Among individuals with gastroesophageal reflux disease (GERD), a negative upper endoscopy is associated with decreased risk in incidence and mortality from gastrointestinal cancer. The benefit persisted through 5-10 years following the procedure.

The finding is similar to the survival benefit seen with colonoscopies and colorectal cancer, and may be attributable to endoscopic treatment of premalignant lesions.

“The relatively high incidence rate of upper gastrointestinal cancer in patients with GERD indicates that a one-time upper endoscopy may be beneficial,” wrote the authors, who were led by Dag Holmberg, MD, PhD, of the department of molecular medicine and surgery at the Karolinska Institutet and Karolinska University Hospital, both in Stockholm. The study was published in Gastroenterology.

GERD is the most frequent reason patients undergo an upper endoscopy, but the results are often negative. It is generally a benign condition, but can lead to Barrett’s esophagus, as well as esophageal and gastric cardia adenocarcinoma. Upper endoscopy can identify other esophageal cancers like gastric noncardia cancer and duodenal cancer, which may cause dyspepsia or GERD-like symptoms.

To determine the potential benefit of upper endoscopy, the researchers conducted a population-based, four-nation cohort study that included 1,062,740 individuals with GERD in Denmark, Finland, Norway, and Sweden. The data were gathered from national patient registries, cancer registries, and cause of death registries. The study encompassed data from 1979 through the end of 2018.

The median age was 58 years, and 52% of participants were women.

The researchers defined a negative endoscopy as no diagnosis of gastrointestinal cancer within 6 months of the procedure; 69.3% of procedures were negative.

During the follow-up period, 0.34% of participants developed and 0.27% died of upper gastrointestinal cancer. Among those with negative endoscopies, 0.23% developed and 0.22% died from upper gastrointestinal cancer.

Participants with a negative endoscopy had a lower risk of being diagnosed with upper gastrointestinal cancer during the follow-up period (adjusted hazard ratio, 0.45; 95% confidence interval, 0.43-0.48). The reduction in risk was similar across age sexes and age groups, but among procedures performed after 2008, the risk reduction was even higher (aHR, 0.34; P < .001).

The effect was strongest in the first year after the procedure, but it persisted out to 5 years before returning to baseline risk levels.

A negative endoscopy was also associated with decreased mortality risk from upper gastrointestinal cancer versus those who hadn’t had an endoscopy (aHR, 0.39; 95% CI, 0.37-0.42). The protective value continued for at least 10 years.

Esophageal adenocarcinoma developed in 0.12% of participants, and 0.10% died of the disease. Among those with a negative endoscopy, 0.09% developed adenocarcinoma, and 0.07% died (aHR vs. no upper endoscopy, 0.33; 95% CI, 0.30-0.37).

The rapid return to baseline risk was notable, and different from what occurs after negative colonoscopies. However, new tumors can readily form within one year, and the risk may reflect early malignant or premalignant lesions that were missed during the procedure.

In fact, a meta-analysis found that 11.3% of upper gastrointestinal cancers had escaped detection during an endoscopy in the previous 3 years before diagnosis, and case reviews of patients diagnosed with gastrointestinal cancer soon after an upper endoscopy usually reveal suspicious or indeterminate results that the endoscopist or pathologist missed.

Quality indicators for upper endoscopy include procedure time, rate of targeted biopsies, and computer-aided detection, but it isn’t clear what impact these measures have on outcomes. However, the greater risk reduction found with endoscopies performed more recently suggests that newer quality indicators and technological improvements may be improving outcomes.

The relatively low incidence of esophageal and gastric cancer in Western countries has discouraged widespread adoption of endoscopic screening, but the researchers point out that the risk of gastrointestinal cancer among individuals with GERD is similar to the risk of colorectal cancer in the 60-69 age group in the United States, for whom colonoscopy is recommended.

“The present study indicates that upper endoscopy may be beneficial for patients with GERD, but to make upper endoscopy screening more cost beneficial at its initiation, the target group may be limited to include patients at highest risk of cancer. Such previous cost-effectiveness studies have indicated that endoscopy is cost effective in men at aged 50 years or older with chronic GERD,” the authors wrote.

The study was funded by Swedish Research Council and Swedish Cancer Society. The authors disclosed no relevant conflicts of interest.

Among individuals with gastroesophageal reflux disease (GERD), a negative upper endoscopy is associated with decreased risk in incidence and mortality from gastrointestinal cancer. The benefit persisted through 5-10 years following the procedure.

The finding is similar to the survival benefit seen with colonoscopies and colorectal cancer, and may be attributable to endoscopic treatment of premalignant lesions.

“The relatively high incidence rate of upper gastrointestinal cancer in patients with GERD indicates that a one-time upper endoscopy may be beneficial,” wrote the authors, who were led by Dag Holmberg, MD, PhD, of the department of molecular medicine and surgery at the Karolinska Institutet and Karolinska University Hospital, both in Stockholm. The study was published in Gastroenterology.

GERD is the most frequent reason patients undergo an upper endoscopy, but the results are often negative. It is generally a benign condition, but can lead to Barrett’s esophagus, as well as esophageal and gastric cardia adenocarcinoma. Upper endoscopy can identify other esophageal cancers like gastric noncardia cancer and duodenal cancer, which may cause dyspepsia or GERD-like symptoms.

To determine the potential benefit of upper endoscopy, the researchers conducted a population-based, four-nation cohort study that included 1,062,740 individuals with GERD in Denmark, Finland, Norway, and Sweden. The data were gathered from national patient registries, cancer registries, and cause of death registries. The study encompassed data from 1979 through the end of 2018.

The median age was 58 years, and 52% of participants were women.

The researchers defined a negative endoscopy as no diagnosis of gastrointestinal cancer within 6 months of the procedure; 69.3% of procedures were negative.

During the follow-up period, 0.34% of participants developed and 0.27% died of upper gastrointestinal cancer. Among those with negative endoscopies, 0.23% developed and 0.22% died from upper gastrointestinal cancer.

Participants with a negative endoscopy had a lower risk of being diagnosed with upper gastrointestinal cancer during the follow-up period (adjusted hazard ratio, 0.45; 95% confidence interval, 0.43-0.48). The reduction in risk was similar across age sexes and age groups, but among procedures performed after 2008, the risk reduction was even higher (aHR, 0.34; P < .001).

