Persistence of oral human papillomavirus (HPV) DNA after primary treatment of HPV-positive oral cavity or oropharyngeal head and neck squamous cell carcinoma (HNSCC) is a strong risk factor for poor outcomes, finds a prospective cohort study.

Investigators working under senior author Maura L. Gillison, MD, PhD, of the department of thoracic head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston, collected serial oral rinses from 396 patients with HNSCC (217 with oropharyngeal cancer, 170 with oral cavity cancer, 9 with unknown primary cancer) treated at two institutions. Overall, 51% had HPV-positive tumors.

Patients with HPV-positive tumors were much more likely to have detectable oral HPV at diagnosis than their counterparts with HPV-negative tumors (84.2% vs 12.4%; P less than .001). Detection of oral HPV-16 DNA had good sensitivity (81%) and excellent specificity (100%) for HPV-16-positive tumors, Dr. Gillison and colleagues reported in JAMA Oncology.

Patients’ odds of having detectable tumor-type HPV fell during primary therapy (odds ratio per each postdiagnosis month, 0.41; P less than .001); in contrast, their odds of having of having detectable nontumor types did not. Current smokers were about half as likely to achieve clearing of tumor-type HPV DNA (hazard ratio, 0.49; P = .01).

Compared with counterparts who no longer had detectable tumor-type DNA after therapy, HPV-positive patients who did had dramatically poorer recurrence-free survival (55% vs. 88%; adjusted hazard ratio, 3.72; P  less than .001) and overall survival (68% vs. 95%; adjusted hazard ratio, 6.61; P = .003).

In contrast, persistence of nontumor-type HPV DNA did not predict these outcomes among either patients with HPV-positive tumors or patients with HPV-negative tumors.

“Analysis of tumor type HPV DNA has considerable promise as a biomarker for treatment response and risk of progression,” Dr. Gillison and coinvestigators maintain.

“Our data suggest that a subset of patients with HPV-positive HNSCC at high-risk for locoregional recurrence can be identified by detection of persistent, oral HPV after treatment. However, the clinical utility may be constrained by a need to identify the tumor-type infection, a low-moderate positive predictive value for recurrence, and weak associations with risk of distant metastases,” they conclude. “Ongoing studies will evaluate whether multiplexed detection of plasma HPV DNA can improve these limitations.”

Dr. Gillison disclosed consulting for Roche Holding AG, Bristol-Myers Squibb, Merck & Co Inc., Celgene Corporation, Amgen, AstraZeneca, Rakuten Aspyrian Inc. (now known as Rakuten Medical), EMD Serono Inc., NewLink Genetics Corporation, and Genocea Biosciences. The study was supported by the Oral Cancer Foundation and The Ohio State University Comprehensive Cancer Center. Dr. Gillison is a Cancer Prevention and Research Institute of Texas Scholar.

SOURCE: Fakhry C et al. JAMA Oncol. 2019 May 2. doi: 10.1001/jamaoncol.2019.0439.

Persistence of oral human papillomavirus (HPV) DNA after primary treatment of HPV-positive oral cavity or oropharyngeal head and neck squamous cell carcinoma (HNSCC) is a strong risk factor for poor outcomes, finds a prospective cohort study.

Investigators working under senior author Maura L. Gillison, MD, PhD, of the department of thoracic head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston, collected serial oral rinses from 396 patients with HNSCC (217 with oropharyngeal cancer, 170 with oral cavity cancer, 9 with unknown primary cancer) treated at two institutions. Overall, 51% had HPV-positive tumors.

Patients with HPV-positive tumors were much more likely to have detectable oral HPV at diagnosis than their counterparts with HPV-negative tumors (84.2% vs 12.4%; P less than .001). Detection of oral HPV-16 DNA had good sensitivity (81%) and excellent specificity (100%) for HPV-16-positive tumors, Dr. Gillison and colleagues reported in JAMA Oncology.

Patients’ odds of having detectable tumor-type HPV fell during primary therapy (odds ratio per each postdiagnosis month, 0.41; P less than .001); in contrast, their odds of having of having detectable nontumor types did not. Current smokers were about half as likely to achieve clearing of tumor-type HPV DNA (hazard ratio, 0.49; P = .01).

Compared with counterparts who no longer had detectable tumor-type DNA after therapy, HPV-positive patients who did had dramatically poorer recurrence-free survival (55% vs. 88%; adjusted hazard ratio, 3.72; P  less than .001) and overall survival (68% vs. 95%; adjusted hazard ratio, 6.61; P = .003).

In contrast, persistence of nontumor-type HPV DNA did not predict these outcomes among either patients with HPV-positive tumors or patients with HPV-negative tumors.

“Analysis of tumor type HPV DNA has considerable promise as a biomarker for treatment response and risk of progression,” Dr. Gillison and coinvestigators maintain.

“Our data suggest that a subset of patients with HPV-positive HNSCC at high-risk for locoregional recurrence can be identified by detection of persistent, oral HPV after treatment. However, the clinical utility may be constrained by a need to identify the tumor-type infection, a low-moderate positive predictive value for recurrence, and weak associations with risk of distant metastases,” they conclude. “Ongoing studies will evaluate whether multiplexed detection of plasma HPV DNA can improve these limitations.”

Dr. Gillison disclosed consulting for Roche Holding AG, Bristol-Myers Squibb, Merck & Co Inc., Celgene Corporation, Amgen, AstraZeneca, Rakuten Aspyrian Inc. (now known as Rakuten Medical), EMD Serono Inc., NewLink Genetics Corporation, and Genocea Biosciences. The study was supported by the Oral Cancer Foundation and The Ohio State University Comprehensive Cancer Center. Dr. Gillison is a Cancer Prevention and Research Institute of Texas Scholar.

SOURCE: Fakhry C et al. JAMA Oncol. 2019 May 2. doi: 10.1001/jamaoncol.2019.0439.

Persistence of oral human papillomavirus (HPV) DNA after primary treatment of HPV-positive oral cavity or oropharyngeal head and neck squamous cell carcinoma (HNSCC) is a strong risk factor for poor outcomes, finds a prospective cohort study.

Investigators working under senior author Maura L. Gillison, MD, PhD, of the department of thoracic head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston, collected serial oral rinses from 396 patients with HNSCC (217 with oropharyngeal cancer, 170 with oral cavity cancer, 9 with unknown primary cancer) treated at two institutions. Overall, 51% had HPV-positive tumors.

Patients with HPV-positive tumors were much more likely to have detectable oral HPV at diagnosis than their counterparts with HPV-negative tumors (84.2% vs 12.4%; P less than .001). Detection of oral HPV-16 DNA had good sensitivity (81%) and excellent specificity (100%) for HPV-16-positive tumors, Dr. Gillison and colleagues reported in JAMA Oncology.

Patients’ odds of having detectable tumor-type HPV fell during primary therapy (odds ratio per each postdiagnosis month, 0.41; P less than .001); in contrast, their odds of having of having detectable nontumor types did not. Current smokers were about half as likely to achieve clearing of tumor-type HPV DNA (hazard ratio, 0.49; P = .01).

Compared with counterparts who no longer had detectable tumor-type DNA after therapy, HPV-positive patients who did had dramatically poorer recurrence-free survival (55% vs. 88%; adjusted hazard ratio, 3.72; P  less than .001) and overall survival (68% vs. 95%; adjusted hazard ratio, 6.61; P = .003).

In contrast, persistence of nontumor-type HPV DNA did not predict these outcomes among either patients with HPV-positive tumors or patients with HPV-negative tumors.

“Analysis of tumor type HPV DNA has considerable promise as a biomarker for treatment response and risk of progression,” Dr. Gillison and coinvestigators maintain.

“Our data suggest that a subset of patients with HPV-positive HNSCC at high-risk for locoregional recurrence can be identified by detection of persistent, oral HPV after treatment. However, the clinical utility may be constrained by a need to identify the tumor-type infection, a low-moderate positive predictive value for recurrence, and weak associations with risk of distant metastases,” they conclude. “Ongoing studies will evaluate whether multiplexed detection of plasma HPV DNA can improve these limitations.”

Dr. Gillison disclosed consulting for Roche Holding AG, Bristol-Myers Squibb, Merck & Co Inc., Celgene Corporation, Amgen, AstraZeneca, Rakuten Aspyrian Inc. (now known as Rakuten Medical), EMD Serono Inc., NewLink Genetics Corporation, and Genocea Biosciences. The study was supported by the Oral Cancer Foundation and The Ohio State University Comprehensive Cancer Center. Dr. Gillison is a Cancer Prevention and Research Institute of Texas Scholar.

SOURCE: Fakhry C et al. JAMA Oncol. 2019 May 2. doi: 10.1001/jamaoncol.2019.0439.

Performing fecal microbiota transplantation in medically uncompromised obese individuals did not result in weight loss nor an increase of the gut hormone glucagon-like peptide 1 (GLP-1) at 12 weeks, but it did contribute to a decrease in primary bile acids as well as alterations in the stool microbiome.

“Currently, fecal microbiota transplantation [FMT] can only be performed clinically in the US to treat recurrent Clostridium difficile infection,” lead study author Jessica R. Allegretti, MD, MPH, said during a media briefing in advance of the annual Digestive Disease Week.

“However, there is ongoing research to find out whether FMT works for other health conditions such as obesity, a condition which affects millions of people worldwide. [It’s] a condition that also increases the risk of developing many other illnesses, including diabetes, heart disease, and certain cancers. In my clinical practice, we regularly see patients who have not yet developed some of these other conditions related to obesity, but really do have difficulty losing weight. Through our research we wanted to focus on a population we call the medically uncompromised obese, and understand if FMT might be a viable treatment option for them,” she said.

Dr. Allegretti, director of the fecal microbiota transplant program at Brigham and Women’s Hospital, Boston, conducted a parallel study of 22 patients with a body mass index of 35 kg/m² or higher who were metabolically healthy – defined as having no type 2 diabetes, nonalcoholic steatohepatitis (NASH), or metabolic syndrome. They randomized study participants 1:1 to receive 30 FMT capsules followed by two doses of 12 capsules over a 12-week period, or identical placebo capsules. A single healthy lean donor with a BMI of 17 kg/m² was used.

The researchers assessed patients with a mixed meal tolerance test at baseline, week 6, and week 12 post-FMT, at which biomarkers GLP-1 and leptin were measured. Stool was collected at baseline and at one, four, six, eight, and 12 weeks post-FMT. The primary outcomes were safety and change in the area under the curve for GLP-1 at 12 weeks compared to baseline. Secondary endpoints include gut microbiome profiles and diversity as well as bile acid profiles at 12 weeks post FMT. Additional endpoints include a decrease in BMI and waist circumference at week 12. Standard stool microbiome and bile acid analysis was performed.

The mean age of the patients at baseline was 43 years, and their mean BMI was 41 kg/m². Between baseline and week 12, the research observed no increase of GLP-1 in either group, while the change in leptin revealed an increase in the placebo group only (P less than .001). At week 12, no early changes in BMI were noted in either group (P = .51). No serious adverse events occurred in either arm.

Dr. Allegretti and her colleagues observed global signals of donor community engraftment following FMT, including an increase in alpha diversity and increased similarity to stool samples from the FMT donor – trends that were not observed in the placebo arm. In addition, bile acid analysis suggested a sustained decrease in taurocholic acid in the FMT arm, comparable with the donor – an effect that was not seen in the placebo arm. “We know that what leads to the germination of C. diff. spores is brought out by bile acids,” she said. “That’s one of the critical components of pathogenesis in that disease. My group has been able to show that after FMT, you regain bile acid homeostasis.”

