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More frequent CT surveillance in NSCLC doesn’t improve survival
More even after researchers controlled for tumor histology and recurrence.
Compared with those followed every 3 months, the hazard ratio for 6-month follow-up with CT scanning was 1.16, and 1.06 for annual follow-up – a nonsignificant difference. Nor did more frequent imaging improve survival among the subgroup of patients who were cancer free 9 months after their surgery or among those who had recurrences, Timothy L. McMurry, PhD, and his colleagues reported in the Annals of Surgery. The paper was presented at the annual meeting of the American Surgical Association.
The results probably reflect the very poor survival rates of any patients who develop recurrent non–small cell lung cancer (NSCLC), wrote Dr. McMurry, a biostatistician at the University of Virginia, Charlottesville, and his coauthors.
“Surveillance recommendations need to be considered in the context of potential harms and benefits to patients and their caregivers,” they said. “Follow-up imaging and office visits increase cost and can lead to patient anxiety. Although it seems intuitive that earlier detection of asymptomatic recurrence could improve outcomes, patients with recurrent NSCLC do very poorly … poor survival after recurrence helps explain why more intense surveillance after surgical resection was not associated with improvement in overall survival.”
However, they noted, treatment advances for recurrent and metastatic disease may already be changing the outlook for these patients, “systemic therapy and targeted agents are demonstrating clinically significant survival benefits for small patient subgroups, which, in the future, may augment the benefits of early recurrence detection.”
The team undertook this retrospective study – the largest of its kind in NSCLC patients – in light of current follow-up recommendations that are based almost solely on expert consensus, with low-level data.
“Because there is a paucity of high-quality data on NSCLC surveillance, practice guidelines are based on small retrospective analyses and expert opinion. This results in wide variation in practice including both underuse and overuse of surveillance services.”
The study plumbed the National Cancer Database, extracting information on patients who underwent surgery for NSCLC stages I-III during 2006-2007. All had complete resection and negative margins. Patients were followed through 2012, or until they had a recurrence, a new primary cancer, or they died.
The cohort comprised 4,463 who were followed with CT imaging: 1,614 every 3 months, 1,999 every 6 months, and 850 annually. These intervals correspond to the three different major recommendations. The most common procedure was a lobectomy (about 80%). Patients with higher-stage cancers were significantly more likely to receive more frequent imaging. The regression model controlled for age, sex, comorbidities, tumor stage, and surgical procedure.
After 14 months, 3,552 patients (79.5%) were alive and cancer free. However, during the rest of the follow-up period, 11% developed a new primary cancer and 24% a recurrence of their lung cancer, with no between-group differences. The regression analysis showed no significant difference in recurrence related to surveillance interval, whether 6 months was compared with 3 months (hazard ratio, 1.16) or 1 year with 3 months (HR, 1.06).
Results were much the same for the subgroup of 3,165 who were alive and cancer free 9 months after surgery. In this group, 11% developed a new primary cancer and 29% a recurrence of their lung cancer, with similar numbers in each of the surveillance groups (HR, 1.12 for 6 months vs. 3 months).
Finally, a model including only those who had recurrence, new cancers, or were lost to follow-up within 14 months of surgery also showed no benefit for more frequent surveillance.
“More recent prerecurrence imaging was not associated with postrecurrence survival (HR, 1.02 per month since imaging), and patients who had gone more than 14 months without imaging were at no greater risk of death (HR, 1.01),” the investigators wrote.
The significant predictors of worse survival were nothing surprising, the authors noted. These included symptomatic recurrence (HR, 1.49), distant recurrence, age, male sex, congestive heart failure, coronary artery disease, and peripheral vascular disease.
The findings are not to say, however, that CT surveillance confers no benefit, the authors noted.
“Historically, 5-year survival for the earliest stage of lung cancer, stage IA, was only 70%. Increased use of CT scanning has, however, resulted in a decrease in the median tumor size of resected NSCLC and a shift toward earlier-stage disease. … The National Lung Screening Trial prospectively evaluated annual low-dose screening CT scans and demonstrated a 20% reduction in mortality from lung cancer. This enormous improvement in survival for NSCLC patients provides great promise for the future and is likely to increase the volume of lung cancer resections performed and the number of lung cancer survivors needing routine surveillance.”
However, the data do show that “at least annual CT surveillance is appropriate but that there is no benefit to more than biannual surveillance.”
The authors reported no financial conflicts.
SOURCE: McMurry TL et al. Ann Surg 2018 Jul 12. doi: 10.1097/SLA.0000000000002955.
More even after researchers controlled for tumor histology and recurrence.
Compared with those followed every 3 months, the hazard ratio for 6-month follow-up with CT scanning was 1.16, and 1.06 for annual follow-up – a nonsignificant difference. Nor did more frequent imaging improve survival among the subgroup of patients who were cancer free 9 months after their surgery or among those who had recurrences, Timothy L. McMurry, PhD, and his colleagues reported in the Annals of Surgery. The paper was presented at the annual meeting of the American Surgical Association.
The results probably reflect the very poor survival rates of any patients who develop recurrent non–small cell lung cancer (NSCLC), wrote Dr. McMurry, a biostatistician at the University of Virginia, Charlottesville, and his coauthors.
“Surveillance recommendations need to be considered in the context of potential harms and benefits to patients and their caregivers,” they said. “Follow-up imaging and office visits increase cost and can lead to patient anxiety. Although it seems intuitive that earlier detection of asymptomatic recurrence could improve outcomes, patients with recurrent NSCLC do very poorly … poor survival after recurrence helps explain why more intense surveillance after surgical resection was not associated with improvement in overall survival.”
However, they noted, treatment advances for recurrent and metastatic disease may already be changing the outlook for these patients, “systemic therapy and targeted agents are demonstrating clinically significant survival benefits for small patient subgroups, which, in the future, may augment the benefits of early recurrence detection.”
The team undertook this retrospective study – the largest of its kind in NSCLC patients – in light of current follow-up recommendations that are based almost solely on expert consensus, with low-level data.
“Because there is a paucity of high-quality data on NSCLC surveillance, practice guidelines are based on small retrospective analyses and expert opinion. This results in wide variation in practice including both underuse and overuse of surveillance services.”
The study plumbed the National Cancer Database, extracting information on patients who underwent surgery for NSCLC stages I-III during 2006-2007. All had complete resection and negative margins. Patients were followed through 2012, or until they had a recurrence, a new primary cancer, or they died.
The cohort comprised 4,463 who were followed with CT imaging: 1,614 every 3 months, 1,999 every 6 months, and 850 annually. These intervals correspond to the three different major recommendations. The most common procedure was a lobectomy (about 80%). Patients with higher-stage cancers were significantly more likely to receive more frequent imaging. The regression model controlled for age, sex, comorbidities, tumor stage, and surgical procedure.
After 14 months, 3,552 patients (79.5%) were alive and cancer free. However, during the rest of the follow-up period, 11% developed a new primary cancer and 24% a recurrence of their lung cancer, with no between-group differences. The regression analysis showed no significant difference in recurrence related to surveillance interval, whether 6 months was compared with 3 months (hazard ratio, 1.16) or 1 year with 3 months (HR, 1.06).
Results were much the same for the subgroup of 3,165 who were alive and cancer free 9 months after surgery. In this group, 11% developed a new primary cancer and 29% a recurrence of their lung cancer, with similar numbers in each of the surveillance groups (HR, 1.12 for 6 months vs. 3 months).
Finally, a model including only those who had recurrence, new cancers, or were lost to follow-up within 14 months of surgery also showed no benefit for more frequent surveillance.
“More recent prerecurrence imaging was not associated with postrecurrence survival (HR, 1.02 per month since imaging), and patients who had gone more than 14 months without imaging were at no greater risk of death (HR, 1.01),” the investigators wrote.
The significant predictors of worse survival were nothing surprising, the authors noted. These included symptomatic recurrence (HR, 1.49), distant recurrence, age, male sex, congestive heart failure, coronary artery disease, and peripheral vascular disease.
The findings are not to say, however, that CT surveillance confers no benefit, the authors noted.
“Historically, 5-year survival for the earliest stage of lung cancer, stage IA, was only 70%. Increased use of CT scanning has, however, resulted in a decrease in the median tumor size of resected NSCLC and a shift toward earlier-stage disease. … The National Lung Screening Trial prospectively evaluated annual low-dose screening CT scans and demonstrated a 20% reduction in mortality from lung cancer. This enormous improvement in survival for NSCLC patients provides great promise for the future and is likely to increase the volume of lung cancer resections performed and the number of lung cancer survivors needing routine surveillance.”
However, the data do show that “at least annual CT surveillance is appropriate but that there is no benefit to more than biannual surveillance.”
The authors reported no financial conflicts.
SOURCE: McMurry TL et al. Ann Surg 2018 Jul 12. doi: 10.1097/SLA.0000000000002955.
More even after researchers controlled for tumor histology and recurrence.
Compared with those followed every 3 months, the hazard ratio for 6-month follow-up with CT scanning was 1.16, and 1.06 for annual follow-up – a nonsignificant difference. Nor did more frequent imaging improve survival among the subgroup of patients who were cancer free 9 months after their surgery or among those who had recurrences, Timothy L. McMurry, PhD, and his colleagues reported in the Annals of Surgery. The paper was presented at the annual meeting of the American Surgical Association.
The results probably reflect the very poor survival rates of any patients who develop recurrent non–small cell lung cancer (NSCLC), wrote Dr. McMurry, a biostatistician at the University of Virginia, Charlottesville, and his coauthors.
“Surveillance recommendations need to be considered in the context of potential harms and benefits to patients and their caregivers,” they said. “Follow-up imaging and office visits increase cost and can lead to patient anxiety. Although it seems intuitive that earlier detection of asymptomatic recurrence could improve outcomes, patients with recurrent NSCLC do very poorly … poor survival after recurrence helps explain why more intense surveillance after surgical resection was not associated with improvement in overall survival.”
However, they noted, treatment advances for recurrent and metastatic disease may already be changing the outlook for these patients, “systemic therapy and targeted agents are demonstrating clinically significant survival benefits for small patient subgroups, which, in the future, may augment the benefits of early recurrence detection.”
The team undertook this retrospective study – the largest of its kind in NSCLC patients – in light of current follow-up recommendations that are based almost solely on expert consensus, with low-level data.
“Because there is a paucity of high-quality data on NSCLC surveillance, practice guidelines are based on small retrospective analyses and expert opinion. This results in wide variation in practice including both underuse and overuse of surveillance services.”
The study plumbed the National Cancer Database, extracting information on patients who underwent surgery for NSCLC stages I-III during 2006-2007. All had complete resection and negative margins. Patients were followed through 2012, or until they had a recurrence, a new primary cancer, or they died.
The cohort comprised 4,463 who were followed with CT imaging: 1,614 every 3 months, 1,999 every 6 months, and 850 annually. These intervals correspond to the three different major recommendations. The most common procedure was a lobectomy (about 80%). Patients with higher-stage cancers were significantly more likely to receive more frequent imaging. The regression model controlled for age, sex, comorbidities, tumor stage, and surgical procedure.
After 14 months, 3,552 patients (79.5%) were alive and cancer free. However, during the rest of the follow-up period, 11% developed a new primary cancer and 24% a recurrence of their lung cancer, with no between-group differences. The regression analysis showed no significant difference in recurrence related to surveillance interval, whether 6 months was compared with 3 months (hazard ratio, 1.16) or 1 year with 3 months (HR, 1.06).
Results were much the same for the subgroup of 3,165 who were alive and cancer free 9 months after surgery. In this group, 11% developed a new primary cancer and 29% a recurrence of their lung cancer, with similar numbers in each of the surveillance groups (HR, 1.12 for 6 months vs. 3 months).
Finally, a model including only those who had recurrence, new cancers, or were lost to follow-up within 14 months of surgery also showed no benefit for more frequent surveillance.
“More recent prerecurrence imaging was not associated with postrecurrence survival (HR, 1.02 per month since imaging), and patients who had gone more than 14 months without imaging were at no greater risk of death (HR, 1.01),” the investigators wrote.
The significant predictors of worse survival were nothing surprising, the authors noted. These included symptomatic recurrence (HR, 1.49), distant recurrence, age, male sex, congestive heart failure, coronary artery disease, and peripheral vascular disease.
The findings are not to say, however, that CT surveillance confers no benefit, the authors noted.
“Historically, 5-year survival for the earliest stage of lung cancer, stage IA, was only 70%. Increased use of CT scanning has, however, resulted in a decrease in the median tumor size of resected NSCLC and a shift toward earlier-stage disease. … The National Lung Screening Trial prospectively evaluated annual low-dose screening CT scans and demonstrated a 20% reduction in mortality from lung cancer. This enormous improvement in survival for NSCLC patients provides great promise for the future and is likely to increase the volume of lung cancer resections performed and the number of lung cancer survivors needing routine surveillance.”
However, the data do show that “at least annual CT surveillance is appropriate but that there is no benefit to more than biannual surveillance.”
The authors reported no financial conflicts.
SOURCE: McMurry TL et al. Ann Surg 2018 Jul 12. doi: 10.1097/SLA.0000000000002955.
FROM THE ANNALS OF SURGERY
Key clinical point: More frequent CT surveillance did not improve survival in patients with resected non–small cell lung cancer.
Major finding: Survival among those who got scans every 6 months was not significantly different than every 3 months (HR, 1.16)
Study details: The retrospective study comprised 4,463 patients.
Disclosures: The authors had no financial conflicts.
Source: McMurry TL et al. Ann Surg. 2018 Jul 12. doi: 10.1097/SLA.0000000000002955.
Mailing out fecal tests may improve CRC screening rates
Mailing fecal immunochemical tests (FITs) to overdue patients improved the rate of colorectal cancer screening in community health centers, results of a recent randomized trial show.
Outreach by mail led to a 3.4–percentage point increase in completion of FIT, compared with clinics who did not participate in the intervention, according to results of the randomized Strategies and Opportunities to STOP Colon Cancer in Priority Populations (STOP CRC) trial.
Although that difference was statistically significant, investigators said the improvement was less than expected based on previous experience, including a pilot study showing that the strategy of mailing fecal tests boosted completion rates by 38%.
Based on that discrepancy, additional strategies may be needed to support implementation of FIT mailing programs in low-resource health centers, reported Gloria D. Coronado, PhD, Kaiser Permanente Center for Health Research, Portland, Ore., and coinvestigators.
“This work demonstrates that mailed FIT outreach programs can have clinical impact when integrated into clinical work flows, but emphasizes the need to identify additional strategies to support program implementation in low-resource health centers,” Dr. Coronado and coauthors said in JAMA Internal Medicine.
The STOP CRC study included 26 federally qualified health center clinics serving low-income populations in Oregon and California. Investigators identified a total of 41,193 adults overdue for colorectal cancer screening between Feb. 4, 2014 and Feb. 3, 2015.
The core of the intervention was a set of electronic health record–embedded tools that identified adults due for screening and allowed staff to generate letters and mailing labels for a series of three mailings. The first mailing was an introductory letter, the second was a FIT kit packet that included wordless instructions, and the third was a reminder letter.
For clinics that participated in the intervention, the rate of FIT completion was 13.9%, versus 10.4%, a difference that was statistically significant (95% confidence interval, 0.1%-6.8%; P = .047), according to investigators. Likewise, the proportion of participants completing any CRC screening was significantly higher in the intervention clinics (18.3% versus 14.5%; 3.8 percentage points difference; 95% CI, 0.6%-7.0%; P = .024).
Somewhat larger effects were seen in an analysis that accounted for delays in implementation of the program. In that analysis, FIT completion rates were 17.6% for the intervention clinics and 12.8% for the usual care clinics (95% CI, 0.9-8.6%; P = .020), with similar increases seen in the proportion of patients receiving any CRC screening.
These increases in screening occurred despite “relatively low” implementation of the program, Dr. Coronado and colleagues said.
