CRC task force updates colonoscopy follow-up guidance

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The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) recently updated recommendations for patient follow-up after colonoscopy and polypectomy.

The new guidance was based on advancements in both research and technology since the last recommendations were published in 2012, reported lead author Samir Gupta, MD, AGAF, of the University of California, San Diego, and colleagues.

“[Since 2012,] a number of articles have been published on risk of CRC based on colonoscopy findings and patient characteristics, as well as the potential impact of screening and surveillance colonoscopy on outcomes, such as incident CRC and polyps,” the investigators wrote in Gastroenterology. “Further, recent studies increasingly reflect the modern era of colonoscopy with more awareness of the importance of quality factors (e.g., adequate bowel preparation, cecal intubation, adequate adenoma detection, and complete polyp resection), and utilization of state of the art technologies (e.g., high-definition colonoscopes).”

The task force, which comprised the American College of Gastroenterology, the American Gastroenterological Association, and the American Society of Gastrointestinal Endoscopy, identified key topics using PICO (patient, intervention, comparison, and outcome) questions before conducting a comprehensive literature review that included 136 articles. Based on these findings, two task force members generated recommendations that were further refined through consensus discussion. The recommendations were copublished in the March issues of the American Journal of Gastroenterology, Gastroenterology, and Gastrointestinal Endoscopy.

According to Dr. Gupta and colleagues, some of the new recommendations, particularly those that advise less stringent follow-up, may encounter resistance from various stakeholders.

“Patients, primary care physicians, and colonoscopists may have concerns about lengthening a previously recommended interval, and will need to engage in shared decision making regarding whether to lengthen the follow-up interval based upon the guidance here or utilize the recommendation made at the time of the prior colonoscopy,” the task force wrote.

The most prominent recommendations of this kind concern patients who undergo removal of tubular adenomas less than 10 mm in size. For patients who have 1-2 of these adenomas removed, the task force now recommends follow-up after 7-10 years, instead of the previously recommended interval of 5-10 years.

“[This decision was] based on the growing body of evidence to support low risk for metachronous advanced neoplasia,” the task force wrote. “In this population, the risk for metachronous advanced neoplasia is similar to that for individuals with no adenoma. Importantly, the observed risk for fatal CRC among individuals with 1-10 adenomas less than 10 mm is lower than average for the general population.”

Along similar lines, patients who undergo removal of 3-4 small adenomas now have a recommended 3-5 year follow-up window, instead of the previously strict recommendation for follow-up at 3 years.

But not all of the new guidance is less stringent. While the task force previously recommended a follow-up period of less than 3 years after removal of more than 10 adenomas, they now recommend follow-up at 1 year. This change was made to simplify guidance, the investigators wrote, noting that the evidence base in this area “has not been markedly strengthened” since 2012.

Compared with the old guidance, the updated publication offers more detailed recommendations for follow-up after removal of serrated polyps. On this topic, 10 clinical scenarios are presented, with follow-up ranging from 6 months after piecemeal resection of a sessile serrated polyp greater than 20 mm to 10 years after removal of 20 or fewer hyperplastic polyps less than 10 mm that were located in the rectum or sigmoid colon. Incidentally, these two recommendations are strong and based on moderate evidence, whereas the remaining recommendations for serrated polyps are weak and based on very-low-quality evidence.

Because of such knowledge gaps, the investigators emphasized the need for more data. The publication includes extensive discussion of pressing research topics and appropriate methods of investigation.

“Our review highlights several opportunities for research to clarify risk stratification and management of patients post-polypectomy,” the task force wrote. “In order to optimize risk-reduction strategies, the mechanisms driving metachronous advanced neoplasia after baseline polypectomy and their relative frequency need to be better understood through studies that include large numbers of patients with interval cancers and/or advanced neoplasia after baseline polypectomy. Mechanisms may include new/incident growth, incomplete baseline resection, and missed neoplasia; each of these potential causes may require different interventions for improvement.”

The task force also suggested that some basic questions beyond risk stratification remain unanswered, such as the impact of surveillance on CRC incidence and mortality.

“Such evidence is needed given the increasing proportion of patients who are having adenomas detected as part of increased participation in CRC screening,” the task force wrote.

Other suggested topics of investigation include age-related analyses that incorporate procedural risk, cost-effectiveness studies, and comparisons of nonendoscopic methods of surveillance, such as fecal immunochemical testing.

The study was funded by the National Institutes of Health and the Department of Veterans Affairs. The investigators reported relationships with Covidien, Ironwood, Medtronic, and others.

SOURCE: Gupta S et al. Gastroenterology. 2020 Feb 7. doi: 10.1053/j.gastro.2019.10.026.

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The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) recently updated recommendations for patient follow-up after colonoscopy and polypectomy.

The new guidance was based on advancements in both research and technology since the last recommendations were published in 2012, reported lead author Samir Gupta, MD, AGAF, of the University of California, San Diego, and colleagues.

“[Since 2012,] a number of articles have been published on risk of CRC based on colonoscopy findings and patient characteristics, as well as the potential impact of screening and surveillance colonoscopy on outcomes, such as incident CRC and polyps,” the investigators wrote in Gastroenterology. “Further, recent studies increasingly reflect the modern era of colonoscopy with more awareness of the importance of quality factors (e.g., adequate bowel preparation, cecal intubation, adequate adenoma detection, and complete polyp resection), and utilization of state of the art technologies (e.g., high-definition colonoscopes).”

The task force, which comprised the American College of Gastroenterology, the American Gastroenterological Association, and the American Society of Gastrointestinal Endoscopy, identified key topics using PICO (patient, intervention, comparison, and outcome) questions before conducting a comprehensive literature review that included 136 articles. Based on these findings, two task force members generated recommendations that were further refined through consensus discussion. The recommendations were copublished in the March issues of the American Journal of Gastroenterology, Gastroenterology, and Gastrointestinal Endoscopy.

According to Dr. Gupta and colleagues, some of the new recommendations, particularly those that advise less stringent follow-up, may encounter resistance from various stakeholders.

“Patients, primary care physicians, and colonoscopists may have concerns about lengthening a previously recommended interval, and will need to engage in shared decision making regarding whether to lengthen the follow-up interval based upon the guidance here or utilize the recommendation made at the time of the prior colonoscopy,” the task force wrote.

The most prominent recommendations of this kind concern patients who undergo removal of tubular adenomas less than 10 mm in size. For patients who have 1-2 of these adenomas removed, the task force now recommends follow-up after 7-10 years, instead of the previously recommended interval of 5-10 years.

“[This decision was] based on the growing body of evidence to support low risk for metachronous advanced neoplasia,” the task force wrote. “In this population, the risk for metachronous advanced neoplasia is similar to that for individuals with no adenoma. Importantly, the observed risk for fatal CRC among individuals with 1-10 adenomas less than 10 mm is lower than average for the general population.”

Along similar lines, patients who undergo removal of 3-4 small adenomas now have a recommended 3-5 year follow-up window, instead of the previously strict recommendation for follow-up at 3 years.

But not all of the new guidance is less stringent. While the task force previously recommended a follow-up period of less than 3 years after removal of more than 10 adenomas, they now recommend follow-up at 1 year. This change was made to simplify guidance, the investigators wrote, noting that the evidence base in this area “has not been markedly strengthened” since 2012.

Compared with the old guidance, the updated publication offers more detailed recommendations for follow-up after removal of serrated polyps. On this topic, 10 clinical scenarios are presented, with follow-up ranging from 6 months after piecemeal resection of a sessile serrated polyp greater than 20 mm to 10 years after removal of 20 or fewer hyperplastic polyps less than 10 mm that were located in the rectum or sigmoid colon. Incidentally, these two recommendations are strong and based on moderate evidence, whereas the remaining recommendations for serrated polyps are weak and based on very-low-quality evidence.

Because of such knowledge gaps, the investigators emphasized the need for more data. The publication includes extensive discussion of pressing research topics and appropriate methods of investigation.

“Our review highlights several opportunities for research to clarify risk stratification and management of patients post-polypectomy,” the task force wrote. “In order to optimize risk-reduction strategies, the mechanisms driving metachronous advanced neoplasia after baseline polypectomy and their relative frequency need to be better understood through studies that include large numbers of patients with interval cancers and/or advanced neoplasia after baseline polypectomy. Mechanisms may include new/incident growth, incomplete baseline resection, and missed neoplasia; each of these potential causes may require different interventions for improvement.”

The task force also suggested that some basic questions beyond risk stratification remain unanswered, such as the impact of surveillance on CRC incidence and mortality.

“Such evidence is needed given the increasing proportion of patients who are having adenomas detected as part of increased participation in CRC screening,” the task force wrote.

Other suggested topics of investigation include age-related analyses that incorporate procedural risk, cost-effectiveness studies, and comparisons of nonendoscopic methods of surveillance, such as fecal immunochemical testing.

The study was funded by the National Institutes of Health and the Department of Veterans Affairs. The investigators reported relationships with Covidien, Ironwood, Medtronic, and others.

SOURCE: Gupta S et al. Gastroenterology. 2020 Feb 7. doi: 10.1053/j.gastro.2019.10.026.

The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) recently updated recommendations for patient follow-up after colonoscopy and polypectomy.

The new guidance was based on advancements in both research and technology since the last recommendations were published in 2012, reported lead author Samir Gupta, MD, AGAF, of the University of California, San Diego, and colleagues.

“[Since 2012,] a number of articles have been published on risk of CRC based on colonoscopy findings and patient characteristics, as well as the potential impact of screening and surveillance colonoscopy on outcomes, such as incident CRC and polyps,” the investigators wrote in Gastroenterology. “Further, recent studies increasingly reflect the modern era of colonoscopy with more awareness of the importance of quality factors (e.g., adequate bowel preparation, cecal intubation, adequate adenoma detection, and complete polyp resection), and utilization of state of the art technologies (e.g., high-definition colonoscopes).”

The task force, which comprised the American College of Gastroenterology, the American Gastroenterological Association, and the American Society of Gastrointestinal Endoscopy, identified key topics using PICO (patient, intervention, comparison, and outcome) questions before conducting a comprehensive literature review that included 136 articles. Based on these findings, two task force members generated recommendations that were further refined through consensus discussion. The recommendations were copublished in the March issues of the American Journal of Gastroenterology, Gastroenterology, and Gastrointestinal Endoscopy.

According to Dr. Gupta and colleagues, some of the new recommendations, particularly those that advise less stringent follow-up, may encounter resistance from various stakeholders.

“Patients, primary care physicians, and colonoscopists may have concerns about lengthening a previously recommended interval, and will need to engage in shared decision making regarding whether to lengthen the follow-up interval based upon the guidance here or utilize the recommendation made at the time of the prior colonoscopy,” the task force wrote.

The most prominent recommendations of this kind concern patients who undergo removal of tubular adenomas less than 10 mm in size. For patients who have 1-2 of these adenomas removed, the task force now recommends follow-up after 7-10 years, instead of the previously recommended interval of 5-10 years.

“[This decision was] based on the growing body of evidence to support low risk for metachronous advanced neoplasia,” the task force wrote. “In this population, the risk for metachronous advanced neoplasia is similar to that for individuals with no adenoma. Importantly, the observed risk for fatal CRC among individuals with 1-10 adenomas less than 10 mm is lower than average for the general population.”

Along similar lines, patients who undergo removal of 3-4 small adenomas now have a recommended 3-5 year follow-up window, instead of the previously strict recommendation for follow-up at 3 years.

But not all of the new guidance is less stringent. While the task force previously recommended a follow-up period of less than 3 years after removal of more than 10 adenomas, they now recommend follow-up at 1 year. This change was made to simplify guidance, the investigators wrote, noting that the evidence base in this area “has not been markedly strengthened” since 2012.

Compared with the old guidance, the updated publication offers more detailed recommendations for follow-up after removal of serrated polyps. On this topic, 10 clinical scenarios are presented, with follow-up ranging from 6 months after piecemeal resection of a sessile serrated polyp greater than 20 mm to 10 years after removal of 20 or fewer hyperplastic polyps less than 10 mm that were located in the rectum or sigmoid colon. Incidentally, these two recommendations are strong and based on moderate evidence, whereas the remaining recommendations for serrated polyps are weak and based on very-low-quality evidence.

Because of such knowledge gaps, the investigators emphasized the need for more data. The publication includes extensive discussion of pressing research topics and appropriate methods of investigation.

“Our review highlights several opportunities for research to clarify risk stratification and management of patients post-polypectomy,” the task force wrote. “In order to optimize risk-reduction strategies, the mechanisms driving metachronous advanced neoplasia after baseline polypectomy and their relative frequency need to be better understood through studies that include large numbers of patients with interval cancers and/or advanced neoplasia after baseline polypectomy. Mechanisms may include new/incident growth, incomplete baseline resection, and missed neoplasia; each of these potential causes may require different interventions for improvement.”

