Nearly half of patients in the general population who test positive for hepatitis C virus (HCV) do not have the disease, according to Dr. Anne Moorman and her associates.

From a sample of 22,359 National Health and Nutrition Examination Study participants, 479 people received positive HCV antibody test results from 2007 to 2012. Of this group, 477 participants underwent further follow-up testing using a recombinant immunoblot assay. RIBA testing confirmed positive test results for 323 participants, while 105 patients received negative test results and 49 received indeterminate test results.

Jarun011/Thinkstock

lfranki@frontlinemedcom.com

Nearly half of patients in the general population who test positive for hepatitis C virus (HCV) do not have the disease, according to Dr. Anne Moorman and her associates.

From a sample of 22,359 National Health and Nutrition Examination Study participants, 479 people received positive HCV antibody test results from 2007 to 2012. Of this group, 477 participants underwent further follow-up testing using a recombinant immunoblot assay. RIBA testing confirmed positive test results for 323 participants, while 105 patients received negative test results and 49 received indeterminate test results.

Jarun011/Thinkstock

lfranki@frontlinemedcom.com

Nearly half of patients in the general population who test positive for hepatitis C virus (HCV) do not have the disease, according to Dr. Anne Moorman and her associates.

From a sample of 22,359 National Health and Nutrition Examination Study participants, 479 people received positive HCV antibody test results from 2007 to 2012. Of this group, 477 participants underwent further follow-up testing using a recombinant immunoblot assay. RIBA testing confirmed positive test results for 323 participants, while 105 patients received negative test results and 49 received indeterminate test results.

Jarun011/Thinkstock

lfranki@frontlinemedcom.com

In extensive new clinical practice guidelines, the Endocrine Society and two others offer updated recommendations about the treatment of pediatric obesity. Among other things, the guidelines offer new insight into the role of genetics in childhood obesity, provide more extensive guidance regarding bariatric surgery in adolescents, and suggest that measurements of insulin concentrations aren’t useful barometers.

The guidelines also point to research gaps in several areas and call for more studies.

Why issue new guidelines now? “Eight years have passed since the last publication. We did a very thorough job, but there’s been an incredible amount of interest in child obesity, and more information is available,” lead author Dennis M. Styne, MD, professor of pediatrics and the Yocha Dehe endowed chair in pediatric endocrinology at the University of California at Davis, said in an interview. Indeed, recent years have produced hundreds of studies into pediatric obesity, he noted.

The 49-page guidelines are cosponsored by the European Society of Endocrinology and the Pediatric Endocrine Society (J Clin Endocrinol Metab. 2017 March;102[3]:1-49).

Pediatric obesity is of special interest to endocrinologists, Dr. Styne said. “While there’s interest from many specialists now, we are at the forefront of evaluation and treatment of complications like polycystic ovary syndrome, metabolic syndrome, dyslipidemia, and type 2 diabetes.”

The guidelines provide recommendations about a wide variety of obesity-related topics including screening, diagnosis, and treatment. The Endocrine Society commissioned two systematic reviews to support the guidelines: One examined longer randomized controlled trials into medication, surgery, lifestyle, and community-based intervention treatments. The other examined how changing body mass index levels corresponded to cardiometabolic changes.

Several updated areas in the guidelines should be of special interest to endocrinologists: guidance regarding the genetic causes of pediatric obesity, the use of weight-loss medication and surgery, and the roles of insulin tests and breast-feeding, according to Dr. Styne.

In regard to genetics, the guidelines note that research suggests 7% of patients with extreme pediatric obesity “may have rare chromosomal abnormalities and/or highly penetrant genetic mutations that drive their obesity. This percentage is likely to increase with newer methods for genetic testing.”

Dr. Styne calls this finding “remarkable.” As he put it, “we didn’t appreciate that so much in the past.”

The guidelines suggest genetic testing for patients who become obese before the age of 5 years, have a family history of extreme obesity, or show clinical signs of genetic obesity syndromes, especially extreme hyperphagia.

As for the most extreme treatments for the most obese children, the guidelines recommend against weight-loss medication outside of clinical trials and note that “increasing evidence” supports bariatric surgery in teens who haven’t been able to lose enough pounds through lifestyle modification. However, “the use of surgery requires experienced teams with resources for long-term follow-up.”

The guidelines also recommend against measuring serum insulin concentrations as part of pediatric screening for obesity. “A lot of people like to get insulin levels and think it tells them about the future of the child,” Dr. Styne said. “But it doesn’t work very well.”

In another area that reflects new information, the guidelines note that breast-feeding hasn’t been definitively shown to be effective in reducing childhood obesity. “The literature is contradictory,” Dr. Styne said, although he noted that breast-feeding still has many other benefits.

The guidelines point to research gaps in several areas, including the prevention and treatment of pediatric obesity. There’s also “uncharted territory” regarding how to “effectively transition to adult care, with continued necessary monitoring, support, and intervention.”

In regard to the best treatment programs, “we didn’t come up with an answer regarding overall effectiveness,” Dr. Styne said. “School- and community-based programs have promise, but I can’t give you the percentage of success.”

As for the overall picture of pediatric obesity in the United States, “we’re in a better situation than we were 8 years ago,” he said. “Everyone is talking about the problem, and when you talk to families, they’re more aware of it.”

Still, he said, the prevalence of obesity in kids is high, estimated at 17% of those aged 2-19 years in 2014. “That’s not a good place to be,” he said. “We still have to work harder.”

The Endocrine Society funded the guidelines. Dr. Styne reports ownership interests in Teva, Bristol Myers and Organovo. Other authors report various disclosures.

In extensive new clinical practice guidelines, the Endocrine Society and two others offer updated recommendations about the treatment of pediatric obesity. Among other things, the guidelines offer new insight into the role of genetics in childhood obesity, provide more extensive guidance regarding bariatric surgery in adolescents, and suggest that measurements of insulin concentrations aren’t useful barometers.

The guidelines also point to research gaps in several areas and call for more studies.

Why issue new guidelines now? “Eight years have passed since the last publication. We did a very thorough job, but there’s been an incredible amount of interest in child obesity, and more information is available,” lead author Dennis M. Styne, MD, professor of pediatrics and the Yocha Dehe endowed chair in pediatric endocrinology at the University of California at Davis, said in an interview. Indeed, recent years have produced hundreds of studies into pediatric obesity, he noted.

The 49-page guidelines are cosponsored by the European Society of Endocrinology and the Pediatric Endocrine Society (J Clin Endocrinol Metab. 2017 March;102[3]:1-49).

Pediatric obesity is of special interest to endocrinologists, Dr. Styne said. “While there’s interest from many specialists now, we are at the forefront of evaluation and treatment of complications like polycystic ovary syndrome, metabolic syndrome, dyslipidemia, and type 2 diabetes.”

The guidelines provide recommendations about a wide variety of obesity-related topics including screening, diagnosis, and treatment. The Endocrine Society commissioned two systematic reviews to support the guidelines: One examined longer randomized controlled trials into medication, surgery, lifestyle, and community-based intervention treatments. The other examined how changing body mass index levels corresponded to cardiometabolic changes.

Several updated areas in the guidelines should be of special interest to endocrinologists: guidance regarding the genetic causes of pediatric obesity, the use of weight-loss medication and surgery, and the roles of insulin tests and breast-feeding, according to Dr. Styne.

In regard to genetics, the guidelines note that research suggests 7% of patients with extreme pediatric obesity “may have rare chromosomal abnormalities and/or highly penetrant genetic mutations that drive their obesity. This percentage is likely to increase with newer methods for genetic testing.”

Dr. Styne calls this finding “remarkable.” As he put it, “we didn’t appreciate that so much in the past.”

The guidelines suggest genetic testing for patients who become obese before the age of 5 years, have a family history of extreme obesity, or show clinical signs of genetic obesity syndromes, especially extreme hyperphagia.

As for the most extreme treatments for the most obese children, the guidelines recommend against weight-loss medication outside of clinical trials and note that “increasing evidence” supports bariatric surgery in teens who haven’t been able to lose enough pounds through lifestyle modification. However, “the use of surgery requires experienced teams with resources for long-term follow-up.”

The guidelines also recommend against measuring serum insulin concentrations as part of pediatric screening for obesity. “A lot of people like to get insulin levels and think it tells them about the future of the child,” Dr. Styne said. “But it doesn’t work very well.”

In another area that reflects new information, the guidelines note that breast-feeding hasn’t been definitively shown to be effective in reducing childhood obesity. “The literature is contradictory,” Dr. Styne said, although he noted that breast-feeding still has many other benefits.

The guidelines point to research gaps in several areas, including the prevention and treatment of pediatric obesity. There’s also “uncharted territory” regarding how to “effectively transition to adult care, with continued necessary monitoring, support, and intervention.”

In regard to the best treatment programs, “we didn’t come up with an answer regarding overall effectiveness,” Dr. Styne said. “School- and community-based programs have promise, but I can’t give you the percentage of success.”

As for the overall picture of pediatric obesity in the United States, “we’re in a better situation than we were 8 years ago,” he said. “Everyone is talking about the problem, and when you talk to families, they’re more aware of it.”

Still, he said, the prevalence of obesity in kids is high, estimated at 17% of those aged 2-19 years in 2014. “That’s not a good place to be,” he said. “We still have to work harder.”

The Endocrine Society funded the guidelines. Dr. Styne reports ownership interests in Teva, Bristol Myers and Organovo. Other authors report various disclosures.

In extensive new clinical practice guidelines, the Endocrine Society and two others offer updated recommendations about the treatment of pediatric obesity. Among other things, the guidelines offer new insight into the role of genetics in childhood obesity, provide more extensive guidance regarding bariatric surgery in adolescents, and suggest that measurements of insulin concentrations aren’t useful barometers.

The guidelines also point to research gaps in several areas and call for more studies.

Why issue new guidelines now? “Eight years have passed since the last publication. We did a very thorough job, but there’s been an incredible amount of interest in child obesity, and more information is available,” lead author Dennis M. Styne, MD, professor of pediatrics and the Yocha Dehe endowed chair in pediatric endocrinology at the University of California at Davis, said in an interview. Indeed, recent years have produced hundreds of studies into pediatric obesity, he noted.

The 49-page guidelines are cosponsored by the European Society of Endocrinology and the Pediatric Endocrine Society (J Clin Endocrinol Metab. 2017 March;102[3]:1-49).

Pediatric obesity is of special interest to endocrinologists, Dr. Styne said. “While there’s interest from many specialists now, we are at the forefront of evaluation and treatment of complications like polycystic ovary syndrome, metabolic syndrome, dyslipidemia, and type 2 diabetes.”

The guidelines provide recommendations about a wide variety of obesity-related topics including screening, diagnosis, and treatment. The Endocrine Society commissioned two systematic reviews to support the guidelines: One examined longer randomized controlled trials into medication, surgery, lifestyle, and community-based intervention treatments. The other examined how changing body mass index levels corresponded to cardiometabolic changes.

Several updated areas in the guidelines should be of special interest to endocrinologists: guidance regarding the genetic causes of pediatric obesity, the use of weight-loss medication and surgery, and the roles of insulin tests and breast-feeding, according to Dr. Styne.

In regard to genetics, the guidelines note that research suggests 7% of patients with extreme pediatric obesity “may have rare chromosomal abnormalities and/or highly penetrant genetic mutations that drive their obesity. This percentage is likely to increase with newer methods for genetic testing.”

Dr. Styne calls this finding “remarkable.” As he put it, “we didn’t appreciate that so much in the past.”

The guidelines suggest genetic testing for patients who become obese before the age of 5 years, have a family history of extreme obesity, or show clinical signs of genetic obesity syndromes, especially extreme hyperphagia.

As for the most extreme treatments for the most obese children, the guidelines recommend against weight-loss medication outside of clinical trials and note that “increasing evidence” supports bariatric surgery in teens who haven’t been able to lose enough pounds through lifestyle modification. However, “the use of surgery requires experienced teams with resources for long-term follow-up.”

The guidelines also recommend against measuring serum insulin concentrations as part of pediatric screening for obesity. “A lot of people like to get insulin levels and think it tells them about the future of the child,” Dr. Styne said. “But it doesn’t work very well.”

In another area that reflects new information, the guidelines note that breast-feeding hasn’t been definitively shown to be effective in reducing childhood obesity. “The literature is contradictory,” Dr. Styne said, although he noted that breast-feeding still has many other benefits.