In the pilot study, a concerted effort was made to ensure all eligible adults got the intervention; in this study, 6,925 out of 21,134 intervention participants (33%) got an introductory letter, and of those, 91% received the FIT and 59% got the reminder letter.
Implementation varied widely by health center, ranging from 6.5% to 68.2%, investigators said in their report.
One reason for low implementation may be that the program competed with other priorities in the clinics. In interviews, health center leaders said challenges in the clinic included time burden, limited organizational capacity, and challenges with the EHR and associated reporting tools.
“For most participating health centers, STOP CRC represented the first time EHR tools were used to deliver cancer screening services outside the clinic,” Dr. Coronado said. “Implementation might have increased with experience.”
The research reported by Dr. Coronado and coinvestigators was supported by the National Institutes of Health. Dr. Coronado reported serving as a coinvestigator on a study of an experimental blood test for colorectal cancer funded by EpiGenomics and as principal investigator on a study of an experimental FIT funded by Quidel Corporation. No other disclosures were reported.
AGA patient education materials on colorectal cancer will help your patients better understand all of their screening options. Learn more at patient.gastro.org.
SOURCE: Coronado GD et al. JAMA Intern Med. 2018 Aug 6. doi: 10.1001/jamainternmed.2018.3629.
Mailing fecal immunochemical tests (FITs) to overdue patients improved the rate of colorectal cancer screening in community health centers, results of a recent randomized trial show.
Outreach by mail led to a 3.4–percentage point increase in completion of FIT, compared with clinics who did not participate in the intervention, according to results of the randomized Strategies and Opportunities to STOP Colon Cancer in Priority Populations (STOP CRC) trial.
Although that difference was statistically significant, investigators said the improvement was less than expected based on previous experience, including a pilot study showing that the strategy of mailing fecal tests boosted completion rates by 38%.
Based on that discrepancy, additional strategies may be needed to support implementation of FIT mailing programs in low-resource health centers, reported Gloria D. Coronado, PhD, Kaiser Permanente Center for Health Research, Portland, Ore., and coinvestigators.
“This work demonstrates that mailed FIT outreach programs can have clinical impact when integrated into clinical work flows, but emphasizes the need to identify additional strategies to support program implementation in low-resource health centers,” Dr. Coronado and coauthors said in JAMA Internal Medicine.
The STOP CRC study included 26 federally qualified health center clinics serving low-income populations in Oregon and California. Investigators identified a total of 41,193 adults overdue for colorectal cancer screening between Feb. 4, 2014 and Feb. 3, 2015.
The core of the intervention was a set of electronic health record–embedded tools that identified adults due for screening and allowed staff to generate letters and mailing labels for a series of three mailings. The first mailing was an introductory letter, the second was a FIT kit packet that included wordless instructions, and the third was a reminder letter.
For clinics that participated in the intervention, the rate of FIT completion was 13.9%, versus 10.4%, a difference that was statistically significant (95% confidence interval, 0.1%-6.8%; P = .047), according to investigators. Likewise, the proportion of participants completing any CRC screening was significantly higher in the intervention clinics (18.3% versus 14.5%; 3.8 percentage points difference; 95% CI, 0.6%-7.0%; P = .024).
Somewhat larger effects were seen in an analysis that accounted for delays in implementation of the program. In that analysis, FIT completion rates were 17.6% for the intervention clinics and 12.8% for the usual care clinics (95% CI, 0.9-8.6%; P = .020), with similar increases seen in the proportion of patients receiving any CRC screening.
These increases in screening occurred despite “relatively low” implementation of the program, Dr. Coronado and colleagues said.
In the pilot study, a concerted effort was made to ensure all eligible adults got the intervention; in this study, 6,925 out of 21,134 intervention participants (33%) got an introductory letter, and of those, 91% received the FIT and 59% got the reminder letter.
Implementation varied widely by health center, ranging from 6.5% to 68.2%, investigators said in their report.
One reason for low implementation may be that the program competed with other priorities in the clinics. In interviews, health center leaders said challenges in the clinic included time burden, limited organizational capacity, and challenges with the EHR and associated reporting tools.
“For most participating health centers, STOP CRC represented the first time EHR tools were used to deliver cancer screening services outside the clinic,” Dr. Coronado said. “Implementation might have increased with experience.”
The research reported by Dr. Coronado and coinvestigators was supported by the National Institutes of Health. Dr. Coronado reported serving as a coinvestigator on a study of an experimental blood test for colorectal cancer funded by EpiGenomics and as principal investigator on a study of an experimental FIT funded by Quidel Corporation. No other disclosures were reported.
AGA patient education materials on colorectal cancer will help your patients better understand all of their screening options. Learn more at patient.gastro.org.
SOURCE: Coronado GD et al. JAMA Intern Med. 2018 Aug 6. doi: 10.1001/jamainternmed.2018.3629.
Mailing fecal immunochemical tests (FITs) to overdue patients improved the rate of colorectal cancer screening in community health centers, results of a recent randomized trial show.
Outreach by mail led to a 3.4–percentage point increase in completion of FIT, compared with clinics who did not participate in the intervention, according to results of the randomized Strategies and Opportunities to STOP Colon Cancer in Priority Populations (STOP CRC) trial.
Although that difference was statistically significant, investigators said the improvement was less than expected based on previous experience, including a pilot study showing that the strategy of mailing fecal tests boosted completion rates by 38%.
Based on that discrepancy, additional strategies may be needed to support implementation of FIT mailing programs in low-resource health centers, reported Gloria D. Coronado, PhD, Kaiser Permanente Center for Health Research, Portland, Ore., and coinvestigators.
“This work demonstrates that mailed FIT outreach programs can have clinical impact when integrated into clinical work flows, but emphasizes the need to identify additional strategies to support program implementation in low-resource health centers,” Dr. Coronado and coauthors said in JAMA Internal Medicine.
The STOP CRC study included 26 federally qualified health center clinics serving low-income populations in Oregon and California. Investigators identified a total of 41,193 adults overdue for colorectal cancer screening between Feb. 4, 2014 and Feb. 3, 2015.
The core of the intervention was a set of electronic health record–embedded tools that identified adults due for screening and allowed staff to generate letters and mailing labels for a series of three mailings. The first mailing was an introductory letter, the second was a FIT kit packet that included wordless instructions, and the third was a reminder letter.
For clinics that participated in the intervention, the rate of FIT completion was 13.9%, versus 10.4%, a difference that was statistically significant (95% confidence interval, 0.1%-6.8%; P = .047), according to investigators. Likewise, the proportion of participants completing any CRC screening was significantly higher in the intervention clinics (18.3% versus 14.5%; 3.8 percentage points difference; 95% CI, 0.6%-7.0%; P = .024).
Somewhat larger effects were seen in an analysis that accounted for delays in implementation of the program. In that analysis, FIT completion rates were 17.6% for the intervention clinics and 12.8% for the usual care clinics (95% CI, 0.9-8.6%; P = .020), with similar increases seen in the proportion of patients receiving any CRC screening.
These increases in screening occurred despite “relatively low” implementation of the program, Dr. Coronado and colleagues said.
In the pilot study, a concerted effort was made to ensure all eligible adults got the intervention; in this study, 6,925 out of 21,134 intervention participants (33%) got an introductory letter, and of those, 91% received the FIT and 59% got the reminder letter.
Implementation varied widely by health center, ranging from 6.5% to 68.2%, investigators said in their report.
One reason for low implementation may be that the program competed with other priorities in the clinics. In interviews, health center leaders said challenges in the clinic included time burden, limited organizational capacity, and challenges with the EHR and associated reporting tools.
“For most participating health centers, STOP CRC represented the first time EHR tools were used to deliver cancer screening services outside the clinic,” Dr. Coronado said. “Implementation might have increased with experience.”
The research reported by Dr. Coronado and coinvestigators was supported by the National Institutes of Health. Dr. Coronado reported serving as a coinvestigator on a study of an experimental blood test for colorectal cancer funded by EpiGenomics and as principal investigator on a study of an experimental FIT funded by Quidel Corporation. No other disclosures were reported.
AGA patient education materials on colorectal cancer will help your patients better understand all of their screening options. Learn more at patient.gastro.org.
SOURCE: Coronado GD et al. JAMA Intern Med. 2018 Aug 6. doi: 10.1001/jamainternmed.2018.3629.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Mailing fecal immunochemical tests (FITs) to overdue patients improved the rate of colorectal cancer screening, though not to the extent that had been seen in a pilot study.
Major finding: Outreach by mail led to a 3.4–percentage point increase in FIT completion for participating clinics versus clinics that implemented usual care.
Study details: STOP CRC, a cluster-randomized pragmatic clinical trial including 26 federally qualified health center clinics and a total of 41,193 adults overdue for colorectal cancer screening.
Disclosures: The research was supported by the National Institutes of Health. One investigator reported disclosures related to EpiGenomics and Quidel Corporation.
Source: Coronado GD et al. JAMA Intern Med. 2018 Aug 6. doi: 10.1001/jamainternmed.2018.3629.
Early HbA1c levels may predict gestational diabetes
according to a case-control study drawn from the prospective NICHD Fetal Growth Studies-Singleton cohort.
Women who went on to develop GDM had higher HbA1c levels, and measuring this factor improved prediction when added to traditional GDM risk factors, Stefanie N. Hinkle, PhD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and her associates reported in Scientific Reports.
A previous report showed that GDM-associated fetal overgrowth begins before GDM diagnosis, which suggests a need to identify GDM earlier in pregnancy (Int J Epidemiol. 2018 Feb;47[1]:25–25l).
HbA1c is already used to screen for type 2 diabetes mellitus outside of pregnancy. Previous studies that examined its potential utility for GDM have focused on high-risk patients, examined an HbA1c threshold of 5.7%, used GDM during the first trimester only as the outcome, or had other limitations. There is little research on HbA1c levels and GDM in population-based samples.
Dr. Hinkle and her associates conducted a secondary analysis of a case-control study that involved 2,334 low-risk pregnancies among nonobese women and 468 low-risk pregnancies among obese women (n = 2,802) at 12 U.S. centers. The women were recruited during gestational weeks 8-13 and then followed until the end of the pregnancy. The researchers did a nested GDM case-control study of 107 GDM cases and 214 matched non-GDM controls.
GDM cases had higher HbA1c levels throughout their pregnancies (P less than .03). The researchers found a linear association between HbA1c at enrollment and GDM risk (P = .001). Women with a first trimester HbA1c level of 5.7% had an odds ratio of 2.73 for GDM, compared with women at the median level of 5.2%.
In the adjusted model, for each increment of 0.1% at enrollment, women had an OR of 1.22 for GDM (P less than .001). For every 0.1% difference between HbA1c levels at enrollment and the second visit (24-29 weeks), the OR was 1.21 (P = .04). When the researchers excluded women who were obese, had smoked, had prior GDM, or had a hematologic disorder, the OR per 0.1% increase was similar (OR, 1.23; 95% confidence interval, 1.10-1.38).
A potential optimal cutoff point is 5.1%, which had a sensitivity of 47% (95% CI, 34%-60%) and a specificity of 79% (95% CI, 62%-88%). At 5.7%, which is used as the cutoff for prediabetes in nonpregnant women, the sensitivity was 21% (95% CI, 8%-36%) and the specificity was 95% (95% CI, 91%-99%).
When the model was added to conventional risk factors such as age, race/ethnicity, being overweight or obese before pregnancy, family history of diabetes, previous GDM, and nulliparity, the area under the curve of HbA1c levels at enrollment increased from 0.59 to 0.65.
Robert Atlas, MD, chair of obstetrics and gynecology at Mercy Medical Center, Baltimore, said in an interview, “This is just the first study that needs to be replicated in different patient populations. No one has looked at a continuum of HbA1c and what value above puts you at an increased risk. I think this is a very powerful study that sets the stage for further investigation into how to utilize HbA1c in a better way than we’ve ever looked at it before.”
The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural funding and by American Recovery and Reinvestment Act funding. Dr. Hinkle and her associates had no relevant financial disclosures. Dr. Atlas had no relevant financial disclosures.
SOURCE: Hinkle SN et al. Sci Rep. 2018 Aug 16;8(1):12249.
“I don’t think clinically this particular finding can make a change right off the bat. What it shows us is we need to understand, at a deeper level, what mechanistic processes might be going on. What underlying process is going on in the woman that looks apparently normal but has a slightly elevated HbA1c. What are the factors that are making this woman become at (greater) risk?”
Suchi Chandrasekaran, MD, MSCE, is an assistant professor of obstetrics and gynecology in the division of maternal fetal medicine at the University of Washington, Yakima. She had no relevant financial disclosures. She was not associated with the study.
“I don’t think clinically this particular finding can make a change right off the bat. What it shows us is we need to understand, at a deeper level, what mechanistic processes might be going on. What underlying process is going on in the woman that looks apparently normal but has a slightly elevated HbA1c. What are the factors that are making this woman become at (greater) risk?”
Suchi Chandrasekaran, MD, MSCE, is an assistant professor of obstetrics and gynecology in the division of maternal fetal medicine at the University of Washington, Yakima. She had no relevant financial disclosures. She was not associated with the study.
“I don’t think clinically this particular finding can make a change right off the bat. What it shows us is we need to understand, at a deeper level, what mechanistic processes might be going on. What underlying process is going on in the woman that looks apparently normal but has a slightly elevated HbA1c. What are the factors that are making this woman become at (greater) risk?”
Suchi Chandrasekaran, MD, MSCE, is an assistant professor of obstetrics and gynecology in the division of maternal fetal medicine at the University of Washington, Yakima. She had no relevant financial disclosures. She was not associated with the study.
according to a case-control study drawn from the prospective NICHD Fetal Growth Studies-Singleton cohort.
Women who went on to develop GDM had higher HbA1c levels, and measuring this factor improved prediction when added to traditional GDM risk factors, Stefanie N. Hinkle, PhD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and her associates reported in Scientific Reports.
A previous report showed that GDM-associated fetal overgrowth begins before GDM diagnosis, which suggests a need to identify GDM earlier in pregnancy (Int J Epidemiol. 2018 Feb;47[1]:25–25l).
HbA1c is already used to screen for type 2 diabetes mellitus outside of pregnancy. Previous studies that examined its potential utility for GDM have focused on high-risk patients, examined an HbA1c threshold of 5.7%, used GDM during the first trimester only as the outcome, or had other limitations. There is little research on HbA1c levels and GDM in population-based samples.
Dr. Hinkle and her associates conducted a secondary analysis of a case-control study that involved 2,334 low-risk pregnancies among nonobese women and 468 low-risk pregnancies among obese women (n = 2,802) at 12 U.S. centers. The women were recruited during gestational weeks 8-13 and then followed until the end of the pregnancy. The researchers did a nested GDM case-control study of 107 GDM cases and 214 matched non-GDM controls.
GDM cases had higher HbA1c levels throughout their pregnancies (P less than .03). The researchers found a linear association between HbA1c at enrollment and GDM risk (P = .001). Women with a first trimester HbA1c level of 5.7% had an odds ratio of 2.73 for GDM, compared with women at the median level of 5.2%.
In the adjusted model, for each increment of 0.1% at enrollment, women had an OR of 1.22 for GDM (P less than .001). For every 0.1% difference between HbA1c levels at enrollment and the second visit (24-29 weeks), the OR was 1.21 (P = .04). When the researchers excluded women who were obese, had smoked, had prior GDM, or had a hematologic disorder, the OR per 0.1% increase was similar (OR, 1.23; 95% confidence interval, 1.10-1.38).
A potential optimal cutoff point is 5.1%, which had a sensitivity of 47% (95% CI, 34%-60%) and a specificity of 79% (95% CI, 62%-88%). At 5.7%, which is used as the cutoff for prediabetes in nonpregnant women, the sensitivity was 21% (95% CI, 8%-36%) and the specificity was 95% (95% CI, 91%-99%).
When the model was added to conventional risk factors such as age, race/ethnicity, being overweight or obese before pregnancy, family history of diabetes, previous GDM, and nulliparity, the area under the curve of HbA1c levels at enrollment increased from 0.59 to 0.65.