The effect was strongest in the first year after the procedure, but it persisted out to 5 years before returning to baseline risk levels.

A negative endoscopy was also associated with decreased mortality risk from upper gastrointestinal cancer versus those who hadn’t had an endoscopy (aHR, 0.39; 95% CI, 0.37-0.42). The protective value continued for at least 10 years.

Esophageal adenocarcinoma developed in 0.12% of participants, and 0.10% died of the disease. Among those with a negative endoscopy, 0.09% developed adenocarcinoma, and 0.07% died (aHR vs. no upper endoscopy, 0.33; 95% CI, 0.30-0.37).

The rapid return to baseline risk was notable, and different from what occurs after negative colonoscopies. However, new tumors can readily form within one year, and the risk may reflect early malignant or premalignant lesions that were missed during the procedure.

In fact, a meta-analysis found that 11.3% of upper gastrointestinal cancers had escaped detection during an endoscopy in the previous 3 years before diagnosis, and case reviews of patients diagnosed with gastrointestinal cancer soon after an upper endoscopy usually reveal suspicious or indeterminate results that the endoscopist or pathologist missed.

Quality indicators for upper endoscopy include procedure time, rate of targeted biopsies, and computer-aided detection, but it isn’t clear what impact these measures have on outcomes. However, the greater risk reduction found with endoscopies performed more recently suggests that newer quality indicators and technological improvements may be improving outcomes.

The relatively low incidence of esophageal and gastric cancer in Western countries has discouraged widespread adoption of endoscopic screening, but the researchers point out that the risk of gastrointestinal cancer among individuals with GERD is similar to the risk of colorectal cancer in the 60-69 age group in the United States, for whom colonoscopy is recommended.

“The present study indicates that upper endoscopy may be beneficial for patients with GERD, but to make upper endoscopy screening more cost beneficial at its initiation, the target group may be limited to include patients at highest risk of cancer. Such previous cost-effectiveness studies have indicated that endoscopy is cost effective in men at aged 50 years or older with chronic GERD,” the authors wrote.

The study was funded by Swedish Research Council and Swedish Cancer Society. The authors disclosed no relevant conflicts of interest.

Among individuals with gastroesophageal reflux disease (GERD), a negative upper endoscopy is associated with decreased risk in incidence and mortality from gastrointestinal cancer. The benefit persisted through 5-10 years following the procedure.

The finding is similar to the survival benefit seen with colonoscopies and colorectal cancer, and may be attributable to endoscopic treatment of premalignant lesions.

“The relatively high incidence rate of upper gastrointestinal cancer in patients with GERD indicates that a one-time upper endoscopy may be beneficial,” wrote the authors, who were led by Dag Holmberg, MD, PhD, of the department of molecular medicine and surgery at the Karolinska Institutet and Karolinska University Hospital, both in Stockholm. The study was published in Gastroenterology.

GERD is the most frequent reason patients undergo an upper endoscopy, but the results are often negative. It is generally a benign condition, but can lead to Barrett’s esophagus, as well as esophageal and gastric cardia adenocarcinoma. Upper endoscopy can identify other esophageal cancers like gastric noncardia cancer and duodenal cancer, which may cause dyspepsia or GERD-like symptoms.

To determine the potential benefit of upper endoscopy, the researchers conducted a population-based, four-nation cohort study that included 1,062,740 individuals with GERD in Denmark, Finland, Norway, and Sweden. The data were gathered from national patient registries, cancer registries, and cause of death registries. The study encompassed data from 1979 through the end of 2018.

The median age was 58 years, and 52% of participants were women.

The researchers defined a negative endoscopy as no diagnosis of gastrointestinal cancer within 6 months of the procedure; 69.3% of procedures were negative.

During the follow-up period, 0.34% of participants developed and 0.27% died of upper gastrointestinal cancer. Among those with negative endoscopies, 0.23% developed and 0.22% died from upper gastrointestinal cancer.

Participants with a negative endoscopy had a lower risk of being diagnosed with upper gastrointestinal cancer during the follow-up period (adjusted hazard ratio, 0.45; 95% confidence interval, 0.43-0.48). The reduction in risk was similar across age sexes and age groups, but among procedures performed after 2008, the risk reduction was even higher (aHR, 0.34; P < .001).

The effect was strongest in the first year after the procedure, but it persisted out to 5 years before returning to baseline risk levels.

A negative endoscopy was also associated with decreased mortality risk from upper gastrointestinal cancer versus those who hadn’t had an endoscopy (aHR, 0.39; 95% CI, 0.37-0.42). The protective value continued for at least 10 years.

Esophageal adenocarcinoma developed in 0.12% of participants, and 0.10% died of the disease. Among those with a negative endoscopy, 0.09% developed adenocarcinoma, and 0.07% died (aHR vs. no upper endoscopy, 0.33; 95% CI, 0.30-0.37).

The rapid return to baseline risk was notable, and different from what occurs after negative colonoscopies. However, new tumors can readily form within one year, and the risk may reflect early malignant or premalignant lesions that were missed during the procedure.

In fact, a meta-analysis found that 11.3% of upper gastrointestinal cancers had escaped detection during an endoscopy in the previous 3 years before diagnosis, and case reviews of patients diagnosed with gastrointestinal cancer soon after an upper endoscopy usually reveal suspicious or indeterminate results that the endoscopist or pathologist missed.

Quality indicators for upper endoscopy include procedure time, rate of targeted biopsies, and computer-aided detection, but it isn’t clear what impact these measures have on outcomes. However, the greater risk reduction found with endoscopies performed more recently suggests that newer quality indicators and technological improvements may be improving outcomes.

The relatively low incidence of esophageal and gastric cancer in Western countries has discouraged widespread adoption of endoscopic screening, but the researchers point out that the risk of gastrointestinal cancer among individuals with GERD is similar to the risk of colorectal cancer in the 60-69 age group in the United States, for whom colonoscopy is recommended.

“The present study indicates that upper endoscopy may be beneficial for patients with GERD, but to make upper endoscopy screening more cost beneficial at its initiation, the target group may be limited to include patients at highest risk of cancer. Such previous cost-effectiveness studies have indicated that endoscopy is cost effective in men at aged 50 years or older with chronic GERD,” the authors wrote.

