For preterm, low-birth-weight infants, probiotic formulations containing Lactobacillus and Bifidobacterium strains appear to be superior to single-strain probiotics and to other multiple-strain formulations for reducing the risk of all-cause mortality, according to the findings of a network meta-analysis of randomized clinical trials.

The results of a prior Cochrane review indicated that probiotics can help prevent severe necrotizing enterocolitis and all-cause mortality in preterm infants, but the most effective formulations remained unclear. Therefore, Rebecca L. Morgan, PhD, MPH, and her associates searched MEDLINE, EMBASE, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, BIOSIS Previews, and Google Scholar through Jan. 1, 2019, to identify studies of single-strain and multistrain probiotic formulations in preterm, low-birth-weight neonates. A total of 63 studies involving 15,712 infants met inclusion criteria. “We used a frequentist approach for network meta-analysis and [a] GRADE approach to assess certainty of evidence,” they noted.

“High-certainty” evidence indicated that combination therapy with one or more Lactobacillus species and one or more Bifidobacterium species significantly reduced all-cause mortality, compared with placebo (odds ratio, 0.56; 95% confidence interval, 0.39-0.80), wrote Dr. Morgan, of McMaster University, Hamilton, Canada, and her coinvestigators. This was the only intervention to have moderate- or high-quality evidence for a reduction in mortality, the researchers wrote in Gastroenterology.

They added that, among the probiotic formulations with moderate- or high-quality evidence for efficacy, compared with placebo, those containing at least one species of Lactobacillus and at least one species of Bifidobacterium, and the single-strain probiotics containing Bifidobacterium animalis subspecies lactis, Lactobacillus reuteri, or Lactobacillus rhamnosus significantly reduced the risk of severe necrotizing enterocolitis (Bell stage II or higher), with statistically significant odds ratios of 0.35, 0.31, 0.55, and 0.44, respectively.

Three formulations were associated with “low-” or “very low-certainty” evidence for a reduction in risk for severe necrotizing enterocolitis, compared with placebo: Bacillus plus Enterococcus species, Lactobacillus plus Bifidobacterium plus Enterococcus species and Bifidobacterium plus Streptococcus salivarius subspecies thermophilus. Estimated odds ratios were 0.23 (risk difference, –4.9%), 0.28 (RD, –4.9%), and 0.38 (RD, –3.9%), respectively.

“The combinations of Bacillus species and Enterococcus species, and one or more Bifidobacterium species and S. salivarius subspecies thermophilus, might produce the largest reduction in necrotizing enterocolitis development,” the investigators wrote. “Further trials are needed.”

Compared with placebo, no probiotic formulation significantly improved the third primary outcome in the meta-analysis, culture-confirmed sepsis. However, several formulations were associated with moderate- or high-quality evidence for efficacy on secondary outcome measures. Compared with placebo, combinations of Lactobacillus and Bifidobacterium and Saccharomyces boulardii were associated with a significant decrease in the number of days to reach full feeding (mean reduction, 3.3 days; 95% CI, 5.9-0.7 days). Compared with placebo, single-strain therapy with B. animalis subspecies lactis or Lactobacillus reuteri was associated with a shorter duration of hospitalization, with mean reductions of 13.0 days (95% CI, 22.7-3.3 days) and 7.9 days (95% CI, 11.6-4.2 days), respectively.

“Multicenter and large randomized controlled trials should be prioritized to distinguish between the efficacy of single- and multiple-strain probiotics among preterm infants,” Dr. Morgan and her associates concluded. Such studies would further clarify the safety of probiotic formulations in this “fragile population,” they wrote. “Although the primary concern of live microbe administration, intestinal barrier translocation leading to sepsis, is decreased by several probiotic formulations, sound clinical judgement should be exercised.”

Partial support was provided by Mitacs Canada, in partnership with Nestlé Canada. The funder was not involved in designing or conducting the study or writing the manuscript. Dr. Morgan reported having no relevant conflicts of interest. One coinvestigator disclosed ties to AbbVie, Ferring, Janssen, and Takeda.

SOURCE: Morgan RL et al. Gastroenterology. 2020 Jun 24. doi: 10.1053/j.gastro.2020.05.096.

For preterm, low-birth-weight infants, probiotic formulations containing Lactobacillus and Bifidobacterium strains appear to be superior to single-strain probiotics and to other multiple-strain formulations for reducing the risk of all-cause mortality, according to the findings of a network meta-analysis of randomized clinical trials.

The results of a prior Cochrane review indicated that probiotics can help prevent severe necrotizing enterocolitis and all-cause mortality in preterm infants, but the most effective formulations remained unclear. Therefore, Rebecca L. Morgan, PhD, MPH, and her associates searched MEDLINE, EMBASE, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, BIOSIS Previews, and Google Scholar through Jan. 1, 2019, to identify studies of single-strain and multistrain probiotic formulations in preterm, low-birth-weight neonates. A total of 63 studies involving 15,712 infants met inclusion criteria. “We used a frequentist approach for network meta-analysis and [a] GRADE approach to assess certainty of evidence,” they noted.

“High-certainty” evidence indicated that combination therapy with one or more Lactobacillus species and one or more Bifidobacterium species significantly reduced all-cause mortality, compared with placebo (odds ratio, 0.56; 95% confidence interval, 0.39-0.80), wrote Dr. Morgan, of McMaster University, Hamilton, Canada, and her coinvestigators. This was the only intervention to have moderate- or high-quality evidence for a reduction in mortality, the researchers wrote in Gastroenterology.

They added that, among the probiotic formulations with moderate- or high-quality evidence for efficacy, compared with placebo, those containing at least one species of Lactobacillus and at least one species of Bifidobacterium, and the single-strain probiotics containing Bifidobacterium animalis subspecies lactis, Lactobacillus reuteri, or Lactobacillus rhamnosus significantly reduced the risk of severe necrotizing enterocolitis (Bell stage II or higher), with statistically significant odds ratios of 0.35, 0.31, 0.55, and 0.44, respectively.

Three formulations were associated with “low-” or “very low-certainty” evidence for a reduction in risk for severe necrotizing enterocolitis, compared with placebo: Bacillus plus Enterococcus species, Lactobacillus plus Bifidobacterium plus Enterococcus species and Bifidobacterium plus Streptococcus salivarius subspecies thermophilus. Estimated odds ratios were 0.23 (risk difference, –4.9%), 0.28 (RD, –4.9%), and 0.38 (RD, –3.9%), respectively.

“The combinations of Bacillus species and Enterococcus species, and one or more Bifidobacterium species and S. salivarius subspecies thermophilus, might produce the largest reduction in necrotizing enterocolitis development,” the investigators wrote. “Further trials are needed.”

Compared with placebo, no probiotic formulation significantly improved the third primary outcome in the meta-analysis, culture-confirmed sepsis. However, several formulations were associated with moderate- or high-quality evidence for efficacy on secondary outcome measures. Compared with placebo, combinations of Lactobacillus and Bifidobacterium and Saccharomyces boulardii were associated with a significant decrease in the number of days to reach full feeding (mean reduction, 3.3 days; 95% CI, 5.9-0.7 days). Compared with placebo, single-strain therapy with B. animalis subspecies lactis or Lactobacillus reuteri was associated with a shorter duration of hospitalization, with mean reductions of 13.0 days (95% CI, 22.7-3.3 days) and 7.9 days (95% CI, 11.6-4.2 days), respectively.

“Multicenter and large randomized controlled trials should be prioritized to distinguish between the efficacy of single- and multiple-strain probiotics among preterm infants,” Dr. Morgan and her associates concluded. Such studies would further clarify the safety of probiotic formulations in this “fragile population,” they wrote. “Although the primary concern of live microbe administration, intestinal barrier translocation leading to sepsis, is decreased by several probiotic formulations, sound clinical judgement should be exercised.”

Partial support was provided by Mitacs Canada, in partnership with Nestlé Canada. The funder was not involved in designing or conducting the study or writing the manuscript. Dr. Morgan reported having no relevant conflicts of interest. One coinvestigator disclosed ties to AbbVie, Ferring, Janssen, and Takeda.

SOURCE: Morgan RL et al. Gastroenterology. 2020 Jun 24. doi: 10.1053/j.gastro.2020.05.096.

For preterm, low-birth-weight infants, probiotic formulations containing Lactobacillus and Bifidobacterium strains appear to be superior to single-strain probiotics and to other multiple-strain formulations for reducing the risk of all-cause mortality, according to the findings of a network meta-analysis of randomized clinical trials.

The results of a prior Cochrane review indicated that probiotics can help prevent severe necrotizing enterocolitis and all-cause mortality in preterm infants, but the most effective formulations remained unclear. Therefore, Rebecca L. Morgan, PhD, MPH, and her associates searched MEDLINE, EMBASE, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, BIOSIS Previews, and Google Scholar through Jan. 1, 2019, to identify studies of single-strain and multistrain probiotic formulations in preterm, low-birth-weight neonates. A total of 63 studies involving 15,712 infants met inclusion criteria. “We used a frequentist approach for network meta-analysis and [a] GRADE approach to assess certainty of evidence,” they noted.

“High-certainty” evidence indicated that combination therapy with one or more Lactobacillus species and one or more Bifidobacterium species significantly reduced all-cause mortality, compared with placebo (odds ratio, 0.56; 95% confidence interval, 0.39-0.80), wrote Dr. Morgan, of McMaster University, Hamilton, Canada, and her coinvestigators. This was the only intervention to have moderate- or high-quality evidence for a reduction in mortality, the researchers wrote in Gastroenterology.

They added that, among the probiotic formulations with moderate- or high-quality evidence for efficacy, compared with placebo, those containing at least one species of Lactobacillus and at least one species of Bifidobacterium, and the single-strain probiotics containing Bifidobacterium animalis subspecies lactis, Lactobacillus reuteri, or Lactobacillus rhamnosus significantly reduced the risk of severe necrotizing enterocolitis (Bell stage II or higher), with statistically significant odds ratios of 0.35, 0.31, 0.55, and 0.44, respectively.

Three formulations were associated with “low-” or “very low-certainty” evidence for a reduction in risk for severe necrotizing enterocolitis, compared with placebo: Bacillus plus Enterococcus species, Lactobacillus plus Bifidobacterium plus Enterococcus species and Bifidobacterium plus Streptococcus salivarius subspecies thermophilus. Estimated odds ratios were 0.23 (risk difference, –4.9%), 0.28 (RD, –4.9%), and 0.38 (RD, –3.9%), respectively.

“The combinations of Bacillus species and Enterococcus species, and one or more Bifidobacterium species and S. salivarius subspecies thermophilus, might produce the largest reduction in necrotizing enterocolitis development,” the investigators wrote. “Further trials are needed.”

Compared with placebo, no probiotic formulation significantly improved the third primary outcome in the meta-analysis, culture-confirmed sepsis. However, several formulations were associated with moderate- or high-quality evidence for efficacy on secondary outcome measures. Compared with placebo, combinations of Lactobacillus and Bifidobacterium and Saccharomyces boulardii were associated with a significant decrease in the number of days to reach full feeding (mean reduction, 3.3 days; 95% CI, 5.9-0.7 days). Compared with placebo, single-strain therapy with B. animalis subspecies lactis or Lactobacillus reuteri was associated with a shorter duration of hospitalization, with mean reductions of 13.0 days (95% CI, 22.7-3.3 days) and 7.9 days (95% CI, 11.6-4.2 days), respectively.

“Multicenter and large randomized controlled trials should be prioritized to distinguish between the efficacy of single- and multiple-strain probiotics among preterm infants,” Dr. Morgan and her associates concluded. Such studies would further clarify the safety of probiotic formulations in this “fragile population,” they wrote. “Although the primary concern of live microbe administration, intestinal barrier translocation leading to sepsis, is decreased by several probiotic formulations, sound clinical judgement should be exercised.”

Partial support was provided by Mitacs Canada, in partnership with Nestlé Canada. The funder was not involved in designing or conducting the study or writing the manuscript. Dr. Morgan reported having no relevant conflicts of interest. One coinvestigator disclosed ties to AbbVie, Ferring, Janssen, and Takeda.

SOURCE: Morgan RL et al. Gastroenterology. 2020 Jun 24. doi: 10.1053/j.gastro.2020.05.096.

Diabetes was by far the most common delayed pediatric presentation in emergency care during the COVID-19 pandemic, according to a snapshot survey of nearly 2,500 pediatricians in the United Kingdom and Ireland.

There were also nine deaths where delayed presentation was considered a contributing factor, resulting mainly from sepsis and malignancy.

By comparison, over the same 2-week period of the survey there were three child deaths from COVID-19 directly, according to senior study author Shamez Ladhani, MRCPCH, PhD, chair of the British Paediatric Surveillance Unit (BPSU), Royal College of Paediatrics and Child Health, London.

“The unintended consequences of COVID are far greater, in children, than the disease itself. The way we are trying to prevent this is causing more harm than the disease,” he lamented.

One-third of senior U.K. pediatric specialists who responded to the survey reported dealing with so-called emergency delayed presentations in children who they would normally have expected to present much earlier.

After diabetes, the most commonly reported delayed diagnoses were sepsis and child protection issues. Cancer also featured prominently.

“We’ve found that there is great concern that children are not accessing healthcare as they should during lockdown and after,” Dr. Ladhani stressed. “Our emergency departments saw a 50% reduction during the peak, and now it is still 40% less than expected. The problem is improving but it remains.”

The survey findings were recently published online in Archives of Disease in Childhood, by first author Richard M. Lynn, MSc, of the Institute of Child Health, department of epidemiology and public health, University College London Research, and colleagues.
 

New diabetes cases presented very late during lockdown

Over the 2-week reporting period in mid-April 2020, type 1 diabetes was the most frequently reported delayed diagnosis, with 44 cases overall, 23 of which involved diabetic ketoacidosis.

“If you talk to the diabetes specialists, they tell us that generally, most cases of new diabetes arrive late because it has very nonspecific symptoms,” Dr. Ladhani explained.

However, he added, “pediatricians on the frontline know what to expect with diabetes. Those children who would have come in late prior to the pandemic are now arriving very late. Those consultants surveyed were not junior doctors but consultant pediatricians with many years of experience.”

In a recent article looking at pediatric delayed presentations, one patient with diabetes entered intensive care, and the BPSU report recorded one death possibly associated with diabetes, Dr. Ladhani pointed out.

“Pediatricians are worried that children are coming in late. We need to raise awareness that parents need to access healthcare and this message needs to go out now,” he said. “We can’t wait until a second wave. It has to be now because A&E [accident and emergency] attendance is still 40% [lower than] ... expected.”
 

BPSU survey covers over 90% of pediatricians in U.K. and Ireland

After numerous anecdotal reports of delayed presentations in the United Kingdom and abroad, the snapshot survey was conducted as part of routine monthly reports where pediatricians are asked to document any cases of rare conditions seen.

“We had heard stories of delayed presentations, but we wanted to know was this a real problem or just anecdotal?” Dr. Ladhani said.

The regular BPSU survey covers over 90% of U.K.- and Ireland-based pediatric consultants (numbering 4,075). On the back of this established communication, the BPSU decided to gauge the extent of delayed presentations during the peak weeks of the COVID-19 pandemic.

Over the next 7 days, 2,433 pediatricians, representing 60% of BPSU participants, responded.

“This response rate in 7 days highlights the importance given to the survey by pediatricians ... and the widespread professional concern about delayed presentations,” the authors wrote.

Participants were asked whether they had seen any children during the previous 14 days who, in their opinion, presented later than they would have expected prior to the COVID-19 pandemic.

“There’s no one definition for this but these senior clinicians know when something is unusual,” said Dr. Ladhani.

ED attendances were compared with figures for the same period last year. Overall, a total of 32% of 752 pediatricians working in EDs and pediatric assessment units reported witnessing delayed presentations, with 57 (8%) reporting at least three patients with delayed presentation.

“It was clear that those doctors on the frontline were seeing a lot of delayed presentations. Also, neonatologists reported women arriving late for labor, and community physicians said they just weren’t witnessing child protection cases anymore,” added Dr. Ladhani.

Other issues included early discharges following births because of COVID-19 concerns, before feeding had been established, prompting return visits because of feeding problems and dehydration.

The top five delayed diagnoses were diabetes (n = 44), sepsis (n = 21), child protection (n = 14), malignancy (n = 8), and appendicitis (n = 6). There were 10 delayed perinatal presentations.

Of the nine deaths, for which delayed presentation was considered to play a role, three were caused by sepsis, three were caused by new malignancy diagnoses, one was caused by new diagnosis of metabolic disease, and two did not have the cause reported.

The delays in presentation are likely to have been influenced by the U.K. government’s message to “stay at home” during the strict lockdown period, which perhaps was sometimes interpreted too literally, Dr. Ladhani suggested. “It was the right message socially, but not medically.”

Russell Viner, MB, PhD, president of the Royal College of Paediatrics and Child Health, said in a statement: “The impact for children is what we call ‘collateral damage’, including long absences from school and delays or interruptions to vital services. We know that parents adhered very strongly to the ‘stay at home’ [message] and we need to say clearly that this doesn’t apply if your child is very sick. Should we experience a second wave or regional outbreaks, it is vital that we get the message out to parents that we want to see unwell children at the earliest possible stage.”

Dr. Ladhani reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Diabetes was by far the most common delayed pediatric presentation in emergency care during the COVID-19 pandemic, according to a snapshot survey of nearly 2,500 pediatricians in the United Kingdom and Ireland.

There were also nine deaths where delayed presentation was considered a contributing factor, resulting mainly from sepsis and malignancy.

By comparison, over the same 2-week period of the survey there were three child deaths from COVID-19 directly, according to senior study author Shamez Ladhani, MRCPCH, PhD, chair of the British Paediatric Surveillance Unit (BPSU), Royal College of Paediatrics and Child Health, London.

“The unintended consequences of COVID are far greater, in children, than the disease itself. The way we are trying to prevent this is causing more harm than the disease,” he lamented.

One-third of senior U.K. pediatric specialists who responded to the survey reported dealing with so-called emergency delayed presentations in children who they would normally have expected to present much earlier.

After diabetes, the most commonly reported delayed diagnoses were sepsis and child protection issues. Cancer also featured prominently.

“We’ve found that there is great concern that children are not accessing healthcare as they should during lockdown and after,” Dr. Ladhani stressed. “Our emergency departments saw a 50% reduction during the peak, and now it is still 40% less than expected. The problem is improving but it remains.”

The survey findings were recently published online in Archives of Disease in Childhood, by first author Richard M. Lynn, MSc, of the Institute of Child Health, department of epidemiology and public health, University College London Research, and colleagues.
 

New diabetes cases presented very late during lockdown

Over the 2-week reporting period in mid-April 2020, type 1 diabetes was the most frequently reported delayed diagnosis, with 44 cases overall, 23 of which involved diabetic ketoacidosis.

“If you talk to the diabetes specialists, they tell us that generally, most cases of new diabetes arrive late because it has very nonspecific symptoms,” Dr. Ladhani explained.

However, he added, “pediatricians on the frontline know what to expect with diabetes. Those children who would have come in late prior to the pandemic are now arriving very late. Those consultants surveyed were not junior doctors but consultant pediatricians with many years of experience.”

In a recent article looking at pediatric delayed presentations, one patient with diabetes entered intensive care, and the BPSU report recorded one death possibly associated with diabetes, Dr. Ladhani pointed out.

“Pediatricians are worried that children are coming in late. We need to raise awareness that parents need to access healthcare and this message needs to go out now,” he said. “We can’t wait until a second wave. It has to be now because A&E [accident and emergency] attendance is still 40% [lower than] ... expected.”
 

BPSU survey covers over 90% of pediatricians in U.K. and Ireland

After numerous anecdotal reports of delayed presentations in the United Kingdom and abroad, the snapshot survey was conducted as part of routine monthly reports where pediatricians are asked to document any cases of rare conditions seen.

“We had heard stories of delayed presentations, but we wanted to know was this a real problem or just anecdotal?” Dr. Ladhani said.

The regular BPSU survey covers over 90% of U.K.- and Ireland-based pediatric consultants (numbering 4,075). On the back of this established communication, the BPSU decided to gauge the extent of delayed presentations during the peak weeks of the COVID-19 pandemic.

Over the next 7 days, 2,433 pediatricians, representing 60% of BPSU participants, responded.

“This response rate in 7 days highlights the importance given to the survey by pediatricians ... and the widespread professional concern about delayed presentations,” the authors wrote.

Participants were asked whether they had seen any children during the previous 14 days who, in their opinion, presented later than they would have expected prior to the COVID-19 pandemic.

“There’s no one definition for this but these senior clinicians know when something is unusual,” said Dr. Ladhani.

ED attendances were compared with figures for the same period last year. Overall, a total of 32% of 752 pediatricians working in EDs and pediatric assessment units reported witnessing delayed presentations, with 57 (8%) reporting at least three patients with delayed presentation.

“It was clear that those doctors on the frontline were seeing a lot of delayed presentations. Also, neonatologists reported women arriving late for labor, and community physicians said they just weren’t witnessing child protection cases anymore,” added Dr. Ladhani.

Other issues included early discharges following births because of COVID-19 concerns, before feeding had been established, prompting return visits because of feeding problems and dehydration.

The top five delayed diagnoses were diabetes (n = 44), sepsis (n = 21), child protection (n = 14), malignancy (n = 8), and appendicitis (n = 6). There were 10 delayed perinatal presentations.

