The combination of neratinib and capecitabine showed positive efficacy outcomes, but also a high degree of toxicity, in patients with progressive HER2-positive breast cancer and brain metastases, according to results from a phase 2 study.

“Neratinib [is] an irreversible pan-HER tyrosine kinase inhibitor that inhibits signal transduction,” wrote Rachel A Freedman, MD, MPH, of the Dana-Farber Cancer Institute in Boston, and her colleagues. Their report is in the Journal of Clinical Oncology. The researchers grouped patients into two cohorts, those without previous lapatinib (n = 37) and those with previous lapatinib exposure (n = 12), which were termed cohort 3A and 3B, respectively. All study participants were given neratinib 240 mg once daily in combination with capecitabine 750 mg/m² twice daily for a total of 14 days, followed by 7 days without capecitabine.

The primary outcome measured was the composite central nervous system (CNS) objective response rate (ORR) of each individual cohort, which was defined as a decrease of at least 50% in the total target CNS lesion volumes, in the absence of other markers of further progression.

After analysis, Dr. Freedman and her colleagues found that the CNS ORR was 49% (95% confidence interval, 32%-66%) and 33% (95% CI, 10%-65%) in cohorts 3A and 3B, respectively. In addition, the team reported that the median progression-free survival was 5.5 and 3.1 months in the same respective cohorts.

With respect to safety, the most frequently seen adverse event was diarrhea, with 29% of study participants having grade 3 toxicity. The researchers reported that no grade 4 adverse events were seen.

“It is possible that selection bias affected toxicity events, because no patients in cohort 3B stopped treatment [due to] toxicity,” they said.

A key limitation of the study was the lack of a comparison group, which could be added in future trials.

“Future studies could examine local therapy versus systemic therapy in CNS disease and additionally explore the role of other neratinib-based combination regimens,” they concluded.

The study was supported by grant funding from Puma Biotechnology, the Translational Breast Cancer Research Consortium’s foundation partners, the American Cancer Society, Susan G. Komen for the Cure, the Breast Cancer Research Foundation, and the Dana-Farber/Harvard Cancer Center. The authors reported financial affiliations with Puma Biotechnology, Genentech, Eli Lilly, Novartis, Pfizer, and others.

SOURCE: Freedman RA et al. J Clin Oncol. 2019 Mar 12. doi: 10.1200/JCO.18.01511.

The combination of neratinib and capecitabine showed positive efficacy outcomes, but also a high degree of toxicity, in patients with progressive HER2-positive breast cancer and brain metastases, according to results from a phase 2 study.

“Neratinib [is] an irreversible pan-HER tyrosine kinase inhibitor that inhibits signal transduction,” wrote Rachel A Freedman, MD, MPH, of the Dana-Farber Cancer Institute in Boston, and her colleagues. Their report is in the Journal of Clinical Oncology. The researchers grouped patients into two cohorts, those without previous lapatinib (n = 37) and those with previous lapatinib exposure (n = 12), which were termed cohort 3A and 3B, respectively. All study participants were given neratinib 240 mg once daily in combination with capecitabine 750 mg/m² twice daily for a total of 14 days, followed by 7 days without capecitabine.

The primary outcome measured was the composite central nervous system (CNS) objective response rate (ORR) of each individual cohort, which was defined as a decrease of at least 50% in the total target CNS lesion volumes, in the absence of other markers of further progression.

After analysis, Dr. Freedman and her colleagues found that the CNS ORR was 49% (95% confidence interval, 32%-66%) and 33% (95% CI, 10%-65%) in cohorts 3A and 3B, respectively. In addition, the team reported that the median progression-free survival was 5.5 and 3.1 months in the same respective cohorts.

With respect to safety, the most frequently seen adverse event was diarrhea, with 29% of study participants having grade 3 toxicity. The researchers reported that no grade 4 adverse events were seen.

“It is possible that selection bias affected toxicity events, because no patients in cohort 3B stopped treatment [due to] toxicity,” they said.

A key limitation of the study was the lack of a comparison group, which could be added in future trials.

“Future studies could examine local therapy versus systemic therapy in CNS disease and additionally explore the role of other neratinib-based combination regimens,” they concluded.

The study was supported by grant funding from Puma Biotechnology, the Translational Breast Cancer Research Consortium’s foundation partners, the American Cancer Society, Susan G. Komen for the Cure, the Breast Cancer Research Foundation, and the Dana-Farber/Harvard Cancer Center. The authors reported financial affiliations with Puma Biotechnology, Genentech, Eli Lilly, Novartis, Pfizer, and others.

SOURCE: Freedman RA et al. J Clin Oncol. 2019 Mar 12. doi: 10.1200/JCO.18.01511.

The combination of neratinib and capecitabine showed positive efficacy outcomes, but also a high degree of toxicity, in patients with progressive HER2-positive breast cancer and brain metastases, according to results from a phase 2 study.

“Neratinib [is] an irreversible pan-HER tyrosine kinase inhibitor that inhibits signal transduction,” wrote Rachel A Freedman, MD, MPH, of the Dana-Farber Cancer Institute in Boston, and her colleagues. Their report is in the Journal of Clinical Oncology. The researchers grouped patients into two cohorts, those without previous lapatinib (n = 37) and those with previous lapatinib exposure (n = 12), which were termed cohort 3A and 3B, respectively. All study participants were given neratinib 240 mg once daily in combination with capecitabine 750 mg/m² twice daily for a total of 14 days, followed by 7 days without capecitabine.

The primary outcome measured was the composite central nervous system (CNS) objective response rate (ORR) of each individual cohort, which was defined as a decrease of at least 50% in the total target CNS lesion volumes, in the absence of other markers of further progression.

After analysis, Dr. Freedman and her colleagues found that the CNS ORR was 49% (95% confidence interval, 32%-66%) and 33% (95% CI, 10%-65%) in cohorts 3A and 3B, respectively. In addition, the team reported that the median progression-free survival was 5.5 and 3.1 months in the same respective cohorts.

With respect to safety, the most frequently seen adverse event was diarrhea, with 29% of study participants having grade 3 toxicity. The researchers reported that no grade 4 adverse events were seen.

“It is possible that selection bias affected toxicity events, because no patients in cohort 3B stopped treatment [due to] toxicity,” they said.

A key limitation of the study was the lack of a comparison group, which could be added in future trials.

“Future studies could examine local therapy versus systemic therapy in CNS disease and additionally explore the role of other neratinib-based combination regimens,” they concluded.

The study was supported by grant funding from Puma Biotechnology, the Translational Breast Cancer Research Consortium’s foundation partners, the American Cancer Society, Susan G. Komen for the Cure, the Breast Cancer Research Foundation, and the Dana-Farber/Harvard Cancer Center. The authors reported financial affiliations with Puma Biotechnology, Genentech, Eli Lilly, Novartis, Pfizer, and others.

SOURCE: Freedman RA et al. J Clin Oncol. 2019 Mar 12. doi: 10.1200/JCO.18.01511.

The Journal of Hospital Medicine, the official peer-reviewed journal of the Society of Hospital Medicine, has launched its second new series this year, entitled Clinical Guideline Highlights for the Hospitalist. Alongside the new Leadership and Professional Development series, this addition plays a large role in the vision for the future of the journal, spearheaded by new editor in chief, Samir Shah, MD, MSCE, MHM.

“As a new deputy editor for reviews and perspectives, I’m thrilled to help execute Dr. Shah’s vision for a series of articles that aims to facilitate the rapid translation of the latest evidence-based guidelines into hospitalist practice,” said Erin Shaughnessy, MD. “My coeditor, Dr. Read Pierce, and I envision these reviews as tools to enable busy clinicians to quickly understand the latest research and apply it to practice.”

The March issue of JHM features an introduction to the series as well as the first two articles, “The Use of Intravenous Fluids in the Hospitalized Adult” and “Maintenance Intravenous Fluids in Infants and Children.” The introduction provides details on the formatting of the series and discusses a second format that will be introduced in 2019 called Progress Notes, which will be shorter than JHM’s traditional review format. Progress Notes will accept two types or articles, clinical and methodological, and will focus on diagnostics, therapeutics, or risk assessment and prevention of a clinical problem relevant to hospitalists.

“National guidelines and society position statements are important in informing care standards but can be time consuming to read, and only a small portion may be pertinent to the practice of hospital medicine,” Dr. Shah said. “Our Clinical Guideline Highlights for the Hospitalist series, under the leadership of Dr. Shaughnessy and Dr. Pierce, will distill the key elements of national guidelines with a focus on recommendations that are most relevant to the practicing hospitalist. Authors include a brief critique to ensure hospitalists understand the strength of evidence behind the guideline when making decisions.”

Along with this series comes another new feature for the journal, Hospital Medicine: The Year in Review. This annual feature “concisely compiles and critiques the top articles in both adult and pediatric hospital medicine in the past year” and “will serve as a written corollary to the popular ‘Updates in Hospital Medicine’ presentation at the SHM Annual Conference.”