The study was funded by Swedish Research Council and Swedish Cancer Society. The authors disclosed no relevant conflicts of interest.

The EXALT Model-D single-use duodenoscope is a cost-effective alternative to high-level disinfection (HLD) of reusable duodenoscopes, according to a new analysis.

The study compared the EXALT Model-D, HLD, culture-and-quarantine (CQ), and ethylene oxide sterilization (ETO). The results came from a simulated cohort of patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) to treat choledocholithiasis.

Although EXALT was the costliest option and HLD the cheapest, EXALT produced the most quality-adjusted life years (QALYs) and allowed the hospital to decrease net costs, and sensitivity analysis showed that it was a better option than HLD over a range of willingness-to-pay values.

“When evaluating technologies based on cost-effectiveness and additionally in the context of TPT [transitional passthrough] or NTAP [new technology add-on payment], the EXALT approach meets typically used cost-effectiveness thresholds compared to all other evaluated strategies and should be considered for standard practice,” wrote the authors, who were led by Ananya Das, MD, of the Arizona Centers for Digestive Health, Gilbert. The study was published in Techniques and Innovations in Gastrointestinal Endoscopy.

Duodenoscope contamination has resulted in outbreaks of various multidrug-resistant organisms in hospital settings, which has led to the publication of various reprocessing guidelines. Although many hospitals have adopted HLD protocols, others use additional or alternative reprocessing methods such as CQ or ETO. Despite these efforts, a recent Food and Drug Administration study found that 1.9%-22% of samples taken from duodenoscopes tested positive for bacteria of concern, such as pathogens. Those and other findings have led some to suggest that it would be best to move away from HLD, and instead employ sterilizable or disposable endoscopes.

In another study, The EXALT Model-D (Boston Scientific) had been shown to be a good alternative to standard reusable duodenoscopes.

The researchers used a Markov-model to determine the cost-effectiveness of EXALT Model-D against other approaches in a simulated cohort. They found that EXALT Model-D created the most QALYs (21.9265) at the highest cost ($3,000), and HLD the fewest QALYs (21.8938) at the lowest cost ($962). Compared with HLD, the incremental cost-effectiveness ratio (ICER) of EXALT was $62,185, and $38,461 for ETO gas sterilization. CQ was dominated, indicating that it had a higher cost but was not more effective than HLD.

The researchers conducted a subanalysis of ERCP and Medicare patients to consider the recently approved TPT payment and the NTAP, in both hospital outpatient and inpatient settings. With TPT, EXALT had no cost after reimbursement, with a net saving of $962 per patient when compared with HLD, plus an increase in 0.033 QALYs (0.15%). The other procedures cost more and were less effective. With NTAP, EXALT had a net cost of $323 versus HLD, with a similar QALY benefit.

A Monte Carlo analysis of EXALT versus HLD found reductions in duodenoscope infection-related ICU admission (relative risk reduction, 0.996; 95% confidence interval, 0.936-1.0; number needed to treat, 79; 95% CI, 67-95) and death (RRR, 0.973; 95% CI, 0.552-0.998; number needed to treat, 556; 95% CI, 350-997).

In willingness-to-pay estimates from $50,000 to $100,000, EXALT was cost effective in 67.28% of trials with ICER under $100,000 per QALY.

The study did not consider medicolegal costs, which could lead to an underestimation of EXALT’s cost-effectiveness. The study also relied on available published information to determine cost per patient of hospital outbreaks in the United States and Europe since 2012, but the authors did not include costs of administrative sanctions, litigation, and poor publicity due to inconsistencies in the literature.

“While more research is needed to understand and quantify the determinants of the natural history after exposure to contaminated duodenoscopes, such as the risk of transmission and the subsequent development of serious clinical infections, this economic analysis demonstrates an approach using EXALT Model-D is cost effective in the U.S. health care system when compared to the currently utilized strategies of duodenoscope reprocessing,” the researchers concluded.

The study did not receive any funding. One of the authors is an employee and stockholder of Boston Scientific, which manufactures and markets EXALT. The other two authors have consulted for Boston Scientific.

The EXALT Model-D single-use duodenoscope is a cost-effective alternative to high-level disinfection (HLD) of reusable duodenoscopes, according to a new analysis.

The study compared the EXALT Model-D, HLD, culture-and-quarantine (CQ), and ethylene oxide sterilization (ETO). The results came from a simulated cohort of patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) to treat choledocholithiasis.

Although EXALT was the costliest option and HLD the cheapest, EXALT produced the most quality-adjusted life years (QALYs) and allowed the hospital to decrease net costs, and sensitivity analysis showed that it was a better option than HLD over a range of willingness-to-pay values.

“When evaluating technologies based on cost-effectiveness and additionally in the context of TPT [transitional passthrough] or NTAP [new technology add-on payment], the EXALT approach meets typically used cost-effectiveness thresholds compared to all other evaluated strategies and should be considered for standard practice,” wrote the authors, who were led by Ananya Das, MD, of the Arizona Centers for Digestive Health, Gilbert. The study was published in Techniques and Innovations in Gastrointestinal Endoscopy.

Duodenoscope contamination has resulted in outbreaks of various multidrug-resistant organisms in hospital settings, which has led to the publication of various reprocessing guidelines. Although many hospitals have adopted HLD protocols, others use additional or alternative reprocessing methods such as CQ or ETO. Despite these efforts, a recent Food and Drug Administration study found that 1.9%-22% of samples taken from duodenoscopes tested positive for bacteria of concern, such as pathogens. Those and other findings have led some to suggest that it would be best to move away from HLD, and instead employ sterilizable or disposable endoscopes.

In another study, The EXALT Model-D (Boston Scientific) had been shown to be a good alternative to standard reusable duodenoscopes.

The researchers used a Markov-model to determine the cost-effectiveness of EXALT Model-D against other approaches in a simulated cohort. They found that EXALT Model-D created the most QALYs (21.9265) at the highest cost ($3,000), and HLD the fewest QALYs (21.8938) at the lowest cost ($962). Compared with HLD, the incremental cost-effectiveness ratio (ICER) of EXALT was $62,185, and $38,461 for ETO gas sterilization. CQ was dominated, indicating that it had a higher cost but was not more effective than HLD.