Robert Atlas, MD, chair of obstetrics and gynecology at Mercy Medical Center, Baltimore, said in an interview, “This is just the first study that needs to be replicated in different patient populations. No one has looked at a continuum of HbA1c and what value above puts you at an increased risk. I think this is a very powerful study that sets the stage for further investigation into how to utilize HbA1c in a better way than we’ve ever looked at it before.”
The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural funding and by American Recovery and Reinvestment Act funding. Dr. Hinkle and her associates had no relevant financial disclosures. Dr. Atlas had no relevant financial disclosures.
SOURCE: Hinkle SN et al. Sci Rep. 2018 Aug 16;8(1):12249.
according to a case-control study drawn from the prospective NICHD Fetal Growth Studies-Singleton cohort.
Women who went on to develop GDM had higher HbA1c levels, and measuring this factor improved prediction when added to traditional GDM risk factors, Stefanie N. Hinkle, PhD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and her associates reported in Scientific Reports.
A previous report showed that GDM-associated fetal overgrowth begins before GDM diagnosis, which suggests a need to identify GDM earlier in pregnancy (Int J Epidemiol. 2018 Feb;47[1]:25–25l).
HbA1c is already used to screen for type 2 diabetes mellitus outside of pregnancy. Previous studies that examined its potential utility for GDM have focused on high-risk patients, examined an HbA1c threshold of 5.7%, used GDM during the first trimester only as the outcome, or had other limitations. There is little research on HbA1c levels and GDM in population-based samples.
Dr. Hinkle and her associates conducted a secondary analysis of a case-control study that involved 2,334 low-risk pregnancies among nonobese women and 468 low-risk pregnancies among obese women (n = 2,802) at 12 U.S. centers. The women were recruited during gestational weeks 8-13 and then followed until the end of the pregnancy. The researchers did a nested GDM case-control study of 107 GDM cases and 214 matched non-GDM controls.
GDM cases had higher HbA1c levels throughout their pregnancies (P less than .03). The researchers found a linear association between HbA1c at enrollment and GDM risk (P = .001). Women with a first trimester HbA1c level of 5.7% had an odds ratio of 2.73 for GDM, compared with women at the median level of 5.2%.
In the adjusted model, for each increment of 0.1% at enrollment, women had an OR of 1.22 for GDM (P less than .001). For every 0.1% difference between HbA1c levels at enrollment and the second visit (24-29 weeks), the OR was 1.21 (P = .04). When the researchers excluded women who were obese, had smoked, had prior GDM, or had a hematologic disorder, the OR per 0.1% increase was similar (OR, 1.23; 95% confidence interval, 1.10-1.38).
A potential optimal cutoff point is 5.1%, which had a sensitivity of 47% (95% CI, 34%-60%) and a specificity of 79% (95% CI, 62%-88%). At 5.7%, which is used as the cutoff for prediabetes in nonpregnant women, the sensitivity was 21% (95% CI, 8%-36%) and the specificity was 95% (95% CI, 91%-99%).
When the model was added to conventional risk factors such as age, race/ethnicity, being overweight or obese before pregnancy, family history of diabetes, previous GDM, and nulliparity, the area under the curve of HbA1c levels at enrollment increased from 0.59 to 0.65.
Robert Atlas, MD, chair of obstetrics and gynecology at Mercy Medical Center, Baltimore, said in an interview, “This is just the first study that needs to be replicated in different patient populations. No one has looked at a continuum of HbA1c and what value above puts you at an increased risk. I think this is a very powerful study that sets the stage for further investigation into how to utilize HbA1c in a better way than we’ve ever looked at it before.”
The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural funding and by American Recovery and Reinvestment Act funding. Dr. Hinkle and her associates had no relevant financial disclosures. Dr. Atlas had no relevant financial disclosures.
SOURCE: Hinkle SN et al. Sci Rep. 2018 Aug 16;8(1):12249.
FROM SCIENTIFIC REPORTS
Key clinical point: First trimester HbA1c levels could improve early diagnosis.
Major finding: HbA1c levels of 5.1% predicted later gestational diabetes with a sensitivity of 47% and a specificity of 79%
Study details: Nested case-control study of 107 gestational diabetes cases and 214 controls.
Disclosures: The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural funding and by the American Recovery and Reinvestment Act funding. .
Source: Hinkle SN et al. Sci Rep. 2018 Aug 16;8(1):12249.
Baseline steroids may reduce efficacy of checkpoint inhibitors
Immune checkpoint inhibitor therapy may be less effective if the patient is receiving corticosteroids at the time that treatment is initiated, results of a retrospective, two-center analysis suggest.
Corticosteroid use at the time of starting a PD-1 or PD-L1 inhibitor was associated with significantly reduced overall survival and progression-free survival in patients with non–small-cell lung cancer, the authors of the analysis reported.
“Prudent use of corticosteroids at the time of initiating PD-1/PD-L1 blockade is warranted,” said Matthew D. Hellmann, MD, of Memorial Sloan Kettering Cancer Center, New York, and his coauthors. The report is in the Journal of Clinical Oncology.
The retrospective analysis from Dr. Hellmann and his colleagues comprised 640 patients treated with single-agent atezolizumab, durvalumab, nivolumab, or pembrolizumab at Memorial Sloan Kettering Cancer Center or Gustave Roussy Cancer Center, Villejuif, France, between April 2011 and September 2017.
Ninety of those patients (14%) were receiving at least 10 mg of prednisone equivalent at the time the immune checkpoint inhibitor was started, a review of patient records revealed. About one-third were receiving corticosteroids for dyspnea or other respiratory symptoms. Another 21% had fatigue and 19% had brain metastases prompting corticosteroid treatment.
Corticosteroid use at the time of PD-1/PD-L1 blockade was associated with decreased progression-free survival (hazard ratio, 1.31; P = .03) and overall survival (HR, 1.66; P less than .001), as well as decreased overall response rate in a multivariable analysis adjusted for performance status, history of smoking, and history of brain metastases, the investigators reported.
Reduced efficacy also was seen in analyses that looked at each center separately. For the Memorial Sloan Kettering cohort (455 patients), baseline corticosteroid use was associated with significantly decreased overall response rate, shorter progression-free survival, and shorter overall survival.
For the smaller French cohort, (185 patients), there was a statistically nonsignificant decrease in overall response rate, along with significant reductions in progression-free survival and overall survival.
Based on these data, it may be prudent to try other pharmacologic or nonpharmacologic strategies to manage cancer symptoms if treatment with a PD-1/PD-L1 blocker is planned, Dr. Hellmann and his coauthors said.
“These strategies could enable patients to be tapered off corticosteroids before the start of PD-1/PD-L1 blockade to potentially achieve maximum benefit from these agents,” they wrote.
However, medically necessary corticosteroids should not be avoided, such as those given for management of brain metastases, they added.
Interestingly, other recent studies have suggested that patients already on PD-1/PD-L1 inhibitors do not seem to have decreased efficacy when corticosteroids are prescribed to manage emergent immune-related adverse events.
That’s “fortunate,” given that corticosteroids are a mainstay for the management of these characteristic adverse events in patients receiving immune checkpoint inhibitors, they said.
Dr. Hellmann reported research funding from Bristol-Myers Squibb, and a consulting or advisory role with AstraZeneca, Bristol-Myers Squibb, Genentech, Janssen Pharmaceuticals, MedImmune, Merck, Mirati Therapeutics, Shattuck Labs, and Syndax. Coauthors reported disclosures related to Amgen, Boehringer Ingelheim, Pfizer, and Roche, among others.
SOURCE: Arbour KC et al. J Clin Oncol. 2018 Aug 20. doi: 10.1200/JCO.2018.79.0006.
Immune checkpoint inhibitor therapy may be less effective if the patient is receiving corticosteroids at the time that treatment is initiated, results of a retrospective, two-center analysis suggest.
Corticosteroid use at the time of starting a PD-1 or PD-L1 inhibitor was associated with significantly reduced overall survival and progression-free survival in patients with non–small-cell lung cancer, the authors of the analysis reported.
“Prudent use of corticosteroids at the time of initiating PD-1/PD-L1 blockade is warranted,” said Matthew D. Hellmann, MD, of Memorial Sloan Kettering Cancer Center, New York, and his coauthors. The report is in the Journal of Clinical Oncology.
The retrospective analysis from Dr. Hellmann and his colleagues comprised 640 patients treated with single-agent atezolizumab, durvalumab, nivolumab, or pembrolizumab at Memorial Sloan Kettering Cancer Center or Gustave Roussy Cancer Center, Villejuif, France, between April 2011 and September 2017.
Ninety of those patients (14%) were receiving at least 10 mg of prednisone equivalent at the time the immune checkpoint inhibitor was started, a review of patient records revealed. About one-third were receiving corticosteroids for dyspnea or other respiratory symptoms. Another 21% had fatigue and 19% had brain metastases prompting corticosteroid treatment.
Corticosteroid use at the time of PD-1/PD-L1 blockade was associated with decreased progression-free survival (hazard ratio, 1.31; P = .03) and overall survival (HR, 1.66; P less than .001), as well as decreased overall response rate in a multivariable analysis adjusted for performance status, history of smoking, and history of brain metastases, the investigators reported.
Reduced efficacy also was seen in analyses that looked at each center separately. For the Memorial Sloan Kettering cohort (455 patients), baseline corticosteroid use was associated with significantly decreased overall response rate, shorter progression-free survival, and shorter overall survival.
For the smaller French cohort, (185 patients), there was a statistically nonsignificant decrease in overall response rate, along with significant reductions in progression-free survival and overall survival.
Based on these data, it may be prudent to try other pharmacologic or nonpharmacologic strategies to manage cancer symptoms if treatment with a PD-1/PD-L1 blocker is planned, Dr. Hellmann and his coauthors said.
“These strategies could enable patients to be tapered off corticosteroids before the start of PD-1/PD-L1 blockade to potentially achieve maximum benefit from these agents,” they wrote.
However, medically necessary corticosteroids should not be avoided, such as those given for management of brain metastases, they added.
Interestingly, other recent studies have suggested that patients already on PD-1/PD-L1 inhibitors do not seem to have decreased efficacy when corticosteroids are prescribed to manage emergent immune-related adverse events.
That’s “fortunate,” given that corticosteroids are a mainstay for the management of these characteristic adverse events in patients receiving immune checkpoint inhibitors, they said.
Dr. Hellmann reported research funding from Bristol-Myers Squibb, and a consulting or advisory role with AstraZeneca, Bristol-Myers Squibb, Genentech, Janssen Pharmaceuticals, MedImmune, Merck, Mirati Therapeutics, Shattuck Labs, and Syndax. Coauthors reported disclosures related to Amgen, Boehringer Ingelheim, Pfizer, and Roche, among others.
SOURCE: Arbour KC et al. J Clin Oncol. 2018 Aug 20. doi: 10.1200/JCO.2018.79.0006.
Immune checkpoint inhibitor therapy may be less effective if the patient is receiving corticosteroids at the time that treatment is initiated, results of a retrospective, two-center analysis suggest.
Corticosteroid use at the time of starting a PD-1 or PD-L1 inhibitor was associated with significantly reduced overall survival and progression-free survival in patients with non–small-cell lung cancer, the authors of the analysis reported.
“Prudent use of corticosteroids at the time of initiating PD-1/PD-L1 blockade is warranted,” said Matthew D. Hellmann, MD, of Memorial Sloan Kettering Cancer Center, New York, and his coauthors. The report is in the Journal of Clinical Oncology.
The retrospective analysis from Dr. Hellmann and his colleagues comprised 640 patients treated with single-agent atezolizumab, durvalumab, nivolumab, or pembrolizumab at Memorial Sloan Kettering Cancer Center or Gustave Roussy Cancer Center, Villejuif, France, between April 2011 and September 2017.
Ninety of those patients (14%) were receiving at least 10 mg of prednisone equivalent at the time the immune checkpoint inhibitor was started, a review of patient records revealed. About one-third were receiving corticosteroids for dyspnea or other respiratory symptoms. Another 21% had fatigue and 19% had brain metastases prompting corticosteroid treatment.
Corticosteroid use at the time of PD-1/PD-L1 blockade was associated with decreased progression-free survival (hazard ratio, 1.31; P = .03) and overall survival (HR, 1.66; P less than .001), as well as decreased overall response rate in a multivariable analysis adjusted for performance status, history of smoking, and history of brain metastases, the investigators reported.
Reduced efficacy also was seen in analyses that looked at each center separately. For the Memorial Sloan Kettering cohort (455 patients), baseline corticosteroid use was associated with significantly decreased overall response rate, shorter progression-free survival, and shorter overall survival.
For the smaller French cohort, (185 patients), there was a statistically nonsignificant decrease in overall response rate, along with significant reductions in progression-free survival and overall survival.
Based on these data, it may be prudent to try other pharmacologic or nonpharmacologic strategies to manage cancer symptoms if treatment with a PD-1/PD-L1 blocker is planned, Dr. Hellmann and his coauthors said.
“These strategies could enable patients to be tapered off corticosteroids before the start of PD-1/PD-L1 blockade to potentially achieve maximum benefit from these agents,” they wrote.
However, medically necessary corticosteroids should not be avoided, such as those given for management of brain metastases, they added.
Interestingly, other recent studies have suggested that patients already on PD-1/PD-L1 inhibitors do not seem to have decreased efficacy when corticosteroids are prescribed to manage emergent immune-related adverse events.
That’s “fortunate,” given that corticosteroids are a mainstay for the management of these characteristic adverse events in patients receiving immune checkpoint inhibitors, they said.
Dr. Hellmann reported research funding from Bristol-Myers Squibb, and a consulting or advisory role with AstraZeneca, Bristol-Myers Squibb, Genentech, Janssen Pharmaceuticals, MedImmune, Merck, Mirati Therapeutics, Shattuck Labs, and Syndax. Coauthors reported disclosures related to Amgen, Boehringer Ingelheim, Pfizer, and Roche, among others.
SOURCE: Arbour KC et al. J Clin Oncol. 2018 Aug 20. doi: 10.1200/JCO.2018.79.0006.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Immune checkpoint inhibitors may be less effective if the patient is receiving corticosteroids at the time treatment is started.
Major finding: Corticosteroid use at the time of PD-1/PD-L1 blockade was associated with decreased progression-free survival (hazard ratio, 1.31; P = .03) and overall survival (HR, 1.66; P less than .001) in multivariate analysis.
Study details: Retrospective analysis of 640 patients treated with atezolizumab, durvalumab, nivolumab, or pembrolizumab at Memorial Sloan Kettering Cancer Center or Gustave Roussy Cancer Center.
Disclosures: The authors reported disclosures related to Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Janssen Pharmaceuticals, MedImmune, Merck, Mirati Therapeutics, Pfizer, Roche, Shattuck Labs, and Syndax, among others.
Source: Arbour KC et al. J Clin Oncol. 2018 Aug 20. doi: 10.1200/JCO.2018.79.0006.
Applications for the 2019 Resident Corner Column Now Being Accepted
The Cutis Editorial Board is now accepting applications for the 2019 Resident Corner column. The Editorial Board will select 2 residents to serve as the Resident Corner columnists for 1 year (3 articles each). Articles are posted online only but will be referenced in Index Medicus. All applicants must be current residents and will still be in residency throughout 2019.
For consideration, send your curriculum vitae along with a brief (not to exceed 500 words) statement of why you enjoy Cutis and what you can offer your fellow residents in contributing a monthly column.
All materials should be submitted via email as 1 Word document to Melissa Sears by November 1. The residents who are selected to write the column for the upcoming year will be notified by November 15.
We look forward to continuing to educate dermatology residents on topics that are most important to them!
The Cutis Editorial Board is now accepting applications for the 2019 Resident Corner column. The Editorial Board will select 2 residents to serve as the Resident Corner columnists for 1 year (3 articles each). Articles are posted online only but will be referenced in Index Medicus. All applicants must be current residents and will still be in residency throughout 2019.
