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Prehospital antibiotics improved some aspects of sepsis care
SAN ANTONIO – according to results of a randomized trial.
Emergency medical service (EMS) personnel were able to recognize sepsis more quickly, obtain blood cultures, and give antibiotics after the training, reported investigator Prabath Nanayakkara, MD, PhD, FRCP, at the Society of Critical Care Medicine’s Critical Care Congress.
At 28 days, 120 patients (8%) in the prehospital antibiotics group had died, compared with 93 patients (8%) in the usual care group (relative risk, 0.95; 95% confidence interval, 0.74-1.24), according to the study’s results that were simultaneously published online in Lancet Respiratory Medicine.
The intervention group received antibiotics a median of 26 minutes prior to emergency department (ED) arrival. In the usual care group, median time to antibiotics after ED arrival was 70 minutes, versus 93 minutes prior to the sepsis recognition training (P = .142), the report further says.
“We do not advise prehospital antibiotics at the moment for patients with suspected sepsis,” Dr. Nanayakkara said, during his presentation at the conference.
Other countries might see different results, he cautioned.
In the Netherlands, ambulances reach the emergency scene within 15 minutes 93% of the time, and the average time from dispatch call to ED arrival is 40 minutes, Dr. Nanayakkara noted in the report.
“In part, due to the relatively short response times in the Netherlands, we don’t know if there are other countries with longer response times that would have other results, and whether they should use antibiotics in their ambulances,” Dr. Nanayakkara said in his presentation.
The study was the first-ever prospective randomized, controlled open-label trial to compare early prehospital antibiotics with standard care.
Before the study was started, EMS personnel at 10 large regional ambulance services serving 34 secondary or tertiary hospitals were trained in recognizing sepsis, the report says.
A total of 2,672 patients with suspected sepsis were included in the intention-to-treat analysis, of whom 1,535 were randomized to receive prehospital antibiotics and 1,137 to usual EMS care, which consisted of fluid resuscitation and supplementary oxygen.
The primary end point of the study was all-cause mortality at 28 days.
The negative mortality results of this trial are “not surprising,” given that the trial’s inclusion criteria allowed individuals with suspected infection but without organ dysfunction, said Jean-Louis Vincent, MD, PhD, of Erasmus Hospital, Brussels, in a related editorial appearing in the Lancet Respiratory Medicine (2018 Jan. doi: 10.1016/S2213-2600[17]30446-0).
Recent consensus definitions of sepsis recognize that sepsis is the association of an infection with some degree of organ dysfunction, according to Dr. Vincent.
“After this initial experience, I believe that a randomized, controlled trial could be done to assess the potential benefit of early antibiotic administration in the ambulance for patients with organ dysfunction associated with infection,” Dr. Vincent wrote in his editorial.
Dr. Nanayakkara and his coauthors declared no competing interests related to their study.
SOURCE: Alam N et al. Lancet Respir Med. 2018 Jan;6(1):40-50.
SAN ANTONIO – according to results of a randomized trial.
Emergency medical service (EMS) personnel were able to recognize sepsis more quickly, obtain blood cultures, and give antibiotics after the training, reported investigator Prabath Nanayakkara, MD, PhD, FRCP, at the Society of Critical Care Medicine’s Critical Care Congress.
At 28 days, 120 patients (8%) in the prehospital antibiotics group had died, compared with 93 patients (8%) in the usual care group (relative risk, 0.95; 95% confidence interval, 0.74-1.24), according to the study’s results that were simultaneously published online in Lancet Respiratory Medicine.
The intervention group received antibiotics a median of 26 minutes prior to emergency department (ED) arrival. In the usual care group, median time to antibiotics after ED arrival was 70 minutes, versus 93 minutes prior to the sepsis recognition training (P = .142), the report further says.
“We do not advise prehospital antibiotics at the moment for patients with suspected sepsis,” Dr. Nanayakkara said, during his presentation at the conference.
Other countries might see different results, he cautioned.
In the Netherlands, ambulances reach the emergency scene within 15 minutes 93% of the time, and the average time from dispatch call to ED arrival is 40 minutes, Dr. Nanayakkara noted in the report.
“In part, due to the relatively short response times in the Netherlands, we don’t know if there are other countries with longer response times that would have other results, and whether they should use antibiotics in their ambulances,” Dr. Nanayakkara said in his presentation.
The study was the first-ever prospective randomized, controlled open-label trial to compare early prehospital antibiotics with standard care.
Before the study was started, EMS personnel at 10 large regional ambulance services serving 34 secondary or tertiary hospitals were trained in recognizing sepsis, the report says.
A total of 2,672 patients with suspected sepsis were included in the intention-to-treat analysis, of whom 1,535 were randomized to receive prehospital antibiotics and 1,137 to usual EMS care, which consisted of fluid resuscitation and supplementary oxygen.
The primary end point of the study was all-cause mortality at 28 days.
The negative mortality results of this trial are “not surprising,” given that the trial’s inclusion criteria allowed individuals with suspected infection but without organ dysfunction, said Jean-Louis Vincent, MD, PhD, of Erasmus Hospital, Brussels, in a related editorial appearing in the Lancet Respiratory Medicine (2018 Jan. doi: 10.1016/S2213-2600[17]30446-0).
Recent consensus definitions of sepsis recognize that sepsis is the association of an infection with some degree of organ dysfunction, according to Dr. Vincent.
“After this initial experience, I believe that a randomized, controlled trial could be done to assess the potential benefit of early antibiotic administration in the ambulance for patients with organ dysfunction associated with infection,” Dr. Vincent wrote in his editorial.
Dr. Nanayakkara and his coauthors declared no competing interests related to their study.
SOURCE: Alam N et al. Lancet Respir Med. 2018 Jan;6(1):40-50.
SAN ANTONIO – according to results of a randomized trial.
Emergency medical service (EMS) personnel were able to recognize sepsis more quickly, obtain blood cultures, and give antibiotics after the training, reported investigator Prabath Nanayakkara, MD, PhD, FRCP, at the Society of Critical Care Medicine’s Critical Care Congress.
At 28 days, 120 patients (8%) in the prehospital antibiotics group had died, compared with 93 patients (8%) in the usual care group (relative risk, 0.95; 95% confidence interval, 0.74-1.24), according to the study’s results that were simultaneously published online in Lancet Respiratory Medicine.
The intervention group received antibiotics a median of 26 minutes prior to emergency department (ED) arrival. In the usual care group, median time to antibiotics after ED arrival was 70 minutes, versus 93 minutes prior to the sepsis recognition training (P = .142), the report further says.
“We do not advise prehospital antibiotics at the moment for patients with suspected sepsis,” Dr. Nanayakkara said, during his presentation at the conference.
Other countries might see different results, he cautioned.
In the Netherlands, ambulances reach the emergency scene within 15 minutes 93% of the time, and the average time from dispatch call to ED arrival is 40 minutes, Dr. Nanayakkara noted in the report.
“In part, due to the relatively short response times in the Netherlands, we don’t know if there are other countries with longer response times that would have other results, and whether they should use antibiotics in their ambulances,” Dr. Nanayakkara said in his presentation.
The study was the first-ever prospective randomized, controlled open-label trial to compare early prehospital antibiotics with standard care.
Before the study was started, EMS personnel at 10 large regional ambulance services serving 34 secondary or tertiary hospitals were trained in recognizing sepsis, the report says.
A total of 2,672 patients with suspected sepsis were included in the intention-to-treat analysis, of whom 1,535 were randomized to receive prehospital antibiotics and 1,137 to usual EMS care, which consisted of fluid resuscitation and supplementary oxygen.
The primary end point of the study was all-cause mortality at 28 days.
The negative mortality results of this trial are “not surprising,” given that the trial’s inclusion criteria allowed individuals with suspected infection but without organ dysfunction, said Jean-Louis Vincent, MD, PhD, of Erasmus Hospital, Brussels, in a related editorial appearing in the Lancet Respiratory Medicine (2018 Jan. doi: 10.1016/S2213-2600[17]30446-0).
Recent consensus definitions of sepsis recognize that sepsis is the association of an infection with some degree of organ dysfunction, according to Dr. Vincent.
“After this initial experience, I believe that a randomized, controlled trial could be done to assess the potential benefit of early antibiotic administration in the ambulance for patients with organ dysfunction associated with infection,” Dr. Vincent wrote in his editorial.
Dr. Nanayakkara and his coauthors declared no competing interests related to their study.
SOURCE: Alam N et al. Lancet Respir Med. 2018 Jan;6(1):40-50.
REPORTING FROM CCC47
Key clinical point: In patients with suspected sepsis, prehospital antibiotics delivered by EMS personnel improved some aspects of care, but did not reduce mortality.
Major finding: At 28 days, 120 patients (8%) in the prehospital antibiotics group had died, compared with 93 patients (8%) in the usual care group (relative risk, 0.95; 95% CI, 0.74-1.24).
Data source: Intention-to-treat analysis of 2,672 patients in a prospective randomized, controlled open-label trial comparing early prehospital antibiotics to standard care.
Disclosures: The study authors declared no competing interests related to the study.
Source: Alam N et al. Lancet Respir Med. 2018 Jan;6(1):40-50.
Ibrutinib linked to invasive fungal infections
The tyrosine kinase inhibitor ibrutinib (Imbruvica) may be associated with early-onset invasive fungal infections (IFI) in patients with hematologic malignancies, investigators caution.
French investigators identified 33 cases of invasive fungal infections occurring among patients who had been treated with ibrutinib as monotherapy or in combination with other agents. Of the 33 cases, 27 were invasive aspergillosis, and 40% of these were localized in the central nervous system. The findings were published in the journal Blood.
“IFI tend to occur within the first months of treatment and are infrequent thereafter. Whilst it seems difficult at this point to advocate for systematic antifungal prophylaxis in all patients, an increased awareness about the potential risk of IFI after initiating ibrutinib is warranted, especially when other predisposing factors are associated,” wrote David Ghez, MD, PhD, and colleagues at the Gustave Roussy Institute in Villejuif and other centers in France.
Although ibrutinib, an inhibitor of Bruton’s tyrosine kinase, is generally considered to be less immunosuppressive than other therapies, it was associated with five cases of Pneumocystis jirovecii pneumonia in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib monotherapy in a 2016 report (Blood. 2016;128:1940-3). Of these five patients, four were treatment naive, suggesting that ibrutinib itself could increase risk for invasive opportunistic infections, Dr. Ghez and his colleagues noted.
Based on this finding and on case reports of invasive infections in other patients being treated with ibrutinib, the authors conducted a retrospective survey of centers in the French Innovative Leukemia Organization CLL group.
They identified 33 cases, including 30 patients with CLL (15 of whom had deleterious 17p deletions), 1 with mantle cell lymphoma, and 2 with Waldenstrom macroglobulinemia.
Invasive aspergillosis accounted for 27 of the 33 cases, and 11 cases had CNS localization. There were four cases of disseminated cryptococcosis, and one each of mucormycosis and pneumocystis pneumonia.
The median time between the start of ibrutinib therapy and a diagnosis of invasive fungal infection was 3 months, with some cases occurring as early as 1 month, and others occurring 30 months out. However, the majority of cases – 28 – were diagnosed within 6 months of the start of therapy, including 20 that occurred within 3 months of ibrutinib initiation.
In 21 patients, the diagnosis of an invasive fungal infection led to drug discontinuation. In the remaining patients, the drug was either resumed after resolution of the IFI, or continued at a lower dose because of potential for interaction between ibrutinib and the antifungal agent voriconazole.
Dr. Ghez reported receiving a research grant from Janssen, and coauthor Loic Ysebaert, MD, PhD, reported consultancy fees from the company. All other authors declared no competing financial interests.
SOURCE: Ghez D et al., Blood. 2018 Feb 1. doi: 10.1182/blood-2017-11-818286.
The tyrosine kinase inhibitor ibrutinib (Imbruvica) may be associated with early-onset invasive fungal infections (IFI) in patients with hematologic malignancies, investigators caution.
French investigators identified 33 cases of invasive fungal infections occurring among patients who had been treated with ibrutinib as monotherapy or in combination with other agents. Of the 33 cases, 27 were invasive aspergillosis, and 40% of these were localized in the central nervous system. The findings were published in the journal Blood.
