and systems learning.
Readiness is focused largely on setting up clinical and administrative protocols, including mental health screening that is seamlessly integrated into the patient visit, established algorithms that are triggered according to screening results, and designated staff to both educate colleagues on the protocols and to drive their implementation.
The goal for physicians in all settings, according to the authors, is to balance cost, availability of tools, ease of use, and the validity of the tools against the need to capture often unrecognized signs and symptoms of mood and anxiety disorders, including changes in sleep patterns, appetite, or anxiety levels that often are attributed to the physiologic and neuroendocrinologic changes inherent in childbirth. More than 80% of women know something is “off” but do not bring up their symptoms to their clinician, according to the recommendation document.
“Coordination and team cohesiveness is not necessarily dependent on co-location,” Ms. Kendig said. “Virtual teams, where care is coordinated among providers at different locations, can also achieve positive outcomes.”
The follow-on to this – recognition and prevention – views every patient visit as an opportunity to draw a thorough picture of mental and physical health by taking a complete family and patient history, maintaining routine screening, and offering psychoeducation to patients and their families or others on whom they rely for emotional support.
When a woman does screen positive for perinatal mood or anxiety disorders, the next bundle offers a rough outline of a stage-based response for intervention and follow-up.
“Screening alone does not appear to improve pregnancy or maternal-child outcomes,” the authors wrote.
Several possible algorithms are included in the document, including for emergent mental health concerns such as suicidal or homicidal ideation.
The final domain relies on data capture, taking a systems approach to not only delivering care, but also improving it. This includes scheduling regular staff debriefings after severe maternal mental health crises, troubleshooting why some patients become lost to follow-up, and examining data to see patterns.
On Twitter @whitneymcknight
CORRECTION, 3/20/17: An earlier version of this article misstated the citation.
A new consensus bundle of recommendations calls on ob.gyns. to integrate mental health care into their care of pregnant and postpartum women.
The interdisciplinary Council on Patient Safety in Women’s Health Care issued a consensus document summarizing existing recommendations on maternal mental health and pairing them with appropriate screening and other resources. The bundle of recommendations was jointly issued by the American College of Obstetricians and Gynecologists, the National Association of Nurse Practitioners in Women’s Health, and other groups (Obstet Gynecol. 2017 Mar;129(3):422-430)*.
While no novel information is included in the bundle, the goal is to provide a streamlined document that pairs previous recommendations with resources and tools.
“Embedding a mental health professional with the women’s health care provider would seem to be the ideal, [but] in reality, this may not be available in every setting or geographic location,” Susan Kendig, JD, MSN, WHNP-BC, FAANP, policy director for the National Association of Nurse Practitioners in Women’s Health, and one of the authors of the document, said in an interview. “The purpose of the consensus bundle is to provide a framework for women’s health care providers to use in developing a system of care that includes standardized risk assessment for existing or emerging mental health issues, strategies for brief interventions, identification of community resources available to the woman, and/or resources to support the provider in addressing the woman’s needs and facilitating appropriate referrals, and addressing emergencies to prevent harm.”
The framework is grouped in four domains: readiness, recognition and prevention, response, and reporting and systems learning.
Readiness is focused largely on setting up clinical and administrative protocols, including mental health screening that is seamlessly integrated into the patient visit, established algorithms that are triggered according to screening results, and designated staff to both educate colleagues on the protocols and to drive their implementation.
The goal for physicians in all settings, according to the authors, is to balance cost, availability of tools, ease of use, and the validity of the tools against the need to capture often unrecognized signs and symptoms of mood and anxiety disorders, including changes in sleep patterns, appetite, or anxiety levels that often are attributed to the physiologic and neuroendocrinologic changes inherent in childbirth. More than 80% of women know something is “off” but do not bring up their symptoms to their clinician, according to the recommendation document.
“Coordination and team cohesiveness is not necessarily dependent on co-location,” Ms. Kendig said. “Virtual teams, where care is coordinated among providers at different locations, can also achieve positive outcomes.”
The follow-on to this – recognition and prevention – views every patient visit as an opportunity to draw a thorough picture of mental and physical health by taking a complete family and patient history, maintaining routine screening, and offering psychoeducation to patients and their families or others on whom they rely for emotional support.
When a woman does screen positive for perinatal mood or anxiety disorders, the next bundle offers a rough outline of a stage-based response for intervention and follow-up.
“Screening alone does not appear to improve pregnancy or maternal-child outcomes,” the authors wrote.
Several possible algorithms are included in the document, including for emergent mental health concerns such as suicidal or homicidal ideation.
The final domain relies on data capture, taking a systems approach to not only delivering care, but also improving it. This includes scheduling regular staff debriefings after severe maternal mental health crises, troubleshooting why some patients become lost to follow-up, and examining data to see patterns.
On Twitter @whitneymcknight
CORRECTION, 3/20/17: An earlier version of this article misstated the citation.
FROM OBSTETRICS & GYNECOLOGY
Crusted scabies outbreak: How much prophylaxis?
, a small case series suggests.
What remains a matter of debate is how widely to use prophylaxis, according to authors of a study of two approaches published in Infection, Disease & Health.
The case series, coauthored by Dr. Nikki R. Adler and her colleagues at Alfred Hospital in Melbourne, compares and contrasts two approaches to a scabies outbreak in a tertiary care setting (Infect Dis Health. 2017. doi: 10.1016/j.idh.2017.01.001).
One scenario involved an elderly woman who had been transferred from a rehabilitation facility for hip replacement surgery. Although upon admission the patient reported a pruritic truncal rash of 2 weeks’ duration, it was associated by the care team with either a cutaneous adverse drug reaction or with paraneoplastic syndrome, as she had recently been diagnosed with multiple myeloma. As a result, it wasn’t until after the patient’s emergent care needs were met 4 weeks later that she was given a formal dermatology consult, at which time several punch biopsies confirmed crusted scabies; she was treated with 5% permethrin cream for a week, weekly oral ivermectin 200 mcg/kg for 1 month, as well as with topical keratolytics.
Meanwhile, because the delayed diagnosis meant the patient – who had been treated across several wards – had potentially exposed multiple health care workers and patients to Sarcoptes scabiei, the hospital immediately instituted contact precautions and implemented its outbreak protocols: communication statements, prophylactic treatment of asymptomatic staff and close patients, and treatment and quarantine for those with clinical symptoms.
The second case involved an elderly man admitted through the emergency department after presenting with fever, hypotension, and a 3-week history of a progressive, hyperkeratotic, pruritic rash on his trunk and arms. A recent heart transplant recipient, he was taking cyclosporine, mycophenolate, and prednisolone, and he had hemodialysis-dependent end-stage kidney disease. After an ED dermatologic review, he was diagnosed with S. scabiei, immediately triggering contact precautions in the ED and elsewhere. He was treated with ivermectin, 5% permethrin, and topical keratolytics. All staff thought to have been exposed to the patient were treated prophylactically with 5% permethrin single-dose therapy.
Because thickened skin flakes that slough off in crusted scabies may house hundreds of mites for longer than 48 hours, environmental cleaning was enhanced in both cases.
The latter case did not feature a prolonged outbreak thanks to early diagnosis and quick preventive action. The outbreak in the first case lasted 7 weeks and 5 days. The hospital in that case opted not to employ a mass prophylaxis strategy, instead treating 306 persons identified to have been in contact with the patient. In all, 54 symptomatic patients and health care workers were identified.
The authors cited data that, across 19 nosocomial outbreaks between 1990 and 2003, the mean number of infested patients was 18; the mean number for health care workers was 39. The attack rate, defined as the number of new cases divided by the total number of persons at risk, was 13% for patients and 35% in health care workers. The median duration of outbreak was 14.5 weeks (range, 4-52 weeks).
“The variation of outbreak size and duration in the reported literature suggests that there may be important differences in the efficacy of various infection control strategies,” Dr. Adler and her colleagues wrote, noting that while some institutions might prefer simultaneous mass prophylaxis to rapidly and efficiently control a scabies outbreak, the cost of doing so can be prohibitive, and might not be more effective than the information-centered management model used in Case 1 that relied on close tracking of all patient contacts, and use of the hospital intranet and internal memos.
This strategy does run the risk of overreaction, however: “The communication strategy may have contributed to heightened levels of concern among staff and arguably, excessive prophylaxis and/or overdiagnosis,” the authors wrote.
To help diagnose potential cases of crusted scabies quickly, Dr. Adler and her colleagues suggested clinicians consider that various dermatoses can mimic a scabies infestation and that care teams have a high index of suspicion in patients most at risk for scabies: the elderly and those who are immunocompromised, such as the heart transplant patient in Case 2, and also those with altered T-cell function.
[email protected]
On Twitter @whitneymcknight
, a small case series suggests.
What remains a matter of debate is how widely to use prophylaxis, according to authors of a study of two approaches published in Infection, Disease & Health.
The case series, coauthored by Dr. Nikki R. Adler and her colleagues at Alfred Hospital in Melbourne, compares and contrasts two approaches to a scabies outbreak in a tertiary care setting (Infect Dis Health. 2017. doi: 10.1016/j.idh.2017.01.001).
One scenario involved an elderly woman who had been transferred from a rehabilitation facility for hip replacement surgery. Although upon admission the patient reported a pruritic truncal rash of 2 weeks’ duration, it was associated by the care team with either a cutaneous adverse drug reaction or with paraneoplastic syndrome, as she had recently been diagnosed with multiple myeloma. As a result, it wasn’t until after the patient’s emergent care needs were met 4 weeks later that she was given a formal dermatology consult, at which time several punch biopsies confirmed crusted scabies; she was treated with 5% permethrin cream for a week, weekly oral ivermectin 200 mcg/kg for 1 month, as well as with topical keratolytics.
Meanwhile, because the delayed diagnosis meant the patient – who had been treated across several wards – had potentially exposed multiple health care workers and patients to Sarcoptes scabiei, the hospital immediately instituted contact precautions and implemented its outbreak protocols: communication statements, prophylactic treatment of asymptomatic staff and close patients, and treatment and quarantine for those with clinical symptoms.
The second case involved an elderly man admitted through the emergency department after presenting with fever, hypotension, and a 3-week history of a progressive, hyperkeratotic, pruritic rash on his trunk and arms. A recent heart transplant recipient, he was taking cyclosporine, mycophenolate, and prednisolone, and he had hemodialysis-dependent end-stage kidney disease. After an ED dermatologic review, he was diagnosed with S. scabiei, immediately triggering contact precautions in the ED and elsewhere. He was treated with ivermectin, 5% permethrin, and topical keratolytics. All staff thought to have been exposed to the patient were treated prophylactically with 5% permethrin single-dose therapy.
Because thickened skin flakes that slough off in crusted scabies may house hundreds of mites for longer than 48 hours, environmental cleaning was enhanced in both cases.
The latter case did not feature a prolonged outbreak thanks to early diagnosis and quick preventive action. The outbreak in the first case lasted 7 weeks and 5 days. The hospital in that case opted not to employ a mass prophylaxis strategy, instead treating 306 persons identified to have been in contact with the patient. In all, 54 symptomatic patients and health care workers were identified.
The authors cited data that, across 19 nosocomial outbreaks between 1990 and 2003, the mean number of infested patients was 18; the mean number for health care workers was 39. The attack rate, defined as the number of new cases divided by the total number of persons at risk, was 13% for patients and 35% in health care workers. The median duration of outbreak was 14.5 weeks (range, 4-52 weeks).
“The variation of outbreak size and duration in the reported literature suggests that there may be important differences in the efficacy of various infection control strategies,” Dr. Adler and her colleagues wrote, noting that while some institutions might prefer simultaneous mass prophylaxis to rapidly and efficiently control a scabies outbreak, the cost of doing so can be prohibitive, and might not be more effective than the information-centered management model used in Case 1 that relied on close tracking of all patient contacts, and use of the hospital intranet and internal memos.
This strategy does run the risk of overreaction, however: “The communication strategy may have contributed to heightened levels of concern among staff and arguably, excessive prophylaxis and/or overdiagnosis,” the authors wrote.
To help diagnose potential cases of crusted scabies quickly, Dr. Adler and her colleagues suggested clinicians consider that various dermatoses can mimic a scabies infestation and that care teams have a high index of suspicion in patients most at risk for scabies: the elderly and those who are immunocompromised, such as the heart transplant patient in Case 2, and also those with altered T-cell function.
[email protected]
On Twitter @whitneymcknight
, a small case series suggests.
What remains a matter of debate is how widely to use prophylaxis, according to authors of a study of two approaches published in Infection, Disease & Health.
The case series, coauthored by Dr. Nikki R. Adler and her colleagues at Alfred Hospital in Melbourne, compares and contrasts two approaches to a scabies outbreak in a tertiary care setting (Infect Dis Health. 2017. doi: 10.1016/j.idh.2017.01.001).
One scenario involved an elderly woman who had been transferred from a rehabilitation facility for hip replacement surgery. Although upon admission the patient reported a pruritic truncal rash of 2 weeks’ duration, it was associated by the care team with either a cutaneous adverse drug reaction or with paraneoplastic syndrome, as she had recently been diagnosed with multiple myeloma. As a result, it wasn’t until after the patient’s emergent care needs were met 4 weeks later that she was given a formal dermatology consult, at which time several punch biopsies confirmed crusted scabies; she was treated with 5% permethrin cream for a week, weekly oral ivermectin 200 mcg/kg for 1 month, as well as with topical keratolytics.
Meanwhile, because the delayed diagnosis meant the patient – who had been treated across several wards – had potentially exposed multiple health care workers and patients to Sarcoptes scabiei, the hospital immediately instituted contact precautions and implemented its outbreak protocols: communication statements, prophylactic treatment of asymptomatic staff and close patients, and treatment and quarantine for those with clinical symptoms.
