Nearly a quarter of resources used by the intensive care unit (ICU) are for substance abuse-related admissions, according to results from a retrospective chart review.

Hemera Technologies/Thinkstock

The abuse of illicit drugs topped substance abuse–related ICU stays, accounting for 13% of total admissions, which represented 11% of total charges.

“We conducted a study to provide updated data on ICU utilization and costs related to licit and illicit abuse at a large county hospital,” wrote Donald Westerhausen, MD, of Indiana University, Indianapolis, and colleagues. The findings were reported in Chest .

The single-center study comprised 594 patients who were admitted for prescription, alcohol, or illicit drug use between May 2017 and October 2017. The team used laboratory data, in addition to medical history, to define substance abuse–related admissions.

A total of 611 admissions occurred during the 6-month study period. The researchers collected information on patient demographics, hospital charges, insurance coverage, and other clinical parameters.

After analysis, they found that patients admitted for substance abuse were generally younger than were those admitted for other reasons (44 years vs. 59 years; P less than .001). In addition, patients were more often male (64% vs. 48%), had greater mortality (14%), and experienced longer hospital stays (median, 6 days).

In total, 25.7% of ICU admissions were related to substance abuse, which comprised 23.1% of charges. In particular, 9.5% and 2.9% of admissions were related to alcohol use and prescription drugs, which represented 7.6% and 4.2% of total charges, respectively.

“Polysubstance abuse was the most frequent subcategory of illicit and prescription drug admissions,” the researchers wrote.

They acknowledged two limitations of the study: the short duration and single-center design. Future studies should account for seasonal differences in ICU admissions, they noted.

“Identifying and accurately describing the landscape of this current health crisis will help us take appropriate action in the future,” they concluded.

No funding sources were reported. The authors did not disclose any conflicts of interest.

SOURCE: Westerhausen D et al. Chest. 2019 Sep 5. doi: 10.1016/j.chest.2019.08.2180.

Nearly a quarter of resources used by the intensive care unit (ICU) are for substance abuse-related admissions, according to results from a retrospective chart review.

Hemera Technologies/Thinkstock

The abuse of illicit drugs topped substance abuse–related ICU stays, accounting for 13% of total admissions, which represented 11% of total charges.

“We conducted a study to provide updated data on ICU utilization and costs related to licit and illicit abuse at a large county hospital,” wrote Donald Westerhausen, MD, of Indiana University, Indianapolis, and colleagues. The findings were reported in Chest .

The single-center study comprised 594 patients who were admitted for prescription, alcohol, or illicit drug use between May 2017 and October 2017. The team used laboratory data, in addition to medical history, to define substance abuse–related admissions.

A total of 611 admissions occurred during the 6-month study period. The researchers collected information on patient demographics, hospital charges, insurance coverage, and other clinical parameters.

After analysis, they found that patients admitted for substance abuse were generally younger than were those admitted for other reasons (44 years vs. 59 years; P less than .001). In addition, patients were more often male (64% vs. 48%), had greater mortality (14%), and experienced longer hospital stays (median, 6 days).

In total, 25.7% of ICU admissions were related to substance abuse, which comprised 23.1% of charges. In particular, 9.5% and 2.9% of admissions were related to alcohol use and prescription drugs, which represented 7.6% and 4.2% of total charges, respectively.

“Polysubstance abuse was the most frequent subcategory of illicit and prescription drug admissions,” the researchers wrote.

They acknowledged two limitations of the study: the short duration and single-center design. Future studies should account for seasonal differences in ICU admissions, they noted.

“Identifying and accurately describing the landscape of this current health crisis will help us take appropriate action in the future,” they concluded.

No funding sources were reported. The authors did not disclose any conflicts of interest.

SOURCE: Westerhausen D et al. Chest. 2019 Sep 5. doi: 10.1016/j.chest.2019.08.2180.

Nearly a quarter of resources used by the intensive care unit (ICU) are for substance abuse-related admissions, according to results from a retrospective chart review.

Hemera Technologies/Thinkstock

The abuse of illicit drugs topped substance abuse–related ICU stays, accounting for 13% of total admissions, which represented 11% of total charges.

“We conducted a study to provide updated data on ICU utilization and costs related to licit and illicit abuse at a large county hospital,” wrote Donald Westerhausen, MD, of Indiana University, Indianapolis, and colleagues. The findings were reported in Chest .

The single-center study comprised 594 patients who were admitted for prescription, alcohol, or illicit drug use between May 2017 and October 2017. The team used laboratory data, in addition to medical history, to define substance abuse–related admissions.

A total of 611 admissions occurred during the 6-month study period. The researchers collected information on patient demographics, hospital charges, insurance coverage, and other clinical parameters.

After analysis, they found that patients admitted for substance abuse were generally younger than were those admitted for other reasons (44 years vs. 59 years; P less than .001). In addition, patients were more often male (64% vs. 48%), had greater mortality (14%), and experienced longer hospital stays (median, 6 days).

In total, 25.7% of ICU admissions were related to substance abuse, which comprised 23.1% of charges. In particular, 9.5% and 2.9% of admissions were related to alcohol use and prescription drugs, which represented 7.6% and 4.2% of total charges, respectively.

“Polysubstance abuse was the most frequent subcategory of illicit and prescription drug admissions,” the researchers wrote.

They acknowledged two limitations of the study: the short duration and single-center design. Future studies should account for seasonal differences in ICU admissions, they noted.

“Identifying and accurately describing the landscape of this current health crisis will help us take appropriate action in the future,” they concluded.

No funding sources were reported. The authors did not disclose any conflicts of interest.

SOURCE: Westerhausen D et al. Chest. 2019 Sep 5. doi: 10.1016/j.chest.2019.08.2180.

Combined hormone therapy and targeted therapy should be the first choice for most postmenopausal women with recently diagnosed hormone receptor–positive, HER2-negative metastatic breast cancer, new data suggest.

Although guidelines support use of hormone therapies with or without targeted therapies in this population, up-front chemotherapy is still commonly used even in the absence of a visceral crisis, noted lead investigator Mario Giuliano, MD, PhD, of the department of clinical medicine and surgery at the University of Naples (Italy) Federico II, and colleagues.

The investigators undertook a systematic review and network meta-analysis of 140 randomized, controlled trials among 50,029 postmenopausal patients with hormone receptor–positive, HER2-negative metastatic breast cancer treated in the first- and/or second-line setting.

Study results, reported in Lancet Oncology, showed that relative to standard hormone therapy alone, the combination of hormone therapy with a targeted therapy – a CDK4/6 inhibitor, an mammalian target of rapamycin inhibitor, or an indicated phosphoinositide 3-kinase inhibitor – had significantly better efficacy, reducing the risk of progression-free survival events by more than half. In addition, no chemotherapy regimen, with or without targeted therapy, significantly outperformed the combination of hormone therapy with a CDK4/6 inhibitor.

Meanwhile, the hormone therapy–targeted therapy combinations had manageable toxicity, with the severity of adverse effects intermediate between that of hormone therapy alone and that of chemotherapy with or without targeted therapies.

“This study is, to our knowledge, the first to compare the efficacy and activity of all currently available chemotherapy and hormone therapy regimens, in combination with or without targeted therapies,” Dr. Giuliano and coinvestigators wrote. “[O]ur results corroborate the treatment algorithms recommended by the official oncology guidelines, supporting the use of new combinations of hormone therapies plus targeted therapies in the first-line or second-line setting in patients with hormone receptor-positive, HER2-negative metastatic breast cancer without visceral crisis.”

For the study, the investigators identified relevant phase 2 and phase 3 randomized, controlled trials published between 2000 and 2017, with the addition of several recently reported trials such as BOLERO-6 (JAMA Oncol. 2018;4:1367-74). Of the 140 trials ultimately included, 114 were used in the analysis of progression-free survival and time to progression, and 135 were used in the analysis of overall response.

Study results showed that when anastrozole (Arimidex) alone was the comparator, progression-free survival was significantly better with palbociclib (Ibrance) plus letrozole (Femara) (hazard ratio for events, 0.42); ribociclib (Kisqali) plus letrozole (HR, 0.43); abemaciclib (Verzenio) plus anastrozole or letrozole (HR, 0.42); palbociclib plus fulvestrant (Faslodex) (HR, 0.37); ribociclib plus fulvestrant (HR, 0.48); abemaciclib plus fulvestrant (HR, 0.44); everolimus (Afinitor) plus exemestane (Aromasin) (HR, 0.42); and, in patients with a PIK3CA mutation, the PI3K inhibitor alpelisib (Piqray) plus fulvestrant (HR, 0.39).

Several chemotherapy-based regimens, including anthracycline- and taxane-containing regimens, were also superior to anastrozole alone (hazard ratios, 0.41-0.47).

When palbociclib plus letrozole was the comparator, no chemotherapy or hormone therapy regimen yielded significantly better progression-free survival.

For the outcome of overall response, paclitaxel (Taxol) plus bevacizumab (Avastin) was the only clinically relevant regimen that significantly improved the likelihood of response relative to palbociclib plus letrozole (odds ratio, 8.95).

Dr. Giuliano reported that he receives honoraria from Amgen, AstraZeneca, Celgene, Eisai, Eli Lilly, Novartis, Pfizer,and Roche. The study did not receive any funding.

SOURCE: Giuliano M et al. Lancet Oncol. 2019 Sep 4. doi: 10.1016/S1470-2045(19)30420-6.

Combined hormone therapy and targeted therapy should be the first choice for most postmenopausal women with recently diagnosed hormone receptor–positive, HER2-negative metastatic breast cancer, new data suggest.

Although guidelines support use of hormone therapies with or without targeted therapies in this population, up-front chemotherapy is still commonly used even in the absence of a visceral crisis, noted lead investigator Mario Giuliano, MD, PhD, of the department of clinical medicine and surgery at the University of Naples (Italy) Federico II, and colleagues.

The investigators undertook a systematic review and network meta-analysis of 140 randomized, controlled trials among 50,029 postmenopausal patients with hormone receptor–positive, HER2-negative metastatic breast cancer treated in the first- and/or second-line setting.

Study results, reported in Lancet Oncology, showed that relative to standard hormone therapy alone, the combination of hormone therapy with a targeted therapy – a CDK4/6 inhibitor, an mammalian target of rapamycin inhibitor, or an indicated phosphoinositide 3-kinase inhibitor – had significantly better efficacy, reducing the risk of progression-free survival events by more than half. In addition, no chemotherapy regimen, with or without targeted therapy, significantly outperformed the combination of hormone therapy with a CDK4/6 inhibitor.

Meanwhile, the hormone therapy–targeted therapy combinations had manageable toxicity, with the severity of adverse effects intermediate between that of hormone therapy alone and that of chemotherapy with or without targeted therapies.

“This study is, to our knowledge, the first to compare the efficacy and activity of all currently available chemotherapy and hormone therapy regimens, in combination with or without targeted therapies,” Dr. Giuliano and coinvestigators wrote. “[O]ur results corroborate the treatment algorithms recommended by the official oncology guidelines, supporting the use of new combinations of hormone therapies plus targeted therapies in the first-line or second-line setting in patients with hormone receptor-positive, HER2-negative metastatic breast cancer without visceral crisis.”

For the study, the investigators identified relevant phase 2 and phase 3 randomized, controlled trials published between 2000 and 2017, with the addition of several recently reported trials such as BOLERO-6 (JAMA Oncol. 2018;4:1367-74). Of the 140 trials ultimately included, 114 were used in the analysis of progression-free survival and time to progression, and 135 were used in the analysis of overall response.

Study results showed that when anastrozole (Arimidex) alone was the comparator, progression-free survival was significantly better with palbociclib (Ibrance) plus letrozole (Femara) (hazard ratio for events, 0.42); ribociclib (Kisqali) plus letrozole (HR, 0.43); abemaciclib (Verzenio) plus anastrozole or letrozole (HR, 0.42); palbociclib plus fulvestrant (Faslodex) (HR, 0.37); ribociclib plus fulvestrant (HR, 0.48); abemaciclib plus fulvestrant (HR, 0.44); everolimus (Afinitor) plus exemestane (Aromasin) (HR, 0.42); and, in patients with a PIK3CA mutation, the PI3K inhibitor alpelisib (Piqray) plus fulvestrant (HR, 0.39).

