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MALMO, SWEDEN – A French national study has documented a sharp increase in pneumococcal meningitis since 2015 in children under age 15 years.

Bruce Jancin/MDedge News

The culprit has been identified as serotype 24F, which is not covered by the infant 13-valent conjugate pneumococcal vaccine (PCV13), Naim Ouldali, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

The rapid emergence of serotype 24F has been accompanied by a disturbing change in its penicillin susceptibility. Indeed, penicillin resistance was present in only 18% of serotype 24F isolates in France during 2000-2014, then jumped to 74% during 2015-2016, according to Dr. Ouldali of René Descartes University in Paris.

“PCV13 has strongly reduced the pneumococcal meningitis burden in children, but its benefit now seems to be jeopardized, at least in France. So serum 24F could become a major concern in the coming years because of its characteristics. And now the question is, is this emergence an epidemic phenomenon or not? And if it’s confirmed in future studies and in other countries, probably it should drive the development of next-generation PCV formulations,” he said.

Dr. Ouldali presented a population-based interrupted time-series analysis of a nationwide prospective survey conducted in France during 2001-2016. He noted that the Cochrane Collaboration has deemed this study design second only to the randomized controlled trial in terms of quality of evidence.

The study, which included 227 French pediatric wards and 168 microbiology departments, identified 1,778 children under age 15 years with pneumococcal meningitis. This is believed to be more than 60% of all cases that occurred in the country during the study years.

The purpose of the study was to determine the impact of implementation of routine PCV13 as part of the national vaccine strategy. Rates of PCV13 coverage in French children are very high: in excess of 90% during 2015 to 2016.

Implementation of PCV13 led to a dramatic 38% reduction in the monthly incidence of pneumococcal meningitis, from 0.12 cases per 100,000 children before PCV13 to a low of 0.07 cases per 100,000 in December 2014. But after that the rate rebounded sharply, by 2.3% per month during 2015-2016, to a high of 0.13 cases per 100,000 per month by the end of 2016. Drilling down into the data, Dr. Ouldali and his coinvestigators learned that the resurgence of pneumococcal meningitis was due largely to the emergence of serotype 24F.

“This serotype is of particular concern because of two characteristics: First, it is already known to have a high disease potential – one of the highest, along with serotype 12F – and second, this rapid emergence was accompanied by a change in its penicillin susceptibility,” he noted.

Most of the French rebound in pneumococcal meningitis has occurred in children under 2 years of age. Of note, German investigators also have recently reported a rebound in invasive pneumococcal disease in German children under 16 years of age. Non-PCV13 serotypes accounted for 84% of all invasive pneumococcal disease during 2015-2016, with serotypes 10A and 24F leading the way. As in France, most of the resurgence has involved children less than 2 years old. However, unlike in France, most of the German increase has been in nonmeningitis forms of invasive pneumococcal disease (Vaccine. 2018 Jan 25;36[4]:572-7).

In response to a question from a concerned audience member, Dr. Ouldali said that while the penicillin susceptibility of serotype 24F has taken a sharp turn for the worse, cephalosporin susceptibility has not.

“To date, we have not seen any cephalosporin-resistant strains. To date, there is no need to use vancomycin,” he said.

Dr. Ouldali said the next step he and his colleagues plan to take is to see if there is a clonal expansion or a particular underlying genetic pattern which could explain the explosive emergence of 24F.

The study was funded by a research grant from Pfizer and by the French Pediatric Infectious Diseases Group.

bjancin@mdedge.com

MALMO, SWEDEN – A French national study has documented a sharp increase in pneumococcal meningitis since 2015 in children under age 15 years.

Bruce Jancin/MDedge News

The culprit has been identified as serotype 24F, which is not covered by the infant 13-valent conjugate pneumococcal vaccine (PCV13), Naim Ouldali, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

The rapid emergence of serotype 24F has been accompanied by a disturbing change in its penicillin susceptibility. Indeed, penicillin resistance was present in only 18% of serotype 24F isolates in France during 2000-2014, then jumped to 74% during 2015-2016, according to Dr. Ouldali of René Descartes University in Paris.

“PCV13 has strongly reduced the pneumococcal meningitis burden in children, but its benefit now seems to be jeopardized, at least in France. So serum 24F could become a major concern in the coming years because of its characteristics. And now the question is, is this emergence an epidemic phenomenon or not? And if it’s confirmed in future studies and in other countries, probably it should drive the development of next-generation PCV formulations,” he said.

Dr. Ouldali presented a population-based interrupted time-series analysis of a nationwide prospective survey conducted in France during 2001-2016. He noted that the Cochrane Collaboration has deemed this study design second only to the randomized controlled trial in terms of quality of evidence.

The study, which included 227 French pediatric wards and 168 microbiology departments, identified 1,778 children under age 15 years with pneumococcal meningitis. This is believed to be more than 60% of all cases that occurred in the country during the study years.

The purpose of the study was to determine the impact of implementation of routine PCV13 as part of the national vaccine strategy. Rates of PCV13 coverage in French children are very high: in excess of 90% during 2015 to 2016.

Implementation of PCV13 led to a dramatic 38% reduction in the monthly incidence of pneumococcal meningitis, from 0.12 cases per 100,000 children before PCV13 to a low of 0.07 cases per 100,000 in December 2014. But after that the rate rebounded sharply, by 2.3% per month during 2015-2016, to a high of 0.13 cases per 100,000 per month by the end of 2016. Drilling down into the data, Dr. Ouldali and his coinvestigators learned that the resurgence of pneumococcal meningitis was due largely to the emergence of serotype 24F.

“This serotype is of particular concern because of two characteristics: First, it is already known to have a high disease potential – one of the highest, along with serotype 12F – and second, this rapid emergence was accompanied by a change in its penicillin susceptibility,” he noted.

Most of the French rebound in pneumococcal meningitis has occurred in children under 2 years of age. Of note, German investigators also have recently reported a rebound in invasive pneumococcal disease in German children under 16 years of age. Non-PCV13 serotypes accounted for 84% of all invasive pneumococcal disease during 2015-2016, with serotypes 10A and 24F leading the way. As in France, most of the resurgence has involved children less than 2 years old. However, unlike in France, most of the German increase has been in nonmeningitis forms of invasive pneumococcal disease (Vaccine. 2018 Jan 25;36[4]:572-7).

In response to a question from a concerned audience member, Dr. Ouldali said that while the penicillin susceptibility of serotype 24F has taken a sharp turn for the worse, cephalosporin susceptibility has not.

“To date, we have not seen any cephalosporin-resistant strains. To date, there is no need to use vancomycin,” he said.

Dr. Ouldali said the next step he and his colleagues plan to take is to see if there is a clonal expansion or a particular underlying genetic pattern which could explain the explosive emergence of 24F.

The study was funded by a research grant from Pfizer and by the French Pediatric Infectious Diseases Group.

bjancin@mdedge.com

MALMO, SWEDEN – A French national study has documented a sharp increase in pneumococcal meningitis since 2015 in children under age 15 years.

Bruce Jancin/MDedge News

The culprit has been identified as serotype 24F, which is not covered by the infant 13-valent conjugate pneumococcal vaccine (PCV13), Naim Ouldali, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

The rapid emergence of serotype 24F has been accompanied by a disturbing change in its penicillin susceptibility. Indeed, penicillin resistance was present in only 18% of serotype 24F isolates in France during 2000-2014, then jumped to 74% during 2015-2016, according to Dr. Ouldali of René Descartes University in Paris.

“PCV13 has strongly reduced the pneumococcal meningitis burden in children, but its benefit now seems to be jeopardized, at least in France. So serum 24F could become a major concern in the coming years because of its characteristics. And now the question is, is this emergence an epidemic phenomenon or not? And if it’s confirmed in future studies and in other countries, probably it should drive the development of next-generation PCV formulations,” he said.

Dr. Ouldali presented a population-based interrupted time-series analysis of a nationwide prospective survey conducted in France during 2001-2016. He noted that the Cochrane Collaboration has deemed this study design second only to the randomized controlled trial in terms of quality of evidence.

The study, which included 227 French pediatric wards and 168 microbiology departments, identified 1,778 children under age 15 years with pneumococcal meningitis. This is believed to be more than 60% of all cases that occurred in the country during the study years.

The purpose of the study was to determine the impact of implementation of routine PCV13 as part of the national vaccine strategy. Rates of PCV13 coverage in French children are very high: in excess of 90% during 2015 to 2016.

Implementation of PCV13 led to a dramatic 38% reduction in the monthly incidence of pneumococcal meningitis, from 0.12 cases per 100,000 children before PCV13 to a low of 0.07 cases per 100,000 in December 2014. But after that the rate rebounded sharply, by 2.3% per month during 2015-2016, to a high of 0.13 cases per 100,000 per month by the end of 2016. Drilling down into the data, Dr. Ouldali and his coinvestigators learned that the resurgence of pneumococcal meningitis was due largely to the emergence of serotype 24F.

“This serotype is of particular concern because of two characteristics: First, it is already known to have a high disease potential – one of the highest, along with serotype 12F – and second, this rapid emergence was accompanied by a change in its penicillin susceptibility,” he noted.

