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ALT-70 score outperformed thermal imaging for cellulitis diagnosis
SAN DIEGO – A simple scoring system surpassed thermal imaging for diagnosing lower extremity cellulitis in a head-to-head, single-center comparison in 67 patients.
The ALT-70 score – which tallies points for asymmetry, leukocytosis, tachycardia, and age of at least 70 years – produced a positive predictive value for lower-extremity cellulitis (LEC) of 80.4% and a negative predictive value of 90.9%, compared with values of 75.5% and 57.1%, respectively, for thermal imaging when researchers applied both methods to 67 patients, said David G. Li, a clinical research fellow in the department of dermatology at Brigham and Women’s Hospital, Boston, where the study was conducted.
The senior author of Mr. Li’s report, Arash Mostaghimi, MD, director of the inpatient consultation service, department of dermatology at Brigham and Women’s, was also lead investigator for the team of dermatology researchers – from his center and from Massachusetts General Hospital in Boston – who recently devised the ALT-70 scoring system for diagnosing LEC (J Amer Acad Dermatol. 2017 April;76[4]:618-25.e2).
The four-item survey can generate a score of 0-7, with a score of 0-2 suggesting need for additional monitoring, a score of 3-4 initiating a dermatology consult, and a score of 5-7 triggering immediate treatment for cellulitis, Mr. Li said. The 2017 review of ALT-70 showed that among 259 patients, those with a score of 0-2 had an 83% likelihood of having pseudocellulitis, while patients with a score of 5-7 had an 82% likelihood of having true cellulitis.
The current study enrolled 67 patients who had a presumptive diagnosis of LEC while in the emergency department or inpatient wards during a 7-month period. In addition to undergoing blinded assessment by both thermal imaging and by ALT-70 scoring, all patients also underwent blinded assessment by a board-certified dermatologist, who provided the definitive diagnosis. The attending dermatologists determined that 46 of the patients had true LEC and 21 patients did not.
The calculated sensitivity of ALT-70 was 97.8%, compared with 87.0% for thermal imaging. Specificity was 47.6% for ALT-70 and 38.1% for thermal imaging, Mr. Li reported at the annual meeting of the American Academy of Dermatology.
He also presented an analysis of the results when he combined both methods, with a positive on both assessments required to produce a positive LEC diagnosis. This resulted in a positive predictive value of 86.7%, slightly higher than the 80.4% from ALT-70 alone, but the combination produced a negative predictive value of 68.2%, substantially less than the 90.9% rate with ALT-70 alone. This demonstrated the “marginal benefit” from combining the two methods, he said.
In a receiver operating characteristic curve analysis, in which the area under the curve (c-statistic) reflects a diagnostic test’s validity, ALT-70 produced a c-statistic of 0.85, thermal imaging had a c-statistic of 0.63, and when combined, the c-statistic was 0.88.
Mr. Li called for validation of the findings using larger and different patient populations.
He had no reported disclosures.
SOURCE: Li DG et al. AAD 18, Abstract 6744.
SAN DIEGO – A simple scoring system surpassed thermal imaging for diagnosing lower extremity cellulitis in a head-to-head, single-center comparison in 67 patients.
The ALT-70 score – which tallies points for asymmetry, leukocytosis, tachycardia, and age of at least 70 years – produced a positive predictive value for lower-extremity cellulitis (LEC) of 80.4% and a negative predictive value of 90.9%, compared with values of 75.5% and 57.1%, respectively, for thermal imaging when researchers applied both methods to 67 patients, said David G. Li, a clinical research fellow in the department of dermatology at Brigham and Women’s Hospital, Boston, where the study was conducted.
The senior author of Mr. Li’s report, Arash Mostaghimi, MD, director of the inpatient consultation service, department of dermatology at Brigham and Women’s, was also lead investigator for the team of dermatology researchers – from his center and from Massachusetts General Hospital in Boston – who recently devised the ALT-70 scoring system for diagnosing LEC (J Amer Acad Dermatol. 2017 April;76[4]:618-25.e2).