The task force also suggested that some basic questions beyond risk stratification remain unanswered, such as the impact of surveillance on CRC incidence and mortality.

“Such evidence is needed given the increasing proportion of patients who are having adenomas detected as part of increased participation in CRC screening,” the task force wrote.

Other suggested topics of investigation include age-related analyses that incorporate procedural risk, cost-effectiveness studies, and comparisons of nonendoscopic methods of surveillance, such as fecal immunochemical testing.

The study was funded by the National Institutes of Health and the Department of Veterans Affairs. The investigators reported relationships with Covidien, Ironwood, Medtronic, and others.

SOURCE: Gupta S et al. Gastroenterology. 2020 Feb 7. doi: 10.1053/j.gastro.2019.10.026.

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C. auris Infection: Rare, But Raising Concerns About Pan-Resistance

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CDC researchers say the infection is “globally emerging” and cases with resistance to all 3 classes of commonly prescribed antifungal drugs have been reported in multiple countries.

Candida auris (C. auris) infection was first detected in New York, in July 2016. As of June 2019, 801 patients have been identified in New York as having C auris—and of those, 3 had pan-resistant infection.

CDC researchers say C auris is “a globally emerging yeast.” Cases with resistance to all 3 classes of commonly prescribed antifungal drugs have been reported in multiple countries.

In New York, of the first 277 available clinical isolates, 276 were resistant to fluconazole and 170 were resistant to amphotericin B. None were resistant to echinocandins. Subsequent testing found 99.7% of 331 isolates from infected patients with susceptibilities were resistant to fluconazole, 63% were resistant to amphotericin B, and 4% were resistant to echinocandins. Three of the subsequent isolates were pan-resistant.

The first 2 of those 3 patients were > 50 years old and residents of long-term care facilities. Each had multiple medical conditions, including ventilator dependence and colonization with multidrug-resistant bacteria. Neither patient was known to have received antifungal medications before the diagnosis of C. auris infection, but both were treated with prolonged courses of echinocandins after the diagnosis. Cultures taken after echinocandin therapy showed resistance to fluconazole, amphotericin B, and echinocandins. Both patients died, but the role of C. auris in their deaths is unclear.

The researchers found no epidemiologic links between the 2 patients. They were residents at different health care facilities, neither had any known domestic or foreign travel. No pan-resistant isolates were identified among contacts or on environmental surfaces from their rooms or common equipment at the 3 facilities where they had been patients. Although C. auris was isolated from other patients, none was pan-resistant.

A retrospective review of all New York C. auris isolates turned up a third pan-resistant patient. The patient also was aged > 50 years old , had multiple comorbidities, and a prolonged hospital and long-term care stay. However, the patient received care at a third unique facility. This third patient, who died from underlying medical conditions, was also not known to have traveled recently, and had no known contact with the other 2 patients.

Isolates from all 3 patients were initially sensitive to echinocandins. Resistance was detected after treatment, indicating it emerged during treatment with the drugs. The researchers found no evidence of transmission.

Approximately 3 years after the beginning of the New York outbreak, the pan-resistant isolates still appear to be rare, the researchers say, but “their emergence is concerning.” They urge close monitoring for patients on antifungal treatment for C. auris, along with follow-up cultures and repeat susceptibility testing, especially in patients previously treated with echinocandins.

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CDC researchers say the infection is “globally emerging” and cases with resistance to all 3 classes of commonly prescribed antifungal drugs have been reported in multiple countries.
CDC researchers say the infection is “globally emerging” and cases with resistance to all 3 classes of commonly prescribed antifungal drugs have been reported in multiple countries.

Candida auris (C. auris) infection was first detected in New York, in July 2016. As of June 2019, 801 patients have been identified in New York as having C auris—and of those, 3 had pan-resistant infection.

CDC researchers say C auris is “a globally emerging yeast.” Cases with resistance to all 3 classes of commonly prescribed antifungal drugs have been reported in multiple countries.

In New York, of the first 277 available clinical isolates, 276 were resistant to fluconazole and 170 were resistant to amphotericin B. None were resistant to echinocandins. Subsequent testing found 99.7% of 331 isolates from infected patients with susceptibilities were resistant to fluconazole, 63% were resistant to amphotericin B, and 4% were resistant to echinocandins. Three of the subsequent isolates were pan-resistant.

The first 2 of those 3 patients were > 50 years old and residents of long-term care facilities. Each had multiple medical conditions, including ventilator dependence and colonization with multidrug-resistant bacteria. Neither patient was known to have received antifungal medications before the diagnosis of C. auris infection, but both were treated with prolonged courses of echinocandins after the diagnosis. Cultures taken after echinocandin therapy showed resistance to fluconazole, amphotericin B, and echinocandins. Both patients died, but the role of C. auris in their deaths is unclear.

The researchers found no epidemiologic links between the 2 patients. They were residents at different health care facilities, neither had any known domestic or foreign travel. No pan-resistant isolates were identified among contacts or on environmental surfaces from their rooms or common equipment at the 3 facilities where they had been patients. Although C. auris was isolated from other patients, none was pan-resistant.

A retrospective review of all New York C. auris isolates turned up a third pan-resistant patient. The patient also was aged > 50 years old , had multiple comorbidities, and a prolonged hospital and long-term care stay. However, the patient received care at a third unique facility. This third patient, who died from underlying medical conditions, was also not known to have traveled recently, and had no known contact with the other 2 patients.

Isolates from all 3 patients were initially sensitive to echinocandins. Resistance was detected after treatment, indicating it emerged during treatment with the drugs. The researchers found no evidence of transmission.

Approximately 3 years after the beginning of the New York outbreak, the pan-resistant isolates still appear to be rare, the researchers say, but “their emergence is concerning.” They urge close monitoring for patients on antifungal treatment for C. auris, along with follow-up cultures and repeat susceptibility testing, especially in patients previously treated with echinocandins.

Candida auris (C. auris) infection was first detected in New York, in July 2016. As of June 2019, 801 patients have been identified in New York as having C auris—and of those, 3 had pan-resistant infection.

CDC researchers say C auris is “a globally emerging yeast.” Cases with resistance to all 3 classes of commonly prescribed antifungal drugs have been reported in multiple countries.

In New York, of the first 277 available clinical isolates, 276 were resistant to fluconazole and 170 were resistant to amphotericin B. None were resistant to echinocandins. Subsequent testing found 99.7% of 331 isolates from infected patients with susceptibilities were resistant to fluconazole, 63% were resistant to amphotericin B, and 4% were resistant to echinocandins. Three of the subsequent isolates were pan-resistant.

The first 2 of those 3 patients were > 50 years old and residents of long-term care facilities. Each had multiple medical conditions, including ventilator dependence and colonization with multidrug-resistant bacteria. Neither patient was known to have received antifungal medications before the diagnosis of C. auris infection, but both were treated with prolonged courses of echinocandins after the diagnosis. Cultures taken after echinocandin therapy showed resistance to fluconazole, amphotericin B, and echinocandins. Both patients died, but the role of C. auris in their deaths is unclear.

The researchers found no epidemiologic links between the 2 patients. They were residents at different health care facilities, neither had any known domestic or foreign travel. No pan-resistant isolates were identified among contacts or on environmental surfaces from their rooms or common equipment at the 3 facilities where they had been patients. Although C. auris was isolated from other patients, none was pan-resistant.

A retrospective review of all New York C. auris isolates turned up a third pan-resistant patient. The patient also was aged > 50 years old , had multiple comorbidities, and a prolonged hospital and long-term care stay. However, the patient received care at a third unique facility. This third patient, who died from underlying medical conditions, was also not known to have traveled recently, and had no known contact with the other 2 patients.

Isolates from all 3 patients were initially sensitive to echinocandins. Resistance was detected after treatment, indicating it emerged during treatment with the drugs. The researchers found no evidence of transmission.

Approximately 3 years after the beginning of the New York outbreak, the pan-resistant isolates still appear to be rare, the researchers say, but “their emergence is concerning.” They urge close monitoring for patients on antifungal treatment for C. auris, along with follow-up cultures and repeat susceptibility testing, especially in patients previously treated with echinocandins.

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Study Warns of the Risk of Carbon Monoxide Poisoning in the Military

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Preventable CO exposures present a “unique and potentially lethal” risk for active duty service members and their beneficiaries.

Carbon monoxide (CO)—colorless, odorless, tasteless and highly toxic—is one of the most common causes of unintentional poisoning deaths in the US. Researchers who described their analysis of CO-related incidents in the military for the Medical Surveillance Monthly Report say military activities, materials, and settings pose “unique and potentially lethal sources of significant CO exposure.”

They reported on episodes of CO poisoning among members of the US Armed Forces between 2009 and 2019 and expanded on reports that dated back to 2001. Their analysis included reserve members and nonservice member beneficiaries.

Over the 10 years, there were 1,288 confirmed/probable cases of CO poisoning among active component service members, 366 among reserve component service members, and 4,754 among nonservice member beneficiaries. The highest number of active-duty members with CO confirmed/probable poisoning were reported at Fort Carson, Colorado (60) and NMC San Diego, California (52).

Of the confirmed/probable cases among active-duty members, 613 were classified as having unintentional intent, 538 undetermined intent, and 136 self-harm intent. One was due to assault. Most of the cases were related to work in repair/engineering occupations. Although the majority of sources were “other or unspecified,” motor vehicle exhaust accounted for 17% of the confirmed cases and all of the probable cases. Similarly, in the reserve component and among nonservice member beneficiaries, vehicle exhaust was the second-most common source.

The researchers found that CO poisoning-related injuries/diagnoses in the military often involved a single exposure that affected multiple personnel. For example, 21 soldiers showed symptoms during a multi-day exercise at the Yukon Training Center.

Excessive CO exposure is “entirely preventable,” the researchers say. Primary medical care providers—including unit medics and emergency medical technicians—should be knowledgeable about and sensitive to the “diverse and nonspecific” early clinical manifestations of CO intoxication, such as dizziness, headache, malaise, fatigue, disorientation, nausea, and vomiting. High CO exposure can cause more pronounced and severe symptoms, including syncope, seizures, acute stroke-like syndromes, and coma.

 It’s important to remember, the researchers add, that increased oxygen demand from muscular activity exacerbates the symptoms of CO exposure, but individuals at rest may experience no other symptoms before losing consciousness.

An editorial comment notes that the full impact of morbidity and mortality from CO poisoning is difficult to estimate. For one thing, because the symptoms can be so nonspecific, clinicians may not consider CO poisoning when patients present for care.

This study differs from previous ones in that it uses code data from both the Ninth and Tenth Revisions of the International Classification of Diseases. Such data, the editorial comment says, can be used at national and Military Health System–wide levels with relatively few resources, providing useful information on trends and risk factors that can be used in designing interventions

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Preventable CO exposures present a “unique and potentially lethal” risk for active duty service members and their beneficiaries.
Preventable CO exposures present a “unique and potentially lethal” risk for active duty service members and their beneficiaries.

Carbon monoxide (CO)—colorless, odorless, tasteless and highly toxic—is one of the most common causes of unintentional poisoning deaths in the US. Researchers who described their analysis of CO-related incidents in the military for the Medical Surveillance Monthly Report say military activities, materials, and settings pose “unique and potentially lethal sources of significant CO exposure.”

They reported on episodes of CO poisoning among members of the US Armed Forces between 2009 and 2019 and expanded on reports that dated back to 2001. Their analysis included reserve members and nonservice member beneficiaries.

Over the 10 years, there were 1,288 confirmed/probable cases of CO poisoning among active component service members, 366 among reserve component service members, and 4,754 among nonservice member beneficiaries. The highest number of active-duty members with CO confirmed/probable poisoning were reported at Fort Carson, Colorado (60) and NMC San Diego, California (52).

Of the confirmed/probable cases among active-duty members, 613 were classified as having unintentional intent, 538 undetermined intent, and 136 self-harm intent. One was due to assault. Most of the cases were related to work in repair/engineering occupations. Although the majority of sources were “other or unspecified,” motor vehicle exhaust accounted for 17% of the confirmed cases and all of the probable cases. Similarly, in the reserve component and among nonservice member beneficiaries, vehicle exhaust was the second-most common source.

The researchers found that CO poisoning-related injuries/diagnoses in the military often involved a single exposure that affected multiple personnel. For example, 21 soldiers showed symptoms during a multi-day exercise at the Yukon Training Center.

Excessive CO exposure is “entirely preventable,” the researchers say. Primary medical care providers—including unit medics and emergency medical technicians—should be knowledgeable about and sensitive to the “diverse and nonspecific” early clinical manifestations of CO intoxication, such as dizziness, headache, malaise, fatigue, disorientation, nausea, and vomiting. High CO exposure can cause more pronounced and severe symptoms, including syncope, seizures, acute stroke-like syndromes, and coma.

 It’s important to remember, the researchers add, that increased oxygen demand from muscular activity exacerbates the symptoms of CO exposure, but individuals at rest may experience no other symptoms before losing consciousness.