Dr. Allegretti concluded her remarks by noting that the current study “adds an encouraging first step in trying to understand the role that the gut microbiome is playing in the pathogenesis of medically uncompromised obese patients. As a next step, we plan to seek more sensitive measures of GLP-1, as well as conduct additional research into varied doses of FMT capsules, as well as potentially investigating other microbial pathways to better understand the role the microbiome is playing in obesity.”

Somerville, Mass.–based Finch Therapeutics provided funding for the research. Dr. Allegretti reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: Allegretti J et al. DDW 2019. Abstract 621.

Performing fecal microbiota transplantation in medically uncompromised obese individuals did not result in weight loss nor an increase of the gut hormone glucagon-like peptide 1 (GLP-1) at 12 weeks, but it did contribute to a decrease in primary bile acids as well as alterations in the stool microbiome.

“Currently, fecal microbiota transplantation [FMT] can only be performed clinically in the US to treat recurrent Clostridium difficile infection,” lead study author Jessica R. Allegretti, MD, MPH, said during a media briefing in advance of the annual Digestive Disease Week.

“However, there is ongoing research to find out whether FMT works for other health conditions such as obesity, a condition which affects millions of people worldwide. [It’s] a condition that also increases the risk of developing many other illnesses, including diabetes, heart disease, and certain cancers. In my clinical practice, we regularly see patients who have not yet developed some of these other conditions related to obesity, but really do have difficulty losing weight. Through our research we wanted to focus on a population we call the medically uncompromised obese, and understand if FMT might be a viable treatment option for them,” she said.

Dr. Allegretti, director of the fecal microbiota transplant program at Brigham and Women’s Hospital, Boston, conducted a parallel study of 22 patients with a body mass index of 35 kg/m² or higher who were metabolically healthy – defined as having no type 2 diabetes, nonalcoholic steatohepatitis (NASH), or metabolic syndrome. They randomized study participants 1:1 to receive 30 FMT capsules followed by two doses of 12 capsules over a 12-week period, or identical placebo capsules. A single healthy lean donor with a BMI of 17 kg/m² was used.

The researchers assessed patients with a mixed meal tolerance test at baseline, week 6, and week 12 post-FMT, at which biomarkers GLP-1 and leptin were measured. Stool was collected at baseline and at one, four, six, eight, and 12 weeks post-FMT. The primary outcomes were safety and change in the area under the curve for GLP-1 at 12 weeks compared to baseline. Secondary endpoints include gut microbiome profiles and diversity as well as bile acid profiles at 12 weeks post FMT. Additional endpoints include a decrease in BMI and waist circumference at week 12. Standard stool microbiome and bile acid analysis was performed.

The mean age of the patients at baseline was 43 years, and their mean BMI was 41 kg/m². Between baseline and week 12, the research observed no increase of GLP-1 in either group, while the change in leptin revealed an increase in the placebo group only (P less than .001). At week 12, no early changes in BMI were noted in either group (P = .51). No serious adverse events occurred in either arm.

Dr. Allegretti and her colleagues observed global signals of donor community engraftment following FMT, including an increase in alpha diversity and increased similarity to stool samples from the FMT donor – trends that were not observed in the placebo arm. In addition, bile acid analysis suggested a sustained decrease in taurocholic acid in the FMT arm, comparable with the donor – an effect that was not seen in the placebo arm. “We know that what leads to the germination of C. diff. spores is brought out by bile acids,” she said. “That’s one of the critical components of pathogenesis in that disease. My group has been able to show that after FMT, you regain bile acid homeostasis.”

Dr. Allegretti concluded her remarks by noting that the current study “adds an encouraging first step in trying to understand the role that the gut microbiome is playing in the pathogenesis of medically uncompromised obese patients. As a next step, we plan to seek more sensitive measures of GLP-1, as well as conduct additional research into varied doses of FMT capsules, as well as potentially investigating other microbial pathways to better understand the role the microbiome is playing in obesity.”

Somerville, Mass.–based Finch Therapeutics provided funding for the research. Dr. Allegretti reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: Allegretti J et al. DDW 2019. Abstract 621.

Performing fecal microbiota transplantation in medically uncompromised obese individuals did not result in weight loss nor an increase of the gut hormone glucagon-like peptide 1 (GLP-1) at 12 weeks, but it did contribute to a decrease in primary bile acids as well as alterations in the stool microbiome.

“Currently, fecal microbiota transplantation [FMT] can only be performed clinically in the US to treat recurrent Clostridium difficile infection,” lead study author Jessica R. Allegretti, MD, MPH, said during a media briefing in advance of the annual Digestive Disease Week.

“However, there is ongoing research to find out whether FMT works for other health conditions such as obesity, a condition which affects millions of people worldwide. [It’s] a condition that also increases the risk of developing many other illnesses, including diabetes, heart disease, and certain cancers. In my clinical practice, we regularly see patients who have not yet developed some of these other conditions related to obesity, but really do have difficulty losing weight. Through our research we wanted to focus on a population we call the medically uncompromised obese, and understand if FMT might be a viable treatment option for them,” she said.

Dr. Allegretti, director of the fecal microbiota transplant program at Brigham and Women’s Hospital, Boston, conducted a parallel study of 22 patients with a body mass index of 35 kg/m² or higher who were metabolically healthy – defined as having no type 2 diabetes, nonalcoholic steatohepatitis (NASH), or metabolic syndrome. They randomized study participants 1:1 to receive 30 FMT capsules followed by two doses of 12 capsules over a 12-week period, or identical placebo capsules. A single healthy lean donor with a BMI of 17 kg/m² was used.

The researchers assessed patients with a mixed meal tolerance test at baseline, week 6, and week 12 post-FMT, at which biomarkers GLP-1 and leptin were measured. Stool was collected at baseline and at one, four, six, eight, and 12 weeks post-FMT. The primary outcomes were safety and change in the area under the curve for GLP-1 at 12 weeks compared to baseline. Secondary endpoints include gut microbiome profiles and diversity as well as bile acid profiles at 12 weeks post FMT. Additional endpoints include a decrease in BMI and waist circumference at week 12. Standard stool microbiome and bile acid analysis was performed.

The mean age of the patients at baseline was 43 years, and their mean BMI was 41 kg/m². Between baseline and week 12, the research observed no increase of GLP-1 in either group, while the change in leptin revealed an increase in the placebo group only (P less than .001). At week 12, no early changes in BMI were noted in either group (P = .51). No serious adverse events occurred in either arm.

Dr. Allegretti and her colleagues observed global signals of donor community engraftment following FMT, including an increase in alpha diversity and increased similarity to stool samples from the FMT donor – trends that were not observed in the placebo arm. In addition, bile acid analysis suggested a sustained decrease in taurocholic acid in the FMT arm, comparable with the donor – an effect that was not seen in the placebo arm. “We know that what leads to the germination of C. diff. spores is brought out by bile acids,” she said. “That’s one of the critical components of pathogenesis in that disease. My group has been able to show that after FMT, you regain bile acid homeostasis.”

Dr. Allegretti concluded her remarks by noting that the current study “adds an encouraging first step in trying to understand the role that the gut microbiome is playing in the pathogenesis of medically uncompromised obese patients. As a next step, we plan to seek more sensitive measures of GLP-1, as well as conduct additional research into varied doses of FMT capsules, as well as potentially investigating other microbial pathways to better understand the role the microbiome is playing in obesity.”

Somerville, Mass.–based Finch Therapeutics provided funding for the research. Dr. Allegretti reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: Allegretti J et al. DDW 2019. Abstract 621.

LOS ANGELES – The dose of testosterone required to maintain a therapeutic level in transgender men is not correlated with body mass index but does decrease with age, results from a single-center study have shown.

“At this point, there are limited data regarding the dosing of testosterone in relation to age and BMI, which is what makes our work unique,” one of the study authors, Sushmitha Echt, MD, said in an interview following the annual scientific and clinical congress of the American Association of Clinical Endocrinologists.

“Although we have guidelines regarding initiating hormonal therapy for transgender patients, such as the Endocrine Society’s Clinical Practice Guidelines from 2017, we do not have much data regarding the optimal dosing of testosterone in transgender men. We hope that with more research, we will have more data to drive our treatment decisions for our transgender patients.”

Dr. Echt, an endocrinology fellow at North Shore University Hospital, Manhassett, NY, and her colleague, Aren Skolnick, DO, retrospectively evaluated 40 transgender men who were treated at the medical center between July 1, 2014 and July 1, 2018. They performed univariate and multivariate mixed-model analyses to determine the relationship between testosterone dose, age, and body mass index (BMI), and Cox regression analysis to determine the relationship between time to development of each physical attribute, testosterone dose, and route of administration.

The patients ranged in age from 18 to 54 years, and their mean baseline age was 25 years. At the time of their first visit, 32 of the patients were on intramuscular testosterone, four were on subcutaneous testosterone, and five were on the transdermal form.

By the end of the study, 28 patients remained on intramuscular testosterone, six were on the subcutaneous form, five were on the transdermal form, and one had transitioned to testosterone pellets. The majority of patients (37) became therapeutic during the course of the study, and the average therapeutic testosterone level was 551.7 ng/dL.

During an average follow-up time of one year, the researchers observed no correlation between testosterone dose and BMI. However, they found a negative correlation between testosterone dose and age, with or without adjustment for BMI (P = .016 and P = .020, respectively). Adjusted for BMI, the dose decreased by 2.0 mg for every one-year increase in age.

A subgroup analysis of the new patients again revealed a negative correlation between testosterone dose and age, with or without adjustment for BMI (P = .013 and P = .019, respectively). Adjusted for BMI, the dose decreased by 2.5 mg for every one-year increase in age.

Subgroup analysis of the patients already on testosterone therapy revealed no association between testosterone dose, age, and BMI. Among the new patients, no association was observed between time to development of each physical attribute and testosterone dose or route of administration. Among the new patients, 73% reported hair growth (mean time, 89 days), deepening of voice (51 days), and cessation of menses (136 days), and 59% reported clitoromegaly (51 days).

“The finding that surprised us the most is that the testosterone dose needed to maintain a therapeutic testosterone level in transgender men is not related to BMI,” Dr. Echt said. “Some medications are dosed based on body weight, and it was surprising to us that testosterone dosing was not related to weight in kilograms or BMI. Although the findings from our project suggest that the testosterone dose needed for hormonal therapy for transgender men may decrease with older age, further research and larger studies are needed in this field to help guide management of transgender patients.”

Dr. Echt acknowledged certain limitations of the study, including its small sample size. “At this point, our population of transgender patients has been increasing in our practice,” she said. “In the future, we would like to build upon our study by including more patients in our retrospective analysis and then stratify the results by mode of administration of testosterone.”

The researchers reported having no financial disclosures.

dbrunk@mdedge.com

LOS ANGELES – The dose of testosterone required to maintain a therapeutic level in transgender men is not correlated with body mass index but does decrease with age, results from a single-center study have shown.

“At this point, there are limited data regarding the dosing of testosterone in relation to age and BMI, which is what makes our work unique,” one of the study authors, Sushmitha Echt, MD, said in an interview following the annual scientific and clinical congress of the American Association of Clinical Endocrinologists.

“Although we have guidelines regarding initiating hormonal therapy for transgender patients, such as the Endocrine Society’s Clinical Practice Guidelines from 2017, we do not have much data regarding the optimal dosing of testosterone in transgender men. We hope that with more research, we will have more data to drive our treatment decisions for our transgender patients.”

Dr. Echt, an endocrinology fellow at North Shore University Hospital, Manhassett, NY, and her colleague, Aren Skolnick, DO, retrospectively evaluated 40 transgender men who were treated at the medical center between July 1, 2014 and July 1, 2018. They performed univariate and multivariate mixed-model analyses to determine the relationship between testosterone dose, age, and body mass index (BMI), and Cox regression analysis to determine the relationship between time to development of each physical attribute, testosterone dose, and route of administration.