The four-item survey can generate a score of 0-7, with a score of 0-2 suggesting need for additional monitoring, a score of 3-4 initiating a dermatology consult, and a score of 5-7 triggering immediate treatment for cellulitis, Mr. Li said. The 2017 review of ALT-70 showed that among 259 patients, those with a score of 0-2 had an 83% likelihood of having pseudocellulitis, while patients with a score of 5-7 had an 82% likelihood of having true cellulitis.
The current study enrolled 67 patients who had a presumptive diagnosis of LEC while in the emergency department or inpatient wards during a 7-month period. In addition to undergoing blinded assessment by both thermal imaging and by ALT-70 scoring, all patients also underwent blinded assessment by a board-certified dermatologist, who provided the definitive diagnosis. The attending dermatologists determined that 46 of the patients had true LEC and 21 patients did not.
The calculated sensitivity of ALT-70 was 97.8%, compared with 87.0% for thermal imaging. Specificity was 47.6% for ALT-70 and 38.1% for thermal imaging, Mr. Li reported at the annual meeting of the American Academy of Dermatology.
He also presented an analysis of the results when he combined both methods, with a positive on both assessments required to produce a positive LEC diagnosis. This resulted in a positive predictive value of 86.7%, slightly higher than the 80.4% from ALT-70 alone, but the combination produced a negative predictive value of 68.2%, substantially less than the 90.9% rate with ALT-70 alone. This demonstrated the “marginal benefit” from combining the two methods, he said.
In a receiver operating characteristic curve analysis, in which the area under the curve (c-statistic) reflects a diagnostic test’s validity, ALT-70 produced a c-statistic of 0.85, thermal imaging had a c-statistic of 0.63, and when combined, the c-statistic was 0.88.
Mr. Li called for validation of the findings using larger and different patient populations.
He had no reported disclosures.
SOURCE: Li DG et al. AAD 18, Abstract 6744.
SAN DIEGO – A simple scoring system surpassed thermal imaging for diagnosing lower extremity cellulitis in a head-to-head, single-center comparison in 67 patients.
The ALT-70 score – which tallies points for asymmetry, leukocytosis, tachycardia, and age of at least 70 years – produced a positive predictive value for lower-extremity cellulitis (LEC) of 80.4% and a negative predictive value of 90.9%, compared with values of 75.5% and 57.1%, respectively, for thermal imaging when researchers applied both methods to 67 patients, said David G. Li, a clinical research fellow in the department of dermatology at Brigham and Women’s Hospital, Boston, where the study was conducted.
The senior author of Mr. Li’s report, Arash Mostaghimi, MD, director of the inpatient consultation service, department of dermatology at Brigham and Women’s, was also lead investigator for the team of dermatology researchers – from his center and from Massachusetts General Hospital in Boston – who recently devised the ALT-70 scoring system for diagnosing LEC (J Amer Acad Dermatol. 2017 April;76[4]:618-25.e2).
The four-item survey can generate a score of 0-7, with a score of 0-2 suggesting need for additional monitoring, a score of 3-4 initiating a dermatology consult, and a score of 5-7 triggering immediate treatment for cellulitis, Mr. Li said. The 2017 review of ALT-70 showed that among 259 patients, those with a score of 0-2 had an 83% likelihood of having pseudocellulitis, while patients with a score of 5-7 had an 82% likelihood of having true cellulitis.
The current study enrolled 67 patients who had a presumptive diagnosis of LEC while in the emergency department or inpatient wards during a 7-month period. In addition to undergoing blinded assessment by both thermal imaging and by ALT-70 scoring, all patients also underwent blinded assessment by a board-certified dermatologist, who provided the definitive diagnosis. The attending dermatologists determined that 46 of the patients had true LEC and 21 patients did not.
The calculated sensitivity of ALT-70 was 97.8%, compared with 87.0% for thermal imaging. Specificity was 47.6% for ALT-70 and 38.1% for thermal imaging, Mr. Li reported at the annual meeting of the American Academy of Dermatology.
He also presented an analysis of the results when he combined both methods, with a positive on both assessments required to produce a positive LEC diagnosis. This resulted in a positive predictive value of 86.7%, slightly higher than the 80.4% from ALT-70 alone, but the combination produced a negative predictive value of 68.2%, substantially less than the 90.9% rate with ALT-70 alone. This demonstrated the “marginal benefit” from combining the two methods, he said.
