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Zika topped Lyme in 2016
Ticks are the arthropod ride of choice for vector-borne diseases in the United States, but the Zika virus and its mosquito minions gave the ticks and their bacterial passengers a run for their money in 2016, according to the Centers for Disease Control and Prevention.
There were 41,680 cases of Zika virus that year, more than any other vector-borne disease, including Lyme disease, which had been the most common transmissible pathogen going back to at least 2004, when arthropod-borne viral diseases became nationally notifiable, said Ronald Rosenberg, ScD, and his associates at the CDC’s National Center for Emerging and Zoonotic Infectious Diseases in Fort Collins, Colo.
Since 2004, there have been 643,000 reported cases of vector-borne disease in the United States: 492,000 cases of tick-borne disease, of which over 402,000 were Lyme disease; 151,000 cases of mosquito-borne disease; and 89 cases of plague carried by the third type of vector, fleas, Dr. Rosenberg and his associates said based on data from the National Notifiable Disease Surveillance System.
In 2004, there were 22,527 cases of tick-borne disease and 4,858 cases of mosquito-borne disease, and the increases since then reflect the dynamics of the pathogens and vectors involved. Growth of tick-borne disease has been gradual: “Tick-borne pathogens rarely cause sudden epidemics because humans are typically incidental hosts who do not transmit further, and tick mobility is mostly limited to that of its animal hosts,” the researchers explained.
The number of mosquito-borne disease cases, on the other hand, varies considerably from year to year: There were 5,800 cases in 2015, almost 15,000 in 2013, and only 4,400 in 2011. Unlike ticks, which may feed on blood only once in a year, the more mobile mosquitoes feed every 48-72 hours and transmit their pathogens “directly between humans … resulting in explosive epidemics,” the investigators wrote.
SOURCE: Rosenberg R et al. MMWR 2018 May 4;67(17):496-501.
Ticks are the arthropod ride of choice for vector-borne diseases in the United States, but the Zika virus and its mosquito minions gave the ticks and their bacterial passengers a run for their money in 2016, according to the Centers for Disease Control and Prevention.
There were 41,680 cases of Zika virus that year, more than any other vector-borne disease, including Lyme disease, which had been the most common transmissible pathogen going back to at least 2004, when arthropod-borne viral diseases became nationally notifiable, said Ronald Rosenberg, ScD, and his associates at the CDC’s National Center for Emerging and Zoonotic Infectious Diseases in Fort Collins, Colo.
Since 2004, there have been 643,000 reported cases of vector-borne disease in the United States: 492,000 cases of tick-borne disease, of which over 402,000 were Lyme disease; 151,000 cases of mosquito-borne disease; and 89 cases of plague carried by the third type of vector, fleas, Dr. Rosenberg and his associates said based on data from the National Notifiable Disease Surveillance System.
In 2004, there were 22,527 cases of tick-borne disease and 4,858 cases of mosquito-borne disease, and the increases since then reflect the dynamics of the pathogens and vectors involved. Growth of tick-borne disease has been gradual: “Tick-borne pathogens rarely cause sudden epidemics because humans are typically incidental hosts who do not transmit further, and tick mobility is mostly limited to that of its animal hosts,” the researchers explained.
The number of mosquito-borne disease cases, on the other hand, varies considerably from year to year: There were 5,800 cases in 2015, almost 15,000 in 2013, and only 4,400 in 2011. Unlike ticks, which may feed on blood only once in a year, the more mobile mosquitoes feed every 48-72 hours and transmit their pathogens “directly between humans … resulting in explosive epidemics,” the investigators wrote.
SOURCE: Rosenberg R et al. MMWR 2018 May 4;67(17):496-501.
Ticks are the arthropod ride of choice for vector-borne diseases in the United States, but the Zika virus and its mosquito minions gave the ticks and their bacterial passengers a run for their money in 2016, according to the Centers for Disease Control and Prevention.
There were 41,680 cases of Zika virus that year, more than any other vector-borne disease, including Lyme disease, which had been the most common transmissible pathogen going back to at least 2004, when arthropod-borne viral diseases became nationally notifiable, said Ronald Rosenberg, ScD, and his associates at the CDC’s National Center for Emerging and Zoonotic Infectious Diseases in Fort Collins, Colo.
Since 2004, there have been 643,000 reported cases of vector-borne disease in the United States: 492,000 cases of tick-borne disease, of which over 402,000 were Lyme disease; 151,000 cases of mosquito-borne disease; and 89 cases of plague carried by the third type of vector, fleas, Dr. Rosenberg and his associates said based on data from the National Notifiable Disease Surveillance System.
In 2004, there were 22,527 cases of tick-borne disease and 4,858 cases of mosquito-borne disease, and the increases since then reflect the dynamics of the pathogens and vectors involved. Growth of tick-borne disease has been gradual: “Tick-borne pathogens rarely cause sudden epidemics because humans are typically incidental hosts who do not transmit further, and tick mobility is mostly limited to that of its animal hosts,” the researchers explained.
The number of mosquito-borne disease cases, on the other hand, varies considerably from year to year: There were 5,800 cases in 2015, almost 15,000 in 2013, and only 4,400 in 2011. Unlike ticks, which may feed on blood only once in a year, the more mobile mosquitoes feed every 48-72 hours and transmit their pathogens “directly between humans … resulting in explosive epidemics,” the investigators wrote.
SOURCE: Rosenberg R et al. MMWR 2018 May 4;67(17):496-501.
FROM MMWR
Sorafenib Improves Survival for Patients With Rare Sarcomas
Promising results from a phase 3 trial could represent a paradigm shift in treatment of patients with desmoid tumors, say National Cancer Institute (NCI) researchers. Sorafenib tosylate extended progression-free survival (PFS) compared with that of placebo in 87 patients with desmoid tumors or aggressive fibromatosis (DT/DF).
Desmoid tumors or aggressive fibromatosis are rare sarcomas, usually found in the extremities or the abdomen and occasionally associated with familial adenomatous polyposis or Gardner syndrome. Effectiveness of current treatments—surgery, radiation, chemotherapy—is generally limited, says Jeff Abrams, MD, clinical director of NCI’s Division of Cancer Treatment and Diagnosis.
Sorafenib is a targeted treatment that interferes with the growth of cancer cells and new blood vessels that feed the tumors. It is approved for some patients with advanced kidney, liver, and thyroid cancers. It was chosen for the NCI trial because in earlier studies DT shrank in patients on sorafenib, and patients had fewer symptoms, including less pain.
Patients were assigned to receive sorafenib 400 mg/d or placebo. The trial was designed to assess improvement in PFS from 6 months for placebo to 15 months for sorafenib. Based on an interim analysis of the first 75 patients enrolled, the observed improvement in PFS exceeded the target. Patients on sorafenib were more likely to experience drug-related adverse effects, but those were generally not severe.
Treatment assignments have been disclosed to patients still receiving treatment and their physicians. Those who were receiving sorafenib can continue therapy, and those on placebo can switch to sorafenib.
Promising results from a phase 3 trial could represent a paradigm shift in treatment of patients with desmoid tumors, say National Cancer Institute (NCI) researchers. Sorafenib tosylate extended progression-free survival (PFS) compared with that of placebo in 87 patients with desmoid tumors or aggressive fibromatosis (DT/DF).
Desmoid tumors or aggressive fibromatosis are rare sarcomas, usually found in the extremities or the abdomen and occasionally associated with familial adenomatous polyposis or Gardner syndrome. Effectiveness of current treatments—surgery, radiation, chemotherapy—is generally limited, says Jeff Abrams, MD, clinical director of NCI’s Division of Cancer Treatment and Diagnosis.
Sorafenib is a targeted treatment that interferes with the growth of cancer cells and new blood vessels that feed the tumors. It is approved for some patients with advanced kidney, liver, and thyroid cancers. It was chosen for the NCI trial because in earlier studies DT shrank in patients on sorafenib, and patients had fewer symptoms, including less pain.
Patients were assigned to receive sorafenib 400 mg/d or placebo. The trial was designed to assess improvement in PFS from 6 months for placebo to 15 months for sorafenib. Based on an interim analysis of the first 75 patients enrolled, the observed improvement in PFS exceeded the target. Patients on sorafenib were more likely to experience drug-related adverse effects, but those were generally not severe.
Treatment assignments have been disclosed to patients still receiving treatment and their physicians. Those who were receiving sorafenib can continue therapy, and those on placebo can switch to sorafenib.
Promising results from a phase 3 trial could represent a paradigm shift in treatment of patients with desmoid tumors, say National Cancer Institute (NCI) researchers. Sorafenib tosylate extended progression-free survival (PFS) compared with that of placebo in 87 patients with desmoid tumors or aggressive fibromatosis (DT/DF).
Desmoid tumors or aggressive fibromatosis are rare sarcomas, usually found in the extremities or the abdomen and occasionally associated with familial adenomatous polyposis or Gardner syndrome. Effectiveness of current treatments—surgery, radiation, chemotherapy—is generally limited, says Jeff Abrams, MD, clinical director of NCI’s Division of Cancer Treatment and Diagnosis.
