BROOKLYN, N.Y. – Three steps in the progressive pathology of anxiety and other pediatric psychiatric disorders are important to recognize for their critical role in guiding treatment, John T. Walkup, MD, said at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

After the onset of symptoms and over the course of time, those with untreated anxiety disorders are at risk for developing impairment in adaptation and coping, and also the development of maladaptive behaviors like substance abuse and suicidal behavior, said Dr. Walkup, chair of the department of psychiatry at Ann and Robert H. Lurie Children’s Hospital of Chicago.

The focus of his presentation was on the treatment of anxiety disorders in children, but Dr. Walkup said the impact of the three-tier progression is likely relevant to any psychiatric disorder that begins in childhood.

In essence, the scope of problems becomes more complicated over time, and without early treatment, children continue to be symptomatic. But they also develop a lifestyle based on avoidance coping and might engage in maladaptive behaviors, Dr. Walkup said. As a result, the complexity of treatment increases substantially beyond just symptom control.

Providing an example, Dr. Walkup described a child of 7 years of age with separation anxiety. If treated at the time symptoms begin, Dr. Walkup explained, cognitive-behavioral therapy and medication would be expected to be both straightforward and highly effective. If left untreated until age 14, the child might accumulate impairment in independent functioning (due to avoidance coping) at a particularly important time in development.

“In those kids, you can reduce their anxiety burden with acute treatments like [cognitive-behavioral therapy] or meds, but now you also have 7 or 8 years of accumulated impairment due to avoidance coping and parental accommodation,” Dr. Walkup said. “If those kids are going to catch up developmentally, they also need life skill support in addition to symptomatic treatment for their anxiety.”

In the case of any pediatric psychiatric disorder, early treatment has the potential to thwart progression to a more complex and treatment-resistant form, but anxiety is a particularly prominent example. In most children, anxiety is relatively easy to control if caught early but a greater challenge when fears are not contained and the child accumulates ongoing impairment.

The obstacle is that many children are not diagnosed at the time of onset, said Dr. Walkup. The solution, he suggested, is better training of pediatricians and other primary care physicians not only to identify those children but to initiate treatment in uncomplicated cases.

“The person who has that longitudinal relationship with the child is their primary care provider, and this is really the person who is going to do the best job in getting to these kids early and initiating treatment,” Dr. Walkup said.

“We have a program in Chicago where we have trained primary care physicians not only to treat anxiety and depression, but we have specifically focused them on the easiest cases in their caseload, the classic phenotypes,” Dr. Walkup reported. Using a collaborative care model, this approach has been effective in building the confidence of primary care clinicians and in reaching children when symptoms are easier to control.

Importantly, anti-anxiety medication delivered in primary care could be sufficient to help children to manage anxiety effectively when parents cooperate in helping their children manage their fears.

“People suggest that we always start with CBT, but there [are no data] to support that. I think it is a conclusion drawn from the fact that CBT works and medication has side effects,” Dr. Walkup said. He appreciates the evidence that CBT is effective, but he cautioned that this therapy is not available everywhere, and pharmacologic therapies may be as or potentially more effective for some anxiety symptoms like anxiety-related physical symptoms.
 

Conversely, some have expressed the opinion that drugs might be a better option in late adolescence, when the efficacy of CBT appears to diminish, but Dr. Walkup objected to that characterization as well.

“My sense is that if you treat a 7-year-old for symptoms that have lasted a year it’s very different from treating a 17-year-old who has had symptoms for a decade,” Dr. Walkup said. Referring back to the contention that psychiatric disease in children becomes more complicated with a longer duration, this might explain why “you don’t see as much immediate success” with CBT and medication in the older age groups even if this is an effective treatment tool.

Some psychiatric disorders in children, including anxiety, might resolve with age, but early recognition and treatment should be a goal because of the potential to reduce symptoms and avoidance coping, and improve long-term outcomes, Dr. Walkup reported. Ironically, it might not be just anxiety symptoms, but poor adaptation and coping that might be the most important driver of ongoing impairment.

Dr. Walkup has served as an unpaid adviser to the Anxiety Disorders of Association of America. In addition, he has received royalties from Wolters Kluwer for CME activity on childhood anxiety.

This story was updated 2/11/2019.

BROOKLYN, N.Y. – Three steps in the progressive pathology of anxiety and other pediatric psychiatric disorders are important to recognize for their critical role in guiding treatment, John T. Walkup, MD, said at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

After the onset of symptoms and over the course of time, those with untreated anxiety disorders are at risk for developing impairment in adaptation and coping, and also the development of maladaptive behaviors like substance abuse and suicidal behavior, said Dr. Walkup, chair of the department of psychiatry at Ann and Robert H. Lurie Children’s Hospital of Chicago.

The focus of his presentation was on the treatment of anxiety disorders in children, but Dr. Walkup said the impact of the three-tier progression is likely relevant to any psychiatric disorder that begins in childhood.

In essence, the scope of problems becomes more complicated over time, and without early treatment, children continue to be symptomatic. But they also develop a lifestyle based on avoidance coping and might engage in maladaptive behaviors, Dr. Walkup said. As a result, the complexity of treatment increases substantially beyond just symptom control.

Providing an example, Dr. Walkup described a child of 7 years of age with separation anxiety. If treated at the time symptoms begin, Dr. Walkup explained, cognitive-behavioral therapy and medication would be expected to be both straightforward and highly effective. If left untreated until age 14, the child might accumulate impairment in independent functioning (due to avoidance coping) at a particularly important time in development.

“In those kids, you can reduce their anxiety burden with acute treatments like [cognitive-behavioral therapy] or meds, but now you also have 7 or 8 years of accumulated impairment due to avoidance coping and parental accommodation,” Dr. Walkup said. “If those kids are going to catch up developmentally, they also need life skill support in addition to symptomatic treatment for their anxiety.”

In the case of any pediatric psychiatric disorder, early treatment has the potential to thwart progression to a more complex and treatment-resistant form, but anxiety is a particularly prominent example. In most children, anxiety is relatively easy to control if caught early but a greater challenge when fears are not contained and the child accumulates ongoing impairment.

The obstacle is that many children are not diagnosed at the time of onset, said Dr. Walkup. The solution, he suggested, is better training of pediatricians and other primary care physicians not only to identify those children but to initiate treatment in uncomplicated cases.

“The person who has that longitudinal relationship with the child is their primary care provider, and this is really the person who is going to do the best job in getting to these kids early and initiating treatment,” Dr. Walkup said.

“We have a program in Chicago where we have trained primary care physicians not only to treat anxiety and depression, but we have specifically focused them on the easiest cases in their caseload, the classic phenotypes,” Dr. Walkup reported. Using a collaborative care model, this approach has been effective in building the confidence of primary care clinicians and in reaching children when symptoms are easier to control.

Importantly, anti-anxiety medication delivered in primary care could be sufficient to help children to manage anxiety effectively when parents cooperate in helping their children manage their fears.

“People suggest that we always start with CBT, but there [are no data] to support that. I think it is a conclusion drawn from the fact that CBT works and medication has side effects,” Dr. Walkup said. He appreciates the evidence that CBT is effective, but he cautioned that this therapy is not available everywhere, and pharmacologic therapies may be as or potentially more effective for some anxiety symptoms like anxiety-related physical symptoms.
 

Conversely, some have expressed the opinion that drugs might be a better option in late adolescence, when the efficacy of CBT appears to diminish, but Dr. Walkup objected to that characterization as well.

“My sense is that if you treat a 7-year-old for symptoms that have lasted a year it’s very different from treating a 17-year-old who has had symptoms for a decade,” Dr. Walkup said. Referring back to the contention that psychiatric disease in children becomes more complicated with a longer duration, this might explain why “you don’t see as much immediate success” with CBT and medication in the older age groups even if this is an effective treatment tool.

Some psychiatric disorders in children, including anxiety, might resolve with age, but early recognition and treatment should be a goal because of the potential to reduce symptoms and avoidance coping, and improve long-term outcomes, Dr. Walkup reported. Ironically, it might not be just anxiety symptoms, but poor adaptation and coping that might be the most important driver of ongoing impairment.

Dr. Walkup has served as an unpaid adviser to the Anxiety Disorders of Association of America. In addition, he has received royalties from Wolters Kluwer for CME activity on childhood anxiety.

This story was updated 2/11/2019.

BROOKLYN, N.Y. – Three steps in the progressive pathology of anxiety and other pediatric psychiatric disorders are important to recognize for their critical role in guiding treatment, John T. Walkup, MD, said at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

After the onset of symptoms and over the course of time, those with untreated anxiety disorders are at risk for developing impairment in adaptation and coping, and also the development of maladaptive behaviors like substance abuse and suicidal behavior, said Dr. Walkup, chair of the department of psychiatry at Ann and Robert H. Lurie Children’s Hospital of Chicago.