The guidelines point to research gaps in several areas, including the prevention and treatment of pediatric obesity. There’s also “uncharted territory” regarding how to “effectively transition to adult care, with continued necessary monitoring, support, and intervention.”

In regard to the best treatment programs, “we didn’t come up with an answer regarding overall effectiveness,” Dr. Styne said. “School- and community-based programs have promise, but I can’t give you the percentage of success.”

As for the overall picture of pediatric obesity in the United States, “we’re in a better situation than we were 8 years ago,” he said. “Everyone is talking about the problem, and when you talk to families, they’re more aware of it.”

Still, he said, the prevalence of obesity in kids is high, estimated at 17% of those aged 2-19 years in 2014. “That’s not a good place to be,” he said. “We still have to work harder.”

The Endocrine Society funded the guidelines. Dr. Styne reports ownership interests in Teva, Bristol Myers and Organovo. Other authors report various disclosures.

HOLLYWOOD, FLA. – A three-parameter scoring system predicts which patients are likely to experience complications from surgery for a small bowel obstruction.

The new tool – dubbed FAS (Functional status, American Society of Anesthesiologists [ASA] classification, and Sepsis) – focuses mostly on preoperative functional status and the presence of preoperative sepsis. It’s as accurate as a time-consuming 10-item Margenthaler system published in 2006, which requires data on blood chemistry, neurologic status, and cardiac and lung function as well as age, sepsis, and preoperative functional measures.

Michele G. Sullivan/Frontline Medical News

• History of congestive heart failure

• Neurological deficit or stroke

• Chronic obstructive pulmonary disease

• Elevated white cell count

• Preoperative functional health status

• Surgery type

• Preoperative creatinine

• Wound classification

• ASA class

• Age

Dr. Asuzu and his mentor, Kevin Y. Pei, MD, FACS, wanted to come up with a more user-friendly risk assessment tool for patients undergoing open small bowel adhesiolysis. They focused on two measures of preoperative functional status: dependent vs. independent and ASA classification. Another measure – preoperative sepsis – estimated the impact of the patient’s current medical problem.

The tool was tested retrospectively in two independent cohorts extracted from the ACS National Surgery Quality Improvement Project (NSQIP) database. The initial discovery cohort comprised 6,036 patients; the replication cohort, 9,000. These patients had a mean age of 60 years and were relatively healthy, with low rates of congestive obstructive pulmonary disease, renal failure, cancer, bleeding disorders, and ascites. About half were taking antihypertensive medications and 5%, steroids.

Using multivariable regression, the authors developed a scoring system as follows:

• 6 points for each level of preoperative functional status (1 – independent, 2 – partially dependent, 3 – totally dependent)

• 6 points for each level of ASA classification (1 – no disturbance, 2 – mild disturbance, 3 – severe disturbance, 4 – life-threatening disturbance, and 5 – moribund state)

• 4 points for each level of perioperative sepsis (1 – systemic inflammatory response syndrome [SIRS], 2 – sepsis, 3 – septic shock)

In the discovery cohort, the three-item FAS tool was just as accurate as the Margenthaler tool, with an odds ratio of 1.11 vs 1.10 for any complication. The areas under the curve were 0.69 vs. 0.68. These results were virtually identical in the replication cohort.

With a combined total score of 32 as the cutoff, FAS yielded a specificity of 93% for predicting any complication and 92% for any of the six most common complications (ventilator dependence greater than 48 hours, pneumonia, superficial surgical site infection, postoperative sepsis, urinary tract infection, or unplanned intubation) in the replication cohort. The positive predictive value was 50% for any complication and 45% for the six most common complications, and the negative predictive values were 81% and nearly 85%, respectively.

“We are very pleased with how this performs,” Dr. Asuzu said in an interview. “It’s apparent that these three parameters are sufficient to tell us with a high level of specificity which patients could benefit from a more conservative approach. The next step is to prospectively validate it in a single center dataset.”

He said discriminating the most meaningful risk factors plainly showed that preoperative physical status is the best indicator of how well a patient will handle the surgery.

“It turns out that the biggest predictor of you how do after surgery is how you are doing before surgery. We can look at it as the how big the hit is, and the patient’s ability to take that hit. If their ability is already compromised, it’s a sign they might not do well.”

The “functional status” parameter may seem overly simplistic at first glance, he said. “But it really takes into account everything: the gout, the hypertension, the smoking, heart and respiratory and kidney function. All of this plays a role in functional status. I think this is why some of these more complex scores suffer. They’re not clear because there is so much overlap there.”

Dr. Asuzu had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

HOLLYWOOD, FLA. – A three-parameter scoring system predicts which patients are likely to experience complications from surgery for a small bowel obstruction.

The new tool – dubbed FAS (Functional status, American Society of Anesthesiologists [ASA] classification, and Sepsis) – focuses mostly on preoperative functional status and the presence of preoperative sepsis. It’s as accurate as a time-consuming 10-item Margenthaler system published in 2006, which requires data on blood chemistry, neurologic status, and cardiac and lung function as well as age, sepsis, and preoperative functional measures.

Michele G. Sullivan/Frontline Medical News

• History of congestive heart failure

• Neurological deficit or stroke

• Chronic obstructive pulmonary disease

• Elevated white cell count

• Preoperative functional health status

• Surgery type

• Preoperative creatinine

• Wound classification

• ASA class

• Age

Dr. Asuzu and his mentor, Kevin Y. Pei, MD, FACS, wanted to come up with a more user-friendly risk assessment tool for patients undergoing open small bowel adhesiolysis. They focused on two measures of preoperative functional status: dependent vs. independent and ASA classification. Another measure – preoperative sepsis – estimated the impact of the patient’s current medical problem.

The tool was tested retrospectively in two independent cohorts extracted from the ACS National Surgery Quality Improvement Project (NSQIP) database. The initial discovery cohort comprised 6,036 patients; the replication cohort, 9,000. These patients had a mean age of 60 years and were relatively healthy, with low rates of congestive obstructive pulmonary disease, renal failure, cancer, bleeding disorders, and ascites. About half were taking antihypertensive medications and 5%, steroids.

Using multivariable regression, the authors developed a scoring system as follows:

• 6 points for each level of preoperative functional status (1 – independent, 2 – partially dependent, 3 – totally dependent)

• 6 points for each level of ASA classification (1 – no disturbance, 2 – mild disturbance, 3 – severe disturbance, 4 – life-threatening disturbance, and 5 – moribund state)

• 4 points for each level of perioperative sepsis (1 – systemic inflammatory response syndrome [SIRS], 2 – sepsis, 3 – septic shock)

In the discovery cohort, the three-item FAS tool was just as accurate as the Margenthaler tool, with an odds ratio of 1.11 vs 1.10 for any complication. The areas under the curve were 0.69 vs. 0.68. These results were virtually identical in the replication cohort.

With a combined total score of 32 as the cutoff, FAS yielded a specificity of 93% for predicting any complication and 92% for any of the six most common complications (ventilator dependence greater than 48 hours, pneumonia, superficial surgical site infection, postoperative sepsis, urinary tract infection, or unplanned intubation) in the replication cohort. The positive predictive value was 50% for any complication and 45% for the six most common complications, and the negative predictive values were 81% and nearly 85%, respectively.

“We are very pleased with how this performs,” Dr. Asuzu said in an interview. “It’s apparent that these three parameters are sufficient to tell us with a high level of specificity which patients could benefit from a more conservative approach. The next step is to prospectively validate it in a single center dataset.”

He said discriminating the most meaningful risk factors plainly showed that preoperative physical status is the best indicator of how well a patient will handle the surgery.

“It turns out that the biggest predictor of you how do after surgery is how you are doing before surgery. We can look at it as the how big the hit is, and the patient’s ability to take that hit. If their ability is already compromised, it’s a sign they might not do well.”

The “functional status” parameter may seem overly simplistic at first glance, he said. “But it really takes into account everything: the gout, the hypertension, the smoking, heart and respiratory and kidney function. All of this plays a role in functional status. I think this is why some of these more complex scores suffer. They’re not clear because there is so much overlap there.”

Dr. Asuzu had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

HOLLYWOOD, FLA. – A three-parameter scoring system predicts which patients are likely to experience complications from surgery for a small bowel obstruction.

The new tool – dubbed FAS (Functional status, American Society of Anesthesiologists [ASA] classification, and Sepsis) – focuses mostly on preoperative functional status and the presence of preoperative sepsis. It’s as accurate as a time-consuming 10-item Margenthaler system published in 2006, which requires data on blood chemistry, neurologic status, and cardiac and lung function as well as age, sepsis, and preoperative functional measures.

Michele G. Sullivan/Frontline Medical News

• History of congestive heart failure

• Neurological deficit or stroke

• Chronic obstructive pulmonary disease

• Elevated white cell count

• Preoperative functional health status

• Surgery type

• Preoperative creatinine

• Wound classification

• ASA class

• Age

Dr. Asuzu and his mentor, Kevin Y. Pei, MD, FACS, wanted to come up with a more user-friendly risk assessment tool for patients undergoing open small bowel adhesiolysis. They focused on two measures of preoperative functional status: dependent vs. independent and ASA classification. Another measure – preoperative sepsis – estimated the impact of the patient’s current medical problem.

The tool was tested retrospectively in two independent cohorts extracted from the ACS National Surgery Quality Improvement Project (NSQIP) database. The initial discovery cohort comprised 6,036 patients; the replication cohort, 9,000. These patients had a mean age of 60 years and were relatively healthy, with low rates of congestive obstructive pulmonary disease, renal failure, cancer, bleeding disorders, and ascites. About half were taking antihypertensive medications and 5%, steroids.

Using multivariable regression, the authors developed a scoring system as follows:

• 6 points for each level of preoperative functional status (1 – independent, 2 – partially dependent, 3 – totally dependent)

• 6 points for each level of ASA classification (1 – no disturbance, 2 – mild disturbance, 3 – severe disturbance, 4 – life-threatening disturbance, and 5 – moribund state)

• 4 points for each level of perioperative sepsis (1 – systemic inflammatory response syndrome [SIRS], 2 – sepsis, 3 – septic shock)

In the discovery cohort, the three-item FAS tool was just as accurate as the Margenthaler tool, with an odds ratio of 1.11 vs 1.10 for any complication. The areas under the curve were 0.69 vs. 0.68. These results were virtually identical in the replication cohort.

With a combined total score of 32 as the cutoff, FAS yielded a specificity of 93% for predicting any complication and 92% for any of the six most common complications (ventilator dependence greater than 48 hours, pneumonia, superficial surgical site infection, postoperative sepsis, urinary tract infection, or unplanned intubation) in the replication cohort. The positive predictive value was 50% for any complication and 45% for the six most common complications, and the negative predictive values were 81% and nearly 85%, respectively.

“We are very pleased with how this performs,” Dr. Asuzu said in an interview. “It’s apparent that these three parameters are sufficient to tell us with a high level of specificity which patients could benefit from a more conservative approach. The next step is to prospectively validate it in a single center dataset.”

He said discriminating the most meaningful risk factors plainly showed that preoperative physical status is the best indicator of how well a patient will handle the surgery.

“It turns out that the biggest predictor of you how do after surgery is how you are doing before surgery. We can look at it as the how big the hit is, and the patient’s ability to take that hit. If their ability is already compromised, it’s a sign they might not do well.”

The “functional status” parameter may seem overly simplistic at first glance, he said. “But it really takes into account everything: the gout, the hypertension, the smoking, heart and respiratory and kidney function. All of this plays a role in functional status. I think this is why some of these more complex scores suffer. They’re not clear because there is so much overlap there.”

Dr. Asuzu had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – Incretin-based antidiabetic drugs do not appear to increase risk for pancreatic cancer, but the acute need for these drugs because of rapid worsening of type 2 diabetes may be a marker for early, occult pancreatic adenocarcinoma, investigators cautioned.

Results of a study of nearly 825,000 patients with type 2 diabetes in Belgium and northern Italy showed that patients who required a first-time prescription for an incretin-based antidiabetic drug had a 3.5-fold greater risk of being diagnosed with pancreatic cancer within 3 months, compared with patients who could be safely maintained on an oral noninsulin, nonincretin antidiabetic drug (NIAD), reported Alice Koechlin of the International Prevention Research Institute in Lyon, France, on behalf of coauthor Phillipe Autier, MD, also of the institute.

op@frontlinemedcom.com

AMSTERDAM – Incretin-based antidiabetic drugs do not appear to increase risk for pancreatic cancer, but the acute need for these drugs because of rapid worsening of type 2 diabetes may be a marker for early, occult pancreatic adenocarcinoma, investigators cautioned.