Sorafenib is a targeted treatment that interferes with the growth of cancer cells and new blood vessels that feed the tumors. It is approved for some patients with advanced kidney, liver, and thyroid cancers. It was chosen for the NCI trial because in earlier studies DT shrank in patients on sorafenib, and patients had fewer symptoms, including less pain.
Patients were assigned to receive sorafenib 400 mg/d or placebo. The trial was designed to assess improvement in PFS from 6 months for placebo to 15 months for sorafenib. Based on an interim analysis of the first 75 patients enrolled, the observed improvement in PFS exceeded the target. Patients on sorafenib were more likely to experience drug-related adverse effects, but those were generally not severe.
Treatment assignments have been disclosed to patients still receiving treatment and their physicians. Those who were receiving sorafenib can continue therapy, and those on placebo can switch to sorafenib.
Restrictive fluids tied to kidney injury after major abdominal surgery
among high-risk patients undergoing major abdominal surgery and led to a significantly increased risk of acute kidney injury, researchers reported.
In an international, randomized trial with 366 median days of follow-up, estimated 1-year rates of disability-free survival were 81.9% with the restrictive intravenous fluid regimen and 82.3% with the liberal regimen (hazard ratio for death or disability, 1.05; P = .61), according to Paul S. Myles, MPH, DSc, and his associates.
Rates of acute renal injury were 8.6% in the restrictive IV fluid group and 5.0% with the liberal fluid therapy (P less than .001), the researchers reported online May 10 in the New England Journal of Medicine.
Guidelines recommend a restrictive intravenous fluid strategy to promote early recovery after major abdominal surgery, noted Dr. Myles of Alfred Hospital in Melbourne and his colleagues. “However, the supporting evidence is limited, and there is concern about impaired organ perfusion.”
Therefore, they randomly assigned, 3,000 patients to receive either the restrictive fluid regimen or a liberal regimen during major abdominal surgery and up to 24 hours after. Median intravenous volume was 3.7 L (interquartile range, 2.9-4.9 L) in the restrictive group and 6.1 L (IQR, 5.0-7.4 L) in the liberal fluid group. All patients were deemed high risk based on their age (at least 70 years) or because they had heart disease, diabetes, kidney disease, or morbid obesity.
Patients who received the restrictive regimen had higher rates of surgical site infection (16.5% vs. 13.6% with liberal fluids; P = .02) and were more likely to receive renal replacement therapy (0.9% vs. 0.3%; P = .048). However, these trends were no longer significant after the researchers controlled for the effects of testing for multiple variables.
“Our findings should not be used to support excessive administration of intravenous fluid,” the researchers cautioned. “Rather, they show that a regimen that includes a modestly liberal administration of fluid is safer than a restrictive regimen.”
Funders included the Australian National Health and Medical Research Council (NHMRC), the Health Research Council of New Zealand, the Australian and New Zealand College of Anaesthetists, and Monash University, Melbourne. Dr. Myles reported receiving grant support from NHMRC. He had no other disclosures.
SOURCE: Myles PS et al. New Engl J Med. 2018 May 10. doi: 10.1056/NEJMoa1801601.
Effective blinding was impossible in this randomized study, wrote Birgitte Brandstrup, PhD, in an accompanying editorial. Differences in fluid volume cause symptoms that clinicians can easily identify, she noted.
She recalled the 1990s, when “surgical patients received so much intravenous saline on the day of surgery that they often gained 4 to 6 kg, and by postoperative day 2 or 3, [and] pulmonary congestion and cardiac arrhythmias were commonplace.” Subsequent trials changed this practice, and patients in the current study received much less fluid than they would have in the old days, she noted.
Nonetheless, the findings indicate “that physiologic principles remain valid: Both hypovolemia and oliguria must be recognized and treated with fluid.” While that does not justify excessive perioperative fluid therapy, “a modestly liberal fluid regimen is safer than a truly restrictive regimen.”
Dr. Brandstrup is with the department of surgery at Holbaek (Denmark) Hospital. She reported having no relevant conflicts of interest. These comments recap her editorial (New Engl J Med. 2018 May 10. doi: 10.1056/NEJMe1805615).
Effective blinding was impossible in this randomized study, wrote Birgitte Brandstrup, PhD, in an accompanying editorial. Differences in fluid volume cause symptoms that clinicians can easily identify, she noted.
She recalled the 1990s, when “surgical patients received so much intravenous saline on the day of surgery that they often gained 4 to 6 kg, and by postoperative day 2 or 3, [and] pulmonary congestion and cardiac arrhythmias were commonplace.” Subsequent trials changed this practice, and patients in the current study received much less fluid than they would have in the old days, she noted.
Nonetheless, the findings indicate “that physiologic principles remain valid: Both hypovolemia and oliguria must be recognized and treated with fluid.” While that does not justify excessive perioperative fluid therapy, “a modestly liberal fluid regimen is safer than a truly restrictive regimen.”
Dr. Brandstrup is with the department of surgery at Holbaek (Denmark) Hospital. She reported having no relevant conflicts of interest. These comments recap her editorial (New Engl J Med. 2018 May 10. doi: 10.1056/NEJMe1805615).
Effective blinding was impossible in this randomized study, wrote Birgitte Brandstrup, PhD, in an accompanying editorial. Differences in fluid volume cause symptoms that clinicians can easily identify, she noted.
She recalled the 1990s, when “surgical patients received so much intravenous saline on the day of surgery that they often gained 4 to 6 kg, and by postoperative day 2 or 3, [and] pulmonary congestion and cardiac arrhythmias were commonplace.” Subsequent trials changed this practice, and patients in the current study received much less fluid than they would have in the old days, she noted.
Nonetheless, the findings indicate “that physiologic principles remain valid: Both hypovolemia and oliguria must be recognized and treated with fluid.” While that does not justify excessive perioperative fluid therapy, “a modestly liberal fluid regimen is safer than a truly restrictive regimen.”
Dr. Brandstrup is with the department of surgery at Holbaek (Denmark) Hospital. She reported having no relevant conflicts of interest. These comments recap her editorial (New Engl J Med. 2018 May 10. doi: 10.1056/NEJMe1805615).
among high-risk patients undergoing major abdominal surgery and led to a significantly increased risk of acute kidney injury, researchers reported.
In an international, randomized trial with 366 median days of follow-up, estimated 1-year rates of disability-free survival were 81.9% with the restrictive intravenous fluid regimen and 82.3% with the liberal regimen (hazard ratio for death or disability, 1.05; P = .61), according to Paul S. Myles, MPH, DSc, and his associates.
Rates of acute renal injury were 8.6% in the restrictive IV fluid group and 5.0% with the liberal fluid therapy (P less than .001), the researchers reported online May 10 in the New England Journal of Medicine.
Guidelines recommend a restrictive intravenous fluid strategy to promote early recovery after major abdominal surgery, noted Dr. Myles of Alfred Hospital in Melbourne and his colleagues. “However, the supporting evidence is limited, and there is concern about impaired organ perfusion.”
Therefore, they randomly assigned, 3,000 patients to receive either the restrictive fluid regimen or a liberal regimen during major abdominal surgery and up to 24 hours after. Median intravenous volume was 3.7 L (interquartile range, 2.9-4.9 L) in the restrictive group and 6.1 L (IQR, 5.0-7.4 L) in the liberal fluid group. All patients were deemed high risk based on their age (at least 70 years) or because they had heart disease, diabetes, kidney disease, or morbid obesity.
Patients who received the restrictive regimen had higher rates of surgical site infection (16.5% vs. 13.6% with liberal fluids; P = .02) and were more likely to receive renal replacement therapy (0.9% vs. 0.3%; P = .048). However, these trends were no longer significant after the researchers controlled for the effects of testing for multiple variables.
“Our findings should not be used to support excessive administration of intravenous fluid,” the researchers cautioned. “Rather, they show that a regimen that includes a modestly liberal administration of fluid is safer than a restrictive regimen.”
Funders included the Australian National Health and Medical Research Council (NHMRC), the Health Research Council of New Zealand, the Australian and New Zealand College of Anaesthetists, and Monash University, Melbourne. Dr. Myles reported receiving grant support from NHMRC. He had no other disclosures.
SOURCE: Myles PS et al. New Engl J Med. 2018 May 10. doi: 10.1056/NEJMoa1801601.
among high-risk patients undergoing major abdominal surgery and led to a significantly increased risk of acute kidney injury, researchers reported.
In an international, randomized trial with 366 median days of follow-up, estimated 1-year rates of disability-free survival were 81.9% with the restrictive intravenous fluid regimen and 82.3% with the liberal regimen (hazard ratio for death or disability, 1.05; P = .61), according to Paul S. Myles, MPH, DSc, and his associates.
Rates of acute renal injury were 8.6% in the restrictive IV fluid group and 5.0% with the liberal fluid therapy (P less than .001), the researchers reported online May 10 in the New England Journal of Medicine.