The focus of his presentation was on the treatment of anxiety disorders in children, but Dr. Walkup said the impact of the three-tier progression is likely relevant to any psychiatric disorder that begins in childhood.

In essence, the scope of problems becomes more complicated over time, and without early treatment, children continue to be symptomatic. But they also develop a lifestyle based on avoidance coping and might engage in maladaptive behaviors, Dr. Walkup said. As a result, the complexity of treatment increases substantially beyond just symptom control.

Providing an example, Dr. Walkup described a child of 7 years of age with separation anxiety. If treated at the time symptoms begin, Dr. Walkup explained, cognitive-behavioral therapy and medication would be expected to be both straightforward and highly effective. If left untreated until age 14, the child might accumulate impairment in independent functioning (due to avoidance coping) at a particularly important time in development.

“In those kids, you can reduce their anxiety burden with acute treatments like [cognitive-behavioral therapy] or meds, but now you also have 7 or 8 years of accumulated impairment due to avoidance coping and parental accommodation,” Dr. Walkup said. “If those kids are going to catch up developmentally, they also need life skill support in addition to symptomatic treatment for their anxiety.”

In the case of any pediatric psychiatric disorder, early treatment has the potential to thwart progression to a more complex and treatment-resistant form, but anxiety is a particularly prominent example. In most children, anxiety is relatively easy to control if caught early but a greater challenge when fears are not contained and the child accumulates ongoing impairment.

The obstacle is that many children are not diagnosed at the time of onset, said Dr. Walkup. The solution, he suggested, is better training of pediatricians and other primary care physicians not only to identify those children but to initiate treatment in uncomplicated cases.

“The person who has that longitudinal relationship with the child is their primary care provider, and this is really the person who is going to do the best job in getting to these kids early and initiating treatment,” Dr. Walkup said.

“We have a program in Chicago where we have trained primary care physicians not only to treat anxiety and depression, but we have specifically focused them on the easiest cases in their caseload, the classic phenotypes,” Dr. Walkup reported. Using a collaborative care model, this approach has been effective in building the confidence of primary care clinicians and in reaching children when symptoms are easier to control.

Importantly, anti-anxiety medication delivered in primary care could be sufficient to help children to manage anxiety effectively when parents cooperate in helping their children manage their fears.

“People suggest that we always start with CBT, but there [are no data] to support that. I think it is a conclusion drawn from the fact that CBT works and medication has side effects,” Dr. Walkup said. He appreciates the evidence that CBT is effective, but he cautioned that this therapy is not available everywhere, and pharmacologic therapies may be as or potentially more effective for some anxiety symptoms like anxiety-related physical symptoms.
 

Conversely, some have expressed the opinion that drugs might be a better option in late adolescence, when the efficacy of CBT appears to diminish, but Dr. Walkup objected to that characterization as well.

“My sense is that if you treat a 7-year-old for symptoms that have lasted a year it’s very different from treating a 17-year-old who has had symptoms for a decade,” Dr. Walkup said. Referring back to the contention that psychiatric disease in children becomes more complicated with a longer duration, this might explain why “you don’t see as much immediate success” with CBT and medication in the older age groups even if this is an effective treatment tool.

Some psychiatric disorders in children, including anxiety, might resolve with age, but early recognition and treatment should be a goal because of the potential to reduce symptoms and avoidance coping, and improve long-term outcomes, Dr. Walkup reported. Ironically, it might not be just anxiety symptoms, but poor adaptation and coping that might be the most important driver of ongoing impairment.

Dr. Walkup has served as an unpaid adviser to the Anxiety Disorders of Association of America. In addition, he has received royalties from Wolters Kluwer for CME activity on childhood anxiety.

This story was updated 2/11/2019.

Daratumumab is safe but ineffective for the treatment of patients with relapsed or refractory non-Hodgkin lymphoma (NHL) and CD38 expression of at least 50%, according to findings from a recent phase 2 trial.

Unfortunately, the study met headwinds early on, when initial screening of 112 patients with available tumor samples showed that only about half (56%) had CD38 expression of at least 50%, reported lead author Giles Salles, MD, PhD, of Claude Bernard University in Lyon, France, and his colleagues. The cutoff was based on preclinical models, suggesting that daratumumab-induced cytotoxicity depends on a high level of CD38 expression.

“Only 36 [patients] were eligible for study enrollment, questioning the generalizability of the study population,” the investigators wrote in Clinical Lymphoma, Myeloma & Leukemia.

Of these 36 patients, 15 had diffuse large B-cell lymphoma (DLBCL), 16 had follicular lymphoma (FL), and 5 had mantle cell lymphoma (MCL). Median CD38 expression was 70%. Patients were given 16 mg/kg of IV daratumumab once a week for two cycles, then every 2 weeks for four cycles, and finally on a monthly basis. Cycles were 28 days long. The primary endpoint was overall response rate. Safety and pharmacokinetics were also evaluated.

Results were generally disappointing, with ORR occurring in two patients (12.5%) with FL and one patient (6.7%) with DLBCL. No patients with MCL responded before the study was terminated. On a more encouraging note, 10 of 16 patients with FL maintained stable disease.

“All 16 patients in the FL cohort had progressed/relapsed on their prior treatment regimen; therefore, the maintenance of stable disease in the FL cohort may suggest some clinical benefit of daratumumab in this subset of NHL,” the investigators wrote.

Pharmacokinetics and safety data were similar to those from multiple myeloma studies of daratumumab; no new safety signals or instances of immunogenicity were encountered. The most common grade 3 or higher treatment-related adverse event was thrombocytopenia, which occurred in 11.1% of patients. Infusion-related reactions occurred in 72.2% of patients, but none were grade 4 and only three reactions were grade 3.

The investigators suggested that daratumumab may still play a role in NHL treatment, but not as a single agent.

“It is possible that daratumumab-based combination therapy would have allowed for more responses to be achieved within the current study,” the investigators wrote. “NHL is an extremely heterogeneous disease and the identification of predictive biomarkers and molecular genetics may provide new personalized therapies.”

The study was funded by Janssen Research & Development; two study authors reported employment by Janssen. Others reported financial ties to Janssen, Celgene, Roche, Gilead, Novartis, Amgen, and others.

SOURCE: Salles G et al. Clin Lymphoma Myeloma Leuk. 2019 Jan 2. doi: 10.1016/j.clml.2018.12.013.

Daratumumab is safe but ineffective for the treatment of patients with relapsed or refractory non-Hodgkin lymphoma (NHL) and CD38 expression of at least 50%, according to findings from a recent phase 2 trial.

Unfortunately, the study met headwinds early on, when initial screening of 112 patients with available tumor samples showed that only about half (56%) had CD38 expression of at least 50%, reported lead author Giles Salles, MD, PhD, of Claude Bernard University in Lyon, France, and his colleagues. The cutoff was based on preclinical models, suggesting that daratumumab-induced cytotoxicity depends on a high level of CD38 expression.

“Only 36 [patients] were eligible for study enrollment, questioning the generalizability of the study population,” the investigators wrote in Clinical Lymphoma, Myeloma & Leukemia.

Of these 36 patients, 15 had diffuse large B-cell lymphoma (DLBCL), 16 had follicular lymphoma (FL), and 5 had mantle cell lymphoma (MCL). Median CD38 expression was 70%. Patients were given 16 mg/kg of IV daratumumab once a week for two cycles, then every 2 weeks for four cycles, and finally on a monthly basis. Cycles were 28 days long. The primary endpoint was overall response rate. Safety and pharmacokinetics were also evaluated.

Results were generally disappointing, with ORR occurring in two patients (12.5%) with FL and one patient (6.7%) with DLBCL. No patients with MCL responded before the study was terminated. On a more encouraging note, 10 of 16 patients with FL maintained stable disease.

“All 16 patients in the FL cohort had progressed/relapsed on their prior treatment regimen; therefore, the maintenance of stable disease in the FL cohort may suggest some clinical benefit of daratumumab in this subset of NHL,” the investigators wrote.

Pharmacokinetics and safety data were similar to those from multiple myeloma studies of daratumumab; no new safety signals or instances of immunogenicity were encountered. The most common grade 3 or higher treatment-related adverse event was thrombocytopenia, which occurred in 11.1% of patients. Infusion-related reactions occurred in 72.2% of patients, but none were grade 4 and only three reactions were grade 3.

The investigators suggested that daratumumab may still play a role in NHL treatment, but not as a single agent.