An editorial comment notes that the full impact of morbidity and mortality from CO poisoning is difficult to estimate. For one thing, because the symptoms can be so nonspecific, clinicians may not consider CO poisoning when patients present for care.

This study differs from previous ones in that it uses code data from both the Ninth and Tenth Revisions of the International Classification of Diseases. Such data, the editorial comment says, can be used at national and Military Health System–wide levels with relatively few resources, providing useful information on trends and risk factors that can be used in designing interventions

Carbon monoxide (CO)—colorless, odorless, tasteless and highly toxic—is one of the most common causes of unintentional poisoning deaths in the US. Researchers who described their analysis of CO-related incidents in the military for the Medical Surveillance Monthly Report say military activities, materials, and settings pose “unique and potentially lethal sources of significant CO exposure.”

They reported on episodes of CO poisoning among members of the US Armed Forces between 2009 and 2019 and expanded on reports that dated back to 2001. Their analysis included reserve members and nonservice member beneficiaries.

Over the 10 years, there were 1,288 confirmed/probable cases of CO poisoning among active component service members, 366 among reserve component service members, and 4,754 among nonservice member beneficiaries. The highest number of active-duty members with CO confirmed/probable poisoning were reported at Fort Carson, Colorado (60) and NMC San Diego, California (52).

Of the confirmed/probable cases among active-duty members, 613 were classified as having unintentional intent, 538 undetermined intent, and 136 self-harm intent. One was due to assault. Most of the cases were related to work in repair/engineering occupations. Although the majority of sources were “other or unspecified,” motor vehicle exhaust accounted for 17% of the confirmed cases and all of the probable cases. Similarly, in the reserve component and among nonservice member beneficiaries, vehicle exhaust was the second-most common source.

The researchers found that CO poisoning-related injuries/diagnoses in the military often involved a single exposure that affected multiple personnel. For example, 21 soldiers showed symptoms during a multi-day exercise at the Yukon Training Center.

Excessive CO exposure is “entirely preventable,” the researchers say. Primary medical care providers—including unit medics and emergency medical technicians—should be knowledgeable about and sensitive to the “diverse and nonspecific” early clinical manifestations of CO intoxication, such as dizziness, headache, malaise, fatigue, disorientation, nausea, and vomiting. High CO exposure can cause more pronounced and severe symptoms, including syncope, seizures, acute stroke-like syndromes, and coma.

 It’s important to remember, the researchers add, that increased oxygen demand from muscular activity exacerbates the symptoms of CO exposure, but individuals at rest may experience no other symptoms before losing consciousness.

An editorial comment notes that the full impact of morbidity and mortality from CO poisoning is difficult to estimate. For one thing, because the symptoms can be so nonspecific, clinicians may not consider CO poisoning when patients present for care.

This study differs from previous ones in that it uses code data from both the Ninth and Tenth Revisions of the International Classification of Diseases. Such data, the editorial comment says, can be used at national and Military Health System–wide levels with relatively few resources, providing useful information on trends and risk factors that can be used in designing interventions

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Functional outcomes of SLAH may be superior to those of open resection

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Among patients with medial temporal lobe epilepsy, functional outcomes of stereotactic laser amygdalohippocampotomy (SLAH) are superior to those of open resection, according to data presented at the annual meeting of the American Epilepsy Society. In addition, improvements in functional status are strongly associated with improvements in global cognitive performance.

Dr. Daniel Drane

Previous data have indicated that SLAH results in superior cognitive outcomes, compared with selective and standard open resection, in the treatment of medial temporal lobe epilepsy. The rates of seizure freedom following these procedures are equivalent. Daniel Drane, PhD, associate professor of neurology at Emory University in Atlanta, and colleagues hypothesized that the preservation of cognitive skills following SLAH would be apparent in real-world settings. To test this hypothesis, they investigated changes in functional status following SLAH.
 

Functional status correlated with neurocognitive change

Dr. Drane and colleagues compared functional outcomes in 53 patients who underwent SLAH at the Emory University Epilepsy Center and 20 patients who underwent open resection at the same center. The investigators created a hierarchical classification of functional status using the following criteria (from best to worst): employed and independent with all activities of daily living (ADLs), unemployed and independent with all ADLs, unemployed and independent with lower ADLs only (i.e., independent with self-care, but not with management of finances, medications, etc.), and unemployed and unable to manage any ADLs without assistance. Dr. Drane and colleagues rated all patients on these criteria at baseline and at 1 year after surgery. They classified patients as improving, declining, or remaining stable in functional status. Finally, the investigators used Fisher’s exact test to compare the proportional ratings of change between surgical procedures.

At baseline, the proportions of patients in each functional group were similar between patients who later underwent SLAH and those who later underwent open resection. Significantly more patients who underwent SLAH, however, had functional improvement, compared with patients who underwent open resection (13.2% vs. 0%). Furthermore, fewer patients who underwent SLAH had functional decline, compared with those who underwent open resection (3.7% vs. 35%).

Dr. Drane and colleagues found a strong correlation between functional status and global ratings of neurocognitive change, but no correlation between functional status and seizure-freedom status. Patients who underwent SLAH were less likely to have a decline in employment status than were patients who underwent open resection were (4.2% vs. 45.4%).
 

Weighing surgical options for a given patient

“This study provides a real-world metric of meaningful change following surgery, which is, critically, independent of seizure freedom outcome,” said Dr. Drane. “If a patient becomes seizure free but declines in functional status, presumably due to compromised cognitive function, this outcome is likely not going to lead to a better quality of life. Overall, our data suggest that functional status is driven more by cognitive outcome than by seizure freedom, and that it is an equally important metric for determining whether or not surgery has been successful. We would hope that the epilepsy surgical team would try to balance the desire to achieve seizure freedom against the potential risks and benefits of surgery on cognitive performance and functional status.”

 

 

Neurologists must consider various factors when deciding whether open resection or SLAH is the better option for a given patient. “Our prior work has shown that SLAH will not cause naming or object recognition deficits, while such deficits will result in a substantial proportion of patients undergoing open resection procedures,” said Dr. Drane. “Declarative memory can seemingly be hurt by either procedure, although it would appear that rates of decline are substantially less following SLAH. As functional status appears to be related to cognitive outcome, SLAH would always be the better choice from the standpoint of risk analysis, particularly since one can almost always go back an complete an open resection at a later date.

“Seizure freedom rates appear to be slightly higher with open resection than with SLAH,” Dr. Drane continued. “This [result] would be the one factor that would represent the one reason to opt for an open resection rather than SLAH. Factors that might push one in this direction could be risk for SUDEP (i.e., someone at very high risk may want to just be done with the seizures) and impaired baseline cognitive functioning (i.e., someone with severely impaired cognitive functioning might be viewed as having less to lose). In the latter case, however, we would caution that low-functioning individuals can sometimes lose their remaining functional abilities even if we cannot do a very good job of measuring cognitive change in such cases due to their poor baseline performance.”

The hemisphere to undergo operation also may influence the choice of procedure. “Some epileptologists will suggest that the choice of using SLAH is more important for patients having surgery involving their language-dominant cerebral hemisphere,” said Dr. Drane. “While postsurgical deficits in these patients are clearly more easy to identify, I would argue that a case can be made for starting with SLAH in the nondominant temporal lobe cases as well. Many of the functions that can be potentially harmed by surgical procedures involving the nondominant (typically right) hemisphere have more subtle effects, but their cumulative impact can yet be harmful.”

The study was partially supported by funding from the National Institutes of Health and Medtronic. The investigators did not report any conflicts of interest.

SOURCE: Drane DL et al. AES 2019. Abstract 1.34.

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Among patients with medial temporal lobe epilepsy, functional outcomes of stereotactic laser amygdalohippocampotomy (SLAH) are superior to those of open resection, according to data presented at the annual meeting of the American Epilepsy Society. In addition, improvements in functional status are strongly associated with improvements in global cognitive performance.

Dr. Daniel Drane

Previous data have indicated that SLAH results in superior cognitive outcomes, compared with selective and standard open resection, in the treatment of medial temporal lobe epilepsy. The rates of seizure freedom following these procedures are equivalent. Daniel Drane, PhD, associate professor of neurology at Emory University in Atlanta, and colleagues hypothesized that the preservation of cognitive skills following SLAH would be apparent in real-world settings. To test this hypothesis, they investigated changes in functional status following SLAH.
 

Functional status correlated with neurocognitive change

Dr. Drane and colleagues compared functional outcomes in 53 patients who underwent SLAH at the Emory University Epilepsy Center and 20 patients who underwent open resection at the same center. The investigators created a hierarchical classification of functional status using the following criteria (from best to worst): employed and independent with all activities of daily living (ADLs), unemployed and independent with all ADLs, unemployed and independent with lower ADLs only (i.e., independent with self-care, but not with management of finances, medications, etc.), and unemployed and unable to manage any ADLs without assistance. Dr. Drane and colleagues rated all patients on these criteria at baseline and at 1 year after surgery. They classified patients as improving, declining, or remaining stable in functional status. Finally, the investigators used Fisher’s exact test to compare the proportional ratings of change between surgical procedures.

At baseline, the proportions of patients in each functional group were similar between patients who later underwent SLAH and those who later underwent open resection. Significantly more patients who underwent SLAH, however, had functional improvement, compared with patients who underwent open resection (13.2% vs. 0%). Furthermore, fewer patients who underwent SLAH had functional decline, compared with those who underwent open resection (3.7% vs. 35%).

Dr. Drane and colleagues found a strong correlation between functional status and global ratings of neurocognitive change, but no correlation between functional status and seizure-freedom status. Patients who underwent SLAH were less likely to have a decline in employment status than were patients who underwent open resection were (4.2% vs. 45.4%).
 

Weighing surgical options for a given patient

“This study provides a real-world metric of meaningful change following surgery, which is, critically, independent of seizure freedom outcome,” said Dr. Drane. “If a patient becomes seizure free but declines in functional status, presumably due to compromised cognitive function, this outcome is likely not going to lead to a better quality of life. Overall, our data suggest that functional status is driven more by cognitive outcome than by seizure freedom, and that it is an equally important metric for determining whether or not surgery has been successful. We would hope that the epilepsy surgical team would try to balance the desire to achieve seizure freedom against the potential risks and benefits of surgery on cognitive performance and functional status.”

 

 

Neurologists must consider various factors when deciding whether open resection or SLAH is the better option for a given patient. “Our prior work has shown that SLAH will not cause naming or object recognition deficits, while such deficits will result in a substantial proportion of patients undergoing open resection procedures,” said Dr. Drane. “Declarative memory can seemingly be hurt by either procedure, although it would appear that rates of decline are substantially less following SLAH. As functional status appears to be related to cognitive outcome, SLAH would always be the better choice from the standpoint of risk analysis, particularly since one can almost always go back an complete an open resection at a later date.

“Seizure freedom rates appear to be slightly higher with open resection than with SLAH,” Dr. Drane continued. “This [result] would be the one factor that would represent the one reason to opt for an open resection rather than SLAH. Factors that might push one in this direction could be risk for SUDEP (i.e., someone at very high risk may want to just be done with the seizures) and impaired baseline cognitive functioning (i.e., someone with severely impaired cognitive functioning might be viewed as having less to lose). In the latter case, however, we would caution that low-functioning individuals can sometimes lose their remaining functional abilities even if we cannot do a very good job of measuring cognitive change in such cases due to their poor baseline performance.”

The hemisphere to undergo operation also may influence the choice of procedure. “Some epileptologists will suggest that the choice of using SLAH is more important for patients having surgery involving their language-dominant cerebral hemisphere,” said Dr. Drane. “While postsurgical deficits in these patients are clearly more easy to identify, I would argue that a case can be made for starting with SLAH in the nondominant temporal lobe cases as well. Many of the functions that can be potentially harmed by surgical procedures involving the nondominant (typically right) hemisphere have more subtle effects, but their cumulative impact can yet be harmful.”

The study was partially supported by funding from the National Institutes of Health and Medtronic. The investigators did not report any conflicts of interest.

SOURCE: Drane DL et al. AES 2019. Abstract 1.34.

Among patients with medial temporal lobe epilepsy, functional outcomes of stereotactic laser amygdalohippocampotomy (SLAH) are superior to those of open resection, according to data presented at the annual meeting of the American Epilepsy Society. In addition, improvements in functional status are strongly associated with improvements in global cognitive performance.

Dr. Daniel Drane

Previous data have indicated that SLAH results in superior cognitive outcomes, compared with selective and standard open resection, in the treatment of medial temporal lobe epilepsy. The rates of seizure freedom following these procedures are equivalent. Daniel Drane, PhD, associate professor of neurology at Emory University in Atlanta, and colleagues hypothesized that the preservation of cognitive skills following SLAH would be apparent in real-world settings. To test this hypothesis, they investigated changes in functional status following SLAH.
 

