SAN FRANCISCO – Recent U.S. outbreaks of pertussis, influenza, and measles have revealed shifts in the diseases’ epidemiology, shifts that pose new prevention and management challenges, explained Yvonne Maldonado, MD, at the annual meeting of the American Academy of Pediatrics.

Routine immunizations prevent 33,000 child deaths a year in the United States, having reduced vaccine-preventable diseases by more than 90%, but outbreaks still occur, she said. The recent announcement that measles was eliminated from the Western Hemisphere, for example, doesn’t mean we won’t see cases, said Dr. Maldonado, vice chair of the AAP Committee on Infectious Diseases and chief of the division of pediatric infectious diseases at Stanford (Calif.) University.

Influenza

The biggest challenges with controlling influenza are the failure to vaccinate children and the variable circulating strains each season, which can impact the performance of that year’s vaccine. Those changing strains and other factors also mean that the populations most at risk for serious complications also vary each season.

The two new mechanisms of change in influenza strains are antigenic drift and antigenic shift. Antigenic drift involves mutations that occur during repeated replications in the RNA strains of the virus, shifting its configuration over time so that it may not respond to the same antigens that the original strain responded to. Antigenic shift, however, is responsible for the periodic pandemics, when a complete genetic reassortment abruptly occurs because a new major protein from a strain jumps from an animal population into the human population, forming a new hybrid strain in humans.
 

Pertussis

Unlike flu, pertussis did become very uncommon because of widespread vaccination up until the early 2000s. But rates have begun to climb again, largely because of problems with the vaccine over time. Until the 1990s, the DTP vaccine, which includes a whole pertussis bacterium, was highly effective at preventing pertussis but could cause febrile seizures, an adverse event that proved too intolerable for many families.

It was replaced with the acellular pertussis vaccine DTaP, but research in the past 5-10 years has revealed that the effectiveness of DTaP and Tdap vaccines wanes much more quickly than anticipated. Subsequently, pertussis rates have almost continuously climbed from the early 2000s through the present, reaching an incidence of more than 100 cases per 100,000 among children younger than 1 year.

One of the biggest challenges now is improving vaccination rates among pregnant women, who were recommended in 2015 to get the Tdap vaccine in every pregnancy so that the newborn would have some passively acquired protection during the first few months of life.

Ongoing outbreaks then become exacerbated by pockets of lower vaccination rates among children in general.
 

Measles

The only chink in the armor against measles is failure to vaccinate against it, Dr. Maldonado said. Though the disease was eliminated from the United States in 2000, measles cases peaked recently in 2014, when 31 outbreaks involving 667 cases occurred because of imported cases from the Philippines. The next year, 60% of the 189 cases in 2015 resulted from the multistate measles outbreak starting at Disneyland in California.

Most of the individuals in both those years’ outbreaks were not vaccinated or had an unknown vaccination status. Of the 110 individuals with measles in California from the Disneyland outbreak, 45% were not immunized. Twelve were too young for vaccination, but 37 were eligible to have been vaccinated, and 67% of these were not vaccinated because of personal beliefs.

Vaccination rates for measles must be considerably higher, around 92%-94% of the population, to prevent outbreaks than for most other diseases, because the virus is so incredibly contagious.

“Measles is so infectious because it can exist in tiny microdroplets less than 5 mcg that can sit in the air up to 2 hours,” Dr. Maldonado explained. Yet only 92.6% of kindergartners had had both their MMR doses in 2014, compared with the peak of 97% between 2002 to 2007.

When children across all ages who have not received both doses of the vaccine are taken into account, 12.5% of all U.S. children and adolescents are currently susceptible to measles – and a quarter of those aged 3 years and younger are, Maldonado said.

The keys to preventing measles are high national coverage rates, an aggressive public health response (because early diagnosis can limit transmission), and improved implementation of health care worker recommendations.

“We have to keep measles in mind whenever we see fevers and rashes,” Dr. Maldonado cautioned. “Unfortunately, we see fevers and rashes all the time, so what really helps is a history of international travel or a parent with international travel.”

For families planning overseas travel, parents are recommended to give their infants the MMR as young as 6 months. But that dose does not count toward the child’s two doses recommended by the Centers for Disease Control and Prevention schedule.

“It’s a very tough call with measles, because we never know when it might pop up,” Dr. Maldonado said. “Measles will be sporadic, but when it happens, it’s a really big deal. You basically have to reach out to your entire patient log for several days before the child came in.”
 

Managing suspected/confirmed outbreaks

To prepare for and manage suspected outbreaks of an infectious disease, Dr. Maldonado advised taking the following steps:

• Establish a plan for evaluating suspected or confirmed infectious disease outbreaks in your office setting.

• Identify and eliminate the source of the infection, such as providing a separate waiting room for coughing children.

• Prevent additional cases using screening questions at the front desk.

• Provide prompt and consistent ongoing evaluation to prevent or minimize transmission to others.

• Track disease trends and advice from the AAP, CDC, and local county public health officials and disease experts to engage in ongoing surveillance and communication.

• Identify the initial source and route of exposure to understand why an outbreak occurred and how to prevent similar ones in the future.

Dr. Maldonado reporting being a member of a data safety monitoring board for Pfizer.

SAN FRANCISCO – Recent U.S. outbreaks of pertussis, influenza, and measles have revealed shifts in the diseases’ epidemiology, shifts that pose new prevention and management challenges, explained Yvonne Maldonado, MD, at the annual meeting of the American Academy of Pediatrics.

Routine immunizations prevent 33,000 child deaths a year in the United States, having reduced vaccine-preventable diseases by more than 90%, but outbreaks still occur, she said. The recent announcement that measles was eliminated from the Western Hemisphere, for example, doesn’t mean we won’t see cases, said Dr. Maldonado, vice chair of the AAP Committee on Infectious Diseases and chief of the division of pediatric infectious diseases at Stanford (Calif.) University.

Influenza

The biggest challenges with controlling influenza are the failure to vaccinate children and the variable circulating strains each season, which can impact the performance of that year’s vaccine. Those changing strains and other factors also mean that the populations most at risk for serious complications also vary each season.

The two new mechanisms of change in influenza strains are antigenic drift and antigenic shift. Antigenic drift involves mutations that occur during repeated replications in the RNA strains of the virus, shifting its configuration over time so that it may not respond to the same antigens that the original strain responded to. Antigenic shift, however, is responsible for the periodic pandemics, when a complete genetic reassortment abruptly occurs because a new major protein from a strain jumps from an animal population into the human population, forming a new hybrid strain in humans.
 

Pertussis

Unlike flu, pertussis did become very uncommon because of widespread vaccination up until the early 2000s. But rates have begun to climb again, largely because of problems with the vaccine over time. Until the 1990s, the DTP vaccine, which includes a whole pertussis bacterium, was highly effective at preventing pertussis but could cause febrile seizures, an adverse event that proved too intolerable for many families.

It was replaced with the acellular pertussis vaccine DTaP, but research in the past 5-10 years has revealed that the effectiveness of DTaP and Tdap vaccines wanes much more quickly than anticipated. Subsequently, pertussis rates have almost continuously climbed from the early 2000s through the present, reaching an incidence of more than 100 cases per 100,000 among children younger than 1 year.

One of the biggest challenges now is improving vaccination rates among pregnant women, who were recommended in 2015 to get the Tdap vaccine in every pregnancy so that the newborn would have some passively acquired protection during the first few months of life.

Ongoing outbreaks then become exacerbated by pockets of lower vaccination rates among children in general.
 

Measles

The only chink in the armor against measles is failure to vaccinate against it, Dr. Maldonado said. Though the disease was eliminated from the United States in 2000, measles cases peaked recently in 2014, when 31 outbreaks involving 667 cases occurred because of imported cases from the Philippines. The next year, 60% of the 189 cases in 2015 resulted from the multistate measles outbreak starting at Disneyland in California.

Most of the individuals in both those years’ outbreaks were not vaccinated or had an unknown vaccination status. Of the 110 individuals with measles in California from the Disneyland outbreak, 45% were not immunized. Twelve were too young for vaccination, but 37 were eligible to have been vaccinated, and 67% of these were not vaccinated because of personal beliefs.

Vaccination rates for measles must be considerably higher, around 92%-94% of the population, to prevent outbreaks than for most other diseases, because the virus is so incredibly contagious.

“Measles is so infectious because it can exist in tiny microdroplets less than 5 mcg that can sit in the air up to 2 hours,” Dr. Maldonado explained. Yet only 92.6% of kindergartners had had both their MMR doses in 2014, compared with the peak of 97% between 2002 to 2007.

When children across all ages who have not received both doses of the vaccine are taken into account, 12.5% of all U.S. children and adolescents are currently susceptible to measles – and a quarter of those aged 3 years and younger are, Maldonado said.

The keys to preventing measles are high national coverage rates, an aggressive public health response (because early diagnosis can limit transmission), and improved implementation of health care worker recommendations.

“We have to keep measles in mind whenever we see fevers and rashes,” Dr. Maldonado cautioned. “Unfortunately, we see fevers and rashes all the time, so what really helps is a history of international travel or a parent with international travel.”

For families planning overseas travel, parents are recommended to give their infants the MMR as young as 6 months. But that dose does not count toward the child’s two doses recommended by the Centers for Disease Control and Prevention schedule.

“It’s a very tough call with measles, because we never know when it might pop up,” Dr. Maldonado said. “Measles will be sporadic, but when it happens, it’s a really big deal. You basically have to reach out to your entire patient log for several days before the child came in.”
 

Managing suspected/confirmed outbreaks

To prepare for and manage suspected outbreaks of an infectious disease, Dr. Maldonado advised taking the following steps:

• Establish a plan for evaluating suspected or confirmed infectious disease outbreaks in your office setting.

• Identify and eliminate the source of the infection, such as providing a separate waiting room for coughing children.

• Prevent additional cases using screening questions at the front desk.

• Provide prompt and consistent ongoing evaluation to prevent or minimize transmission to others.

• Track disease trends and advice from the AAP, CDC, and local county public health officials and disease experts to engage in ongoing surveillance and communication.

• Identify the initial source and route of exposure to understand why an outbreak occurred and how to prevent similar ones in the future.

Dr. Maldonado reporting being a member of a data safety monitoring board for Pfizer.

SAN FRANCISCO – Recent U.S. outbreaks of pertussis, influenza, and measles have revealed shifts in the diseases’ epidemiology, shifts that pose new prevention and management challenges, explained Yvonne Maldonado, MD, at the annual meeting of the American Academy of Pediatrics.