“It is possible that daratumumab-based combination therapy would have allowed for more responses to be achieved within the current study,” the investigators wrote. “NHL is an extremely heterogeneous disease and the identification of predictive biomarkers and molecular genetics may provide new personalized therapies.”

The study was funded by Janssen Research & Development; two study authors reported employment by Janssen. Others reported financial ties to Janssen, Celgene, Roche, Gilead, Novartis, Amgen, and others.

SOURCE: Salles G et al. Clin Lymphoma Myeloma Leuk. 2019 Jan 2. doi: 10.1016/j.clml.2018.12.013.

Daratumumab is safe but ineffective for the treatment of patients with relapsed or refractory non-Hodgkin lymphoma (NHL) and CD38 expression of at least 50%, according to findings from a recent phase 2 trial.

Unfortunately, the study met headwinds early on, when initial screening of 112 patients with available tumor samples showed that only about half (56%) had CD38 expression of at least 50%, reported lead author Giles Salles, MD, PhD, of Claude Bernard University in Lyon, France, and his colleagues. The cutoff was based on preclinical models, suggesting that daratumumab-induced cytotoxicity depends on a high level of CD38 expression.

“Only 36 [patients] were eligible for study enrollment, questioning the generalizability of the study population,” the investigators wrote in Clinical Lymphoma, Myeloma & Leukemia.

Of these 36 patients, 15 had diffuse large B-cell lymphoma (DLBCL), 16 had follicular lymphoma (FL), and 5 had mantle cell lymphoma (MCL). Median CD38 expression was 70%. Patients were given 16 mg/kg of IV daratumumab once a week for two cycles, then every 2 weeks for four cycles, and finally on a monthly basis. Cycles were 28 days long. The primary endpoint was overall response rate. Safety and pharmacokinetics were also evaluated.

Results were generally disappointing, with ORR occurring in two patients (12.5%) with FL and one patient (6.7%) with DLBCL. No patients with MCL responded before the study was terminated. On a more encouraging note, 10 of 16 patients with FL maintained stable disease.

“All 16 patients in the FL cohort had progressed/relapsed on their prior treatment regimen; therefore, the maintenance of stable disease in the FL cohort may suggest some clinical benefit of daratumumab in this subset of NHL,” the investigators wrote.

Pharmacokinetics and safety data were similar to those from multiple myeloma studies of daratumumab; no new safety signals or instances of immunogenicity were encountered. The most common grade 3 or higher treatment-related adverse event was thrombocytopenia, which occurred in 11.1% of patients. Infusion-related reactions occurred in 72.2% of patients, but none were grade 4 and only three reactions were grade 3.

The investigators suggested that daratumumab may still play a role in NHL treatment, but not as a single agent.

“It is possible that daratumumab-based combination therapy would have allowed for more responses to be achieved within the current study,” the investigators wrote. “NHL is an extremely heterogeneous disease and the identification of predictive biomarkers and molecular genetics may provide new personalized therapies.”

The study was funded by Janssen Research & Development; two study authors reported employment by Janssen. Others reported financial ties to Janssen, Celgene, Roche, Gilead, Novartis, Amgen, and others.

SOURCE: Salles G et al. Clin Lymphoma Myeloma Leuk. 2019 Jan 2. doi: 10.1016/j.clml.2018.12.013.

SAN FRANCISCO – Interrogation of the pancreatic cancer genome and transcriptome identifies distinct molecular subtypes that have differing prognosis and response to chemotherapy, according to new data from the COMPASS trial reported at the 2019 GI Cancers Symposium.

“We now have two standard chemotherapy regimens that we use in the first-line setting, modified FOLFIRINOX (mFOLFIRINOX) and gemcitabine–nab-paclitaxel, but we lack any real biomarker strategies on which to choose for treatments, and many of our clinical trials in pancreas cancer have failed,” noted senior investigator Jennifer J. Knox, MD, FRCPC, codirector of the McCain Centre for Pancreatic Cancer, Princess Margaret Cancer Centre, Toronto.

In the past year, genomic profiling studies using different platforms have yielded similar results, suggesting that about 30% of patients with pancreatic cancer have actionable mutations that could help guide treatment choices.

The COMPASS trial prospectively recruited patients with advanced pancreatic ductal adenocarcinoma prior to first-line chemotherapy for tumor whole-genome sequencing and RNA sequencing. The trial previously established feasibility, with sequencing successfully completed in more than 90% of patients and availability of whole-genome results before the first disease assessment CT scan at 8 weeks (Clin Cancer Res. 2018;24[6]:1344-54).

New outcomes data for the 150 patients in the intention-to-treat population showed that overall survival was almost 4 months longer for those having a classic modified Moffitt RNA expression signature compared with those having a basal-like one. Similarly, it was more than 2 months longer for those having high versus low expression of the transcription factor GATA6.

In addition, among the subset of patients given mFOLFIRINOX, those having the classic signature were two-thirds less likely to die than were those having the basal-like signature.

“The RNA signature and GATA6 seem to discriminate two prognostic groups in advanced pancreas cancer. The basal-like cohort, or GATA6-low, may be particularly resistant to mFOLFIRINOX,” Dr. Knox said. “GATA6, and perhaps other markers, need to be validated as predictive biomarkers so that we can discover and use more effective therapies earlier on for our patients.

“COMPASS provides a very rich discovery set for other hypotheses and collaborators,” she said, noting that the investigators are adding trial data to the Enhanced Pancreatic Cancer Profiling for Individualized Care (EPPIC) project and to the Accelerate Research in Genomic Oncology (ARGO) project of the International Cancer Genome Consortium.

Rationally based treatment decisions

The COMPASS trial “will show us ... how we should move forward,” said invited discussant Heinz-Josef Lenz, MD, associate director for adult oncology and coleader of the Gastrointestinal Cancers Program, USC Norris Comprehensive Cancer Center, Los Angeles. “We don’t necessarily have the answer today to what the best treatment options are, but this is the first step to understand and develop rationally based treatment decisions for these molecularly characterized groups,” he said.

Susan London/MDedge

Whole-genome sequencing has been critically important for finding mutations in single genes, the proverbial needles in the haystack, he maintained. But in the future, the emphasis will likely be on combinations of mutations and other alterations.

Study details

Most of the 150 COMPASS patients had metastatic disease (87%), and they were about evenly split between receiving mFOLFIRINOX versus gemcitabine plus nab-paclitaxel as first-line chemotherapy, Dr. Knox reported at the 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.

Genomic profiling revealed that roughly 40% overall had potentially actionable variants: alterations in the presence of KRAS wild type (8%), homologous recombination deficiency involving BRCA (6%), and others (25%) such as activating PIK3CA mutations or HER2 amplification.

In findings that Dr. Knox called “quite striking,” among patients given mFOLFIRINOX, median progression-free survival was 7.17 months for those with the RNA classic expression signature versus 2.50 months for those with the RNA basal-like signature (hazard ratio, 0.17; P less than .0001). In contrast, among patients given gemcitabine plus nab-paclitaxel, there was no significant difference by signature (5.65 vs. 4.93 months; P = .69).

GATA6 expression was strongly related to signature type, with classic tumors having high expression and basal-like tumors having low expression (P less than .0001).

Overall survival was similarly better for patients with classic versus basal-like tumors (8.8 vs. 5.2 months; HR, 0.53; P = .006) and for patients with GATA6 high- versus low-expression tumors (8.2 vs. 5.8 months; HR, 0.66; P = .08).

In the whole cohort, overall survival differed across subsets according to RNA signature and type of chemotherapy received (P = .0134). When analysis was restricted to patients given mFOLFIRINOX, median overall survival was 10.1 months with the classic signature but just 5.3 months with the basal-like signature (HR, 0.33; P = .0005).

A multivariate analysis among all chemotherapy-treated patients confirmed the survival benefit of classic signature over basal-like signature (HR, 0.55; P = .03).

Dr. Knox disclosed that she has a consulting or advisory role with Lilly, Merck, and Bristol-Myers Squibb; that she receives honoraria from Novartis; and that she receives research funding from AstraZeneca and Merck. The study is sponsored by University Health Network, Toronto.

SOURCE: O’Kane GM et al. GI Cancers Symposium, Abstract 188.

SAN FRANCISCO – Interrogation of the pancreatic cancer genome and transcriptome identifies distinct molecular subtypes that have differing prognosis and response to chemotherapy, according to new data from the COMPASS trial reported at the 2019 GI Cancers Symposium.