Several chemotherapy-based regimens, including anthracycline- and taxane-containing regimens, were also superior to anastrozole alone (hazard ratios, 0.41-0.47).

When palbociclib plus letrozole was the comparator, no chemotherapy or hormone therapy regimen yielded significantly better progression-free survival.

For the outcome of overall response, paclitaxel (Taxol) plus bevacizumab (Avastin) was the only clinically relevant regimen that significantly improved the likelihood of response relative to palbociclib plus letrozole (odds ratio, 8.95).

Dr. Giuliano reported that he receives honoraria from Amgen, AstraZeneca, Celgene, Eisai, Eli Lilly, Novartis, Pfizer,and Roche. The study did not receive any funding.

SOURCE: Giuliano M et al. Lancet Oncol. 2019 Sep 4. doi: 10.1016/S1470-2045(19)30420-6.

Combined hormone therapy and targeted therapy should be the first choice for most postmenopausal women with recently diagnosed hormone receptor–positive, HER2-negative metastatic breast cancer, new data suggest.

Although guidelines support use of hormone therapies with or without targeted therapies in this population, up-front chemotherapy is still commonly used even in the absence of a visceral crisis, noted lead investigator Mario Giuliano, MD, PhD, of the department of clinical medicine and surgery at the University of Naples (Italy) Federico II, and colleagues.

The investigators undertook a systematic review and network meta-analysis of 140 randomized, controlled trials among 50,029 postmenopausal patients with hormone receptor–positive, HER2-negative metastatic breast cancer treated in the first- and/or second-line setting.

Study results, reported in Lancet Oncology, showed that relative to standard hormone therapy alone, the combination of hormone therapy with a targeted therapy – a CDK4/6 inhibitor, an mammalian target of rapamycin inhibitor, or an indicated phosphoinositide 3-kinase inhibitor – had significantly better efficacy, reducing the risk of progression-free survival events by more than half. In addition, no chemotherapy regimen, with or without targeted therapy, significantly outperformed the combination of hormone therapy with a CDK4/6 inhibitor.

Meanwhile, the hormone therapy–targeted therapy combinations had manageable toxicity, with the severity of adverse effects intermediate between that of hormone therapy alone and that of chemotherapy with or without targeted therapies.

“This study is, to our knowledge, the first to compare the efficacy and activity of all currently available chemotherapy and hormone therapy regimens, in combination with or without targeted therapies,” Dr. Giuliano and coinvestigators wrote. “[O]ur results corroborate the treatment algorithms recommended by the official oncology guidelines, supporting the use of new combinations of hormone therapies plus targeted therapies in the first-line or second-line setting in patients with hormone receptor-positive, HER2-negative metastatic breast cancer without visceral crisis.”

For the study, the investigators identified relevant phase 2 and phase 3 randomized, controlled trials published between 2000 and 2017, with the addition of several recently reported trials such as BOLERO-6 (JAMA Oncol. 2018;4:1367-74). Of the 140 trials ultimately included, 114 were used in the analysis of progression-free survival and time to progression, and 135 were used in the analysis of overall response.

Study results showed that when anastrozole (Arimidex) alone was the comparator, progression-free survival was significantly better with palbociclib (Ibrance) plus letrozole (Femara) (hazard ratio for events, 0.42); ribociclib (Kisqali) plus letrozole (HR, 0.43); abemaciclib (Verzenio) plus anastrozole or letrozole (HR, 0.42); palbociclib plus fulvestrant (Faslodex) (HR, 0.37); ribociclib plus fulvestrant (HR, 0.48); abemaciclib plus fulvestrant (HR, 0.44); everolimus (Afinitor) plus exemestane (Aromasin) (HR, 0.42); and, in patients with a PIK3CA mutation, the PI3K inhibitor alpelisib (Piqray) plus fulvestrant (HR, 0.39).

Several chemotherapy-based regimens, including anthracycline- and taxane-containing regimens, were also superior to anastrozole alone (hazard ratios, 0.41-0.47).

When palbociclib plus letrozole was the comparator, no chemotherapy or hormone therapy regimen yielded significantly better progression-free survival.

For the outcome of overall response, paclitaxel (Taxol) plus bevacizumab (Avastin) was the only clinically relevant regimen that significantly improved the likelihood of response relative to palbociclib plus letrozole (odds ratio, 8.95).

Dr. Giuliano reported that he receives honoraria from Amgen, AstraZeneca, Celgene, Eisai, Eli Lilly, Novartis, Pfizer,and Roche. The study did not receive any funding.

SOURCE: Giuliano M et al. Lancet Oncol. 2019 Sep 4. doi: 10.1016/S1470-2045(19)30420-6.

Parental sensitive responsiveness, more than warmth, was associated with better child language skills, according to a meta-analysis in Pediatrics.

Mapodile/E+/Getty Images

Sheri Madigan, PhD, of the department of psychology at the University of Calgary (Alta.) and the Alberta Children’s Hospital Research Institute, also in Calgary, and colleagues brought together 37 studies of the association of either parental sensitive responsiveness, warmth, or both with children’s language skills. The studies ranged in sample sizes from 9 mother-child dyads to 1,026. For the purposes of the study, sensitive responsiveness was defined as “a parent’s ability to perceive and interpret the child’s signals and cues and to respond to those signals and cues promptly and appropriately,” and warmth was defined as “caregiver physical affection or their positive affective quality during contact and involvement with the child.”

Across 36 samples with a total of 7,315 dyads, an association was seen between sensitive responsiveness and child language, with a correlation coefficient of 0.26 (95% confidence interval, 0.21-0.33), whereas the analysis exploring parental warmth with 13 samples (1,961 dyads) found a somewhat weaker association, with a correlation coefficient of 0.16 (95% CI, 0.09-0.21), according to the investigators.

“A sensitive-responsive parent can build on the moment-to-moment shifts in children’s attention, providing a finely tuned enhancement to the child’s experience,” the researchers suggested in regard to the greater effect seen with sensitive responsiveness. “Neural development is thought to occur through internalization of these finely tuned, reciprocal interactions. Warmth, on the other hand, does not involve contingency or reciprocity.”

Interestingly, moderator analyses revealed variations in effect sizes according to socioeconomic status – with greater effect sizes associated with lower socioeconomic status.

“A possible interpretation of this finding is that maternal sensitive responsiveness is particularly advantageous to children’s language when they are raise in socially disadvantaged families,” they wrote, noting that such an interpretation would be in line with previous research that showed “the protective effect of high-quality parent-child interactions in the context of adversity.”

Limitations of the analysis include that meta-analyses of observational studies are correlational in nature and are generally unable to demonstrate inferences about causality. Another is that the studies in this analysis were limited to children who developed in typical fashion, which limits generalizability to children with language delay, intellectual disability, autism, or hearing/vision difficulties. The analysis was also limited to only mother-child dyads, so the effects of paternal parenting are absent.

“The findings indicate a moderate association between sensitive-responsive parenting and children’s language skills,” the researchers concluded. “Sensitive responsiveness is a modifiable risk that has been successfully trained in parents in randomized trials and shown to improve language development of children.”

A grant from the Social Sciences and Humanities Research Council was awarded to the two of the study’s authors. Two authors’ individual contributions were supported by funding from the Alberta Children’s Hospital Foundation. The authors indicated they have no financial relationships relevant to this article or conflicts of interest to disclose.

[email protected]

SOURCE: Madigan S et al. Pediatrics. 2019 Sep 24. doi: 10.1542/peds.2018-3556.

Parental sensitive responsiveness, more than warmth, was associated with better child language skills, according to a meta-analysis in Pediatrics.

Mapodile/E+/Getty Images

Sheri Madigan, PhD, of the department of psychology at the University of Calgary (Alta.) and the Alberta Children’s Hospital Research Institute, also in Calgary, and colleagues brought together 37 studies of the association of either parental sensitive responsiveness, warmth, or both with children’s language skills. The studies ranged in sample sizes from 9 mother-child dyads to 1,026. For the purposes of the study, sensitive responsiveness was defined as “a parent’s ability to perceive and interpret the child’s signals and cues and to respond to those signals and cues promptly and appropriately,” and warmth was defined as “caregiver physical affection or their positive affective quality during contact and involvement with the child.”

Across 36 samples with a total of 7,315 dyads, an association was seen between sensitive responsiveness and child language, with a correlation coefficient of 0.26 (95% confidence interval, 0.21-0.33), whereas the analysis exploring parental warmth with 13 samples (1,961 dyads) found a somewhat weaker association, with a correlation coefficient of 0.16 (95% CI, 0.09-0.21), according to the investigators.

“A sensitive-responsive parent can build on the moment-to-moment shifts in children’s attention, providing a finely tuned enhancement to the child’s experience,” the researchers suggested in regard to the greater effect seen with sensitive responsiveness. “Neural development is thought to occur through internalization of these finely tuned, reciprocal interactions. Warmth, on the other hand, does not involve contingency or reciprocity.”

Interestingly, moderator analyses revealed variations in effect sizes according to socioeconomic status – with greater effect sizes associated with lower socioeconomic status.

“A possible interpretation of this finding is that maternal sensitive responsiveness is particularly advantageous to children’s language when they are raise in socially disadvantaged families,” they wrote, noting that such an interpretation would be in line with previous research that showed “the protective effect of high-quality parent-child interactions in the context of adversity.”

Limitations of the analysis include that meta-analyses of observational studies are correlational in nature and are generally unable to demonstrate inferences about causality. Another is that the studies in this analysis were limited to children who developed in typical fashion, which limits generalizability to children with language delay, intellectual disability, autism, or hearing/vision difficulties. The analysis was also limited to only mother-child dyads, so the effects of paternal parenting are absent.

“The findings indicate a moderate association between sensitive-responsive parenting and children’s language skills,” the researchers concluded. “Sensitive responsiveness is a modifiable risk that has been successfully trained in parents in randomized trials and shown to improve language development of children.”

A grant from the Social Sciences and Humanities Research Council was awarded to the two of the study’s authors. Two authors’ individual contributions were supported by funding from the Alberta Children’s Hospital Foundation. The authors indicated they have no financial relationships relevant to this article or conflicts of interest to disclose.

[email protected]

SOURCE: Madigan S et al. Pediatrics. 2019 Sep 24. doi: 10.1542/peds.2018-3556.

Parental sensitive responsiveness, more than warmth, was associated with better child language skills, according to a meta-analysis in Pediatrics.

Mapodile/E+/Getty Images

Sheri Madigan, PhD, of the department of psychology at the University of Calgary (Alta.) and the Alberta Children’s Hospital Research Institute, also in Calgary, and colleagues brought together 37 studies of the association of either parental sensitive responsiveness, warmth, or both with children’s language skills. The studies ranged in sample sizes from 9 mother-child dyads to 1,026. For the purposes of the study, sensitive responsiveness was defined as “a parent’s ability to perceive and interpret the child’s signals and cues and to respond to those signals and cues promptly and appropriately,” and warmth was defined as “caregiver physical affection or their positive affective quality during contact and involvement with the child.”

Across 36 samples with a total of 7,315 dyads, an association was seen between sensitive responsiveness and child language, with a correlation coefficient of 0.26 (95% confidence interval, 0.21-0.33), whereas the analysis exploring parental warmth with 13 samples (1,961 dyads) found a somewhat weaker association, with a correlation coefficient of 0.16 (95% CI, 0.09-0.21), according to the investigators.

“A sensitive-responsive parent can build on the moment-to-moment shifts in children’s attention, providing a finely tuned enhancement to the child’s experience,” the researchers suggested in regard to the greater effect seen with sensitive responsiveness. “Neural development is thought to occur through internalization of these finely tuned, reciprocal interactions. Warmth, on the other hand, does not involve contingency or reciprocity.”

