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‘Extensive’ evidence for altered brain-gut-microbiome system in IBS
The view of irritable bowel syndrome (IBS) as a disorder of altered interactions within the brain-gut-microbiome system is supported today by “extensive clinical, brain and microbiome-derived evidence,” Emeran A. Mayer, MD, of the University of California, Los Angeles, said at the annual Gut Microbiota for Health World Summit.
A recently published genome-wide analysis from the United Kingdom of more than 53,000 people with IBS found shared genetic pathways with mood and anxiety disorders and “is one of the most convincing studies to date [showing] that we’re not dealing with separate disorders, but that we’re dealing with the brain-gut-microbiome system,” said Dr. Mayer, director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience, and codirector of the Cure: Digestive Diseases Research Center at UCLA.
Meanwhile, multi-omics analyses from his team have established significant differences in the composition and function of the gut microbiome between IBS and healthy controls and, significantly, between IBS subgroups, he reported.
The genome analysis, published in Nature Genetics, utilized the UK Biobank, which contains genome-wide SNP genotyping data and health data for a half a million individuals. People with IBS were identified with a digestive health questionnaire that included Rome III symptom criteria.
In their cohort of 53,400 IBS cases and 433,201 healthy controls, the researchers identified 6 genetic susceptibility loci for IBS, 3 of which have previously been shown to be associated with depression, neuroticism, and other psychiatric disorders. (Significant associations were replicated in a 23andMe panel.) “The study emphasizes that GI symptoms [of IBS] and mood and anxiety disorders are two sides of the same coin,” Dr. Mayer said.
Differences in IBS subtypes
The team’s multi-omics profiles of the intestinal microbiota in IBS and its subtypes, based on bowel habits, have shown that IBS is characterized by “altered abundances of certain bacterial taxa, transcripts, and metabolites,” he said.
The research, awaiting publication, has also shown that IBS metabolites, transcripts, and transcript/gene ratios differentiate IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C) with high accuracy. In addition, the IBS-D subtype is differentiated from IBS-C by “diverse functional shifts including increased polyamines, bile acids, glutamate synthesis, and ethanolamine utilization,” Dr. Mayer said.
In related multi-omics research incorporating brain imaging data, Dr. Mayer’s team has identified greater alterations in measures of brain connectivity in the IBS-D group, “just as we saw for the microbiome parameters as well,” he said at the meeting, which was sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology & Motility.
These “are all associations,” he noted. The microbiome is an established integral player in gut-brain communication, but “a casual role between the gut microbiome and IBS remains to be established.”
Although mechanistic studies are still in earlier stages, it’s clear that the microbiome is a potentially important site for therapeutic interventions. “Microbiome-targeted therapies are likely to be effective in subsets of IBS patients, based on their bowel habits, and on microbiome features,” said Dr. Mayer.
Impact of probiotics
In reviewing key research, Dr. Mayer also pointed to interventional studies that support bidirectional relationships between the brain and the gut microbiome.
Studies of gut microbiome-targeted therapies in patients with IBS have shown mixed results – both positive and negative findings – and have been of variable quality. However, a couple of well-done small studies “have shown that probiotics can modulate brain activity and affect psychiatric symptoms,” Dr. Mayer said.
One of these studies, a randomized, double-blind placebo-controlled study of 44 adults with IBS, found reductions in depression scores and changes in brain activation patterns in those who took the probiotic Bifidobacterium longum.
Studies in healthy women are also telling. One of his team’s studies looked at the impact of 4 weeks of a fermented milk product with a 5-strain probiotic consortium on brain intrinsic connectivity and responses to emotional attention tasks.
“We saw significant changes in the connectivity of multiple brain regions ... networks related to emotional regulation circuits within the brain,” he said. “We have to assume that the perturbation happened at the gut-microbiome level.”
A study from Germany demonstrated that the probiotic Bifidobacterium longum modulated brain activity of healthy individuals during social stress.
Impact of cognitive-behavioral therapy
Emanating from the brain, nonpharmaceutical brain-targeted therapies have been shown to reduce IBS symptom severity, he said. In one randomized controlled trial of more than 400 patients with refractory IBS, a primarily home-based version of cognitive behavioral therapy (CBT) produced significant and sustained improvement in symptoms compared with education.
And a study published last year by Dr. Mayer and coinvestigators demonstrated that a positive clinical response to CBT was associated with changes in both the brain (changes in functional and structural connectivity) and the gut microbiota.
Eighty-four IBS patients underwent multimodal brain imaging and psychological assessments before and after CBT, and 34 of the participants underwent microbiome assessments with 16S rRNA A gene sequencing, untargeted metabolomics, and measurement of short-chain fatty acid from fecal samples collected at baseline and post treatment.
In comparing responders (58) and nonresponders (26), the researchers found that response to CBT could be predicted from baseline microbiota composition (including increased Clostridiales and decreased Bacteroides), and that responders had microbial shifts after therapy – including expansion of Bacteroides – in addition to distinct brain changes. “We know which brain networks [in patients with IBS] are sensitive to CBT,” said Dr. Mayer.
Eugene B. Chang, MD, the Martin Boyer Distinguished Professor of Medicine at the University of Chicago and director of the university’s Microbiome Medicine Program, said in an interview after the meeting that the brain-gut-microbiome system “is a very important area for investigation” not only for IBS but for hepatic encephalopathy and other problems and disorders such as neurodegenerative disorders (e.g., Alzheimer’s and Parkinson’s) and circadian disruption, “where gut dysbiosis has been implicated as causative or contributory.”
The specialty still has very little understanding of IBS, and “clinical practice remains largely empirical,” he said, noting that his program is embarking on studies of the brain-gut microbiome system.
Dr. Mayer reported that he serves on the advisory board of Axial Biotherapeutics, Pendulum, Bloom Science, and several other companies. Dr. Chang reported that he has no relevant disclosures.
The view of irritable bowel syndrome (IBS) as a disorder of altered interactions within the brain-gut-microbiome system is supported today by “extensive clinical, brain and microbiome-derived evidence,” Emeran A. Mayer, MD, of the University of California, Los Angeles, said at the annual Gut Microbiota for Health World Summit.
A recently published genome-wide analysis from the United Kingdom of more than 53,000 people with IBS found shared genetic pathways with mood and anxiety disorders and “is one of the most convincing studies to date [showing] that we’re not dealing with separate disorders, but that we’re dealing with the brain-gut-microbiome system,” said Dr. Mayer, director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience, and codirector of the Cure: Digestive Diseases Research Center at UCLA.
Meanwhile, multi-omics analyses from his team have established significant differences in the composition and function of the gut microbiome between IBS and healthy controls and, significantly, between IBS subgroups, he reported.
The genome analysis, published in Nature Genetics, utilized the UK Biobank, which contains genome-wide SNP genotyping data and health data for a half a million individuals. People with IBS were identified with a digestive health questionnaire that included Rome III symptom criteria.
In their cohort of 53,400 IBS cases and 433,201 healthy controls, the researchers identified 6 genetic susceptibility loci for IBS, 3 of which have previously been shown to be associated with depression, neuroticism, and other psychiatric disorders. (Significant associations were replicated in a 23andMe panel.) “The study emphasizes that GI symptoms [of IBS] and mood and anxiety disorders are two sides of the same coin,” Dr. Mayer said.
Differences in IBS subtypes
The team’s multi-omics profiles of the intestinal microbiota in IBS and its subtypes, based on bowel habits, have shown that IBS is characterized by “altered abundances of certain bacterial taxa, transcripts, and metabolites,” he said.
The research, awaiting publication, has also shown that IBS metabolites, transcripts, and transcript/gene ratios differentiate IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C) with high accuracy. In addition, the IBS-D subtype is differentiated from IBS-C by “diverse functional shifts including increased polyamines, bile acids, glutamate synthesis, and ethanolamine utilization,” Dr. Mayer said.
In related multi-omics research incorporating brain imaging data, Dr. Mayer’s team has identified greater alterations in measures of brain connectivity in the IBS-D group, “just as we saw for the microbiome parameters as well,” he said at the meeting, which was sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology & Motility.
These “are all associations,” he noted. The microbiome is an established integral player in gut-brain communication, but “a casual role between the gut microbiome and IBS remains to be established.”
Although mechanistic studies are still in earlier stages, it’s clear that the microbiome is a potentially important site for therapeutic interventions. “Microbiome-targeted therapies are likely to be effective in subsets of IBS patients, based on their bowel habits, and on microbiome features,” said Dr. Mayer.
Impact of probiotics
In reviewing key research, Dr. Mayer also pointed to interventional studies that support bidirectional relationships between the brain and the gut microbiome.
Studies of gut microbiome-targeted therapies in patients with IBS have shown mixed results – both positive and negative findings – and have been of variable quality. However, a couple of well-done small studies “have shown that probiotics can modulate brain activity and affect psychiatric symptoms,” Dr. Mayer said.
One of these studies, a randomized, double-blind placebo-controlled study of 44 adults with IBS, found reductions in depression scores and changes in brain activation patterns in those who took the probiotic Bifidobacterium longum.
Studies in healthy women are also telling. One of his team’s studies looked at the impact of 4 weeks of a fermented milk product with a 5-strain probiotic consortium on brain intrinsic connectivity and responses to emotional attention tasks.
“We saw significant changes in the connectivity of multiple brain regions ... networks related to emotional regulation circuits within the brain,” he said. “We have to assume that the perturbation happened at the gut-microbiome level.”
A study from Germany demonstrated that the probiotic Bifidobacterium longum modulated brain activity of healthy individuals during social stress.
Impact of cognitive-behavioral therapy
Emanating from the brain, nonpharmaceutical brain-targeted therapies have been shown to reduce IBS symptom severity, he said. In one randomized controlled trial of more than 400 patients with refractory IBS, a primarily home-based version of cognitive behavioral therapy (CBT) produced significant and sustained improvement in symptoms compared with education.
And a study published last year by Dr. Mayer and coinvestigators demonstrated that a positive clinical response to CBT was associated with changes in both the brain (changes in functional and structural connectivity) and the gut microbiota.
Eighty-four IBS patients underwent multimodal brain imaging and psychological assessments before and after CBT, and 34 of the participants underwent microbiome assessments with 16S rRNA A gene sequencing, untargeted metabolomics, and measurement of short-chain fatty acid from fecal samples collected at baseline and post treatment.
In comparing responders (58) and nonresponders (26), the researchers found that response to CBT could be predicted from baseline microbiota composition (including increased Clostridiales and decreased Bacteroides), and that responders had microbial shifts after therapy – including expansion of Bacteroides – in addition to distinct brain changes. “We know which brain networks [in patients with IBS] are sensitive to CBT,” said Dr. Mayer.
Eugene B. Chang, MD, the Martin Boyer Distinguished Professor of Medicine at the University of Chicago and director of the university’s Microbiome Medicine Program, said in an interview after the meeting that the brain-gut-microbiome system “is a very important area for investigation” not only for IBS but for hepatic encephalopathy and other problems and disorders such as neurodegenerative disorders (e.g., Alzheimer’s and Parkinson’s) and circadian disruption, “where gut dysbiosis has been implicated as causative or contributory.”
The specialty still has very little understanding of IBS, and “clinical practice remains largely empirical,” he said, noting that his program is embarking on studies of the brain-gut microbiome system.
Dr. Mayer reported that he serves on the advisory board of Axial Biotherapeutics, Pendulum, Bloom Science, and several other companies. Dr. Chang reported that he has no relevant disclosures.
The view of irritable bowel syndrome (IBS) as a disorder of altered interactions within the brain-gut-microbiome system is supported today by “extensive clinical, brain and microbiome-derived evidence,” Emeran A. Mayer, MD, of the University of California, Los Angeles, said at the annual Gut Microbiota for Health World Summit.
A recently published genome-wide analysis from the United Kingdom of more than 53,000 people with IBS found shared genetic pathways with mood and anxiety disorders and “is one of the most convincing studies to date [showing] that we’re not dealing with separate disorders, but that we’re dealing with the brain-gut-microbiome system,” said Dr. Mayer, director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience, and codirector of the Cure: Digestive Diseases Research Center at UCLA.
Meanwhile, multi-omics analyses from his team have established significant differences in the composition and function of the gut microbiome between IBS and healthy controls and, significantly, between IBS subgroups, he reported.
The genome analysis, published in Nature Genetics, utilized the UK Biobank, which contains genome-wide SNP genotyping data and health data for a half a million individuals. People with IBS were identified with a digestive health questionnaire that included Rome III symptom criteria.
In their cohort of 53,400 IBS cases and 433,201 healthy controls, the researchers identified 6 genetic susceptibility loci for IBS, 3 of which have previously been shown to be associated with depression, neuroticism, and other psychiatric disorders. (Significant associations were replicated in a 23andMe panel.) “The study emphasizes that GI symptoms [of IBS] and mood and anxiety disorders are two sides of the same coin,” Dr. Mayer said.
Differences in IBS subtypes
The team’s multi-omics profiles of the intestinal microbiota in IBS and its subtypes, based on bowel habits, have shown that IBS is characterized by “altered abundances of certain bacterial taxa, transcripts, and metabolites,” he said.
The research, awaiting publication, has also shown that IBS metabolites, transcripts, and transcript/gene ratios differentiate IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C) with high accuracy. In addition, the IBS-D subtype is differentiated from IBS-C by “diverse functional shifts including increased polyamines, bile acids, glutamate synthesis, and ethanolamine utilization,” Dr. Mayer said.
In related multi-omics research incorporating brain imaging data, Dr. Mayer’s team has identified greater alterations in measures of brain connectivity in the IBS-D group, “just as we saw for the microbiome parameters as well,” he said at the meeting, which was sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology & Motility.
These “are all associations,” he noted. The microbiome is an established integral player in gut-brain communication, but “a casual role between the gut microbiome and IBS remains to be established.”
Although mechanistic studies are still in earlier stages, it’s clear that the microbiome is a potentially important site for therapeutic interventions. “Microbiome-targeted therapies are likely to be effective in subsets of IBS patients, based on their bowel habits, and on microbiome features,” said Dr. Mayer.
Impact of probiotics
In reviewing key research, Dr. Mayer also pointed to interventional studies that support bidirectional relationships between the brain and the gut microbiome.
Studies of gut microbiome-targeted therapies in patients with IBS have shown mixed results – both positive and negative findings – and have been of variable quality. However, a couple of well-done small studies “have shown that probiotics can modulate brain activity and affect psychiatric symptoms,” Dr. Mayer said.
One of these studies, a randomized, double-blind placebo-controlled study of 44 adults with IBS, found reductions in depression scores and changes in brain activation patterns in those who took the probiotic Bifidobacterium longum.
Studies in healthy women are also telling. One of his team’s studies looked at the impact of 4 weeks of a fermented milk product with a 5-strain probiotic consortium on brain intrinsic connectivity and responses to emotional attention tasks.
“We saw significant changes in the connectivity of multiple brain regions ... networks related to emotional regulation circuits within the brain,” he said. “We have to assume that the perturbation happened at the gut-microbiome level.”
A study from Germany demonstrated that the probiotic Bifidobacterium longum modulated brain activity of healthy individuals during social stress.
Impact of cognitive-behavioral therapy
Emanating from the brain, nonpharmaceutical brain-targeted therapies have been shown to reduce IBS symptom severity, he said. In one randomized controlled trial of more than 400 patients with refractory IBS, a primarily home-based version of cognitive behavioral therapy (CBT) produced significant and sustained improvement in symptoms compared with education.
And a study published last year by Dr. Mayer and coinvestigators demonstrated that a positive clinical response to CBT was associated with changes in both the brain (changes in functional and structural connectivity) and the gut microbiota.
Eighty-four IBS patients underwent multimodal brain imaging and psychological assessments before and after CBT, and 34 of the participants underwent microbiome assessments with 16S rRNA A gene sequencing, untargeted metabolomics, and measurement of short-chain fatty acid from fecal samples collected at baseline and post treatment.