“We now have two standard chemotherapy regimens that we use in the first-line setting, modified FOLFIRINOX (mFOLFIRINOX) and gemcitabine–nab-paclitaxel, but we lack any real biomarker strategies on which to choose for treatments, and many of our clinical trials in pancreas cancer have failed,” noted senior investigator Jennifer J. Knox, MD, FRCPC, codirector of the McCain Centre for Pancreatic Cancer, Princess Margaret Cancer Centre, Toronto.

In the past year, genomic profiling studies using different platforms have yielded similar results, suggesting that about 30% of patients with pancreatic cancer have actionable mutations that could help guide treatment choices.

The COMPASS trial prospectively recruited patients with advanced pancreatic ductal adenocarcinoma prior to first-line chemotherapy for tumor whole-genome sequencing and RNA sequencing. The trial previously established feasibility, with sequencing successfully completed in more than 90% of patients and availability of whole-genome results before the first disease assessment CT scan at 8 weeks (Clin Cancer Res. 2018;24[6]:1344-54).

New outcomes data for the 150 patients in the intention-to-treat population showed that overall survival was almost 4 months longer for those having a classic modified Moffitt RNA expression signature compared with those having a basal-like one. Similarly, it was more than 2 months longer for those having high versus low expression of the transcription factor GATA6.

In addition, among the subset of patients given mFOLFIRINOX, those having the classic signature were two-thirds less likely to die than were those having the basal-like signature.

“The RNA signature and GATA6 seem to discriminate two prognostic groups in advanced pancreas cancer. The basal-like cohort, or GATA6-low, may be particularly resistant to mFOLFIRINOX,” Dr. Knox said. “GATA6, and perhaps other markers, need to be validated as predictive biomarkers so that we can discover and use more effective therapies earlier on for our patients.

“COMPASS provides a very rich discovery set for other hypotheses and collaborators,” she said, noting that the investigators are adding trial data to the Enhanced Pancreatic Cancer Profiling for Individualized Care (EPPIC) project and to the Accelerate Research in Genomic Oncology (ARGO) project of the International Cancer Genome Consortium.

Rationally based treatment decisions

The COMPASS trial “will show us ... how we should move forward,” said invited discussant Heinz-Josef Lenz, MD, associate director for adult oncology and coleader of the Gastrointestinal Cancers Program, USC Norris Comprehensive Cancer Center, Los Angeles. “We don’t necessarily have the answer today to what the best treatment options are, but this is the first step to understand and develop rationally based treatment decisions for these molecularly characterized groups,” he said.

Susan London/MDedge

Whole-genome sequencing has been critically important for finding mutations in single genes, the proverbial needles in the haystack, he maintained. But in the future, the emphasis will likely be on combinations of mutations and other alterations.

Study details

Most of the 150 COMPASS patients had metastatic disease (87%), and they were about evenly split between receiving mFOLFIRINOX versus gemcitabine plus nab-paclitaxel as first-line chemotherapy, Dr. Knox reported at the 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.

Genomic profiling revealed that roughly 40% overall had potentially actionable variants: alterations in the presence of KRAS wild type (8%), homologous recombination deficiency involving BRCA (6%), and others (25%) such as activating PIK3CA mutations or HER2 amplification.

In findings that Dr. Knox called “quite striking,” among patients given mFOLFIRINOX, median progression-free survival was 7.17 months for those with the RNA classic expression signature versus 2.50 months for those with the RNA basal-like signature (hazard ratio, 0.17; P less than .0001). In contrast, among patients given gemcitabine plus nab-paclitaxel, there was no significant difference by signature (5.65 vs. 4.93 months; P = .69).

GATA6 expression was strongly related to signature type, with classic tumors having high expression and basal-like tumors having low expression (P less than .0001).

Overall survival was similarly better for patients with classic versus basal-like tumors (8.8 vs. 5.2 months; HR, 0.53; P = .006) and for patients with GATA6 high- versus low-expression tumors (8.2 vs. 5.8 months; HR, 0.66; P = .08).

In the whole cohort, overall survival differed across subsets according to RNA signature and type of chemotherapy received (P = .0134). When analysis was restricted to patients given mFOLFIRINOX, median overall survival was 10.1 months with the classic signature but just 5.3 months with the basal-like signature (HR, 0.33; P = .0005).

A multivariate analysis among all chemotherapy-treated patients confirmed the survival benefit of classic signature over basal-like signature (HR, 0.55; P = .03).

Dr. Knox disclosed that she has a consulting or advisory role with Lilly, Merck, and Bristol-Myers Squibb; that she receives honoraria from Novartis; and that she receives research funding from AstraZeneca and Merck. The study is sponsored by University Health Network, Toronto.

SOURCE: O’Kane GM et al. GI Cancers Symposium, Abstract 188.

SAN FRANCISCO – Interrogation of the pancreatic cancer genome and transcriptome identifies distinct molecular subtypes that have differing prognosis and response to chemotherapy, according to new data from the COMPASS trial reported at the 2019 GI Cancers Symposium.

“We now have two standard chemotherapy regimens that we use in the first-line setting, modified FOLFIRINOX (mFOLFIRINOX) and gemcitabine–nab-paclitaxel, but we lack any real biomarker strategies on which to choose for treatments, and many of our clinical trials in pancreas cancer have failed,” noted senior investigator Jennifer J. Knox, MD, FRCPC, codirector of the McCain Centre for Pancreatic Cancer, Princess Margaret Cancer Centre, Toronto.

In the past year, genomic profiling studies using different platforms have yielded similar results, suggesting that about 30% of patients with pancreatic cancer have actionable mutations that could help guide treatment choices.

The COMPASS trial prospectively recruited patients with advanced pancreatic ductal adenocarcinoma prior to first-line chemotherapy for tumor whole-genome sequencing and RNA sequencing. The trial previously established feasibility, with sequencing successfully completed in more than 90% of patients and availability of whole-genome results before the first disease assessment CT scan at 8 weeks (Clin Cancer Res. 2018;24[6]:1344-54).

New outcomes data for the 150 patients in the intention-to-treat population showed that overall survival was almost 4 months longer for those having a classic modified Moffitt RNA expression signature compared with those having a basal-like one. Similarly, it was more than 2 months longer for those having high versus low expression of the transcription factor GATA6.

In addition, among the subset of patients given mFOLFIRINOX, those having the classic signature were two-thirds less likely to die than were those having the basal-like signature.

“The RNA signature and GATA6 seem to discriminate two prognostic groups in advanced pancreas cancer. The basal-like cohort, or GATA6-low, may be particularly resistant to mFOLFIRINOX,” Dr. Knox said. “GATA6, and perhaps other markers, need to be validated as predictive biomarkers so that we can discover and use more effective therapies earlier on for our patients.

“COMPASS provides a very rich discovery set for other hypotheses and collaborators,” she said, noting that the investigators are adding trial data to the Enhanced Pancreatic Cancer Profiling for Individualized Care (EPPIC) project and to the Accelerate Research in Genomic Oncology (ARGO) project of the International Cancer Genome Consortium.

Rationally based treatment decisions

The COMPASS trial “will show us ... how we should move forward,” said invited discussant Heinz-Josef Lenz, MD, associate director for adult oncology and coleader of the Gastrointestinal Cancers Program, USC Norris Comprehensive Cancer Center, Los Angeles. “We don’t necessarily have the answer today to what the best treatment options are, but this is the first step to understand and develop rationally based treatment decisions for these molecularly characterized groups,” he said.

Susan London/MDedge

Whole-genome sequencing has been critically important for finding mutations in single genes, the proverbial needles in the haystack, he maintained. But in the future, the emphasis will likely be on combinations of mutations and other alterations.

Study details

Most of the 150 COMPASS patients had metastatic disease (87%), and they were about evenly split between receiving mFOLFIRINOX versus gemcitabine plus nab-paclitaxel as first-line chemotherapy, Dr. Knox reported at the 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.

Genomic profiling revealed that roughly 40% overall had potentially actionable variants: alterations in the presence of KRAS wild type (8%), homologous recombination deficiency involving BRCA (6%), and others (25%) such as activating PIK3CA mutations or HER2 amplification.

In findings that Dr. Knox called “quite striking,” among patients given mFOLFIRINOX, median progression-free survival was 7.17 months for those with the RNA classic expression signature versus 2.50 months for those with the RNA basal-like signature (hazard ratio, 0.17; P less than .0001). In contrast, among patients given gemcitabine plus nab-paclitaxel, there was no significant difference by signature (5.65 vs. 4.93 months; P = .69).

GATA6 expression was strongly related to signature type, with classic tumors having high expression and basal-like tumors having low expression (P less than .0001).

Overall survival was similarly better for patients with classic versus basal-like tumors (8.8 vs. 5.2 months; HR, 0.53; P = .006) and for patients with GATA6 high- versus low-expression tumors (8.2 vs. 5.8 months; HR, 0.66; P = .08).