Most of the French rebound in pneumococcal meningitis has occurred in children under 2 years of age. Of note, German investigators also have recently reported a rebound in invasive pneumococcal disease in German children under 16 years of age. Non-PCV13 serotypes accounted for 84% of all invasive pneumococcal disease during 2015-2016, with serotypes 10A and 24F leading the way. As in France, most of the resurgence has involved children less than 2 years old. However, unlike in France, most of the German increase has been in nonmeningitis forms of invasive pneumococcal disease (Vaccine. 2018 Jan 25;36[4]:572-7).

In response to a question from a concerned audience member, Dr. Ouldali said that while the penicillin susceptibility of serotype 24F has taken a sharp turn for the worse, cephalosporin susceptibility has not.

“To date, we have not seen any cephalosporin-resistant strains. To date, there is no need to use vancomycin,” he said.

Dr. Ouldali said the next step he and his colleagues plan to take is to see if there is a clonal expansion or a particular underlying genetic pattern which could explain the explosive emergence of 24F.

The study was funded by a research grant from Pfizer and by the French Pediatric Infectious Diseases Group.

bjancin@mdedge.com

A small study of discussions between clinicians and patients about lung cancer screening with low-dose computed tomography has highlighted a lack of shared decision making and information about potential harms.

“Our findings are consistent with increasingly robust evidence that patients, members of the public, and clinicians tend to overestimate the benefits and underestimate the harms of medical interventions, including treatments, tests, or screening tests,” wrote Alison T. Brenner, PhD, and her colleagues at the University of North Carolina at Chapel Hill, in a presentation of the findings in JAMA Internal Medicine.

The researchers transcribed conversations between 14 patients – who were eligible for lung cancer screening because of their age – and their primary care or pulmonary care physicians. They found that not one physician adequately explained false positives or their consequences, such as the possibility of additional imaging and invasive diagnostic procedures, nor did any discuss the potential for diagnosis and treatment of cancer that would not have affected the individual during his or her lifetime (overdiagnosis).

Researchers used a 12-item scoring system for physician behaviors, with 0-4 points allocated to each item. The items included telling patients there was more than one way to deal with the identified problem, explaining the pros and cons of the available options, exploring patients’ fears and concerns, and offering the patient clear opportunities to ask questions.

Mean scores for each item ranged from 0 to 0.79. Two conversations met the baseline skill criteria – a score of two points – for one item each, two other conversations met the baseline skill criteria for two items. But for 8 of the 12 items, not one conversation achieved even a baseline skill score. The mean total visit length was 13:07 minutes, and the mean time spent discussing LCS was 0:59 minute (range, 0:16-2:19 minutes).

“Although experts disagree on how well the existing evidence suggests an overall net benefit of LCS [lung cancer screening], consensus has emerged on the importance of shared decision making,” wrote the investigators. Current U.S. Preventive Services Task Force recommendations stress that lung cancer screening should not occur without a shared decision-making process, including a thorough discussion of benefits and harms.

The authors said that, while their study was small, it did raise concerns that shared decision making in practice is a long way from what is recommended by the guidelines.

“The fact that the main drivers of harms from LCS (false positives and their sequelae, as well as overdiagnosis) were not adequately explained by physicians is troubling,” they wrote. “However, these findings are consistent with other evidence that discussions between patients and physicians regarding preference-sensitive cancer screening decisions are imbalanced with respect to explaining the pros and cons.”

Based on these findings, the authors called for urgent discussions between clinical leaders, policy makers, and researchers about how to involve patients more meaningfully in discussions about lung cancer screening.

“Until more is known, we believe that guideline and policy makers should not assume that recommending SDM [shared decision-making] for cancer-screening decisions with a ‘tenuous balance of benefits and harms,’ like LCS, will protect patients who would value avoiding screening harms.”

The study was supported by the North Carolina Translational and Clinical Sciences Institute and the National Cancer Institute. No conflicts of interest were declared.

SOURCE: Brenner A et al. JAMA Intern Med. 2018; Aug 13. doi: 10.1001/jamainternmed.2018.3054.

A small study of discussions between clinicians and patients about lung cancer screening with low-dose computed tomography has highlighted a lack of shared decision making and information about potential harms.

“Our findings are consistent with increasingly robust evidence that patients, members of the public, and clinicians tend to overestimate the benefits and underestimate the harms of medical interventions, including treatments, tests, or screening tests,” wrote Alison T. Brenner, PhD, and her colleagues at the University of North Carolina at Chapel Hill, in a presentation of the findings in JAMA Internal Medicine.

The researchers transcribed conversations between 14 patients – who were eligible for lung cancer screening because of their age – and their primary care or pulmonary care physicians. They found that not one physician adequately explained false positives or their consequences, such as the possibility of additional imaging and invasive diagnostic procedures, nor did any discuss the potential for diagnosis and treatment of cancer that would not have affected the individual during his or her lifetime (overdiagnosis).

Researchers used a 12-item scoring system for physician behaviors, with 0-4 points allocated to each item. The items included telling patients there was more than one way to deal with the identified problem, explaining the pros and cons of the available options, exploring patients’ fears and concerns, and offering the patient clear opportunities to ask questions.

Mean scores for each item ranged from 0 to 0.79. Two conversations met the baseline skill criteria – a score of two points – for one item each, two other conversations met the baseline skill criteria for two items. But for 8 of the 12 items, not one conversation achieved even a baseline skill score. The mean total visit length was 13:07 minutes, and the mean time spent discussing LCS was 0:59 minute (range, 0:16-2:19 minutes).

“Although experts disagree on how well the existing evidence suggests an overall net benefit of LCS [lung cancer screening], consensus has emerged on the importance of shared decision making,” wrote the investigators. Current U.S. Preventive Services Task Force recommendations stress that lung cancer screening should not occur without a shared decision-making process, including a thorough discussion of benefits and harms.

The authors said that, while their study was small, it did raise concerns that shared decision making in practice is a long way from what is recommended by the guidelines.

“The fact that the main drivers of harms from LCS (false positives and their sequelae, as well as overdiagnosis) were not adequately explained by physicians is troubling,” they wrote. “However, these findings are consistent with other evidence that discussions between patients and physicians regarding preference-sensitive cancer screening decisions are imbalanced with respect to explaining the pros and cons.”

Based on these findings, the authors called for urgent discussions between clinical leaders, policy makers, and researchers about how to involve patients more meaningfully in discussions about lung cancer screening.

“Until more is known, we believe that guideline and policy makers should not assume that recommending SDM [shared decision-making] for cancer-screening decisions with a ‘tenuous balance of benefits and harms,’ like LCS, will protect patients who would value avoiding screening harms.”

The study was supported by the North Carolina Translational and Clinical Sciences Institute and the National Cancer Institute. No conflicts of interest were declared.

SOURCE: Brenner A et al. JAMA Intern Med. 2018; Aug 13. doi: 10.1001/jamainternmed.2018.3054.

A small study of discussions between clinicians and patients about lung cancer screening with low-dose computed tomography has highlighted a lack of shared decision making and information about potential harms.

“Our findings are consistent with increasingly robust evidence that patients, members of the public, and clinicians tend to overestimate the benefits and underestimate the harms of medical interventions, including treatments, tests, or screening tests,” wrote Alison T. Brenner, PhD, and her colleagues at the University of North Carolina at Chapel Hill, in a presentation of the findings in JAMA Internal Medicine.

The researchers transcribed conversations between 14 patients – who were eligible for lung cancer screening because of their age – and their primary care or pulmonary care physicians. They found that not one physician adequately explained false positives or their consequences, such as the possibility of additional imaging and invasive diagnostic procedures, nor did any discuss the potential for diagnosis and treatment of cancer that would not have affected the individual during his or her lifetime (overdiagnosis).

Researchers used a 12-item scoring system for physician behaviors, with 0-4 points allocated to each item. The items included telling patients there was more than one way to deal with the identified problem, explaining the pros and cons of the available options, exploring patients’ fears and concerns, and offering the patient clear opportunities to ask questions.

Mean scores for each item ranged from 0 to 0.79. Two conversations met the baseline skill criteria – a score of two points – for one item each, two other conversations met the baseline skill criteria for two items. But for 8 of the 12 items, not one conversation achieved even a baseline skill score. The mean total visit length was 13:07 minutes, and the mean time spent discussing LCS was 0:59 minute (range, 0:16-2:19 minutes).

“Although experts disagree on how well the existing evidence suggests an overall net benefit of LCS [lung cancer screening], consensus has emerged on the importance of shared decision making,” wrote the investigators. Current U.S. Preventive Services Task Force recommendations stress that lung cancer screening should not occur without a shared decision-making process, including a thorough discussion of benefits and harms.

The authors said that, while their study was small, it did raise concerns that shared decision making in practice is a long way from what is recommended by the guidelines.

“The fact that the main drivers of harms from LCS (false positives and their sequelae, as well as overdiagnosis) were not adequately explained by physicians is troubling,” they wrote. “However, these findings are consistent with other evidence that discussions between patients and physicians regarding preference-sensitive cancer screening decisions are imbalanced with respect to explaining the pros and cons.”

Based on these findings, the authors called for urgent discussions between clinical leaders, policy makers, and researchers about how to involve patients more meaningfully in discussions about lung cancer screening.