Guidelines recommend a restrictive intravenous fluid strategy to promote early recovery after major abdominal surgery, noted Dr. Myles of Alfred Hospital in Melbourne and his colleagues. “However, the supporting evidence is limited, and there is concern about impaired organ perfusion.”
Therefore, they randomly assigned, 3,000 patients to receive either the restrictive fluid regimen or a liberal regimen during major abdominal surgery and up to 24 hours after. Median intravenous volume was 3.7 L (interquartile range, 2.9-4.9 L) in the restrictive group and 6.1 L (IQR, 5.0-7.4 L) in the liberal fluid group. All patients were deemed high risk based on their age (at least 70 years) or because they had heart disease, diabetes, kidney disease, or morbid obesity.
Patients who received the restrictive regimen had higher rates of surgical site infection (16.5% vs. 13.6% with liberal fluids; P = .02) and were more likely to receive renal replacement therapy (0.9% vs. 0.3%; P = .048). However, these trends were no longer significant after the researchers controlled for the effects of testing for multiple variables.
“Our findings should not be used to support excessive administration of intravenous fluid,” the researchers cautioned. “Rather, they show that a regimen that includes a modestly liberal administration of fluid is safer than a restrictive regimen.”
Funders included the Australian National Health and Medical Research Council (NHMRC), the Health Research Council of New Zealand, the Australian and New Zealand College of Anaesthetists, and Monash University, Melbourne. Dr. Myles reported receiving grant support from NHMRC. He had no other disclosures.
SOURCE: Myles PS et al. New Engl J Med. 2018 May 10. doi: 10.1056/NEJMoa1801601.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Compared with a liberal fluid regimen, restricting fluids did not improve disability-free survival and was tied to a significantly increased risk of acute kidney injury among high-risk patients undergoing major abdominal surgery.
Major finding: Rates of acute renal injury were 8.6% with restrictive fluids and 5.0% with liberal fluids.
Study details: International randomized trial of 3,000 patients undergoing major abdominal surgery.
Disclosures: Funders included the Australian National Health and Medical Research Council, the Health Research Council of New Zealand, the Australian and New Zealand College of Anaesthetists, and Monash University, Melbourne. Dr. Myles reported receiving grant support from NHMRC. He had no other disclosures.
Source: Myles PS et al. New Engl J Med. 2018 May 10. doi: 10.1056/NEJMoa1801601
Team identifies new prognostic factor for MF
New research suggests DNA sequencing can reveal which patients with early stage mycosis fungoides (MF) will develop aggressive disease.
By sequencing the T-cell receptor beta gene (TCRB) in skin biopsies from MF patients, investigators were able to measure the tumor clone frequency (TCF), or the percentage of all T cells that represent the MF clone.
The researchers found the TCF could predict progression-free survival (PFS) and overall survival (OS).
In fact, for patients with early stage MF, TCF was a stronger predictor of PFS than other established prognostic factors.
“While more work needs to be done, we think this approach has the potential to prospectively identify a subgroup of patients who are destined to develop aggressive, life-threatening disease and treat them in a more aggressive fashion with the intent to better manage and, ideally, cure their cancer,” said Thomas Kupper, MD, of Brigham and Women’s Hospital in Boston, Massachusetts.
“At the same time, we believe we can provide reassurance to patients with a low-risk (low TCF) profile that they are likely to survive indefinitely with conventional conservative therapies. As a physician who has treated this disease for decades, I am excited to be involved with work that so directly and profoundly affects the care and management of these patients.”
Dr Kupper and his colleagues described this work in Science Translational Medicine.
The researchers had previously published a study showing that high-throughput sequencing of the TCRB gene was an accurate way to diagnose cutaneous T-cell lymphoma (CTCL), including MF.
With the current study, the investigators set out to determine if the method could be used to predict progression and survival in patients with CTCL.
The team sequenced TCRB in lesional skin biopsies from 309 CTCL patients, most of whom had MF. The discovery cohort had 208 patients (177 with MF), and the validation cohort had 101 patients (87 with MF).
The sequencing produced a snapshot of the TCRB genes from a large number of cells at the site of the lesion. And the researchers could use this to measure TCF.
The team tested the association of TCF with prognosis in all CTCL patients in the discovery cohort and found a TCF greater than 25% in the skin was significantly associated with reduced PFS (P<0.001) and OS (P<0.001). Results were similar in the validation cohort (P<0.001 for PFS and OS).
The investigators also found that TCF was significantly associated with PFS (P<0.001) and OS (P<0.001) in MF patients but not in patients with Sézary syndrome. The team noted that they did not assess the predictive value of TCF in the blood of Sézary patients.
In a multivariable analysis, TCF was still significantly associated with PFS (P<0.001) and OS (P<0.001) in the MF patients.
The researchers also assessed potential prognostic variables in the early stage MF patients and found a TCF greater than 25% was a stronger predictor of PFS than any other established prognostic factor. This includes disease stage, presence of plaques, elevated lactate dehydrogenase, age, large-cell transformation, and CLIPI score.
“In reviewing the results, 2 different patients could have identical-looking skin lesions, but one might have a TCF of 8%, and one would have a TCF of 40%,” Dr Kupper noted. “The latter patient was highly likely to progress—something we would never have been able to predict before this discovery.”
“The TCF was independent of how thick or thin the skin lesions were. Most importantly, compared to all other currently used means of trying to predict which patients would progress, TCF was by far the most sensitive and specific.”
The high-throughput sequencing in this study was performed using ImmunoSEQ, an assay developed by Adaptive Biotechnologies. The company did not sponsor the study, but company employees were involved in the research.
New research suggests DNA sequencing can reveal which patients with early stage mycosis fungoides (MF) will develop aggressive disease.
By sequencing the T-cell receptor beta gene (TCRB) in skin biopsies from MF patients, investigators were able to measure the tumor clone frequency (TCF), or the percentage of all T cells that represent the MF clone.
The researchers found the TCF could predict progression-free survival (PFS) and overall survival (OS).
In fact, for patients with early stage MF, TCF was a stronger predictor of PFS than other established prognostic factors.
“While more work needs to be done, we think this approach has the potential to prospectively identify a subgroup of patients who are destined to develop aggressive, life-threatening disease and treat them in a more aggressive fashion with the intent to better manage and, ideally, cure their cancer,” said Thomas Kupper, MD, of Brigham and Women’s Hospital in Boston, Massachusetts.
“At the same time, we believe we can provide reassurance to patients with a low-risk (low TCF) profile that they are likely to survive indefinitely with conventional conservative therapies. As a physician who has treated this disease for decades, I am excited to be involved with work that so directly and profoundly affects the care and management of these patients.”
Dr Kupper and his colleagues described this work in Science Translational Medicine.
The researchers had previously published a study showing that high-throughput sequencing of the TCRB gene was an accurate way to diagnose cutaneous T-cell lymphoma (CTCL), including MF.
With the current study, the investigators set out to determine if the method could be used to predict progression and survival in patients with CTCL.
The team sequenced TCRB in lesional skin biopsies from 309 CTCL patients, most of whom had MF. The discovery cohort had 208 patients (177 with MF), and the validation cohort had 101 patients (87 with MF).
The sequencing produced a snapshot of the TCRB genes from a large number of cells at the site of the lesion. And the researchers could use this to measure TCF.
The team tested the association of TCF with prognosis in all CTCL patients in the discovery cohort and found a TCF greater than 25% in the skin was significantly associated with reduced PFS (P<0.001) and OS (P<0.001). Results were similar in the validation cohort (P<0.001 for PFS and OS).
The investigators also found that TCF was significantly associated with PFS (P<0.001) and OS (P<0.001) in MF patients but not in patients with Sézary syndrome. The team noted that they did not assess the predictive value of TCF in the blood of Sézary patients.
In a multivariable analysis, TCF was still significantly associated with PFS (P<0.001) and OS (P<0.001) in the MF patients.
The researchers also assessed potential prognostic variables in the early stage MF patients and found a TCF greater than 25% was a stronger predictor of PFS than any other established prognostic factor. This includes disease stage, presence of plaques, elevated lactate dehydrogenase, age, large-cell transformation, and CLIPI score.
“In reviewing the results, 2 different patients could have identical-looking skin lesions, but one might have a TCF of 8%, and one would have a TCF of 40%,” Dr Kupper noted. “The latter patient was highly likely to progress—something we would never have been able to predict before this discovery.”
“The TCF was independent of how thick or thin the skin lesions were. Most importantly, compared to all other currently used means of trying to predict which patients would progress, TCF was by far the most sensitive and specific.”
The high-throughput sequencing in this study was performed using ImmunoSEQ, an assay developed by Adaptive Biotechnologies. The company did not sponsor the study, but company employees were involved in the research.
New research suggests DNA sequencing can reveal which patients with early stage mycosis fungoides (MF) will develop aggressive disease.