With so many updates, “JHM’s overarching commitment remains unchanged: support clinicians, leaders, and scholars in our field in their pursuit of delivering evidence-based, high-value clinical care.” The journal will continue to accept traditional, long-form review on topics relevant to hospitalists.

Visit www.journalofhospitalmedicine.com for the Clinical Guideline Highlights for the Hospitalist series and additional research.






 

The Journal of Hospital Medicine, the official peer-reviewed journal of the Society of Hospital Medicine, has launched its second new series this year, entitled Clinical Guideline Highlights for the Hospitalist. Alongside the new Leadership and Professional Development series, this addition plays a large role in the vision for the future of the journal, spearheaded by new editor in chief, Samir Shah, MD, MSCE, MHM.

“As a new deputy editor for reviews and perspectives, I’m thrilled to help execute Dr. Shah’s vision for a series of articles that aims to facilitate the rapid translation of the latest evidence-based guidelines into hospitalist practice,” said Erin Shaughnessy, MD. “My coeditor, Dr. Read Pierce, and I envision these reviews as tools to enable busy clinicians to quickly understand the latest research and apply it to practice.”

The March issue of JHM features an introduction to the series as well as the first two articles, “The Use of Intravenous Fluids in the Hospitalized Adult” and “Maintenance Intravenous Fluids in Infants and Children.” The introduction provides details on the formatting of the series and discusses a second format that will be introduced in 2019 called Progress Notes, which will be shorter than JHM’s traditional review format. Progress Notes will accept two types or articles, clinical and methodological, and will focus on diagnostics, therapeutics, or risk assessment and prevention of a clinical problem relevant to hospitalists.

“National guidelines and society position statements are important in informing care standards but can be time consuming to read, and only a small portion may be pertinent to the practice of hospital medicine,” Dr. Shah said. “Our Clinical Guideline Highlights for the Hospitalist series, under the leadership of Dr. Shaughnessy and Dr. Pierce, will distill the key elements of national guidelines with a focus on recommendations that are most relevant to the practicing hospitalist. Authors include a brief critique to ensure hospitalists understand the strength of evidence behind the guideline when making decisions.”

Along with this series comes another new feature for the journal, Hospital Medicine: The Year in Review. This annual feature “concisely compiles and critiques the top articles in both adult and pediatric hospital medicine in the past year” and “will serve as a written corollary to the popular ‘Updates in Hospital Medicine’ presentation at the SHM Annual Conference.”

With so many updates, “JHM’s overarching commitment remains unchanged: support clinicians, leaders, and scholars in our field in their pursuit of delivering evidence-based, high-value clinical care.” The journal will continue to accept traditional, long-form review on topics relevant to hospitalists.

Visit www.journalofhospitalmedicine.com for the Clinical Guideline Highlights for the Hospitalist series and additional research.






 

The Journal of Hospital Medicine, the official peer-reviewed journal of the Society of Hospital Medicine, has launched its second new series this year, entitled Clinical Guideline Highlights for the Hospitalist. Alongside the new Leadership and Professional Development series, this addition plays a large role in the vision for the future of the journal, spearheaded by new editor in chief, Samir Shah, MD, MSCE, MHM.

“As a new deputy editor for reviews and perspectives, I’m thrilled to help execute Dr. Shah’s vision for a series of articles that aims to facilitate the rapid translation of the latest evidence-based guidelines into hospitalist practice,” said Erin Shaughnessy, MD. “My coeditor, Dr. Read Pierce, and I envision these reviews as tools to enable busy clinicians to quickly understand the latest research and apply it to practice.”

The March issue of JHM features an introduction to the series as well as the first two articles, “The Use of Intravenous Fluids in the Hospitalized Adult” and “Maintenance Intravenous Fluids in Infants and Children.” The introduction provides details on the formatting of the series and discusses a second format that will be introduced in 2019 called Progress Notes, which will be shorter than JHM’s traditional review format. Progress Notes will accept two types or articles, clinical and methodological, and will focus on diagnostics, therapeutics, or risk assessment and prevention of a clinical problem relevant to hospitalists.

“National guidelines and society position statements are important in informing care standards but can be time consuming to read, and only a small portion may be pertinent to the practice of hospital medicine,” Dr. Shah said. “Our Clinical Guideline Highlights for the Hospitalist series, under the leadership of Dr. Shaughnessy and Dr. Pierce, will distill the key elements of national guidelines with a focus on recommendations that are most relevant to the practicing hospitalist. Authors include a brief critique to ensure hospitalists understand the strength of evidence behind the guideline when making decisions.”

Along with this series comes another new feature for the journal, Hospital Medicine: The Year in Review. This annual feature “concisely compiles and critiques the top articles in both adult and pediatric hospital medicine in the past year” and “will serve as a written corollary to the popular ‘Updates in Hospital Medicine’ presentation at the SHM Annual Conference.”

With so many updates, “JHM’s overarching commitment remains unchanged: support clinicians, leaders, and scholars in our field in their pursuit of delivering evidence-based, high-value clinical care.” The journal will continue to accept traditional, long-form review on topics relevant to hospitalists.

Visit www.journalofhospitalmedicine.com for the Clinical Guideline Highlights for the Hospitalist series and additional research.






 

WASHINGTON – During a session at the annual meeting of the American Academy of Dermatology, Adam Friedman, MD, presented on off-label use of immunomodulators for inflammatory skin diseases, the highlights of which he shared with fellow George Washington University dermatologist, A. Yasmine Kirkorian, MD, in an interview following the session.

Vidyard Video

Dr. Friedman, professor and interim chair of dermatology at George Washington University, Washington, provides his top list of immunomodulators, used off-label, ranging from dapsone and hydroxychloroquine, to pentoxifylline and low-dose naltrexone.

For example, as reflected in PubMed searches, low-dose naltrexone, which has to be compounded, is being used for such diseases as Hailey-Hailey and lichen planopilaris, said Dr. Friedman, who is using it for his mast cell activation syndrome patients. During the interview, he also describes his treatment approach for urticaria.

In his final remarks, Dr. Friedman encourages colleagues to “get creative,” publish, and talk about their experiences with off-label treatments in dermatology, citing the example of an article that mentioned using pioglitazone for lichen planopilaris. This article stimulated interest in using the type 2 diabetes agent pioglitazone to treat this skin disease, he notes.

Dr. Friedman and Dr. Kirkorian, a pediatric dermatologist at George Washington University and interim chief of pediatric dermatology at Children’s National in Washington had no relevant disclosures.

[email protected]

WASHINGTON – During a session at the annual meeting of the American Academy of Dermatology, Adam Friedman, MD, presented on off-label use of immunomodulators for inflammatory skin diseases, the highlights of which he shared with fellow George Washington University dermatologist, A. Yasmine Kirkorian, MD, in an interview following the session.

Vidyard Video

Dr. Friedman, professor and interim chair of dermatology at George Washington University, Washington, provides his top list of immunomodulators, used off-label, ranging from dapsone and hydroxychloroquine, to pentoxifylline and low-dose naltrexone.

For example, as reflected in PubMed searches, low-dose naltrexone, which has to be compounded, is being used for such diseases as Hailey-Hailey and lichen planopilaris, said Dr. Friedman, who is using it for his mast cell activation syndrome patients. During the interview, he also describes his treatment approach for urticaria.

In his final remarks, Dr. Friedman encourages colleagues to “get creative,” publish, and talk about their experiences with off-label treatments in dermatology, citing the example of an article that mentioned using pioglitazone for lichen planopilaris. This article stimulated interest in using the type 2 diabetes agent pioglitazone to treat this skin disease, he notes.

Dr. Friedman and Dr. Kirkorian, a pediatric dermatologist at George Washington University and interim chief of pediatric dermatology at Children’s National in Washington had no relevant disclosures.

[email protected]

WASHINGTON – During a session at the annual meeting of the American Academy of Dermatology, Adam Friedman, MD, presented on off-label use of immunomodulators for inflammatory skin diseases, the highlights of which he shared with fellow George Washington University dermatologist, A. Yasmine Kirkorian, MD, in an interview following the session.

Vidyard Video

Dr. Friedman, professor and interim chair of dermatology at George Washington University, Washington, provides his top list of immunomodulators, used off-label, ranging from dapsone and hydroxychloroquine, to pentoxifylline and low-dose naltrexone.

For example, as reflected in PubMed searches, low-dose naltrexone, which has to be compounded, is being used for such diseases as Hailey-Hailey and lichen planopilaris, said Dr. Friedman, who is using it for his mast cell activation syndrome patients. During the interview, he also describes his treatment approach for urticaria.

In his final remarks, Dr. Friedman encourages colleagues to “get creative,” publish, and talk about their experiences with off-label treatments in dermatology, citing the example of an article that mentioned using pioglitazone for lichen planopilaris. This article stimulated interest in using the type 2 diabetes agent pioglitazone to treat this skin disease, he notes.