Of the nine deaths, for which delayed presentation was considered to play a role, three were caused by sepsis, three were caused by new malignancy diagnoses, one was caused by new diagnosis of metabolic disease, and two did not have the cause reported.

The delays in presentation are likely to have been influenced by the U.K. government’s message to “stay at home” during the strict lockdown period, which perhaps was sometimes interpreted too literally, Dr. Ladhani suggested. “It was the right message socially, but not medically.”

Russell Viner, MB, PhD, president of the Royal College of Paediatrics and Child Health, said in a statement: “The impact for children is what we call ‘collateral damage’, including long absences from school and delays or interruptions to vital services. We know that parents adhered very strongly to the ‘stay at home’ [message] and we need to say clearly that this doesn’t apply if your child is very sick. Should we experience a second wave or regional outbreaks, it is vital that we get the message out to parents that we want to see unwell children at the earliest possible stage.”

Dr. Ladhani reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Diabetes was by far the most common delayed pediatric presentation in emergency care during the COVID-19 pandemic, according to a snapshot survey of nearly 2,500 pediatricians in the United Kingdom and Ireland.

There were also nine deaths where delayed presentation was considered a contributing factor, resulting mainly from sepsis and malignancy.

By comparison, over the same 2-week period of the survey there were three child deaths from COVID-19 directly, according to senior study author Shamez Ladhani, MRCPCH, PhD, chair of the British Paediatric Surveillance Unit (BPSU), Royal College of Paediatrics and Child Health, London.

“The unintended consequences of COVID are far greater, in children, than the disease itself. The way we are trying to prevent this is causing more harm than the disease,” he lamented.

One-third of senior U.K. pediatric specialists who responded to the survey reported dealing with so-called emergency delayed presentations in children who they would normally have expected to present much earlier.

After diabetes, the most commonly reported delayed diagnoses were sepsis and child protection issues. Cancer also featured prominently.

“We’ve found that there is great concern that children are not accessing healthcare as they should during lockdown and after,” Dr. Ladhani stressed. “Our emergency departments saw a 50% reduction during the peak, and now it is still 40% less than expected. The problem is improving but it remains.”

The survey findings were recently published online in Archives of Disease in Childhood, by first author Richard M. Lynn, MSc, of the Institute of Child Health, department of epidemiology and public health, University College London Research, and colleagues.
 

New diabetes cases presented very late during lockdown

Over the 2-week reporting period in mid-April 2020, type 1 diabetes was the most frequently reported delayed diagnosis, with 44 cases overall, 23 of which involved diabetic ketoacidosis.

“If you talk to the diabetes specialists, they tell us that generally, most cases of new diabetes arrive late because it has very nonspecific symptoms,” Dr. Ladhani explained.

However, he added, “pediatricians on the frontline know what to expect with diabetes. Those children who would have come in late prior to the pandemic are now arriving very late. Those consultants surveyed were not junior doctors but consultant pediatricians with many years of experience.”

In a recent article looking at pediatric delayed presentations, one patient with diabetes entered intensive care, and the BPSU report recorded one death possibly associated with diabetes, Dr. Ladhani pointed out.

“Pediatricians are worried that children are coming in late. We need to raise awareness that parents need to access healthcare and this message needs to go out now,” he said. “We can’t wait until a second wave. It has to be now because A&E [accident and emergency] attendance is still 40% [lower than] ... expected.”
 

BPSU survey covers over 90% of pediatricians in U.K. and Ireland

After numerous anecdotal reports of delayed presentations in the United Kingdom and abroad, the snapshot survey was conducted as part of routine monthly reports where pediatricians are asked to document any cases of rare conditions seen.

“We had heard stories of delayed presentations, but we wanted to know was this a real problem or just anecdotal?” Dr. Ladhani said.

The regular BPSU survey covers over 90% of U.K.- and Ireland-based pediatric consultants (numbering 4,075). On the back of this established communication, the BPSU decided to gauge the extent of delayed presentations during the peak weeks of the COVID-19 pandemic.

Over the next 7 days, 2,433 pediatricians, representing 60% of BPSU participants, responded.

“This response rate in 7 days highlights the importance given to the survey by pediatricians ... and the widespread professional concern about delayed presentations,” the authors wrote.

Participants were asked whether they had seen any children during the previous 14 days who, in their opinion, presented later than they would have expected prior to the COVID-19 pandemic.

“There’s no one definition for this but these senior clinicians know when something is unusual,” said Dr. Ladhani.

ED attendances were compared with figures for the same period last year. Overall, a total of 32% of 752 pediatricians working in EDs and pediatric assessment units reported witnessing delayed presentations, with 57 (8%) reporting at least three patients with delayed presentation.

“It was clear that those doctors on the frontline were seeing a lot of delayed presentations. Also, neonatologists reported women arriving late for labor, and community physicians said they just weren’t witnessing child protection cases anymore,” added Dr. Ladhani.

Other issues included early discharges following births because of COVID-19 concerns, before feeding had been established, prompting return visits because of feeding problems and dehydration.

The top five delayed diagnoses were diabetes (n = 44), sepsis (n = 21), child protection (n = 14), malignancy (n = 8), and appendicitis (n = 6). There were 10 delayed perinatal presentations.

Of the nine deaths, for which delayed presentation was considered to play a role, three were caused by sepsis, three were caused by new malignancy diagnoses, one was caused by new diagnosis of metabolic disease, and two did not have the cause reported.

The delays in presentation are likely to have been influenced by the U.K. government’s message to “stay at home” during the strict lockdown period, which perhaps was sometimes interpreted too literally, Dr. Ladhani suggested. “It was the right message socially, but not medically.”

Russell Viner, MB, PhD, president of the Royal College of Paediatrics and Child Health, said in a statement: “The impact for children is what we call ‘collateral damage’, including long absences from school and delays or interruptions to vital services. We know that parents adhered very strongly to the ‘stay at home’ [message] and we need to say clearly that this doesn’t apply if your child is very sick. Should we experience a second wave or regional outbreaks, it is vital that we get the message out to parents that we want to see unwell children at the earliest possible stage.”

Dr. Ladhani reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Patients in the Veterans Health Administration (VHA) system 75 years or older, free of cardiovascular (CV) disease and prescribed statins for the first time, had a one-fourth lower risk for death and a 20% lower risk for CV death over an average 7 years than that of comparable patients not prescribed the drugs in an observational study.

The findings, based on more than 320,000 predominantly white male patients, initially without atherosclerotic cardiovascular disease (ASCVD), underscore the notion that “age on its own shouldn’t be a criterion not to use these drugs,” Ariela R. Orkaby, MD, MPH, lead author on the study, published in the July 7 issue of JAMA, said in an interview.

The very elderly are frequently undertreated, particularly in primary prevention, as many physicians consider it unnecessary for them to initiate or continue preventive measures, said Dr. Orkaby, of VA Boston Healthcare System and Harvard Medical School, Boston.

“From available data, we don’t really expect statins to start providing benefit in primary prevention until they’ve been taken for about 2 to 5 years. So for people who have very limited life expectancy, it may not be a great idea to add to their pill burden or increase the possibility that they might decline functionally,” Dr. Orkaby said.

“But what we saw in this study is that there is benefit to prescribing statins even in elderly patients, even within 2 years” of follow-up.

Despite being among the most studied drugs in the world, statins are understudied in older people. Fewer than 2% of the 186,854 participants in 28 statin trials were aged 75 years or older, wrote Dr. Orkaby and associates.

Most of what is known about initiating statin therapy in the 75-and-older age group comes from underpowered subgroup analyses and a few observational studies, Steven J. Nicholls, MBBS, PhD, Monash University, Melbourne, and Adam J. Nelson, MBBS, PhD, Duke Clinical Research Institute, Durham, N.C., wrote in an accompanying editorial. As a result, the evidence is conflicting, with some reports suggesting marked benefit and others possible harm.

The current findings, they wrote, “provide additional support for treatment guidelines that have increasingly advocated for more widespread use of statin therapy for ASCVD prevention in older individuals.”

Of the 326,981 people in the analysis, 57,178 (17.5%) were new statin users or initiated a statin during the study period, usually simvastatin. Their mean age was about 81 years, and 97.3% of the patients were men, 90% were white, and 72% were former smokers.

Using propensity scoring, the authors compared statin users with the other remaining patients who had the same likelihood of being prescribed a statin based on clinical characteristics but did not receive a prescription for a statin.

Michael W. Rich, MD, Washington University, St. Louis, who was not involved in the study but has previously worked with Dr. Orkaby, praised the analysis.

“It’s one of the best studies I’ve seen addressing this particular issue. It’s a large sample size, the analysis was very well done, and I think that it comes to a pretty unequivocal conclusion that, at least in this population, those individuals who were started on statins for the first time, and having no known prior ASCVD, clearly had a lower all-cause mortality and cardiovascular mortality, as well as a lower risk of composite cardiovascular events,” he said in an interview.

But the data have limitations, he added. The findings are still observational and could be confounded by unknown variables, and the select population – mostly white, male veterans – is known to be at somewhat higher risk for events than the general population.

Perhaps even more impressive than the risk reductions seen at a mean 6.8 years of follow-up, Dr. Rich said, are the sensitivity analyses at 2, 4, and 6 years that showed the benefit manifesting early.

The researchers saw a 32% reduction in all-cause mortality risk (P < .05) at 2 years, 21% at 4 years, and 13% at 6 years (P < .05 for all). Risk reductions for CV death followed a similar pattern, they wrote.

Dr. Rich said that the trial, although not a “slam dunk,” has persuaded him to shift from being very conservative about prescribing statins to elderly patients to being much more willing to consider it.

“This doesn’t mean that I will be running to routinely prescribe my 90-plus patients a statin, nor should we should be starting statins in everyone over 75, not even in all male former smokers over 75 – the type of people in this study – but I do think that it provides a stronger basis for talking to these patients about the possibility of starting a statin.”

There are two ongoing trials that may provide greater clarity, the authors observed. The STAREE trial has enrolled adults 70 years and older in Australia and includes serial evaluation of cognitive scores. Also, PREVENTABLE will examine the role of statins for prevention of dementia and disability-free survival in adults 75 years and older.

However, neither trial may fully resolve the question of primary prevention statin use in the elderly, they wrote. “While these trials are necessary to broaden the evidence base for older adults, it is unlikely that any trial will enroll large numbers of individuals at very advanced ages, black individuals, and those with dementia, as were included in this study.”

Dr. Orkaby had no disclosures; potential conflicts for the other authors are in the report. Dr. Rich reported having no conflicts of interest. Dr. Nicholls disclosed receiving research support from AstraZeneca, Amgen, Anthera, Eli Lilly, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and receiving consulting fees or honoraria from AstraZeneca, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Dr. Nelson had no disclosures.

A version of this article originally appeared on Medscape.com.

Patients in the Veterans Health Administration (VHA) system 75 years or older, free of cardiovascular (CV) disease and prescribed statins for the first time, had a one-fourth lower risk for death and a 20% lower risk for CV death over an average 7 years than that of comparable patients not prescribed the drugs in an observational study.

The findings, based on more than 320,000 predominantly white male patients, initially without atherosclerotic cardiovascular disease (ASCVD), underscore the notion that “age on its own shouldn’t be a criterion not to use these drugs,” Ariela R. Orkaby, MD, MPH, lead author on the study, published in the July 7 issue of JAMA, said in an interview.

The very elderly are frequently undertreated, particularly in primary prevention, as many physicians consider it unnecessary for them to initiate or continue preventive measures, said Dr. Orkaby, of VA Boston Healthcare System and Harvard Medical School, Boston.

“From available data, we don’t really expect statins to start providing benefit in primary prevention until they’ve been taken for about 2 to 5 years. So for people who have very limited life expectancy, it may not be a great idea to add to their pill burden or increase the possibility that they might decline functionally,” Dr. Orkaby said.

“But what we saw in this study is that there is benefit to prescribing statins even in elderly patients, even within 2 years” of follow-up.

Despite being among the most studied drugs in the world, statins are understudied in older people. Fewer than 2% of the 186,854 participants in 28 statin trials were aged 75 years or older, wrote Dr. Orkaby and associates.

Most of what is known about initiating statin therapy in the 75-and-older age group comes from underpowered subgroup analyses and a few observational studies, Steven J. Nicholls, MBBS, PhD, Monash University, Melbourne, and Adam J. Nelson, MBBS, PhD, Duke Clinical Research Institute, Durham, N.C., wrote in an accompanying editorial. As a result, the evidence is conflicting, with some reports suggesting marked benefit and others possible harm.

The current findings, they wrote, “provide additional support for treatment guidelines that have increasingly advocated for more widespread use of statin therapy for ASCVD prevention in older individuals.”

Of the 326,981 people in the analysis, 57,178 (17.5%) were new statin users or initiated a statin during the study period, usually simvastatin. Their mean age was about 81 years, and 97.3% of the patients were men, 90% were white, and 72% were former smokers.

Using propensity scoring, the authors compared statin users with the other remaining patients who had the same likelihood of being prescribed a statin based on clinical characteristics but did not receive a prescription for a statin.

Michael W. Rich, MD, Washington University, St. Louis, who was not involved in the study but has previously worked with Dr. Orkaby, praised the analysis.

“It’s one of the best studies I’ve seen addressing this particular issue. It’s a large sample size, the analysis was very well done, and I think that it comes to a pretty unequivocal conclusion that, at least in this population, those individuals who were started on statins for the first time, and having no known prior ASCVD, clearly had a lower all-cause mortality and cardiovascular mortality, as well as a lower risk of composite cardiovascular events,” he said in an interview.

But the data have limitations, he added. The findings are still observational and could be confounded by unknown variables, and the select population – mostly white, male veterans – is known to be at somewhat higher risk for events than the general population.

Perhaps even more impressive than the risk reductions seen at a mean 6.8 years of follow-up, Dr. Rich said, are the sensitivity analyses at 2, 4, and 6 years that showed the benefit manifesting early.

The researchers saw a 32% reduction in all-cause mortality risk (P < .05) at 2 years, 21% at 4 years, and 13% at 6 years (P < .05 for all). Risk reductions for CV death followed a similar pattern, they wrote.

Dr. Rich said that the trial, although not a “slam dunk,” has persuaded him to shift from being very conservative about prescribing statins to elderly patients to being much more willing to consider it.

“This doesn’t mean that I will be running to routinely prescribe my 90-plus patients a statin, nor should we should be starting statins in everyone over 75, not even in all male former smokers over 75 – the type of people in this study – but I do think that it provides a stronger basis for talking to these patients about the possibility of starting a statin.”

There are two ongoing trials that may provide greater clarity, the authors observed. The STAREE trial has enrolled adults 70 years and older in Australia and includes serial evaluation of cognitive scores. Also, PREVENTABLE will examine the role of statins for prevention of dementia and disability-free survival in adults 75 years and older.

However, neither trial may fully resolve the question of primary prevention statin use in the elderly, they wrote. “While these trials are necessary to broaden the evidence base for older adults, it is unlikely that any trial will enroll large numbers of individuals at very advanced ages, black individuals, and those with dementia, as were included in this study.”

Dr. Orkaby had no disclosures; potential conflicts for the other authors are in the report. Dr. Rich reported having no conflicts of interest. Dr. Nicholls disclosed receiving research support from AstraZeneca, Amgen, Anthera, Eli Lilly, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and receiving consulting fees or honoraria from AstraZeneca, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Dr. Nelson had no disclosures.

A version of this article originally appeared on Medscape.com.

Patients in the Veterans Health Administration (VHA) system 75 years or older, free of cardiovascular (CV) disease and prescribed statins for the first time, had a one-fourth lower risk for death and a 20% lower risk for CV death over an average 7 years than that of comparable patients not prescribed the drugs in an observational study.

The findings, based on more than 320,000 predominantly white male patients, initially without atherosclerotic cardiovascular disease (ASCVD), underscore the notion that “age on its own shouldn’t be a criterion not to use these drugs,” Ariela R. Orkaby, MD, MPH, lead author on the study, published in the July 7 issue of JAMA, said in an interview.

The very elderly are frequently undertreated, particularly in primary prevention, as many physicians consider it unnecessary for them to initiate or continue preventive measures, said Dr. Orkaby, of VA Boston Healthcare System and Harvard Medical School, Boston.

“From available data, we don’t really expect statins to start providing benefit in primary prevention until they’ve been taken for about 2 to 5 years. So for people who have very limited life expectancy, it may not be a great idea to add to their pill burden or increase the possibility that they might decline functionally,” Dr. Orkaby said.

“But what we saw in this study is that there is benefit to prescribing statins even in elderly patients, even within 2 years” of follow-up.

Despite being among the most studied drugs in the world, statins are understudied in older people. Fewer than 2% of the 186,854 participants in 28 statin trials were aged 75 years or older, wrote Dr. Orkaby and associates.

Most of what is known about initiating statin therapy in the 75-and-older age group comes from underpowered subgroup analyses and a few observational studies, Steven J. Nicholls, MBBS, PhD, Monash University, Melbourne, and Adam J. Nelson, MBBS, PhD, Duke Clinical Research Institute, Durham, N.C., wrote in an accompanying editorial. As a result, the evidence is conflicting, with some reports suggesting marked benefit and others possible harm.

The current findings, they wrote, “provide additional support for treatment guidelines that have increasingly advocated for more widespread use of statin therapy for ASCVD prevention in older individuals.”

Of the 326,981 people in the analysis, 57,178 (17.5%) were new statin users or initiated a statin during the study period, usually simvastatin. Their mean age was about 81 years, and 97.3% of the patients were men, 90% were white, and 72% were former smokers.

Using propensity scoring, the authors compared statin users with the other remaining patients who had the same likelihood of being prescribed a statin based on clinical characteristics but did not receive a prescription for a statin.

Michael W. Rich, MD, Washington University, St. Louis, who was not involved in the study but has previously worked with Dr. Orkaby, praised the analysis.

“It’s one of the best studies I’ve seen addressing this particular issue. It’s a large sample size, the analysis was very well done, and I think that it comes to a pretty unequivocal conclusion that, at least in this population, those individuals who were started on statins for the first time, and having no known prior ASCVD, clearly had a lower all-cause mortality and cardiovascular mortality, as well as a lower risk of composite cardiovascular events,” he said in an interview.

But the data have limitations, he added. The findings are still observational and could be confounded by unknown variables, and the select population – mostly white, male veterans – is known to be at somewhat higher risk for events than the general population.

Perhaps even more impressive than the risk reductions seen at a mean 6.8 years of follow-up, Dr. Rich said, are the sensitivity analyses at 2, 4, and 6 years that showed the benefit manifesting early.

The researchers saw a 32% reduction in all-cause mortality risk (P < .05) at 2 years, 21% at 4 years, and 13% at 6 years (P < .05 for all). Risk reductions for CV death followed a similar pattern, they wrote.

Dr. Rich said that the trial, although not a “slam dunk,” has persuaded him to shift from being very conservative about prescribing statins to elderly patients to being much more willing to consider it.

“This doesn’t mean that I will be running to routinely prescribe my 90-plus patients a statin, nor should we should be starting statins in everyone over 75, not even in all male former smokers over 75 – the type of people in this study – but I do think that it provides a stronger basis for talking to these patients about the possibility of starting a statin.”

There are two ongoing trials that may provide greater clarity, the authors observed. The STAREE trial has enrolled adults 70 years and older in Australia and includes serial evaluation of cognitive scores. Also, PREVENTABLE will examine the role of statins for prevention of dementia and disability-free survival in adults 75 years and older.

However, neither trial may fully resolve the question of primary prevention statin use in the elderly, they wrote. “While these trials are necessary to broaden the evidence base for older adults, it is unlikely that any trial will enroll large numbers of individuals at very advanced ages, black individuals, and those with dementia, as were included in this study.”

Dr. Orkaby had no disclosures; potential conflicts for the other authors are in the report. Dr. Rich reported having no conflicts of interest. Dr. Nicholls disclosed receiving research support from AstraZeneca, Amgen, Anthera, Eli Lilly, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and receiving consulting fees or honoraria from AstraZeneca, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Dr. Nelson had no disclosures.

A version of this article originally appeared on Medscape.com.

Background: National guidelines recommend that surgical prophylactic antimicrobials be initiated within 1 hour prior to incision and discontinued 24 hours postoperatively. However, the risks and benefits of longer duration of antimicrobials are uncertain.

However, the odds of postoperative AKI increased with each additional day of prophylaxis (adjusted odds ratios, 1.82; 95% confidence interval,1.54-2.16 and aOR, 1.79; 95% CI, 1.27-2.53) with longer than 72 hours prophylaxis for cardiac and noncardiac surgery, respectively). Similarly, C. difficile infections increased with each additional day beyond 24 hours (aOR, 3.65; 95% CI, 2.40-5.55 with more than 72 hours of use).

Bottom line: Each day of perioperative antimicrobial prophylaxis beyond 24 hours increases the risk for postoperative AKI or C. difficile infection without reducing the risk of surgical site infection.

Citation: Branch-Elliman W et al. Association of duration and type of surgical prophylaxis with antimicrobial-associated adverse events. JAMA Surg. 2019 Apr 24. doi: 10.1001/jamasurg.2019.0569.

Dr. Miller is a hospitalist at the University of Colorado at Denver, Aurora.

Background: National guidelines recommend that surgical prophylactic antimicrobials be initiated within 1 hour prior to incision and discontinued 24 hours postoperatively. However, the risks and benefits of longer duration of antimicrobials are uncertain.