Routine immunizations prevent 33,000 child deaths a year in the United States, having reduced vaccine-preventable diseases by more than 90%, but outbreaks still occur, she said. The recent announcement that measles was eliminated from the Western Hemisphere, for example, doesn’t mean we won’t see cases, said Dr. Maldonado, vice chair of the AAP Committee on Infectious Diseases and chief of the division of pediatric infectious diseases at Stanford (Calif.) University.

Influenza

The biggest challenges with controlling influenza are the failure to vaccinate children and the variable circulating strains each season, which can impact the performance of that year’s vaccine. Those changing strains and other factors also mean that the populations most at risk for serious complications also vary each season.

The two new mechanisms of change in influenza strains are antigenic drift and antigenic shift. Antigenic drift involves mutations that occur during repeated replications in the RNA strains of the virus, shifting its configuration over time so that it may not respond to the same antigens that the original strain responded to. Antigenic shift, however, is responsible for the periodic pandemics, when a complete genetic reassortment abruptly occurs because a new major protein from a strain jumps from an animal population into the human population, forming a new hybrid strain in humans.
 

Pertussis

Unlike flu, pertussis did become very uncommon because of widespread vaccination up until the early 2000s. But rates have begun to climb again, largely because of problems with the vaccine over time. Until the 1990s, the DTP vaccine, which includes a whole pertussis bacterium, was highly effective at preventing pertussis but could cause febrile seizures, an adverse event that proved too intolerable for many families.

It was replaced with the acellular pertussis vaccine DTaP, but research in the past 5-10 years has revealed that the effectiveness of DTaP and Tdap vaccines wanes much more quickly than anticipated. Subsequently, pertussis rates have almost continuously climbed from the early 2000s through the present, reaching an incidence of more than 100 cases per 100,000 among children younger than 1 year.

One of the biggest challenges now is improving vaccination rates among pregnant women, who were recommended in 2015 to get the Tdap vaccine in every pregnancy so that the newborn would have some passively acquired protection during the first few months of life.

Ongoing outbreaks then become exacerbated by pockets of lower vaccination rates among children in general.
 

Measles

The only chink in the armor against measles is failure to vaccinate against it, Dr. Maldonado said. Though the disease was eliminated from the United States in 2000, measles cases peaked recently in 2014, when 31 outbreaks involving 667 cases occurred because of imported cases from the Philippines. The next year, 60% of the 189 cases in 2015 resulted from the multistate measles outbreak starting at Disneyland in California.

Most of the individuals in both those years’ outbreaks were not vaccinated or had an unknown vaccination status. Of the 110 individuals with measles in California from the Disneyland outbreak, 45% were not immunized. Twelve were too young for vaccination, but 37 were eligible to have been vaccinated, and 67% of these were not vaccinated because of personal beliefs.

Vaccination rates for measles must be considerably higher, around 92%-94% of the population, to prevent outbreaks than for most other diseases, because the virus is so incredibly contagious.

“Measles is so infectious because it can exist in tiny microdroplets less than 5 mcg that can sit in the air up to 2 hours,” Dr. Maldonado explained. Yet only 92.6% of kindergartners had had both their MMR doses in 2014, compared with the peak of 97% between 2002 to 2007.

When children across all ages who have not received both doses of the vaccine are taken into account, 12.5% of all U.S. children and adolescents are currently susceptible to measles – and a quarter of those aged 3 years and younger are, Maldonado said.

The keys to preventing measles are high national coverage rates, an aggressive public health response (because early diagnosis can limit transmission), and improved implementation of health care worker recommendations.

“We have to keep measles in mind whenever we see fevers and rashes,” Dr. Maldonado cautioned. “Unfortunately, we see fevers and rashes all the time, so what really helps is a history of international travel or a parent with international travel.”

For families planning overseas travel, parents are recommended to give their infants the MMR as young as 6 months. But that dose does not count toward the child’s two doses recommended by the Centers for Disease Control and Prevention schedule.

“It’s a very tough call with measles, because we never know when it might pop up,” Dr. Maldonado said. “Measles will be sporadic, but when it happens, it’s a really big deal. You basically have to reach out to your entire patient log for several days before the child came in.”
 

Managing suspected/confirmed outbreaks

To prepare for and manage suspected outbreaks of an infectious disease, Dr. Maldonado advised taking the following steps:

• Establish a plan for evaluating suspected or confirmed infectious disease outbreaks in your office setting.

• Identify and eliminate the source of the infection, such as providing a separate waiting room for coughing children.

• Prevent additional cases using screening questions at the front desk.

• Provide prompt and consistent ongoing evaluation to prevent or minimize transmission to others.

• Track disease trends and advice from the AAP, CDC, and local county public health officials and disease experts to engage in ongoing surveillance and communication.

• Identify the initial source and route of exposure to understand why an outbreak occurred and how to prevent similar ones in the future.

Dr. Maldonado reporting being a member of a data safety monitoring board for Pfizer.

NEW ORLEANS – Overweight and obese patients with inadequately controlled type 2 diabetes have a new evidence-based treatment option in the form of the standard commercial Weight Watchers program enhanced by telephone and email consultations with a certified diabetes educator.

This intervention resulted in clinically meaningful improvements in glycemic control and weight loss, compared with a control group on standard care in a 12-month randomized clinical trial conducted at 16 U.S. centers, Patrick M. O’Neil, PhD, reported at Obesity Week 2016.

Boarding1Now/Thinkstock

“Patients and providers alike need a broader arsenal of treatment options for managing diabetes; in particular, options that are more accessible to the majority of people with diabetes,” he said. “The number of adults with diabetes is large and growing, and a variety of accessible treatment approaches is needed. The results of this and related trials suggest that adapted, nationally available weight loss programs emphasizing lifestyle changes may represent accessible and effective adjunctive health management resources for people with overweight or obesity and type 2 diabetes.”

Dr. O’Neil reported on a racially and geographically diverse group of 563 overweight or obese adults with inadequately controlled type 2 diabetes who were randomized to the off-the-shelf commercial Weight Watchers program featuring regular community meetings and online tools enhanced with telephone and email consultation with a certified diabetes educator, or to a control group who got an initial face-to-face diabetes nutrition counseling visit with follow-up written information materials.

Control group participants received current standard care, although national survey data indicate that only about 55% of patients with diabetes get any diabetes education at all at diagnosis, he observed.

At enrollment, all study participants were already receiving treatment for their diabetes from a physician not connected to the randomized trial. Ninety-five percent of them were on one or more diabetes medications. Yet their baseline hemoglobin A_1clevel was 7%-11% and their body mass index was 27-50 kg/m².

Both weight loss and improvement in HbA_1c were significantly greater in the Weight Watchers group than controls at each of the prespecified interim follow-ups at 13, 26, and 39 weeks.

When the study concluded at 52 weeks, the Weight Watchers group averaged a 0.32% reduction from baseline in HbA_1c, and 24% of patients in that study arm had achieved an HbA_1c below 7.0%. In contrast, the control group averaged a 0.16% increase in HbA_1c, and only 14% of controls got their HbA_1c below 7.0%, even though all participants continued to received ongoing background diabetes management from their outside physician throughout the study.

While the 0.48% difference in HbA_1c between the Weight Watchers group and controls may not be jaw-dropping, it is equivalent to the placebo-subtracted decrease in HbA_1c seen in 2-year long clinical trials of obesity medications in overweight or obese patients with type 2 diabetes, Dr. O’Neil said at the meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

The Weight Watchers group averaged a 4% weight loss at 52 weeks, significantly greater than the 1.9% reduction in controls.

Twenty-six percent of the Weight Watchers group had reduced their diabetes medications at the 52-week mark, compared with 12% of controls. Of the 213 patients on insulin for their type 2 diabetes at baseline, 9 in the Weight Watchers group and 4 controls on standard care were no longer on insulin at 52 weeks. That’s an important secondary outcome because insulin promotes weight gain.

Turning to changes in cardiovascular risk factors, Dr. O’Neil noted that the Weight Watchers group averaged a 3.7-cm reduction in waist circumference from a baseline of 116.3 cm, significantly better than the mean 1.4-cm reduction in controls. C-reactive protein levels dropped significantly in the Weight Watchers group over the course of a year, from 7.3 to 6.3 mg/L, but rose by 0.53 mg/L in the control arm. However, the two groups didn’t differ over time in blood pressure or lipid levels.

Simultaneous with Dr. O’Neil’s presentation, the study findings were published online in the journal Obesity (2016 Nov 2. doi:10.1002/oby.21616).

The study was funded by Weight Watchers International. Dr. O’Neil reported receiving a research grant from the company and serving on advisory boards for several pharmaceutical companies.

[email protected]

NEW ORLEANS – Overweight and obese patients with inadequately controlled type 2 diabetes have a new evidence-based treatment option in the form of the standard commercial Weight Watchers program enhanced by telephone and email consultations with a certified diabetes educator.

This intervention resulted in clinically meaningful improvements in glycemic control and weight loss, compared with a control group on standard care in a 12-month randomized clinical trial conducted at 16 U.S. centers, Patrick M. O’Neil, PhD, reported at Obesity Week 2016.

Boarding1Now/Thinkstock

“Patients and providers alike need a broader arsenal of treatment options for managing diabetes; in particular, options that are more accessible to the majority of people with diabetes,” he said. “The number of adults with diabetes is large and growing, and a variety of accessible treatment approaches is needed. The results of this and related trials suggest that adapted, nationally available weight loss programs emphasizing lifestyle changes may represent accessible and effective adjunctive health management resources for people with overweight or obesity and type 2 diabetes.”

Dr. O’Neil reported on a racially and geographically diverse group of 563 overweight or obese adults with inadequately controlled type 2 diabetes who were randomized to the off-the-shelf commercial Weight Watchers program featuring regular community meetings and online tools enhanced with telephone and email consultation with a certified diabetes educator, or to a control group who got an initial face-to-face diabetes nutrition counseling visit with follow-up written information materials.

Control group participants received current standard care, although national survey data indicate that only about 55% of patients with diabetes get any diabetes education at all at diagnosis, he observed.

At enrollment, all study participants were already receiving treatment for their diabetes from a physician not connected to the randomized trial. Ninety-five percent of them were on one or more diabetes medications. Yet their baseline hemoglobin A_1clevel was 7%-11% and their body mass index was 27-50 kg/m².

Both weight loss and improvement in HbA_1c were significantly greater in the Weight Watchers group than controls at each of the prespecified interim follow-ups at 13, 26, and 39 weeks.

When the study concluded at 52 weeks, the Weight Watchers group averaged a 0.32% reduction from baseline in HbA_1c, and 24% of patients in that study arm had achieved an HbA_1c below 7.0%. In contrast, the control group averaged a 0.16% increase in HbA_1c, and only 14% of controls got their HbA_1c below 7.0%, even though all participants continued to received ongoing background diabetes management from their outside physician throughout the study.