Dr. Friedman and Dr. Kirkorian, a pediatric dermatologist at George Washington University and interim chief of pediatric dermatology at Children’s National in Washington had no relevant disclosures.

[email protected]

A telomere-length analysis tool appears to identify reliably which chronic lymphocytic leukemia (CLL) patients will benefit from frontline chemotherapy, according to an analysis of 260 patients across two separate trials.

VashiDonsk/Wikimedia Commons/Creative Commons BY-SA 3.0

The analysis compared the use of high-throughput, single telomere–length analysis (HTSTELA) with other commonly used markers including beta-2 microglobulin, fluorescence-in-situ hybridization (FISH) cytogenetics, CD38 expression, ZAP70 expression, and IGHV mutation status. The researchers looked specifically at whether telomere length could predict response to frontline treatment with fludarabine, cyclophosphamide, rituximab (FCR)–based regimens.

“[T]elomere length is a powerful predictor of both [progression-free survival] and [overall survival] in patients treated with FCR-based therapies. In contrast, CD38 expression and beta-2 microglobulin expression were not predictive, and IGHV mutation status was only predictive of PFS (progression-free survival),” Kevin Norris, PhD, of Cardiff (Wales) University and his colleagues wrote in Leukemia.

Previous studies have shown that telomere-length analysis offers independent prognostic information in all stages of CLL. In the present study, the researchers used HTSTELA to analyze patient samples taken from two concurrent, phase 2 clinical trials of frontline FCR-based treatment – ARCTIC and ADMIRE.

The researchers divided the cohort based on a threshold of telomere dysfunction – the point at which the chromosome end-capping function is lost and there is genomic instability. Shorter telomeres are inside the fusogenic range (TL-IFR) and longer telomeres are outside fusogenic range (TL-OFR).

Patients with TL-IFR had significantly shorter PFS on FCR-based treatment (P less than .0001). They also had reduced overall survival (OS; P = .0002). In the same cohort of patients, IGHV mutation status was predictive of PFS (P = .0016), but it was not predictive for OS (P = .38), while CD38 and beta-2 microglobulin were not predictive of PFS or OS.

The researchers also looked at the value of telomere length in predicting outcomes among IGHV-mutated and -unmutated patients.

Patients with IGHV-mutated disease and TL-IFR had worse PFS and OS than did patients with TL-OFR. TL-IFR patients in this cohort were more likely to progress (hazard ratio, 4.35; P less than .0001) and more likely to die from their disease (HR, 3.81; P = .006).

“Although the number of IGHV-mutated patients with TL-IFR was relatively small (n = 16), our data suggests that telomere length can identify a subset of “bad risk” IGHV-mutated patients who do not respond well to FCR,” the researchers wrote.

Among IGHV unmutated patients, those with short telomeres had worse PFS (HR, 1.48; P = .08) and OS (HR, 2.18; P = .025) than did those with longer telomeres.

In multivariate modeling of all the potential markers, telomere length was the statistically significant dominant covariable for both PFS and OS.

The study was funded by a Bloodwise grant and the Wales Cancer Research Center. Dr. Norris and three coauthors reported that they are coinventors of patents relevant to the study and hold shares in a company set to provide telomere length testing.

[email protected]

SOURCE: Norris K et al. Leukemia. 2019 Jan 30. doi: 10.1038/s41375-019-0389-9.
 

A telomere-length analysis tool appears to identify reliably which chronic lymphocytic leukemia (CLL) patients will benefit from frontline chemotherapy, according to an analysis of 260 patients across two separate trials.

VashiDonsk/Wikimedia Commons/Creative Commons BY-SA 3.0

The analysis compared the use of high-throughput, single telomere–length analysis (HTSTELA) with other commonly used markers including beta-2 microglobulin, fluorescence-in-situ hybridization (FISH) cytogenetics, CD38 expression, ZAP70 expression, and IGHV mutation status. The researchers looked specifically at whether telomere length could predict response to frontline treatment with fludarabine, cyclophosphamide, rituximab (FCR)–based regimens.

“[T]elomere length is a powerful predictor of both [progression-free survival] and [overall survival] in patients treated with FCR-based therapies. In contrast, CD38 expression and beta-2 microglobulin expression were not predictive, and IGHV mutation status was only predictive of PFS (progression-free survival),” Kevin Norris, PhD, of Cardiff (Wales) University and his colleagues wrote in Leukemia.

Previous studies have shown that telomere-length analysis offers independent prognostic information in all stages of CLL. In the present study, the researchers used HTSTELA to analyze patient samples taken from two concurrent, phase 2 clinical trials of frontline FCR-based treatment – ARCTIC and ADMIRE.

The researchers divided the cohort based on a threshold of telomere dysfunction – the point at which the chromosome end-capping function is lost and there is genomic instability. Shorter telomeres are inside the fusogenic range (TL-IFR) and longer telomeres are outside fusogenic range (TL-OFR).

Patients with TL-IFR had significantly shorter PFS on FCR-based treatment (P less than .0001). They also had reduced overall survival (OS; P = .0002). In the same cohort of patients, IGHV mutation status was predictive of PFS (P = .0016), but it was not predictive for OS (P = .38), while CD38 and beta-2 microglobulin were not predictive of PFS or OS.

The researchers also looked at the value of telomere length in predicting outcomes among IGHV-mutated and -unmutated patients.

Patients with IGHV-mutated disease and TL-IFR had worse PFS and OS than did patients with TL-OFR. TL-IFR patients in this cohort were more likely to progress (hazard ratio, 4.35; P less than .0001) and more likely to die from their disease (HR, 3.81; P = .006).

“Although the number of IGHV-mutated patients with TL-IFR was relatively small (n = 16), our data suggests that telomere length can identify a subset of “bad risk” IGHV-mutated patients who do not respond well to FCR,” the researchers wrote.

Among IGHV unmutated patients, those with short telomeres had worse PFS (HR, 1.48; P = .08) and OS (HR, 2.18; P = .025) than did those with longer telomeres.

In multivariate modeling of all the potential markers, telomere length was the statistically significant dominant covariable for both PFS and OS.

The study was funded by a Bloodwise grant and the Wales Cancer Research Center. Dr. Norris and three coauthors reported that they are coinventors of patents relevant to the study and hold shares in a company set to provide telomere length testing.

[email protected]

SOURCE: Norris K et al. Leukemia. 2019 Jan 30. doi: 10.1038/s41375-019-0389-9.
 

A telomere-length analysis tool appears to identify reliably which chronic lymphocytic leukemia (CLL) patients will benefit from frontline chemotherapy, according to an analysis of 260 patients across two separate trials.

VashiDonsk/Wikimedia Commons/Creative Commons BY-SA 3.0

The analysis compared the use of high-throughput, single telomere–length analysis (HTSTELA) with other commonly used markers including beta-2 microglobulin, fluorescence-in-situ hybridization (FISH) cytogenetics, CD38 expression, ZAP70 expression, and IGHV mutation status. The researchers looked specifically at whether telomere length could predict response to frontline treatment with fludarabine, cyclophosphamide, rituximab (FCR)–based regimens.

“[T]elomere length is a powerful predictor of both [progression-free survival] and [overall survival] in patients treated with FCR-based therapies. In contrast, CD38 expression and beta-2 microglobulin expression were not predictive, and IGHV mutation status was only predictive of PFS (progression-free survival),” Kevin Norris, PhD, of Cardiff (Wales) University and his colleagues wrote in Leukemia.

Previous studies have shown that telomere-length analysis offers independent prognostic information in all stages of CLL. In the present study, the researchers used HTSTELA to analyze patient samples taken from two concurrent, phase 2 clinical trials of frontline FCR-based treatment – ARCTIC and ADMIRE.

The researchers divided the cohort based on a threshold of telomere dysfunction – the point at which the chromosome end-capping function is lost and there is genomic instability. Shorter telomeres are inside the fusogenic range (TL-IFR) and longer telomeres are outside fusogenic range (TL-OFR).

Patients with TL-IFR had significantly shorter PFS on FCR-based treatment (P less than .0001). They also had reduced overall survival (OS; P = .0002). In the same cohort of patients, IGHV mutation status was predictive of PFS (P = .0016), but it was not predictive for OS (P = .38), while CD38 and beta-2 microglobulin were not predictive of PFS or OS.

The researchers also looked at the value of telomere length in predicting outcomes among IGHV-mutated and -unmutated patients.

Patients with IGHV-mutated disease and TL-IFR had worse PFS and OS than did patients with TL-OFR. TL-IFR patients in this cohort were more likely to progress (hazard ratio, 4.35; P less than .0001) and more likely to die from their disease (HR, 3.81; P = .006).

“Although the number of IGHV-mutated patients with TL-IFR was relatively small (n = 16), our data suggests that telomere length can identify a subset of “bad risk” IGHV-mutated patients who do not respond well to FCR,” the researchers wrote.