“Until more is known, we believe that guideline and policy makers should not assume that recommending SDM [shared decision-making] for cancer-screening decisions with a ‘tenuous balance of benefits and harms,’ like LCS, will protect patients who would value avoiding screening harms.”

The study was supported by the North Carolina Translational and Clinical Sciences Institute and the National Cancer Institute. No conflicts of interest were declared.

SOURCE: Brenner A et al. JAMA Intern Med. 2018; Aug 13. doi: 10.1001/jamainternmed.2018.3054.

A retrospective cohort study in more than 80,000 children has found no evidence of an increased risk of autism spectrum disorder associated with prenatal tetanus, diphtheria, and acellular pertussis (Tdap) immunization.

Piotr Marcinski/Thinkstock

Of 81,993 children born between 2011 and 2014, 1,341 children (1.6%) were diagnosed with autism spectrum disorder. The incidence of autism spectrum disorder was 3.78 per 1,000 person-years in the Tdap-vaccinated group, and 4.05 per 1,000 person years in the unvaccinated group, representing an unadjusted hazard ratio of 0.98 and an adjusted hazard ratio of 0.85. This was consistent across all the birth cohorts.

Prenatal immunization rates with the prenatal Tdap vaccine ranged from 26% of the 2012 birth cohort to 79% of the 2014 birth cohort, and mean gestational age at vaccination was 28 weeks.

Tracy A. Becerra-Culqui, PhD, MPH, and colleagues of the department of research and evaluation at Kaiser Permanente Southern California, Pasadena, said this was the first study to look at the risk of autism spectrum disorder after maternal exposure to the Tdap vaccine, to their knowledge. “Our results potentially indicate that the maternal Tdap vaccine affects immune trajectories protecting infants against infections that would otherwise lead to neurodevelopmental alterations.”

They highlighted several strengths of their study. One was that maternal Tdap vaccination and information on autism spectrum disorder both were derived from EHRs and therefore not subject to recall bias. The study, published online in Pediatrics, also included children diagnosed with autism spectrum disorder from age 1 year onwards, reflecting the latest evidence on screening and diagnosis of autism.

“Our weighting procedures enabled us to balance the Tdap-exposed and -unexposed groups to compare two populations that were comparable in important measured confounding factors,” Dr. Becerra-Culqui and associates noted.

The investigators found that women who received the Tdap vaccine during pregnancy were more likely to be Asian American or Pacific Islander, to have a bachelor’s degree or higher, be nulliparous, to have also been vaccinated prenatally against influenza, and to deliver at term, compared with unvaccinated women.

However the authors did note that their follow-up was limited to 6.5 years for the earliest birth cohort, and 3.5 years for the latest cohort, so they may not have picked up children who received a later diagnosis of autism spectrum disorder.

The study was supported by Kaiser Permanente Southern California. Five authors declared funding from GlaxoSmithKline, Bayer AG, or the Centers for Disease Control and Prevention for unrelated or separate studies.

SOURCE: Becerra-Culqui T et al. Pediatrics. 2018;142(3):e20180120.

A retrospective cohort study in more than 80,000 children has found no evidence of an increased risk of autism spectrum disorder associated with prenatal tetanus, diphtheria, and acellular pertussis (Tdap) immunization.

Piotr Marcinski/Thinkstock

Of 81,993 children born between 2011 and 2014, 1,341 children (1.6%) were diagnosed with autism spectrum disorder. The incidence of autism spectrum disorder was 3.78 per 1,000 person-years in the Tdap-vaccinated group, and 4.05 per 1,000 person years in the unvaccinated group, representing an unadjusted hazard ratio of 0.98 and an adjusted hazard ratio of 0.85. This was consistent across all the birth cohorts.

Prenatal immunization rates with the prenatal Tdap vaccine ranged from 26% of the 2012 birth cohort to 79% of the 2014 birth cohort, and mean gestational age at vaccination was 28 weeks.

Tracy A. Becerra-Culqui, PhD, MPH, and colleagues of the department of research and evaluation at Kaiser Permanente Southern California, Pasadena, said this was the first study to look at the risk of autism spectrum disorder after maternal exposure to the Tdap vaccine, to their knowledge. “Our results potentially indicate that the maternal Tdap vaccine affects immune trajectories protecting infants against infections that would otherwise lead to neurodevelopmental alterations.”

They highlighted several strengths of their study. One was that maternal Tdap vaccination and information on autism spectrum disorder both were derived from EHRs and therefore not subject to recall bias. The study, published online in Pediatrics, also included children diagnosed with autism spectrum disorder from age 1 year onwards, reflecting the latest evidence on screening and diagnosis of autism.

“Our weighting procedures enabled us to balance the Tdap-exposed and -unexposed groups to compare two populations that were comparable in important measured confounding factors,” Dr. Becerra-Culqui and associates noted.

The investigators found that women who received the Tdap vaccine during pregnancy were more likely to be Asian American or Pacific Islander, to have a bachelor’s degree or higher, be nulliparous, to have also been vaccinated prenatally against influenza, and to deliver at term, compared with unvaccinated women.

However the authors did note that their follow-up was limited to 6.5 years for the earliest birth cohort, and 3.5 years for the latest cohort, so they may not have picked up children who received a later diagnosis of autism spectrum disorder.

The study was supported by Kaiser Permanente Southern California. Five authors declared funding from GlaxoSmithKline, Bayer AG, or the Centers for Disease Control and Prevention for unrelated or separate studies.

SOURCE: Becerra-Culqui T et al. Pediatrics. 2018;142(3):e20180120.

A retrospective cohort study in more than 80,000 children has found no evidence of an increased risk of autism spectrum disorder associated with prenatal tetanus, diphtheria, and acellular pertussis (Tdap) immunization.

Piotr Marcinski/Thinkstock

Of 81,993 children born between 2011 and 2014, 1,341 children (1.6%) were diagnosed with autism spectrum disorder. The incidence of autism spectrum disorder was 3.78 per 1,000 person-years in the Tdap-vaccinated group, and 4.05 per 1,000 person years in the unvaccinated group, representing an unadjusted hazard ratio of 0.98 and an adjusted hazard ratio of 0.85. This was consistent across all the birth cohorts.

Prenatal immunization rates with the prenatal Tdap vaccine ranged from 26% of the 2012 birth cohort to 79% of the 2014 birth cohort, and mean gestational age at vaccination was 28 weeks.

Tracy A. Becerra-Culqui, PhD, MPH, and colleagues of the department of research and evaluation at Kaiser Permanente Southern California, Pasadena, said this was the first study to look at the risk of autism spectrum disorder after maternal exposure to the Tdap vaccine, to their knowledge. “Our results potentially indicate that the maternal Tdap vaccine affects immune trajectories protecting infants against infections that would otherwise lead to neurodevelopmental alterations.”

They highlighted several strengths of their study. One was that maternal Tdap vaccination and information on autism spectrum disorder both were derived from EHRs and therefore not subject to recall bias. The study, published online in Pediatrics, also included children diagnosed with autism spectrum disorder from age 1 year onwards, reflecting the latest evidence on screening and diagnosis of autism.

“Our weighting procedures enabled us to balance the Tdap-exposed and -unexposed groups to compare two populations that were comparable in important measured confounding factors,” Dr. Becerra-Culqui and associates noted.

The investigators found that women who received the Tdap vaccine during pregnancy were more likely to be Asian American or Pacific Islander, to have a bachelor’s degree or higher, be nulliparous, to have also been vaccinated prenatally against influenza, and to deliver at term, compared with unvaccinated women.

However the authors did note that their follow-up was limited to 6.5 years for the earliest birth cohort, and 3.5 years for the latest cohort, so they may not have picked up children who received a later diagnosis of autism spectrum disorder.

The study was supported by Kaiser Permanente Southern California. Five authors declared funding from GlaxoSmithKline, Bayer AG, or the Centers for Disease Control and Prevention for unrelated or separate studies.

SOURCE: Becerra-Culqui T et al. Pediatrics. 2018;142(3):e20180120.

Patients undergoing autologous hematopoietic cell transplantation for lymphoma or plasma cell myeloma have 10-100 times the risk of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) seen in the general population, according to a retrospective cohort study.

The elevated risk also exceeds that of similar patients largely untreated with autotransplant.

Exposure to DNA-damaging drugs and ionizing radiation – both used in autotransplant – is known to increase risk of these treatment-related myeloid neoplasms, according to Tomas Radivoyevitch, PhD, of the Cleveland Clinic Foundation and his colleagues. Concern about this complication has been growing as long-term survivorship after transplant improves.

The investigators analyzed data reported to the Center for International Blood and Marrow Transplant Research. Analyses were based on 9,028 patients undergoing autotransplant during 1995-2010 for Hodgkin lymphoma (916 patients), non-Hodgkin lymphoma (3,546 patients), or plasma cell myeloma (4,566 patients). Their median duration of follow-up was 90 months, 110 months, and 97 months, respectively.

Overall, 3.7% of the cohort developed AML or MDS after their transplant. More aggressive transplantation protocols increased the likelihood of this outcome: Risk was higher for patients with Hodgkin lymphoma who received conditioning with total body radiation versus chemotherapy alone (hazard ratio, 4.0); patients with non-Hodgkin lymphoma who received conditioning with total body radiation (HR, 1.7) or with busulfan and melphalan or cyclophosphamide (HR, 1.8) versus the BEAM regimen; patients with non-Hodgkin lymphoma or plasma cell myeloma who received three or more lines of chemotherapy versus just one line (HR, 1.9 and 1.8, respectively); and patients with non-Hodgkin lymphoma who underwent transplantation in 2005-2010 versus 1995-1999 (HR, 2.1).