However, the odds of postoperative AKI increased with each additional day of prophylaxis (adjusted odds ratios, 1.82; 95% confidence interval,1.54-2.16 and aOR, 1.79; 95% CI, 1.27-2.53) with longer than 72 hours prophylaxis for cardiac and noncardiac surgery, respectively). Similarly, C. difficile infections increased with each additional day beyond 24 hours (aOR, 3.65; 95% CI, 2.40-5.55 with more than 72 hours of use).

Bottom line: Each day of perioperative antimicrobial prophylaxis beyond 24 hours increases the risk for postoperative AKI or C. difficile infection without reducing the risk of surgical site infection.

Citation: Branch-Elliman W et al. Association of duration and type of surgical prophylaxis with antimicrobial-associated adverse events. JAMA Surg. 2019 Apr 24. doi: 10.1001/jamasurg.2019.0569.

Dr. Miller is a hospitalist at the University of Colorado at Denver, Aurora.

Background: National guidelines recommend that surgical prophylactic antimicrobials be initiated within 1 hour prior to incision and discontinued 24 hours postoperatively. However, the risks and benefits of longer duration of antimicrobials are uncertain.

However, the odds of postoperative AKI increased with each additional day of prophylaxis (adjusted odds ratios, 1.82; 95% confidence interval,1.54-2.16 and aOR, 1.79; 95% CI, 1.27-2.53) with longer than 72 hours prophylaxis for cardiac and noncardiac surgery, respectively). Similarly, C. difficile infections increased with each additional day beyond 24 hours (aOR, 3.65; 95% CI, 2.40-5.55 with more than 72 hours of use).

Bottom line: Each day of perioperative antimicrobial prophylaxis beyond 24 hours increases the risk for postoperative AKI or C. difficile infection without reducing the risk of surgical site infection.

Citation: Branch-Elliman W et al. Association of duration and type of surgical prophylaxis with antimicrobial-associated adverse events. JAMA Surg. 2019 Apr 24. doi: 10.1001/jamasurg.2019.0569.

Dr. Miller is a hospitalist at the University of Colorado at Denver, Aurora.

Although the adverse effects of systemic glucocorticoids (GCs) are well known, their association with hypertension in rheumatoid arthritis (RA) has been unclear. Now, a large population-based study shows that the drugs are linked to a 17% overall increased risk for incident hypertension among patients with RA.

Further, when the researchers stratified participants by dose category, they found that doses higher than 7.5 mg were significantly associated with hypertension. Cumulative dosage was not tied to any clear pattern of risk.

The authors, led by Ruth E. Costello, a researcher at the Centre for Epidemiology Versus Arthritis in the Centre for Musculoskeletal Research at the University of Manchester (England) concluded that patients who are taking these drugs for the treatment of RA should be monitored for high blood pressure, which is an important but modifiable cardiovascular risk factor, and treated appropriately.

The results of Ms. Costello and colleagues’ study were published June 27 in Rheumatology.

“While fractures associated with these steroid drugs are well studied, hypertension is a side effect that seems to have been less well studied, and yet it is an important cardiovascular risk factor that can be managed,” Ms. Costello said in an interview.

To better understand the possible association, Ms. Costello and colleagues identified 17,760 patients who were newly diagnosed with RA between 1992 and 2019 and were included in the Clinical Practice Research Datalink, which represents about 7% of the U.K. population. None of the patients had hypertension at initial RA diagnosis. Slightly more than two-thirds were women (68.1%), and the mean age was 56.3 years.

Of those patients, 7,421 (41.8%) were prescribed GCs during postdiagnosis follow-up. Most patients (73%) were followed for at least 2 years.

Patients who used GCs were slightly older than never-users (mean age, 57.7 vs. 55.3 years), were predominantly women, had a history of smoking, and had more comorbidities.

The overall incidence rate (IR) of hypertension was 64.1 per 1,000 person-years (95% confidence interval, 62.5-65.7). There were 6,243 cases of incident hypertension over 97,547 person-years of follow-up.

Among those exposed to GCs, 1,321 patients developed hypertension, for an IR of 87.6 per 1,000 person-years. Among unexposed participants, the IR for hypertension was 59.7 per 1,000 person-years. In Cox proportional hazards modeling, GC use was associated with a 17% increased risk for hypertension (hazard ratio, 1.17; 95% CI, 1.10-1.24).

The researchers noted that 40% of GC users with hypertension were not prescribed an antihypertensive agent at any point during the study. “Whilst some may have been offered lifestyle advice, left untreated this has important implications in terms of addressing modifiable risk factors in an RA population already at increased risk of CV disease,” they wrote.

They noted that cardiovascular disease is a major driver of the elevated mortality risk seen among adults with RA compared with the general population and that recent treatment recommendations address management of cardiovascular risks in these patients.

“There are several routes by which GCs may promote cardiovascular disease, including hypertension, metabolic changes, diabetes, and weight gain. We don’t currently know the extent to which each of these individual mechanisms may be increasing cardiovascular disease,” said Ms. Costello.

“Glucocorticoids increase fluid retention and promote obesity and hypertension,” said Rajat S. Bhatt, MD, a rheumatologist at Prime Rheumatology and Memorial Hermann Katy Hospital in Richmond, Texas, who sees hypertension in GC users in his clinical practice. “So patients need to be monitored for these risk factors,” he said in an interview.

Although hypertension may be a significant factor in the increase in cardiovascular disease in the RA population, Dr. Bhatt said the major driver is likely the intrinsic inflammatory state caused by the disease itself. As to why the GC-hypertension connection has flown under the radar in RA, he added, “That specific link has been difficult to tease out since RA patients are often on multiple medications.”

In regard to the role of dosage, Dr. Bhatt said that hypertension risk increases with higher GC doses, as the U.K. study indicates, and usually subsides when patients stop using GCs.

“Whether the observed dose association is causal or influenced by the underlying disease severity, our results suggest we should be vigilant in patients on all doses of GC, especially higher doses,” Ms. Costello added.

In regard to using drugs that are less cardiotoxic than GCs, Dr. Bhatt said that there are clinical scenarios in which GC therapy is the best choice, so just switching to nonsteroidal drugs is no panacea. “All RA drugs have adverse side effects, and anyway, the goal of rheumatology treatment is always to get patients off corticosteroids as soon as possible,” he said.

Ms. Costello and colleagues noted that their results are consonant with earlier research, including a single-center, cross-sectional study in which less than 6 months’ use of prednisolone at a median dose of 7.5 mg was associated with hypertension. In a German registry study, among patients who received doses of less than 7.5 mg for less than 6 months, there were higher rates of self-reported elevations in blood pressure.

The findings are at odds, however, with a recent matched-cohort study, which also used data from the Clinical Practice Research Datalink. That study found no association between GC use and hypertension.

GCs have come under increasing scrutiny in regard to several diseases. A study published July 7 found that even short-term courses of a few days’ duration entail risks for serious adverse events.

Ms. Costello’s group says that an estimate of GC-related incident hypertension in RA should allow more informed treatment decisions and that their findings highlight the ongoing need to monitor for and address this risk.

The study was supported by the Centre for Epidemiology Versus Arthritis and by the National Institute for Health Research Manchester Biomedical Research Centre. Coauthor William G. Dixon, PhD, has received consultancy fees from Google and Bayer unrelated to this study. Dr. Bhatt has disclosed no relevant financial relationships.

SOURCE: Costello RE et al. Rheumatology. 2020 June 27. doi: 10.1093/rheumatology/keaa209.

A version of this article originally appeared on Medscape.com.

Although the adverse effects of systemic glucocorticoids (GCs) are well known, their association with hypertension in rheumatoid arthritis (RA) has been unclear. Now, a large population-based study shows that the drugs are linked to a 17% overall increased risk for incident hypertension among patients with RA.

Further, when the researchers stratified participants by dose category, they found that doses higher than 7.5 mg were significantly associated with hypertension. Cumulative dosage was not tied to any clear pattern of risk.

The authors, led by Ruth E. Costello, a researcher at the Centre for Epidemiology Versus Arthritis in the Centre for Musculoskeletal Research at the University of Manchester (England) concluded that patients who are taking these drugs for the treatment of RA should be monitored for high blood pressure, which is an important but modifiable cardiovascular risk factor, and treated appropriately.

The results of Ms. Costello and colleagues’ study were published June 27 in Rheumatology.

“While fractures associated with these steroid drugs are well studied, hypertension is a side effect that seems to have been less well studied, and yet it is an important cardiovascular risk factor that can be managed,” Ms. Costello said in an interview.

To better understand the possible association, Ms. Costello and colleagues identified 17,760 patients who were newly diagnosed with RA between 1992 and 2019 and were included in the Clinical Practice Research Datalink, which represents about 7% of the U.K. population. None of the patients had hypertension at initial RA diagnosis. Slightly more than two-thirds were women (68.1%), and the mean age was 56.3 years.

Of those patients, 7,421 (41.8%) were prescribed GCs during postdiagnosis follow-up. Most patients (73%) were followed for at least 2 years.

Patients who used GCs were slightly older than never-users (mean age, 57.7 vs. 55.3 years), were predominantly women, had a history of smoking, and had more comorbidities.

The overall incidence rate (IR) of hypertension was 64.1 per 1,000 person-years (95% confidence interval, 62.5-65.7). There were 6,243 cases of incident hypertension over 97,547 person-years of follow-up.

Among those exposed to GCs, 1,321 patients developed hypertension, for an IR of 87.6 per 1,000 person-years. Among unexposed participants, the IR for hypertension was 59.7 per 1,000 person-years. In Cox proportional hazards modeling, GC use was associated with a 17% increased risk for hypertension (hazard ratio, 1.17; 95% CI, 1.10-1.24).

The researchers noted that 40% of GC users with hypertension were not prescribed an antihypertensive agent at any point during the study. “Whilst some may have been offered lifestyle advice, left untreated this has important implications in terms of addressing modifiable risk factors in an RA population already at increased risk of CV disease,” they wrote.

They noted that cardiovascular disease is a major driver of the elevated mortality risk seen among adults with RA compared with the general population and that recent treatment recommendations address management of cardiovascular risks in these patients.

“There are several routes by which GCs may promote cardiovascular disease, including hypertension, metabolic changes, diabetes, and weight gain. We don’t currently know the extent to which each of these individual mechanisms may be increasing cardiovascular disease,” said Ms. Costello.

“Glucocorticoids increase fluid retention and promote obesity and hypertension,” said Rajat S. Bhatt, MD, a rheumatologist at Prime Rheumatology and Memorial Hermann Katy Hospital in Richmond, Texas, who sees hypertension in GC users in his clinical practice. “So patients need to be monitored for these risk factors,” he said in an interview.

Although hypertension may be a significant factor in the increase in cardiovascular disease in the RA population, Dr. Bhatt said the major driver is likely the intrinsic inflammatory state caused by the disease itself. As to why the GC-hypertension connection has flown under the radar in RA, he added, “That specific link has been difficult to tease out since RA patients are often on multiple medications.”

In regard to the role of dosage, Dr. Bhatt said that hypertension risk increases with higher GC doses, as the U.K. study indicates, and usually subsides when patients stop using GCs.

“Whether the observed dose association is causal or influenced by the underlying disease severity, our results suggest we should be vigilant in patients on all doses of GC, especially higher doses,” Ms. Costello added.

In regard to using drugs that are less cardiotoxic than GCs, Dr. Bhatt said that there are clinical scenarios in which GC therapy is the best choice, so just switching to nonsteroidal drugs is no panacea. “All RA drugs have adverse side effects, and anyway, the goal of rheumatology treatment is always to get patients off corticosteroids as soon as possible,” he said.

Ms. Costello and colleagues noted that their results are consonant with earlier research, including a single-center, cross-sectional study in which less than 6 months’ use of prednisolone at a median dose of 7.5 mg was associated with hypertension. In a German registry study, among patients who received doses of less than 7.5 mg for less than 6 months, there were higher rates of self-reported elevations in blood pressure.

The findings are at odds, however, with a recent matched-cohort study, which also used data from the Clinical Practice Research Datalink. That study found no association between GC use and hypertension.

GCs have come under increasing scrutiny in regard to several diseases. A study published July 7 found that even short-term courses of a few days’ duration entail risks for serious adverse events.

Ms. Costello’s group says that an estimate of GC-related incident hypertension in RA should allow more informed treatment decisions and that their findings highlight the ongoing need to monitor for and address this risk.

The study was supported by the Centre for Epidemiology Versus Arthritis and by the National Institute for Health Research Manchester Biomedical Research Centre. Coauthor William G. Dixon, PhD, has received consultancy fees from Google and Bayer unrelated to this study. Dr. Bhatt has disclosed no relevant financial relationships.

SOURCE: Costello RE et al. Rheumatology. 2020 June 27. doi: 10.1093/rheumatology/keaa209.

A version of this article originally appeared on Medscape.com.

Although the adverse effects of systemic glucocorticoids (GCs) are well known, their association with hypertension in rheumatoid arthritis (RA) has been unclear. Now, a large population-based study shows that the drugs are linked to a 17% overall increased risk for incident hypertension among patients with RA.

Further, when the researchers stratified participants by dose category, they found that doses higher than 7.5 mg were significantly associated with hypertension. Cumulative dosage was not tied to any clear pattern of risk.

The authors, led by Ruth E. Costello, a researcher at the Centre for Epidemiology Versus Arthritis in the Centre for Musculoskeletal Research at the University of Manchester (England) concluded that patients who are taking these drugs for the treatment of RA should be monitored for high blood pressure, which is an important but modifiable cardiovascular risk factor, and treated appropriately.

The results of Ms. Costello and colleagues’ study were published June 27 in Rheumatology.

“While fractures associated with these steroid drugs are well studied, hypertension is a side effect that seems to have been less well studied, and yet it is an important cardiovascular risk factor that can be managed,” Ms. Costello said in an interview.

To better understand the possible association, Ms. Costello and colleagues identified 17,760 patients who were newly diagnosed with RA between 1992 and 2019 and were included in the Clinical Practice Research Datalink, which represents about 7% of the U.K. population. None of the patients had hypertension at initial RA diagnosis. Slightly more than two-thirds were women (68.1%), and the mean age was 56.3 years.

Of those patients, 7,421 (41.8%) were prescribed GCs during postdiagnosis follow-up. Most patients (73%) were followed for at least 2 years.

Patients who used GCs were slightly older than never-users (mean age, 57.7 vs. 55.3 years), were predominantly women, had a history of smoking, and had more comorbidities.

The overall incidence rate (IR) of hypertension was 64.1 per 1,000 person-years (95% confidence interval, 62.5-65.7). There were 6,243 cases of incident hypertension over 97,547 person-years of follow-up.

Among those exposed to GCs, 1,321 patients developed hypertension, for an IR of 87.6 per 1,000 person-years. Among unexposed participants, the IR for hypertension was 59.7 per 1,000 person-years. In Cox proportional hazards modeling, GC use was associated with a 17% increased risk for hypertension (hazard ratio, 1.17; 95% CI, 1.10-1.24).

The researchers noted that 40% of GC users with hypertension were not prescribed an antihypertensive agent at any point during the study. “Whilst some may have been offered lifestyle advice, left untreated this has important implications in terms of addressing modifiable risk factors in an RA population already at increased risk of CV disease,” they wrote.

They noted that cardiovascular disease is a major driver of the elevated mortality risk seen among adults with RA compared with the general population and that recent treatment recommendations address management of cardiovascular risks in these patients.

“There are several routes by which GCs may promote cardiovascular disease, including hypertension, metabolic changes, diabetes, and weight gain. We don’t currently know the extent to which each of these individual mechanisms may be increasing cardiovascular disease,” said Ms. Costello.

“Glucocorticoids increase fluid retention and promote obesity and hypertension,” said Rajat S. Bhatt, MD, a rheumatologist at Prime Rheumatology and Memorial Hermann Katy Hospital in Richmond, Texas, who sees hypertension in GC users in his clinical practice. “So patients need to be monitored for these risk factors,” he said in an interview.

Although hypertension may be a significant factor in the increase in cardiovascular disease in the RA population, Dr. Bhatt said the major driver is likely the intrinsic inflammatory state caused by the disease itself. As to why the GC-hypertension connection has flown under the radar in RA, he added, “That specific link has been difficult to tease out since RA patients are often on multiple medications.”

In regard to the role of dosage, Dr. Bhatt said that hypertension risk increases with higher GC doses, as the U.K. study indicates, and usually subsides when patients stop using GCs.

“Whether the observed dose association is causal or influenced by the underlying disease severity, our results suggest we should be vigilant in patients on all doses of GC, especially higher doses,” Ms. Costello added.

In regard to using drugs that are less cardiotoxic than GCs, Dr. Bhatt said that there are clinical scenarios in which GC therapy is the best choice, so just switching to nonsteroidal drugs is no panacea. “All RA drugs have adverse side effects, and anyway, the goal of rheumatology treatment is always to get patients off corticosteroids as soon as possible,” he said.

Ms. Costello and colleagues noted that their results are consonant with earlier research, including a single-center, cross-sectional study in which less than 6 months’ use of prednisolone at a median dose of 7.5 mg was associated with hypertension. In a German registry study, among patients who received doses of less than 7.5 mg for less than 6 months, there were higher rates of self-reported elevations in blood pressure.

The findings are at odds, however, with a recent matched-cohort study, which also used data from the Clinical Practice Research Datalink. That study found no association between GC use and hypertension.

GCs have come under increasing scrutiny in regard to several diseases. A study published July 7 found that even short-term courses of a few days’ duration entail risks for serious adverse events.

Ms. Costello’s group says that an estimate of GC-related incident hypertension in RA should allow more informed treatment decisions and that their findings highlight the ongoing need to monitor for and address this risk.

The study was supported by the Centre for Epidemiology Versus Arthritis and by the National Institute for Health Research Manchester Biomedical Research Centre. Coauthor William G. Dixon, PhD, has received consultancy fees from Google and Bayer unrelated to this study. Dr. Bhatt has disclosed no relevant financial relationships.

SOURCE: Costello RE et al. Rheumatology. 2020 June 27. doi: 10.1093/rheumatology/keaa209.

A version of this article originally appeared on Medscape.com.

Proposed changes in the eligibility criteria for lung cancer screening with low-dose CT could result in a near doubling of eligibility, and could especially benefit Black persons and women, say lung cancer experts.

The new proposals include lowering the age at which screening starts from 55 to 50 years, and to reduce the smoking history from 30 to 20 pack-years.

The draft recommendation from the United States Preventive Service Task Force (USPSTF) is available for public comment until August 3.

The task force recommends that adults age 50 to 80 who have a 20 pack-year or greater smoking history and currently smoke or have quit within the last 15 years undergo annual screening for lung cancer with low-dose CT,

“In my opinion, the proposed criteria by USPSTF represent a huge step in the right direction,” Lecia Sequist, MD, director of innovation at the Mass General Cancer Center in Boston, told Medscape Medical News.

“If these are adopted and implemented, we could see the benefit of screening (measured as reduction in lung cancer mortality) go from 9.8% with current parameters up to 13% with the broader parameters,” she said. “In addition, the new criteria should reduce racial disparities in screening eligibility.”

The recommendation also earned high marks from the American Lung Association.

The USPSTF has continued its ‘B’ recommendation – allowing for coverage of the screening with no cost for many under the Affordable Care Act – and is now proposing to expand the eligibility criteria “so that even more Americans at higher risk for lung cancer can be screened,” the ALA commented.

Start screening at 50  

Lowering the minimum age of screening to 50 would likely mean that more Black individuals and women would be eligible for screening, the recommendation authors contend. The current screening age of 55 is currently recommended under guidelines issued by the American Association for Thoracic Surgery, American Cancer Society, American College of Chest Physicians, and National Comprehensive Cancer Network.

“African Americans have a higher risk of lung cancer, compared with whites, and this risk difference is more apparent at lower levels of smoking intensity,” they write.

As previously reported by Medscape Medical News, lung cancer screening in an urban, largely black cohort yielded roughly double the rates of positive screens and detected lung cancers compared with results from the National Lung Screening Trial, which enrolled mostly White individuals.

In addition, although lung cancer risk is greater for men than women who smoke, and women generally accumulate fewer pack-years than men, there is evidence to suggest that women who smoke may develop lung cancer earlier and with lower levels of exposure.

Therefore, “a strategy of screening persons ages 50 to 80 years who have at least a 20 pack-year smoking history and currently smoke or have quit within the past 15 years (A-50-80-20-15) would lead to a relative increase in the percentage of persons eligible for screening by 81% in men and by 96% in women,” the proposed recommendation states.

What’s the harm?

One of the major concerns about low-dose CT screening for lung cancer is the relatively high rate of false-positive results reported in two large scale clinical trials, the recommendation authors acknowledged.

For example, in the NLST, which was the basis for an earlier USPSTF recommendation (for annual screening of adults 55 to 80 years of age who have a 30 pack-year smoking history and currently smoke or have quit in the previous 15 years), the false-positive rates were 26.3% at baseline, 27.2% at year 1, and 15.9% at year 2.

Similarly, in the NELSON trial, results of which were published earlier this year, false-positive rates for men were 19.8% at baseline, 7.1% at year 1, 9% at year 3, and 3.9% at year 5.5 of screening, they noted.

“Yes, false-positive results are one of the things we need to think carefully about when embarking on lung screening,” Dr. Sequist told Medscape Medical News. “The potential harm of a false-positive (unnecessary scans, biopsies or even surgery) can be minimized by having a multidisciplinary team with experience working up lung nodules see patients who have a positive screening test. In fact, the American College of Radiology recommends that all lung screening programs be paired with such a team.”