In a receiver operating characteristic curve analysis, in which the area under the curve (c-statistic) reflects a diagnostic test’s validity, ALT-70 produced a c-statistic of 0.85, thermal imaging had a c-statistic of 0.63, and when combined, the c-statistic was 0.88.
Mr. Li called for validation of the findings using larger and different patient populations.
He had no reported disclosures.
SOURCE: Li DG et al. AAD 18, Abstract 6744.
REPORTING FROM AAD 18
Key clinical point: The ALT-70 score surpassed thermal imaging for diagnosing lower-extremity cellulitis.
Major finding: Positive and negative predictive values were 80.4% and 90.9% for ALT-70 and 75.5% and 57.1% for thermal imaging.
Study details: A single-center study with 67 patients.
Disclosures: Mr. Li had no disclosures.
Source: Li DG et al. AAD 18, Abstract 6744.
HCV infection tied to premature ovarian senescence and a high miscarriage rate
Premenopausal women with hepatitis C virus (HCV) showed increased ovarian senescence, which was associated with a lower chance of live birth. Such women also had a greater risk of infertility, as reported in the Journal of Hepatology.
Researchers examined three cohort studies, which comprised an age-matched prospectively enrolled cohort study of 100 women who were HCV positive and had chronic liver disease, 50 women who were HBV positive and had CLD, and 100 healthy women; 1,998 HCV-infected women enrolled in the Platform for the Study of Viral Hepatitis Therapies (PITER) trial from Italy; and 6,085 women infected with HCV plus 20,415 uninfected women from a United States database, according to Aimilia Karampatou, MD, of the University of Bologna, Modena, Italy, and colleagues.
In the second group examined, the women from the PITER trial, miscarriages occurred in 42% of the HCV-infected women with 44.6% of these women experiencing multiple miscarriages. The total fertility rate, defined as the average number of children that would be born in a lifetime, was 0.7 for the HCV-infected women, compared with 1.37 in the general Italian population.
Infertility data from the large U.S. study was assessed from a total of 27,525 women (20,415 HCV negative and HIV negative; 6,805 HCV positive; and 305 HCV positive/HIV positive). Women with HCV showed a significantly higher probability of infertility compared with uninfected controls (odds ratio, 2.44), and those women dually infected with HCV and HIV were affected even more (OR, 3.64).
Primarily based on the observations of AMH, which in many of the HCV-positive women fell into the menopausal range, the researchers suggested that “the reduced reproductive capacity of women who are HCV positive is related to failing ovarian function and subsequent follicular depletion in the context of a more generalized dysfunction of other fertility-related factors.”
With regard to the effect of antiviral therapy, AMH levels remained stable in women who attained a sustained virologic response but continued to fall in those for whom the therapy was a failure.
“HCV infection significantly and negatively affects many aspects of fertility. It remains to be assessed whether antiviral therapy at a very early age can positively influence the occurrence of miscarriages and can prevent ovarian senescence because the latter has broader health implications than simply preserving fertility,” the researchers concluded.
The authors reported that they had no conflicts of interest.
AGA provides resources and education for your patients about hepatitis C at www.gastro.org/HCV
SOURCE: Karampatou A et al. J Hepatology. 2018;68:33-41.
Premenopausal women with hepatitis C virus (HCV) showed increased ovarian senescence, which was associated with a lower chance of live birth. Such women also had a greater risk of infertility, as reported in the Journal of Hepatology.
Researchers examined three cohort studies, which comprised an age-matched prospectively enrolled cohort study of 100 women who were HCV positive and had chronic liver disease, 50 women who were HBV positive and had CLD, and 100 healthy women; 1,998 HCV-infected women enrolled in the Platform for the Study of Viral Hepatitis Therapies (PITER) trial from Italy; and 6,085 women infected with HCV plus 20,415 uninfected women from a United States database, according to Aimilia Karampatou, MD, of the University of Bologna, Modena, Italy, and colleagues.
In the second group examined, the women from the PITER trial, miscarriages occurred in 42% of the HCV-infected women with 44.6% of these women experiencing multiple miscarriages. The total fertility rate, defined as the average number of children that would be born in a lifetime, was 0.7 for the HCV-infected women, compared with 1.37 in the general Italian population.