While the 0.48% difference in HbA_1c between the Weight Watchers group and controls may not be jaw-dropping, it is equivalent to the placebo-subtracted decrease in HbA_1c seen in 2-year long clinical trials of obesity medications in overweight or obese patients with type 2 diabetes, Dr. O’Neil said at the meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

The Weight Watchers group averaged a 4% weight loss at 52 weeks, significantly greater than the 1.9% reduction in controls.

Twenty-six percent of the Weight Watchers group had reduced their diabetes medications at the 52-week mark, compared with 12% of controls. Of the 213 patients on insulin for their type 2 diabetes at baseline, 9 in the Weight Watchers group and 4 controls on standard care were no longer on insulin at 52 weeks. That’s an important secondary outcome because insulin promotes weight gain.

Turning to changes in cardiovascular risk factors, Dr. O’Neil noted that the Weight Watchers group averaged a 3.7-cm reduction in waist circumference from a baseline of 116.3 cm, significantly better than the mean 1.4-cm reduction in controls. C-reactive protein levels dropped significantly in the Weight Watchers group over the course of a year, from 7.3 to 6.3 mg/L, but rose by 0.53 mg/L in the control arm. However, the two groups didn’t differ over time in blood pressure or lipid levels.

Simultaneous with Dr. O’Neil’s presentation, the study findings were published online in the journal Obesity (2016 Nov 2. doi:10.1002/oby.21616).

The study was funded by Weight Watchers International. Dr. O’Neil reported receiving a research grant from the company and serving on advisory boards for several pharmaceutical companies.

[email protected]

NEW ORLEANS – Overweight and obese patients with inadequately controlled type 2 diabetes have a new evidence-based treatment option in the form of the standard commercial Weight Watchers program enhanced by telephone and email consultations with a certified diabetes educator.

This intervention resulted in clinically meaningful improvements in glycemic control and weight loss, compared with a control group on standard care in a 12-month randomized clinical trial conducted at 16 U.S. centers, Patrick M. O’Neil, PhD, reported at Obesity Week 2016.

Boarding1Now/Thinkstock

“Patients and providers alike need a broader arsenal of treatment options for managing diabetes; in particular, options that are more accessible to the majority of people with diabetes,” he said. “The number of adults with diabetes is large and growing, and a variety of accessible treatment approaches is needed. The results of this and related trials suggest that adapted, nationally available weight loss programs emphasizing lifestyle changes may represent accessible and effective adjunctive health management resources for people with overweight or obesity and type 2 diabetes.”

Dr. O’Neil reported on a racially and geographically diverse group of 563 overweight or obese adults with inadequately controlled type 2 diabetes who were randomized to the off-the-shelf commercial Weight Watchers program featuring regular community meetings and online tools enhanced with telephone and email consultation with a certified diabetes educator, or to a control group who got an initial face-to-face diabetes nutrition counseling visit with follow-up written information materials.

Control group participants received current standard care, although national survey data indicate that only about 55% of patients with diabetes get any diabetes education at all at diagnosis, he observed.

At enrollment, all study participants were already receiving treatment for their diabetes from a physician not connected to the randomized trial. Ninety-five percent of them were on one or more diabetes medications. Yet their baseline hemoglobin A_1clevel was 7%-11% and their body mass index was 27-50 kg/m².

Both weight loss and improvement in HbA_1c were significantly greater in the Weight Watchers group than controls at each of the prespecified interim follow-ups at 13, 26, and 39 weeks.

When the study concluded at 52 weeks, the Weight Watchers group averaged a 0.32% reduction from baseline in HbA_1c, and 24% of patients in that study arm had achieved an HbA_1c below 7.0%. In contrast, the control group averaged a 0.16% increase in HbA_1c, and only 14% of controls got their HbA_1c below 7.0%, even though all participants continued to received ongoing background diabetes management from their outside physician throughout the study.

While the 0.48% difference in HbA_1c between the Weight Watchers group and controls may not be jaw-dropping, it is equivalent to the placebo-subtracted decrease in HbA_1c seen in 2-year long clinical trials of obesity medications in overweight or obese patients with type 2 diabetes, Dr. O’Neil said at the meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

The Weight Watchers group averaged a 4% weight loss at 52 weeks, significantly greater than the 1.9% reduction in controls.

Twenty-six percent of the Weight Watchers group had reduced their diabetes medications at the 52-week mark, compared with 12% of controls. Of the 213 patients on insulin for their type 2 diabetes at baseline, 9 in the Weight Watchers group and 4 controls on standard care were no longer on insulin at 52 weeks. That’s an important secondary outcome because insulin promotes weight gain.

Turning to changes in cardiovascular risk factors, Dr. O’Neil noted that the Weight Watchers group averaged a 3.7-cm reduction in waist circumference from a baseline of 116.3 cm, significantly better than the mean 1.4-cm reduction in controls. C-reactive protein levels dropped significantly in the Weight Watchers group over the course of a year, from 7.3 to 6.3 mg/L, but rose by 0.53 mg/L in the control arm. However, the two groups didn’t differ over time in blood pressure or lipid levels.

Simultaneous with Dr. O’Neil’s presentation, the study findings were published online in the journal Obesity (2016 Nov 2. doi:10.1002/oby.21616).

The study was funded by Weight Watchers International. Dr. O’Neil reported receiving a research grant from the company and serving on advisory boards for several pharmaceutical companies.

[email protected]

NEW ORLEANS – Blood pressure and cholesterol lowering in elderly patients with moderate vascular risk did not prevent cognitive decline in HOPE-3, the large randomized Heart Outcomes and Prevention Evaluation-3 trial, Jackie Bosch, PhD, reported at the American Heart Association scientific sessions.

Disappointing, but the study also brought some welcome glass-half-full good news: Although treatment did not slow cognitive decline, it didn’t worsen it, either, as some had feared. That means the clinically meaningful reduction in cardiovascular events conferred with blood pressure and cholesterol lowering previously reported in HOPE-3 does not come at the cost of an increased risk of dementia.
Rosuvastatin had no adverse effect on cognitive function in HOPE-3. This is an important finding, given the black box warning for statins mandated by the Food and Drug Administration, which was based only on observational postmarketing surveillance data,” observed Dr. Bosch of the Population Health Research Institute at McMaster University in Hamilton, Ont.

[email protected]

NEW ORLEANS – Blood pressure and cholesterol lowering in elderly patients with moderate vascular risk did not prevent cognitive decline in HOPE-3, the large randomized Heart Outcomes and Prevention Evaluation-3 trial, Jackie Bosch, PhD, reported at the American Heart Association scientific sessions.

Disappointing, but the study also brought some welcome glass-half-full good news: Although treatment did not slow cognitive decline, it didn’t worsen it, either, as some had feared. That means the clinically meaningful reduction in cardiovascular events conferred with blood pressure and cholesterol lowering previously reported in HOPE-3 does not come at the cost of an increased risk of dementia.
Rosuvastatin had no adverse effect on cognitive function in HOPE-3. This is an important finding, given the black box warning for statins mandated by the Food and Drug Administration, which was based only on observational postmarketing surveillance data,” observed Dr. Bosch of the Population Health Research Institute at McMaster University in Hamilton, Ont.

[email protected]

NEW ORLEANS – Blood pressure and cholesterol lowering in elderly patients with moderate vascular risk did not prevent cognitive decline in HOPE-3, the large randomized Heart Outcomes and Prevention Evaluation-3 trial, Jackie Bosch, PhD, reported at the American Heart Association scientific sessions.

Disappointing, but the study also brought some welcome glass-half-full good news: Although treatment did not slow cognitive decline, it didn’t worsen it, either, as some had feared. That means the clinically meaningful reduction in cardiovascular events conferred with blood pressure and cholesterol lowering previously reported in HOPE-3 does not come at the cost of an increased risk of dementia.
Rosuvastatin had no adverse effect on cognitive function in HOPE-3. This is an important finding, given the black box warning for statins mandated by the Food and Drug Administration, which was based only on observational postmarketing surveillance data,” observed Dr. Bosch of the Population Health Research Institute at McMaster University in Hamilton, Ont.

[email protected]

BOSTON – Obeticholic acid resulted in a significant reduction of a biomarker for liver fibrosis in patients with primary biliary cholangitis, according to a retrospective analysis of clinical trial data. In addition, patients taking obeticholic acid had a mean reduction in liver stiffness as measured by transient elastography.

Gideon Hirschfield, MD, PhD, presented the re-analysis of clinical trial data at the annual meeting of the American Association for the Study of Liver Diseases.

POISE was a phase III randomized, double-blind, placebo-controlled study of obeticholic acid for patients with primary biliary cholangitis (PBC). The clinical trial’s primary composite endpoint was an alkaline phosphatase level less than 1.67 times the upper limit of normal, with at least a 15% reduction in alkaline phosphatase and normal serum bilirubin.

The cohort of POISE patients on obeticholic acid met this biochemical surrogate endpoint, resulting in approval of the farnesoid X receptor agonist for treatment of PBC as an add-on to ursodeoxycholic acid (UDCA), or for patients who cannot tolerate UDCA.

However, transient elastography and the aspartate transaminase (AST) to platelet ratio index (APRI) have both been used to assess fibrosis in PBC, and have been found to predict clinical outcomes in PBC. These measures have the advantage of being noninvasive methods to measure the quality of liver tissue.

Dr. Hirschfield, a transplant hepatologist at the institute of immunology and immunotherapy at the University of Birmingham, England, and his coinvestigators reevaluated data from the POISE trial. They determined that APRI dropped significantly over 12 months of obeticholic acid treatment compared to placebo (P less than .01 for each of the two dosing arms of the POISE trial). Patients who switched to 5-10 mg of obeticholic acid daily from placebo during an open-label extension of POISE also had significant reductions in APRI scores (P less than .05); the reduction for placebo-switchers on a fixed 10-mg dose during the open-label study was not significant

Liver stiffness, as measured by transient elastography, was reduced for both arms of the POISE study at 12 months, but increased for those in the placebo arm. “Fewer patients receiving obeticholic acid 10 mg progressed” to a level associated with histological cirrhosis, “and patients receiving obeticholic acid showed an improvement in liver stiffness,” said Dr. Hirschfield.

Pruritis is a feature of PBC, and worsening pruritis can be a side effect of deoxycholic acid. However, the worsening is often transitory, so patients should be encouraged to try to stay the course, said Dr. Hirschfield. Managing patient expectations; sharing improved biomarkers; and considering the addition of a bile acid sequestrant or rifampicin, or reducing the obeticholic acid dose are all strategies to consider when caring for PBC patients, said Dr. Hirschfield.