For consideration, send your curriculum vitae along with a brief (not to exceed 500 words) statement of why you enjoy Cutis and what you can offer your fellow residents in contributing a monthly column.
All materials should be submitted via email as 1 Word document to Melissa Sears by November 1. The residents who are selected to write the column for the upcoming year will be notified by November 15.
We look forward to continuing to educate dermatology residents on topics that are most important to them!
The Cutis Editorial Board is now accepting applications for the 2019 Resident Corner column. The Editorial Board will select 2 residents to serve as the Resident Corner columnists for 1 year (3 articles each). Articles are posted online only but will be referenced in Index Medicus. All applicants must be current residents and will still be in residency throughout 2019.
For consideration, send your curriculum vitae along with a brief (not to exceed 500 words) statement of why you enjoy Cutis and what you can offer your fellow residents in contributing a monthly column.
All materials should be submitted via email as 1 Word document to Melissa Sears by November 1. The residents who are selected to write the column for the upcoming year will be notified by November 15.
We look forward to continuing to educate dermatology residents on topics that are most important to them!
Mindfulness training for migraine just beginning to gather steam
SAN FRANCISCO – A brief course of mindfulness training for chronic migraine patients after their withdrawal from overuse of acute migraine medications proved as effective as prophylactic medication over the course of 12 months of follow-up, Frank Andrasik, PhD, reported at the annual meeting of the American Headache Society.
“The effects of mindfulness by and large rivaled those for medication alone. And although not specifically assessed, patients commented that mindfulness didn’t have side effects and promoted greater involvement and adherence,” said Dr. Andrasik, professor and chair, department of psychology, and director of the Center for Behavioral Medicine at the University of Memphis.
He noted that his recently published study (J Headache Pain. 2017 Dec;18[1]:15. doi: 10.1186/s10194-017-0728-z) is best considered exploratory because of its small size and nonrandomized design. Participants, after 5 days of structured acute medication withdrawal in a day hospital setting, got to choose whether to opt for pharmacologic prophylaxis for migraine – most often using botulinum toxin – or a brief course in mindfulness training entailing six once-weekly 45-minute sessions plus home practice for 7-10 minutes per day. And while this study design doesn’t rise to the status of level 1 randomized trial evidence, it does reflect real-world clinical practice, where patients often have a big say in choosing their treatment plan, the psychologist observed.
At baseline, all 44 patients met diagnostic criteria for chronic migraine with associated acute medication overuse. They averaged 20.5 headache days per month, with 18.4 days of acute migraine medication use.
At 3, 6, and 12 months of follow-up, the 22 patients in the mindfulness group averaged 8.3, 10.4, and 12.4 headache days per month, while the 22 on preventive migraine drugs averaged 8.8, 11, and 8.6 headache days per month. Both groups averaged similar 7- to 10-day reductions in days of acute migraine medication use per month.
Using the widely accepted endpoint of at least a 50% reduction in headache days per month, 50% of the mindfulness-only group and 52.6% of the prophylactic medication-only group met that standard at 12 months of follow-up. Moreover, at 12 months, 65% of the mindfulness therapy group and a similar 73.7% of the preventive medication group no longer met diagnostic criteria for chronic migraine.
The mindfulness protocol used in the study was based upon the popular mindfulness-based stress reduction program developed by Jon Kabat-Zinn, PhD.
Scores on the Migraine Disability Assessment (MIDAS) measure improved significantly and to a similar extent over baseline in both groups. So did scores on the Beck Depression Inventory. In contrast, scores on the State-Trait Anxiety Inventory didn’t change significantly in either study arm.
Both Dr. Andrasik and session chair Elizabeth K. Seng, PhD, cautioned that despite solid evidence of efficacy for mindfulness training in the treatment of depression and a number of chronic pain disorders, . Large randomized, controlled clinical trials are ongoing or in the planning stages, with no results yet available.
Dr. Seng, a clinical psychologist at Albert Einstein College of Medicine in New York, described mindfulness and acceptance as “third wave” behavioral treatments for migraine. The first wave therapies focused on fostering behavioral changes to reduce perceived stress in order to avoid triggering migraine attacks. The second wave involved therapeutic interactions aimed at helping patients reframe maladaptive automatic thoughts to reduce stress stemming from the daily hassles of life.
“The focus in the first- and second-wave therapies is, ‘Change something and your life will be better. Change your behaviors, clean up your act, change your thoughts because your thoughts are not helping you, and thereby reduce stress and reduce migraine.’ These mindfulness therapies are incredibly different from that,” she explained.
Indeed, the third-wave therapies aren’t trying to change daily hassles or automatic thoughts; instead, they seek to change the patient’s relationship to them such that they no longer create barriers to engaging in life activities that the patient finds nourishing and meaningful. It’s a matter of creating a willingness to experience pain in order to achieve worthwhile objectives, Dr. Seng continued.
It’s unclear that a reduction in migraine days – the traditional yardstick for therapeutic efficacy in migraine research – is the right primary outcome measure for third-wave therapies, according to the psychologist.
“So far, our evidence would suggest that mindfulness-based therapies do not reduce migraine days as much as other behavioral treatments, but what they’re doing is increasing migraine-related quality of life and reducing migraine-related disability to the same or possibly larger extent than our other behavioral treatments,“ she said. “Maybe what these third-wave therapies are actually doing is impacting our cognitive and emotional functioning, and that even if patients still experience similar levels of headache frequency, their reaction to those headache days no longer leads to a bunch of suffering. And that could be a clinically relevant outcome.”
Dr. Seng is particularly eager to formally study mindfulness therapies in a subgroup of migraine patients with high levels of depression. They might respond especially well, since mindfulness was originally developed as a treatment for severe depression. “Patients who are depressed have a hard time overcoming barriers to engaging in nourishing life activities, and when they have a headache day it’s even worse. That’s one of the things that’s leading them to have migraine-related disability,” she said.
Dr. Andrasik, whose study was supported by the European Commission and an Italian research foundation, reported having no financial conflicts of interest regarding his presentation. Dr. Seng reported serving as a consultant to GlaxoSmithKline.
SAN FRANCISCO – A brief course of mindfulness training for chronic migraine patients after their withdrawal from overuse of acute migraine medications proved as effective as prophylactic medication over the course of 12 months of follow-up, Frank Andrasik, PhD, reported at the annual meeting of the American Headache Society.
“The effects of mindfulness by and large rivaled those for medication alone. And although not specifically assessed, patients commented that mindfulness didn’t have side effects and promoted greater involvement and adherence,” said Dr. Andrasik, professor and chair, department of psychology, and director of the Center for Behavioral Medicine at the University of Memphis.
He noted that his recently published study (J Headache Pain. 2017 Dec;18[1]:15. doi: 10.1186/s10194-017-0728-z) is best considered exploratory because of its small size and nonrandomized design. Participants, after 5 days of structured acute medication withdrawal in a day hospital setting, got to choose whether to opt for pharmacologic prophylaxis for migraine – most often using botulinum toxin – or a brief course in mindfulness training entailing six once-weekly 45-minute sessions plus home practice for 7-10 minutes per day. And while this study design doesn’t rise to the status of level 1 randomized trial evidence, it does reflect real-world clinical practice, where patients often have a big say in choosing their treatment plan, the psychologist observed.
At baseline, all 44 patients met diagnostic criteria for chronic migraine with associated acute medication overuse. They averaged 20.5 headache days per month, with 18.4 days of acute migraine medication use.
At 3, 6, and 12 months of follow-up, the 22 patients in the mindfulness group averaged 8.3, 10.4, and 12.4 headache days per month, while the 22 on preventive migraine drugs averaged 8.8, 11, and 8.6 headache days per month. Both groups averaged similar 7- to 10-day reductions in days of acute migraine medication use per month.
Using the widely accepted endpoint of at least a 50% reduction in headache days per month, 50% of the mindfulness-only group and 52.6% of the prophylactic medication-only group met that standard at 12 months of follow-up. Moreover, at 12 months, 65% of the mindfulness therapy group and a similar 73.7% of the preventive medication group no longer met diagnostic criteria for chronic migraine.
The mindfulness protocol used in the study was based upon the popular mindfulness-based stress reduction program developed by Jon Kabat-Zinn, PhD.
Scores on the Migraine Disability Assessment (MIDAS) measure improved significantly and to a similar extent over baseline in both groups. So did scores on the Beck Depression Inventory. In contrast, scores on the State-Trait Anxiety Inventory didn’t change significantly in either study arm.
Both Dr. Andrasik and session chair Elizabeth K. Seng, PhD, cautioned that despite solid evidence of efficacy for mindfulness training in the treatment of depression and a number of chronic pain disorders, . Large randomized, controlled clinical trials are ongoing or in the planning stages, with no results yet available.
Dr. Seng, a clinical psychologist at Albert Einstein College of Medicine in New York, described mindfulness and acceptance as “third wave” behavioral treatments for migraine. The first wave therapies focused on fostering behavioral changes to reduce perceived stress in order to avoid triggering migraine attacks. The second wave involved therapeutic interactions aimed at helping patients reframe maladaptive automatic thoughts to reduce stress stemming from the daily hassles of life.
“The focus in the first- and second-wave therapies is, ‘Change something and your life will be better. Change your behaviors, clean up your act, change your thoughts because your thoughts are not helping you, and thereby reduce stress and reduce migraine.’ These mindfulness therapies are incredibly different from that,” she explained.
Indeed, the third-wave therapies aren’t trying to change daily hassles or automatic thoughts; instead, they seek to change the patient’s relationship to them such that they no longer create barriers to engaging in life activities that the patient finds nourishing and meaningful. It’s a matter of creating a willingness to experience pain in order to achieve worthwhile objectives, Dr. Seng continued.
It’s unclear that a reduction in migraine days – the traditional yardstick for therapeutic efficacy in migraine research – is the right primary outcome measure for third-wave therapies, according to the psychologist.
“So far, our evidence would suggest that mindfulness-based therapies do not reduce migraine days as much as other behavioral treatments, but what they’re doing is increasing migraine-related quality of life and reducing migraine-related disability to the same or possibly larger extent than our other behavioral treatments,“ she said. “Maybe what these third-wave therapies are actually doing is impacting our cognitive and emotional functioning, and that even if patients still experience similar levels of headache frequency, their reaction to those headache days no longer leads to a bunch of suffering. And that could be a clinically relevant outcome.”
Dr. Seng is particularly eager to formally study mindfulness therapies in a subgroup of migraine patients with high levels of depression. They might respond especially well, since mindfulness was originally developed as a treatment for severe depression. “Patients who are depressed have a hard time overcoming barriers to engaging in nourishing life activities, and when they have a headache day it’s even worse. That’s one of the things that’s leading them to have migraine-related disability,” she said.
Dr. Andrasik, whose study was supported by the European Commission and an Italian research foundation, reported having no financial conflicts of interest regarding his presentation. Dr. Seng reported serving as a consultant to GlaxoSmithKline.
SAN FRANCISCO – A brief course of mindfulness training for chronic migraine patients after their withdrawal from overuse of acute migraine medications proved as effective as prophylactic medication over the course of 12 months of follow-up, Frank Andrasik, PhD, reported at the annual meeting of the American Headache Society.
“The effects of mindfulness by and large rivaled those for medication alone. And although not specifically assessed, patients commented that mindfulness didn’t have side effects and promoted greater involvement and adherence,” said Dr. Andrasik, professor and chair, department of psychology, and director of the Center for Behavioral Medicine at the University of Memphis.
He noted that his recently published study (J Headache Pain. 2017 Dec;18[1]:15. doi: 10.1186/s10194-017-0728-z) is best considered exploratory because of its small size and nonrandomized design. Participants, after 5 days of structured acute medication withdrawal in a day hospital setting, got to choose whether to opt for pharmacologic prophylaxis for migraine – most often using botulinum toxin – or a brief course in mindfulness training entailing six once-weekly 45-minute sessions plus home practice for 7-10 minutes per day. And while this study design doesn’t rise to the status of level 1 randomized trial evidence, it does reflect real-world clinical practice, where patients often have a big say in choosing their treatment plan, the psychologist observed.
At baseline, all 44 patients met diagnostic criteria for chronic migraine with associated acute medication overuse. They averaged 20.5 headache days per month, with 18.4 days of acute migraine medication use.
At 3, 6, and 12 months of follow-up, the 22 patients in the mindfulness group averaged 8.3, 10.4, and 12.4 headache days per month, while the 22 on preventive migraine drugs averaged 8.8, 11, and 8.6 headache days per month. Both groups averaged similar 7- to 10-day reductions in days of acute migraine medication use per month.
Using the widely accepted endpoint of at least a 50% reduction in headache days per month, 50% of the mindfulness-only group and 52.6% of the prophylactic medication-only group met that standard at 12 months of follow-up. Moreover, at 12 months, 65% of the mindfulness therapy group and a similar 73.7% of the preventive medication group no longer met diagnostic criteria for chronic migraine.
The mindfulness protocol used in the study was based upon the popular mindfulness-based stress reduction program developed by Jon Kabat-Zinn, PhD.
Scores on the Migraine Disability Assessment (MIDAS) measure improved significantly and to a similar extent over baseline in both groups. So did scores on the Beck Depression Inventory. In contrast, scores on the State-Trait Anxiety Inventory didn’t change significantly in either study arm.
Both Dr. Andrasik and session chair Elizabeth K. Seng, PhD, cautioned that despite solid evidence of efficacy for mindfulness training in the treatment of depression and a number of chronic pain disorders, . Large randomized, controlled clinical trials are ongoing or in the planning stages, with no results yet available.
Dr. Seng, a clinical psychologist at Albert Einstein College of Medicine in New York, described mindfulness and acceptance as “third wave” behavioral treatments for migraine. The first wave therapies focused on fostering behavioral changes to reduce perceived stress in order to avoid triggering migraine attacks. The second wave involved therapeutic interactions aimed at helping patients reframe maladaptive automatic thoughts to reduce stress stemming from the daily hassles of life.
“The focus in the first- and second-wave therapies is, ‘Change something and your life will be better. Change your behaviors, clean up your act, change your thoughts because your thoughts are not helping you, and thereby reduce stress and reduce migraine.’ These mindfulness therapies are incredibly different from that,” she explained.
Indeed, the third-wave therapies aren’t trying to change daily hassles or automatic thoughts; instead, they seek to change the patient’s relationship to them such that they no longer create barriers to engaging in life activities that the patient finds nourishing and meaningful. It’s a matter of creating a willingness to experience pain in order to achieve worthwhile objectives, Dr. Seng continued.
It’s unclear that a reduction in migraine days – the traditional yardstick for therapeutic efficacy in migraine research – is the right primary outcome measure for third-wave therapies, according to the psychologist.
“So far, our evidence would suggest that mindfulness-based therapies do not reduce migraine days as much as other behavioral treatments, but what they’re doing is increasing migraine-related quality of life and reducing migraine-related disability to the same or possibly larger extent than our other behavioral treatments,“ she said. “Maybe what these third-wave therapies are actually doing is impacting our cognitive and emotional functioning, and that even if patients still experience similar levels of headache frequency, their reaction to those headache days no longer leads to a bunch of suffering. And that could be a clinically relevant outcome.”
Dr. Seng is particularly eager to formally study mindfulness therapies in a subgroup of migraine patients with high levels of depression. They might respond especially well, since mindfulness was originally developed as a treatment for severe depression. “Patients who are depressed have a hard time overcoming barriers to engaging in nourishing life activities, and when they have a headache day it’s even worse. That’s one of the things that’s leading them to have migraine-related disability,” she said.
Dr. Andrasik, whose study was supported by the European Commission and an Italian research foundation, reported having no financial conflicts of interest regarding his presentation. Dr. Seng reported serving as a consultant to GlaxoSmithKline.
REPORTING FROM THE AHS ANNUAL MEETING
Study sheds new light on prognostic factors in PRCC
Although the two major subtypes of papillary renal cell carcinoma (PRCC) differ on a variety of measures of aggressiveness, subtype is not independently prognostic, according to a retrospective cohort study conducted by the German Network of Kidney Cancer.