Interestingly, moderator analyses revealed variations in effect sizes according to socioeconomic status – with greater effect sizes associated with lower socioeconomic status.

“A possible interpretation of this finding is that maternal sensitive responsiveness is particularly advantageous to children’s language when they are raise in socially disadvantaged families,” they wrote, noting that such an interpretation would be in line with previous research that showed “the protective effect of high-quality parent-child interactions in the context of adversity.”

Limitations of the analysis include that meta-analyses of observational studies are correlational in nature and are generally unable to demonstrate inferences about causality. Another is that the studies in this analysis were limited to children who developed in typical fashion, which limits generalizability to children with language delay, intellectual disability, autism, or hearing/vision difficulties. The analysis was also limited to only mother-child dyads, so the effects of paternal parenting are absent.

“The findings indicate a moderate association between sensitive-responsive parenting and children’s language skills,” the researchers concluded. “Sensitive responsiveness is a modifiable risk that has been successfully trained in parents in randomized trials and shown to improve language development of children.”

A grant from the Social Sciences and Humanities Research Council was awarded to the two of the study’s authors. Two authors’ individual contributions were supported by funding from the Alberta Children’s Hospital Foundation. The authors indicated they have no financial relationships relevant to this article or conflicts of interest to disclose.

[email protected]

SOURCE: Madigan S et al. Pediatrics. 2019 Sep 24. doi: 10.1542/peds.2018-3556.

If you are still struggling to understand the ADHD phenomenon and its meteoric rise to prominence over the last 3 or 4 decades, a study published in the September 2019 Pediatrics may help you make sense of why you are spending a large part of your professional day counseling parents and treating children whose lives are disrupted by their impulsivity, distractibility, and inattentiveness (“24-hour movement behaviors and impulsivity.” doi: 10.1542/peds.2019-0187). Researchers at the Children’s Hospital of Eastern Ontario (Canada) Research Institute used data collected over 10 years in 21 sites across the United States on more than 4,500 children aged 8-11 years, looking for possible associations between impulsivity and three factors – sleep duration, screen time, and physical activity.

Goads Agency/Getty Images

They found that children who were exposed to fewer than 2 hours of recreational screen time each day and slept 9-11 hours nightly had significantly reduced scores on a range of impulsivity scores. While participating in at least 60 minutes of vigorous physical activity per day also was associated with less impulsivity, the effect added little to the benefit of the sleep/screen time combination. Although these nonpharmacologic strategies aimed at decreasing impulsivity may not be a cure-all for every child with symptoms that suggest ADHD, the data are compelling.

I hope that the associations these Canadian researchers have unearthed is not news to you. But their observation that 30% of the sample population met none of the recommendations for sleep, screen time, and activity and that only 5% of the sample did suggests that too few of us are delivering the message with sufficient enthusiasm and/or too many parents aren’t taking it seriously.

Over the last several years I have been encouraged to find sleep and screen time limits mentioned in articles on ADHD for both professionals and parents, but these potent contributors to impulsivity and distractibility always seem to be relegated to the oh-by-the-way category at the end of the article after a lengthy discussion of the relative values of medication and cognitive-behavioral therapy. And unfortunately, meeting these behavioral guidelines can be difficult to achieve and cannot be subcontracted out to a therapist or a pharmacist. They require parents to set and enforce limits. Saying no is difficult for all of us, particularly those without much prior experience.

Have you observed the association between inadequate sleep, excessive screen time, and impulsivity? How robustly have you bought into the idea that more sleep and less screen time are, if not THE answers, at least are the two we should start with? Where do your recommendations about screen time, sleep, and physical activity fit into the script when you are talking with parents about their child’s ADHD-ish behaviors? Have you put them in the oh-by-the-way category?

Do you ever say, “I know you may be expecting me to talk about medication at this visit, but I suggest you try setting and enforcing these limits on sleep and screen time for a few months and we will see how things are going”? “And I am going to give you some suggestions on how you can do this, and we will meet again as often as you feel is necessary to ease the process.”

Do you think you have the time to try this approach? Do you feel you have the skills to counsel on sleep and behavior? Do you think you can find someone with the time and experience who shares your priorities about screen time and sleep to do the parental coaching for you? It’s an approach worth considering when you step back and take the longer look at why we are living through this decades-long ADHD phenomenon.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

If you are still struggling to understand the ADHD phenomenon and its meteoric rise to prominence over the last 3 or 4 decades, a study published in the September 2019 Pediatrics may help you make sense of why you are spending a large part of your professional day counseling parents and treating children whose lives are disrupted by their impulsivity, distractibility, and inattentiveness (“24-hour movement behaviors and impulsivity.” doi: 10.1542/peds.2019-0187). Researchers at the Children’s Hospital of Eastern Ontario (Canada) Research Institute used data collected over 10 years in 21 sites across the United States on more than 4,500 children aged 8-11 years, looking for possible associations between impulsivity and three factors – sleep duration, screen time, and physical activity.

Goads Agency/Getty Images

They found that children who were exposed to fewer than 2 hours of recreational screen time each day and slept 9-11 hours nightly had significantly reduced scores on a range of impulsivity scores. While participating in at least 60 minutes of vigorous physical activity per day also was associated with less impulsivity, the effect added little to the benefit of the sleep/screen time combination. Although these nonpharmacologic strategies aimed at decreasing impulsivity may not be a cure-all for every child with symptoms that suggest ADHD, the data are compelling.

I hope that the associations these Canadian researchers have unearthed is not news to you. But their observation that 30% of the sample population met none of the recommendations for sleep, screen time, and activity and that only 5% of the sample did suggests that too few of us are delivering the message with sufficient enthusiasm and/or too many parents aren’t taking it seriously.

Over the last several years I have been encouraged to find sleep and screen time limits mentioned in articles on ADHD for both professionals and parents, but these potent contributors to impulsivity and distractibility always seem to be relegated to the oh-by-the-way category at the end of the article after a lengthy discussion of the relative values of medication and cognitive-behavioral therapy. And unfortunately, meeting these behavioral guidelines can be difficult to achieve and cannot be subcontracted out to a therapist or a pharmacist. They require parents to set and enforce limits. Saying no is difficult for all of us, particularly those without much prior experience.

Have you observed the association between inadequate sleep, excessive screen time, and impulsivity? How robustly have you bought into the idea that more sleep and less screen time are, if not THE answers, at least are the two we should start with? Where do your recommendations about screen time, sleep, and physical activity fit into the script when you are talking with parents about their child’s ADHD-ish behaviors? Have you put them in the oh-by-the-way category?

Do you ever say, “I know you may be expecting me to talk about medication at this visit, but I suggest you try setting and enforcing these limits on sleep and screen time for a few months and we will see how things are going”? “And I am going to give you some suggestions on how you can do this, and we will meet again as often as you feel is necessary to ease the process.”

Do you think you have the time to try this approach? Do you feel you have the skills to counsel on sleep and behavior? Do you think you can find someone with the time and experience who shares your priorities about screen time and sleep to do the parental coaching for you? It’s an approach worth considering when you step back and take the longer look at why we are living through this decades-long ADHD phenomenon.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

If you are still struggling to understand the ADHD phenomenon and its meteoric rise to prominence over the last 3 or 4 decades, a study published in the September 2019 Pediatrics may help you make sense of why you are spending a large part of your professional day counseling parents and treating children whose lives are disrupted by their impulsivity, distractibility, and inattentiveness (“24-hour movement behaviors and impulsivity.” doi: 10.1542/peds.2019-0187). Researchers at the Children’s Hospital of Eastern Ontario (Canada) Research Institute used data collected over 10 years in 21 sites across the United States on more than 4,500 children aged 8-11 years, looking for possible associations between impulsivity and three factors – sleep duration, screen time, and physical activity.

Goads Agency/Getty Images

They found that children who were exposed to fewer than 2 hours of recreational screen time each day and slept 9-11 hours nightly had significantly reduced scores on a range of impulsivity scores. While participating in at least 60 minutes of vigorous physical activity per day also was associated with less impulsivity, the effect added little to the benefit of the sleep/screen time combination. Although these nonpharmacologic strategies aimed at decreasing impulsivity may not be a cure-all for every child with symptoms that suggest ADHD, the data are compelling.

I hope that the associations these Canadian researchers have unearthed is not news to you. But their observation that 30% of the sample population met none of the recommendations for sleep, screen time, and activity and that only 5% of the sample did suggests that too few of us are delivering the message with sufficient enthusiasm and/or too many parents aren’t taking it seriously.

Over the last several years I have been encouraged to find sleep and screen time limits mentioned in articles on ADHD for both professionals and parents, but these potent contributors to impulsivity and distractibility always seem to be relegated to the oh-by-the-way category at the end of the article after a lengthy discussion of the relative values of medication and cognitive-behavioral therapy. And unfortunately, meeting these behavioral guidelines can be difficult to achieve and cannot be subcontracted out to a therapist or a pharmacist. They require parents to set and enforce limits. Saying no is difficult for all of us, particularly those without much prior experience.

Have you observed the association between inadequate sleep, excessive screen time, and impulsivity? How robustly have you bought into the idea that more sleep and less screen time are, if not THE answers, at least are the two we should start with? Where do your recommendations about screen time, sleep, and physical activity fit into the script when you are talking with parents about their child’s ADHD-ish behaviors? Have you put them in the oh-by-the-way category?

Do you ever say, “I know you may be expecting me to talk about medication at this visit, but I suggest you try setting and enforcing these limits on sleep and screen time for a few months and we will see how things are going”? “And I am going to give you some suggestions on how you can do this, and we will meet again as often as you feel is necessary to ease the process.”

Do you think you have the time to try this approach? Do you feel you have the skills to counsel on sleep and behavior? Do you think you can find someone with the time and experience who shares your priorities about screen time and sleep to do the parental coaching for you? It’s an approach worth considering when you step back and take the longer look at why we are living through this decades-long ADHD phenomenon.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

Most patients with stage III non–small cell lung cancer (NSCLC) who have distant progression on standard therapy typically have one or two new lesions, often in the same organ, which suggests a role for local ablative therapy, according to investigators.

This conclusion was drawn from an exploratory analysis of the phase 3 PACIFIC trial, which previously showed that durvalumab prolonged survival among patients with NSCLC who did not progress after chemoradiotherapy, which turned the trial protocol into a new standard of care.

At the annual meeting of the American Society for Radiation Oncology, coauthor Andreas Rimner, MD, of the Memorial Sloan Kettering Cancer Center in New York presented findings.

“There were always questions regarding detailed patterns of failure and disease progression in [the PACIFIC] trial,” Dr. Rimner said. “This study ... focuses on these patterns of failure, including the type of first progression in the patients on the PACIFIC trial.”

During the trial, 713 patients with NSCLC were randomized in a 2:1 ratio to receive either durvalumab or placebo. After a median follow-up of 25.2 months, the superiority of durvalumab was clear, with a lower rate of progression (45.4% vs. 64.6%).

But the present analysis dug deeper into this finding by dividing patients into three groups based on site or sites of first progression: local (intrathoracic) progression only, distant (extrathoracic) progression only, or simultaneously local and distant progression. Scans were reviewed by an independent radiologist who was not involved in the original PACIFIC trial. In addition to spatial data, the investigators reported times until progression.

Regardless of site, durvalumab was associated with a longer time until progression or death. Although comparative values were not reached for distant or simultaneous spread, median time until local progression or death was reportable, at 25.2 months in the durvalumab group versus with 9.2 months in the placebo group.

These values were available, in part, because local spread was the most common type of progression: It occurred in 80.6% of patients who progressed on durvalumab and 74.5% of progressors in the placebo group.