In comparing responders (58) and nonresponders (26), the researchers found that response to CBT could be predicted from baseline microbiota composition (including increased Clostridiales and decreased Bacteroides), and that responders had microbial shifts after therapy – including expansion of Bacteroides – in addition to distinct brain changes. “We know which brain networks [in patients with IBS] are sensitive to CBT,” said Dr. Mayer.
Eugene B. Chang, MD, the Martin Boyer Distinguished Professor of Medicine at the University of Chicago and director of the university’s Microbiome Medicine Program, said in an interview after the meeting that the brain-gut-microbiome system “is a very important area for investigation” not only for IBS but for hepatic encephalopathy and other problems and disorders such as neurodegenerative disorders (e.g., Alzheimer’s and Parkinson’s) and circadian disruption, “where gut dysbiosis has been implicated as causative or contributory.”
The specialty still has very little understanding of IBS, and “clinical practice remains largely empirical,” he said, noting that his program is embarking on studies of the brain-gut microbiome system.
Dr. Mayer reported that he serves on the advisory board of Axial Biotherapeutics, Pendulum, Bloom Science, and several other companies. Dr. Chang reported that he has no relevant disclosures.
FROM GMFH 2022
Cardiac monitoring suggested for advanced RCC patients with high troponin T levels after combo treatment
Among patients with advanced renal cell cancer treated with a combination of immune checkpoint inhibitors (ICI) and vascular endothelial growth factor (VEGF) inhibitors, , according to a planned post hoc analysis of data from the phase III JAVELIN Renal 101 trial.
The therapeutic combination is effective against several solid tumors, but ICIs are associated with cardiovascular events, including myocarditis in about 1% of patients. Although rare, the condition has a 46% mortality and 80% of the time occurs within 6 weeks of the start of treatment. It is unknown whether combination with VEGF inhibitors could heighten that risk.
“One of the areas that has been uncertain in kidney cancer with these VEGF combos is, what are the potential cardiac toxicities? How intensive monitoring do we need? How do we predict which patients might be at risk for these relatively rare but potentially serious events? So I think the value of the study is that it is a large prospective study where these measurements and endpoints were prospectively defined,” said lead author Brian Rini, MD, chief of clinical trials at Vanderbilt-Ingram Cancer Center.
The study, published online March 3 in the Journal of Clinical Oncology, doesn’t create specific recommendations for handling patients, Dr. Rini said. He suggests that physicians should consider more intense monitoring of patients on the regimen, along with upfront consultation with cardiologists, as well as keeping other treatment regimens in mind. “It’s hard to go much beyond just sort of an alert that this patient may be at higher risk than a patient without [heightened troponin T levels],” Dr. Rini said.
He also noted the finding that LVEF decline (≥10-point reduction from baseline to a value below the lower limit of normal) didn’t predict major adverse cardiac events (MACE), suggesting that echocardiograms, which have been done routinely since VEGF-targeted therapy was introduced, may not have much value in the general patient population. “It’s not that there’s no risk, but doing a lot of ECHOs on every single patient is just not an efficient way, as opposed to doing it in a more targeted fashion to patients with the relevant history and/or who developed suggestive symptoms,” Dr. Rini said.
The JAVELIN study randomized 442 patients (median age, 62.0; 71.5% male) to intravenous avelumab (Bavencio, Merck/Pfizer, 10 mg/kg) every 2 weeks plus oral axitinib (Inlyta, Pfizer, 5 mg) twice per day, and 439 patients (median age, 61.0; 77.5% male) to oral sunitinib (Sutent, Pfizer, 50 mg) once per day for 4 weeks. MACE were more common in the avelumab/axitinib group (7.1% vs. 3.9%). Left ventricular ejection fraction (LVEF) decline occurred more often in the avelumab/axitinib arm (8.5% vs. 1.6%; P < .0001), but there was no correlation between MACE and LVEF decline in either arm.
Patients in the avelumab/axitinib group with baseline levels of troponin T above the upper limit of normal were more likely to experience a MACE (17.1% vs. 5.2%; relative risk, 3.31; P = .022), but there was no difference in the sunitinib arm.
The study was funded by Pfizer. Dr. Rini has consulted for and received research funding from Pfizer.
Among patients with advanced renal cell cancer treated with a combination of immune checkpoint inhibitors (ICI) and vascular endothelial growth factor (VEGF) inhibitors, , according to a planned post hoc analysis of data from the phase III JAVELIN Renal 101 trial.
The therapeutic combination is effective against several solid tumors, but ICIs are associated with cardiovascular events, including myocarditis in about 1% of patients. Although rare, the condition has a 46% mortality and 80% of the time occurs within 6 weeks of the start of treatment. It is unknown whether combination with VEGF inhibitors could heighten that risk.
“One of the areas that has been uncertain in kidney cancer with these VEGF combos is, what are the potential cardiac toxicities? How intensive monitoring do we need? How do we predict which patients might be at risk for these relatively rare but potentially serious events? So I think the value of the study is that it is a large prospective study where these measurements and endpoints were prospectively defined,” said lead author Brian Rini, MD, chief of clinical trials at Vanderbilt-Ingram Cancer Center.
The study, published online March 3 in the Journal of Clinical Oncology, doesn’t create specific recommendations for handling patients, Dr. Rini said. He suggests that physicians should consider more intense monitoring of patients on the regimen, along with upfront consultation with cardiologists, as well as keeping other treatment regimens in mind. “It’s hard to go much beyond just sort of an alert that this patient may be at higher risk than a patient without [heightened troponin T levels],” Dr. Rini said.
He also noted the finding that LVEF decline (≥10-point reduction from baseline to a value below the lower limit of normal) didn’t predict major adverse cardiac events (MACE), suggesting that echocardiograms, which have been done routinely since VEGF-targeted therapy was introduced, may not have much value in the general patient population. “It’s not that there’s no risk, but doing a lot of ECHOs on every single patient is just not an efficient way, as opposed to doing it in a more targeted fashion to patients with the relevant history and/or who developed suggestive symptoms,” Dr. Rini said.
The JAVELIN study randomized 442 patients (median age, 62.0; 71.5% male) to intravenous avelumab (Bavencio, Merck/Pfizer, 10 mg/kg) every 2 weeks plus oral axitinib (Inlyta, Pfizer, 5 mg) twice per day, and 439 patients (median age, 61.0; 77.5% male) to oral sunitinib (Sutent, Pfizer, 50 mg) once per day for 4 weeks. MACE were more common in the avelumab/axitinib group (7.1% vs. 3.9%). Left ventricular ejection fraction (LVEF) decline occurred more often in the avelumab/axitinib arm (8.5% vs. 1.6%; P < .0001), but there was no correlation between MACE and LVEF decline in either arm.
Patients in the avelumab/axitinib group with baseline levels of troponin T above the upper limit of normal were more likely to experience a MACE (17.1% vs. 5.2%; relative risk, 3.31; P = .022), but there was no difference in the sunitinib arm.
The study was funded by Pfizer. Dr. Rini has consulted for and received research funding from Pfizer.
Among patients with advanced renal cell cancer treated with a combination of immune checkpoint inhibitors (ICI) and vascular endothelial growth factor (VEGF) inhibitors, , according to a planned post hoc analysis of data from the phase III JAVELIN Renal 101 trial.
The therapeutic combination is effective against several solid tumors, but ICIs are associated with cardiovascular events, including myocarditis in about 1% of patients. Although rare, the condition has a 46% mortality and 80% of the time occurs within 6 weeks of the start of treatment. It is unknown whether combination with VEGF inhibitors could heighten that risk.
“One of the areas that has been uncertain in kidney cancer with these VEGF combos is, what are the potential cardiac toxicities? How intensive monitoring do we need? How do we predict which patients might be at risk for these relatively rare but potentially serious events? So I think the value of the study is that it is a large prospective study where these measurements and endpoints were prospectively defined,” said lead author Brian Rini, MD, chief of clinical trials at Vanderbilt-Ingram Cancer Center.
The study, published online March 3 in the Journal of Clinical Oncology, doesn’t create specific recommendations for handling patients, Dr. Rini said. He suggests that physicians should consider more intense monitoring of patients on the regimen, along with upfront consultation with cardiologists, as well as keeping other treatment regimens in mind. “It’s hard to go much beyond just sort of an alert that this patient may be at higher risk than a patient without [heightened troponin T levels],” Dr. Rini said.
He also noted the finding that LVEF decline (≥10-point reduction from baseline to a value below the lower limit of normal) didn’t predict major adverse cardiac events (MACE), suggesting that echocardiograms, which have been done routinely since VEGF-targeted therapy was introduced, may not have much value in the general patient population. “It’s not that there’s no risk, but doing a lot of ECHOs on every single patient is just not an efficient way, as opposed to doing it in a more targeted fashion to patients with the relevant history and/or who developed suggestive symptoms,” Dr. Rini said.
The JAVELIN study randomized 442 patients (median age, 62.0; 71.5% male) to intravenous avelumab (Bavencio, Merck/Pfizer, 10 mg/kg) every 2 weeks plus oral axitinib (Inlyta, Pfizer, 5 mg) twice per day, and 439 patients (median age, 61.0; 77.5% male) to oral sunitinib (Sutent, Pfizer, 50 mg) once per day for 4 weeks. MACE were more common in the avelumab/axitinib group (7.1% vs. 3.9%). Left ventricular ejection fraction (LVEF) decline occurred more often in the avelumab/axitinib arm (8.5% vs. 1.6%; P < .0001), but there was no correlation between MACE and LVEF decline in either arm.
Patients in the avelumab/axitinib group with baseline levels of troponin T above the upper limit of normal were more likely to experience a MACE (17.1% vs. 5.2%; relative risk, 3.31; P = .022), but there was no difference in the sunitinib arm.
The study was funded by Pfizer. Dr. Rini has consulted for and received research funding from Pfizer.
FROM JOURNAL OF CLINICAL ONCOLOGY
Topical options for treating melasma continue to expand
BOSTON – In the opinion of Seemal R. Desai, MD, dermatologists are obligated to tell their patients with melasma that their condition is a chronic disease with no cure.
“We have to set expectations upfront, because you all know the history,” Dr. Desai, founder and medical director of Innovative Dermatology in Dallas, said at the annual meeting of the American Academy of Dermatology. “You get someone better, their melasma gets lighter, and then they’re lost to follow-up for a year. Then they’re back to your office after that beach vacation because their melasma has come back with a vengeance because they were out in the sun too much. We have to tell our patients that melasma therapy is a journey of skin lightening but it’s not going to be a one-stop shop of getting it completely cured.”
As for treatment of melasma, “hydroquinone is still our workhorse, our gold standard.” Dr. Desai said. “I tell patients, ‘I’m going to keep you on it for 16 weeks. Then you’re going to come back. I’m going to see where you are, and we’ll move into the nonhydroquinone therapies once your disease is under control.’ ”
However, new therapies for melasma are needed because long-term use of hydroquinone can lead to complications such as ochronosis, nail discoloration, conjunctival melanosis, and corneal degeneration.
Emerging treatments
. Dr. Desai described azelaic acid as his “go to” nonhydroquinone option for skin lightening. In one study, 20% azelaic acid was used twice daily in 155 patients with facial melasma. Of these, 73% showed improvement after 6 months of therapy. Side effects were minimal and included erythema, pruritus, and burning.
Another option is topically compounded methimazole, a potent peroxidase inhibitor that causes morphologic change in melanocytes. “You can get it compounded as a 5% cream,” he said of the antithyroid agent. “It’s not that expensive, and even high concentrations are not melanocytotoxic. There’s minimal systemic absorption because the molecule is large, so there really is not any effect on TSH [thyroid-stimulating hormone] or T4 levels.”
Kojic acid dipalmitate, an antibiotic produced by many species of Aspergillus and Penicillium, can also be used as a second-line melasma treatment. Unlike kojic acid, kojic acid dipalmitate is more stable to light, heat, pH, and oxidation, and is also compatible with most organic sunscreens. It works by inhibiting tyrosinase. “It’s already available overseas and will soon be available in the U.S. as a derivative of kojic acid,” he said.
There is also vitamin C serum, which reduces tyrosinase activity via an antioxidant effect. “When you combine it with azelaic acid or sunscreen, vitamin C helps to augment the response,” Dr. Desai said. In one study that compared 5% ascorbic acid with 4% hydroquinone, 62.5% vs. 93% of patients improved, respectively, but side effects were more prominent in those who received 4% hydroquinone (68.7% vs. 6.2%).
An additional off-label option for melasma is oral tranexamic acid, which controls pigmentation by inhibiting the release of inflammatory mediators, specifically prostaglandins and arachidonic acid, which are involved in melanogenesis.
Dr. Desai often uses a dose of 325 mg twice daily. “Think of tranexamic acid as an anti-inflammatory,” he said. Tranexamic acid is contraindicated in patients who are currently taking or have previously taken anticoagulant medications; those who are pregnant or breastfeeding, or are smokers; and in those with renal, cardiac, and/or pulmonary disease. It has a half-life of about 7.5 hours, so the twice daily dosing “is quite effective,” he said.
“Do I leave my patients on this for years at a time to see if it’s going to work? No. When this works in treating melasma it works very quickly. I tell patients they’re going to see results in the first 8-12 weeks. That’s the beauty of using this orally.”
Another emerging therapy is Rubus occidentalis (black raspberry), a botanical-based ingredient in a 3% topical suspension that was compared with 4% hydroquinone in a randomized placebo-controlled trial. In the study, efficacy of Rubus occidentalis was considered comparable to that of hydroquinone. “This not only blocks melanogenesis, it also helps to block melanosome transfer,” said Dr. Desai, who is a past president of the Skin of Color Society.
Another natural option for melasma patients is topical cysteamine, which is the simplest aminothiol physiologically produced in human cells from the essential amino acid cysteine. “This is great for patients with recalcitrant disease, or for patients who, after 12-16 weeks of hydroquinone, you want them to have a break. I use it as a 5% concentration, and it works nicely,” he said. Cysteamine is also highly concentrated in human milk.
Dr. Desai disclosed that he performs clinical trials and consulting for many companies including L’Oréal, Galderma, Allergan, and AbbVie.
BOSTON – In the opinion of Seemal R. Desai, MD, dermatologists are obligated to tell their patients with melasma that their condition is a chronic disease with no cure.
“We have to set expectations upfront, because you all know the history,” Dr. Desai, founder and medical director of Innovative Dermatology in Dallas, said at the annual meeting of the American Academy of Dermatology. “You get someone better, their melasma gets lighter, and then they’re lost to follow-up for a year. Then they’re back to your office after that beach vacation because their melasma has come back with a vengeance because they were out in the sun too much. We have to tell our patients that melasma therapy is a journey of skin lightening but it’s not going to be a one-stop shop of getting it completely cured.”
As for treatment of melasma, “hydroquinone is still our workhorse, our gold standard.” Dr. Desai said. “I tell patients, ‘I’m going to keep you on it for 16 weeks. Then you’re going to come back. I’m going to see where you are, and we’ll move into the nonhydroquinone therapies once your disease is under control.’ ”
However, new therapies for melasma are needed because long-term use of hydroquinone can lead to complications such as ochronosis, nail discoloration, conjunctival melanosis, and corneal degeneration.
Emerging treatments
. Dr. Desai described azelaic acid as his “go to” nonhydroquinone option for skin lightening. In one study, 20% azelaic acid was used twice daily in 155 patients with facial melasma. Of these, 73% showed improvement after 6 months of therapy. Side effects were minimal and included erythema, pruritus, and burning.
Another option is topically compounded methimazole, a potent peroxidase inhibitor that causes morphologic change in melanocytes. “You can get it compounded as a 5% cream,” he said of the antithyroid agent. “It’s not that expensive, and even high concentrations are not melanocytotoxic. There’s minimal systemic absorption because the molecule is large, so there really is not any effect on TSH [thyroid-stimulating hormone] or T4 levels.”