Infertility data from the large U.S. study was assessed from a total of 27,525 women (20,415 HCV negative and HIV negative; 6,805 HCV positive; and 305 HCV positive/HIV positive). Women with HCV showed a significantly higher probability of infertility compared with uninfected controls (odds ratio, 2.44), and those women dually infected with HCV and HIV were affected even more (OR, 3.64).
Primarily based on the observations of AMH, which in many of the HCV-positive women fell into the menopausal range, the researchers suggested that “the reduced reproductive capacity of women who are HCV positive is related to failing ovarian function and subsequent follicular depletion in the context of a more generalized dysfunction of other fertility-related factors.”
With regard to the effect of antiviral therapy, AMH levels remained stable in women who attained a sustained virologic response but continued to fall in those for whom the therapy was a failure.
“HCV infection significantly and negatively affects many aspects of fertility. It remains to be assessed whether antiviral therapy at a very early age can positively influence the occurrence of miscarriages and can prevent ovarian senescence because the latter has broader health implications than simply preserving fertility,” the researchers concluded.
The authors reported that they had no conflicts of interest.
AGA provides resources and education for your patients about hepatitis C at www.gastro.org/HCV
SOURCE: Karampatou A et al. J Hepatology. 2018;68:33-41.
Premenopausal women with hepatitis C virus (HCV) showed increased ovarian senescence, which was associated with a lower chance of live birth. Such women also had a greater risk of infertility, as reported in the Journal of Hepatology.
Researchers examined three cohort studies, which comprised an age-matched prospectively enrolled cohort study of 100 women who were HCV positive and had chronic liver disease, 50 women who were HBV positive and had CLD, and 100 healthy women; 1,998 HCV-infected women enrolled in the Platform for the Study of Viral Hepatitis Therapies (PITER) trial from Italy; and 6,085 women infected with HCV plus 20,415 uninfected women from a United States database, according to Aimilia Karampatou, MD, of the University of Bologna, Modena, Italy, and colleagues.
In the second group examined, the women from the PITER trial, miscarriages occurred in 42% of the HCV-infected women with 44.6% of these women experiencing multiple miscarriages. The total fertility rate, defined as the average number of children that would be born in a lifetime, was 0.7 for the HCV-infected women, compared with 1.37 in the general Italian population.
Infertility data from the large U.S. study was assessed from a total of 27,525 women (20,415 HCV negative and HIV negative; 6,805 HCV positive; and 305 HCV positive/HIV positive). Women with HCV showed a significantly higher probability of infertility compared with uninfected controls (odds ratio, 2.44), and those women dually infected with HCV and HIV were affected even more (OR, 3.64).
Primarily based on the observations of AMH, which in many of the HCV-positive women fell into the menopausal range, the researchers suggested that “the reduced reproductive capacity of women who are HCV positive is related to failing ovarian function and subsequent follicular depletion in the context of a more generalized dysfunction of other fertility-related factors.”
With regard to the effect of antiviral therapy, AMH levels remained stable in women who attained a sustained virologic response but continued to fall in those for whom the therapy was a failure.
“HCV infection significantly and negatively affects many aspects of fertility. It remains to be assessed whether antiviral therapy at a very early age can positively influence the occurrence of miscarriages and can prevent ovarian senescence because the latter has broader health implications than simply preserving fertility,” the researchers concluded.
The authors reported that they had no conflicts of interest.
AGA provides resources and education for your patients about hepatitis C at www.gastro.org/HCV
SOURCE: Karampatou A et al. J Hepatology. 2018;68:33-41.
FROM THE JOURNAL OF HEPATOLOGY
Key clinical point: HCV-positive women appear to undergo increased ovarian senescence.
Major finding: The fertility rate of HCV-positive women was 0.7 vs. 1.37 in the general population.
Study details: Three separate studies together comprising more than 30,000 HCV-infected and -uninfected women.
Disclosures: The authors reported that they had no conflicts of interest.
Source: Karampatou A et al. J Hepatology. 2018;68:33-41.