Functional status correlated with neurocognitive change

Dr. Drane and colleagues compared functional outcomes in 53 patients who underwent SLAH at the Emory University Epilepsy Center and 20 patients who underwent open resection at the same center. The investigators created a hierarchical classification of functional status using the following criteria (from best to worst): employed and independent with all activities of daily living (ADLs), unemployed and independent with all ADLs, unemployed and independent with lower ADLs only (i.e., independent with self-care, but not with management of finances, medications, etc.), and unemployed and unable to manage any ADLs without assistance. Dr. Drane and colleagues rated all patients on these criteria at baseline and at 1 year after surgery. They classified patients as improving, declining, or remaining stable in functional status. Finally, the investigators used Fisher’s exact test to compare the proportional ratings of change between surgical procedures.

At baseline, the proportions of patients in each functional group were similar between patients who later underwent SLAH and those who later underwent open resection. Significantly more patients who underwent SLAH, however, had functional improvement, compared with patients who underwent open resection (13.2% vs. 0%). Furthermore, fewer patients who underwent SLAH had functional decline, compared with those who underwent open resection (3.7% vs. 35%).

Dr. Drane and colleagues found a strong correlation between functional status and global ratings of neurocognitive change, but no correlation between functional status and seizure-freedom status. Patients who underwent SLAH were less likely to have a decline in employment status than were patients who underwent open resection were (4.2% vs. 45.4%).
 

Weighing surgical options for a given patient

“This study provides a real-world metric of meaningful change following surgery, which is, critically, independent of seizure freedom outcome,” said Dr. Drane. “If a patient becomes seizure free but declines in functional status, presumably due to compromised cognitive function, this outcome is likely not going to lead to a better quality of life. Overall, our data suggest that functional status is driven more by cognitive outcome than by seizure freedom, and that it is an equally important metric for determining whether or not surgery has been successful. We would hope that the epilepsy surgical team would try to balance the desire to achieve seizure freedom against the potential risks and benefits of surgery on cognitive performance and functional status.”

 

 

Neurologists must consider various factors when deciding whether open resection or SLAH is the better option for a given patient. “Our prior work has shown that SLAH will not cause naming or object recognition deficits, while such deficits will result in a substantial proportion of patients undergoing open resection procedures,” said Dr. Drane. “Declarative memory can seemingly be hurt by either procedure, although it would appear that rates of decline are substantially less following SLAH. As functional status appears to be related to cognitive outcome, SLAH would always be the better choice from the standpoint of risk analysis, particularly since one can almost always go back an complete an open resection at a later date.

“Seizure freedom rates appear to be slightly higher with open resection than with SLAH,” Dr. Drane continued. “This [result] would be the one factor that would represent the one reason to opt for an open resection rather than SLAH. Factors that might push one in this direction could be risk for SUDEP (i.e., someone at very high risk may want to just be done with the seizures) and impaired baseline cognitive functioning (i.e., someone with severely impaired cognitive functioning might be viewed as having less to lose). In the latter case, however, we would caution that low-functioning individuals can sometimes lose their remaining functional abilities even if we cannot do a very good job of measuring cognitive change in such cases due to their poor baseline performance.”

The hemisphere to undergo operation also may influence the choice of procedure. “Some epileptologists will suggest that the choice of using SLAH is more important for patients having surgery involving their language-dominant cerebral hemisphere,” said Dr. Drane. “While postsurgical deficits in these patients are clearly more easy to identify, I would argue that a case can be made for starting with SLAH in the nondominant temporal lobe cases as well. Many of the functions that can be potentially harmed by surgical procedures involving the nondominant (typically right) hemisphere have more subtle effects, but their cumulative impact can yet be harmful.”

The study was partially supported by funding from the National Institutes of Health and Medtronic. The investigators did not report any conflicts of interest.

SOURCE: Drane DL et al. AES 2019. Abstract 1.34.

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Epidermolysis bullosa classification criteria refined and ready

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Revised classification criteria for epidermolysis bullosa (EB) demonstrate how far researchers and clinicians have come in understanding this debilitating group of genetic skin diseases, but also how far there is still to go towards improving the management of those affected.

Sara Freeman/MDedge News
Dr. Christina Has

Previous criteria issued in 2014 represented “important progress” and “built on the achievements of several generations of physicians and researchers who described the phenotypes, the level of skin cleavage, developed and characterized antibodies, and discovered EB-associated genes,” Cristina Has, MD, said at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA).

Dr. Has, a senior dermatologist and professor of experimental dermatology at the University of Freiburg (Germany), observed that prior criteria had “introduced genetic and molecular data in a so-called onion-skin classification of EB, and removed most of the eponyms,” which had been maintained in the latest update.

“What is new, and probably the most important change, is making the distinction between classical EB and other disorders with skin fragility,” she said, noting that the revised classification criteria for EB included minor changes to the nomenclature of EB. Six new EB subtypes and genes have also been added, and there are new sections on genotype/phenotype correlations, disease modifying factors, and the natural history of EB. Furthermore, supporting information included a concise description of clinical and genetic features of all EB types and subtypes.

The updated criteria are the result of an expert meeting held in April 2019 and have been accepted for publication. The expert panel that developed the criteria think that the revised classification criteria will be “useful and, we hope, inspiring and motivating for the young generation of dermatologists, pediatricians, and for the researchers who work in this field,” Dr. Has said.

“The term EB has been used in the last years for many new disorders, and this is the reason why we thought we have to somehow control this, and to make the distinction between classical epidermolysis bullosa due to defects at the dermal junction and other disorders with skin fragility where the anomalies occur within other layers of the epidermis or in the dermis,” Dr. Has explained.

There are still 4 main types of classical EB: EB simplex (EBS), dystrophic EB (DEB), junctional EB, and Kindler EB, but there are now 34 subtypes, slightly fewer than before. The updated criteria distinguish between the types and subtypes according to the level of skin cleavage, the inheritance pattern, the mutated gene, and the targeted protein, Dr. Has said.

As for peeling disorders, these have been classified as being erosive or hyperkeratotic, or as affecting the connective tissue with skin blistering. Similar to classical EB, these disorders are associated with fragility of the skin and mucosa and share some pathogenetic mechanisms. Moreover, as “the suffering of the patient is similar,” Dr. Has said, “we’d like to consider them under the umbrella of EB.” Most of the disorders she listed were inherited via an autosomal recessive mechanism, with intraepidermal disorders inherited via an autosomal dominant mechanism. New genes are being identified the time, she added, so these groupings will no doubt be subject to future revisions.

Minor changes to nomenclature were made to avoid confusion among clinicians and those living with the condition. As such, Kindler EB replaces Kindler syndrome, names of some subtypes were simplified, and a new “self-improving” type of DEB was introduced to replace the term “transient dermolysis of the newborn.” Altogether, there are now 11 subtypes of DEB. A distinction was also made between syndromic and nonsyndromic EB. “We all know that EB can be a systemic disorder with secondary manifestations within different organs,” Dr. Has told conference attendees. Anemia and failure to thrive can be associated, but it still remains a nonsyndromic disorder, she said. By contrast, “syndromic EB is due to genetic defects, which are also expressed in other organs than the skin or mucosal membranes, and lead to primary extracutaneous manifestations, such as cardiomyopathy, nephropathy, and so on.”

There are fewer subtypes of EBS and “we think they are better defined,” Dr. Has stated. “EB simplex is the most heterogenous EB type, clinically and genetically, and includes several syndromic disorders,” and the new classification criteria should be useful in helping categorize individuals with EBS and thus help target their management.

One of the six new subtypes of EB included in the revised classification criteria is “syndromic EBS with cardiomyopathy” caused by the KLH24 mutation. This gene was discovered in 2016 and more than 40 cases have so far been identified, 50% of which have been sporadic de novo mutations.

Other new EB subtypes are:

  • “EBS with localized nephropathy” caused by a mutation in the CD151 gene.
  • An autosomal recessive EBS linked to the KRT5 gene.
  • A new phenotype that manifests with oral mucosal blisters linked to the DSG3 gene. (Although only a single case has been reported to date, it was felt worthy of inclusion.)
  • Another linked to DSG3 that leads to skin fragility and hypertrichosis.
  • A new dystrophic EB subtype linked to mutations in the PLOD3 gene.

In an interview, Dr. Has reiterated the importance of keeping classification criteria updated in line with current research findings. She emphasized that there were many types of EB and how important it was to refine how these were classified based on the underlying genetics.

“We brought much more genetic data into the paper, because we are in the era of personalized medicine,” she said. “There are specific therapies for mutations and for different subtypes and that’s why we think that, step by step, we have to bring in more and more data into the classification.”

There are many people with EBS, she observed, and while these individuals may not have such a dramatic clinical presentation as those with recessive DEB, for example, the effect of the condition on their daily lives is no less. “These people are active, they have jobs, they have to work, and they have pain, they have blister,” Dr. Has said.

While the criteria are intended only for classification of EB, they might help in practice. Dr. Has gave an anecdotal example of a woman that has been misdiagnosed as having a type of DEB with a high risk of squamous cell carcinoma but in fact had a different form of EB with no risk of developing SCC. “That’s why criteria are important,” she said.

Dr. Has had no conflicts of interest to disclose.
 

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Revised classification criteria for epidermolysis bullosa (EB) demonstrate how far researchers and clinicians have come in understanding this debilitating group of genetic skin diseases, but also how far there is still to go towards improving the management of those affected.

Sara Freeman/MDedge News
Dr. Christina Has

Previous criteria issued in 2014 represented “important progress” and “built on the achievements of several generations of physicians and researchers who described the phenotypes, the level of skin cleavage, developed and characterized antibodies, and discovered EB-associated genes,” Cristina Has, MD, said at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA).

Dr. Has, a senior dermatologist and professor of experimental dermatology at the University of Freiburg (Germany), observed that prior criteria had “introduced genetic and molecular data in a so-called onion-skin classification of EB, and removed most of the eponyms,” which had been maintained in the latest update.

“What is new, and probably the most important change, is making the distinction between classical EB and other disorders with skin fragility,” she said, noting that the revised classification criteria for EB included minor changes to the nomenclature of EB. Six new EB subtypes and genes have also been added, and there are new sections on genotype/phenotype correlations, disease modifying factors, and the natural history of EB. Furthermore, supporting information included a concise description of clinical and genetic features of all EB types and subtypes.

The updated criteria are the result of an expert meeting held in April 2019 and have been accepted for publication. The expert panel that developed the criteria think that the revised classification criteria will be “useful and, we hope, inspiring and motivating for the young generation of dermatologists, pediatricians, and for the researchers who work in this field,” Dr. Has said.

“The term EB has been used in the last years for many new disorders, and this is the reason why we thought we have to somehow control this, and to make the distinction between classical epidermolysis bullosa due to defects at the dermal junction and other disorders with skin fragility where the anomalies occur within other layers of the epidermis or in the dermis,” Dr. Has explained.

There are still 4 main types of classical EB: EB simplex (EBS), dystrophic EB (DEB), junctional EB, and Kindler EB, but there are now 34 subtypes, slightly fewer than before. The updated criteria distinguish between the types and subtypes according to the level of skin cleavage, the inheritance pattern, the mutated gene, and the targeted protein, Dr. Has said.

As for peeling disorders, these have been classified as being erosive or hyperkeratotic, or as affecting the connective tissue with skin blistering. Similar to classical EB, these disorders are associated with fragility of the skin and mucosa and share some pathogenetic mechanisms. Moreover, as “the suffering of the patient is similar,” Dr. Has said, “we’d like to consider them under the umbrella of EB.” Most of the disorders she listed were inherited via an autosomal recessive mechanism, with intraepidermal disorders inherited via an autosomal dominant mechanism. New genes are being identified the time, she added, so these groupings will no doubt be subject to future revisions.

Minor changes to nomenclature were made to avoid confusion among clinicians and those living with the condition. As such, Kindler EB replaces Kindler syndrome, names of some subtypes were simplified, and a new “self-improving” type of DEB was introduced to replace the term “transient dermolysis of the newborn.” Altogether, there are now 11 subtypes of DEB. A distinction was also made between syndromic and nonsyndromic EB. “We all know that EB can be a systemic disorder with secondary manifestations within different organs,” Dr. Has told conference attendees. Anemia and failure to thrive can be associated, but it still remains a nonsyndromic disorder, she said. By contrast, “syndromic EB is due to genetic defects, which are also expressed in other organs than the skin or mucosal membranes, and lead to primary extracutaneous manifestations, such as cardiomyopathy, nephropathy, and so on.”

There are fewer subtypes of EBS and “we think they are better defined,” Dr. Has stated. “EB simplex is the most heterogenous EB type, clinically and genetically, and includes several syndromic disorders,” and the new classification criteria should be useful in helping categorize individuals with EBS and thus help target their management.

One of the six new subtypes of EB included in the revised classification criteria is “syndromic EBS with cardiomyopathy” caused by the KLH24 mutation. This gene was discovered in 2016 and more than 40 cases have so far been identified, 50% of which have been sporadic de novo mutations.