Among IGHV unmutated patients, those with short telomeres had worse PFS (HR, 1.48; P = .08) and OS (HR, 2.18; P = .025) than did those with longer telomeres.

In multivariate modeling of all the potential markers, telomere length was the statistically significant dominant covariable for both PFS and OS.

The study was funded by a Bloodwise grant and the Wales Cancer Research Center. Dr. Norris and three coauthors reported that they are coinventors of patents relevant to the study and hold shares in a company set to provide telomere length testing.

[email protected]

SOURCE: Norris K et al. Leukemia. 2019 Jan 30. doi: 10.1038/s41375-019-0389-9.
 

Every year the Society of Hospital Medicine’s Annual Conference Committee examines prior attendee surveys, reviews the content presented the preceding year, and asks itself what new areas of learning are needed by hospitalists, said Dustin Smith, MD, SFHM, hospitalist and associate professor of medicine at Emory University School of Medicine in Atlanta, and HM19 course director.

“The conference’s schedule-at-a-glance of content can be overwhelming, so we have tried to use distinct educational tracks to provide focus and clarity for conference attendees,” he said. “Every year there are a few areas where questions often come up about complex clinical situations where established medical guidelines aren’t much help.”

As a result, for HM19 an educational mini-track called “Between the Guidelines” was developed to gather up several of these areas of clinical complexity where what’s available in established clinical practice guidelines doesn’t offer clear answers, Dr. Smith said. These include controversies around antithrombotic therapy in patients with major bleeds, and a debate on controversial aspects of guidelines to direct inpatient care.

Another planned session, “The History of Hospitals via Arts and Stories,” fits nicely into this mini-track, Dr. Smith noted.

“It’s a history lesson you can’t glean from medical guidelines, which maybe points us toward what to incorporate and what not to repeat from across the history of hospitals,” he said. “That could help us better appreciate the work hospitalists are doing today and into the future.”

Jordan Messler, MD, a hospitalist with the Morton Plant Hospitalist group in Clearwater, Fla., will lead the session and thinks that modern physicians can learn a lot from both the history of medicine and the evolution of hospitals, starting with the ancient Greek physician, Galen (129-200 AD), who directed the celebrated Asclepeion or hospital in Pergamon (present-day Bergama, Turkey). Dr. Messler said this ancient hospital’s treatment of disease also addressed the senses, the emotions, and the spirit – an early prototype for whole-person care – with an emphasis on self-therapy through rest, relaxation, exercise, and the promotion of healthy lifestyles.¹

A different perspective on hospitals

“People used to travel to Pergamon for healing at the Asclepeion, next to the amphitheater, where plays and music were presented, and to be outdoors in the natural elements. Now we’re seeing hospitals being built with healing gardens, and a new emphasis on how artwork and music and environmental design can assist in healing,” Dr. Messler said.

Dr. Messler explained that his “History of Hospitals” presentation will also survey the advent of more recent hospitals in France in the 18th century, pioneering work done at Johns Hopkins Hospital in Baltimore and Bellevue Hospital in New York, and the influence on the modern hospital of nursing pioneer Florence Nightingale (1820-1910). Dr. Messler said she helped improve hospitals in her day, which still influences their modern design, and fundamentally changed the role of nursing in hospitals, introducing professional training standards for nurses.

He also noted that the portico of the beautiful 15th century Hospital of the Innocents in Florence, Italy, the first organic creation of Filippo Brunelleschi (1377-1446), marks the birth of Renaissance architecture in Florence. The Hospital of Santa Maria Nuova, founded in 1288, is the oldest hospital still active in Florence.

Part of the goal for this new annual conference session is to take a break from more clinically focused presentations, and to think about the hospital from a different perspective, Dr. Messler said. His session will emphasize the power of stories and storytelling to inform and inspire medical practice.

“This is not something that can be applied clinically the next day, but lessons from the past can inform the design of hospitals and how we manage patients,” he said. “We need to ask ourselves, ‘How can we analyze hospital history to inform what we do today?’ ”
 

References

“Asclepeion.” Wikipedia. Accessed Jan. 28, 2019: https://en.wikipedia.org/wiki/Asclepeion.

Every year the Society of Hospital Medicine’s Annual Conference Committee examines prior attendee surveys, reviews the content presented the preceding year, and asks itself what new areas of learning are needed by hospitalists, said Dustin Smith, MD, SFHM, hospitalist and associate professor of medicine at Emory University School of Medicine in Atlanta, and HM19 course director.

“The conference’s schedule-at-a-glance of content can be overwhelming, so we have tried to use distinct educational tracks to provide focus and clarity for conference attendees,” he said. “Every year there are a few areas where questions often come up about complex clinical situations where established medical guidelines aren’t much help.”

As a result, for HM19 an educational mini-track called “Between the Guidelines” was developed to gather up several of these areas of clinical complexity where what’s available in established clinical practice guidelines doesn’t offer clear answers, Dr. Smith said. These include controversies around antithrombotic therapy in patients with major bleeds, and a debate on controversial aspects of guidelines to direct inpatient care.

Another planned session, “The History of Hospitals via Arts and Stories,” fits nicely into this mini-track, Dr. Smith noted.

“It’s a history lesson you can’t glean from medical guidelines, which maybe points us toward what to incorporate and what not to repeat from across the history of hospitals,” he said. “That could help us better appreciate the work hospitalists are doing today and into the future.”

Jordan Messler, MD, a hospitalist with the Morton Plant Hospitalist group in Clearwater, Fla., will lead the session and thinks that modern physicians can learn a lot from both the history of medicine and the evolution of hospitals, starting with the ancient Greek physician, Galen (129-200 AD), who directed the celebrated Asclepeion or hospital in Pergamon (present-day Bergama, Turkey). Dr. Messler said this ancient hospital’s treatment of disease also addressed the senses, the emotions, and the spirit – an early prototype for whole-person care – with an emphasis on self-therapy through rest, relaxation, exercise, and the promotion of healthy lifestyles.¹

A different perspective on hospitals

“People used to travel to Pergamon for healing at the Asclepeion, next to the amphitheater, where plays and music were presented, and to be outdoors in the natural elements. Now we’re seeing hospitals being built with healing gardens, and a new emphasis on how artwork and music and environmental design can assist in healing,” Dr. Messler said.

Dr. Messler explained that his “History of Hospitals” presentation will also survey the advent of more recent hospitals in France in the 18th century, pioneering work done at Johns Hopkins Hospital in Baltimore and Bellevue Hospital in New York, and the influence on the modern hospital of nursing pioneer Florence Nightingale (1820-1910). Dr. Messler said she helped improve hospitals in her day, which still influences their modern design, and fundamentally changed the role of nursing in hospitals, introducing professional training standards for nurses.

He also noted that the portico of the beautiful 15th century Hospital of the Innocents in Florence, Italy, the first organic creation of Filippo Brunelleschi (1377-1446), marks the birth of Renaissance architecture in Florence. The Hospital of Santa Maria Nuova, founded in 1288, is the oldest hospital still active in Florence.

Part of the goal for this new annual conference session is to take a break from more clinically focused presentations, and to think about the hospital from a different perspective, Dr. Messler said. His session will emphasize the power of stories and storytelling to inform and inspire medical practice.

“This is not something that can be applied clinically the next day, but lessons from the past can inform the design of hospitals and how we manage patients,” he said. “We need to ask ourselves, ‘How can we analyze hospital history to inform what we do today?’ ”
 

References

“Asclepeion.” Wikipedia. Accessed Jan. 28, 2019: https://en.wikipedia.org/wiki/Asclepeion.

Every year the Society of Hospital Medicine’s Annual Conference Committee examines prior attendee surveys, reviews the content presented the preceding year, and asks itself what new areas of learning are needed by hospitalists, said Dustin Smith, MD, SFHM, hospitalist and associate professor of medicine at Emory University School of Medicine in Atlanta, and HM19 course director.

“The conference’s schedule-at-a-glance of content can be overwhelming, so we have tried to use distinct educational tracks to provide focus and clarity for conference attendees,” he said. “Every year there are a few areas where questions often come up about complex clinical situations where established medical guidelines aren’t much help.”

As a result, for HM19 an educational mini-track called “Between the Guidelines” was developed to gather up several of these areas of clinical complexity where what’s available in established clinical practice guidelines doesn’t offer clear answers, Dr. Smith said. These include controversies around antithrombotic therapy in patients with major bleeds, and a debate on controversial aspects of guidelines to direct inpatient care.

Another planned session, “The History of Hospitals via Arts and Stories,” fits nicely into this mini-track, Dr. Smith noted.

“It’s a history lesson you can’t glean from medical guidelines, which maybe points us toward what to incorporate and what not to repeat from across the history of hospitals,” he said. “That could help us better appreciate the work hospitalists are doing today and into the future.”