Durvalumab reduced the rate of progression across the three spatial categories, compared with placebo, including local only (36.6% vs. 48.1%, respectively), distant only (6.9% vs. 13.1%), and simultaneously local and distant (1.9% vs. 3.4%). This means that, at first progression, new distant lesions were found in 8.8% of patients treated with durvalumab, compared with 16.5% of those treated with placebo. Of note, approximately two-thirds of patients with distant progression had only one or two distant lesions, often confined to one organ, most commonly the brain. This pattern of progression was observed in both treatment arms.

According to Dr. Rimner, this finding is clinically relevant because it suggests a potential role for local ablative therapy.

Expert perspective on the analysis was provided by Benjamin Movsas, MD, chair of radiation oncology at the Henry Ford Cancer Institute in Detroit.

“The PACIFIC trial has really transformed the standard of care for patients with locally advanced, inoperable non–small cell lung cancer by adding immunotherapy to the prior standard of care combining chemotherapy and radiation, and this has shown a dramatic improvement in survival,” Dr. Movsas said.

“By adding the immunotherapy durvalumab, you can reduce risk of local failure, you can reduce the risk of distant failure, and interestingly enough, when patients do fail distantly, and this is true in both arms, they tended to fail in only one or two spots, which is encouraging because that suggests maybe a window of opportunity to treat those one or two spots, and we have newer technologies that allow us to consider that. So we really have a new paradigm.”

The study was funded by AstraZeneca. The investigators disclosed additional relationships with Merck, Nanobiotix, Boehringer Ingelheim, and others.

SOURCE: Rimner A et al. ASTRO 2019, Abstract LBA6.

Most patients with stage III non–small cell lung cancer (NSCLC) who have distant progression on standard therapy typically have one or two new lesions, often in the same organ, which suggests a role for local ablative therapy, according to investigators.

This conclusion was drawn from an exploratory analysis of the phase 3 PACIFIC trial, which previously showed that durvalumab prolonged survival among patients with NSCLC who did not progress after chemoradiotherapy, which turned the trial protocol into a new standard of care.

At the annual meeting of the American Society for Radiation Oncology, coauthor Andreas Rimner, MD, of the Memorial Sloan Kettering Cancer Center in New York presented findings.

“There were always questions regarding detailed patterns of failure and disease progression in [the PACIFIC] trial,” Dr. Rimner said. “This study ... focuses on these patterns of failure, including the type of first progression in the patients on the PACIFIC trial.”

During the trial, 713 patients with NSCLC were randomized in a 2:1 ratio to receive either durvalumab or placebo. After a median follow-up of 25.2 months, the superiority of durvalumab was clear, with a lower rate of progression (45.4% vs. 64.6%).

But the present analysis dug deeper into this finding by dividing patients into three groups based on site or sites of first progression: local (intrathoracic) progression only, distant (extrathoracic) progression only, or simultaneously local and distant progression. Scans were reviewed by an independent radiologist who was not involved in the original PACIFIC trial. In addition to spatial data, the investigators reported times until progression.

Regardless of site, durvalumab was associated with a longer time until progression or death. Although comparative values were not reached for distant or simultaneous spread, median time until local progression or death was reportable, at 25.2 months in the durvalumab group versus with 9.2 months in the placebo group.

These values were available, in part, because local spread was the most common type of progression: It occurred in 80.6% of patients who progressed on durvalumab and 74.5% of progressors in the placebo group.

Durvalumab reduced the rate of progression across the three spatial categories, compared with placebo, including local only (36.6% vs. 48.1%, respectively), distant only (6.9% vs. 13.1%), and simultaneously local and distant (1.9% vs. 3.4%). This means that, at first progression, new distant lesions were found in 8.8% of patients treated with durvalumab, compared with 16.5% of those treated with placebo. Of note, approximately two-thirds of patients with distant progression had only one or two distant lesions, often confined to one organ, most commonly the brain. This pattern of progression was observed in both treatment arms.

According to Dr. Rimner, this finding is clinically relevant because it suggests a potential role for local ablative therapy.

Expert perspective on the analysis was provided by Benjamin Movsas, MD, chair of radiation oncology at the Henry Ford Cancer Institute in Detroit.

“The PACIFIC trial has really transformed the standard of care for patients with locally advanced, inoperable non–small cell lung cancer by adding immunotherapy to the prior standard of care combining chemotherapy and radiation, and this has shown a dramatic improvement in survival,” Dr. Movsas said.

“By adding the immunotherapy durvalumab, you can reduce risk of local failure, you can reduce the risk of distant failure, and interestingly enough, when patients do fail distantly, and this is true in both arms, they tended to fail in only one or two spots, which is encouraging because that suggests maybe a window of opportunity to treat those one or two spots, and we have newer technologies that allow us to consider that. So we really have a new paradigm.”

The study was funded by AstraZeneca. The investigators disclosed additional relationships with Merck, Nanobiotix, Boehringer Ingelheim, and others.

SOURCE: Rimner A et al. ASTRO 2019, Abstract LBA6.

Most patients with stage III non–small cell lung cancer (NSCLC) who have distant progression on standard therapy typically have one or two new lesions, often in the same organ, which suggests a role for local ablative therapy, according to investigators.

This conclusion was drawn from an exploratory analysis of the phase 3 PACIFIC trial, which previously showed that durvalumab prolonged survival among patients with NSCLC who did not progress after chemoradiotherapy, which turned the trial protocol into a new standard of care.

At the annual meeting of the American Society for Radiation Oncology, coauthor Andreas Rimner, MD, of the Memorial Sloan Kettering Cancer Center in New York presented findings.

“There were always questions regarding detailed patterns of failure and disease progression in [the PACIFIC] trial,” Dr. Rimner said. “This study ... focuses on these patterns of failure, including the type of first progression in the patients on the PACIFIC trial.”

During the trial, 713 patients with NSCLC were randomized in a 2:1 ratio to receive either durvalumab or placebo. After a median follow-up of 25.2 months, the superiority of durvalumab was clear, with a lower rate of progression (45.4% vs. 64.6%).

But the present analysis dug deeper into this finding by dividing patients into three groups based on site or sites of first progression: local (intrathoracic) progression only, distant (extrathoracic) progression only, or simultaneously local and distant progression. Scans were reviewed by an independent radiologist who was not involved in the original PACIFIC trial. In addition to spatial data, the investigators reported times until progression.

Regardless of site, durvalumab was associated with a longer time until progression or death. Although comparative values were not reached for distant or simultaneous spread, median time until local progression or death was reportable, at 25.2 months in the durvalumab group versus with 9.2 months in the placebo group.

These values were available, in part, because local spread was the most common type of progression: It occurred in 80.6% of patients who progressed on durvalumab and 74.5% of progressors in the placebo group.

Durvalumab reduced the rate of progression across the three spatial categories, compared with placebo, including local only (36.6% vs. 48.1%, respectively), distant only (6.9% vs. 13.1%), and simultaneously local and distant (1.9% vs. 3.4%). This means that, at first progression, new distant lesions were found in 8.8% of patients treated with durvalumab, compared with 16.5% of those treated with placebo. Of note, approximately two-thirds of patients with distant progression had only one or two distant lesions, often confined to one organ, most commonly the brain. This pattern of progression was observed in both treatment arms.

According to Dr. Rimner, this finding is clinically relevant because it suggests a potential role for local ablative therapy.

Expert perspective on the analysis was provided by Benjamin Movsas, MD, chair of radiation oncology at the Henry Ford Cancer Institute in Detroit.

“The PACIFIC trial has really transformed the standard of care for patients with locally advanced, inoperable non–small cell lung cancer by adding immunotherapy to the prior standard of care combining chemotherapy and radiation, and this has shown a dramatic improvement in survival,” Dr. Movsas said.

“By adding the immunotherapy durvalumab, you can reduce risk of local failure, you can reduce the risk of distant failure, and interestingly enough, when patients do fail distantly, and this is true in both arms, they tended to fail in only one or two spots, which is encouraging because that suggests maybe a window of opportunity to treat those one or two spots, and we have newer technologies that allow us to consider that. So we really have a new paradigm.”

The study was funded by AstraZeneca. The investigators disclosed additional relationships with Merck, Nanobiotix, Boehringer Ingelheim, and others.

SOURCE: Rimner A et al. ASTRO 2019, Abstract LBA6.

Stereotactic ablative radiation therapy (SABR) may be able to extend progression-free survival (PFS) among patients with oligometastatic prostate cancer, based on results from the phase 2 ORIOLE trial.

Will Pass/MDedge News

SABR appeared to control disease, in part, by triggering a systemic immune response, reported lead author Ryan Phillips, MD, PhD, chief resident of radiation oncology at Johns Hopkins Sidney Kimmel Cancer Center in Baltimore, at the annual meeting of the American Society for Radiation Oncology. This is a particularly noteworthy finding, since prostate cancer is generally considered to be immunologically cold, Dr. Phillips explained.

The ORIOLE trial also demonstrated how prostate-specific membrane antigen (PSMA)–based PET/CT scans can be used to more accurately predict metastasis by detecting lesions that would otherwise be missed by standard imaging.

“There’s a hypothesis that these first few sites of spread pave the way for additional widespread metastasis down the road,” Dr. Phillips said, “and that if we can treat all detectable disease early enough, we may be able to provide long-term control or in the best-case scenario, be able to cure these patients of early metastatic disease.”

The trial involved 54 men with recurrent, hormone-sensitive prostate cancer who had been previously treated with radiation therapy or surgery. Additional eligibility requirements included one to three lesions that were 5 cm or smaller, detectable by MRI, CT, or bone scan; a prostate-specific antigen (PSA) doubling time of less than 15 months; and an Eastern Cooperative Oncology Group performance status of 2 or less.

Patients were randomized in a 2:1 ratio to receive either SABR or observation, with follow-up every 3 months including physical exam and PSA measurement, and at 6 months, CT and bone scan. The primary endpoint was disease progression at 6 months.

In addition to this protocol, biomarker correlative analyses were performed, including PSMA-based PET/CT, T-cell clonality testing, and circulating tumor DNA (ctDNA) assessment.

Results showed that significantly fewer men treated with SABR had disease progression at 6 months (19% vs. 61%; P = .005). This benefit extended beyond the primary endpoint, as median PFS among patients treated with SABR was not yet reached after more than a year of follow-up, while those in the observation group had a median PFS of 5.8 months (P = .0023).

“Clinically, this is promising,” Dr. Phillips said, “but we also were really interested in learning more about oligometastatic prostate cancer, and something that sets ORIOLE apart are the correlative studies.”

The first of these studies involved PSMA-based PET/CT, which can identify lesions that may be missed or underappreciated with conventional imaging. Within the SABR group, 35 of 36 men had PSMA-based PET/CT performed at baseline and 6 months later. Of these, 19 had all PSMA-based PET/CT–detectable lesions treated with SABR (total consolidation), while 16 had subtotal consolidation. This difference was predictive of outcome, as only 16% of patients with total consolidation developed new lesions 6 months later, compared with 63% of those who had subtotal consolidation (P = .006).

“Not only are we treating the disease we’re detecting, but it seems to be preventing the development of new metastases outside the areas that we treated,” Dr. Phillips said. “This also held when we looked at points beyond 6 months,” he added.

Further testing showed that SABR triggered a systemic adaptive immune response involving expansion of T-cell clones. “There’s a lot more activity and changes within the immune system that were only seen within the SABR arm,” Dr. Phillips said, noting that these changes were “similar in scope to what we see after a vaccination.”

Finally, the investigators assessed ctDNA, which showed that men with at least one high-risk mutation had similar outcomes regardless of treatment group; in contrast, those without any high-risk mutations had significantly better PFS when treated with SABR.

“These are low sample size, hypothesis-generating experiments,” Dr. Phillips said, “but it is promising that there may be measurable baseline factors that will help us decide which patients are likely to benefit from this approach, and which would really be better served with an alternate treatment strategy.”