“IFI tend to occur within the first months of treatment and are infrequent thereafter. Whilst it seems difficult at this point to advocate for systematic antifungal prophylaxis in all patients, an increased awareness about the potential risk of IFI after initiating ibrutinib is warranted, especially when other predisposing factors are associated,” wrote David Ghez, MD, PhD, and colleagues at the Gustave Roussy Institute in Villejuif and other centers in France.
Although ibrutinib, an inhibitor of Bruton’s tyrosine kinase, is generally considered to be less immunosuppressive than other therapies, it was associated with five cases of Pneumocystis jirovecii pneumonia in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib monotherapy in a 2016 report (Blood. 2016;128:1940-3). Of these five patients, four were treatment naive, suggesting that ibrutinib itself could increase risk for invasive opportunistic infections, Dr. Ghez and his colleagues noted.
Based on this finding and on case reports of invasive infections in other patients being treated with ibrutinib, the authors conducted a retrospective survey of centers in the French Innovative Leukemia Organization CLL group.
They identified 33 cases, including 30 patients with CLL (15 of whom had deleterious 17p deletions), 1 with mantle cell lymphoma, and 2 with Waldenstrom macroglobulinemia.
Invasive aspergillosis accounted for 27 of the 33 cases, and 11 cases had CNS localization. There were four cases of disseminated cryptococcosis, and one each of mucormycosis and pneumocystis pneumonia.
The median time between the start of ibrutinib therapy and a diagnosis of invasive fungal infection was 3 months, with some cases occurring as early as 1 month, and others occurring 30 months out. However, the majority of cases – 28 – were diagnosed within 6 months of the start of therapy, including 20 that occurred within 3 months of ibrutinib initiation.
In 21 patients, the diagnosis of an invasive fungal infection led to drug discontinuation. In the remaining patients, the drug was either resumed after resolution of the IFI, or continued at a lower dose because of potential for interaction between ibrutinib and the antifungal agent voriconazole.
Dr. Ghez reported receiving a research grant from Janssen, and coauthor Loic Ysebaert, MD, PhD, reported consultancy fees from the company. All other authors declared no competing financial interests.
SOURCE: Ghez D et al., Blood. 2018 Feb 1. doi: 10.1182/blood-2017-11-818286.
The tyrosine kinase inhibitor ibrutinib (Imbruvica) may be associated with early-onset invasive fungal infections (IFI) in patients with hematologic malignancies, investigators caution.
French investigators identified 33 cases of invasive fungal infections occurring among patients who had been treated with ibrutinib as monotherapy or in combination with other agents. Of the 33 cases, 27 were invasive aspergillosis, and 40% of these were localized in the central nervous system. The findings were published in the journal Blood.
“IFI tend to occur within the first months of treatment and are infrequent thereafter. Whilst it seems difficult at this point to advocate for systematic antifungal prophylaxis in all patients, an increased awareness about the potential risk of IFI after initiating ibrutinib is warranted, especially when other predisposing factors are associated,” wrote David Ghez, MD, PhD, and colleagues at the Gustave Roussy Institute in Villejuif and other centers in France.
Although ibrutinib, an inhibitor of Bruton’s tyrosine kinase, is generally considered to be less immunosuppressive than other therapies, it was associated with five cases of Pneumocystis jirovecii pneumonia in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib monotherapy in a 2016 report (Blood. 2016;128:1940-3). Of these five patients, four were treatment naive, suggesting that ibrutinib itself could increase risk for invasive opportunistic infections, Dr. Ghez and his colleagues noted.
Based on this finding and on case reports of invasive infections in other patients being treated with ibrutinib, the authors conducted a retrospective survey of centers in the French Innovative Leukemia Organization CLL group.
They identified 33 cases, including 30 patients with CLL (15 of whom had deleterious 17p deletions), 1 with mantle cell lymphoma, and 2 with Waldenstrom macroglobulinemia.
Invasive aspergillosis accounted for 27 of the 33 cases, and 11 cases had CNS localization. There were four cases of disseminated cryptococcosis, and one each of mucormycosis and pneumocystis pneumonia.
The median time between the start of ibrutinib therapy and a diagnosis of invasive fungal infection was 3 months, with some cases occurring as early as 1 month, and others occurring 30 months out. However, the majority of cases – 28 – were diagnosed within 6 months of the start of therapy, including 20 that occurred within 3 months of ibrutinib initiation.
In 21 patients, the diagnosis of an invasive fungal infection led to drug discontinuation. In the remaining patients, the drug was either resumed after resolution of the IFI, or continued at a lower dose because of potential for interaction between ibrutinib and the antifungal agent voriconazole.
Dr. Ghez reported receiving a research grant from Janssen, and coauthor Loic Ysebaert, MD, PhD, reported consultancy fees from the company. All other authors declared no competing financial interests.
SOURCE: Ghez D et al., Blood. 2018 Feb 1. doi: 10.1182/blood-2017-11-818286.
FROM BLOOD
Key clinical point:
Major finding: Of 33 identified cases, 27 were invasive aspergillosis.
Study details: Retrospective review of case reports from 16 French centers.
Disclosures: Dr. Ghez reported receiving a research grant from Janssen, and coauthor Loic Ysebaert, MD, PhD, reported consultancy fees with the company. All other authors declared no competing financial interests.
Source: Ghez D et al. Blood. 2018 Feb 1. doi: 10.1182/blood-2017-11-818286.
Functional capacity, life skills critical for patients with schizophrenia
Improving the ability of people with schizophrenia to perform tasks that are important to daily functioning is a key component for any therapeutic intervention, a cross-sectional study of 740 patients shows.
“Our study confirms that [the four domains of] social cognition, neurocognition, resilience, and real-life functioning represent robust and independent constructs,” wrote Silvana Galderisi, MD, and her associates. The report was published in JAMA Psychiatry.
Dr. Galderisi and her associates recruited community-dwelling patients with schizophrenia as defined in the DSM-IV over an 18-month period. The patients were stabilized on antipsychotics and were seen in the outpatient units of 26 psychiatric clinics and/or mental health departments in Italy.
Several measures were administered, including the Brief Negative Symptom Scale (BNSS), the Calgary Depression Scale for Schizophrenia (CDSS), the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB), and the Positive and Negative Syndrome Scale (PANSS).
Using network analysis, the researchers analyzed the results found by the measures and the relationships between the four domains. “The study clearly shows that functional capacity and everyday life skills play a key role,” Dr. Galderisi and her associates wrote. “Functional capacity ... links neurocognition and social cognition with real-life functioning nodes, in particular with everyday life skills, such as household activities, handling of personal finances, and use of the telephone or public transportation.”
Dr. Galderisi and her associates said their findings show that patients with schizophrenia need treatment that goes beyond antipsychotics. “Therefore, with schizophrenia,” they wrote.
Read the full study in JAMA Psychiatry. 2018 Feb 14. doi: 10.1001/jamapsychiatry.2017.4607.
Improving the ability of people with schizophrenia to perform tasks that are important to daily functioning is a key component for any therapeutic intervention, a cross-sectional study of 740 patients shows.
“Our study confirms that [the four domains of] social cognition, neurocognition, resilience, and real-life functioning represent robust and independent constructs,” wrote Silvana Galderisi, MD, and her associates. The report was published in JAMA Psychiatry.
Dr. Galderisi and her associates recruited community-dwelling patients with schizophrenia as defined in the DSM-IV over an 18-month period. The patients were stabilized on antipsychotics and were seen in the outpatient units of 26 psychiatric clinics and/or mental health departments in Italy.
Several measures were administered, including the Brief Negative Symptom Scale (BNSS), the Calgary Depression Scale for Schizophrenia (CDSS), the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB), and the Positive and Negative Syndrome Scale (PANSS).
Using network analysis, the researchers analyzed the results found by the measures and the relationships between the four domains. “The study clearly shows that functional capacity and everyday life skills play a key role,” Dr. Galderisi and her associates wrote. “Functional capacity ... links neurocognition and social cognition with real-life functioning nodes, in particular with everyday life skills, such as household activities, handling of personal finances, and use of the telephone or public transportation.”
Dr. Galderisi and her associates said their findings show that patients with schizophrenia need treatment that goes beyond antipsychotics. “Therefore, with schizophrenia,” they wrote.
Read the full study in JAMA Psychiatry. 2018 Feb 14. doi: 10.1001/jamapsychiatry.2017.4607.
Improving the ability of people with schizophrenia to perform tasks that are important to daily functioning is a key component for any therapeutic intervention, a cross-sectional study of 740 patients shows.
“Our study confirms that [the four domains of] social cognition, neurocognition, resilience, and real-life functioning represent robust and independent constructs,” wrote Silvana Galderisi, MD, and her associates. The report was published in JAMA Psychiatry.
Dr. Galderisi and her associates recruited community-dwelling patients with schizophrenia as defined in the DSM-IV over an 18-month period. The patients were stabilized on antipsychotics and were seen in the outpatient units of 26 psychiatric clinics and/or mental health departments in Italy.
Several measures were administered, including the Brief Negative Symptom Scale (BNSS), the Calgary Depression Scale for Schizophrenia (CDSS), the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB), and the Positive and Negative Syndrome Scale (PANSS).
Using network analysis, the researchers analyzed the results found by the measures and the relationships between the four domains. “The study clearly shows that functional capacity and everyday life skills play a key role,” Dr. Galderisi and her associates wrote. “Functional capacity ... links neurocognition and social cognition with real-life functioning nodes, in particular with everyday life skills, such as household activities, handling of personal finances, and use of the telephone or public transportation.”
Dr. Galderisi and her associates said their findings show that patients with schizophrenia need treatment that goes beyond antipsychotics. “Therefore, with schizophrenia,” they wrote.
Read the full study in JAMA Psychiatry. 2018 Feb 14. doi: 10.1001/jamapsychiatry.2017.4607.
FROM JAMA PSYCHIATRY
Preparing to respond to workplace violence
SAN ANTONIO – , Lewis J. Kaplan, MD, said in a late-breaking session at the Critical Care Congress.
“Workplace violence is not just active shooter – it’s ubiquitous, and we only know a little bit about it,” noted Dr. Kaplan, section chief, surgical critical care, Corporal Michael J. Crescenz VA Medical Center, Philadelphia. “The facility and everyone in the health care team have a role in being an active participant, rather than a passive one.”
To actively prepare for premeditated events, Dr. Kaplan recommended that clinicians develop partnerships with local law enforcement officials and initiate active training that involves anyone who could come into contact with an active shooter.
There are many steps that can be taken to protect the facility, including visitor screening and management, security that extends to the perimeter of the facility, building design that limits access to specific places in the facility, and deployment of firearm detection canines, Dr. Kaplan said, during the session at the Critical Care Congress, sponsored by the Society of Critical Care Medicine.
In all, Dr. Kaplan listed 19 steps that facilities could take to avert a planned attack, drawing in part on recommendations from the FBI publication, Workplace violence: Issues in response.
“This is a lot, and you don’t need to do all of it,” Dr. Kaplan said. “But you need to have an internally consistent plan for how you will do this at your facility, and it must involve everyone. They all need to be able to be part of your team.”
Recent data on workplace violence
The latest data show that the great majority of workplace violence is perpetrated by individuals outside the organization. According to the IAHSS Foundation 2017 Healthcare Crime Survey, 89% of events involved a customer or patient of the workplace or employees.
In-hospital violence is prevalent, according to 2016 data from Occupational Safety and Health Administration that identified 24,000 workplace assaults in a 3-year span covering 2013-2015, including 33 homicides, 30 assaults, and 74 rapes.
Many in-hospital incidents are marked by failures in communication, patient observation, noncompliance with workplace violence policies or lack of such policies, and perhaps most importantly, an inadequate assessment for the violent potential of the perpetrator, according to Dr. Kaplan.
In a 2017 survey of 150 trauma nurses, 67% said they had been the victim of physical violence at work, though many did not report the incidents, Dr. Kaplan noted. Some reasons nurses gave for not reporting violence included the feeling that it was “just part of the job” in 27% of cases, and concerns about patient satisfaction scores in 10% of the cases.
Active shooter events in the workplace are of particular concern, though they are relatively rare; one recent report identified 160 events that occurred during 2000-2013 in which 1,043 individuals were injured, according to Dr. Kaplan.
Other presentations in the late-breaking session covered issues related to disaster preparedness and the Charlie Gard case.