By sequencing the T-cell receptor beta gene (TCRB) in skin biopsies from MF patients, investigators were able to measure the tumor clone frequency (TCF), or the percentage of all T cells that represent the MF clone.
The researchers found the TCF could predict progression-free survival (PFS) and overall survival (OS).
In fact, for patients with early stage MF, TCF was a stronger predictor of PFS than other established prognostic factors.
“While more work needs to be done, we think this approach has the potential to prospectively identify a subgroup of patients who are destined to develop aggressive, life-threatening disease and treat them in a more aggressive fashion with the intent to better manage and, ideally, cure their cancer,” said Thomas Kupper, MD, of Brigham and Women’s Hospital in Boston, Massachusetts.
“At the same time, we believe we can provide reassurance to patients with a low-risk (low TCF) profile that they are likely to survive indefinitely with conventional conservative therapies. As a physician who has treated this disease for decades, I am excited to be involved with work that so directly and profoundly affects the care and management of these patients.”
Dr Kupper and his colleagues described this work in Science Translational Medicine.
The researchers had previously published a study showing that high-throughput sequencing of the TCRB gene was an accurate way to diagnose cutaneous T-cell lymphoma (CTCL), including MF.
With the current study, the investigators set out to determine if the method could be used to predict progression and survival in patients with CTCL.
The team sequenced TCRB in lesional skin biopsies from 309 CTCL patients, most of whom had MF. The discovery cohort had 208 patients (177 with MF), and the validation cohort had 101 patients (87 with MF).
The sequencing produced a snapshot of the TCRB genes from a large number of cells at the site of the lesion. And the researchers could use this to measure TCF.
The team tested the association of TCF with prognosis in all CTCL patients in the discovery cohort and found a TCF greater than 25% in the skin was significantly associated with reduced PFS (P<0.001) and OS (P<0.001). Results were similar in the validation cohort (P<0.001 for PFS and OS).
The investigators also found that TCF was significantly associated with PFS (P<0.001) and OS (P<0.001) in MF patients but not in patients with Sézary syndrome. The team noted that they did not assess the predictive value of TCF in the blood of Sézary patients.
In a multivariable analysis, TCF was still significantly associated with PFS (P<0.001) and OS (P<0.001) in the MF patients.
The researchers also assessed potential prognostic variables in the early stage MF patients and found a TCF greater than 25% was a stronger predictor of PFS than any other established prognostic factor. This includes disease stage, presence of plaques, elevated lactate dehydrogenase, age, large-cell transformation, and CLIPI score.
“In reviewing the results, 2 different patients could have identical-looking skin lesions, but one might have a TCF of 8%, and one would have a TCF of 40%,” Dr Kupper noted. “The latter patient was highly likely to progress—something we would never have been able to predict before this discovery.”
“The TCF was independent of how thick or thin the skin lesions were. Most importantly, compared to all other currently used means of trying to predict which patients would progress, TCF was by far the most sensitive and specific.”
The high-throughput sequencing in this study was performed using ImmunoSEQ, an assay developed by Adaptive Biotechnologies. The company did not sponsor the study, but company employees were involved in the research.
Producing compatible RBCs for transfusion
Researchers say they have found a way to generate customized red blood cells (RBCs) that might one day be used to avoid transfusion incompatibilities.
The team used genome editing to modify an erythroblast cell line, making it deficient in antigens responsible for common transfusion incompatibilities.
The cells in this line could then be differentiated to generate RBCs with broad transfusion compatibility.
The researchers stressed that many obstacles must be overcome before this approach can be translated to a clinical product. However, this work does demonstrate proof of principle.
Ashley Mark Toye, PhD, of the University of Bristol in Bristol, UK, and his colleagues described this work in EMBO Molecular Medicine.
With previous work, Dr Toye and his colleagues generated an immortalized human erythroblast cell line known as the Bristol Erythroid Line Adult (BEL-A). The team showed that this cell line can be induced to generate RBCs in the lab.
With the current study, the researchers engineered BEL-A to express fewer antigens and therefore be less immunogenic.
The team first conducted a 15-month survey in England to investigate which antigens most commonly caused challenges in identifying a matched donated unit for transfusion recipients. The survey revealed 56 patients who had rare blood types with alloantibodies against RBC antigens.
Twenty-two of the patients had alloantibodies to antigens located on glycophorin B (GPB), U, S, or s. Nineteen patients had alloantibodies to antigens within the Rh blood group system.
Ten patients had alloantibodies to the Duffy blood group, and 2 previously untransfused patients had Fy (a-b-). Ten patients had Kell antigen alloantibodies. Eight patients had the Bombay or para-Bombay phenotype. And 3 patients each had alloantibodies to Lu and Kidd antigens.
To create compatible RBCs, the researchers first removed these blood groups from BEL-A using CRISPR-Cas9 genome editing.
The team created several new cell lines that lacked individual blood groups before creating a single cell line in which the 5 most common blood groups were removed—ABO (Bombay phenotype), Rh (Rhnull), Kell (K0), Duffy (Duffynull), and GPB (S-s-U-).
RBCs derived from this modified cell line could, theoretically, serve most of the challenging cases the researchers identified.
“Blood made using genetically edited cells could one day provide compatible transfusions for a group of patients for whom blood matching is difficult or impossible to achieve within the donor population,” Dr Toye said. “However, much more work will still be needed to produce blood cells suitable for patient use.”
Researchers say they have found a way to generate customized red blood cells (RBCs) that might one day be used to avoid transfusion incompatibilities.
The team used genome editing to modify an erythroblast cell line, making it deficient in antigens responsible for common transfusion incompatibilities.
The cells in this line could then be differentiated to generate RBCs with broad transfusion compatibility.
The researchers stressed that many obstacles must be overcome before this approach can be translated to a clinical product. However, this work does demonstrate proof of principle.
Ashley Mark Toye, PhD, of the University of Bristol in Bristol, UK, and his colleagues described this work in EMBO Molecular Medicine.
With previous work, Dr Toye and his colleagues generated an immortalized human erythroblast cell line known as the Bristol Erythroid Line Adult (BEL-A). The team showed that this cell line can be induced to generate RBCs in the lab.
With the current study, the researchers engineered BEL-A to express fewer antigens and therefore be less immunogenic.
The team first conducted a 15-month survey in England to investigate which antigens most commonly caused challenges in identifying a matched donated unit for transfusion recipients. The survey revealed 56 patients who had rare blood types with alloantibodies against RBC antigens.
Twenty-two of the patients had alloantibodies to antigens located on glycophorin B (GPB), U, S, or s. Nineteen patients had alloantibodies to antigens within the Rh blood group system.
Ten patients had alloantibodies to the Duffy blood group, and 2 previously untransfused patients had Fy (a-b-). Ten patients had Kell antigen alloantibodies. Eight patients had the Bombay or para-Bombay phenotype. And 3 patients each had alloantibodies to Lu and Kidd antigens.
To create compatible RBCs, the researchers first removed these blood groups from BEL-A using CRISPR-Cas9 genome editing.
The team created several new cell lines that lacked individual blood groups before creating a single cell line in which the 5 most common blood groups were removed—ABO (Bombay phenotype), Rh (Rhnull), Kell (K0), Duffy (Duffynull), and GPB (S-s-U-).
RBCs derived from this modified cell line could, theoretically, serve most of the challenging cases the researchers identified.
“Blood made using genetically edited cells could one day provide compatible transfusions for a group of patients for whom blood matching is difficult or impossible to achieve within the donor population,” Dr Toye said. “However, much more work will still be needed to produce blood cells suitable for patient use.”
Researchers say they have found a way to generate customized red blood cells (RBCs) that might one day be used to avoid transfusion incompatibilities.
The team used genome editing to modify an erythroblast cell line, making it deficient in antigens responsible for common transfusion incompatibilities.
The cells in this line could then be differentiated to generate RBCs with broad transfusion compatibility.
The researchers stressed that many obstacles must be overcome before this approach can be translated to a clinical product. However, this work does demonstrate proof of principle.
Ashley Mark Toye, PhD, of the University of Bristol in Bristol, UK, and his colleagues described this work in EMBO Molecular Medicine.
With previous work, Dr Toye and his colleagues generated an immortalized human erythroblast cell line known as the Bristol Erythroid Line Adult (BEL-A). The team showed that this cell line can be induced to generate RBCs in the lab.
With the current study, the researchers engineered BEL-A to express fewer antigens and therefore be less immunogenic.
The team first conducted a 15-month survey in England to investigate which antigens most commonly caused challenges in identifying a matched donated unit for transfusion recipients. The survey revealed 56 patients who had rare blood types with alloantibodies against RBC antigens.
Twenty-two of the patients had alloantibodies to antigens located on glycophorin B (GPB), U, S, or s. Nineteen patients had alloantibodies to antigens within the Rh blood group system.
Ten patients had alloantibodies to the Duffy blood group, and 2 previously untransfused patients had Fy (a-b-). Ten patients had Kell antigen alloantibodies. Eight patients had the Bombay or para-Bombay phenotype. And 3 patients each had alloantibodies to Lu and Kidd antigens.