Clinical trials to assess the safety and efficacy of obeticholic acid for individuals with nonalcoholic fatty liver disease and steatohepatitis are underway.

Dr. Hirschfield discussed his findings in a video interview.

[email protected]
On Twitter @karioakes

BOSTON – Obeticholic acid resulted in a significant reduction of a biomarker for liver fibrosis in patients with primary biliary cholangitis, according to a retrospective analysis of clinical trial data. In addition, patients taking obeticholic acid had a mean reduction in liver stiffness as measured by transient elastography.

Gideon Hirschfield, MD, PhD, presented the re-analysis of clinical trial data at the annual meeting of the American Association for the Study of Liver Diseases.

POISE was a phase III randomized, double-blind, placebo-controlled study of obeticholic acid for patients with primary biliary cholangitis (PBC). The clinical trial’s primary composite endpoint was an alkaline phosphatase level less than 1.67 times the upper limit of normal, with at least a 15% reduction in alkaline phosphatase and normal serum bilirubin.

The cohort of POISE patients on obeticholic acid met this biochemical surrogate endpoint, resulting in approval of the farnesoid X receptor agonist for treatment of PBC as an add-on to ursodeoxycholic acid (UDCA), or for patients who cannot tolerate UDCA.

However, transient elastography and the aspartate transaminase (AST) to platelet ratio index (APRI) have both been used to assess fibrosis in PBC, and have been found to predict clinical outcomes in PBC. These measures have the advantage of being noninvasive methods to measure the quality of liver tissue.

Dr. Hirschfield, a transplant hepatologist at the institute of immunology and immunotherapy at the University of Birmingham, England, and his coinvestigators reevaluated data from the POISE trial. They determined that APRI dropped significantly over 12 months of obeticholic acid treatment compared to placebo (P less than .01 for each of the two dosing arms of the POISE trial). Patients who switched to 5-10 mg of obeticholic acid daily from placebo during an open-label extension of POISE also had significant reductions in APRI scores (P less than .05); the reduction for placebo-switchers on a fixed 10-mg dose during the open-label study was not significant

Liver stiffness, as measured by transient elastography, was reduced for both arms of the POISE study at 12 months, but increased for those in the placebo arm. “Fewer patients receiving obeticholic acid 10 mg progressed” to a level associated with histological cirrhosis, “and patients receiving obeticholic acid showed an improvement in liver stiffness,” said Dr. Hirschfield.

Pruritis is a feature of PBC, and worsening pruritis can be a side effect of deoxycholic acid. However, the worsening is often transitory, so patients should be encouraged to try to stay the course, said Dr. Hirschfield. Managing patient expectations; sharing improved biomarkers; and considering the addition of a bile acid sequestrant or rifampicin, or reducing the obeticholic acid dose are all strategies to consider when caring for PBC patients, said Dr. Hirschfield.

Clinical trials to assess the safety and efficacy of obeticholic acid for individuals with nonalcoholic fatty liver disease and steatohepatitis are underway.

Dr. Hirschfield discussed his findings in a video interview.

[email protected]
On Twitter @karioakes

BOSTON – Obeticholic acid resulted in a significant reduction of a biomarker for liver fibrosis in patients with primary biliary cholangitis, according to a retrospective analysis of clinical trial data. In addition, patients taking obeticholic acid had a mean reduction in liver stiffness as measured by transient elastography.

Gideon Hirschfield, MD, PhD, presented the re-analysis of clinical trial data at the annual meeting of the American Association for the Study of Liver Diseases.

POISE was a phase III randomized, double-blind, placebo-controlled study of obeticholic acid for patients with primary biliary cholangitis (PBC). The clinical trial’s primary composite endpoint was an alkaline phosphatase level less than 1.67 times the upper limit of normal, with at least a 15% reduction in alkaline phosphatase and normal serum bilirubin.

The cohort of POISE patients on obeticholic acid met this biochemical surrogate endpoint, resulting in approval of the farnesoid X receptor agonist for treatment of PBC as an add-on to ursodeoxycholic acid (UDCA), or for patients who cannot tolerate UDCA.

However, transient elastography and the aspartate transaminase (AST) to platelet ratio index (APRI) have both been used to assess fibrosis in PBC, and have been found to predict clinical outcomes in PBC. These measures have the advantage of being noninvasive methods to measure the quality of liver tissue.

Dr. Hirschfield, a transplant hepatologist at the institute of immunology and immunotherapy at the University of Birmingham, England, and his coinvestigators reevaluated data from the POISE trial. They determined that APRI dropped significantly over 12 months of obeticholic acid treatment compared to placebo (P less than .01 for each of the two dosing arms of the POISE trial). Patients who switched to 5-10 mg of obeticholic acid daily from placebo during an open-label extension of POISE also had significant reductions in APRI scores (P less than .05); the reduction for placebo-switchers on a fixed 10-mg dose during the open-label study was not significant

Liver stiffness, as measured by transient elastography, was reduced for both arms of the POISE study at 12 months, but increased for those in the placebo arm. “Fewer patients receiving obeticholic acid 10 mg progressed” to a level associated with histological cirrhosis, “and patients receiving obeticholic acid showed an improvement in liver stiffness,” said Dr. Hirschfield.

Pruritis is a feature of PBC, and worsening pruritis can be a side effect of deoxycholic acid. However, the worsening is often transitory, so patients should be encouraged to try to stay the course, said Dr. Hirschfield. Managing patient expectations; sharing improved biomarkers; and considering the addition of a bile acid sequestrant or rifampicin, or reducing the obeticholic acid dose are all strategies to consider when caring for PBC patients, said Dr. Hirschfield.

Clinical trials to assess the safety and efficacy of obeticholic acid for individuals with nonalcoholic fatty liver disease and steatohepatitis are underway.

Dr. Hirschfield discussed his findings in a video interview.

[email protected]
On Twitter @karioakes

NEW ORLEANS – The cardiovascular safety profile of the nonsteroidal anti-inflammatory drug (NSAID) celecoxib, a selective inhibitor of COX-2, is no worse than those of the nonselective NSAIDs naproxen and ibuprofen, according to a trial reported at the American Heart Association scientific sessions.

The trial, known as PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen Or Naproxen) was undertaken after another selective COX-2 inhibitor, rofecoxib (Vioxx), was withdrawn from the market because of associated cardiovascular events. It compared the three drugs among more than 24,000 patients with painful arthritis and elevated cardiovascular risk.
Main results showed that 2%-3% of patients experienced a cardiovascular event (cardiovascular death, myocardial infarction, or stroke) during a follow-up approaching 3 years, regardless of which drug they were assigned to take, with the slight differences falling within predefined margins for noninferiority of celecoxib, investigators reported in a session and related press conference.

Additionally, celecoxib yielded a lower rate of gastrointestinal events when compared with each of the other drugs and a lower rate of renal events when compared with ibuprofen.

“After the withdrawal of rofecoxib, everybody thought they knew the answer, that COX-2 inhibitors had an unfavorable cardiovascular profile,” commented first author Steven E. Nissen, MD, chair of cardiovascular medicine at the Cleveland Clinic in Ohio. “We didn’t find that. And this is the type of study that once again teaches us that if we jump to conclusions about this based on mechanistic considerations, we often make very bad decisions.”

A cautionary view

“The investigators addressed an extremely important question, which is what is the cardiovascular safety of agents that we administer for a general medical condition over the long term,” commented invited discussant Elliott M. Antman, MD, a senior physician at Brigham and Women’s Hospital and associate dean for Clinical and Translational Research at Harvard Medical School in Boston. “We don’t see a lot of trials like that, but we do need this information.”

Trial details

Patients were eligible for PRECISION, a Pfizer-funded trial, if they had osteoarthritis or rheumatoid arthritis and were at increased cardiovascular risk.

In all, 24,081 patients from 926 centers globally were randomly assigned to double-blind treatment with celecoxib, naproxen, or ibuprofen, all of which are now available as generics in the United States.

“Patients were randomized to the FDA-approved doses of these drugs, and they could have their dose increased if they had unrelieved pain up to the maximum allowed by regulatory authorities in the local jurisdictions where the study was done,” Dr. Nissen noted, pointing out that studies initially generating some concern about celecoxib used a supratherapeutic dose of 800 mg daily.

As COX-2 inhibitors are less likely than nonselective NSAIDs to cause ulcers, which might affect compliance and outcomes, all patients additionally received esomeprazole for gastroprotection “to try to level the playing field,” he explained.

The mean treatment duration was 20.3 months, and the mean follow-up duration was 34.1 months, according to data reported at the meeting and simultaneously published (N Engl J Med. 2016 Nov 13. doi: 10.1056/NEJMoa1611593). On average, the daily dose of drug received was 209 mg for celecoxib, 852 mg for naproxen, and 2,045 mg for ibuprofen.

In intention-to-treat analyses, the rate of the primary composite outcome of cardiovascular death (including hemorrhagic death), nonfatal myocardial infarction, or nonfatal stroke was 2.3% in the celecoxib group, 2.5% in the naproxen group, and 2.7% in the ibuprofen group. The hazard ratio was 0.93 for celecoxib versus naproxen (P less than .001 for noninferiority) and 0.85 for celecoxib versus ibuprofen (P less than .001 for noninferiority).

Differences were more marked in the on-treatment population. Here, the rate of the primary outcome was 1.7% in the celecoxib group, 1.8% in the naproxen group, and 1.9% in the ibuprofen group. The HR was 0.90 for celecoxib versus naproxen (P less than .001 for noninferiority) and 0.81 for celecoxib versus ibuprofen (P less than .001 for noninferiority).

Secondary outcomes, which tested for superiority, showed that the rate of major adverse cardiovascular events was 15% higher in the ibuprofen group as compared with the celecoxib group in the intent-to-treat population. The difference translated to a near-significant reduction in risk with the latter (HR, 0.87; P = .06) that appeared greater in the on-treatment population.

However, Dr. Nissen cautioned that he could not state that celecoxib was superior. “Secondary and tertiary endpoints in a clinical trial are hypothesis generating, and they are not considered definitive evidence,” he commented. At the same time, “the FDA is going to have to deal with that because what do they do with labeling? What do they do with over-the-counter access to these various drugs?”

The rate of all-cause mortality was 25% higher with naproxen than with celecoxib (HR, 0.80; P = .052).

The rate of gastrointestinal events was 54% higher with ibuprofen (HR, 0.65; P = .002) and 41% higher with naproxen (HR, 0.71; P = .01) as compared with celecoxib. And the rate of renal events was 64% higher with ibuprofen than with celecoxib (HR, 0.61; P = .004).