Jordan Messler, MD, a hospitalist with the Morton Plant Hospitalist group in Clearwater, Fla., will lead the session and thinks that modern physicians can learn a lot from both the history of medicine and the evolution of hospitals, starting with the ancient Greek physician, Galen (129-200 AD), who directed the celebrated Asclepeion or hospital in Pergamon (present-day Bergama, Turkey). Dr. Messler said this ancient hospital’s treatment of disease also addressed the senses, the emotions, and the spirit – an early prototype for whole-person care – with an emphasis on self-therapy through rest, relaxation, exercise, and the promotion of healthy lifestyles.¹

A different perspective on hospitals

“People used to travel to Pergamon for healing at the Asclepeion, next to the amphitheater, where plays and music were presented, and to be outdoors in the natural elements. Now we’re seeing hospitals being built with healing gardens, and a new emphasis on how artwork and music and environmental design can assist in healing,” Dr. Messler said.

Dr. Messler explained that his “History of Hospitals” presentation will also survey the advent of more recent hospitals in France in the 18th century, pioneering work done at Johns Hopkins Hospital in Baltimore and Bellevue Hospital in New York, and the influence on the modern hospital of nursing pioneer Florence Nightingale (1820-1910). Dr. Messler said she helped improve hospitals in her day, which still influences their modern design, and fundamentally changed the role of nursing in hospitals, introducing professional training standards for nurses.

He also noted that the portico of the beautiful 15th century Hospital of the Innocents in Florence, Italy, the first organic creation of Filippo Brunelleschi (1377-1446), marks the birth of Renaissance architecture in Florence. The Hospital of Santa Maria Nuova, founded in 1288, is the oldest hospital still active in Florence.

Part of the goal for this new annual conference session is to take a break from more clinically focused presentations, and to think about the hospital from a different perspective, Dr. Messler said. His session will emphasize the power of stories and storytelling to inform and inspire medical practice.

“This is not something that can be applied clinically the next day, but lessons from the past can inform the design of hospitals and how we manage patients,” he said. “We need to ask ourselves, ‘How can we analyze hospital history to inform what we do today?’ ”
 

References

“Asclepeion.” Wikipedia. Accessed Jan. 28, 2019: https://en.wikipedia.org/wiki/Asclepeion.

SEATTLE – The most important thing to know about the apparent HIV cure widely reported in the press recently is that the treatment was worse than the infection, according to John Mellors, MD, chief of the division of infectious diseases at the University of Pittsburgh.

M. Alexander Otto/MDedge News

Dr. Mellors moderated a presentation at the Conference on Retroviruses and Opportunistic Infections about what the cure involved.

An HIV-positive man with advanced Hodgkin’s lymphoma had an allogeneic bone marrow transplant in 2016 after failing first-line chemotherapy and multiple salvage regimens. His donor was homozygous for a gene mutation that prevents HIV from entering new cells. The transplant took; the man’s hematopoietic system was replaced by one with the anti-HIV mutation; and there’s been no trace of active virus in his system since. He’s been off of antiretrovirals for a year and a half. The cancer hasn’t returned.

He’s been dubbed the “London patient.” He joins the “Berlin patient” as the second person who appears to have been freed of infection following a stem cell transplant with the anti-HIV mutation. The Berlin patient recently identified himself as Timothy Ray Brown; he was in the audience at CROI and was applauded for coming forward and sharing his story.

Mr. Brown received a transplant for acute myeloid leukemia and has been off antiretrovirals now for about a decade with no evidence of viral rebound.

M. Alexander Otto/MDedge News

Although it didn’t get much attention at CROI, there was a poster of a similar approach seeming to work in a third patient, also with leukemia. It’s been tried – but failed – in two others: one patient died of their lymphoma and the transplant failed in the other, said lead investigator on the London patient case, Ravindra Gupta, MD, a professor in the division of infection & immunity at University College London.

Dr. Mellors pointed out that “the two people who have been cured had lethal malignancies that were unresponsive to conventional therapy and had the extreme measure of an allogeneic bone marrow transplant. Allogeneic bone marrow transplant is not a walk in the park. It has a mortality of 10%-25%, which is completely unacceptable” when “patients feel great on one pill a day” for HIV remission and pretty much have a normal life span.

The transplant reactivated both cytomegalovirus and Epstein Barr virus in the London patient, and he developed graft-versus-host colitis. He survived all three complications.

The take-home message is that “these cases are inspirational. The work ahead is to find out how to deliver the same results with less-extreme measures,” Dr. Mellors said.

The donors for both the London and Berlin patients were homozygous for a delta 32 deletion in the receptor most commonly used by HIV-1 to enter host cells, CCR5. Cells that carry the mutation don’t express the receptor, preventing infection. The mutation prevalence is about 1% among Europeans.

Of the two failed cases, the person who died of lymphoma had a strain of HIV-1 that used a different receptor – CXCR4 – so it’s doubtful the transplant would have worked even if he had survived his cancer.

The London patient wasn’t what’s called an “elite controller,” one of those rare people who suppress HIV without antiretrovirals. His viral loads bounced right back when we was taken off them prior to transplant.

He’s not interested in an active sex life at the moment, Dr. Gupta said, but he might be soon, so Dr. Gupta plans a discussion with him in the near future. Although the London patient could well be immune to HIV that uses the CCR5 receptor, he might not be immune to CXCR4 virus, and he might still be able to produce infectious CCR5 particles. Time will tell.

There was no industry funding for the work. Dr. Gupta is a consultant for ViiV Healthcare and a speaker for Gilead.

[email protected]

SOURCE: Gupta RK et al. CROI 2019, Abstract 29.

SEATTLE – The most important thing to know about the apparent HIV cure widely reported in the press recently is that the treatment was worse than the infection, according to John Mellors, MD, chief of the division of infectious diseases at the University of Pittsburgh.

M. Alexander Otto/MDedge News

Dr. Mellors moderated a presentation at the Conference on Retroviruses and Opportunistic Infections about what the cure involved.

An HIV-positive man with advanced Hodgkin’s lymphoma had an allogeneic bone marrow transplant in 2016 after failing first-line chemotherapy and multiple salvage regimens. His donor was homozygous for a gene mutation that prevents HIV from entering new cells. The transplant took; the man’s hematopoietic system was replaced by one with the anti-HIV mutation; and there’s been no trace of active virus in his system since. He’s been off of antiretrovirals for a year and a half. The cancer hasn’t returned.

He’s been dubbed the “London patient.” He joins the “Berlin patient” as the second person who appears to have been freed of infection following a stem cell transplant with the anti-HIV mutation. The Berlin patient recently identified himself as Timothy Ray Brown; he was in the audience at CROI and was applauded for coming forward and sharing his story.

Mr. Brown received a transplant for acute myeloid leukemia and has been off antiretrovirals now for about a decade with no evidence of viral rebound.

M. Alexander Otto/MDedge News

Although it didn’t get much attention at CROI, there was a poster of a similar approach seeming to work in a third patient, also with leukemia. It’s been tried – but failed – in two others: one patient died of their lymphoma and the transplant failed in the other, said lead investigator on the London patient case, Ravindra Gupta, MD, a professor in the division of infection & immunity at University College London.

Dr. Mellors pointed out that “the two people who have been cured had lethal malignancies that were unresponsive to conventional therapy and had the extreme measure of an allogeneic bone marrow transplant. Allogeneic bone marrow transplant is not a walk in the park. It has a mortality of 10%-25%, which is completely unacceptable” when “patients feel great on one pill a day” for HIV remission and pretty much have a normal life span.

The transplant reactivated both cytomegalovirus and Epstein Barr virus in the London patient, and he developed graft-versus-host colitis. He survived all three complications.

The take-home message is that “these cases are inspirational. The work ahead is to find out how to deliver the same results with less-extreme measures,” Dr. Mellors said.

The donors for both the London and Berlin patients were homozygous for a delta 32 deletion in the receptor most commonly used by HIV-1 to enter host cells, CCR5. Cells that carry the mutation don’t express the receptor, preventing infection. The mutation prevalence is about 1% among Europeans.

Of the two failed cases, the person who died of lymphoma had a strain of HIV-1 that used a different receptor – CXCR4 – so it’s doubtful the transplant would have worked even if he had survived his cancer.

The London patient wasn’t what’s called an “elite controller,” one of those rare people who suppress HIV without antiretrovirals. His viral loads bounced right back when we was taken off them prior to transplant.

He’s not interested in an active sex life at the moment, Dr. Gupta said, but he might be soon, so Dr. Gupta plans a discussion with him in the near future. Although the London patient could well be immune to HIV that uses the CCR5 receptor, he might not be immune to CXCR4 virus, and he might still be able to produce infectious CCR5 particles. Time will tell.

There was no industry funding for the work. Dr. Gupta is a consultant for ViiV Healthcare and a speaker for Gilead.

[email protected]

SOURCE: Gupta RK et al. CROI 2019, Abstract 29.