To create compatible RBCs, the researchers first removed these blood groups from BEL-A using CRISPR-Cas9 genome editing.
The team created several new cell lines that lacked individual blood groups before creating a single cell line in which the 5 most common blood groups were removed—ABO (Bombay phenotype), Rh (Rhnull), Kell (K0), Duffy (Duffynull), and GPB (S-s-U-).
RBCs derived from this modified cell line could, theoretically, serve most of the challenging cases the researchers identified.
“Blood made using genetically edited cells could one day provide compatible transfusions for a group of patients for whom blood matching is difficult or impossible to achieve within the donor population,” Dr Toye said. “However, much more work will still be needed to produce blood cells suitable for patient use.”
Cooperation can drive T-ALL, study shows
Overexpression of HOXA9 and activated JAK/STAT signaling cooperate to drive the development of T-cell acute lymphoblastic leukemia (ALL), according to researchers.
The team found that JAK3 mutations are significantly associated with elevated HOXA9 expression in T-ALL, and co-expression of HOXA9 and JAK3 mutations prompt “rapid” leukemia development in mice.
In addition, STAT5 and HOXA9 occupy similar genetic loci, which results in increased JAK-STAT signaling in leukemia cells.
These discoveries, and results of subsequent experiments, suggested that PIM1 and JAK1 are potential therapeutic targets for T-ALL.
Jan Cools, PhD, of VIB-KU Leuven Center for Cancer Biology in Leuven, Belgium, and his colleagues described this research in Cancer Discovery.
“JAK3/STAT5 mutations are important in ALL since they stimulate the growth of the cells,” Dr Cools said. “[W]e found that JAK3/STAT5 mutations frequently occur together with HOXA9 mutations.”
In analyzing data from 2 cohorts of T-ALL patients, the researchers found that IL7R/JAK/STAT5 mutations were more frequent in HOXA+ cases, and HOXA9 was “the most important upregulated gene of the HOXA cluster.” (HOXA9 expression levels were significantly higher than HOXA10 or HOXA11 levels.)
“We examined the cooperation between JAK3/STAT5 mutation and HOXA9, [and] we observed that HOXA9 boosts the effects of other genes, leading to tumor development,” said study author Charles de Bock, PhD, of VIB-KU Leuven.
“As a result, when JAK3/STAT5 mutations and HOXA9 are both present, leukemia develops more rapidly and aggressively.”
The researchers found that co-expression of HOXA9 and the JAK3 M511I mutation led to rapid leukemia development in mice. Animals with co-expression of HOXA9 and JAK3 (M511I) developed leukemia that was characterized by an increase in peripheral white blood cell counts that exceeded 10,000 cells/mm3 within 30 days.
In addition, these mice had a significant decrease in disease-free survival compared to mice with JAK3 (M511I) alone. The median disease-free survival was 25 days and 126.5 days, respectively (P<0.0001).
Further analysis revealed co-localization of HOXA9 and STAT5. The researchers also found that HOXA9 enhances transcriptional activity of STAT5 in leukemia cells.
The team said this reconfirms STAT5 as “a major central player” in T-ALL, and it suggests that STAT5 target genes such as PIM1 could be therapeutic targets for T-ALL.
To test this theory, the researchers inhibited both PIM1 and JAK1 in JAK/STAT mutant T-ALL. The PIM1 inhibitor AZD1208 and the JAK1/2 inhibitor ruxolitinib demonstrated synergy and significantly reduced leukemia burden in vivo.
Overexpression of HOXA9 and activated JAK/STAT signaling cooperate to drive the development of T-cell acute lymphoblastic leukemia (ALL), according to researchers.
The team found that JAK3 mutations are significantly associated with elevated HOXA9 expression in T-ALL, and co-expression of HOXA9 and JAK3 mutations prompt “rapid” leukemia development in mice.
In addition, STAT5 and HOXA9 occupy similar genetic loci, which results in increased JAK-STAT signaling in leukemia cells.
These discoveries, and results of subsequent experiments, suggested that PIM1 and JAK1 are potential therapeutic targets for T-ALL.
Jan Cools, PhD, of VIB-KU Leuven Center for Cancer Biology in Leuven, Belgium, and his colleagues described this research in Cancer Discovery.
“JAK3/STAT5 mutations are important in ALL since they stimulate the growth of the cells,” Dr Cools said. “[W]e found that JAK3/STAT5 mutations frequently occur together with HOXA9 mutations.”
In analyzing data from 2 cohorts of T-ALL patients, the researchers found that IL7R/JAK/STAT5 mutations were more frequent in HOXA+ cases, and HOXA9 was “the most important upregulated gene of the HOXA cluster.” (HOXA9 expression levels were significantly higher than HOXA10 or HOXA11 levels.)
“We examined the cooperation between JAK3/STAT5 mutation and HOXA9, [and] we observed that HOXA9 boosts the effects of other genes, leading to tumor development,” said study author Charles de Bock, PhD, of VIB-KU Leuven.
“As a result, when JAK3/STAT5 mutations and HOXA9 are both present, leukemia develops more rapidly and aggressively.”
The researchers found that co-expression of HOXA9 and the JAK3 M511I mutation led to rapid leukemia development in mice. Animals with co-expression of HOXA9 and JAK3 (M511I) developed leukemia that was characterized by an increase in peripheral white blood cell counts that exceeded 10,000 cells/mm3 within 30 days.
In addition, these mice had a significant decrease in disease-free survival compared to mice with JAK3 (M511I) alone. The median disease-free survival was 25 days and 126.5 days, respectively (P<0.0001).
Further analysis revealed co-localization of HOXA9 and STAT5. The researchers also found that HOXA9 enhances transcriptional activity of STAT5 in leukemia cells.
The team said this reconfirms STAT5 as “a major central player” in T-ALL, and it suggests that STAT5 target genes such as PIM1 could be therapeutic targets for T-ALL.
To test this theory, the researchers inhibited both PIM1 and JAK1 in JAK/STAT mutant T-ALL. The PIM1 inhibitor AZD1208 and the JAK1/2 inhibitor ruxolitinib demonstrated synergy and significantly reduced leukemia burden in vivo.
Overexpression of HOXA9 and activated JAK/STAT signaling cooperate to drive the development of T-cell acute lymphoblastic leukemia (ALL), according to researchers.
The team found that JAK3 mutations are significantly associated with elevated HOXA9 expression in T-ALL, and co-expression of HOXA9 and JAK3 mutations prompt “rapid” leukemia development in mice.
In addition, STAT5 and HOXA9 occupy similar genetic loci, which results in increased JAK-STAT signaling in leukemia cells.
These discoveries, and results of subsequent experiments, suggested that PIM1 and JAK1 are potential therapeutic targets for T-ALL.
Jan Cools, PhD, of VIB-KU Leuven Center for Cancer Biology in Leuven, Belgium, and his colleagues described this research in Cancer Discovery.
“JAK3/STAT5 mutations are important in ALL since they stimulate the growth of the cells,” Dr Cools said. “[W]e found that JAK3/STAT5 mutations frequently occur together with HOXA9 mutations.”
In analyzing data from 2 cohorts of T-ALL patients, the researchers found that IL7R/JAK/STAT5 mutations were more frequent in HOXA+ cases, and HOXA9 was “the most important upregulated gene of the HOXA cluster.” (HOXA9 expression levels were significantly higher than HOXA10 or HOXA11 levels.)
“We examined the cooperation between JAK3/STAT5 mutation and HOXA9, [and] we observed that HOXA9 boosts the effects of other genes, leading to tumor development,” said study author Charles de Bock, PhD, of VIB-KU Leuven.
“As a result, when JAK3/STAT5 mutations and HOXA9 are both present, leukemia develops more rapidly and aggressively.”
The researchers found that co-expression of HOXA9 and the JAK3 M511I mutation led to rapid leukemia development in mice. Animals with co-expression of HOXA9 and JAK3 (M511I) developed leukemia that was characterized by an increase in peripheral white blood cell counts that exceeded 10,000 cells/mm3 within 30 days.
In addition, these mice had a significant decrease in disease-free survival compared to mice with JAK3 (M511I) alone. The median disease-free survival was 25 days and 126.5 days, respectively (P<0.0001).
Further analysis revealed co-localization of HOXA9 and STAT5. The researchers also found that HOXA9 enhances transcriptional activity of STAT5 in leukemia cells.
The team said this reconfirms STAT5 as “a major central player” in T-ALL, and it suggests that STAT5 target genes such as PIM1 could be therapeutic targets for T-ALL.
To test this theory, the researchers inhibited both PIM1 and JAK1 in JAK/STAT mutant T-ALL. The PIM1 inhibitor AZD1208 and the JAK1/2 inhibitor ruxolitinib demonstrated synergy and significantly reduced leukemia burden in vivo.
Emotional regulation training lowers risk of adolescents having sex
Emotional regulation (ER) skills training lowers the likelihood that young adolescents with mental health symptoms will have vaginal sex.