Will Pass/MDedge News

Session moderator Anthony Zietman, MD, of Massachusetts General Hospital, Boston, suggested that the ORIOLE trial could have a big future. “This is a small study, but it’s a prospective study, and the findings are really provocative,” Dr. Zietman said. “Just imagine, if there was a patient with just two or three metastatic lesions, and by irradiating those, you could liberate proteins from the destroyed metastases, generate an immune response, and suppress the development of new metastases, that will be something extraordinary. So this trial will be followed very closely as it seems to be hinting at something that’s a bit of a Holy Grail in oncology.”

The investigators disclosed relationships with RefleXion Medical, Pfizer, Genentech, and others.

SOURCE: Phillips R et al. ASTRO 2019. Abstract LBA3.

Stereotactic ablative radiation therapy (SABR) may be able to extend progression-free survival (PFS) among patients with oligometastatic prostate cancer, based on results from the phase 2 ORIOLE trial.

Will Pass/MDedge News

SABR appeared to control disease, in part, by triggering a systemic immune response, reported lead author Ryan Phillips, MD, PhD, chief resident of radiation oncology at Johns Hopkins Sidney Kimmel Cancer Center in Baltimore, at the annual meeting of the American Society for Radiation Oncology. This is a particularly noteworthy finding, since prostate cancer is generally considered to be immunologically cold, Dr. Phillips explained.

The ORIOLE trial also demonstrated how prostate-specific membrane antigen (PSMA)–based PET/CT scans can be used to more accurately predict metastasis by detecting lesions that would otherwise be missed by standard imaging.

“There’s a hypothesis that these first few sites of spread pave the way for additional widespread metastasis down the road,” Dr. Phillips said, “and that if we can treat all detectable disease early enough, we may be able to provide long-term control or in the best-case scenario, be able to cure these patients of early metastatic disease.”

The trial involved 54 men with recurrent, hormone-sensitive prostate cancer who had been previously treated with radiation therapy or surgery. Additional eligibility requirements included one to three lesions that were 5 cm or smaller, detectable by MRI, CT, or bone scan; a prostate-specific antigen (PSA) doubling time of less than 15 months; and an Eastern Cooperative Oncology Group performance status of 2 or less.

Patients were randomized in a 2:1 ratio to receive either SABR or observation, with follow-up every 3 months including physical exam and PSA measurement, and at 6 months, CT and bone scan. The primary endpoint was disease progression at 6 months.

In addition to this protocol, biomarker correlative analyses were performed, including PSMA-based PET/CT, T-cell clonality testing, and circulating tumor DNA (ctDNA) assessment.

Results showed that significantly fewer men treated with SABR had disease progression at 6 months (19% vs. 61%; P = .005). This benefit extended beyond the primary endpoint, as median PFS among patients treated with SABR was not yet reached after more than a year of follow-up, while those in the observation group had a median PFS of 5.8 months (P = .0023).

“Clinically, this is promising,” Dr. Phillips said, “but we also were really interested in learning more about oligometastatic prostate cancer, and something that sets ORIOLE apart are the correlative studies.”

The first of these studies involved PSMA-based PET/CT, which can identify lesions that may be missed or underappreciated with conventional imaging. Within the SABR group, 35 of 36 men had PSMA-based PET/CT performed at baseline and 6 months later. Of these, 19 had all PSMA-based PET/CT–detectable lesions treated with SABR (total consolidation), while 16 had subtotal consolidation. This difference was predictive of outcome, as only 16% of patients with total consolidation developed new lesions 6 months later, compared with 63% of those who had subtotal consolidation (P = .006).

“Not only are we treating the disease we’re detecting, but it seems to be preventing the development of new metastases outside the areas that we treated,” Dr. Phillips said. “This also held when we looked at points beyond 6 months,” he added.

Further testing showed that SABR triggered a systemic adaptive immune response involving expansion of T-cell clones. “There’s a lot more activity and changes within the immune system that were only seen within the SABR arm,” Dr. Phillips said, noting that these changes were “similar in scope to what we see after a vaccination.”

Finally, the investigators assessed ctDNA, which showed that men with at least one high-risk mutation had similar outcomes regardless of treatment group; in contrast, those without any high-risk mutations had significantly better PFS when treated with SABR.

“These are low sample size, hypothesis-generating experiments,” Dr. Phillips said, “but it is promising that there may be measurable baseline factors that will help us decide which patients are likely to benefit from this approach, and which would really be better served with an alternate treatment strategy.”

Will Pass/MDedge News

Session moderator Anthony Zietman, MD, of Massachusetts General Hospital, Boston, suggested that the ORIOLE trial could have a big future. “This is a small study, but it’s a prospective study, and the findings are really provocative,” Dr. Zietman said. “Just imagine, if there was a patient with just two or three metastatic lesions, and by irradiating those, you could liberate proteins from the destroyed metastases, generate an immune response, and suppress the development of new metastases, that will be something extraordinary. So this trial will be followed very closely as it seems to be hinting at something that’s a bit of a Holy Grail in oncology.”

The investigators disclosed relationships with RefleXion Medical, Pfizer, Genentech, and others.

SOURCE: Phillips R et al. ASTRO 2019. Abstract LBA3.

Stereotactic ablative radiation therapy (SABR) may be able to extend progression-free survival (PFS) among patients with oligometastatic prostate cancer, based on results from the phase 2 ORIOLE trial.

Will Pass/MDedge News

SABR appeared to control disease, in part, by triggering a systemic immune response, reported lead author Ryan Phillips, MD, PhD, chief resident of radiation oncology at Johns Hopkins Sidney Kimmel Cancer Center in Baltimore, at the annual meeting of the American Society for Radiation Oncology. This is a particularly noteworthy finding, since prostate cancer is generally considered to be immunologically cold, Dr. Phillips explained.

The ORIOLE trial also demonstrated how prostate-specific membrane antigen (PSMA)–based PET/CT scans can be used to more accurately predict metastasis by detecting lesions that would otherwise be missed by standard imaging.

“There’s a hypothesis that these first few sites of spread pave the way for additional widespread metastasis down the road,” Dr. Phillips said, “and that if we can treat all detectable disease early enough, we may be able to provide long-term control or in the best-case scenario, be able to cure these patients of early metastatic disease.”

The trial involved 54 men with recurrent, hormone-sensitive prostate cancer who had been previously treated with radiation therapy or surgery. Additional eligibility requirements included one to three lesions that were 5 cm or smaller, detectable by MRI, CT, or bone scan; a prostate-specific antigen (PSA) doubling time of less than 15 months; and an Eastern Cooperative Oncology Group performance status of 2 or less.

Patients were randomized in a 2:1 ratio to receive either SABR or observation, with follow-up every 3 months including physical exam and PSA measurement, and at 6 months, CT and bone scan. The primary endpoint was disease progression at 6 months.

In addition to this protocol, biomarker correlative analyses were performed, including PSMA-based PET/CT, T-cell clonality testing, and circulating tumor DNA (ctDNA) assessment.

Results showed that significantly fewer men treated with SABR had disease progression at 6 months (19% vs. 61%; P = .005). This benefit extended beyond the primary endpoint, as median PFS among patients treated with SABR was not yet reached after more than a year of follow-up, while those in the observation group had a median PFS of 5.8 months (P = .0023).

“Clinically, this is promising,” Dr. Phillips said, “but we also were really interested in learning more about oligometastatic prostate cancer, and something that sets ORIOLE apart are the correlative studies.”

The first of these studies involved PSMA-based PET/CT, which can identify lesions that may be missed or underappreciated with conventional imaging. Within the SABR group, 35 of 36 men had PSMA-based PET/CT performed at baseline and 6 months later. Of these, 19 had all PSMA-based PET/CT–detectable lesions treated with SABR (total consolidation), while 16 had subtotal consolidation. This difference was predictive of outcome, as only 16% of patients with total consolidation developed new lesions 6 months later, compared with 63% of those who had subtotal consolidation (P = .006).

“Not only are we treating the disease we’re detecting, but it seems to be preventing the development of new metastases outside the areas that we treated,” Dr. Phillips said. “This also held when we looked at points beyond 6 months,” he added.

Further testing showed that SABR triggered a systemic adaptive immune response involving expansion of T-cell clones. “There’s a lot more activity and changes within the immune system that were only seen within the SABR arm,” Dr. Phillips said, noting that these changes were “similar in scope to what we see after a vaccination.”

Finally, the investigators assessed ctDNA, which showed that men with at least one high-risk mutation had similar outcomes regardless of treatment group; in contrast, those without any high-risk mutations had significantly better PFS when treated with SABR.

“These are low sample size, hypothesis-generating experiments,” Dr. Phillips said, “but it is promising that there may be measurable baseline factors that will help us decide which patients are likely to benefit from this approach, and which would really be better served with an alternate treatment strategy.”

Will Pass/MDedge News

Session moderator Anthony Zietman, MD, of Massachusetts General Hospital, Boston, suggested that the ORIOLE trial could have a big future. “This is a small study, but it’s a prospective study, and the findings are really provocative,” Dr. Zietman said. “Just imagine, if there was a patient with just two or three metastatic lesions, and by irradiating those, you could liberate proteins from the destroyed metastases, generate an immune response, and suppress the development of new metastases, that will be something extraordinary. So this trial will be followed very closely as it seems to be hinting at something that’s a bit of a Holy Grail in oncology.”

The investigators disclosed relationships with RefleXion Medical, Pfizer, Genentech, and others.

SOURCE: Phillips R et al. ASTRO 2019. Abstract LBA3.

NEW YORK –The work of the dermatologist doesn’t need to stop at the lips, according to Nasim Fazel, MD, DDS, a board-certified dermatologist and dentist. With a light touch driven by understanding of the oral mucosa, dermatologists can confidently obtain high-quality specimens and manage many intra-oral cutaneous conditions, she said, speaking at a session focused on oral health and procedures at the American Academy of Dermatology summer meeting.

Whether to perform an incisional or excisional biopsy on the lips or within the oral cavity is a decision driven by the clinical scenario, said Dr. Fazel, professor of clinical dermatology and director of the oral mucosal disease clinic at the University of California, Davis. Variables to consider, she said, include the size of the lesion, as well as whether the lesion is symptomatic or there’s any functional impairment. Other factors to bear in mind are whether the patient has any comorbid inflammatory conditions and whether the lesion could be malignant.

An excisional biopsy is a good procedure for small lesions that are thought to be benign, especially if they are exophytic, she noted. An example would be a traumatic fibroma, she said. This technique is also appropriate if there’s concern for dysplasia or malignancy if an office excisional biopsy is feasible given lesion size and location.

On the labial mucosa, an elliptical incision is often a good choice.
 

Cutaneous lip procedures

On the cutaneous lip, a punch incision can be feasible. The vermilion border should be marked to maintain orientation. “Avoid transecting the vermilion border to the extent that it’s possible,” said Dr. Fazel. Keep the vascular anatomy in mind as well, she added, since there’s a risk of severing the superior or inferior labial artery with procedures in this area. If this should happen, the branch can be identified and ligated with 4-0 fast gut or chromic gut suture material, she advised.

Another option on the cutaneous lip is shave removal. Here, a chalazion clamp can be used for both exposure and hemostasis. “Always suture parallel to the lip lines, and caution the patient that there may be significant, noticeable blanching when lip anesthesia’s used,” she said.
 

Gingival and tongue procedures

Moving to territory that may be less familiar for some dermatologists, Dr. Fazel walked through the process of a gingival punch biopsy. “Use local anesthetic, but a small quantity is sufficient,” she said. Using gentle pressure, the operator can work the punch instrument down to periosteal bone. At that point, just scissors can be used for undermining the specimen, with minimal disturbance of the mucosal surface.

Hemostasis after a gingival punch can be accomplished with silver nitrate or aluminum chloride or by electrocautery. A permanent defect in the gingiva can occur even with good technique, she said – a fact that should be included in the informed consent document for the procedure.

For lesions on the tongue, a shave removal can be considered, as can an incisional punch biopsy. An assistant’s hands are invaluable for stabilizing the tongue, said Dr. Fazel, illustrating that small dry gauze squares help achieve a good grip.
 