The second case involved an elderly man admitted through the emergency department after presenting with fever, hypotension, and a 3-week history of a progressive, hyperkeratotic, pruritic rash on his trunk and arms. A recent heart transplant recipient, he was taking cyclosporine, mycophenolate, and prednisolone, and he had hemodialysis-dependent end-stage kidney disease. After an ED dermatologic review, he was diagnosed with S. scabiei, immediately triggering contact precautions in the ED and elsewhere. He was treated with ivermectin, 5% permethrin, and topical keratolytics. All staff thought to have been exposed to the patient were treated prophylactically with 5% permethrin single-dose therapy.
Because thickened skin flakes that slough off in crusted scabies may house hundreds of mites for longer than 48 hours, environmental cleaning was enhanced in both cases.
The latter case did not feature a prolonged outbreak thanks to early diagnosis and quick preventive action. The outbreak in the first case lasted 7 weeks and 5 days. The hospital in that case opted not to employ a mass prophylaxis strategy, instead treating 306 persons identified to have been in contact with the patient. In all, 54 symptomatic patients and health care workers were identified.
The authors cited data that, across 19 nosocomial outbreaks between 1990 and 2003, the mean number of infested patients was 18; the mean number for health care workers was 39. The attack rate, defined as the number of new cases divided by the total number of persons at risk, was 13% for patients and 35% in health care workers. The median duration of outbreak was 14.5 weeks (range, 4-52 weeks).
“The variation of outbreak size and duration in the reported literature suggests that there may be important differences in the efficacy of various infection control strategies,” Dr. Adler and her colleagues wrote, noting that while some institutions might prefer simultaneous mass prophylaxis to rapidly and efficiently control a scabies outbreak, the cost of doing so can be prohibitive, and might not be more effective than the information-centered management model used in Case 1 that relied on close tracking of all patient contacts, and use of the hospital intranet and internal memos.
This strategy does run the risk of overreaction, however: “The communication strategy may have contributed to heightened levels of concern among staff and arguably, excessive prophylaxis and/or overdiagnosis,” the authors wrote.
To help diagnose potential cases of crusted scabies quickly, Dr. Adler and her colleagues suggested clinicians consider that various dermatoses can mimic a scabies infestation and that care teams have a high index of suspicion in patients most at risk for scabies: the elderly and those who are immunocompromised, such as the heart transplant patient in Case 2, and also those with altered T-cell function.
[email protected]
On Twitter @whitneymcknight
FROM INFECTION, DISEASE, & HEALTH
New CF guidelines include lower sweat chloride threshold
Updated guidelines for the diagnosis and treatment of cystic fibrosis (CF) include two major changes.
The first important update is that clinicians use the latest classifications of the specific CF transmembrane conductance regulator (CFTR) gene mutations, from the Clinical and Functional TRanslation of CFTR (CFTR2) database, to aid with making a CF diagnosis in any patient, newborn to adult. The other of these changes relates to the chloride concentration level used to confirm CF diagnosis through a sweat test. Under the new guidelines, the sweat chloride threshold for “possible” CF or a CF-related disease was reduced to 30 mmol/L of chloride concentration from 40 mmol/L across all ages. The guidelines, written by an international team of collaborators and published by the Cystic Fibrosis Foundation, are available online in the Journal of Pediatrics (J Pediatr 2017 Feb;181(suppl):S4-S15.e1. doi: 10.1016/j.jpeds.2016.09.064).
Since its inception in 2008, the CFTR2 project has described 300 of the 2,000 known CF-related mutations and their various functional and clinical impacts. The project involves amassing phenotypic and genotypic information from patient registries to collect, quantify, and describe mutations reported in individuals with CF. Such mutations are categorized as CF-causing, carrying a variety of potential clinical consequences, non–cystic fibrosis causing, or unknown. The previous guidelines, written in 2008, relied on a 23-mutation panel from the American College of Medical Genetics and Genomics and the American Congress of Obstetricians and Gynecologists.
“We’ve more precisely defined what cystic fibrosis is,” Patrick R. Sosnay, MD, assistant professor of medicine at Johns Hopkins University, Baltimore, and coauthor of the guidelines, said in a statement. “The stakes in categorizing a mutation are particularly high. For example, claiming that a mutation 100% causes cystic fibrosis may affect people’s reproductive decisions if they believe their child will have the mutation.”
In the CFTR2 project, the “disease-liability” of each mutation is evaluated through a combination of sweat chloride and functional activity identified in cell-based systems, according to a supplement published simultaneously with the updated guidelines (J Pediatr 2017 Feb;181(suppl):S52-S57.e2. doi: 10.1016/j.jpeds.2016.09.068). Data from this project led to the discovery of a cohort of 746 persons diagnosed with CF despite sweat chloride levels less than 60 mmol/L. These findings were the basis for the guideline authors’ decision to lower the threshold of chloride concentration in sweat in order for an individual to be considered having a possible CF diagnosis, according to the supplement.
The guidelines include 27 approved consensus statements spanning four overlapping categories, and applying to screened and nonscreened populations; newborn screened populations and fetuses undergoing prenatal testing; infants with an uncertain diagnosis and designated as having either CFTR gene-related metabolic syndrome or being CF-screen positive, inconclusive diagnosis; and nonscreened patients who present with symptoms, including children before newborn screening implementation, those with false negative tests and older, nonscreened patients.
Although not specified in the consensus statements, the authors of a second supplement published simultaneously with the updated guidelines (J Pediatr 2017;181(suppl):S27-S32.e1. doi: 10.1016/j.jpeds.2016.09.063), wrote that they supported genotyping all individuals diagnosed with CF, even if physiologic tests establish the diagnosis, to better understand the disease’s genetic epidemiology and to refine future therapies. “If the identified mutations are known to be associated with variable outcomes, or have unknown consequence, that genotype may not result in a CF phenotype. In these cases, other tests of CFTR function may help,” this supplement’s authors concluded.
The updated guideline authors recommend avoiding the use of terms such as “atypical” or “nonclassical” CF, as there is no consensus on the specific taxonomy of CF, since the genetic data are still emerging.
When administering a newborn test, the guidelines warn that the heterogenous nature of newborn screening often leads to false positive results, thus the need for the sweat test. Although obtaining an adequate sweat specimen for chloride measurements can be difficult, the authors say it is possible, especially in full-term infants aged 1 month. Repeat sweat testing is recommended, as is nasal potential difference (NPD) and intestinal current measurement (ICM) in some cases.
Another change to the guidelines is that newborns with a high immunoreactive trypsinogen level and inconclusive CFTR functional and genetic testing may now be designated as having CFTR-related metabolic syndrome/CF screen positive inconclusive diagnosis (CRMS/CFSPID), instead of CFTR-related metabolic syndrome or CF screen positive, inconclusive diagnosis. Regarding changes to screening for CRMS/CFSPID, the older guidelines called for such an assessment by age 2 months, repeated every 6-12 months, while the new guidelines say their recommendation on the duration and frequency of follow-up “remains to be determined.”
The authors of the first supplement decry the lack of standardized CF diagnostic criteria for those diagnosed with CF outside of the neonatal period, and urge clinicians to rely on clinical evidence including organ pathologies typical in CF, such as bronchiectasis or pancreatic insufficiency, along with testing for the presence of CFTR dysfunction with sweat chloride testing, CFTR molecular genetic analysis, or CFTR physiologic tests.
In contrast, the second supplement states that “clinical suspicion should always take precedence” in making a CF diagnoses for individuals in this age group.
Dr. Sosnay and Philip M. Farrell, MD, PhD, a coauthor of the guidelines, received funds from the Cystic Fibrosis Foundation, where guideline coauthor Terry B. White, PhD, is an employee. Kris De Boeck, MD, a coauthor of the first supplement, receives funding from Vertex Pharmaceuticals, Ablynx, Aptalis, Galapagos, Gilead, Pharmaxis, and PTC Therapeutics. The guideline and supplements’ other authors have no disclosures.
[email protected]
On Twitter @whitneymcknight
Susan Millard, MD, FCCP, comments: A comprehensive supplement in the Journal of Pediatrics entitled, “Introduction to ‘Cystic Fibrosis Foundation Consensus Guidelines for Diagnosis of Cystic Fibrosis,’ ” reflects information introduced at the North American Cystic Fibrosis Conference in the fall 2016 (J Pediatr.2017 Feb;181[suppl]:S1-3. doi:10.1016/jpeds.2016.09.062).
Susan Millard, MD, FCCP, comments: A comprehensive supplement in the Journal of Pediatrics entitled, “Introduction to ‘Cystic Fibrosis Foundation Consensus Guidelines for Diagnosis of Cystic Fibrosis,’ ” reflects information introduced at the North American Cystic Fibrosis Conference in the fall 2016 (J Pediatr.2017 Feb;181[suppl]:S1-3. doi:10.1016/jpeds.2016.09.062).
Susan Millard, MD, FCCP, comments: A comprehensive supplement in the Journal of Pediatrics entitled, “Introduction to ‘Cystic Fibrosis Foundation Consensus Guidelines for Diagnosis of Cystic Fibrosis,’ ” reflects information introduced at the North American Cystic Fibrosis Conference in the fall 2016 (J Pediatr.2017 Feb;181[suppl]:S1-3. doi:10.1016/jpeds.2016.09.062).
Updated guidelines for the diagnosis and treatment of cystic fibrosis (CF) include two major changes.
The first important update is that clinicians use the latest classifications of the specific CF transmembrane conductance regulator (CFTR) gene mutations, from the Clinical and Functional TRanslation of CFTR (CFTR2) database, to aid with making a CF diagnosis in any patient, newborn to adult. The other of these changes relates to the chloride concentration level used to confirm CF diagnosis through a sweat test. Under the new guidelines, the sweat chloride threshold for “possible” CF or a CF-related disease was reduced to 30 mmol/L of chloride concentration from 40 mmol/L across all ages. The guidelines, written by an international team of collaborators and published by the Cystic Fibrosis Foundation, are available online in the Journal of Pediatrics (J Pediatr 2017 Feb;181(suppl):S4-S15.e1. doi: 10.1016/j.jpeds.2016.09.064).
Since its inception in 2008, the CFTR2 project has described 300 of the 2,000 known CF-related mutations and their various functional and clinical impacts. The project involves amassing phenotypic and genotypic information from patient registries to collect, quantify, and describe mutations reported in individuals with CF. Such mutations are categorized as CF-causing, carrying a variety of potential clinical consequences, non–cystic fibrosis causing, or unknown. The previous guidelines, written in 2008, relied on a 23-mutation panel from the American College of Medical Genetics and Genomics and the American Congress of Obstetricians and Gynecologists.
“We’ve more precisely defined what cystic fibrosis is,” Patrick R. Sosnay, MD, assistant professor of medicine at Johns Hopkins University, Baltimore, and coauthor of the guidelines, said in a statement. “The stakes in categorizing a mutation are particularly high. For example, claiming that a mutation 100% causes cystic fibrosis may affect people’s reproductive decisions if they believe their child will have the mutation.”
In the CFTR2 project, the “disease-liability” of each mutation is evaluated through a combination of sweat chloride and functional activity identified in cell-based systems, according to a supplement published simultaneously with the updated guidelines (J Pediatr 2017 Feb;181(suppl):S52-S57.e2. doi: 10.1016/j.jpeds.2016.09.068). Data from this project led to the discovery of a cohort of 746 persons diagnosed with CF despite sweat chloride levels less than 60 mmol/L. These findings were the basis for the guideline authors’ decision to lower the threshold of chloride concentration in sweat in order for an individual to be considered having a possible CF diagnosis, according to the supplement.
The guidelines include 27 approved consensus statements spanning four overlapping categories, and applying to screened and nonscreened populations; newborn screened populations and fetuses undergoing prenatal testing; infants with an uncertain diagnosis and designated as having either CFTR gene-related metabolic syndrome or being CF-screen positive, inconclusive diagnosis; and nonscreened patients who present with symptoms, including children before newborn screening implementation, those with false negative tests and older, nonscreened patients.
Although not specified in the consensus statements, the authors of a second supplement published simultaneously with the updated guidelines (J Pediatr 2017;181(suppl):S27-S32.e1. doi: 10.1016/j.jpeds.2016.09.063), wrote that they supported genotyping all individuals diagnosed with CF, even if physiologic tests establish the diagnosis, to better understand the disease’s genetic epidemiology and to refine future therapies. “If the identified mutations are known to be associated with variable outcomes, or have unknown consequence, that genotype may not result in a CF phenotype. In these cases, other tests of CFTR function may help,” this supplement’s authors concluded.
The updated guideline authors recommend avoiding the use of terms such as “atypical” or “nonclassical” CF, as there is no consensus on the specific taxonomy of CF, since the genetic data are still emerging.
When administering a newborn test, the guidelines warn that the heterogenous nature of newborn screening often leads to false positive results, thus the need for the sweat test. Although obtaining an adequate sweat specimen for chloride measurements can be difficult, the authors say it is possible, especially in full-term infants aged 1 month. Repeat sweat testing is recommended, as is nasal potential difference (NPD) and intestinal current measurement (ICM) in some cases.
Another change to the guidelines is that newborns with a high immunoreactive trypsinogen level and inconclusive CFTR functional and genetic testing may now be designated as having CFTR-related metabolic syndrome/CF screen positive inconclusive diagnosis (CRMS/CFSPID), instead of CFTR-related metabolic syndrome or CF screen positive, inconclusive diagnosis. Regarding changes to screening for CRMS/CFSPID, the older guidelines called for such an assessment by age 2 months, repeated every 6-12 months, while the new guidelines say their recommendation on the duration and frequency of follow-up “remains to be determined.”