Mass General has a pulmonary nodule clinic to evaluate screen-detected lung nodules, with the goal of minimizing unnecessary procedures, she noted.

Asked about the potential harm from radiation exposure, Sequist said that exposure from low-dose CT screening is fairly minimal, comparable to that from solar radiation at sea level over a 6-month period, or about the level from three cross-country airplane trips.

“While it is not zero radiation, there is very little concern that this low level of radiation would cause a cancer or damage one’s lungs,” she said.

Albert Rizzo, MD, chief medical officer of the ALA, said that the potential harms of unnecessary interventions are outweighed by the benefits of detecting lung cancer at an early stage.

“I think what has been learned over the last 5 years is that the original recommendations that were put out really allowed the overall rate of positivity well within what’s seen with mammography, for example, and the number of patients who have needlessly gone on to procedures remains very low, and the morbidity of those procedures remains low as well,” Dr. Rizzo told Medscape Medical News.

Not enough takers

Despite the clear benefits of low-dose CT screening, however, US screening rates for high-risk individuals are still very low, ranging from 12.3% in Massachusetts to a low of 0.5% in Nevada, according to a 2019 research report on the state of lung cancer from the ALA.

“For screening to be most effective, more of the high-risk population should be screened. Currently, screening rates are very low among those at high risk. This may be because of a lack of access or low awareness and knowledge among patients and providers. As rates vary tremendously between states, it is clear that more can be done to increase screening rates,” the report stated.

“I think that there are some mixed messages sent out into the population as to whether or not an individual patient should be screened,” Dr. Rizzo said.

He noted that some physicians may be reluctant to take on the nuanced risk–benefit discussion required, or may not have the time during a brief patient visit.

“It really boils down to that discussion between the physician and the patient who falls under these risk categories, to say, ‘Look, this is what these studies have found, and you fall under a category where if we find a cancer early, it’s very likely you’re going to be saved,’ as compared for waiting for it to present by itself,” he said.

Dr. Sequist and Dr. Rizzo have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Proposed changes in the eligibility criteria for lung cancer screening with low-dose CT could result in a near doubling of eligibility, and could especially benefit Black persons and women, say lung cancer experts.

The new proposals include lowering the age at which screening starts from 55 to 50 years, and to reduce the smoking history from 30 to 20 pack-years.

The draft recommendation from the United States Preventive Service Task Force (USPSTF) is available for public comment until August 3.

The task force recommends that adults age 50 to 80 who have a 20 pack-year or greater smoking history and currently smoke or have quit within the last 15 years undergo annual screening for lung cancer with low-dose CT,

“In my opinion, the proposed criteria by USPSTF represent a huge step in the right direction,” Lecia Sequist, MD, director of innovation at the Mass General Cancer Center in Boston, told Medscape Medical News.

“If these are adopted and implemented, we could see the benefit of screening (measured as reduction in lung cancer mortality) go from 9.8% with current parameters up to 13% with the broader parameters,” she said. “In addition, the new criteria should reduce racial disparities in screening eligibility.”

The recommendation also earned high marks from the American Lung Association.

The USPSTF has continued its ‘B’ recommendation – allowing for coverage of the screening with no cost for many under the Affordable Care Act – and is now proposing to expand the eligibility criteria “so that even more Americans at higher risk for lung cancer can be screened,” the ALA commented.

Start screening at 50  

Lowering the minimum age of screening to 50 would likely mean that more Black individuals and women would be eligible for screening, the recommendation authors contend. The current screening age of 55 is currently recommended under guidelines issued by the American Association for Thoracic Surgery, American Cancer Society, American College of Chest Physicians, and National Comprehensive Cancer Network.

“African Americans have a higher risk of lung cancer, compared with whites, and this risk difference is more apparent at lower levels of smoking intensity,” they write.

As previously reported by Medscape Medical News, lung cancer screening in an urban, largely black cohort yielded roughly double the rates of positive screens and detected lung cancers compared with results from the National Lung Screening Trial, which enrolled mostly White individuals.

In addition, although lung cancer risk is greater for men than women who smoke, and women generally accumulate fewer pack-years than men, there is evidence to suggest that women who smoke may develop lung cancer earlier and with lower levels of exposure.

Therefore, “a strategy of screening persons ages 50 to 80 years who have at least a 20 pack-year smoking history and currently smoke or have quit within the past 15 years (A-50-80-20-15) would lead to a relative increase in the percentage of persons eligible for screening by 81% in men and by 96% in women,” the proposed recommendation states.

What’s the harm?

One of the major concerns about low-dose CT screening for lung cancer is the relatively high rate of false-positive results reported in two large scale clinical trials, the recommendation authors acknowledged.

For example, in the NLST, which was the basis for an earlier USPSTF recommendation (for annual screening of adults 55 to 80 years of age who have a 30 pack-year smoking history and currently smoke or have quit in the previous 15 years), the false-positive rates were 26.3% at baseline, 27.2% at year 1, and 15.9% at year 2.

Similarly, in the NELSON trial, results of which were published earlier this year, false-positive rates for men were 19.8% at baseline, 7.1% at year 1, 9% at year 3, and 3.9% at year 5.5 of screening, they noted.

“Yes, false-positive results are one of the things we need to think carefully about when embarking on lung screening,” Dr. Sequist told Medscape Medical News. “The potential harm of a false-positive (unnecessary scans, biopsies or even surgery) can be minimized by having a multidisciplinary team with experience working up lung nodules see patients who have a positive screening test. In fact, the American College of Radiology recommends that all lung screening programs be paired with such a team.”

Mass General has a pulmonary nodule clinic to evaluate screen-detected lung nodules, with the goal of minimizing unnecessary procedures, she noted.

Asked about the potential harm from radiation exposure, Sequist said that exposure from low-dose CT screening is fairly minimal, comparable to that from solar radiation at sea level over a 6-month period, or about the level from three cross-country airplane trips.

“While it is not zero radiation, there is very little concern that this low level of radiation would cause a cancer or damage one’s lungs,” she said.

Albert Rizzo, MD, chief medical officer of the ALA, said that the potential harms of unnecessary interventions are outweighed by the benefits of detecting lung cancer at an early stage.

“I think what has been learned over the last 5 years is that the original recommendations that were put out really allowed the overall rate of positivity well within what’s seen with mammography, for example, and the number of patients who have needlessly gone on to procedures remains very low, and the morbidity of those procedures remains low as well,” Dr. Rizzo told Medscape Medical News.

Not enough takers

Despite the clear benefits of low-dose CT screening, however, US screening rates for high-risk individuals are still very low, ranging from 12.3% in Massachusetts to a low of 0.5% in Nevada, according to a 2019 research report on the state of lung cancer from the ALA.

“For screening to be most effective, more of the high-risk population should be screened. Currently, screening rates are very low among those at high risk. This may be because of a lack of access or low awareness and knowledge among patients and providers. As rates vary tremendously between states, it is clear that more can be done to increase screening rates,” the report stated.

“I think that there are some mixed messages sent out into the population as to whether or not an individual patient should be screened,” Dr. Rizzo said.

He noted that some physicians may be reluctant to take on the nuanced risk–benefit discussion required, or may not have the time during a brief patient visit.

“It really boils down to that discussion between the physician and the patient who falls under these risk categories, to say, ‘Look, this is what these studies have found, and you fall under a category where if we find a cancer early, it’s very likely you’re going to be saved,’ as compared for waiting for it to present by itself,” he said.

Dr. Sequist and Dr. Rizzo have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Proposed changes in the eligibility criteria for lung cancer screening with low-dose CT could result in a near doubling of eligibility, and could especially benefit Black persons and women, say lung cancer experts.

The new proposals include lowering the age at which screening starts from 55 to 50 years, and to reduce the smoking history from 30 to 20 pack-years.

The draft recommendation from the United States Preventive Service Task Force (USPSTF) is available for public comment until August 3.

The task force recommends that adults age 50 to 80 who have a 20 pack-year or greater smoking history and currently smoke or have quit within the last 15 years undergo annual screening for lung cancer with low-dose CT,

“In my opinion, the proposed criteria by USPSTF represent a huge step in the right direction,” Lecia Sequist, MD, director of innovation at the Mass General Cancer Center in Boston, told Medscape Medical News.

“If these are adopted and implemented, we could see the benefit of screening (measured as reduction in lung cancer mortality) go from 9.8% with current parameters up to 13% with the broader parameters,” she said. “In addition, the new criteria should reduce racial disparities in screening eligibility.”

The recommendation also earned high marks from the American Lung Association.

The USPSTF has continued its ‘B’ recommendation – allowing for coverage of the screening with no cost for many under the Affordable Care Act – and is now proposing to expand the eligibility criteria “so that even more Americans at higher risk for lung cancer can be screened,” the ALA commented.

Start screening at 50  

Lowering the minimum age of screening to 50 would likely mean that more Black individuals and women would be eligible for screening, the recommendation authors contend. The current screening age of 55 is currently recommended under guidelines issued by the American Association for Thoracic Surgery, American Cancer Society, American College of Chest Physicians, and National Comprehensive Cancer Network.

“African Americans have a higher risk of lung cancer, compared with whites, and this risk difference is more apparent at lower levels of smoking intensity,” they write.

As previously reported by Medscape Medical News, lung cancer screening in an urban, largely black cohort yielded roughly double the rates of positive screens and detected lung cancers compared with results from the National Lung Screening Trial, which enrolled mostly White individuals.

In addition, although lung cancer risk is greater for men than women who smoke, and women generally accumulate fewer pack-years than men, there is evidence to suggest that women who smoke may develop lung cancer earlier and with lower levels of exposure.

Therefore, “a strategy of screening persons ages 50 to 80 years who have at least a 20 pack-year smoking history and currently smoke or have quit within the past 15 years (A-50-80-20-15) would lead to a relative increase in the percentage of persons eligible for screening by 81% in men and by 96% in women,” the proposed recommendation states.

What’s the harm?

One of the major concerns about low-dose CT screening for lung cancer is the relatively high rate of false-positive results reported in two large scale clinical trials, the recommendation authors acknowledged.

For example, in the NLST, which was the basis for an earlier USPSTF recommendation (for annual screening of adults 55 to 80 years of age who have a 30 pack-year smoking history and currently smoke or have quit in the previous 15 years), the false-positive rates were 26.3% at baseline, 27.2% at year 1, and 15.9% at year 2.

Similarly, in the NELSON trial, results of which were published earlier this year, false-positive rates for men were 19.8% at baseline, 7.1% at year 1, 9% at year 3, and 3.9% at year 5.5 of screening, they noted.

“Yes, false-positive results are one of the things we need to think carefully about when embarking on lung screening,” Dr. Sequist told Medscape Medical News. “The potential harm of a false-positive (unnecessary scans, biopsies or even surgery) can be minimized by having a multidisciplinary team with experience working up lung nodules see patients who have a positive screening test. In fact, the American College of Radiology recommends that all lung screening programs be paired with such a team.”

Mass General has a pulmonary nodule clinic to evaluate screen-detected lung nodules, with the goal of minimizing unnecessary procedures, she noted.

Asked about the potential harm from radiation exposure, Sequist said that exposure from low-dose CT screening is fairly minimal, comparable to that from solar radiation at sea level over a 6-month period, or about the level from three cross-country airplane trips.

“While it is not zero radiation, there is very little concern that this low level of radiation would cause a cancer or damage one’s lungs,” she said.

Albert Rizzo, MD, chief medical officer of the ALA, said that the potential harms of unnecessary interventions are outweighed by the benefits of detecting lung cancer at an early stage.

“I think what has been learned over the last 5 years is that the original recommendations that were put out really allowed the overall rate of positivity well within what’s seen with mammography, for example, and the number of patients who have needlessly gone on to procedures remains very low, and the morbidity of those procedures remains low as well,” Dr. Rizzo told Medscape Medical News.

Not enough takers

Despite the clear benefits of low-dose CT screening, however, US screening rates for high-risk individuals are still very low, ranging from 12.3% in Massachusetts to a low of 0.5% in Nevada, according to a 2019 research report on the state of lung cancer from the ALA.

“For screening to be most effective, more of the high-risk population should be screened. Currently, screening rates are very low among those at high risk. This may be because of a lack of access or low awareness and knowledge among patients and providers. As rates vary tremendously between states, it is clear that more can be done to increase screening rates,” the report stated.

“I think that there are some mixed messages sent out into the population as to whether or not an individual patient should be screened,” Dr. Rizzo said.

He noted that some physicians may be reluctant to take on the nuanced risk–benefit discussion required, or may not have the time during a brief patient visit.

“It really boils down to that discussion between the physician and the patient who falls under these risk categories, to say, ‘Look, this is what these studies have found, and you fall under a category where if we find a cancer early, it’s very likely you’re going to be saved,’ as compared for waiting for it to present by itself,” he said.

Dr. Sequist and Dr. Rizzo have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Opioid overdose deaths in the United States have more than tripled in recent years, from 6.1 deaths per 100,000 individuals in 1999 to 20.7 per 100,000 individuals in 2018.¹ Although the availability of medication-assisted treatment (MAT) has expanded over the past decade, this lifesaving treatment remains largely inaccessible to some of the most vulnerable members of our communities: opioid users facing reentry after incarceration.

Just as abstinence in the community brings a loss of tolerance to opioids, individuals who are incarcerated lose tolerance as well. Clinicians who treat patients with opioid use disorders (OUD) are accustomed to warning patients about the risk of returning to prior levels of use too quickly. Harm reduction strategies include using slowly, using with friends, and having naloxone on hand to prevent unintended overdose.

The risks of opioid use are magnified for those facing reentry; incarceration contributes to a loss of employment, social supports, and connection to care. Those changes can create an exceptionally stressful reentry period – one that places individuals at an acutely high risk of relapse and overdose. Within the first 2 years of release, an individual with a history of incarceration has a risk of death 3.5 times higher than that of someone in the general population. Within the first 2 weeks, those recently incarcerated are 129 times more likely to overdose on opioids and 12.7 times more likely to die than members of the general population.2

Treatment with MAT dramatically reduces deaths during this crucial period. In Rhode Island, for example, implementation of a corrections MAT program decreased all-cause death rates after release by an astonishing 60.5%.³ In England, large national studies have shown a similar 75% decrease in all-cause mortality within the first 4 weeks of release among individuals with OUD.⁴ In California, the counties with the highest overdose death rates are consistently those with fewer opioid treatment programs, which suggests that access to treatment is necessary to prolong the lives of those suffering from OUD.⁵ In-custody overdose deaths are quite rare, and access to MAT during incarceration has decreased in-custody deaths by 74%.⁶

Decreased opioid overdose deaths is not the only outcome of MAT. Pharmacotherapy for OUD also has been shown to increase treatment retention,⁷ reduce reincarceration,⁸ prevent communicable infections,⁹ and decrease use of other illicit substances.¹⁰ The provision of MAT also has been shown to be cost effective.¹¹

Despite those benefits, as of 2017, only 30 out of 5,100 jails and prisons in the United States provided treatment with methadone or buprenorphine.¹² When individuals on maintenance therapy are incarcerated, most correctional facilities force them to taper and discontinue those medications. This practice can cause distressing withdrawal symptoms and actively increase the risk of death for these individuals.

Concerns related to the provision of MAT, and specifically buprenorphine, in the correctional health setting often are related to diversion. Although safe administration of opioid full and partial agonists is a priority, recent literature has suggested that buprenorphine is not a medication frequently used for euphoric properties. In fact, the literature suggests that individuals using illicit buprenorphine primarily do so to treat withdrawal symptoms and that illicit use diminishes with access to formal treatment.^13,14

Another concern is that pharmacotherapy for OUD should not be used without adjunctive psychotherapies and social supports. While dual pharmacotherapy and psychotherapy is ideal, the American Society for Addiction Medicine 2020 National Practice Guidelines for the treatment of OUD state: “a patient’s decision to decline psychosocial treatment or the absence of available psychosocial treatment should not preclude or delay pharmacotherapy, with appropriate medication management.”¹⁵ Just as some patients wish to engage in mutual help or psychotherapeutic modalities only, some patients wish to engage only in psychopharmacologic interventions. Declaring one modality of treatment better, or worse, or more worthwhile is not borne out by the literature and often places clinicians’ preferences over the preferences of patients.

Individuals who suffer from substance use disorders are at high risk of incarceration, relapse, and overdose death. These patients also suffer from stigmatization from peers and health care workers alike, making the process of engaging in care incredibly burdensome. Because of the disease of addiction, many of our patients cannot envision a healthy future: a future with the potential for intimate relationships, meaningful community engagement, and a rich inner life. The provision of MAT is lifesaving and improves the chances of a successful reentry – an intuitive first step in a long, but worthwhile, journey.
 

References

1. Hedegaard H et al; National Center for Health Statistics. Drug overdose deaths in the United States, 1999–2018. NCHS Data Brief, 2020 Jan, No. 356.

2. Binswanger IA et al. N Engl J Med. 2007;356:157-65.

3. Green TC et al. JAMA Psychiatry. 2018;75(4):405-7.

4. Marsden J et al. Addiction. 2017;112(8):1408-18.

5. Joshi V and Urada D. State Targeted Response to the Opioid Crisis: California Strategic Plan. 2017 Aug 30.

6. Larney S et al. BMJ Open. 2014. doi: 10.1136/bmjopen-2013-004666.

7. Rich JD et al. Lancet. 2015;386(9991):350-9.

8. Deck D et al. J Addict Dis. 2009. 28(2):89-102.

9. MacArthur GJ et al. BMJ. 2012. doi: 10.1136/bmj.e5945.

10. Tsui J et al. J Subst Abuse Treat. 2019. 109:80-5.

11. Gisev N et al. Addiction. 2015 Dec;110(12):1975-84.

12. National Mental Health and Substance Use Policy Laboratory. “Use of Medication-Assisted Treatment for Opioid Use Disorder in Criminal Justice Settings.” HHS Publication No. PEP19-MATUSECJS. Rockville, Md.: Substance Abuse and Mental Health Services Administration, 2019.

13. Bazazi AR et al. J Addict Med. 2011;5(3):175-80.

14. Schuman-Olivier Z. et al. J Subst Abuse Treat. 2010 Jul;39(1):41-50.

15. Crotty K et al. J Addict Med. 2020;14(2)99-112.
 

Dr. Barnes is chief resident at San Mateo County Behavioral Health and Recovery Services in California. He disclosed no relevant financial relationships. Dr. Lenane is resident* at San Mateo County Behavioral Health and Recovery Services. He disclosed no relevant financial relationships. The opinions shared in this article represent the viewpoints of the authors and are not necessarily representative of the viewpoints or policies of their academic program or employer.

*This article was updated 7/9/2020.

Opioid overdose deaths in the United States have more than tripled in recent years, from 6.1 deaths per 100,000 individuals in 1999 to 20.7 per 100,000 individuals in 2018.¹ Although the availability of medication-assisted treatment (MAT) has expanded over the past decade, this lifesaving treatment remains largely inaccessible to some of the most vulnerable members of our communities: opioid users facing reentry after incarceration.

Just as abstinence in the community brings a loss of tolerance to opioids, individuals who are incarcerated lose tolerance as well. Clinicians who treat patients with opioid use disorders (OUD) are accustomed to warning patients about the risk of returning to prior levels of use too quickly. Harm reduction strategies include using slowly, using with friends, and having naloxone on hand to prevent unintended overdose.

The risks of opioid use are magnified for those facing reentry; incarceration contributes to a loss of employment, social supports, and connection to care. Those changes can create an exceptionally stressful reentry period – one that places individuals at an acutely high risk of relapse and overdose. Within the first 2 years of release, an individual with a history of incarceration has a risk of death 3.5 times higher than that of someone in the general population. Within the first 2 weeks, those recently incarcerated are 129 times more likely to overdose on opioids and 12.7 times more likely to die than members of the general population.2

Treatment with MAT dramatically reduces deaths during this crucial period. In Rhode Island, for example, implementation of a corrections MAT program decreased all-cause death rates after release by an astonishing 60.5%.³ In England, large national studies have shown a similar 75% decrease in all-cause mortality within the first 4 weeks of release among individuals with OUD.⁴ In California, the counties with the highest overdose death rates are consistently those with fewer opioid treatment programs, which suggests that access to treatment is necessary to prolong the lives of those suffering from OUD.⁵ In-custody overdose deaths are quite rare, and access to MAT during incarceration has decreased in-custody deaths by 74%.⁶

Decreased opioid overdose deaths is not the only outcome of MAT. Pharmacotherapy for OUD also has been shown to increase treatment retention,⁷ reduce reincarceration,⁸ prevent communicable infections,⁹ and decrease use of other illicit substances.¹⁰ The provision of MAT also has been shown to be cost effective.¹¹

Despite those benefits, as of 2017, only 30 out of 5,100 jails and prisons in the United States provided treatment with methadone or buprenorphine.¹² When individuals on maintenance therapy are incarcerated, most correctional facilities force them to taper and discontinue those medications. This practice can cause distressing withdrawal symptoms and actively increase the risk of death for these individuals.