The researchers conducted a subanalysis of ERCP and Medicare patients to consider the recently approved TPT payment and the NTAP, in both hospital outpatient and inpatient settings. With TPT, EXALT had no cost after reimbursement, with a net saving of $962 per patient when compared with HLD, plus an increase in 0.033 QALYs (0.15%). The other procedures cost more and were less effective. With NTAP, EXALT had a net cost of $323 versus HLD, with a similar QALY benefit.

A Monte Carlo analysis of EXALT versus HLD found reductions in duodenoscope infection-related ICU admission (relative risk reduction, 0.996; 95% confidence interval, 0.936-1.0; number needed to treat, 79; 95% CI, 67-95) and death (RRR, 0.973; 95% CI, 0.552-0.998; number needed to treat, 556; 95% CI, 350-997).

In willingness-to-pay estimates from $50,000 to $100,000, EXALT was cost effective in 67.28% of trials with ICER under $100,000 per QALY.

The study did not consider medicolegal costs, which could lead to an underestimation of EXALT’s cost-effectiveness. The study also relied on available published information to determine cost per patient of hospital outbreaks in the United States and Europe since 2012, but the authors did not include costs of administrative sanctions, litigation, and poor publicity due to inconsistencies in the literature.

“While more research is needed to understand and quantify the determinants of the natural history after exposure to contaminated duodenoscopes, such as the risk of transmission and the subsequent development of serious clinical infections, this economic analysis demonstrates an approach using EXALT Model-D is cost effective in the U.S. health care system when compared to the currently utilized strategies of duodenoscope reprocessing,” the researchers concluded.

The study did not receive any funding. One of the authors is an employee and stockholder of Boston Scientific, which manufactures and markets EXALT. The other two authors have consulted for Boston Scientific.

The EXALT Model-D single-use duodenoscope is a cost-effective alternative to high-level disinfection (HLD) of reusable duodenoscopes, according to a new analysis.

The study compared the EXALT Model-D, HLD, culture-and-quarantine (CQ), and ethylene oxide sterilization (ETO). The results came from a simulated cohort of patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) to treat choledocholithiasis.

Although EXALT was the costliest option and HLD the cheapest, EXALT produced the most quality-adjusted life years (QALYs) and allowed the hospital to decrease net costs, and sensitivity analysis showed that it was a better option than HLD over a range of willingness-to-pay values.

“When evaluating technologies based on cost-effectiveness and additionally in the context of TPT [transitional passthrough] or NTAP [new technology add-on payment], the EXALT approach meets typically used cost-effectiveness thresholds compared to all other evaluated strategies and should be considered for standard practice,” wrote the authors, who were led by Ananya Das, MD, of the Arizona Centers for Digestive Health, Gilbert. The study was published in Techniques and Innovations in Gastrointestinal Endoscopy.

Duodenoscope contamination has resulted in outbreaks of various multidrug-resistant organisms in hospital settings, which has led to the publication of various reprocessing guidelines. Although many hospitals have adopted HLD protocols, others use additional or alternative reprocessing methods such as CQ or ETO. Despite these efforts, a recent Food and Drug Administration study found that 1.9%-22% of samples taken from duodenoscopes tested positive for bacteria of concern, such as pathogens. Those and other findings have led some to suggest that it would be best to move away from HLD, and instead employ sterilizable or disposable endoscopes.

In another study, The EXALT Model-D (Boston Scientific) had been shown to be a good alternative to standard reusable duodenoscopes.

The researchers used a Markov-model to determine the cost-effectiveness of EXALT Model-D against other approaches in a simulated cohort. They found that EXALT Model-D created the most QALYs (21.9265) at the highest cost ($3,000), and HLD the fewest QALYs (21.8938) at the lowest cost ($962). Compared with HLD, the incremental cost-effectiveness ratio (ICER) of EXALT was $62,185, and $38,461 for ETO gas sterilization. CQ was dominated, indicating that it had a higher cost but was not more effective than HLD.

The researchers conducted a subanalysis of ERCP and Medicare patients to consider the recently approved TPT payment and the NTAP, in both hospital outpatient and inpatient settings. With TPT, EXALT had no cost after reimbursement, with a net saving of $962 per patient when compared with HLD, plus an increase in 0.033 QALYs (0.15%). The other procedures cost more and were less effective. With NTAP, EXALT had a net cost of $323 versus HLD, with a similar QALY benefit.

A Monte Carlo analysis of EXALT versus HLD found reductions in duodenoscope infection-related ICU admission (relative risk reduction, 0.996; 95% confidence interval, 0.936-1.0; number needed to treat, 79; 95% CI, 67-95) and death (RRR, 0.973; 95% CI, 0.552-0.998; number needed to treat, 556; 95% CI, 350-997).

In willingness-to-pay estimates from $50,000 to $100,000, EXALT was cost effective in 67.28% of trials with ICER under $100,000 per QALY.

The study did not consider medicolegal costs, which could lead to an underestimation of EXALT’s cost-effectiveness. The study also relied on available published information to determine cost per patient of hospital outbreaks in the United States and Europe since 2012, but the authors did not include costs of administrative sanctions, litigation, and poor publicity due to inconsistencies in the literature.

“While more research is needed to understand and quantify the determinants of the natural history after exposure to contaminated duodenoscopes, such as the risk of transmission and the subsequent development of serious clinical infections, this economic analysis demonstrates an approach using EXALT Model-D is cost effective in the U.S. health care system when compared to the currently utilized strategies of duodenoscope reprocessing,” the researchers concluded.

The study did not receive any funding. One of the authors is an employee and stockholder of Boston Scientific, which manufactures and markets EXALT. The other two authors have consulted for Boston Scientific.

Phoenix has only a few months each year to use my hot tub, so winter is when I catch up on a lot of my reading. Recently I was reading the November Lancet, which had some interesting statistics about migraine.

• It’s the second leading cause (behind back pain) of years lived with disability.
• There are 10 million people with migraines in the United Kingdom (population roughly 70 million).
• In the last 5 years, migraine use of emergency rooms has increased 14%.
• According to the U.K. National Health Service, over 16,000 ER visits for migraine could be avoided.