Patients reported to Surveillance, Epidemiology and End Results (SEER) database with the same lymphoma and plasma cell myeloma diagnoses, few of whom underwent autotransplant, had risks of AML and MDS that were 5-10 times higher than the background level in the population. But the study autotransplant cohort had a risk of AML that was 10-50 times higher, and a relative risk of MDS that was roughly 100 times higher than the background level.

“These increases may be related to exposure to high doses of DNA-damaging drugs given for the autotransplant, but this hypothesis can only be tested in a prospective study,” Dr. Radivoyevitch and his coinvestigators wrote.

The reason for the greater elevation of MDS risk, compared with AML risk, is unknown. “One possible explanation is that many cases of MDS evolve to AML, and that earlier diagnosis from increased posttransplant surveillance resulted in a deficiency of AML,” they wrote. “A second is based on steeper MDS versus AML incidences versus age … and the possibility that transplantation recipient marrow ages (i.e., marrow biological ages) are perhaps decades older than calendar ages.”

The Center for International Blood and Marrow Transplant Research is supported by several U.S. government agencies and numerous pharmaceutical companies. The authors reported that they had no relevant conflicts of interest.

SOURCE: Radivoyevitch T et al. Leuk Res. 2018 Jul 19. pii: S0145-2126(18)30160-7.

Patients undergoing autologous hematopoietic cell transplantation for lymphoma or plasma cell myeloma have 10-100 times the risk of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) seen in the general population, according to a retrospective cohort study.

The elevated risk also exceeds that of similar patients largely untreated with autotransplant.

Exposure to DNA-damaging drugs and ionizing radiation – both used in autotransplant – is known to increase risk of these treatment-related myeloid neoplasms, according to Tomas Radivoyevitch, PhD, of the Cleveland Clinic Foundation and his colleagues. Concern about this complication has been growing as long-term survivorship after transplant improves.

The investigators analyzed data reported to the Center for International Blood and Marrow Transplant Research. Analyses were based on 9,028 patients undergoing autotransplant during 1995-2010 for Hodgkin lymphoma (916 patients), non-Hodgkin lymphoma (3,546 patients), or plasma cell myeloma (4,566 patients). Their median duration of follow-up was 90 months, 110 months, and 97 months, respectively.

Overall, 3.7% of the cohort developed AML or MDS after their transplant. More aggressive transplantation protocols increased the likelihood of this outcome: Risk was higher for patients with Hodgkin lymphoma who received conditioning with total body radiation versus chemotherapy alone (hazard ratio, 4.0); patients with non-Hodgkin lymphoma who received conditioning with total body radiation (HR, 1.7) or with busulfan and melphalan or cyclophosphamide (HR, 1.8) versus the BEAM regimen; patients with non-Hodgkin lymphoma or plasma cell myeloma who received three or more lines of chemotherapy versus just one line (HR, 1.9 and 1.8, respectively); and patients with non-Hodgkin lymphoma who underwent transplantation in 2005-2010 versus 1995-1999 (HR, 2.1).

Patients reported to Surveillance, Epidemiology and End Results (SEER) database with the same lymphoma and plasma cell myeloma diagnoses, few of whom underwent autotransplant, had risks of AML and MDS that were 5-10 times higher than the background level in the population. But the study autotransplant cohort had a risk of AML that was 10-50 times higher, and a relative risk of MDS that was roughly 100 times higher than the background level.

“These increases may be related to exposure to high doses of DNA-damaging drugs given for the autotransplant, but this hypothesis can only be tested in a prospective study,” Dr. Radivoyevitch and his coinvestigators wrote.

The reason for the greater elevation of MDS risk, compared with AML risk, is unknown. “One possible explanation is that many cases of MDS evolve to AML, and that earlier diagnosis from increased posttransplant surveillance resulted in a deficiency of AML,” they wrote. “A second is based on steeper MDS versus AML incidences versus age … and the possibility that transplantation recipient marrow ages (i.e., marrow biological ages) are perhaps decades older than calendar ages.”

The Center for International Blood and Marrow Transplant Research is supported by several U.S. government agencies and numerous pharmaceutical companies. The authors reported that they had no relevant conflicts of interest.

SOURCE: Radivoyevitch T et al. Leuk Res. 2018 Jul 19. pii: S0145-2126(18)30160-7.

Patients undergoing autologous hematopoietic cell transplantation for lymphoma or plasma cell myeloma have 10-100 times the risk of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) seen in the general population, according to a retrospective cohort study.

The elevated risk also exceeds that of similar patients largely untreated with autotransplant.

Exposure to DNA-damaging drugs and ionizing radiation – both used in autotransplant – is known to increase risk of these treatment-related myeloid neoplasms, according to Tomas Radivoyevitch, PhD, of the Cleveland Clinic Foundation and his colleagues. Concern about this complication has been growing as long-term survivorship after transplant improves.

The investigators analyzed data reported to the Center for International Blood and Marrow Transplant Research. Analyses were based on 9,028 patients undergoing autotransplant during 1995-2010 for Hodgkin lymphoma (916 patients), non-Hodgkin lymphoma (3,546 patients), or plasma cell myeloma (4,566 patients). Their median duration of follow-up was 90 months, 110 months, and 97 months, respectively.

Overall, 3.7% of the cohort developed AML or MDS after their transplant. More aggressive transplantation protocols increased the likelihood of this outcome: Risk was higher for patients with Hodgkin lymphoma who received conditioning with total body radiation versus chemotherapy alone (hazard ratio, 4.0); patients with non-Hodgkin lymphoma who received conditioning with total body radiation (HR, 1.7) or with busulfan and melphalan or cyclophosphamide (HR, 1.8) versus the BEAM regimen; patients with non-Hodgkin lymphoma or plasma cell myeloma who received three or more lines of chemotherapy versus just one line (HR, 1.9 and 1.8, respectively); and patients with non-Hodgkin lymphoma who underwent transplantation in 2005-2010 versus 1995-1999 (HR, 2.1).

Patients reported to Surveillance, Epidemiology and End Results (SEER) database with the same lymphoma and plasma cell myeloma diagnoses, few of whom underwent autotransplant, had risks of AML and MDS that were 5-10 times higher than the background level in the population. But the study autotransplant cohort had a risk of AML that was 10-50 times higher, and a relative risk of MDS that was roughly 100 times higher than the background level.

“These increases may be related to exposure to high doses of DNA-damaging drugs given for the autotransplant, but this hypothesis can only be tested in a prospective study,” Dr. Radivoyevitch and his coinvestigators wrote.

The reason for the greater elevation of MDS risk, compared with AML risk, is unknown. “One possible explanation is that many cases of MDS evolve to AML, and that earlier diagnosis from increased posttransplant surveillance resulted in a deficiency of AML,” they wrote. “A second is based on steeper MDS versus AML incidences versus age … and the possibility that transplantation recipient marrow ages (i.e., marrow biological ages) are perhaps decades older than calendar ages.”

The Center for International Blood and Marrow Transplant Research is supported by several U.S. government agencies and numerous pharmaceutical companies. The authors reported that they had no relevant conflicts of interest.

SOURCE: Radivoyevitch T et al. Leuk Res. 2018 Jul 19. pii: S0145-2126(18)30160-7.

Teens who were exposed to any type of secondhand tobacco smoke were significantly more likely to visit emergency departments and to have more such visits, compared with unexposed controls, based on data from more than 7,000 adolescents.

pmphoto/iStockphoto

Approximately 35% of U.S. teens spent more than an hour exposed to secondhand smoke in a given week, wrote Ashley L. Merianos, PhD, of the University of Cincinnati and her colleagues.

In a study published in Pediatrics, the researchers conducted a secondary analysis of nonsmoking adolescents aged 12-17 years who had not been diagnosed with asthma and who were part of the PATH (Population Assessment of Tobacco and Health) study, a longitudinal cohort trial of tobacco use behavior and related health outcomes in adolescents and adults in the United States. The data were collected between Oct. 3, 2014, and Oct. 30, 2015. The researchers reviewed three main measures of tobacco smoke exposure (TSE): living with a smoker, being exposed to secondhand smoke at home, and being exposed to secondhand smoke for an hour or more in the past 7 days.

Overall, teens who lived with a smoker, had secondary exposure at home, or had at least 1 hour of TSE had significantly more emergency department and/or urgent care visits (mean ranged from 1.62 to 1.65), compared with unexposed peers (mean visits ranged from 1.42 to 1.48). Those who both lived with a smoker and had at least 1 hour of TSE exposure were significantly more likely to visit an ED or urgent care center.

In addition, teens who lived with a smoker, had secondary exposure at home, and had at least 1 hour of TSE were significantly more likely than were unexposed peers to report shortness of breath, difficulty exercising, wheezing during and after exercise, and a dry cough at night (P less than .001).