“We picked these three topics to be in a late-breaker session not only because of the recent events that had happened, but because they have a common thread – it’s not a matter of if it will happen, but when will it happen, and are you ready and how do we prepare,” said session chair Gloria M. Rodriguez Vega, MD.
“One of the things I learned as a fellow was that part of the success in critical care was attention to detail and layers of safety,” said Dr. Rodriguez Vega, an intensivist in Bayamon, Puerto Rico. “I think you can apply that to all these situations.”
Dr. Kaplan had no industry disclosures related to his presentation.
SAN ANTONIO – , Lewis J. Kaplan, MD, said in a late-breaking session at the Critical Care Congress.
“Workplace violence is not just active shooter – it’s ubiquitous, and we only know a little bit about it,” noted Dr. Kaplan, section chief, surgical critical care, Corporal Michael J. Crescenz VA Medical Center, Philadelphia. “The facility and everyone in the health care team have a role in being an active participant, rather than a passive one.”
To actively prepare for premeditated events, Dr. Kaplan recommended that clinicians develop partnerships with local law enforcement officials and initiate active training that involves anyone who could come into contact with an active shooter.
There are many steps that can be taken to protect the facility, including visitor screening and management, security that extends to the perimeter of the facility, building design that limits access to specific places in the facility, and deployment of firearm detection canines, Dr. Kaplan said, during the session at the Critical Care Congress, sponsored by the Society of Critical Care Medicine.
In all, Dr. Kaplan listed 19 steps that facilities could take to avert a planned attack, drawing in part on recommendations from the FBI publication, Workplace violence: Issues in response.
“This is a lot, and you don’t need to do all of it,” Dr. Kaplan said. “But you need to have an internally consistent plan for how you will do this at your facility, and it must involve everyone. They all need to be able to be part of your team.”
Recent data on workplace violence
The latest data show that the great majority of workplace violence is perpetrated by individuals outside the organization. According to the IAHSS Foundation 2017 Healthcare Crime Survey, 89% of events involved a customer or patient of the workplace or employees.
In-hospital violence is prevalent, according to 2016 data from Occupational Safety and Health Administration that identified 24,000 workplace assaults in a 3-year span covering 2013-2015, including 33 homicides, 30 assaults, and 74 rapes.
Many in-hospital incidents are marked by failures in communication, patient observation, noncompliance with workplace violence policies or lack of such policies, and perhaps most importantly, an inadequate assessment for the violent potential of the perpetrator, according to Dr. Kaplan.
In a 2017 survey of 150 trauma nurses, 67% said they had been the victim of physical violence at work, though many did not report the incidents, Dr. Kaplan noted. Some reasons nurses gave for not reporting violence included the feeling that it was “just part of the job” in 27% of cases, and concerns about patient satisfaction scores in 10% of the cases.
Active shooter events in the workplace are of particular concern, though they are relatively rare; one recent report identified 160 events that occurred during 2000-2013 in which 1,043 individuals were injured, according to Dr. Kaplan.
Other presentations in the late-breaking session covered issues related to disaster preparedness and the Charlie Gard case.
“We picked these three topics to be in a late-breaker session not only because of the recent events that had happened, but because they have a common thread – it’s not a matter of if it will happen, but when will it happen, and are you ready and how do we prepare,” said session chair Gloria M. Rodriguez Vega, MD.
“One of the things I learned as a fellow was that part of the success in critical care was attention to detail and layers of safety,” said Dr. Rodriguez Vega, an intensivist in Bayamon, Puerto Rico. “I think you can apply that to all these situations.”
Dr. Kaplan had no industry disclosures related to his presentation.
SAN ANTONIO – , Lewis J. Kaplan, MD, said in a late-breaking session at the Critical Care Congress.
“Workplace violence is not just active shooter – it’s ubiquitous, and we only know a little bit about it,” noted Dr. Kaplan, section chief, surgical critical care, Corporal Michael J. Crescenz VA Medical Center, Philadelphia. “The facility and everyone in the health care team have a role in being an active participant, rather than a passive one.”
To actively prepare for premeditated events, Dr. Kaplan recommended that clinicians develop partnerships with local law enforcement officials and initiate active training that involves anyone who could come into contact with an active shooter.
There are many steps that can be taken to protect the facility, including visitor screening and management, security that extends to the perimeter of the facility, building design that limits access to specific places in the facility, and deployment of firearm detection canines, Dr. Kaplan said, during the session at the Critical Care Congress, sponsored by the Society of Critical Care Medicine.
In all, Dr. Kaplan listed 19 steps that facilities could take to avert a planned attack, drawing in part on recommendations from the FBI publication, Workplace violence: Issues in response.
“This is a lot, and you don’t need to do all of it,” Dr. Kaplan said. “But you need to have an internally consistent plan for how you will do this at your facility, and it must involve everyone. They all need to be able to be part of your team.”
Recent data on workplace violence
The latest data show that the great majority of workplace violence is perpetrated by individuals outside the organization. According to the IAHSS Foundation 2017 Healthcare Crime Survey, 89% of events involved a customer or patient of the workplace or employees.
In-hospital violence is prevalent, according to 2016 data from Occupational Safety and Health Administration that identified 24,000 workplace assaults in a 3-year span covering 2013-2015, including 33 homicides, 30 assaults, and 74 rapes.
Many in-hospital incidents are marked by failures in communication, patient observation, noncompliance with workplace violence policies or lack of such policies, and perhaps most importantly, an inadequate assessment for the violent potential of the perpetrator, according to Dr. Kaplan.
In a 2017 survey of 150 trauma nurses, 67% said they had been the victim of physical violence at work, though many did not report the incidents, Dr. Kaplan noted. Some reasons nurses gave for not reporting violence included the feeling that it was “just part of the job” in 27% of cases, and concerns about patient satisfaction scores in 10% of the cases.
Active shooter events in the workplace are of particular concern, though they are relatively rare; one recent report identified 160 events that occurred during 2000-2013 in which 1,043 individuals were injured, according to Dr. Kaplan.
Other presentations in the late-breaking session covered issues related to disaster preparedness and the Charlie Gard case.
“We picked these three topics to be in a late-breaker session not only because of the recent events that had happened, but because they have a common thread – it’s not a matter of if it will happen, but when will it happen, and are you ready and how do we prepare,” said session chair Gloria M. Rodriguez Vega, MD.
“One of the things I learned as a fellow was that part of the success in critical care was attention to detail and layers of safety,” said Dr. Rodriguez Vega, an intensivist in Bayamon, Puerto Rico. “I think you can apply that to all these situations.”
Dr. Kaplan had no industry disclosures related to his presentation.
REPORTING FROM CCC47
New treatment options emerge for intermediate, advanced HCC
SAN FRANCISCO – Two new therapies that target vascular endothelial growth factor signaling are efficacious and may expand the treatment armamentarium for intermediate and advanced hepatocellular carcinoma, data from a pair of randomized trials suggest.
In the phase 2 TACTICS (Transcatheter Arterial Chemoembolization Therapy in Combination With Sorafenib) trial, median progression-free survival, using a new, more narrow definition of progression, was almost a year longer when the oral tyrosine kinase inhibitor sorafenib (Nexavar) was added to transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC), translating to a 41% reduction in risk of events. This benefit came at the price of higher rates of certain grade 3 adverse events, but the combination was overall feasible and safe.
Results of both trials were reported at the 2018 GI Cancers Symposium, sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
As welcome as such new therapeutic options are, they will likely increase the complexity of the treatment landscape for HCC and could muddy the ability of future trials to establish survival benefit, Jordi Bruix, MD, PhD, cautioned in an invited discussion. In addition, patients who cannot receive anti–vascular endothelial growth factor (VEGF) therapy because of comorbidities still represent an unmet need, underscoring the importance of continued research on other fronts.
TACTICS trial
“Because TACE has been shown to lead to a spike in the intratumoral concentration of VEGF, blockade of VEGF receptors may prevent the effects of a surge in proangiogenic factors,” said TACTICS lead investigator Masatoshi Kudo, MD, professor and chairman of the department of gastroenterology and hepatology at Kindai University, Osaka, Japan. “Since TACE and sorafenib have been shown to prolong survival in patients with unresectable HCC, their combination may improve clinical outcomes.”
The 156 patients enrolled in the TACTICS trial, sponsored by the Japan Liver Oncology Group, had unresectable HCC, a Child-Pugh score of 7 or lower, and no vascular invasion or extrahepatic spread.
They were randomly assigned to as-needed TACE alone or TACE plus sorafenib, which inhibits VEGF receptors, platelet-derived growth factor receptors, and Raf kinases, reducing growth signaling and angiogenesis. Sorafenib therapy was interrupted only for several days before and after each TACE session.
With a median follow-up of 2.4 years, median progression-free survival using a new definition of progression – either untreatable “unTACEable” disease or TACE failure/refractoriness (by Japanese Society of Hepatology criteria) – was 25.2 months with TACE plus sorafenib compared with 13.5 months with TACE alone (hazard ratio, 0.59; P = .006). Benefit was similar across patient subgroups.
Overall survival results are not yet mature, according to Dr. Kudo. Overall response rate and disease control rate did not differ significantly between groups.
Adding sorafenib to TACE led to higher rates of certain grade 3 adverse events, including thrombocytopenia (12.8% vs. 2.8%), hand-foot skin reaction (5.1% vs. 0%), and hypertension (10.3% vs. 4.2%). But there were no unexpected events.
The trial’s positive results contrast with those of the earlier randomized Post-TACE trial, SPACE trial, and TACE 2 trial, noted Dr. Kudo. This may be due to both the new, narrower definition of progression and the longer duration of sorafenib therapy in TACTICS (median 38.7 weeks) as compared with those trials (17.0-21.0 weeks).
“The TACTICS trial clearly showed TACE in combination with sorafenib is a treatment option to improve clinical outcome and may be a standard of care in patients with intermediate-stage HCC,” he concluded.
CELESTIAL trial
The 707 patients in the phase 3 CELESTIAL trial, sponsored by Exelixis, had advanced HCC with Child-Pugh class A and had previously received sorafenib. About 70% had received only one prior systemic regimen for their advanced disease, according to lead investigator Ghassan K. Abou-Alfa, MD, a medical oncologist at the Memorial Sloan Kettering Cancer Center, New York.
Median overall survival was 10.2 months with cabozantinib and 8.0 months with placebo (HR, 0.76; P = .0049). Median progression-free survival was 5.2 months and 1.9 months, respectively (HR, 0.44; P less than .0001). For both outcomes, benefit was similar across most patient subgroups and among patients whose only prior therapy was sorafenib.
The objective response rate was 4% with cabozantinib (all partial responses) and 0.4% with placebo. Median time to subsequent systemic anticancer therapy – most commonly cytotoxic chemotherapy – was 6.6 months with the drug and 3.3 months with placebo.
Median duration of treatment was 3.8 months and 2.0 months, respectively. The rate of discontinuation from treatment-related adverse events was 16% and 3%.
Grade 3 or 4 adverse events occurred in 68% of patients in the cabozantinib group (mainly hand-foot syndrome, hypertension, and gastrointestinal events) and 36% in the placebo group. Six patients in the former group and one in the latter group had grade 5 treatment-related adverse events, most due to worsening of hepatic function.
“Cabozantinib represents a new treatment option for advanced HCC patients after prior systemic anticancer therapy,” concluded Dr. Abou-Alfa.
New treatments increase options, complexity
The new endpoint of unTACEable progression used in TACTICS “is an interesting potential surrogate endpoint for survival. It probably needs to be refined. I would not follow exactly the Japanese methodology,” said Dr. Bruix, the invited discussant.
“More importantly, it needs to be validated,” he added. “The survival data need to be there to see what is the value of the surrogate intermediate endpoint.”
The pattern of overall survival thus far suggests that an early advantage from adding sorafenib to TACE is lost over time. “Potentially, what we have here is the treatment maintained a bit beyond what would be recommended in the Western guidelines,” proposed Dr. Bruix, professor of medicine at the University of Barcelona and director of the Barcelona Clinic Liver Cancer Group. “The longer duration of sorafenib obviously may be related to the specific management in Japan, but also to the fact that progression recognition is delayed. If you delay recognition, you delay the definition of treatment interruption.”
Results of TACTICS probably will not lead to incorporation of sorafenib in clinical practice at this time, he concluded. “This will take a while. There is lots of noise in the chemoembolization trials, there are lots of discussions about what should be done.” In addition, “this should be studied in the West and in a large sample size.”