Results of a study of nearly 825,000 patients with type 2 diabetes in Belgium and northern Italy showed that patients who required a first-time prescription for an incretin-based antidiabetic drug had a 3.5-fold greater risk of being diagnosed with pancreatic cancer within 3 months, compared with patients who could be safely maintained on an oral noninsulin, nonincretin antidiabetic drug (NIAD), reported Alice Koechlin of the International Prevention Research Institute in Lyon, France, on behalf of coauthor Phillipe Autier, MD, also of the institute.

op@frontlinemedcom.com

AMSTERDAM – Incretin-based antidiabetic drugs do not appear to increase risk for pancreatic cancer, but the acute need for these drugs because of rapid worsening of type 2 diabetes may be a marker for early, occult pancreatic adenocarcinoma, investigators cautioned.

Results of a study of nearly 825,000 patients with type 2 diabetes in Belgium and northern Italy showed that patients who required a first-time prescription for an incretin-based antidiabetic drug had a 3.5-fold greater risk of being diagnosed with pancreatic cancer within 3 months, compared with patients who could be safely maintained on an oral noninsulin, nonincretin antidiabetic drug (NIAD), reported Alice Koechlin of the International Prevention Research Institute in Lyon, France, on behalf of coauthor Phillipe Autier, MD, also of the institute.

op@frontlinemedcom.com

Updated guidelines for the diagnosis and treatment of cystic fibrosis (CF) include two major changes.

The first important update is that clinicians use the latest classifications of the specific CF transmembrane conductance regulator (CFTR) gene mutations, from the Clinical and Functional TRanslation of CFTR (CFTR2) database, to aid with making a CF diagnosis in any patient, newborn to adult. The other of these changes relates to the chloride concentration level used to confirm CF diagnosis through a sweat test. Under the new guidelines, the sweat chloride threshold for “possible” CF or a CF-related disease was reduced to 30 mmol/L of chloride concentration from 40 mmol/L across all ages. The guidelines, written by an international team of collaborators and published by the Cystic Fibrosis Foundation, are available online in the Journal of Pediatrics (J Pediatr 2017 Feb;181(suppl):S4-S15.e1. doi: 10.1016/j.jpeds.2016.09.064).

Since its inception in 2008, the CFTR2 project has described 300 of the 2,000 known CF-related mutations and their various functional and clinical impacts. The project involves amassing phenotypic and genotypic information from patient registries to collect, quantify, and describe mutations reported in individuals with CF. Such mutations are categorized as CF-causing, carrying a variety of potential clinical consequences, non–cystic fibrosis causing, or unknown. The previous guidelines, written in 2008, relied on a 23-mutation panel from the American College of Medical Genetics and Genomics and the American Congress of Obstetricians and Gynecologists.

“We’ve more precisely defined what cystic fibrosis is,” Patrick R. Sosnay, MD, assistant professor of medicine at Johns Hopkins University, Baltimore, and coauthor of the guidelines, said in a statement. “The stakes in categorizing a mutation are particularly high. For example, claiming that a mutation 100% causes cystic fibrosis may affect people’s reproductive decisions if they believe their child will have the mutation.”

In the CFTR2 project, the “disease-liability” of each mutation is evaluated through a combination of sweat chloride and functional activity identified in cell-based systems, according to a supplement published simultaneously with the updated guidelines (J Pediatr 2017 Feb;181(suppl):S52-S57.e2. doi: 10.1016/j.jpeds.2016.09.068). Data from this project led to the discovery of a cohort of 746 persons diagnosed with CF despite sweat chloride levels less than 60 mmol/L. These findings were the basis for the guideline authors’ decision to lower the threshold of chloride concentration in sweat in order for an individual to be considered having a possible CF diagnosis, according to the supplement.

The guidelines include 27 approved consensus statements spanning four overlapping categories, and applying to screened and nonscreened populations; newborn screened populations and fetuses undergoing prenatal testing; infants with an uncertain diagnosis and designated as having either CFTR gene-related metabolic syndrome or being CF-screen positive, inconclusive diagnosis; and nonscreened patients who present with symptoms, including children before newborn screening implementation, those with false negative tests and older, nonscreened patients.

Although not specified in the consensus statements, the authors of a second supplement published simultaneously with the updated guidelines (J Pediatr 2017;181(suppl):S27-S32.e1. doi: 10.1016/j.jpeds.2016.09.063), wrote that they supported genotyping all individuals diagnosed with CF, even if physiologic tests establish the diagnosis, to better understand the disease’s genetic epidemiology and to refine future therapies. “If the identified mutations are known to be associated with variable outcomes, or have unknown consequence, that genotype may not result in a CF phenotype. In these cases, other tests of CFTR function may help,” this supplement’s authors concluded.

The updated guideline authors recommend avoiding the use of terms such as “atypical” or “nonclassical” CF, as there is no consensus on the specific taxonomy of CF, since the genetic data are still emerging.

When administering a newborn test, the guidelines warn that the heterogenous nature of newborn screening often leads to false positive results, thus the need for the sweat test. Although obtaining an adequate sweat specimen for chloride measurements can be difficult, the authors say it is possible, especially in full-term infants aged 1 month. Repeat sweat testing is recommended, as is nasal potential difference (NPD) and intestinal current measurement (ICM) in some cases.

Another change to the guidelines is that newborns with a high immunoreactive trypsinogen level and inconclusive CFTR functional and genetic testing may now be designated as having CFTR-related metabolic syndrome/CF screen positive inconclusive diagnosis (CRMS/CFSPID), instead of CFTR-related metabolic syndrome or CF screen positive, inconclusive diagnosis. Regarding changes to screening for CRMS/CFSPID, the older guidelines called for such an assessment by age 2 months, repeated every 6-12 months, while the new guidelines say their recommendation on the duration and frequency of follow-up “remains to be determined.”

The authors of the first supplement decry the lack of standardized CF diagnostic criteria for those diagnosed with CF outside of the neonatal period, and urge clinicians to rely on clinical evidence including organ pathologies typical in CF, such as bronchiectasis or pancreatic insufficiency, along with testing for the presence of CFTR dysfunction with sweat chloride testing, CFTR molecular genetic analysis, or CFTR physiologic tests.

In contrast, the second supplement states that “clinical suspicion should always take precedence” in making a CF diagnoses for individuals in this age group.

Dr. Sosnay and Philip M. Farrell, MD, PhD, a coauthor of the guidelines, received funds from the Cystic Fibrosis Foundation, where guideline coauthor Terry B. White, PhD, is an employee. Kris De Boeck, MD, a coauthor of the first supplement, receives funding from Vertex Pharmaceuticals, Ablynx, Aptalis, Galapagos, Gilead, Pharmaxis, and PTC Therapeutics. The guideline and supplements’ other authors have no disclosures.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

Updated guidelines for the diagnosis and treatment of cystic fibrosis (CF) include two major changes.

The first important update is that clinicians use the latest classifications of the specific CF transmembrane conductance regulator (CFTR) gene mutations, from the Clinical and Functional TRanslation of CFTR (CFTR2) database, to aid with making a CF diagnosis in any patient, newborn to adult. The other of these changes relates to the chloride concentration level used to confirm CF diagnosis through a sweat test. Under the new guidelines, the sweat chloride threshold for “possible” CF or a CF-related disease was reduced to 30 mmol/L of chloride concentration from 40 mmol/L across all ages. The guidelines, written by an international team of collaborators and published by the Cystic Fibrosis Foundation, are available online in the Journal of Pediatrics (J Pediatr 2017 Feb;181(suppl):S4-S15.e1. doi: 10.1016/j.jpeds.2016.09.064).

Since its inception in 2008, the CFTR2 project has described 300 of the 2,000 known CF-related mutations and their various functional and clinical impacts. The project involves amassing phenotypic and genotypic information from patient registries to collect, quantify, and describe mutations reported in individuals with CF. Such mutations are categorized as CF-causing, carrying a variety of potential clinical consequences, non–cystic fibrosis causing, or unknown. The previous guidelines, written in 2008, relied on a 23-mutation panel from the American College of Medical Genetics and Genomics and the American Congress of Obstetricians and Gynecologists.

“We’ve more precisely defined what cystic fibrosis is,” Patrick R. Sosnay, MD, assistant professor of medicine at Johns Hopkins University, Baltimore, and coauthor of the guidelines, said in a statement. “The stakes in categorizing a mutation are particularly high. For example, claiming that a mutation 100% causes cystic fibrosis may affect people’s reproductive decisions if they believe their child will have the mutation.”

In the CFTR2 project, the “disease-liability” of each mutation is evaluated through a combination of sweat chloride and functional activity identified in cell-based systems, according to a supplement published simultaneously with the updated guidelines (J Pediatr 2017 Feb;181(suppl):S52-S57.e2. doi: 10.1016/j.jpeds.2016.09.068). Data from this project led to the discovery of a cohort of 746 persons diagnosed with CF despite sweat chloride levels less than 60 mmol/L. These findings were the basis for the guideline authors’ decision to lower the threshold of chloride concentration in sweat in order for an individual to be considered having a possible CF diagnosis, according to the supplement.

The guidelines include 27 approved consensus statements spanning four overlapping categories, and applying to screened and nonscreened populations; newborn screened populations and fetuses undergoing prenatal testing; infants with an uncertain diagnosis and designated as having either CFTR gene-related metabolic syndrome or being CF-screen positive, inconclusive diagnosis; and nonscreened patients who present with symptoms, including children before newborn screening implementation, those with false negative tests and older, nonscreened patients.

Although not specified in the consensus statements, the authors of a second supplement published simultaneously with the updated guidelines (J Pediatr 2017;181(suppl):S27-S32.e1. doi: 10.1016/j.jpeds.2016.09.063), wrote that they supported genotyping all individuals diagnosed with CF, even if physiologic tests establish the diagnosis, to better understand the disease’s genetic epidemiology and to refine future therapies. “If the identified mutations are known to be associated with variable outcomes, or have unknown consequence, that genotype may not result in a CF phenotype. In these cases, other tests of CFTR function may help,” this supplement’s authors concluded.

The updated guideline authors recommend avoiding the use of terms such as “atypical” or “nonclassical” CF, as there is no consensus on the specific taxonomy of CF, since the genetic data are still emerging.

When administering a newborn test, the guidelines warn that the heterogenous nature of newborn screening often leads to false positive results, thus the need for the sweat test. Although obtaining an adequate sweat specimen for chloride measurements can be difficult, the authors say it is possible, especially in full-term infants aged 1 month. Repeat sweat testing is recommended, as is nasal potential difference (NPD) and intestinal current measurement (ICM) in some cases.

Another change to the guidelines is that newborns with a high immunoreactive trypsinogen level and inconclusive CFTR functional and genetic testing may now be designated as having CFTR-related metabolic syndrome/CF screen positive inconclusive diagnosis (CRMS/CFSPID), instead of CFTR-related metabolic syndrome or CF screen positive, inconclusive diagnosis. Regarding changes to screening for CRMS/CFSPID, the older guidelines called for such an assessment by age 2 months, repeated every 6-12 months, while the new guidelines say their recommendation on the duration and frequency of follow-up “remains to be determined.”

The authors of the first supplement decry the lack of standardized CF diagnostic criteria for those diagnosed with CF outside of the neonatal period, and urge clinicians to rely on clinical evidence including organ pathologies typical in CF, such as bronchiectasis or pancreatic insufficiency, along with testing for the presence of CFTR dysfunction with sweat chloride testing, CFTR molecular genetic analysis, or CFTR physiologic tests.

In contrast, the second supplement states that “clinical suspicion should always take precedence” in making a CF diagnoses for individuals in this age group.

Dr. Sosnay and Philip M. Farrell, MD, PhD, a coauthor of the guidelines, received funds from the Cystic Fibrosis Foundation, where guideline coauthor Terry B. White, PhD, is an employee. Kris De Boeck, MD, a coauthor of the first supplement, receives funding from Vertex Pharmaceuticals, Ablynx, Aptalis, Galapagos, Gilead, Pharmaxis, and PTC Therapeutics. The guideline and supplements’ other authors have no disclosures.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

Updated guidelines for the diagnosis and treatment of cystic fibrosis (CF) include two major changes.