The researchers also assessed other health indicators, and found that teens with TSE exposure were significantly less likely than were unexposed peers to report very good or excellent health and were approximately 1.50 times more likely than unexposed peers to report missing school because of poor health.

The results were limited by several factors including the use of self-reports of TSE and parent reports of emergency or urgent care visits, and by the inclusion only of other public use variables in the PATH database, the researchers noted. But they adjusted for potentially confounding factors such as household income level, parent education, and health insurance status. However, “Because adolescents are high users of EDs and/or [urgent care] for primary care reasons, these venues are high-volume settings that should be used to offer interventions to adolescents with TSE and their families,” they said.

The researchers had no financial conflicts to disclose. The study was funded by the National Institutes of Health via the National Institute on Drug Abuse and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

SOURCE: Merianos AL et al. Pediatrics 2018 Aug 6. doi: org/10.1542/peds.2018-0266.

Teens who were exposed to any type of secondhand tobacco smoke were significantly more likely to visit emergency departments and to have more such visits, compared with unexposed controls, based on data from more than 7,000 adolescents.

pmphoto/iStockphoto

Approximately 35% of U.S. teens spent more than an hour exposed to secondhand smoke in a given week, wrote Ashley L. Merianos, PhD, of the University of Cincinnati and her colleagues.

In a study published in Pediatrics, the researchers conducted a secondary analysis of nonsmoking adolescents aged 12-17 years who had not been diagnosed with asthma and who were part of the PATH (Population Assessment of Tobacco and Health) study, a longitudinal cohort trial of tobacco use behavior and related health outcomes in adolescents and adults in the United States. The data were collected between Oct. 3, 2014, and Oct. 30, 2015. The researchers reviewed three main measures of tobacco smoke exposure (TSE): living with a smoker, being exposed to secondhand smoke at home, and being exposed to secondhand smoke for an hour or more in the past 7 days.

Overall, teens who lived with a smoker, had secondary exposure at home, or had at least 1 hour of TSE had significantly more emergency department and/or urgent care visits (mean ranged from 1.62 to 1.65), compared with unexposed peers (mean visits ranged from 1.42 to 1.48). Those who both lived with a smoker and had at least 1 hour of TSE exposure were significantly more likely to visit an ED or urgent care center.

In addition, teens who lived with a smoker, had secondary exposure at home, and had at least 1 hour of TSE were significantly more likely than were unexposed peers to report shortness of breath, difficulty exercising, wheezing during and after exercise, and a dry cough at night (P less than .001).

The researchers also assessed other health indicators, and found that teens with TSE exposure were significantly less likely than were unexposed peers to report very good or excellent health and were approximately 1.50 times more likely than unexposed peers to report missing school because of poor health.

The results were limited by several factors including the use of self-reports of TSE and parent reports of emergency or urgent care visits, and by the inclusion only of other public use variables in the PATH database, the researchers noted. But they adjusted for potentially confounding factors such as household income level, parent education, and health insurance status. However, “Because adolescents are high users of EDs and/or [urgent care] for primary care reasons, these venues are high-volume settings that should be used to offer interventions to adolescents with TSE and their families,” they said.

The researchers had no financial conflicts to disclose. The study was funded by the National Institutes of Health via the National Institute on Drug Abuse and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

SOURCE: Merianos AL et al. Pediatrics 2018 Aug 6. doi: org/10.1542/peds.2018-0266.

Teens who were exposed to any type of secondhand tobacco smoke were significantly more likely to visit emergency departments and to have more such visits, compared with unexposed controls, based on data from more than 7,000 adolescents.

pmphoto/iStockphoto

Approximately 35% of U.S. teens spent more than an hour exposed to secondhand smoke in a given week, wrote Ashley L. Merianos, PhD, of the University of Cincinnati and her colleagues.

In a study published in Pediatrics, the researchers conducted a secondary analysis of nonsmoking adolescents aged 12-17 years who had not been diagnosed with asthma and who were part of the PATH (Population Assessment of Tobacco and Health) study, a longitudinal cohort trial of tobacco use behavior and related health outcomes in adolescents and adults in the United States. The data were collected between Oct. 3, 2014, and Oct. 30, 2015. The researchers reviewed three main measures of tobacco smoke exposure (TSE): living with a smoker, being exposed to secondhand smoke at home, and being exposed to secondhand smoke for an hour or more in the past 7 days.

Overall, teens who lived with a smoker, had secondary exposure at home, or had at least 1 hour of TSE had significantly more emergency department and/or urgent care visits (mean ranged from 1.62 to 1.65), compared with unexposed peers (mean visits ranged from 1.42 to 1.48). Those who both lived with a smoker and had at least 1 hour of TSE exposure were significantly more likely to visit an ED or urgent care center.

In addition, teens who lived with a smoker, had secondary exposure at home, and had at least 1 hour of TSE were significantly more likely than were unexposed peers to report shortness of breath, difficulty exercising, wheezing during and after exercise, and a dry cough at night (P less than .001).

The researchers also assessed other health indicators, and found that teens with TSE exposure were significantly less likely than were unexposed peers to report very good or excellent health and were approximately 1.50 times more likely than unexposed peers to report missing school because of poor health.

The results were limited by several factors including the use of self-reports of TSE and parent reports of emergency or urgent care visits, and by the inclusion only of other public use variables in the PATH database, the researchers noted. But they adjusted for potentially confounding factors such as household income level, parent education, and health insurance status. However, “Because adolescents are high users of EDs and/or [urgent care] for primary care reasons, these venues are high-volume settings that should be used to offer interventions to adolescents with TSE and their families,” they said.

The researchers had no financial conflicts to disclose. The study was funded by the National Institutes of Health via the National Institute on Drug Abuse and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

SOURCE: Merianos AL et al. Pediatrics 2018 Aug 6. doi: org/10.1542/peds.2018-0266.

BALTIMORE – Given the prevalence of opioid use in the general population, sleep specialists need to be alert to the effects of opioid use on sleep and the link between chronic use and sleep disorders, a pulmonologist recommended at the annual meeting of the Associated Professional Sleep Societies.

Chronic opioid use has multiple effects on sleep that render continuous positive airway pressure (CPAP) all but ineffective, said Bernardo J. Selim, MD, of Mayo Clinic, Rochester, Minn. Characteristic signs of the effects of chronic opioid use on sleep include ataxic central sleep apnea (CSA) and sustained hypoxemia, for which CPAP is generally not effective. Obtaining arterial blood gas measures in these patients is also important to rule out a hypoventilative condition, he added.

In his review of opioid-induced sleep disorders, Dr. Selim cited a small “landmark” study of 24 chronic pain patients on opioids that found 46% had sleep disordered breathing and that the risk rose with the morphine equivalent dose they were taking (J Clin Sleep Med. 2014 Aug 15; 10[8]:847-52).

A meta-analysis also found a dose-dependent relationship with the severity of CSA in patients on opioids, Dr. Selim noted (Anesth Analg. 2015 Jun;120[6]:1273-85). The prevalence of CSA was 24% in the study, which defined two risk factors for CSA severity: a morphine equivalent dose exceeding 200 mg/day and a low or normal body mass index.

Dr. Selim noted that opioids reduce respiration rate more than tidal volume and cause changes to respiratory rhythm. “[Opioids] decrease hypercapnia but increase hypoxic ventilatory response, decrease the arousal index, decrease upper-airway muscle tone, and decrease and also act on chest and abdominal wall compliance.”

Further, different opioids and injection methods can influence breathing. For example, REM and slow-wave sleep decreased across all three categories – intravenous morphine, oral morphine or methadone, and heroin use.

Sleep specialists should be aware that all opioid receptor agonists, whether legal or illegal, have respiratory side effects, Dr. Selim said. “They can present in any way, in any form – CSA, obstructive sleep apnea [OSA], ataxic breathing or sustained hypoxemia. Most of the time [respiratory side effects] present as a combination of complex respiratory patterns.”

BALTIMORE – Given the prevalence of opioid use in the general population, sleep specialists need to be alert to the effects of opioid use on sleep and the link between chronic use and sleep disorders, a pulmonologist recommended at the annual meeting of the Associated Professional Sleep Societies.

Chronic opioid use has multiple effects on sleep that render continuous positive airway pressure (CPAP) all but ineffective, said Bernardo J. Selim, MD, of Mayo Clinic, Rochester, Minn. Characteristic signs of the effects of chronic opioid use on sleep include ataxic central sleep apnea (CSA) and sustained hypoxemia, for which CPAP is generally not effective. Obtaining arterial blood gas measures in these patients is also important to rule out a hypoventilative condition, he added.

In his review of opioid-induced sleep disorders, Dr. Selim cited a small “landmark” study of 24 chronic pain patients on opioids that found 46% had sleep disordered breathing and that the risk rose with the morphine equivalent dose they were taking (J Clin Sleep Med. 2014 Aug 15; 10[8]:847-52).

A meta-analysis also found a dose-dependent relationship with the severity of CSA in patients on opioids, Dr. Selim noted (Anesth Analg. 2015 Jun;120[6]:1273-85). The prevalence of CSA was 24% in the study, which defined two risk factors for CSA severity: a morphine equivalent dose exceeding 200 mg/day and a low or normal body mass index.