Young diabetics are at sevenfold increased risk of sudden cardiac death
ANAHEIM, CALIF. – Children and young adults with type 1 or type 2 diabetes have a 7.4-fold increased risk of sudden cardiac death, compared with nondiabetic, age-matched controls, according to a first-of-its-kind Danish national study.
“Luckily the absolute risk is low, but we hope these data will make [young patients with diabetes] think more about taking their insulin and following their physicians’ recommendations about treatment,” Jesper Svane said in presenting the study findings at the American Heart Association scientific sessions.
Sudden cardiac death (SCD) was the No. 1 cause of mortality in the diabetic cohort with a rate of 34.8 deaths/100,000 person-years, compared with 4.7 deaths/100,000 person-years in an age-matched nondiabetic cohort. That translates to a 7.4-fold increased risk of SCD in the diabetic cohort, noted Mr. Svane, a medical student at Copenhagen University.
When deaths caused by SCD were combined with those from other cardiac diseases, the young diabetic cohort had a rate of 68.3 deaths/100,000 person-years versus 8.2 deaths/100,000 person-years in age-matched controls, for an 8.3-fold increased risk. This observation underscores an important point: Monitoring cardiovascular risk needs to start early in young patients with diabetes.
“It’s important to pay attention when a young person with diabetes comes in complaining of chest pain or syncope,” Mr. Svane said.
The second and third most common causes of death in young Danish diabetic patients were pulmonary and endocrine diseases, which occurred at rates 7.2- and 79.2-fold greater in these patients, respectively, than in controls.
All-cause mortality occurred at a rate of 234.9 deaths/100,000 person-years in young patients with diabetes versus 50.9 deaths/100,000 person-years in matched controls, for a 4.6-fold increased risk.
Autopsies showed that the most common cause of death in diabetic persons aged 36-49 years was coronary artery disease, while in those up to age 35, it was sudden arrhythmic death syndrome, a label bestowed when a medical examiner can’t find an apparent cause of death.
Session moderator Robert H. Eckle, MD, a past AHA president, cautioned against routinely attributing the deaths without apparent cause at autopsy in young people with diabetes to sudden arrhythmic death syndrome. Given that the Danish registry data don’t include data on diabetic patients’ degree of metabolic control, it seems likely that an uncertain number of those deaths were really caused by hypoglycemia, observed Dr. Eckle, professor of medicine at the University of Colorado at Denver, Aurora.
Mr. Svane reported having no financial conflicts of interest.
SOURCE: Svane J. 2017 AHA Sessions.
ANAHEIM, CALIF. – Children and young adults with type 1 or type 2 diabetes have a 7.4-fold increased risk of sudden cardiac death, compared with nondiabetic, age-matched controls, according to a first-of-its-kind Danish national study.
“Luckily the absolute risk is low, but we hope these data will make [young patients with diabetes] think more about taking their insulin and following their physicians’ recommendations about treatment,” Jesper Svane said in presenting the study findings at the American Heart Association scientific sessions.
Sudden cardiac death (SCD) was the No. 1 cause of mortality in the diabetic cohort with a rate of 34.8 deaths/100,000 person-years, compared with 4.7 deaths/100,000 person-years in an age-matched nondiabetic cohort. That translates to a 7.4-fold increased risk of SCD in the diabetic cohort, noted Mr. Svane, a medical student at Copenhagen University.
When deaths caused by SCD were combined with those from other cardiac diseases, the young diabetic cohort had a rate of 68.3 deaths/100,000 person-years versus 8.2 deaths/100,000 person-years in age-matched controls, for an 8.3-fold increased risk. This observation underscores an important point: Monitoring cardiovascular risk needs to start early in young patients with diabetes.
“It’s important to pay attention when a young person with diabetes comes in complaining of chest pain or syncope,” Mr. Svane said.
The second and third most common causes of death in young Danish diabetic patients were pulmonary and endocrine diseases, which occurred at rates 7.2- and 79.2-fold greater in these patients, respectively, than in controls.
All-cause mortality occurred at a rate of 234.9 deaths/100,000 person-years in young patients with diabetes versus 50.9 deaths/100,000 person-years in matched controls, for a 4.6-fold increased risk.