“The inclusion of ER training in a small-group behavioral intervention reduced sexual risk behaviors among seventh-graders with suspected mental health symptoms over a 2.5-year follow-up beyond that achieved with more traditional health education,” wrote Chistopher Houck, PhD, and his colleagues at Bradley Hasbro Children’s Research Center, Providence, R.I., in Pediatrics. “This was true across a range of behaviors, such as engaging in fewer condom-less sex acts, being less likely to have multiple partners, and being less likely to use substances before sex.”
Students in the study participated in one of two after school intervention programs, either ER or health promotion (HP). Both programs consisted of 12 twice-weekly, hour-long sessions composed of single-sex groups of 4-8 adolescents. Two follow-up sessions were provided for both groups at 6 and 12 months. Both interventions used identical techniques, such as interactive games, videos, group discussions, and workbook assignments. ER sessions focused more on recognizing feelings, strategies for reducing momentary emotional arousal, and sexual health topics. HP exclusively focused on health topics like sexual risk and substance abuse but did not include emotional education.
During the 30-month study, 63 in the ER group (31%) and 68 students in the HP group (39%) reported having vaginal sex for the first time. This equated to an adjusted hazard ratio that indicated a delay in vaginal sex in the ER group (0.61; 95% confidence interval,0.42-0.89). Overall, students in the ER group were much less likely to endorse risky sexual behaviors than did participants in the HP group: Students in the ER group were less likely to endorse any risky sexual behavior (adjusted odds ratio, 0.52; 95% CI, 0.32-0.84), to support having multiple partners within 6 months (aOR, 0.54; 95% CI, 0.30-0.99), and to support the use of drugs before sex (aOR, 0.42; 95% CI, 0.23-0.75). Students in the ER group also reported fewer condom-less sex acts, compared with students in the HP group (adjusted rate ratio, 0.36; 95% CI, 0.14-0.90).
According to Dr. Houck and his colleagues, this study had several limitations that are common to sexual risk studies. One limitation is the reliance on self-report data, which can be biased. Dr. Houck and his associates utilized computer-assisted self-interviews to minimize biases. Another, and potentially larger, limitation is that the study was powered to assess delay of vaginal sex. Part of the patient sample was not sexually experienced, which provided less power for comparisons to other sexual behaviors.
Dr. Houck and his colleagues also spoke to the potential that ER training has in reducing risky behaviors of adolescents, as well as the issues in implementing it.
“Because ER is a skill that could influence other adolescent risk behaviors, such as substance use, violence, and truancy, addressing ER during this sensitive period in adolescent development promises significant public health benefits,” they wrote. “The challenge is the scale-up and dissemination of ER interventions. Increasing the reach of programs in which health education is enhanced with emotion education may be an important step toward improving the lives of adolescents because they are prone to beginning risk behavior.”
Dr. Houck and his associates have no relevant financial disclosures. This study received funding from the National Institutes of Health and the Providence/Boston Center for AIDS Research.
SOURCE: Houck C et al. Pediatrics. 2018 May 10. doi: 10.1542/peds.2017-2525.
The work of Houck et al. provides an important contribution in understanding strategies to reduce sexually transmitted infections (STIs) and HIV in adolescents by utilizing emotional regulation skills.
By helping young people understand their emotions and how that relates to behavior in the context of a sexual encounter, the after school intervention program helped teens regulate positive and negative emotions. Specifically, it utilized three strategies: get out, let it out, and think it out. Games and role playing gave teens a chance to practice these strategies in scenarios of varying risk.
Teenagers who underwent emotional regulation training, rather than simply being taught about adolescent health topics, fared much better in reducing the transition to vaginal sex over a 30-month period.
Carol Ford, MD, and her colleague James Jaccard, PhD, pointed out the superiority of the emotional training, compared with just sexual health information.
“Together, these findings reveal the importance of gearing more attention toward emotions and the regulation of emotions when developing interventions aimed at influencing adolescent sexual behavior,” they wrote. “Behavioral decision theory implicates the role of adolescent cognitions about engaging in sex, norms and peer pressure, and adolescent image prototypes surrounding sex.”
More broadly, Dr. Ford and Dr. Jaccard, believe that this research is the beginning to designing better interventions.
“As we come to understand the types of cognitions and emotions that dominate working memory in high-risk sexual situations, we can effectively design interventions that help shape cognitive and affective appraisals and how youth process those appraisals when making choices.”
Carol Ford, MD, is the chief of the Craig-Dalsimer Division of Adolescent Medicine at the Children’s Hospital of Philadelphia; she holds the Orton P. Jackson Endowed Chair in Adolescent Medicine. James Jaccard, PhD, is a professor of social work at New York University Silver School of Social Work. This is a summary of their commentary that accompanied the article by Houck et al. (Pediatrics. 2018 May 10. doi: 10.1542/peds.2017-4143). They had no financial disclosures, and there was no external funding.
The work of Houck et al. provides an important contribution in understanding strategies to reduce sexually transmitted infections (STIs) and HIV in adolescents by utilizing emotional regulation skills.
By helping young people understand their emotions and how that relates to behavior in the context of a sexual encounter, the after school intervention program helped teens regulate positive and negative emotions. Specifically, it utilized three strategies: get out, let it out, and think it out. Games and role playing gave teens a chance to practice these strategies in scenarios of varying risk.
Teenagers who underwent emotional regulation training, rather than simply being taught about adolescent health topics, fared much better in reducing the transition to vaginal sex over a 30-month period.
Carol Ford, MD, and her colleague James Jaccard, PhD, pointed out the superiority of the emotional training, compared with just sexual health information.
“Together, these findings reveal the importance of gearing more attention toward emotions and the regulation of emotions when developing interventions aimed at influencing adolescent sexual behavior,” they wrote. “Behavioral decision theory implicates the role of adolescent cognitions about engaging in sex, norms and peer pressure, and adolescent image prototypes surrounding sex.”
More broadly, Dr. Ford and Dr. Jaccard, believe that this research is the beginning to designing better interventions.
“As we come to understand the types of cognitions and emotions that dominate working memory in high-risk sexual situations, we can effectively design interventions that help shape cognitive and affective appraisals and how youth process those appraisals when making choices.”
Carol Ford, MD, is the chief of the Craig-Dalsimer Division of Adolescent Medicine at the Children’s Hospital of Philadelphia; she holds the Orton P. Jackson Endowed Chair in Adolescent Medicine. James Jaccard, PhD, is a professor of social work at New York University Silver School of Social Work. This is a summary of their commentary that accompanied the article by Houck et al. (Pediatrics. 2018 May 10. doi: 10.1542/peds.2017-4143). They had no financial disclosures, and there was no external funding.
The work of Houck et al. provides an important contribution in understanding strategies to reduce sexually transmitted infections (STIs) and HIV in adolescents by utilizing emotional regulation skills.
By helping young people understand their emotions and how that relates to behavior in the context of a sexual encounter, the after school intervention program helped teens regulate positive and negative emotions. Specifically, it utilized three strategies: get out, let it out, and think it out. Games and role playing gave teens a chance to practice these strategies in scenarios of varying risk.
Teenagers who underwent emotional regulation training, rather than simply being taught about adolescent health topics, fared much better in reducing the transition to vaginal sex over a 30-month period.
Carol Ford, MD, and her colleague James Jaccard, PhD, pointed out the superiority of the emotional training, compared with just sexual health information.
“Together, these findings reveal the importance of gearing more attention toward emotions and the regulation of emotions when developing interventions aimed at influencing adolescent sexual behavior,” they wrote. “Behavioral decision theory implicates the role of adolescent cognitions about engaging in sex, norms and peer pressure, and adolescent image prototypes surrounding sex.”
More broadly, Dr. Ford and Dr. Jaccard, believe that this research is the beginning to designing better interventions.
“As we come to understand the types of cognitions and emotions that dominate working memory in high-risk sexual situations, we can effectively design interventions that help shape cognitive and affective appraisals and how youth process those appraisals when making choices.”
Carol Ford, MD, is the chief of the Craig-Dalsimer Division of Adolescent Medicine at the Children’s Hospital of Philadelphia; she holds the Orton P. Jackson Endowed Chair in Adolescent Medicine. James Jaccard, PhD, is a professor of social work at New York University Silver School of Social Work. This is a summary of their commentary that accompanied the article by Houck et al. (Pediatrics. 2018 May 10. doi: 10.1542/peds.2017-4143). They had no financial disclosures, and there was no external funding.
Emotional regulation (ER) skills training lowers the likelihood that young adolescents with mental health symptoms will have vaginal sex.
“The inclusion of ER training in a small-group behavioral intervention reduced sexual risk behaviors among seventh-graders with suspected mental health symptoms over a 2.5-year follow-up beyond that achieved with more traditional health education,” wrote Chistopher Houck, PhD, and his colleagues at Bradley Hasbro Children’s Research Center, Providence, R.I., in Pediatrics. “This was true across a range of behaviors, such as engaging in fewer condom-less sex acts, being less likely to have multiple partners, and being less likely to use substances before sex.”