These are compelling statistics, and probably (taking into account population differences) similar to numbers here in the United States or Canada.

Like all neurologists, I see my share of migraine.

Like many neurologists, I also get migraines. Not many, maybe 2-3 per month, effectively treated with a triptan. So I have a decent understanding that they aren’t pleasant.

Fortunately, migraine advances have been impressive, with seven new CGRP drugs in the last 3 years, bringing successful treatment closer for many.

But the problem is far from solved, a point that was driven home yesterday.

I awoke early yesterday morning with a migraine, and took an Imitrex. But instead of feeling better in an hour, it kept worsening until I was literally disabled by it. I took some Excedrin Migraine. The last time I had a migraine this bad was in 1998, during my fellowship, and my attending had to drive me home (thanks, Joe).

It was showing no signs of letting up. I thought about going to emergency department. After all, aren’t we trained for that when we hear “worst headache of my life?” but figured it was more likely just a migraine, and didn’t want to bog down my ED colleagues in the midst of another COVID-19 wave.

I took another Imitrex. I found a sample of Ubrelvy that I’d brought home out of curiosity, and took that, too. I think I have an old, nearly empty, bottle of Norco, somewhere, from a 2014 dental surgery, but was too photophobic to go looking for it (if I still have it at all).

I lay down in bed under the ceiling fan, and somehow fell asleep.

When I woke about 90 minutes later it was gone, like a switch had been flipped. Maybe it was all, or just one of, the meds I’d taken. I’ll never know. I could now resume my regularly scheduled program.

The migraine had cost me 7 hours. Like most small business owners, I’m trying to get all the year-end paperwork wrapped up, in addition to reviewing cases, writing up reports, and spending time with my family. So none of that happened that Saturday morning. If I’d had to see patients that morning there’s no way I could have done it.

Fortunately, as I said, that’s only the second time that’s happened to me, and it’s been 25 years since the last one.

But I’m lucky. There are those who have them far more frequently, limiting their ability to work, raise families, spend time with friends. … Have a life.

Migraine is far from a deadly disease. In neurology we treat far worse conditions. But in sheer numbers migraine affects far more people, and (indirectly) an even larger group of coworkers, parents, friends, and children who have to cover unpredictably when the other person is out with one.

For all of them, improved migraine treatment approaches can’t come soon enough.

Phoenix has only a few months each year to use my hot tub, so winter is when I catch up on a lot of my reading. Recently I was reading the November Lancet, which had some interesting statistics about migraine.

• It’s the second leading cause (behind back pain) of years lived with disability.
• There are 10 million people with migraines in the United Kingdom (population roughly 70 million).
• In the last 5 years, migraine use of emergency rooms has increased 14%.
• According to the U.K. National Health Service, over 16,000 ER visits for migraine could be avoided.

These are compelling statistics, and probably (taking into account population differences) similar to numbers here in the United States or Canada.

Like all neurologists, I see my share of migraine.

Like many neurologists, I also get migraines. Not many, maybe 2-3 per month, effectively treated with a triptan. So I have a decent understanding that they aren’t pleasant.

Fortunately, migraine advances have been impressive, with seven new CGRP drugs in the last 3 years, bringing successful treatment closer for many.

But the problem is far from solved, a point that was driven home yesterday.

I awoke early yesterday morning with a migraine, and took an Imitrex. But instead of feeling better in an hour, it kept worsening until I was literally disabled by it. I took some Excedrin Migraine. The last time I had a migraine this bad was in 1998, during my fellowship, and my attending had to drive me home (thanks, Joe).

It was showing no signs of letting up. I thought about going to emergency department. After all, aren’t we trained for that when we hear “worst headache of my life?” but figured it was more likely just a migraine, and didn’t want to bog down my ED colleagues in the midst of another COVID-19 wave.

I took another Imitrex. I found a sample of Ubrelvy that I’d brought home out of curiosity, and took that, too. I think I have an old, nearly empty, bottle of Norco, somewhere, from a 2014 dental surgery, but was too photophobic to go looking for it (if I still have it at all).

I lay down in bed under the ceiling fan, and somehow fell asleep.

When I woke about 90 minutes later it was gone, like a switch had been flipped. Maybe it was all, or just one of, the meds I’d taken. I’ll never know. I could now resume my regularly scheduled program.

The migraine had cost me 7 hours. Like most small business owners, I’m trying to get all the year-end paperwork wrapped up, in addition to reviewing cases, writing up reports, and spending time with my family. So none of that happened that Saturday morning. If I’d had to see patients that morning there’s no way I could have done it.

Fortunately, as I said, that’s only the second time that’s happened to me, and it’s been 25 years since the last one.

But I’m lucky. There are those who have them far more frequently, limiting their ability to work, raise families, spend time with friends. … Have a life.

Migraine is far from a deadly disease. In neurology we treat far worse conditions. But in sheer numbers migraine affects far more people, and (indirectly) an even larger group of coworkers, parents, friends, and children who have to cover unpredictably when the other person is out with one.

For all of them, improved migraine treatment approaches can’t come soon enough.

Phoenix has only a few months each year to use my hot tub, so winter is when I catch up on a lot of my reading. Recently I was reading the November Lancet, which had some interesting statistics about migraine.

• It’s the second leading cause (behind back pain) of years lived with disability.
• There are 10 million people with migraines in the United Kingdom (population roughly 70 million).
• In the last 5 years, migraine use of emergency rooms has increased 14%.
• According to the U.K. National Health Service, over 16,000 ER visits for migraine could be avoided.

These are compelling statistics, and probably (taking into account population differences) similar to numbers here in the United States or Canada.

Like all neurologists, I see my share of migraine.

Like many neurologists, I also get migraines. Not many, maybe 2-3 per month, effectively treated with a triptan. So I have a decent understanding that they aren’t pleasant.

Fortunately, migraine advances have been impressive, with seven new CGRP drugs in the last 3 years, bringing successful treatment closer for many.

But the problem is far from solved, a point that was driven home yesterday.

I awoke early yesterday morning with a migraine, and took an Imitrex. But instead of feeling better in an hour, it kept worsening until I was literally disabled by it. I took some Excedrin Migraine. The last time I had a migraine this bad was in 1998, during my fellowship, and my attending had to drive me home (thanks, Joe).