Kojic acid dipalmitate, an antibiotic produced by many species of Aspergillus and Penicillium, can also be used as a second-line melasma treatment. Unlike kojic acid, kojic acid dipalmitate is more stable to light, heat, pH, and oxidation, and is also compatible with most organic sunscreens. It works by inhibiting tyrosinase. “It’s already available overseas and will soon be available in the U.S. as a derivative of kojic acid,” he said.
There is also vitamin C serum, which reduces tyrosinase activity via an antioxidant effect. “When you combine it with azelaic acid or sunscreen, vitamin C helps to augment the response,” Dr. Desai said. In one study that compared 5% ascorbic acid with 4% hydroquinone, 62.5% vs. 93% of patients improved, respectively, but side effects were more prominent in those who received 4% hydroquinone (68.7% vs. 6.2%).
An additional off-label option for melasma is oral tranexamic acid, which controls pigmentation by inhibiting the release of inflammatory mediators, specifically prostaglandins and arachidonic acid, which are involved in melanogenesis.
Dr. Desai often uses a dose of 325 mg twice daily. “Think of tranexamic acid as an anti-inflammatory,” he said. Tranexamic acid is contraindicated in patients who are currently taking or have previously taken anticoagulant medications; those who are pregnant or breastfeeding, or are smokers; and in those with renal, cardiac, and/or pulmonary disease. It has a half-life of about 7.5 hours, so the twice daily dosing “is quite effective,” he said.
“Do I leave my patients on this for years at a time to see if it’s going to work? No. When this works in treating melasma it works very quickly. I tell patients they’re going to see results in the first 8-12 weeks. That’s the beauty of using this orally.”
Another emerging therapy is Rubus occidentalis (black raspberry), a botanical-based ingredient in a 3% topical suspension that was compared with 4% hydroquinone in a randomized placebo-controlled trial. In the study, efficacy of Rubus occidentalis was considered comparable to that of hydroquinone. “This not only blocks melanogenesis, it also helps to block melanosome transfer,” said Dr. Desai, who is a past president of the Skin of Color Society.
Another natural option for melasma patients is topical cysteamine, which is the simplest aminothiol physiologically produced in human cells from the essential amino acid cysteine. “This is great for patients with recalcitrant disease, or for patients who, after 12-16 weeks of hydroquinone, you want them to have a break. I use it as a 5% concentration, and it works nicely,” he said. Cysteamine is also highly concentrated in human milk.
Dr. Desai disclosed that he performs clinical trials and consulting for many companies including L’Oréal, Galderma, Allergan, and AbbVie.
BOSTON – In the opinion of Seemal R. Desai, MD, dermatologists are obligated to tell their patients with melasma that their condition is a chronic disease with no cure.
“We have to set expectations upfront, because you all know the history,” Dr. Desai, founder and medical director of Innovative Dermatology in Dallas, said at the annual meeting of the American Academy of Dermatology. “You get someone better, their melasma gets lighter, and then they’re lost to follow-up for a year. Then they’re back to your office after that beach vacation because their melasma has come back with a vengeance because they were out in the sun too much. We have to tell our patients that melasma therapy is a journey of skin lightening but it’s not going to be a one-stop shop of getting it completely cured.”
As for treatment of melasma, “hydroquinone is still our workhorse, our gold standard.” Dr. Desai said. “I tell patients, ‘I’m going to keep you on it for 16 weeks. Then you’re going to come back. I’m going to see where you are, and we’ll move into the nonhydroquinone therapies once your disease is under control.’ ”
However, new therapies for melasma are needed because long-term use of hydroquinone can lead to complications such as ochronosis, nail discoloration, conjunctival melanosis, and corneal degeneration.
Emerging treatments
. Dr. Desai described azelaic acid as his “go to” nonhydroquinone option for skin lightening. In one study, 20% azelaic acid was used twice daily in 155 patients with facial melasma. Of these, 73% showed improvement after 6 months of therapy. Side effects were minimal and included erythema, pruritus, and burning.
Another option is topically compounded methimazole, a potent peroxidase inhibitor that causes morphologic change in melanocytes. “You can get it compounded as a 5% cream,” he said of the antithyroid agent. “It’s not that expensive, and even high concentrations are not melanocytotoxic. There’s minimal systemic absorption because the molecule is large, so there really is not any effect on TSH [thyroid-stimulating hormone] or T4 levels.”
Kojic acid dipalmitate, an antibiotic produced by many species of Aspergillus and Penicillium, can also be used as a second-line melasma treatment. Unlike kojic acid, kojic acid dipalmitate is more stable to light, heat, pH, and oxidation, and is also compatible with most organic sunscreens. It works by inhibiting tyrosinase. “It’s already available overseas and will soon be available in the U.S. as a derivative of kojic acid,” he said.
There is also vitamin C serum, which reduces tyrosinase activity via an antioxidant effect. “When you combine it with azelaic acid or sunscreen, vitamin C helps to augment the response,” Dr. Desai said. In one study that compared 5% ascorbic acid with 4% hydroquinone, 62.5% vs. 93% of patients improved, respectively, but side effects were more prominent in those who received 4% hydroquinone (68.7% vs. 6.2%).
An additional off-label option for melasma is oral tranexamic acid, which controls pigmentation by inhibiting the release of inflammatory mediators, specifically prostaglandins and arachidonic acid, which are involved in melanogenesis.
Dr. Desai often uses a dose of 325 mg twice daily. “Think of tranexamic acid as an anti-inflammatory,” he said. Tranexamic acid is contraindicated in patients who are currently taking or have previously taken anticoagulant medications; those who are pregnant or breastfeeding, or are smokers; and in those with renal, cardiac, and/or pulmonary disease. It has a half-life of about 7.5 hours, so the twice daily dosing “is quite effective,” he said.
“Do I leave my patients on this for years at a time to see if it’s going to work? No. When this works in treating melasma it works very quickly. I tell patients they’re going to see results in the first 8-12 weeks. That’s the beauty of using this orally.”
Another emerging therapy is Rubus occidentalis (black raspberry), a botanical-based ingredient in a 3% topical suspension that was compared with 4% hydroquinone in a randomized placebo-controlled trial. In the study, efficacy of Rubus occidentalis was considered comparable to that of hydroquinone. “This not only blocks melanogenesis, it also helps to block melanosome transfer,” said Dr. Desai, who is a past president of the Skin of Color Society.
Another natural option for melasma patients is topical cysteamine, which is the simplest aminothiol physiologically produced in human cells from the essential amino acid cysteine. “This is great for patients with recalcitrant disease, or for patients who, after 12-16 weeks of hydroquinone, you want them to have a break. I use it as a 5% concentration, and it works nicely,” he said. Cysteamine is also highly concentrated in human milk.
Dr. Desai disclosed that he performs clinical trials and consulting for many companies including L’Oréal, Galderma, Allergan, and AbbVie.
AT AAD 2022
Older adults with schizophrenia need ‘person-centered’ care
For example, individuals in a group characterized by substance use disorders (SUDs) had a depression prevalence of about 60% and relatively high death rates from unintentional injury and hepatitis.
“The health care needs of older adults with schizophrenia can vary widely, so aging persons with schizophrenia can’t be considered a uniform population,” study investigator Alison Hwong, MD, PhD, University of California, San Francisco, National Clinicians Scholars Program and San Francisco Veterans Affairs, told this news organization.
“For patients with multiple chronic conditions, we need to be proactive in coordinating specialty care. At the same time, we need novel models of person-centered care to help aging adults with schizophrenia live longer, healthier lives,” Dr. Hwong added.
The findings were presented as part of the American Association for Geriatric Psychiatry annual meeting.
Widening mortality gap
The life expectancy of patients with schizophrenia is lower by 8-15 years, compared with those without schizophrenia and this “mortality gap” has widened in recent years, Dr. Hwong noted. Those with schizophrenia also have high rates of health care utilization and high direct and indirect health care costs.
Most previous research looking at illness in schizophrenia focused on a single medical condition, “but by midlife, adults with schizophrenia may have multiple medical conditions,” said Dr. Hwong. “Little is known about multimorbidity in aging adults with schizophrenia and how that could be related to mortality outcomes.”
The study included 82,858 U.S. veterans aged 50 years and older who had at least one inpatient or two outpatient encounters associated with a diagnosis of schizophrenia in the previous 2 years. The study period ran from 2012 to 2018.
Using health care records and data linkages, researchers examined 20 common medical and psychiatric conditions other than schizophrenia that required medical attention. The investigators used the “latent class analysis” statistical model to assess differences across classes.
The study included three distinct patient classes: minimal morbidity (43% of the cohort), depression and medical comorbidity (34.2%), and SUDs and related conditions (22.8%).
The SUD group tended to be younger, with a mean age of 57.9 years versus 60.4 years for the minimal comorbidity group and 65.9 years for the depression group.
The SUD group was also less likely to be female (4.8% vs. 6.7% and 6%, respectively), less likely to be White, and more likely to be Black. This group was also less likely to be married and more likely to have a history of homelessness.
Disease prevalence rates
Results showed the minimal morbidity group had prevalence rates of less than 10% for all major conditions, except for tobacco dependence, which had a rate of 11.8%.
The depression and medical comorbidity group had very high prevalence rates (more than 20%) for heart attack, heart failure, stroke, cancer, dementia, arthritis, renal disease, sleep disorders, depression, and tobacco dependence. In addition, the rate was 60% for chronic obstructive pulmonary disease.
Participants in the SUD and related conditions group had rates of more than 70% for alcohol use disorder, other drug use disorders, and tobacco dependence. They also had high rates of COPD, hepatitis C, chronic pain, sleep disorders, depression, and PTSD.
On average, the SUD group was younger and may explain why they were less likely to have heart failure and renal disease, Dr. Hwong noted. These results may help inform treatment approaches, she added.
“For the group with largely substance use–related conditions, perhaps we can better address their needs with, for example, specific addiction and infectious disease services instead of a one-size-fits-all model,” said Dr. Hwong.
The investigators also examined mortality rates. Those in the depression and morbidity group had the highest rate of overall mortality; 47.5% of this class died during the observation period, compared with 27.2% of the SUD group.
More research is needed to understand why the mortality rate is so high in the depression and morbidity group, she said.
High rates of accidental death
The SUD group had the highest rates of death from accidents, possibly from overdoses, suicide, hepatitis C, and alcohol use–related deaths. “Their risks are very specific and appear largely related to substance use,” Dr. Hwong said.
The minimal comorbidity group showed the lowest rates of overall mortality rate (18%) and of cause-specific mortality for most of the included conditions.
Dr. Hwong noted she would like to study this class further. “I’m interested to know who are the people with schizophrenia who are thriving and are successfully aging – to learn what is going well for them.”
The researchers also plan to examine the subgroups in more detail to understand differences in treatments, health care utilization, and outcomes across groups. They are also interested in assessing other predictors of mortality outcomes in addition to multimorbidity.
One limitation of the study is that its cohort consisted of male veterans, so the findings may not be generalizable to other populations. In addition, these were observational data and so the results do not imply causality, Dr. Hwong said.
Dr. Hwong reported no relevant financial relationships, but she is supported by the VA and the UCSF National Clinician Scholars Program.
A version of this article first appeared on Medscape.com.
For example, individuals in a group characterized by substance use disorders (SUDs) had a depression prevalence of about 60% and relatively high death rates from unintentional injury and hepatitis.
“The health care needs of older adults with schizophrenia can vary widely, so aging persons with schizophrenia can’t be considered a uniform population,” study investigator Alison Hwong, MD, PhD, University of California, San Francisco, National Clinicians Scholars Program and San Francisco Veterans Affairs, told this news organization.
“For patients with multiple chronic conditions, we need to be proactive in coordinating specialty care. At the same time, we need novel models of person-centered care to help aging adults with schizophrenia live longer, healthier lives,” Dr. Hwong added.
The findings were presented as part of the American Association for Geriatric Psychiatry annual meeting.
Widening mortality gap
The life expectancy of patients with schizophrenia is lower by 8-15 years, compared with those without schizophrenia and this “mortality gap” has widened in recent years, Dr. Hwong noted. Those with schizophrenia also have high rates of health care utilization and high direct and indirect health care costs.
Most previous research looking at illness in schizophrenia focused on a single medical condition, “but by midlife, adults with schizophrenia may have multiple medical conditions,” said Dr. Hwong. “Little is known about multimorbidity in aging adults with schizophrenia and how that could be related to mortality outcomes.”
The study included 82,858 U.S. veterans aged 50 years and older who had at least one inpatient or two outpatient encounters associated with a diagnosis of schizophrenia in the previous 2 years. The study period ran from 2012 to 2018.
Using health care records and data linkages, researchers examined 20 common medical and psychiatric conditions other than schizophrenia that required medical attention. The investigators used the “latent class analysis” statistical model to assess differences across classes.
The study included three distinct patient classes: minimal morbidity (43% of the cohort), depression and medical comorbidity (34.2%), and SUDs and related conditions (22.8%).
The SUD group tended to be younger, with a mean age of 57.9 years versus 60.4 years for the minimal comorbidity group and 65.9 years for the depression group.
The SUD group was also less likely to be female (4.8% vs. 6.7% and 6%, respectively), less likely to be White, and more likely to be Black. This group was also less likely to be married and more likely to have a history of homelessness.
Disease prevalence rates
Results showed the minimal morbidity group had prevalence rates of less than 10% for all major conditions, except for tobacco dependence, which had a rate of 11.8%.
The depression and medical comorbidity group had very high prevalence rates (more than 20%) for heart attack, heart failure, stroke, cancer, dementia, arthritis, renal disease, sleep disorders, depression, and tobacco dependence. In addition, the rate was 60% for chronic obstructive pulmonary disease.
Participants in the SUD and related conditions group had rates of more than 70% for alcohol use disorder, other drug use disorders, and tobacco dependence. They also had high rates of COPD, hepatitis C, chronic pain, sleep disorders, depression, and PTSD.
On average, the SUD group was younger and may explain why they were less likely to have heart failure and renal disease, Dr. Hwong noted. These results may help inform treatment approaches, she added.
“For the group with largely substance use–related conditions, perhaps we can better address their needs with, for example, specific addiction and infectious disease services instead of a one-size-fits-all model,” said Dr. Hwong.
The investigators also examined mortality rates. Those in the depression and morbidity group had the highest rate of overall mortality; 47.5% of this class died during the observation period, compared with 27.2% of the SUD group.
More research is needed to understand why the mortality rate is so high in the depression and morbidity group, she said.
High rates of accidental death
The SUD group had the highest rates of death from accidents, possibly from overdoses, suicide, hepatitis C, and alcohol use–related deaths. “Their risks are very specific and appear largely related to substance use,” Dr. Hwong said.
The minimal comorbidity group showed the lowest rates of overall mortality rate (18%) and of cause-specific mortality for most of the included conditions.
Dr. Hwong noted she would like to study this class further. “I’m interested to know who are the people with schizophrenia who are thriving and are successfully aging – to learn what is going well for them.”
The researchers also plan to examine the subgroups in more detail to understand differences in treatments, health care utilization, and outcomes across groups. They are also interested in assessing other predictors of mortality outcomes in addition to multimorbidity.
One limitation of the study is that its cohort consisted of male veterans, so the findings may not be generalizable to other populations. In addition, these were observational data and so the results do not imply causality, Dr. Hwong said.
Dr. Hwong reported no relevant financial relationships, but she is supported by the VA and the UCSF National Clinician Scholars Program.
A version of this article first appeared on Medscape.com.
For example, individuals in a group characterized by substance use disorders (SUDs) had a depression prevalence of about 60% and relatively high death rates from unintentional injury and hepatitis.