Investigators led by Iris Polifka, an intern at the Institute of Pathology at the University Hospital Erlangen (Germany), characterized 376 renal tumors initially diagnosed as PRCC. They reviewed histologic features and performed immunohistochemical staining for a range of markers.
Main study results, which were reported in Human Pathology, showed that 65.4% of the tumors were PRCC subtype 1 and 34.6% were PRCC subtype 2. The former more commonly had foamy macrophages and expressed cytokeratin 7, whereas the latter more commonly had abundant cytoplasm, expressed E-cadherin and p53, and had high MIB1 expression (staining of more than 15% of cells), which indicated a high proliferation rate (P less than .05 for each). The latter also had higher stage and higher grade.
Univariate analysis in the entire study cohort showed that racemase expression and cytokeratin 7 expression were favorable prognostic factors for overall survival, whereas presence of abundant cytoplasm and psammoma bodies, high MIB1 expression, and PRCC subtype 2 were unfavorable prognostic factors.
However, in multivariate analysis, only four factors were independent predictors of death: high tumor MIB1 expression (hazard ratio, 2.465; P = .033), higher T stage (P = .036), metastases (HR, 4.334; P = .011), and age older than the median of 63 years at surgery (HR, 2.384; P = .005). Notably, tumor subtype did not independently predict this outcome.
“[T]he better [overall survival] in PRCC1 is mainly a reflection of its encapsulated nature associated with lower TNM stage … while enhanced proliferation might add to the aggressive nature of high grade and high stage tumors independently from PRCC subtype,” the investigators propose.
“PRCC subtype on its own is not suitable for estimating survival. More data focusing on PRCC tumor biology is needed to define prognostic subgroups, especially in PRCC2,” they conclude.
The investigators disclosed that they had no relevant conflicts of interest. The study did not receive any specific funding.
SOURCE: Polifka I et al. Hum Pathol. 2018 Aug 16. doi: 10.1016/j.humpath.2018.08.006.
Although the two major subtypes of papillary renal cell carcinoma (PRCC) differ on a variety of measures of aggressiveness, subtype is not independently prognostic, according to a retrospective cohort study conducted by the German Network of Kidney Cancer.
Investigators led by Iris Polifka, an intern at the Institute of Pathology at the University Hospital Erlangen (Germany), characterized 376 renal tumors initially diagnosed as PRCC. They reviewed histologic features and performed immunohistochemical staining for a range of markers.
Main study results, which were reported in Human Pathology, showed that 65.4% of the tumors were PRCC subtype 1 and 34.6% were PRCC subtype 2. The former more commonly had foamy macrophages and expressed cytokeratin 7, whereas the latter more commonly had abundant cytoplasm, expressed E-cadherin and p53, and had high MIB1 expression (staining of more than 15% of cells), which indicated a high proliferation rate (P less than .05 for each). The latter also had higher stage and higher grade.
Univariate analysis in the entire study cohort showed that racemase expression and cytokeratin 7 expression were favorable prognostic factors for overall survival, whereas presence of abundant cytoplasm and psammoma bodies, high MIB1 expression, and PRCC subtype 2 were unfavorable prognostic factors.
However, in multivariate analysis, only four factors were independent predictors of death: high tumor MIB1 expression (hazard ratio, 2.465; P = .033), higher T stage (P = .036), metastases (HR, 4.334; P = .011), and age older than the median of 63 years at surgery (HR, 2.384; P = .005). Notably, tumor subtype did not independently predict this outcome.
“[T]he better [overall survival] in PRCC1 is mainly a reflection of its encapsulated nature associated with lower TNM stage … while enhanced proliferation might add to the aggressive nature of high grade and high stage tumors independently from PRCC subtype,” the investigators propose.
“PRCC subtype on its own is not suitable for estimating survival. More data focusing on PRCC tumor biology is needed to define prognostic subgroups, especially in PRCC2,” they conclude.
The investigators disclosed that they had no relevant conflicts of interest. The study did not receive any specific funding.
SOURCE: Polifka I et al. Hum Pathol. 2018 Aug 16. doi: 10.1016/j.humpath.2018.08.006.
Although the two major subtypes of papillary renal cell carcinoma (PRCC) differ on a variety of measures of aggressiveness, subtype is not independently prognostic, according to a retrospective cohort study conducted by the German Network of Kidney Cancer.
Investigators led by Iris Polifka, an intern at the Institute of Pathology at the University Hospital Erlangen (Germany), characterized 376 renal tumors initially diagnosed as PRCC. They reviewed histologic features and performed immunohistochemical staining for a range of markers.
Main study results, which were reported in Human Pathology, showed that 65.4% of the tumors were PRCC subtype 1 and 34.6% were PRCC subtype 2. The former more commonly had foamy macrophages and expressed cytokeratin 7, whereas the latter more commonly had abundant cytoplasm, expressed E-cadherin and p53, and had high MIB1 expression (staining of more than 15% of cells), which indicated a high proliferation rate (P less than .05 for each). The latter also had higher stage and higher grade.
Univariate analysis in the entire study cohort showed that racemase expression and cytokeratin 7 expression were favorable prognostic factors for overall survival, whereas presence of abundant cytoplasm and psammoma bodies, high MIB1 expression, and PRCC subtype 2 were unfavorable prognostic factors.
However, in multivariate analysis, only four factors were independent predictors of death: high tumor MIB1 expression (hazard ratio, 2.465; P = .033), higher T stage (P = .036), metastases (HR, 4.334; P = .011), and age older than the median of 63 years at surgery (HR, 2.384; P = .005). Notably, tumor subtype did not independently predict this outcome.
“[T]he better [overall survival] in PRCC1 is mainly a reflection of its encapsulated nature associated with lower TNM stage … while enhanced proliferation might add to the aggressive nature of high grade and high stage tumors independently from PRCC subtype,” the investigators propose.
“PRCC subtype on its own is not suitable for estimating survival. More data focusing on PRCC tumor biology is needed to define prognostic subgroups, especially in PRCC2,” they conclude.
The investigators disclosed that they had no relevant conflicts of interest. The study did not receive any specific funding.
SOURCE: Polifka I et al. Hum Pathol. 2018 Aug 16. doi: 10.1016/j.humpath.2018.08.006.
FROM HUMAN PATHOLOGY
Key clinical point: Tumor proliferation, TNM stage, and patient age are independently prognostic in PRCC, whereas tumor subtype is not.
Major finding: Patients had poorer overall survival if they had high tumor MIB1 expression (hazard ratio, 2.465), higher tumor T stage (P = .036), or metastases (hazard ratio, 4.334), or were older (hazard ratio, 2.384).
Study details: A multicenter retrospective cohort study of 376 renal tumors initially diagnosed as PRCC.
Disclosures: The investigators disclosed that they had no relevant conflicts of interest. The study did not receive any specific funding.
Source: Polifka I et al. Hum Pathol. 2018 Aug 16. doi: 10.1016/j.humpath.2018.08.006.
Metastatic Vulvovaginal Crohn Disease in the Setting of Well-Controlled Intestinal Disease
The cutaneous manifestations of Crohn disease (CD) are varied, including pyoderma gangrenosum, erythema nodosum, and metastatic CD (MCD). First described by Parks et al,1 MCD is defined as the occurrence of granulomatous lesions at a skin site distant from the gastrointestinal tract.1-20 Metastatic CD presents a diagnostic challenge because it is a rare component in the spectrum of inflammatory bowel disease complications, and many physicians are unaware of its existence. It may precede, coincide with, or develop after the diagnosis of intestinal disease.2-5 Vulvoperineal involvement is particularly problematic because a multitude of other, more likely disease processes are considered first. Typically it is initially diagnosed as a presumed infection prompting reflexive treatment with antivirals, antifungals, and antibiotics. Patients may experience symptoms for years prior to correct diagnosis and institution of proper therapy. A variety of clinical presentations have been described, including nonspecific pain and swelling, erythematous papules and plaques, and nonhealing ulcers. Skin biopsy characteristically confirms the diagnosis and reveals dermal noncaseating granulomas. Multiple oral and parenteral therapies are available, with surgical intervention reserved for resistant cases. We present a case of vulvovaginal MCD in the setting of well-controlled intestinal disease. We also provide a review of the literature regarding genital CD and emphasize the need to keep MCD in the differential of vulvoperineal pathology.
Case Report
A 29-year-old woman was referred to the dermatology clinic with vulvar pain, swelling, and pruritus of 14 months’ duration. Her medical history was remarkable for CD following a colectomy with colostomy. Prior therapies included methotrexate with infliximab for 5 years followed by a 2-year regimen with adalimumab, which induced remission of the intestinal disease.
The patient previously had taken a variety of topical and oral antimicrobials based on treatment from a primary care physician because fungal, bacterial, and viral infections initially were suspected; however, the vulvar disease persisted, and drug-induced immunosuppression was considered to be an underlying factor. Thus, adalimumab was discontinued. Despite elimination of the biologic, the vulvar disease progressed, which prompted referral to the dermatology clinic.
Physical examination revealed diffuse vulvar edema with overlying erythema and scale (Figure 1A). Upon closer inspection, scattered violaceous papules atop a backdrop of lichenification were evident, imparting a cobblestone appearance (Figure 1B). Additionally, a fissure was present on the gluteal cleft. Biopsy from the left labia majora demonstrated well-formed granulomas within a fibrotic reticular dermis (Figures 2A and 2B). The granulomas consisted of both mononucleated and multinucleated histiocytes, rimmed peripherally by lymphocytes and plasma cells (Figure 2C). Periodic acid–Schiff–diastase and acid-fast bacilli stains as well as polarizing microscopy were negative.
Given the patient’s history, a diagnosis of vulvoperineal MCD was rendered. The patient was started on oral metronidazole 250 mg 3 times daily with topical fluocinonide and tacrolimus. She responded well to this treatment regimen and was referred back to the gastroenterologist for management of the intestinal disease.
Comment
Crohn disease is an idiopathic chronic inflammatory condition that primarily affects the gastrointestinal tract, anywhere from the mouth to the anus. It is characterized by transmural inflammation and fissures that can extend beyond the muscularis propria.4,6 Extraintestinal manifestations are common.3
Cutaneous CD often presents as perianal, perifistular, or peristomal inflammation or ulceration.7 Other skin manifestations include pyoderma gangrenosum, erythema nodosum, erythema multiforme, epidermolysis bullosa acquisita, and palmar erythema.7 Metastatic CD involves skin noncontiguous with the gastrointestinal tract1-20 and may involve any portion of the cutis. Although rare, MCD is the typical etiology underlying vulvar CD.8
Approximately 20% of MCD patients have cutaneous lesions without a history of gastrointestinal disease. More than half of cases in adults and approximately two-thirds in children involve the genitalia. Although more common in adults, vulvar involvement has been reported in children as young as 6 years of age.2 Diagnosis is especially challenging when bowel symptoms are absent; those patients should be evaluated and followed for subsequent intestinal involvement.6
Clinically, symptoms may include general discomfort, pain, pruritus, and dyspareunia. Psychosocial and sexual dysfunction are prevalent and also should be addressed.9 Depending on the stage of the disease, physical examination may reveal erythema, edema, papules, pustules, nodules, condylomatous lesions, abscesses, fissures, fistulas, ulceration, acrochordons, and scarring.2-6,10,11
A host of infections (ie, mycobacterial, actinomycosis, deep fungal, sexually transmitted, schistosomiasis), inflammatory conditions (ie, sarcoid, hidradenitis suppurativa), foreign body reactions, Melkersson-Rosenthal syndrome, and sexual abuse should be included in the differential diagnosis.2,6,10-12 Once infection, sarcoid, and foreign body reaction have been ruled out, noncaseating granulomas in skin are highly suggestive of CD.7
Histopathologic findings of MCD reveal myriad morphological reaction patterns,5,13 including high-grade dysplasia and carcinoma of the vulva; therefore, it may be imprudent to withhold diagnosis based on the absence of the historically pathognomonic noncaseating granulomas.5
The etiopathogenesis of MCD remains an enigma. Dermatopathologic examinations consistently reveal a vascular injury syndrome,13 implicating a possible circulatory system contribution via deposition of immune complexes or antigens in skin.7 Bacterial infection has been implicated in the intestinal manifestations of CD; however, failure to detect microbial ribosomal RNA in MCD biopsies refutes theories of hematogenous spread of microbes.13 Another plausible explanation is that antibodies are formed to conserved microbial epitopes following loss of tolerance to gut flora, which results in an excessive immunologic response at distinct sites in susceptible individuals.13 A T-lymphocyte–mediated type IV hypersensitivity reaction also has been proposed via cross-reactivity of lymphocytes, with skin antigens precipitating extraintestinal granuloma formation and vascular injury.3 Clearly, further investigation is needed.
Magnetic resonanance imaging can identify the extent and anatomy of intestinal and pelvic disease and can assist in the diagnosis of vulvar CD.10,11,14 For these reasons, some experts propose that imaging should be instituted prior to therapy,12,15,16 especially when direct extension is suspected.17
Treatment is challenging and often involves collaboration among several specialties.12 Many treatment options exist because therapeutic responses vary and genital MCD is frequently recalcitrant to therapy.4 Medical therapy includes antibiotics such as metronidazole, corticosteroids (ie, topical, intralesional, systemic), and immune modulators (eg, azathioprine, 6-mercaptopurine, cyclosporine, methotrexate, mycophenolate mofetil, tumor necrosis factor α inhibitors).2,3,6,10,16,18 Thalidomide has been used for refractory cases.19 These treatments can be used alone or in combination. Patients should be monitored for side effects and informed that many treatment regimens may be required before a sustained response is achieved.4,16,18 Surgery is reserved for the most resistant cases. Extensive radical excision of the involved area is the best approach, as limited local excision often is followed by recurrence.20
Conclusion
Our case highlights that vulvar CD can develop in the setting of well-controlled intestinal disease. Vulvoperineal CD should be considered in the differential diagnosis of chronic vulvar pain, swelling, and pruritus, especially in cases resistant to standard therapies and regardless of whether or not gastrointestinal tract symptoms are present. Physicians must be cognizant that vulvar signs and symptoms may precede, coincide with, or follow the diagnosis of intestinal CD. Increased awareness of this entity may facilitate its early recognition and prompt more timely treatment among women with vulvar disease caused by MCD.
- Parks AG, Morson BC, Pegum JS. Crohn’s disease with cutaneous involvement. Proc R Soc Med. 1965;58:241-242.
- Ploysangam T, Heubi JE, Eisen D, et al. Cutaneous Crohn’s disease in children. J Am Acad Dermatol. 1997;36:697-704.
- Palamaras I, El-Jabbour J, Pietropaolo N, et al. Metastatic Crohn’s disease: a review. J Eur Acad Dermatol Venereol. 2008;22:1033-1043.
- Leu S, Sun PK, Collyer J, et al. Clinical spectrum of vulvar metastatic Crohn’s disease. Dig Dis Sci. 2009;54:1565-1571.
- Foo WC, Papalas JA, Robboy SJ, et al. Vulvar manifestations of Crohn’s disease. Am J Dermatopathol. 2001;33:588-593.
- Urbanek M, Neill SM, McKee PH. Vulval Crohn’s disease: difficulties in diagnosis. Clin Exp Dermatol. 1996;21:211-214.
- Burgdorf W. Cutaneous manifestations of Crohn’s disease. J Am Acad Dermatol. 1981;5:689-695.
- Andreani SM, Ratnasingham K, Dang HH, et al. Crohn’s disease of the vulva. Int J Surg. 2010;8:2-5.
- Feller E, Ribaudo S, Jackson N. Gynecologic aspects of Crohn’s disease. Am Fam Physician. 2001;64:1725-1728.
- Corbett SL, Walsh CM, Spitzer RF, et al. Vulvar inflammation as the only clinical manifestation of Crohn disease in an 8-year-old girl [published online May 10, 2010]. Pediatrics. 2010;125:E1518-E1522.