In the CELESTIAL trial, it would have been helpful to see biomarker data (given that tumor MET status may influence benefit from cabozantinib) and patient stratification according to reason for stopping prior sorafenib (intolerance versus progression), according to Dr. Bruix.
Furthermore, pattern of progression was not reported. “What drives a poorer outcome [in HCC] is the extrahepatic dissemination, meaning vascular invasion or extrahepatic spread. The trials, at least as a post hoc analysis, should have nowadays this kind of analysis that I think is not going to be available in the cabozantinib trial,” he said.
The fact that time to progression with cabozantinib was longer than time on the drug hints at possible safety and tolerability issues, according to Dr. Bruix. “This makes me suspect that some patients had something prior to progression that primed treatment interruption. This is something that I would like to see better explored … to understand to what extent the drug is safe, can be managed, or whether there are too many treatment interruptions that can lead to this discrepancy.”
All of the emerging systemic therapies for first- and second-line therapy in HCC, now also including immune checkpoint inhibitors, are likely to complicate the treatment landscape in the next few years, he cautioned. “The positioning of agents and the sequencing of treatments is different across the world. So there may be confusion in the field and that will affect all the trials that are going to be run by different companies, because if we do not maintain the discipline, patients will jump from one trial to the other and the follow-up after progression will be contaminated.” Ultimately, this could lead to noninformative trials.
Finally, “something that needs to be stated is that all the agents that are positive act on the VEGF pathway. This leaves a proportion of patients that cannot benefit from these agents because of comorbidity that are still in need of something that improves survival,” Dr. Bruix concluded. “We all should focus beyond VEGF and try to develop new strategies.”
SOURCE: Kudo M et al. GI Cancers Symposium, Abstract 206. Abou-Alfa GK et al. GI Cancers Symposium, Abstract 207.
SAN FRANCISCO – Two new therapies that target vascular endothelial growth factor signaling are efficacious and may expand the treatment armamentarium for intermediate and advanced hepatocellular carcinoma, data from a pair of randomized trials suggest.
In the phase 2 TACTICS (Transcatheter Arterial Chemoembolization Therapy in Combination With Sorafenib) trial, median progression-free survival, using a new, more narrow definition of progression, was almost a year longer when the oral tyrosine kinase inhibitor sorafenib (Nexavar) was added to transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC), translating to a 41% reduction in risk of events. This benefit came at the price of higher rates of certain grade 3 adverse events, but the combination was overall feasible and safe.
Results of both trials were reported at the 2018 GI Cancers Symposium, sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
As welcome as such new therapeutic options are, they will likely increase the complexity of the treatment landscape for HCC and could muddy the ability of future trials to establish survival benefit, Jordi Bruix, MD, PhD, cautioned in an invited discussion. In addition, patients who cannot receive anti–vascular endothelial growth factor (VEGF) therapy because of comorbidities still represent an unmet need, underscoring the importance of continued research on other fronts.
TACTICS trial
“Because TACE has been shown to lead to a spike in the intratumoral concentration of VEGF, blockade of VEGF receptors may prevent the effects of a surge in proangiogenic factors,” said TACTICS lead investigator Masatoshi Kudo, MD, professor and chairman of the department of gastroenterology and hepatology at Kindai University, Osaka, Japan. “Since TACE and sorafenib have been shown to prolong survival in patients with unresectable HCC, their combination may improve clinical outcomes.”
The 156 patients enrolled in the TACTICS trial, sponsored by the Japan Liver Oncology Group, had unresectable HCC, a Child-Pugh score of 7 or lower, and no vascular invasion or extrahepatic spread.
They were randomly assigned to as-needed TACE alone or TACE plus sorafenib, which inhibits VEGF receptors, platelet-derived growth factor receptors, and Raf kinases, reducing growth signaling and angiogenesis. Sorafenib therapy was interrupted only for several days before and after each TACE session.
With a median follow-up of 2.4 years, median progression-free survival using a new definition of progression – either untreatable “unTACEable” disease or TACE failure/refractoriness (by Japanese Society of Hepatology criteria) – was 25.2 months with TACE plus sorafenib compared with 13.5 months with TACE alone (hazard ratio, 0.59; P = .006). Benefit was similar across patient subgroups.
Overall survival results are not yet mature, according to Dr. Kudo. Overall response rate and disease control rate did not differ significantly between groups.
Adding sorafenib to TACE led to higher rates of certain grade 3 adverse events, including thrombocytopenia (12.8% vs. 2.8%), hand-foot skin reaction (5.1% vs. 0%), and hypertension (10.3% vs. 4.2%). But there were no unexpected events.
The trial’s positive results contrast with those of the earlier randomized Post-TACE trial, SPACE trial, and TACE 2 trial, noted Dr. Kudo. This may be due to both the new, narrower definition of progression and the longer duration of sorafenib therapy in TACTICS (median 38.7 weeks) as compared with those trials (17.0-21.0 weeks).
“The TACTICS trial clearly showed TACE in combination with sorafenib is a treatment option to improve clinical outcome and may be a standard of care in patients with intermediate-stage HCC,” he concluded.
CELESTIAL trial
The 707 patients in the phase 3 CELESTIAL trial, sponsored by Exelixis, had advanced HCC with Child-Pugh class A and had previously received sorafenib. About 70% had received only one prior systemic regimen for their advanced disease, according to lead investigator Ghassan K. Abou-Alfa, MD, a medical oncologist at the Memorial Sloan Kettering Cancer Center, New York.
Median overall survival was 10.2 months with cabozantinib and 8.0 months with placebo (HR, 0.76; P = .0049). Median progression-free survival was 5.2 months and 1.9 months, respectively (HR, 0.44; P less than .0001). For both outcomes, benefit was similar across most patient subgroups and among patients whose only prior therapy was sorafenib.
The objective response rate was 4% with cabozantinib (all partial responses) and 0.4% with placebo. Median time to subsequent systemic anticancer therapy – most commonly cytotoxic chemotherapy – was 6.6 months with the drug and 3.3 months with placebo.
Median duration of treatment was 3.8 months and 2.0 months, respectively. The rate of discontinuation from treatment-related adverse events was 16% and 3%.
Grade 3 or 4 adverse events occurred in 68% of patients in the cabozantinib group (mainly hand-foot syndrome, hypertension, and gastrointestinal events) and 36% in the placebo group. Six patients in the former group and one in the latter group had grade 5 treatment-related adverse events, most due to worsening of hepatic function.
“Cabozantinib represents a new treatment option for advanced HCC patients after prior systemic anticancer therapy,” concluded Dr. Abou-Alfa.
New treatments increase options, complexity
The new endpoint of unTACEable progression used in TACTICS “is an interesting potential surrogate endpoint for survival. It probably needs to be refined. I would not follow exactly the Japanese methodology,” said Dr. Bruix, the invited discussant.
“More importantly, it needs to be validated,” he added. “The survival data need to be there to see what is the value of the surrogate intermediate endpoint.”
The pattern of overall survival thus far suggests that an early advantage from adding sorafenib to TACE is lost over time. “Potentially, what we have here is the treatment maintained a bit beyond what would be recommended in the Western guidelines,” proposed Dr. Bruix, professor of medicine at the University of Barcelona and director of the Barcelona Clinic Liver Cancer Group. “The longer duration of sorafenib obviously may be related to the specific management in Japan, but also to the fact that progression recognition is delayed. If you delay recognition, you delay the definition of treatment interruption.”
Results of TACTICS probably will not lead to incorporation of sorafenib in clinical practice at this time, he concluded. “This will take a while. There is lots of noise in the chemoembolization trials, there are lots of discussions about what should be done.” In addition, “this should be studied in the West and in a large sample size.”
In the CELESTIAL trial, it would have been helpful to see biomarker data (given that tumor MET status may influence benefit from cabozantinib) and patient stratification according to reason for stopping prior sorafenib (intolerance versus progression), according to Dr. Bruix.
Furthermore, pattern of progression was not reported. “What drives a poorer outcome [in HCC] is the extrahepatic dissemination, meaning vascular invasion or extrahepatic spread. The trials, at least as a post hoc analysis, should have nowadays this kind of analysis that I think is not going to be available in the cabozantinib trial,” he said.
The fact that time to progression with cabozantinib was longer than time on the drug hints at possible safety and tolerability issues, according to Dr. Bruix. “This makes me suspect that some patients had something prior to progression that primed treatment interruption. This is something that I would like to see better explored … to understand to what extent the drug is safe, can be managed, or whether there are too many treatment interruptions that can lead to this discrepancy.”
All of the emerging systemic therapies for first- and second-line therapy in HCC, now also including immune checkpoint inhibitors, are likely to complicate the treatment landscape in the next few years, he cautioned. “The positioning of agents and the sequencing of treatments is different across the world. So there may be confusion in the field and that will affect all the trials that are going to be run by different companies, because if we do not maintain the discipline, patients will jump from one trial to the other and the follow-up after progression will be contaminated.” Ultimately, this could lead to noninformative trials.
Finally, “something that needs to be stated is that all the agents that are positive act on the VEGF pathway. This leaves a proportion of patients that cannot benefit from these agents because of comorbidity that are still in need of something that improves survival,” Dr. Bruix concluded. “We all should focus beyond VEGF and try to develop new strategies.”
SOURCE: Kudo M et al. GI Cancers Symposium, Abstract 206. Abou-Alfa GK et al. GI Cancers Symposium, Abstract 207.
SAN FRANCISCO – Two new therapies that target vascular endothelial growth factor signaling are efficacious and may expand the treatment armamentarium for intermediate and advanced hepatocellular carcinoma, data from a pair of randomized trials suggest.
In the phase 2 TACTICS (Transcatheter Arterial Chemoembolization Therapy in Combination With Sorafenib) trial, median progression-free survival, using a new, more narrow definition of progression, was almost a year longer when the oral tyrosine kinase inhibitor sorafenib (Nexavar) was added to transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC), translating to a 41% reduction in risk of events. This benefit came at the price of higher rates of certain grade 3 adverse events, but the combination was overall feasible and safe.
Results of both trials were reported at the 2018 GI Cancers Symposium, sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
As welcome as such new therapeutic options are, they will likely increase the complexity of the treatment landscape for HCC and could muddy the ability of future trials to establish survival benefit, Jordi Bruix, MD, PhD, cautioned in an invited discussion. In addition, patients who cannot receive anti–vascular endothelial growth factor (VEGF) therapy because of comorbidities still represent an unmet need, underscoring the importance of continued research on other fronts.
TACTICS trial
“Because TACE has been shown to lead to a spike in the intratumoral concentration of VEGF, blockade of VEGF receptors may prevent the effects of a surge in proangiogenic factors,” said TACTICS lead investigator Masatoshi Kudo, MD, professor and chairman of the department of gastroenterology and hepatology at Kindai University, Osaka, Japan. “Since TACE and sorafenib have been shown to prolong survival in patients with unresectable HCC, their combination may improve clinical outcomes.”
The 156 patients enrolled in the TACTICS trial, sponsored by the Japan Liver Oncology Group, had unresectable HCC, a Child-Pugh score of 7 or lower, and no vascular invasion or extrahepatic spread.
They were randomly assigned to as-needed TACE alone or TACE plus sorafenib, which inhibits VEGF receptors, platelet-derived growth factor receptors, and Raf kinases, reducing growth signaling and angiogenesis. Sorafenib therapy was interrupted only for several days before and after each TACE session.
With a median follow-up of 2.4 years, median progression-free survival using a new definition of progression – either untreatable “unTACEable” disease or TACE failure/refractoriness (by Japanese Society of Hepatology criteria) – was 25.2 months with TACE plus sorafenib compared with 13.5 months with TACE alone (hazard ratio, 0.59; P = .006). Benefit was similar across patient subgroups.
Overall survival results are not yet mature, according to Dr. Kudo. Overall response rate and disease control rate did not differ significantly between groups.
Adding sorafenib to TACE led to higher rates of certain grade 3 adverse events, including thrombocytopenia (12.8% vs. 2.8%), hand-foot skin reaction (5.1% vs. 0%), and hypertension (10.3% vs. 4.2%). But there were no unexpected events.