The patients ranged in age from 18 to 54 years, and their mean baseline age was 25 years. At the time of their first visit, 32 of the patients were on intramuscular testosterone, four were on subcutaneous testosterone, and five were on the transdermal form.

By the end of the study, 28 patients remained on intramuscular testosterone, six were on the subcutaneous form, five were on the transdermal form, and one had transitioned to testosterone pellets. The majority of patients (37) became therapeutic during the course of the study, and the average therapeutic testosterone level was 551.7 ng/dL.

During an average follow-up time of one year, the researchers observed no correlation between testosterone dose and BMI. However, they found a negative correlation between testosterone dose and age, with or without adjustment for BMI (P = .016 and P = .020, respectively). Adjusted for BMI, the dose decreased by 2.0 mg for every one-year increase in age.

A subgroup analysis of the new patients again revealed a negative correlation between testosterone dose and age, with or without adjustment for BMI (P = .013 and P = .019, respectively). Adjusted for BMI, the dose decreased by 2.5 mg for every one-year increase in age.

Subgroup analysis of the patients already on testosterone therapy revealed no association between testosterone dose, age, and BMI. Among the new patients, no association was observed between time to development of each physical attribute and testosterone dose or route of administration. Among the new patients, 73% reported hair growth (mean time, 89 days), deepening of voice (51 days), and cessation of menses (136 days), and 59% reported clitoromegaly (51 days).

“The finding that surprised us the most is that the testosterone dose needed to maintain a therapeutic testosterone level in transgender men is not related to BMI,” Dr. Echt said. “Some medications are dosed based on body weight, and it was surprising to us that testosterone dosing was not related to weight in kilograms or BMI. Although the findings from our project suggest that the testosterone dose needed for hormonal therapy for transgender men may decrease with older age, further research and larger studies are needed in this field to help guide management of transgender patients.”

Dr. Echt acknowledged certain limitations of the study, including its small sample size. “At this point, our population of transgender patients has been increasing in our practice,” she said. “In the future, we would like to build upon our study by including more patients in our retrospective analysis and then stratify the results by mode of administration of testosterone.”

The researchers reported having no financial disclosures.

dbrunk@mdedge.com

LOS ANGELES – The dose of testosterone required to maintain a therapeutic level in transgender men is not correlated with body mass index but does decrease with age, results from a single-center study have shown.

“At this point, there are limited data regarding the dosing of testosterone in relation to age and BMI, which is what makes our work unique,” one of the study authors, Sushmitha Echt, MD, said in an interview following the annual scientific and clinical congress of the American Association of Clinical Endocrinologists.

“Although we have guidelines regarding initiating hormonal therapy for transgender patients, such as the Endocrine Society’s Clinical Practice Guidelines from 2017, we do not have much data regarding the optimal dosing of testosterone in transgender men. We hope that with more research, we will have more data to drive our treatment decisions for our transgender patients.”

Dr. Echt, an endocrinology fellow at North Shore University Hospital, Manhassett, NY, and her colleague, Aren Skolnick, DO, retrospectively evaluated 40 transgender men who were treated at the medical center between July 1, 2014 and July 1, 2018. They performed univariate and multivariate mixed-model analyses to determine the relationship between testosterone dose, age, and body mass index (BMI), and Cox regression analysis to determine the relationship between time to development of each physical attribute, testosterone dose, and route of administration.

The patients ranged in age from 18 to 54 years, and their mean baseline age was 25 years. At the time of their first visit, 32 of the patients were on intramuscular testosterone, four were on subcutaneous testosterone, and five were on the transdermal form.

By the end of the study, 28 patients remained on intramuscular testosterone, six were on the subcutaneous form, five were on the transdermal form, and one had transitioned to testosterone pellets. The majority of patients (37) became therapeutic during the course of the study, and the average therapeutic testosterone level was 551.7 ng/dL.

During an average follow-up time of one year, the researchers observed no correlation between testosterone dose and BMI. However, they found a negative correlation between testosterone dose and age, with or without adjustment for BMI (P = .016 and P = .020, respectively). Adjusted for BMI, the dose decreased by 2.0 mg for every one-year increase in age.

A subgroup analysis of the new patients again revealed a negative correlation between testosterone dose and age, with or without adjustment for BMI (P = .013 and P = .019, respectively). Adjusted for BMI, the dose decreased by 2.5 mg for every one-year increase in age.

Subgroup analysis of the patients already on testosterone therapy revealed no association between testosterone dose, age, and BMI. Among the new patients, no association was observed between time to development of each physical attribute and testosterone dose or route of administration. Among the new patients, 73% reported hair growth (mean time, 89 days), deepening of voice (51 days), and cessation of menses (136 days), and 59% reported clitoromegaly (51 days).

“The finding that surprised us the most is that the testosterone dose needed to maintain a therapeutic testosterone level in transgender men is not related to BMI,” Dr. Echt said. “Some medications are dosed based on body weight, and it was surprising to us that testosterone dosing was not related to weight in kilograms or BMI. Although the findings from our project suggest that the testosterone dose needed for hormonal therapy for transgender men may decrease with older age, further research and larger studies are needed in this field to help guide management of transgender patients.”

Dr. Echt acknowledged certain limitations of the study, including its small sample size. “At this point, our population of transgender patients has been increasing in our practice,” she said. “In the future, we would like to build upon our study by including more patients in our retrospective analysis and then stratify the results by mode of administration of testosterone.”

The researchers reported having no financial disclosures.

dbrunk@mdedge.com

MILWAUKEE – Exposure to green light therapy may significantly reduce pain in patients with chronic pain conditions, including migraine and fibromyalgia, an expert reported at the scientific meeting of the American Pain Society.

“There’s a subset of patients in every clinic whose pain doesn’t respond to medical therapies,” said Mohab M. Ibrahim, MD, PhD. “I always wonder what could be done with these patients.”

Dr. Ibrahim, who directs the chronic pain clinic at the University of Arizona, Tucson, walked attendees through an experimental process that began with an observation and has led to human clinical trials of green light therapy.

“Despite being a pharmacologist, I’m really interested in nonpharmacologic methods to manage pain,” he said.

Dr. Ibrahim said the idea for green light therapy came to him when he was speaking with his brother, who experiences migraines. His brother said his headaches were alleviated with time outside, in his back yard, or in one of the many parks in the city where he lives.

Knowing that spending time in nature had salutary effects in general, Dr. Ibrahim, an anesthesiologist and pain management specialist, wondered whether exposure to the sort of light found in nature, with blue skies and the green of a tree canopy, could help control pain.

To begin with, Dr. Ibrahim said, “the question was, do different colors have different behavior aspects on animals?”

Dr. Ibrahim and his collaborators exposed rats to light of various wavelengths across the color spectrum, as well as white and infrared light. They found that the rats who were exposed to blue and green light had a significantly longer latency period before withdrawing their hands and feet from a painfully hot stimulus, showing an antinociceptive effect with these wavelengths similar to that seen with analgesic medication.

“At that point, I decided to pursue green light and to forego blue, because blue can change the circadian rhythm,” said Dr. Ibrahim, adding, “Most pain patients have sleep disturbances to begin with, so to compound that issue is probably not a good idea.”

Dr. Ibrahim and his colleagues wanted to determine whether the analgesic effect had to do with rats seeing the green light or just being exposed to the light. Accordingly, the researchers fitted some rats with tiny, specially manufactured, completely opaque contact lenses. As a control, the researchers applied completely clear contact lenses to another group of rats. “I can’t tell you how many times we got bit, but by the end we got pretty good at it,” said Dr. Ibrahim.

Only the rats with clear lenses had prolonged latency in paw withdrawal to a noxious stimulus with green light exposure; for the rats with the blackout contact lenses, the effect was gone, “suggesting that the visual system is essential in mediating this effect,” noted Dr. Ibrahim.

This series of experiments also showed durable effects of green light exposure. In addition, the analgesic effect of green light did not wane over time, and higher “doses” were not required to achieve the same effect (as is the case with opioids, for example) (Pain. 2017 Feb;158[2]:347-60).

Clues to the mechanism of action came when Dr. Ibrahim and his colleagues administered naloxone to green light-exposed rats. “Naloxone reversed the effects of the green light, suggesting that the endogenous opioid system plays a role in this,” he said, adding that enkephalins were increased two- to threefold in the green light-exposed rats’ spinal cords, and astrocyte activation was reduced as well.

Similar experiments using a rat model of neuropathic pain showed a reversal of pain symptoms with green light exposure, offering promise that green light therapy could be effective in alleviating chronic as well as acute pain.

Moving to humans, Dr. Ibrahim enrolled a small group of individuals from his pain clinic who had refractory migraine into a study that exposed them either to white light or to green light. “These are patients who have failed everything…They have come to me, but I have nothing else to offer them,” he said.

The study had a crossover design. Participants in the small study had baseline pain scores of about 8/10, with no significant drop in pain with white light exposure. However, when the white light patients were crossed over to green light exposure, pain scores dropped to about 3/10. “That’s a greater than 50% reduction in the intensity of their migraine.”

Similar effects were seen in patients with fibromyalgia: “It was exactly the same story…When patients with white light exposure were crossed over [to green light], they had significant reductions in pain,” said Dr. Ibrahim.

“Their opioid use also decreased,” said Dr. Ibrahim. Medication use dropped in green light-exposed patients with migraine and fibromyalgia from an aggregate of about 280 morphine milligram equivalents (MME) to about 150 MME by the end of the study. The small size of the pilot study meant that those differences were not statistically significant.

“A multimodal approach to manage chronic pain patients is probably the best approach that we have so far,” said Dr. Ibrahim. An ongoing clinical trial randomizes patients with chronic pain to white light or green light therapy for two hours daily for 10 weeks, tracking pain scores, medication, and quality of life measures.

Future directions, said Dr. Ibrahim, include a study of the efficacy of green light therapy for patients with interstitial cystitis; another study will investigate green light for postoperative pain control. Sleep may also be improved by green light exposure, and Dr. Ibrahim and his colleagues plan to study this as well.

Dr. Ibrahim reported that his research was supported by the National Institutes of Health. He reported that he had no relevant conflicts of interest.

koakes@mdedge.com

MILWAUKEE – Exposure to green light therapy may significantly reduce pain in patients with chronic pain conditions, including migraine and fibromyalgia, an expert reported at the scientific meeting of the American Pain Society.

“There’s a subset of patients in every clinic whose pain doesn’t respond to medical therapies,” said Mohab M. Ibrahim, MD, PhD. “I always wonder what could be done with these patients.”

Dr. Ibrahim, who directs the chronic pain clinic at the University of Arizona, Tucson, walked attendees through an experimental process that began with an observation and has led to human clinical trials of green light therapy.

“Despite being a pharmacologist, I’m really interested in nonpharmacologic methods to manage pain,” he said.

Dr. Ibrahim said the idea for green light therapy came to him when he was speaking with his brother, who experiences migraines. His brother said his headaches were alleviated with time outside, in his back yard, or in one of the many parks in the city where he lives.

Knowing that spending time in nature had salutary effects in general, Dr. Ibrahim, an anesthesiologist and pain management specialist, wondered whether exposure to the sort of light found in nature, with blue skies and the green of a tree canopy, could help control pain.

To begin with, Dr. Ibrahim said, “the question was, do different colors have different behavior aspects on animals?”

Dr. Ibrahim and his collaborators exposed rats to light of various wavelengths across the color spectrum, as well as white and infrared light. They found that the rats who were exposed to blue and green light had a significantly longer latency period before withdrawing their hands and feet from a painfully hot stimulus, showing an antinociceptive effect with these wavelengths similar to that seen with analgesic medication.

“At that point, I decided to pursue green light and to forego blue, because blue can change the circadian rhythm,” said Dr. Ibrahim, adding, “Most pain patients have sleep disturbances to begin with, so to compound that issue is probably not a good idea.”