Students in the study participated in one of two after school intervention programs, either ER or health promotion (HP). Both programs consisted of 12 twice-weekly, hour-long sessions composed of single-sex groups of 4-8 adolescents. Two follow-up sessions were provided for both groups at 6 and 12 months. Both interventions used identical techniques, such as interactive games, videos, group discussions, and workbook assignments. ER sessions focused more on recognizing feelings, strategies for reducing momentary emotional arousal, and sexual health topics. HP exclusively focused on health topics like sexual risk and substance abuse but did not include emotional education.
During the 30-month study, 63 in the ER group (31%) and 68 students in the HP group (39%) reported having vaginal sex for the first time. This equated to an adjusted hazard ratio that indicated a delay in vaginal sex in the ER group (0.61; 95% confidence interval,0.42-0.89). Overall, students in the ER group were much less likely to endorse risky sexual behaviors than did participants in the HP group: Students in the ER group were less likely to endorse any risky sexual behavior (adjusted odds ratio, 0.52; 95% CI, 0.32-0.84), to support having multiple partners within 6 months (aOR, 0.54; 95% CI, 0.30-0.99), and to support the use of drugs before sex (aOR, 0.42; 95% CI, 0.23-0.75). Students in the ER group also reported fewer condom-less sex acts, compared with students in the HP group (adjusted rate ratio, 0.36; 95% CI, 0.14-0.90).
According to Dr. Houck and his colleagues, this study had several limitations that are common to sexual risk studies. One limitation is the reliance on self-report data, which can be biased. Dr. Houck and his associates utilized computer-assisted self-interviews to minimize biases. Another, and potentially larger, limitation is that the study was powered to assess delay of vaginal sex. Part of the patient sample was not sexually experienced, which provided less power for comparisons to other sexual behaviors.
Dr. Houck and his colleagues also spoke to the potential that ER training has in reducing risky behaviors of adolescents, as well as the issues in implementing it.
“Because ER is a skill that could influence other adolescent risk behaviors, such as substance use, violence, and truancy, addressing ER during this sensitive period in adolescent development promises significant public health benefits,” they wrote. “The challenge is the scale-up and dissemination of ER interventions. Increasing the reach of programs in which health education is enhanced with emotion education may be an important step toward improving the lives of adolescents because they are prone to beginning risk behavior.”
Dr. Houck and his associates have no relevant financial disclosures. This study received funding from the National Institutes of Health and the Providence/Boston Center for AIDS Research.
SOURCE: Houck C et al. Pediatrics. 2018 May 10. doi: 10.1542/peds.2017-2525.
Emotional regulation (ER) skills training lowers the likelihood that young adolescents with mental health symptoms will have vaginal sex.
“The inclusion of ER training in a small-group behavioral intervention reduced sexual risk behaviors among seventh-graders with suspected mental health symptoms over a 2.5-year follow-up beyond that achieved with more traditional health education,” wrote Chistopher Houck, PhD, and his colleagues at Bradley Hasbro Children’s Research Center, Providence, R.I., in Pediatrics. “This was true across a range of behaviors, such as engaging in fewer condom-less sex acts, being less likely to have multiple partners, and being less likely to use substances before sex.”
Students in the study participated in one of two after school intervention programs, either ER or health promotion (HP). Both programs consisted of 12 twice-weekly, hour-long sessions composed of single-sex groups of 4-8 adolescents. Two follow-up sessions were provided for both groups at 6 and 12 months. Both interventions used identical techniques, such as interactive games, videos, group discussions, and workbook assignments. ER sessions focused more on recognizing feelings, strategies for reducing momentary emotional arousal, and sexual health topics. HP exclusively focused on health topics like sexual risk and substance abuse but did not include emotional education.
During the 30-month study, 63 in the ER group (31%) and 68 students in the HP group (39%) reported having vaginal sex for the first time. This equated to an adjusted hazard ratio that indicated a delay in vaginal sex in the ER group (0.61; 95% confidence interval,0.42-0.89). Overall, students in the ER group were much less likely to endorse risky sexual behaviors than did participants in the HP group: Students in the ER group were less likely to endorse any risky sexual behavior (adjusted odds ratio, 0.52; 95% CI, 0.32-0.84), to support having multiple partners within 6 months (aOR, 0.54; 95% CI, 0.30-0.99), and to support the use of drugs before sex (aOR, 0.42; 95% CI, 0.23-0.75). Students in the ER group also reported fewer condom-less sex acts, compared with students in the HP group (adjusted rate ratio, 0.36; 95% CI, 0.14-0.90).
According to Dr. Houck and his colleagues, this study had several limitations that are common to sexual risk studies. One limitation is the reliance on self-report data, which can be biased. Dr. Houck and his associates utilized computer-assisted self-interviews to minimize biases. Another, and potentially larger, limitation is that the study was powered to assess delay of vaginal sex. Part of the patient sample was not sexually experienced, which provided less power for comparisons to other sexual behaviors.
Dr. Houck and his colleagues also spoke to the potential that ER training has in reducing risky behaviors of adolescents, as well as the issues in implementing it.
“Because ER is a skill that could influence other adolescent risk behaviors, such as substance use, violence, and truancy, addressing ER during this sensitive period in adolescent development promises significant public health benefits,” they wrote. “The challenge is the scale-up and dissemination of ER interventions. Increasing the reach of programs in which health education is enhanced with emotion education may be an important step toward improving the lives of adolescents because they are prone to beginning risk behavior.”
Dr. Houck and his associates have no relevant financial disclosures. This study received funding from the National Institutes of Health and the Providence/Boston Center for AIDS Research.
SOURCE: Houck C et al. Pediatrics. 2018 May 10. doi: 10.1542/peds.2017-2525.
FROM PEDIATRICS
Key clinical point: Emotional regulation (ER) training reduces the likelihood adolescents will have sex.
Major finding: There was a delay in vaginal sex in the ER group (adusted hazard ratio, 0.61; 95% confidence interval, 0.42-0.89), compared with the health promotion group.
Study details: The study included 420 seventh grade students aged 12-14 years from five urban Rhode Island middle schools between September 2009 and February 2012.
Disclosures: Dr. Houck and his associates have no relevant financial disclosures. This study received funding from the National Institutes of Health and the Providence/Boston Center for AIDS Research.
Source: Houck C et al. Pediatrics. 2018 May 10. doi: 10.1542/peds.2017-2525.
Growing mole on breast
The FP recognized this lesion as a congenital nevus.
He was aware that nevi might become more raised during early adulthood, though this was not necessarily a sign of malignant degeneration. He looked at the nevus carefully and saw that it was relatively symmetrical with one predominant color and a light brown coloration on the left edge. (The patient stated it had always been this way.) The surface texture, which could be described as mamillated, was not unusual for congenital nevi. The FP examined the nevus using a dermatoscope and did not see any melanoma-specific structures.
The FP encouraged the patient to monitor the nevus and return for further evaluation if there were any changes or symptoms. He also offered her the option of a biopsy, but stated that it was not medically required. The patient noted that the changes of increased height of the congenital nevus had been very slow over the past 2 years, and she was willing to keep an eye on it. The patient returned in 6 months, and there were no visible changes to the congenital nevus.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Congenital nevi. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:953-957.
To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.
You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.
The FP recognized this lesion as a congenital nevus.
He was aware that nevi might become more raised during early adulthood, though this was not necessarily a sign of malignant degeneration. He looked at the nevus carefully and saw that it was relatively symmetrical with one predominant color and a light brown coloration on the left edge. (The patient stated it had always been this way.) The surface texture, which could be described as mamillated, was not unusual for congenital nevi. The FP examined the nevus using a dermatoscope and did not see any melanoma-specific structures.
The FP encouraged the patient to monitor the nevus and return for further evaluation if there were any changes or symptoms. He also offered her the option of a biopsy, but stated that it was not medically required. The patient noted that the changes of increased height of the congenital nevus had been very slow over the past 2 years, and she was willing to keep an eye on it. The patient returned in 6 months, and there were no visible changes to the congenital nevus.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Congenital nevi. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:953-957.
To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.
You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.
The FP recognized this lesion as a congenital nevus.
He was aware that nevi might become more raised during early adulthood, though this was not necessarily a sign of malignant degeneration. He looked at the nevus carefully and saw that it was relatively symmetrical with one predominant color and a light brown coloration on the left edge. (The patient stated it had always been this way.) The surface texture, which could be described as mamillated, was not unusual for congenital nevi. The FP examined the nevus using a dermatoscope and did not see any melanoma-specific structures.
The FP encouraged the patient to monitor the nevus and return for further evaluation if there were any changes or symptoms. He also offered her the option of a biopsy, but stated that it was not medically required. The patient noted that the changes of increased height of the congenital nevus had been very slow over the past 2 years, and she was willing to keep an eye on it. The patient returned in 6 months, and there were no visible changes to the congenital nevus.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Congenital nevi. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:953-957.