Considerations in biopsy technique

Dr. Fazel offered some tips and considerations when a punch biopsy is being done in the context of a chronic oral inflammatory condition, and the plan is to submit for hematoxylin and eosin (H&E) staining and direct immunofluorescence (DIF). Conditions where an intraoral punch biopsy would be considered include bullous or mucous membrane pemphigoid, pemphigus, lichen planus, and systemic lupus erythematosus, she said.

“Select a site with the most significant inflammatory changes” and aim for the most anterior site that exhibits these characteristics to maximize exposure and ensure a good specimen. The labial mucosa is a better choice in general than buccal mucosa, she said. “Maxillary and mandibular sulci are tricky sites,” especially when perilesional and lesional tissue should be included in the biopsies.

Next, Dr. Fazel walked attendees through general principles of preparing for and performing punch biopsies for H&E and DIF. In planning the biopsies, the DIF specimen should ideally be collected before the H&E specimen because the former technique will have higher yield when the specimen is taken from a less bloody field. “The yield of DIF is higher from the gingiva than from nonkeratinized surfaces.”

When infiltrating the biopsy site with local anesthesia, the needle should be centered within the lesion or general area to be biopsied, and care should be taken to maintain the orientation of the lesion to the surrounding tissue. Anesthesia can be infiltrated within the submucosal plane; the resultant ballooning will elevate the tissue to be biopsied and ease the procedure, she said.

Choose a 3-mm punch tool for gingival biopsies; 4 mm is a good size for other nonkeratinized surfaces. Unlike the procedure used for cutaneous biopsies, on delicate oral tissues, “you don’t need to hub your punch tool,” Dr. Fazel said. Similarly, the tool can be driven with firm rotation in one direction, rather than ratcheting back and forth, which may fray and deform the biopsy margins, she added. The specimen can be freed from surrounding mucosa with scissors alone and a gentle snipping motion; everting the tissue will help achieve the desired clean and gentle technique.

Because of the delicacy of the tissue, “it’s important to minimize the use of forceps, as well as any unnecessary manipulation of tissue in the process of specimen collection,” she said.
 

Salivary gland biopsies and intraoral suturing

Even minor salivary glands can be biopsied in a fairly straightforward way, though there’s a risk of short- and long-term loss of sensation, as well as more scarring than in other routine intraoral biopsies. Though these salivary glands lie just beneath the oral mucosa, care must be taken to avoid laceration of the orbicularis oris muscle during excision, noted Dr. Fazel. With a minor salivary gland biopsy, as with some other intraoral procedures, sutures will be needed. Consideration for the friability of the oral mucosa should drive suture material choice and closure technique.

First, “take bigger bites on each side of the incision, to minimize the risk of the suture tearing through the mucosa,” she said. Avoid forceps while suturing if possible, but be gentle if they are employed, “and be gentle tying knots: retract the mucosa as little as possible and cinch the knots down tightly with your fingers.”

Electrocautery, silver nitrate, and aluminum chloride are all reasonable options for hemostasis, although patients should be alerted that the tissue will have a charred appearance if electrocautery is used. Primary closure may be all that’s needed for hemostasis, said Dr. Fazel.

If nonabsorbable suture materials are used, nylon and prolene should be avoided since they tend to tear through the oral mucosa. Soft or braided silk are good choices, she said, and sutures can come out in 5-7 days.

Absorbable sutures have the advantage of not requiring removal, but they can be more irritating to the surrounding mucosa. Chromic or fast gut are the choices here, said Dr. Fazel. Whether absorbable or nonabsorbable sutures are placed, the size should be 4-0 or 5-0, she said.
 

Postoperative care, complications, and the limits of the dermatologist

Postoperatively, patients should know that swelling is to be expected, especially with procedures like minor salivary gland biopsies that involve the lip. Icing 15 minutes per hour for the first few hours will help with swelling; wound care is optimized with gentle salt water rinses. A bland diet that avoids acidic, spicy, and excessively hot foods and beverages will minimize wound irritation. Foods with sharp edges like chips, crackers, and nuts can actually catch sutures and cause pain and bleeding, so these too should be avoided.

As with dental work, care should be taken with eating or drinking until anesthesia has worn off, which may take up to 3 hours. Patients should also be cautioned that sutures are likely to come out prematurely just because of the mobility of the structures of the mouth with normal activities such as eating and talking.

Should a wound infection occur, said Dr. Fazel, it’s likely that mixed aerobic and anaerobic bacteria are to blame; accordingly, broad-spectrum beta-lactam antibiotics can be a good first-line course. More severe infections are more likely to have an anaerobic or gram-negative etiology; metronidazole is a reasonable choice for anaerobic coverage, she noted. The life-threatening complication not to miss is cellulitis of the floor of the mouth, or Ludwig angina. The swelling results in superior and posterior displacement of the tongue, obstructing the upper airway, so any patient suspected of having Ludwig angina needs emergent evaluation and treatment.

When should a dermatologist consider referral to an otolaryngologist rather than diving into a biopsy in the dermatology clinic? If the area of concern is on the posterior third of the tongue, access without special tools or higher levels of anesthesia becomes tricky, Dr. Fazel pointed out. The posterior hard palate, the soft palate, and the floor of the mouth are also regions best left to otolaryngologists, she said.

[email protected]

NEW YORK –The work of the dermatologist doesn’t need to stop at the lips, according to Nasim Fazel, MD, DDS, a board-certified dermatologist and dentist. With a light touch driven by understanding of the oral mucosa, dermatologists can confidently obtain high-quality specimens and manage many intra-oral cutaneous conditions, she said, speaking at a session focused on oral health and procedures at the American Academy of Dermatology summer meeting.

Whether to perform an incisional or excisional biopsy on the lips or within the oral cavity is a decision driven by the clinical scenario, said Dr. Fazel, professor of clinical dermatology and director of the oral mucosal disease clinic at the University of California, Davis. Variables to consider, she said, include the size of the lesion, as well as whether the lesion is symptomatic or there’s any functional impairment. Other factors to bear in mind are whether the patient has any comorbid inflammatory conditions and whether the lesion could be malignant.

An excisional biopsy is a good procedure for small lesions that are thought to be benign, especially if they are exophytic, she noted. An example would be a traumatic fibroma, she said. This technique is also appropriate if there’s concern for dysplasia or malignancy if an office excisional biopsy is feasible given lesion size and location.

On the labial mucosa, an elliptical incision is often a good choice.
 

Cutaneous lip procedures

On the cutaneous lip, a punch incision can be feasible. The vermilion border should be marked to maintain orientation. “Avoid transecting the vermilion border to the extent that it’s possible,” said Dr. Fazel. Keep the vascular anatomy in mind as well, she added, since there’s a risk of severing the superior or inferior labial artery with procedures in this area. If this should happen, the branch can be identified and ligated with 4-0 fast gut or chromic gut suture material, she advised.

Another option on the cutaneous lip is shave removal. Here, a chalazion clamp can be used for both exposure and hemostasis. “Always suture parallel to the lip lines, and caution the patient that there may be significant, noticeable blanching when lip anesthesia’s used,” she said.
 

Gingival and tongue procedures

Moving to territory that may be less familiar for some dermatologists, Dr. Fazel walked through the process of a gingival punch biopsy. “Use local anesthetic, but a small quantity is sufficient,” she said. Using gentle pressure, the operator can work the punch instrument down to periosteal bone. At that point, just scissors can be used for undermining the specimen, with minimal disturbance of the mucosal surface.

Hemostasis after a gingival punch can be accomplished with silver nitrate or aluminum chloride or by electrocautery. A permanent defect in the gingiva can occur even with good technique, she said – a fact that should be included in the informed consent document for the procedure.

For lesions on the tongue, a shave removal can be considered, as can an incisional punch biopsy. An assistant’s hands are invaluable for stabilizing the tongue, said Dr. Fazel, illustrating that small dry gauze squares help achieve a good grip.
 

Considerations in biopsy technique

Dr. Fazel offered some tips and considerations when a punch biopsy is being done in the context of a chronic oral inflammatory condition, and the plan is to submit for hematoxylin and eosin (H&E) staining and direct immunofluorescence (DIF). Conditions where an intraoral punch biopsy would be considered include bullous or mucous membrane pemphigoid, pemphigus, lichen planus, and systemic lupus erythematosus, she said.

“Select a site with the most significant inflammatory changes” and aim for the most anterior site that exhibits these characteristics to maximize exposure and ensure a good specimen. The labial mucosa is a better choice in general than buccal mucosa, she said. “Maxillary and mandibular sulci are tricky sites,” especially when perilesional and lesional tissue should be included in the biopsies.

Next, Dr. Fazel walked attendees through general principles of preparing for and performing punch biopsies for H&E and DIF. In planning the biopsies, the DIF specimen should ideally be collected before the H&E specimen because the former technique will have higher yield when the specimen is taken from a less bloody field. “The yield of DIF is higher from the gingiva than from nonkeratinized surfaces.”

When infiltrating the biopsy site with local anesthesia, the needle should be centered within the lesion or general area to be biopsied, and care should be taken to maintain the orientation of the lesion to the surrounding tissue. Anesthesia can be infiltrated within the submucosal plane; the resultant ballooning will elevate the tissue to be biopsied and ease the procedure, she said.

Choose a 3-mm punch tool for gingival biopsies; 4 mm is a good size for other nonkeratinized surfaces. Unlike the procedure used for cutaneous biopsies, on delicate oral tissues, “you don’t need to hub your punch tool,” Dr. Fazel said. Similarly, the tool can be driven with firm rotation in one direction, rather than ratcheting back and forth, which may fray and deform the biopsy margins, she added. The specimen can be freed from surrounding mucosa with scissors alone and a gentle snipping motion; everting the tissue will help achieve the desired clean and gentle technique.

Because of the delicacy of the tissue, “it’s important to minimize the use of forceps, as well as any unnecessary manipulation of tissue in the process of specimen collection,” she said.
 

Salivary gland biopsies and intraoral suturing

Even minor salivary glands can be biopsied in a fairly straightforward way, though there’s a risk of short- and long-term loss of sensation, as well as more scarring than in other routine intraoral biopsies. Though these salivary glands lie just beneath the oral mucosa, care must be taken to avoid laceration of the orbicularis oris muscle during excision, noted Dr. Fazel. With a minor salivary gland biopsy, as with some other intraoral procedures, sutures will be needed. Consideration for the friability of the oral mucosa should drive suture material choice and closure technique.

First, “take bigger bites on each side of the incision, to minimize the risk of the suture tearing through the mucosa,” she said. Avoid forceps while suturing if possible, but be gentle if they are employed, “and be gentle tying knots: retract the mucosa as little as possible and cinch the knots down tightly with your fingers.”

Electrocautery, silver nitrate, and aluminum chloride are all reasonable options for hemostasis, although patients should be alerted that the tissue will have a charred appearance if electrocautery is used. Primary closure may be all that’s needed for hemostasis, said Dr. Fazel.

If nonabsorbable suture materials are used, nylon and prolene should be avoided since they tend to tear through the oral mucosa. Soft or braided silk are good choices, she said, and sutures can come out in 5-7 days.

Absorbable sutures have the advantage of not requiring removal, but they can be more irritating to the surrounding mucosa. Chromic or fast gut are the choices here, said Dr. Fazel. Whether absorbable or nonabsorbable sutures are placed, the size should be 4-0 or 5-0, she said.
 

Postoperative care, complications, and the limits of the dermatologist

Postoperatively, patients should know that swelling is to be expected, especially with procedures like minor salivary gland biopsies that involve the lip. Icing 15 minutes per hour for the first few hours will help with swelling; wound care is optimized with gentle salt water rinses. A bland diet that avoids acidic, spicy, and excessively hot foods and beverages will minimize wound irritation. Foods with sharp edges like chips, crackers, and nuts can actually catch sutures and cause pain and bleeding, so these too should be avoided.