The trial’s positive results contrast with those of the earlier randomized Post-TACE trial, SPACE trial, and TACE 2 trial, noted Dr. Kudo. This may be due to both the new, narrower definition of progression and the longer duration of sorafenib therapy in TACTICS (median 38.7 weeks) as compared with those trials (17.0-21.0 weeks).
“The TACTICS trial clearly showed TACE in combination with sorafenib is a treatment option to improve clinical outcome and may be a standard of care in patients with intermediate-stage HCC,” he concluded.
CELESTIAL trial
The 707 patients in the phase 3 CELESTIAL trial, sponsored by Exelixis, had advanced HCC with Child-Pugh class A and had previously received sorafenib. About 70% had received only one prior systemic regimen for their advanced disease, according to lead investigator Ghassan K. Abou-Alfa, MD, a medical oncologist at the Memorial Sloan Kettering Cancer Center, New York.
Median overall survival was 10.2 months with cabozantinib and 8.0 months with placebo (HR, 0.76; P = .0049). Median progression-free survival was 5.2 months and 1.9 months, respectively (HR, 0.44; P less than .0001). For both outcomes, benefit was similar across most patient subgroups and among patients whose only prior therapy was sorafenib.
The objective response rate was 4% with cabozantinib (all partial responses) and 0.4% with placebo. Median time to subsequent systemic anticancer therapy – most commonly cytotoxic chemotherapy – was 6.6 months with the drug and 3.3 months with placebo.
Median duration of treatment was 3.8 months and 2.0 months, respectively. The rate of discontinuation from treatment-related adverse events was 16% and 3%.
Grade 3 or 4 adverse events occurred in 68% of patients in the cabozantinib group (mainly hand-foot syndrome, hypertension, and gastrointestinal events) and 36% in the placebo group. Six patients in the former group and one in the latter group had grade 5 treatment-related adverse events, most due to worsening of hepatic function.
“Cabozantinib represents a new treatment option for advanced HCC patients after prior systemic anticancer therapy,” concluded Dr. Abou-Alfa.
New treatments increase options, complexity
The new endpoint of unTACEable progression used in TACTICS “is an interesting potential surrogate endpoint for survival. It probably needs to be refined. I would not follow exactly the Japanese methodology,” said Dr. Bruix, the invited discussant.
“More importantly, it needs to be validated,” he added. “The survival data need to be there to see what is the value of the surrogate intermediate endpoint.”
The pattern of overall survival thus far suggests that an early advantage from adding sorafenib to TACE is lost over time. “Potentially, what we have here is the treatment maintained a bit beyond what would be recommended in the Western guidelines,” proposed Dr. Bruix, professor of medicine at the University of Barcelona and director of the Barcelona Clinic Liver Cancer Group. “The longer duration of sorafenib obviously may be related to the specific management in Japan, but also to the fact that progression recognition is delayed. If you delay recognition, you delay the definition of treatment interruption.”
Results of TACTICS probably will not lead to incorporation of sorafenib in clinical practice at this time, he concluded. “This will take a while. There is lots of noise in the chemoembolization trials, there are lots of discussions about what should be done.” In addition, “this should be studied in the West and in a large sample size.”
In the CELESTIAL trial, it would have been helpful to see biomarker data (given that tumor MET status may influence benefit from cabozantinib) and patient stratification according to reason for stopping prior sorafenib (intolerance versus progression), according to Dr. Bruix.
Furthermore, pattern of progression was not reported. “What drives a poorer outcome [in HCC] is the extrahepatic dissemination, meaning vascular invasion or extrahepatic spread. The trials, at least as a post hoc analysis, should have nowadays this kind of analysis that I think is not going to be available in the cabozantinib trial,” he said.
The fact that time to progression with cabozantinib was longer than time on the drug hints at possible safety and tolerability issues, according to Dr. Bruix. “This makes me suspect that some patients had something prior to progression that primed treatment interruption. This is something that I would like to see better explored … to understand to what extent the drug is safe, can be managed, or whether there are too many treatment interruptions that can lead to this discrepancy.”
All of the emerging systemic therapies for first- and second-line therapy in HCC, now also including immune checkpoint inhibitors, are likely to complicate the treatment landscape in the next few years, he cautioned. “The positioning of agents and the sequencing of treatments is different across the world. So there may be confusion in the field and that will affect all the trials that are going to be run by different companies, because if we do not maintain the discipline, patients will jump from one trial to the other and the follow-up after progression will be contaminated.” Ultimately, this could lead to noninformative trials.
Finally, “something that needs to be stated is that all the agents that are positive act on the VEGF pathway. This leaves a proportion of patients that cannot benefit from these agents because of comorbidity that are still in need of something that improves survival,” Dr. Bruix concluded. “We all should focus beyond VEGF and try to develop new strategies.”
SOURCE: Kudo M et al. GI Cancers Symposium, Abstract 206. Abou-Alfa GK et al. GI Cancers Symposium, Abstract 207.
REPORTING FROM THE 2018 GI CANCERS SYMPOSIUM
Key clinical point:
Major finding: Progression-free survival was longer with TACE plus sorafenib vs. TACE alone (25.2 vs. 13.5 months; P = .006). Overall survival was longer with cabozantinib vs. placebo (10.2 vs. 8.0 months; P = .0049).
Data source: A randomized phase 2 trial among 156 patients with unresectable HCC (TACTICS trial). A randomized phase 3 trial among 707 patients with advanced HCC previously treated with sorafenib (CELESTIAL trial).
Disclosures: Dr. Kudo disclosed that he receives honoraria and research funding from, and has a consulting or advisory role with Bayer, among other disclosures; TACTICS was sponsored by the Japan Liver Oncology Group. Dr. Abou-Alfa disclosed that his institution receives research funding from Exelixis, among other disclosures; CELESTIAL was sponsored by Exelixis.
Source: Kudo M et al. GI Cancers Symposium, Abstract 206. Abou-Alfa GK et al. GI Cancers Symposium, Abstract 207.
Reconstruction may reduce chest-related distress in transmasculine youth
, according to study results.
This study is one of the first to document the ongoing impact of chest dysphoria in transgender youths, defined as individuals assigned female at birth who have a masculine gender identity.
“Given these findings, professional guidelines and clinical practice should consider patients for chest surgery based on individual need rather than chronologic age,” said Johanna Olson-Kennedy, MD, of the division of adolescent medicine at Children’s Hospital Los Angeles, and her coauthors.
National guidelines on transgender health care are unclear as to whether minors should be referred for chest surgery because of a lack of data documenting effects of chest surgery in individuals younger than 18 years of age, Dr. Olson-Kennedy and her colleagues wrote in the study, published in JAMA Pediatrics.
To evaluate the discomfort and subsequent consequences of chest dysphoria, the researchers developed a 10-minute, 21-item survey based on Dr. Olson-Kennedy’s 11 years of experience providing care for transgender youth. It was reviewed by a small number of transmasculine youth and adults to determine whether the questions contained the elements of chest dysphoria effectively, used appropriate language, and was otherwise acceptable. From the survey, the researchers derived a chest dysphoria composite score of 0-51, with higher scores indicating increased distress.
Some of the items on the chest dysphoria survey included avoiding exercise, not seeking medical care, and not swimming because of “my chest,” and that taking a shower is difficult as is dating and physical intimacy.
The study included surveys completed by nonsurgical (n = 68) and postsurgical (n = 68) cohorts of transmasculine individuals aged 13-25 years.
The chest dysphoria composite score was significantly higher for minors and young adults who had not undergone chest reconstruction, compared with those who had undergone the procedure (29.6 vs. 3.3; P less than .001), the investigators reported.
Among transmasculine youths who had not undergone surgery, 94% perceived the procedure as very important, Dr. Olson-Kennedy and her coauthors noted.
Moreover, chest dysphoria increased by 0.33 points for every month that passed between a youth starting testosterone therapy and undergoing surgery, results of a linear regression analysis showed.
Most survey respondents reported that they were currently taking testosterone: 87% of the nonsurgical group and 97% of the postsurgical group.
Of the individuals who had undergone chest reconstruction, one (less than 1%) reported regretting the procedure “sometimes,” said Dr. Olson-Kennedy and her coauthors.
The mean age of survey participants was 17 (13-23 years) and 19 years (14-25 years) in the nonsurgical and postsurgical cohorts, respectively.Based on the results, Dr. Olson-Kennedy and her associates called for changes to clinical practice and to insurance plans, which sometimes require 12 months of continuous testosterone therapy prior to chest surgery. “Individualized, patient-centered care plans should be considered the standard of care for all transgender adolescents, and referrals should be made accordingly.”
Dr. Olson-Kennedy and her coauthors reported no conflicts of interest related to the study, which was funded by the Eunice Kennedy Shriver National Institute for Child Health and Human Development.
SOURCE: Olson-Kennedy J et al. JAMA Pediatrics. 2018 Mar 5. doi: 10.1001/jamapediatrics.2017.5440.
, according to study results.
This study is one of the first to document the ongoing impact of chest dysphoria in transgender youths, defined as individuals assigned female at birth who have a masculine gender identity.
“Given these findings, professional guidelines and clinical practice should consider patients for chest surgery based on individual need rather than chronologic age,” said Johanna Olson-Kennedy, MD, of the division of adolescent medicine at Children’s Hospital Los Angeles, and her coauthors.
National guidelines on transgender health care are unclear as to whether minors should be referred for chest surgery because of a lack of data documenting effects of chest surgery in individuals younger than 18 years of age, Dr. Olson-Kennedy and her colleagues wrote in the study, published in JAMA Pediatrics.
To evaluate the discomfort and subsequent consequences of chest dysphoria, the researchers developed a 10-minute, 21-item survey based on Dr. Olson-Kennedy’s 11 years of experience providing care for transgender youth. It was reviewed by a small number of transmasculine youth and adults to determine whether the questions contained the elements of chest dysphoria effectively, used appropriate language, and was otherwise acceptable. From the survey, the researchers derived a chest dysphoria composite score of 0-51, with higher scores indicating increased distress.
Some of the items on the chest dysphoria survey included avoiding exercise, not seeking medical care, and not swimming because of “my chest,” and that taking a shower is difficult as is dating and physical intimacy.
The study included surveys completed by nonsurgical (n = 68) and postsurgical (n = 68) cohorts of transmasculine individuals aged 13-25 years.
The chest dysphoria composite score was significantly higher for minors and young adults who had not undergone chest reconstruction, compared with those who had undergone the procedure (29.6 vs. 3.3; P less than .001), the investigators reported.
Among transmasculine youths who had not undergone surgery, 94% perceived the procedure as very important, Dr. Olson-Kennedy and her coauthors noted.
Moreover, chest dysphoria increased by 0.33 points for every month that passed between a youth starting testosterone therapy and undergoing surgery, results of a linear regression analysis showed.
Most survey respondents reported that they were currently taking testosterone: 87% of the nonsurgical group and 97% of the postsurgical group.
Of the individuals who had undergone chest reconstruction, one (less than 1%) reported regretting the procedure “sometimes,” said Dr. Olson-Kennedy and her coauthors.
The mean age of survey participants was 17 (13-23 years) and 19 years (14-25 years) in the nonsurgical and postsurgical cohorts, respectively.Based on the results, Dr. Olson-Kennedy and her associates called for changes to clinical practice and to insurance plans, which sometimes require 12 months of continuous testosterone therapy prior to chest surgery. “Individualized, patient-centered care plans should be considered the standard of care for all transgender adolescents, and referrals should be made accordingly.”
Dr. Olson-Kennedy and her coauthors reported no conflicts of interest related to the study, which was funded by the Eunice Kennedy Shriver National Institute for Child Health and Human Development.
SOURCE: Olson-Kennedy J et al. JAMA Pediatrics. 2018 Mar 5. doi: 10.1001/jamapediatrics.2017.5440.
, according to study results.
This study is one of the first to document the ongoing impact of chest dysphoria in transgender youths, defined as individuals assigned female at birth who have a masculine gender identity.
“Given these findings, professional guidelines and clinical practice should consider patients for chest surgery based on individual need rather than chronologic age,” said Johanna Olson-Kennedy, MD, of the division of adolescent medicine at Children’s Hospital Los Angeles, and her coauthors.
National guidelines on transgender health care are unclear as to whether minors should be referred for chest surgery because of a lack of data documenting effects of chest surgery in individuals younger than 18 years of age, Dr. Olson-Kennedy and her colleagues wrote in the study, published in JAMA Pediatrics.