SEATTLE – The most important thing to know about the apparent HIV cure widely reported in the press recently is that the treatment was worse than the infection, according to John Mellors, MD, chief of the division of infectious diseases at the University of Pittsburgh.

M. Alexander Otto/MDedge News

Dr. Mellors moderated a presentation at the Conference on Retroviruses and Opportunistic Infections about what the cure involved.

An HIV-positive man with advanced Hodgkin’s lymphoma had an allogeneic bone marrow transplant in 2016 after failing first-line chemotherapy and multiple salvage regimens. His donor was homozygous for a gene mutation that prevents HIV from entering new cells. The transplant took; the man’s hematopoietic system was replaced by one with the anti-HIV mutation; and there’s been no trace of active virus in his system since. He’s been off of antiretrovirals for a year and a half. The cancer hasn’t returned.

He’s been dubbed the “London patient.” He joins the “Berlin patient” as the second person who appears to have been freed of infection following a stem cell transplant with the anti-HIV mutation. The Berlin patient recently identified himself as Timothy Ray Brown; he was in the audience at CROI and was applauded for coming forward and sharing his story.

Mr. Brown received a transplant for acute myeloid leukemia and has been off antiretrovirals now for about a decade with no evidence of viral rebound.

M. Alexander Otto/MDedge News

Although it didn’t get much attention at CROI, there was a poster of a similar approach seeming to work in a third patient, also with leukemia. It’s been tried – but failed – in two others: one patient died of their lymphoma and the transplant failed in the other, said lead investigator on the London patient case, Ravindra Gupta, MD, a professor in the division of infection & immunity at University College London.

Dr. Mellors pointed out that “the two people who have been cured had lethal malignancies that were unresponsive to conventional therapy and had the extreme measure of an allogeneic bone marrow transplant. Allogeneic bone marrow transplant is not a walk in the park. It has a mortality of 10%-25%, which is completely unacceptable” when “patients feel great on one pill a day” for HIV remission and pretty much have a normal life span.

The transplant reactivated both cytomegalovirus and Epstein Barr virus in the London patient, and he developed graft-versus-host colitis. He survived all three complications.

The take-home message is that “these cases are inspirational. The work ahead is to find out how to deliver the same results with less-extreme measures,” Dr. Mellors said.

The donors for both the London and Berlin patients were homozygous for a delta 32 deletion in the receptor most commonly used by HIV-1 to enter host cells, CCR5. Cells that carry the mutation don’t express the receptor, preventing infection. The mutation prevalence is about 1% among Europeans.

Of the two failed cases, the person who died of lymphoma had a strain of HIV-1 that used a different receptor – CXCR4 – so it’s doubtful the transplant would have worked even if he had survived his cancer.

The London patient wasn’t what’s called an “elite controller,” one of those rare people who suppress HIV without antiretrovirals. His viral loads bounced right back when we was taken off them prior to transplant.

He’s not interested in an active sex life at the moment, Dr. Gupta said, but he might be soon, so Dr. Gupta plans a discussion with him in the near future. Although the London patient could well be immune to HIV that uses the CCR5 receptor, he might not be immune to CXCR4 virus, and he might still be able to produce infectious CCR5 particles. Time will tell.

There was no industry funding for the work. Dr. Gupta is a consultant for ViiV Healthcare and a speaker for Gilead.

[email protected]

SOURCE: Gupta RK et al. CROI 2019, Abstract 29.

At 8:07 am on January 13, 2018, people in Hawaii received an emergency alert advising them to seek shelter from an incoming ballistic missile.

A very long 38 minutes later, the message was retracted via the same systems that had sent it—the Wireless Emergency Alert system, which sends location-based warnings to wireless carrier systems, and the Emergency Alert System, which sends television and radio alerts.

The Federal Communications Commission report that covered the debacle noted that, among other errors, the employee responsible for triggering the false alert believed the missile threat was real. Moreover, the exercise plans did not document a process for disseminating an all-clear message. And on top of that, the established ballistic missile alert checklist did not include a step to notify the Hawaii Emergency Management Agency’s public information officer responsible for communicating with the public, media, other agencies, and other stakeholders during an incident.

Researchers from the CDC and Hawaii Department of Health analyzed tweets sent during 2 periods: early (8:07-8:45 am), the 38 minutes during which the alert circulated; and the late period (8:46-9:24 am), the same amount of elapsed time after the correction had been issued.

They found 4 themes dominated the early period: information processing, information sharing, authentication, and emotional reaction (shock, fear, panic, terror). Information processing was defined as any indication of initial mental processing of the alert. Many of the tweets dealt with coming to terms with the threat.

During the late period, information sharing and emotional reaction persisted, but they were joined by new themes that, according to the researchers, were “fundamentally different” from the early-period themes and reflected reactions to misinformation: denunciation, insufficient knowledge to act, and mistrust of authority. “Insufficient knowledge to act” involved reacting to the lack of a response plan, particularly not knowing how to properly take shelter. Denunciations blamed the emergency warning and response, especially the time it took to correct the mistake. Mistrust of authority involved doubting the emergency alert system or governmental response.

How can a situation like this be better handled? The researchers say public health messaging during an emergency is complicated. For instance, it is influenced by how messages are perceived and interpreted by different people, and by the fact that messages need to be sent over multiple platforms to ensure that the information is disseminated accurately and quickly.

Which is why social media is both a handicap and a boon in public health emergencies. Tweets spread misinformation as fast as information (if not faster), so the first messages are critical. In addition to conveying timely messages, the researchers advise, public health authorities need to address the reactions during each phase of a crisis. They also need to establish credibility to prevent the public from mistrusting the public health message and its issuers.

Most important, perhaps: Alerts should carry clear instructions for persons in the affected area to carry out during an emergency.

At 8:07 am on January 13, 2018, people in Hawaii received an emergency alert advising them to seek shelter from an incoming ballistic missile.

A very long 38 minutes later, the message was retracted via the same systems that had sent it—the Wireless Emergency Alert system, which sends location-based warnings to wireless carrier systems, and the Emergency Alert System, which sends television and radio alerts.

The Federal Communications Commission report that covered the debacle noted that, among other errors, the employee responsible for triggering the false alert believed the missile threat was real. Moreover, the exercise plans did not document a process for disseminating an all-clear message. And on top of that, the established ballistic missile alert checklist did not include a step to notify the Hawaii Emergency Management Agency’s public information officer responsible for communicating with the public, media, other agencies, and other stakeholders during an incident.

Researchers from the CDC and Hawaii Department of Health analyzed tweets sent during 2 periods: early (8:07-8:45 am), the 38 minutes during which the alert circulated; and the late period (8:46-9:24 am), the same amount of elapsed time after the correction had been issued.

They found 4 themes dominated the early period: information processing, information sharing, authentication, and emotional reaction (shock, fear, panic, terror). Information processing was defined as any indication of initial mental processing of the alert. Many of the tweets dealt with coming to terms with the threat.

During the late period, information sharing and emotional reaction persisted, but they were joined by new themes that, according to the researchers, were “fundamentally different” from the early-period themes and reflected reactions to misinformation: denunciation, insufficient knowledge to act, and mistrust of authority. “Insufficient knowledge to act” involved reacting to the lack of a response plan, particularly not knowing how to properly take shelter. Denunciations blamed the emergency warning and response, especially the time it took to correct the mistake. Mistrust of authority involved doubting the emergency alert system or governmental response.

How can a situation like this be better handled? The researchers say public health messaging during an emergency is complicated. For instance, it is influenced by how messages are perceived and interpreted by different people, and by the fact that messages need to be sent over multiple platforms to ensure that the information is disseminated accurately and quickly.

Which is why social media is both a handicap and a boon in public health emergencies. Tweets spread misinformation as fast as information (if not faster), so the first messages are critical. In addition to conveying timely messages, the researchers advise, public health authorities need to address the reactions during each phase of a crisis. They also need to establish credibility to prevent the public from mistrusting the public health message and its issuers.

Most important, perhaps: Alerts should carry clear instructions for persons in the affected area to carry out during an emergency.

At 8:07 am on January 13, 2018, people in Hawaii received an emergency alert advising them to seek shelter from an incoming ballistic missile.

A very long 38 minutes later, the message was retracted via the same systems that had sent it—the Wireless Emergency Alert system, which sends location-based warnings to wireless carrier systems, and the Emergency Alert System, which sends television and radio alerts.

The Federal Communications Commission report that covered the debacle noted that, among other errors, the employee responsible for triggering the false alert believed the missile threat was real. Moreover, the exercise plans did not document a process for disseminating an all-clear message. And on top of that, the established ballistic missile alert checklist did not include a step to notify the Hawaii Emergency Management Agency’s public information officer responsible for communicating with the public, media, other agencies, and other stakeholders during an incident.

Researchers from the CDC and Hawaii Department of Health analyzed tweets sent during 2 periods: early (8:07-8:45 am), the 38 minutes during which the alert circulated; and the late period (8:46-9:24 am), the same amount of elapsed time after the correction had been issued.