The authors of the first supplement decry the lack of standardized CF diagnostic criteria for those diagnosed with CF outside of the neonatal period, and urge clinicians to rely on clinical evidence including organ pathologies typical in CF, such as bronchiectasis or pancreatic insufficiency, along with testing for the presence of CFTR dysfunction with sweat chloride testing, CFTR molecular genetic analysis, or CFTR physiologic tests.
In contrast, the second supplement states that “clinical suspicion should always take precedence” in making a CF diagnoses for individuals in this age group.
Dr. Sosnay and Philip M. Farrell, MD, PhD, a coauthor of the guidelines, received funds from the Cystic Fibrosis Foundation, where guideline coauthor Terry B. White, PhD, is an employee. Kris De Boeck, MD, a coauthor of the first supplement, receives funding from Vertex Pharmaceuticals, Ablynx, Aptalis, Galapagos, Gilead, Pharmaxis, and PTC Therapeutics. The guideline and supplements’ other authors have no disclosures.
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On Twitter @whitneymcknight
Updated guidelines for the diagnosis and treatment of cystic fibrosis (CF) include two major changes.
The first important update is that clinicians use the latest classifications of the specific CF transmembrane conductance regulator (CFTR) gene mutations, from the Clinical and Functional TRanslation of CFTR (CFTR2) database, to aid with making a CF diagnosis in any patient, newborn to adult. The other of these changes relates to the chloride concentration level used to confirm CF diagnosis through a sweat test. Under the new guidelines, the sweat chloride threshold for “possible” CF or a CF-related disease was reduced to 30 mmol/L of chloride concentration from 40 mmol/L across all ages. The guidelines, written by an international team of collaborators and published by the Cystic Fibrosis Foundation, are available online in the Journal of Pediatrics (J Pediatr 2017 Feb;181(suppl):S4-S15.e1. doi: 10.1016/j.jpeds.2016.09.064).
Since its inception in 2008, the CFTR2 project has described 300 of the 2,000 known CF-related mutations and their various functional and clinical impacts. The project involves amassing phenotypic and genotypic information from patient registries to collect, quantify, and describe mutations reported in individuals with CF. Such mutations are categorized as CF-causing, carrying a variety of potential clinical consequences, non–cystic fibrosis causing, or unknown. The previous guidelines, written in 2008, relied on a 23-mutation panel from the American College of Medical Genetics and Genomics and the American Congress of Obstetricians and Gynecologists.
“We’ve more precisely defined what cystic fibrosis is,” Patrick R. Sosnay, MD, assistant professor of medicine at Johns Hopkins University, Baltimore, and coauthor of the guidelines, said in a statement. “The stakes in categorizing a mutation are particularly high. For example, claiming that a mutation 100% causes cystic fibrosis may affect people’s reproductive decisions if they believe their child will have the mutation.”
In the CFTR2 project, the “disease-liability” of each mutation is evaluated through a combination of sweat chloride and functional activity identified in cell-based systems, according to a supplement published simultaneously with the updated guidelines (J Pediatr 2017 Feb;181(suppl):S52-S57.e2. doi: 10.1016/j.jpeds.2016.09.068). Data from this project led to the discovery of a cohort of 746 persons diagnosed with CF despite sweat chloride levels less than 60 mmol/L. These findings were the basis for the guideline authors’ decision to lower the threshold of chloride concentration in sweat in order for an individual to be considered having a possible CF diagnosis, according to the supplement.
The guidelines include 27 approved consensus statements spanning four overlapping categories, and applying to screened and nonscreened populations; newborn screened populations and fetuses undergoing prenatal testing; infants with an uncertain diagnosis and designated as having either CFTR gene-related metabolic syndrome or being CF-screen positive, inconclusive diagnosis; and nonscreened patients who present with symptoms, including children before newborn screening implementation, those with false negative tests and older, nonscreened patients.
Although not specified in the consensus statements, the authors of a second supplement published simultaneously with the updated guidelines (J Pediatr 2017;181(suppl):S27-S32.e1. doi: 10.1016/j.jpeds.2016.09.063), wrote that they supported genotyping all individuals diagnosed with CF, even if physiologic tests establish the diagnosis, to better understand the disease’s genetic epidemiology and to refine future therapies. “If the identified mutations are known to be associated with variable outcomes, or have unknown consequence, that genotype may not result in a CF phenotype. In these cases, other tests of CFTR function may help,” this supplement’s authors concluded.
The updated guideline authors recommend avoiding the use of terms such as “atypical” or “nonclassical” CF, as there is no consensus on the specific taxonomy of CF, since the genetic data are still emerging.
When administering a newborn test, the guidelines warn that the heterogenous nature of newborn screening often leads to false positive results, thus the need for the sweat test. Although obtaining an adequate sweat specimen for chloride measurements can be difficult, the authors say it is possible, especially in full-term infants aged 1 month. Repeat sweat testing is recommended, as is nasal potential difference (NPD) and intestinal current measurement (ICM) in some cases.
Another change to the guidelines is that newborns with a high immunoreactive trypsinogen level and inconclusive CFTR functional and genetic testing may now be designated as having CFTR-related metabolic syndrome/CF screen positive inconclusive diagnosis (CRMS/CFSPID), instead of CFTR-related metabolic syndrome or CF screen positive, inconclusive diagnosis. Regarding changes to screening for CRMS/CFSPID, the older guidelines called for such an assessment by age 2 months, repeated every 6-12 months, while the new guidelines say their recommendation on the duration and frequency of follow-up “remains to be determined.”
The authors of the first supplement decry the lack of standardized CF diagnostic criteria for those diagnosed with CF outside of the neonatal period, and urge clinicians to rely on clinical evidence including organ pathologies typical in CF, such as bronchiectasis or pancreatic insufficiency, along with testing for the presence of CFTR dysfunction with sweat chloride testing, CFTR molecular genetic analysis, or CFTR physiologic tests.
In contrast, the second supplement states that “clinical suspicion should always take precedence” in making a CF diagnoses for individuals in this age group.
Dr. Sosnay and Philip M. Farrell, MD, PhD, a coauthor of the guidelines, received funds from the Cystic Fibrosis Foundation, where guideline coauthor Terry B. White, PhD, is an employee. Kris De Boeck, MD, a coauthor of the first supplement, receives funding from Vertex Pharmaceuticals, Ablynx, Aptalis, Galapagos, Gilead, Pharmaxis, and PTC Therapeutics. The guideline and supplements’ other authors have no disclosures.
[email protected]
On Twitter @whitneymcknight
FROM JOURNAL OF PEDIATRICS
HFNC bests conventional O2 therapy
In patients with acute respiratory failure, high-flow nasal cannula (HFNC) is more reliable than is conventional oxygen therapy at reducing rates of endotracheal intubation, although no significant difference was found when HFNC was compared with noninvasive positive pressure ventilation, a new study found.
An increasing awareness of the high rate of adverse events and mortality rates associated with invasive mechanical ventilation in hospitals has led to a rise in the use of noninvasive positive pressure ventilation (NIPPV). While this has effectively cut the use of conventional oxygen therapy (COT), its application in clinical practice is limited by a host of complications such as interface intolerance, skin damage, and other hazards. HFNC, because of its demonstrated efficacy and relatively easier application, and better tolerance in patients, also has been gaining popularity. Despite the known benefits HFNC, this therapy is not given to all adults with acute respiratory failure (ARF). This may be due to the lack of consistency in data regarding how HFNC’s effectiveness at decreasing intubation and reintubation rates compares with COT’s and NIPPV’s.
Researchers in China conducted a meta-analysis and systematic review of all superiority and nonsuperiority data on the outcomes of using HFNC, COT, and NIPPV to treat ARF. Their examination included 18 trials comprising 3,881 patients, which compared the results of receiving HFNC with the results of receiving NIPPV or COT. The study is published in CHEST (10.1016/j.chest.2017.01.004).
The investigators concluded that HFNC was associated with significantly lower rates of the need for endotracheal intubation, compared with COT (P = .01). When HFNC was compared with NIPPV, however, the rates of patients needing intubation were not statistically different from each other (P = .16). HFNC was not associated with significant improvements in mortality rates or lengths of stay in the intensive care units, when compared with both COT and NIPPV.
According to the researchers’ subgroup analysis conducted of HFNC in 2,741 patients following extubation, those patients who received HFNC had a significantly lower reintubation rate than that of those who received COT (OR = 0.39, P = .0003). In this analysis, again, no significant differences in outcomes were seen between patients who received HFNC and NIPPV (OR = 1.07, P = .60)
Bin-Miao Liang, MD, PhD, a researcher in the department of respiratory and critical care medicine at Sichuan University in China, and coauthors noted that “concomitant complications such as acute kidney dysfunction and cardiac impairment may contribute to ICU mortality and ICU [lengths-of-stay] besides respiratory status itself.” Factors such as available beds, a patient’s insurance status, and other resources may also have impacted outcomes, they said.
The researchers wrote that they found “[significant] statistical heterogeneity” in the rates of endotracheal intubation and ICU mortality between HFNC and NIPPV. A lack of raw data, which prevented a subanalysis of individual respiratory failure from being performed, is one possible cause of the statistical heterogeneity, the authors concluded.
China-Japan Friendship Hospital is continuing the search for more data on the success rates of HFNC and NIPPV at reducing intubation and mortality rates. The hospital is sponsoring a multicenter, randomized, noninferiority trial titled, “High Flow Nasal Cannula vs. NPPV in Moderate Chronic Obstructive Pulmonary Disease Exacerbation,” according to ClinicalTrials.gov. No results were available for this trial as of Feb. 6.
None of the authors had relevant disclosures.
[email protected]
On Twitter @whitneymcknight
The introduction of high-flow nasal cannula (HFNC) fundamentally has changed how patients with acute respiratory failure are treated – both in avoidance of intubation and prevention of reintubation. Its use is supported by some very high quality studies over the last few years done in a variety of types of critically-ill patients. While its clinical superiority to noninvasive ventilation (NIV) is still open to debate, the comfort and other attributes that HFNC provides increasingly are making it the first-choice modality (e.g., the patient can continue to eat, speak, and wear for longer periods of time).
Eric J. Gartman, MD , is assistant professor of medicine at Brown University, Providence, R.I. He is an editorial board member of CHEST.
The introduction of high-flow nasal cannula (HFNC) fundamentally has changed how patients with acute respiratory failure are treated – both in avoidance of intubation and prevention of reintubation. Its use is supported by some very high quality studies over the last few years done in a variety of types of critically-ill patients. While its clinical superiority to noninvasive ventilation (NIV) is still open to debate, the comfort and other attributes that HFNC provides increasingly are making it the first-choice modality (e.g., the patient can continue to eat, speak, and wear for longer periods of time).
Eric J. Gartman, MD , is assistant professor of medicine at Brown University, Providence, R.I. He is an editorial board member of CHEST.
The introduction of high-flow nasal cannula (HFNC) fundamentally has changed how patients with acute respiratory failure are treated – both in avoidance of intubation and prevention of reintubation. Its use is supported by some very high quality studies over the last few years done in a variety of types of critically-ill patients. While its clinical superiority to noninvasive ventilation (NIV) is still open to debate, the comfort and other attributes that HFNC provides increasingly are making it the first-choice modality (e.g., the patient can continue to eat, speak, and wear for longer periods of time).
Eric J. Gartman, MD , is assistant professor of medicine at Brown University, Providence, R.I. He is an editorial board member of CHEST.
In patients with acute respiratory failure, high-flow nasal cannula (HFNC) is more reliable than is conventional oxygen therapy at reducing rates of endotracheal intubation, although no significant difference was found when HFNC was compared with noninvasive positive pressure ventilation, a new study found.
An increasing awareness of the high rate of adverse events and mortality rates associated with invasive mechanical ventilation in hospitals has led to a rise in the use of noninvasive positive pressure ventilation (NIPPV). While this has effectively cut the use of conventional oxygen therapy (COT), its application in clinical practice is limited by a host of complications such as interface intolerance, skin damage, and other hazards. HFNC, because of its demonstrated efficacy and relatively easier application, and better tolerance in patients, also has been gaining popularity. Despite the known benefits HFNC, this therapy is not given to all adults with acute respiratory failure (ARF). This may be due to the lack of consistency in data regarding how HFNC’s effectiveness at decreasing intubation and reintubation rates compares with COT’s and NIPPV’s.
Researchers in China conducted a meta-analysis and systematic review of all superiority and nonsuperiority data on the outcomes of using HFNC, COT, and NIPPV to treat ARF. Their examination included 18 trials comprising 3,881 patients, which compared the results of receiving HFNC with the results of receiving NIPPV or COT. The study is published in CHEST (10.1016/j.chest.2017.01.004).
The investigators concluded that HFNC was associated with significantly lower rates of the need for endotracheal intubation, compared with COT (P = .01). When HFNC was compared with NIPPV, however, the rates of patients needing intubation were not statistically different from each other (P = .16). HFNC was not associated with significant improvements in mortality rates or lengths of stay in the intensive care units, when compared with both COT and NIPPV.
According to the researchers’ subgroup analysis conducted of HFNC in 2,741 patients following extubation, those patients who received HFNC had a significantly lower reintubation rate than that of those who received COT (OR = 0.39, P = .0003). In this analysis, again, no significant differences in outcomes were seen between patients who received HFNC and NIPPV (OR = 1.07, P = .60)
Bin-Miao Liang, MD, PhD, a researcher in the department of respiratory and critical care medicine at Sichuan University in China, and coauthors noted that “concomitant complications such as acute kidney dysfunction and cardiac impairment may contribute to ICU mortality and ICU [lengths-of-stay] besides respiratory status itself.” Factors such as available beds, a patient’s insurance status, and other resources may also have impacted outcomes, they said.