As with dental work, care should be taken with eating or drinking until anesthesia has worn off, which may take up to 3 hours. Patients should also be cautioned that sutures are likely to come out prematurely just because of the mobility of the structures of the mouth with normal activities such as eating and talking.

Should a wound infection occur, said Dr. Fazel, it’s likely that mixed aerobic and anaerobic bacteria are to blame; accordingly, broad-spectrum beta-lactam antibiotics can be a good first-line course. More severe infections are more likely to have an anaerobic or gram-negative etiology; metronidazole is a reasonable choice for anaerobic coverage, she noted. The life-threatening complication not to miss is cellulitis of the floor of the mouth, or Ludwig angina. The swelling results in superior and posterior displacement of the tongue, obstructing the upper airway, so any patient suspected of having Ludwig angina needs emergent evaluation and treatment.

When should a dermatologist consider referral to an otolaryngologist rather than diving into a biopsy in the dermatology clinic? If the area of concern is on the posterior third of the tongue, access without special tools or higher levels of anesthesia becomes tricky, Dr. Fazel pointed out. The posterior hard palate, the soft palate, and the floor of the mouth are also regions best left to otolaryngologists, she said.

[email protected]

NEW YORK –The work of the dermatologist doesn’t need to stop at the lips, according to Nasim Fazel, MD, DDS, a board-certified dermatologist and dentist. With a light touch driven by understanding of the oral mucosa, dermatologists can confidently obtain high-quality specimens and manage many intra-oral cutaneous conditions, she said, speaking at a session focused on oral health and procedures at the American Academy of Dermatology summer meeting.

Whether to perform an incisional or excisional biopsy on the lips or within the oral cavity is a decision driven by the clinical scenario, said Dr. Fazel, professor of clinical dermatology and director of the oral mucosal disease clinic at the University of California, Davis. Variables to consider, she said, include the size of the lesion, as well as whether the lesion is symptomatic or there’s any functional impairment. Other factors to bear in mind are whether the patient has any comorbid inflammatory conditions and whether the lesion could be malignant.

An excisional biopsy is a good procedure for small lesions that are thought to be benign, especially if they are exophytic, she noted. An example would be a traumatic fibroma, she said. This technique is also appropriate if there’s concern for dysplasia or malignancy if an office excisional biopsy is feasible given lesion size and location.

On the labial mucosa, an elliptical incision is often a good choice.
 

Cutaneous lip procedures

On the cutaneous lip, a punch incision can be feasible. The vermilion border should be marked to maintain orientation. “Avoid transecting the vermilion border to the extent that it’s possible,” said Dr. Fazel. Keep the vascular anatomy in mind as well, she added, since there’s a risk of severing the superior or inferior labial artery with procedures in this area. If this should happen, the branch can be identified and ligated with 4-0 fast gut or chromic gut suture material, she advised.

Another option on the cutaneous lip is shave removal. Here, a chalazion clamp can be used for both exposure and hemostasis. “Always suture parallel to the lip lines, and caution the patient that there may be significant, noticeable blanching when lip anesthesia’s used,” she said.
 

Gingival and tongue procedures

Moving to territory that may be less familiar for some dermatologists, Dr. Fazel walked through the process of a gingival punch biopsy. “Use local anesthetic, but a small quantity is sufficient,” she said. Using gentle pressure, the operator can work the punch instrument down to periosteal bone. At that point, just scissors can be used for undermining the specimen, with minimal disturbance of the mucosal surface.

Hemostasis after a gingival punch can be accomplished with silver nitrate or aluminum chloride or by electrocautery. A permanent defect in the gingiva can occur even with good technique, she said – a fact that should be included in the informed consent document for the procedure.

For lesions on the tongue, a shave removal can be considered, as can an incisional punch biopsy. An assistant’s hands are invaluable for stabilizing the tongue, said Dr. Fazel, illustrating that small dry gauze squares help achieve a good grip.
 

Considerations in biopsy technique

Dr. Fazel offered some tips and considerations when a punch biopsy is being done in the context of a chronic oral inflammatory condition, and the plan is to submit for hematoxylin and eosin (H&E) staining and direct immunofluorescence (DIF). Conditions where an intraoral punch biopsy would be considered include bullous or mucous membrane pemphigoid, pemphigus, lichen planus, and systemic lupus erythematosus, she said.

“Select a site with the most significant inflammatory changes” and aim for the most anterior site that exhibits these characteristics to maximize exposure and ensure a good specimen. The labial mucosa is a better choice in general than buccal mucosa, she said. “Maxillary and mandibular sulci are tricky sites,” especially when perilesional and lesional tissue should be included in the biopsies.

Next, Dr. Fazel walked attendees through general principles of preparing for and performing punch biopsies for H&E and DIF. In planning the biopsies, the DIF specimen should ideally be collected before the H&E specimen because the former technique will have higher yield when the specimen is taken from a less bloody field. “The yield of DIF is higher from the gingiva than from nonkeratinized surfaces.”

When infiltrating the biopsy site with local anesthesia, the needle should be centered within the lesion or general area to be biopsied, and care should be taken to maintain the orientation of the lesion to the surrounding tissue. Anesthesia can be infiltrated within the submucosal plane; the resultant ballooning will elevate the tissue to be biopsied and ease the procedure, she said.

Choose a 3-mm punch tool for gingival biopsies; 4 mm is a good size for other nonkeratinized surfaces. Unlike the procedure used for cutaneous biopsies, on delicate oral tissues, “you don’t need to hub your punch tool,” Dr. Fazel said. Similarly, the tool can be driven with firm rotation in one direction, rather than ratcheting back and forth, which may fray and deform the biopsy margins, she added. The specimen can be freed from surrounding mucosa with scissors alone and a gentle snipping motion; everting the tissue will help achieve the desired clean and gentle technique.

Because of the delicacy of the tissue, “it’s important to minimize the use of forceps, as well as any unnecessary manipulation of tissue in the process of specimen collection,” she said.
 

Salivary gland biopsies and intraoral suturing

Even minor salivary glands can be biopsied in a fairly straightforward way, though there’s a risk of short- and long-term loss of sensation, as well as more scarring than in other routine intraoral biopsies. Though these salivary glands lie just beneath the oral mucosa, care must be taken to avoid laceration of the orbicularis oris muscle during excision, noted Dr. Fazel. With a minor salivary gland biopsy, as with some other intraoral procedures, sutures will be needed. Consideration for the friability of the oral mucosa should drive suture material choice and closure technique.

First, “take bigger bites on each side of the incision, to minimize the risk of the suture tearing through the mucosa,” she said. Avoid forceps while suturing if possible, but be gentle if they are employed, “and be gentle tying knots: retract the mucosa as little as possible and cinch the knots down tightly with your fingers.”

Electrocautery, silver nitrate, and aluminum chloride are all reasonable options for hemostasis, although patients should be alerted that the tissue will have a charred appearance if electrocautery is used. Primary closure may be all that’s needed for hemostasis, said Dr. Fazel.

If nonabsorbable suture materials are used, nylon and prolene should be avoided since they tend to tear through the oral mucosa. Soft or braided silk are good choices, she said, and sutures can come out in 5-7 days.

Absorbable sutures have the advantage of not requiring removal, but they can be more irritating to the surrounding mucosa. Chromic or fast gut are the choices here, said Dr. Fazel. Whether absorbable or nonabsorbable sutures are placed, the size should be 4-0 or 5-0, she said.
 

Postoperative care, complications, and the limits of the dermatologist

Postoperatively, patients should know that swelling is to be expected, especially with procedures like minor salivary gland biopsies that involve the lip. Icing 15 minutes per hour for the first few hours will help with swelling; wound care is optimized with gentle salt water rinses. A bland diet that avoids acidic, spicy, and excessively hot foods and beverages will minimize wound irritation. Foods with sharp edges like chips, crackers, and nuts can actually catch sutures and cause pain and bleeding, so these too should be avoided.

As with dental work, care should be taken with eating or drinking until anesthesia has worn off, which may take up to 3 hours. Patients should also be cautioned that sutures are likely to come out prematurely just because of the mobility of the structures of the mouth with normal activities such as eating and talking.

Should a wound infection occur, said Dr. Fazel, it’s likely that mixed aerobic and anaerobic bacteria are to blame; accordingly, broad-spectrum beta-lactam antibiotics can be a good first-line course. More severe infections are more likely to have an anaerobic or gram-negative etiology; metronidazole is a reasonable choice for anaerobic coverage, she noted. The life-threatening complication not to miss is cellulitis of the floor of the mouth, or Ludwig angina. The swelling results in superior and posterior displacement of the tongue, obstructing the upper airway, so any patient suspected of having Ludwig angina needs emergent evaluation and treatment.

When should a dermatologist consider referral to an otolaryngologist rather than diving into a biopsy in the dermatology clinic? If the area of concern is on the posterior third of the tongue, access without special tools or higher levels of anesthesia becomes tricky, Dr. Fazel pointed out. The posterior hard palate, the soft palate, and the floor of the mouth are also regions best left to otolaryngologists, she said.

[email protected]

I don’t want to rule the world.

Some doctors do, albeit in a non–Attila-the-Hun sort of way. They want to have offices on every street corner, in every suburb of a given city, sometimes more than one city. Like the Starbucks of medicine.

That’s not me. I’m happy in my little one-office world.

Maybe I just don’t have the ambition, or the business mindset, or whatever it takes to want to do that. I understand it’s all part of wanting to be successful, and obviously those doctors are more driven in that direction than I am. The more offices, the more patients can be seen, and the more money you make.

It’s not quite that simple, though. No one can be in more than one place at the same time, so to see more patients at more places you need more doctors. To pay more doctors requires more money, which in turn requires more patients.

There’s nothing wrong with taking over the world (or at least a suburb) if you like that sort of thing. But to me, more money brings more headaches. More offices to rent, more staff to hire, more people to handle billing, IT, HR, payroll, accounting, contracts, and so on.

You can have it. I’ve taken over all the world I want, in my case a 1,200-square-foot suite on the second floor of a small-to-medium-size medical building. To some that may sound unambitious, but to me, it’s perfect.

I know where my Keurig, Sodastream, and office supplies are. Except for my secretary and her cheerfully rambunctious young daughter, I don’t have to worry about sharing stuff here, or if anyone wants a different carpet color, or what’s going on at a satellite office halfway across town.

If other doctors want to try and take over the world, more power to them, but I’m happy with this. Enough is as good as a feast.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I don’t want to rule the world.

Some doctors do, albeit in a non–Attila-the-Hun sort of way. They want to have offices on every street corner, in every suburb of a given city, sometimes more than one city. Like the Starbucks of medicine.

That’s not me. I’m happy in my little one-office world.

Maybe I just don’t have the ambition, or the business mindset, or whatever it takes to want to do that. I understand it’s all part of wanting to be successful, and obviously those doctors are more driven in that direction than I am. The more offices, the more patients can be seen, and the more money you make.

It’s not quite that simple, though. No one can be in more than one place at the same time, so to see more patients at more places you need more doctors. To pay more doctors requires more money, which in turn requires more patients.

There’s nothing wrong with taking over the world (or at least a suburb) if you like that sort of thing. But to me, more money brings more headaches. More offices to rent, more staff to hire, more people to handle billing, IT, HR, payroll, accounting, contracts, and so on.

You can have it. I’ve taken over all the world I want, in my case a 1,200-square-foot suite on the second floor of a small-to-medium-size medical building. To some that may sound unambitious, but to me, it’s perfect.

I know where my Keurig, Sodastream, and office supplies are. Except for my secretary and her cheerfully rambunctious young daughter, I don’t have to worry about sharing stuff here, or if anyone wants a different carpet color, or what’s going on at a satellite office halfway across town.

If other doctors want to try and take over the world, more power to them, but I’m happy with this. Enough is as good as a feast.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I don’t want to rule the world.

Some doctors do, albeit in a non–Attila-the-Hun sort of way. They want to have offices on every street corner, in every suburb of a given city, sometimes more than one city. Like the Starbucks of medicine.