In the whole cohort, overall survival differed across subsets according to RNA signature and type of chemotherapy received (P = .0134). When analysis was restricted to patients given mFOLFIRINOX, median overall survival was 10.1 months with the classic signature but just 5.3 months with the basal-like signature (HR, 0.33; P = .0005).

A multivariate analysis among all chemotherapy-treated patients confirmed the survival benefit of classic signature over basal-like signature (HR, 0.55; P = .03).

Dr. Knox disclosed that she has a consulting or advisory role with Lilly, Merck, and Bristol-Myers Squibb; that she receives honoraria from Novartis; and that she receives research funding from AstraZeneca and Merck. The study is sponsored by University Health Network, Toronto.

SOURCE: O’Kane GM et al. GI Cancers Symposium, Abstract 188.

By increasing urine color, 400 mg of oral riboflavin the night before gynecologic surgery makes it easier to see and confirm urine flow during intraoperative cystoscopy, according to results of a randomized, blinded, placebo-controlled trial.

The traditional go-to for that purpose, intravenous indigo carmine, has been in short supply, if possible to get at all, so surgeons have been looking for other options. Alternatives include intravenous methylene blue, intravenous fluorescein, and oral phenazopyridine, but each have their own problems, including cost, contraindications, and anaphylaxis.

So the study team turned to riboflavin – vitamin B₂ – which, in excess, turns the urine bright, sometimes almost neon yellow. It’s “safe, readily available without prescription, and inexpensive ... and should be considered for routine use,” wrote investigators led by Michael L. Stitely, MD, an ob.gyn. at the University of Otago in Dunedin, New Zealand.

The team randomized 33 women to four 100-mg capsules of riboflavin the night before surgery and 33 to four 1,000-IU capsules of vitamin D₃, which served as the placebo. Participants, clinicians, researchers, and study staff all were blinded to group allocation, the investigators noted in Obstetrics & Gynecology.

During cystoscopy, operating surgeons observed and videoed urine flow from both ureters for at least 3 minutes.

Surgeons rated urine color a median of 2 (slight yellow) in the riboflavin group, compared with 1 (clear) in the placebo arm, on a 3-point scale (P less than .001). About 13 women on riboflavin got a rating of 3 – strong yellow – versus 1 woman in the placebo arm.

The operating surgeons also said it was easier to visualize urine flow in the riboflavin group, giving a median of 5, compared with 4 in the placebo group, on a 5-point scale (P less than .013). They gave a score of 5 to 19 women in the riboflavin group but only to 8 placebo women, meaning that they “strongly agreed” that it was easy to see urine flow; a score of 4 meant that they simply agreed with the statement.

Overall, surgeons confirmed bilateral urine flow in 30 women (91%) in the riboflavin group, compared with 28 women (85%) in the placebo group (P = .71). When a blinded investigator checked the videos, their assessments of the same parameters correlated with those of the surgeons.

No significant differences were found between the groups in age, height, weight, body mass index, or ethnicity. The most common procedure was a midurethral sling (10 in the riboflavin group; 4 in the placebo arm), followed by cystoscopy with botox (4 in the riboflavin group; 7 in the placebo group). None of the women required intervention for urinary tract injury.

Among the limitations cited was the use of subjective and nonvalidated measures of urine color.

The work was funded by the Healthcare Otago Charitable Trust and the Australasian Gynaecological Endoscopy and Surgery Society. The authors reported no conflicts of interest.
 

[email protected]

SOURCE: Stitely ML et al. Obstet Gynecol. 2019 Jan 8. doi: 10.1097/AOG.0000000000003063.

By increasing urine color, 400 mg of oral riboflavin the night before gynecologic surgery makes it easier to see and confirm urine flow during intraoperative cystoscopy, according to results of a randomized, blinded, placebo-controlled trial.

The traditional go-to for that purpose, intravenous indigo carmine, has been in short supply, if possible to get at all, so surgeons have been looking for other options. Alternatives include intravenous methylene blue, intravenous fluorescein, and oral phenazopyridine, but each have their own problems, including cost, contraindications, and anaphylaxis.

So the study team turned to riboflavin – vitamin B₂ – which, in excess, turns the urine bright, sometimes almost neon yellow. It’s “safe, readily available without prescription, and inexpensive ... and should be considered for routine use,” wrote investigators led by Michael L. Stitely, MD, an ob.gyn. at the University of Otago in Dunedin, New Zealand.

The team randomized 33 women to four 100-mg capsules of riboflavin the night before surgery and 33 to four 1,000-IU capsules of vitamin D₃, which served as the placebo. Participants, clinicians, researchers, and study staff all were blinded to group allocation, the investigators noted in Obstetrics & Gynecology.

During cystoscopy, operating surgeons observed and videoed urine flow from both ureters for at least 3 minutes.

Surgeons rated urine color a median of 2 (slight yellow) in the riboflavin group, compared with 1 (clear) in the placebo arm, on a 3-point scale (P less than .001). About 13 women on riboflavin got a rating of 3 – strong yellow – versus 1 woman in the placebo arm.

The operating surgeons also said it was easier to visualize urine flow in the riboflavin group, giving a median of 5, compared with 4 in the placebo group, on a 5-point scale (P less than .013). They gave a score of 5 to 19 women in the riboflavin group but only to 8 placebo women, meaning that they “strongly agreed” that it was easy to see urine flow; a score of 4 meant that they simply agreed with the statement.

Overall, surgeons confirmed bilateral urine flow in 30 women (91%) in the riboflavin group, compared with 28 women (85%) in the placebo group (P = .71). When a blinded investigator checked the videos, their assessments of the same parameters correlated with those of the surgeons.

No significant differences were found between the groups in age, height, weight, body mass index, or ethnicity. The most common procedure was a midurethral sling (10 in the riboflavin group; 4 in the placebo arm), followed by cystoscopy with botox (4 in the riboflavin group; 7 in the placebo group). None of the women required intervention for urinary tract injury.

Among the limitations cited was the use of subjective and nonvalidated measures of urine color.

The work was funded by the Healthcare Otago Charitable Trust and the Australasian Gynaecological Endoscopy and Surgery Society. The authors reported no conflicts of interest.
 

[email protected]

SOURCE: Stitely ML et al. Obstet Gynecol. 2019 Jan 8. doi: 10.1097/AOG.0000000000003063.

By increasing urine color, 400 mg of oral riboflavin the night before gynecologic surgery makes it easier to see and confirm urine flow during intraoperative cystoscopy, according to results of a randomized, blinded, placebo-controlled trial.

The traditional go-to for that purpose, intravenous indigo carmine, has been in short supply, if possible to get at all, so surgeons have been looking for other options. Alternatives include intravenous methylene blue, intravenous fluorescein, and oral phenazopyridine, but each have their own problems, including cost, contraindications, and anaphylaxis.

So the study team turned to riboflavin – vitamin B₂ – which, in excess, turns the urine bright, sometimes almost neon yellow. It’s “safe, readily available without prescription, and inexpensive ... and should be considered for routine use,” wrote investigators led by Michael L. Stitely, MD, an ob.gyn. at the University of Otago in Dunedin, New Zealand.

The team randomized 33 women to four 100-mg capsules of riboflavin the night before surgery and 33 to four 1,000-IU capsules of vitamin D₃, which served as the placebo. Participants, clinicians, researchers, and study staff all were blinded to group allocation, the investigators noted in Obstetrics & Gynecology.

During cystoscopy, operating surgeons observed and videoed urine flow from both ureters for at least 3 minutes.

Surgeons rated urine color a median of 2 (slight yellow) in the riboflavin group, compared with 1 (clear) in the placebo arm, on a 3-point scale (P less than .001). About 13 women on riboflavin got a rating of 3 – strong yellow – versus 1 woman in the placebo arm.

The operating surgeons also said it was easier to visualize urine flow in the riboflavin group, giving a median of 5, compared with 4 in the placebo group, on a 5-point scale (P less than .013). They gave a score of 5 to 19 women in the riboflavin group but only to 8 placebo women, meaning that they “strongly agreed” that it was easy to see urine flow; a score of 4 meant that they simply agreed with the statement.

Overall, surgeons confirmed bilateral urine flow in 30 women (91%) in the riboflavin group, compared with 28 women (85%) in the placebo group (P = .71). When a blinded investigator checked the videos, their assessments of the same parameters correlated with those of the surgeons.

No significant differences were found between the groups in age, height, weight, body mass index, or ethnicity. The most common procedure was a midurethral sling (10 in the riboflavin group; 4 in the placebo arm), followed by cystoscopy with botox (4 in the riboflavin group; 7 in the placebo group). None of the women required intervention for urinary tract injury.