In a post hoc analysis of global safety, the rate of serious cardiovascular, gastrointestinal, and renal events was 28% higher with ibuprofen (HR, 0.78; P less than .001) and 15% higher with naproxen (HR, 0.87; P = .03) than with celecoxib.

Of note, the findings for the primary endpoint were similar regardless of whether patients were taking low-dose aspirin or not. “There was no interaction with aspirin use,” Dr. Nissen stated. “This was not about the interference of ibuprofen or naproxen with aspirin use.”

Analyses of pain relief using a visual analogue scale showed no clinically meaningful differences, suggesting that the drug doses used were equally analgesic, he said. Stopping of study drug because of lack of efficacy was slightly more common in the celecoxib group.

“We didn’t study the low-dose, intermittent use of these drugs that most of the public engages in, and it’s really important that we crisply communicate that to the public because somebody who takes occasionally ibuprofen or naproxen for a headache should not look at these comparative data in a way that should necessarily influence their behavior. We just don’t know the answer,” cautioned Dr. Nissen, who disclosed that he received grant support from Pfizer during the conduct of the trial.

But the findings are relevant for individuals who take over-the-counter NSAIDs at doses exceeding the label, a phenomenon known as dose creep. “We need to reemphasize to the public that the labeled over-the-counter dose is what you should take. You shouldn’t double up or triple up on the drugs because the issue of high-dose therapy, which is what we studied, suggests that there are really potentially important gastrointestinal, renal, and cardiovascular risks,” he said.

NEW ORLEANS – The cardiovascular safety profile of the nonsteroidal anti-inflammatory drug (NSAID) celecoxib, a selective inhibitor of COX-2, is no worse than those of the nonselective NSAIDs naproxen and ibuprofen, according to a trial reported at the American Heart Association scientific sessions.

The trial, known as PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen Or Naproxen) was undertaken after another selective COX-2 inhibitor, rofecoxib (Vioxx), was withdrawn from the market because of associated cardiovascular events. It compared the three drugs among more than 24,000 patients with painful arthritis and elevated cardiovascular risk.
Main results showed that 2%-3% of patients experienced a cardiovascular event (cardiovascular death, myocardial infarction, or stroke) during a follow-up approaching 3 years, regardless of which drug they were assigned to take, with the slight differences falling within predefined margins for noninferiority of celecoxib, investigators reported in a session and related press conference.

Additionally, celecoxib yielded a lower rate of gastrointestinal events when compared with each of the other drugs and a lower rate of renal events when compared with ibuprofen.

“After the withdrawal of rofecoxib, everybody thought they knew the answer, that COX-2 inhibitors had an unfavorable cardiovascular profile,” commented first author Steven E. Nissen, MD, chair of cardiovascular medicine at the Cleveland Clinic in Ohio. “We didn’t find that. And this is the type of study that once again teaches us that if we jump to conclusions about this based on mechanistic considerations, we often make very bad decisions.”

A cautionary view

“The investigators addressed an extremely important question, which is what is the cardiovascular safety of agents that we administer for a general medical condition over the long term,” commented invited discussant Elliott M. Antman, MD, a senior physician at Brigham and Women’s Hospital and associate dean for Clinical and Translational Research at Harvard Medical School in Boston. “We don’t see a lot of trials like that, but we do need this information.”

Trial details

Patients were eligible for PRECISION, a Pfizer-funded trial, if they had osteoarthritis or rheumatoid arthritis and were at increased cardiovascular risk.

In all, 24,081 patients from 926 centers globally were randomly assigned to double-blind treatment with celecoxib, naproxen, or ibuprofen, all of which are now available as generics in the United States.

“Patients were randomized to the FDA-approved doses of these drugs, and they could have their dose increased if they had unrelieved pain up to the maximum allowed by regulatory authorities in the local jurisdictions where the study was done,” Dr. Nissen noted, pointing out that studies initially generating some concern about celecoxib used a supratherapeutic dose of 800 mg daily.

As COX-2 inhibitors are less likely than nonselective NSAIDs to cause ulcers, which might affect compliance and outcomes, all patients additionally received esomeprazole for gastroprotection “to try to level the playing field,” he explained.

The mean treatment duration was 20.3 months, and the mean follow-up duration was 34.1 months, according to data reported at the meeting and simultaneously published (N Engl J Med. 2016 Nov 13. doi: 10.1056/NEJMoa1611593). On average, the daily dose of drug received was 209 mg for celecoxib, 852 mg for naproxen, and 2,045 mg for ibuprofen.

In intention-to-treat analyses, the rate of the primary composite outcome of cardiovascular death (including hemorrhagic death), nonfatal myocardial infarction, or nonfatal stroke was 2.3% in the celecoxib group, 2.5% in the naproxen group, and 2.7% in the ibuprofen group. The hazard ratio was 0.93 for celecoxib versus naproxen (P less than .001 for noninferiority) and 0.85 for celecoxib versus ibuprofen (P less than .001 for noninferiority).

Differences were more marked in the on-treatment population. Here, the rate of the primary outcome was 1.7% in the celecoxib group, 1.8% in the naproxen group, and 1.9% in the ibuprofen group. The HR was 0.90 for celecoxib versus naproxen (P less than .001 for noninferiority) and 0.81 for celecoxib versus ibuprofen (P less than .001 for noninferiority).

Secondary outcomes, which tested for superiority, showed that the rate of major adverse cardiovascular events was 15% higher in the ibuprofen group as compared with the celecoxib group in the intent-to-treat population. The difference translated to a near-significant reduction in risk with the latter (HR, 0.87; P = .06) that appeared greater in the on-treatment population.

However, Dr. Nissen cautioned that he could not state that celecoxib was superior. “Secondary and tertiary endpoints in a clinical trial are hypothesis generating, and they are not considered definitive evidence,” he commented. At the same time, “the FDA is going to have to deal with that because what do they do with labeling? What do they do with over-the-counter access to these various drugs?”

The rate of all-cause mortality was 25% higher with naproxen than with celecoxib (HR, 0.80; P = .052).

The rate of gastrointestinal events was 54% higher with ibuprofen (HR, 0.65; P = .002) and 41% higher with naproxen (HR, 0.71; P = .01) as compared with celecoxib. And the rate of renal events was 64% higher with ibuprofen than with celecoxib (HR, 0.61; P = .004).

In a post hoc analysis of global safety, the rate of serious cardiovascular, gastrointestinal, and renal events was 28% higher with ibuprofen (HR, 0.78; P less than .001) and 15% higher with naproxen (HR, 0.87; P = .03) than with celecoxib.

Of note, the findings for the primary endpoint were similar regardless of whether patients were taking low-dose aspirin or not. “There was no interaction with aspirin use,” Dr. Nissen stated. “This was not about the interference of ibuprofen or naproxen with aspirin use.”

Analyses of pain relief using a visual analogue scale showed no clinically meaningful differences, suggesting that the drug doses used were equally analgesic, he said. Stopping of study drug because of lack of efficacy was slightly more common in the celecoxib group.

“We didn’t study the low-dose, intermittent use of these drugs that most of the public engages in, and it’s really important that we crisply communicate that to the public because somebody who takes occasionally ibuprofen or naproxen for a headache should not look at these comparative data in a way that should necessarily influence their behavior. We just don’t know the answer,” cautioned Dr. Nissen, who disclosed that he received grant support from Pfizer during the conduct of the trial.

But the findings are relevant for individuals who take over-the-counter NSAIDs at doses exceeding the label, a phenomenon known as dose creep. “We need to reemphasize to the public that the labeled over-the-counter dose is what you should take. You shouldn’t double up or triple up on the drugs because the issue of high-dose therapy, which is what we studied, suggests that there are really potentially important gastrointestinal, renal, and cardiovascular risks,” he said.

NEW ORLEANS – The cardiovascular safety profile of the nonsteroidal anti-inflammatory drug (NSAID) celecoxib, a selective inhibitor of COX-2, is no worse than those of the nonselective NSAIDs naproxen and ibuprofen, according to a trial reported at the American Heart Association scientific sessions.

The trial, known as PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen Or Naproxen) was undertaken after another selective COX-2 inhibitor, rofecoxib (Vioxx), was withdrawn from the market because of associated cardiovascular events. It compared the three drugs among more than 24,000 patients with painful arthritis and elevated cardiovascular risk.
Main results showed that 2%-3% of patients experienced a cardiovascular event (cardiovascular death, myocardial infarction, or stroke) during a follow-up approaching 3 years, regardless of which drug they were assigned to take, with the slight differences falling within predefined margins for noninferiority of celecoxib, investigators reported in a session and related press conference.

Additionally, celecoxib yielded a lower rate of gastrointestinal events when compared with each of the other drugs and a lower rate of renal events when compared with ibuprofen.

“After the withdrawal of rofecoxib, everybody thought they knew the answer, that COX-2 inhibitors had an unfavorable cardiovascular profile,” commented first author Steven E. Nissen, MD, chair of cardiovascular medicine at the Cleveland Clinic in Ohio. “We didn’t find that. And this is the type of study that once again teaches us that if we jump to conclusions about this based on mechanistic considerations, we often make very bad decisions.”

A cautionary view

“The investigators addressed an extremely important question, which is what is the cardiovascular safety of agents that we administer for a general medical condition over the long term,” commented invited discussant Elliott M. Antman, MD, a senior physician at Brigham and Women’s Hospital and associate dean for Clinical and Translational Research at Harvard Medical School in Boston. “We don’t see a lot of trials like that, but we do need this information.”

Trial details

Patients were eligible for PRECISION, a Pfizer-funded trial, if they had osteoarthritis or rheumatoid arthritis and were at increased cardiovascular risk.

In all, 24,081 patients from 926 centers globally were randomly assigned to double-blind treatment with celecoxib, naproxen, or ibuprofen, all of which are now available as generics in the United States.

“Patients were randomized to the FDA-approved doses of these drugs, and they could have their dose increased if they had unrelieved pain up to the maximum allowed by regulatory authorities in the local jurisdictions where the study was done,” Dr. Nissen noted, pointing out that studies initially generating some concern about celecoxib used a supratherapeutic dose of 800 mg daily.

As COX-2 inhibitors are less likely than nonselective NSAIDs to cause ulcers, which might affect compliance and outcomes, all patients additionally received esomeprazole for gastroprotection “to try to level the playing field,” he explained.

The mean treatment duration was 20.3 months, and the mean follow-up duration was 34.1 months, according to data reported at the meeting and simultaneously published (N Engl J Med. 2016 Nov 13. doi: 10.1056/NEJMoa1611593). On average, the daily dose of drug received was 209 mg for celecoxib, 852 mg for naproxen, and 2,045 mg for ibuprofen.