The first important update is that clinicians use the latest classifications of the specific CF transmembrane conductance regulator (CFTR) gene mutations, from the Clinical and Functional TRanslation of CFTR (CFTR2) database, to aid with making a CF diagnosis in any patient, newborn to adult. The other of these changes relates to the chloride concentration level used to confirm CF diagnosis through a sweat test. Under the new guidelines, the sweat chloride threshold for “possible” CF or a CF-related disease was reduced to 30 mmol/L of chloride concentration from 40 mmol/L across all ages. The guidelines, written by an international team of collaborators and published by the Cystic Fibrosis Foundation, are available online in the Journal of Pediatrics (J Pediatr 2017 Feb;181(suppl):S4-S15.e1. doi: 10.1016/j.jpeds.2016.09.064).

Since its inception in 2008, the CFTR2 project has described 300 of the 2,000 known CF-related mutations and their various functional and clinical impacts. The project involves amassing phenotypic and genotypic information from patient registries to collect, quantify, and describe mutations reported in individuals with CF. Such mutations are categorized as CF-causing, carrying a variety of potential clinical consequences, non–cystic fibrosis causing, or unknown. The previous guidelines, written in 2008, relied on a 23-mutation panel from the American College of Medical Genetics and Genomics and the American Congress of Obstetricians and Gynecologists.

“We’ve more precisely defined what cystic fibrosis is,” Patrick R. Sosnay, MD, assistant professor of medicine at Johns Hopkins University, Baltimore, and coauthor of the guidelines, said in a statement. “The stakes in categorizing a mutation are particularly high. For example, claiming that a mutation 100% causes cystic fibrosis may affect people’s reproductive decisions if they believe their child will have the mutation.”

In the CFTR2 project, the “disease-liability” of each mutation is evaluated through a combination of sweat chloride and functional activity identified in cell-based systems, according to a supplement published simultaneously with the updated guidelines (J Pediatr 2017 Feb;181(suppl):S52-S57.e2. doi: 10.1016/j.jpeds.2016.09.068). Data from this project led to the discovery of a cohort of 746 persons diagnosed with CF despite sweat chloride levels less than 60 mmol/L. These findings were the basis for the guideline authors’ decision to lower the threshold of chloride concentration in sweat in order for an individual to be considered having a possible CF diagnosis, according to the supplement.

The guidelines include 27 approved consensus statements spanning four overlapping categories, and applying to screened and nonscreened populations; newborn screened populations and fetuses undergoing prenatal testing; infants with an uncertain diagnosis and designated as having either CFTR gene-related metabolic syndrome or being CF-screen positive, inconclusive diagnosis; and nonscreened patients who present with symptoms, including children before newborn screening implementation, those with false negative tests and older, nonscreened patients.

Although not specified in the consensus statements, the authors of a second supplement published simultaneously with the updated guidelines (J Pediatr 2017;181(suppl):S27-S32.e1. doi: 10.1016/j.jpeds.2016.09.063), wrote that they supported genotyping all individuals diagnosed with CF, even if physiologic tests establish the diagnosis, to better understand the disease’s genetic epidemiology and to refine future therapies. “If the identified mutations are known to be associated with variable outcomes, or have unknown consequence, that genotype may not result in a CF phenotype. In these cases, other tests of CFTR function may help,” this supplement’s authors concluded.

The updated guideline authors recommend avoiding the use of terms such as “atypical” or “nonclassical” CF, as there is no consensus on the specific taxonomy of CF, since the genetic data are still emerging.

When administering a newborn test, the guidelines warn that the heterogenous nature of newborn screening often leads to false positive results, thus the need for the sweat test. Although obtaining an adequate sweat specimen for chloride measurements can be difficult, the authors say it is possible, especially in full-term infants aged 1 month. Repeat sweat testing is recommended, as is nasal potential difference (NPD) and intestinal current measurement (ICM) in some cases.

Another change to the guidelines is that newborns with a high immunoreactive trypsinogen level and inconclusive CFTR functional and genetic testing may now be designated as having CFTR-related metabolic syndrome/CF screen positive inconclusive diagnosis (CRMS/CFSPID), instead of CFTR-related metabolic syndrome or CF screen positive, inconclusive diagnosis. Regarding changes to screening for CRMS/CFSPID, the older guidelines called for such an assessment by age 2 months, repeated every 6-12 months, while the new guidelines say their recommendation on the duration and frequency of follow-up “remains to be determined.”

The authors of the first supplement decry the lack of standardized CF diagnostic criteria for those diagnosed with CF outside of the neonatal period, and urge clinicians to rely on clinical evidence including organ pathologies typical in CF, such as bronchiectasis or pancreatic insufficiency, along with testing for the presence of CFTR dysfunction with sweat chloride testing, CFTR molecular genetic analysis, or CFTR physiologic tests.

In contrast, the second supplement states that “clinical suspicion should always take precedence” in making a CF diagnoses for individuals in this age group.

Dr. Sosnay and Philip M. Farrell, MD, PhD, a coauthor of the guidelines, received funds from the Cystic Fibrosis Foundation, where guideline coauthor Terry B. White, PhD, is an employee. Kris De Boeck, MD, a coauthor of the first supplement, receives funding from Vertex Pharmaceuticals, Ablynx, Aptalis, Galapagos, Gilead, Pharmaxis, and PTC Therapeutics. The guideline and supplements’ other authors have no disclosures.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

African Americans who have sickle cell trait show lower hemoglobin A_1c levels at any given concentration of fasting glucose than do those who don’t have sickle cell trait, according to a report published online Feb. 7 in JAMA.

This suggests that HbA_1c levels systematically underestimate glucose levels in black patients who carry the trait, who comprise approximately 10% of the African American population, said Mary E. Lacy, a doctoral candidate in the department of epidemiology, Brown University School of Public Health, Providence, R.I., and her associates.

The investigators examined a possible link between HbA_1c and sickle cell trait, which affects hemoglobin even though it doesn’t confer sickle cell disease, by analyzing data from two cohort studies involving African American adults. They focused on 4,620 participants who underwent serial HbA_1c and plasma glucose measurements during 5-25 years of follow-up. A total of 367 of them had sickle cell trait.

Analysis of 9,062 concurrent assessments of fasting glucose and HbA_1c plus 2,001 concurrent assessments of 2-hour postprandial glucose and HbA_1c showed mean HbA_1c was consistently significantly lower in people with sickle cell trait (mean level, 5.7%) than in those without the trait (mean level, 6%) despite similar glucose values.

“Our results suggest that currently accepted clinical measures of HbA_1c do not reflect recent past glycemia in the same way in African Americans with and without sickle cell trait,” Ms. Lacy and her associates said (JAMA 2017 Feb 7. doi: 10.1001/jama.2016.21035).

When used as a screen for prediabetes or diabetes, HbA_1c values “systematically underestimate long-term glucose levels,” which means a significant proportion of African American patients will miss the opportunity for treatment. In this study, “using standard clinical HbA_1c criteria to identify prediabetes and diabetes resulted in identifying 40% fewer cases of prediabetes and 48% fewer cases of diabetes among participants with sickle cell trait, compared to those without sickle cell trait,” the investigators noted.

“Because black people typically have a higher prevalence of diabetes and experience a number of diabetic complications at higher rates than [those of] white people, the cost of inaccurately assessing risk and treatment response is high,” they added.

The National Heart, Lung, and Blood Institute, the National Institute on Aging, the National Institute on Minority Health Disparities, the Providence VA Medical Center, and the National Institute of Diabetes and Digestive and Kidney Diseases supported the study. Ms. Lacy and her associates reported having no relevant financial disclosures.

African Americans who have sickle cell trait show lower hemoglobin A_1c levels at any given concentration of fasting glucose than do those who don’t have sickle cell trait, according to a report published online Feb. 7 in JAMA.

This suggests that HbA_1c levels systematically underestimate glucose levels in black patients who carry the trait, who comprise approximately 10% of the African American population, said Mary E. Lacy, a doctoral candidate in the department of epidemiology, Brown University School of Public Health, Providence, R.I., and her associates.

The investigators examined a possible link between HbA_1c and sickle cell trait, which affects hemoglobin even though it doesn’t confer sickle cell disease, by analyzing data from two cohort studies involving African American adults. They focused on 4,620 participants who underwent serial HbA_1c and plasma glucose measurements during 5-25 years of follow-up. A total of 367 of them had sickle cell trait.

Analysis of 9,062 concurrent assessments of fasting glucose and HbA_1c plus 2,001 concurrent assessments of 2-hour postprandial glucose and HbA_1c showed mean HbA_1c was consistently significantly lower in people with sickle cell trait (mean level, 5.7%) than in those without the trait (mean level, 6%) despite similar glucose values.

“Our results suggest that currently accepted clinical measures of HbA_1c do not reflect recent past glycemia in the same way in African Americans with and without sickle cell trait,” Ms. Lacy and her associates said (JAMA 2017 Feb 7. doi: 10.1001/jama.2016.21035).

When used as a screen for prediabetes or diabetes, HbA_1c values “systematically underestimate long-term glucose levels,” which means a significant proportion of African American patients will miss the opportunity for treatment. In this study, “using standard clinical HbA_1c criteria to identify prediabetes and diabetes resulted in identifying 40% fewer cases of prediabetes and 48% fewer cases of diabetes among participants with sickle cell trait, compared to those without sickle cell trait,” the investigators noted.

“Because black people typically have a higher prevalence of diabetes and experience a number of diabetic complications at higher rates than [those of] white people, the cost of inaccurately assessing risk and treatment response is high,” they added.

The National Heart, Lung, and Blood Institute, the National Institute on Aging, the National Institute on Minority Health Disparities, the Providence VA Medical Center, and the National Institute of Diabetes and Digestive and Kidney Diseases supported the study. Ms. Lacy and her associates reported having no relevant financial disclosures.

African Americans who have sickle cell trait show lower hemoglobin A_1c levels at any given concentration of fasting glucose than do those who don’t have sickle cell trait, according to a report published online Feb. 7 in JAMA.

This suggests that HbA_1c levels systematically underestimate glucose levels in black patients who carry the trait, who comprise approximately 10% of the African American population, said Mary E. Lacy, a doctoral candidate in the department of epidemiology, Brown University School of Public Health, Providence, R.I., and her associates.

The investigators examined a possible link between HbA_1c and sickle cell trait, which affects hemoglobin even though it doesn’t confer sickle cell disease, by analyzing data from two cohort studies involving African American adults. They focused on 4,620 participants who underwent serial HbA_1c and plasma glucose measurements during 5-25 years of follow-up. A total of 367 of them had sickle cell trait.

Analysis of 9,062 concurrent assessments of fasting glucose and HbA_1c plus 2,001 concurrent assessments of 2-hour postprandial glucose and HbA_1c showed mean HbA_1c was consistently significantly lower in people with sickle cell trait (mean level, 5.7%) than in those without the trait (mean level, 6%) despite similar glucose values.

“Our results suggest that currently accepted clinical measures of HbA_1c do not reflect recent past glycemia in the same way in African Americans with and without sickle cell trait,” Ms. Lacy and her associates said (JAMA 2017 Feb 7. doi: 10.1001/jama.2016.21035).

When used as a screen for prediabetes or diabetes, HbA_1c values “systematically underestimate long-term glucose levels,” which means a significant proportion of African American patients will miss the opportunity for treatment. In this study, “using standard clinical HbA_1c criteria to identify prediabetes and diabetes resulted in identifying 40% fewer cases of prediabetes and 48% fewer cases of diabetes among participants with sickle cell trait, compared to those without sickle cell trait,” the investigators noted.

“Because black people typically have a higher prevalence of diabetes and experience a number of diabetic complications at higher rates than [those of] white people, the cost of inaccurately assessing risk and treatment response is high,” they added.

The National Heart, Lung, and Blood Institute, the National Institute on Aging, the National Institute on Minority Health Disparities, the Providence VA Medical Center, and the National Institute of Diabetes and Digestive and Kidney Diseases supported the study. Ms. Lacy and her associates reported having no relevant financial disclosures.

Take-Home Points

• Prescription opioid abuse and overdose-related deaths are on the rise in the United States.
• Following Open Reduction Internal Fixation (ORIF) of a distal radius fracture (DRF), patients consumed an average of 14.6 opioid pills. We recommend prescribing no more than 15-20 opioid pills after DRF ORIF.
• There was no difference in opioid consumption between patients who underwent general anesthesia vs regional anesthesia.
• There was a significant trend towards less opioid consumption with increasing age.
• There was a trend towards increased opioid consumption in patients with worsening fracture type as well as in self-pay/Medicaid patients.