To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.
You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.
Screening blood donations for Zika proved costly, low yield
Testing donated blood for Zika virus in the United States confirmed just 8 authentic cases and cost nearly $42 million over a period of 15 months, investigators reported online May 10 in the New England Journal of Medicine.
That price did not reflect a commercial price hike, said Paula Saá, PhD, of the American Red Cross in Gaithersburg, MD, and her associates. Furthermore, more than half of the Zika cases had a low viral level that might not be infectious.
Among more than 4 million screened donations, 9% were tested in pools. All pooled tests were negative. The other 3.9 million donations were screened individually. Only 160 were positive, and just 6 were confirmed positive on repeat TMA. Two of these six confirmed positives also were RNA-positive on reverse transcription polymerase chain reaction, while two were equivocal and two were negative. The positive and equivocal donations were negative for Zika immunoglobulin M on enzyme-linked immunosorbent assay, which indicated acute infections. The RNA-negative infections were IgM-positive, indicating prior infections.
Three more donations were initially positive on TMA, were negative on repeat TMA, and were IgM-positive, bringing the total case count to nine. Among these, two donors had been infected in Florida, six had traveled to Zika-endemic areas, and one had received an experimental Zika vaccine, according to the researchers.
For each detection of authentic Zika virus RNA infection in U.S.-donated blood, testing had cost $5.3 million, they concluded. They called the current FDA recommendation to individually screen all U.S. blood donations for Zika virus “low-yield” and “high cost.” Of three acute infections with enough sample left for pooled testing, all were positive, they noted.
The American Red Cross and Grifols Diagnostic Solutions provided funding. Dr. Saá disclosed research support from Grifols, which makes the TMA test used in the study. She had no other conflicts of interest.
SOURCE: Saá P et al. New Engl J Med. 2018;378:1778-88.
Despite these findings, it would be premature to stop testing U.S. blood donations for Zika virus, wrote Evan M. Bloch, MBChB; Paul M. Ness, MD; Aaron A.R. Tobian, MD, PhD; and Jeremy Sugarman, MD, MPH, in an editorial accompanying the study.
Nonetheless, “actual and perceived risks to the blood supply seem to be conflated,” the experts wrote. They noted that the United States currently has no active areas of Zika virus transmission and that confirmed mosquito-borne, locally acquired infections fell from 226 in 2016 to two the following year.
There is no historical precedent for ending a policy of testing blood donations for pathogens, they added. Consequently, ending widespread screening “may actually prove to be far more challenging than the decision to start.” For now, a precautionary, risk-based approach should entail “continuous review” of screening policies and “reassessment as new data emerge.”
The editorialists are with Johns Hopkins University and Johns Hopkins University’s Bergman Institute of Bioethics, both in Baltimore. They reported having no relevant conflicts of interest. These comments are from their editorial (New Engl J Med. 2018;378:19:1837-41).
Despite these findings, it would be premature to stop testing U.S. blood donations for Zika virus, wrote Evan M. Bloch, MBChB; Paul M. Ness, MD; Aaron A.R. Tobian, MD, PhD; and Jeremy Sugarman, MD, MPH, in an editorial accompanying the study.
Nonetheless, “actual and perceived risks to the blood supply seem to be conflated,” the experts wrote. They noted that the United States currently has no active areas of Zika virus transmission and that confirmed mosquito-borne, locally acquired infections fell from 226 in 2016 to two the following year.
There is no historical precedent for ending a policy of testing blood donations for pathogens, they added. Consequently, ending widespread screening “may actually prove to be far more challenging than the decision to start.” For now, a precautionary, risk-based approach should entail “continuous review” of screening policies and “reassessment as new data emerge.”
The editorialists are with Johns Hopkins University and Johns Hopkins University’s Bergman Institute of Bioethics, both in Baltimore. They reported having no relevant conflicts of interest. These comments are from their editorial (New Engl J Med. 2018;378:19:1837-41).
Despite these findings, it would be premature to stop testing U.S. blood donations for Zika virus, wrote Evan M. Bloch, MBChB; Paul M. Ness, MD; Aaron A.R. Tobian, MD, PhD; and Jeremy Sugarman, MD, MPH, in an editorial accompanying the study.
Nonetheless, “actual and perceived risks to the blood supply seem to be conflated,” the experts wrote. They noted that the United States currently has no active areas of Zika virus transmission and that confirmed mosquito-borne, locally acquired infections fell from 226 in 2016 to two the following year.
There is no historical precedent for ending a policy of testing blood donations for pathogens, they added. Consequently, ending widespread screening “may actually prove to be far more challenging than the decision to start.” For now, a precautionary, risk-based approach should entail “continuous review” of screening policies and “reassessment as new data emerge.”
The editorialists are with Johns Hopkins University and Johns Hopkins University’s Bergman Institute of Bioethics, both in Baltimore. They reported having no relevant conflicts of interest. These comments are from their editorial (New Engl J Med. 2018;378:19:1837-41).
Testing donated blood for Zika virus in the United States confirmed just 8 authentic cases and cost nearly $42 million over a period of 15 months, investigators reported online May 10 in the New England Journal of Medicine.
That price did not reflect a commercial price hike, said Paula Saá, PhD, of the American Red Cross in Gaithersburg, MD, and her associates. Furthermore, more than half of the Zika cases had a low viral level that might not be infectious.
Among more than 4 million screened donations, 9% were tested in pools. All pooled tests were negative. The other 3.9 million donations were screened individually. Only 160 were positive, and just 6 were confirmed positive on repeat TMA. Two of these six confirmed positives also were RNA-positive on reverse transcription polymerase chain reaction, while two were equivocal and two were negative. The positive and equivocal donations were negative for Zika immunoglobulin M on enzyme-linked immunosorbent assay, which indicated acute infections. The RNA-negative infections were IgM-positive, indicating prior infections.
Three more donations were initially positive on TMA, were negative on repeat TMA, and were IgM-positive, bringing the total case count to nine. Among these, two donors had been infected in Florida, six had traveled to Zika-endemic areas, and one had received an experimental Zika vaccine, according to the researchers.
For each detection of authentic Zika virus RNA infection in U.S.-donated blood, testing had cost $5.3 million, they concluded. They called the current FDA recommendation to individually screen all U.S. blood donations for Zika virus “low-yield” and “high cost.” Of three acute infections with enough sample left for pooled testing, all were positive, they noted.
The American Red Cross and Grifols Diagnostic Solutions provided funding. Dr. Saá disclosed research support from Grifols, which makes the TMA test used in the study. She had no other conflicts of interest.
SOURCE: Saá P et al. New Engl J Med. 2018;378:1778-88.
Testing donated blood for Zika virus in the United States confirmed just 8 authentic cases and cost nearly $42 million over a period of 15 months, investigators reported online May 10 in the New England Journal of Medicine.
That price did not reflect a commercial price hike, said Paula Saá, PhD, of the American Red Cross in Gaithersburg, MD, and her associates. Furthermore, more than half of the Zika cases had a low viral level that might not be infectious.
Among more than 4 million screened donations, 9% were tested in pools. All pooled tests were negative. The other 3.9 million donations were screened individually. Only 160 were positive, and just 6 were confirmed positive on repeat TMA. Two of these six confirmed positives also were RNA-positive on reverse transcription polymerase chain reaction, while two were equivocal and two were negative. The positive and equivocal donations were negative for Zika immunoglobulin M on enzyme-linked immunosorbent assay, which indicated acute infections. The RNA-negative infections were IgM-positive, indicating prior infections.
Three more donations were initially positive on TMA, were negative on repeat TMA, and were IgM-positive, bringing the total case count to nine. Among these, two donors had been infected in Florida, six had traveled to Zika-endemic areas, and one had received an experimental Zika vaccine, according to the researchers.
For each detection of authentic Zika virus RNA infection in U.S.-donated blood, testing had cost $5.3 million, they concluded. They called the current FDA recommendation to individually screen all U.S. blood donations for Zika virus “low-yield” and “high cost.” Of three acute infections with enough sample left for pooled testing, all were positive, they noted.
The American Red Cross and Grifols Diagnostic Solutions provided funding. Dr. Saá disclosed research support from Grifols, which makes the TMA test used in the study. She had no other conflicts of interest.
SOURCE: Saá P et al. New Engl J Med. 2018;378:1778-88.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Individually screening all blood donations for Zika virus was low yield and costly.
Major finding: Testing confirmed only 8 authentic cases and cost nearly $42 million over 15 months.
Study details: Screening and confirmatory testing of 4,325,889 donations of blood in the United States during 2016-2017.
Disclosures: American Red Cross and Grifols Diagnostic Solutions provided funding. Grifols makes a test used in the study. Dr. Saá disclosed research support from Grifols but had no other conflicts of interest.
Source: Saá P et al. New Engl J Med. 2018;378:1778-88. doi: 10.1056/NEJMoa1714977