In intention-to-treat analyses, the rate of the primary composite outcome of cardiovascular death (including hemorrhagic death), nonfatal myocardial infarction, or nonfatal stroke was 2.3% in the celecoxib group, 2.5% in the naproxen group, and 2.7% in the ibuprofen group. The hazard ratio was 0.93 for celecoxib versus naproxen (P less than .001 for noninferiority) and 0.85 for celecoxib versus ibuprofen (P less than .001 for noninferiority).

Differences were more marked in the on-treatment population. Here, the rate of the primary outcome was 1.7% in the celecoxib group, 1.8% in the naproxen group, and 1.9% in the ibuprofen group. The HR was 0.90 for celecoxib versus naproxen (P less than .001 for noninferiority) and 0.81 for celecoxib versus ibuprofen (P less than .001 for noninferiority).

Secondary outcomes, which tested for superiority, showed that the rate of major adverse cardiovascular events was 15% higher in the ibuprofen group as compared with the celecoxib group in the intent-to-treat population. The difference translated to a near-significant reduction in risk with the latter (HR, 0.87; P = .06) that appeared greater in the on-treatment population.

However, Dr. Nissen cautioned that he could not state that celecoxib was superior. “Secondary and tertiary endpoints in a clinical trial are hypothesis generating, and they are not considered definitive evidence,” he commented. At the same time, “the FDA is going to have to deal with that because what do they do with labeling? What do they do with over-the-counter access to these various drugs?”

The rate of all-cause mortality was 25% higher with naproxen than with celecoxib (HR, 0.80; P = .052).

The rate of gastrointestinal events was 54% higher with ibuprofen (HR, 0.65; P = .002) and 41% higher with naproxen (HR, 0.71; P = .01) as compared with celecoxib. And the rate of renal events was 64% higher with ibuprofen than with celecoxib (HR, 0.61; P = .004).

In a post hoc analysis of global safety, the rate of serious cardiovascular, gastrointestinal, and renal events was 28% higher with ibuprofen (HR, 0.78; P less than .001) and 15% higher with naproxen (HR, 0.87; P = .03) than with celecoxib.

Of note, the findings for the primary endpoint were similar regardless of whether patients were taking low-dose aspirin or not. “There was no interaction with aspirin use,” Dr. Nissen stated. “This was not about the interference of ibuprofen or naproxen with aspirin use.”

Analyses of pain relief using a visual analogue scale showed no clinically meaningful differences, suggesting that the drug doses used were equally analgesic, he said. Stopping of study drug because of lack of efficacy was slightly more common in the celecoxib group.

“We didn’t study the low-dose, intermittent use of these drugs that most of the public engages in, and it’s really important that we crisply communicate that to the public because somebody who takes occasionally ibuprofen or naproxen for a headache should not look at these comparative data in a way that should necessarily influence their behavior. We just don’t know the answer,” cautioned Dr. Nissen, who disclosed that he received grant support from Pfizer during the conduct of the trial.

But the findings are relevant for individuals who take over-the-counter NSAIDs at doses exceeding the label, a phenomenon known as dose creep. “We need to reemphasize to the public that the labeled over-the-counter dose is what you should take. You shouldn’t double up or triple up on the drugs because the issue of high-dose therapy, which is what we studied, suggests that there are really potentially important gastrointestinal, renal, and cardiovascular risks,” he said.

WASHINGTON – Tocilizumab treatment every week or every other week for 52 weeks with a 26-week prednisone taper was superior to a short and long course of tapered prednisone and also cut the rate of steroid use in half when compared with long-course prednisone in patients with giant cell arteritis in the largest-ever trial of patients with the disease.

The treatment represents a milestone in the treatment of giant cell arteritis (GCA), “a chronic, often devastating, difficult to manage disease,” John Stone, MD, said in his presentation of the results of the randomized, double-blind, placebo-controlled GiACTA trial at the annual meeting of the American College of Rheumatology.

Remissions rise while flares and steroid use decline

GiACTA enrolled 251 GCA patients over 22 months from 14 countries and 76 sites (61 in Europe and 15 in North America). Median age was 69 years; 74% were female; and 97% were white.

“This trial was 2.5 times as large as any trial conducted in GCA,” Dr. Stone said.

Patients with GCA were eligible for the study if they met modified 1990 ACR classification criteria for GCA as follows: elevated C-reactive protein (CRP) with unequivocal cranial symptoms or unequivocal symptoms of polymyalgia rheumatica; and imaging evidence of large-vessel vasculitis (ultrasound was not permitted).

Patients were randomized to one of four treatment arms: Group 1, prednisone with 6-month taper until week 52 on no other therapy; Group 2, prednisone with 52 weeks of taper; Group 3, weekly tocilizumab injection plus the same steroid taper as Group 1; and Group 4, tocilizumab every other week with same steroid taper as Group 1.

Investigators were blinded to the prednisone taper regimen and the treatment.

Dr. Stone reported 52-week results for the primary endpoint of GiACTA (i.e., sustained remission from week 12 to 52 for tocilizumab versus prednisone 26-week taper). The study is continuing open-label for another year.

The rates of sustained remission at 52 weeks were significantly higher for both weekly tocilizumab (56% of 100 patients; P less than .0001) and every-other-week tocilizumab (53% of 49 patients; P = .0002) versus 14% for short-course prednisone (14% of 50 patients). The rate of sustained remission at 52 weeks was 18% of 51 patients for long-course prednisone.

“The inclusion of CRP did not affect the outcome. After removing CRP from the primary analysis, both endpoints were highly statistically significant for the tocilizumab groups,” Dr. Stone noted.

The same pattern was evident for time to first flare following clinical remission, with the best results in Group 3 and Group 4 – the two tocilizumab groups. The weekly tocilizumab group had a sustained response following the cessation of prednisone, but the every-other-week tocilizumab group had a drop-off after stopping prednisone. More flares were seen in Groups 1 and 2.

Flares were defined as recurrence of GCA signs or symptoms; increased erythrocyte sedimentation rate greater than 30 mm/h attributed to GCA; or two consecutive CRP elevations. Flares were treated by increase in prednisone dose. The cumulative dose of prednisone was cut in half in both tocilizumab arms, compared with the long-course prednisone treatment arm.

“The reduction in prednisone use in patients taking tocilizumab was clinically significant,” Dr. Stone said.

According to the Short-Form 36, a patient-reported outcomes measure, tocilizumab improved global quality of life while quality of life declined in both prednisone taper groups.

There were no new safety signals related to tocilizumab reported during the trial. No cases of vision loss and no deaths occurred. Two malignancies were reported in the prednisone groups.

“Adverse events were not disproportionate in the tocilizumab-treated groups,” Dr. Stone said.

Some of the investigators had financial relationships with Roche, which sponsored the study, or other pharmaceutical companies. Several investigators were employees of Roche or its wholly-owned subsidiary, Genentech.

WASHINGTON – Tocilizumab treatment every week or every other week for 52 weeks with a 26-week prednisone taper was superior to a short and long course of tapered prednisone and also cut the rate of steroid use in half when compared with long-course prednisone in patients with giant cell arteritis in the largest-ever trial of patients with the disease.

The treatment represents a milestone in the treatment of giant cell arteritis (GCA), “a chronic, often devastating, difficult to manage disease,” John Stone, MD, said in his presentation of the results of the randomized, double-blind, placebo-controlled GiACTA trial at the annual meeting of the American College of Rheumatology.

Remissions rise while flares and steroid use decline

GiACTA enrolled 251 GCA patients over 22 months from 14 countries and 76 sites (61 in Europe and 15 in North America). Median age was 69 years; 74% were female; and 97% were white.

“This trial was 2.5 times as large as any trial conducted in GCA,” Dr. Stone said.

Patients with GCA were eligible for the study if they met modified 1990 ACR classification criteria for GCA as follows: elevated C-reactive protein (CRP) with unequivocal cranial symptoms or unequivocal symptoms of polymyalgia rheumatica; and imaging evidence of large-vessel vasculitis (ultrasound was not permitted).

Patients were randomized to one of four treatment arms: Group 1, prednisone with 6-month taper until week 52 on no other therapy; Group 2, prednisone with 52 weeks of taper; Group 3, weekly tocilizumab injection plus the same steroid taper as Group 1; and Group 4, tocilizumab every other week with same steroid taper as Group 1.

Investigators were blinded to the prednisone taper regimen and the treatment.

Dr. Stone reported 52-week results for the primary endpoint of GiACTA (i.e., sustained remission from week 12 to 52 for tocilizumab versus prednisone 26-week taper). The study is continuing open-label for another year.

The rates of sustained remission at 52 weeks were significantly higher for both weekly tocilizumab (56% of 100 patients; P less than .0001) and every-other-week tocilizumab (53% of 49 patients; P = .0002) versus 14% for short-course prednisone (14% of 50 patients). The rate of sustained remission at 52 weeks was 18% of 51 patients for long-course prednisone.

“The inclusion of CRP did not affect the outcome. After removing CRP from the primary analysis, both endpoints were highly statistically significant for the tocilizumab groups,” Dr. Stone noted.

The same pattern was evident for time to first flare following clinical remission, with the best results in Group 3 and Group 4 – the two tocilizumab groups. The weekly tocilizumab group had a sustained response following the cessation of prednisone, but the every-other-week tocilizumab group had a drop-off after stopping prednisone. More flares were seen in Groups 1 and 2.

Flares were defined as recurrence of GCA signs or symptoms; increased erythrocyte sedimentation rate greater than 30 mm/h attributed to GCA; or two consecutive CRP elevations. Flares were treated by increase in prednisone dose. The cumulative dose of prednisone was cut in half in both tocilizumab arms, compared with the long-course prednisone treatment arm.

“The reduction in prednisone use in patients taking tocilizumab was clinically significant,” Dr. Stone said.

According to the Short-Form 36, a patient-reported outcomes measure, tocilizumab improved global quality of life while quality of life declined in both prednisone taper groups.

There were no new safety signals related to tocilizumab reported during the trial. No cases of vision loss and no deaths occurred. Two malignancies were reported in the prednisone groups.

“Adverse events were not disproportionate in the tocilizumab-treated groups,” Dr. Stone said.

Some of the investigators had financial relationships with Roche, which sponsored the study, or other pharmaceutical companies. Several investigators were employees of Roche or its wholly-owned subsidiary, Genentech.

WASHINGTON – Tocilizumab treatment every week or every other week for 52 weeks with a 26-week prednisone taper was superior to a short and long course of tapered prednisone and also cut the rate of steroid use in half when compared with long-course prednisone in patients with giant cell arteritis in the largest-ever trial of patients with the disease.