Concerns related to the provision of MAT, and specifically buprenorphine, in the correctional health setting often are related to diversion. Although safe administration of opioid full and partial agonists is a priority, recent literature has suggested that buprenorphine is not a medication frequently used for euphoric properties. In fact, the literature suggests that individuals using illicit buprenorphine primarily do so to treat withdrawal symptoms and that illicit use diminishes with access to formal treatment.^13,14

Another concern is that pharmacotherapy for OUD should not be used without adjunctive psychotherapies and social supports. While dual pharmacotherapy and psychotherapy is ideal, the American Society for Addiction Medicine 2020 National Practice Guidelines for the treatment of OUD state: “a patient’s decision to decline psychosocial treatment or the absence of available psychosocial treatment should not preclude or delay pharmacotherapy, with appropriate medication management.”¹⁵ Just as some patients wish to engage in mutual help or psychotherapeutic modalities only, some patients wish to engage only in psychopharmacologic interventions. Declaring one modality of treatment better, or worse, or more worthwhile is not borne out by the literature and often places clinicians’ preferences over the preferences of patients.

Individuals who suffer from substance use disorders are at high risk of incarceration, relapse, and overdose death. These patients also suffer from stigmatization from peers and health care workers alike, making the process of engaging in care incredibly burdensome. Because of the disease of addiction, many of our patients cannot envision a healthy future: a future with the potential for intimate relationships, meaningful community engagement, and a rich inner life. The provision of MAT is lifesaving and improves the chances of a successful reentry – an intuitive first step in a long, but worthwhile, journey.
 

References

1. Hedegaard H et al; National Center for Health Statistics. Drug overdose deaths in the United States, 1999–2018. NCHS Data Brief, 2020 Jan, No. 356.

2. Binswanger IA et al. N Engl J Med. 2007;356:157-65.

3. Green TC et al. JAMA Psychiatry. 2018;75(4):405-7.

4. Marsden J et al. Addiction. 2017;112(8):1408-18.

5. Joshi V and Urada D. State Targeted Response to the Opioid Crisis: California Strategic Plan. 2017 Aug 30.

6. Larney S et al. BMJ Open. 2014. doi: 10.1136/bmjopen-2013-004666.

7. Rich JD et al. Lancet. 2015;386(9991):350-9.

8. Deck D et al. J Addict Dis. 2009. 28(2):89-102.

9. MacArthur GJ et al. BMJ. 2012. doi: 10.1136/bmj.e5945.

10. Tsui J et al. J Subst Abuse Treat. 2019. 109:80-5.

11. Gisev N et al. Addiction. 2015 Dec;110(12):1975-84.

12. National Mental Health and Substance Use Policy Laboratory. “Use of Medication-Assisted Treatment for Opioid Use Disorder in Criminal Justice Settings.” HHS Publication No. PEP19-MATUSECJS. Rockville, Md.: Substance Abuse and Mental Health Services Administration, 2019.

13. Bazazi AR et al. J Addict Med. 2011;5(3):175-80.

14. Schuman-Olivier Z. et al. J Subst Abuse Treat. 2010 Jul;39(1):41-50.

15. Crotty K et al. J Addict Med. 2020;14(2)99-112.
 

Dr. Barnes is chief resident at San Mateo County Behavioral Health and Recovery Services in California. He disclosed no relevant financial relationships. Dr. Lenane is resident* at San Mateo County Behavioral Health and Recovery Services. He disclosed no relevant financial relationships. The opinions shared in this article represent the viewpoints of the authors and are not necessarily representative of the viewpoints or policies of their academic program or employer.

*This article was updated 7/9/2020.

Opioid overdose deaths in the United States have more than tripled in recent years, from 6.1 deaths per 100,000 individuals in 1999 to 20.7 per 100,000 individuals in 2018.¹ Although the availability of medication-assisted treatment (MAT) has expanded over the past decade, this lifesaving treatment remains largely inaccessible to some of the most vulnerable members of our communities: opioid users facing reentry after incarceration.

Just as abstinence in the community brings a loss of tolerance to opioids, individuals who are incarcerated lose tolerance as well. Clinicians who treat patients with opioid use disorders (OUD) are accustomed to warning patients about the risk of returning to prior levels of use too quickly. Harm reduction strategies include using slowly, using with friends, and having naloxone on hand to prevent unintended overdose.

The risks of opioid use are magnified for those facing reentry; incarceration contributes to a loss of employment, social supports, and connection to care. Those changes can create an exceptionally stressful reentry period – one that places individuals at an acutely high risk of relapse and overdose. Within the first 2 years of release, an individual with a history of incarceration has a risk of death 3.5 times higher than that of someone in the general population. Within the first 2 weeks, those recently incarcerated are 129 times more likely to overdose on opioids and 12.7 times more likely to die than members of the general population.2

Treatment with MAT dramatically reduces deaths during this crucial period. In Rhode Island, for example, implementation of a corrections MAT program decreased all-cause death rates after release by an astonishing 60.5%.³ In England, large national studies have shown a similar 75% decrease in all-cause mortality within the first 4 weeks of release among individuals with OUD.⁴ In California, the counties with the highest overdose death rates are consistently those with fewer opioid treatment programs, which suggests that access to treatment is necessary to prolong the lives of those suffering from OUD.⁵ In-custody overdose deaths are quite rare, and access to MAT during incarceration has decreased in-custody deaths by 74%.⁶

Decreased opioid overdose deaths is not the only outcome of MAT. Pharmacotherapy for OUD also has been shown to increase treatment retention,⁷ reduce reincarceration,⁸ prevent communicable infections,⁹ and decrease use of other illicit substances.¹⁰ The provision of MAT also has been shown to be cost effective.¹¹

Despite those benefits, as of 2017, only 30 out of 5,100 jails and prisons in the United States provided treatment with methadone or buprenorphine.¹² When individuals on maintenance therapy are incarcerated, most correctional facilities force them to taper and discontinue those medications. This practice can cause distressing withdrawal symptoms and actively increase the risk of death for these individuals.

Concerns related to the provision of MAT, and specifically buprenorphine, in the correctional health setting often are related to diversion. Although safe administration of opioid full and partial agonists is a priority, recent literature has suggested that buprenorphine is not a medication frequently used for euphoric properties. In fact, the literature suggests that individuals using illicit buprenorphine primarily do so to treat withdrawal symptoms and that illicit use diminishes with access to formal treatment.^13,14

Another concern is that pharmacotherapy for OUD should not be used without adjunctive psychotherapies and social supports. While dual pharmacotherapy and psychotherapy is ideal, the American Society for Addiction Medicine 2020 National Practice Guidelines for the treatment of OUD state: “a patient’s decision to decline psychosocial treatment or the absence of available psychosocial treatment should not preclude or delay pharmacotherapy, with appropriate medication management.”¹⁵ Just as some patients wish to engage in mutual help or psychotherapeutic modalities only, some patients wish to engage only in psychopharmacologic interventions. Declaring one modality of treatment better, or worse, or more worthwhile is not borne out by the literature and often places clinicians’ preferences over the preferences of patients.

Individuals who suffer from substance use disorders are at high risk of incarceration, relapse, and overdose death. These patients also suffer from stigmatization from peers and health care workers alike, making the process of engaging in care incredibly burdensome. Because of the disease of addiction, many of our patients cannot envision a healthy future: a future with the potential for intimate relationships, meaningful community engagement, and a rich inner life. The provision of MAT is lifesaving and improves the chances of a successful reentry – an intuitive first step in a long, but worthwhile, journey.
 

References

1. Hedegaard H et al; National Center for Health Statistics. Drug overdose deaths in the United States, 1999–2018. NCHS Data Brief, 2020 Jan, No. 356.

2. Binswanger IA et al. N Engl J Med. 2007;356:157-65.

3. Green TC et al. JAMA Psychiatry. 2018;75(4):405-7.

4. Marsden J et al. Addiction. 2017;112(8):1408-18.

5. Joshi V and Urada D. State Targeted Response to the Opioid Crisis: California Strategic Plan. 2017 Aug 30.

6. Larney S et al. BMJ Open. 2014. doi: 10.1136/bmjopen-2013-004666.

7. Rich JD et al. Lancet. 2015;386(9991):350-9.

8. Deck D et al. J Addict Dis. 2009. 28(2):89-102.

9. MacArthur GJ et al. BMJ. 2012. doi: 10.1136/bmj.e5945.

10. Tsui J et al. J Subst Abuse Treat. 2019. 109:80-5.

11. Gisev N et al. Addiction. 2015 Dec;110(12):1975-84.

12. National Mental Health and Substance Use Policy Laboratory. “Use of Medication-Assisted Treatment for Opioid Use Disorder in Criminal Justice Settings.” HHS Publication No. PEP19-MATUSECJS. Rockville, Md.: Substance Abuse and Mental Health Services Administration, 2019.

13. Bazazi AR et al. J Addict Med. 2011;5(3):175-80.

14. Schuman-Olivier Z. et al. J Subst Abuse Treat. 2010 Jul;39(1):41-50.

15. Crotty K et al. J Addict Med. 2020;14(2)99-112.
 

Dr. Barnes is chief resident at San Mateo County Behavioral Health and Recovery Services in California. He disclosed no relevant financial relationships. Dr. Lenane is resident* at San Mateo County Behavioral Health and Recovery Services. He disclosed no relevant financial relationships. The opinions shared in this article represent the viewpoints of the authors and are not necessarily representative of the viewpoints or policies of their academic program or employer.

*This article was updated 7/9/2020.

Transitioning from parenteral bortezomib-based induction to all-oral ixazomib-lenalidomide-dexamethasone therapy increased proteasome inhibitor (PI)–based treatment adherence and duration, according to early results from a clinical trial designed to include patients representing the real-world U.S. multiple myeloma population.

The US MM-6 study was designed to evaluate a novel in-class therapy (iCT) transitioning approach from intravenous to oral treatment in the community-based setting with the aims of increasing PI-based treatment duration and adherence, maintaining health-related quality of life (HRQoL), and improving outcomes in a representative, real-world, community population of multiple myeloma patients, according to Sudhir Manda, MD, of Arizona Oncology/U.S. Oncology Research, Tucson, and colleagues.

Dr. Manda and colleagues reported on the early results of the US MM-6 trial (NCT03173092), which is a community-based, real-world, open-label, single-arm, phase 4 study of adult multiple myeloma patients who do not meet transplant-eligibility criteria, or for whom transplant would be delayed for 2 years or more, and who are receiving first-line bortezomib-based induction. All patients in the study had no evidence of progressive disease after three treatment cycles.

By the data cutoff for the reported analysis, 84 patients had been treated. The patients had a median age of 73 years; 49% were men; 15% black/African American; 10% Hispanic/Latino. A total of 62% of the patients remain on therapy, with a mean duration of total PI therapy of 10.1 months and of ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) of 7.3 months.

The overall response rate was 62% (complete response, 4%; very good partial response, 25%; partial response, 33%) after bortezomib-based induction and 70% (complete response, 26%; very good partial response, 29%; partial response, 15%) after induction to all-oral ixazomib-Rd.

“The use of this novel iCT approach from parenteral bortezomib-based to oral ixazomib-based therapy facilitates long-term PI-based treatment that is well tolerated in real-world, nontransplant [newly diagnosed multiple myeloma] patients,” according to Dr. Manda and colleagues. In addition, “preliminary findings indicate that the iCT approach results in promising efficacy and high medication adherence, with no adverse impact on patients’ HRQoL or treatment satisfaction.”

The study was sponsored by Millennium Pharmaceuticals. Four of the authors are employees of Millennium Pharmaceuticals and several authors disclosed relationships with various pharmaceutical companies, including Millennium Pharmaceuticals.

mlesney@mdedge.com

SOURCE: Manda S et al. Clin Lymphoma Myeloma Leuk. 2020 Jun 30. doi: 10.1016/j.clml.2020.06.024.

Transitioning from parenteral bortezomib-based induction to all-oral ixazomib-lenalidomide-dexamethasone therapy increased proteasome inhibitor (PI)–based treatment adherence and duration, according to early results from a clinical trial designed to include patients representing the real-world U.S. multiple myeloma population.

The US MM-6 study was designed to evaluate a novel in-class therapy (iCT) transitioning approach from intravenous to oral treatment in the community-based setting with the aims of increasing PI-based treatment duration and adherence, maintaining health-related quality of life (HRQoL), and improving outcomes in a representative, real-world, community population of multiple myeloma patients, according to Sudhir Manda, MD, of Arizona Oncology/U.S. Oncology Research, Tucson, and colleagues.

Dr. Manda and colleagues reported on the early results of the US MM-6 trial (NCT03173092), which is a community-based, real-world, open-label, single-arm, phase 4 study of adult multiple myeloma patients who do not meet transplant-eligibility criteria, or for whom transplant would be delayed for 2 years or more, and who are receiving first-line bortezomib-based induction. All patients in the study had no evidence of progressive disease after three treatment cycles.

By the data cutoff for the reported analysis, 84 patients had been treated. The patients had a median age of 73 years; 49% were men; 15% black/African American; 10% Hispanic/Latino. A total of 62% of the patients remain on therapy, with a mean duration of total PI therapy of 10.1 months and of ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) of 7.3 months.

The overall response rate was 62% (complete response, 4%; very good partial response, 25%; partial response, 33%) after bortezomib-based induction and 70% (complete response, 26%; very good partial response, 29%; partial response, 15%) after induction to all-oral ixazomib-Rd.

“The use of this novel iCT approach from parenteral bortezomib-based to oral ixazomib-based therapy facilitates long-term PI-based treatment that is well tolerated in real-world, nontransplant [newly diagnosed multiple myeloma] patients,” according to Dr. Manda and colleagues. In addition, “preliminary findings indicate that the iCT approach results in promising efficacy and high medication adherence, with no adverse impact on patients’ HRQoL or treatment satisfaction.”

The study was sponsored by Millennium Pharmaceuticals. Four of the authors are employees of Millennium Pharmaceuticals and several authors disclosed relationships with various pharmaceutical companies, including Millennium Pharmaceuticals.

mlesney@mdedge.com

SOURCE: Manda S et al. Clin Lymphoma Myeloma Leuk. 2020 Jun 30. doi: 10.1016/j.clml.2020.06.024.

Transitioning from parenteral bortezomib-based induction to all-oral ixazomib-lenalidomide-dexamethasone therapy increased proteasome inhibitor (PI)–based treatment adherence and duration, according to early results from a clinical trial designed to include patients representing the real-world U.S. multiple myeloma population.

The US MM-6 study was designed to evaluate a novel in-class therapy (iCT) transitioning approach from intravenous to oral treatment in the community-based setting with the aims of increasing PI-based treatment duration and adherence, maintaining health-related quality of life (HRQoL), and improving outcomes in a representative, real-world, community population of multiple myeloma patients, according to Sudhir Manda, MD, of Arizona Oncology/U.S. Oncology Research, Tucson, and colleagues.

Dr. Manda and colleagues reported on the early results of the US MM-6 trial (NCT03173092), which is a community-based, real-world, open-label, single-arm, phase 4 study of adult multiple myeloma patients who do not meet transplant-eligibility criteria, or for whom transplant would be delayed for 2 years or more, and who are receiving first-line bortezomib-based induction. All patients in the study had no evidence of progressive disease after three treatment cycles.

By the data cutoff for the reported analysis, 84 patients had been treated. The patients had a median age of 73 years; 49% were men; 15% black/African American; 10% Hispanic/Latino. A total of 62% of the patients remain on therapy, with a mean duration of total PI therapy of 10.1 months and of ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) of 7.3 months.

The overall response rate was 62% (complete response, 4%; very good partial response, 25%; partial response, 33%) after bortezomib-based induction and 70% (complete response, 26%; very good partial response, 29%; partial response, 15%) after induction to all-oral ixazomib-Rd.

“The use of this novel iCT approach from parenteral bortezomib-based to oral ixazomib-based therapy facilitates long-term PI-based treatment that is well tolerated in real-world, nontransplant [newly diagnosed multiple myeloma] patients,” according to Dr. Manda and colleagues. In addition, “preliminary findings indicate that the iCT approach results in promising efficacy and high medication adherence, with no adverse impact on patients’ HRQoL or treatment satisfaction.”

The study was sponsored by Millennium Pharmaceuticals. Four of the authors are employees of Millennium Pharmaceuticals and several authors disclosed relationships with various pharmaceutical companies, including Millennium Pharmaceuticals.

mlesney@mdedge.com

SOURCE: Manda S et al. Clin Lymphoma Myeloma Leuk. 2020 Jun 30. doi: 10.1016/j.clml.2020.06.024.

Extended use of corticosteroids for chronic inflammatory conditions puts patients at risk for serious adverse events (AEs), including cardiovascular disease, osteoporosis, cataracts, and diabetes. Now, a growing body of evidence suggests that even short bursts of these drugs are associated with serious risks.

Most recently, a population-based study of more than 2.6 million people found that taking corticosteroids for 14 days or less was associated with a substantially greater risk for gastrointestinal (GI) bleeding, sepsis, and heart failure, particularly within the first 30 days after therapy.

In the study, Tsung-Chieh Yao, MD, PhD, a professor in the division of allergy, asthma, and rheumatology in the department of pediatrics at Chang Gung Memorial Hospital in Taoyuan, Taiwan, and colleagues used a self-controlled case series to analyze data from Taiwan’s National Health Insurance Research Database of medical claims. They compared patients’ conditions in the period from 5 to 90 days before treatment to conditions from the periods from 5 to 30 days and from 31 to 90 days after therapy.

With a median duration of 3 days of treatment, the incidence rate ratios (IRRs) were 1.80 (95% confidence interval, 1.75-1.84) for GI bleeding, 1.99 (95% CI, 1.70-2.32) for sepsis, and 2.37 (95% CI, 2.13-2.63) for heart failure.

Given the findings, physicians should weigh the benefits against the risks of rare but potentially serious consequences of these anti-inflammatory drugs, according to the authors.

“After initiating patients on oral steroid bursts, physicians should be on the lookout for these severe adverse events, particularly within the first month after initiation of steroid therapy,” Dr. Yao said in an interview.

The findings were published online July 6 in Annals of Internal Medicine.

Of the 15,859,129 adult Asians in the Taiwanese database, the study included 2,623,327 adults aged 20-64 years who received single steroid bursts (14 days or less) between Jan. 1, 2013, and Dec. 31, 2015.

Almost 60% of the indications were for skin disorders, such as eczema and urticaria, and for respiratory tract infections, such as sinusitis and acute pharyngitis. Among specialties, dermatology, otolaryngology, family practice, internal medicine, and pediatrics accounted for 88% of prescriptions.

“Our findings are important for physicians and guideline developers because short-term use of oral corticosteroids is common and the real-world safety of this approach remains unclear,” the authors wrote. They acknowledged that the database did not provide information on such potential confounders as disease severity and lifestyle factors, nor did it include children and vulnerable individuals, which may limit the generalizability of the results.

The findings echo those of a 2017 cohort study conducted by researchers at the University of Michigan in Ann Arbor. That study, by Akbar K. Waljee, MD, assistant professor of gastroenterology, University of Michigan, Ann Arbor, and colleagues, included data on more than 1.5 million privately insured U.S. adults. The researchers included somewhat longer steroid bursts of up to 30 days’ duration and found that use of the drugs was associated with a greater than fivefold increased risk for sepsis, a more than threefold increased risk for venous thromboembolism, and a nearly twofold increased risk for fracture within 30 days of starting treatment.

Furthermore, the elevated risk persisted at prednisone-equivalent doses of less than 20 mg/d (IRR, 4.02 for sepsis, 3.61 for venous thromboembolism, and 1.83 for fracture; all P < .001).

The U.S. study also found that during the 3-year period from 2012 to 2014, more than 20% of patients were prescribed short-term oral corticosteroids.

“Both studies indicate that these short-term regimens are more common in the real world than was previously thought and are not risk free,” Dr. Yao said.

Recognition that corticosteroids are associated with adverse events has been building for decades, according to the authors of an editorial that accompanies the new study.

“However, we commonly use short corticosteroid ‘bursts’ for minor ailments despite a lack of evidence for meaningful benefit. We are now learning that bursts as short as 3 days may increase risk for serious AEs, even in young and healthy people,” wrote editorialists Beth I. Wallace, MD, of the Center for Clinical Management Research at the VA Ann Arbor Healthcare System and the Institute for Healthcare Policy and Innovation at Michigan Medicine, Ann Arbor, and Dr. Waljee, who led the 2017 study.

Dr. Wallace and Dr. Waljee drew parallels between corticosteroid bursts and other short-term regimens, such as of antibiotics and opiates, in which prescriber preference and sometimes patient pressure play a role. “All of these treatments have well-defined indications but can cause net harm when used. We can thus conceive of a corticosteroid stewardship model of targeted interventions that aims to reduce inappropriate prescribing,” they wrote.

In an interview, Dr. Wallace, a rheumatologist who prescribes oral steroids fairly frequently, noted that the Taiwan study is the first to investigate steroid bursts. “Up till now, these very short courses have flown under the radar. Clinicians very commonly prescribe short courses to help relieve symptoms of self-limited conditions like bronchitis, and we assume that because the exposure duration is short, the risks are low, especially for patients who are otherwise healthy.”

She warned that the data in the current study indicate that these short bursts – even at the lower end of the 1- to 2-week courses American physicians prescribe most often – carry small but real increases in risk for serious AEs. “And these increases were seen in young, healthy people, not just in people with preexisting conditions,” she said. “So, we might need to start thinking harder about how we are prescribing even these very short courses of steroids and try to use steroids only when their meaningful benefits really outweigh the risk.”

She noted that a patient with a chronic inflammatory condition such as rheumatoid arthritis may benefit substantially from short-term steroids to treat a disease flare. In that specific case, the benefits of short-term steroids may outweigh the risks, Dr. Wallace said.