- Tonolini M, Villa C, Campari A, et al. Common and unusual urogenital Crohn’s disease complications: spectrum of cross-sectional imaging findings. Abdom Imaging. 2013;38:32-41.
- Bhaduri S, Jenkinson S, Lewis F. Vulval Crohn’s disease—a multi-specialty approach. Int J STD AIDS. 2005;16:512-514.
- Crowson AN, Nuovo GJ, Mihm MC Jr, et al. Cutaneous manifestations of Crohn’s disease, its spectrum, and its pathogenesis: intracellular consensus bacterial 16S rRNA is associated with the gastrointestinal but not the cutaneous manifestations of Crohn’s disease. Hum Pathol. 2003;34:1185-1192.
- Pai D, Dillman JR, Mahani MG, et al. MRI of vulvar Crohn disease. Pediatr Radiol. 2011;41:537-541.
- Madnani NA, Desai D, Gandhi N, et al. Isolated Crohn’s disease of the vulva. Indian J Dermatol Venereol Leprol. 2011;77:342-344.
- Makhija S, Trotter M, Wagner E, et al. Refractory Crohn’s disease of the vulva treated with infliximab: a case report. Can J Gastroenterol. 2007;21:835-837.
- Fahmy N, Kalidindi M, Khan R. Direct colo-labial Crohn’s abscess mimicking bartholinitis. Am J Obstret Gynecol. 2010;30:741-742.
- Preston PW, Hudson N, Lewis FM. Treatment of vulval Crohn’s disease with infliximab. Clin Exp Derm. 2006;31:378-380.
- Kolivras A, De Maubeuge J, André J, et al. Thalidomide in refractory vulvar ulcerations associated with Crohn’s disease. Dermatology. 2003;206:381-383.
- Kao MS, Paulson JD, Askin FB. Crohn’s disease of the vulva. Obstet Gynecol. 1975;46:329-333.
The cutaneous manifestations of Crohn disease (CD) are varied, including pyoderma gangrenosum, erythema nodosum, and metastatic CD (MCD). First described by Parks et al,1 MCD is defined as the occurrence of granulomatous lesions at a skin site distant from the gastrointestinal tract.1-20 Metastatic CD presents a diagnostic challenge because it is a rare component in the spectrum of inflammatory bowel disease complications, and many physicians are unaware of its existence. It may precede, coincide with, or develop after the diagnosis of intestinal disease.2-5 Vulvoperineal involvement is particularly problematic because a multitude of other, more likely disease processes are considered first. Typically it is initially diagnosed as a presumed infection prompting reflexive treatment with antivirals, antifungals, and antibiotics. Patients may experience symptoms for years prior to correct diagnosis and institution of proper therapy. A variety of clinical presentations have been described, including nonspecific pain and swelling, erythematous papules and plaques, and nonhealing ulcers. Skin biopsy characteristically confirms the diagnosis and reveals dermal noncaseating granulomas. Multiple oral and parenteral therapies are available, with surgical intervention reserved for resistant cases. We present a case of vulvovaginal MCD in the setting of well-controlled intestinal disease. We also provide a review of the literature regarding genital CD and emphasize the need to keep MCD in the differential of vulvoperineal pathology.
Case Report
A 29-year-old woman was referred to the dermatology clinic with vulvar pain, swelling, and pruritus of 14 months’ duration. Her medical history was remarkable for CD following a colectomy with colostomy. Prior therapies included methotrexate with infliximab for 5 years followed by a 2-year regimen with adalimumab, which induced remission of the intestinal disease.
The patient previously had taken a variety of topical and oral antimicrobials based on treatment from a primary care physician because fungal, bacterial, and viral infections initially were suspected; however, the vulvar disease persisted, and drug-induced immunosuppression was considered to be an underlying factor. Thus, adalimumab was discontinued. Despite elimination of the biologic, the vulvar disease progressed, which prompted referral to the dermatology clinic.
Physical examination revealed diffuse vulvar edema with overlying erythema and scale (Figure 1A). Upon closer inspection, scattered violaceous papules atop a backdrop of lichenification were evident, imparting a cobblestone appearance (Figure 1B). Additionally, a fissure was present on the gluteal cleft. Biopsy from the left labia majora demonstrated well-formed granulomas within a fibrotic reticular dermis (Figures 2A and 2B). The granulomas consisted of both mononucleated and multinucleated histiocytes, rimmed peripherally by lymphocytes and plasma cells (Figure 2C). Periodic acid–Schiff–diastase and acid-fast bacilli stains as well as polarizing microscopy were negative.
Given the patient’s history, a diagnosis of vulvoperineal MCD was rendered. The patient was started on oral metronidazole 250 mg 3 times daily with topical fluocinonide and tacrolimus. She responded well to this treatment regimen and was referred back to the gastroenterologist for management of the intestinal disease.
Comment
Crohn disease is an idiopathic chronic inflammatory condition that primarily affects the gastrointestinal tract, anywhere from the mouth to the anus. It is characterized by transmural inflammation and fissures that can extend beyond the muscularis propria.4,6 Extraintestinal manifestations are common.3
Cutaneous CD often presents as perianal, perifistular, or peristomal inflammation or ulceration.7 Other skin manifestations include pyoderma gangrenosum, erythema nodosum, erythema multiforme, epidermolysis bullosa acquisita, and palmar erythema.7 Metastatic CD involves skin noncontiguous with the gastrointestinal tract1-20 and may involve any portion of the cutis. Although rare, MCD is the typical etiology underlying vulvar CD.8
Approximately 20% of MCD patients have cutaneous lesions without a history of gastrointestinal disease. More than half of cases in adults and approximately two-thirds in children involve the genitalia. Although more common in adults, vulvar involvement has been reported in children as young as 6 years of age.2 Diagnosis is especially challenging when bowel symptoms are absent; those patients should be evaluated and followed for subsequent intestinal involvement.6
Clinically, symptoms may include general discomfort, pain, pruritus, and dyspareunia. Psychosocial and sexual dysfunction are prevalent and also should be addressed.9 Depending on the stage of the disease, physical examination may reveal erythema, edema, papules, pustules, nodules, condylomatous lesions, abscesses, fissures, fistulas, ulceration, acrochordons, and scarring.2-6,10,11
A host of infections (ie, mycobacterial, actinomycosis, deep fungal, sexually transmitted, schistosomiasis), inflammatory conditions (ie, sarcoid, hidradenitis suppurativa), foreign body reactions, Melkersson-Rosenthal syndrome, and sexual abuse should be included in the differential diagnosis.2,6,10-12 Once infection, sarcoid, and foreign body reaction have been ruled out, noncaseating granulomas in skin are highly suggestive of CD.7
Histopathologic findings of MCD reveal myriad morphological reaction patterns,5,13 including high-grade dysplasia and carcinoma of the vulva; therefore, it may be imprudent to withhold diagnosis based on the absence of the historically pathognomonic noncaseating granulomas.5
The etiopathogenesis of MCD remains an enigma. Dermatopathologic examinations consistently reveal a vascular injury syndrome,13 implicating a possible circulatory system contribution via deposition of immune complexes or antigens in skin.7 Bacterial infection has been implicated in the intestinal manifestations of CD; however, failure to detect microbial ribosomal RNA in MCD biopsies refutes theories of hematogenous spread of microbes.13 Another plausible explanation is that antibodies are formed to conserved microbial epitopes following loss of tolerance to gut flora, which results in an excessive immunologic response at distinct sites in susceptible individuals.13 A T-lymphocyte–mediated type IV hypersensitivity reaction also has been proposed via cross-reactivity of lymphocytes, with skin antigens precipitating extraintestinal granuloma formation and vascular injury.3 Clearly, further investigation is needed.
Magnetic resonanance imaging can identify the extent and anatomy of intestinal and pelvic disease and can assist in the diagnosis of vulvar CD.10,11,14 For these reasons, some experts propose that imaging should be instituted prior to therapy,12,15,16 especially when direct extension is suspected.17
Treatment is challenging and often involves collaboration among several specialties.12 Many treatment options exist because therapeutic responses vary and genital MCD is frequently recalcitrant to therapy.4 Medical therapy includes antibiotics such as metronidazole, corticosteroids (ie, topical, intralesional, systemic), and immune modulators (eg, azathioprine, 6-mercaptopurine, cyclosporine, methotrexate, mycophenolate mofetil, tumor necrosis factor α inhibitors).2,3,6,10,16,18 Thalidomide has been used for refractory cases.19 These treatments can be used alone or in combination. Patients should be monitored for side effects and informed that many treatment regimens may be required before a sustained response is achieved.4,16,18 Surgery is reserved for the most resistant cases. Extensive radical excision of the involved area is the best approach, as limited local excision often is followed by recurrence.20
Conclusion
Our case highlights that vulvar CD can develop in the setting of well-controlled intestinal disease. Vulvoperineal CD should be considered in the differential diagnosis of chronic vulvar pain, swelling, and pruritus, especially in cases resistant to standard therapies and regardless of whether or not gastrointestinal tract symptoms are present. Physicians must be cognizant that vulvar signs and symptoms may precede, coincide with, or follow the diagnosis of intestinal CD. Increased awareness of this entity may facilitate its early recognition and prompt more timely treatment among women with vulvar disease caused by MCD.
The cutaneous manifestations of Crohn disease (CD) are varied, including pyoderma gangrenosum, erythema nodosum, and metastatic CD (MCD). First described by Parks et al,1 MCD is defined as the occurrence of granulomatous lesions at a skin site distant from the gastrointestinal tract.1-20 Metastatic CD presents a diagnostic challenge because it is a rare component in the spectrum of inflammatory bowel disease complications, and many physicians are unaware of its existence. It may precede, coincide with, or develop after the diagnosis of intestinal disease.2-5 Vulvoperineal involvement is particularly problematic because a multitude of other, more likely disease processes are considered first. Typically it is initially diagnosed as a presumed infection prompting reflexive treatment with antivirals, antifungals, and antibiotics. Patients may experience symptoms for years prior to correct diagnosis and institution of proper therapy. A variety of clinical presentations have been described, including nonspecific pain and swelling, erythematous papules and plaques, and nonhealing ulcers. Skin biopsy characteristically confirms the diagnosis and reveals dermal noncaseating granulomas. Multiple oral and parenteral therapies are available, with surgical intervention reserved for resistant cases. We present a case of vulvovaginal MCD in the setting of well-controlled intestinal disease. We also provide a review of the literature regarding genital CD and emphasize the need to keep MCD in the differential of vulvoperineal pathology.
Case Report
A 29-year-old woman was referred to the dermatology clinic with vulvar pain, swelling, and pruritus of 14 months’ duration. Her medical history was remarkable for CD following a colectomy with colostomy. Prior therapies included methotrexate with infliximab for 5 years followed by a 2-year regimen with adalimumab, which induced remission of the intestinal disease.
The patient previously had taken a variety of topical and oral antimicrobials based on treatment from a primary care physician because fungal, bacterial, and viral infections initially were suspected; however, the vulvar disease persisted, and drug-induced immunosuppression was considered to be an underlying factor. Thus, adalimumab was discontinued. Despite elimination of the biologic, the vulvar disease progressed, which prompted referral to the dermatology clinic.
Physical examination revealed diffuse vulvar edema with overlying erythema and scale (Figure 1A). Upon closer inspection, scattered violaceous papules atop a backdrop of lichenification were evident, imparting a cobblestone appearance (Figure 1B). Additionally, a fissure was present on the gluteal cleft. Biopsy from the left labia majora demonstrated well-formed granulomas within a fibrotic reticular dermis (Figures 2A and 2B). The granulomas consisted of both mononucleated and multinucleated histiocytes, rimmed peripherally by lymphocytes and plasma cells (Figure 2C). Periodic acid–Schiff–diastase and acid-fast bacilli stains as well as polarizing microscopy were negative.
Given the patient’s history, a diagnosis of vulvoperineal MCD was rendered. The patient was started on oral metronidazole 250 mg 3 times daily with topical fluocinonide and tacrolimus. She responded well to this treatment regimen and was referred back to the gastroenterologist for management of the intestinal disease.
Comment
Crohn disease is an idiopathic chronic inflammatory condition that primarily affects the gastrointestinal tract, anywhere from the mouth to the anus. It is characterized by transmural inflammation and fissures that can extend beyond the muscularis propria.4,6 Extraintestinal manifestations are common.3
Cutaneous CD often presents as perianal, perifistular, or peristomal inflammation or ulceration.7 Other skin manifestations include pyoderma gangrenosum, erythema nodosum, erythema multiforme, epidermolysis bullosa acquisita, and palmar erythema.7 Metastatic CD involves skin noncontiguous with the gastrointestinal tract1-20 and may involve any portion of the cutis. Although rare, MCD is the typical etiology underlying vulvar CD.8
Approximately 20% of MCD patients have cutaneous lesions without a history of gastrointestinal disease. More than half of cases in adults and approximately two-thirds in children involve the genitalia. Although more common in adults, vulvar involvement has been reported in children as young as 6 years of age.2 Diagnosis is especially challenging when bowel symptoms are absent; those patients should be evaluated and followed for subsequent intestinal involvement.6
Clinically, symptoms may include general discomfort, pain, pruritus, and dyspareunia. Psychosocial and sexual dysfunction are prevalent and also should be addressed.9 Depending on the stage of the disease, physical examination may reveal erythema, edema, papules, pustules, nodules, condylomatous lesions, abscesses, fissures, fistulas, ulceration, acrochordons, and scarring.2-6,10,11
A host of infections (ie, mycobacterial, actinomycosis, deep fungal, sexually transmitted, schistosomiasis), inflammatory conditions (ie, sarcoid, hidradenitis suppurativa), foreign body reactions, Melkersson-Rosenthal syndrome, and sexual abuse should be included in the differential diagnosis.2,6,10-12 Once infection, sarcoid, and foreign body reaction have been ruled out, noncaseating granulomas in skin are highly suggestive of CD.7
Histopathologic findings of MCD reveal myriad morphological reaction patterns,5,13 including high-grade dysplasia and carcinoma of the vulva; therefore, it may be imprudent to withhold diagnosis based on the absence of the historically pathognomonic noncaseating granulomas.5
The etiopathogenesis of MCD remains an enigma. Dermatopathologic examinations consistently reveal a vascular injury syndrome,13 implicating a possible circulatory system contribution via deposition of immune complexes or antigens in skin.7 Bacterial infection has been implicated in the intestinal manifestations of CD; however, failure to detect microbial ribosomal RNA in MCD biopsies refutes theories of hematogenous spread of microbes.13 Another plausible explanation is that antibodies are formed to conserved microbial epitopes following loss of tolerance to gut flora, which results in an excessive immunologic response at distinct sites in susceptible individuals.13 A T-lymphocyte–mediated type IV hypersensitivity reaction also has been proposed via cross-reactivity of lymphocytes, with skin antigens precipitating extraintestinal granuloma formation and vascular injury.3 Clearly, further investigation is needed.
Magnetic resonanance imaging can identify the extent and anatomy of intestinal and pelvic disease and can assist in the diagnosis of vulvar CD.10,11,14 For these reasons, some experts propose that imaging should be instituted prior to therapy,12,15,16 especially when direct extension is suspected.17
Treatment is challenging and often involves collaboration among several specialties.12 Many treatment options exist because therapeutic responses vary and genital MCD is frequently recalcitrant to therapy.4 Medical therapy includes antibiotics such as metronidazole, corticosteroids (ie, topical, intralesional, systemic), and immune modulators (eg, azathioprine, 6-mercaptopurine, cyclosporine, methotrexate, mycophenolate mofetil, tumor necrosis factor α inhibitors).2,3,6,10,16,18 Thalidomide has been used for refractory cases.19 These treatments can be used alone or in combination. Patients should be monitored for side effects and informed that many treatment regimens may be required before a sustained response is achieved.4,16,18 Surgery is reserved for the most resistant cases. Extensive radical excision of the involved area is the best approach, as limited local excision often is followed by recurrence.20
Conclusion
Our case highlights that vulvar CD can develop in the setting of well-controlled intestinal disease. Vulvoperineal CD should be considered in the differential diagnosis of chronic vulvar pain, swelling, and pruritus, especially in cases resistant to standard therapies and regardless of whether or not gastrointestinal tract symptoms are present. Physicians must be cognizant that vulvar signs and symptoms may precede, coincide with, or follow the diagnosis of intestinal CD. Increased awareness of this entity may facilitate its early recognition and prompt more timely treatment among women with vulvar disease caused by MCD.