Autopsies showed that the most common cause of death in diabetic persons aged 36-49 years was coronary artery disease, while in those up to age 35, it was sudden arrhythmic death syndrome, a label bestowed when a medical examiner can’t find an apparent cause of death.
Session moderator Robert H. Eckle, MD, a past AHA president, cautioned against routinely attributing the deaths without apparent cause at autopsy in young people with diabetes to sudden arrhythmic death syndrome. Given that the Danish registry data don’t include data on diabetic patients’ degree of metabolic control, it seems likely that an uncertain number of those deaths were really caused by hypoglycemia, observed Dr. Eckle, professor of medicine at the University of Colorado at Denver, Aurora.
Mr. Svane reported having no financial conflicts of interest.
SOURCE: Svane J. 2017 AHA Sessions.
ANAHEIM, CALIF. – Children and young adults with type 1 or type 2 diabetes have a 7.4-fold increased risk of sudden cardiac death, compared with nondiabetic, age-matched controls, according to a first-of-its-kind Danish national study.
“Luckily the absolute risk is low, but we hope these data will make [young patients with diabetes] think more about taking their insulin and following their physicians’ recommendations about treatment,” Jesper Svane said in presenting the study findings at the American Heart Association scientific sessions.
Sudden cardiac death (SCD) was the No. 1 cause of mortality in the diabetic cohort with a rate of 34.8 deaths/100,000 person-years, compared with 4.7 deaths/100,000 person-years in an age-matched nondiabetic cohort. That translates to a 7.4-fold increased risk of SCD in the diabetic cohort, noted Mr. Svane, a medical student at Copenhagen University.
When deaths caused by SCD were combined with those from other cardiac diseases, the young diabetic cohort had a rate of 68.3 deaths/100,000 person-years versus 8.2 deaths/100,000 person-years in age-matched controls, for an 8.3-fold increased risk. This observation underscores an important point: Monitoring cardiovascular risk needs to start early in young patients with diabetes.
“It’s important to pay attention when a young person with diabetes comes in complaining of chest pain or syncope,” Mr. Svane said.
The second and third most common causes of death in young Danish diabetic patients were pulmonary and endocrine diseases, which occurred at rates 7.2- and 79.2-fold greater in these patients, respectively, than in controls.
All-cause mortality occurred at a rate of 234.9 deaths/100,000 person-years in young patients with diabetes versus 50.9 deaths/100,000 person-years in matched controls, for a 4.6-fold increased risk.
Autopsies showed that the most common cause of death in diabetic persons aged 36-49 years was coronary artery disease, while in those up to age 35, it was sudden arrhythmic death syndrome, a label bestowed when a medical examiner can’t find an apparent cause of death.
Session moderator Robert H. Eckle, MD, a past AHA president, cautioned against routinely attributing the deaths without apparent cause at autopsy in young people with diabetes to sudden arrhythmic death syndrome. Given that the Danish registry data don’t include data on diabetic patients’ degree of metabolic control, it seems likely that an uncertain number of those deaths were really caused by hypoglycemia, observed Dr. Eckle, professor of medicine at the University of Colorado at Denver, Aurora.
Mr. Svane reported having no financial conflicts of interest.
SOURCE: Svane J. 2017 AHA Sessions.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point: Young persons with diabetes are 8.3-fold more likely to die of cardiac causes.
Major finding: In particular, the risk of sudden cardiac death in Danish children and young adults with diabetes was 7.4-fold greater than in age-matched controls.
Study details: This was a Danish national registry study of more than 14,000 children and young adults with diabetes and their rate of sudden cardiac death.
Disclosures: The study presenter reported having no financial conflicts.
Source: Svane J. 2017 AHA Sessions.
Breast cancer care delayed when patients have high deductibles
High-deductible health insurance plans may be bad for women’s health, suggest results of a new study.
An analysis of data on women without evidence of breast cancer who were covered for at least 1 year in a low annual deductible plan and then switched by their employers to high annual deductible plans showed that when women were forced to shell out substantially more money before their insurance kicked in, they were significantly more likely to have delays in diagnostic breast imaging, breast biopsy, and initiation of chemotherapy.