“The health care needs of older adults with schizophrenia can vary widely, so aging persons with schizophrenia can’t be considered a uniform population,” study investigator Alison Hwong, MD, PhD, University of California, San Francisco, National Clinicians Scholars Program and San Francisco Veterans Affairs, told this news organization.
“For patients with multiple chronic conditions, we need to be proactive in coordinating specialty care. At the same time, we need novel models of person-centered care to help aging adults with schizophrenia live longer, healthier lives,” Dr. Hwong added.
The findings were presented as part of the American Association for Geriatric Psychiatry annual meeting.
Widening mortality gap
The life expectancy of patients with schizophrenia is lower by 8-15 years, compared with those without schizophrenia and this “mortality gap” has widened in recent years, Dr. Hwong noted. Those with schizophrenia also have high rates of health care utilization and high direct and indirect health care costs.
Most previous research looking at illness in schizophrenia focused on a single medical condition, “but by midlife, adults with schizophrenia may have multiple medical conditions,” said Dr. Hwong. “Little is known about multimorbidity in aging adults with schizophrenia and how that could be related to mortality outcomes.”
The study included 82,858 U.S. veterans aged 50 years and older who had at least one inpatient or two outpatient encounters associated with a diagnosis of schizophrenia in the previous 2 years. The study period ran from 2012 to 2018.
Using health care records and data linkages, researchers examined 20 common medical and psychiatric conditions other than schizophrenia that required medical attention. The investigators used the “latent class analysis” statistical model to assess differences across classes.
The study included three distinct patient classes: minimal morbidity (43% of the cohort), depression and medical comorbidity (34.2%), and SUDs and related conditions (22.8%).
The SUD group tended to be younger, with a mean age of 57.9 years versus 60.4 years for the minimal comorbidity group and 65.9 years for the depression group.
The SUD group was also less likely to be female (4.8% vs. 6.7% and 6%, respectively), less likely to be White, and more likely to be Black. This group was also less likely to be married and more likely to have a history of homelessness.
Disease prevalence rates
Results showed the minimal morbidity group had prevalence rates of less than 10% for all major conditions, except for tobacco dependence, which had a rate of 11.8%.
The depression and medical comorbidity group had very high prevalence rates (more than 20%) for heart attack, heart failure, stroke, cancer, dementia, arthritis, renal disease, sleep disorders, depression, and tobacco dependence. In addition, the rate was 60% for chronic obstructive pulmonary disease.
Participants in the SUD and related conditions group had rates of more than 70% for alcohol use disorder, other drug use disorders, and tobacco dependence. They also had high rates of COPD, hepatitis C, chronic pain, sleep disorders, depression, and PTSD.
On average, the SUD group was younger and may explain why they were less likely to have heart failure and renal disease, Dr. Hwong noted. These results may help inform treatment approaches, she added.
“For the group with largely substance use–related conditions, perhaps we can better address their needs with, for example, specific addiction and infectious disease services instead of a one-size-fits-all model,” said Dr. Hwong.
The investigators also examined mortality rates. Those in the depression and morbidity group had the highest rate of overall mortality; 47.5% of this class died during the observation period, compared with 27.2% of the SUD group.
More research is needed to understand why the mortality rate is so high in the depression and morbidity group, she said.
High rates of accidental death
The SUD group had the highest rates of death from accidents, possibly from overdoses, suicide, hepatitis C, and alcohol use–related deaths. “Their risks are very specific and appear largely related to substance use,” Dr. Hwong said.
The minimal comorbidity group showed the lowest rates of overall mortality rate (18%) and of cause-specific mortality for most of the included conditions.
Dr. Hwong noted she would like to study this class further. “I’m interested to know who are the people with schizophrenia who are thriving and are successfully aging – to learn what is going well for them.”
The researchers also plan to examine the subgroups in more detail to understand differences in treatments, health care utilization, and outcomes across groups. They are also interested in assessing other predictors of mortality outcomes in addition to multimorbidity.
One limitation of the study is that its cohort consisted of male veterans, so the findings may not be generalizable to other populations. In addition, these were observational data and so the results do not imply causality, Dr. Hwong said.
Dr. Hwong reported no relevant financial relationships, but she is supported by the VA and the UCSF National Clinician Scholars Program.
A version of this article first appeared on Medscape.com.
FROM AAGP 2022
Shoulder arthritis surgery: Depression complicates care
CHICAGO – new data show.
The abstract was presented at the annual meeting of the American Academy of Orthopedic Surgeons.
Researchers, led by Keith Diamond, MD, an orthopedic surgeon at Maimonides Medical Center in New York, queried a private payer database looking for patients who had primary RSA for treatment of glenohumeral OA and also had a diagnosis of depressive disorder (DD) from 2010 to 2019. Patients without DD served as the controls.
After the randomized matching with controls at a 1:5 ratio, the study consisted of 28,410 patients: 4,084 in the DD group and 24,326 in the control group.
Researchers found that patients with depression had longer hospital stays (3 vs. 2 days, P = .0007). They also had higher frequency and odds of developing side effects within the period of care (47.4% vs. 14.7%; odds ratio, 2.27; 95% CI, 2.10-2.45, P < .0001).
Patients with depression also had significantly higher rates of medical complications surrounding the surgery and costs were higher ($19,363 vs. $17,927, P < .0001).
Pneumonia rates were much higher in patients with DD (10% vs. 1.8%; OR, 2.88; P < .0001).
Patients with depression had higher odds of cerebrovascular accident (3.1% vs. 0.7%; OR, 2.69, P < .0001); myocardial infarctions (2% vs. 0.4%; OR, 2.54; P < .0001); acute kidney injuries (11.1% vs. 2.3%; OR, 2.11, P < .0001); surgical site infections (4.4% vs. 2.4%; OR, 1.52, P < .0001); and other complications, the authors wrote.
Dr. Diamond said in an interview that there may be a few potential reasons for the associations.
In regard to the strong association with pneumonia, Dr. Diamond hypothesized, “patients with depression can be shown to have lower respiratory drive. If a patient isn’t motivated to get out of bed, that can lead to decreased inflation of the lungs.”
Acute kidney injury could be linked with depression-related lack of self-care in properly hydrating, he said. Surgical site infections could come from suboptimal hygiene related to managing the cast after surgery, which may be more difficult when patients also struggle with depression.
Asked to comment on Dr. Diamond’s study, Grant Garrigues, MD, an associate professor at Rush University Medical Center, Chicago, and director of upper extremity research, told this news organization the study helps confirm known associations between depression and arthritis.
“We know that people with depression and anxiety feel pain differently,” he said. “It might have to do with your outlook – are you catastrophizing or thinking it’s a minor inconvenience? It’s not that it’s just in your head – you physically feel it differently. That is something we’re certainly attuned to. We want to make sure the mental health part of the picture is optimized as much as possible.”
He added that there is increasing evidence of links between depression and the development of arthritis.
“I’m not saying that everyone with arthritis has depression, but with arthritis being multifactorial, there’s a relatively high incidence of symptomatic arthritis in patients with depression,” Dr. Garrigues said.
“We think it may have something to do with the fight-or-flight hormones in your body that may be revved up if you are living in a stressful environment or are living with a mental health problem. Those will actually change – on a cellular and biochemical basis – some of the things that affect arthritis.”
Stronger emphasis on mental health
Dr. Diamond said the field needs more emphasis on perioperative state of mind.
“As orthopedic surgeons, we are preoccupied with the mechanical, the structural aspects of health care as we try to fix bones, ligaments, and tendons. But I think we need to recognize and explore the connection between the psychiatric and psychological health with our musculoskeletal health.”
He noted that, in the preoperative setting, providers look for hypertension, diabetes, smoking status, and other conditions that could complicate surgical outcomes and said mental health should be a factor in whether a surgery proceeds.
“If someone’s diabetes isn’t controlled you can delay an elective case until their [hemoglobin] A1c is under the recommended limit and you get clearance from their primary care doctor. I think that’s something that should be applied to patients with depressive disorders,” Dr. Diamond said.
This study did not distinguish between patients who were being treated for depression at the time of surgery and those not on treatment. More study related to whether treatment affects depression’s association with RSA outcomes is needed, Dr. Diamond added.
Dr. Garrigues said he talks candidly with patients considering surgery about how they are managing their mental health struggles.
“If they say they haven’t seen their psychiatrist or are off their medications, that’s a nonstarter,” he said.
“Anything outside of the surgery you can optimize, whether it’s mental health, medical, social situations – you want to have all your ducks in a row before you dive into surgery,” Dr. Garrigues said.
He added that patients’ mental health status may even affect the venue for the patient – whether outpatient or inpatient, where they can get more supervision and help in making transitions after surgery.
Dr. Diamond and coauthors and Dr. Garrigues disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – new data show.
The abstract was presented at the annual meeting of the American Academy of Orthopedic Surgeons.
Researchers, led by Keith Diamond, MD, an orthopedic surgeon at Maimonides Medical Center in New York, queried a private payer database looking for patients who had primary RSA for treatment of glenohumeral OA and also had a diagnosis of depressive disorder (DD) from 2010 to 2019. Patients without DD served as the controls.
After the randomized matching with controls at a 1:5 ratio, the study consisted of 28,410 patients: 4,084 in the DD group and 24,326 in the control group.
Researchers found that patients with depression had longer hospital stays (3 vs. 2 days, P = .0007). They also had higher frequency and odds of developing side effects within the period of care (47.4% vs. 14.7%; odds ratio, 2.27; 95% CI, 2.10-2.45, P < .0001).
Patients with depression also had significantly higher rates of medical complications surrounding the surgery and costs were higher ($19,363 vs. $17,927, P < .0001).
Pneumonia rates were much higher in patients with DD (10% vs. 1.8%; OR, 2.88; P < .0001).
Patients with depression had higher odds of cerebrovascular accident (3.1% vs. 0.7%; OR, 2.69, P < .0001); myocardial infarctions (2% vs. 0.4%; OR, 2.54; P < .0001); acute kidney injuries (11.1% vs. 2.3%; OR, 2.11, P < .0001); surgical site infections (4.4% vs. 2.4%; OR, 1.52, P < .0001); and other complications, the authors wrote.
Dr. Diamond said in an interview that there may be a few potential reasons for the associations.
In regard to the strong association with pneumonia, Dr. Diamond hypothesized, “patients with depression can be shown to have lower respiratory drive. If a patient isn’t motivated to get out of bed, that can lead to decreased inflation of the lungs.”
Acute kidney injury could be linked with depression-related lack of self-care in properly hydrating, he said. Surgical site infections could come from suboptimal hygiene related to managing the cast after surgery, which may be more difficult when patients also struggle with depression.
Asked to comment on Dr. Diamond’s study, Grant Garrigues, MD, an associate professor at Rush University Medical Center, Chicago, and director of upper extremity research, told this news organization the study helps confirm known associations between depression and arthritis.
“We know that people with depression and anxiety feel pain differently,” he said. “It might have to do with your outlook – are you catastrophizing or thinking it’s a minor inconvenience? It’s not that it’s just in your head – you physically feel it differently. That is something we’re certainly attuned to. We want to make sure the mental health part of the picture is optimized as much as possible.”
He added that there is increasing evidence of links between depression and the development of arthritis.
“I’m not saying that everyone with arthritis has depression, but with arthritis being multifactorial, there’s a relatively high incidence of symptomatic arthritis in patients with depression,” Dr. Garrigues said.
“We think it may have something to do with the fight-or-flight hormones in your body that may be revved up if you are living in a stressful environment or are living with a mental health problem. Those will actually change – on a cellular and biochemical basis – some of the things that affect arthritis.”
Stronger emphasis on mental health
Dr. Diamond said the field needs more emphasis on perioperative state of mind.
“As orthopedic surgeons, we are preoccupied with the mechanical, the structural aspects of health care as we try to fix bones, ligaments, and tendons. But I think we need to recognize and explore the connection between the psychiatric and psychological health with our musculoskeletal health.”
He noted that, in the preoperative setting, providers look for hypertension, diabetes, smoking status, and other conditions that could complicate surgical outcomes and said mental health should be a factor in whether a surgery proceeds.
“If someone’s diabetes isn’t controlled you can delay an elective case until their [hemoglobin] A1c is under the recommended limit and you get clearance from their primary care doctor. I think that’s something that should be applied to patients with depressive disorders,” Dr. Diamond said.
This study did not distinguish between patients who were being treated for depression at the time of surgery and those not on treatment. More study related to whether treatment affects depression’s association with RSA outcomes is needed, Dr. Diamond added.
Dr. Garrigues said he talks candidly with patients considering surgery about how they are managing their mental health struggles.
“If they say they haven’t seen their psychiatrist or are off their medications, that’s a nonstarter,” he said.
“Anything outside of the surgery you can optimize, whether it’s mental health, medical, social situations – you want to have all your ducks in a row before you dive into surgery,” Dr. Garrigues said.
He added that patients’ mental health status may even affect the venue for the patient – whether outpatient or inpatient, where they can get more supervision and help in making transitions after surgery.
Dr. Diamond and coauthors and Dr. Garrigues disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – new data show.
The abstract was presented at the annual meeting of the American Academy of Orthopedic Surgeons.
Researchers, led by Keith Diamond, MD, an orthopedic surgeon at Maimonides Medical Center in New York, queried a private payer database looking for patients who had primary RSA for treatment of glenohumeral OA and also had a diagnosis of depressive disorder (DD) from 2010 to 2019. Patients without DD served as the controls.
After the randomized matching with controls at a 1:5 ratio, the study consisted of 28,410 patients: 4,084 in the DD group and 24,326 in the control group.
Researchers found that patients with depression had longer hospital stays (3 vs. 2 days, P = .0007). They also had higher frequency and odds of developing side effects within the period of care (47.4% vs. 14.7%; odds ratio, 2.27; 95% CI, 2.10-2.45, P < .0001).
Patients with depression also had significantly higher rates of medical complications surrounding the surgery and costs were higher ($19,363 vs. $17,927, P < .0001).
Pneumonia rates were much higher in patients with DD (10% vs. 1.8%; OR, 2.88; P < .0001).
Patients with depression had higher odds of cerebrovascular accident (3.1% vs. 0.7%; OR, 2.69, P < .0001); myocardial infarctions (2% vs. 0.4%; OR, 2.54; P < .0001); acute kidney injuries (11.1% vs. 2.3%; OR, 2.11, P < .0001); surgical site infections (4.4% vs. 2.4%; OR, 1.52, P < .0001); and other complications, the authors wrote.
Dr. Diamond said in an interview that there may be a few potential reasons for the associations.
In regard to the strong association with pneumonia, Dr. Diamond hypothesized, “patients with depression can be shown to have lower respiratory drive. If a patient isn’t motivated to get out of bed, that can lead to decreased inflation of the lungs.”
Acute kidney injury could be linked with depression-related lack of self-care in properly hydrating, he said. Surgical site infections could come from suboptimal hygiene related to managing the cast after surgery, which may be more difficult when patients also struggle with depression.
Asked to comment on Dr. Diamond’s study, Grant Garrigues, MD, an associate professor at Rush University Medical Center, Chicago, and director of upper extremity research, told this news organization the study helps confirm known associations between depression and arthritis.
“We know that people with depression and anxiety feel pain differently,” he said. “It might have to do with your outlook – are you catastrophizing or thinking it’s a minor inconvenience? It’s not that it’s just in your head – you physically feel it differently. That is something we’re certainly attuned to. We want to make sure the mental health part of the picture is optimized as much as possible.”
He added that there is increasing evidence of links between depression and the development of arthritis.
“I’m not saying that everyone with arthritis has depression, but with arthritis being multifactorial, there’s a relatively high incidence of symptomatic arthritis in patients with depression,” Dr. Garrigues said.
“We think it may have something to do with the fight-or-flight hormones in your body that may be revved up if you are living in a stressful environment or are living with a mental health problem. Those will actually change – on a cellular and biochemical basis – some of the things that affect arthritis.”