They found 4 themes dominated the early period: information processing, information sharing, authentication, and emotional reaction (shock, fear, panic, terror). Information processing was defined as any indication of initial mental processing of the alert. Many of the tweets dealt with coming to terms with the threat.

During the late period, information sharing and emotional reaction persisted, but they were joined by new themes that, according to the researchers, were “fundamentally different” from the early-period themes and reflected reactions to misinformation: denunciation, insufficient knowledge to act, and mistrust of authority. “Insufficient knowledge to act” involved reacting to the lack of a response plan, particularly not knowing how to properly take shelter. Denunciations blamed the emergency warning and response, especially the time it took to correct the mistake. Mistrust of authority involved doubting the emergency alert system or governmental response.

How can a situation like this be better handled? The researchers say public health messaging during an emergency is complicated. For instance, it is influenced by how messages are perceived and interpreted by different people, and by the fact that messages need to be sent over multiple platforms to ensure that the information is disseminated accurately and quickly.

Which is why social media is both a handicap and a boon in public health emergencies. Tweets spread misinformation as fast as information (if not faster), so the first messages are critical. In addition to conveying timely messages, the researchers advise, public health authorities need to address the reactions during each phase of a crisis. They also need to establish credibility to prevent the public from mistrusting the public health message and its issuers.

Most important, perhaps: Alerts should carry clear instructions for persons in the affected area to carry out during an emergency.

SEATTLE – Hepatocellular carcinoma (HCC) is on the rise in HIV-positive individuals, its incidence having quadrupled since 1996, and HIV-positive individuals have about a 300% increase risk of HCC, compared with the general population. However, more than 40% of patients with HIV who develop HCC have a Fibrosis-4 score (FIB-4) suggesting a lack of cirrhosis, according to a new retrospective analysis. By contrast, only about 13% of typical HCC patients have no cirrhosis.

Wavebreakmedia Ltd/ThinkStockPhotos.com

The study also revealed some of the risk factors associated with HCC in this population, including longer duration of HIV viremia and lower CD4 cell counts, as well as markers of metabolic syndrome. “There was some signal that perhaps other markers of metabolic syndrome, obesity and diabetes, were more prevalent in those [who developed HCC] without advanced fibrosis or cirrhosis, suggesting that there may be other underlying etiologies of liver disease that we should be wary of when evaluating somebody for their risk of HCC,” Jessie Torgersen, MD, said in an interview.

Dr. Torgersen is an instructor of medicine at the University of Pennsylvania, Philadelphia. She presented the study at the Conference on Retroviruses & Opportunistic Infections.

The results of the study are tantalizing, but not yet practice changing. “I don’t think we have enough information from this study to recommend a dramatic overhaul of the current HCC screening guidelines, but with the anticipated elimination of hepatitis C, I think the emergence of [metabolic factors and their] contributions to our HIV-positive population’s risk of HCC needs to be better understood. Hopefully this will serve as a first step in further understanding those risks,” Dr. Torgersen said.

She also hopes to get a better handle on the biological mechanisms that might drive HCC in the absence of cirrhosis. “While the mechanisms are unclear as to why HCC would develop in HIV-positive patients without cirrhosis, there are a lot of biologically plausible mechanisms that seem to make [sense],” said Dr. Torgersen. The team hopes to get a better understanding of those mechanisms in order to information evaluation and screening for HCC.

The researchers analyzed data from the Veterans Affairs Cancer Registry as well as EMRs for HIV-positive veterans across the United States. The study included 2,497 participants with a FIB-4 score greater than 3.25, and 29,836 with an FIB-4 score less than or equal to 3.25. At baseline, subjects with FIB-4 greater than 3.25 were more likely to have an alcohol-related diagnosis (47% vs. 29%), be positive for hepatitis C virus RNA (59% vs. 30%), be positive for the hepatitis B surface antigen (10% versus 5%), have HIV RNA greater than or equal to 500 copies/mL (63% vs. 56%), and to have a CD4+ cell count less than 200 cells/m³ (39% vs. 26%).

A total of 278 subjects were diagnosed with HCC; 43% had an FIB-4 less than or equal to 3.25. Among those 43%, more patients had a body mass index of 30 or higher (16% vs. 12%), had diabetes (31% vs. 25%), and tested positive for the hepatitis B surface antigen (26% vs. 17%).

Among subjects with FIB-4 less than or equal to 3.25, factors associated with greater HCC risk included higher HIV RNA level (hazard ratio, 1.24 per 1.0 log¹⁰ copies/mL), CD4+ cell count less than 200 cells/m³ (HR, 1.78), hepatitis C virus infection (HR, 6.32), and positive hepatitis B surface antigen (HR, 4.93).

Among subjects with FIB-4 greater than 3.25, increased HCC risk was associated with HCV infection (HR, 6.18) and positive hepatitis B surface antigen (HR, 2.12).

The study was funded by the National Institutes of Health. Dr. Torgersen reported no financial disclosures.

SOURCE: Torgersen J et al. CROI 2019, Abstract 90.

SEATTLE – Hepatocellular carcinoma (HCC) is on the rise in HIV-positive individuals, its incidence having quadrupled since 1996, and HIV-positive individuals have about a 300% increase risk of HCC, compared with the general population. However, more than 40% of patients with HIV who develop HCC have a Fibrosis-4 score (FIB-4) suggesting a lack of cirrhosis, according to a new retrospective analysis. By contrast, only about 13% of typical HCC patients have no cirrhosis.

Wavebreakmedia Ltd/ThinkStockPhotos.com

The study also revealed some of the risk factors associated with HCC in this population, including longer duration of HIV viremia and lower CD4 cell counts, as well as markers of metabolic syndrome. “There was some signal that perhaps other markers of metabolic syndrome, obesity and diabetes, were more prevalent in those [who developed HCC] without advanced fibrosis or cirrhosis, suggesting that there may be other underlying etiologies of liver disease that we should be wary of when evaluating somebody for their risk of HCC,” Jessie Torgersen, MD, said in an interview.

Dr. Torgersen is an instructor of medicine at the University of Pennsylvania, Philadelphia. She presented the study at the Conference on Retroviruses & Opportunistic Infections.

The results of the study are tantalizing, but not yet practice changing. “I don’t think we have enough information from this study to recommend a dramatic overhaul of the current HCC screening guidelines, but with the anticipated elimination of hepatitis C, I think the emergence of [metabolic factors and their] contributions to our HIV-positive population’s risk of HCC needs to be better understood. Hopefully this will serve as a first step in further understanding those risks,” Dr. Torgersen said.

She also hopes to get a better handle on the biological mechanisms that might drive HCC in the absence of cirrhosis. “While the mechanisms are unclear as to why HCC would develop in HIV-positive patients without cirrhosis, there are a lot of biologically plausible mechanisms that seem to make [sense],” said Dr. Torgersen. The team hopes to get a better understanding of those mechanisms in order to information evaluation and screening for HCC.

The researchers analyzed data from the Veterans Affairs Cancer Registry as well as EMRs for HIV-positive veterans across the United States. The study included 2,497 participants with a FIB-4 score greater than 3.25, and 29,836 with an FIB-4 score less than or equal to 3.25. At baseline, subjects with FIB-4 greater than 3.25 were more likely to have an alcohol-related diagnosis (47% vs. 29%), be positive for hepatitis C virus RNA (59% vs. 30%), be positive for the hepatitis B surface antigen (10% versus 5%), have HIV RNA greater than or equal to 500 copies/mL (63% vs. 56%), and to have a CD4+ cell count less than 200 cells/m³ (39% vs. 26%).

A total of 278 subjects were diagnosed with HCC; 43% had an FIB-4 less than or equal to 3.25. Among those 43%, more patients had a body mass index of 30 or higher (16% vs. 12%), had diabetes (31% vs. 25%), and tested positive for the hepatitis B surface antigen (26% vs. 17%).

Among subjects with FIB-4 less than or equal to 3.25, factors associated with greater HCC risk included higher HIV RNA level (hazard ratio, 1.24 per 1.0 log¹⁰ copies/mL), CD4+ cell count less than 200 cells/m³ (HR, 1.78), hepatitis C virus infection (HR, 6.32), and positive hepatitis B surface antigen (HR, 4.93).

Among subjects with FIB-4 greater than 3.25, increased HCC risk was associated with HCV infection (HR, 6.18) and positive hepatitis B surface antigen (HR, 2.12).

The study was funded by the National Institutes of Health. Dr. Torgersen reported no financial disclosures.

SOURCE: Torgersen J et al. CROI 2019, Abstract 90.

SEATTLE – Hepatocellular carcinoma (HCC) is on the rise in HIV-positive individuals, its incidence having quadrupled since 1996, and HIV-positive individuals have about a 300% increase risk of HCC, compared with the general population. However, more than 40% of patients with HIV who develop HCC have a Fibrosis-4 score (FIB-4) suggesting a lack of cirrhosis, according to a new retrospective analysis. By contrast, only about 13% of typical HCC patients have no cirrhosis.