To evaluate the discomfort and subsequent consequences of chest dysphoria, the researchers developed a 10-minute, 21-item survey based on Dr. Olson-Kennedy’s 11 years of experience providing care for transgender youth. It was reviewed by a small number of transmasculine youth and adults to determine whether the questions contained the elements of chest dysphoria effectively, used appropriate language, and was otherwise acceptable. From the survey, the researchers derived a chest dysphoria composite score of 0-51, with higher scores indicating increased distress.
Some of the items on the chest dysphoria survey included avoiding exercise, not seeking medical care, and not swimming because of “my chest,” and that taking a shower is difficult as is dating and physical intimacy.
The study included surveys completed by nonsurgical (n = 68) and postsurgical (n = 68) cohorts of transmasculine individuals aged 13-25 years.
The chest dysphoria composite score was significantly higher for minors and young adults who had not undergone chest reconstruction, compared with those who had undergone the procedure (29.6 vs. 3.3; P less than .001), the investigators reported.
Among transmasculine youths who had not undergone surgery, 94% perceived the procedure as very important, Dr. Olson-Kennedy and her coauthors noted.
Moreover, chest dysphoria increased by 0.33 points for every month that passed between a youth starting testosterone therapy and undergoing surgery, results of a linear regression analysis showed.
Most survey respondents reported that they were currently taking testosterone: 87% of the nonsurgical group and 97% of the postsurgical group.
Of the individuals who had undergone chest reconstruction, one (less than 1%) reported regretting the procedure “sometimes,” said Dr. Olson-Kennedy and her coauthors.
The mean age of survey participants was 17 (13-23 years) and 19 years (14-25 years) in the nonsurgical and postsurgical cohorts, respectively.Based on the results, Dr. Olson-Kennedy and her associates called for changes to clinical practice and to insurance plans, which sometimes require 12 months of continuous testosterone therapy prior to chest surgery. “Individualized, patient-centered care plans should be considered the standard of care for all transgender adolescents, and referrals should be made accordingly.”
Dr. Olson-Kennedy and her coauthors reported no conflicts of interest related to the study, which was funded by the Eunice Kennedy Shriver National Institute for Child Health and Human Development.
SOURCE: Olson-Kennedy J et al. JAMA Pediatrics. 2018 Mar 5. doi: 10.1001/jamapediatrics.2017.5440.
FROM JAMA PEDIATRICS
Key clinical point: Chest surgery for transmasculine youths should be considered based on individual needs, rather than chronologic age.
Major finding: Chest dysphoria composite score was higher for minors and young adults who had not undergone chest reconstruction, compared with those who had undergone the procedure (P less than .001).
Study details: Comparison of surveys completed by nonsurgical (n = 68) and postsurgical (n = 68) cohorts of individuals 13-25years old who were assigned female at birth but identified as masculine.
Disclosures: The Eunice Kennedy Shriver National Institute for Child Health and Human Development funded the study. The authors reported no conflicts of interest.
Source: Olson-Kennedy J et al. JAMA Pediatrics. 2018 Mar 5. doi: 10.1001/jamapediatrics.2017.5440.
Excellent prognosis for cystic RCC evaluated with radiologic threshold of greater than 50%
When a standardized radiologic threshold of greater than 50% is used, patients with unifocal cystic renal cell carcinoma (cRCC) have an excellent prognosis with active surveillance and following surgical resection, findings from a new study show.
At a median follow-up of 5.4 years (IQR 2.8-7.8), none of the 138 patients in the cohort experienced a tumor recurrence or metastasis from cRCC, and 7 (5.1%) died from non–renal-related causes. When comparing patients who initially underwent surgery to those who were initially managed with active surveillance, the researchers found that there was no significant difference in overall survival (P = .07). There were no deaths due to kidney cancer in the entire cohort.
The terminology of cRCC has historically been used to describe an indolent version of RCC that consists primarily of cysts, and the threshold of cystic involvement has traditionally been greater than 75% cystic on pathologic examination.
However, this classification does not contribute to the preoperative decision-making process, the study authors noted in Journal of Urology.
“Cross-sectional imaging provides the benefit of assessing tumor morphology without surgical manipulation, allowing for an accurate assessment of the solid and cystic components and classification of cRCC ,” write Ari Hakimi, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues.
Studies evaluating radiologic criteria for cRCC diagnosis have suggested that cystic changes in 5%-45% of the total mass observed on imaging are associated with favorable survival. Thus, the authors sought to improve the preoperative assessment of cystic renal masses by evaluating cRCC as an enhancing renal lesion that is greater than 50% cystic on cross-sectional imaging. The goal of the current study was then to compare the long-term outcomes of patients with cRCC who underwent surgery and active surveillance using this hypothesized threshold.
The cohort included 138 patients who underwent surgery at Memorial Sloan Kettering Cancer Center for a renal mass from January 2000 to December 2015, and of this group, 102 (73.9%) had renal cell carcinoma and 36 (26.1%) had benign masses. Most of the tumors were Fuhrman grade 1-2 (77.5%), ≤pT2 stage (83.4%) and clear cell histology (65.9%), while the majority of cRCC lesions were Bosniak 3 and 4 (93.5%) and had a solid component of less than 25% (83.3%). On multivariate analysis, men (P = .007) were more likely to have malignant lesions and Bosniak 3 lesions were more likely to be malignant (P = .01).
In the subgroup of 38 active surveillance patients, 27 (71.1%) remained on active surveillance while 11 (28.9%) subsequently had surgery, of which all underwent partial nephrectomy. The median overall growth rate for lesions was 1.0 mm/year (IQR 0-2.8) over 25.3 months (IQR 16.3-44.8), and no evidence of recurrence or metastasis was reported in any of these patients at a median follow-up of 4.3 years (IQR 2.1-5.7) from first imaging diagnosis or 6.9 years (IQR 4.9-8.5) after surgery.
“We believe that our radiologic definition allows for more inclusive criteria of cRCC and would encourage kidney sparing approaches or implementation of AS protocols when feasible,” the authors concluded.
SOURCE: Hakimi A et al. J Urol. 2018 Feb 26 doi: 10.1016/j.juro.2018.02.3087
When a standardized radiologic threshold of greater than 50% is used, patients with unifocal cystic renal cell carcinoma (cRCC) have an excellent prognosis with active surveillance and following surgical resection, findings from a new study show.
At a median follow-up of 5.4 years (IQR 2.8-7.8), none of the 138 patients in the cohort experienced a tumor recurrence or metastasis from cRCC, and 7 (5.1%) died from non–renal-related causes. When comparing patients who initially underwent surgery to those who were initially managed with active surveillance, the researchers found that there was no significant difference in overall survival (P = .07). There were no deaths due to kidney cancer in the entire cohort.
The terminology of cRCC has historically been used to describe an indolent version of RCC that consists primarily of cysts, and the threshold of cystic involvement has traditionally been greater than 75% cystic on pathologic examination.
However, this classification does not contribute to the preoperative decision-making process, the study authors noted in Journal of Urology.
“Cross-sectional imaging provides the benefit of assessing tumor morphology without surgical manipulation, allowing for an accurate assessment of the solid and cystic components and classification of cRCC ,” write Ari Hakimi, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues.
Studies evaluating radiologic criteria for cRCC diagnosis have suggested that cystic changes in 5%-45% of the total mass observed on imaging are associated with favorable survival. Thus, the authors sought to improve the preoperative assessment of cystic renal masses by evaluating cRCC as an enhancing renal lesion that is greater than 50% cystic on cross-sectional imaging. The goal of the current study was then to compare the long-term outcomes of patients with cRCC who underwent surgery and active surveillance using this hypothesized threshold.
The cohort included 138 patients who underwent surgery at Memorial Sloan Kettering Cancer Center for a renal mass from January 2000 to December 2015, and of this group, 102 (73.9%) had renal cell carcinoma and 36 (26.1%) had benign masses. Most of the tumors were Fuhrman grade 1-2 (77.5%), ≤pT2 stage (83.4%) and clear cell histology (65.9%), while the majority of cRCC lesions were Bosniak 3 and 4 (93.5%) and had a solid component of less than 25% (83.3%). On multivariate analysis, men (P = .007) were more likely to have malignant lesions and Bosniak 3 lesions were more likely to be malignant (P = .01).
In the subgroup of 38 active surveillance patients, 27 (71.1%) remained on active surveillance while 11 (28.9%) subsequently had surgery, of which all underwent partial nephrectomy. The median overall growth rate for lesions was 1.0 mm/year (IQR 0-2.8) over 25.3 months (IQR 16.3-44.8), and no evidence of recurrence or metastasis was reported in any of these patients at a median follow-up of 4.3 years (IQR 2.1-5.7) from first imaging diagnosis or 6.9 years (IQR 4.9-8.5) after surgery.
“We believe that our radiologic definition allows for more inclusive criteria of cRCC and would encourage kidney sparing approaches or implementation of AS protocols when feasible,” the authors concluded.
SOURCE: Hakimi A et al. J Urol. 2018 Feb 26 doi: 10.1016/j.juro.2018.02.3087
When a standardized radiologic threshold of greater than 50% is used, patients with unifocal cystic renal cell carcinoma (cRCC) have an excellent prognosis with active surveillance and following surgical resection, findings from a new study show.
At a median follow-up of 5.4 years (IQR 2.8-7.8), none of the 138 patients in the cohort experienced a tumor recurrence or metastasis from cRCC, and 7 (5.1%) died from non–renal-related causes. When comparing patients who initially underwent surgery to those who were initially managed with active surveillance, the researchers found that there was no significant difference in overall survival (P = .07). There were no deaths due to kidney cancer in the entire cohort.
The terminology of cRCC has historically been used to describe an indolent version of RCC that consists primarily of cysts, and the threshold of cystic involvement has traditionally been greater than 75% cystic on pathologic examination.
However, this classification does not contribute to the preoperative decision-making process, the study authors noted in Journal of Urology.
“Cross-sectional imaging provides the benefit of assessing tumor morphology without surgical manipulation, allowing for an accurate assessment of the solid and cystic components and classification of cRCC ,” write Ari Hakimi, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues.
Studies evaluating radiologic criteria for cRCC diagnosis have suggested that cystic changes in 5%-45% of the total mass observed on imaging are associated with favorable survival. Thus, the authors sought to improve the preoperative assessment of cystic renal masses by evaluating cRCC as an enhancing renal lesion that is greater than 50% cystic on cross-sectional imaging. The goal of the current study was then to compare the long-term outcomes of patients with cRCC who underwent surgery and active surveillance using this hypothesized threshold.
The cohort included 138 patients who underwent surgery at Memorial Sloan Kettering Cancer Center for a renal mass from January 2000 to December 2015, and of this group, 102 (73.9%) had renal cell carcinoma and 36 (26.1%) had benign masses. Most of the tumors were Fuhrman grade 1-2 (77.5%), ≤pT2 stage (83.4%) and clear cell histology (65.9%), while the majority of cRCC lesions were Bosniak 3 and 4 (93.5%) and had a solid component of less than 25% (83.3%). On multivariate analysis, men (P = .007) were more likely to have malignant lesions and Bosniak 3 lesions were more likely to be malignant (P = .01).
In the subgroup of 38 active surveillance patients, 27 (71.1%) remained on active surveillance while 11 (28.9%) subsequently had surgery, of which all underwent partial nephrectomy. The median overall growth rate for lesions was 1.0 mm/year (IQR 0-2.8) over 25.3 months (IQR 16.3-44.8), and no evidence of recurrence or metastasis was reported in any of these patients at a median follow-up of 4.3 years (IQR 2.1-5.7) from first imaging diagnosis or 6.9 years (IQR 4.9-8.5) after surgery.
“We believe that our radiologic definition allows for more inclusive criteria of cRCC and would encourage kidney sparing approaches or implementation of AS protocols when feasible,” the authors concluded.
SOURCE: Hakimi A et al. J Urol. 2018 Feb 26 doi: 10.1016/j.juro.2018.02.3087
FROM THE JOURNAL OF UROLOGY
Key clinical point: Patients with unifocal cystic renal cell carcinoma have an excellent prognosis for both active surveillance and following surgery when evaluated with a standardized radiologic threshold of greater than 50% cystic.