Stronger emphasis on mental health
Dr. Diamond said the field needs more emphasis on perioperative state of mind.
“As orthopedic surgeons, we are preoccupied with the mechanical, the structural aspects of health care as we try to fix bones, ligaments, and tendons. But I think we need to recognize and explore the connection between the psychiatric and psychological health with our musculoskeletal health.”
He noted that, in the preoperative setting, providers look for hypertension, diabetes, smoking status, and other conditions that could complicate surgical outcomes and said mental health should be a factor in whether a surgery proceeds.
“If someone’s diabetes isn’t controlled you can delay an elective case until their [hemoglobin] A1c is under the recommended limit and you get clearance from their primary care doctor. I think that’s something that should be applied to patients with depressive disorders,” Dr. Diamond said.
This study did not distinguish between patients who were being treated for depression at the time of surgery and those not on treatment. More study related to whether treatment affects depression’s association with RSA outcomes is needed, Dr. Diamond added.
Dr. Garrigues said he talks candidly with patients considering surgery about how they are managing their mental health struggles.
“If they say they haven’t seen their psychiatrist or are off their medications, that’s a nonstarter,” he said.
“Anything outside of the surgery you can optimize, whether it’s mental health, medical, social situations – you want to have all your ducks in a row before you dive into surgery,” Dr. Garrigues said.
He added that patients’ mental health status may even affect the venue for the patient – whether outpatient or inpatient, where they can get more supervision and help in making transitions after surgery.
Dr. Diamond and coauthors and Dr. Garrigues disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT AAOS 2022
Surgery groups push back on VARC-3 valve trial definitions
Five international cardiac surgery associations have banded together to address “substantive concerns” regarding the recently updated Valve Academic Research Consortium 3 (VARC-3) clinical endpoint definitions for aortic valve research.
The VARC-3 update was a multidisciplinary effort that included more than a dozen new or modified definitions for use in transcatheter and surgical aortic valve replacement (TAVR/SAVR) clinical trials, but drew criticism last year from surgeons that some of its definitions favor TAVR over surgery and that its writing committee had deep ties to industry and lacked diversity.
The new surgical associations’ position statement calls out five specific VARC-3 definitions – rehospitalization, valve thrombosis, bleeding, myocardial infarction (MI), and left bundle-branch block (LBBB).
The statement was jointly issued by the Society of Thoracic Surgeons (STS), the American Association for Thoracic Surgery, the European Association for Cardio-Thoracic Surgery, the Asian Society for Cardiovascular and Thoracic Surgery, and the Latin American Association of Cardiac and Endovascular Surgery.
It was copublished in Annals of Thoracic Surgery, the Journal of Thoracic and Cardiovascular Surgery, the European Journal of Cardio-Thoracic Surgery, and the Asian Cardiovascular and Thoracic Annals.
“We hope that this message can be seen, even if it’s somewhat difficult to hear sometimes, as positive constructive criticism compared to some of the dialogue that we’ve had on social media,” lead author Patrick O. Myers, MD, Lausanne (Switzerland) University Hospital, said in an interview. “It’s not criticizing people or the process but just trying to make these definitions better to ensure the good design of clinical trials.”
The president of each surgical association recommended representatives to help write the position statement, and once completed over Zoom meetings, it received formal endorsement from each association prior to publication, he said.
Reached for comment, VARC-3 lead author Philippe Généreux, MD, Gagnon Cardiovascular Institute, Morristown (N.J.) Medical Center, said, “I was pleasantly surprised that their comments were actually pretty minor and that most of these comments are really more a reflection, not of the validity of the definitions, but rather their applications.”
He noted that all the potential issues with the definitions were already discussed during the making of VARC-3 and resolved by consensus of more than 50 experts including the STS president at the time, Food and Drug Administration officials, and experts from the community.
“To be quite honest, I’m not sure they have consensus,” Dr. Généreux said. He added that the writing committee welcomes input from anyone, but “we’re not going to change the definitions to please eight individuals if we strongly believe by consensus of experts in the field that this is not the right thing to do.”
Rehospitalizations and valve thrombosis
The surgical associations praise VARC-3 for providing a standardized definition of bioprosthetic valve failure, but say they will not endorse the inclusion of rehospitalization as a component of the primary efficacy composite endpoint along with all-cause mortality, stroke, and quality of life.
They note that rehospitalizations outnumber mortality events, especially in short follow-up trials, and that the superiority of TAVR at 1 year in the PARTNER 3 trial of low-risk patients was driven primarily by more rehospitalizations in the surgical arm, but that this superiority was waning at 2 years of follow-up.
“The first thing we are calling for is that it shouldn’t be part of the primary composite outcome measure,” Dr. Myers said. But if it really has to be included, a 30-day blanking period for rehospitalization “would acknowledge that there’s a greater risk of rehospitalization during the acute phase of recovering from surgery.”
Dr. Généreux said that VARC-3 provides granular details for defining the different types of hospitalizations, but that a 30-day blanking period makes no sense. “If you close your eyes to anything within 30 days because you don’t like it, you’re missing the opportunity to improve your procedure, to improve your treatment, and to characterize precisely what happened with your patient.”
The new document lauds VARC-3’s focus on patient-centered and clinically relevant endpoints but questions the definition of valve thrombosis as a “clinically significant” thrombus. It points out that the incidence of valve thrombosis was significantly higher with TAVR versus SAVR in PARTNER 3 using the older VARC-2 definition, which did not require evidence of clinical sequelae (2.6% vs. 0.7%; P = .02). Under the new definition, however, half of the thrombi would be relabeled as “nothing there,” Dr. Myers said.
“As we’re doing this in younger and younger patients who will survive longer, there is a question of thrombus having an effect on the valve and leading to earlier structural valve deterioration,” he added. “All this is conjecture. We don’t have the data. So mainly what we’re advocating is that all thrombi should be reported.”
MIs, bleeding, and LBBB
The policy statement also criticizes VARC-3’s decision to define periprocedural (type 5) MI using a biomarker-only definition without need of clinical confirmation. Such definitions have been shown to have a very poor prognostic significance in surgical series compared with the Universal Definitions of Myocardial Infarction, Dr. Myers said.
“What’s interesting is that for thrombus and bleeding, they require clinical correlation, but on the perioperative MI they now use a definition that does not require clinical significance, meaning no ECG changes, no regional wall motion abnormalities or things like that,” he observed.
The decision also seems to disregard the EXCEL trial controversy that illustrated how outcomes and a trial’s message can change depending on which definition of periprocedural MI is used.
With regard to bleeding, the surgical associations agree with the VARC-3 recommendation to use different thresholds when bleeding is integrated into a composite endpoint (type 2 or greater for TAVR and types 3 or greater for SAVR) but suggest this important point should be featured in the chapter on bleeding rather than the section on composite endpoints.
The surgical associations say VARC-3 also got it right adding the need for a new permanent pacemaker to the early composite safety endpoint, but that it was a “missed opportunity” not to include new left bundle-branch block in the safety composite, despite recognizing that this may become an important endpoint to consider in the future.
Dr. Myers said that left bundle-branch block could have implications for survival as TAVR moves into lower-risk, younger patients, as some data with 1-year follow-up suggest it has a prognostic impact, even in the higher-risk older patients with more competing risks.
Finally, the surgical associations point out that only two of the 23 VARC-3 authors were practicing cardiac surgeons and say that a more diverse writing group “may help mitigate issues related to the duality of interests.”
Dr. Généreux said that the final author list is not a reflection of the rigorous work done by 11 cardiac surgeons including the two surgeon authors. The VARC-3 writing committee also had a good representation of women, unlike the surgical position statement, which was penned by eight men.
Dr. Myers reported no relevant financial relationships. Coauthors disclosed ties with EACTS, Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, CryoLife, Shockwave, and JenaValve. Dr. Généreux disclosed ties with Abbott Vascular, Abiomed, Boston Scientific, Cardinal Health, Cardiovascular Systems, Edwards Lifesciences, Medtronic, Opsens, Siemens, SoundBite Medical Solutions, Sig.Num, Saranas, Teleflex, Tryton Medical, Pi-Cardia, and Puzzle Medical.
A version of this article first appeared on Medscape.com.
Five international cardiac surgery associations have banded together to address “substantive concerns” regarding the recently updated Valve Academic Research Consortium 3 (VARC-3) clinical endpoint definitions for aortic valve research.
The VARC-3 update was a multidisciplinary effort that included more than a dozen new or modified definitions for use in transcatheter and surgical aortic valve replacement (TAVR/SAVR) clinical trials, but drew criticism last year from surgeons that some of its definitions favor TAVR over surgery and that its writing committee had deep ties to industry and lacked diversity.
The new surgical associations’ position statement calls out five specific VARC-3 definitions – rehospitalization, valve thrombosis, bleeding, myocardial infarction (MI), and left bundle-branch block (LBBB).
The statement was jointly issued by the Society of Thoracic Surgeons (STS), the American Association for Thoracic Surgery, the European Association for Cardio-Thoracic Surgery, the Asian Society for Cardiovascular and Thoracic Surgery, and the Latin American Association of Cardiac and Endovascular Surgery.
It was copublished in Annals of Thoracic Surgery, the Journal of Thoracic and Cardiovascular Surgery, the European Journal of Cardio-Thoracic Surgery, and the Asian Cardiovascular and Thoracic Annals.
“We hope that this message can be seen, even if it’s somewhat difficult to hear sometimes, as positive constructive criticism compared to some of the dialogue that we’ve had on social media,” lead author Patrick O. Myers, MD, Lausanne (Switzerland) University Hospital, said in an interview. “It’s not criticizing people or the process but just trying to make these definitions better to ensure the good design of clinical trials.”
The president of each surgical association recommended representatives to help write the position statement, and once completed over Zoom meetings, it received formal endorsement from each association prior to publication, he said.
Reached for comment, VARC-3 lead author Philippe Généreux, MD, Gagnon Cardiovascular Institute, Morristown (N.J.) Medical Center, said, “I was pleasantly surprised that their comments were actually pretty minor and that most of these comments are really more a reflection, not of the validity of the definitions, but rather their applications.”
He noted that all the potential issues with the definitions were already discussed during the making of VARC-3 and resolved by consensus of more than 50 experts including the STS president at the time, Food and Drug Administration officials, and experts from the community.
“To be quite honest, I’m not sure they have consensus,” Dr. Généreux said. He added that the writing committee welcomes input from anyone, but “we’re not going to change the definitions to please eight individuals if we strongly believe by consensus of experts in the field that this is not the right thing to do.”
Rehospitalizations and valve thrombosis
The surgical associations praise VARC-3 for providing a standardized definition of bioprosthetic valve failure, but say they will not endorse the inclusion of rehospitalization as a component of the primary efficacy composite endpoint along with all-cause mortality, stroke, and quality of life.
They note that rehospitalizations outnumber mortality events, especially in short follow-up trials, and that the superiority of TAVR at 1 year in the PARTNER 3 trial of low-risk patients was driven primarily by more rehospitalizations in the surgical arm, but that this superiority was waning at 2 years of follow-up.
“The first thing we are calling for is that it shouldn’t be part of the primary composite outcome measure,” Dr. Myers said. But if it really has to be included, a 30-day blanking period for rehospitalization “would acknowledge that there’s a greater risk of rehospitalization during the acute phase of recovering from surgery.”
Dr. Généreux said that VARC-3 provides granular details for defining the different types of hospitalizations, but that a 30-day blanking period makes no sense. “If you close your eyes to anything within 30 days because you don’t like it, you’re missing the opportunity to improve your procedure, to improve your treatment, and to characterize precisely what happened with your patient.”
The new document lauds VARC-3’s focus on patient-centered and clinically relevant endpoints but questions the definition of valve thrombosis as a “clinically significant” thrombus. It points out that the incidence of valve thrombosis was significantly higher with TAVR versus SAVR in PARTNER 3 using the older VARC-2 definition, which did not require evidence of clinical sequelae (2.6% vs. 0.7%; P = .02). Under the new definition, however, half of the thrombi would be relabeled as “nothing there,” Dr. Myers said.
“As we’re doing this in younger and younger patients who will survive longer, there is a question of thrombus having an effect on the valve and leading to earlier structural valve deterioration,” he added. “All this is conjecture. We don’t have the data. So mainly what we’re advocating is that all thrombi should be reported.”
MIs, bleeding, and LBBB
The policy statement also criticizes VARC-3’s decision to define periprocedural (type 5) MI using a biomarker-only definition without need of clinical confirmation. Such definitions have been shown to have a very poor prognostic significance in surgical series compared with the Universal Definitions of Myocardial Infarction, Dr. Myers said.
“What’s interesting is that for thrombus and bleeding, they require clinical correlation, but on the perioperative MI they now use a definition that does not require clinical significance, meaning no ECG changes, no regional wall motion abnormalities or things like that,” he observed.
The decision also seems to disregard the EXCEL trial controversy that illustrated how outcomes and a trial’s message can change depending on which definition of periprocedural MI is used.
With regard to bleeding, the surgical associations agree with the VARC-3 recommendation to use different thresholds when bleeding is integrated into a composite endpoint (type 2 or greater for TAVR and types 3 or greater for SAVR) but suggest this important point should be featured in the chapter on bleeding rather than the section on composite endpoints.
The surgical associations say VARC-3 also got it right adding the need for a new permanent pacemaker to the early composite safety endpoint, but that it was a “missed opportunity” not to include new left bundle-branch block in the safety composite, despite recognizing that this may become an important endpoint to consider in the future.
Dr. Myers said that left bundle-branch block could have implications for survival as TAVR moves into lower-risk, younger patients, as some data with 1-year follow-up suggest it has a prognostic impact, even in the higher-risk older patients with more competing risks.
Finally, the surgical associations point out that only two of the 23 VARC-3 authors were practicing cardiac surgeons and say that a more diverse writing group “may help mitigate issues related to the duality of interests.”
Dr. Généreux said that the final author list is not a reflection of the rigorous work done by 11 cardiac surgeons including the two surgeon authors. The VARC-3 writing committee also had a good representation of women, unlike the surgical position statement, which was penned by eight men.
Dr. Myers reported no relevant financial relationships. Coauthors disclosed ties with EACTS, Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, CryoLife, Shockwave, and JenaValve. Dr. Généreux disclosed ties with Abbott Vascular, Abiomed, Boston Scientific, Cardinal Health, Cardiovascular Systems, Edwards Lifesciences, Medtronic, Opsens, Siemens, SoundBite Medical Solutions, Sig.Num, Saranas, Teleflex, Tryton Medical, Pi-Cardia, and Puzzle Medical.
A version of this article first appeared on Medscape.com.
Five international cardiac surgery associations have banded together to address “substantive concerns” regarding the recently updated Valve Academic Research Consortium 3 (VARC-3) clinical endpoint definitions for aortic valve research.
The VARC-3 update was a multidisciplinary effort that included more than a dozen new or modified definitions for use in transcatheter and surgical aortic valve replacement (TAVR/SAVR) clinical trials, but drew criticism last year from surgeons that some of its definitions favor TAVR over surgery and that its writing committee had deep ties to industry and lacked diversity.
The new surgical associations’ position statement calls out five specific VARC-3 definitions – rehospitalization, valve thrombosis, bleeding, myocardial infarction (MI), and left bundle-branch block (LBBB).
The statement was jointly issued by the Society of Thoracic Surgeons (STS), the American Association for Thoracic Surgery, the European Association for Cardio-Thoracic Surgery, the Asian Society for Cardiovascular and Thoracic Surgery, and the Latin American Association of Cardiac and Endovascular Surgery.
It was copublished in Annals of Thoracic Surgery, the Journal of Thoracic and Cardiovascular Surgery, the European Journal of Cardio-Thoracic Surgery, and the Asian Cardiovascular and Thoracic Annals.