The researchers wrote that they found “[significant] statistical heterogeneity” in the rates of endotracheal intubation and ICU mortality between HFNC and NIPPV. A lack of raw data, which prevented a subanalysis of individual respiratory failure from being performed, is one possible cause of the statistical heterogeneity, the authors concluded.
China-Japan Friendship Hospital is continuing the search for more data on the success rates of HFNC and NIPPV at reducing intubation and mortality rates. The hospital is sponsoring a multicenter, randomized, noninferiority trial titled, “High Flow Nasal Cannula vs. NPPV in Moderate Chronic Obstructive Pulmonary Disease Exacerbation,” according to ClinicalTrials.gov. No results were available for this trial as of Feb. 6.
None of the authors had relevant disclosures.
[email protected]
On Twitter @whitneymcknight
In patients with acute respiratory failure, high-flow nasal cannula (HFNC) is more reliable than is conventional oxygen therapy at reducing rates of endotracheal intubation, although no significant difference was found when HFNC was compared with noninvasive positive pressure ventilation, a new study found.
An increasing awareness of the high rate of adverse events and mortality rates associated with invasive mechanical ventilation in hospitals has led to a rise in the use of noninvasive positive pressure ventilation (NIPPV). While this has effectively cut the use of conventional oxygen therapy (COT), its application in clinical practice is limited by a host of complications such as interface intolerance, skin damage, and other hazards. HFNC, because of its demonstrated efficacy and relatively easier application, and better tolerance in patients, also has been gaining popularity. Despite the known benefits HFNC, this therapy is not given to all adults with acute respiratory failure (ARF). This may be due to the lack of consistency in data regarding how HFNC’s effectiveness at decreasing intubation and reintubation rates compares with COT’s and NIPPV’s.
Researchers in China conducted a meta-analysis and systematic review of all superiority and nonsuperiority data on the outcomes of using HFNC, COT, and NIPPV to treat ARF. Their examination included 18 trials comprising 3,881 patients, which compared the results of receiving HFNC with the results of receiving NIPPV or COT. The study is published in CHEST (10.1016/j.chest.2017.01.004).
The investigators concluded that HFNC was associated with significantly lower rates of the need for endotracheal intubation, compared with COT (P = .01). When HFNC was compared with NIPPV, however, the rates of patients needing intubation were not statistically different from each other (P = .16). HFNC was not associated with significant improvements in mortality rates or lengths of stay in the intensive care units, when compared with both COT and NIPPV.
According to the researchers’ subgroup analysis conducted of HFNC in 2,741 patients following extubation, those patients who received HFNC had a significantly lower reintubation rate than that of those who received COT (OR = 0.39, P = .0003). In this analysis, again, no significant differences in outcomes were seen between patients who received HFNC and NIPPV (OR = 1.07, P = .60)
Bin-Miao Liang, MD, PhD, a researcher in the department of respiratory and critical care medicine at Sichuan University in China, and coauthors noted that “concomitant complications such as acute kidney dysfunction and cardiac impairment may contribute to ICU mortality and ICU [lengths-of-stay] besides respiratory status itself.” Factors such as available beds, a patient’s insurance status, and other resources may also have impacted outcomes, they said.
The researchers wrote that they found “[significant] statistical heterogeneity” in the rates of endotracheal intubation and ICU mortality between HFNC and NIPPV. A lack of raw data, which prevented a subanalysis of individual respiratory failure from being performed, is one possible cause of the statistical heterogeneity, the authors concluded.
China-Japan Friendship Hospital is continuing the search for more data on the success rates of HFNC and NIPPV at reducing intubation and mortality rates. The hospital is sponsoring a multicenter, randomized, noninferiority trial titled, “High Flow Nasal Cannula vs. NPPV in Moderate Chronic Obstructive Pulmonary Disease Exacerbation,” according to ClinicalTrials.gov. No results were available for this trial as of Feb. 6.
None of the authors had relevant disclosures.
[email protected]
On Twitter @whitneymcknight
FROM CHEST
Key clinical point:
Major finding: Endotracheal intubation rates in adults with acute respiratory failure who received HFNC and NIPPV were not significantly different from each other (P = .16).
Data source: Meta-analysis and systematic review of 18 trials with 3,881 patients.
Disclosures: None of the authors had relevant disclosures.
Model: Quadrivalent vaccine could cost effectively cut MSM’s HPV-related cancers
Use of a quadrivalent HPV vaccine in men who have sex with men, administered in genitourinary specialty clinics, would cost effectively provide herd immunity against the ill effects of the virus, particularly anogenital warts and male HPV-related cancers, according to an English mathematical model.
Mark Jit, PhD, a professor of vaccine epidemiology at the London School of Hygiene & Tropical Medicine, and his colleagues considered in which settings HPV vaccination delivery would have the greatest effect size; the patterns of sexual behavior in MSM leading to the transmission of HPV 6, 11, 16, and 18; and the costs and quality adjusted life year (QALY) implications of disease outcomes (Clin Infect Dis. 2016 Dec 23. doi: 10.1093/cid/ciw845).
Clinic attendance rates were based on genitourinary clinic returns in England recorded in public health surveillance data recorded between 2009 and 2012, stratified according to diagnosed HIV-positive status. Also modeled were the effects of vaccination in MSM between the ages of 16 and 40 years, according to groups aged 16-25 years, 16-30 years, 16-35 years, and 16-40 years. Models for ages on either side of 16 or 40 years were not considered because of confidentiality constraints in the former and limited specialty clinic use in the latter.
Herd protection likely would be notable in the first year, because of the breadth of the age ranges modeled, Dr. Jit and his colleagues determined. Specifically, the models predicted a 35% decline in incidence rates of anogenital warts within 5 years of initiating the vaccine across all MSM men seen in specialty clinics. If only HIV-positive MSM across the age groups were vaccinated, the models predicted a 5-year decline of 15%.
Declines predicted in HPV-related cancers would happen more slowly, because progression from infection to malignancies tends to occur over years. For example, there would be a 55% reduction over 100 years for anal cancer if all 16- to 40-year-old MSM attending specialty clinics are offered vaccination. However, the reduction rate would drop to 40% in that same time period if only HIV-positive men across the age groups were vaccinated.
Using a cost-effectiveness threshold of 20,000 British pounds (about $24,500) per QALY, with no more than a 10% probability that the incremental cost-effectiveness ratio would exceed 30,000 pounds per QALY ($36,710), Dr. Jit and his colleagues determined that using a quadrivalent HPV vaccination in MSM between ages 16 and 40 years in the specialty clinic setting would be cost effective if delivery cost an average of 63 pounds ($77) per dose.
By offering vaccination only to HIV-positive MSM between 16 and 40 years, even if the quadrivalent vaccine were to cost as much as 96.50 pounds ($118), it would still be cost effective. A nonavalent vaccine at the same price would also be cost effective, because nearly all HPV-related cancers are linked to HPV 16 and 18. However, a bivalent vaccine was not shown by the models to be cost effective in such a limited program.
The investigators theorized that HIV infection is associated with the rate of HPV-related disease progression. To simplify computation, however, their models only considered the overall cost effectiveness of offering HPV vaccination to either HIV-positive MSM or to MSM regardless of current HIV status. That could mean “the cost effectiveness of MSM vaccination may be even better than reported,” the researchers noted.
This study was funded primarily by the National Institute for Health Research and Public Health England in the United Kingdom. The authors had no relevant disclosures.
[email protected]On Twitter @whitneymcknight
Use of a quadrivalent HPV vaccine in men who have sex with men, administered in genitourinary specialty clinics, would cost effectively provide herd immunity against the ill effects of the virus, particularly anogenital warts and male HPV-related cancers, according to an English mathematical model.
Mark Jit, PhD, a professor of vaccine epidemiology at the London School of Hygiene & Tropical Medicine, and his colleagues considered in which settings HPV vaccination delivery would have the greatest effect size; the patterns of sexual behavior in MSM leading to the transmission of HPV 6, 11, 16, and 18; and the costs and quality adjusted life year (QALY) implications of disease outcomes (Clin Infect Dis. 2016 Dec 23. doi: 10.1093/cid/ciw845).
Clinic attendance rates were based on genitourinary clinic returns in England recorded in public health surveillance data recorded between 2009 and 2012, stratified according to diagnosed HIV-positive status. Also modeled were the effects of vaccination in MSM between the ages of 16 and 40 years, according to groups aged 16-25 years, 16-30 years, 16-35 years, and 16-40 years. Models for ages on either side of 16 or 40 years were not considered because of confidentiality constraints in the former and limited specialty clinic use in the latter.
Herd protection likely would be notable in the first year, because of the breadth of the age ranges modeled, Dr. Jit and his colleagues determined. Specifically, the models predicted a 35% decline in incidence rates of anogenital warts within 5 years of initiating the vaccine across all MSM men seen in specialty clinics. If only HIV-positive MSM across the age groups were vaccinated, the models predicted a 5-year decline of 15%.
Declines predicted in HPV-related cancers would happen more slowly, because progression from infection to malignancies tends to occur over years. For example, there would be a 55% reduction over 100 years for anal cancer if all 16- to 40-year-old MSM attending specialty clinics are offered vaccination. However, the reduction rate would drop to 40% in that same time period if only HIV-positive men across the age groups were vaccinated.
Using a cost-effectiveness threshold of 20,000 British pounds (about $24,500) per QALY, with no more than a 10% probability that the incremental cost-effectiveness ratio would exceed 30,000 pounds per QALY ($36,710), Dr. Jit and his colleagues determined that using a quadrivalent HPV vaccination in MSM between ages 16 and 40 years in the specialty clinic setting would be cost effective if delivery cost an average of 63 pounds ($77) per dose.
By offering vaccination only to HIV-positive MSM between 16 and 40 years, even if the quadrivalent vaccine were to cost as much as 96.50 pounds ($118), it would still be cost effective. A nonavalent vaccine at the same price would also be cost effective, because nearly all HPV-related cancers are linked to HPV 16 and 18. However, a bivalent vaccine was not shown by the models to be cost effective in such a limited program.
The investigators theorized that HIV infection is associated with the rate of HPV-related disease progression. To simplify computation, however, their models only considered the overall cost effectiveness of offering HPV vaccination to either HIV-positive MSM or to MSM regardless of current HIV status. That could mean “the cost effectiveness of MSM vaccination may be even better than reported,” the researchers noted.
This study was funded primarily by the National Institute for Health Research and Public Health England in the United Kingdom. The authors had no relevant disclosures.
[email protected]On Twitter @whitneymcknight
Use of a quadrivalent HPV vaccine in men who have sex with men, administered in genitourinary specialty clinics, would cost effectively provide herd immunity against the ill effects of the virus, particularly anogenital warts and male HPV-related cancers, according to an English mathematical model.
Mark Jit, PhD, a professor of vaccine epidemiology at the London School of Hygiene & Tropical Medicine, and his colleagues considered in which settings HPV vaccination delivery would have the greatest effect size; the patterns of sexual behavior in MSM leading to the transmission of HPV 6, 11, 16, and 18; and the costs and quality adjusted life year (QALY) implications of disease outcomes (Clin Infect Dis. 2016 Dec 23. doi: 10.1093/cid/ciw845).
Clinic attendance rates were based on genitourinary clinic returns in England recorded in public health surveillance data recorded between 2009 and 2012, stratified according to diagnosed HIV-positive status. Also modeled were the effects of vaccination in MSM between the ages of 16 and 40 years, according to groups aged 16-25 years, 16-30 years, 16-35 years, and 16-40 years. Models for ages on either side of 16 or 40 years were not considered because of confidentiality constraints in the former and limited specialty clinic use in the latter.
Herd protection likely would be notable in the first year, because of the breadth of the age ranges modeled, Dr. Jit and his colleagues determined. Specifically, the models predicted a 35% decline in incidence rates of anogenital warts within 5 years of initiating the vaccine across all MSM men seen in specialty clinics. If only HIV-positive MSM across the age groups were vaccinated, the models predicted a 5-year decline of 15%.
Declines predicted in HPV-related cancers would happen more slowly, because progression from infection to malignancies tends to occur over years. For example, there would be a 55% reduction over 100 years for anal cancer if all 16- to 40-year-old MSM attending specialty clinics are offered vaccination. However, the reduction rate would drop to 40% in that same time period if only HIV-positive men across the age groups were vaccinated.
Using a cost-effectiveness threshold of 20,000 British pounds (about $24,500) per QALY, with no more than a 10% probability that the incremental cost-effectiveness ratio would exceed 30,000 pounds per QALY ($36,710), Dr. Jit and his colleagues determined that using a quadrivalent HPV vaccination in MSM between ages 16 and 40 years in the specialty clinic setting would be cost effective if delivery cost an average of 63 pounds ($77) per dose.
By offering vaccination only to HIV-positive MSM between 16 and 40 years, even if the quadrivalent vaccine were to cost as much as 96.50 pounds ($118), it would still be cost effective. A nonavalent vaccine at the same price would also be cost effective, because nearly all HPV-related cancers are linked to HPV 16 and 18. However, a bivalent vaccine was not shown by the models to be cost effective in such a limited program.
The investigators theorized that HIV infection is associated with the rate of HPV-related disease progression. To simplify computation, however, their models only considered the overall cost effectiveness of offering HPV vaccination to either HIV-positive MSM or to MSM regardless of current HIV status. That could mean “the cost effectiveness of MSM vaccination may be even better than reported,” the researchers noted.
This study was funded primarily by the National Institute for Health Research and Public Health England in the United Kingdom. The authors had no relevant disclosures.
[email protected]On Twitter @whitneymcknight
Key clinical point:
Major finding: Substantial declines in HPV-related events in MSM were projected within 5 years of vaccination between ages 16 and 40 years in this cohort.