But not everyone thinks a new strategy is needed. For Whitney A. High, MD, associate professor of dermatology and pathology at the University of Colorado at Denver, Aurora, the overprescribing of short-term corticosteroids is not a problem, and dermatologists are already exercising caution.

Bruce Jancin/MDedge News

“I only prescribe these drugs short term to, at a guess, about 1 in 40 patients and only when a patient is miserable and quality of life is being seriously affected,” he said in an interview. “And that’s something that can’t be measured in a database study like the one from Taiwan but only in a risk-benefit analysis,” he said.

Furthermore, dermatologists have other drugs and technologies in their armamentarium, including topical steroids with occlusion or with wet wraps, phototherapy, phosphodiesterase inhibitors, calcipotriene, methotrexate and other immunosuppressive agents, and biologics. “In fact, many of these agents are specifically referred to as steroid-sparing,” Dr. High said.

Nor does he experience much pressure from patients to prescribe these drugs. “While occasionally I may encounter a patient who places pressure on me for oral steroids, it’s probably not nearly as frequently as providers in other fields are pressured to prescribe antibiotics or narcotics,” he said.

According to the Taiwanese researchers, the next step is to conduct more studies, including clinical trials, to determine optimal use of corticosteroids by monitoring adverse events. In the meantime, for practitioners such as Dr. Wallace and Dr. High, there is ample evidence from several recent studies of the harms of short-term corticosteroids, whereas the benefits for patients with self-limiting conditions remain uncertain. “This and other studies like it quite appropriately remind providers to avoid oral steroids when they’re not necessary and to seek alternatives where possible,” Dr. High said.

The study was supported by the National Health Research Institutes of Taiwan, the Ministry of Science and Technology of Taiwan, the Chang Gung Medical Foundation, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH). Dr. Yao has disclosed no relevant financial relationships. Dr. Wu has received grants from GlaxoSmithKline outside the submitted work. The editorialists and Dr. High have disclosed no relevant financial relationships. Dr. Wallace received an NIH grant during the writing of the editorial.
 

A version of this article originally appeared on Medscape.com.

Extended use of corticosteroids for chronic inflammatory conditions puts patients at risk for serious adverse events (AEs), including cardiovascular disease, osteoporosis, cataracts, and diabetes. Now, a growing body of evidence suggests that even short bursts of these drugs are associated with serious risks.

Most recently, a population-based study of more than 2.6 million people found that taking corticosteroids for 14 days or less was associated with a substantially greater risk for gastrointestinal (GI) bleeding, sepsis, and heart failure, particularly within the first 30 days after therapy.

In the study, Tsung-Chieh Yao, MD, PhD, a professor in the division of allergy, asthma, and rheumatology in the department of pediatrics at Chang Gung Memorial Hospital in Taoyuan, Taiwan, and colleagues used a self-controlled case series to analyze data from Taiwan’s National Health Insurance Research Database of medical claims. They compared patients’ conditions in the period from 5 to 90 days before treatment to conditions from the periods from 5 to 30 days and from 31 to 90 days after therapy.

With a median duration of 3 days of treatment, the incidence rate ratios (IRRs) were 1.80 (95% confidence interval, 1.75-1.84) for GI bleeding, 1.99 (95% CI, 1.70-2.32) for sepsis, and 2.37 (95% CI, 2.13-2.63) for heart failure.

Given the findings, physicians should weigh the benefits against the risks of rare but potentially serious consequences of these anti-inflammatory drugs, according to the authors.

“After initiating patients on oral steroid bursts, physicians should be on the lookout for these severe adverse events, particularly within the first month after initiation of steroid therapy,” Dr. Yao said in an interview.

The findings were published online July 6 in Annals of Internal Medicine.

Of the 15,859,129 adult Asians in the Taiwanese database, the study included 2,623,327 adults aged 20-64 years who received single steroid bursts (14 days or less) between Jan. 1, 2013, and Dec. 31, 2015.

Almost 60% of the indications were for skin disorders, such as eczema and urticaria, and for respiratory tract infections, such as sinusitis and acute pharyngitis. Among specialties, dermatology, otolaryngology, family practice, internal medicine, and pediatrics accounted for 88% of prescriptions.

“Our findings are important for physicians and guideline developers because short-term use of oral corticosteroids is common and the real-world safety of this approach remains unclear,” the authors wrote. They acknowledged that the database did not provide information on such potential confounders as disease severity and lifestyle factors, nor did it include children and vulnerable individuals, which may limit the generalizability of the results.

The findings echo those of a 2017 cohort study conducted by researchers at the University of Michigan in Ann Arbor. That study, by Akbar K. Waljee, MD, assistant professor of gastroenterology, University of Michigan, Ann Arbor, and colleagues, included data on more than 1.5 million privately insured U.S. adults. The researchers included somewhat longer steroid bursts of up to 30 days’ duration and found that use of the drugs was associated with a greater than fivefold increased risk for sepsis, a more than threefold increased risk for venous thromboembolism, and a nearly twofold increased risk for fracture within 30 days of starting treatment.

Furthermore, the elevated risk persisted at prednisone-equivalent doses of less than 20 mg/d (IRR, 4.02 for sepsis, 3.61 for venous thromboembolism, and 1.83 for fracture; all P < .001).

The U.S. study also found that during the 3-year period from 2012 to 2014, more than 20% of patients were prescribed short-term oral corticosteroids.

“Both studies indicate that these short-term regimens are more common in the real world than was previously thought and are not risk free,” Dr. Yao said.

Recognition that corticosteroids are associated with adverse events has been building for decades, according to the authors of an editorial that accompanies the new study.

“However, we commonly use short corticosteroid ‘bursts’ for minor ailments despite a lack of evidence for meaningful benefit. We are now learning that bursts as short as 3 days may increase risk for serious AEs, even in young and healthy people,” wrote editorialists Beth I. Wallace, MD, of the Center for Clinical Management Research at the VA Ann Arbor Healthcare System and the Institute for Healthcare Policy and Innovation at Michigan Medicine, Ann Arbor, and Dr. Waljee, who led the 2017 study.

Dr. Wallace and Dr. Waljee drew parallels between corticosteroid bursts and other short-term regimens, such as of antibiotics and opiates, in which prescriber preference and sometimes patient pressure play a role. “All of these treatments have well-defined indications but can cause net harm when used. We can thus conceive of a corticosteroid stewardship model of targeted interventions that aims to reduce inappropriate prescribing,” they wrote.

In an interview, Dr. Wallace, a rheumatologist who prescribes oral steroids fairly frequently, noted that the Taiwan study is the first to investigate steroid bursts. “Up till now, these very short courses have flown under the radar. Clinicians very commonly prescribe short courses to help relieve symptoms of self-limited conditions like bronchitis, and we assume that because the exposure duration is short, the risks are low, especially for patients who are otherwise healthy.”

She warned that the data in the current study indicate that these short bursts – even at the lower end of the 1- to 2-week courses American physicians prescribe most often – carry small but real increases in risk for serious AEs. “And these increases were seen in young, healthy people, not just in people with preexisting conditions,” she said. “So, we might need to start thinking harder about how we are prescribing even these very short courses of steroids and try to use steroids only when their meaningful benefits really outweigh the risk.”

She noted that a patient with a chronic inflammatory condition such as rheumatoid arthritis may benefit substantially from short-term steroids to treat a disease flare. In that specific case, the benefits of short-term steroids may outweigh the risks, Dr. Wallace said.

But not everyone thinks a new strategy is needed. For Whitney A. High, MD, associate professor of dermatology and pathology at the University of Colorado at Denver, Aurora, the overprescribing of short-term corticosteroids is not a problem, and dermatologists are already exercising caution.

Bruce Jancin/MDedge News

“I only prescribe these drugs short term to, at a guess, about 1 in 40 patients and only when a patient is miserable and quality of life is being seriously affected,” he said in an interview. “And that’s something that can’t be measured in a database study like the one from Taiwan but only in a risk-benefit analysis,” he said.

Furthermore, dermatologists have other drugs and technologies in their armamentarium, including topical steroids with occlusion or with wet wraps, phototherapy, phosphodiesterase inhibitors, calcipotriene, methotrexate and other immunosuppressive agents, and biologics. “In fact, many of these agents are specifically referred to as steroid-sparing,” Dr. High said.

Nor does he experience much pressure from patients to prescribe these drugs. “While occasionally I may encounter a patient who places pressure on me for oral steroids, it’s probably not nearly as frequently as providers in other fields are pressured to prescribe antibiotics or narcotics,” he said.

According to the Taiwanese researchers, the next step is to conduct more studies, including clinical trials, to determine optimal use of corticosteroids by monitoring adverse events. In the meantime, for practitioners such as Dr. Wallace and Dr. High, there is ample evidence from several recent studies of the harms of short-term corticosteroids, whereas the benefits for patients with self-limiting conditions remain uncertain. “This and other studies like it quite appropriately remind providers to avoid oral steroids when they’re not necessary and to seek alternatives where possible,” Dr. High said.

The study was supported by the National Health Research Institutes of Taiwan, the Ministry of Science and Technology of Taiwan, the Chang Gung Medical Foundation, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH). Dr. Yao has disclosed no relevant financial relationships. Dr. Wu has received grants from GlaxoSmithKline outside the submitted work. The editorialists and Dr. High have disclosed no relevant financial relationships. Dr. Wallace received an NIH grant during the writing of the editorial.
 

A version of this article originally appeared on Medscape.com.

Extended use of corticosteroids for chronic inflammatory conditions puts patients at risk for serious adverse events (AEs), including cardiovascular disease, osteoporosis, cataracts, and diabetes. Now, a growing body of evidence suggests that even short bursts of these drugs are associated with serious risks.

Most recently, a population-based study of more than 2.6 million people found that taking corticosteroids for 14 days or less was associated with a substantially greater risk for gastrointestinal (GI) bleeding, sepsis, and heart failure, particularly within the first 30 days after therapy.

In the study, Tsung-Chieh Yao, MD, PhD, a professor in the division of allergy, asthma, and rheumatology in the department of pediatrics at Chang Gung Memorial Hospital in Taoyuan, Taiwan, and colleagues used a self-controlled case series to analyze data from Taiwan’s National Health Insurance Research Database of medical claims. They compared patients’ conditions in the period from 5 to 90 days before treatment to conditions from the periods from 5 to 30 days and from 31 to 90 days after therapy.

With a median duration of 3 days of treatment, the incidence rate ratios (IRRs) were 1.80 (95% confidence interval, 1.75-1.84) for GI bleeding, 1.99 (95% CI, 1.70-2.32) for sepsis, and 2.37 (95% CI, 2.13-2.63) for heart failure.

Given the findings, physicians should weigh the benefits against the risks of rare but potentially serious consequences of these anti-inflammatory drugs, according to the authors.

“After initiating patients on oral steroid bursts, physicians should be on the lookout for these severe adverse events, particularly within the first month after initiation of steroid therapy,” Dr. Yao said in an interview.

The findings were published online July 6 in Annals of Internal Medicine.

Of the 15,859,129 adult Asians in the Taiwanese database, the study included 2,623,327 adults aged 20-64 years who received single steroid bursts (14 days or less) between Jan. 1, 2013, and Dec. 31, 2015.

Almost 60% of the indications were for skin disorders, such as eczema and urticaria, and for respiratory tract infections, such as sinusitis and acute pharyngitis. Among specialties, dermatology, otolaryngology, family practice, internal medicine, and pediatrics accounted for 88% of prescriptions.

“Our findings are important for physicians and guideline developers because short-term use of oral corticosteroids is common and the real-world safety of this approach remains unclear,” the authors wrote. They acknowledged that the database did not provide information on such potential confounders as disease severity and lifestyle factors, nor did it include children and vulnerable individuals, which may limit the generalizability of the results.

The findings echo those of a 2017 cohort study conducted by researchers at the University of Michigan in Ann Arbor. That study, by Akbar K. Waljee, MD, assistant professor of gastroenterology, University of Michigan, Ann Arbor, and colleagues, included data on more than 1.5 million privately insured U.S. adults. The researchers included somewhat longer steroid bursts of up to 30 days’ duration and found that use of the drugs was associated with a greater than fivefold increased risk for sepsis, a more than threefold increased risk for venous thromboembolism, and a nearly twofold increased risk for fracture within 30 days of starting treatment.

Furthermore, the elevated risk persisted at prednisone-equivalent doses of less than 20 mg/d (IRR, 4.02 for sepsis, 3.61 for venous thromboembolism, and 1.83 for fracture; all P < .001).

The U.S. study also found that during the 3-year period from 2012 to 2014, more than 20% of patients were prescribed short-term oral corticosteroids.

“Both studies indicate that these short-term regimens are more common in the real world than was previously thought and are not risk free,” Dr. Yao said.

Recognition that corticosteroids are associated with adverse events has been building for decades, according to the authors of an editorial that accompanies the new study.

“However, we commonly use short corticosteroid ‘bursts’ for minor ailments despite a lack of evidence for meaningful benefit. We are now learning that bursts as short as 3 days may increase risk for serious AEs, even in young and healthy people,” wrote editorialists Beth I. Wallace, MD, of the Center for Clinical Management Research at the VA Ann Arbor Healthcare System and the Institute for Healthcare Policy and Innovation at Michigan Medicine, Ann Arbor, and Dr. Waljee, who led the 2017 study.

Dr. Wallace and Dr. Waljee drew parallels between corticosteroid bursts and other short-term regimens, such as of antibiotics and opiates, in which prescriber preference and sometimes patient pressure play a role. “All of these treatments have well-defined indications but can cause net harm when used. We can thus conceive of a corticosteroid stewardship model of targeted interventions that aims to reduce inappropriate prescribing,” they wrote.

In an interview, Dr. Wallace, a rheumatologist who prescribes oral steroids fairly frequently, noted that the Taiwan study is the first to investigate steroid bursts. “Up till now, these very short courses have flown under the radar. Clinicians very commonly prescribe short courses to help relieve symptoms of self-limited conditions like bronchitis, and we assume that because the exposure duration is short, the risks are low, especially for patients who are otherwise healthy.”

She warned that the data in the current study indicate that these short bursts – even at the lower end of the 1- to 2-week courses American physicians prescribe most often – carry small but real increases in risk for serious AEs. “And these increases were seen in young, healthy people, not just in people with preexisting conditions,” she said. “So, we might need to start thinking harder about how we are prescribing even these very short courses of steroids and try to use steroids only when their meaningful benefits really outweigh the risk.”

She noted that a patient with a chronic inflammatory condition such as rheumatoid arthritis may benefit substantially from short-term steroids to treat a disease flare. In that specific case, the benefits of short-term steroids may outweigh the risks, Dr. Wallace said.

But not everyone thinks a new strategy is needed. For Whitney A. High, MD, associate professor of dermatology and pathology at the University of Colorado at Denver, Aurora, the overprescribing of short-term corticosteroids is not a problem, and dermatologists are already exercising caution.

Bruce Jancin/MDedge News

“I only prescribe these drugs short term to, at a guess, about 1 in 40 patients and only when a patient is miserable and quality of life is being seriously affected,” he said in an interview. “And that’s something that can’t be measured in a database study like the one from Taiwan but only in a risk-benefit analysis,” he said.

Furthermore, dermatologists have other drugs and technologies in their armamentarium, including topical steroids with occlusion or with wet wraps, phototherapy, phosphodiesterase inhibitors, calcipotriene, methotrexate and other immunosuppressive agents, and biologics. “In fact, many of these agents are specifically referred to as steroid-sparing,” Dr. High said.

Nor does he experience much pressure from patients to prescribe these drugs. “While occasionally I may encounter a patient who places pressure on me for oral steroids, it’s probably not nearly as frequently as providers in other fields are pressured to prescribe antibiotics or narcotics,” he said.

According to the Taiwanese researchers, the next step is to conduct more studies, including clinical trials, to determine optimal use of corticosteroids by monitoring adverse events. In the meantime, for practitioners such as Dr. Wallace and Dr. High, there is ample evidence from several recent studies of the harms of short-term corticosteroids, whereas the benefits for patients with self-limiting conditions remain uncertain. “This and other studies like it quite appropriately remind providers to avoid oral steroids when they’re not necessary and to seek alternatives where possible,” Dr. High said.

The study was supported by the National Health Research Institutes of Taiwan, the Ministry of Science and Technology of Taiwan, the Chang Gung Medical Foundation, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH). Dr. Yao has disclosed no relevant financial relationships. Dr. Wu has received grants from GlaxoSmithKline outside the submitted work. The editorialists and Dr. High have disclosed no relevant financial relationships. Dr. Wallace received an NIH grant during the writing of the editorial.
 

A version of this article originally appeared on Medscape.com.

Chronic pain is common in veterans, and early engagement in pain treatment is recommended to forestall consequences of untreated pain, including depression, disability, and substance use disorders. The Veterans Health Administration (VHA) employs a stepped care model of pain treatment, with the majority of pain care based in primary care (step 1), and an array of specialty/multimodal treatment options made available at each step in the model for patients with more complex problems, or those who do not respond to more conservative interventions.¹

Recognizing the need for comprehensive pain care, the US Congress passed the Comprehensive Addiction and Recovery Act, 21 USC §1521 (2016), which included provisions for VHA facilities to offer multimodal pain treatment and to report the availability of pain care options at each step in the stepped care model.^2, With the passage of the Veterans Access, Choice, and Accountability Act of 2014, 38 USC §101 (2014) and now the MISSION Act of 2018, 38 USC §703 (2018) veterans whose VHA facilities are too distant, who require care unavailable at that facility, or who have to wait too long to receive care are eligible for treatment at either VHA or non-VHA facilities.³ These laws allocate the same pool of funds to both VHA and community care and thus create an incentive to engage veterans in care within the VHA network so the funds are not spent out of network.⁴

An opportunity to connect veterans with VHA care arises at specialized VHA Compensation and Pension (C&P) clinics during examinations that determine whether a veteran’s health conditions were caused or exacerbated by their military service. Veterans file claims with the US Department of Veterans Affairs (VA) Veterans Benefits Administration (VBA), which sends the patient to either a VHA facility or private practitioners for these examinations. Although the number of examinations conducted each year is not available, there were 274,528 veterans newly awarded compensation in fiscal year 2018, and a substantial number of the total of 4,743,108 veterans with C&P awards had reevaluation examinations for at least 1 of their conditions during that year.⁵ Based largely on the compensation examination results, military service records, and medical records, veterans are granted a service-connected rating for conditions deemed related to military service. A service-connection rating between 0% and 100% is assigned by the VBA, with higher ratings indicating more impairment and, consequently, more financial compensation. Service-connection ratings also are used to decide which veterans are in the highest priority groups for receipt of VHA health care services and are exempt from copayments.

Although traditionally thought of as a forensic evaluation with no clinical purpose, the C&P examination process affords many opportunities to explain VHA care to veterans in distress who file claims.⁶ A randomized clinical trials (RCT) involving veterans with mental health claims and a second RCT including veterans with musculoskeletal claims each found that veterans use more VHA services if offered outreach at the time of the C&P examination.^7,8 In addition to clinical benefits, outreach around the time of C&P examinations also might mitigate the well documented adversarial aspects of the service-connection claims process.^6,9,10 Currently, such outreach is not part of routine VHA procedures. Ironically, it is the VBA and not VHA that contacts veterans who are awarded service-connection with information about their eligibility for VHA care based on their award.

Connecting veterans to pain treatment can involve clarifying eligibility for VHA care for veterans in whom eligibility is unknown, involving primary care providers (PCPs) who are the fulcrum of VHA pain care referrals, and motivating veterans to seek specific pain treatment modalities. Connecting veterans to treatment at the time of their compensation examinations also likely involves bidirectional cooperation between the specialized C&P clinics where veterans are examined and the clinics that provide treatment.

Relational coordination is a theoretical framework that can describe the horizontal relationships between different teams within the same medical facility. Relational coordination theorizes that communication between workgroups is related synergistically to the quality of relationships between workgroups. Relational coordination is better between workgroups that share goals and often have high levels of relational coordination, which is thought to be especially important when activities are ambiguous, require cooperation, and are conducted under time pressure.¹¹ High relational coordination also has been associated with high staff job satisfaction, high satisfaction with delivered services, and adherence to treatment guidelines.^12-14 An observational cohort study suggested that relational coordination can be improved by targeted interventions that bring workgroups together and facilitate intercommunication.¹⁵

To better understand referral and engagement for pain treatment at compensation examinations, VA staff from primary care, mental health, pain management, and C&P teams at the 8 VHA medical centers in New England were invited to complete a validated relational coordination survey.^11,16 A subset of invited staff participated in a semistructured interview about pain treatment referral practices within their medical centers.

Methods

Assessments were conducted as part of a mixed methods formative evaluation involving quantitative and qualitative methods for a clinical trial at the 8 VHA medical centers in New England. The trial is testing an intervention in which veterans presenting for service-connection examinations for musculoskeletal conditions receive brief counseling to engage them in nonopioid pain treatments. The VHA Central Institutional Review Board approved this formative evaluation and the clinical trial has begun (ClinicalTrials.gov NCT04062214).

Potential interviewees were involved in referrals to and provision of nonpharmacologic pain treatment and were identified by site investigators in the randomized trial. Identified interviewees were clinical and administrative staff belonging to VHA Primary Care, Pain Management, and Compensation and Pension clinics. A total of 83 staff were identified.