“We hope that this message can be seen, even if it’s somewhat difficult to hear sometimes, as positive constructive criticism compared to some of the dialogue that we’ve had on social media,” lead author Patrick O. Myers, MD, Lausanne (Switzerland) University Hospital, said in an interview. “It’s not criticizing people or the process but just trying to make these definitions better to ensure the good design of clinical trials.”
The president of each surgical association recommended representatives to help write the position statement, and once completed over Zoom meetings, it received formal endorsement from each association prior to publication, he said.
Reached for comment, VARC-3 lead author Philippe Généreux, MD, Gagnon Cardiovascular Institute, Morristown (N.J.) Medical Center, said, “I was pleasantly surprised that their comments were actually pretty minor and that most of these comments are really more a reflection, not of the validity of the definitions, but rather their applications.”
He noted that all the potential issues with the definitions were already discussed during the making of VARC-3 and resolved by consensus of more than 50 experts including the STS president at the time, Food and Drug Administration officials, and experts from the community.
“To be quite honest, I’m not sure they have consensus,” Dr. Généreux said. He added that the writing committee welcomes input from anyone, but “we’re not going to change the definitions to please eight individuals if we strongly believe by consensus of experts in the field that this is not the right thing to do.”
Rehospitalizations and valve thrombosis
The surgical associations praise VARC-3 for providing a standardized definition of bioprosthetic valve failure, but say they will not endorse the inclusion of rehospitalization as a component of the primary efficacy composite endpoint along with all-cause mortality, stroke, and quality of life.
They note that rehospitalizations outnumber mortality events, especially in short follow-up trials, and that the superiority of TAVR at 1 year in the PARTNER 3 trial of low-risk patients was driven primarily by more rehospitalizations in the surgical arm, but that this superiority was waning at 2 years of follow-up.
“The first thing we are calling for is that it shouldn’t be part of the primary composite outcome measure,” Dr. Myers said. But if it really has to be included, a 30-day blanking period for rehospitalization “would acknowledge that there’s a greater risk of rehospitalization during the acute phase of recovering from surgery.”
Dr. Généreux said that VARC-3 provides granular details for defining the different types of hospitalizations, but that a 30-day blanking period makes no sense. “If you close your eyes to anything within 30 days because you don’t like it, you’re missing the opportunity to improve your procedure, to improve your treatment, and to characterize precisely what happened with your patient.”
The new document lauds VARC-3’s focus on patient-centered and clinically relevant endpoints but questions the definition of valve thrombosis as a “clinically significant” thrombus. It points out that the incidence of valve thrombosis was significantly higher with TAVR versus SAVR in PARTNER 3 using the older VARC-2 definition, which did not require evidence of clinical sequelae (2.6% vs. 0.7%; P = .02). Under the new definition, however, half of the thrombi would be relabeled as “nothing there,” Dr. Myers said.
“As we’re doing this in younger and younger patients who will survive longer, there is a question of thrombus having an effect on the valve and leading to earlier structural valve deterioration,” he added. “All this is conjecture. We don’t have the data. So mainly what we’re advocating is that all thrombi should be reported.”
MIs, bleeding, and LBBB
The policy statement also criticizes VARC-3’s decision to define periprocedural (type 5) MI using a biomarker-only definition without need of clinical confirmation. Such definitions have been shown to have a very poor prognostic significance in surgical series compared with the Universal Definitions of Myocardial Infarction, Dr. Myers said.
“What’s interesting is that for thrombus and bleeding, they require clinical correlation, but on the perioperative MI they now use a definition that does not require clinical significance, meaning no ECG changes, no regional wall motion abnormalities or things like that,” he observed.
The decision also seems to disregard the EXCEL trial controversy that illustrated how outcomes and a trial’s message can change depending on which definition of periprocedural MI is used.
With regard to bleeding, the surgical associations agree with the VARC-3 recommendation to use different thresholds when bleeding is integrated into a composite endpoint (type 2 or greater for TAVR and types 3 or greater for SAVR) but suggest this important point should be featured in the chapter on bleeding rather than the section on composite endpoints.
The surgical associations say VARC-3 also got it right adding the need for a new permanent pacemaker to the early composite safety endpoint, but that it was a “missed opportunity” not to include new left bundle-branch block in the safety composite, despite recognizing that this may become an important endpoint to consider in the future.
Dr. Myers said that left bundle-branch block could have implications for survival as TAVR moves into lower-risk, younger patients, as some data with 1-year follow-up suggest it has a prognostic impact, even in the higher-risk older patients with more competing risks.
Finally, the surgical associations point out that only two of the 23 VARC-3 authors were practicing cardiac surgeons and say that a more diverse writing group “may help mitigate issues related to the duality of interests.”
Dr. Généreux said that the final author list is not a reflection of the rigorous work done by 11 cardiac surgeons including the two surgeon authors. The VARC-3 writing committee also had a good representation of women, unlike the surgical position statement, which was penned by eight men.
Dr. Myers reported no relevant financial relationships. Coauthors disclosed ties with EACTS, Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, CryoLife, Shockwave, and JenaValve. Dr. Généreux disclosed ties with Abbott Vascular, Abiomed, Boston Scientific, Cardinal Health, Cardiovascular Systems, Edwards Lifesciences, Medtronic, Opsens, Siemens, SoundBite Medical Solutions, Sig.Num, Saranas, Teleflex, Tryton Medical, Pi-Cardia, and Puzzle Medical.
A version of this article first appeared on Medscape.com.
Cancer survivors: Move more, sit less for a longer life, study says
Being physically active, on the other hand, lowers the risk of early death, new research shows.
What’s “alarming” is that so many cancer survivors have a sedentary lifestyle, Chao Cao and Lin Yang, PhD, with Alberta Health Services in Calgary, who worked on the study, said in an interview.
The American Cancer Society recommends that cancer survivors follow the same physical activity guidance as the general population. The target is 150-300 minutes of moderate activity or 75-150 minutes of vigorous activity each week (or a combination of these).
“Getting to or exceeding the upper limit of 300 minutes is ideal,” Mr. Cao and Dr. Yang say.
Yet in their study of more than 1,500 cancer survivors, more than half (57%) were inactive, reporting no weekly leisure-time physical activity in the past week.
About 16% were “insufficiently” active, or getting less than 150 minutes per week. Meanwhile, 28% were active, achieving more than 150 minutes of weekly physical activity.
Digging deeper, the researchers found that more than one-third of cancer survivors reported sitting for 6-8 hours each day, and one-quarter reported sitting for more than 8 hours per day.
Over the course of up to 9 years, 293 of the cancer survivors died – 114 from cancer, 41 from heart diseases, and 138 from other causes.
After accounting for things that might influence the results, the risk of dying from any cause or cancer was about 65% lower in cancer survivors who were physically active, relative to their inactive peers.
Sitting for long periods was especially risky, according to the study in JAMA Oncology.
Compared with cancer survivors who sat for less than 4 hours each day, cancer survivors who reported sitting for more than 8 hours a day had nearly twice the risk of dying from any cause and more than twice the risk of dying from cancer.
Cancer survivors who sat for more than 8 hours a day, and were inactive or not active enough, had as much as five times the risk of death from any cause or cancer.
“Be active and sit less, move more, and move frequently,” advise Mr. Cao and Dr. Yang. “Avoiding prolonged sitting is essential for most cancer survivors to reduce excess mortality risks.”
A version of this article first appeared on WebMD.com.
Being physically active, on the other hand, lowers the risk of early death, new research shows.
What’s “alarming” is that so many cancer survivors have a sedentary lifestyle, Chao Cao and Lin Yang, PhD, with Alberta Health Services in Calgary, who worked on the study, said in an interview.
The American Cancer Society recommends that cancer survivors follow the same physical activity guidance as the general population. The target is 150-300 minutes of moderate activity or 75-150 minutes of vigorous activity each week (or a combination of these).
“Getting to or exceeding the upper limit of 300 minutes is ideal,” Mr. Cao and Dr. Yang say.
Yet in their study of more than 1,500 cancer survivors, more than half (57%) were inactive, reporting no weekly leisure-time physical activity in the past week.
About 16% were “insufficiently” active, or getting less than 150 minutes per week. Meanwhile, 28% were active, achieving more than 150 minutes of weekly physical activity.
Digging deeper, the researchers found that more than one-third of cancer survivors reported sitting for 6-8 hours each day, and one-quarter reported sitting for more than 8 hours per day.
Over the course of up to 9 years, 293 of the cancer survivors died – 114 from cancer, 41 from heart diseases, and 138 from other causes.
After accounting for things that might influence the results, the risk of dying from any cause or cancer was about 65% lower in cancer survivors who were physically active, relative to their inactive peers.
Sitting for long periods was especially risky, according to the study in JAMA Oncology.
Compared with cancer survivors who sat for less than 4 hours each day, cancer survivors who reported sitting for more than 8 hours a day had nearly twice the risk of dying from any cause and more than twice the risk of dying from cancer.
Cancer survivors who sat for more than 8 hours a day, and were inactive or not active enough, had as much as five times the risk of death from any cause or cancer.
“Be active and sit less, move more, and move frequently,” advise Mr. Cao and Dr. Yang. “Avoiding prolonged sitting is essential for most cancer survivors to reduce excess mortality risks.”
A version of this article first appeared on WebMD.com.
Being physically active, on the other hand, lowers the risk of early death, new research shows.
What’s “alarming” is that so many cancer survivors have a sedentary lifestyle, Chao Cao and Lin Yang, PhD, with Alberta Health Services in Calgary, who worked on the study, said in an interview.
The American Cancer Society recommends that cancer survivors follow the same physical activity guidance as the general population. The target is 150-300 minutes of moderate activity or 75-150 minutes of vigorous activity each week (or a combination of these).
“Getting to or exceeding the upper limit of 300 minutes is ideal,” Mr. Cao and Dr. Yang say.
Yet in their study of more than 1,500 cancer survivors, more than half (57%) were inactive, reporting no weekly leisure-time physical activity in the past week.
About 16% were “insufficiently” active, or getting less than 150 minutes per week. Meanwhile, 28% were active, achieving more than 150 minutes of weekly physical activity.
Digging deeper, the researchers found that more than one-third of cancer survivors reported sitting for 6-8 hours each day, and one-quarter reported sitting for more than 8 hours per day.
Over the course of up to 9 years, 293 of the cancer survivors died – 114 from cancer, 41 from heart diseases, and 138 from other causes.
After accounting for things that might influence the results, the risk of dying from any cause or cancer was about 65% lower in cancer survivors who were physically active, relative to their inactive peers.
Sitting for long periods was especially risky, according to the study in JAMA Oncology.
Compared with cancer survivors who sat for less than 4 hours each day, cancer survivors who reported sitting for more than 8 hours a day had nearly twice the risk of dying from any cause and more than twice the risk of dying from cancer.
Cancer survivors who sat for more than 8 hours a day, and were inactive or not active enough, had as much as five times the risk of death from any cause or cancer.
“Be active and sit less, move more, and move frequently,” advise Mr. Cao and Dr. Yang. “Avoiding prolonged sitting is essential for most cancer survivors to reduce excess mortality risks.”
A version of this article first appeared on WebMD.com.
FROM JAMA ONCOLOGY
Pandemic showed pediatric centers are key to aiding victims of intimate partner violence
Pediatric care centers are a significant point of access for intimate partner violence referrals, according to data from an IPV prevention program embedded in Boston Children’s Hospital.
The pediatric hospital’s embedded Advocacy for Women and Kids in Emergencies (AWAKE) program found an increase in IPV consults and referrals during the COVID-19 pandemic, particularly for emotional abuse. Despite the shift away from in-office consultations, care was effectively delivered remotely by telehealth.
The findings highlight the importance of pediatric primary care as a point of access for IPV survivor support, the authors concluded.
”Programming for survivors (including patients, family members, and staff) of intimate partner violence is critical in the pediatric hospital setting, especially during the COVID-19 pandemic,” Rehana Rahman, MSW, and colleagues wrote in Pediatrics.
Their results align with other research demonstrating an overall increase in violence against women and girls during the pandemic – a phenomenon the World Health Organization has called the “shadow pandemic.”
The challenges of accessing care during the COVID-19 restrictions demonstrate the utility of telehealth as a modality for providing assessment, support, and referrals, the authors stated.
They pointed to certain advantages in supporting IPV survivors virtually, including the ability to speak alone with the survivor, which is often not possible during in-person visits with children in the room.
Other research has documented that health care delivery via telemedicine, especially video teleconferencing, during the pandemic can be as effective as in-office visits. In fact, care providers may be able to pick up on significant visual cues on video that go unnoticed in the immediacy of the office setting.
The study
The researchers examined COVID-19–related variations in consultations and referrals in the 11 months before the COVID-19 pandemic (April 1, 2019, to Feb. 29, 2020) and those following its emergence (April 1, 2020, to Feb. 28, 2021).
Face-to-face consults declined from 28% to 2% (P < .001) after COVID-19 emergence, while total consults increased from 240 to 295 (P < .001), primarily for emotional abuse (from 195 to 264, P = .007).
There were no significant changes in the number of consults for other reasons or in the number of reasons recorded for each consult.
Psychoeducation referrals also rose significantly from 199 to 273 (P < .001), while referrals to community resources decreased significantly from 111 to 95 (P < .001).
Primary care was the only practice setting demonstrating significant differences in the overall number of and specific reasons for consultation, as well as associated referral types before and after COVID emergence.
“We hypothesize that this increase may be attributable to the fact that, although many survivors were at home with partners who use abusive behaviors, obligatory pediatric primary care visits may have been a rare opportunity for them to leave their residence and seek support,” the investigators wrote. “Our data support the importance of a domestic violence program in pediatric hospitals and suggest that such support be available as a standard part of care.”
They further suggested that support and assessment may be effective regardless of whether that care is performed face-to-face or via telehealth.
Commentary
An accompanying editorial noted that intimate partner violence affects one in five children and has profound health effects on survivors and their children.
“The health, economic, and social ramifications of the COVID-19 pandemic have created unique challenges for families experiencing IPV, by increasing isolation, decreasing available safe and secure services and spaces (e.g., schools), and compounding preexisting inequities, especially for families from marginalized communities,” wrote Maya Ragavan, MD, MS, MPH, and Elizabeth Miller, MD, PhD, of the department of pediatrics at the University of Pittsburgh.
They stressed that pediatric health care providers should be aware of the emotionally coercive control used by abusive partners during the pandemic, including social isolation, manipulating child custody, and taking stimulus money.
Dr. Ragavan and Dr. Miller agreed with the authors that pediatric health care settings can play an important role in supporting families exposed to intimate partner violence, particularly by developing partnerships with IPV aid agencies.
Many pediatric offices may not have access to a comprehensive service like AWAKE, highlighting the importance of developing partnerships with community-based IPV agencies, which have been working innovatively during the pandemic to support families experiencing IPV. “Pediatric health care providers should work to develop formalized partnerships with IPV agencies to assist with staff training, clinical protocols and policies to address IPV, including survivor-centered approaches to care when IPV is disclosed,” they wrote. “Health care settings must recognize that IPV agencies are integral to the pediatric medical home and essential collaborators in the provision of healing-centered care for IPV survivors and their children.”
Among these, Futures Without Violence, a national violence-prevention advocacy and policy organization, offers recommendations on collaboration via the IPV Health Partners website.
Matthew I. Harris, MD, a pediatric emergency physician at Cohen Children’s Medical Center in New York, concurred that the pediatric care setting can be an access point for IPV referrals. “Whether a child comes into our center with an ear infection or an injury, there’s a standard screening process for safety in the home,” he said in an interview. That standard filtering identifies the presence of smoking, alcohol, guns, and potential abusers. “It’s not uncommon that we discover violence or physical, verbal, or sexual abuse not only toward the child but also another family member, including IPV.”
Children’s hospitals are well positioned to identify at-risk families and refer them to appropriate protective services, Dr. Harris said. “Ultimately, we are charged with the responsibility of ensuring children have a safe home environment and that involves minimizing any harmful impact on other family members, including those exposed to IPV.”