Dr. Ibrahim and his colleagues wanted to determine whether the analgesic effect had to do with rats seeing the green light or just being exposed to the light. Accordingly, the researchers fitted some rats with tiny, specially manufactured, completely opaque contact lenses. As a control, the researchers applied completely clear contact lenses to another group of rats. “I can’t tell you how many times we got bit, but by the end we got pretty good at it,” said Dr. Ibrahim.

Only the rats with clear lenses had prolonged latency in paw withdrawal to a noxious stimulus with green light exposure; for the rats with the blackout contact lenses, the effect was gone, “suggesting that the visual system is essential in mediating this effect,” noted Dr. Ibrahim.

This series of experiments also showed durable effects of green light exposure. In addition, the analgesic effect of green light did not wane over time, and higher “doses” were not required to achieve the same effect (as is the case with opioids, for example) (Pain. 2017 Feb;158[2]:347-60).

Clues to the mechanism of action came when Dr. Ibrahim and his colleagues administered naloxone to green light-exposed rats. “Naloxone reversed the effects of the green light, suggesting that the endogenous opioid system plays a role in this,” he said, adding that enkephalins were increased two- to threefold in the green light-exposed rats’ spinal cords, and astrocyte activation was reduced as well.

Similar experiments using a rat model of neuropathic pain showed a reversal of pain symptoms with green light exposure, offering promise that green light therapy could be effective in alleviating chronic as well as acute pain.

Moving to humans, Dr. Ibrahim enrolled a small group of individuals from his pain clinic who had refractory migraine into a study that exposed them either to white light or to green light. “These are patients who have failed everything…They have come to me, but I have nothing else to offer them,” he said.

The study had a crossover design. Participants in the small study had baseline pain scores of about 8/10, with no significant drop in pain with white light exposure. However, when the white light patients were crossed over to green light exposure, pain scores dropped to about 3/10. “That’s a greater than 50% reduction in the intensity of their migraine.”

Similar effects were seen in patients with fibromyalgia: “It was exactly the same story…When patients with white light exposure were crossed over [to green light], they had significant reductions in pain,” said Dr. Ibrahim.

“Their opioid use also decreased,” said Dr. Ibrahim. Medication use dropped in green light-exposed patients with migraine and fibromyalgia from an aggregate of about 280 morphine milligram equivalents (MME) to about 150 MME by the end of the study. The small size of the pilot study meant that those differences were not statistically significant.

“A multimodal approach to manage chronic pain patients is probably the best approach that we have so far,” said Dr. Ibrahim. An ongoing clinical trial randomizes patients with chronic pain to white light or green light therapy for two hours daily for 10 weeks, tracking pain scores, medication, and quality of life measures.

Future directions, said Dr. Ibrahim, include a study of the efficacy of green light therapy for patients with interstitial cystitis; another study will investigate green light for postoperative pain control. Sleep may also be improved by green light exposure, and Dr. Ibrahim and his colleagues plan to study this as well.

Dr. Ibrahim reported that his research was supported by the National Institutes of Health. He reported that he had no relevant conflicts of interest.

koakes@mdedge.com

MILWAUKEE – Exposure to green light therapy may significantly reduce pain in patients with chronic pain conditions, including migraine and fibromyalgia, an expert reported at the scientific meeting of the American Pain Society.

“There’s a subset of patients in every clinic whose pain doesn’t respond to medical therapies,” said Mohab M. Ibrahim, MD, PhD. “I always wonder what could be done with these patients.”

Dr. Ibrahim, who directs the chronic pain clinic at the University of Arizona, Tucson, walked attendees through an experimental process that began with an observation and has led to human clinical trials of green light therapy.

“Despite being a pharmacologist, I’m really interested in nonpharmacologic methods to manage pain,” he said.

Dr. Ibrahim said the idea for green light therapy came to him when he was speaking with his brother, who experiences migraines. His brother said his headaches were alleviated with time outside, in his back yard, or in one of the many parks in the city where he lives.

Knowing that spending time in nature had salutary effects in general, Dr. Ibrahim, an anesthesiologist and pain management specialist, wondered whether exposure to the sort of light found in nature, with blue skies and the green of a tree canopy, could help control pain.

To begin with, Dr. Ibrahim said, “the question was, do different colors have different behavior aspects on animals?”

Dr. Ibrahim and his collaborators exposed rats to light of various wavelengths across the color spectrum, as well as white and infrared light. They found that the rats who were exposed to blue and green light had a significantly longer latency period before withdrawing their hands and feet from a painfully hot stimulus, showing an antinociceptive effect with these wavelengths similar to that seen with analgesic medication.

“At that point, I decided to pursue green light and to forego blue, because blue can change the circadian rhythm,” said Dr. Ibrahim, adding, “Most pain patients have sleep disturbances to begin with, so to compound that issue is probably not a good idea.”

Dr. Ibrahim and his colleagues wanted to determine whether the analgesic effect had to do with rats seeing the green light or just being exposed to the light. Accordingly, the researchers fitted some rats with tiny, specially manufactured, completely opaque contact lenses. As a control, the researchers applied completely clear contact lenses to another group of rats. “I can’t tell you how many times we got bit, but by the end we got pretty good at it,” said Dr. Ibrahim.

Only the rats with clear lenses had prolonged latency in paw withdrawal to a noxious stimulus with green light exposure; for the rats with the blackout contact lenses, the effect was gone, “suggesting that the visual system is essential in mediating this effect,” noted Dr. Ibrahim.

This series of experiments also showed durable effects of green light exposure. In addition, the analgesic effect of green light did not wane over time, and higher “doses” were not required to achieve the same effect (as is the case with opioids, for example) (Pain. 2017 Feb;158[2]:347-60).

Clues to the mechanism of action came when Dr. Ibrahim and his colleagues administered naloxone to green light-exposed rats. “Naloxone reversed the effects of the green light, suggesting that the endogenous opioid system plays a role in this,” he said, adding that enkephalins were increased two- to threefold in the green light-exposed rats’ spinal cords, and astrocyte activation was reduced as well.

Similar experiments using a rat model of neuropathic pain showed a reversal of pain symptoms with green light exposure, offering promise that green light therapy could be effective in alleviating chronic as well as acute pain.

Moving to humans, Dr. Ibrahim enrolled a small group of individuals from his pain clinic who had refractory migraine into a study that exposed them either to white light or to green light. “These are patients who have failed everything…They have come to me, but I have nothing else to offer them,” he said.

The study had a crossover design. Participants in the small study had baseline pain scores of about 8/10, with no significant drop in pain with white light exposure. However, when the white light patients were crossed over to green light exposure, pain scores dropped to about 3/10. “That’s a greater than 50% reduction in the intensity of their migraine.”

Similar effects were seen in patients with fibromyalgia: “It was exactly the same story…When patients with white light exposure were crossed over [to green light], they had significant reductions in pain,” said Dr. Ibrahim.

“Their opioid use also decreased,” said Dr. Ibrahim. Medication use dropped in green light-exposed patients with migraine and fibromyalgia from an aggregate of about 280 morphine milligram equivalents (MME) to about 150 MME by the end of the study. The small size of the pilot study meant that those differences were not statistically significant.

“A multimodal approach to manage chronic pain patients is probably the best approach that we have so far,” said Dr. Ibrahim. An ongoing clinical trial randomizes patients with chronic pain to white light or green light therapy for two hours daily for 10 weeks, tracking pain scores, medication, and quality of life measures.

Future directions, said Dr. Ibrahim, include a study of the efficacy of green light therapy for patients with interstitial cystitis; another study will investigate green light for postoperative pain control. Sleep may also be improved by green light exposure, and Dr. Ibrahim and his colleagues plan to study this as well.

Dr. Ibrahim reported that his research was supported by the National Institutes of Health. He reported that he had no relevant conflicts of interest.

koakes@mdedge.com

LOS ANGELES – There is no consistent evidence to suggest that subclinical hypothyroidism is linked to an increased risk of incident breast, prostate, or colon cancer. The condition, however, may be linked to an increased risk of thyroid malignancy and to an increased risk of overall cancer mortality.

These findings come from the first systematic review to examine the effect of subclinical hypothyroidism on the risk of incident cancer and cancer mortality.

“Subclinical hypothyroidism is very prevalent,” lead study author Oriana Yu, MD, MSc, said in an interview at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “It affects up to 10% of people, yet at this time we are uncertain as to whether or not [we should] treat them. Most studies have focused on cardiovascular outcomes, because we know that thyroid hormone is very important in lipid metabolism.”

Dr. Yu, an endocrinologist at McGill University, Montreal, and her colleagues searched the Ovid MEDLINE database for articles published from the date of its inception until Nov. 13, 2017, and combined words related to thyroid function and cancer in their search. They limited the analysis to randomized clinical trials and cohort and case-control studies in which the thyroid dysfunction chronologically preceded the cancer incidence or mortality by at least one year.

Of the 180 records screened, 51 full-text articles were assessed for eligibility. Of those, nine met the criteria for systematic review – seven related to cancer risk and two to cancer mortality. The studies were deemed to be of good to medium quality, but six of the nine were cohort studies, the rest case-control studies. “We had hoped to do a systematic review and meta-analysis, but there was high heterogeneity in the studies, especially in terms of different risk measures and outcomes reported,” Dr. Yu said. “As a result, we were not able to perform a meta-analysis.”

The researchers found that the studies had inconsistent findings when it came to the impact of subclinical hypothyroidism on the risk of breast, prostate, and colon cancer. For example, one prospective cohort study of 2,738 patients found no association between subclinical hypothyroidism and the risk of breast cancer (odds ratio, 1.9; 95% confidence interval, 0.8-4.9; Thyroid. 2005;15[11]:1253-9). Women with breast cancer, however, were more likely to have thyroid autoantibodies.

Meanwhile, a case-control study of 1,201 men found that those with elevated TSH levels had a decreased risk of prostate cancer (OR, 0.71; 95% CI, 0.47-1.06; PLoS One. 2012 Oct 30. doi: 10.1371/journal.pone.0047730). “That was a bit surprising to us,” Dr. Yu said. In addition, a nested case-control study of 103,044 patients found that subclinical hypothyroidism was linked to an increased risk for colon cancer (OR, 1.16; 95% CI, 1.08-1.24; J Natl Cancer Inst. 2015 Apr 8. doi: 10.1093/jnci/djv084).

Of the two studies that focused on cancer mortality, one retrospective cohort analysis of 4,735 patients showed that treatment of subclinical hypothyroidism was associated with a decreased risk of cancer mortality in those aged 40-70 years (hazard ratio, 0.59; 95% CI, 0.21-0.99; Arch Intern Med. 2012;172[10]:811-7). The other study, a retrospective cohort analysis of 115,746 patients, found that subclinical hypothyroidism was associated with an increased risk of cancer mortality (relative risk, 1.51; 95% CI, 1.06-2.15; PLoS One. 2015 Apr 1. doi: 10.1371/journal.pone.0122955).

“We need to interpret the cancer-related mortality findings with caution,” Dr. Yu said. “There’s concern about whether patients who are treated might be [generally] healthier or were less frail, compared with those who were not treated. Although these studies adjusted for a number of confounders, it may be difficult to measure and adjust for [those two] factors. That might explain the findings in the two studies on cancer-related mortality.”

Dr. Yu and two coauthors have received salary awards from the Fonds de recherche du Québec–Santé.

dbrunk@mdedge.com

LOS ANGELES – There is no consistent evidence to suggest that subclinical hypothyroidism is linked to an increased risk of incident breast, prostate, or colon cancer. The condition, however, may be linked to an increased risk of thyroid malignancy and to an increased risk of overall cancer mortality.

These findings come from the first systematic review to examine the effect of subclinical hypothyroidism on the risk of incident cancer and cancer mortality.