“Such delays might lead to adverse long-term breast cancer outcomes. Policymakers, health insurers, and employers should consider designing or incentivizing health insurance benefits that facilitate transitions through key steps along the cancer care pathway,” wrote J. Frank Wharam, MB, and colleagues at Harvard Medical School and Harvard Pilgrim Health Care Institute in Boston. The report was published in Journal of Clinical Oncology.
The investigators conducted a controlled pre-post study to measure the occurrence of outcomes both before and after women were switched from a low-deductible health plan, defined as a maximum annual deductible of $500 or less, to a high-deductible plan, defined as an annual deductible of $1,000 or more.
The study population comprised 273,499 women aged 25-64 years who had no evidence of breast cancer before they were included in the study. The women had all been enrolled in a low-deductible plan for at least 1 year, and were then switched by employer mandate to a high-deductible plan and followed for up to 4 additional years.
Controls included 2.4 million women matched by time of inclusion whose employers continued to offer only low-deductible health plans.
Although at baseline there were no differences between the study sample and the controls in time to first diagnostic breast imaging, breast biopsy, diagnosis of early stage breast cancer, or initiation of breast cancer chemotherapy, at follow-up the women who had been switched to the high-deductible plans had significant delays in all categories.
Compared with controls, the hazard ratios (HR) for each parameter were as follows:
Time to first diagnostic breast imaging: HR = 0.96 (95% confidence interval 0.94-0.96)
Time to first breast biopsy: HR = 0.92 (0.89-0.95)
Time to early stage breast cancer diagnosis: HR = 0.83 (0.78-0.90)
Time to breast cancer chemotherapy: HR = 0.79 (0.72-0.86)
“The findings imply that the high out-of-pocket obligations under HDHPs [high-deductible health plans] might be a barrier to timely receipt of essential breast cancer services. Women in HDHPs might either delay presenting for concerning symptoms or, if proceeding along the pathway from breast cancer screening to diagnostic testing to treatment, be hesitant to undergo subsequent (and generally more expensive) care,” the authors wrote.
They noted that initially modest delays in diagnostic imaging appeared to snowball into longer delays as women proceeded through stages of care.
They recommend a strategy whereby insurers carve out exemptions to high deductibles for services such as diagnostic imaging and breast biopsy.
SOURCE: Wharam et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.2501.
High-deductible health insurance plans may be bad for women’s health, suggest results of a new study.
An analysis of data on women without evidence of breast cancer who were covered for at least 1 year in a low annual deductible plan and then switched by their employers to high annual deductible plans showed that when women were forced to shell out substantially more money before their insurance kicked in, they were significantly more likely to have delays in diagnostic breast imaging, breast biopsy, and initiation of chemotherapy.
“Such delays might lead to adverse long-term breast cancer outcomes. Policymakers, health insurers, and employers should consider designing or incentivizing health insurance benefits that facilitate transitions through key steps along the cancer care pathway,” wrote J. Frank Wharam, MB, and colleagues at Harvard Medical School and Harvard Pilgrim Health Care Institute in Boston. The report was published in Journal of Clinical Oncology.
The investigators conducted a controlled pre-post study to measure the occurrence of outcomes both before and after women were switched from a low-deductible health plan, defined as a maximum annual deductible of $500 or less, to a high-deductible plan, defined as an annual deductible of $1,000 or more.
The study population comprised 273,499 women aged 25-64 years who had no evidence of breast cancer before they were included in the study. The women had all been enrolled in a low-deductible plan for at least 1 year, and were then switched by employer mandate to a high-deductible plan and followed for up to 4 additional years.
Controls included 2.4 million women matched by time of inclusion whose employers continued to offer only low-deductible health plans.
Although at baseline there were no differences between the study sample and the controls in time to first diagnostic breast imaging, breast biopsy, diagnosis of early stage breast cancer, or initiation of breast cancer chemotherapy, at follow-up the women who had been switched to the high-deductible plans had significant delays in all categories.