The authors received no funding for this study and reported no competing interests. Dr. Ragavan had no relevant conflicts of interest to disclose. Dr. Miller reported royalties for writing content for UpToDate. Dr. Harris disclosed no competing interests.
This article was updated 3/25/22.
Pediatric care centers are a significant point of access for intimate partner violence referrals, according to data from an IPV prevention program embedded in Boston Children’s Hospital.
The pediatric hospital’s embedded Advocacy for Women and Kids in Emergencies (AWAKE) program found an increase in IPV consults and referrals during the COVID-19 pandemic, particularly for emotional abuse. Despite the shift away from in-office consultations, care was effectively delivered remotely by telehealth.
The findings highlight the importance of pediatric primary care as a point of access for IPV survivor support, the authors concluded.
”Programming for survivors (including patients, family members, and staff) of intimate partner violence is critical in the pediatric hospital setting, especially during the COVID-19 pandemic,” Rehana Rahman, MSW, and colleagues wrote in Pediatrics.
Their results align with other research demonstrating an overall increase in violence against women and girls during the pandemic – a phenomenon the World Health Organization has called the “shadow pandemic.”
The challenges of accessing care during the COVID-19 restrictions demonstrate the utility of telehealth as a modality for providing assessment, support, and referrals, the authors stated.
They pointed to certain advantages in supporting IPV survivors virtually, including the ability to speak alone with the survivor, which is often not possible during in-person visits with children in the room.
Other research has documented that health care delivery via telemedicine, especially video teleconferencing, during the pandemic can be as effective as in-office visits. In fact, care providers may be able to pick up on significant visual cues on video that go unnoticed in the immediacy of the office setting.
The study
The researchers examined COVID-19–related variations in consultations and referrals in the 11 months before the COVID-19 pandemic (April 1, 2019, to Feb. 29, 2020) and those following its emergence (April 1, 2020, to Feb. 28, 2021).
Face-to-face consults declined from 28% to 2% (P < .001) after COVID-19 emergence, while total consults increased from 240 to 295 (P < .001), primarily for emotional abuse (from 195 to 264, P = .007).
There were no significant changes in the number of consults for other reasons or in the number of reasons recorded for each consult.
Psychoeducation referrals also rose significantly from 199 to 273 (P < .001), while referrals to community resources decreased significantly from 111 to 95 (P < .001).
Primary care was the only practice setting demonstrating significant differences in the overall number of and specific reasons for consultation, as well as associated referral types before and after COVID emergence.
“We hypothesize that this increase may be attributable to the fact that, although many survivors were at home with partners who use abusive behaviors, obligatory pediatric primary care visits may have been a rare opportunity for them to leave their residence and seek support,” the investigators wrote. “Our data support the importance of a domestic violence program in pediatric hospitals and suggest that such support be available as a standard part of care.”
They further suggested that support and assessment may be effective regardless of whether that care is performed face-to-face or via telehealth.
Commentary
An accompanying editorial noted that intimate partner violence affects one in five children and has profound health effects on survivors and their children.
“The health, economic, and social ramifications of the COVID-19 pandemic have created unique challenges for families experiencing IPV, by increasing isolation, decreasing available safe and secure services and spaces (e.g., schools), and compounding preexisting inequities, especially for families from marginalized communities,” wrote Maya Ragavan, MD, MS, MPH, and Elizabeth Miller, MD, PhD, of the department of pediatrics at the University of Pittsburgh.
They stressed that pediatric health care providers should be aware of the emotionally coercive control used by abusive partners during the pandemic, including social isolation, manipulating child custody, and taking stimulus money.
Dr. Ragavan and Dr. Miller agreed with the authors that pediatric health care settings can play an important role in supporting families exposed to intimate partner violence, particularly by developing partnerships with IPV aid agencies.
Many pediatric offices may not have access to a comprehensive service like AWAKE, highlighting the importance of developing partnerships with community-based IPV agencies, which have been working innovatively during the pandemic to support families experiencing IPV. “Pediatric health care providers should work to develop formalized partnerships with IPV agencies to assist with staff training, clinical protocols and policies to address IPV, including survivor-centered approaches to care when IPV is disclosed,” they wrote. “Health care settings must recognize that IPV agencies are integral to the pediatric medical home and essential collaborators in the provision of healing-centered care for IPV survivors and their children.”
Among these, Futures Without Violence, a national violence-prevention advocacy and policy organization, offers recommendations on collaboration via the IPV Health Partners website.
Matthew I. Harris, MD, a pediatric emergency physician at Cohen Children’s Medical Center in New York, concurred that the pediatric care setting can be an access point for IPV referrals. “Whether a child comes into our center with an ear infection or an injury, there’s a standard screening process for safety in the home,” he said in an interview. That standard filtering identifies the presence of smoking, alcohol, guns, and potential abusers. “It’s not uncommon that we discover violence or physical, verbal, or sexual abuse not only toward the child but also another family member, including IPV.”
Children’s hospitals are well positioned to identify at-risk families and refer them to appropriate protective services, Dr. Harris said. “Ultimately, we are charged with the responsibility of ensuring children have a safe home environment and that involves minimizing any harmful impact on other family members, including those exposed to IPV.”
The authors received no funding for this study and reported no competing interests. Dr. Ragavan had no relevant conflicts of interest to disclose. Dr. Miller reported royalties for writing content for UpToDate. Dr. Harris disclosed no competing interests.
This article was updated 3/25/22.
Pediatric care centers are a significant point of access for intimate partner violence referrals, according to data from an IPV prevention program embedded in Boston Children’s Hospital.
The pediatric hospital’s embedded Advocacy for Women and Kids in Emergencies (AWAKE) program found an increase in IPV consults and referrals during the COVID-19 pandemic, particularly for emotional abuse. Despite the shift away from in-office consultations, care was effectively delivered remotely by telehealth.
The findings highlight the importance of pediatric primary care as a point of access for IPV survivor support, the authors concluded.
”Programming for survivors (including patients, family members, and staff) of intimate partner violence is critical in the pediatric hospital setting, especially during the COVID-19 pandemic,” Rehana Rahman, MSW, and colleagues wrote in Pediatrics.
Their results align with other research demonstrating an overall increase in violence against women and girls during the pandemic – a phenomenon the World Health Organization has called the “shadow pandemic.”
The challenges of accessing care during the COVID-19 restrictions demonstrate the utility of telehealth as a modality for providing assessment, support, and referrals, the authors stated.
They pointed to certain advantages in supporting IPV survivors virtually, including the ability to speak alone with the survivor, which is often not possible during in-person visits with children in the room.
Other research has documented that health care delivery via telemedicine, especially video teleconferencing, during the pandemic can be as effective as in-office visits. In fact, care providers may be able to pick up on significant visual cues on video that go unnoticed in the immediacy of the office setting.
The study
The researchers examined COVID-19–related variations in consultations and referrals in the 11 months before the COVID-19 pandemic (April 1, 2019, to Feb. 29, 2020) and those following its emergence (April 1, 2020, to Feb. 28, 2021).
Face-to-face consults declined from 28% to 2% (P < .001) after COVID-19 emergence, while total consults increased from 240 to 295 (P < .001), primarily for emotional abuse (from 195 to 264, P = .007).
There were no significant changes in the number of consults for other reasons or in the number of reasons recorded for each consult.
Psychoeducation referrals also rose significantly from 199 to 273 (P < .001), while referrals to community resources decreased significantly from 111 to 95 (P < .001).
Primary care was the only practice setting demonstrating significant differences in the overall number of and specific reasons for consultation, as well as associated referral types before and after COVID emergence.
“We hypothesize that this increase may be attributable to the fact that, although many survivors were at home with partners who use abusive behaviors, obligatory pediatric primary care visits may have been a rare opportunity for them to leave their residence and seek support,” the investigators wrote. “Our data support the importance of a domestic violence program in pediatric hospitals and suggest that such support be available as a standard part of care.”
They further suggested that support and assessment may be effective regardless of whether that care is performed face-to-face or via telehealth.
Commentary
An accompanying editorial noted that intimate partner violence affects one in five children and has profound health effects on survivors and their children.
“The health, economic, and social ramifications of the COVID-19 pandemic have created unique challenges for families experiencing IPV, by increasing isolation, decreasing available safe and secure services and spaces (e.g., schools), and compounding preexisting inequities, especially for families from marginalized communities,” wrote Maya Ragavan, MD, MS, MPH, and Elizabeth Miller, MD, PhD, of the department of pediatrics at the University of Pittsburgh.
They stressed that pediatric health care providers should be aware of the emotionally coercive control used by abusive partners during the pandemic, including social isolation, manipulating child custody, and taking stimulus money.
Dr. Ragavan and Dr. Miller agreed with the authors that pediatric health care settings can play an important role in supporting families exposed to intimate partner violence, particularly by developing partnerships with IPV aid agencies.
Many pediatric offices may not have access to a comprehensive service like AWAKE, highlighting the importance of developing partnerships with community-based IPV agencies, which have been working innovatively during the pandemic to support families experiencing IPV. “Pediatric health care providers should work to develop formalized partnerships with IPV agencies to assist with staff training, clinical protocols and policies to address IPV, including survivor-centered approaches to care when IPV is disclosed,” they wrote. “Health care settings must recognize that IPV agencies are integral to the pediatric medical home and essential collaborators in the provision of healing-centered care for IPV survivors and their children.”
Among these, Futures Without Violence, a national violence-prevention advocacy and policy organization, offers recommendations on collaboration via the IPV Health Partners website.
Matthew I. Harris, MD, a pediatric emergency physician at Cohen Children’s Medical Center in New York, concurred that the pediatric care setting can be an access point for IPV referrals. “Whether a child comes into our center with an ear infection or an injury, there’s a standard screening process for safety in the home,” he said in an interview. That standard filtering identifies the presence of smoking, alcohol, guns, and potential abusers. “It’s not uncommon that we discover violence or physical, verbal, or sexual abuse not only toward the child but also another family member, including IPV.”
Children’s hospitals are well positioned to identify at-risk families and refer them to appropriate protective services, Dr. Harris said. “Ultimately, we are charged with the responsibility of ensuring children have a safe home environment and that involves minimizing any harmful impact on other family members, including those exposed to IPV.”
The authors received no funding for this study and reported no competing interests. Dr. Ragavan had no relevant conflicts of interest to disclose. Dr. Miller reported royalties for writing content for UpToDate. Dr. Harris disclosed no competing interests.
This article was updated 3/25/22.
FROM PEDIATRICS
Two leading oral cancer treatment guidelines differ on recurrence and survival predictions
(OCSCC), according to a retrospective study.
Treatment of OCSCC involves resection of the primary tumor, followed by neck dissection or postoperative radiotherapy when needed, but choice of treatment requires an accurate assessment of resection margins. Previous studies have failed to consistently show a correlation between margin status and clinical outcomes. Tumor size, depth of invasion, and other factors may explain inconsistent findings, but another possibility is the variability in how margin status is defined.
RCPath and CAP are among the most commonly used definitions. RCPath defines a positive margin as invasive tumor within 1 mm of the surgical margin, while CAP defines a positive margin as the presence of primary tumor or high-grade dysplasia at the margin itself. CAP recommends determination of a “final margin status” that also considers separately submitted extra tumor bed margins. Nevertheless, multiple studies have shown that reliance on the main tumor specimen outperformed the combined approach in predicting recurrence and survival.
In a study published online March 7 in Oral Oncology, researchers examined records from 300 patients (33.7% of whom were female) at South Infirmary Victoria University Hospital in Ireland between 2007 and 2020. The researchers found that 28.7% had margins determined by the RCPath definition and 16.7% according to the CAP definition. Forty-nine percent underwent extra tumor bed resections.
The mean follow-up period was 49 months, 64 months for surviving patients. Multivariate analyses accounting for other established prognosticators found that local recurrence was associated with CAP margins (odds ratio [OR], 1.86; 955 confidence interval [CI], 1.02-3.48) and T3/T4 classification (OR, 2.80; 95% CI, 1.53-5.13). CAP margins predicted disease-specific survival (OR, 2.28; 95% CI, 1.53-5.13) and narrowly missed significance in predicting overall survival (OR, 1.65; 95% CI, 0.99-2.75). RCPath margins were not predictive.
The researchers found a significant association between RCPath definition and metastatic nodal disease and extranodal extension, but there was no such relationship between these negative predictors and CAP and final margin status. “This finding may explain the superior independent prognostic ability of CAP margin status over RCPath in our cohort and is consistent with that of previous studies, which concluded that other histological risk factors are more important than margin status in predicting outcome,” the authors wrote.
Studies suggest that margins fewer than 1 mm remain a high-risk group, with worse survival outcomes than those of patients with 1- to 5-mm margins, even if the risk is lower than tumor at margins. “The optimum cut-off between low-risk and high-risk margins in OCSCC remains unresolved,” the authors wrote.
The study was retrospective and relied on data from a single center, and the patients included in the study may not be directly comparable to other OCSCC patients. The study was funded by the Head and Neck Oncology Fund, South Infirmary Victoria University Hospital.
(OCSCC), according to a retrospective study.
Treatment of OCSCC involves resection of the primary tumor, followed by neck dissection or postoperative radiotherapy when needed, but choice of treatment requires an accurate assessment of resection margins. Previous studies have failed to consistently show a correlation between margin status and clinical outcomes. Tumor size, depth of invasion, and other factors may explain inconsistent findings, but another possibility is the variability in how margin status is defined.
RCPath and CAP are among the most commonly used definitions. RCPath defines a positive margin as invasive tumor within 1 mm of the surgical margin, while CAP defines a positive margin as the presence of primary tumor or high-grade dysplasia at the margin itself. CAP recommends determination of a “final margin status” that also considers separately submitted extra tumor bed margins. Nevertheless, multiple studies have shown that reliance on the main tumor specimen outperformed the combined approach in predicting recurrence and survival.
In a study published online March 7 in Oral Oncology, researchers examined records from 300 patients (33.7% of whom were female) at South Infirmary Victoria University Hospital in Ireland between 2007 and 2020. The researchers found that 28.7% had margins determined by the RCPath definition and 16.7% according to the CAP definition. Forty-nine percent underwent extra tumor bed resections.
The mean follow-up period was 49 months, 64 months for surviving patients. Multivariate analyses accounting for other established prognosticators found that local recurrence was associated with CAP margins (odds ratio [OR], 1.86; 955 confidence interval [CI], 1.02-3.48) and T3/T4 classification (OR, 2.80; 95% CI, 1.53-5.13). CAP margins predicted disease-specific survival (OR, 2.28; 95% CI, 1.53-5.13) and narrowly missed significance in predicting overall survival (OR, 1.65; 95% CI, 0.99-2.75). RCPath margins were not predictive.
The researchers found a significant association between RCPath definition and metastatic nodal disease and extranodal extension, but there was no such relationship between these negative predictors and CAP and final margin status. “This finding may explain the superior independent prognostic ability of CAP margin status over RCPath in our cohort and is consistent with that of previous studies, which concluded that other histological risk factors are more important than margin status in predicting outcome,” the authors wrote.
Studies suggest that margins fewer than 1 mm remain a high-risk group, with worse survival outcomes than those of patients with 1- to 5-mm margins, even if the risk is lower than tumor at margins. “The optimum cut-off between low-risk and high-risk margins in OCSCC remains unresolved,” the authors wrote.
The study was retrospective and relied on data from a single center, and the patients included in the study may not be directly comparable to other OCSCC patients. The study was funded by the Head and Neck Oncology Fund, South Infirmary Victoria University Hospital.
(OCSCC), according to a retrospective study.
Treatment of OCSCC involves resection of the primary tumor, followed by neck dissection or postoperative radiotherapy when needed, but choice of treatment requires an accurate assessment of resection margins. Previous studies have failed to consistently show a correlation between margin status and clinical outcomes. Tumor size, depth of invasion, and other factors may explain inconsistent findings, but another possibility is the variability in how margin status is defined.