Wavebreakmedia Ltd/ThinkStockPhotos.com

The study also revealed some of the risk factors associated with HCC in this population, including longer duration of HIV viremia and lower CD4 cell counts, as well as markers of metabolic syndrome. “There was some signal that perhaps other markers of metabolic syndrome, obesity and diabetes, were more prevalent in those [who developed HCC] without advanced fibrosis or cirrhosis, suggesting that there may be other underlying etiologies of liver disease that we should be wary of when evaluating somebody for their risk of HCC,” Jessie Torgersen, MD, said in an interview.

Dr. Torgersen is an instructor of medicine at the University of Pennsylvania, Philadelphia. She presented the study at the Conference on Retroviruses & Opportunistic Infections.

The results of the study are tantalizing, but not yet practice changing. “I don’t think we have enough information from this study to recommend a dramatic overhaul of the current HCC screening guidelines, but with the anticipated elimination of hepatitis C, I think the emergence of [metabolic factors and their] contributions to our HIV-positive population’s risk of HCC needs to be better understood. Hopefully this will serve as a first step in further understanding those risks,” Dr. Torgersen said.

She also hopes to get a better handle on the biological mechanisms that might drive HCC in the absence of cirrhosis. “While the mechanisms are unclear as to why HCC would develop in HIV-positive patients without cirrhosis, there are a lot of biologically plausible mechanisms that seem to make [sense],” said Dr. Torgersen. The team hopes to get a better understanding of those mechanisms in order to information evaluation and screening for HCC.

The researchers analyzed data from the Veterans Affairs Cancer Registry as well as EMRs for HIV-positive veterans across the United States. The study included 2,497 participants with a FIB-4 score greater than 3.25, and 29,836 with an FIB-4 score less than or equal to 3.25. At baseline, subjects with FIB-4 greater than 3.25 were more likely to have an alcohol-related diagnosis (47% vs. 29%), be positive for hepatitis C virus RNA (59% vs. 30%), be positive for the hepatitis B surface antigen (10% versus 5%), have HIV RNA greater than or equal to 500 copies/mL (63% vs. 56%), and to have a CD4+ cell count less than 200 cells/m³ (39% vs. 26%).

A total of 278 subjects were diagnosed with HCC; 43% had an FIB-4 less than or equal to 3.25. Among those 43%, more patients had a body mass index of 30 or higher (16% vs. 12%), had diabetes (31% vs. 25%), and tested positive for the hepatitis B surface antigen (26% vs. 17%).

Among subjects with FIB-4 less than or equal to 3.25, factors associated with greater HCC risk included higher HIV RNA level (hazard ratio, 1.24 per 1.0 log¹⁰ copies/mL), CD4+ cell count less than 200 cells/m³ (HR, 1.78), hepatitis C virus infection (HR, 6.32), and positive hepatitis B surface antigen (HR, 4.93).

Among subjects with FIB-4 greater than 3.25, increased HCC risk was associated with HCV infection (HR, 6.18) and positive hepatitis B surface antigen (HR, 2.12).

The study was funded by the National Institutes of Health. Dr. Torgersen reported no financial disclosures.

SOURCE: Torgersen J et al. CROI 2019, Abstract 90.

This week in MDedge Cardiocast: A novel drug lowers LDL in on top of maximums statins, invasive cardiology is a top money maker for hospitals, a meta-analysis parses the heart and kidney benefits of new diabetes drugs, and the AHA warns that heart-harming toxins may hurt hookah smokers.
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This week in MDedge Cardiocast: A novel drug lowers LDL in on top of maximums statins, invasive cardiology is a top money maker for hospitals, a meta-analysis parses the heart and kidney benefits of new diabetes drugs, and the AHA warns that heart-harming toxins may hurt hookah smokers.
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This week in MDedge Cardiocast: A novel drug lowers LDL in on top of maximums statins, invasive cardiology is a top money maker for hospitals, a meta-analysis parses the heart and kidney benefits of new diabetes drugs, and the AHA warns that heart-harming toxins may hurt hookah smokers.
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HONOLULU – Carotid endarterectomy and carotid artery stenting with embolic protection have comparable efficacy and safety for asymptomatic patients with severe carotid artery stenosis, according to a pooled analysis presented at the International Stroke Conference sponsored by the American Heart Association. The treatments have similar rates of procedural complications and 4-year ipsilateral stroke, said Jon S. Matsumura, MD, chairman of the division of vascular surgery at the University of Wisconsin in Madison.

Asymptomatic severe carotid stenosis is the most common indication for carotid operations in the United States. Data support carotid endarterectomy in selected asymptomatic patients. Carotid artery stenting with embolic protection is a newer treatment option. Two of the five most recent large, randomized trials – CREST and ACT I – compared carotid stenting with endarterectomy in asymptomatic patients. Dr. Matsumura and his colleagues conducted a pooled analysis of these two trials to help inform the choice of treatment.

The investigators analyzed data from the CREST and ACT I studies, which had many similarities. The researchers in these trials carefully selected the surgeons and the interventionalists who participated in them. Each trial used single carotid stent systems, and both trials used routine, distally placed embolic protection. The trials had independent neurologic assessment, routine cardiac enzyme screening, and central clinical and adjudication committees.

Dr. Matsumura and his colleagues decided to conduct a patient-level pooled analysis and defined the primary endpoint as a composite of death, stroke, and myocardial infarction in the periprocedural period and any ipsilateral stroke within 4 years of randomization. They included in their analysis all randomized, asymptomatic patients who were younger than 80 years.

[email protected]

SOURCE: Hanlon B et al. ISC 2019, Abstract LB13.

HONOLULU – Carotid endarterectomy and carotid artery stenting with embolic protection have comparable efficacy and safety for asymptomatic patients with severe carotid artery stenosis, according to a pooled analysis presented at the International Stroke Conference sponsored by the American Heart Association. The treatments have similar rates of procedural complications and 4-year ipsilateral stroke, said Jon S. Matsumura, MD, chairman of the division of vascular surgery at the University of Wisconsin in Madison.

Asymptomatic severe carotid stenosis is the most common indication for carotid operations in the United States. Data support carotid endarterectomy in selected asymptomatic patients. Carotid artery stenting with embolic protection is a newer treatment option. Two of the five most recent large, randomized trials – CREST and ACT I – compared carotid stenting with endarterectomy in asymptomatic patients. Dr. Matsumura and his colleagues conducted a pooled analysis of these two trials to help inform the choice of treatment.

The investigators analyzed data from the CREST and ACT I studies, which had many similarities. The researchers in these trials carefully selected the surgeons and the interventionalists who participated in them. Each trial used single carotid stent systems, and both trials used routine, distally placed embolic protection. The trials had independent neurologic assessment, routine cardiac enzyme screening, and central clinical and adjudication committees.

Dr. Matsumura and his colleagues decided to conduct a patient-level pooled analysis and defined the primary endpoint as a composite of death, stroke, and myocardial infarction in the periprocedural period and any ipsilateral stroke within 4 years of randomization. They included in their analysis all randomized, asymptomatic patients who were younger than 80 years.

[email protected]

SOURCE: Hanlon B et al. ISC 2019, Abstract LB13.

HONOLULU – Carotid endarterectomy and carotid artery stenting with embolic protection have comparable efficacy and safety for asymptomatic patients with severe carotid artery stenosis, according to a pooled analysis presented at the International Stroke Conference sponsored by the American Heart Association. The treatments have similar rates of procedural complications and 4-year ipsilateral stroke, said Jon S. Matsumura, MD, chairman of the division of vascular surgery at the University of Wisconsin in Madison.

Asymptomatic severe carotid stenosis is the most common indication for carotid operations in the United States. Data support carotid endarterectomy in selected asymptomatic patients. Carotid artery stenting with embolic protection is a newer treatment option. Two of the five most recent large, randomized trials – CREST and ACT I – compared carotid stenting with endarterectomy in asymptomatic patients. Dr. Matsumura and his colleagues conducted a pooled analysis of these two trials to help inform the choice of treatment.

The investigators analyzed data from the CREST and ACT I studies, which had many similarities. The researchers in these trials carefully selected the surgeons and the interventionalists who participated in them. Each trial used single carotid stent systems, and both trials used routine, distally placed embolic protection. The trials had independent neurologic assessment, routine cardiac enzyme screening, and central clinical and adjudication committees.

Dr. Matsumura and his colleagues decided to conduct a patient-level pooled analysis and defined the primary endpoint as a composite of death, stroke, and myocardial infarction in the periprocedural period and any ipsilateral stroke within 4 years of randomization. They included in their analysis all randomized, asymptomatic patients who were younger than 80 years.

[email protected]

SOURCE: Hanlon B et al. ISC 2019, Abstract LB13.