Data source: Mathematical modeling of HPV 6, 11, 16, and 18 sexual transmission in the MSM population of England.
Disclosures: This study was funded primarily by the National Institute for Health Research and Public Health England in the United Kingdom. The authors had no relevant disclosures.
Unpublished study on Bendectin prompts questions on hidden data
Doubt is being cast on the efficacy of Diclegis – the only prescription drug approved in the United States for treating nausea and vomiting in pregnancy – after researchers exposed flaws in previously unpublished data that served as the basis for the drug’s approval.
But the larger point, according to the researcher who brought the unpublished study to light, is the danger of relying too heavily on hidden data.
“It’s not like there’s some special concern over the safety of Diclegis. It’s that there is this commonly prescribed medication that hasn’t been proven to be effective,” Navindra Persaud, MD, a family physician and researcher at St. Michael’s Hospital in Toronto, said in an interview.
The 8-Way Bendectin Study was a double-blind, multicentered, randomized, placebo-controlled study of 2,359 women with morning sickness in the first trimester, conducted in the United States across multiple sites in 1976 by the now-defunct Wm. S. Merrell Co. The aim was to find a replacement formulation of a three-agent formula (Bendectin) for morning sickness, after one of the ingredients – dicyclomine hydrochloride – was determined ineffective for pregnancy-related nausea and vomiting.
Participants in the study, which had seven treatment arms and one control group, were asked to keep diaries for a week, detailing their bouts of nausea and vomiting. Clinicians then evaluated and rated the diary entries. In all, data for 1,599 of the women were analyzed, with all seven treatment arms besting placebo. Doxylamine-pyridoxine was rated “moderate or excellent” with a 21% absolute difference, compared with placebo (95% confidence interval, 11-30). The most commonly reported side effect across the study was drowsiness.
Dr. Persaud said he thinks the study was never published because of multiple flaws. For instance, there was not a clear baseline for symptoms, or clear parameters for how the clinicians rated those symptoms; outcome data for more than a third of controls were missing, as were completed reports about potential adverse outcomes; and P values were one sided and not adjusted to account for all eight study arms, he said.
“While the analyzed data indicate differences from placebo for several combinations, the questionable data integrity, high dropout rate, and other methodological concerns mean that the prescribing of this medication should not be based on this trial,” wrote Dr. Persaud and Dr. Zhang in their analysis.
The newly published analysis brings back the rocky history of morning sickness treatments in the United States, notably the withdrawal of Bendectin in 1983 following a barrage of teratogenicity claims against the drug maker that made it unprofitable to continue marketing.
This is all beside the point, according to Dr. Persaud. “For every medication, you’re going to find some of these associations. They might be real; they might be not. So you have to weigh potential harm against the benefit. The real problem here is that there is no demonstrated benefit even though the claim seems to be that there is,” he said.
Duchesnay defended the efficacy of the drug.
“The conclusions expressed in the report published in PLOS ONE are highly inconsistent with the large and comprehensive body of evidence regarding this combination drug,” Michael Gallo, Duchesnay vice president for regulatory and medical affairs, said in a statement posted on the company’s website. In its response to Dr. Persaud and Dr. Zhang’s analysis, the company also said that doxylamine succinate and pyridoxine hydrochloride – the two agents in the treatment – are “ the most studied drug combination used in pregnancy. The safety and efficacy of [Diclegis] have been proven in 16 cohort studies, two meta-analyses, an ecological study, a neurological development study, and numerous others.”
“It’s unclear if the [unpublished] study was carefully reassessed in the lead-up to the recent approval of Diclegis,” he said. “The available FDA review documents for the recent approval of Diclectin [pyridoxine/doxylamine] do not mention the problems with the study.”
One factor in the treatment’s place in standard of care might be anecdotal influences from some of the more than 35 million women around the world thought to have used the treatment, according to Dr. Persaud. “Lots of women have taken this medication and felt better shortly after, so they feel strongly that the medication is effective,” he said, but because nausea and vomiting in pregnancy is common in more than three-quarters of women, and typically does not last more than several weeks, most likely the patients would have gotten better over time anyway.
“Some women suffer greatly and do seem to get relief from medication,” Dr. Chambers said, but noted that Diclegis is not the only option available for women.
When Bendectin was pulled from the U.S. market, for example, Dr. Chambers said women turned to combinations of vitamin B6 and over-the-counter medications that contain the antihistamine doxylamine.
Dr. Persaud said his interest in the review started after a patient expressed her concerns over the medication. “She was reluctant to take it, and asked me if I was sure about it. I reassured her, but then after she left, I did wonder if I was correct,” he recalled. He said he checked all the guidelines, but could not find anything to justify its use other than the manufacturer’s monograph.
He said he suspects this is not the only prescription medication that would not withstand such scrutiny, but that uncovering the necessary data would be very difficult. “I was shocked it was very difficult to get access to this information as a clinician,” he said, adding that it also is impractical to expect physicians to spend 5 years to track the information down.
In their analysis of the study, Dr. Persaud and Dr. Zhang stated that their objective is to contribute to a movement across all of medicine to end the risks of data secrecy, and instead “restore invisible and abandoned trials” (RIAT). The U.S. Department of Health & Human Services has been pushing to make more clinical trials data public through ClinicalTrials.gov, including issuing federal regulations requiring information to be made public for certain trials involving drugs and devices regulated by the FDA.
As for how his own practice has been impacted by this research, Dr. Persaud said he no longer prescribes Diclegis.
Dr. Persaud, Dr. Zhang, and Dr. Chambers had no relevant financial disclosures.
[email protected]
On Twitter @whitneymcknight
Between 1956 and 1983, the primary treatment for nausea/vomiting of pregnancy (NVP) was Bendectin, a combination of doxylamine and pyridoxine. In 1983, it was removed from the market by the manufacturer because of litigation expense. Following this, there was a marked increase in the incidence of hyperemesis gravidarum, the most severe form of NVP, which was probably due to ineffective treatment of the condition.
Several organizations have stated that the combination of doxylamine/pyridoxine is safe and effective for use in pregnancy. In 2002, the Society of Obstetricians and Gynaecologists of Canada concluded that the doxylamine/pyridoxine combination should be the standard of care because it had the greatest evidence to support its efficacy and safety. In 2004, the American College of Obstetricians and Gynecologists stated that the combination was safe and effective and was the first-line treatment for NVP. 
If NVP is not controlled with 2 tablets at bedtime, the Diclegis dose can be increased up to 4 tablets per day – 1 in the morning, 1 in midafternoon, and 2 at bedtime.
Gerald G. Briggs, BPharm, FCCP, is a clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, and Washington State University, Spokane. He is coauthor of “Drugs in Pregnancy and Lactation,” and coeditor of “Diseases, Complications, and Drug Therapy in Obstetrics.” He reported having no relevant financial disclosures.
Between 1956 and 1983, the primary treatment for nausea/vomiting of pregnancy (NVP) was Bendectin, a combination of doxylamine and pyridoxine. In 1983, it was removed from the market by the manufacturer because of litigation expense. Following this, there was a marked increase in the incidence of hyperemesis gravidarum, the most severe form of NVP, which was probably due to ineffective treatment of the condition.
Several organizations have stated that the combination of doxylamine/pyridoxine is safe and effective for use in pregnancy. In 2002, the Society of Obstetricians and Gynaecologists of Canada concluded that the doxylamine/pyridoxine combination should be the standard of care because it had the greatest evidence to support its efficacy and safety. In 2004, the American College of Obstetricians and Gynecologists stated that the combination was safe and effective and was the first-line treatment for NVP.
If NVP is not controlled with 2 tablets at bedtime, the Diclegis dose can be increased up to 4 tablets per day – 1 in the morning, 1 in midafternoon, and 2 at bedtime.
Gerald G. Briggs, BPharm, FCCP, is a clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, and Washington State University, Spokane. He is coauthor of “Drugs in Pregnancy and Lactation,” and coeditor of “Diseases, Complications, and Drug Therapy in Obstetrics.” He reported having no relevant financial disclosures.
Between 1956 and 1983, the primary treatment for nausea/vomiting of pregnancy (NVP) was Bendectin, a combination of doxylamine and pyridoxine. In 1983, it was removed from the market by the manufacturer because of litigation expense. Following this, there was a marked increase in the incidence of hyperemesis gravidarum, the most severe form of NVP, which was probably due to ineffective treatment of the condition.
Several organizations have stated that the combination of doxylamine/pyridoxine is safe and effective for use in pregnancy. In 2002, the Society of Obstetricians and Gynaecologists of Canada concluded that the doxylamine/pyridoxine combination should be the standard of care because it had the greatest evidence to support its efficacy and safety. In 2004, the American College of Obstetricians and Gynecologists stated that the combination was safe and effective and was the first-line treatment for NVP.
If NVP is not controlled with 2 tablets at bedtime, the Diclegis dose can be increased up to 4 tablets per day – 1 in the morning, 1 in midafternoon, and 2 at bedtime.
Gerald G. Briggs, BPharm, FCCP, is a clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, and Washington State University, Spokane. He is coauthor of “Drugs in Pregnancy and Lactation,” and coeditor of “Diseases, Complications, and Drug Therapy in Obstetrics.” He reported having no relevant financial disclosures.
Doubt is being cast on the efficacy of Diclegis – the only prescription drug approved in the United States for treating nausea and vomiting in pregnancy – after researchers exposed flaws in previously unpublished data that served as the basis for the drug’s approval.
But the larger point, according to the researcher who brought the unpublished study to light, is the danger of relying too heavily on hidden data.
“It’s not like there’s some special concern over the safety of Diclegis. It’s that there is this commonly prescribed medication that hasn’t been proven to be effective,” Navindra Persaud, MD, a family physician and researcher at St. Michael’s Hospital in Toronto, said in an interview.
The 8-Way Bendectin Study was a double-blind, multicentered, randomized, placebo-controlled study of 2,359 women with morning sickness in the first trimester, conducted in the United States across multiple sites in 1976 by the now-defunct Wm. S. Merrell Co. The aim was to find a replacement formulation of a three-agent formula (Bendectin) for morning sickness, after one of the ingredients – dicyclomine hydrochloride – was determined ineffective for pregnancy-related nausea and vomiting.
Participants in the study, which had seven treatment arms and one control group, were asked to keep diaries for a week, detailing their bouts of nausea and vomiting. Clinicians then evaluated and rated the diary entries. In all, data for 1,599 of the women were analyzed, with all seven treatment arms besting placebo. Doxylamine-pyridoxine was rated “moderate or excellent” with a 21% absolute difference, compared with placebo (95% confidence interval, 11-30). The most commonly reported side effect across the study was drowsiness.
Dr. Persaud said he thinks the study was never published because of multiple flaws. For instance, there was not a clear baseline for symptoms, or clear parameters for how the clinicians rated those symptoms; outcome data for more than a third of controls were missing, as were completed reports about potential adverse outcomes; and P values were one sided and not adjusted to account for all eight study arms, he said.
“While the analyzed data indicate differences from placebo for several combinations, the questionable data integrity, high dropout rate, and other methodological concerns mean that the prescribing of this medication should not be based on this trial,” wrote Dr. Persaud and Dr. Zhang in their analysis.
The newly published analysis brings back the rocky history of morning sickness treatments in the United States, notably the withdrawal of Bendectin in 1983 following a barrage of teratogenicity claims against the drug maker that made it unprofitable to continue marketing.
This is all beside the point, according to Dr. Persaud. “For every medication, you’re going to find some of these associations. They might be real; they might be not. So you have to weigh potential harm against the benefit. The real problem here is that there is no demonstrated benefit even though the claim seems to be that there is,” he said.
Duchesnay defended the efficacy of the drug.
“The conclusions expressed in the report published in PLOS ONE are highly inconsistent with the large and comprehensive body of evidence regarding this combination drug,” Michael Gallo, Duchesnay vice president for regulatory and medical affairs, said in a statement posted on the company’s website. In its response to Dr. Persaud and Dr. Zhang’s analysis, the company also said that doxylamine succinate and pyridoxine hydrochloride – the two agents in the treatment – are “ the most studied drug combination used in pregnancy. The safety and efficacy of [Diclegis] have been proven in 16 cohort studies, two meta-analyses, an ecological study, a neurological development study, and numerous others.”
“It’s unclear if the [unpublished] study was carefully reassessed in the lead-up to the recent approval of Diclegis,” he said. “The available FDA review documents for the recent approval of Diclectin [pyridoxine/doxylamine] do not mention the problems with the study.”
One factor in the treatment’s place in standard of care might be anecdotal influences from some of the more than 35 million women around the world thought to have used the treatment, according to Dr. Persaud. “Lots of women have taken this medication and felt better shortly after, so they feel strongly that the medication is effective,” he said, but because nausea and vomiting in pregnancy is common in more than three-quarters of women, and typically does not last more than several weeks, most likely the patients would have gotten better over time anyway.
“Some women suffer greatly and do seem to get relief from medication,” Dr. Chambers said, but noted that Diclegis is not the only option available for women.
When Bendectin was pulled from the U.S. market, for example, Dr. Chambers said women turned to combinations of vitamin B6 and over-the-counter medications that contain the antihistamine doxylamine.
Dr. Persaud said his interest in the review started after a patient expressed her concerns over the medication. “She was reluctant to take it, and asked me if I was sure about it. I reassured her, but then after she left, I did wonder if I was correct,” he recalled. He said he checked all the guidelines, but could not find anything to justify its use other than the manufacturer’s monograph.
He said he suspects this is not the only prescription medication that would not withstand such scrutiny, but that uncovering the necessary data would be very difficult. “I was shocked it was very difficult to get access to this information as a clinician,” he said, adding that it also is impractical to expect physicians to spend 5 years to track the information down.