“Subclinical hypothyroidism is very prevalent,” lead study author Oriana Yu, MD, MSc, said in an interview at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “It affects up to 10% of people, yet at this time we are uncertain as to whether or not [we should] treat them. Most studies have focused on cardiovascular outcomes, because we know that thyroid hormone is very important in lipid metabolism.”

Dr. Yu, an endocrinologist at McGill University, Montreal, and her colleagues searched the Ovid MEDLINE database for articles published from the date of its inception until Nov. 13, 2017, and combined words related to thyroid function and cancer in their search. They limited the analysis to randomized clinical trials and cohort and case-control studies in which the thyroid dysfunction chronologically preceded the cancer incidence or mortality by at least one year.

Of the 180 records screened, 51 full-text articles were assessed for eligibility. Of those, nine met the criteria for systematic review – seven related to cancer risk and two to cancer mortality. The studies were deemed to be of good to medium quality, but six of the nine were cohort studies, the rest case-control studies. “We had hoped to do a systematic review and meta-analysis, but there was high heterogeneity in the studies, especially in terms of different risk measures and outcomes reported,” Dr. Yu said. “As a result, we were not able to perform a meta-analysis.”

The researchers found that the studies had inconsistent findings when it came to the impact of subclinical hypothyroidism on the risk of breast, prostate, and colon cancer. For example, one prospective cohort study of 2,738 patients found no association between subclinical hypothyroidism and the risk of breast cancer (odds ratio, 1.9; 95% confidence interval, 0.8-4.9; Thyroid. 2005;15[11]:1253-9). Women with breast cancer, however, were more likely to have thyroid autoantibodies.

Meanwhile, a case-control study of 1,201 men found that those with elevated TSH levels had a decreased risk of prostate cancer (OR, 0.71; 95% CI, 0.47-1.06; PLoS One. 2012 Oct 30. doi: 10.1371/journal.pone.0047730). “That was a bit surprising to us,” Dr. Yu said. In addition, a nested case-control study of 103,044 patients found that subclinical hypothyroidism was linked to an increased risk for colon cancer (OR, 1.16; 95% CI, 1.08-1.24; J Natl Cancer Inst. 2015 Apr 8. doi: 10.1093/jnci/djv084).

Of the two studies that focused on cancer mortality, one retrospective cohort analysis of 4,735 patients showed that treatment of subclinical hypothyroidism was associated with a decreased risk of cancer mortality in those aged 40-70 years (hazard ratio, 0.59; 95% CI, 0.21-0.99; Arch Intern Med. 2012;172[10]:811-7). The other study, a retrospective cohort analysis of 115,746 patients, found that subclinical hypothyroidism was associated with an increased risk of cancer mortality (relative risk, 1.51; 95% CI, 1.06-2.15; PLoS One. 2015 Apr 1. doi: 10.1371/journal.pone.0122955).

“We need to interpret the cancer-related mortality findings with caution,” Dr. Yu said. “There’s concern about whether patients who are treated might be [generally] healthier or were less frail, compared with those who were not treated. Although these studies adjusted for a number of confounders, it may be difficult to measure and adjust for [those two] factors. That might explain the findings in the two studies on cancer-related mortality.”

Dr. Yu and two coauthors have received salary awards from the Fonds de recherche du Québec–Santé.

dbrunk@mdedge.com

LOS ANGELES – There is no consistent evidence to suggest that subclinical hypothyroidism is linked to an increased risk of incident breast, prostate, or colon cancer. The condition, however, may be linked to an increased risk of thyroid malignancy and to an increased risk of overall cancer mortality.

These findings come from the first systematic review to examine the effect of subclinical hypothyroidism on the risk of incident cancer and cancer mortality.

“Subclinical hypothyroidism is very prevalent,” lead study author Oriana Yu, MD, MSc, said in an interview at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “It affects up to 10% of people, yet at this time we are uncertain as to whether or not [we should] treat them. Most studies have focused on cardiovascular outcomes, because we know that thyroid hormone is very important in lipid metabolism.”

Dr. Yu, an endocrinologist at McGill University, Montreal, and her colleagues searched the Ovid MEDLINE database for articles published from the date of its inception until Nov. 13, 2017, and combined words related to thyroid function and cancer in their search. They limited the analysis to randomized clinical trials and cohort and case-control studies in which the thyroid dysfunction chronologically preceded the cancer incidence or mortality by at least one year.

Of the 180 records screened, 51 full-text articles were assessed for eligibility. Of those, nine met the criteria for systematic review – seven related to cancer risk and two to cancer mortality. The studies were deemed to be of good to medium quality, but six of the nine were cohort studies, the rest case-control studies. “We had hoped to do a systematic review and meta-analysis, but there was high heterogeneity in the studies, especially in terms of different risk measures and outcomes reported,” Dr. Yu said. “As a result, we were not able to perform a meta-analysis.”

The researchers found that the studies had inconsistent findings when it came to the impact of subclinical hypothyroidism on the risk of breast, prostate, and colon cancer. For example, one prospective cohort study of 2,738 patients found no association between subclinical hypothyroidism and the risk of breast cancer (odds ratio, 1.9; 95% confidence interval, 0.8-4.9; Thyroid. 2005;15[11]:1253-9). Women with breast cancer, however, were more likely to have thyroid autoantibodies.

Meanwhile, a case-control study of 1,201 men found that those with elevated TSH levels had a decreased risk of prostate cancer (OR, 0.71; 95% CI, 0.47-1.06; PLoS One. 2012 Oct 30. doi: 10.1371/journal.pone.0047730). “That was a bit surprising to us,” Dr. Yu said. In addition, a nested case-control study of 103,044 patients found that subclinical hypothyroidism was linked to an increased risk for colon cancer (OR, 1.16; 95% CI, 1.08-1.24; J Natl Cancer Inst. 2015 Apr 8. doi: 10.1093/jnci/djv084).

Of the two studies that focused on cancer mortality, one retrospective cohort analysis of 4,735 patients showed that treatment of subclinical hypothyroidism was associated with a decreased risk of cancer mortality in those aged 40-70 years (hazard ratio, 0.59; 95% CI, 0.21-0.99; Arch Intern Med. 2012;172[10]:811-7). The other study, a retrospective cohort analysis of 115,746 patients, found that subclinical hypothyroidism was associated with an increased risk of cancer mortality (relative risk, 1.51; 95% CI, 1.06-2.15; PLoS One. 2015 Apr 1. doi: 10.1371/journal.pone.0122955).

“We need to interpret the cancer-related mortality findings with caution,” Dr. Yu said. “There’s concern about whether patients who are treated might be [generally] healthier or were less frail, compared with those who were not treated. Although these studies adjusted for a number of confounders, it may be difficult to measure and adjust for [those two] factors. That might explain the findings in the two studies on cancer-related mortality.”

Dr. Yu and two coauthors have received salary awards from the Fonds de recherche du Québec–Santé.

dbrunk@mdedge.com

NEW ORLEANS – Researchers are organizing a master trial in an attempt to improve the treatment of pediatric acute myeloid leukemia (AML).

The Pediatric Acute Leukemia (PedAL) trial is an effort to collect data on all pediatric AML patients. The plan is to use these data to match patients to clinical trials, better understand pediatric AML, and bring new treatments to this population.

E. Anders Kolb, MD, of Nemours Center for Cancer and Blood Disorders in Wilmington, Del., described the initiative at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Dr. Kolb noted that several drugs have been approved to treat adult AML in the last 2 years, but most of them are not approved for use in children.

“What we see in childhood AML is a lot different than what we see in adult AML, and this challenges the paradigm that we have traditionally followed where we use the adult as the 'preclinical model' for pediatric AML,” he said. “I think we are learning more and more that children have a unique disease, unique targets, and need unique therapies.”

The PedAL initiative is an attempt to address these unique needs. PedAL is part of the Leukemia & Lymphoma Society’s Children’s Initiative, and it involves researchers from academic centers and the Children’s Oncology Group.

The PedAL initiative includes preclinical, biomarker, and informatics research, as well as the master clinical trial. The main goal of the master trial is to collect genomic, proteomic, metabolomic, flow cytometry, and clinical data from all children with AML and use these data to match patients to clinical trials.

The PedAL trial will leverage Project:EveryChild, an effort by the Children’s Oncology Group to study every child with cancer. Each child enrolled in this program has an identification number that follows the child through all clinical interventions.

The goal is that Project:EveryChild will capture all pediatric AML patients at the time of diagnosis, although patients can join the project at any time. Then, sequencing, clinical, and other data will be collected from these patients and stored in a data commons.

If patients relapse after standard or other therapies, the GEARBOX algorithm (genomic eligibility algorithm at relapse for better outcomes) can be used to match the patient’s information to clinical trial eligibility criteria and provide a list of appropriate trials.

Dr. Kolb said this process should reduce logistical barriers and get relapsed patients to trials more quickly. Additionally, the data collected through PedAL should help researchers design better trials for pediatric patients with relapsed AML.

“Ultimately, we’ll create the largest data set that will give us a better understanding of all the risks and benefits associated with postrelapse AML,” Dr. Kolb said. “No matter what happens to the patient, no matter where that patient enrolls, we’re going to have the capacity to collect data and present that data to the community for analysis for improved understanding of outcomes.”

Dr. Kolb and his colleagues are already working with researchers in Europe and Japan to make this a global effort and create an international data commons. In addition, the researchers are planning to collaborate with the pharmaceutical industry to unite efforts in pediatric AML drug development.

“We can’t just test drugs in kids because they worked in adults,” Dr. Kolb said. “We really need to maintain the integrity of the science and ask relevant questions in children but do so with the intent to make sure these drugs are licensed for use in kids.”

Dr. Kolb reported having no conflicts of interest. The PedAL trial is sponsored by the Leukemia & Lymphoma Society.

jensmith@mdedge.com

NEW ORLEANS – Researchers are organizing a master trial in an attempt to improve the treatment of pediatric acute myeloid leukemia (AML).

The Pediatric Acute Leukemia (PedAL) trial is an effort to collect data on all pediatric AML patients. The plan is to use these data to match patients to clinical trials, better understand pediatric AML, and bring new treatments to this population.

E. Anders Kolb, MD, of Nemours Center for Cancer and Blood Disorders in Wilmington, Del., described the initiative at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Dr. Kolb noted that several drugs have been approved to treat adult AML in the last 2 years, but most of them are not approved for use in children.

“What we see in childhood AML is a lot different than what we see in adult AML, and this challenges the paradigm that we have traditionally followed where we use the adult as the 'preclinical model' for pediatric AML,” he said. “I think we are learning more and more that children have a unique disease, unique targets, and need unique therapies.”

The PedAL initiative is an attempt to address these unique needs. PedAL is part of the Leukemia & Lymphoma Society’s Children’s Initiative, and it involves researchers from academic centers and the Children’s Oncology Group.

The PedAL initiative includes preclinical, biomarker, and informatics research, as well as the master clinical trial. The main goal of the master trial is to collect genomic, proteomic, metabolomic, flow cytometry, and clinical data from all children with AML and use these data to match patients to clinical trials.

The PedAL trial will leverage Project:EveryChild, an effort by the Children’s Oncology Group to study every child with cancer. Each child enrolled in this program has an identification number that follows the child through all clinical interventions.

The goal is that Project:EveryChild will capture all pediatric AML patients at the time of diagnosis, although patients can join the project at any time. Then, sequencing, clinical, and other data will be collected from these patients and stored in a data commons.

If patients relapse after standard or other therapies, the GEARBOX algorithm (genomic eligibility algorithm at relapse for better outcomes) can be used to match the patient’s information to clinical trial eligibility criteria and provide a list of appropriate trials.

Dr. Kolb said this process should reduce logistical barriers and get relapsed patients to trials more quickly. Additionally, the data collected through PedAL should help researchers design better trials for pediatric patients with relapsed AML.