Compared with controls, the hazard ratios (HR) for each parameter were as follows:
Time to first diagnostic breast imaging: HR = 0.96 (95% confidence interval 0.94-0.96)
Time to first breast biopsy: HR = 0.92 (0.89-0.95)
Time to early stage breast cancer diagnosis: HR = 0.83 (0.78-0.90)
Time to breast cancer chemotherapy: HR = 0.79 (0.72-0.86)
“The findings imply that the high out-of-pocket obligations under HDHPs [high-deductible health plans] might be a barrier to timely receipt of essential breast cancer services. Women in HDHPs might either delay presenting for concerning symptoms or, if proceeding along the pathway from breast cancer screening to diagnostic testing to treatment, be hesitant to undergo subsequent (and generally more expensive) care,” the authors wrote.
They noted that initially modest delays in diagnostic imaging appeared to snowball into longer delays as women proceeded through stages of care.
They recommend a strategy whereby insurers carve out exemptions to high deductibles for services such as diagnostic imaging and breast biopsy.
SOURCE: Wharam et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.2501.
High-deductible health insurance plans may be bad for women’s health, suggest results of a new study.
An analysis of data on women without evidence of breast cancer who were covered for at least 1 year in a low annual deductible plan and then switched by their employers to high annual deductible plans showed that when women were forced to shell out substantially more money before their insurance kicked in, they were significantly more likely to have delays in diagnostic breast imaging, breast biopsy, and initiation of chemotherapy.
“Such delays might lead to adverse long-term breast cancer outcomes. Policymakers, health insurers, and employers should consider designing or incentivizing health insurance benefits that facilitate transitions through key steps along the cancer care pathway,” wrote J. Frank Wharam, MB, and colleagues at Harvard Medical School and Harvard Pilgrim Health Care Institute in Boston. The report was published in Journal of Clinical Oncology.
The investigators conducted a controlled pre-post study to measure the occurrence of outcomes both before and after women were switched from a low-deductible health plan, defined as a maximum annual deductible of $500 or less, to a high-deductible plan, defined as an annual deductible of $1,000 or more.
The study population comprised 273,499 women aged 25-64 years who had no evidence of breast cancer before they were included in the study. The women had all been enrolled in a low-deductible plan for at least 1 year, and were then switched by employer mandate to a high-deductible plan and followed for up to 4 additional years.
Controls included 2.4 million women matched by time of inclusion whose employers continued to offer only low-deductible health plans.
Although at baseline there were no differences between the study sample and the controls in time to first diagnostic breast imaging, breast biopsy, diagnosis of early stage breast cancer, or initiation of breast cancer chemotherapy, at follow-up the women who had been switched to the high-deductible plans had significant delays in all categories.
Compared with controls, the hazard ratios (HR) for each parameter were as follows:
Time to first diagnostic breast imaging: HR = 0.96 (95% confidence interval 0.94-0.96)
Time to first breast biopsy: HR = 0.92 (0.89-0.95)
Time to early stage breast cancer diagnosis: HR = 0.83 (0.78-0.90)
Time to breast cancer chemotherapy: HR = 0.79 (0.72-0.86)
“The findings imply that the high out-of-pocket obligations under HDHPs [high-deductible health plans] might be a barrier to timely receipt of essential breast cancer services. Women in HDHPs might either delay presenting for concerning symptoms or, if proceeding along the pathway from breast cancer screening to diagnostic testing to treatment, be hesitant to undergo subsequent (and generally more expensive) care,” the authors wrote.
They noted that initially modest delays in diagnostic imaging appeared to snowball into longer delays as women proceeded through stages of care.
They recommend a strategy whereby insurers carve out exemptions to high deductibles for services such as diagnostic imaging and breast biopsy.
SOURCE: Wharam et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.2501.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Many women have high-deductible health plans that may discourage them from seeking essential care when needed.
Major finding: Women with an employer-mandated switch from a low- to high-deductible health plan had significant delays in diagnostic imaging, biopsy, diagnosis, and cancer care.
Study details: Controlled pre-post study of data on 273,499 women and 2.4 million controls.
Disclosures: The study was supported by National Cancer Institute and National Institute of Health grants. Dr. Wharam and three coauthors reported no conflicts of interest. Three coauthors reported honoraria and/or consulting/advisory roles with various companies.
Source: Wharam et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.2501.
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.
hematologynews@frontlinemedcom.com
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.
hematologynews@frontlinemedcom.com
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.
hematologynews@frontlinemedcom.com
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.