In their analysis of the study, Dr. Persaud and Dr. Zhang stated that their objective is to contribute to a movement across all of medicine to end the risks of data secrecy, and instead “restore invisible and abandoned trials” (RIAT). The U.S. Department of Health & Human Services has been pushing to make more clinical trials data public through ClinicalTrials.gov, including issuing federal regulations requiring information to be made public for certain trials involving drugs and devices regulated by the FDA.
As for how his own practice has been impacted by this research, Dr. Persaud said he no longer prescribes Diclegis.
Dr. Persaud, Dr. Zhang, and Dr. Chambers had no relevant financial disclosures.
[email protected]
On Twitter @whitneymcknight
Doubt is being cast on the efficacy of Diclegis – the only prescription drug approved in the United States for treating nausea and vomiting in pregnancy – after researchers exposed flaws in previously unpublished data that served as the basis for the drug’s approval.
But the larger point, according to the researcher who brought the unpublished study to light, is the danger of relying too heavily on hidden data.
“It’s not like there’s some special concern over the safety of Diclegis. It’s that there is this commonly prescribed medication that hasn’t been proven to be effective,” Navindra Persaud, MD, a family physician and researcher at St. Michael’s Hospital in Toronto, said in an interview.
The 8-Way Bendectin Study was a double-blind, multicentered, randomized, placebo-controlled study of 2,359 women with morning sickness in the first trimester, conducted in the United States across multiple sites in 1976 by the now-defunct Wm. S. Merrell Co. The aim was to find a replacement formulation of a three-agent formula (Bendectin) for morning sickness, after one of the ingredients – dicyclomine hydrochloride – was determined ineffective for pregnancy-related nausea and vomiting.
Participants in the study, which had seven treatment arms and one control group, were asked to keep diaries for a week, detailing their bouts of nausea and vomiting. Clinicians then evaluated and rated the diary entries. In all, data for 1,599 of the women were analyzed, with all seven treatment arms besting placebo. Doxylamine-pyridoxine was rated “moderate or excellent” with a 21% absolute difference, compared with placebo (95% confidence interval, 11-30). The most commonly reported side effect across the study was drowsiness.
Dr. Persaud said he thinks the study was never published because of multiple flaws. For instance, there was not a clear baseline for symptoms, or clear parameters for how the clinicians rated those symptoms; outcome data for more than a third of controls were missing, as were completed reports about potential adverse outcomes; and P values were one sided and not adjusted to account for all eight study arms, he said.
“While the analyzed data indicate differences from placebo for several combinations, the questionable data integrity, high dropout rate, and other methodological concerns mean that the prescribing of this medication should not be based on this trial,” wrote Dr. Persaud and Dr. Zhang in their analysis.
The newly published analysis brings back the rocky history of morning sickness treatments in the United States, notably the withdrawal of Bendectin in 1983 following a barrage of teratogenicity claims against the drug maker that made it unprofitable to continue marketing.
This is all beside the point, according to Dr. Persaud. “For every medication, you’re going to find some of these associations. They might be real; they might be not. So you have to weigh potential harm against the benefit. The real problem here is that there is no demonstrated benefit even though the claim seems to be that there is,” he said.
Duchesnay defended the efficacy of the drug.
“The conclusions expressed in the report published in PLOS ONE are highly inconsistent with the large and comprehensive body of evidence regarding this combination drug,” Michael Gallo, Duchesnay vice president for regulatory and medical affairs, said in a statement posted on the company’s website. In its response to Dr. Persaud and Dr. Zhang’s analysis, the company also said that doxylamine succinate and pyridoxine hydrochloride – the two agents in the treatment – are “ the most studied drug combination used in pregnancy. The safety and efficacy of [Diclegis] have been proven in 16 cohort studies, two meta-analyses, an ecological study, a neurological development study, and numerous others.”
“It’s unclear if the [unpublished] study was carefully reassessed in the lead-up to the recent approval of Diclegis,” he said. “The available FDA review documents for the recent approval of Diclectin [pyridoxine/doxylamine] do not mention the problems with the study.”
One factor in the treatment’s place in standard of care might be anecdotal influences from some of the more than 35 million women around the world thought to have used the treatment, according to Dr. Persaud. “Lots of women have taken this medication and felt better shortly after, so they feel strongly that the medication is effective,” he said, but because nausea and vomiting in pregnancy is common in more than three-quarters of women, and typically does not last more than several weeks, most likely the patients would have gotten better over time anyway.
“Some women suffer greatly and do seem to get relief from medication,” Dr. Chambers said, but noted that Diclegis is not the only option available for women.
When Bendectin was pulled from the U.S. market, for example, Dr. Chambers said women turned to combinations of vitamin B6 and over-the-counter medications that contain the antihistamine doxylamine.
Dr. Persaud said his interest in the review started after a patient expressed her concerns over the medication. “She was reluctant to take it, and asked me if I was sure about it. I reassured her, but then after she left, I did wonder if I was correct,” he recalled. He said he checked all the guidelines, but could not find anything to justify its use other than the manufacturer’s monograph.
He said he suspects this is not the only prescription medication that would not withstand such scrutiny, but that uncovering the necessary data would be very difficult. “I was shocked it was very difficult to get access to this information as a clinician,” he said, adding that it also is impractical to expect physicians to spend 5 years to track the information down.
In their analysis of the study, Dr. Persaud and Dr. Zhang stated that their objective is to contribute to a movement across all of medicine to end the risks of data secrecy, and instead “restore invisible and abandoned trials” (RIAT). The U.S. Department of Health & Human Services has been pushing to make more clinical trials data public through ClinicalTrials.gov, including issuing federal regulations requiring information to be made public for certain trials involving drugs and devices regulated by the FDA.
As for how his own practice has been impacted by this research, Dr. Persaud said he no longer prescribes Diclegis.
Dr. Persaud, Dr. Zhang, and Dr. Chambers had no relevant financial disclosures.
[email protected]
On Twitter @whitneymcknight
Racial disparity in cervical cancer deaths higher than previously reported
Corrected mortality rates for cervical cancer indicate a greater disparity between races, according to a report in Cancer.
Because previous estimates did not adjust for women who’d had a hysterectomy or who were otherwise not at risk for cervical cancer, investigators performed a “corrected” analysis using data from the Behavioral Risk Factor Surveillance System and from the National Center for Health Statistics and the National Cancer Institute’s Surveillance, Epidemiology, and End Results program, for the years 2002 through 2012.
The corrected mortality rate in black women is 10.1 per 100,000 women (95% confidence interval, 9.6-10.6) and 4.7 per 100,000 in white women (95% CI, 4.6-4.8), an overall difference of 44%. The previous, uncorrected mortality rate for black women was 5.7 per 100,000 (95% CI, 5.5-6.0) and 3.2 per 100,000 (95% CI, 3.1-3.2) for white women, reported Anne F. Rositch, PhD, of Johns Hopkins Bloomberg School of Public Health, Baltimore, and her colleagues.
The corrected findings do not indicate a rise in the overall cervical cancer death rate, but do show that the disparity between the races is higher, despite declines in such deaths among black women over the years: The corrected analysis over the decade showed that the rate of decrease in cervical cancer mortality rates was 0.8% in white women and 3.6% in black women (P less than .05), Dr. Rositch and her associates reported (Cancer 2017 Jan 23 doi: 10.1002/cncr.30507). Both corrected and uncorrected rates were significantly higher in older black women, especially those 85 years and older at 18.6 per 100,000 (95% CI, 15.4-21.7) before correction, and 37.2 per 100,000 (95% CI, 31.0-43.5) after correction.
“Future research should focus on overcoming the underlying factors that contribute to this mortality gap (differential follow-up for abnormal Papanicolaou test results and barriers to care after diagnosis) and on determining why black women and older women receive different and inadequate treatment for the same disease,” wrote Dr. Rositch and her colleagues.
The elimination of mortality differences across the two races in women aged 20-29 years and those 35-39 years was “encouraging ... because these age cohorts correspond to the patients who are most likely to have been vaccinated against the human papillomavirus (HPV) virus,” Heather J. Dalton, MD, and John Farley, MD, of Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center, Phoenix, Ariz., wrote in an accompanying editorial (Cancer 2017 Jan. 23 doi: 10.1002/cncr.30501).
High-risk HPV infections and lack of adequate screening are the “only factors definitely associated with the incidence of cervical cancer,” they noted.
[email protected]
On Twitter @whitneymcknight
Corrected mortality rates for cervical cancer indicate a greater disparity between races, according to a report in Cancer.
Because previous estimates did not adjust for women who’d had a hysterectomy or who were otherwise not at risk for cervical cancer, investigators performed a “corrected” analysis using data from the Behavioral Risk Factor Surveillance System and from the National Center for Health Statistics and the National Cancer Institute’s Surveillance, Epidemiology, and End Results program, for the years 2002 through 2012.
The corrected mortality rate in black women is 10.1 per 100,000 women (95% confidence interval, 9.6-10.6) and 4.7 per 100,000 in white women (95% CI, 4.6-4.8), an overall difference of 44%. The previous, uncorrected mortality rate for black women was 5.7 per 100,000 (95% CI, 5.5-6.0) and 3.2 per 100,000 (95% CI, 3.1-3.2) for white women, reported Anne F. Rositch, PhD, of Johns Hopkins Bloomberg School of Public Health, Baltimore, and her colleagues.
The corrected findings do not indicate a rise in the overall cervical cancer death rate, but do show that the disparity between the races is higher, despite declines in such deaths among black women over the years: The corrected analysis over the decade showed that the rate of decrease in cervical cancer mortality rates was 0.8% in white women and 3.6% in black women (P less than .05), Dr. Rositch and her associates reported (Cancer 2017 Jan 23 doi: 10.1002/cncr.30507). Both corrected and uncorrected rates were significantly higher in older black women, especially those 85 years and older at 18.6 per 100,000 (95% CI, 15.4-21.7) before correction, and 37.2 per 100,000 (95% CI, 31.0-43.5) after correction.
“Future research should focus on overcoming the underlying factors that contribute to this mortality gap (differential follow-up for abnormal Papanicolaou test results and barriers to care after diagnosis) and on determining why black women and older women receive different and inadequate treatment for the same disease,” wrote Dr. Rositch and her colleagues.
The elimination of mortality differences across the two races in women aged 20-29 years and those 35-39 years was “encouraging ... because these age cohorts correspond to the patients who are most likely to have been vaccinated against the human papillomavirus (HPV) virus,” Heather J. Dalton, MD, and John Farley, MD, of Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center, Phoenix, Ariz., wrote in an accompanying editorial (Cancer 2017 Jan. 23 doi: 10.1002/cncr.30501).
High-risk HPV infections and lack of adequate screening are the “only factors definitely associated with the incidence of cervical cancer,” they noted.
[email protected]
On Twitter @whitneymcknight
Corrected mortality rates for cervical cancer indicate a greater disparity between races, according to a report in Cancer.
Because previous estimates did not adjust for women who’d had a hysterectomy or who were otherwise not at risk for cervical cancer, investigators performed a “corrected” analysis using data from the Behavioral Risk Factor Surveillance System and from the National Center for Health Statistics and the National Cancer Institute’s Surveillance, Epidemiology, and End Results program, for the years 2002 through 2012.
The corrected mortality rate in black women is 10.1 per 100,000 women (95% confidence interval, 9.6-10.6) and 4.7 per 100,000 in white women (95% CI, 4.6-4.8), an overall difference of 44%. The previous, uncorrected mortality rate for black women was 5.7 per 100,000 (95% CI, 5.5-6.0) and 3.2 per 100,000 (95% CI, 3.1-3.2) for white women, reported Anne F. Rositch, PhD, of Johns Hopkins Bloomberg School of Public Health, Baltimore, and her colleagues.
The corrected findings do not indicate a rise in the overall cervical cancer death rate, but do show that the disparity between the races is higher, despite declines in such deaths among black women over the years: The corrected analysis over the decade showed that the rate of decrease in cervical cancer mortality rates was 0.8% in white women and 3.6% in black women (P less than .05), Dr. Rositch and her associates reported (Cancer 2017 Jan 23 doi: 10.1002/cncr.30507). Both corrected and uncorrected rates were significantly higher in older black women, especially those 85 years and older at 18.6 per 100,000 (95% CI, 15.4-21.7) before correction, and 37.2 per 100,000 (95% CI, 31.0-43.5) after correction.
“Future research should focus on overcoming the underlying factors that contribute to this mortality gap (differential follow-up for abnormal Papanicolaou test results and barriers to care after diagnosis) and on determining why black women and older women receive different and inadequate treatment for the same disease,” wrote Dr. Rositch and her colleagues.
The elimination of mortality differences across the two races in women aged 20-29 years and those 35-39 years was “encouraging ... because these age cohorts correspond to the patients who are most likely to have been vaccinated against the human papillomavirus (HPV) virus,” Heather J. Dalton, MD, and John Farley, MD, of Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center, Phoenix, Ariz., wrote in an accompanying editorial (Cancer 2017 Jan. 23 doi: 10.1002/cncr.30501).
High-risk HPV infections and lack of adequate screening are the “only factors definitely associated with the incidence of cervical cancer,” they noted.
[email protected]
On Twitter @whitneymcknight
FROM CANCER
Key clinical point:
Major finding: Black women die from cervical cancer at a rate of 10.1 per 100,000 women; the rate for white women is 4.7 per 100,000, a 44% disparity.
Data source: National population database study from 2002 to 2012, adjusted for women not at risk for cervical cancer.
Disclosures: Dr. Patti E. Gravitt reported support from Hologic for research not related to this study.