Major finding: There was no evidence of tumor recurrence or metastasis from cRCC at a median follow-up of 5.4 years, and seven patients died of other causes.
Study details: Retrospective single-center study that looked at outcomes and clinicopathologic and oncologic features of 138 cases of cystic renal cell carcinoma.
Disclosures: The study was supported by the Sidney Kimmel Center for Prostate and Urologic Cancers and an NIH/NCI Cancer Center Support Grant. There were no author disclosures listed.
Source: Hakimi A et al. J Urol. 2018 Feb 26 doi: 10.1016/j.juro.2018.02.3087.
CMS issues split decision on Arkansas Medicaid waiver
The Trump administration on March 5 approved Arkansas’ request for a Medicaid work requirement but deferred a decision on the state’s request to roll back its Medicaid expansion that has added 300,000 adults to the program.
Arkansas had sought to reduce the number of people eligible for Medicaid by allowing only those with incomes below the federal poverty level, or about $12,140 for an individual, to qualify. For the past 4 years, Arkansas Medicaid covered everyone with incomes under 138% of the poverty level, or about $16,750. The new policy would have cut the number of people eligible for Medicaid in the state by about 60,000 people.
Seema Verma, administrator of the Centers for Medicare & Medicaid Services, who announced the decision, has said her goal as head of the program was to grant states more flexibility in running their Medicaid programs than they’ve had before.
Arkansas follows Indiana and Kentucky this year in winning CMS’ approval for the work requirement. Arkansas plans to start the new requirement affecting adults under age 50 years by June, making it the first to do so.
Ms. Verma recused herself on CMS’ decisions involving Indiana and Kentucky because she used to consult with those state Medicaid agencies before joining the Trump administration in 2017. As a health care consultant, she also worked with Arkansas. But
CMS officials did not respond to questions about why she did not recuse herself again.
But a top Senate Democrat lambasted Ms. Verma’s decision.
“She pledged during her confirmation to recuse herself from working on many states’ Medicaid waivers to avoid conflicts of interest, including Arkansas, Sen. Ron Wyden (D-Ore.) said in a statement. “The Trump administration has simply made a mockery of the HHS ethics process.”
It is unclear why she deferred deciding on Arkansas’ request to scale back its Medicaid decision. Deferring a decision on rolling back expansion could be a way of rejecting the application but in a less politically harsh way. Arkansas was one of the few Southern states to expand Medicaid under the ACA, a decision that brought hundreds of millions of federal dollars into the state.
Nine other states have requests pending with CMS to enact a Medicaid work requirement.
In Arkansas, enrollees who don’t work or volunteer at least 80 hours a month could lose coverage as early as September. The work requirement exempts many people, such as those with opioid addiction and parents with dependent children.
Ms. Verma said the work requirement “is about helping people rise out of poverty to achieve the American dream.”
But advocates for the poor blasted the move, noting most Medicaid enrollees already work, go to school, or are taking care of sick relatives.
“The Trump administration’s approval of Arkansas’ harsh work requirement in Medicaid will likely set back the state’s considerable progress under the Affordable Care Act in increasing coverage and improving access to care, health and financial stability for low-income Arkansans,” said Judith Solomon, vice president for health policy at the left-leaning Center on Budget and Policy Priorities.
Arkansas officials said they need the work requirement because without it many enrollees won’t seek out work or job training. Since January 2017, fewer than 5% of Medicaid enrollees who were referred to the state Department of Workforce Services to help with job training followed through and accessed services.
Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
The Trump administration on March 5 approved Arkansas’ request for a Medicaid work requirement but deferred a decision on the state’s request to roll back its Medicaid expansion that has added 300,000 adults to the program.
Arkansas had sought to reduce the number of people eligible for Medicaid by allowing only those with incomes below the federal poverty level, or about $12,140 for an individual, to qualify. For the past 4 years, Arkansas Medicaid covered everyone with incomes under 138% of the poverty level, or about $16,750. The new policy would have cut the number of people eligible for Medicaid in the state by about 60,000 people.
Seema Verma, administrator of the Centers for Medicare & Medicaid Services, who announced the decision, has said her goal as head of the program was to grant states more flexibility in running their Medicaid programs than they’ve had before.
Arkansas follows Indiana and Kentucky this year in winning CMS’ approval for the work requirement. Arkansas plans to start the new requirement affecting adults under age 50 years by June, making it the first to do so.
Ms. Verma recused herself on CMS’ decisions involving Indiana and Kentucky because she used to consult with those state Medicaid agencies before joining the Trump administration in 2017. As a health care consultant, she also worked with Arkansas. But
CMS officials did not respond to questions about why she did not recuse herself again.
But a top Senate Democrat lambasted Ms. Verma’s decision.
“She pledged during her confirmation to recuse herself from working on many states’ Medicaid waivers to avoid conflicts of interest, including Arkansas, Sen. Ron Wyden (D-Ore.) said in a statement. “The Trump administration has simply made a mockery of the HHS ethics process.”
It is unclear why she deferred deciding on Arkansas’ request to scale back its Medicaid decision. Deferring a decision on rolling back expansion could be a way of rejecting the application but in a less politically harsh way. Arkansas was one of the few Southern states to expand Medicaid under the ACA, a decision that brought hundreds of millions of federal dollars into the state.
Nine other states have requests pending with CMS to enact a Medicaid work requirement.
In Arkansas, enrollees who don’t work or volunteer at least 80 hours a month could lose coverage as early as September. The work requirement exempts many people, such as those with opioid addiction and parents with dependent children.
Ms. Verma said the work requirement “is about helping people rise out of poverty to achieve the American dream.”
But advocates for the poor blasted the move, noting most Medicaid enrollees already work, go to school, or are taking care of sick relatives.
“The Trump administration’s approval of Arkansas’ harsh work requirement in Medicaid will likely set back the state’s considerable progress under the Affordable Care Act in increasing coverage and improving access to care, health and financial stability for low-income Arkansans,” said Judith Solomon, vice president for health policy at the left-leaning Center on Budget and Policy Priorities.
Arkansas officials said they need the work requirement because without it many enrollees won’t seek out work or job training. Since January 2017, fewer than 5% of Medicaid enrollees who were referred to the state Department of Workforce Services to help with job training followed through and accessed services.
Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
The Trump administration on March 5 approved Arkansas’ request for a Medicaid work requirement but deferred a decision on the state’s request to roll back its Medicaid expansion that has added 300,000 adults to the program.
Arkansas had sought to reduce the number of people eligible for Medicaid by allowing only those with incomes below the federal poverty level, or about $12,140 for an individual, to qualify. For the past 4 years, Arkansas Medicaid covered everyone with incomes under 138% of the poverty level, or about $16,750. The new policy would have cut the number of people eligible for Medicaid in the state by about 60,000 people.
Seema Verma, administrator of the Centers for Medicare & Medicaid Services, who announced the decision, has said her goal as head of the program was to grant states more flexibility in running their Medicaid programs than they’ve had before.
Arkansas follows Indiana and Kentucky this year in winning CMS’ approval for the work requirement. Arkansas plans to start the new requirement affecting adults under age 50 years by June, making it the first to do so.
Ms. Verma recused herself on CMS’ decisions involving Indiana and Kentucky because she used to consult with those state Medicaid agencies before joining the Trump administration in 2017. As a health care consultant, she also worked with Arkansas. But
CMS officials did not respond to questions about why she did not recuse herself again.
But a top Senate Democrat lambasted Ms. Verma’s decision.
“She pledged during her confirmation to recuse herself from working on many states’ Medicaid waivers to avoid conflicts of interest, including Arkansas, Sen. Ron Wyden (D-Ore.) said in a statement. “The Trump administration has simply made a mockery of the HHS ethics process.”
It is unclear why she deferred deciding on Arkansas’ request to scale back its Medicaid decision. Deferring a decision on rolling back expansion could be a way of rejecting the application but in a less politically harsh way. Arkansas was one of the few Southern states to expand Medicaid under the ACA, a decision that brought hundreds of millions of federal dollars into the state.
Nine other states have requests pending with CMS to enact a Medicaid work requirement.
In Arkansas, enrollees who don’t work or volunteer at least 80 hours a month could lose coverage as early as September. The work requirement exempts many people, such as those with opioid addiction and parents with dependent children.
Ms. Verma said the work requirement “is about helping people rise out of poverty to achieve the American dream.”
But advocates for the poor blasted the move, noting most Medicaid enrollees already work, go to school, or are taking care of sick relatives.
“The Trump administration’s approval of Arkansas’ harsh work requirement in Medicaid will likely set back the state’s considerable progress under the Affordable Care Act in increasing coverage and improving access to care, health and financial stability for low-income Arkansans,” said Judith Solomon, vice president for health policy at the left-leaning Center on Budget and Policy Priorities.
Arkansas officials said they need the work requirement because without it many enrollees won’t seek out work or job training. Since January 2017, fewer than 5% of Medicaid enrollees who were referred to the state Department of Workforce Services to help with job training followed through and accessed services.
Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
Lurasidone approved for bipolar I depression for children aged 10-17
The Food and Drug Administration has approved lurasidone HCI (Latuda) for treating bipolar I depression in children and adolescents, according to a March 6 statement from the drug’s manufacturer.
“We know that children who have been diagnosed with bipolar depression can be at risk for poor school performance and impairments in social functioning,” said Robert L. Findling, MD, professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, in the statement.
Approval of the atypical antipsychotic is based on results of a 6-week, randomized placebo-controlled phase 3 study of 347 children and adolescents diagnosed with bipolar I depression. Patients received either 20-80 mg/day of lurasidone or placebo.
Patients who received lurasidone reportedly experienced improved bipolar depression symptoms, compared with placebo, based on “the primary efficacy endpoint of change from baseline to week 6 on the Children’s Depression Rating Scale–Revised total score (–21.0 vs. –15.3; effect size = 0.45; P less than .0001),” the statement said. Clinically relevant changes also were found among patients who took the medication on other measures, including the Clinical Global Impressions-Bipolar Scale.
The most common adverse effects were nausea (16% vs. 5.8%), weight gain (6.9% vs. 1.7%), and insomnia (5.1% vs. 2.3%).
Lurasidone also has been approved for treating schizophrenia and bipolar I depression in adults. Last year, the drug was approved for treating schizophrenia in adolescents.
The Food and Drug Administration has approved lurasidone HCI (Latuda) for treating bipolar I depression in children and adolescents, according to a March 6 statement from the drug’s manufacturer.
“We know that children who have been diagnosed with bipolar depression can be at risk for poor school performance and impairments in social functioning,” said Robert L. Findling, MD, professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, in the statement.
Approval of the atypical antipsychotic is based on results of a 6-week, randomized placebo-controlled phase 3 study of 347 children and adolescents diagnosed with bipolar I depression. Patients received either 20-80 mg/day of lurasidone or placebo.
Patients who received lurasidone reportedly experienced improved bipolar depression symptoms, compared with placebo, based on “the primary efficacy endpoint of change from baseline to week 6 on the Children’s Depression Rating Scale–Revised total score (–21.0 vs. –15.3; effect size = 0.45; P less than .0001),” the statement said. Clinically relevant changes also were found among patients who took the medication on other measures, including the Clinical Global Impressions-Bipolar Scale.
The most common adverse effects were nausea (16% vs. 5.8%), weight gain (6.9% vs. 1.7%), and insomnia (5.1% vs. 2.3%).
Lurasidone also has been approved for treating schizophrenia and bipolar I depression in adults. Last year, the drug was approved for treating schizophrenia in adolescents.
The Food and Drug Administration has approved lurasidone HCI (Latuda) for treating bipolar I depression in children and adolescents, according to a March 6 statement from the drug’s manufacturer.
“We know that children who have been diagnosed with bipolar depression can be at risk for poor school performance and impairments in social functioning,” said Robert L. Findling, MD, professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, in the statement.
Approval of the atypical antipsychotic is based on results of a 6-week, randomized placebo-controlled phase 3 study of 347 children and adolescents diagnosed with bipolar I depression. Patients received either 20-80 mg/day of lurasidone or placebo.
Patients who received lurasidone reportedly experienced improved bipolar depression symptoms, compared with placebo, based on “the primary efficacy endpoint of change from baseline to week 6 on the Children’s Depression Rating Scale–Revised total score (–21.0 vs. –15.3; effect size = 0.45; P less than .0001),” the statement said. Clinically relevant changes also were found among patients who took the medication on other measures, including the Clinical Global Impressions-Bipolar Scale.