“Ultimately, we’ll create the largest data set that will give us a better understanding of all the risks and benefits associated with postrelapse AML,” Dr. Kolb said. “No matter what happens to the patient, no matter where that patient enrolls, we’re going to have the capacity to collect data and present that data to the community for analysis for improved understanding of outcomes.”

Dr. Kolb and his colleagues are already working with researchers in Europe and Japan to make this a global effort and create an international data commons. In addition, the researchers are planning to collaborate with the pharmaceutical industry to unite efforts in pediatric AML drug development.

“We can’t just test drugs in kids because they worked in adults,” Dr. Kolb said. “We really need to maintain the integrity of the science and ask relevant questions in children but do so with the intent to make sure these drugs are licensed for use in kids.”

Dr. Kolb reported having no conflicts of interest. The PedAL trial is sponsored by the Leukemia & Lymphoma Society.

jensmith@mdedge.com

NEW ORLEANS – Researchers are organizing a master trial in an attempt to improve the treatment of pediatric acute myeloid leukemia (AML).

The Pediatric Acute Leukemia (PedAL) trial is an effort to collect data on all pediatric AML patients. The plan is to use these data to match patients to clinical trials, better understand pediatric AML, and bring new treatments to this population.

E. Anders Kolb, MD, of Nemours Center for Cancer and Blood Disorders in Wilmington, Del., described the initiative at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Dr. Kolb noted that several drugs have been approved to treat adult AML in the last 2 years, but most of them are not approved for use in children.

“What we see in childhood AML is a lot different than what we see in adult AML, and this challenges the paradigm that we have traditionally followed where we use the adult as the 'preclinical model' for pediatric AML,” he said. “I think we are learning more and more that children have a unique disease, unique targets, and need unique therapies.”

The PedAL initiative is an attempt to address these unique needs. PedAL is part of the Leukemia & Lymphoma Society’s Children’s Initiative, and it involves researchers from academic centers and the Children’s Oncology Group.

The PedAL initiative includes preclinical, biomarker, and informatics research, as well as the master clinical trial. The main goal of the master trial is to collect genomic, proteomic, metabolomic, flow cytometry, and clinical data from all children with AML and use these data to match patients to clinical trials.

The PedAL trial will leverage Project:EveryChild, an effort by the Children’s Oncology Group to study every child with cancer. Each child enrolled in this program has an identification number that follows the child through all clinical interventions.

The goal is that Project:EveryChild will capture all pediatric AML patients at the time of diagnosis, although patients can join the project at any time. Then, sequencing, clinical, and other data will be collected from these patients and stored in a data commons.

If patients relapse after standard or other therapies, the GEARBOX algorithm (genomic eligibility algorithm at relapse for better outcomes) can be used to match the patient’s information to clinical trial eligibility criteria and provide a list of appropriate trials.

Dr. Kolb said this process should reduce logistical barriers and get relapsed patients to trials more quickly. Additionally, the data collected through PedAL should help researchers design better trials for pediatric patients with relapsed AML.

“Ultimately, we’ll create the largest data set that will give us a better understanding of all the risks and benefits associated with postrelapse AML,” Dr. Kolb said. “No matter what happens to the patient, no matter where that patient enrolls, we’re going to have the capacity to collect data and present that data to the community for analysis for improved understanding of outcomes.”

Dr. Kolb and his colleagues are already working with researchers in Europe and Japan to make this a global effort and create an international data commons. In addition, the researchers are planning to collaborate with the pharmaceutical industry to unite efforts in pediatric AML drug development.

“We can’t just test drugs in kids because they worked in adults,” Dr. Kolb said. “We really need to maintain the integrity of the science and ask relevant questions in children but do so with the intent to make sure these drugs are licensed for use in kids.”

Dr. Kolb reported having no conflicts of interest. The PedAL trial is sponsored by the Leukemia & Lymphoma Society.

jensmith@mdedge.com

BALTIMORE – Over the past 2 years, Northwell Health, a large medical system in the metropolitan New York area, increased cytomegalovirus screening for infants who fail hearing tests from 6.6% to 95% at five of its birth hospitals, according to a presentation at the Pediatric Academic Societies annual meeting.

Three cases of congenital cytomegalovirus (CMV) have been picked up so far. The plan is to roll the program out to all 10 of the system’s birth hospitals, where over 40,000 children are born each year.

“We feel very satisfied and proud” of the progress that’s been made at Northwell in such a short time, said Alia Chauhan, MD, a Northwell pediatrician who presented the findings.

Northwell launched its “Hearing Plus” program in 2017 to catch the infection before infants leave the hospital. Several other health systems around the country have launched similar programs, and a handful of states – including New York – now require CMV screening for infants who fail mandated hearing tests.

The issue is gaining traction because hearing loss is often the only sign of congenital CMV, so it’s a bellwether for infection. Screening children with hearing loss is an easy way to pick it up early, so steps can be taken to prevent problems down the road. As it is, congenital CMV is the leading nongenetic cause of hearing loss in infants, accounting for at least 10% of cases.

The Northwell program kicked off with an education campaign to build consensus among pediatricians, hospitalists, and nurses. A flyer was made about CMV screening for moms whose infants fail hearing tests, printed in both English and Spanish.

Initially, the program used urine PCR [polymerase chain reaction] to screen for CMV, but waiting for infants to produce a sample often delayed discharge, so a switch was soon made to saliva swab PCRs, which take seconds, with urine PCR held in reserve to confirm positive swabs.

To streamline the process, a standing order was added to the electronic records system so nurses could order saliva PCRs without having to get physician approval. “I think [that] was one of the biggest things that’s helped us,” Dr. Chauhan said.

Children who test positive must have urine confirmation within 21 days of birth; most are long gone from the hospital by then and have to be called back in. “We haven’t lost anyone to follow-up, but it can be stressful trying to get someone to come back,” she said.

Six of 449 infants have screened positive on saliva – three were false positives with negative urine screens. Of the three confirmed cases, two infants later turned out to have normal hearing on repeat testing and were otherwise asymptomatic.

These days, Dr. Chauhan said, if children have a positive saliva PCR but later turn out to have normal hearing, and are otherwise free of symptoms with no CMV risk factors, “we are not confirming with urine.”

Dr. Chauhan did not have any disclosures. No funding source was mentioned.

aotto@mdedge.com

SOURCE: Chauhan A et al. PAS 2019. Abstract 306

BALTIMORE – Over the past 2 years, Northwell Health, a large medical system in the metropolitan New York area, increased cytomegalovirus screening for infants who fail hearing tests from 6.6% to 95% at five of its birth hospitals, according to a presentation at the Pediatric Academic Societies annual meeting.

Three cases of congenital cytomegalovirus (CMV) have been picked up so far. The plan is to roll the program out to all 10 of the system’s birth hospitals, where over 40,000 children are born each year.

“We feel very satisfied and proud” of the progress that’s been made at Northwell in such a short time, said Alia Chauhan, MD, a Northwell pediatrician who presented the findings.

Northwell launched its “Hearing Plus” program in 2017 to catch the infection before infants leave the hospital. Several other health systems around the country have launched similar programs, and a handful of states – including New York – now require CMV screening for infants who fail mandated hearing tests.

The issue is gaining traction because hearing loss is often the only sign of congenital CMV, so it’s a bellwether for infection. Screening children with hearing loss is an easy way to pick it up early, so steps can be taken to prevent problems down the road. As it is, congenital CMV is the leading nongenetic cause of hearing loss in infants, accounting for at least 10% of cases.

The Northwell program kicked off with an education campaign to build consensus among pediatricians, hospitalists, and nurses. A flyer was made about CMV screening for moms whose infants fail hearing tests, printed in both English and Spanish.

Initially, the program used urine PCR [polymerase chain reaction] to screen for CMV, but waiting for infants to produce a sample often delayed discharge, so a switch was soon made to saliva swab PCRs, which take seconds, with urine PCR held in reserve to confirm positive swabs.

To streamline the process, a standing order was added to the electronic records system so nurses could order saliva PCRs without having to get physician approval. “I think [that] was one of the biggest things that’s helped us,” Dr. Chauhan said.

Children who test positive must have urine confirmation within 21 days of birth; most are long gone from the hospital by then and have to be called back in. “We haven’t lost anyone to follow-up, but it can be stressful trying to get someone to come back,” she said.

Six of 449 infants have screened positive on saliva – three were false positives with negative urine screens. Of the three confirmed cases, two infants later turned out to have normal hearing on repeat testing and were otherwise asymptomatic.

These days, Dr. Chauhan said, if children have a positive saliva PCR but later turn out to have normal hearing, and are otherwise free of symptoms with no CMV risk factors, “we are not confirming with urine.”

Dr. Chauhan did not have any disclosures. No funding source was mentioned.

aotto@mdedge.com

SOURCE: Chauhan A et al. PAS 2019. Abstract 306

BALTIMORE – Over the past 2 years, Northwell Health, a large medical system in the metropolitan New York area, increased cytomegalovirus screening for infants who fail hearing tests from 6.6% to 95% at five of its birth hospitals, according to a presentation at the Pediatric Academic Societies annual meeting.

Three cases of congenital cytomegalovirus (CMV) have been picked up so far. The plan is to roll the program out to all 10 of the system’s birth hospitals, where over 40,000 children are born each year.

“We feel very satisfied and proud” of the progress that’s been made at Northwell in such a short time, said Alia Chauhan, MD, a Northwell pediatrician who presented the findings.

Northwell launched its “Hearing Plus” program in 2017 to catch the infection before infants leave the hospital. Several other health systems around the country have launched similar programs, and a handful of states – including New York – now require CMV screening for infants who fail mandated hearing tests.

The issue is gaining traction because hearing loss is often the only sign of congenital CMV, so it’s a bellwether for infection. Screening children with hearing loss is an easy way to pick it up early, so steps can be taken to prevent problems down the road. As it is, congenital CMV is the leading nongenetic cause of hearing loss in infants, accounting for at least 10% of cases.

The Northwell program kicked off with an education campaign to build consensus among pediatricians, hospitalists, and nurses. A flyer was made about CMV screening for moms whose infants fail hearing tests, printed in both English and Spanish.

Initially, the program used urine PCR [polymerase chain reaction] to screen for CMV, but waiting for infants to produce a sample often delayed discharge, so a switch was soon made to saliva swab PCRs, which take seconds, with urine PCR held in reserve to confirm positive swabs.

To streamline the process, a standing order was added to the electronic records system so nurses could order saliva PCRs without having to get physician approval. “I think [that] was one of the biggest things that’s helped us,” Dr. Chauhan said.

Children who test positive must have urine confirmation within 21 days of birth; most are long gone from the hospital by then and have to be called back in. “We haven’t lost anyone to follow-up, but it can be stressful trying to get someone to come back,” she said.

Six of 449 infants have screened positive on saliva – three were false positives with negative urine screens. Of the three confirmed cases, two infants later turned out to have normal hearing on repeat testing and were otherwise asymptomatic.

These days, Dr. Chauhan said, if children have a positive saliva PCR but later turn out to have normal hearing, and are otherwise free of symptoms with no CMV risk factors, “we are not confirming with urine.”

Dr. Chauhan did not have any disclosures. No funding source was mentioned.

aotto@mdedge.com

SOURCE: Chauhan A et al. PAS 2019. Abstract 306

PHILADELPHIA – The benefit of deutetrabenazine treatment of tardive dyskinesia is maintained over the long term and may increase over time, according to results of an open-label extension study reported at the annual meeting of the American Academy of Neurology.

The mean Abnormal Involuntary Movement Scale (AIMS) score in the study continued to increase over 3 years of treatment with this VMAT2 inhibitor, which was safe and well tolerated over the course of the study, said investigator Robert A. Hauser, MD, MBA, director of the Parkinson’s and Movement Disorder Center and professor in the department of neurology at the University of South Florida in Tampa.