COBRA trial takes the long view of absorbable biosynthetic mesh outcomes
Absorbable, biosynthetic surgical mesh used to repair ventral hernia defects may be a good alternative to biologic and permanent synthetic mesh products both in terms of long-term durability and cost, according to a longitudinal cohort study.
The results of the COBRA (Complex Open Bioabsorbable Reconstruction of the Abdominal Wall) study published in the January issue of Annals of Surgery represent the longest follow-up of patients in whom this product was used. Lead author of the study, Michael J. Rosen, MD, professor of surgery at Case Western Reserve University, Cleveland, and his colleagues wrote: “Absorbable synthetic mesh has the prospective advantages of a reduced cost, minimal constraints in manufacturing alternative sizes (lengths, widths, and thicknesses), informed consent in certain religious or cultural groups, and ability to be iterative in generational improvements in mesh constructs based on outcome studies, compared with allogeneic or xenogenic mesh.”
Contaminated wounds were present in 77% of participants. About one-fourth of patients had concomitant procedures for fistula takedown; a quarter of the cohort also required the removal of infected, previously placed mesh. More than a fifth of patients required a concomitant repair of both a midline and parastomal hernia; the mean size for the hernia defects was 137 cm2, and the average width was 9 cm.
Placement of the biosynthetic mesh was left to the discretion of the surgeon, but 90% chose retrorectus placement. Primary fascial closure using a single unit of the material was successful in all patients, 68 of whom required concomitant component separation; 21 of these had an external oblique release. Another 50 of these had transversus abdominis release.
At 24 months, when 84% of patients completed follow-up, 17% were found to have a hernia recurrence. Intraperitoneal placement of the material was found to significantly increase the risk of hernia recurrence (P less than or equal to .04). Infections at the surgical site were associated with a higher risk of recurrence (P less than .01). Patient-reported physical and mental quality-of-life scores at 24 months improved significantly from baseline (P less than .05), showing sustained improvement at 6 and 12 months post procedure.
While more studies are needed, the COBRA findings suggest absorbable, biosynthetic mesh compares favorably with biologic mesh when it comes to recurrence. “The Repair of Infected and Contaminated Hernias (RICH) trial is the only long-term, multicentered, prospective trial to evaluate biologic mesh in CDC [Centers for Disease Control and Prevention] class II to IV wounds. The RICH trial reported 66% surgical site occurrence and 28% hernia recurrence after 2 years’ follow-up in patients who underwent ventral hernia repair with a non–cross-linked porcine dermis,” the investigators noted.
Cost is another area in which bioabsorbable synthetic mesh compares favorably with the biologics, not only in terms of savings from fewer recurrences but also the cost of the mesh itself. Biologic mesh can cost $10,000 or more while synthetics run about a quarter of that (Clin Colon Rectal Surg. 2014 Dec; 27[4]:140-8).
In conclusion, the investigators commented that despite the lack of a control group and random assignment in the study, the results “should not be underestimated” when considering alternatives to biologic and costlier, permanent synthetic meshes.
The study was funded by W.L. Gore. The authors had no relevant financial disclosures.
Absorbable, biosynthetic surgical mesh used to repair ventral hernia defects may be a good alternative to biologic and permanent synthetic mesh products both in terms of long-term durability and cost, according to a longitudinal cohort study.
The results of the COBRA (Complex Open Bioabsorbable Reconstruction of the Abdominal Wall) study published in the January issue of Annals of Surgery represent the longest follow-up of patients in whom this product was used. Lead author of the study, Michael J. Rosen, MD, professor of surgery at Case Western Reserve University, Cleveland, and his colleagues wrote: “Absorbable synthetic mesh has the prospective advantages of a reduced cost, minimal constraints in manufacturing alternative sizes (lengths, widths, and thicknesses), informed consent in certain religious or cultural groups, and ability to be iterative in generational improvements in mesh constructs based on outcome studies, compared with allogeneic or xenogenic mesh.”
Contaminated wounds were present in 77% of participants. About one-fourth of patients had concomitant procedures for fistula takedown; a quarter of the cohort also required the removal of infected, previously placed mesh. More than a fifth of patients required a concomitant repair of both a midline and parastomal hernia; the mean size for the hernia defects was 137 cm2, and the average width was 9 cm.
Placement of the biosynthetic mesh was left to the discretion of the surgeon, but 90% chose retrorectus placement. Primary fascial closure using a single unit of the material was successful in all patients, 68 of whom required concomitant component separation; 21 of these had an external oblique release. Another 50 of these had transversus abdominis release.
At 24 months, when 84% of patients completed follow-up, 17% were found to have a hernia recurrence. Intraperitoneal placement of the material was found to significantly increase the risk of hernia recurrence (P less than or equal to .04). Infections at the surgical site were associated with a higher risk of recurrence (P less than .01). Patient-reported physical and mental quality-of-life scores at 24 months improved significantly from baseline (P less than .05), showing sustained improvement at 6 and 12 months post procedure.
While more studies are needed, the COBRA findings suggest absorbable, biosynthetic mesh compares favorably with biologic mesh when it comes to recurrence. “The Repair of Infected and Contaminated Hernias (RICH) trial is the only long-term, multicentered, prospective trial to evaluate biologic mesh in CDC [Centers for Disease Control and Prevention] class II to IV wounds. The RICH trial reported 66% surgical site occurrence and 28% hernia recurrence after 2 years’ follow-up in patients who underwent ventral hernia repair with a non–cross-linked porcine dermis,” the investigators noted.
Cost is another area in which bioabsorbable synthetic mesh compares favorably with the biologics, not only in terms of savings from fewer recurrences but also the cost of the mesh itself. Biologic mesh can cost $10,000 or more while synthetics run about a quarter of that (Clin Colon Rectal Surg. 2014 Dec; 27[4]:140-8).
In conclusion, the investigators commented that despite the lack of a control group and random assignment in the study, the results “should not be underestimated” when considering alternatives to biologic and costlier, permanent synthetic meshes.
The study was funded by W.L. Gore. The authors had no relevant financial disclosures.
Absorbable, biosynthetic surgical mesh used to repair ventral hernia defects may be a good alternative to biologic and permanent synthetic mesh products both in terms of long-term durability and cost, according to a longitudinal cohort study.
The results of the COBRA (Complex Open Bioabsorbable Reconstruction of the Abdominal Wall) study published in the January issue of Annals of Surgery represent the longest follow-up of patients in whom this product was used. Lead author of the study, Michael J. Rosen, MD, professor of surgery at Case Western Reserve University, Cleveland, and his colleagues wrote: “Absorbable synthetic mesh has the prospective advantages of a reduced cost, minimal constraints in manufacturing alternative sizes (lengths, widths, and thicknesses), informed consent in certain religious or cultural groups, and ability to be iterative in generational improvements in mesh constructs based on outcome studies, compared with allogeneic or xenogenic mesh.”
Contaminated wounds were present in 77% of participants. About one-fourth of patients had concomitant procedures for fistula takedown; a quarter of the cohort also required the removal of infected, previously placed mesh. More than a fifth of patients required a concomitant repair of both a midline and parastomal hernia; the mean size for the hernia defects was 137 cm2, and the average width was 9 cm.
Placement of the biosynthetic mesh was left to the discretion of the surgeon, but 90% chose retrorectus placement. Primary fascial closure using a single unit of the material was successful in all patients, 68 of whom required concomitant component separation; 21 of these had an external oblique release. Another 50 of these had transversus abdominis release.
At 24 months, when 84% of patients completed follow-up, 17% were found to have a hernia recurrence. Intraperitoneal placement of the material was found to significantly increase the risk of hernia recurrence (P less than or equal to .04). Infections at the surgical site were associated with a higher risk of recurrence (P less than .01). Patient-reported physical and mental quality-of-life scores at 24 months improved significantly from baseline (P less than .05), showing sustained improvement at 6 and 12 months post procedure.
While more studies are needed, the COBRA findings suggest absorbable, biosynthetic mesh compares favorably with biologic mesh when it comes to recurrence. “The Repair of Infected and Contaminated Hernias (RICH) trial is the only long-term, multicentered, prospective trial to evaluate biologic mesh in CDC [Centers for Disease Control and Prevention] class II to IV wounds. The RICH trial reported 66% surgical site occurrence and 28% hernia recurrence after 2 years’ follow-up in patients who underwent ventral hernia repair with a non–cross-linked porcine dermis,” the investigators noted.
Cost is another area in which bioabsorbable synthetic mesh compares favorably with the biologics, not only in terms of savings from fewer recurrences but also the cost of the mesh itself. Biologic mesh can cost $10,000 or more while synthetics run about a quarter of that (Clin Colon Rectal Surg. 2014 Dec; 27[4]:140-8).
In conclusion, the investigators commented that despite the lack of a control group and random assignment in the study, the results “should not be underestimated” when considering alternatives to biologic and costlier, permanent synthetic meshes.
The study was funded by W.L. Gore. The authors had no relevant financial disclosures.
Key clinical point:
Major finding: At 24 months, 17% of patients were found to have a hernia recurrence.
Data source: An international, multisite, prospective, intention-to-treat cohort analysis of 104 patients with contaminated or noncontaminated hernia defects of at least 9 cm2 in size.
Disclosures: The study was funded by W.L. Gore. The authors had no relevant financial disclosures.
Expert reviews options for refractory pediatric warts
For refractory warts, there are some “last resort” treatments every dermatologist should have on hand, according to pediatric dermatologist Fred E. Ghali, MD.
“It’s good to know about these, although it’s also good to know that sometimes you just have to wait out the warts and let them clear up on their own,” said Dr. Ghali, of the departments of dermatology at University of Texas, Dallas, and Baylor College of Medicine, Houston. Because very few treatment options are approved for warts, Dr. Ghali shared some of his preferred off-label approaches at the meeting provided by Global Academy for Medical Education.
By the time patients make it to his clinic, Dr. Ghali noted that many patients have failed home remedies such as salicylic acid or duct tape. In some cases, however, warts may not respond well to the standard in-office options such as cryotherapy. For refractory cases, he said that one of the following approaches can be considered:
Sectional cryotherapy
For larger, solitary warts, especially ring warts, freezing them in sections can be a good option, according to Dr. Ghali. This can be done best using a cotton-tip applicator rather than the traditional spray gun. In his experience, this minimizes the risk of ring wart formation, which may occur from aggressive cryotherapy focused primarily on the central portion of the wart, sometimes creating a resultant blister much larger than the original wart, with the formation of a ring wart.
Topical immunotherapy
When it comes to refractory cases in younger children, or in cases with multiple warts on the hands and feet, topical immunotherapy is often a preferred treatment. In these cases, Dr. Ghali recommended squaric acid. “The general principle with topical immunotherapy is that you would induce contact allergy with the treatment by applying it to one place on the skin, usually the arm, in the office setting,” he said. If using squaric acid, he recommended starting with 2% to sensitize in the office; then for home use, prescribing a lower concentration of the treatment – usually 0.6% – painted directly onto the lesions to provoke an immune response. This should be done three times a week at first, and then adding one application each week until the warts are being treated daily.
“If there is no response in 2 months, then increase the strength used at home,” Dr. Ghali said.
With this treatment, there is the potential for contact dermatitis, which is usually localized, but can be widespread beyond the areas of application, he cautioned. When this occurs, he recommended decreasing or discontinuing the applications and considering a topical steroid or oral steroid depending upon the severity of the reaction. “I mainly use squaric acid for the hands and feet, and almost always avoid it on the face, neck, and groin,” Dr. Ghali said.
In his practice, he finds this treatment is effective about three-quarters of the time, and seems to work particularly well with plantar warts, clearing them up in 2-4 months. The advantages of this approach are that it is not painful, is relatively easy for patients to comply with, and can be combined with other treatments if desired.
Intralesional immunotherapy
When squaric acid or cryotherapy fails, Candida antigen injection is a commonly used technique used to train the immune system to attack the warts, inducing a delayed hypersensitivity reaction. “Injectable immunotherapy is ideal in cases of a solitary [wart] or a limited number of warts,” Dr. Ghali said in an interview. “For most patients, I typically inject 0.1-0.2 cc of Candida antigen per wart. In the case of larger, ring-type warts, especially on the knees and elbows, we may need to use larger volumes, up to 0.2 cc-0.6cc,” he added.
“It’s important to remind patients that temporary, localized swelling may occur after injections; thus, care should be taken when injecting near periungual locations,” Dr. Ghali continued, noting that “it’s probably best practice to avoid subungual injections.”
Immunotherapy has relatively few side effects, and may be effective in about three-quarters of cases, according to Dr. Ghali, although he cautioned that younger children may be anxious about receiving injections and may resist treatment.
Electrodessication and curettage
For challenging warts, such as stubborn palmar or plantar warts, Dr. Ghali suggested using local anesthesia plus electrodessication and curettage.
“Sometimes with these refractory warts, we resort to off-label therapies compounded for home use,” he added. Such therapies may include salicylic acid with 5-fluorouracil, or topical cidofovir 2%-3%. These compounds can be costly depending upon the patient’s insurance coverage.
Dr. Ghali concluded by presenting his top three rules to consider when treating warts, regardless of treatment: There is no cure for warts, no therapy is uniformly effective, and the chosen therapy should take into account the family’s costs, according to their insurance coverage.
Since the landscape of insurance coverage has changed over recent years, the code most often used to treat warts in the office, often applies to the patient’s or family’s deductible. “It’s important to discuss this with the family beforehand, especially since treatment for warts may require several visits,” he said.
Dr. Ghali disclosed several financial relationships with the pharmaceutical industry including Astellas, Galderma, and Valeant, among others.
Global Academy and this news organization are owned by the same parent company.
[email protected]
On Twitter @whitneymcknight
For refractory warts, there are some “last resort” treatments every dermatologist should have on hand, according to pediatric dermatologist Fred E. Ghali, MD.