Over the past 2 decades, prescription opioid abuse in the United States has risen steadily.^1,2 Although use of opioid analgesics in the US far exceeds use in other countries, US patients do not report less pain or more satisfaction with pain relief.^3-5 Between 1999 and 2002, oxycodone prescriptions increased by 50%, fentanyl prescriptions by 150%, and morphine prescriptions by 60%.⁶ Furthermore, the Centers for Disease Control and Prevention (CDC) reported in 2012 that, for every 100 people in the United States, US physicians wrote a mean of 82.5 opioid prescriptions and 37.6 benzodiazepine prescriptions; in total, US clinicians wrote 259 million opioid prescriptions in 2012, enough for every adult to have a bottle.⁷ The increase in prescription opioid abuse, not surprisingly, has paralleled a 124% increase in opioid overdose-related deaths.⁸ Cicero and colleagues^2,9 recently found that, over the past 50 years, heroin use has dramatically shifted from being a problem mainly of urban centers and minorities toward one of older, suburban Caucasians with a previous history of prescription pain killer abuse. Deaths from prescription opioid overdoses now exceed deaths from heroin and cocaine overdoses combined.¹⁰ According to the CDC, emergency department visits related to nonmedical use of prescription opioid medications jumped 111% between 2004 and 2008.¹¹

Opioid analgesics are often prescribed for the management of musculoskeletal pain and injuries.^12-16 Orthopedic surgeons, who prescribe more opioids than physicians in any other surgical field, represent the third largest group of opioid prescribers, trailing only primary care physicians and internists, who far outnumber them.¹⁷ A study focused on opioid consumption after upper extremity surgery found that upper extremity surgeons tended to overprescribe opioids for postoperative analgesia.¹⁸ Many patients saved their remaining medication for later use and were never instructed on proper disposal. There is a developing consensus that opioid medication is not as safe and effective as once thought, and that a high-dose prescription or prolonged opioid therapy do not improve outcomes.¹⁹ In addition, patients may experience numerous opioid-associated adverse effects, including nausea, vomiting, constipation, lightheadedness, dizziness, blurred vision, headache, dry mouth, sweating, and itching.

In October 2012, patient satisfaction scores on the Hospital Consumer Assessment of Healthcare Providers and Systems started affecting Medicare reimbursements.²⁰ By 2017, up to 6% of Medicare reimbursement will be at risk, given the poor outcomes caused by uncontrolled pain.^21-24 The US healthcare culture has made it more important than ever for physicians to adequately manage postoperative pain while limiting opioid availability and the risk for abuse.

Distal radius fracture (DRF) open reduction and internal fixation (ORIF) is commonly performed by orthopedic surgeons and hand surgeons. Pain management and opioid consumption after DRF repair may be influenced by several variables. We conducted a study to investigate the impact of several clinical variables on postoperative opioid use; to test the hypothesis that post-DRF-ORIF opioid consumption would increase with worsening fracture classification and certain patient demographics; and to seek postoperative opioid consumption insights that would facilitate optimization of future opioid prescribing.

Materials and Methods

Institutional Review Board approval was obtained before initiation of the study. All outpatients who underwent DRF-ORIF (performed by 9 hand surgery fellowship-trained orthopedic surgeons) were consecutively enrolled over a 6-month period in 2014. All procedures were performed with a standard volar plating technique through a flexor carpi radialis approach. The postoperative rehabilitation protocol was standardized for all patients. Data collected on each patient included age, sex, payer type, fracture type, opioid prescribed, amount prescribed, amount consumed, reasons for stopping, adverse events, and any postoperative adjunctive pain medications. The data were taken from questionnaires completed by patients at their first visit within 2 weeks after surgery. Anesthesia type (general or regional) was noted as well. All fractures were classified by Dr. O’Neil using the AO/OTA (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association) classification of long-bone fractures based on preoperative radiographs.

Amount of opioid analgesic consumed was converted into morphine equivalents to adjust for the different opioids prescribed after surgery: oxycodone/acetaminophen or oxycodone equivalent, hydrocodone/acetaminophen or hydrocodone equivalent, and acetaminophen/codeine.

Patients were excluded from the study if their procedure was performed on an inpatient basis, if they sustained other injuries or fractures from their trauma, or if an adjunctive procedure (including carpal tunnel release) was performed during the DRF repair.

We used the Spearman rank correlation coefficient and a count data model to examine the relationship between opioid use and age. The Kruskal-Wallis test was used to examine the relationships between opioid use and payer type, anesthesia type, and fracture type.

Results

Of the 109 patients eligible for the study, 11 were excluded for incomplete postoperative questionnaires, leaving 98 patients (79 females, 19 males) for analysis. Mean age was 58 years (range, 13-92 years). Of the 98 patients, 45 received general anesthesia, and 53 received regional anesthesia with a single-shot peripheral nerve block before surgery and sedation perioperatively (Table).

Of the 98 study patients, 61 reported using over-the-counter adjunctive pain medications during the postoperative period, and 37 reported no use. Mean opioid consumption was 64.7 mg of morphine equivalents for the adjunctive medication users and 48.3 mg for the nonusers (P = .1947).

Demographic analysis revealed an inverse relationship between age and opioid use (Figure 2). The Spearman ρ between age and opioid consumption was –0.2958, which suggests decreased opioid use by older patients (P = .003).

Discussion

The US healthcare culture has elevated physicians’ responsibility in adequately and aggressively managing their patients’ pain experience. Moreover, reimbursement may be affected by patient satisfaction scores, which are partly predicated on pain control.^20-24 However, as rates of opioid use and abuse rise, it is important that physicians prescribe such medications judiciously. This is particularly germane to orthopedic surgeons, who prescribe more opioid analgesics than surgeons in any other field.¹⁷ Rodgers and colleagues¹⁸ found upper extremity surgeons, in particular, tended to overprescribe postoperative opioid analgesics. In the present study, we sought to identify the crucial risk factors that influence post-DRF-ORIF pain management and opioid consumption.

Mean postoperative opioid consumption (morphine equivalents) was 58.5 mg, roughly equivalent to 14.6 tabs of oxycodone/acetaminophen 5/325 mg, an opioid analgesic commonly used during the acute postoperative period. In addition, almost 70% of our patients required <75 mg of morphine equivalents, or <20 tabs of oxycodone/acetaminophen 5/325 mg. For upper extremity surgeons, these numbers may be better guides in determining the most appropriate amount of opioid to prescribe after DRF repair.

As for predicting levels of postoperative opioid medication, there was a significant trend toward less consumption with increasing age. Given this finding, surgeons prescribing for elderly patients should expect less opioid use. Regarding payer type, there was a trend toward more opioid use by self-pay/Medicaid patients; however, there were only 3 patients in this group. The situation in the study by Rodgers and colleagues¹⁸ is similar: Their finding that Medicaid patients consumed more pain pills after surgery was underpowered (only 5 patients in the group).

In the orthopedic community, support for use of regional anesthesia has been widespread for several reasons, including the belief that it reduces postoperative pain and therefore should reduce postoperative opioid consumption.²⁵ However, we found no significant difference in postoperative opioid consumption between patients who received general anesthesia (with and without local anesthesia) and patients who received regional anesthesia (nerve block). Mean opioid consumption was 57.93 mg in the general anesthesia group and 58.98 mg in the regional anesthesia group. However, this finding could have been confounded by the variability in success and operator dependence inherent in regional anesthesia. In addition, the anatomical location for the peripheral nerve block and anesthetic could have affected the efficacy of the block and played a role in postoperative opioid consumption.

In this study, we tested the hypothesis that there would be more postoperative opioid consumption with worsening fracture type. Although our results did not reach statistical significance, there was a trend toward increased opioid consumption in patients with a complete intra-articular fracture (AO/OTA class C) vs patients with a partial articular fracture (class B) or an extra-articular fracture (class A). In addition, patients with a partial articular fracture tended to use more postoperative opioids than patients with an extra-articular fracture. In short, postoperative opioid consumption tended to be higher with increasing articular involvement of the fracture.

This study was limited in that it relied on patient self-reporting. Given the social stigma attached to opioid use, patients may have underreported their postoperative opioid consumption, been affected by recall bias, or both. The study also did not control for preoperative opioid use or history of opioid or substance abuse. Chronic preoperative opioid consumption may have affected postoperative opioid use. Other patient-related factors, such as body mass index (BMI) and hepatorenal dysfunction, can create tremendous variability in opioid metabolism across a population. Such factors were not controlled for in this study and therefore may have affected its results. That could help explain why older patients, who are more likely to have lower BMI and less efficient organ function for opioid metabolism, had lower postoperative opioid consumption. In addition, although we excluded patients with concomitant injuries and procedures, we did not screen patients for concomitant complex regional pain syndrome, fibromyalgia, or other medical conditions that might have had a significant impact on postoperative pain management needs. Last, some findings, such as the relationship between opioid use and payer type, were underpowered: Although self-pay/Medicaid patients had higher postoperative opioid consumption, they were few in number. The same was true of the Medicaid patients in the study by Rodgers and colleagues.¹⁸Our results demonstrated that post-DRF-ORIF opioid consumption decreased with age and was independent of type of perioperative anesthesia. There was a trend toward more opioid consumption with both self- and Medicaid payment and worsening fracture classification. It has become more important than ever for orthopedic surgeons to adequately manage postoperative pain while limiting opioid availability and the risk for abuse. Surgeons must remain aware of the variables in their patients’ postoperative pain experience in order to better optimize prescribing patterns and provide a safe and effective postoperative pain regimen.

Am J Orthop. 2017;46(1):E35-E40. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Prescription opioid abuse and overdose-related deaths are on the rise in the United States.
• Following Open Reduction Internal Fixation (ORIF) of a distal radius fracture (DRF), patients consumed an average of 14.6 opioid pills. We recommend prescribing no more than 15-20 opioid pills after DRF ORIF.
• There was no difference in opioid consumption between patients who underwent general anesthesia vs regional anesthesia.
• There was a significant trend towards less opioid consumption with increasing age.
• There was a trend towards increased opioid consumption in patients with worsening fracture type as well as in self-pay/Medicaid patients.

Over the past 2 decades, prescription opioid abuse in the United States has risen steadily.^1,2 Although use of opioid analgesics in the US far exceeds use in other countries, US patients do not report less pain or more satisfaction with pain relief.^3-5 Between 1999 and 2002, oxycodone prescriptions increased by 50%, fentanyl prescriptions by 150%, and morphine prescriptions by 60%.⁶ Furthermore, the Centers for Disease Control and Prevention (CDC) reported in 2012 that, for every 100 people in the United States, US physicians wrote a mean of 82.5 opioid prescriptions and 37.6 benzodiazepine prescriptions; in total, US clinicians wrote 259 million opioid prescriptions in 2012, enough for every adult to have a bottle.⁷ The increase in prescription opioid abuse, not surprisingly, has paralleled a 124% increase in opioid overdose-related deaths.⁸ Cicero and colleagues^2,9 recently found that, over the past 50 years, heroin use has dramatically shifted from being a problem mainly of urban centers and minorities toward one of older, suburban Caucasians with a previous history of prescription pain killer abuse. Deaths from prescription opioid overdoses now exceed deaths from heroin and cocaine overdoses combined.¹⁰ According to the CDC, emergency department visits related to nonmedical use of prescription opioid medications jumped 111% between 2004 and 2008.¹¹

Opioid analgesics are often prescribed for the management of musculoskeletal pain and injuries.^12-16 Orthopedic surgeons, who prescribe more opioids than physicians in any other surgical field, represent the third largest group of opioid prescribers, trailing only primary care physicians and internists, who far outnumber them.¹⁷ A study focused on opioid consumption after upper extremity surgery found that upper extremity surgeons tended to overprescribe opioids for postoperative analgesia.¹⁸ Many patients saved their remaining medication for later use and were never instructed on proper disposal. There is a developing consensus that opioid medication is not as safe and effective as once thought, and that a high-dose prescription or prolonged opioid therapy do not improve outcomes.¹⁹ In addition, patients may experience numerous opioid-associated adverse effects, including nausea, vomiting, constipation, lightheadedness, dizziness, blurred vision, headache, dry mouth, sweating, and itching.

In October 2012, patient satisfaction scores on the Hospital Consumer Assessment of Healthcare Providers and Systems started affecting Medicare reimbursements.²⁰ By 2017, up to 6% of Medicare reimbursement will be at risk, given the poor outcomes caused by uncontrolled pain.^21-24 The US healthcare culture has made it more important than ever for physicians to adequately manage postoperative pain while limiting opioid availability and the risk for abuse.