Semistructured Interviews

A subset of the 83 staff were invited to participate in a semistructured interview because their position impacted coordination of pain care at their facilities or they worked in C&P. Staff at a site were interviewed until no new themes emerged from additional interviews, and each of the 8 sites was represented. Interviews were conducted between June and August 2018. Standardized scripts describing the study and inviting participation in a semistructured interview were e-mailed to VA staff. At the time of the interview the study purpose was restated and consent for audiotaping was obtained. The interviews followed a guide designed to assess a relational coordination framework among various workgroups. The data in this manuscript were elicited by specific prompts concerning: (1) How veterans learn about pain care when they come through C&P; and (2) How staff in C&P communicate with treatment providers about veterans who have chronic pain. Each interview lasted about 30 minutes.

Relational Coordination Survey

All identified staff were invited to participate in a relational coordination survey. The survey was administered through VA REDCap. Survey invitations were e-mailed from REDCap to VA staff and included a description of the study and assurances of the confidentiality of data collected. Surveys took < 10 minutes to complete. To begin, respondents identified their primary workgroup (C&P, primary care, pain management, or administrative leadership or staff), secondary workgroup (if they were in > 1), and site. Respondents provided no other identifying information and were assured their responses would be confidential.

The survey consisted of 7 questions regarding beliefs about the quality of communication and interactions among workgroup members in obtaining a shared goal.¹¹ The shared goal in the survey used in this study was providing pain care services for veterans with musculoskeletal conditions. Using a 5-point Likert scale, the 7 questions concerned frequency, timeliness, and accuracy of communication; response to problems providing pain services; sharing goals; and knowledge and respect for respondent’s job function. Higher scores indicated better relational coordination among members of a workgroup. Using the survey’s 7 items, composite mean relational coordination scores were calculated for each of the 4 primary workgroups. To account for the possibility that a member rated their own workgroups, 2 scores were created for each workgroup; one included members of the workgroup and another excluded them.

Data Analysis

The audio-recorded semistructured interviews were transcribed and entered into Atlas.ti qualitative data analysis software. To identify cross-cutting themes, a semistructured telephone interview guide was developed by the qualitative study team that emphasized interrelationships between different clinical teams. The transcripts were then analyzed using the grounded theory approach, a systematic methodology to reduce themes from collected qualitative data. Two research staff read each transcript twice; first to familiarize themselves with the text and then, using open coding, to identify important concepts that emerged from the language and assign codes to segments of text. To ensure accuracy, researchers included suitable contextual information in the coding. Using the constant comparative method, research staff then met to examine the themes that emerged in the interviews, discuss and coalesce coding discrepancies, and compare perspectives.¹⁷

The composite score (mean of the 7 items and 95% CI) of the survey responses was analyzed to identify significant differences in coordination across the 4 workgroups. Analysis of variance (ANOVA) was used to examine each relational coordination score by respondents’ workgroup. Post hoc analyses examined relational coordination survey differences among the 4 respondent groups.

Results

Thirty-nine survey respondents participated in the semistructured interviews. C&P examiners expressed varying degrees of comfort with their role in extending access to pain care for veterans. Some of the examiners strongly believed that their role was purely forensic, and going beyond this forensic role to refer or recommend treatment to veterans would be a violation of their role to conduct a forensic examination. “We don’t have an ongoing therapeutic relationship with any of the patients,” a C&P examiner explained: “We see them once; they’re out the door. It’s forensic. We’re investigating the person as a claimant, we’re investigating it and using our tools to go and review information from 30, 40 years ago.”

Other examiners had a less strict approach for working with veterans in C&P, even though examiners are asked not to provide advice or therapy. One C&P examiner noted that because he “can’t watch people in pain,” during the examination this doctor recommends that patients go to the office that determines whether they are eligible for benefits and choose a PCP. Another C&P examiner concurred with this approach. “I certainly spend a little time with the veteran talking to them about their personal life, who they are, what they do, what they’ve done, what they’re going to do to kind of break the ice between us,” the second examiner explained. “At the end, I will make some suggestions to them. I’m comfortable doing that. I don’t know that everybody is.”

Many of the VHA providers we interviewed had little knowledge of the C&P process or whether C&P examiners had any role or responsibilities in referring veterans for pain care. Most VHA providers could not name any C&P examiners at their facility and were generally unfamiliar with the content of C&P examinations. One provider bluntly said, “I’ve never communicated with anyone in comp and pen [C&P].”

Another PCP also expressed concerns with referrals, suggesting that C&P and primary care “are totally separate and should remain separate,” the PCP explained. “My concern with getting referral from comp and pen is that is it then they’re seeking all sorts of treatment that they wouldn’t necessarily need or ask for otherwise.”

Conversely a different PCP had a positive outlook on how C&P examiners might help ease the transition into the VHA for veterans with pain, especially for newly discharged veterans. “Having comp and pen address these issues is really going to be helpful. I think it could be significant that the topic is introduced early on.”

Relational Coordination Survey

Relational coordination surveys were sent to 83 participants of whom 66 responded. Respondents were from C&P (n = 7), primary care (n = 16), pain medicine (n = 32), and administration (n = 11). Of the 66 respondents, 18 indicated a secondary workgroup. Respondents on 2 teams (primary/secondary) were primary care/administrative (n = 4), pain management/primary care (n = 4), primary care/pain management (n = 3), administrative/primary care (n = 3), and C&P/administrative (n = 1).

The relational coordination composite scores were lowest for C&P. This finding remained whether C&P staff surveys were included or removed from the C&P responses. As demonstrated by the 95% CI, when team members’ surveys were included, C&P scores (95% CI, 2.01-2.42) were significantly lower than the primary care (95% CI, 3.34-3.64) and pain management (95% CI, 3.61-3.96) groups. All the relational coordination composite scores were slightly lower when staff who described their own workgroup were removed (ie, respondents rated their own workgroups as having higher relational coordination than others did). Using the composite scores excluding same workgroup members, the composite scores of the C&P remained significantly lower than all 3 other workgroups (Table). Means values for each individual item in the C&P group were significantly less than all other group means for each item except for the question on responses to problems providing pain services (data not shown). On this item only, the mean C&P rating was > 3 (3.19), but this was still lower than the means of the primary care and pain management workgroups.

Further analyses were undertaken to understand the importance of stakeholders’ ratings of their own workgroup compared with ratings by others of that workgroup. A 1-way ANOVA of workgroup was conducted and displayed significant workgroup differences between member and nonmember relational coordination ratings on 3 of the 4 workgroup’s scores C&P (F = 5.75, 3, 62 df; P < .01) primary care (F = 4.30, 3, 62 df; P < .008) and pain management (F = 8.22, 3, 62 df; P < .001). Post hoc contrasts between the different workgroups doing the rating revealed: (1) significant differences in the assessment of the C&P workgroup between the C&P workgroup and both the primary care (P < .01) and pain management groups (P < .001) with C&P rating their own workgroup significantly higher; (2) a significant difference in the scoring of the primary care workgroup with the primary care group rating themselves significantly higher than the C&P group; and (3) significant differences in the scoring of the pain management workgroup with both pain management and primary care groups rating the pain management group significantly higher than the C&P group. The results were not substantially changed by removing the 18 respondents who identified themselves as being part of > 1 workgroup .

Discussion

Mixed methods revealed disparate viewpoints about the role of C&P in referring veterans to pain care services. Overall, C&P teams coordinated less with other workgroups than the other groups coordinated with each other, and the C&P clinics took only limited steps to engage veterans in VHA treatment. The relational coordination results appeared to be valid. The mean scores were near the middle of the relational coordination rating scale, with standard deviations indicating a range of responses. The lower relational coordination scores of the C&P group remained after removing stakeholders who were rating their own workgroup. Further support for the validity of the relational coordination survey results is that they were consistent with the reports of C&P clinic isolation in the semistructured interviews.

The interview data suggest that one reason the C&P teams had low relational coordination scores is that VA staff interpret the emphasis on evaluative rather than therapeutic examinations to preclude other attempts to engage veterans into VHA treatment, even though such treatment engagement is permitted within existing guidelines. VBA referrals for examinations say nothing, either way, about engaging veterans in VHA care. The relational coordination results suggest that an intervention that might increase treatment referrals from the C&P clinics would be to explain the (existing) policy allowing for outreach around the time of compensation examinations to VHA staff so this goal is clearly agreed-upon. Another approach to facilitating treatment engagement at the C&P examination is to use other interventions that have been associated with better relational coordination such as intergroup meetings, horizontal integration more generally, and an atmosphere is which people from different backgrounds feel empowered to speak frankly to each other.^15,18,19 An important linkage to forge is between C&P teams and the administrative workgroups responsible for verifying a veteran’s eligibility for VHA care and enrolling eligible veterans in VHA treatment. Having C&P clinicians who are familiar with the eligibility and treatment engagement processes would facilitate providing that information to veterans, without compromising the evaluative format of the compensation examination.

An interesting ancillary finding is that relational coordination ratings by members of 3 of the 4 workgroups were higher than ratings by other staff of that workgroup. A possible explanation for this finding is that workgroup members are more aware of the relational coordination efforts made by their own workgroup than those by other workgroups, and therefore rate their own workgroup higher. This also might be part of a broader self-aggrandizement heuristic that has been described in multiple domains.²⁰ Staff may apply this heuristic in reporting that their staff engage in more relational coordination, reflecting the social desirability of being cooperative.

There are simple facility-level interventions that would facilitate veterans access to care such as conducting C&P examinations for potentially treatment-eligible veterans at VHA facilities (vs conducted outside VHA) and having access to materials that explain the treatment options to veterans when they check in for their compensation examinations. The approach to C&P-based treatment engagement that was successfully employed in 2 clinical trials involved having counselors not connected with the C&P clinic contact veterans around the time of their compensation examination to explain VA treatment options and motivate veterans to pursue treatment.^8,9 This independent counselor approach is being evaluated in a larger study.

Limitations

These data are from a small number of VA staff evaluating veterans in a single region of the US. They do not show causation, and it is possible that relational coordination is not necessary for referrals from C&P clinics. Relational coordination might not be necessary when referral processes can be simply routinized with little need for communication.¹¹ However, other analyses in these clinics have found that pain treatment referrals in fact are not routinized, with substantial variability within and across institutions. Another possibility is that features that have been associated with less relational coordination, such as male gender and medical specialist guild, were disproportionately present in C&P clinics compared to the other clinics.²¹Finally, veterans may be eligible for priority VA care for reasons that do not involve service-connection claims (38 CFR § 17.37).

Conclusions

There have been public calls to improve the evaluation of service-connection claims such that this process includes approaches to engage veterans in treatment.²² Referring veterans to treatment when they come for C&P examinations will likely involve improving relational coordination between the C&P service and other parts of VHA. Nationwide, sites that integrate C&P more fully may have valuable lessons to impart about the benefits of such integration. An important step towards better relational coordination will be clarifying that engaging veterans in VHA care around the time of their C&P examinations is a facility-wide goal.

Acknowledgments

The authors thank Brian Linde and Efia James for their perspectives on C&P procedures. This work was supported by the Veterans Integrated Service Network 1 Mental Illness Research Education and Clinical Center (MIRECC) and National Institute of Health, National Center for Complementary and Integrative Health Project # 5UG3AT009758-02. (MIR, SM mPIs).

Chronic pain is common in veterans, and early engagement in pain treatment is recommended to forestall consequences of untreated pain, including depression, disability, and substance use disorders. The Veterans Health Administration (VHA) employs a stepped care model of pain treatment, with the majority of pain care based in primary care (step 1), and an array of specialty/multimodal treatment options made available at each step in the model for patients with more complex problems, or those who do not respond to more conservative interventions.¹

Recognizing the need for comprehensive pain care, the US Congress passed the Comprehensive Addiction and Recovery Act, 21 USC §1521 (2016), which included provisions for VHA facilities to offer multimodal pain treatment and to report the availability of pain care options at each step in the stepped care model.^2, With the passage of the Veterans Access, Choice, and Accountability Act of 2014, 38 USC §101 (2014) and now the MISSION Act of 2018, 38 USC §703 (2018) veterans whose VHA facilities are too distant, who require care unavailable at that facility, or who have to wait too long to receive care are eligible for treatment at either VHA or non-VHA facilities.³ These laws allocate the same pool of funds to both VHA and community care and thus create an incentive to engage veterans in care within the VHA network so the funds are not spent out of network.⁴

An opportunity to connect veterans with VHA care arises at specialized VHA Compensation and Pension (C&P) clinics during examinations that determine whether a veteran’s health conditions were caused or exacerbated by their military service. Veterans file claims with the US Department of Veterans Affairs (VA) Veterans Benefits Administration (VBA), which sends the patient to either a VHA facility or private practitioners for these examinations. Although the number of examinations conducted each year is not available, there were 274,528 veterans newly awarded compensation in fiscal year 2018, and a substantial number of the total of 4,743,108 veterans with C&P awards had reevaluation examinations for at least 1 of their conditions during that year.⁵ Based largely on the compensation examination results, military service records, and medical records, veterans are granted a service-connected rating for conditions deemed related to military service. A service-connection rating between 0% and 100% is assigned by the VBA, with higher ratings indicating more impairment and, consequently, more financial compensation. Service-connection ratings also are used to decide which veterans are in the highest priority groups for receipt of VHA health care services and are exempt from copayments.

Although traditionally thought of as a forensic evaluation with no clinical purpose, the C&P examination process affords many opportunities to explain VHA care to veterans in distress who file claims.⁶ A randomized clinical trials (RCT) involving veterans with mental health claims and a second RCT including veterans with musculoskeletal claims each found that veterans use more VHA services if offered outreach at the time of the C&P examination.^7,8 In addition to clinical benefits, outreach around the time of C&P examinations also might mitigate the well documented adversarial aspects of the service-connection claims process.^6,9,10 Currently, such outreach is not part of routine VHA procedures. Ironically, it is the VBA and not VHA that contacts veterans who are awarded service-connection with information about their eligibility for VHA care based on their award.

Connecting veterans to pain treatment can involve clarifying eligibility for VHA care for veterans in whom eligibility is unknown, involving primary care providers (PCPs) who are the fulcrum of VHA pain care referrals, and motivating veterans to seek specific pain treatment modalities. Connecting veterans to treatment at the time of their compensation examinations also likely involves bidirectional cooperation between the specialized C&P clinics where veterans are examined and the clinics that provide treatment.

Relational coordination is a theoretical framework that can describe the horizontal relationships between different teams within the same medical facility. Relational coordination theorizes that communication between workgroups is related synergistically to the quality of relationships between workgroups. Relational coordination is better between workgroups that share goals and often have high levels of relational coordination, which is thought to be especially important when activities are ambiguous, require cooperation, and are conducted under time pressure.¹¹ High relational coordination also has been associated with high staff job satisfaction, high satisfaction with delivered services, and adherence to treatment guidelines.^12-14 An observational cohort study suggested that relational coordination can be improved by targeted interventions that bring workgroups together and facilitate intercommunication.¹⁵

To better understand referral and engagement for pain treatment at compensation examinations, VA staff from primary care, mental health, pain management, and C&P teams at the 8 VHA medical centers in New England were invited to complete a validated relational coordination survey.^11,16 A subset of invited staff participated in a semistructured interview about pain treatment referral practices within their medical centers.

Methods

Assessments were conducted as part of a mixed methods formative evaluation involving quantitative and qualitative methods for a clinical trial at the 8 VHA medical centers in New England. The trial is testing an intervention in which veterans presenting for service-connection examinations for musculoskeletal conditions receive brief counseling to engage them in nonopioid pain treatments. The VHA Central Institutional Review Board approved this formative evaluation and the clinical trial has begun (ClinicalTrials.gov NCT04062214).

Potential interviewees were involved in referrals to and provision of nonpharmacologic pain treatment and were identified by site investigators in the randomized trial. Identified interviewees were clinical and administrative staff belonging to VHA Primary Care, Pain Management, and Compensation and Pension clinics. A total of 83 staff were identified.

Semistructured Interviews

A subset of the 83 staff were invited to participate in a semistructured interview because their position impacted coordination of pain care at their facilities or they worked in C&P. Staff at a site were interviewed until no new themes emerged from additional interviews, and each of the 8 sites was represented. Interviews were conducted between June and August 2018. Standardized scripts describing the study and inviting participation in a semistructured interview were e-mailed to VA staff. At the time of the interview the study purpose was restated and consent for audiotaping was obtained. The interviews followed a guide designed to assess a relational coordination framework among various workgroups. The data in this manuscript were elicited by specific prompts concerning: (1) How veterans learn about pain care when they come through C&P; and (2) How staff in C&P communicate with treatment providers about veterans who have chronic pain. Each interview lasted about 30 minutes.

Relational Coordination Survey

All identified staff were invited to participate in a relational coordination survey. The survey was administered through VA REDCap. Survey invitations were e-mailed from REDCap to VA staff and included a description of the study and assurances of the confidentiality of data collected. Surveys took < 10 minutes to complete. To begin, respondents identified their primary workgroup (C&P, primary care, pain management, or administrative leadership or staff), secondary workgroup (if they were in > 1), and site. Respondents provided no other identifying information and were assured their responses would be confidential.

The survey consisted of 7 questions regarding beliefs about the quality of communication and interactions among workgroup members in obtaining a shared goal.¹¹ The shared goal in the survey used in this study was providing pain care services for veterans with musculoskeletal conditions. Using a 5-point Likert scale, the 7 questions concerned frequency, timeliness, and accuracy of communication; response to problems providing pain services; sharing goals; and knowledge and respect for respondent’s job function. Higher scores indicated better relational coordination among members of a workgroup. Using the survey’s 7 items, composite mean relational coordination scores were calculated for each of the 4 primary workgroups. To account for the possibility that a member rated their own workgroups, 2 scores were created for each workgroup; one included members of the workgroup and another excluded them.

Data Analysis

The audio-recorded semistructured interviews were transcribed and entered into Atlas.ti qualitative data analysis software. To identify cross-cutting themes, a semistructured telephone interview guide was developed by the qualitative study team that emphasized interrelationships between different clinical teams. The transcripts were then analyzed using the grounded theory approach, a systematic methodology to reduce themes from collected qualitative data. Two research staff read each transcript twice; first to familiarize themselves with the text and then, using open coding, to identify important concepts that emerged from the language and assign codes to segments of text. To ensure accuracy, researchers included suitable contextual information in the coding. Using the constant comparative method, research staff then met to examine the themes that emerged in the interviews, discuss and coalesce coding discrepancies, and compare perspectives.¹⁷

The composite score (mean of the 7 items and 95% CI) of the survey responses was analyzed to identify significant differences in coordination across the 4 workgroups. Analysis of variance (ANOVA) was used to examine each relational coordination score by respondents’ workgroup. Post hoc analyses examined relational coordination survey differences among the 4 respondent groups.

Results

Thirty-nine survey respondents participated in the semistructured interviews. C&P examiners expressed varying degrees of comfort with their role in extending access to pain care for veterans. Some of the examiners strongly believed that their role was purely forensic, and going beyond this forensic role to refer or recommend treatment to veterans would be a violation of their role to conduct a forensic examination. “We don’t have an ongoing therapeutic relationship with any of the patients,” a C&P examiner explained: “We see them once; they’re out the door. It’s forensic. We’re investigating the person as a claimant, we’re investigating it and using our tools to go and review information from 30, 40 years ago.”

Other examiners had a less strict approach for working with veterans in C&P, even though examiners are asked not to provide advice or therapy. One C&P examiner noted that because he “can’t watch people in pain,” during the examination this doctor recommends that patients go to the office that determines whether they are eligible for benefits and choose a PCP. Another C&P examiner concurred with this approach. “I certainly spend a little time with the veteran talking to them about their personal life, who they are, what they do, what they’ve done, what they’re going to do to kind of break the ice between us,” the second examiner explained. “At the end, I will make some suggestions to them. I’m comfortable doing that. I don’t know that everybody is.”

Many of the VHA providers we interviewed had little knowledge of the C&P process or whether C&P examiners had any role or responsibilities in referring veterans for pain care. Most VHA providers could not name any C&P examiners at their facility and were generally unfamiliar with the content of C&P examinations. One provider bluntly said, “I’ve never communicated with anyone in comp and pen [C&P].”

Another PCP also expressed concerns with referrals, suggesting that C&P and primary care “are totally separate and should remain separate,” the PCP explained. “My concern with getting referral from comp and pen is that is it then they’re seeking all sorts of treatment that they wouldn’t necessarily need or ask for otherwise.”

Conversely a different PCP had a positive outlook on how C&P examiners might help ease the transition into the VHA for veterans with pain, especially for newly discharged veterans. “Having comp and pen address these issues is really going to be helpful. I think it could be significant that the topic is introduced early on.”

Relational Coordination Survey

Relational coordination surveys were sent to 83 participants of whom 66 responded. Respondents were from C&P (n = 7), primary care (n = 16), pain medicine (n = 32), and administration (n = 11). Of the 66 respondents, 18 indicated a secondary workgroup. Respondents on 2 teams (primary/secondary) were primary care/administrative (n = 4), pain management/primary care (n = 4), primary care/pain management (n = 3), administrative/primary care (n = 3), and C&P/administrative (n = 1).