The apparent improvement over time was “fascinating” to observe, Dr. Hauser said. The finding deserves further study to identify potential confounders, such as rater bias over time or placebo effects, and if those “trivial” causes can be ruled out to determine a potential mechanism of action.

“I will also say that the mechanism may not be that important if we can really show this important clinical effect,” he said. “So I think this needs more work.”

The FDA approved deutetrabenazine (Austedo, Teva) for tardive dyskinesia treatment based on ARM-TD and AIM-TD, two randomized, double-blind, placebo-controlled trials. Those studies demonstrated improvements in AIMS scores for the VMAT2 inhibitor versus placebo, with low rates of adverse events and discontinuations, Dr. Hauser said.

Dr. Hauser presented results up to week 145 from C-20, an ongoing, 3-year, open-label extension study designed to evaluate the agent’s long-term safety and efficacy.

A total of 343 patients from ARM-TD and AIM-TD rolled over directly into C-20, started at 12 mg/day of deutetrabenazine, and titrated until adequate tardive dyskinesia control was achieved, up to 48 mg/day. Sixty percent of the patients had psychotic disorders as the background comorbid illness, while 40% had mood disorders, according to the interim report.

The mean AIMS score was 10.9 at baseline, 6.0 at 54 weeks, 5.8 at 106 weeks, and 4.1 at 145 weeks, the report showed. The corresponding change in AIMS score decreased from baseline for patients who remained in the study, from –4.8 at 54 weeks to –5.6 at 106 weeks and –7.0 at 145 weeks.*

A subsequent completer analysis showed that the apparent improvement in efficacy over the long term was not due to poor responders dropping out over time, Dr. Hauser said.

“I think the data clearly show the benefit is maintained, and intriguingly, I think they suggest that there may be increasing benefit over time,” he added.

The treatment was safe and well tolerated in long-term use. The most common adverse events were anxiety, somnolence, fatigue, insomnia, and headache. Adverse events did not increase in frequency from the parent studies to the open-label study, he noted.

The study was sponsored by Teva Pharmaceuticals. Dr. Hauser reported disclosures related to Teva, AbbVie, AstraZeneca, Biotie Thrapies, Cynapsus Therapeutics, Neurocrine Biosciences, Sunovion Pharmaceuticals, and Pfizer, among others.

SOURCE: Hauser RA et al. AAN 2019. Abstract S4.009.

*Correction, 6/26/19 An earlier version of this article mischaracterized changes in the mean Abnormal Involuntary Movement Scale scores during treatment.  

PHILADELPHIA – The benefit of deutetrabenazine treatment of tardive dyskinesia is maintained over the long term and may increase over time, according to results of an open-label extension study reported at the annual meeting of the American Academy of Neurology.

The mean Abnormal Involuntary Movement Scale (AIMS) score in the study continued to increase over 3 years of treatment with this VMAT2 inhibitor, which was safe and well tolerated over the course of the study, said investigator Robert A. Hauser, MD, MBA, director of the Parkinson’s and Movement Disorder Center and professor in the department of neurology at the University of South Florida in Tampa.

The apparent improvement over time was “fascinating” to observe, Dr. Hauser said. The finding deserves further study to identify potential confounders, such as rater bias over time or placebo effects, and if those “trivial” causes can be ruled out to determine a potential mechanism of action.

“I will also say that the mechanism may not be that important if we can really show this important clinical effect,” he said. “So I think this needs more work.”

The FDA approved deutetrabenazine (Austedo, Teva) for tardive dyskinesia treatment based on ARM-TD and AIM-TD, two randomized, double-blind, placebo-controlled trials. Those studies demonstrated improvements in AIMS scores for the VMAT2 inhibitor versus placebo, with low rates of adverse events and discontinuations, Dr. Hauser said.

Dr. Hauser presented results up to week 145 from C-20, an ongoing, 3-year, open-label extension study designed to evaluate the agent’s long-term safety and efficacy.

A total of 343 patients from ARM-TD and AIM-TD rolled over directly into C-20, started at 12 mg/day of deutetrabenazine, and titrated until adequate tardive dyskinesia control was achieved, up to 48 mg/day. Sixty percent of the patients had psychotic disorders as the background comorbid illness, while 40% had mood disorders, according to the interim report.

The mean AIMS score was 10.9 at baseline, 6.0 at 54 weeks, 5.8 at 106 weeks, and 4.1 at 145 weeks, the report showed. The corresponding change in AIMS score decreased from baseline for patients who remained in the study, from –4.8 at 54 weeks to –5.6 at 106 weeks and –7.0 at 145 weeks.*

A subsequent completer analysis showed that the apparent improvement in efficacy over the long term was not due to poor responders dropping out over time, Dr. Hauser said.

“I think the data clearly show the benefit is maintained, and intriguingly, I think they suggest that there may be increasing benefit over time,” he added.

The treatment was safe and well tolerated in long-term use. The most common adverse events were anxiety, somnolence, fatigue, insomnia, and headache. Adverse events did not increase in frequency from the parent studies to the open-label study, he noted.

The study was sponsored by Teva Pharmaceuticals. Dr. Hauser reported disclosures related to Teva, AbbVie, AstraZeneca, Biotie Thrapies, Cynapsus Therapeutics, Neurocrine Biosciences, Sunovion Pharmaceuticals, and Pfizer, among others.

SOURCE: Hauser RA et al. AAN 2019. Abstract S4.009.

*Correction, 6/26/19 An earlier version of this article mischaracterized changes in the mean Abnormal Involuntary Movement Scale scores during treatment.  

PHILADELPHIA – The benefit of deutetrabenazine treatment of tardive dyskinesia is maintained over the long term and may increase over time, according to results of an open-label extension study reported at the annual meeting of the American Academy of Neurology.

The mean Abnormal Involuntary Movement Scale (AIMS) score in the study continued to increase over 3 years of treatment with this VMAT2 inhibitor, which was safe and well tolerated over the course of the study, said investigator Robert A. Hauser, MD, MBA, director of the Parkinson’s and Movement Disorder Center and professor in the department of neurology at the University of South Florida in Tampa.

The apparent improvement over time was “fascinating” to observe, Dr. Hauser said. The finding deserves further study to identify potential confounders, such as rater bias over time or placebo effects, and if those “trivial” causes can be ruled out to determine a potential mechanism of action.

“I will also say that the mechanism may not be that important if we can really show this important clinical effect,” he said. “So I think this needs more work.”

The FDA approved deutetrabenazine (Austedo, Teva) for tardive dyskinesia treatment based on ARM-TD and AIM-TD, two randomized, double-blind, placebo-controlled trials. Those studies demonstrated improvements in AIMS scores for the VMAT2 inhibitor versus placebo, with low rates of adverse events and discontinuations, Dr. Hauser said.

Dr. Hauser presented results up to week 145 from C-20, an ongoing, 3-year, open-label extension study designed to evaluate the agent’s long-term safety and efficacy.

A total of 343 patients from ARM-TD and AIM-TD rolled over directly into C-20, started at 12 mg/day of deutetrabenazine, and titrated until adequate tardive dyskinesia control was achieved, up to 48 mg/day. Sixty percent of the patients had psychotic disorders as the background comorbid illness, while 40% had mood disorders, according to the interim report.

The mean AIMS score was 10.9 at baseline, 6.0 at 54 weeks, 5.8 at 106 weeks, and 4.1 at 145 weeks, the report showed. The corresponding change in AIMS score decreased from baseline for patients who remained in the study, from –4.8 at 54 weeks to –5.6 at 106 weeks and –7.0 at 145 weeks.*

A subsequent completer analysis showed that the apparent improvement in efficacy over the long term was not due to poor responders dropping out over time, Dr. Hauser said.

“I think the data clearly show the benefit is maintained, and intriguingly, I think they suggest that there may be increasing benefit over time,” he added.

The treatment was safe and well tolerated in long-term use. The most common adverse events were anxiety, somnolence, fatigue, insomnia, and headache. Adverse events did not increase in frequency from the parent studies to the open-label study, he noted.

The study was sponsored by Teva Pharmaceuticals. Dr. Hauser reported disclosures related to Teva, AbbVie, AstraZeneca, Biotie Thrapies, Cynapsus Therapeutics, Neurocrine Biosciences, Sunovion Pharmaceuticals, and Pfizer, among others.

SOURCE: Hauser RA et al. AAN 2019. Abstract S4.009.

*Correction, 6/26/19 An earlier version of this article mischaracterized changes in the mean Abnormal Involuntary Movement Scale scores during treatment.  

NEW ORLEANS – People diagnosed with atrial fibrillation by screening with a wearable ECG patch had significantly fewer emergency department visits or hospital admissions, compared with similar people diagnosed with atrial fibrillation by usual-care surveillance in an observational study with 5,109 total participants.

People diagnosed with atrial fibrillation (AFib) through screening had a statistically significant 80% relative cut in hospitalizations and a 65% cut in emergency department visits during 12 months of follow-up, compared with controls in the study who had their AFib identified and diagnosed as part of routine practice, Steven R. Steinhubl, MD, said at the annual meeting of the American College of Cardiology.

Mitchel L. Zoler/MDedge News

The data also showed no difference between the screened and control patients identified with AFib in the average number of cardiologist consultations during a year of follow-up, and a trend that missed statistical significance for 16% fewer primary care physician visits in Afib patients diagnosed by screening rather than by routine surveillance.

These findings provided some insight into the potential clinical impact of AFib screening in at-risk people. Dr. Steinhubl and his associates plan to report on the incidence of strokes and MIs in the two study subgroups after 3 years of follow-up, but he noted that preliminary findings for these two outcomes after 1 year indicated that active screening for AFib also had reduced these rates, compared with waiting for the arrhythmia to become apparent by emergence of symptoms.

The data came from the mSToPS (mHealth Screening to Prevent Strokes) study, which randomized 2,659 U.S. residents enrolled in a large health plan who had risk factors for AFib to either immediate or delayed arrhythmia assessment by ECG patches. Half the participants used a patch for about 14 days immediately and then a second time 3 months later, while the other half waited 4 months and then wore an ECG patch for 2 weeks and again 3 months later. The primary endpoint, first reported at the ACC annual meeting a year before and subsequently published, was the incidence of newly diagnosed AFib during the first 4 months in the actively monitored cohort, compared with a cohort followed by usual care. The results showed that screening identified AFib in 3.9% of people, while no screening and usual-practice follow-up identified a 0.9% incidence of AFib, showing that screening worked better for AFib case identification (JAMA. 2018 Jul 10;320[2]:146-55).

To examine the clinical impact of screening and an increased incidence of diagnosed AFib cases, Dr. Steinhubl and his associates focused on 1,725 of the original 2,659 patients who underwent ECG patch assessment, either immediate or delayed, and continued through 12 months of follow-up, and compared them with 3,384 matched controls who never underwent ECG patch screening but were also followed for 12 months for incident AFib identified during routine care and surveillance. This resulted in a cumulative incidence of newly diagnosed AFib of 6.3% in those who had worn two ECG patches and 2.3% among the matched controls.

During follow-up, use of various interventions was more common among the screened people than the controls. Initiation of anticoagulation treatment started in 4.0% of the entire screened group, compared with 1.9% of the controls, The screened people also had a 0.9% rate of receiving a pacemaker or defibrillator, a 0.8% rate of starting on treatment with an antiarrhythmic drug, and a 0.3% rate of undergoing catheter ablation, compared with none, 0.3%, and one of the controls, respectively, said Dr. Steinhubl, director of digital medicine at the Scripps Research Translational Institute in La Jolla, Calif.