Dr. Selim noted that opioids reduce respiration rate more than tidal volume and cause changes to respiratory rhythm. “[Opioids] decrease hypercapnia but increase hypoxic ventilatory response, decrease the arousal index, decrease upper-airway muscle tone, and decrease and also act on chest and abdominal wall compliance.”

Further, different opioids and injection methods can influence breathing. For example, REM and slow-wave sleep decreased across all three categories – intravenous morphine, oral morphine or methadone, and heroin use.

Sleep specialists should be aware that all opioid receptor agonists, whether legal or illegal, have respiratory side effects, Dr. Selim said. “They can present in any way, in any form – CSA, obstructive sleep apnea [OSA], ataxic breathing or sustained hypoxemia. Most of the time [respiratory side effects] present as a combination of complex respiratory patterns.”

BALTIMORE – Given the prevalence of opioid use in the general population, sleep specialists need to be alert to the effects of opioid use on sleep and the link between chronic use and sleep disorders, a pulmonologist recommended at the annual meeting of the Associated Professional Sleep Societies.

Chronic opioid use has multiple effects on sleep that render continuous positive airway pressure (CPAP) all but ineffective, said Bernardo J. Selim, MD, of Mayo Clinic, Rochester, Minn. Characteristic signs of the effects of chronic opioid use on sleep include ataxic central sleep apnea (CSA) and sustained hypoxemia, for which CPAP is generally not effective. Obtaining arterial blood gas measures in these patients is also important to rule out a hypoventilative condition, he added.

In his review of opioid-induced sleep disorders, Dr. Selim cited a small “landmark” study of 24 chronic pain patients on opioids that found 46% had sleep disordered breathing and that the risk rose with the morphine equivalent dose they were taking (J Clin Sleep Med. 2014 Aug 15; 10[8]:847-52).

A meta-analysis also found a dose-dependent relationship with the severity of CSA in patients on opioids, Dr. Selim noted (Anesth Analg. 2015 Jun;120[6]:1273-85). The prevalence of CSA was 24% in the study, which defined two risk factors for CSA severity: a morphine equivalent dose exceeding 200 mg/day and a low or normal body mass index.

Dr. Selim noted that opioids reduce respiration rate more than tidal volume and cause changes to respiratory rhythm. “[Opioids] decrease hypercapnia but increase hypoxic ventilatory response, decrease the arousal index, decrease upper-airway muscle tone, and decrease and also act on chest and abdominal wall compliance.”

Further, different opioids and injection methods can influence breathing. For example, REM and slow-wave sleep decreased across all three categories – intravenous morphine, oral morphine or methadone, and heroin use.

Sleep specialists should be aware that all opioid receptor agonists, whether legal or illegal, have respiratory side effects, Dr. Selim said. “They can present in any way, in any form – CSA, obstructive sleep apnea [OSA], ataxic breathing or sustained hypoxemia. Most of the time [respiratory side effects] present as a combination of complex respiratory patterns.”

NEW ORLEANS – A next-generation lower respiratory tract sputum polymerase chain reaction (PCR) film array panel identified etiologic pathogens in 100% of a group of patients hospitalized for community-acquired pneumonia, Kathryn Hendrickson, MD, reported at the annual meeting of the American College of Physicians.

Courtesy CDC

The investigational new diagnostic assay, the BioFire Pneumonia Panel, is now under Food and Drug Administration review for marketing clearance. It offers great potential for targeted therapy along with reduced overuse of antibiotics in patients with community-acquired pneumonia (CAP), observed Dr. Hendrickson, an internal medicine resident at Providence Portland (Ore.) Medical Center. The new product is designed to complement the currently available respiratory panels from BioFire.

“Rapid-detection results in less empiric antibiotic use in hospitalized patients. When it’s FDA approved, this investigational sputum PCR panel will simplify the diagnostic bundle while improving antibiotic stewardship,” she observed.

She presented a prospective study of 63 patients with CAP hospitalized at the medical center, all of whom were evaluated by two laboratory methods: the hospital’s standard bundle of diagnostic tests and the new BioFire film array panel. The purpose was to determine if there was a difference between the two tests in the detection rate of viral and/or bacterial pathogens as well as the clinical significance of any such differences; that is, was there an impact on days of treatment and length of hospital stay?

Traditional diagnostic methods detect an etiologic pathogen in at best half of hospitalized CAP patients, and the results take too much time. So Providence Portland Medical Center adopted as its standard diagnostic bundle a nasopharyngeal swab and a BioFire film array PCR that’s currently on the market and can detect nine viruses and three bacteria, along with urine antigens for Legionella sp. and Streptococcus pneumoniae, nucleic acid amplification testing for S. pneumoniae and Staphylococcus aureus, and blood and sputum cultures. In contrast, the investigational panel probes for 17 viruses, 18 bacterial pathogens, and seven antibiotic-resistant genes; it also measures procalcitonin levels in order to distinguish between bacterial colonization and invasion.

The new BioFire Pneumonia Panel detected a mean of 1.4 species of pathogenic bacteria in 79% of patients, while the standard diagnostic bundle detected 0.7 species in 59% of patients. The investigational panel identified a mean of 1.0 species of viral pathogens in 86% of the CAP patients; the standard bundle detected a mean of 0.6 species in 56%.

All told, any CAP pathogen was detected in 100% of patients using the new panel, with a mean of 2.5 different pathogens identified. The standard bundle detected any pathogen in 84% of patients, with half as many different pathogens found, according to Dr. Hendrickson.

A peak procalcitonin level of 0.25 ng/mL or less, which was defined as bacterial colonization, was associated with a mean 7 days of treatment, while a level above that threshold was associated with 11.3 days of treatment. Patients with a peak procalcitonin of 0.25 ng/mL or less had an average hospital length of stay of 5.9 days, versus 7.8 days for those with a higher procalcitonin indicative of bacterial invasion.

The new biofilm assay reports information about the abundance of 15 of the 18 bacterial targets in the sample. However, in contrast to peak procalcitonin, Dr. Hendrickson and her coinvestigators didn’t find this bacterial quantitation feature to be substantially more useful than a coin flip in distinguishing bacterial colonization from invasion.

She reported having no financial conflicts regarding the head-to-head comparative study, which was supported by BioFire Diagnostics.

bjancin@mdedge.com

NEW ORLEANS – A next-generation lower respiratory tract sputum polymerase chain reaction (PCR) film array panel identified etiologic pathogens in 100% of a group of patients hospitalized for community-acquired pneumonia, Kathryn Hendrickson, MD, reported at the annual meeting of the American College of Physicians.

Courtesy CDC

The investigational new diagnostic assay, the BioFire Pneumonia Panel, is now under Food and Drug Administration review for marketing clearance. It offers great potential for targeted therapy along with reduced overuse of antibiotics in patients with community-acquired pneumonia (CAP), observed Dr. Hendrickson, an internal medicine resident at Providence Portland (Ore.) Medical Center. The new product is designed to complement the currently available respiratory panels from BioFire.

“Rapid-detection results in less empiric antibiotic use in hospitalized patients. When it’s FDA approved, this investigational sputum PCR panel will simplify the diagnostic bundle while improving antibiotic stewardship,” she observed.

She presented a prospective study of 63 patients with CAP hospitalized at the medical center, all of whom were evaluated by two laboratory methods: the hospital’s standard bundle of diagnostic tests and the new BioFire film array panel. The purpose was to determine if there was a difference between the two tests in the detection rate of viral and/or bacterial pathogens as well as the clinical significance of any such differences; that is, was there an impact on days of treatment and length of hospital stay?

Traditional diagnostic methods detect an etiologic pathogen in at best half of hospitalized CAP patients, and the results take too much time. So Providence Portland Medical Center adopted as its standard diagnostic bundle a nasopharyngeal swab and a BioFire film array PCR that’s currently on the market and can detect nine viruses and three bacteria, along with urine antigens for Legionella sp. and Streptococcus pneumoniae, nucleic acid amplification testing for S. pneumoniae and Staphylococcus aureus, and blood and sputum cultures. In contrast, the investigational panel probes for 17 viruses, 18 bacterial pathogens, and seven antibiotic-resistant genes; it also measures procalcitonin levels in order to distinguish between bacterial colonization and invasion.

The new BioFire Pneumonia Panel detected a mean of 1.4 species of pathogenic bacteria in 79% of patients, while the standard diagnostic bundle detected 0.7 species in 59% of patients. The investigational panel identified a mean of 1.0 species of viral pathogens in 86% of the CAP patients; the standard bundle detected a mean of 0.6 species in 56%.

All told, any CAP pathogen was detected in 100% of patients using the new panel, with a mean of 2.5 different pathogens identified. The standard bundle detected any pathogen in 84% of patients, with half as many different pathogens found, according to Dr. Hendrickson.

A peak procalcitonin level of 0.25 ng/mL or less, which was defined as bacterial colonization, was associated with a mean 7 days of treatment, while a level above that threshold was associated with 11.3 days of treatment. Patients with a peak procalcitonin of 0.25 ng/mL or less had an average hospital length of stay of 5.9 days, versus 7.8 days for those with a higher procalcitonin indicative of bacterial invasion.

The new biofilm assay reports information about the abundance of 15 of the 18 bacterial targets in the sample. However, in contrast to peak procalcitonin, Dr. Hendrickson and her coinvestigators didn’t find this bacterial quantitation feature to be substantially more useful than a coin flip in distinguishing bacterial colonization from invasion.