That’s not me. I’m happy in my little one-office world.

Maybe I just don’t have the ambition, or the business mindset, or whatever it takes to want to do that. I understand it’s all part of wanting to be successful, and obviously those doctors are more driven in that direction than I am. The more offices, the more patients can be seen, and the more money you make.

It’s not quite that simple, though. No one can be in more than one place at the same time, so to see more patients at more places you need more doctors. To pay more doctors requires more money, which in turn requires more patients.

There’s nothing wrong with taking over the world (or at least a suburb) if you like that sort of thing. But to me, more money brings more headaches. More offices to rent, more staff to hire, more people to handle billing, IT, HR, payroll, accounting, contracts, and so on.

You can have it. I’ve taken over all the world I want, in my case a 1,200-square-foot suite on the second floor of a small-to-medium-size medical building. To some that may sound unambitious, but to me, it’s perfect.

I know where my Keurig, Sodastream, and office supplies are. Except for my secretary and her cheerfully rambunctious young daughter, I don’t have to worry about sharing stuff here, or if anyone wants a different carpet color, or what’s going on at a satellite office halfway across town.

If other doctors want to try and take over the world, more power to them, but I’m happy with this. Enough is as good as a feast.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Unmet medical needs are of concern to patients who experience migraine treated with triptans and there may be an undertreatment with preventive therapies whose benefit is insufficient, a new study found. The study cohort consisted of participants with ≥4 triptan dose units per month, selected from the general population. Patients were stratified into: possible Low-Frequency Episodic Migraine (pLF-EM: 4-9 triptan dose units per month), possible High-Frequency Episodic Migraine (pHF-EM: 10-14 triptan dose units per month), and possible Chronic Migraine (pCM: 14 triptan dose units per month). Researchers found:

• Of 10,270,683 adults, 8 per 1000 were triptan users and of these, 38.2% were migraineurs with unmet medical needs.
• 72.3% of patients were affected by pLF-EM, 17.4% by pHF-EM, and 10.3% by pCM.
• 19.1% of patients used oral preventive drugs.
• Triptan use reduction was found in 22.3% of patients, decreasing with the intensification of need levels.

Piccinni C, Cevoli S, Martini N. A real-world study on unmet medical needs in triptan-treated migraine: prevalence, preventive therapies and triptan use modification from a large Italian population along two years. [Published online ahead of print June 27, 2019]. J Headache Pain. doi: 10.1186/s10194-019-1027-7.

Unmet medical needs are of concern to patients who experience migraine treated with triptans and there may be an undertreatment with preventive therapies whose benefit is insufficient, a new study found. The study cohort consisted of participants with ≥4 triptan dose units per month, selected from the general population. Patients were stratified into: possible Low-Frequency Episodic Migraine (pLF-EM: 4-9 triptan dose units per month), possible High-Frequency Episodic Migraine (pHF-EM: 10-14 triptan dose units per month), and possible Chronic Migraine (pCM: 14 triptan dose units per month). Researchers found:

• Of 10,270,683 adults, 8 per 1000 were triptan users and of these, 38.2% were migraineurs with unmet medical needs.
• 72.3% of patients were affected by pLF-EM, 17.4% by pHF-EM, and 10.3% by pCM.
• 19.1% of patients used oral preventive drugs.
• Triptan use reduction was found in 22.3% of patients, decreasing with the intensification of need levels.

Piccinni C, Cevoli S, Martini N. A real-world study on unmet medical needs in triptan-treated migraine: prevalence, preventive therapies and triptan use modification from a large Italian population along two years. [Published online ahead of print June 27, 2019]. J Headache Pain. doi: 10.1186/s10194-019-1027-7.

Unmet medical needs are of concern to patients who experience migraine treated with triptans and there may be an undertreatment with preventive therapies whose benefit is insufficient, a new study found. The study cohort consisted of participants with ≥4 triptan dose units per month, selected from the general population. Patients were stratified into: possible Low-Frequency Episodic Migraine (pLF-EM: 4-9 triptan dose units per month), possible High-Frequency Episodic Migraine (pHF-EM: 10-14 triptan dose units per month), and possible Chronic Migraine (pCM: 14 triptan dose units per month). Researchers found:

• Of 10,270,683 adults, 8 per 1000 were triptan users and of these, 38.2% were migraineurs with unmet medical needs.
• 72.3% of patients were affected by pLF-EM, 17.4% by pHF-EM, and 10.3% by pCM.
• 19.1% of patients used oral preventive drugs.
• Triptan use reduction was found in 22.3% of patients, decreasing with the intensification of need levels.

Piccinni C, Cevoli S, Martini N. A real-world study on unmet medical needs in triptan-treated migraine: prevalence, preventive therapies and triptan use modification from a large Italian population along two years. [Published online ahead of print June 27, 2019]. J Headache Pain. doi: 10.1186/s10194-019-1027-7.

Hearn Jay Cho, MD, PhD, has been appointed chief medical officer of the Multiple Myeloma Research Foundation (MMRF). In this role, Dr. Cho will develop a clinical research strategy and accelerate drug development programs for the MMRF. He will also lead the Multiple Myeloma Research Consortium, a group of 25 research centers focused on multiple myeloma.

Dr. Cho will continue on as an associate professor of medicine at the Icahn School of Medicine at Mt. Sinai in New York, and as an attending physician with the multiple myeloma service at the Mt. Sinai Tisch Cancer Institute. He will also continue to manage his lab at Mt. Sinai.

Michael Jay Styler, MD, has joined the department of hematology/oncology as an associate professor in the academic clinician track as part of the bone marrow transplant program at Fox Chase Cancer Center in Philadelphia.

Dr. Styler was previously medical director of the transplant center, apheresis center, and collection center at Hahnemann University Hospital in Philadelphia, as well as medical director of the stem cell transplant program and the clinical service chief of hematology/oncology. Dr. Styler was also an associate professor at Drexel University, Philadelphia, where he served as division director of hematology/oncology and associate fellowship director of the hematology/oncology program.

Jaspreet Chahal, MD, has joined the Oncology Institute of Hope and Innovation, which has locations in Arizona, California, and Nevada. Dr. Chahal will serve patients in Tucson and Green Valley, Ariz.

Dr. Chahal has a doctor of medicine degree from St. George’s University in West Indies, Grenada. She completed her internship in hematology and oncology at Hofstra University, Hempstead, N.Y., and her residency in internal medicine at the University of Arizona in Tucson.

Marcin Chwistek, MD, has been appointed editor in chief of AAHPM Quarterly, which is published by the American Academy of Hospice and Palliative Medicine. Dr. Chwistek is an associate professor in the department of hematology/oncology at Fox Chase Cancer Center in Philadelphia, where he is also director of the pain and palliative care program.

As editor in chief of AAHPM Quarterly, Dr. Chwistek will work with other members of the editorial board to develop content related to hospice care and palliative medicine. Dr. Chwistek previously served as the associate editor in chief of AAHPM Quarterly and writes a column that appears in every issue.
 

Movers in Medicine highlights career moves and personal achievements by hematologists and oncologists. Did you switch jobs, take on a new role, climb a mountain? Tell us all about it at [email protected] , and you could be featured in Movers in Medicine.

[email protected]

Hearn Jay Cho, MD, PhD, has been appointed chief medical officer of the Multiple Myeloma Research Foundation (MMRF). In this role, Dr. Cho will develop a clinical research strategy and accelerate drug development programs for the MMRF. He will also lead the Multiple Myeloma Research Consortium, a group of 25 research centers focused on multiple myeloma.

Dr. Cho will continue on as an associate professor of medicine at the Icahn School of Medicine at Mt. Sinai in New York, and as an attending physician with the multiple myeloma service at the Mt. Sinai Tisch Cancer Institute. He will also continue to manage his lab at Mt. Sinai.

Michael Jay Styler, MD, has joined the department of hematology/oncology as an associate professor in the academic clinician track as part of the bone marrow transplant program at Fox Chase Cancer Center in Philadelphia.

Dr. Styler was previously medical director of the transplant center, apheresis center, and collection center at Hahnemann University Hospital in Philadelphia, as well as medical director of the stem cell transplant program and the clinical service chief of hematology/oncology. Dr. Styler was also an associate professor at Drexel University, Philadelphia, where he served as division director of hematology/oncology and associate fellowship director of the hematology/oncology program.

Jaspreet Chahal, MD, has joined the Oncology Institute of Hope and Innovation, which has locations in Arizona, California, and Nevada. Dr. Chahal will serve patients in Tucson and Green Valley, Ariz.

Dr. Chahal has a doctor of medicine degree from St. George’s University in West Indies, Grenada. She completed her internship in hematology and oncology at Hofstra University, Hempstead, N.Y., and her residency in internal medicine at the University of Arizona in Tucson.

Marcin Chwistek, MD, has been appointed editor in chief of AAHPM Quarterly, which is published by the American Academy of Hospice and Palliative Medicine. Dr. Chwistek is an associate professor in the department of hematology/oncology at Fox Chase Cancer Center in Philadelphia, where he is also director of the pain and palliative care program.

As editor in chief of AAHPM Quarterly, Dr. Chwistek will work with other members of the editorial board to develop content related to hospice care and palliative medicine. Dr. Chwistek previously served as the associate editor in chief of AAHPM Quarterly and writes a column that appears in every issue.
 

Movers in Medicine highlights career moves and personal achievements by hematologists and oncologists. Did you switch jobs, take on a new role, climb a mountain? Tell us all about it at [email protected] , and you could be featured in Movers in Medicine.

[email protected]

Hearn Jay Cho, MD, PhD, has been appointed chief medical officer of the Multiple Myeloma Research Foundation (MMRF). In this role, Dr. Cho will develop a clinical research strategy and accelerate drug development programs for the MMRF. He will also lead the Multiple Myeloma Research Consortium, a group of 25 research centers focused on multiple myeloma.

Dr. Cho will continue on as an associate professor of medicine at the Icahn School of Medicine at Mt. Sinai in New York, and as an attending physician with the multiple myeloma service at the Mt. Sinai Tisch Cancer Institute. He will also continue to manage his lab at Mt. Sinai.

Michael Jay Styler, MD, has joined the department of hematology/oncology as an associate professor in the academic clinician track as part of the bone marrow transplant program at Fox Chase Cancer Center in Philadelphia.

Dr. Styler was previously medical director of the transplant center, apheresis center, and collection center at Hahnemann University Hospital in Philadelphia, as well as medical director of the stem cell transplant program and the clinical service chief of hematology/oncology. Dr. Styler was also an associate professor at Drexel University, Philadelphia, where he served as division director of hematology/oncology and associate fellowship director of the hematology/oncology program.

Jaspreet Chahal, MD, has joined the Oncology Institute of Hope and Innovation, which has locations in Arizona, California, and Nevada. Dr. Chahal will serve patients in Tucson and Green Valley, Ariz.

Dr. Chahal has a doctor of medicine degree from St. George’s University in West Indies, Grenada. She completed her internship in hematology and oncology at Hofstra University, Hempstead, N.Y., and her residency in internal medicine at the University of Arizona in Tucson.

Marcin Chwistek, MD, has been appointed editor in chief of AAHPM Quarterly, which is published by the American Academy of Hospice and Palliative Medicine. Dr. Chwistek is an associate professor in the department of hematology/oncology at Fox Chase Cancer Center in Philadelphia, where he is also director of the pain and palliative care program.

As editor in chief of AAHPM Quarterly, Dr. Chwistek will work with other members of the editorial board to develop content related to hospice care and palliative medicine. Dr. Chwistek previously served as the associate editor in chief of AAHPM Quarterly and writes a column that appears in every issue.
 

Movers in Medicine highlights career moves and personal achievements by hematologists and oncologists. Did you switch jobs, take on a new role, climb a mountain? Tell us all about it at [email protected] , and you could be featured in Movers in Medicine.

[email protected]