It was showing no signs of letting up. I thought about going to emergency department. After all, aren’t we trained for that when we hear “worst headache of my life?” but figured it was more likely just a migraine, and didn’t want to bog down my ED colleagues in the midst of another COVID-19 wave.

I took another Imitrex. I found a sample of Ubrelvy that I’d brought home out of curiosity, and took that, too. I think I have an old, nearly empty, bottle of Norco, somewhere, from a 2014 dental surgery, but was too photophobic to go looking for it (if I still have it at all).

I lay down in bed under the ceiling fan, and somehow fell asleep.

When I woke about 90 minutes later it was gone, like a switch had been flipped. Maybe it was all, or just one of, the meds I’d taken. I’ll never know. I could now resume my regularly scheduled program.

The migraine had cost me 7 hours. Like most small business owners, I’m trying to get all the year-end paperwork wrapped up, in addition to reviewing cases, writing up reports, and spending time with my family. So none of that happened that Saturday morning. If I’d had to see patients that morning there’s no way I could have done it.

Fortunately, as I said, that’s only the second time that’s happened to me, and it’s been 25 years since the last one.

But I’m lucky. There are those who have them far more frequently, limiting their ability to work, raise families, spend time with friends. … Have a life.

Migraine is far from a deadly disease. In neurology we treat far worse conditions. But in sheer numbers migraine affects far more people, and (indirectly) an even larger group of coworkers, parents, friends, and children who have to cover unpredictably when the other person is out with one.

For all of them, improved migraine treatment approaches can’t come soon enough.

Low-power, low-density 1,927-nm and 1,440-nm fractional diode lasers are safe to pair with botulinum neurotoxin type A and soft-tissue fillers during the same treatment session, results from a 6-year, single-center review showed.

“These treatments can be complementary in single-session treatments and can offer increased convenience for both patients and physicians,” primary study author Jordan V. Wang, MD, MBE, MBA, said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery.

To date, limited studies have demonstrated the safety of pairing botulinum neurotoxin type A and soft-tissue fillers with laser and other energy-based devices during the same treatment session on the same day, said Dr. Wang, medical research director at the Laser & Skin Surgery Center of New York. “Some concerns remain, though, regarding patient safety and efficacy,” he said. “Data on single-session treatment with low-power, low-density 1,927-nm and 1,440-nm fractional diode lasers and either botulinum neurotoxin or fillers are lacking.”

In a retrospective review of electronic medical records conducted from May 2015 to April 2021, Dr. Wang, Roy G. Geronemus, MD, and Carolyn Kushner, MD evaluated patients who received a single-session facial treatment with either BoNT-A or soft-tissue fillers and the low-power, low-density 1,927-nm and 1,440-nm fractional diode lasers (Clear+Brilliant Perméa and Original, Solta, Pleasanton, Calif.). Safety was assessed by documenting adverse events related to the spread of BoNT-A and fillers or laser treatment of filled areas within 4 weeks.

Adverse events they looked for related to botulinum neurotoxin use included eyelid ptosis; neck weakness or spasms; impairments in chewing, swallowing, speech, and respiration; and prescriptions of apraclonidine eye drops. Filler-related adverse events they looked for included product migration, unexpected loss of filler volume, vascular occlusion, acute pain, necrosis, blindness, and burn. “For both, we looked at hospital or emergency room transfers or admissions and referrals to ENT or ophthalmology,” Dr. Wang said.

During the 6-year study period, 525 patients had 1,562 single-session laser treatments with a mean 46.4 units of BoNT-A, and 398 patients had 1,237 single-session treatments with a mean 1.6 soft-tissue filler syringes. Among those who received BoNT-A, most (93%) were female, their mean age was 51 years, and 99% were treated with a 1,927-nm wavelength at a medium setting in 87% of cases. The top five injection sites were glabella (82%), forehead (69%), periorbital area (64%), neck (40%), and jawline and/or masseters (13%).

The researchers noted one case (0.06%) where apraclonidine eye drops were prescribed for ptosis. The patient had undergone eight other single-session treatments without issue. There were no other documented adverse events directly related to spread of BoNT-A. According to Dr. Wang, this rate of ptosis is lower than the incidence with BoNT-A alone in two landmark trials studying its effects on glabellar lines, which was reported as 5.4% and 1.0%.

Among the 398 patients who received soft-tissue fillers, most (94%) were female, their mean age was 54 years, and 99% were treated with a 1927nm wavelength at a medium setting in 97% of cases. The top five injection sites were cheeks and/or tear troughs (89%), perioral area and/or marionette lines (77%), lips (34%), nasolabial folds (19%), and temples (11%), and the mean number of filler syringes per treatment was 1.6. Slightly more than half (51%) had 1 session, while the remainder had 2 to greater than 10 sessions. The researchers observed no documented adverse events related to spread of fillers or laser treatment of filled areas.

“This laser is a low-powered device that creates small, superficial, and transient microchannels, which likely contributes to the safety of single-session treatments with cosmetic injectables,” Dr. Wang said. However, prospective studies are needed to further validate these results, he added.

“With this very mild laser, it is not surprising that combined treatment had no effect,” said Eric F. Bernstein, MD, MSE, director of the Main Line Center for Laser Surgery in Ardmore, Pa., who was asked to comment on the study results. “There have been numerous anecdotal reports of spreading of botulinum toxin effect to areas not in the target area for treatment following a variety of lasers, including the more powerful version of the laser used in this study. In addition, spread following vascular and other lasers has been reported,” he noted

The laser used in this study, Dr. Bernstein continued, “is low powered and emits a wavelength that is very superficially absorbed, resulting in injury to the stratum corneum, superficial epidermis, or possibly the very superficial dermis, and is often used by physician extenders and not physicians – although I suspect this is not the case in the current study. One can have a reasonable degree of confidence when combining this laser with injectables, but these results cannot be extrapolated to other devices.”

The abstract received the annual ASDS Carruthers Award during the meeting. Dr. Wang reported that he is a consultant or advisor to Allergan, Alastin, AVAVA, Cynosure, Lutronic, Novoxel, Sofwave, and Solta. Dr. Bernstein reported having received research funding from Cynosure, Candela, and Acclaro. He also has received consulting fees from Cynosure and holds ownership interest in Candela, Novoxel, OnSite, Joylux, and Acclaro and has served on the advisory board for Novoxel, Cynosure, and Acclaro.