Among the limitations cited was the use of subjective and nonvalidated measures of urine color.

The work was funded by the Healthcare Otago Charitable Trust and the Australasian Gynaecological Endoscopy and Surgery Society. The authors reported no conflicts of interest.
 

[email protected]

SOURCE: Stitely ML et al. Obstet Gynecol. 2019 Jan 8. doi: 10.1097/AOG.0000000000003063.

For patients with systemic heart failure but without diabetes, oral SGLT2s are the focus of multiple ongoing phase 3 clinical trials. Also today, influenza activity hits a seasonal high, the U.S. Supreme Court halts a Louisiana abortion law from taking effect, and cilostazol plus aspirin or clopidogrel reduces the risk of recurrent stroke.
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Spotify
 

For patients with systemic heart failure but without diabetes, oral SGLT2s are the focus of multiple ongoing phase 3 clinical trials. Also today, influenza activity hits a seasonal high, the U.S. Supreme Court halts a Louisiana abortion law from taking effect, and cilostazol plus aspirin or clopidogrel reduces the risk of recurrent stroke.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

For patients with systemic heart failure but without diabetes, oral SGLT2s are the focus of multiple ongoing phase 3 clinical trials. Also today, influenza activity hits a seasonal high, the U.S. Supreme Court halts a Louisiana abortion law from taking effect, and cilostazol plus aspirin or clopidogrel reduces the risk of recurrent stroke.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

The numbers are stunning: 1,643% increase in rates of deaths involving synthetic opioids. A 915% increase for heroin, 830% for benzodiazepines. Even more stunning: Those are the increases only in overdose death rates for women aged 30 to 64 years.

According to CDC data, between 1999 and 2010, the largest percentage change in the rates of overall drug overdose deaths was among women aged between 45 and 64 years. But that research did not account for trends in specific drugs or consider changes in age group distributions, say researchers from the CDC’s National Center for Injury Prevention and Control.

They examined overdose death rates among women aged 30 to 64 years between 1999 and 2017. The unadjusted death rate jumped 260%, from 4,314 deaths to 18,110 deaths. Among women aged 55 to 59 years, the number of deaths involving antidepressants increased approximately 300%; among women aged 60 to 64 years, nearly 400%. The crude rate of deaths involving prescription opioids skyrocketed > 1,000%.

The drug epidemic is “evolving,” the researchers note. In 1999, overdose death rates were highest among women aged 40 to 44 years. In 2017, they were highest among women aged 50 to 54 years. And as demographics shift, prevention programs need to shift as well. As women age, the researchers say, individual experiences can change the type of substance used or misused and in the experiences of pain that might result in an opioid prescription.

The researchers note that “substantial work” has focused on informing women of childbearing age about the risks and benefits of certain drugs. The current analysis demonstrates “the remaining need” to consider middle-aged women who are at risk.

Targeted efforts are needed, and the researchers suggest interventions: Medicaid and other health insurance programs can review records of controlled substance prescribing. States and local communities can expand capacity of drug use disorder treatments and links to care, particularly adding “gender-responsive” substance use disorder treatment centers.

A “multifaceted approach involving the full spectrum of care services is likely necessary,” the researchers say. Health care practitioners who treat women for pain, depression, or anxiety can discuss treatment options that consider the unique biopsychosocial needs of women.

Health care practitioners also can consider implementing the CDC Guideline for Prescribing Opioids for Chronic Pain, which says “Opioids are not first-line or routine therapy for chronic pain.” The guideline also says before starting and periodically during opioid therapy, clinicians should discuss with patients the “known risks and realistic benefits of opioid therapy.”  In other words, listen to the women and prescribe carefully.

The numbers are stunning: 1,643% increase in rates of deaths involving synthetic opioids. A 915% increase for heroin, 830% for benzodiazepines. Even more stunning: Those are the increases only in overdose death rates for women aged 30 to 64 years.

According to CDC data, between 1999 and 2010, the largest percentage change in the rates of overall drug overdose deaths was among women aged between 45 and 64 years. But that research did not account for trends in specific drugs or consider changes in age group distributions, say researchers from the CDC’s National Center for Injury Prevention and Control.

They examined overdose death rates among women aged 30 to 64 years between 1999 and 2017. The unadjusted death rate jumped 260%, from 4,314 deaths to 18,110 deaths. Among women aged 55 to 59 years, the number of deaths involving antidepressants increased approximately 300%; among women aged 60 to 64 years, nearly 400%. The crude rate of deaths involving prescription opioids skyrocketed > 1,000%.

The drug epidemic is “evolving,” the researchers note. In 1999, overdose death rates were highest among women aged 40 to 44 years. In 2017, they were highest among women aged 50 to 54 years. And as demographics shift, prevention programs need to shift as well. As women age, the researchers say, individual experiences can change the type of substance used or misused and in the experiences of pain that might result in an opioid prescription.

The researchers note that “substantial work” has focused on informing women of childbearing age about the risks and benefits of certain drugs. The current analysis demonstrates “the remaining need” to consider middle-aged women who are at risk.

Targeted efforts are needed, and the researchers suggest interventions: Medicaid and other health insurance programs can review records of controlled substance prescribing. States and local communities can expand capacity of drug use disorder treatments and links to care, particularly adding “gender-responsive” substance use disorder treatment centers.

A “multifaceted approach involving the full spectrum of care services is likely necessary,” the researchers say. Health care practitioners who treat women for pain, depression, or anxiety can discuss treatment options that consider the unique biopsychosocial needs of women.

Health care practitioners also can consider implementing the CDC Guideline for Prescribing Opioids for Chronic Pain, which says “Opioids are not first-line or routine therapy for chronic pain.” The guideline also says before starting and periodically during opioid therapy, clinicians should discuss with patients the “known risks and realistic benefits of opioid therapy.”  In other words, listen to the women and prescribe carefully.

The numbers are stunning: 1,643% increase in rates of deaths involving synthetic opioids. A 915% increase for heroin, 830% for benzodiazepines. Even more stunning: Those are the increases only in overdose death rates for women aged 30 to 64 years.

According to CDC data, between 1999 and 2010, the largest percentage change in the rates of overall drug overdose deaths was among women aged between 45 and 64 years. But that research did not account for trends in specific drugs or consider changes in age group distributions, say researchers from the CDC’s National Center for Injury Prevention and Control.

They examined overdose death rates among women aged 30 to 64 years between 1999 and 2017. The unadjusted death rate jumped 260%, from 4,314 deaths to 18,110 deaths. Among women aged 55 to 59 years, the number of deaths involving antidepressants increased approximately 300%; among women aged 60 to 64 years, nearly 400%. The crude rate of deaths involving prescription opioids skyrocketed > 1,000%.

The drug epidemic is “evolving,” the researchers note. In 1999, overdose death rates were highest among women aged 40 to 44 years. In 2017, they were highest among women aged 50 to 54 years. And as demographics shift, prevention programs need to shift as well. As women age, the researchers say, individual experiences can change the type of substance used or misused and in the experiences of pain that might result in an opioid prescription.

The researchers note that “substantial work” has focused on informing women of childbearing age about the risks and benefits of certain drugs. The current analysis demonstrates “the remaining need” to consider middle-aged women who are at risk.

Targeted efforts are needed, and the researchers suggest interventions: Medicaid and other health insurance programs can review records of controlled substance prescribing. States and local communities can expand capacity of drug use disorder treatments and links to care, particularly adding “gender-responsive” substance use disorder treatment centers.

A “multifaceted approach involving the full spectrum of care services is likely necessary,” the researchers say. Health care practitioners who treat women for pain, depression, or anxiety can discuss treatment options that consider the unique biopsychosocial needs of women.

Health care practitioners also can consider implementing the CDC Guideline for Prescribing Opioids for Chronic Pain, which says “Opioids are not first-line or routine therapy for chronic pain.” The guideline also says before starting and periodically during opioid therapy, clinicians should discuss with patients the “known risks and realistic benefits of opioid therapy.”  In other words, listen to the women and prescribe carefully.

Children with a diagnosis of autism spectrum disorder or another developmental delay or disorder that includes autistic characteristics are twice as likely to have sleeping problems, a multisite case-control study has found.

iStock/Getty Images Plus

The findings match up with previous similar studies, but this study is among the largest to measure sleeping problems in children with autism spectrum disorder (ASD) with two control groups.

“The higher reported occurrence of sleep problems in children with ASD may be due to multiple contributing factors, including physiologic differences, sleep disorders, developmental comorbidities, medical comorbidities causing sleep disruption, communication impairments, and behavioral disturbances,” Ann M. Reynolds, MD, of the University of Colorado and Children’s Hospital Colorado, both in Aurora, and her associates reported in Pediatrics.