She reported having no financial conflicts regarding the head-to-head comparative study, which was supported by BioFire Diagnostics.

bjancin@mdedge.com

NEW ORLEANS – A next-generation lower respiratory tract sputum polymerase chain reaction (PCR) film array panel identified etiologic pathogens in 100% of a group of patients hospitalized for community-acquired pneumonia, Kathryn Hendrickson, MD, reported at the annual meeting of the American College of Physicians.

Courtesy CDC

The investigational new diagnostic assay, the BioFire Pneumonia Panel, is now under Food and Drug Administration review for marketing clearance. It offers great potential for targeted therapy along with reduced overuse of antibiotics in patients with community-acquired pneumonia (CAP), observed Dr. Hendrickson, an internal medicine resident at Providence Portland (Ore.) Medical Center. The new product is designed to complement the currently available respiratory panels from BioFire.

“Rapid-detection results in less empiric antibiotic use in hospitalized patients. When it’s FDA approved, this investigational sputum PCR panel will simplify the diagnostic bundle while improving antibiotic stewardship,” she observed.

She presented a prospective study of 63 patients with CAP hospitalized at the medical center, all of whom were evaluated by two laboratory methods: the hospital’s standard bundle of diagnostic tests and the new BioFire film array panel. The purpose was to determine if there was a difference between the two tests in the detection rate of viral and/or bacterial pathogens as well as the clinical significance of any such differences; that is, was there an impact on days of treatment and length of hospital stay?

Traditional diagnostic methods detect an etiologic pathogen in at best half of hospitalized CAP patients, and the results take too much time. So Providence Portland Medical Center adopted as its standard diagnostic bundle a nasopharyngeal swab and a BioFire film array PCR that’s currently on the market and can detect nine viruses and three bacteria, along with urine antigens for Legionella sp. and Streptococcus pneumoniae, nucleic acid amplification testing for S. pneumoniae and Staphylococcus aureus, and blood and sputum cultures. In contrast, the investigational panel probes for 17 viruses, 18 bacterial pathogens, and seven antibiotic-resistant genes; it also measures procalcitonin levels in order to distinguish between bacterial colonization and invasion.

The new BioFire Pneumonia Panel detected a mean of 1.4 species of pathogenic bacteria in 79% of patients, while the standard diagnostic bundle detected 0.7 species in 59% of patients. The investigational panel identified a mean of 1.0 species of viral pathogens in 86% of the CAP patients; the standard bundle detected a mean of 0.6 species in 56%.

All told, any CAP pathogen was detected in 100% of patients using the new panel, with a mean of 2.5 different pathogens identified. The standard bundle detected any pathogen in 84% of patients, with half as many different pathogens found, according to Dr. Hendrickson.

A peak procalcitonin level of 0.25 ng/mL or less, which was defined as bacterial colonization, was associated with a mean 7 days of treatment, while a level above that threshold was associated with 11.3 days of treatment. Patients with a peak procalcitonin of 0.25 ng/mL or less had an average hospital length of stay of 5.9 days, versus 7.8 days for those with a higher procalcitonin indicative of bacterial invasion.

The new biofilm assay reports information about the abundance of 15 of the 18 bacterial targets in the sample. However, in contrast to peak procalcitonin, Dr. Hendrickson and her coinvestigators didn’t find this bacterial quantitation feature to be substantially more useful than a coin flip in distinguishing bacterial colonization from invasion.

She reported having no financial conflicts regarding the head-to-head comparative study, which was supported by BioFire Diagnostics.

bjancin@mdedge.com

New estimates of chronic obstructive pulmonary disease (COPD) may have Utah residents breathing a sigh of relief. West Virginians, not so much.

The Beehive State has the lowest prevalence of COPD in the country at 2,710 per 100,000 population, while the Mountain State tops the charts at 11,130 per 100,000, according to estimates from the American Lung Association. (Crude rates were calculated by MDedge News using the ALA’s estimates for total persons with COPD in each state and Census Bureau estimates for population.)

Other states with freer-breathing residents include Minnesota, which was just behind Utah with an estimated rate of 3,000 per 100,000 population, Hawaii (3,182), Colorado (3,334), and California (3,409). West Virginia’s rate, however, seems to be an outlier. The state with the next-highest rate, Kentucky, has a calculated prevalence of 8,890 per 100,000 population, followed by Tennessee at 7,880, Alabama at 7,400, and Arkansas at 7,330, using the ALA’s estimates, which were based on data from the 2016 Behavioral Risk Factor Surveillance System survey.

rfranki@mdedge.com

New estimates of chronic obstructive pulmonary disease (COPD) may have Utah residents breathing a sigh of relief. West Virginians, not so much.

The Beehive State has the lowest prevalence of COPD in the country at 2,710 per 100,000 population, while the Mountain State tops the charts at 11,130 per 100,000, according to estimates from the American Lung Association. (Crude rates were calculated by MDedge News using the ALA’s estimates for total persons with COPD in each state and Census Bureau estimates for population.)

Other states with freer-breathing residents include Minnesota, which was just behind Utah with an estimated rate of 3,000 per 100,000 population, Hawaii (3,182), Colorado (3,334), and California (3,409). West Virginia’s rate, however, seems to be an outlier. The state with the next-highest rate, Kentucky, has a calculated prevalence of 8,890 per 100,000 population, followed by Tennessee at 7,880, Alabama at 7,400, and Arkansas at 7,330, using the ALA’s estimates, which were based on data from the 2016 Behavioral Risk Factor Surveillance System survey.

rfranki@mdedge.com

New estimates of chronic obstructive pulmonary disease (COPD) may have Utah residents breathing a sigh of relief. West Virginians, not so much.

The Beehive State has the lowest prevalence of COPD in the country at 2,710 per 100,000 population, while the Mountain State tops the charts at 11,130 per 100,000, according to estimates from the American Lung Association. (Crude rates were calculated by MDedge News using the ALA’s estimates for total persons with COPD in each state and Census Bureau estimates for population.)

Other states with freer-breathing residents include Minnesota, which was just behind Utah with an estimated rate of 3,000 per 100,000 population, Hawaii (3,182), Colorado (3,334), and California (3,409). West Virginia’s rate, however, seems to be an outlier. The state with the next-highest rate, Kentucky, has a calculated prevalence of 8,890 per 100,000 population, followed by Tennessee at 7,880, Alabama at 7,400, and Arkansas at 7,330, using the ALA’s estimates, which were based on data from the 2016 Behavioral Risk Factor Surveillance System survey.

rfranki@mdedge.com

After just 4 months, the National Institute of Alcohol Abuse and Alcoholism (NIAAA) is ending funding for the Moderate Alcohol and Cardiovascular Health (MACH) trial, citing concerns about the study design.

The MACH study was designed as a multicenter randomized trial to determine the effects of 1 serving of alcohol (approximately 15 g) a day compared with no alcohol intake on the rate of new cases of cardiovascular disease and new cases of diabetes among participants free of diabetes at baseline. The study was launched because some epidemiologic research had shown that moderate alcohol consumption had health benefits by reducing risk for coronary artery disease, type 2 diabetes, and rheumatoid arthritis.

The study began enrollment in February 2018 and was suspended on May 10. The NIAAA expected to commit $20 million to the project over 10 years, of which $4 million has been spent; remaining funding came from private donations of $67.7 million, of which $11.8 million has been spent.

The “orderly closeout” is based on recommendations from the advisory committee to the director working group, which found “significant process irregularities in the development of funding opportunities for the MACH funding awards undermined the integrity of the research process.” Additionally, a preliminary report from the National Institutes of Health (NIH) Office of Management Assessment determined that a small number of NIAAA employees violated NIH policies in soliciting gift funding and circumvented standard operating procedures.

After just 4 months, the National Institute of Alcohol Abuse and Alcoholism (NIAAA) is ending funding for the Moderate Alcohol and Cardiovascular Health (MACH) trial, citing concerns about the study design.

The MACH study was designed as a multicenter randomized trial to determine the effects of 1 serving of alcohol (approximately 15 g) a day compared with no alcohol intake on the rate of new cases of cardiovascular disease and new cases of diabetes among participants free of diabetes at baseline. The study was launched because some epidemiologic research had shown that moderate alcohol consumption had health benefits by reducing risk for coronary artery disease, type 2 diabetes, and rheumatoid arthritis.

The study began enrollment in February 2018 and was suspended on May 10. The NIAAA expected to commit $20 million to the project over 10 years, of which $4 million has been spent; remaining funding came from private donations of $67.7 million, of which $11.8 million has been spent.

The “orderly closeout” is based on recommendations from the advisory committee to the director working group, which found “significant process irregularities in the development of funding opportunities for the MACH funding awards undermined the integrity of the research process.” Additionally, a preliminary report from the National Institutes of Health (NIH) Office of Management Assessment determined that a small number of NIAAA employees violated NIH policies in soliciting gift funding and circumvented standard operating procedures.

After just 4 months, the National Institute of Alcohol Abuse and Alcoholism (NIAAA) is ending funding for the Moderate Alcohol and Cardiovascular Health (MACH) trial, citing concerns about the study design.