The relational coordination composite scores were lowest for C&P. This finding remained whether C&P staff surveys were included or removed from the C&P responses. As demonstrated by the 95% CI, when team members’ surveys were included, C&P scores (95% CI, 2.01-2.42) were significantly lower than the primary care (95% CI, 3.34-3.64) and pain management (95% CI, 3.61-3.96) groups. All the relational coordination composite scores were slightly lower when staff who described their own workgroup were removed (ie, respondents rated their own workgroups as having higher relational coordination than others did). Using the composite scores excluding same workgroup members, the composite scores of the C&P remained significantly lower than all 3 other workgroups (Table). Means values for each individual item in the C&P group were significantly less than all other group means for each item except for the question on responses to problems providing pain services (data not shown). On this item only, the mean C&P rating was > 3 (3.19), but this was still lower than the means of the primary care and pain management workgroups.

Further analyses were undertaken to understand the importance of stakeholders’ ratings of their own workgroup compared with ratings by others of that workgroup. A 1-way ANOVA of workgroup was conducted and displayed significant workgroup differences between member and nonmember relational coordination ratings on 3 of the 4 workgroup’s scores C&P (F = 5.75, 3, 62 df; P < .01) primary care (F = 4.30, 3, 62 df; P < .008) and pain management (F = 8.22, 3, 62 df; P < .001). Post hoc contrasts between the different workgroups doing the rating revealed: (1) significant differences in the assessment of the C&P workgroup between the C&P workgroup and both the primary care (P < .01) and pain management groups (P < .001) with C&P rating their own workgroup significantly higher; (2) a significant difference in the scoring of the primary care workgroup with the primary care group rating themselves significantly higher than the C&P group; and (3) significant differences in the scoring of the pain management workgroup with both pain management and primary care groups rating the pain management group significantly higher than the C&P group. The results were not substantially changed by removing the 18 respondents who identified themselves as being part of > 1 workgroup .

Discussion

Mixed methods revealed disparate viewpoints about the role of C&P in referring veterans to pain care services. Overall, C&P teams coordinated less with other workgroups than the other groups coordinated with each other, and the C&P clinics took only limited steps to engage veterans in VHA treatment. The relational coordination results appeared to be valid. The mean scores were near the middle of the relational coordination rating scale, with standard deviations indicating a range of responses. The lower relational coordination scores of the C&P group remained after removing stakeholders who were rating their own workgroup. Further support for the validity of the relational coordination survey results is that they were consistent with the reports of C&P clinic isolation in the semistructured interviews.

The interview data suggest that one reason the C&P teams had low relational coordination scores is that VA staff interpret the emphasis on evaluative rather than therapeutic examinations to preclude other attempts to engage veterans into VHA treatment, even though such treatment engagement is permitted within existing guidelines. VBA referrals for examinations say nothing, either way, about engaging veterans in VHA care. The relational coordination results suggest that an intervention that might increase treatment referrals from the C&P clinics would be to explain the (existing) policy allowing for outreach around the time of compensation examinations to VHA staff so this goal is clearly agreed-upon. Another approach to facilitating treatment engagement at the C&P examination is to use other interventions that have been associated with better relational coordination such as intergroup meetings, horizontal integration more generally, and an atmosphere is which people from different backgrounds feel empowered to speak frankly to each other.^15,18,19 An important linkage to forge is between C&P teams and the administrative workgroups responsible for verifying a veteran’s eligibility for VHA care and enrolling eligible veterans in VHA treatment. Having C&P clinicians who are familiar with the eligibility and treatment engagement processes would facilitate providing that information to veterans, without compromising the evaluative format of the compensation examination.

An interesting ancillary finding is that relational coordination ratings by members of 3 of the 4 workgroups were higher than ratings by other staff of that workgroup. A possible explanation for this finding is that workgroup members are more aware of the relational coordination efforts made by their own workgroup than those by other workgroups, and therefore rate their own workgroup higher. This also might be part of a broader self-aggrandizement heuristic that has been described in multiple domains.²⁰ Staff may apply this heuristic in reporting that their staff engage in more relational coordination, reflecting the social desirability of being cooperative.

There are simple facility-level interventions that would facilitate veterans access to care such as conducting C&P examinations for potentially treatment-eligible veterans at VHA facilities (vs conducted outside VHA) and having access to materials that explain the treatment options to veterans when they check in for their compensation examinations. The approach to C&P-based treatment engagement that was successfully employed in 2 clinical trials involved having counselors not connected with the C&P clinic contact veterans around the time of their compensation examination to explain VA treatment options and motivate veterans to pursue treatment.^8,9 This independent counselor approach is being evaluated in a larger study.

Limitations

These data are from a small number of VA staff evaluating veterans in a single region of the US. They do not show causation, and it is possible that relational coordination is not necessary for referrals from C&P clinics. Relational coordination might not be necessary when referral processes can be simply routinized with little need for communication.¹¹ However, other analyses in these clinics have found that pain treatment referrals in fact are not routinized, with substantial variability within and across institutions. Another possibility is that features that have been associated with less relational coordination, such as male gender and medical specialist guild, were disproportionately present in C&P clinics compared to the other clinics.²¹Finally, veterans may be eligible for priority VA care for reasons that do not involve service-connection claims (38 CFR § 17.37).

Conclusions

There have been public calls to improve the evaluation of service-connection claims such that this process includes approaches to engage veterans in treatment.²² Referring veterans to treatment when they come for C&P examinations will likely involve improving relational coordination between the C&P service and other parts of VHA. Nationwide, sites that integrate C&P more fully may have valuable lessons to impart about the benefits of such integration. An important step towards better relational coordination will be clarifying that engaging veterans in VHA care around the time of their C&P examinations is a facility-wide goal.

Acknowledgments

The authors thank Brian Linde and Efia James for their perspectives on C&P procedures. This work was supported by the Veterans Integrated Service Network 1 Mental Illness Research Education and Clinical Center (MIRECC) and National Institute of Health, National Center for Complementary and Integrative Health Project # 5UG3AT009758-02. (MIR, SM mPIs).

Chronic pain is common in veterans, and early engagement in pain treatment is recommended to forestall consequences of untreated pain, including depression, disability, and substance use disorders. The Veterans Health Administration (VHA) employs a stepped care model of pain treatment, with the majority of pain care based in primary care (step 1), and an array of specialty/multimodal treatment options made available at each step in the model for patients with more complex problems, or those who do not respond to more conservative interventions.¹

Recognizing the need for comprehensive pain care, the US Congress passed the Comprehensive Addiction and Recovery Act, 21 USC §1521 (2016), which included provisions for VHA facilities to offer multimodal pain treatment and to report the availability of pain care options at each step in the stepped care model.^2, With the passage of the Veterans Access, Choice, and Accountability Act of 2014, 38 USC §101 (2014) and now the MISSION Act of 2018, 38 USC §703 (2018) veterans whose VHA facilities are too distant, who require care unavailable at that facility, or who have to wait too long to receive care are eligible for treatment at either VHA or non-VHA facilities.³ These laws allocate the same pool of funds to both VHA and community care and thus create an incentive to engage veterans in care within the VHA network so the funds are not spent out of network.⁴

An opportunity to connect veterans with VHA care arises at specialized VHA Compensation and Pension (C&P) clinics during examinations that determine whether a veteran’s health conditions were caused or exacerbated by their military service. Veterans file claims with the US Department of Veterans Affairs (VA) Veterans Benefits Administration (VBA), which sends the patient to either a VHA facility or private practitioners for these examinations. Although the number of examinations conducted each year is not available, there were 274,528 veterans newly awarded compensation in fiscal year 2018, and a substantial number of the total of 4,743,108 veterans with C&P awards had reevaluation examinations for at least 1 of their conditions during that year.⁵ Based largely on the compensation examination results, military service records, and medical records, veterans are granted a service-connected rating for conditions deemed related to military service. A service-connection rating between 0% and 100% is assigned by the VBA, with higher ratings indicating more impairment and, consequently, more financial compensation. Service-connection ratings also are used to decide which veterans are in the highest priority groups for receipt of VHA health care services and are exempt from copayments.

Although traditionally thought of as a forensic evaluation with no clinical purpose, the C&P examination process affords many opportunities to explain VHA care to veterans in distress who file claims.⁶ A randomized clinical trials (RCT) involving veterans with mental health claims and a second RCT including veterans with musculoskeletal claims each found that veterans use more VHA services if offered outreach at the time of the C&P examination.^7,8 In addition to clinical benefits, outreach around the time of C&P examinations also might mitigate the well documented adversarial aspects of the service-connection claims process.^6,9,10 Currently, such outreach is not part of routine VHA procedures. Ironically, it is the VBA and not VHA that contacts veterans who are awarded service-connection with information about their eligibility for VHA care based on their award.

Connecting veterans to pain treatment can involve clarifying eligibility for VHA care for veterans in whom eligibility is unknown, involving primary care providers (PCPs) who are the fulcrum of VHA pain care referrals, and motivating veterans to seek specific pain treatment modalities. Connecting veterans to treatment at the time of their compensation examinations also likely involves bidirectional cooperation between the specialized C&P clinics where veterans are examined and the clinics that provide treatment.

Relational coordination is a theoretical framework that can describe the horizontal relationships between different teams within the same medical facility. Relational coordination theorizes that communication between workgroups is related synergistically to the quality of relationships between workgroups. Relational coordination is better between workgroups that share goals and often have high levels of relational coordination, which is thought to be especially important when activities are ambiguous, require cooperation, and are conducted under time pressure.¹¹ High relational coordination also has been associated with high staff job satisfaction, high satisfaction with delivered services, and adherence to treatment guidelines.^12-14 An observational cohort study suggested that relational coordination can be improved by targeted interventions that bring workgroups together and facilitate intercommunication.¹⁵

To better understand referral and engagement for pain treatment at compensation examinations, VA staff from primary care, mental health, pain management, and C&P teams at the 8 VHA medical centers in New England were invited to complete a validated relational coordination survey.^11,16 A subset of invited staff participated in a semistructured interview about pain treatment referral practices within their medical centers.

Methods

Assessments were conducted as part of a mixed methods formative evaluation involving quantitative and qualitative methods for a clinical trial at the 8 VHA medical centers in New England. The trial is testing an intervention in which veterans presenting for service-connection examinations for musculoskeletal conditions receive brief counseling to engage them in nonopioid pain treatments. The VHA Central Institutional Review Board approved this formative evaluation and the clinical trial has begun (ClinicalTrials.gov NCT04062214).

Potential interviewees were involved in referrals to and provision of nonpharmacologic pain treatment and were identified by site investigators in the randomized trial. Identified interviewees were clinical and administrative staff belonging to VHA Primary Care, Pain Management, and Compensation and Pension clinics. A total of 83 staff were identified.

Semistructured Interviews

A subset of the 83 staff were invited to participate in a semistructured interview because their position impacted coordination of pain care at their facilities or they worked in C&P. Staff at a site were interviewed until no new themes emerged from additional interviews, and each of the 8 sites was represented. Interviews were conducted between June and August 2018. Standardized scripts describing the study and inviting participation in a semistructured interview were e-mailed to VA staff. At the time of the interview the study purpose was restated and consent for audiotaping was obtained. The interviews followed a guide designed to assess a relational coordination framework among various workgroups. The data in this manuscript were elicited by specific prompts concerning: (1) How veterans learn about pain care when they come through C&P; and (2) How staff in C&P communicate with treatment providers about veterans who have chronic pain. Each interview lasted about 30 minutes.

Relational Coordination Survey

All identified staff were invited to participate in a relational coordination survey. The survey was administered through VA REDCap. Survey invitations were e-mailed from REDCap to VA staff and included a description of the study and assurances of the confidentiality of data collected. Surveys took < 10 minutes to complete. To begin, respondents identified their primary workgroup (C&P, primary care, pain management, or administrative leadership or staff), secondary workgroup (if they were in > 1), and site. Respondents provided no other identifying information and were assured their responses would be confidential.

The survey consisted of 7 questions regarding beliefs about the quality of communication and interactions among workgroup members in obtaining a shared goal.¹¹ The shared goal in the survey used in this study was providing pain care services for veterans with musculoskeletal conditions. Using a 5-point Likert scale, the 7 questions concerned frequency, timeliness, and accuracy of communication; response to problems providing pain services; sharing goals; and knowledge and respect for respondent’s job function. Higher scores indicated better relational coordination among members of a workgroup. Using the survey’s 7 items, composite mean relational coordination scores were calculated for each of the 4 primary workgroups. To account for the possibility that a member rated their own workgroups, 2 scores were created for each workgroup; one included members of the workgroup and another excluded them.

Data Analysis

The audio-recorded semistructured interviews were transcribed and entered into Atlas.ti qualitative data analysis software. To identify cross-cutting themes, a semistructured telephone interview guide was developed by the qualitative study team that emphasized interrelationships between different clinical teams. The transcripts were then analyzed using the grounded theory approach, a systematic methodology to reduce themes from collected qualitative data. Two research staff read each transcript twice; first to familiarize themselves with the text and then, using open coding, to identify important concepts that emerged from the language and assign codes to segments of text. To ensure accuracy, researchers included suitable contextual information in the coding. Using the constant comparative method, research staff then met to examine the themes that emerged in the interviews, discuss and coalesce coding discrepancies, and compare perspectives.¹⁷

The composite score (mean of the 7 items and 95% CI) of the survey responses was analyzed to identify significant differences in coordination across the 4 workgroups. Analysis of variance (ANOVA) was used to examine each relational coordination score by respondents’ workgroup. Post hoc analyses examined relational coordination survey differences among the 4 respondent groups.

Results

Thirty-nine survey respondents participated in the semistructured interviews. C&P examiners expressed varying degrees of comfort with their role in extending access to pain care for veterans. Some of the examiners strongly believed that their role was purely forensic, and going beyond this forensic role to refer or recommend treatment to veterans would be a violation of their role to conduct a forensic examination. “We don’t have an ongoing therapeutic relationship with any of the patients,” a C&P examiner explained: “We see them once; they’re out the door. It’s forensic. We’re investigating the person as a claimant, we’re investigating it and using our tools to go and review information from 30, 40 years ago.”

Other examiners had a less strict approach for working with veterans in C&P, even though examiners are asked not to provide advice or therapy. One C&P examiner noted that because he “can’t watch people in pain,” during the examination this doctor recommends that patients go to the office that determines whether they are eligible for benefits and choose a PCP. Another C&P examiner concurred with this approach. “I certainly spend a little time with the veteran talking to them about their personal life, who they are, what they do, what they’ve done, what they’re going to do to kind of break the ice between us,” the second examiner explained. “At the end, I will make some suggestions to them. I’m comfortable doing that. I don’t know that everybody is.”

Many of the VHA providers we interviewed had little knowledge of the C&P process or whether C&P examiners had any role or responsibilities in referring veterans for pain care. Most VHA providers could not name any C&P examiners at their facility and were generally unfamiliar with the content of C&P examinations. One provider bluntly said, “I’ve never communicated with anyone in comp and pen [C&P].”

Another PCP also expressed concerns with referrals, suggesting that C&P and primary care “are totally separate and should remain separate,” the PCP explained. “My concern with getting referral from comp and pen is that is it then they’re seeking all sorts of treatment that they wouldn’t necessarily need or ask for otherwise.”

Conversely a different PCP had a positive outlook on how C&P examiners might help ease the transition into the VHA for veterans with pain, especially for newly discharged veterans. “Having comp and pen address these issues is really going to be helpful. I think it could be significant that the topic is introduced early on.”

Relational Coordination Survey

Relational coordination surveys were sent to 83 participants of whom 66 responded. Respondents were from C&P (n = 7), primary care (n = 16), pain medicine (n = 32), and administration (n = 11). Of the 66 respondents, 18 indicated a secondary workgroup. Respondents on 2 teams (primary/secondary) were primary care/administrative (n = 4), pain management/primary care (n = 4), primary care/pain management (n = 3), administrative/primary care (n = 3), and C&P/administrative (n = 1).

The relational coordination composite scores were lowest for C&P. This finding remained whether C&P staff surveys were included or removed from the C&P responses. As demonstrated by the 95% CI, when team members’ surveys were included, C&P scores (95% CI, 2.01-2.42) were significantly lower than the primary care (95% CI, 3.34-3.64) and pain management (95% CI, 3.61-3.96) groups. All the relational coordination composite scores were slightly lower when staff who described their own workgroup were removed (ie, respondents rated their own workgroups as having higher relational coordination than others did). Using the composite scores excluding same workgroup members, the composite scores of the C&P remained significantly lower than all 3 other workgroups (Table). Means values for each individual item in the C&P group were significantly less than all other group means for each item except for the question on responses to problems providing pain services (data not shown). On this item only, the mean C&P rating was > 3 (3.19), but this was still lower than the means of the primary care and pain management workgroups.

Further analyses were undertaken to understand the importance of stakeholders’ ratings of their own workgroup compared with ratings by others of that workgroup. A 1-way ANOVA of workgroup was conducted and displayed significant workgroup differences between member and nonmember relational coordination ratings on 3 of the 4 workgroup’s scores C&P (F = 5.75, 3, 62 df; P < .01) primary care (F = 4.30, 3, 62 df; P < .008) and pain management (F = 8.22, 3, 62 df; P < .001). Post hoc contrasts between the different workgroups doing the rating revealed: (1) significant differences in the assessment of the C&P workgroup between the C&P workgroup and both the primary care (P < .01) and pain management groups (P < .001) with C&P rating their own workgroup significantly higher; (2) a significant difference in the scoring of the primary care workgroup with the primary care group rating themselves significantly higher than the C&P group; and (3) significant differences in the scoring of the pain management workgroup with both pain management and primary care groups rating the pain management group significantly higher than the C&P group. The results were not substantially changed by removing the 18 respondents who identified themselves as being part of > 1 workgroup .

Discussion

Mixed methods revealed disparate viewpoints about the role of C&P in referring veterans to pain care services. Overall, C&P teams coordinated less with other workgroups than the other groups coordinated with each other, and the C&P clinics took only limited steps to engage veterans in VHA treatment. The relational coordination results appeared to be valid. The mean scores were near the middle of the relational coordination rating scale, with standard deviations indicating a range of responses. The lower relational coordination scores of the C&P group remained after removing stakeholders who were rating their own workgroup. Further support for the validity of the relational coordination survey results is that they were consistent with the reports of C&P clinic isolation in the semistructured interviews.

The interview data suggest that one reason the C&P teams had low relational coordination scores is that VA staff interpret the emphasis on evaluative rather than therapeutic examinations to preclude other attempts to engage veterans into VHA treatment, even though such treatment engagement is permitted within existing guidelines. VBA referrals for examinations say nothing, either way, about engaging veterans in VHA care. The relational coordination results suggest that an intervention that might increase treatment referrals from the C&P clinics would be to explain the (existing) policy allowing for outreach around the time of compensation examinations to VHA staff so this goal is clearly agreed-upon. Another approach to facilitating treatment engagement at the C&P examination is to use other interventions that have been associated with better relational coordination such as intergroup meetings, horizontal integration more generally, and an atmosphere is which people from different backgrounds feel empowered to speak frankly to each other.^15,18,19 An important linkage to forge is between C&P teams and the administrative workgroups responsible for verifying a veteran’s eligibility for VHA care and enrolling eligible veterans in VHA treatment. Having C&P clinicians who are familiar with the eligibility and treatment engagement processes would facilitate providing that information to veterans, without compromising the evaluative format of the compensation examination.

An interesting ancillary finding is that relational coordination ratings by members of 3 of the 4 workgroups were higher than ratings by other staff of that workgroup. A possible explanation for this finding is that workgroup members are more aware of the relational coordination efforts made by their own workgroup than those by other workgroups, and therefore rate their own workgroup higher. This also might be part of a broader self-aggrandizement heuristic that has been described in multiple domains.²⁰ Staff may apply this heuristic in reporting that their staff engage in more relational coordination, reflecting the social desirability of being cooperative.

There are simple facility-level interventions that would facilitate veterans access to care such as conducting C&P examinations for potentially treatment-eligible veterans at VHA facilities (vs conducted outside VHA) and having access to materials that explain the treatment options to veterans when they check in for their compensation examinations. The approach to C&P-based treatment engagement that was successfully employed in 2 clinical trials involved having counselors not connected with the C&P clinic contact veterans around the time of their compensation examination to explain VA treatment options and motivate veterans to pursue treatment.^8,9 This independent counselor approach is being evaluated in a larger study.

Limitations

These data are from a small number of VA staff evaluating veterans in a single region of the US. They do not show causation, and it is possible that relational coordination is not necessary for referrals from C&P clinics. Relational coordination might not be necessary when referral processes can be simply routinized with little need for communication.¹¹ However, other analyses in these clinics have found that pain treatment referrals in fact are not routinized, with substantial variability within and across institutions. Another possibility is that features that have been associated with less relational coordination, such as male gender and medical specialist guild, were disproportionately present in C&P clinics compared to the other clinics.²¹Finally, veterans may be eligible for priority VA care for reasons that do not involve service-connection claims (38 CFR § 17.37).

Conclusions

There have been public calls to improve the evaluation of service-connection claims such that this process includes approaches to engage veterans in treatment.²² Referring veterans to treatment when they come for C&P examinations will likely involve improving relational coordination between the C&P service and other parts of VHA. Nationwide, sites that integrate C&P more fully may have valuable lessons to impart about the benefits of such integration. An important step towards better relational coordination will be clarifying that engaging veterans in VHA care around the time of their C&P examinations is a facility-wide goal.

Acknowledgments

The authors thank Brian Linde and Efia James for their perspectives on C&P procedures. This work was supported by the Veterans Integrated Service Network 1 Mental Illness Research Education and Clinical Center (MIRECC) and National Institute of Health, National Center for Complementary and Integrative Health Project # 5UG3AT009758-02. (MIR, SM mPIs).