The mSToPS study was funded by Janssen. Dr. Steinhubl has received research funding from DynoSense, EasyG, Janssen, the Qualcomm Foundation, and Striv.

mzoler@mdedge.com

SOURCE: Steinhubl SR et al. J Am Coll Cardiol. 2019 Mar 12;73(9)suppl 1:296.

NEW ORLEANS – People diagnosed with atrial fibrillation by screening with a wearable ECG patch had significantly fewer emergency department visits or hospital admissions, compared with similar people diagnosed with atrial fibrillation by usual-care surveillance in an observational study with 5,109 total participants.

People diagnosed with atrial fibrillation (AFib) through screening had a statistically significant 80% relative cut in hospitalizations and a 65% cut in emergency department visits during 12 months of follow-up, compared with controls in the study who had their AFib identified and diagnosed as part of routine practice, Steven R. Steinhubl, MD, said at the annual meeting of the American College of Cardiology.

Mitchel L. Zoler/MDedge News

The data also showed no difference between the screened and control patients identified with AFib in the average number of cardiologist consultations during a year of follow-up, and a trend that missed statistical significance for 16% fewer primary care physician visits in Afib patients diagnosed by screening rather than by routine surveillance.

These findings provided some insight into the potential clinical impact of AFib screening in at-risk people. Dr. Steinhubl and his associates plan to report on the incidence of strokes and MIs in the two study subgroups after 3 years of follow-up, but he noted that preliminary findings for these two outcomes after 1 year indicated that active screening for AFib also had reduced these rates, compared with waiting for the arrhythmia to become apparent by emergence of symptoms.

The data came from the mSToPS (mHealth Screening to Prevent Strokes) study, which randomized 2,659 U.S. residents enrolled in a large health plan who had risk factors for AFib to either immediate or delayed arrhythmia assessment by ECG patches. Half the participants used a patch for about 14 days immediately and then a second time 3 months later, while the other half waited 4 months and then wore an ECG patch for 2 weeks and again 3 months later. The primary endpoint, first reported at the ACC annual meeting a year before and subsequently published, was the incidence of newly diagnosed AFib during the first 4 months in the actively monitored cohort, compared with a cohort followed by usual care. The results showed that screening identified AFib in 3.9% of people, while no screening and usual-practice follow-up identified a 0.9% incidence of AFib, showing that screening worked better for AFib case identification (JAMA. 2018 Jul 10;320[2]:146-55).

To examine the clinical impact of screening and an increased incidence of diagnosed AFib cases, Dr. Steinhubl and his associates focused on 1,725 of the original 2,659 patients who underwent ECG patch assessment, either immediate or delayed, and continued through 12 months of follow-up, and compared them with 3,384 matched controls who never underwent ECG patch screening but were also followed for 12 months for incident AFib identified during routine care and surveillance. This resulted in a cumulative incidence of newly diagnosed AFib of 6.3% in those who had worn two ECG patches and 2.3% among the matched controls.

During follow-up, use of various interventions was more common among the screened people than the controls. Initiation of anticoagulation treatment started in 4.0% of the entire screened group, compared with 1.9% of the controls, The screened people also had a 0.9% rate of receiving a pacemaker or defibrillator, a 0.8% rate of starting on treatment with an antiarrhythmic drug, and a 0.3% rate of undergoing catheter ablation, compared with none, 0.3%, and one of the controls, respectively, said Dr. Steinhubl, director of digital medicine at the Scripps Research Translational Institute in La Jolla, Calif.

The mSToPS study was funded by Janssen. Dr. Steinhubl has received research funding from DynoSense, EasyG, Janssen, the Qualcomm Foundation, and Striv.

mzoler@mdedge.com

SOURCE: Steinhubl SR et al. J Am Coll Cardiol. 2019 Mar 12;73(9)suppl 1:296.

NEW ORLEANS – People diagnosed with atrial fibrillation by screening with a wearable ECG patch had significantly fewer emergency department visits or hospital admissions, compared with similar people diagnosed with atrial fibrillation by usual-care surveillance in an observational study with 5,109 total participants.

People diagnosed with atrial fibrillation (AFib) through screening had a statistically significant 80% relative cut in hospitalizations and a 65% cut in emergency department visits during 12 months of follow-up, compared with controls in the study who had their AFib identified and diagnosed as part of routine practice, Steven R. Steinhubl, MD, said at the annual meeting of the American College of Cardiology.

Mitchel L. Zoler/MDedge News

The data also showed no difference between the screened and control patients identified with AFib in the average number of cardiologist consultations during a year of follow-up, and a trend that missed statistical significance for 16% fewer primary care physician visits in Afib patients diagnosed by screening rather than by routine surveillance.

These findings provided some insight into the potential clinical impact of AFib screening in at-risk people. Dr. Steinhubl and his associates plan to report on the incidence of strokes and MIs in the two study subgroups after 3 years of follow-up, but he noted that preliminary findings for these two outcomes after 1 year indicated that active screening for AFib also had reduced these rates, compared with waiting for the arrhythmia to become apparent by emergence of symptoms.

The data came from the mSToPS (mHealth Screening to Prevent Strokes) study, which randomized 2,659 U.S. residents enrolled in a large health plan who had risk factors for AFib to either immediate or delayed arrhythmia assessment by ECG patches. Half the participants used a patch for about 14 days immediately and then a second time 3 months later, while the other half waited 4 months and then wore an ECG patch for 2 weeks and again 3 months later. The primary endpoint, first reported at the ACC annual meeting a year before and subsequently published, was the incidence of newly diagnosed AFib during the first 4 months in the actively monitored cohort, compared with a cohort followed by usual care. The results showed that screening identified AFib in 3.9% of people, while no screening and usual-practice follow-up identified a 0.9% incidence of AFib, showing that screening worked better for AFib case identification (JAMA. 2018 Jul 10;320[2]:146-55).

To examine the clinical impact of screening and an increased incidence of diagnosed AFib cases, Dr. Steinhubl and his associates focused on 1,725 of the original 2,659 patients who underwent ECG patch assessment, either immediate or delayed, and continued through 12 months of follow-up, and compared them with 3,384 matched controls who never underwent ECG patch screening but were also followed for 12 months for incident AFib identified during routine care and surveillance. This resulted in a cumulative incidence of newly diagnosed AFib of 6.3% in those who had worn two ECG patches and 2.3% among the matched controls.

During follow-up, use of various interventions was more common among the screened people than the controls. Initiation of anticoagulation treatment started in 4.0% of the entire screened group, compared with 1.9% of the controls, The screened people also had a 0.9% rate of receiving a pacemaker or defibrillator, a 0.8% rate of starting on treatment with an antiarrhythmic drug, and a 0.3% rate of undergoing catheter ablation, compared with none, 0.3%, and one of the controls, respectively, said Dr. Steinhubl, director of digital medicine at the Scripps Research Translational Institute in La Jolla, Calif.

The mSToPS study was funded by Janssen. Dr. Steinhubl has received research funding from DynoSense, EasyG, Janssen, the Qualcomm Foundation, and Striv.

mzoler@mdedge.com

SOURCE: Steinhubl SR et al. J Am Coll Cardiol. 2019 Mar 12;73(9)suppl 1:296.

NEW ORLEANS – A next-generation sequencing (NGS) test for pathogen detection demonstrated higher sensitivity than conventional testing methods in a cohort of diverse pediatric patients, according to researchers.

The NGS test, which detects sequences of circulating cell-free DNA in plasma, detected pathogens with 92% sensitivity, compared with 64% sensitivity for all conventional testing methods combined (P less than .01).

Jennifer Smith/MDedge News

Results

Of the 100 NGS tests evaluated, 70 were positive for any organism, and 56 of these were deemed clinically relevant.

“What I think is quite remarkable is that, of those clinically relevant organisms, tests on 14, which is 25% of those, were able to identify clinically relevant or pathogenic organisms when no other conventional testing modality was able to identify them,” Dr. Rossoff said. “And these were often in patients who underwent invasive procedures to try to get at the source of their infectious disease.”

In fact, the study included 42 patients who underwent 54 invasive diagnostic procedures, and 32 of those procedures could have been avoided based on positive NGS results, according to Dr. Rossoff and her colleagues.

Dr. Rossoff noted that the most common sites of infection were the bloodstream and respiratory tract, but the NGS test was able to identify pathogens in the bone, skin, cerebrospinal fluid, and urinary tract. She also pointed out that NGS results were available “in a fairly timely manner,” as 86% of test results were available within 48 hours of sample receipt.

Dr. Rossoff and her colleagues did not receive any funding for this study, but they were previously involved in a study funded by Karius, the company that commercialized the NGS test.

jensmith@mdedge.com

SOURCE: Rossoff J et al. ASPHO 2019. Abstract 439.
 

NEW ORLEANS – A next-generation sequencing (NGS) test for pathogen detection demonstrated higher sensitivity than conventional testing methods in a cohort of diverse pediatric patients, according to researchers.

The NGS test, which detects sequences of circulating cell-free DNA in plasma, detected pathogens with 92% sensitivity, compared with 64% sensitivity for all conventional testing methods combined (P less than .01).

Jennifer Smith/MDedge News

Results

Of the 100 NGS tests evaluated, 70 were positive for any organism, and 56 of these were deemed clinically relevant.

“What I think is quite remarkable is that, of those clinically relevant organisms, tests on 14, which is 25% of those, were able to identify clinically relevant or pathogenic organisms when no other conventional testing modality was able to identify them,” Dr. Rossoff said. “And these were often in patients who underwent invasive procedures to try to get at the source of their infectious disease.”

In fact, the study included 42 patients who underwent 54 invasive diagnostic procedures, and 32 of those procedures could have been avoided based on positive NGS results, according to Dr. Rossoff and her colleagues.

Dr. Rossoff noted that the most common sites of infection were the bloodstream and respiratory tract, but the NGS test was able to identify pathogens in the bone, skin, cerebrospinal fluid, and urinary tract. She also pointed out that NGS results were available “in a fairly timely manner,” as 86% of test results were available within 48 hours of sample receipt.

Dr. Rossoff and her colleagues did not receive any funding for this study, but they were previously involved in a study funded by Karius, the company that commercialized the NGS test.

jensmith@mdedge.com

SOURCE: Rossoff J et al. ASPHO 2019. Abstract 439.
 

NEW ORLEANS – A next-generation sequencing (NGS) test for pathogen detection demonstrated higher sensitivity than conventional testing methods in a cohort of diverse pediatric patients, according to researchers.

The NGS test, which detects sequences of circulating cell-free DNA in plasma, detected pathogens with 92% sensitivity, compared with 64% sensitivity for all conventional testing methods combined (P less than .01).

Jennifer Smith/MDedge News

Results

Of the 100 NGS tests evaluated, 70 were positive for any organism, and 56 of these were deemed clinically relevant.

“What I think is quite remarkable is that, of those clinically relevant organisms, tests on 14, which is 25% of those, were able to identify clinically relevant or pathogenic organisms when no other conventional testing modality was able to identify them,” Dr. Rossoff said. “And these were often in patients who underwent invasive procedures to try to get at the source of their infectious disease.”

In fact, the study included 42 patients who underwent 54 invasive diagnostic procedures, and 32 of those procedures could have been avoided based on positive NGS results, according to Dr. Rossoff and her colleagues.

Dr. Rossoff noted that the most common sites of infection were the bloodstream and respiratory tract, but the NGS test was able to identify pathogens in the bone, skin, cerebrospinal fluid, and urinary tract. She also pointed out that NGS results were available “in a fairly timely manner,” as 86% of test results were available within 48 hours of sample receipt.

Dr. Rossoff and her colleagues did not receive any funding for this study, but they were previously involved in a study funded by Karius, the company that commercialized the NGS test.

jensmith@mdedge.com

SOURCE: Rossoff J et al. ASPHO 2019. Abstract 439.