Distal radius fracture (DRF) open reduction and internal fixation (ORIF) is commonly performed by orthopedic surgeons and hand surgeons. Pain management and opioid consumption after DRF repair may be influenced by several variables. We conducted a study to investigate the impact of several clinical variables on postoperative opioid use; to test the hypothesis that post-DRF-ORIF opioid consumption would increase with worsening fracture classification and certain patient demographics; and to seek postoperative opioid consumption insights that would facilitate optimization of future opioid prescribing.

Materials and Methods

Institutional Review Board approval was obtained before initiation of the study. All outpatients who underwent DRF-ORIF (performed by 9 hand surgery fellowship-trained orthopedic surgeons) were consecutively enrolled over a 6-month period in 2014. All procedures were performed with a standard volar plating technique through a flexor carpi radialis approach. The postoperative rehabilitation protocol was standardized for all patients. Data collected on each patient included age, sex, payer type, fracture type, opioid prescribed, amount prescribed, amount consumed, reasons for stopping, adverse events, and any postoperative adjunctive pain medications. The data were taken from questionnaires completed by patients at their first visit within 2 weeks after surgery. Anesthesia type (general or regional) was noted as well. All fractures were classified by Dr. O’Neil using the AO/OTA (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association) classification of long-bone fractures based on preoperative radiographs.

Amount of opioid analgesic consumed was converted into morphine equivalents to adjust for the different opioids prescribed after surgery: oxycodone/acetaminophen or oxycodone equivalent, hydrocodone/acetaminophen or hydrocodone equivalent, and acetaminophen/codeine.

Patients were excluded from the study if their procedure was performed on an inpatient basis, if they sustained other injuries or fractures from their trauma, or if an adjunctive procedure (including carpal tunnel release) was performed during the DRF repair.

We used the Spearman rank correlation coefficient and a count data model to examine the relationship between opioid use and age. The Kruskal-Wallis test was used to examine the relationships between opioid use and payer type, anesthesia type, and fracture type.

Results

Of the 109 patients eligible for the study, 11 were excluded for incomplete postoperative questionnaires, leaving 98 patients (79 females, 19 males) for analysis. Mean age was 58 years (range, 13-92 years). Of the 98 patients, 45 received general anesthesia, and 53 received regional anesthesia with a single-shot peripheral nerve block before surgery and sedation perioperatively (Table).

Of the 98 study patients, 61 reported using over-the-counter adjunctive pain medications during the postoperative period, and 37 reported no use. Mean opioid consumption was 64.7 mg of morphine equivalents for the adjunctive medication users and 48.3 mg for the nonusers (P = .1947).

Demographic analysis revealed an inverse relationship between age and opioid use (Figure 2). The Spearman ρ between age and opioid consumption was –0.2958, which suggests decreased opioid use by older patients (P = .003).

Discussion

The US healthcare culture has elevated physicians’ responsibility in adequately and aggressively managing their patients’ pain experience. Moreover, reimbursement may be affected by patient satisfaction scores, which are partly predicated on pain control.^20-24 However, as rates of opioid use and abuse rise, it is important that physicians prescribe such medications judiciously. This is particularly germane to orthopedic surgeons, who prescribe more opioid analgesics than surgeons in any other field.¹⁷ Rodgers and colleagues¹⁸ found upper extremity surgeons, in particular, tended to overprescribe postoperative opioid analgesics. In the present study, we sought to identify the crucial risk factors that influence post-DRF-ORIF pain management and opioid consumption.

Mean postoperative opioid consumption (morphine equivalents) was 58.5 mg, roughly equivalent to 14.6 tabs of oxycodone/acetaminophen 5/325 mg, an opioid analgesic commonly used during the acute postoperative period. In addition, almost 70% of our patients required <75 mg of morphine equivalents, or <20 tabs of oxycodone/acetaminophen 5/325 mg. For upper extremity surgeons, these numbers may be better guides in determining the most appropriate amount of opioid to prescribe after DRF repair.

As for predicting levels of postoperative opioid medication, there was a significant trend toward less consumption with increasing age. Given this finding, surgeons prescribing for elderly patients should expect less opioid use. Regarding payer type, there was a trend toward more opioid use by self-pay/Medicaid patients; however, there were only 3 patients in this group. The situation in the study by Rodgers and colleagues¹⁸ is similar: Their finding that Medicaid patients consumed more pain pills after surgery was underpowered (only 5 patients in the group).

In the orthopedic community, support for use of regional anesthesia has been widespread for several reasons, including the belief that it reduces postoperative pain and therefore should reduce postoperative opioid consumption.²⁵ However, we found no significant difference in postoperative opioid consumption between patients who received general anesthesia (with and without local anesthesia) and patients who received regional anesthesia (nerve block). Mean opioid consumption was 57.93 mg in the general anesthesia group and 58.98 mg in the regional anesthesia group. However, this finding could have been confounded by the variability in success and operator dependence inherent in regional anesthesia. In addition, the anatomical location for the peripheral nerve block and anesthetic could have affected the efficacy of the block and played a role in postoperative opioid consumption.

In this study, we tested the hypothesis that there would be more postoperative opioid consumption with worsening fracture type. Although our results did not reach statistical significance, there was a trend toward increased opioid consumption in patients with a complete intra-articular fracture (AO/OTA class C) vs patients with a partial articular fracture (class B) or an extra-articular fracture (class A). In addition, patients with a partial articular fracture tended to use more postoperative opioids than patients with an extra-articular fracture. In short, postoperative opioid consumption tended to be higher with increasing articular involvement of the fracture.

This study was limited in that it relied on patient self-reporting. Given the social stigma attached to opioid use, patients may have underreported their postoperative opioid consumption, been affected by recall bias, or both. The study also did not control for preoperative opioid use or history of opioid or substance abuse. Chronic preoperative opioid consumption may have affected postoperative opioid use. Other patient-related factors, such as body mass index (BMI) and hepatorenal dysfunction, can create tremendous variability in opioid metabolism across a population. Such factors were not controlled for in this study and therefore may have affected its results. That could help explain why older patients, who are more likely to have lower BMI and less efficient organ function for opioid metabolism, had lower postoperative opioid consumption. In addition, although we excluded patients with concomitant injuries and procedures, we did not screen patients for concomitant complex regional pain syndrome, fibromyalgia, or other medical conditions that might have had a significant impact on postoperative pain management needs. Last, some findings, such as the relationship between opioid use and payer type, were underpowered: Although self-pay/Medicaid patients had higher postoperative opioid consumption, they were few in number. The same was true of the Medicaid patients in the study by Rodgers and colleagues.¹⁸Our results demonstrated that post-DRF-ORIF opioid consumption decreased with age and was independent of type of perioperative anesthesia. There was a trend toward more opioid consumption with both self- and Medicaid payment and worsening fracture classification. It has become more important than ever for orthopedic surgeons to adequately manage postoperative pain while limiting opioid availability and the risk for abuse. Surgeons must remain aware of the variables in their patients’ postoperative pain experience in order to better optimize prescribing patterns and provide a safe and effective postoperative pain regimen.

Am J Orthop. 2017;46(1):E35-E40. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Prescription opioid abuse and overdose-related deaths are on the rise in the United States.
• Following Open Reduction Internal Fixation (ORIF) of a distal radius fracture (DRF), patients consumed an average of 14.6 opioid pills. We recommend prescribing no more than 15-20 opioid pills after DRF ORIF.
• There was no difference in opioid consumption between patients who underwent general anesthesia vs regional anesthesia.
• There was a significant trend towards less opioid consumption with increasing age.
• There was a trend towards increased opioid consumption in patients with worsening fracture type as well as in self-pay/Medicaid patients.

Over the past 2 decades, prescription opioid abuse in the United States has risen steadily.^1,2 Although use of opioid analgesics in the US far exceeds use in other countries, US patients do not report less pain or more satisfaction with pain relief.^3-5 Between 1999 and 2002, oxycodone prescriptions increased by 50%, fentanyl prescriptions by 150%, and morphine prescriptions by 60%.⁶ Furthermore, the Centers for Disease Control and Prevention (CDC) reported in 2012 that, for every 100 people in the United States, US physicians wrote a mean of 82.5 opioid prescriptions and 37.6 benzodiazepine prescriptions; in total, US clinicians wrote 259 million opioid prescriptions in 2012, enough for every adult to have a bottle.⁷ The increase in prescription opioid abuse, not surprisingly, has paralleled a 124% increase in opioid overdose-related deaths.⁸ Cicero and colleagues^2,9 recently found that, over the past 50 years, heroin use has dramatically shifted from being a problem mainly of urban centers and minorities toward one of older, suburban Caucasians with a previous history of prescription pain killer abuse. Deaths from prescription opioid overdoses now exceed deaths from heroin and cocaine overdoses combined.¹⁰ According to the CDC, emergency department visits related to nonmedical use of prescription opioid medications jumped 111% between 2004 and 2008.¹¹

Opioid analgesics are often prescribed for the management of musculoskeletal pain and injuries.^12-16 Orthopedic surgeons, who prescribe more opioids than physicians in any other surgical field, represent the third largest group of opioid prescribers, trailing only primary care physicians and internists, who far outnumber them.¹⁷ A study focused on opioid consumption after upper extremity surgery found that upper extremity surgeons tended to overprescribe opioids for postoperative analgesia.¹⁸ Many patients saved their remaining medication for later use and were never instructed on proper disposal. There is a developing consensus that opioid medication is not as safe and effective as once thought, and that a high-dose prescription or prolonged opioid therapy do not improve outcomes.¹⁹ In addition, patients may experience numerous opioid-associated adverse effects, including nausea, vomiting, constipation, lightheadedness, dizziness, blurred vision, headache, dry mouth, sweating, and itching.

In October 2012, patient satisfaction scores on the Hospital Consumer Assessment of Healthcare Providers and Systems started affecting Medicare reimbursements.²⁰ By 2017, up to 6% of Medicare reimbursement will be at risk, given the poor outcomes caused by uncontrolled pain.^21-24 The US healthcare culture has made it more important than ever for physicians to adequately manage postoperative pain while limiting opioid availability and the risk for abuse.

Distal radius fracture (DRF) open reduction and internal fixation (ORIF) is commonly performed by orthopedic surgeons and hand surgeons. Pain management and opioid consumption after DRF repair may be influenced by several variables. We conducted a study to investigate the impact of several clinical variables on postoperative opioid use; to test the hypothesis that post-DRF-ORIF opioid consumption would increase with worsening fracture classification and certain patient demographics; and to seek postoperative opioid consumption insights that would facilitate optimization of future opioid prescribing.

Materials and Methods

Institutional Review Board approval was obtained before initiation of the study. All outpatients who underwent DRF-ORIF (performed by 9 hand surgery fellowship-trained orthopedic surgeons) were consecutively enrolled over a 6-month period in 2014. All procedures were performed with a standard volar plating technique through a flexor carpi radialis approach. The postoperative rehabilitation protocol was standardized for all patients. Data collected on each patient included age, sex, payer type, fracture type, opioid prescribed, amount prescribed, amount consumed, reasons for stopping, adverse events, and any postoperative adjunctive pain medications. The data were taken from questionnaires completed by patients at their first visit within 2 weeks after surgery. Anesthesia type (general or regional) was noted as well. All fractures were classified by Dr. O’Neil using the AO/OTA (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association) classification of long-bone fractures based on preoperative radiographs.

Amount of opioid analgesic consumed was converted into morphine equivalents to adjust for the different opioids prescribed after surgery: oxycodone/acetaminophen or oxycodone equivalent, hydrocodone/acetaminophen or hydrocodone equivalent, and acetaminophen/codeine.

Patients were excluded from the study if their procedure was performed on an inpatient basis, if they sustained other injuries or fractures from their trauma, or if an adjunctive procedure (including carpal tunnel release) was performed during the DRF repair.

We used the Spearman rank correlation coefficient and a count data model to examine the relationship between opioid use and age. The Kruskal-Wallis test was used to examine the relationships between opioid use and payer type, anesthesia type, and fracture type.

Results

Of the 109 patients eligible for the study, 11 were excluded for incomplete postoperative questionnaires, leaving 98 patients (79 females, 19 males) for analysis. Mean age was 58 years (range, 13-92 years). Of the 98 patients, 45 received general anesthesia, and 53 received regional anesthesia with a single-shot peripheral nerve block before surgery and sedation perioperatively (Table).