“It’s good to know about these, although it’s also good to know that sometimes you just have to wait out the warts and let them clear up on their own,” said Dr. Ghali, of the departments of dermatology at University of Texas, Dallas, and Baylor College of Medicine, Houston. Because very few treatment options are approved for warts, Dr. Ghali shared some of his preferred off-label approaches at the meeting provided by Global Academy for Medical Education.
By the time patients make it to his clinic, Dr. Ghali noted that many patients have failed home remedies such as salicylic acid or duct tape. In some cases, however, warts may not respond well to the standard in-office options such as cryotherapy. For refractory cases, he said that one of the following approaches can be considered:
Sectional cryotherapy
For larger, solitary warts, especially ring warts, freezing them in sections can be a good option, according to Dr. Ghali. This can be done best using a cotton-tip applicator rather than the traditional spray gun. In his experience, this minimizes the risk of ring wart formation, which may occur from aggressive cryotherapy focused primarily on the central portion of the wart, sometimes creating a resultant blister much larger than the original wart, with the formation of a ring wart.
Topical immunotherapy
When it comes to refractory cases in younger children, or in cases with multiple warts on the hands and feet, topical immunotherapy is often a preferred treatment. In these cases, Dr. Ghali recommended squaric acid. “The general principle with topical immunotherapy is that you would induce contact allergy with the treatment by applying it to one place on the skin, usually the arm, in the office setting,” he said. If using squaric acid, he recommended starting with 2% to sensitize in the office; then for home use, prescribing a lower concentration of the treatment – usually 0.6% – painted directly onto the lesions to provoke an immune response. This should be done three times a week at first, and then adding one application each week until the warts are being treated daily.
“If there is no response in 2 months, then increase the strength used at home,” Dr. Ghali said.
With this treatment, there is the potential for contact dermatitis, which is usually localized, but can be widespread beyond the areas of application, he cautioned. When this occurs, he recommended decreasing or discontinuing the applications and considering a topical steroid or oral steroid depending upon the severity of the reaction. “I mainly use squaric acid for the hands and feet, and almost always avoid it on the face, neck, and groin,” Dr. Ghali said.
In his practice, he finds this treatment is effective about three-quarters of the time, and seems to work particularly well with plantar warts, clearing them up in 2-4 months. The advantages of this approach are that it is not painful, is relatively easy for patients to comply with, and can be combined with other treatments if desired.
Intralesional immunotherapy
When squaric acid or cryotherapy fails, Candida antigen injection is a commonly used technique used to train the immune system to attack the warts, inducing a delayed hypersensitivity reaction. “Injectable immunotherapy is ideal in cases of a solitary [wart] or a limited number of warts,” Dr. Ghali said in an interview. “For most patients, I typically inject 0.1-0.2 cc of Candida antigen per wart. In the case of larger, ring-type warts, especially on the knees and elbows, we may need to use larger volumes, up to 0.2 cc-0.6cc,” he added.
“It’s important to remind patients that temporary, localized swelling may occur after injections; thus, care should be taken when injecting near periungual locations,” Dr. Ghali continued, noting that “it’s probably best practice to avoid subungual injections.”
Immunotherapy has relatively few side effects, and may be effective in about three-quarters of cases, according to Dr. Ghali, although he cautioned that younger children may be anxious about receiving injections and may resist treatment.
Electrodessication and curettage
For challenging warts, such as stubborn palmar or plantar warts, Dr. Ghali suggested using local anesthesia plus electrodessication and curettage.
“Sometimes with these refractory warts, we resort to off-label therapies compounded for home use,” he added. Such therapies may include salicylic acid with 5-fluorouracil, or topical cidofovir 2%-3%. These compounds can be costly depending upon the patient’s insurance coverage.
Dr. Ghali concluded by presenting his top three rules to consider when treating warts, regardless of treatment: There is no cure for warts, no therapy is uniformly effective, and the chosen therapy should take into account the family’s costs, according to their insurance coverage.
Since the landscape of insurance coverage has changed over recent years, the code most often used to treat warts in the office, often applies to the patient’s or family’s deductible. “It’s important to discuss this with the family beforehand, especially since treatment for warts may require several visits,” he said.
Dr. Ghali disclosed several financial relationships with the pharmaceutical industry including Astellas, Galderma, and Valeant, among others.
Global Academy and this news organization are owned by the same parent company.
[email protected]
On Twitter @whitneymcknight
For refractory warts, there are some “last resort” treatments every dermatologist should have on hand, according to pediatric dermatologist Fred E. Ghali, MD.
“It’s good to know about these, although it’s also good to know that sometimes you just have to wait out the warts and let them clear up on their own,” said Dr. Ghali, of the departments of dermatology at University of Texas, Dallas, and Baylor College of Medicine, Houston. Because very few treatment options are approved for warts, Dr. Ghali shared some of his preferred off-label approaches at the meeting provided by Global Academy for Medical Education.
By the time patients make it to his clinic, Dr. Ghali noted that many patients have failed home remedies such as salicylic acid or duct tape. In some cases, however, warts may not respond well to the standard in-office options such as cryotherapy. For refractory cases, he said that one of the following approaches can be considered:
Sectional cryotherapy
For larger, solitary warts, especially ring warts, freezing them in sections can be a good option, according to Dr. Ghali. This can be done best using a cotton-tip applicator rather than the traditional spray gun. In his experience, this minimizes the risk of ring wart formation, which may occur from aggressive cryotherapy focused primarily on the central portion of the wart, sometimes creating a resultant blister much larger than the original wart, with the formation of a ring wart.
Topical immunotherapy
When it comes to refractory cases in younger children, or in cases with multiple warts on the hands and feet, topical immunotherapy is often a preferred treatment. In these cases, Dr. Ghali recommended squaric acid. “The general principle with topical immunotherapy is that you would induce contact allergy with the treatment by applying it to one place on the skin, usually the arm, in the office setting,” he said. If using squaric acid, he recommended starting with 2% to sensitize in the office; then for home use, prescribing a lower concentration of the treatment – usually 0.6% – painted directly onto the lesions to provoke an immune response. This should be done three times a week at first, and then adding one application each week until the warts are being treated daily.
“If there is no response in 2 months, then increase the strength used at home,” Dr. Ghali said.
With this treatment, there is the potential for contact dermatitis, which is usually localized, but can be widespread beyond the areas of application, he cautioned. When this occurs, he recommended decreasing or discontinuing the applications and considering a topical steroid or oral steroid depending upon the severity of the reaction. “I mainly use squaric acid for the hands and feet, and almost always avoid it on the face, neck, and groin,” Dr. Ghali said.
In his practice, he finds this treatment is effective about three-quarters of the time, and seems to work particularly well with plantar warts, clearing them up in 2-4 months. The advantages of this approach are that it is not painful, is relatively easy for patients to comply with, and can be combined with other treatments if desired.
Intralesional immunotherapy
When squaric acid or cryotherapy fails, Candida antigen injection is a commonly used technique used to train the immune system to attack the warts, inducing a delayed hypersensitivity reaction. “Injectable immunotherapy is ideal in cases of a solitary [wart] or a limited number of warts,” Dr. Ghali said in an interview. “For most patients, I typically inject 0.1-0.2 cc of Candida antigen per wart. In the case of larger, ring-type warts, especially on the knees and elbows, we may need to use larger volumes, up to 0.2 cc-0.6cc,” he added.
“It’s important to remind patients that temporary, localized swelling may occur after injections; thus, care should be taken when injecting near periungual locations,” Dr. Ghali continued, noting that “it’s probably best practice to avoid subungual injections.”
Immunotherapy has relatively few side effects, and may be effective in about three-quarters of cases, according to Dr. Ghali, although he cautioned that younger children may be anxious about receiving injections and may resist treatment.
Electrodessication and curettage
For challenging warts, such as stubborn palmar or plantar warts, Dr. Ghali suggested using local anesthesia plus electrodessication and curettage.
“Sometimes with these refractory warts, we resort to off-label therapies compounded for home use,” he added. Such therapies may include salicylic acid with 5-fluorouracil, or topical cidofovir 2%-3%. These compounds can be costly depending upon the patient’s insurance coverage.
Dr. Ghali concluded by presenting his top three rules to consider when treating warts, regardless of treatment: There is no cure for warts, no therapy is uniformly effective, and the chosen therapy should take into account the family’s costs, according to their insurance coverage.
Since the landscape of insurance coverage has changed over recent years, the code most often used to treat warts in the office, often applies to the patient’s or family’s deductible. “It’s important to discuss this with the family beforehand, especially since treatment for warts may require several visits,” he said.
Dr. Ghali disclosed several financial relationships with the pharmaceutical industry including Astellas, Galderma, and Valeant, among others.
Global Academy and this news organization are owned by the same parent company.
[email protected]
On Twitter @whitneymcknight
EXPERT ANALYSIS FROM THE CARIBBEAN DERMATOLOGY SYMPOSIUM
Topical crisaborole new option for AD
There’s a new addition to the armamentarium for atopic dermatitis: a topical phosphodiesterase 4 (PDE-4) inhibitor.
“It’s a real boon to patients, now that we have crisaborole as a first-line treatment for mild to moderate atopic dermatitis,” Joseph F. Fowler Jr., MD, of the University of Louisville (Ky.), said in an interview. “In the trials leading up to its approval, crisaborole was impressive in that it was well tolerated, and the results held up across all age groups over time.” Dr. Fowler spoke at the meeting provided by Global Academy for Medical Education.
Topical ointment crisaborole 2% (Eucrisa) was approved by the Food and Drug Administration in December 2016 for mild to moderate atopic dermatitis in patients aged 2 years and older. Approval was based on two placebo-controlled trials with more than 1,500 participants between the ages of 2 and 79 years with mild to moderate atopic dermatitis.
“That it’s not a steroid is important since there are so few options for this pesky condition. We have topical steroids, but a lot of patients get nervous about the overuse of those, just as they do about the box warning for cancer risk on topical calcineurin inhibitors,” Dr. Fowler said. The most common treatment-related adverse event recorded during the trials were burning and stinging at the site of application.
“While topical corticosteroids are certainly effective, I am concerned about the risk of atrophy, especially in children and on sensitive areas such as the face and intertriginous areas. This new treatment does not have that potential adverse effect,” he said.
Global Academy and this news organization are owned by the same parent company.
Dr. Fowler disclosed that he has financial relationships with Anacor Pharmaceuticals – the manufacturer of crisaborole – and Pfizer, among other companies.
[email protected]
On Twitter @whitneymcknight
There’s a new addition to the armamentarium for atopic dermatitis: a topical phosphodiesterase 4 (PDE-4) inhibitor.
“It’s a real boon to patients, now that we have crisaborole as a first-line treatment for mild to moderate atopic dermatitis,” Joseph F. Fowler Jr., MD, of the University of Louisville (Ky.), said in an interview. “In the trials leading up to its approval, crisaborole was impressive in that it was well tolerated, and the results held up across all age groups over time.” Dr. Fowler spoke at the meeting provided by Global Academy for Medical Education.
Topical ointment crisaborole 2% (Eucrisa) was approved by the Food and Drug Administration in December 2016 for mild to moderate atopic dermatitis in patients aged 2 years and older. Approval was based on two placebo-controlled trials with more than 1,500 participants between the ages of 2 and 79 years with mild to moderate atopic dermatitis.
“That it’s not a steroid is important since there are so few options for this pesky condition. We have topical steroids, but a lot of patients get nervous about the overuse of those, just as they do about the box warning for cancer risk on topical calcineurin inhibitors,” Dr. Fowler said. The most common treatment-related adverse event recorded during the trials were burning and stinging at the site of application.
“While topical corticosteroids are certainly effective, I am concerned about the risk of atrophy, especially in children and on sensitive areas such as the face and intertriginous areas. This new treatment does not have that potential adverse effect,” he said.
Global Academy and this news organization are owned by the same parent company.
Dr. Fowler disclosed that he has financial relationships with Anacor Pharmaceuticals – the manufacturer of crisaborole – and Pfizer, among other companies.
[email protected]
On Twitter @whitneymcknight
There’s a new addition to the armamentarium for atopic dermatitis: a topical phosphodiesterase 4 (PDE-4) inhibitor.
“It’s a real boon to patients, now that we have crisaborole as a first-line treatment for mild to moderate atopic dermatitis,” Joseph F. Fowler Jr., MD, of the University of Louisville (Ky.), said in an interview. “In the trials leading up to its approval, crisaborole was impressive in that it was well tolerated, and the results held up across all age groups over time.” Dr. Fowler spoke at the meeting provided by Global Academy for Medical Education.
Topical ointment crisaborole 2% (Eucrisa) was approved by the Food and Drug Administration in December 2016 for mild to moderate atopic dermatitis in patients aged 2 years and older. Approval was based on two placebo-controlled trials with more than 1,500 participants between the ages of 2 and 79 years with mild to moderate atopic dermatitis.
“That it’s not a steroid is important since there are so few options for this pesky condition. We have topical steroids, but a lot of patients get nervous about the overuse of those, just as they do about the box warning for cancer risk on topical calcineurin inhibitors,” Dr. Fowler said. The most common treatment-related adverse event recorded during the trials were burning and stinging at the site of application.
“While topical corticosteroids are certainly effective, I am concerned about the risk of atrophy, especially in children and on sensitive areas such as the face and intertriginous areas. This new treatment does not have that potential adverse effect,” he said.
Global Academy and this news organization are owned by the same parent company.
Dr. Fowler disclosed that he has financial relationships with Anacor Pharmaceuticals – the manufacturer of crisaborole – and Pfizer, among other companies.
[email protected]
On Twitter @whitneymcknight
FROM THE CARIBBEAN DERMATOLOGY SYMPOSIUM