The MACH study was designed as a multicenter randomized trial to determine the effects of 1 serving of alcohol (approximately 15 g) a day compared with no alcohol intake on the rate of new cases of cardiovascular disease and new cases of diabetes among participants free of diabetes at baseline. The study was launched because some epidemiologic research had shown that moderate alcohol consumption had health benefits by reducing risk for coronary artery disease, type 2 diabetes, and rheumatoid arthritis.

The study began enrollment in February 2018 and was suspended on May 10. The NIAAA expected to commit $20 million to the project over 10 years, of which $4 million has been spent; remaining funding came from private donations of $67.7 million, of which $11.8 million has been spent.

The “orderly closeout” is based on recommendations from the advisory committee to the director working group, which found “significant process irregularities in the development of funding opportunities for the MACH funding awards undermined the integrity of the research process.” Additionally, a preliminary report from the National Institutes of Health (NIH) Office of Management Assessment determined that a small number of NIAAA employees violated NIH policies in soliciting gift funding and circumvented standard operating procedures.

The Food and Drug Administration has approved mogamulizumab-kpkc (Poteligeo) for the treatment of adults with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy.

Mogamulizumab is a humanized monoclonal antibody directed against CC chemokine receptor 4 (CCR4). It is the first biologic agent targeting CCR4 to be approved for patients in the United States.

Mogamulizumab is expected to be commercially available in the fourth quarter of 2018.

The FDA previously granted mogamulizumab breakthrough therapy and orphan drug designations, as well as priority review.

The approval is supported by the phase 3 MAVORIC trial. Results from this trial were presented at the 10th Annual T-cell Lymphoma Forum in February 2018.

MAVORIC enrolled 372 adults with histologically confirmed MF or SS who had failed at least one systemic therapy. They were randomized to receive mogamulizumab at 1.0 mg/kg (weekly for the first 4-week cycle and then every 2 weeks) or vorinostat at 400 mg daily. Patients were treated until disease progression or unacceptable toxicity. Those receiving vorinostat could cross over to mogamulizumab if they progressed or experienced intolerable toxicity. Baseline characteristics were similar between the treatment arms. The study’s primary endpoint was progression-free survival. The median progression-free survival was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio, 0.53; P less than .0001).

The global overall response rate was 28% (52/189) in the mogamulizumab arm and 5% (9/186) in the vorinostat arm (P less than .0001). For patients with MF, the ORR was 21% with mogamulizumab and 7% with vorinostat; for patients with SS, the ORR was 37% and 2%, respectively. After crossover, the ORR in the mogamulizumab arm was 30% (41/136).

The median duration of response (DOR) was 14 months in the mogamulizumab arm and 9 months in the vorinostat arm. For MF patients, the median DOR was 13 months with mogamulizumab and 9 months with vorinostat; for SS patients, the median DOR was 17 months and 7 months, respectively.

The most common treatment-emergent adverse events (AEs), which occurred in at least 20% of patients in either arm (mogamulizumab and vorinostat, respectively), included the following:

• Infusion-related reactions (33.2% vs. 0.5%).
• Drug eruptions (23.9% vs. 0.5%).
• Diarrhea (23.4% vs. 61.8%).
• Nausea (15.2% vs. 42.5%).
• Thrombocytopenia (11.4% vs. 30.6%).
• Dysgeusia (3.3% vs. 28.0%).
• Increased blood creatinine (3.3% vs. 28.0%).
• Decreased appetite (7.6% vs. 24.7%).

There were no grade 4 AEs in the mogamulizumab arm. Grade 3 AEs in mogamulizumab recipients included drug eruptions (n = 8), infusion-related reactions (n = 3), fatigue (n = 3), decreased appetite (n = 2), nausea (n = 1), pyrexia (n = 1), and diarrhea (n = 1).

The drug is marketed by Kyowa Kirin.

The Food and Drug Administration has approved mogamulizumab-kpkc (Poteligeo) for the treatment of adults with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy.

Mogamulizumab is a humanized monoclonal antibody directed against CC chemokine receptor 4 (CCR4). It is the first biologic agent targeting CCR4 to be approved for patients in the United States.

Mogamulizumab is expected to be commercially available in the fourth quarter of 2018.

The FDA previously granted mogamulizumab breakthrough therapy and orphan drug designations, as well as priority review.

The approval is supported by the phase 3 MAVORIC trial. Results from this trial were presented at the 10th Annual T-cell Lymphoma Forum in February 2018.

MAVORIC enrolled 372 adults with histologically confirmed MF or SS who had failed at least one systemic therapy. They were randomized to receive mogamulizumab at 1.0 mg/kg (weekly for the first 4-week cycle and then every 2 weeks) or vorinostat at 400 mg daily. Patients were treated until disease progression or unacceptable toxicity. Those receiving vorinostat could cross over to mogamulizumab if they progressed or experienced intolerable toxicity. Baseline characteristics were similar between the treatment arms. The study’s primary endpoint was progression-free survival. The median progression-free survival was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio, 0.53; P less than .0001).

The global overall response rate was 28% (52/189) in the mogamulizumab arm and 5% (9/186) in the vorinostat arm (P less than .0001). For patients with MF, the ORR was 21% with mogamulizumab and 7% with vorinostat; for patients with SS, the ORR was 37% and 2%, respectively. After crossover, the ORR in the mogamulizumab arm was 30% (41/136).

The median duration of response (DOR) was 14 months in the mogamulizumab arm and 9 months in the vorinostat arm. For MF patients, the median DOR was 13 months with mogamulizumab and 9 months with vorinostat; for SS patients, the median DOR was 17 months and 7 months, respectively.

The most common treatment-emergent adverse events (AEs), which occurred in at least 20% of patients in either arm (mogamulizumab and vorinostat, respectively), included the following:

• Infusion-related reactions (33.2% vs. 0.5%).
• Drug eruptions (23.9% vs. 0.5%).
• Diarrhea (23.4% vs. 61.8%).
• Nausea (15.2% vs. 42.5%).
• Thrombocytopenia (11.4% vs. 30.6%).
• Dysgeusia (3.3% vs. 28.0%).
• Increased blood creatinine (3.3% vs. 28.0%).
• Decreased appetite (7.6% vs. 24.7%).

There were no grade 4 AEs in the mogamulizumab arm. Grade 3 AEs in mogamulizumab recipients included drug eruptions (n = 8), infusion-related reactions (n = 3), fatigue (n = 3), decreased appetite (n = 2), nausea (n = 1), pyrexia (n = 1), and diarrhea (n = 1).

The drug is marketed by Kyowa Kirin.

The Food and Drug Administration has approved mogamulizumab-kpkc (Poteligeo) for the treatment of adults with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy.

Mogamulizumab is a humanized monoclonal antibody directed against CC chemokine receptor 4 (CCR4). It is the first biologic agent targeting CCR4 to be approved for patients in the United States.

Mogamulizumab is expected to be commercially available in the fourth quarter of 2018.

The FDA previously granted mogamulizumab breakthrough therapy and orphan drug designations, as well as priority review.

The approval is supported by the phase 3 MAVORIC trial. Results from this trial were presented at the 10th Annual T-cell Lymphoma Forum in February 2018.

MAVORIC enrolled 372 adults with histologically confirmed MF or SS who had failed at least one systemic therapy. They were randomized to receive mogamulizumab at 1.0 mg/kg (weekly for the first 4-week cycle and then every 2 weeks) or vorinostat at 400 mg daily. Patients were treated until disease progression or unacceptable toxicity. Those receiving vorinostat could cross over to mogamulizumab if they progressed or experienced intolerable toxicity. Baseline characteristics were similar between the treatment arms. The study’s primary endpoint was progression-free survival. The median progression-free survival was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio, 0.53; P less than .0001).

The global overall response rate was 28% (52/189) in the mogamulizumab arm and 5% (9/186) in the vorinostat arm (P less than .0001). For patients with MF, the ORR was 21% with mogamulizumab and 7% with vorinostat; for patients with SS, the ORR was 37% and 2%, respectively. After crossover, the ORR in the mogamulizumab arm was 30% (41/136).

The median duration of response (DOR) was 14 months in the mogamulizumab arm and 9 months in the vorinostat arm. For MF patients, the median DOR was 13 months with mogamulizumab and 9 months with vorinostat; for SS patients, the median DOR was 17 months and 7 months, respectively.

The most common treatment-emergent adverse events (AEs), which occurred in at least 20% of patients in either arm (mogamulizumab and vorinostat, respectively), included the following:

• Infusion-related reactions (33.2% vs. 0.5%).
• Drug eruptions (23.9% vs. 0.5%).
• Diarrhea (23.4% vs. 61.8%).
• Nausea (15.2% vs. 42.5%).
• Thrombocytopenia (11.4% vs. 30.6%).
• Dysgeusia (3.3% vs. 28.0%).
• Increased blood creatinine (3.3% vs. 28.0%).
• Decreased appetite (7.6% vs. 24.7%).

There were no grade 4 AEs in the mogamulizumab arm. Grade 3 AEs in mogamulizumab recipients included drug eruptions (n = 8), infusion-related reactions (n = 3), fatigue (n = 3), decreased appetite (n = 2), nausea (n = 1), pyrexia (n = 1), and diarrhea (n = 1).

The drug is marketed by Kyowa Kirin.