RCPath and CAP are among the most commonly used definitions. RCPath defines a positive margin as invasive tumor within 1 mm of the surgical margin, while CAP defines a positive margin as the presence of primary tumor or high-grade dysplasia at the margin itself. CAP recommends determination of a “final margin status” that also considers separately submitted extra tumor bed margins. Nevertheless, multiple studies have shown that reliance on the main tumor specimen outperformed the combined approach in predicting recurrence and survival.
In a study published online March 7 in Oral Oncology, researchers examined records from 300 patients (33.7% of whom were female) at South Infirmary Victoria University Hospital in Ireland between 2007 and 2020. The researchers found that 28.7% had margins determined by the RCPath definition and 16.7% according to the CAP definition. Forty-nine percent underwent extra tumor bed resections.
The mean follow-up period was 49 months, 64 months for surviving patients. Multivariate analyses accounting for other established prognosticators found that local recurrence was associated with CAP margins (odds ratio [OR], 1.86; 955 confidence interval [CI], 1.02-3.48) and T3/T4 classification (OR, 2.80; 95% CI, 1.53-5.13). CAP margins predicted disease-specific survival (OR, 2.28; 95% CI, 1.53-5.13) and narrowly missed significance in predicting overall survival (OR, 1.65; 95% CI, 0.99-2.75). RCPath margins were not predictive.
The researchers found a significant association between RCPath definition and metastatic nodal disease and extranodal extension, but there was no such relationship between these negative predictors and CAP and final margin status. “This finding may explain the superior independent prognostic ability of CAP margin status over RCPath in our cohort and is consistent with that of previous studies, which concluded that other histological risk factors are more important than margin status in predicting outcome,” the authors wrote.
Studies suggest that margins fewer than 1 mm remain a high-risk group, with worse survival outcomes than those of patients with 1- to 5-mm margins, even if the risk is lower than tumor at margins. “The optimum cut-off between low-risk and high-risk margins in OCSCC remains unresolved,” the authors wrote.
The study was retrospective and relied on data from a single center, and the patients included in the study may not be directly comparable to other OCSCC patients. The study was funded by the Head and Neck Oncology Fund, South Infirmary Victoria University Hospital.
FROM ORAL ONCOLOGY
Will serrated polyp detection rates be the next CRC metric?
A higher rate of serrated polyp detection was associated with a reduced risk of postcolonoscopy colorectal cancer, based on data from nearly 20,000 patients and 142 endoscopists, according to a study published in Gastrointestinal Endoscopy.
Higher rates of adenoma detection reduce the risk of postcolonoscopy colorectal cancer (PCCRC), but the data on detection rates for clinically significant serrated polyps and traditional serrated adenomas are limited, wrote Joseph C. Anderson, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., and colleagues.
“A unique challenge for endoscopists is that serrated polyps exhibit characteristics that can make them more difficult to detect than conventional adenomas. Thus, it is not surprising that several studies have demonstrated a wide variation in serrated polyp detection rates.” Even so, improved detection and resection of these polyps would likely improve CRC prevention, they noted.
The researchers reviewed data from the New Hampshire Colonoscopy Registry to explore the association between clinically significantly serrated polyp (CSSP) detection rates and subsequent PCCRC risk.
The study population included 19,532 patients with follow-up events at least 6 months after an index colonoscopy. Of these, 128 cases of CRC were diagnosed at least 6 months after an index exam. CSSP was defined as any sessile serrated polyp, traditional serrated adenoma, or any large hyperplastic polyp (> 1 cm) or proximal hyperplastic polyp > 5 mm. The exams were performed by 142 endoscopists, 92 of whom were gastroenterologists. The 50 nongastroenterologists included general surgeons, colorectal surgeons, and family practitioners.
The primary outcome was PCCRC, defined as any CRC diagnosis 6 months or longer after an index exam. Clinically significant serrated polyp detection rate (CSSDR) was determined by dividing the total number of complete screening exams with adequate prep and at least one CSSP by the total number of complete exams with adequate prep. CSSDR was divided into tertiles of less than 3%, 3% up to 9%, and 9% or higher.
Overall, the risk for PCCRC 6 months or more after an index exam was significantly lower for exams performed by endoscopists with detection rates of 3% up to 9% and for those with detection rates of 9% or higher compared to those with detection rates below 3% (hazard ratios 0.57 and 0.39, respectively).
Significantly more gastroenterologists were in the higher CSSDR categories compared to nongastroenterologists (P = .00005). The percentages of gastroenterologists in the three tertiles from lowest to highest detection were 15.2%, 50.0%, and 34.8%; compared to 46%, 44.0%, and 10.0%, respectively, for nongastroenterologists.
In adjusted analysis, higher detection rates were associated with lower CRC risk across all time periods.
The researchers also found higher CSSDR categories associated with lower PCCRC risk for exams by endoscopists with ADR rates of 25% or higher.
“It may be reasonable to question whether a separate serrated detection rate is needed in addition to ADR,” the researchers wrote in their discussion of the findings. “These data support our suggestion that endoscopists, even those with an ADR of 25% or higher, calculate their SDR at least once, a recommendation supported by a recent review of the American Gastroenterological Association,” they noted.
The study findings were limited by several factors, including the lack of information on specific endoscopic techniques, a lack of data on the molecular characteristics of the cancers, and potential residual confounding variables, the researchers noted.
However, the results were strengthened by the large number of participating endoscopists and by the longitudinal database that included detection rates for screening exams and detailed polyp pathology, they said. The results support the need for a serrated polyp detection rate benchmark to endure complete polyp detection and validate the use of CSSDR as a quality measure that adds to the knowledge of both colonoscopy quality and the role of the serrated pathway in colorectal cancer, they concluded.
Serrated pathway serves as predictor
The current study is an important addition to the knowledge of colorectal cancer risk, Atsushi Sakuraba, MD, PhD, associate professor of medicine at the University of Chicago, said in an interview.
“In addition to the conventional adenoma pathway, the serrated pathway has been recognized to account for a significant portion of colorectal cancer, but whether detection of serrated polyps [is] associated with reduction of CRC remains unknown,” he said.
Dr. Sakuraba said he was not surprised by the study findings. Given that the serrated pathway is now considered to account for approximately 10%-20% of all CRC cases, higher detection rates should result in lower risk of CRC, he noted.
The findings support the value of CSSDR in clinical practice, said Dr. Sakuraba. “The study has shown that a clinically significant serrated polyps detection rate of 3% was associated with lower postcolonoscopy CRC, so endoscopists should introduce this to their practice in addition to adenoma detection rates,” he said.
However, Dr. Sakuraba acknowledged the limitations of the current study and emphasized that it needs to be reproduced in other cohorts. Prospective studies might be helpful as well, he said.
The study received no outside funding. The researchers and Dr. Sakuraba had no financial conflicts to disclose.
A higher rate of serrated polyp detection was associated with a reduced risk of postcolonoscopy colorectal cancer, based on data from nearly 20,000 patients and 142 endoscopists, according to a study published in Gastrointestinal Endoscopy.
Higher rates of adenoma detection reduce the risk of postcolonoscopy colorectal cancer (PCCRC), but the data on detection rates for clinically significant serrated polyps and traditional serrated adenomas are limited, wrote Joseph C. Anderson, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., and colleagues.
“A unique challenge for endoscopists is that serrated polyps exhibit characteristics that can make them more difficult to detect than conventional adenomas. Thus, it is not surprising that several studies have demonstrated a wide variation in serrated polyp detection rates.” Even so, improved detection and resection of these polyps would likely improve CRC prevention, they noted.
The researchers reviewed data from the New Hampshire Colonoscopy Registry to explore the association between clinically significantly serrated polyp (CSSP) detection rates and subsequent PCCRC risk.
The study population included 19,532 patients with follow-up events at least 6 months after an index colonoscopy. Of these, 128 cases of CRC were diagnosed at least 6 months after an index exam. CSSP was defined as any sessile serrated polyp, traditional serrated adenoma, or any large hyperplastic polyp (> 1 cm) or proximal hyperplastic polyp > 5 mm. The exams were performed by 142 endoscopists, 92 of whom were gastroenterologists. The 50 nongastroenterologists included general surgeons, colorectal surgeons, and family practitioners.
The primary outcome was PCCRC, defined as any CRC diagnosis 6 months or longer after an index exam. Clinically significant serrated polyp detection rate (CSSDR) was determined by dividing the total number of complete screening exams with adequate prep and at least one CSSP by the total number of complete exams with adequate prep. CSSDR was divided into tertiles of less than 3%, 3% up to 9%, and 9% or higher.
Overall, the risk for PCCRC 6 months or more after an index exam was significantly lower for exams performed by endoscopists with detection rates of 3% up to 9% and for those with detection rates of 9% or higher compared to those with detection rates below 3% (hazard ratios 0.57 and 0.39, respectively).
Significantly more gastroenterologists were in the higher CSSDR categories compared to nongastroenterologists (P = .00005). The percentages of gastroenterologists in the three tertiles from lowest to highest detection were 15.2%, 50.0%, and 34.8%; compared to 46%, 44.0%, and 10.0%, respectively, for nongastroenterologists.
In adjusted analysis, higher detection rates were associated with lower CRC risk across all time periods.
The researchers also found higher CSSDR categories associated with lower PCCRC risk for exams by endoscopists with ADR rates of 25% or higher.
“It may be reasonable to question whether a separate serrated detection rate is needed in addition to ADR,” the researchers wrote in their discussion of the findings. “These data support our suggestion that endoscopists, even those with an ADR of 25% or higher, calculate their SDR at least once, a recommendation supported by a recent review of the American Gastroenterological Association,” they noted.
The study findings were limited by several factors, including the lack of information on specific endoscopic techniques, a lack of data on the molecular characteristics of the cancers, and potential residual confounding variables, the researchers noted.
However, the results were strengthened by the large number of participating endoscopists and by the longitudinal database that included detection rates for screening exams and detailed polyp pathology, they said. The results support the need for a serrated polyp detection rate benchmark to endure complete polyp detection and validate the use of CSSDR as a quality measure that adds to the knowledge of both colonoscopy quality and the role of the serrated pathway in colorectal cancer, they concluded.
Serrated pathway serves as predictor
The current study is an important addition to the knowledge of colorectal cancer risk, Atsushi Sakuraba, MD, PhD, associate professor of medicine at the University of Chicago, said in an interview.
“In addition to the conventional adenoma pathway, the serrated pathway has been recognized to account for a significant portion of colorectal cancer, but whether detection of serrated polyps [is] associated with reduction of CRC remains unknown,” he said.
Dr. Sakuraba said he was not surprised by the study findings. Given that the serrated pathway is now considered to account for approximately 10%-20% of all CRC cases, higher detection rates should result in lower risk of CRC, he noted.
The findings support the value of CSSDR in clinical practice, said Dr. Sakuraba. “The study has shown that a clinically significant serrated polyps detection rate of 3% was associated with lower postcolonoscopy CRC, so endoscopists should introduce this to their practice in addition to adenoma detection rates,” he said.
However, Dr. Sakuraba acknowledged the limitations of the current study and emphasized that it needs to be reproduced in other cohorts. Prospective studies might be helpful as well, he said.
The study received no outside funding. The researchers and Dr. Sakuraba had no financial conflicts to disclose.
A higher rate of serrated polyp detection was associated with a reduced risk of postcolonoscopy colorectal cancer, based on data from nearly 20,000 patients and 142 endoscopists, according to a study published in Gastrointestinal Endoscopy.
Higher rates of adenoma detection reduce the risk of postcolonoscopy colorectal cancer (PCCRC), but the data on detection rates for clinically significant serrated polyps and traditional serrated adenomas are limited, wrote Joseph C. Anderson, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., and colleagues.
“A unique challenge for endoscopists is that serrated polyps exhibit characteristics that can make them more difficult to detect than conventional adenomas. Thus, it is not surprising that several studies have demonstrated a wide variation in serrated polyp detection rates.” Even so, improved detection and resection of these polyps would likely improve CRC prevention, they noted.
The researchers reviewed data from the New Hampshire Colonoscopy Registry to explore the association between clinically significantly serrated polyp (CSSP) detection rates and subsequent PCCRC risk.
The study population included 19,532 patients with follow-up events at least 6 months after an index colonoscopy. Of these, 128 cases of CRC were diagnosed at least 6 months after an index exam. CSSP was defined as any sessile serrated polyp, traditional serrated adenoma, or any large hyperplastic polyp (> 1 cm) or proximal hyperplastic polyp > 5 mm. The exams were performed by 142 endoscopists, 92 of whom were gastroenterologists. The 50 nongastroenterologists included general surgeons, colorectal surgeons, and family practitioners.
The primary outcome was PCCRC, defined as any CRC diagnosis 6 months or longer after an index exam. Clinically significant serrated polyp detection rate (CSSDR) was determined by dividing the total number of complete screening exams with adequate prep and at least one CSSP by the total number of complete exams with adequate prep. CSSDR was divided into tertiles of less than 3%, 3% up to 9%, and 9% or higher.
Overall, the risk for PCCRC 6 months or more after an index exam was significantly lower for exams performed by endoscopists with detection rates of 3% up to 9% and for those with detection rates of 9% or higher compared to those with detection rates below 3% (hazard ratios 0.57 and 0.39, respectively).
Significantly more gastroenterologists were in the higher CSSDR categories compared to nongastroenterologists (P = .00005). The percentages of gastroenterologists in the three tertiles from lowest to highest detection were 15.2%, 50.0%, and 34.8%; compared to 46%, 44.0%, and 10.0%, respectively, for nongastroenterologists.
In adjusted analysis, higher detection rates were associated with lower CRC risk across all time periods.
The researchers also found higher CSSDR categories associated with lower PCCRC risk for exams by endoscopists with ADR rates of 25% or higher.
“It may be reasonable to question whether a separate serrated detection rate is needed in addition to ADR,” the researchers wrote in their discussion of the findings. “These data support our suggestion that endoscopists, even those with an ADR of 25% or higher, calculate their SDR at least once, a recommendation supported by a recent review of the American Gastroenterological Association,” they noted.
The study findings were limited by several factors, including the lack of information on specific endoscopic techniques, a lack of data on the molecular characteristics of the cancers, and potential residual confounding variables, the researchers noted.
However, the results were strengthened by the large number of participating endoscopists and by the longitudinal database that included detection rates for screening exams and detailed polyp pathology, they said. The results support the need for a serrated polyp detection rate benchmark to endure complete polyp detection and validate the use of CSSDR as a quality measure that adds to the knowledge of both colonoscopy quality and the role of the serrated pathway in colorectal cancer, they concluded.
Serrated pathway serves as predictor
The current study is an important addition to the knowledge of colorectal cancer risk, Atsushi Sakuraba, MD, PhD, associate professor of medicine at the University of Chicago, said in an interview.
“In addition to the conventional adenoma pathway, the serrated pathway has been recognized to account for a significant portion of colorectal cancer, but whether detection of serrated polyps [is] associated with reduction of CRC remains unknown,” he said.
Dr. Sakuraba said he was not surprised by the study findings. Given that the serrated pathway is now considered to account for approximately 10%-20% of all CRC cases, higher detection rates should result in lower risk of CRC, he noted.
The findings support the value of CSSDR in clinical practice, said Dr. Sakuraba. “The study has shown that a clinically significant serrated polyps detection rate of 3% was associated with lower postcolonoscopy CRC, so endoscopists should introduce this to their practice in addition to adenoma detection rates,” he said.
However, Dr. Sakuraba acknowledged the limitations of the current study and emphasized that it needs to be reproduced in other cohorts. Prospective studies might be helpful as well, he said.
The study received no outside funding. The researchers and Dr. Sakuraba had no financial conflicts to disclose.
FROM GASTROINTESTINAL ENDOSCOPY