Other new EB subtypes are:

  • “EBS with localized nephropathy” caused by a mutation in the CD151 gene.
  • An autosomal recessive EBS linked to the KRT5 gene.
  • A new phenotype that manifests with oral mucosal blisters linked to the DSG3 gene. (Although only a single case has been reported to date, it was felt worthy of inclusion.)
  • Another linked to DSG3 that leads to skin fragility and hypertrichosis.
  • A new dystrophic EB subtype linked to mutations in the PLOD3 gene.

In an interview, Dr. Has reiterated the importance of keeping classification criteria updated in line with current research findings. She emphasized that there were many types of EB and how important it was to refine how these were classified based on the underlying genetics.

“We brought much more genetic data into the paper, because we are in the era of personalized medicine,” she said. “There are specific therapies for mutations and for different subtypes and that’s why we think that, step by step, we have to bring in more and more data into the classification.”

There are many people with EBS, she observed, and while these individuals may not have such a dramatic clinical presentation as those with recessive DEB, for example, the effect of the condition on their daily lives is no less. “These people are active, they have jobs, they have to work, and they have pain, they have blister,” Dr. Has said.

While the criteria are intended only for classification of EB, they might help in practice. Dr. Has gave an anecdotal example of a woman that has been misdiagnosed as having a type of DEB with a high risk of squamous cell carcinoma but in fact had a different form of EB with no risk of developing SCC. “That’s why criteria are important,” she said.

Dr. Has had no conflicts of interest to disclose.
 

Revised classification criteria for epidermolysis bullosa (EB) demonstrate how far researchers and clinicians have come in understanding this debilitating group of genetic skin diseases, but also how far there is still to go towards improving the management of those affected.

Sara Freeman/MDedge News
Dr. Christina Has

Previous criteria issued in 2014 represented “important progress” and “built on the achievements of several generations of physicians and researchers who described the phenotypes, the level of skin cleavage, developed and characterized antibodies, and discovered EB-associated genes,” Cristina Has, MD, said at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA).

Dr. Has, a senior dermatologist and professor of experimental dermatology at the University of Freiburg (Germany), observed that prior criteria had “introduced genetic and molecular data in a so-called onion-skin classification of EB, and removed most of the eponyms,” which had been maintained in the latest update.

“What is new, and probably the most important change, is making the distinction between classical EB and other disorders with skin fragility,” she said, noting that the revised classification criteria for EB included minor changes to the nomenclature of EB. Six new EB subtypes and genes have also been added, and there are new sections on genotype/phenotype correlations, disease modifying factors, and the natural history of EB. Furthermore, supporting information included a concise description of clinical and genetic features of all EB types and subtypes.

The updated criteria are the result of an expert meeting held in April 2019 and have been accepted for publication. The expert panel that developed the criteria think that the revised classification criteria will be “useful and, we hope, inspiring and motivating for the young generation of dermatologists, pediatricians, and for the researchers who work in this field,” Dr. Has said.

“The term EB has been used in the last years for many new disorders, and this is the reason why we thought we have to somehow control this, and to make the distinction between classical epidermolysis bullosa due to defects at the dermal junction and other disorders with skin fragility where the anomalies occur within other layers of the epidermis or in the dermis,” Dr. Has explained.

There are still 4 main types of classical EB: EB simplex (EBS), dystrophic EB (DEB), junctional EB, and Kindler EB, but there are now 34 subtypes, slightly fewer than before. The updated criteria distinguish between the types and subtypes according to the level of skin cleavage, the inheritance pattern, the mutated gene, and the targeted protein, Dr. Has said.

As for peeling disorders, these have been classified as being erosive or hyperkeratotic, or as affecting the connective tissue with skin blistering. Similar to classical EB, these disorders are associated with fragility of the skin and mucosa and share some pathogenetic mechanisms. Moreover, as “the suffering of the patient is similar,” Dr. Has said, “we’d like to consider them under the umbrella of EB.” Most of the disorders she listed were inherited via an autosomal recessive mechanism, with intraepidermal disorders inherited via an autosomal dominant mechanism. New genes are being identified the time, she added, so these groupings will no doubt be subject to future revisions.

Minor changes to nomenclature were made to avoid confusion among clinicians and those living with the condition. As such, Kindler EB replaces Kindler syndrome, names of some subtypes were simplified, and a new “self-improving” type of DEB was introduced to replace the term “transient dermolysis of the newborn.” Altogether, there are now 11 subtypes of DEB. A distinction was also made between syndromic and nonsyndromic EB. “We all know that EB can be a systemic disorder with secondary manifestations within different organs,” Dr. Has told conference attendees. Anemia and failure to thrive can be associated, but it still remains a nonsyndromic disorder, she said. By contrast, “syndromic EB is due to genetic defects, which are also expressed in other organs than the skin or mucosal membranes, and lead to primary extracutaneous manifestations, such as cardiomyopathy, nephropathy, and so on.”

There are fewer subtypes of EBS and “we think they are better defined,” Dr. Has stated. “EB simplex is the most heterogenous EB type, clinically and genetically, and includes several syndromic disorders,” and the new classification criteria should be useful in helping categorize individuals with EBS and thus help target their management.

One of the six new subtypes of EB included in the revised classification criteria is “syndromic EBS with cardiomyopathy” caused by the KLH24 mutation. This gene was discovered in 2016 and more than 40 cases have so far been identified, 50% of which have been sporadic de novo mutations.

Other new EB subtypes are:

  • “EBS with localized nephropathy” caused by a mutation in the CD151 gene.
  • An autosomal recessive EBS linked to the KRT5 gene.
  • A new phenotype that manifests with oral mucosal blisters linked to the DSG3 gene. (Although only a single case has been reported to date, it was felt worthy of inclusion.)
  • Another linked to DSG3 that leads to skin fragility and hypertrichosis.
  • A new dystrophic EB subtype linked to mutations in the PLOD3 gene.

In an interview, Dr. Has reiterated the importance of keeping classification criteria updated in line with current research findings. She emphasized that there were many types of EB and how important it was to refine how these were classified based on the underlying genetics.

“We brought much more genetic data into the paper, because we are in the era of personalized medicine,” she said. “There are specific therapies for mutations and for different subtypes and that’s why we think that, step by step, we have to bring in more and more data into the classification.”

There are many people with EBS, she observed, and while these individuals may not have such a dramatic clinical presentation as those with recessive DEB, for example, the effect of the condition on their daily lives is no less. “These people are active, they have jobs, they have to work, and they have pain, they have blister,” Dr. Has said.

While the criteria are intended only for classification of EB, they might help in practice. Dr. Has gave an anecdotal example of a woman that has been misdiagnosed as having a type of DEB with a high risk of squamous cell carcinoma but in fact had a different form of EB with no risk of developing SCC. “That’s why criteria are important,” she said.

Dr. Has had no conflicts of interest to disclose.
 

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Work the program for NP/PAs, and the program will work

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A ‘knowledge gap’ in best practices exists

Hospital medicine has been the fastest growing medical specialty since the term “hospitalist” was coined by Bob Wachter, MD, in the famous 1996 New England Journal of Medicine article (doi: 10.1056/NEJM199608153350713). The growth and change within this specialty is also reflected in the changing and migrating target of hospitals and hospital systems as they continue to effectively and safely move from fee-for-service to a payer model that rewards value and improvement in the health of a population – both in and outside of hospital walls.

Tracy Cardin

In a short time, nurse practitioners and physician assistants have become a growing population in the hospital medicine workforce. The 2018 State of Hospital Medicine Report notes a 42% increase in 4 years, and about 75% of hospital medicine groups across the country currently incorporate NP/PAs within a hospital medicine practice. This evolution has occurred in the setting of a looming and well-documented physician shortage, a variety of cost pressures on hospitals that reflect the need for an efficient and cost-effective care delivery model, an increasing NP/PA workforce (the Department of Labor notes increases of 35% and 36% respectively by 2036), and data that indicates similar outcomes, for example, HCAHPS (the Hospital Consumer Assessment of Healthcare Providers and Systems), readmission, and morbidity and mortality in NP/PA-driven care.

This evolution, however, reveals a true knowledge gap in best practices related to integration of these providers. This is impacted by wide variability in the preparation of NPs – they may enter hospitalist practice from a variety of clinical exposures and training, for example, adult gerontology acute care, adult, or even, in some states, family NPs. For PAs, this is reflected in the variety of clinical rotations and pregraduate clinical exposure.

This variability is compounded, too, by the lack of standardization of hospital medicine practices, both with site size and patient acuity, a variety of challenges that drive the need for integration of NP/PA providers, and by-laws that define advanced practice clinical models and function.

In that perspective, it is important to define what constitutes a leading and successful advanced practice provider (APP) integration program. I would suggest:

  • A structured and formalized transition-to-practice program for all new graduates and those new to hospital medicine. This program should consist of clinical volume progression, formalized didactic congruent with the Society of Hospital Medicine Core Competencies, and a process for evaluating knowledge and decision making throughout the program and upon completion.
  • Development of physician competencies related to APP integration. Physicians are not prepared in their medical school training or residency to understand the differences and similarities of NP/PA providers. These competencies should be required and can best be developed through steady leadership, formalized instruction and accountability for professional teamwork.
  • Allowance for NP/PA providers to work at the top of their skills and license. This means utilizing NP/PAs as providers who care for patients – not as scribes or clerical workers. The evolution of the acuity of patients provided for may evolve with the skill set and experience of NP/PAs, but it will evolve – especially if steps 1 and 2 are in place.
  • Productivity expectations that reach near physician level of volume. In 2016 State of Hospital Medicine Report data, yearly billable encounters for NP/PAs were within 10% of that of physicians. I think 15% is a reasonable goal.
  • Implementation and support of APP administrative leadership structure at the system/site level. This can be as simple as having APPs on the same leadership committees as physician team members, being involved in hiring and training newer physicians and NP/PAs or as broad as having all NP/PAs report to an APP leader. Having an intentional leadership structure that demonstrates and reflects inclusivity and belonging is crucial.

Consistent application of these frameworks will provide a strong infrastructure for successful NP/PA practice.

Ms. Cardin is currently the vice president of advanced practice providers at Sound Physicians and serves on SHM’s board of directors as its secretary. This article appeared initially at the Hospital Leader, the official blog of SHM.

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A ‘knowledge gap’ in best practices exists

A ‘knowledge gap’ in best practices exists

Hospital medicine has been the fastest growing medical specialty since the term “hospitalist” was coined by Bob Wachter, MD, in the famous 1996 New England Journal of Medicine article (doi: 10.1056/NEJM199608153350713). The growth and change within this specialty is also reflected in the changing and migrating target of hospitals and hospital systems as they continue to effectively and safely move from fee-for-service to a payer model that rewards value and improvement in the health of a population – both in and outside of hospital walls.

Tracy Cardin

In a short time, nurse practitioners and physician assistants have become a growing population in the hospital medicine workforce. The 2018 State of Hospital Medicine Report notes a 42% increase in 4 years, and about 75% of hospital medicine groups across the country currently incorporate NP/PAs within a hospital medicine practice. This evolution has occurred in the setting of a looming and well-documented physician shortage, a variety of cost pressures on hospitals that reflect the need for an efficient and cost-effective care delivery model, an increasing NP/PA workforce (the Department of Labor notes increases of 35% and 36% respectively by 2036), and data that indicates similar outcomes, for example, HCAHPS (the Hospital Consumer Assessment of Healthcare Providers and Systems), readmission, and morbidity and mortality in NP/PA-driven care.

This evolution, however, reveals a true knowledge gap in best practices related to integration of these providers. This is impacted by wide variability in the preparation of NPs – they may enter hospitalist practice from a variety of clinical exposures and training, for example, adult gerontology acute care, adult, or even, in some states, family NPs. For PAs, this is reflected in the variety of clinical rotations and pregraduate clinical exposure.

This variability is compounded, too, by the lack of standardization of hospital medicine practices, both with site size and patient acuity, a variety of challenges that drive the need for integration of NP/PA providers, and by-laws that define advanced practice clinical models and function.

In that perspective, it is important to define what constitutes a leading and successful advanced practice provider (APP) integration program. I would suggest:

  • A structured and formalized transition-to-practice program for all new graduates and those new to hospital medicine. This program should consist of clinical volume progression, formalized didactic congruent with the Society of Hospital Medicine Core Competencies, and a process for evaluating knowledge and decision making throughout the program and upon completion.
  • Development of physician competencies related to APP integration. Physicians are not prepared in their medical school training or residency to understand the differences and similarities of NP/PA providers. These competencies should be required and can best be developed through steady leadership, formalized instruction and accountability for professional teamwork.
  • Allowance for NP/PA providers to work at the top of their skills and license. This means utilizing NP/PAs as providers who care for patients – not as scribes or clerical workers. The evolution of the acuity of patients provided for may evolve with the skill set and experience of NP/PAs, but it will evolve – especially if steps 1 and 2 are in place.
  • Productivity expectations that reach near physician level of volume. In 2016 State of Hospital Medicine Report data, yearly billable encounters for NP/PAs were within 10% of that of physicians. I think 15% is a reasonable goal.
  • Implementation and support of APP administrative leadership structure at the system/site level. This can be as simple as having APPs on the same leadership committees as physician team members, being involved in hiring and training newer physicians and NP/PAs or as broad as having all NP/PAs report to an APP leader. Having an intentional leadership structure that demonstrates and reflects inclusivity and belonging is crucial.