Of the 98 study patients, 61 reported using over-the-counter adjunctive pain medications during the postoperative period, and 37 reported no use. Mean opioid consumption was 64.7 mg of morphine equivalents for the adjunctive medication users and 48.3 mg for the nonusers (P = .1947).

Demographic analysis revealed an inverse relationship between age and opioid use (Figure 2). The Spearman ρ between age and opioid consumption was –0.2958, which suggests decreased opioid use by older patients (P = .003).

Discussion

The US healthcare culture has elevated physicians’ responsibility in adequately and aggressively managing their patients’ pain experience. Moreover, reimbursement may be affected by patient satisfaction scores, which are partly predicated on pain control.^20-24 However, as rates of opioid use and abuse rise, it is important that physicians prescribe such medications judiciously. This is particularly germane to orthopedic surgeons, who prescribe more opioid analgesics than surgeons in any other field.¹⁷ Rodgers and colleagues¹⁸ found upper extremity surgeons, in particular, tended to overprescribe postoperative opioid analgesics. In the present study, we sought to identify the crucial risk factors that influence post-DRF-ORIF pain management and opioid consumption.

Mean postoperative opioid consumption (morphine equivalents) was 58.5 mg, roughly equivalent to 14.6 tabs of oxycodone/acetaminophen 5/325 mg, an opioid analgesic commonly used during the acute postoperative period. In addition, almost 70% of our patients required <75 mg of morphine equivalents, or <20 tabs of oxycodone/acetaminophen 5/325 mg. For upper extremity surgeons, these numbers may be better guides in determining the most appropriate amount of opioid to prescribe after DRF repair.

As for predicting levels of postoperative opioid medication, there was a significant trend toward less consumption with increasing age. Given this finding, surgeons prescribing for elderly patients should expect less opioid use. Regarding payer type, there was a trend toward more opioid use by self-pay/Medicaid patients; however, there were only 3 patients in this group. The situation in the study by Rodgers and colleagues¹⁸ is similar: Their finding that Medicaid patients consumed more pain pills after surgery was underpowered (only 5 patients in the group).

In the orthopedic community, support for use of regional anesthesia has been widespread for several reasons, including the belief that it reduces postoperative pain and therefore should reduce postoperative opioid consumption.²⁵ However, we found no significant difference in postoperative opioid consumption between patients who received general anesthesia (with and without local anesthesia) and patients who received regional anesthesia (nerve block). Mean opioid consumption was 57.93 mg in the general anesthesia group and 58.98 mg in the regional anesthesia group. However, this finding could have been confounded by the variability in success and operator dependence inherent in regional anesthesia. In addition, the anatomical location for the peripheral nerve block and anesthetic could have affected the efficacy of the block and played a role in postoperative opioid consumption.

In this study, we tested the hypothesis that there would be more postoperative opioid consumption with worsening fracture type. Although our results did not reach statistical significance, there was a trend toward increased opioid consumption in patients with a complete intra-articular fracture (AO/OTA class C) vs patients with a partial articular fracture (class B) or an extra-articular fracture (class A). In addition, patients with a partial articular fracture tended to use more postoperative opioids than patients with an extra-articular fracture. In short, postoperative opioid consumption tended to be higher with increasing articular involvement of the fracture.

This study was limited in that it relied on patient self-reporting. Given the social stigma attached to opioid use, patients may have underreported their postoperative opioid consumption, been affected by recall bias, or both. The study also did not control for preoperative opioid use or history of opioid or substance abuse. Chronic preoperative opioid consumption may have affected postoperative opioid use. Other patient-related factors, such as body mass index (BMI) and hepatorenal dysfunction, can create tremendous variability in opioid metabolism across a population. Such factors were not controlled for in this study and therefore may have affected its results. That could help explain why older patients, who are more likely to have lower BMI and less efficient organ function for opioid metabolism, had lower postoperative opioid consumption. In addition, although we excluded patients with concomitant injuries and procedures, we did not screen patients for concomitant complex regional pain syndrome, fibromyalgia, or other medical conditions that might have had a significant impact on postoperative pain management needs. Last, some findings, such as the relationship between opioid use and payer type, were underpowered: Although self-pay/Medicaid patients had higher postoperative opioid consumption, they were few in number. The same was true of the Medicaid patients in the study by Rodgers and colleagues.¹⁸Our results demonstrated that post-DRF-ORIF opioid consumption decreased with age and was independent of type of perioperative anesthesia. There was a trend toward more opioid consumption with both self- and Medicaid payment and worsening fracture classification. It has become more important than ever for orthopedic surgeons to adequately manage postoperative pain while limiting opioid availability and the risk for abuse. Surgeons must remain aware of the variables in their patients’ postoperative pain experience in order to better optimize prescribing patterns and provide a safe and effective postoperative pain regimen.

Am J Orthop. 2017;46(1):E35-E40. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Epidermodysplasia Verruciformis

Epidermodysplasia verruciformis (EV) is a rare hereditary disorder that predisposes affected individuals to widespread infection with various forms of human papillomavirus (HPV). It is inherited in an autosomal-recessive pattern.¹ The first manifestations generally are seen in childhood. The clinical appearance of lesions can vary, at times mimicking other disease processes. Patients can present with flat wartlike papules resembling verruca plana distributed in sun-exposed areas. Another distinct presentation is multiple salmon-colored, hyperpigmented, or hypopigmented macules, papules, or plaques with overlying scale that can resemble tinea versicolor.^1,2 A large percentage of patients will go on to develop actinic keratosis and squamous cell carcinoma by 40 years of age.² The malignancies most commonly develop in sun-exposed areas, suggesting UV radiation as an important contributor to development along with HPV infection. Mutations in the EVER1 and EVER2 genes that code for transmembrane proteins on the endoplasmic reticulum that are involved in zinc transport lead to EV. The mutations lead to decreased zinc movement into the cytoplasm, which is thought to play a role in preventing HPV infection. The decreased protection against HPV leads to infections from both common subtypes and those that immunocompetent individuals would be resistant to, namely the β-genus HPV-5, -8, -9 and -20.^1,2 Immunosuppressed individuals, such as those with human immunodeficiency virus/AIDS, also are at an increased risk for infection with these HPV subtypes and generally have similar clinical and histological presentations.¹ It is important to promote sunscreen use for preventive care in patients with EV due to the increased risk for squamous cell carcinoma.

Histologically, the lesions in EV are composed of acanthosis and hyperkeratosis with keratinocytes arranged in clusters.^1,3 There is orthokeratosis and parakeratosis.¹ Scattered or clustered keratinocytes in the granular layer or upper stratum spinosum appear swollen with foamy blue-gray cytoplasm (quiz image and Figure 1).^1,4 The keratinocytes may become atypical and progress to squamous cell carcinoma, particularly in sun-exposed regions. Cell differentiation becomes disorganized and nuclei become enlarged and hyperchromatic.¹

Condyloma acuminatum will have pronounced acanthosis and hyperkeratosis with exophytic growth. Rounded parakeratosis is visible. The characteristic cell is the koilocyte, a keratinocyte that has an enlarged nucleus with areas of surrounding clearing, increased dark color in the nucleus, and wrinkled nuclear membrane (Figure 2).^1,3 True koilocytes may be rare in condyloma acuminatum.⁴ Other distinct features include coarse hypergranulosis and a compact stratum corneum.

Herpesvirus lesions typically demonstrate ballooning degeneration of keratinocytes.¹ They will become pale and fuse to form multinucleated giant cells, a feature not found in verruca. The nuclei will be slate gray with margination of the chromatin, which can be identified due to its increased basophilic appearance (Figure 3).^1,4 Inclusion bodies can be found, but unlike molluscum contagiosum (MC), these bodies are intranuclear as opposed to cytoplasmic.¹

The telltale Henderson-Patterson (molluscum) bodies can identify MC histologically.⁴ Located within keratinocytes, these cytoplasmic inclusions can vary in both color and size as they mature. As the keratinocytes develop outward, the molluscum bodies grow larger and become more eosinophilic (Figure 4).^1,4 Another feature of MC that can be used to differentiate it from EV is the scalloped borders located on lesions.⁴

On histology, verruca vulgaris will have pronounced acanthosis with orthokeratosis and vertical tiers of parakeratosis.^3,4 Growth is exophytic. The granular layer will have large irregular basophilic granules. Koilocytes may be seen. A distinctive feature is the papillomatosis with inward bending of rete ridges.^3,4 It is common to see invasion of tortuous blood vessels into the exophytic projections.³ In myrmecia (palmoplantar warts) it is common to see thrombosis of these vessels and inclusions of red cytoplasmic bodies (Figure 5).^1,4

Epidermodysplasia Verruciformis

Epidermodysplasia verruciformis (EV) is a rare hereditary disorder that predisposes affected individuals to widespread infection with various forms of human papillomavirus (HPV). It is inherited in an autosomal-recessive pattern.¹ The first manifestations generally are seen in childhood. The clinical appearance of lesions can vary, at times mimicking other disease processes. Patients can present with flat wartlike papules resembling verruca plana distributed in sun-exposed areas. Another distinct presentation is multiple salmon-colored, hyperpigmented, or hypopigmented macules, papules, or plaques with overlying scale that can resemble tinea versicolor.^1,2 A large percentage of patients will go on to develop actinic keratosis and squamous cell carcinoma by 40 years of age.² The malignancies most commonly develop in sun-exposed areas, suggesting UV radiation as an important contributor to development along with HPV infection. Mutations in the EVER1 and EVER2 genes that code for transmembrane proteins on the endoplasmic reticulum that are involved in zinc transport lead to EV. The mutations lead to decreased zinc movement into the cytoplasm, which is thought to play a role in preventing HPV infection. The decreased protection against HPV leads to infections from both common subtypes and those that immunocompetent individuals would be resistant to, namely the β-genus HPV-5, -8, -9 and -20.^1,2 Immunosuppressed individuals, such as those with human immunodeficiency virus/AIDS, also are at an increased risk for infection with these HPV subtypes and generally have similar clinical and histological presentations.¹ It is important to promote sunscreen use for preventive care in patients with EV due to the increased risk for squamous cell carcinoma.

Histologically, the lesions in EV are composed of acanthosis and hyperkeratosis with keratinocytes arranged in clusters.^1,3 There is orthokeratosis and parakeratosis.¹ Scattered or clustered keratinocytes in the granular layer or upper stratum spinosum appear swollen with foamy blue-gray cytoplasm (quiz image and Figure 1).^1,4 The keratinocytes may become atypical and progress to squamous cell carcinoma, particularly in sun-exposed regions. Cell differentiation becomes disorganized and nuclei become enlarged and hyperchromatic.¹

Condyloma acuminatum will have pronounced acanthosis and hyperkeratosis with exophytic growth. Rounded parakeratosis is visible. The characteristic cell is the koilocyte, a keratinocyte that has an enlarged nucleus with areas of surrounding clearing, increased dark color in the nucleus, and wrinkled nuclear membrane (Figure 2).^1,3 True koilocytes may be rare in condyloma acuminatum.⁴ Other distinct features include coarse hypergranulosis and a compact stratum corneum.