“Children with ASD are more likely to have anxiety, which may predispose them to sleep problems,” the authors added.

The study evaluated sleep habits and problems in 1,987 children aged 2-5 years. The study population included 522 children with ASD, 228 children with other developmental delays and disorders that have ASD characteristics, 534 children with other developmental delays and disorders, and 703 children from the general population.

Parents completed the Children Sleep Habits Questionnaire (CSHQ), a 33-item assessment tool typically used with a total score cutoff of 41 and above for identification of children with sleep disorders. The researchers also used a second, more conservative cutoff of 48 – the cutoff for the highest quartile in the general population group – to avoid overidentification with the lower cutoff.

SOURCE: Reynolds AM et al. Pediatrics. 2019 Feb. 11. doi: 10.1542/peds.2018-0492.

Children with a diagnosis of autism spectrum disorder or another developmental delay or disorder that includes autistic characteristics are twice as likely to have sleeping problems, a multisite case-control study has found.

iStock/Getty Images Plus

The findings match up with previous similar studies, but this study is among the largest to measure sleeping problems in children with autism spectrum disorder (ASD) with two control groups.

“The higher reported occurrence of sleep problems in children with ASD may be due to multiple contributing factors, including physiologic differences, sleep disorders, developmental comorbidities, medical comorbidities causing sleep disruption, communication impairments, and behavioral disturbances,” Ann M. Reynolds, MD, of the University of Colorado and Children’s Hospital Colorado, both in Aurora, and her associates reported in Pediatrics.

“Children with ASD are more likely to have anxiety, which may predispose them to sleep problems,” the authors added.

The study evaluated sleep habits and problems in 1,987 children aged 2-5 years. The study population included 522 children with ASD, 228 children with other developmental delays and disorders that have ASD characteristics, 534 children with other developmental delays and disorders, and 703 children from the general population.

Parents completed the Children Sleep Habits Questionnaire (CSHQ), a 33-item assessment tool typically used with a total score cutoff of 41 and above for identification of children with sleep disorders. The researchers also used a second, more conservative cutoff of 48 – the cutoff for the highest quartile in the general population group – to avoid overidentification with the lower cutoff.

SOURCE: Reynolds AM et al. Pediatrics. 2019 Feb. 11. doi: 10.1542/peds.2018-0492.

Children with a diagnosis of autism spectrum disorder or another developmental delay or disorder that includes autistic characteristics are twice as likely to have sleeping problems, a multisite case-control study has found.

iStock/Getty Images Plus

The findings match up with previous similar studies, but this study is among the largest to measure sleeping problems in children with autism spectrum disorder (ASD) with two control groups.

“The higher reported occurrence of sleep problems in children with ASD may be due to multiple contributing factors, including physiologic differences, sleep disorders, developmental comorbidities, medical comorbidities causing sleep disruption, communication impairments, and behavioral disturbances,” Ann M. Reynolds, MD, of the University of Colorado and Children’s Hospital Colorado, both in Aurora, and her associates reported in Pediatrics.

“Children with ASD are more likely to have anxiety, which may predispose them to sleep problems,” the authors added.

The study evaluated sleep habits and problems in 1,987 children aged 2-5 years. The study population included 522 children with ASD, 228 children with other developmental delays and disorders that have ASD characteristics, 534 children with other developmental delays and disorders, and 703 children from the general population.

Parents completed the Children Sleep Habits Questionnaire (CSHQ), a 33-item assessment tool typically used with a total score cutoff of 41 and above for identification of children with sleep disorders. The researchers also used a second, more conservative cutoff of 48 – the cutoff for the highest quartile in the general population group – to avoid overidentification with the lower cutoff.

SOURCE: Reynolds AM et al. Pediatrics. 2019 Feb. 11. doi: 10.1542/peds.2018-0492.

Lesbian, gay, bisexual, transgender, and questioning (LGBTQ) youth living in foster care or unstable housing are at greater risk for mental health problems, victimization, and getting into fights at school, compared with LGBTQ youth in stable housing and heterosexual youth in foster care, reported Laura Baums, PhD, of the University of Texas at Austin and her coauthors.

This was the finding of analyses of nested data of more than 493,000 students aged 10-18 years from the cross-sectional California Healthy Kids Survey for 2013-2015; 13% identified as LGBTQ. The analyses published in Pediatrics showed LGBTQ youth also were overrepresented in those living situations as compared with the general population.

Less than 1% of the overall sample was in foster care, but 30% of those youth identified as LGBTQ. About 4% of the overall sample lived in unstable housing, and 25% of those youth identified as LGBTQ. So the proportion of LGBTQ youth in foster care or unstable housing was two to three times greater than would be expected than the estimates of LGBTQ youth in nationally representative adolescent samples (that is 11%), Dr. Baums and her associates said.

LGBTQ youth in unstable housing reported lower grades, higher substance/alcohol abuse, higher rates of absenteeism, more fights in school, and more victimization, compared with heterosexual youth in unstable housing and LGBTQ youth in stable housing. Both LGBTQ youth in unstable housing and those in foster care reported higher rates of depression and suicidality in the past year, but the rates for depression were not different from LGBTQ youth in stable housing. Furthermore, African American LGBTQ youth in unstable housing showed poorer outcomes than non-Hispanic white LGBTQ youth in unstable housing, they said.

“LGBTQ youth, in general, showed poor outcomes, which was exacerbated when they lived in unstable housing or foster care,” concluded Dr. Baums and her associates. “The findings of this study point to the need for care that is affirming and respectful of youth’s sexual orientation and gender identity.”

The authors reported no relevant financial disclosures. The study was funded by a Eunice Kennedy Shriver National Institute of Child Health and Human Development grant and supported by the Communities for Just Schools Fund and the Priscilla Pond Flawn Endowment at the university.

[email protected]

SOURCE: Baum L et al. Pediatrics. 2019 Feb 11. doi: 10.1542/peds.2017-4211.

Lesbian, gay, bisexual, transgender, and questioning (LGBTQ) youth living in foster care or unstable housing are at greater risk for mental health problems, victimization, and getting into fights at school, compared with LGBTQ youth in stable housing and heterosexual youth in foster care, reported Laura Baums, PhD, of the University of Texas at Austin and her coauthors.

This was the finding of analyses of nested data of more than 493,000 students aged 10-18 years from the cross-sectional California Healthy Kids Survey for 2013-2015; 13% identified as LGBTQ. The analyses published in Pediatrics showed LGBTQ youth also were overrepresented in those living situations as compared with the general population.

Less than 1% of the overall sample was in foster care, but 30% of those youth identified as LGBTQ. About 4% of the overall sample lived in unstable housing, and 25% of those youth identified as LGBTQ. So the proportion of LGBTQ youth in foster care or unstable housing was two to three times greater than would be expected than the estimates of LGBTQ youth in nationally representative adolescent samples (that is 11%), Dr. Baums and her associates said.

LGBTQ youth in unstable housing reported lower grades, higher substance/alcohol abuse, higher rates of absenteeism, more fights in school, and more victimization, compared with heterosexual youth in unstable housing and LGBTQ youth in stable housing. Both LGBTQ youth in unstable housing and those in foster care reported higher rates of depression and suicidality in the past year, but the rates for depression were not different from LGBTQ youth in stable housing. Furthermore, African American LGBTQ youth in unstable housing showed poorer outcomes than non-Hispanic white LGBTQ youth in unstable housing, they said.

“LGBTQ youth, in general, showed poor outcomes, which was exacerbated when they lived in unstable housing or foster care,” concluded Dr. Baums and her associates. “The findings of this study point to the need for care that is affirming and respectful of youth’s sexual orientation and gender identity.”

The authors reported no relevant financial disclosures. The study was funded by a Eunice Kennedy Shriver National Institute of Child Health and Human Development grant and supported by the Communities for Just Schools Fund and the Priscilla Pond Flawn Endowment at the university.

[email protected]

SOURCE: Baum L et al. Pediatrics. 2019 Feb 11. doi: 10.1542/peds.2017-4211.

Lesbian, gay, bisexual, transgender, and questioning (LGBTQ) youth living in foster care or unstable housing are at greater risk for mental health problems, victimization, and getting into fights at school, compared with LGBTQ youth in stable housing and heterosexual youth in foster care, reported Laura Baums, PhD, of the University of Texas at Austin and her coauthors.