Consistent application of these frameworks will provide a strong infrastructure for successful NP/PA practice.

Ms. Cardin is currently the vice president of advanced practice providers at Sound Physicians and serves on SHM’s board of directors as its secretary. This article appeared initially at the Hospital Leader, the official blog of SHM.

Hospital medicine has been the fastest growing medical specialty since the term “hospitalist” was coined by Bob Wachter, MD, in the famous 1996 New England Journal of Medicine article (doi: 10.1056/NEJM199608153350713). The growth and change within this specialty is also reflected in the changing and migrating target of hospitals and hospital systems as they continue to effectively and safely move from fee-for-service to a payer model that rewards value and improvement in the health of a population – both in and outside of hospital walls.

Tracy Cardin

In a short time, nurse practitioners and physician assistants have become a growing population in the hospital medicine workforce. The 2018 State of Hospital Medicine Report notes a 42% increase in 4 years, and about 75% of hospital medicine groups across the country currently incorporate NP/PAs within a hospital medicine practice. This evolution has occurred in the setting of a looming and well-documented physician shortage, a variety of cost pressures on hospitals that reflect the need for an efficient and cost-effective care delivery model, an increasing NP/PA workforce (the Department of Labor notes increases of 35% and 36% respectively by 2036), and data that indicates similar outcomes, for example, HCAHPS (the Hospital Consumer Assessment of Healthcare Providers and Systems), readmission, and morbidity and mortality in NP/PA-driven care.

This evolution, however, reveals a true knowledge gap in best practices related to integration of these providers. This is impacted by wide variability in the preparation of NPs – they may enter hospitalist practice from a variety of clinical exposures and training, for example, adult gerontology acute care, adult, or even, in some states, family NPs. For PAs, this is reflected in the variety of clinical rotations and pregraduate clinical exposure.

This variability is compounded, too, by the lack of standardization of hospital medicine practices, both with site size and patient acuity, a variety of challenges that drive the need for integration of NP/PA providers, and by-laws that define advanced practice clinical models and function.

In that perspective, it is important to define what constitutes a leading and successful advanced practice provider (APP) integration program. I would suggest:

  • A structured and formalized transition-to-practice program for all new graduates and those new to hospital medicine. This program should consist of clinical volume progression, formalized didactic congruent with the Society of Hospital Medicine Core Competencies, and a process for evaluating knowledge and decision making throughout the program and upon completion.
  • Development of physician competencies related to APP integration. Physicians are not prepared in their medical school training or residency to understand the differences and similarities of NP/PA providers. These competencies should be required and can best be developed through steady leadership, formalized instruction and accountability for professional teamwork.
  • Allowance for NP/PA providers to work at the top of their skills and license. This means utilizing NP/PAs as providers who care for patients – not as scribes or clerical workers. The evolution of the acuity of patients provided for may evolve with the skill set and experience of NP/PAs, but it will evolve – especially if steps 1 and 2 are in place.
  • Productivity expectations that reach near physician level of volume. In 2016 State of Hospital Medicine Report data, yearly billable encounters for NP/PAs were within 10% of that of physicians. I think 15% is a reasonable goal.
  • Implementation and support of APP administrative leadership structure at the system/site level. This can be as simple as having APPs on the same leadership committees as physician team members, being involved in hiring and training newer physicians and NP/PAs or as broad as having all NP/PAs report to an APP leader. Having an intentional leadership structure that demonstrates and reflects inclusivity and belonging is crucial.

Consistent application of these frameworks will provide a strong infrastructure for successful NP/PA practice.

Ms. Cardin is currently the vice president of advanced practice providers at Sound Physicians and serves on SHM’s board of directors as its secretary. This article appeared initially at the Hospital Leader, the official blog of SHM.

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In hysterectomy, consider wider risks of ovary removal

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– While it’s fading in popularity, ovary removal in hysterectomy is still far from uncommon. A gynecologic surgeon urged colleagues to give deeper consideration to whether the ovaries can stay in place.

“Gynecologists should truly familiarize themselves with the data on cardiovascular, endocrine, bone, and sexual health implications of removing the ovaries when there isn’t a medical indication to do so,” Amanda Nickles Fader, MD, director of the Kelly gynecologic oncology service and the director of the center for rare gynecologic cancers at Johns Hopkins Hospital, Baltimore, said in an interview following her presentation at the Pelvic Anatomy and Gynecologic Surgery Symposium.

“Until I started giving this talk, I thought I knew this data. However, once I took a deeper dive into the studies of how hormonally active the postmenopausal ovaries are, as well as the population-based studies demonstrating worse all-cause mortality outcomes in low-risk women who have their ovaries surgically removed prior to their 60s, I was stunned at how compelling this data is,” she said.

The conventional wisdom about ovary removal in hysterectomy has changed dramatically over the decades. As Dr. Nickles Fader explained in the interview, “in the ’80s and early ’90s, the mantra was ‘just take everything out’ at hysterectomy surgery – tubes and ovaries should be removed – without understanding the implications. Then in the late ’90s and early 2000s, it was a more selective strategy of ‘wait until menopause to remove the ovaries.’ ”

Now, “more contemporary data suggests that the ovaries appear to be hormonally active to some degree well into the seventh decade of life, and even women in their early 60s who have their ovaries removed without a medical indication may be harmed.”

Still, ovary removal occurs in about 50%-60% of the 450,000-500,000 hysterectomies performed each year in the United States, Dr. Nickles Fader said at the meeting, which was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.

These findings seem to suggest that messages about the potential benefits of ovary preservation are not getting through to surgeons and patients.

Indeed, a 2017 study of 57,776 benign premenopausal hysterectomies with ovary removal in California from 2005 to 2011 found that 38% had no documented sign of an appropriate diagnosis signaling a need for oophorectomy. These included “ovarian cyst, breast cancer susceptibility gene carrier status, and other diagnoses,” the study authors wrote (Menopause. 2017 Aug;24[8]:947-53).

Dr. Nickles Fader emphasized that ovary removal is appropriate in cases of gynecologic malignancy, while patients at high genetic risk of ovarian cancer may consider salpingo-oophorectomy or salpingectomy.

What about other situations? She offered these pearls in the presentation:

  • Don’t remove ovaries before age 60 “without a good reason” because the procedure may lower lifespan and increase cardiovascular risk.
  • Ovary removal is linked to cognitive decline, Parkinson’s disease, depression and anxiety, glaucoma, sexual dysfunction, and bone fractures.
  • Ovary preservation, in contrast, is linked to improvement of menopausal symptoms, sleep quality, urogenital atrophy, skin conditions, and metabolism.
  • Fallopian tubes may be the true trouble area. “The prevailing theory amongst scientists and clinicians is that ‘ovarian cancer’ is in most cases a misnomer, and most of these malignancies start in the fallopian tube,” Dr. Nickles Fader said in the interview.

“It’s a better time than ever to be thoughtful about removing a woman’s ovaries in someone who is at low risk for ovarian cancer. The new, universal guideline is that instead of removing ovaries in most women undergoing hysterectomy, it’s quite important to consider removing just the fallopian tubes to best optimize cancer risk reduction and general health outcomes.”

Dr. Nickles Fader disclosed consulting work for Ethicon and Merck.

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– While it’s fading in popularity, ovary removal in hysterectomy is still far from uncommon. A gynecologic surgeon urged colleagues to give deeper consideration to whether the ovaries can stay in place.

“Gynecologists should truly familiarize themselves with the data on cardiovascular, endocrine, bone, and sexual health implications of removing the ovaries when there isn’t a medical indication to do so,” Amanda Nickles Fader, MD, director of the Kelly gynecologic oncology service and the director of the center for rare gynecologic cancers at Johns Hopkins Hospital, Baltimore, said in an interview following her presentation at the Pelvic Anatomy and Gynecologic Surgery Symposium.

“Until I started giving this talk, I thought I knew this data. However, once I took a deeper dive into the studies of how hormonally active the postmenopausal ovaries are, as well as the population-based studies demonstrating worse all-cause mortality outcomes in low-risk women who have their ovaries surgically removed prior to their 60s, I was stunned at how compelling this data is,” she said.

The conventional wisdom about ovary removal in hysterectomy has changed dramatically over the decades. As Dr. Nickles Fader explained in the interview, “in the ’80s and early ’90s, the mantra was ‘just take everything out’ at hysterectomy surgery – tubes and ovaries should be removed – without understanding the implications. Then in the late ’90s and early 2000s, it was a more selective strategy of ‘wait until menopause to remove the ovaries.’ ”

Now, “more contemporary data suggests that the ovaries appear to be hormonally active to some degree well into the seventh decade of life, and even women in their early 60s who have their ovaries removed without a medical indication may be harmed.”

Still, ovary removal occurs in about 50%-60% of the 450,000-500,000 hysterectomies performed each year in the United States, Dr. Nickles Fader said at the meeting, which was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.

These findings seem to suggest that messages about the potential benefits of ovary preservation are not getting through to surgeons and patients.

Indeed, a 2017 study of 57,776 benign premenopausal hysterectomies with ovary removal in California from 2005 to 2011 found that 38% had no documented sign of an appropriate diagnosis signaling a need for oophorectomy. These included “ovarian cyst, breast cancer susceptibility gene carrier status, and other diagnoses,” the study authors wrote (Menopause. 2017 Aug;24[8]:947-53).

Dr. Nickles Fader emphasized that ovary removal is appropriate in cases of gynecologic malignancy, while patients at high genetic risk of ovarian cancer may consider salpingo-oophorectomy or salpingectomy.

What about other situations? She offered these pearls in the presentation:

  • Don’t remove ovaries before age 60 “without a good reason” because the procedure may lower lifespan and increase cardiovascular risk.
  • Ovary removal is linked to cognitive decline, Parkinson’s disease, depression and anxiety, glaucoma, sexual dysfunction, and bone fractures.
  • Ovary preservation, in contrast, is linked to improvement of menopausal symptoms, sleep quality, urogenital atrophy, skin conditions, and metabolism.
  • Fallopian tubes may be the true trouble area. “The prevailing theory amongst scientists and clinicians is that ‘ovarian cancer’ is in most cases a misnomer, and most of these malignancies start in the fallopian tube,” Dr. Nickles Fader said in the interview.

“It’s a better time than ever to be thoughtful about removing a woman’s ovaries in someone who is at low risk for ovarian cancer. The new, universal guideline is that instead of removing ovaries in most women undergoing hysterectomy, it’s quite important to consider removing just the fallopian tubes to best optimize cancer risk reduction and general health outcomes.”

Dr. Nickles Fader disclosed consulting work for Ethicon and Merck.

– While it’s fading in popularity, ovary removal in hysterectomy is still far from uncommon. A gynecologic surgeon urged colleagues to give deeper consideration to whether the ovaries can stay in place.

“Gynecologists should truly familiarize themselves with the data on cardiovascular, endocrine, bone, and sexual health implications of removing the ovaries when there isn’t a medical indication to do so,” Amanda Nickles Fader, MD, director of the Kelly gynecologic oncology service and the director of the center for rare gynecologic cancers at Johns Hopkins Hospital, Baltimore, said in an interview following her presentation at the Pelvic Anatomy and Gynecologic Surgery Symposium.

“Until I started giving this talk, I thought I knew this data. However, once I took a deeper dive into the studies of how hormonally active the postmenopausal ovaries are, as well as the population-based studies demonstrating worse all-cause mortality outcomes in low-risk women who have their ovaries surgically removed prior to their 60s, I was stunned at how compelling this data is,” she said.

The conventional wisdom about ovary removal in hysterectomy has changed dramatically over the decades. As Dr. Nickles Fader explained in the interview, “in the ’80s and early ’90s, the mantra was ‘just take everything out’ at hysterectomy surgery – tubes and ovaries should be removed – without understanding the implications. Then in the late ’90s and early 2000s, it was a more selective strategy of ‘wait until menopause to remove the ovaries.’ ”

Now, “more contemporary data suggests that the ovaries appear to be hormonally active to some degree well into the seventh decade of life, and even women in their early 60s who have their ovaries removed without a medical indication may be harmed.”

Still, ovary removal occurs in about 50%-60% of the 450,000-500,000 hysterectomies performed each year in the United States, Dr. Nickles Fader said at the meeting, which was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.

These findings seem to suggest that messages about the potential benefits of ovary preservation are not getting through to surgeons and patients.