Low-power, low-density 1,927-nm and 1,440-nm fractional diode lasers are safe to pair with botulinum neurotoxin type A and soft-tissue fillers during the same treatment session, results from a 6-year, single-center review showed.

“These treatments can be complementary in single-session treatments and can offer increased convenience for both patients and physicians,” primary study author Jordan V. Wang, MD, MBE, MBA, said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery.

To date, limited studies have demonstrated the safety of pairing botulinum neurotoxin type A and soft-tissue fillers with laser and other energy-based devices during the same treatment session on the same day, said Dr. Wang, medical research director at the Laser & Skin Surgery Center of New York. “Some concerns remain, though, regarding patient safety and efficacy,” he said. “Data on single-session treatment with low-power, low-density 1,927-nm and 1,440-nm fractional diode lasers and either botulinum neurotoxin or fillers are lacking.”

In a retrospective review of electronic medical records conducted from May 2015 to April 2021, Dr. Wang, Roy G. Geronemus, MD, and Carolyn Kushner, MD evaluated patients who received a single-session facial treatment with either BoNT-A or soft-tissue fillers and the low-power, low-density 1,927-nm and 1,440-nm fractional diode lasers (Clear+Brilliant Perméa and Original, Solta, Pleasanton, Calif.). Safety was assessed by documenting adverse events related to the spread of BoNT-A and fillers or laser treatment of filled areas within 4 weeks.

Adverse events they looked for related to botulinum neurotoxin use included eyelid ptosis; neck weakness or spasms; impairments in chewing, swallowing, speech, and respiration; and prescriptions of apraclonidine eye drops. Filler-related adverse events they looked for included product migration, unexpected loss of filler volume, vascular occlusion, acute pain, necrosis, blindness, and burn. “For both, we looked at hospital or emergency room transfers or admissions and referrals to ENT or ophthalmology,” Dr. Wang said.

During the 6-year study period, 525 patients had 1,562 single-session laser treatments with a mean 46.4 units of BoNT-A, and 398 patients had 1,237 single-session treatments with a mean 1.6 soft-tissue filler syringes. Among those who received BoNT-A, most (93%) were female, their mean age was 51 years, and 99% were treated with a 1,927-nm wavelength at a medium setting in 87% of cases. The top five injection sites were glabella (82%), forehead (69%), periorbital area (64%), neck (40%), and jawline and/or masseters (13%).

The researchers noted one case (0.06%) where apraclonidine eye drops were prescribed for ptosis. The patient had undergone eight other single-session treatments without issue. There were no other documented adverse events directly related to spread of BoNT-A. According to Dr. Wang, this rate of ptosis is lower than the incidence with BoNT-A alone in two landmark trials studying its effects on glabellar lines, which was reported as 5.4% and 1.0%.

Among the 398 patients who received soft-tissue fillers, most (94%) were female, their mean age was 54 years, and 99% were treated with a 1927nm wavelength at a medium setting in 97% of cases. The top five injection sites were cheeks and/or tear troughs (89%), perioral area and/or marionette lines (77%), lips (34%), nasolabial folds (19%), and temples (11%), and the mean number of filler syringes per treatment was 1.6. Slightly more than half (51%) had 1 session, while the remainder had 2 to greater than 10 sessions. The researchers observed no documented adverse events related to spread of fillers or laser treatment of filled areas.

“This laser is a low-powered device that creates small, superficial, and transient microchannels, which likely contributes to the safety of single-session treatments with cosmetic injectables,” Dr. Wang said. However, prospective studies are needed to further validate these results, he added.

“With this very mild laser, it is not surprising that combined treatment had no effect,” said Eric F. Bernstein, MD, MSE, director of the Main Line Center for Laser Surgery in Ardmore, Pa., who was asked to comment on the study results. “There have been numerous anecdotal reports of spreading of botulinum toxin effect to areas not in the target area for treatment following a variety of lasers, including the more powerful version of the laser used in this study. In addition, spread following vascular and other lasers has been reported,” he noted

The laser used in this study, Dr. Bernstein continued, “is low powered and emits a wavelength that is very superficially absorbed, resulting in injury to the stratum corneum, superficial epidermis, or possibly the very superficial dermis, and is often used by physician extenders and not physicians – although I suspect this is not the case in the current study. One can have a reasonable degree of confidence when combining this laser with injectables, but these results cannot be extrapolated to other devices.”

The abstract received the annual ASDS Carruthers Award during the meeting. Dr. Wang reported that he is a consultant or advisor to Allergan, Alastin, AVAVA, Cynosure, Lutronic, Novoxel, Sofwave, and Solta. Dr. Bernstein reported having received research funding from Cynosure, Candela, and Acclaro. He also has received consulting fees from Cynosure and holds ownership interest in Candela, Novoxel, OnSite, Joylux, and Acclaro and has served on the advisory board for Novoxel, Cynosure, and Acclaro.

Low-power, low-density 1,927-nm and 1,440-nm fractional diode lasers are safe to pair with botulinum neurotoxin type A and soft-tissue fillers during the same treatment session, results from a 6-year, single-center review showed.

“These treatments can be complementary in single-session treatments and can offer increased convenience for both patients and physicians,” primary study author Jordan V. Wang, MD, MBE, MBA, said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery.

To date, limited studies have demonstrated the safety of pairing botulinum neurotoxin type A and soft-tissue fillers with laser and other energy-based devices during the same treatment session on the same day, said Dr. Wang, medical research director at the Laser & Skin Surgery Center of New York. “Some concerns remain, though, regarding patient safety and efficacy,” he said. “Data on single-session treatment with low-power, low-density 1,927-nm and 1,440-nm fractional diode lasers and either botulinum neurotoxin or fillers are lacking.”

In a retrospective review of electronic medical records conducted from May 2015 to April 2021, Dr. Wang, Roy G. Geronemus, MD, and Carolyn Kushner, MD evaluated patients who received a single-session facial treatment with either BoNT-A or soft-tissue fillers and the low-power, low-density 1,927-nm and 1,440-nm fractional diode lasers (Clear+Brilliant Perméa and Original, Solta, Pleasanton, Calif.). Safety was assessed by documenting adverse events related to the spread of BoNT-A and fillers or laser treatment of filled areas within 4 weeks.