The most common adverse effects were nausea (16% vs. 5.8%), weight gain (6.9% vs. 1.7%), and insomnia (5.1% vs. 2.3%).
Lurasidone also has been approved for treating schizophrenia and bipolar I depression in adults. Last year, the drug was approved for treating schizophrenia in adolescents.
HIV diagnosis at home and same-day ART start tied to better outcomes
BOSTON – Diagnosing HIV infections in the home and starting persons who tested positive on antiretroviral therapy on the same day significantly increased the likelihood that the HIV-positive individuals would show up at a clinic for care within 3 months of diagnosis. It also improved their odds for having viral suppression at 12 months, compared with those who tested positive but were referred to a clinic for starting ART therapy, the standard of care.
Among 278 residents of the southern African nation of Lesotho, 68.8% of those randomized to an intervention in which they were offered same-day, home-based ART initiation and were given a 30-day supply of medication had linked to care by 3 months of follow-up, compared with 43.1% of those who were diagnosed and then referred to a health care facility to be started on ART, reported Niklaus D. Labhardt, MD, from the Swiss Tropical and Public Health Institute in Basel, and his colleagues.
“This easy addition to the current practice of home-based testing has the potential to improve practice sub-Saharan African when it will become part of future guidelines and policies,” he said at a media briefing following his presentation of the data in an oral abstract session.
Results from the study were simultaneously published online in JAMA.
Although home-based testing for HIV by trained workers has become common in remote areas such as northern Lesotho, those who test positive may be lost to care and become reservoirs of infection in their communities.
In fact, only 33% of those who test positive at home take the necessary steps to receive care and start on lifelong viral suppression therapy, and “two out of three who tested positive actually remain without ART,” Dr, Labhardt said.
Compressing the testing-to-ART cascade into a single day as a means of getting more patients to start on ART has been accomplished successfully in the clinic, but never before in the home-based setting, he noted.
To see whether same-day ART initiation could be accomplished in the field, Dr. Labhardt and his colleagues designed a multicenter, randomized trial in 278 individuals aged 18 years and older from 268 households. The participants who tested HIV positive and were ART naive were chosen from among 6,655 households in rural villages and 17 urban areas in Lesotho who took part in a home-based testing program.
After giving consent, the participants were randomly assigned to either the same-day or standard of care groups.
In the same-day group, participants were offered home-based ART initiation, given a 1-month supply of drugs, and instructed to visit a specified health facility in 2-4 weeks for their first check-up and refill. The patients were scheduled for additional follow-up visits at 1.5, 3, 6, 9, and 12 months.
In the standard-of-care group, patients received posttest counseling at home and were given an appointment to their nearest health facility within the next 4 weeks; once they were linked to care, they were required to make at least two additional visits for testing prior to starting on ART. Once they started ART, they were given monthly follow-up and drug-refill appointments.
The absolute difference in 3-month linkage rates between the same-day and standard-of-care groups was 25.6% (P = .001), and the difference in 12-month viral suppression rates was 16% (P less than .007).
Retention of care, looking only at those patients who continued visits at their assigned clinics, also was significantly better among patients in the same-day group throughout the study (P = .009).
The investigators acknowledged that the study was limited by being restricted to a rural setting with a very high prevalence of HIV and that they did not have information about the possible development of drug-resistant virus among patients who started on same-day therapy but did not complete the health care link. In addition, there was only limited information available about those patients who neither linked to care or dropped out.
Dr. Labhardt said at the briefing that the same-day intervention could likely be successfully implemented in similar settings in other parts rural Africa with high HIV prevalence.
The study was funded by the Swiss National Science Foundation, Stiftung für Infektiologie beider Basel, and the Gottfried and Julia Bangerter-Rhyner Stiftung. Dr Labhardt reported support from the Stiftung für Infektiologie beider Basel and the Gottfried and Julia Bangerter-Rhyner Foundation and travel support to medical conferences from Gilead Sciences Switzerland Sarl. No other author reported disclosures.
SOURCE: Labhardt ND et al. JAMA. 2018 Mar 1. doi: 10.1001/jama.2018.1818.
BOSTON – Diagnosing HIV infections in the home and starting persons who tested positive on antiretroviral therapy on the same day significantly increased the likelihood that the HIV-positive individuals would show up at a clinic for care within 3 months of diagnosis. It also improved their odds for having viral suppression at 12 months, compared with those who tested positive but were referred to a clinic for starting ART therapy, the standard of care.
Among 278 residents of the southern African nation of Lesotho, 68.8% of those randomized to an intervention in which they were offered same-day, home-based ART initiation and were given a 30-day supply of medication had linked to care by 3 months of follow-up, compared with 43.1% of those who were diagnosed and then referred to a health care facility to be started on ART, reported Niklaus D. Labhardt, MD, from the Swiss Tropical and Public Health Institute in Basel, and his colleagues.
“This easy addition to the current practice of home-based testing has the potential to improve practice sub-Saharan African when it will become part of future guidelines and policies,” he said at a media briefing following his presentation of the data in an oral abstract session.
Results from the study were simultaneously published online in JAMA.
Although home-based testing for HIV by trained workers has become common in remote areas such as northern Lesotho, those who test positive may be lost to care and become reservoirs of infection in their communities.
In fact, only 33% of those who test positive at home take the necessary steps to receive care and start on lifelong viral suppression therapy, and “two out of three who tested positive actually remain without ART,” Dr, Labhardt said.
Compressing the testing-to-ART cascade into a single day as a means of getting more patients to start on ART has been accomplished successfully in the clinic, but never before in the home-based setting, he noted.
To see whether same-day ART initiation could be accomplished in the field, Dr. Labhardt and his colleagues designed a multicenter, randomized trial in 278 individuals aged 18 years and older from 268 households. The participants who tested HIV positive and were ART naive were chosen from among 6,655 households in rural villages and 17 urban areas in Lesotho who took part in a home-based testing program.
After giving consent, the participants were randomly assigned to either the same-day or standard of care groups.
In the same-day group, participants were offered home-based ART initiation, given a 1-month supply of drugs, and instructed to visit a specified health facility in 2-4 weeks for their first check-up and refill. The patients were scheduled for additional follow-up visits at 1.5, 3, 6, 9, and 12 months.
In the standard-of-care group, patients received posttest counseling at home and were given an appointment to their nearest health facility within the next 4 weeks; once they were linked to care, they were required to make at least two additional visits for testing prior to starting on ART. Once they started ART, they were given monthly follow-up and drug-refill appointments.
The absolute difference in 3-month linkage rates between the same-day and standard-of-care groups was 25.6% (P = .001), and the difference in 12-month viral suppression rates was 16% (P less than .007).
Retention of care, looking only at those patients who continued visits at their assigned clinics, also was significantly better among patients in the same-day group throughout the study (P = .009).
The investigators acknowledged that the study was limited by being restricted to a rural setting with a very high prevalence of HIV and that they did not have information about the possible development of drug-resistant virus among patients who started on same-day therapy but did not complete the health care link. In addition, there was only limited information available about those patients who neither linked to care or dropped out.
Dr. Labhardt said at the briefing that the same-day intervention could likely be successfully implemented in similar settings in other parts rural Africa with high HIV prevalence.
The study was funded by the Swiss National Science Foundation, Stiftung für Infektiologie beider Basel, and the Gottfried and Julia Bangerter-Rhyner Stiftung. Dr Labhardt reported support from the Stiftung für Infektiologie beider Basel and the Gottfried and Julia Bangerter-Rhyner Foundation and travel support to medical conferences from Gilead Sciences Switzerland Sarl. No other author reported disclosures.
SOURCE: Labhardt ND et al. JAMA. 2018 Mar 1. doi: 10.1001/jama.2018.1818.
BOSTON – Diagnosing HIV infections in the home and starting persons who tested positive on antiretroviral therapy on the same day significantly increased the likelihood that the HIV-positive individuals would show up at a clinic for care within 3 months of diagnosis. It also improved their odds for having viral suppression at 12 months, compared with those who tested positive but were referred to a clinic for starting ART therapy, the standard of care.
Among 278 residents of the southern African nation of Lesotho, 68.8% of those randomized to an intervention in which they were offered same-day, home-based ART initiation and were given a 30-day supply of medication had linked to care by 3 months of follow-up, compared with 43.1% of those who were diagnosed and then referred to a health care facility to be started on ART, reported Niklaus D. Labhardt, MD, from the Swiss Tropical and Public Health Institute in Basel, and his colleagues.
“This easy addition to the current practice of home-based testing has the potential to improve practice sub-Saharan African when it will become part of future guidelines and policies,” he said at a media briefing following his presentation of the data in an oral abstract session.
Results from the study were simultaneously published online in JAMA.
Although home-based testing for HIV by trained workers has become common in remote areas such as northern Lesotho, those who test positive may be lost to care and become reservoirs of infection in their communities.
In fact, only 33% of those who test positive at home take the necessary steps to receive care and start on lifelong viral suppression therapy, and “two out of three who tested positive actually remain without ART,” Dr, Labhardt said.
Compressing the testing-to-ART cascade into a single day as a means of getting more patients to start on ART has been accomplished successfully in the clinic, but never before in the home-based setting, he noted.
To see whether same-day ART initiation could be accomplished in the field, Dr. Labhardt and his colleagues designed a multicenter, randomized trial in 278 individuals aged 18 years and older from 268 households. The participants who tested HIV positive and were ART naive were chosen from among 6,655 households in rural villages and 17 urban areas in Lesotho who took part in a home-based testing program.
After giving consent, the participants were randomly assigned to either the same-day or standard of care groups.
In the same-day group, participants were offered home-based ART initiation, given a 1-month supply of drugs, and instructed to visit a specified health facility in 2-4 weeks for their first check-up and refill. The patients were scheduled for additional follow-up visits at 1.5, 3, 6, 9, and 12 months.
In the standard-of-care group, patients received posttest counseling at home and were given an appointment to their nearest health facility within the next 4 weeks; once they were linked to care, they were required to make at least two additional visits for testing prior to starting on ART. Once they started ART, they were given monthly follow-up and drug-refill appointments.
The absolute difference in 3-month linkage rates between the same-day and standard-of-care groups was 25.6% (P = .001), and the difference in 12-month viral suppression rates was 16% (P less than .007).
Retention of care, looking only at those patients who continued visits at their assigned clinics, also was significantly better among patients in the same-day group throughout the study (P = .009).
The investigators acknowledged that the study was limited by being restricted to a rural setting with a very high prevalence of HIV and that they did not have information about the possible development of drug-resistant virus among patients who started on same-day therapy but did not complete the health care link. In addition, there was only limited information available about those patients who neither linked to care or dropped out.
Dr. Labhardt said at the briefing that the same-day intervention could likely be successfully implemented in similar settings in other parts rural Africa with high HIV prevalence.
The study was funded by the Swiss National Science Foundation, Stiftung für Infektiologie beider Basel, and the Gottfried and Julia Bangerter-Rhyner Stiftung. Dr Labhardt reported support from the Stiftung für Infektiologie beider Basel and the Gottfried and Julia Bangerter-Rhyner Foundation and travel support to medical conferences from Gilead Sciences Switzerland Sarl. No other author reported disclosures.
SOURCE: Labhardt ND et al. JAMA. 2018 Mar 1. doi: 10.1001/jama.2018.1818.
REPORTING FROM CROI
Key clinical point: A home-based HIV diagnosis and same-day antiretroviral therapy initiation program may improve outcomes in rural areas.
Major finding: 12-month rates of viral suppression were 50.4% for patients started on ART on the day of a home-based diagnosis, vs. 34.3% for those referred to a clinic for ART.
Data source: Randomized, controlled trial with 278 residents of northern Lesotho who tested positive in home-based HIV testing program.
Disclosures: The study was funded by the Swiss National Science Foundation, Stiftung für Infektiologie beider Basel, and the Gottfried und Julia Bangerter-Rhyner Stiftung. Dr. Labhardt reported support from the Stiftung für Infektiologie beider Basel and the Gottfried and Julia Bangerter-Rhyner and travel support to medical conferences from Gilead Sciences Switzerland Sarl. No other author reported disclosures.
Source: Labhardt ND et al. JAMA. 2018 Mar 1. doi: 10.1001/jama.2018.1818.