Indeed, a 2017 study of 57,776 benign premenopausal hysterectomies with ovary removal in California from 2005 to 2011 found that 38% had no documented sign of an appropriate diagnosis signaling a need for oophorectomy. These included “ovarian cyst, breast cancer susceptibility gene carrier status, and other diagnoses,” the study authors wrote (Menopause. 2017 Aug;24[8]:947-53).

Dr. Nickles Fader emphasized that ovary removal is appropriate in cases of gynecologic malignancy, while patients at high genetic risk of ovarian cancer may consider salpingo-oophorectomy or salpingectomy.

What about other situations? She offered these pearls in the presentation:

  • Don’t remove ovaries before age 60 “without a good reason” because the procedure may lower lifespan and increase cardiovascular risk.
  • Ovary removal is linked to cognitive decline, Parkinson’s disease, depression and anxiety, glaucoma, sexual dysfunction, and bone fractures.
  • Ovary preservation, in contrast, is linked to improvement of menopausal symptoms, sleep quality, urogenital atrophy, skin conditions, and metabolism.
  • Fallopian tubes may be the true trouble area. “The prevailing theory amongst scientists and clinicians is that ‘ovarian cancer’ is in most cases a misnomer, and most of these malignancies start in the fallopian tube,” Dr. Nickles Fader said in the interview.

“It’s a better time than ever to be thoughtful about removing a woman’s ovaries in someone who is at low risk for ovarian cancer. The new, universal guideline is that instead of removing ovaries in most women undergoing hysterectomy, it’s quite important to consider removing just the fallopian tubes to best optimize cancer risk reduction and general health outcomes.”

Dr. Nickles Fader disclosed consulting work for Ethicon and Merck.

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EXPERT ANALYSIS FROM PAGS 2019

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Model reveals genes associated with prognosis in ER+, HER2– breast cancer

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A machine learning–assisted prognostication model identified genes in the tumor microenvironment that are strongly associated with worse prognosis in patients with stage III, estrogen receptor-positive, HER2-negative breast cancer, according to new research.

Sharon Worcester/MDedge News
Dr. Yara Abdou

Yara Abdou, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., and colleagues presented this work in a poster at the ASCO-SITC Clinical Immuno-Oncology Symposium.

The model used 50 cycles of machine learning to cluster 98 patients from The Cancer Genome Atlas Program into high- and low-risk groups based on mRNA expression of 26 gene groups.

The gene groups consisted of 191 genes enriched in cellular and noncellular elements of the tumor microenvironment. Mutational burden and clinical outcomes data for the patients also were considered, Dr. Abdou explained in an interview.

Kaplan-Meier curves were created for each group by K-means clustering, survival differences between the two groups were assessed, and correlations among the various gene groups were analyzed.

Five identified genes were associated with poor prognosis: LOXL2, PHEX, ACTA2, MEGF9, and TNFSF4. Fifteen genes were associated with good prognosis: CD8A, CD8B, FCRL3, GZMK, CD3E, CCL5, TP53, ICAM3, CD247, IFNG, IFNGR1, ICAM4, SHH, HLA-DOB, and CXCR3.

The Kaplan-Meier curves showed a significant difference in survival between the two groups (hazard ratio, 2.878; P = .05), confirming the validity of the risk score modeling, Dr. Abdou said.

Immune profiling showed that expression of genes associated with desmoplastic reaction, neutrophils, and immunosuppressive cytokines were higher in the high-risk group, whereas expression of genes related to immune system activation were higher in the low-risk group (P less than .05).

Stroma in the tumor microenvironment is known to affect prognosis and response to therapy in patients with breast cancer, but few mathematical models exist to determine prognosis based on mRNA expressivity in the tumor microenvironment, Dr. Abdou said, explaining the rationale for the study.

The findings suggest that when genomic profile information is available for a given patient in the clinic, this machine learning–assisted risk scoring approach could have prognostic value, she said, noting that the model also will be assessed in patients with other types of breast cancer.

Dr. Abdou reported having no disclosures.

SOURCE: Abdou Y et al. ASCO-SITC. Poster A3.

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A machine learning–assisted prognostication model identified genes in the tumor microenvironment that are strongly associated with worse prognosis in patients with stage III, estrogen receptor-positive, HER2-negative breast cancer, according to new research.

Sharon Worcester/MDedge News
Dr. Yara Abdou

Yara Abdou, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., and colleagues presented this work in a poster at the ASCO-SITC Clinical Immuno-Oncology Symposium.

The model used 50 cycles of machine learning to cluster 98 patients from The Cancer Genome Atlas Program into high- and low-risk groups based on mRNA expression of 26 gene groups.

The gene groups consisted of 191 genes enriched in cellular and noncellular elements of the tumor microenvironment. Mutational burden and clinical outcomes data for the patients also were considered, Dr. Abdou explained in an interview.

Kaplan-Meier curves were created for each group by K-means clustering, survival differences between the two groups were assessed, and correlations among the various gene groups were analyzed.

Five identified genes were associated with poor prognosis: LOXL2, PHEX, ACTA2, MEGF9, and TNFSF4. Fifteen genes were associated with good prognosis: CD8A, CD8B, FCRL3, GZMK, CD3E, CCL5, TP53, ICAM3, CD247, IFNG, IFNGR1, ICAM4, SHH, HLA-DOB, and CXCR3.

The Kaplan-Meier curves showed a significant difference in survival between the two groups (hazard ratio, 2.878; P = .05), confirming the validity of the risk score modeling, Dr. Abdou said.

Immune profiling showed that expression of genes associated with desmoplastic reaction, neutrophils, and immunosuppressive cytokines were higher in the high-risk group, whereas expression of genes related to immune system activation were higher in the low-risk group (P less than .05).

Stroma in the tumor microenvironment is known to affect prognosis and response to therapy in patients with breast cancer, but few mathematical models exist to determine prognosis based on mRNA expressivity in the tumor microenvironment, Dr. Abdou said, explaining the rationale for the study.

The findings suggest that when genomic profile information is available for a given patient in the clinic, this machine learning–assisted risk scoring approach could have prognostic value, she said, noting that the model also will be assessed in patients with other types of breast cancer.

Dr. Abdou reported having no disclosures.

SOURCE: Abdou Y et al. ASCO-SITC. Poster A3.

A machine learning–assisted prognostication model identified genes in the tumor microenvironment that are strongly associated with worse prognosis in patients with stage III, estrogen receptor-positive, HER2-negative breast cancer, according to new research.

Sharon Worcester/MDedge News
Dr. Yara Abdou

Yara Abdou, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., and colleagues presented this work in a poster at the ASCO-SITC Clinical Immuno-Oncology Symposium.

The model used 50 cycles of machine learning to cluster 98 patients from The Cancer Genome Atlas Program into high- and low-risk groups based on mRNA expression of 26 gene groups.

The gene groups consisted of 191 genes enriched in cellular and noncellular elements of the tumor microenvironment. Mutational burden and clinical outcomes data for the patients also were considered, Dr. Abdou explained in an interview.

Kaplan-Meier curves were created for each group by K-means clustering, survival differences between the two groups were assessed, and correlations among the various gene groups were analyzed.

Five identified genes were associated with poor prognosis: LOXL2, PHEX, ACTA2, MEGF9, and TNFSF4. Fifteen genes were associated with good prognosis: CD8A, CD8B, FCRL3, GZMK, CD3E, CCL5, TP53, ICAM3, CD247, IFNG, IFNGR1, ICAM4, SHH, HLA-DOB, and CXCR3.

The Kaplan-Meier curves showed a significant difference in survival between the two groups (hazard ratio, 2.878; P = .05), confirming the validity of the risk score modeling, Dr. Abdou said.

Immune profiling showed that expression of genes associated with desmoplastic reaction, neutrophils, and immunosuppressive cytokines were higher in the high-risk group, whereas expression of genes related to immune system activation were higher in the low-risk group (P less than .05).

Stroma in the tumor microenvironment is known to affect prognosis and response to therapy in patients with breast cancer, but few mathematical models exist to determine prognosis based on mRNA expressivity in the tumor microenvironment, Dr. Abdou said, explaining the rationale for the study.

The findings suggest that when genomic profile information is available for a given patient in the clinic, this machine learning–assisted risk scoring approach could have prognostic value, she said, noting that the model also will be assessed in patients with other types of breast cancer.

Dr. Abdou reported having no disclosures.

SOURCE: Abdou Y et al. ASCO-SITC. Poster A3.

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REPORTING FROM THE CLINICAL IMMUNO-ONCOLOGY SYMPOSIUM

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Product News February 2020

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Product News February 2020

Arazlo Lotion Approved for Acne Vulgaris

Ortho Dermatologics announces US Food and Drug Administration approval of Arazlo (tazarotene) Lotion 0.045% for the topical treatment of acne vulgaris in patients 9 years and older. Arazlo provides the efficacy expected of tazarotene in a lotion formulation that helps minimize dryness and irritation historically associated with retinoids. Arazlo is expected to be available for prescription in the first half of 2020. For more information, visit https://ortho-dermatologics.com.

FDA Clears Lutronic LaseMD Ultra

Lutronic receives US Food and Drug Administration clearance of Lutronic LaseMD Ultra, a 1927-nm nonablative fractional laser to treat lentigos, solar lentigos, ephelides, actinic keratoses, and other benign pigmented lesions in all skin types. Lutronic LaseMD Ultra offers 20 W of power to treat multiple areas quickly and an advanced graphical user interface for customizable outcomes. For more information, visit https://us.aesthetic.lutronic.com.

18th World Congress on Cancers of the Skin

The 18th World Congress on Cancers of the Skin will be held in Buenos Aires, Argentina, from June 24 to June 27, 2020. The event is organized by Colegio Ibero Latinoamericano de Dermatología (CILAD) and cosponsored by The Skin Cancer Foundation. For more information, visit https://www.wccs2020.com/.

Wynzora Cream for Plaque Psoriasis

MC2 Therapeutics announces Wynzora Cream (calcipotriene 0.005% and betamethasone dipropionate 0.064%) has met its primary end point for its phase 3 trial in Europe in adult patients with plaque psoriasis. Wynzora Cream utilizes PAD Technology, which enables stability of both calcipotriene and betamethasone dipropionate in an aqueous cream
formulation. It offers patients with plaque psoriasis a once-daily topical treatment that can be quickly absorbed into the skin, is not greasy, and is convenient for routine use. The US Food and Drug Administration accepted the New Drug Application seeking marketing approval for Wynzora Cream. The combination of clinical efficacy, favorable safety profile, and high convenience of Wynzora Cream demonstrated in clinical trials hold promise to increase treatment adherence and overall patient satisfaction in the real-world setting. For more information, visit https://www.mc2therapeutics.com/.

 

If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].

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Arazlo Lotion Approved for Acne Vulgaris

Ortho Dermatologics announces US Food and Drug Administration approval of Arazlo (tazarotene) Lotion 0.045% for the topical treatment of acne vulgaris in patients 9 years and older. Arazlo provides the efficacy expected of tazarotene in a lotion formulation that helps minimize dryness and irritation historically associated with retinoids. Arazlo is expected to be available for prescription in the first half of 2020. For more information, visit https://ortho-dermatologics.com.

FDA Clears Lutronic LaseMD Ultra

Lutronic receives US Food and Drug Administration clearance of Lutronic LaseMD Ultra, a 1927-nm nonablative fractional laser to treat lentigos, solar lentigos, ephelides, actinic keratoses, and other benign pigmented lesions in all skin types. Lutronic LaseMD Ultra offers 20 W of power to treat multiple areas quickly and an advanced graphical user interface for customizable outcomes. For more information, visit https://us.aesthetic.lutronic.com.

18th World Congress on Cancers of the Skin

The 18th World Congress on Cancers of the Skin will be held in Buenos Aires, Argentina, from June 24 to June 27, 2020. The event is organized by Colegio Ibero Latinoamericano de Dermatología (CILAD) and cosponsored by The Skin Cancer Foundation. For more information, visit https://www.wccs2020.com/.

Wynzora Cream for Plaque Psoriasis

MC2 Therapeutics announces Wynzora Cream (calcipotriene 0.005% and betamethasone dipropionate 0.064%) has met its primary end point for its phase 3 trial in Europe in adult patients with plaque psoriasis. Wynzora Cream utilizes PAD Technology, which enables stability of both calcipotriene and betamethasone dipropionate in an aqueous cream
formulation. It offers patients with plaque psoriasis a once-daily topical treatment that can be quickly absorbed into the skin, is not greasy, and is convenient for routine use. The US Food and Drug Administration accepted the New Drug Application seeking marketing approval for Wynzora Cream. The combination of clinical efficacy, favorable safety profile, and high convenience of Wynzora Cream demonstrated in clinical trials hold promise to increase treatment adherence and overall patient satisfaction in the real-world setting. For more information, visit https://www.mc2therapeutics.com/.

 

If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].