This was the finding of analyses of nested data of more than 493,000 students aged 10-18 years from the cross-sectional California Healthy Kids Survey for 2013-2015; 13% identified as LGBTQ. The analyses published in Pediatrics showed LGBTQ youth also were overrepresented in those living situations as compared with the general population.

Less than 1% of the overall sample was in foster care, but 30% of those youth identified as LGBTQ. About 4% of the overall sample lived in unstable housing, and 25% of those youth identified as LGBTQ. So the proportion of LGBTQ youth in foster care or unstable housing was two to three times greater than would be expected than the estimates of LGBTQ youth in nationally representative adolescent samples (that is 11%), Dr. Baums and her associates said.

LGBTQ youth in unstable housing reported lower grades, higher substance/alcohol abuse, higher rates of absenteeism, more fights in school, and more victimization, compared with heterosexual youth in unstable housing and LGBTQ youth in stable housing. Both LGBTQ youth in unstable housing and those in foster care reported higher rates of depression and suicidality in the past year, but the rates for depression were not different from LGBTQ youth in stable housing. Furthermore, African American LGBTQ youth in unstable housing showed poorer outcomes than non-Hispanic white LGBTQ youth in unstable housing, they said.

“LGBTQ youth, in general, showed poor outcomes, which was exacerbated when they lived in unstable housing or foster care,” concluded Dr. Baums and her associates. “The findings of this study point to the need for care that is affirming and respectful of youth’s sexual orientation and gender identity.”

The authors reported no relevant financial disclosures. The study was funded by a Eunice Kennedy Shriver National Institute of Child Health and Human Development grant and supported by the Communities for Just Schools Fund and the Priscilla Pond Flawn Endowment at the university.

[email protected]

SOURCE: Baum L et al. Pediatrics. 2019 Feb 11. doi: 10.1542/peds.2017-4211.

Steven Q. Simpson, MD, FCCP, is a pulmonologist and intensivist with an extensive background in sepsis and in critical care quality improvement. Dr. Simpson acts as a CHEST Regent-at-Large of the Board of Regents, board liaison for the Guidelines Oversight Committee, sits on numerous board task forces and subcommittees and is a member of the CHEST SEEK Critical Care Medicine Editorial Board. He will serve as CHEST President for the 2020-2021 term.

Dr. Simpson is Professor of Medicine in the Division of Pulmonary and Critical Care Medicine at the University of Kansas. He is also senior advisor to the Solving Sepsis initiative of the Biomedical Advanced Research and Development Authority (BARDA) of the US Department of Health and Human Services. He has conducted research in all areas of severe sepsis, including molecular and cellular mechanisms, translational, quality improvement, and computer modeling studies. He was a founder in 2005 of the Midwest Critical Care Collaborative, a multidisciplinary and interprofessional collaborative effort to improve the quality of critical care services throughout the Midwest. In 2007, he initiated the Kansas Sepsis Project, a statewide program to improve severe sepsis care and outcomes via continuing education both in sepsis and in quality improvement principles and via interprofessional collaborations. Dr. Simpson is an author of the 2016 and 2020 updates of the Surviving Sepsis Campaign Guidelines. He is a member of the board of directors and Chief Medical Officer of Sepsis Alliance, a nationwide patient information and advocacy organization.

During his tenure at the University of New Mexico, he contributed to the discovery of a particular form of sepsis, the hantavirus pulmonary syndrome, and published numerous papers on the clinical description, the hemodynamic description, and the approach to supportive care for patients with the syndrome, including extracorporeal hemodynamic and oxygenation support. Dr. Simpson has authored over 180 scientific articles, book chapters, editorials, abstracts and electronic media publications. He was awarded the 2009 Eli Lilly Distinguished Scholar in Critical Care Medicine Award of the American College of Chest Physicians and the 2013 Roger C. Bone Memorial Lecture in Critical Care Medicine, which recognizes career contributions to the field. He has also been recognized as a Distinguished CHEST Educator in 2017 and 2018.
 

Steven Q. Simpson, MD, FCCP, is a pulmonologist and intensivist with an extensive background in sepsis and in critical care quality improvement. Dr. Simpson acts as a CHEST Regent-at-Large of the Board of Regents, board liaison for the Guidelines Oversight Committee, sits on numerous board task forces and subcommittees and is a member of the CHEST SEEK Critical Care Medicine Editorial Board. He will serve as CHEST President for the 2020-2021 term.

Dr. Simpson is Professor of Medicine in the Division of Pulmonary and Critical Care Medicine at the University of Kansas. He is also senior advisor to the Solving Sepsis initiative of the Biomedical Advanced Research and Development Authority (BARDA) of the US Department of Health and Human Services. He has conducted research in all areas of severe sepsis, including molecular and cellular mechanisms, translational, quality improvement, and computer modeling studies. He was a founder in 2005 of the Midwest Critical Care Collaborative, a multidisciplinary and interprofessional collaborative effort to improve the quality of critical care services throughout the Midwest. In 2007, he initiated the Kansas Sepsis Project, a statewide program to improve severe sepsis care and outcomes via continuing education both in sepsis and in quality improvement principles and via interprofessional collaborations. Dr. Simpson is an author of the 2016 and 2020 updates of the Surviving Sepsis Campaign Guidelines. He is a member of the board of directors and Chief Medical Officer of Sepsis Alliance, a nationwide patient information and advocacy organization.

During his tenure at the University of New Mexico, he contributed to the discovery of a particular form of sepsis, the hantavirus pulmonary syndrome, and published numerous papers on the clinical description, the hemodynamic description, and the approach to supportive care for patients with the syndrome, including extracorporeal hemodynamic and oxygenation support. Dr. Simpson has authored over 180 scientific articles, book chapters, editorials, abstracts and electronic media publications. He was awarded the 2009 Eli Lilly Distinguished Scholar in Critical Care Medicine Award of the American College of Chest Physicians and the 2013 Roger C. Bone Memorial Lecture in Critical Care Medicine, which recognizes career contributions to the field. He has also been recognized as a Distinguished CHEST Educator in 2017 and 2018.
 

Steven Q. Simpson, MD, FCCP, is a pulmonologist and intensivist with an extensive background in sepsis and in critical care quality improvement. Dr. Simpson acts as a CHEST Regent-at-Large of the Board of Regents, board liaison for the Guidelines Oversight Committee, sits on numerous board task forces and subcommittees and is a member of the CHEST SEEK Critical Care Medicine Editorial Board. He will serve as CHEST President for the 2020-2021 term.

Dr. Simpson is Professor of Medicine in the Division of Pulmonary and Critical Care Medicine at the University of Kansas. He is also senior advisor to the Solving Sepsis initiative of the Biomedical Advanced Research and Development Authority (BARDA) of the US Department of Health and Human Services. He has conducted research in all areas of severe sepsis, including molecular and cellular mechanisms, translational, quality improvement, and computer modeling studies. He was a founder in 2005 of the Midwest Critical Care Collaborative, a multidisciplinary and interprofessional collaborative effort to improve the quality of critical care services throughout the Midwest. In 2007, he initiated the Kansas Sepsis Project, a statewide program to improve severe sepsis care and outcomes via continuing education both in sepsis and in quality improvement principles and via interprofessional collaborations. Dr. Simpson is an author of the 2016 and 2020 updates of the Surviving Sepsis Campaign Guidelines. He is a member of the board of directors and Chief Medical Officer of Sepsis Alliance, a nationwide patient information and advocacy organization.

During his tenure at the University of New Mexico, he contributed to the discovery of a particular form of sepsis, the hantavirus pulmonary syndrome, and published numerous papers on the clinical description, the hemodynamic description, and the approach to supportive care for patients with the syndrome, including extracorporeal hemodynamic and oxygenation support. Dr. Simpson has authored over 180 scientific articles, book chapters, editorials, abstracts and electronic media publications. He was awarded the 2009 Eli Lilly Distinguished Scholar in Critical Care Medicine Award of the American College of Chest Physicians and the 2013 Roger C. Bone Memorial Lecture in Critical Care Medicine, which recognizes career contributions to the field. He has also been recognized as a Distinguished CHEST Educator in 2017 and 2018.
 

Physicians’ time is decreasingly their own, and, yet, keeping abreast of clinical literature is increasingly more important. The journal CHEST has introduced a new feature aimed at easing that task and broadening the reach of journal content: visual abstracts.

Physicians’ time is decreasingly their own, and, yet, keeping abreast of clinical literature is increasingly more important. The journal CHEST has introduced a new feature aimed at easing that task and broadening the reach of journal content: visual abstracts.

Physicians’ time is decreasingly their own, and, yet, keeping abreast of clinical literature is increasingly more important. The journal CHEST has introduced a new feature aimed at easing that task and broadening the reach of journal content: visual abstracts.