The treatment represents a milestone in the treatment of giant cell arteritis (GCA), “a chronic, often devastating, difficult to manage disease,” John Stone, MD, said in his presentation of the results of the randomized, double-blind, placebo-controlled GiACTA trial at the annual meeting of the American College of Rheumatology.

Remissions rise while flares and steroid use decline

GiACTA enrolled 251 GCA patients over 22 months from 14 countries and 76 sites (61 in Europe and 15 in North America). Median age was 69 years; 74% were female; and 97% were white.

“This trial was 2.5 times as large as any trial conducted in GCA,” Dr. Stone said.

Patients with GCA were eligible for the study if they met modified 1990 ACR classification criteria for GCA as follows: elevated C-reactive protein (CRP) with unequivocal cranial symptoms or unequivocal symptoms of polymyalgia rheumatica; and imaging evidence of large-vessel vasculitis (ultrasound was not permitted).

Patients were randomized to one of four treatment arms: Group 1, prednisone with 6-month taper until week 52 on no other therapy; Group 2, prednisone with 52 weeks of taper; Group 3, weekly tocilizumab injection plus the same steroid taper as Group 1; and Group 4, tocilizumab every other week with same steroid taper as Group 1.

Investigators were blinded to the prednisone taper regimen and the treatment.

Dr. Stone reported 52-week results for the primary endpoint of GiACTA (i.e., sustained remission from week 12 to 52 for tocilizumab versus prednisone 26-week taper). The study is continuing open-label for another year.

The rates of sustained remission at 52 weeks were significantly higher for both weekly tocilizumab (56% of 100 patients; P less than .0001) and every-other-week tocilizumab (53% of 49 patients; P = .0002) versus 14% for short-course prednisone (14% of 50 patients). The rate of sustained remission at 52 weeks was 18% of 51 patients for long-course prednisone.

“The inclusion of CRP did not affect the outcome. After removing CRP from the primary analysis, both endpoints were highly statistically significant for the tocilizumab groups,” Dr. Stone noted.

The same pattern was evident for time to first flare following clinical remission, with the best results in Group 3 and Group 4 – the two tocilizumab groups. The weekly tocilizumab group had a sustained response following the cessation of prednisone, but the every-other-week tocilizumab group had a drop-off after stopping prednisone. More flares were seen in Groups 1 and 2.

Flares were defined as recurrence of GCA signs or symptoms; increased erythrocyte sedimentation rate greater than 30 mm/h attributed to GCA; or two consecutive CRP elevations. Flares were treated by increase in prednisone dose. The cumulative dose of prednisone was cut in half in both tocilizumab arms, compared with the long-course prednisone treatment arm.

“The reduction in prednisone use in patients taking tocilizumab was clinically significant,” Dr. Stone said.

According to the Short-Form 36, a patient-reported outcomes measure, tocilizumab improved global quality of life while quality of life declined in both prednisone taper groups.

There were no new safety signals related to tocilizumab reported during the trial. No cases of vision loss and no deaths occurred. Two malignancies were reported in the prednisone groups.

“Adverse events were not disproportionate in the tocilizumab-treated groups,” Dr. Stone said.

Some of the investigators had financial relationships with Roche, which sponsored the study, or other pharmaceutical companies. Several investigators were employees of Roche or its wholly-owned subsidiary, Genentech.

WASHINGTON – Readmissions after bariatric surgery are significantly higher among black patients than among whites.

The reasons aren’t entirely clear, but since long-term morbidity and mortality are equivalent, they are probably more related to socioeconomics than clinical factors, Matthew Whealon, MD, said at the annual clinical congress of the American College of Surgeons.

“I think they are multifactorial,” said Dr. Whealon of the University of California, Irvine. “Some of it may be related to comorbidities, but other factors could be socioeconomic status, insurance status, access to primary care and follow-up care, even home support systems and patient expectations after surgery. I think it’s incumbent upon us to try and identify some of these risk factors and address them before surgery to reduce this disparity in readmissions.”

Michele G. Sullivan/Frontline Medical News

[email protected]

On Twitter @Alz_Gal

WASHINGTON – Readmissions after bariatric surgery are significantly higher among black patients than among whites.

The reasons aren’t entirely clear, but since long-term morbidity and mortality are equivalent, they are probably more related to socioeconomics than clinical factors, Matthew Whealon, MD, said at the annual clinical congress of the American College of Surgeons.

“I think they are multifactorial,” said Dr. Whealon of the University of California, Irvine. “Some of it may be related to comorbidities, but other factors could be socioeconomic status, insurance status, access to primary care and follow-up care, even home support systems and patient expectations after surgery. I think it’s incumbent upon us to try and identify some of these risk factors and address them before surgery to reduce this disparity in readmissions.”

Michele G. Sullivan/Frontline Medical News

[email protected]

On Twitter @Alz_Gal

WASHINGTON – Readmissions after bariatric surgery are significantly higher among black patients than among whites.

The reasons aren’t entirely clear, but since long-term morbidity and mortality are equivalent, they are probably more related to socioeconomics than clinical factors, Matthew Whealon, MD, said at the annual clinical congress of the American College of Surgeons.

“I think they are multifactorial,” said Dr. Whealon of the University of California, Irvine. “Some of it may be related to comorbidities, but other factors could be socioeconomic status, insurance status, access to primary care and follow-up care, even home support systems and patient expectations after surgery. I think it’s incumbent upon us to try and identify some of these risk factors and address them before surgery to reduce this disparity in readmissions.”

Michele G. Sullivan/Frontline Medical News

[email protected]

On Twitter @Alz_Gal

WASHINGTON – Chronic cardiac inflammation is present in rheumatoid arthritis patients and appears to resolve when they achieve a good clinical response to medical therapy.

The findings of two cardiac imaging studies offer a tantalizing clue to the link between RA and heart failure, said Isabelle Amigues, MD, who reported the findings at the annual meeting of the American College of Rheumatology.

“We know that the inflammation of RA is not just restricted to joints,” said Dr. Amigues, a rheumatology fellow at Columbia University, New York. “We see it throughout the body, so of course it makes sense that we would see it in the heart as well. And now we see that we may be able to manage this with good disease management.

The study that found improvement of myocarditis with RA therapy was very small – just 8 patients and 12 controls – but the results were surprising and encouraging, Dr. Amigues said.

[email protected]

On Twitter @Alz_Gal

WASHINGTON – Chronic cardiac inflammation is present in rheumatoid arthritis patients and appears to resolve when they achieve a good clinical response to medical therapy.

The findings of two cardiac imaging studies offer a tantalizing clue to the link between RA and heart failure, said Isabelle Amigues, MD, who reported the findings at the annual meeting of the American College of Rheumatology.

“We know that the inflammation of RA is not just restricted to joints,” said Dr. Amigues, a rheumatology fellow at Columbia University, New York. “We see it throughout the body, so of course it makes sense that we would see it in the heart as well. And now we see that we may be able to manage this with good disease management.

The study that found improvement of myocarditis with RA therapy was very small – just 8 patients and 12 controls – but the results were surprising and encouraging, Dr. Amigues said.

[email protected]

On Twitter @Alz_Gal

WASHINGTON – Chronic cardiac inflammation is present in rheumatoid arthritis patients and appears to resolve when they achieve a good clinical response to medical therapy.

The findings of two cardiac imaging studies offer a tantalizing clue to the link between RA and heart failure, said Isabelle Amigues, MD, who reported the findings at the annual meeting of the American College of Rheumatology.

“We know that the inflammation of RA is not just restricted to joints,” said Dr. Amigues, a rheumatology fellow at Columbia University, New York. “We see it throughout the body, so of course it makes sense that we would see it in the heart as well. And now we see that we may be able to manage this with good disease management.

The study that found improvement of myocarditis with RA therapy was very small – just 8 patients and 12 controls – but the results were surprising and encouraging, Dr. Amigues said.

[email protected]

On Twitter @Alz_Gal

Cutaneous larva migrans

Cutaneous larva migrans (CLM) presents as a self-limited cutaneous eruption.  It is also known as creeping eruption.  Animal (dog and cat) hookworms such as Ancylostoma braziliense are responsible for most CLM infestations in the central and southeastern United States. The hookworms are often acquired while walking barefoot in contaminated sand.  Carpenters, plumbers, and gardeners are also likely to be affected.  Ova from the hookworms hatch into larvae that penetrate into skin.

On physical examination, lesions are erythematous, linear and serpiginous.  Exposed sites, such as lower legs, hands, genitals, buttocks, and feet are most commonly involved.  The migration begins about 4 days after onset.  There is often intense pruritus and lesions advance 1-2 cm per day.  Old lesions fade as the larvae migrate.  They may have periods of rest, evidenced as papules.  The differential diagnosis includes other parasites (uncinariasis, gnathostomiasis, strongyloidiasis, myiasis), dermatophytosis, phytophotodermatitis, erythema chronicum migrans, granuloma annulare, and bullous impetigo. 

CLM is often a clinical diagnosis.  Histopathology often reveals an inflammatory infiltrate or, if taken from an advancing lesion, part of the parasite.  Serology may reveal an eosinophilia.

CLM is usually a limited infestation that typically resolves within 2-8 weeks, although longer timelines have been reported.  Complications include cellulitis, abscess formation, and Loeffler syndrome (patchy lung infiltrate and eosinophilia).  Antihistamines alone may be used to alleviate the accompanying pruritus, but curative treatment is often used.  First-line curative therapies include oral albendazole and ivermectin but topical tiabendazole is also effective.  Our patient responded well to oral ivermectin.

Case and photo courtesy of Mark Ash, MS; Brody School of Medicine,Greenville, North Carolina; and Donna Bilu Martin, MD; Premier Dermatology, MD, Aventura, Florida.

Cutaneous larva migrans

Cutaneous larva migrans (CLM) presents as a self-limited cutaneous eruption.  It is also known as creeping eruption.  Animal (dog and cat) hookworms such as Ancylostoma braziliense are responsible for most CLM infestations in the central and southeastern United States. The hookworms are often acquired while walking barefoot in contaminated sand.  Carpenters, plumbers, and gardeners are also likely to be affected.  Ova from the hookworms hatch into larvae that penetrate into skin.

On physical examination, lesions are erythematous, linear and serpiginous.  Exposed sites, such as lower legs, hands, genitals, buttocks, and feet are most commonly involved.  The migration begins about 4 days after onset.  There is often intense pruritus and lesions advance 1-2 cm per day.  Old lesions fade as the larvae migrate.  They may have periods of rest, evidenced as papules.  The differential diagnosis includes other parasites (uncinariasis, gnathostomiasis, strongyloidiasis, myiasis), dermatophytosis, phytophotodermatitis, erythema chronicum migrans, granuloma annulare, and bullous impetigo. 