Arazlo Lotion Approved for Acne Vulgaris

Ortho Dermatologics announces US Food and Drug Administration approval of Arazlo (tazarotene) Lotion 0.045% for the topical treatment of acne vulgaris in patients 9 years and older. Arazlo provides the efficacy expected of tazarotene in a lotion formulation that helps minimize dryness and irritation historically associated with retinoids. Arazlo is expected to be available for prescription in the first half of 2020. For more information, visit https://ortho-dermatologics.com.

FDA Clears Lutronic LaseMD Ultra

Lutronic receives US Food and Drug Administration clearance of Lutronic LaseMD Ultra, a 1927-nm nonablative fractional laser to treat lentigos, solar lentigos, ephelides, actinic keratoses, and other benign pigmented lesions in all skin types. Lutronic LaseMD Ultra offers 20 W of power to treat multiple areas quickly and an advanced graphical user interface for customizable outcomes. For more information, visit https://us.aesthetic.lutronic.com.

18th World Congress on Cancers of the Skin

The 18th World Congress on Cancers of the Skin will be held in Buenos Aires, Argentina, from June 24 to June 27, 2020. The event is organized by Colegio Ibero Latinoamericano de Dermatología (CILAD) and cosponsored by The Skin Cancer Foundation. For more information, visit https://www.wccs2020.com/.

Wynzora Cream for Plaque Psoriasis

MC2 Therapeutics announces Wynzora Cream (calcipotriene 0.005% and betamethasone dipropionate 0.064%) has met its primary end point for its phase 3 trial in Europe in adult patients with plaque psoriasis. Wynzora Cream utilizes PAD Technology, which enables stability of both calcipotriene and betamethasone dipropionate in an aqueous cream
formulation. It offers patients with plaque psoriasis a once-daily topical treatment that can be quickly absorbed into the skin, is not greasy, and is convenient for routine use. The US Food and Drug Administration accepted the New Drug Application seeking marketing approval for Wynzora Cream. The combination of clinical efficacy, favorable safety profile, and high convenience of Wynzora Cream demonstrated in clinical trials hold promise to increase treatment adherence and overall patient satisfaction in the real-world setting. For more information, visit https://www.mc2therapeutics.com/.

 

If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].

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Mobile stroke unit had clinical impact on EVT

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In its first year of operation, a mobile stroke unit in Melbourne demonstrated substantial savings in time to commencement of both thrombolysis and endovascular thrombectomy (EVT), results from a prospective study showed.

“While previously published data from MSU [mobile stroke unit] services in Europe and North America show substantial reductions in time to thrombolysis of approximately 30-45 minutes, little is known about the clinical impact on EVT,” first author Henry Zhao, MBBS, and colleagues wrote in a study published in Stroke.

Launched in November 2017, the Melbourne MSU is based at a large comprehensive stroke center and operates with a 20-km radius, servicing about 1.7 million people within the city of Melbourne. It is staffed with an onboard neurologist or senior stroke fellow who provides primary assessment and treatment decisions, a stroke advanced practice nurse who provides clinical support and treatment administration, a clinician who provides CT imaging, and advanced life support and mobile intensive care paramedics who provide transport logistics and paramedicine support. For the current analysis, MSU patients who received reperfusion therapy were compared with control patients presenting to metropolitan Melbourne stroke units via standard ambulance within MSU operating hours. The primary outcome was median time difference in first ambulance dispatch to treatment, which the researchers used quantile regression analysis to determine. Time savings were subsequently converted to disability-adjusted life years (DALY) avoiding using published estimates.

Dr. Zhao of the Melbourne Brain Centre and department of neurology at Royal Melbourne Hospital and his colleagues reported that, in its first year of operation, the Melbourne MSU administered prehospital thrombolysis to 100 patients with a mean age of nearly 74 years. More than half of the patients (62%) were male. Compared with controls, the median time savings per MSU patient was 26 minutes for dispatch to hospital arrival and 15 minutes for hospital arrival to thrombolysis (P less than .0010 for both associations). The calculated overall time saving from dispatch to thrombolysis was 42.5 minutes.

Over the same time period, 41 MSU patients with a mean age of 76 years received EVT dispatch-to-treatment time saving of 51 minutes (P less than 0.001). This included a median time saving of 17 minutes for EVT hospital arrival to arterial puncture for MSU patients (P = .001). Overall estimated median DALYs saved through earlier provision of reperfusion therapies were 20.9 for thrombolysis and 24.6 for EVT.

“The benefit in EVT patients was primarily driven by prehospital MSU diagnosis of large vessel occlusion, which enabled bypass of a local non-EVT center directly to a comprehensive stroke center in almost 50% of patients with large vessel occlusion,” the researchers wrote. “Even when patients were located close to an EVT center, MSU pre-notification and facilitated workflows achieved a reduction in hospital arrival to arterial puncture by one-third. Furthermore, the time saving was seen despite the majority of EVT patients receiving repeat imaging in hospital to visualize the extracranial circulation.”

The study is scheduled to be presented at the International Stroke Conference on Feb. 20.

The Melbourne MSU received funding from the Australian Commonwealth Government, Victorian State Government, Royal Melbourne Hospital Neurosciences Foundation, Stroke Foundation, the Florey Institute of Neurosciences and Mental Health, the University of Melbourne, Boehringer Ingelheim, and private donation. Dr. Zhao disclosed that he has received grants from the Australian Commonwealth Government and the University of Melbourne and personal fees from Boehringer Ingelheim.

SOURCE: Zhao H et al. Stroke. 2020 Feb 12. doi: 10.1161/strokeaha.119.027843.

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In its first year of operation, a mobile stroke unit in Melbourne demonstrated substantial savings in time to commencement of both thrombolysis and endovascular thrombectomy (EVT), results from a prospective study showed.

“While previously published data from MSU [mobile stroke unit] services in Europe and North America show substantial reductions in time to thrombolysis of approximately 30-45 minutes, little is known about the clinical impact on EVT,” first author Henry Zhao, MBBS, and colleagues wrote in a study published in Stroke.

Launched in November 2017, the Melbourne MSU is based at a large comprehensive stroke center and operates with a 20-km radius, servicing about 1.7 million people within the city of Melbourne. It is staffed with an onboard neurologist or senior stroke fellow who provides primary assessment and treatment decisions, a stroke advanced practice nurse who provides clinical support and treatment administration, a clinician who provides CT imaging, and advanced life support and mobile intensive care paramedics who provide transport logistics and paramedicine support. For the current analysis, MSU patients who received reperfusion therapy were compared with control patients presenting to metropolitan Melbourne stroke units via standard ambulance within MSU operating hours. The primary outcome was median time difference in first ambulance dispatch to treatment, which the researchers used quantile regression analysis to determine. Time savings were subsequently converted to disability-adjusted life years (DALY) avoiding using published estimates.

Dr. Zhao of the Melbourne Brain Centre and department of neurology at Royal Melbourne Hospital and his colleagues reported that, in its first year of operation, the Melbourne MSU administered prehospital thrombolysis to 100 patients with a mean age of nearly 74 years. More than half of the patients (62%) were male. Compared with controls, the median time savings per MSU patient was 26 minutes for dispatch to hospital arrival and 15 minutes for hospital arrival to thrombolysis (P less than .0010 for both associations). The calculated overall time saving from dispatch to thrombolysis was 42.5 minutes.

Over the same time period, 41 MSU patients with a mean age of 76 years received EVT dispatch-to-treatment time saving of 51 minutes (P less than 0.001). This included a median time saving of 17 minutes for EVT hospital arrival to arterial puncture for MSU patients (P = .001). Overall estimated median DALYs saved through earlier provision of reperfusion therapies were 20.9 for thrombolysis and 24.6 for EVT.

“The benefit in EVT patients was primarily driven by prehospital MSU diagnosis of large vessel occlusion, which enabled bypass of a local non-EVT center directly to a comprehensive stroke center in almost 50% of patients with large vessel occlusion,” the researchers wrote. “Even when patients were located close to an EVT center, MSU pre-notification and facilitated workflows achieved a reduction in hospital arrival to arterial puncture by one-third. Furthermore, the time saving was seen despite the majority of EVT patients receiving repeat imaging in hospital to visualize the extracranial circulation.”

The study is scheduled to be presented at the International Stroke Conference on Feb. 20.

The Melbourne MSU received funding from the Australian Commonwealth Government, Victorian State Government, Royal Melbourne Hospital Neurosciences Foundation, Stroke Foundation, the Florey Institute of Neurosciences and Mental Health, the University of Melbourne, Boehringer Ingelheim, and private donation. Dr. Zhao disclosed that he has received grants from the Australian Commonwealth Government and the University of Melbourne and personal fees from Boehringer Ingelheim.

SOURCE: Zhao H et al. Stroke. 2020 Feb 12. doi: 10.1161/strokeaha.119.027843.

 

In its first year of operation, a mobile stroke unit in Melbourne demonstrated substantial savings in time to commencement of both thrombolysis and endovascular thrombectomy (EVT), results from a prospective study showed.

“While previously published data from MSU [mobile stroke unit] services in Europe and North America show substantial reductions in time to thrombolysis of approximately 30-45 minutes, little is known about the clinical impact on EVT,” first author Henry Zhao, MBBS, and colleagues wrote in a study published in Stroke.

Launched in November 2017, the Melbourne MSU is based at a large comprehensive stroke center and operates with a 20-km radius, servicing about 1.7 million people within the city of Melbourne. It is staffed with an onboard neurologist or senior stroke fellow who provides primary assessment and treatment decisions, a stroke advanced practice nurse who provides clinical support and treatment administration, a clinician who provides CT imaging, and advanced life support and mobile intensive care paramedics who provide transport logistics and paramedicine support. For the current analysis, MSU patients who received reperfusion therapy were compared with control patients presenting to metropolitan Melbourne stroke units via standard ambulance within MSU operating hours. The primary outcome was median time difference in first ambulance dispatch to treatment, which the researchers used quantile regression analysis to determine. Time savings were subsequently converted to disability-adjusted life years (DALY) avoiding using published estimates.

Dr. Zhao of the Melbourne Brain Centre and department of neurology at Royal Melbourne Hospital and his colleagues reported that, in its first year of operation, the Melbourne MSU administered prehospital thrombolysis to 100 patients with a mean age of nearly 74 years. More than half of the patients (62%) were male. Compared with controls, the median time savings per MSU patient was 26 minutes for dispatch to hospital arrival and 15 minutes for hospital arrival to thrombolysis (P less than .0010 for both associations). The calculated overall time saving from dispatch to thrombolysis was 42.5 minutes.

Over the same time period, 41 MSU patients with a mean age of 76 years received EVT dispatch-to-treatment time saving of 51 minutes (P less than 0.001). This included a median time saving of 17 minutes for EVT hospital arrival to arterial puncture for MSU patients (P = .001). Overall estimated median DALYs saved through earlier provision of reperfusion therapies were 20.9 for thrombolysis and 24.6 for EVT.

“The benefit in EVT patients was primarily driven by prehospital MSU diagnosis of large vessel occlusion, which enabled bypass of a local non-EVT center directly to a comprehensive stroke center in almost 50% of patients with large vessel occlusion,” the researchers wrote. “Even when patients were located close to an EVT center, MSU pre-notification and facilitated workflows achieved a reduction in hospital arrival to arterial puncture by one-third. Furthermore, the time saving was seen despite the majority of EVT patients receiving repeat imaging in hospital to visualize the extracranial circulation.”

The study is scheduled to be presented at the International Stroke Conference on Feb. 20.

The Melbourne MSU received funding from the Australian Commonwealth Government, Victorian State Government, Royal Melbourne Hospital Neurosciences Foundation, Stroke Foundation, the Florey Institute of Neurosciences and Mental Health, the University of Melbourne, Boehringer Ingelheim, and private donation. Dr. Zhao disclosed that he has received grants from the Australian Commonwealth Government and the University of Melbourne and personal fees from Boehringer Ingelheim.

SOURCE: Zhao H et al. Stroke. 2020 Feb 12. doi: 10.1161/strokeaha.119.027843.

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Key clinical point: A mobile stroke unit (MSU) substantially reduced time to reperfusion therapies.

Major finding: Compared with controls, the median time savings per MSU patient was 26 minutes for dispatch to hospital arrival and 15 minutes for hospital arrival to thrombolysis (P less than .0010 for both associations).

Study details: A prospective study of 100 stroke patients.

Disclosures: The Melbourne MSU received funding from the Australian Commonwealth Government, Victorian State Government, Royal Melbourne Hospital Neurosciences Foundation, Stroke Foundation, the Florey Institute of Neurosciences and Mental Health, the University of Melbourne, Boehringer Ingelheim, and private donation. Dr. Zhao disclosed that he has received grants from the Australian Commonwealth Government and the University of Melbourne and personal fees from Boehringer Ingelheim.

Source: Zhao H et al. Stroke. 2020 Feb 12. doi: 10.1161/strokeaha.119.027843.

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