- Parks AG, Morson BC, Pegum JS. Crohn’s disease with cutaneous involvement. Proc R Soc Med. 1965;58:241-242.
- Ploysangam T, Heubi JE, Eisen D, et al. Cutaneous Crohn’s disease in children. J Am Acad Dermatol. 1997;36:697-704.
- Palamaras I, El-Jabbour J, Pietropaolo N, et al. Metastatic Crohn’s disease: a review. J Eur Acad Dermatol Venereol. 2008;22:1033-1043.
- Leu S, Sun PK, Collyer J, et al. Clinical spectrum of vulvar metastatic Crohn’s disease. Dig Dis Sci. 2009;54:1565-1571.
- Foo WC, Papalas JA, Robboy SJ, et al. Vulvar manifestations of Crohn’s disease. Am J Dermatopathol. 2001;33:588-593.
- Urbanek M, Neill SM, McKee PH. Vulval Crohn’s disease: difficulties in diagnosis. Clin Exp Dermatol. 1996;21:211-214.
- Burgdorf W. Cutaneous manifestations of Crohn’s disease. J Am Acad Dermatol. 1981;5:689-695.
- Andreani SM, Ratnasingham K, Dang HH, et al. Crohn’s disease of the vulva. Int J Surg. 2010;8:2-5.
- Feller E, Ribaudo S, Jackson N. Gynecologic aspects of Crohn’s disease. Am Fam Physician. 2001;64:1725-1728.
- Corbett SL, Walsh CM, Spitzer RF, et al. Vulvar inflammation as the only clinical manifestation of Crohn disease in an 8-year-old girl [published online May 10, 2010]. Pediatrics. 2010;125:E1518-E1522.
- Tonolini M, Villa C, Campari A, et al. Common and unusual urogenital Crohn’s disease complications: spectrum of cross-sectional imaging findings. Abdom Imaging. 2013;38:32-41.
- Bhaduri S, Jenkinson S, Lewis F. Vulval Crohn’s disease—a multi-specialty approach. Int J STD AIDS. 2005;16:512-514.
- Crowson AN, Nuovo GJ, Mihm MC Jr, et al. Cutaneous manifestations of Crohn’s disease, its spectrum, and its pathogenesis: intracellular consensus bacterial 16S rRNA is associated with the gastrointestinal but not the cutaneous manifestations of Crohn’s disease. Hum Pathol. 2003;34:1185-1192.
- Pai D, Dillman JR, Mahani MG, et al. MRI of vulvar Crohn disease. Pediatr Radiol. 2011;41:537-541.
- Madnani NA, Desai D, Gandhi N, et al. Isolated Crohn’s disease of the vulva. Indian J Dermatol Venereol Leprol. 2011;77:342-344.
- Makhija S, Trotter M, Wagner E, et al. Refractory Crohn’s disease of the vulva treated with infliximab: a case report. Can J Gastroenterol. 2007;21:835-837.
- Fahmy N, Kalidindi M, Khan R. Direct colo-labial Crohn’s abscess mimicking bartholinitis. Am J Obstret Gynecol. 2010;30:741-742.
- Preston PW, Hudson N, Lewis FM. Treatment of vulval Crohn’s disease with infliximab. Clin Exp Derm. 2006;31:378-380.
- Kolivras A, De Maubeuge J, André J, et al. Thalidomide in refractory vulvar ulcerations associated with Crohn’s disease. Dermatology. 2003;206:381-383.
- Kao MS, Paulson JD, Askin FB. Crohn’s disease of the vulva. Obstet Gynecol. 1975;46:329-333.
- Parks AG, Morson BC, Pegum JS. Crohn’s disease with cutaneous involvement. Proc R Soc Med. 1965;58:241-242.
- Ploysangam T, Heubi JE, Eisen D, et al. Cutaneous Crohn’s disease in children. J Am Acad Dermatol. 1997;36:697-704.
- Palamaras I, El-Jabbour J, Pietropaolo N, et al. Metastatic Crohn’s disease: a review. J Eur Acad Dermatol Venereol. 2008;22:1033-1043.
- Leu S, Sun PK, Collyer J, et al. Clinical spectrum of vulvar metastatic Crohn’s disease. Dig Dis Sci. 2009;54:1565-1571.
- Foo WC, Papalas JA, Robboy SJ, et al. Vulvar manifestations of Crohn’s disease. Am J Dermatopathol. 2001;33:588-593.
- Urbanek M, Neill SM, McKee PH. Vulval Crohn’s disease: difficulties in diagnosis. Clin Exp Dermatol. 1996;21:211-214.
- Burgdorf W. Cutaneous manifestations of Crohn’s disease. J Am Acad Dermatol. 1981;5:689-695.
- Andreani SM, Ratnasingham K, Dang HH, et al. Crohn’s disease of the vulva. Int J Surg. 2010;8:2-5.
- Feller E, Ribaudo S, Jackson N. Gynecologic aspects of Crohn’s disease. Am Fam Physician. 2001;64:1725-1728.
- Corbett SL, Walsh CM, Spitzer RF, et al. Vulvar inflammation as the only clinical manifestation of Crohn disease in an 8-year-old girl [published online May 10, 2010]. Pediatrics. 2010;125:E1518-E1522.
- Tonolini M, Villa C, Campari A, et al. Common and unusual urogenital Crohn’s disease complications: spectrum of cross-sectional imaging findings. Abdom Imaging. 2013;38:32-41.
- Bhaduri S, Jenkinson S, Lewis F. Vulval Crohn’s disease—a multi-specialty approach. Int J STD AIDS. 2005;16:512-514.
- Crowson AN, Nuovo GJ, Mihm MC Jr, et al. Cutaneous manifestations of Crohn’s disease, its spectrum, and its pathogenesis: intracellular consensus bacterial 16S rRNA is associated with the gastrointestinal but not the cutaneous manifestations of Crohn’s disease. Hum Pathol. 2003;34:1185-1192.
- Pai D, Dillman JR, Mahani MG, et al. MRI of vulvar Crohn disease. Pediatr Radiol. 2011;41:537-541.
- Madnani NA, Desai D, Gandhi N, et al. Isolated Crohn’s disease of the vulva. Indian J Dermatol Venereol Leprol. 2011;77:342-344.
- Makhija S, Trotter M, Wagner E, et al. Refractory Crohn’s disease of the vulva treated with infliximab: a case report. Can J Gastroenterol. 2007;21:835-837.
- Fahmy N, Kalidindi M, Khan R. Direct colo-labial Crohn’s abscess mimicking bartholinitis. Am J Obstret Gynecol. 2010;30:741-742.
- Preston PW, Hudson N, Lewis FM. Treatment of vulval Crohn’s disease with infliximab. Clin Exp Derm. 2006;31:378-380.
- Kolivras A, De Maubeuge J, André J, et al. Thalidomide in refractory vulvar ulcerations associated with Crohn’s disease. Dermatology. 2003;206:381-383.
- Kao MS, Paulson JD, Askin FB. Crohn’s disease of the vulva. Obstet Gynecol. 1975;46:329-333.
Tuition-free med school touches off multimillion-dollar debate
New York University’s School of Medicine is learning that no good deed goes unpunished.
The highly ranked medical school announced with much fanfare Aug. 16 that it is raising $600 million from private donors to eliminate tuition for all its students – even providing refunds to those currently enrolled. Before the announcement, annual tuition was $55,018.
NYU leaders said the move will help address the increasing problem of student debt among young doctors, which many educators argue pushes students to enter higher-paying specialties instead of primary care, or deters them from becoming doctors in the first place.
“A population as diverse as ours is best served by doctors from all walks of life, we believe, and aspiring physicians and surgeons should not be prevented from pursuing a career in medicine because of the prospect of overwhelming financial debt,” Dr. Robert Grossman, the dean of the medical school and CEO of NYU Langone Health, said in a statement. NYU declined a request to elaborate further on its plans.
“As I start rank ordering the various charities I want to give to, the people who can pay for medical school in cash aren’t at the top of my list,” said Craig Garthwaite, a health economist at Northwestern University’s Kellogg School of Management.
“If you had to find some cause to put tons of money behind, this strikes me as an odd one,” said Dr. Aaron Carroll, a pediatrician and researcher at Indiana University.
Still, medical education debt is a big issue in health care. According to the Association of American Medical Colleges, which represents U.S. medical schools and academic health centers, 75 percent of graduating physicians had student loan debt as they launched their careers, with a median tally of $192,000 in 2017. Nearly half owed more than $200,000.
But it is less clear how much of an impact that debt has on students’ choice of medical specialty. The AAMC’s data suggests debt does not play as big a role in specialty selection as some analysts claim.
If debt were a huge factor, one would expect that doctors who owed the most would choose the highest-paying specialties. But that’s not the case.
“Debt doesn’t vary much across the specialties,” said Julie Fresne, AAMC’s director of student financial services and debt management.
Garthwaite agrees. He said surveys in which young doctors claim debt as a reason for choosing a more lucrative specialty should be viewed with suspicion. “No one [who chooses a higher-paying job] says they did it because they want two Teslas,” he said. “They say they have all this debt.”
Carroll questioned how much difference even $200,000 in student debt makes to people who, at the lowest end of the medical spectrum, still stand to make six figures a year. “Doctors in general do just fine,” he said. “The idea we should pity physicians or worry about them strikes me as odd.”
Choice of specialty is also influenced by more than money. Some specialties may bring less demanding lifestyles than primary care or more prestige. Carroll said his surgeon father was not impressed when he opted for pediatrics, calling it a “garbageman” specialty.
There is also an array of government programs that help students afford medical school or forgive their loans, although usually in exchange for agreeing to serve for several years either in the military or in a medically underserved location. The federal National Health Service Corps, for example, provides scholarships and loan repayments to medical professionals who agree to work in mostly rural or inner-city areas with a shortage of medical professionals. And the Department of Education oversees the Public Service Loan Forgiveness program, which cancels outstanding loan balances after 10 years for those who work for nonprofit employers.
Medical schools themselves are addressing the student debt problem. Many – including NYU – have created programs that let students finish medical school in three years rather than four, which reduces the cost by 25 percent. And the Cleveland Clinic, together with Case Western Reserve University, has a tuition-free medical school aimed at training future medical researchers that takes five years but grants graduates who hold both a doctor of medicine title and a special research credential or master’s degree.
This latest move by NYU, however, is part of a continuing race among top-tier medical schools to attract the best students – and possibly improve their national rankings.
In 2014, UCLA announced it would provide merit-based scholarships covering the entire cost of medical education (including not just tuition, like NYU, but also living expenses) to 20 percent of its students. Columbia University announced a similar plan earlier this year, although unlike NYU and UCLA, Columbia’s program is based on students’ financial need.
The programs are funded, in whole or in part, by large donors whose names brand each medical school – entertainment mogul David Geffen at UCLA, former Merck CEO P. Roy Vagelos at Columbia, and Home Depot co-founder Kenneth Langone at NYU.
Economist Garthwaite said it is all well and good if top medical schools want to compete for top students by offering discounts. But if their goal is to encourage more students to enter primary care or to steer more people from lower-income families into medicine, giving free tuition to all “is not the most target-efficient way to reach that goal.”
Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
New York University’s School of Medicine is learning that no good deed goes unpunished.
The highly ranked medical school announced with much fanfare Aug. 16 that it is raising $600 million from private donors to eliminate tuition for all its students – even providing refunds to those currently enrolled. Before the announcement, annual tuition was $55,018.
NYU leaders said the move will help address the increasing problem of student debt among young doctors, which many educators argue pushes students to enter higher-paying specialties instead of primary care, or deters them from becoming doctors in the first place.
“A population as diverse as ours is best served by doctors from all walks of life, we believe, and aspiring physicians and surgeons should not be prevented from pursuing a career in medicine because of the prospect of overwhelming financial debt,” Dr. Robert Grossman, the dean of the medical school and CEO of NYU Langone Health, said in a statement. NYU declined a request to elaborate further on its plans.
“As I start rank ordering the various charities I want to give to, the people who can pay for medical school in cash aren’t at the top of my list,” said Craig Garthwaite, a health economist at Northwestern University’s Kellogg School of Management.
“If you had to find some cause to put tons of money behind, this strikes me as an odd one,” said Dr. Aaron Carroll, a pediatrician and researcher at Indiana University.
Still, medical education debt is a big issue in health care. According to the Association of American Medical Colleges, which represents U.S. medical schools and academic health centers, 75 percent of graduating physicians had student loan debt as they launched their careers, with a median tally of $192,000 in 2017. Nearly half owed more than $200,000.
But it is less clear how much of an impact that debt has on students’ choice of medical specialty. The AAMC’s data suggests debt does not play as big a role in specialty selection as some analysts claim.
If debt were a huge factor, one would expect that doctors who owed the most would choose the highest-paying specialties. But that’s not the case.
“Debt doesn’t vary much across the specialties,” said Julie Fresne, AAMC’s director of student financial services and debt management.
Garthwaite agrees. He said surveys in which young doctors claim debt as a reason for choosing a more lucrative specialty should be viewed with suspicion. “No one [who chooses a higher-paying job] says they did it because they want two Teslas,” he said. “They say they have all this debt.”
Carroll questioned how much difference even $200,000 in student debt makes to people who, at the lowest end of the medical spectrum, still stand to make six figures a year. “Doctors in general do just fine,” he said. “The idea we should pity physicians or worry about them strikes me as odd.”
Choice of specialty is also influenced by more than money. Some specialties may bring less demanding lifestyles than primary care or more prestige. Carroll said his surgeon father was not impressed when he opted for pediatrics, calling it a “garbageman” specialty.
There is also an array of government programs that help students afford medical school or forgive their loans, although usually in exchange for agreeing to serve for several years either in the military or in a medically underserved location. The federal National Health Service Corps, for example, provides scholarships and loan repayments to medical professionals who agree to work in mostly rural or inner-city areas with a shortage of medical professionals. And the Department of Education oversees the Public Service Loan Forgiveness program, which cancels outstanding loan balances after 10 years for those who work for nonprofit employers.
Medical schools themselves are addressing the student debt problem. Many – including NYU – have created programs that let students finish medical school in three years rather than four, which reduces the cost by 25 percent. And the Cleveland Clinic, together with Case Western Reserve University, has a tuition-free medical school aimed at training future medical researchers that takes five years but grants graduates who hold both a doctor of medicine title and a special research credential or master’s degree.
This latest move by NYU, however, is part of a continuing race among top-tier medical schools to attract the best students – and possibly improve their national rankings.
In 2014, UCLA announced it would provide merit-based scholarships covering the entire cost of medical education (including not just tuition, like NYU, but also living expenses) to 20 percent of its students. Columbia University announced a similar plan earlier this year, although unlike NYU and UCLA, Columbia’s program is based on students’ financial need.
The programs are funded, in whole or in part, by large donors whose names brand each medical school – entertainment mogul David Geffen at UCLA, former Merck CEO P. Roy Vagelos at Columbia, and Home Depot co-founder Kenneth Langone at NYU.
Economist Garthwaite said it is all well and good if top medical schools want to compete for top students by offering discounts. But if their goal is to encourage more students to enter primary care or to steer more people from lower-income families into medicine, giving free tuition to all “is not the most target-efficient way to reach that goal.”
Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
New York University’s School of Medicine is learning that no good deed goes unpunished.
The highly ranked medical school announced with much fanfare Aug. 16 that it is raising $600 million from private donors to eliminate tuition for all its students – even providing refunds to those currently enrolled. Before the announcement, annual tuition was $55,018.