Herpesvirus lesions typically demonstrate ballooning degeneration of keratinocytes.¹ They will become pale and fuse to form multinucleated giant cells, a feature not found in verruca. The nuclei will be slate gray with margination of the chromatin, which can be identified due to its increased basophilic appearance (Figure 3).^1,4 Inclusion bodies can be found, but unlike molluscum contagiosum (MC), these bodies are intranuclear as opposed to cytoplasmic.¹

The telltale Henderson-Patterson (molluscum) bodies can identify MC histologically.⁴ Located within keratinocytes, these cytoplasmic inclusions can vary in both color and size as they mature. As the keratinocytes develop outward, the molluscum bodies grow larger and become more eosinophilic (Figure 4).^1,4 Another feature of MC that can be used to differentiate it from EV is the scalloped borders located on lesions.⁴

On histology, verruca vulgaris will have pronounced acanthosis with orthokeratosis and vertical tiers of parakeratosis.^3,4 Growth is exophytic. The granular layer will have large irregular basophilic granules. Koilocytes may be seen. A distinctive feature is the papillomatosis with inward bending of rete ridges.^3,4 It is common to see invasion of tortuous blood vessels into the exophytic projections.³ In myrmecia (palmoplantar warts) it is common to see thrombosis of these vessels and inclusions of red cytoplasmic bodies (Figure 5).^1,4

Epidermodysplasia Verruciformis

Epidermodysplasia verruciformis (EV) is a rare hereditary disorder that predisposes affected individuals to widespread infection with various forms of human papillomavirus (HPV). It is inherited in an autosomal-recessive pattern.¹ The first manifestations generally are seen in childhood. The clinical appearance of lesions can vary, at times mimicking other disease processes. Patients can present with flat wartlike papules resembling verruca plana distributed in sun-exposed areas. Another distinct presentation is multiple salmon-colored, hyperpigmented, or hypopigmented macules, papules, or plaques with overlying scale that can resemble tinea versicolor.^1,2 A large percentage of patients will go on to develop actinic keratosis and squamous cell carcinoma by 40 years of age.² The malignancies most commonly develop in sun-exposed areas, suggesting UV radiation as an important contributor to development along with HPV infection. Mutations in the EVER1 and EVER2 genes that code for transmembrane proteins on the endoplasmic reticulum that are involved in zinc transport lead to EV. The mutations lead to decreased zinc movement into the cytoplasm, which is thought to play a role in preventing HPV infection. The decreased protection against HPV leads to infections from both common subtypes and those that immunocompetent individuals would be resistant to, namely the β-genus HPV-5, -8, -9 and -20.^1,2 Immunosuppressed individuals, such as those with human immunodeficiency virus/AIDS, also are at an increased risk for infection with these HPV subtypes and generally have similar clinical and histological presentations.¹ It is important to promote sunscreen use for preventive care in patients with EV due to the increased risk for squamous cell carcinoma.

Histologically, the lesions in EV are composed of acanthosis and hyperkeratosis with keratinocytes arranged in clusters.^1,3 There is orthokeratosis and parakeratosis.¹ Scattered or clustered keratinocytes in the granular layer or upper stratum spinosum appear swollen with foamy blue-gray cytoplasm (quiz image and Figure 1).^1,4 The keratinocytes may become atypical and progress to squamous cell carcinoma, particularly in sun-exposed regions. Cell differentiation becomes disorganized and nuclei become enlarged and hyperchromatic.¹

Condyloma acuminatum will have pronounced acanthosis and hyperkeratosis with exophytic growth. Rounded parakeratosis is visible. The characteristic cell is the koilocyte, a keratinocyte that has an enlarged nucleus with areas of surrounding clearing, increased dark color in the nucleus, and wrinkled nuclear membrane (Figure 2).^1,3 True koilocytes may be rare in condyloma acuminatum.⁴ Other distinct features include coarse hypergranulosis and a compact stratum corneum.

Herpesvirus lesions typically demonstrate ballooning degeneration of keratinocytes.¹ They will become pale and fuse to form multinucleated giant cells, a feature not found in verruca. The nuclei will be slate gray with margination of the chromatin, which can be identified due to its increased basophilic appearance (Figure 3).^1,4 Inclusion bodies can be found, but unlike molluscum contagiosum (MC), these bodies are intranuclear as opposed to cytoplasmic.¹

The telltale Henderson-Patterson (molluscum) bodies can identify MC histologically.⁴ Located within keratinocytes, these cytoplasmic inclusions can vary in both color and size as they mature. As the keratinocytes develop outward, the molluscum bodies grow larger and become more eosinophilic (Figure 4).^1,4 Another feature of MC that can be used to differentiate it from EV is the scalloped borders located on lesions.⁴

On histology, verruca vulgaris will have pronounced acanthosis with orthokeratosis and vertical tiers of parakeratosis.^3,4 Growth is exophytic. The granular layer will have large irregular basophilic granules. Koilocytes may be seen. A distinctive feature is the papillomatosis with inward bending of rete ridges.^3,4 It is common to see invasion of tortuous blood vessels into the exophytic projections.³ In myrmecia (palmoplantar warts) it is common to see thrombosis of these vessels and inclusions of red cytoplasmic bodies (Figure 5).^1,4

The Diagnosis: Cutaneous Protothecosis

A 4-mm punch biopsy of the plaque on the right forearm was performed. The biopsy showed chronic inflammation with prominent histiocytes, foreign body giant cells, plasma cells, and abundant eosinophils (Figure 1). Grocott-Gomori methenamine-silver stain demonstrated abundant soccer ball-like or floretlike sporangia that were 3 to 11 μm, consistent with a diagnosis of protothecosis (Figure 2).

Cutaneous protothecosis is an infection caused by chlorophyll-lacking algae of the genus Prototheca.¹ It is ubiquitous in nature and can be isolated from various reservoirs such as trees, grass, water, and food sources.² Protothecosis is present worldwide and in the United States; it is most prevalent in the Southeast. Prototheca species are rare but often endemic in cattle and can cause bovine mastitis and enteritis.³ However, they are rare opportunistic infections in humans.

The pathogenesis of cutaneous protothecosis is largely unknown.⁴ However, most infections are thought to be caused by traumatic inoculation into subcutaneous tissues.^1,2 The majority of cases occur in patients older than 30 years. To date, approximately 160 cases have been reported in the literature worldwide.⁵ There are 3 main species of Prototheca, but almost all human infections are caused by Prototheca wickerhamii.² Clinically, most patients with protothecosis present with cutaneous findings, but olecranon bursitis and systemic forms also have been reported.¹

Risk factors for protothecosis include immunosuppression, most often due to steroids, in addition to malignancies, diabetes mellitus, and certain occupations.¹ The presentation can be variable from papules and plaques to even herpetiform appearances.⁴ Protothecosis usually affects the skin and soft tissues of exposed areas such as the extremities or the face.⁶ Diagnosis largely is made on detection of characteristic floretlike sporangia with a prominent cell wall on histopathological examination. Prototheca wickerhamii specifically produces a morula form of sporangia with endospores arranged symmetrically, giving it a characteristic soccer ball appearance.²

Treatment of protothecosis is difficult and remains controversial.¹ There are no established protothecosis treatment protocols or guidelines due to the small number of cases.⁷ In vitro studies have demonstrated sensitivity to amphotericin B and various azoles as well as a wide range of antibiotics.¹ Olecranon bursitis and small skin lesions can be treated by surgical excision. All other Prototheca infections require systemic treatment with azoles or  intravenous amphotericin B for immunocompromised patients or those with disseminated disease.⁵ However, failure to respond to medical management often occurs, requiring surgical excision.^1,6

Our patient was treated with a 3-month course of voriconazole but therapy failed and the plaque continued to expand. The patient underwent a wide excision that was repaired with a partial-thickness skin graft. Rebiopsy of the papule adjacent to the skin graft showed no further recurrence.

In conclusion, protothecosis generally is not clinically suspected and patients are subjected to various treatments without adequate results. A definitive diagnosis easily can be established with a skin biopsy, which can direct timely and appropriate treatment.

The Diagnosis: Cutaneous Protothecosis

A 4-mm punch biopsy of the plaque on the right forearm was performed. The biopsy showed chronic inflammation with prominent histiocytes, foreign body giant cells, plasma cells, and abundant eosinophils (Figure 1). Grocott-Gomori methenamine-silver stain demonstrated abundant soccer ball-like or floretlike sporangia that were 3 to 11 μm, consistent with a diagnosis of protothecosis (Figure 2).

Cutaneous protothecosis is an infection caused by chlorophyll-lacking algae of the genus Prototheca.¹ It is ubiquitous in nature and can be isolated from various reservoirs such as trees, grass, water, and food sources.² Protothecosis is present worldwide and in the United States; it is most prevalent in the Southeast. Prototheca species are rare but often endemic in cattle and can cause bovine mastitis and enteritis.³ However, they are rare opportunistic infections in humans.

The pathogenesis of cutaneous protothecosis is largely unknown.⁴ However, most infections are thought to be caused by traumatic inoculation into subcutaneous tissues.^1,2 The majority of cases occur in patients older than 30 years. To date, approximately 160 cases have been reported in the literature worldwide.⁵ There are 3 main species of Prototheca, but almost all human infections are caused by Prototheca wickerhamii.² Clinically, most patients with protothecosis present with cutaneous findings, but olecranon bursitis and systemic forms also have been reported.¹

Risk factors for protothecosis include immunosuppression, most often due to steroids, in addition to malignancies, diabetes mellitus, and certain occupations.¹ The presentation can be variable from papules and plaques to even herpetiform appearances.⁴ Protothecosis usually affects the skin and soft tissues of exposed areas such as the extremities or the face.⁶ Diagnosis largely is made on detection of characteristic floretlike sporangia with a prominent cell wall on histopathological examination. Prototheca wickerhamii specifically produces a morula form of sporangia with endospores arranged symmetrically, giving it a characteristic soccer ball appearance.²

Treatment of protothecosis is difficult and remains controversial.¹ There are no established protothecosis treatment protocols or guidelines due to the small number of cases.⁷ In vitro studies have demonstrated sensitivity to amphotericin B and various azoles as well as a wide range of antibiotics.¹ Olecranon bursitis and small skin lesions can be treated by surgical excision. All other Prototheca infections require systemic treatment with azoles or  intravenous amphotericin B for immunocompromised patients or those with disseminated disease.⁵ However, failure to respond to medical management often occurs, requiring surgical excision.^1,6

Our patient was treated with a 3-month course of voriconazole but therapy failed and the plaque continued to expand. The patient underwent a wide excision that was repaired with a partial-thickness skin graft. Rebiopsy of the papule adjacent to the skin graft showed no further recurrence.

In conclusion, protothecosis generally is not clinically suspected and patients are subjected to various treatments without adequate results. A definitive diagnosis easily can be established with a skin biopsy, which can direct timely and appropriate treatment.

The Diagnosis: Cutaneous Protothecosis

A 4-mm punch biopsy of the plaque on the right forearm was performed. The biopsy showed chronic inflammation with prominent histiocytes, foreign body giant cells, plasma cells, and abundant eosinophils (Figure 1). Grocott-Gomori methenamine-silver stain demonstrated abundant soccer ball-like or floretlike sporangia that were 3 to 11 μm, consistent with a diagnosis of protothecosis (Figure 2).

Cutaneous protothecosis is an infection caused by chlorophyll-lacking algae of the genus Prototheca.¹ It is ubiquitous in nature and can be isolated from various reservoirs such as trees, grass, water, and food sources.² Protothecosis is present worldwide and in the United States; it is most prevalent in the Southeast. Prototheca species are rare but often endemic in cattle and can cause bovine mastitis and enteritis.³ However, they are rare opportunistic infections in humans.

The pathogenesis of cutaneous protothecosis is largely unknown.⁴ However, most infections are thought to be caused by traumatic inoculation into subcutaneous tissues.^1,2 The majority of cases occur in patients older than 30 years. To date, approximately 160 cases have been reported in the literature worldwide.⁵ There are 3 main species of Prototheca, but almost all human infections are caused by Prototheca wickerhamii.² Clinically, most patients with protothecosis present with cutaneous findings, but olecranon bursitis and systemic forms also have been reported.¹

Risk factors for protothecosis include immunosuppression, most often due to steroids, in addition to malignancies, diabetes mellitus, and certain occupations.¹ The presentation can be variable from papules and plaques to even herpetiform appearances.⁴ Protothecosis usually affects the skin and soft tissues of exposed areas such as the extremities or the face.⁶ Diagnosis largely is made on detection of characteristic floretlike sporangia with a prominent cell wall on histopathological examination. Prototheca wickerhamii specifically produces a morula form of sporangia with endospores arranged symmetrically, giving it a characteristic soccer ball appearance.²

Treatment of protothecosis is difficult and remains controversial.¹ There are no established protothecosis treatment protocols or guidelines due to the small number of cases.⁷ In vitro studies have demonstrated sensitivity to amphotericin B and various azoles as well as a wide range of antibiotics.¹ Olecranon bursitis and small skin lesions can be treated by surgical excision. All other Prototheca infections require systemic treatment with azoles or  intravenous amphotericin B for immunocompromised patients or those with disseminated disease.⁵ However, failure to respond to medical management often occurs, requiring surgical excision.^1,6

Our patient was treated with a 3-month course of voriconazole but therapy failed and the plaque continued to expand. The patient underwent a wide excision that was repaired with a partial-thickness skin graft. Rebiopsy of the papule adjacent to the skin graft showed no further recurrence.

In conclusion, protothecosis generally is not clinically suspected and patients are subjected to various treatments without adequate results. A definitive diagnosis easily can be established with a skin biopsy, which can direct timely and appropriate treatment.