CLM is often a clinical diagnosis.  Histopathology often reveals an inflammatory infiltrate or, if taken from an advancing lesion, part of the parasite.  Serology may reveal an eosinophilia.

CLM is usually a limited infestation that typically resolves within 2-8 weeks, although longer timelines have been reported.  Complications include cellulitis, abscess formation, and Loeffler syndrome (patchy lung infiltrate and eosinophilia).  Antihistamines alone may be used to alleviate the accompanying pruritus, but curative treatment is often used.  First-line curative therapies include oral albendazole and ivermectin but topical tiabendazole is also effective.  Our patient responded well to oral ivermectin.

Case and photo courtesy of Mark Ash, MS; Brody School of Medicine,Greenville, North Carolina; and Donna Bilu Martin, MD; Premier Dermatology, MD, Aventura, Florida.

Cutaneous larva migrans

Cutaneous larva migrans (CLM) presents as a self-limited cutaneous eruption.  It is also known as creeping eruption.  Animal (dog and cat) hookworms such as Ancylostoma braziliense are responsible for most CLM infestations in the central and southeastern United States. The hookworms are often acquired while walking barefoot in contaminated sand.  Carpenters, plumbers, and gardeners are also likely to be affected.  Ova from the hookworms hatch into larvae that penetrate into skin.

On physical examination, lesions are erythematous, linear and serpiginous.  Exposed sites, such as lower legs, hands, genitals, buttocks, and feet are most commonly involved.  The migration begins about 4 days after onset.  There is often intense pruritus and lesions advance 1-2 cm per day.  Old lesions fade as the larvae migrate.  They may have periods of rest, evidenced as papules.  The differential diagnosis includes other parasites (uncinariasis, gnathostomiasis, strongyloidiasis, myiasis), dermatophytosis, phytophotodermatitis, erythema chronicum migrans, granuloma annulare, and bullous impetigo. 

CLM is often a clinical diagnosis.  Histopathology often reveals an inflammatory infiltrate or, if taken from an advancing lesion, part of the parasite.  Serology may reveal an eosinophilia.

CLM is usually a limited infestation that typically resolves within 2-8 weeks, although longer timelines have been reported.  Complications include cellulitis, abscess formation, and Loeffler syndrome (patchy lung infiltrate and eosinophilia).  Antihistamines alone may be used to alleviate the accompanying pruritus, but curative treatment is often used.  First-line curative therapies include oral albendazole and ivermectin but topical tiabendazole is also effective.  Our patient responded well to oral ivermectin.

Case and photo courtesy of Mark Ash, MS; Brody School of Medicine,Greenville, North Carolina; and Donna Bilu Martin, MD; Premier Dermatology, MD, Aventura, Florida.

Instruments used for robotic surgery are “virtually impossible” to clean completely, according to a report published in Infection Control & Hospital Epidemiology.

“A new standard for the cleaning of complex surgical instruments needs to be established, especially for those used in robotic surgery,” wrote Yuhei Saito of the surgical center at the University of Tokyo Hospital and associates.

They assessed the residual contamination of both robotic and regular surgical instruments at their medical center because “hospital staff in central sterile supply departments are troubled by the reprocessing of robotic instruments because they cannot be disassembled for cleaning like other endoscopic instruments. Their complex structure impairs brushing the inner surface of narrow lumens, resulting in failure to [completely] remove contaminants,” the researchers wrote.

In the first phase of the study, the researchers examined 41 instruments immediately after they were used in robotic surgery (7 radical prostatectomies and 2 anterior resections of the rectum) and 27 regular instruments immediately after they were used for open surgery (gastrectomy and colectomy). The robotic instruments were contaminated with 72.3 × 10³ mcg of protein each, compared with 5.5 × 10³ mcg of protein on the regular instruments, the investigators reported (Infect Control Hosp Epidemiol. 2016 Oct 31. doi: 10.1017/ice.2016.249).

In the second phase of the study, the researchers examined another 24 robotic instruments and 40 regular instruments after they were used in surgery and then cleaned according to the manufacturers’ instructions three successive times. For the robotic instruments, this involved manually brushing the outer surface while moving the instrument “wrists” through their full range of motion, followed by 15 minutes of ultrasonication with enzymatic detergent, flushing the lumen with a water gun through flush ports, and rinsing the entire instrument. For regular instruments, cleaning involved washer-disinfectors and included 5 minutes of ultrasonication, 10 minutes of spraying with an alkaline detergent, and 10 minutes of disinfection via heating.

The level of contamination declined with each successive cleaning but still remained comparatively high for the robotic instruments. The amount of protein contaminants released in the three cleanings was 650, 550, and 530 mcg per robotic instrument, compared with 16, 17, and 17 mcg per ordinary instrument.

The efficacy of cleaning was 97.6% for robotic instruments and 99.1% for regular instruments, the researchers reported.

This study was not designed to assess whether residual contamination is associated with adverse events such as infection in subsequent patients, and there are few data available on this topic.

“We have to recognize that there might be a considerable volume of insufficient cleaning or occult surgical site infections,” the investigators wrote.

New instrument washers equipped with a specific cleaning function for narrow lumens are becoming available, they noted, and “further study should be conducted using these washers with improved cleaning efficacy.”

The study was supported by the Japan Society for the Promotion of Science. The investigators reported having no relevant financial disclosures.

Instruments used for robotic surgery are “virtually impossible” to clean completely, according to a report published in Infection Control & Hospital Epidemiology.

“A new standard for the cleaning of complex surgical instruments needs to be established, especially for those used in robotic surgery,” wrote Yuhei Saito of the surgical center at the University of Tokyo Hospital and associates.

They assessed the residual contamination of both robotic and regular surgical instruments at their medical center because “hospital staff in central sterile supply departments are troubled by the reprocessing of robotic instruments because they cannot be disassembled for cleaning like other endoscopic instruments. Their complex structure impairs brushing the inner surface of narrow lumens, resulting in failure to [completely] remove contaminants,” the researchers wrote.

In the first phase of the study, the researchers examined 41 instruments immediately after they were used in robotic surgery (7 radical prostatectomies and 2 anterior resections of the rectum) and 27 regular instruments immediately after they were used for open surgery (gastrectomy and colectomy). The robotic instruments were contaminated with 72.3 × 10³ mcg of protein each, compared with 5.5 × 10³ mcg of protein on the regular instruments, the investigators reported (Infect Control Hosp Epidemiol. 2016 Oct 31. doi: 10.1017/ice.2016.249).

In the second phase of the study, the researchers examined another 24 robotic instruments and 40 regular instruments after they were used in surgery and then cleaned according to the manufacturers’ instructions three successive times. For the robotic instruments, this involved manually brushing the outer surface while moving the instrument “wrists” through their full range of motion, followed by 15 minutes of ultrasonication with enzymatic detergent, flushing the lumen with a water gun through flush ports, and rinsing the entire instrument. For regular instruments, cleaning involved washer-disinfectors and included 5 minutes of ultrasonication, 10 minutes of spraying with an alkaline detergent, and 10 minutes of disinfection via heating.

The level of contamination declined with each successive cleaning but still remained comparatively high for the robotic instruments. The amount of protein contaminants released in the three cleanings was 650, 550, and 530 mcg per robotic instrument, compared with 16, 17, and 17 mcg per ordinary instrument.

The efficacy of cleaning was 97.6% for robotic instruments and 99.1% for regular instruments, the researchers reported.

This study was not designed to assess whether residual contamination is associated with adverse events such as infection in subsequent patients, and there are few data available on this topic.

“We have to recognize that there might be a considerable volume of insufficient cleaning or occult surgical site infections,” the investigators wrote.

New instrument washers equipped with a specific cleaning function for narrow lumens are becoming available, they noted, and “further study should be conducted using these washers with improved cleaning efficacy.”

The study was supported by the Japan Society for the Promotion of Science. The investigators reported having no relevant financial disclosures.

Instruments used for robotic surgery are “virtually impossible” to clean completely, according to a report published in Infection Control & Hospital Epidemiology.

“A new standard for the cleaning of complex surgical instruments needs to be established, especially for those used in robotic surgery,” wrote Yuhei Saito of the surgical center at the University of Tokyo Hospital and associates.

They assessed the residual contamination of both robotic and regular surgical instruments at their medical center because “hospital staff in central sterile supply departments are troubled by the reprocessing of robotic instruments because they cannot be disassembled for cleaning like other endoscopic instruments. Their complex structure impairs brushing the inner surface of narrow lumens, resulting in failure to [completely] remove contaminants,” the researchers wrote.

In the first phase of the study, the researchers examined 41 instruments immediately after they were used in robotic surgery (7 radical prostatectomies and 2 anterior resections of the rectum) and 27 regular instruments immediately after they were used for open surgery (gastrectomy and colectomy). The robotic instruments were contaminated with 72.3 × 10³ mcg of protein each, compared with 5.5 × 10³ mcg of protein on the regular instruments, the investigators reported (Infect Control Hosp Epidemiol. 2016 Oct 31. doi: 10.1017/ice.2016.249).

In the second phase of the study, the researchers examined another 24 robotic instruments and 40 regular instruments after they were used in surgery and then cleaned according to the manufacturers’ instructions three successive times. For the robotic instruments, this involved manually brushing the outer surface while moving the instrument “wrists” through their full range of motion, followed by 15 minutes of ultrasonication with enzymatic detergent, flushing the lumen with a water gun through flush ports, and rinsing the entire instrument. For regular instruments, cleaning involved washer-disinfectors and included 5 minutes of ultrasonication, 10 minutes of spraying with an alkaline detergent, and 10 minutes of disinfection via heating.

The level of contamination declined with each successive cleaning but still remained comparatively high for the robotic instruments. The amount of protein contaminants released in the three cleanings was 650, 550, and 530 mcg per robotic instrument, compared with 16, 17, and 17 mcg per ordinary instrument.

The efficacy of cleaning was 97.6% for robotic instruments and 99.1% for regular instruments, the researchers reported.

This study was not designed to assess whether residual contamination is associated with adverse events such as infection in subsequent patients, and there are few data available on this topic.

“We have to recognize that there might be a considerable volume of insufficient cleaning or occult surgical site infections,” the investigators wrote.

New instrument washers equipped with a specific cleaning function for narrow lumens are becoming available, they noted, and “further study should be conducted using these washers with improved cleaning efficacy.”

The study was supported by the Japan Society for the Promotion of Science. The investigators reported having no relevant financial disclosures.