NYU leaders said the move will help address the increasing problem of student debt among young doctors, which many educators argue pushes students to enter higher-paying specialties instead of primary care, or deters them from becoming doctors in the first place.
“A population as diverse as ours is best served by doctors from all walks of life, we believe, and aspiring physicians and surgeons should not be prevented from pursuing a career in medicine because of the prospect of overwhelming financial debt,” Dr. Robert Grossman, the dean of the medical school and CEO of NYU Langone Health, said in a statement. NYU declined a request to elaborate further on its plans.
“As I start rank ordering the various charities I want to give to, the people who can pay for medical school in cash aren’t at the top of my list,” said Craig Garthwaite, a health economist at Northwestern University’s Kellogg School of Management.
“If you had to find some cause to put tons of money behind, this strikes me as an odd one,” said Dr. Aaron Carroll, a pediatrician and researcher at Indiana University.
Still, medical education debt is a big issue in health care. According to the Association of American Medical Colleges, which represents U.S. medical schools and academic health centers, 75 percent of graduating physicians had student loan debt as they launched their careers, with a median tally of $192,000 in 2017. Nearly half owed more than $200,000.
But it is less clear how much of an impact that debt has on students’ choice of medical specialty. The AAMC’s data suggests debt does not play as big a role in specialty selection as some analysts claim.
If debt were a huge factor, one would expect that doctors who owed the most would choose the highest-paying specialties. But that’s not the case.
“Debt doesn’t vary much across the specialties,” said Julie Fresne, AAMC’s director of student financial services and debt management.
Garthwaite agrees. He said surveys in which young doctors claim debt as a reason for choosing a more lucrative specialty should be viewed with suspicion. “No one [who chooses a higher-paying job] says they did it because they want two Teslas,” he said. “They say they have all this debt.”
Carroll questioned how much difference even $200,000 in student debt makes to people who, at the lowest end of the medical spectrum, still stand to make six figures a year. “Doctors in general do just fine,” he said. “The idea we should pity physicians or worry about them strikes me as odd.”
Choice of specialty is also influenced by more than money. Some specialties may bring less demanding lifestyles than primary care or more prestige. Carroll said his surgeon father was not impressed when he opted for pediatrics, calling it a “garbageman” specialty.
There is also an array of government programs that help students afford medical school or forgive their loans, although usually in exchange for agreeing to serve for several years either in the military or in a medically underserved location. The federal National Health Service Corps, for example, provides scholarships and loan repayments to medical professionals who agree to work in mostly rural or inner-city areas with a shortage of medical professionals. And the Department of Education oversees the Public Service Loan Forgiveness program, which cancels outstanding loan balances after 10 years for those who work for nonprofit employers.
Medical schools themselves are addressing the student debt problem. Many – including NYU – have created programs that let students finish medical school in three years rather than four, which reduces the cost by 25 percent. And the Cleveland Clinic, together with Case Western Reserve University, has a tuition-free medical school aimed at training future medical researchers that takes five years but grants graduates who hold both a doctor of medicine title and a special research credential or master’s degree.
This latest move by NYU, however, is part of a continuing race among top-tier medical schools to attract the best students – and possibly improve their national rankings.
In 2014, UCLA announced it would provide merit-based scholarships covering the entire cost of medical education (including not just tuition, like NYU, but also living expenses) to 20 percent of its students. Columbia University announced a similar plan earlier this year, although unlike NYU and UCLA, Columbia’s program is based on students’ financial need.
The programs are funded, in whole or in part, by large donors whose names brand each medical school – entertainment mogul David Geffen at UCLA, former Merck CEO P. Roy Vagelos at Columbia, and Home Depot co-founder Kenneth Langone at NYU.
Economist Garthwaite said it is all well and good if top medical schools want to compete for top students by offering discounts. But if their goal is to encourage more students to enter primary care or to steer more people from lower-income families into medicine, giving free tuition to all “is not the most target-efficient way to reach that goal.”
Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
Russian Twitter bots and trolls amplify vaccine controversy
Russian trolls and bots significantly intensified the polarization of vaccine messaging on Twitter, fostering discord on the social network, according to researchers who analyzed the content of tweets over a 3-year period.
“Bots and trolls are actively involved in the online public health discourse, skewing discussions about vaccination,” wrote David A. Broniatowski, PhD, of George Washington University, Washington, D.C., and his associates.
in the American Journal of Public Health (Am J Public Health. doi: 10.2105/AJPH.2018.304567).
“This is vital knowledge for risk communicators, especially considering that neither members of the public nor algorithmic approaches may be able to easily identify bots, trolls, or cyborgs.”
The researchers conducted two content analyses and one qualitative analysis of tweets from July 2014 to September 2017. Their data set included 1% of all tweets during that time period and a sample of tweets containing vaccine-related keywords.
First they compared rates of vaccine-related tweets between bots and average users, and then they assessed the attitude of these tweets from different account types. Their qualitative case study focused on the use of the hashtag #vaccinateUS which was predominantly used by Russian trolls.
The researchers relied on seven publicly available lists to identify which accounts were bots or trolls and then compared them to randomly selected tweets posted in the same time period.
In their second analysis, the researchers used Botometer, a program created by the Indiana University Network Science Institute (IUNI) and the Center for Complex Networks and Systems Research (CNetS), to categorize tweets as very likely to be human, very likely to be bots, or of uncertain provenance.
Results revealed that Russian trolls, sophisticated bot accounts, and “content polluters” – those that spread malware and unsolicited content – are more likely than average users to tweet about vaccination. Content polluters tweeted more anti-vaccine messages while Russian trolls and sophisticated bots promoted both anti-vaccine and pro-vaccine messages that amplified the polarization (P less than .001).
The higher rate of antivaccine messages from content polluters suggested that antivaccine advocates may have exploited existing bot networks for their messaging.
“These accounts may also use the compelling nature of antivaccine content as clickbait to drive up advertising revenue and expose users to malware,” Dr. Broniatowski and colleagues wrote. “Antivaccine content may increase the risks of infection by both computer and biological viruses.”
The qualitative analysis of the #VaccinateUS hashtag found that 43% were provaccine, 38% were antivaccine and the other 19% were neutral.
“Whereas most non-neutral vaccine-relevant hashtags were clearly identifiable as either provaccine (#vaccineswork, #vaxwithme) or antivaccine (#Vaxxed, #b1less, #CDCWhistleblower), with limited appropriation by the opposing side, #VaccinateUS is unique in that it appears with very polarized messages on both sides,” the researchers reported.
Tweets using the #VaccinateUS hashtags were also more likely to contain grammatical errors, unnatural word choices, and irregular phrasing – but fewer spelling or punctuation errors than average tweets related to vaccines.
“The #VaccinateUS messages are also distinctive in that they contain no links to outside content, rare @mentions of other users, and no images (but occasionally use some emojis),” the researchers found.
Although messages with that hashtag “mirrored” Twitter’s overall vaccine discourse, subtle differences included greater emphasis on “freedom,” “democracy,” and “constitutional rights” than the more common “parental choice” focus of tweets using other vaccine-related hashtags. The conspiracy-theory targets of #VaccinateUS tweets also focused almost entirely on the U.S. government instead of a wide range of conspiracy theories at large, which was more common in other anti-vaccine tweets.
Antivaccine content was densest among accounts, with accounts falling in the middle bot category of uncertainty.
“Although we speculate that this set of accounts contains more sophisticated bots, trolls, and cyborgs, their provenance is ultimately unknown,” the researchers wrote. “Therefore, beyond attempting to prevent bots from spreading messages over social media, public health practitioners should focus on combating the messages themselves while not feeding the trolls.”
The research was funded by the National Institutes of Health. No conflicts of interest were noted.
SOURCE: Broniatowski DA et al. Am J Public Health. 2018 Aug 23. doi: 10.2105/AJPH.2018.304567.
Russian trolls and bots significantly intensified the polarization of vaccine messaging on Twitter, fostering discord on the social network, according to researchers who analyzed the content of tweets over a 3-year period.
“Bots and trolls are actively involved in the online public health discourse, skewing discussions about vaccination,” wrote David A. Broniatowski, PhD, of George Washington University, Washington, D.C., and his associates.
in the American Journal of Public Health (Am J Public Health. doi: 10.2105/AJPH.2018.304567).
“This is vital knowledge for risk communicators, especially considering that neither members of the public nor algorithmic approaches may be able to easily identify bots, trolls, or cyborgs.”
The researchers conducted two content analyses and one qualitative analysis of tweets from July 2014 to September 2017. Their data set included 1% of all tweets during that time period and a sample of tweets containing vaccine-related keywords.
First they compared rates of vaccine-related tweets between bots and average users, and then they assessed the attitude of these tweets from different account types. Their qualitative case study focused on the use of the hashtag #vaccinateUS which was predominantly used by Russian trolls.
The researchers relied on seven publicly available lists to identify which accounts were bots or trolls and then compared them to randomly selected tweets posted in the same time period.
In their second analysis, the researchers used Botometer, a program created by the Indiana University Network Science Institute (IUNI) and the Center for Complex Networks and Systems Research (CNetS), to categorize tweets as very likely to be human, very likely to be bots, or of uncertain provenance.
Results revealed that Russian trolls, sophisticated bot accounts, and “content polluters” – those that spread malware and unsolicited content – are more likely than average users to tweet about vaccination. Content polluters tweeted more anti-vaccine messages while Russian trolls and sophisticated bots promoted both anti-vaccine and pro-vaccine messages that amplified the polarization (P less than .001).
The higher rate of antivaccine messages from content polluters suggested that antivaccine advocates may have exploited existing bot networks for their messaging.
“These accounts may also use the compelling nature of antivaccine content as clickbait to drive up advertising revenue and expose users to malware,” Dr. Broniatowski and colleagues wrote. “Antivaccine content may increase the risks of infection by both computer and biological viruses.”
The qualitative analysis of the #VaccinateUS hashtag found that 43% were provaccine, 38% were antivaccine and the other 19% were neutral.
“Whereas most non-neutral vaccine-relevant hashtags were clearly identifiable as either provaccine (#vaccineswork, #vaxwithme) or antivaccine (#Vaxxed, #b1less, #CDCWhistleblower), with limited appropriation by the opposing side, #VaccinateUS is unique in that it appears with very polarized messages on both sides,” the researchers reported.
Tweets using the #VaccinateUS hashtags were also more likely to contain grammatical errors, unnatural word choices, and irregular phrasing – but fewer spelling or punctuation errors than average tweets related to vaccines.
“The #VaccinateUS messages are also distinctive in that they contain no links to outside content, rare @mentions of other users, and no images (but occasionally use some emojis),” the researchers found.
Although messages with that hashtag “mirrored” Twitter’s overall vaccine discourse, subtle differences included greater emphasis on “freedom,” “democracy,” and “constitutional rights” than the more common “parental choice” focus of tweets using other vaccine-related hashtags. The conspiracy-theory targets of #VaccinateUS tweets also focused almost entirely on the U.S. government instead of a wide range of conspiracy theories at large, which was more common in other anti-vaccine tweets.
Antivaccine content was densest among accounts, with accounts falling in the middle bot category of uncertainty.
“Although we speculate that this set of accounts contains more sophisticated bots, trolls, and cyborgs, their provenance is ultimately unknown,” the researchers wrote. “Therefore, beyond attempting to prevent bots from spreading messages over social media, public health practitioners should focus on combating the messages themselves while not feeding the trolls.”
The research was funded by the National Institutes of Health. No conflicts of interest were noted.
SOURCE: Broniatowski DA et al. Am J Public Health. 2018 Aug 23. doi: 10.2105/AJPH.2018.304567.
Russian trolls and bots significantly intensified the polarization of vaccine messaging on Twitter, fostering discord on the social network, according to researchers who analyzed the content of tweets over a 3-year period.
“Bots and trolls are actively involved in the online public health discourse, skewing discussions about vaccination,” wrote David A. Broniatowski, PhD, of George Washington University, Washington, D.C., and his associates.
in the American Journal of Public Health (Am J Public Health. doi: 10.2105/AJPH.2018.304567).
“This is vital knowledge for risk communicators, especially considering that neither members of the public nor algorithmic approaches may be able to easily identify bots, trolls, or cyborgs.”
The researchers conducted two content analyses and one qualitative analysis of tweets from July 2014 to September 2017. Their data set included 1% of all tweets during that time period and a sample of tweets containing vaccine-related keywords.
First they compared rates of vaccine-related tweets between bots and average users, and then they assessed the attitude of these tweets from different account types. Their qualitative case study focused on the use of the hashtag #vaccinateUS which was predominantly used by Russian trolls.
The researchers relied on seven publicly available lists to identify which accounts were bots or trolls and then compared them to randomly selected tweets posted in the same time period.
In their second analysis, the researchers used Botometer, a program created by the Indiana University Network Science Institute (IUNI) and the Center for Complex Networks and Systems Research (CNetS), to categorize tweets as very likely to be human, very likely to be bots, or of uncertain provenance.
Results revealed that Russian trolls, sophisticated bot accounts, and “content polluters” – those that spread malware and unsolicited content – are more likely than average users to tweet about vaccination. Content polluters tweeted more anti-vaccine messages while Russian trolls and sophisticated bots promoted both anti-vaccine and pro-vaccine messages that amplified the polarization (P less than .001).
The higher rate of antivaccine messages from content polluters suggested that antivaccine advocates may have exploited existing bot networks for their messaging.
“These accounts may also use the compelling nature of antivaccine content as clickbait to drive up advertising revenue and expose users to malware,” Dr. Broniatowski and colleagues wrote. “Antivaccine content may increase the risks of infection by both computer and biological viruses.”
The qualitative analysis of the #VaccinateUS hashtag found that 43% were provaccine, 38% were antivaccine and the other 19% were neutral.
“Whereas most non-neutral vaccine-relevant hashtags were clearly identifiable as either provaccine (#vaccineswork, #vaxwithme) or antivaccine (#Vaxxed, #b1less, #CDCWhistleblower), with limited appropriation by the opposing side, #VaccinateUS is unique in that it appears with very polarized messages on both sides,” the researchers reported.
Tweets using the #VaccinateUS hashtags were also more likely to contain grammatical errors, unnatural word choices, and irregular phrasing – but fewer spelling or punctuation errors than average tweets related to vaccines.
“The #VaccinateUS messages are also distinctive in that they contain no links to outside content, rare @mentions of other users, and no images (but occasionally use some emojis),” the researchers found.
Although messages with that hashtag “mirrored” Twitter’s overall vaccine discourse, subtle differences included greater emphasis on “freedom,” “democracy,” and “constitutional rights” than the more common “parental choice” focus of tweets using other vaccine-related hashtags. The conspiracy-theory targets of #VaccinateUS tweets also focused almost entirely on the U.S. government instead of a wide range of conspiracy theories at large, which was more common in other anti-vaccine tweets.
Antivaccine content was densest among accounts, with accounts falling in the middle bot category of uncertainty.
“Although we speculate that this set of accounts contains more sophisticated bots, trolls, and cyborgs, their provenance is ultimately unknown,” the researchers wrote. “Therefore, beyond attempting to prevent bots from spreading messages over social media, public health practitioners should focus on combating the messages themselves while not feeding the trolls.”
The research was funded by the National Institutes of Health. No conflicts of interest were noted.
SOURCE: Broniatowski DA et al. Am J Public Health. 2018 Aug 23. doi: 10.2105/AJPH.2018.304567.
FROM THE AMERICAN JOURNAL OF PUBLIC HEALTH
Key clinical point: Twitter bots and trolls are polluting social media vaccine discussions.
Major finding: Russian trolls and bots are more likely to amplify polarization of vaccine Twitter messaging while other trolls and bots are more likely to promote anti-vaccine messages and malware.
Study details: The findings are based on three content analyses of vaccine-related Twitter content samples from July 2014 to September 2017.
Disclosures: The research was funded by the National Institutes of Health. No conflicts of interest were noted.
Source: Broniatowski, D et al. Am J Public Health. doi:10.2105/AJPH.2018.304567.