Adverse events they looked for related to botulinum neurotoxin use included eyelid ptosis; neck weakness or spasms; impairments in chewing, swallowing, speech, and respiration; and prescriptions of apraclonidine eye drops. Filler-related adverse events they looked for included product migration, unexpected loss of filler volume, vascular occlusion, acute pain, necrosis, blindness, and burn. “For both, we looked at hospital or emergency room transfers or admissions and referrals to ENT or ophthalmology,” Dr. Wang said.

During the 6-year study period, 525 patients had 1,562 single-session laser treatments with a mean 46.4 units of BoNT-A, and 398 patients had 1,237 single-session treatments with a mean 1.6 soft-tissue filler syringes. Among those who received BoNT-A, most (93%) were female, their mean age was 51 years, and 99% were treated with a 1,927-nm wavelength at a medium setting in 87% of cases. The top five injection sites were glabella (82%), forehead (69%), periorbital area (64%), neck (40%), and jawline and/or masseters (13%).

The researchers noted one case (0.06%) where apraclonidine eye drops were prescribed for ptosis. The patient had undergone eight other single-session treatments without issue. There were no other documented adverse events directly related to spread of BoNT-A. According to Dr. Wang, this rate of ptosis is lower than the incidence with BoNT-A alone in two landmark trials studying its effects on glabellar lines, which was reported as 5.4% and 1.0%.

Among the 398 patients who received soft-tissue fillers, most (94%) were female, their mean age was 54 years, and 99% were treated with a 1927nm wavelength at a medium setting in 97% of cases. The top five injection sites were cheeks and/or tear troughs (89%), perioral area and/or marionette lines (77%), lips (34%), nasolabial folds (19%), and temples (11%), and the mean number of filler syringes per treatment was 1.6. Slightly more than half (51%) had 1 session, while the remainder had 2 to greater than 10 sessions. The researchers observed no documented adverse events related to spread of fillers or laser treatment of filled areas.

“This laser is a low-powered device that creates small, superficial, and transient microchannels, which likely contributes to the safety of single-session treatments with cosmetic injectables,” Dr. Wang said. However, prospective studies are needed to further validate these results, he added.

“With this very mild laser, it is not surprising that combined treatment had no effect,” said Eric F. Bernstein, MD, MSE, director of the Main Line Center for Laser Surgery in Ardmore, Pa., who was asked to comment on the study results. “There have been numerous anecdotal reports of spreading of botulinum toxin effect to areas not in the target area for treatment following a variety of lasers, including the more powerful version of the laser used in this study. In addition, spread following vascular and other lasers has been reported,” he noted

The laser used in this study, Dr. Bernstein continued, “is low powered and emits a wavelength that is very superficially absorbed, resulting in injury to the stratum corneum, superficial epidermis, or possibly the very superficial dermis, and is often used by physician extenders and not physicians – although I suspect this is not the case in the current study. One can have a reasonable degree of confidence when combining this laser with injectables, but these results cannot be extrapolated to other devices.”

The abstract received the annual ASDS Carruthers Award during the meeting. Dr. Wang reported that he is a consultant or advisor to Allergan, Alastin, AVAVA, Cynosure, Lutronic, Novoxel, Sofwave, and Solta. Dr. Bernstein reported having received research funding from Cynosure, Candela, and Acclaro. He also has received consulting fees from Cynosure and holds ownership interest in Candela, Novoxel, OnSite, Joylux, and Acclaro and has served on the advisory board for Novoxel, Cynosure, and Acclaro.

The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) has lowered the recommended age to start CRC screening from 50 to 45 years of age for all average-risk individuals.

Although no studies have directly demonstrated the result of lowering the age of screening, lead author Swati G. Patel, MD, of University of Colorado Anschutz Medical Center, Aurora, and colleagues suggested that the increasing incidence of advanced CRC among younger individuals, coupled with the net benefit of screening, warrant a lower age threshold.

“Recent data ... show that CRC incidence rates in individuals ages 50 to 64 have increased by 1% annually between 2011 and 2016,” the authors wrote in Gastroenterology. “Similarly, CRC incidence and mortality rates in persons under age 50, termed early-age onset CRC (EAO-CRC), are also increasing.”

The task force of nine experts, representing the American Gastroenterological Association, the American College of Gastroenterology, and the American Society for Gastrointestinal Endoscopy, conducted a literature review and generated recommendations using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition to recommending a lower age for initial screening, Dr. Patel and colleagues provided guidance for cessation of screening among older individuals.
 

Guidance for screening initiation

According to the authors, the present risk of CRC among younger individuals mirrors the historical risk for older individuals before screening was prevalent.

“The current CRC incidence rates in individuals ages 45 to 49 are similar to the incidence rates observed in 50-year-olds in 1992, before widespread CRC screening was performed,” they wrote.

Elevated rates among younger people have been disproportionately driven by rectal cancer, according to the authors. From 2006 to 2015, incidence of rectal cancer among Americans under 50 increased 1.7% per year, compared with 0.7% per year for colon cancer, based on data from the North American Association of Central Cancer Registries.

Associated mortality rates also increased, the authors noted. From 1999-2019, mortality from colon cancer among people 45-49 years increased from 6.4 to 6.6 deaths per 100,000 individuals, while deaths from rectal cancer increased from 1.3 to 1.7 per 100,000, according to the CDC. Concurrently, CRC-associated mortality rates among older individuals generally declined.

While these findings suggest a growing disease burden among the under-50-year age group, controlled data demonstrating the effects of earlier screening are lacking, Dr. Patel and colleagues noted. Still, they predicted that expanded screening would generate a net benefit.

“Although there are no CRC screening safety data for average-risk individuals [younger than] 50, there are ample data that colonoscopy for other indications (screening based on family history, symptom evaluation, etc.) is safer when comparing younger versus older individuals,” they wrote.

Supporting this claim, the authors cited three independently generated microsimulation models from the Agency for Healthcare Research and Quality that “showed a favorable balance of life-years gained compared with adverse events,” given 100% compliance.
 

Guidance for screening cessation

Like the situation with younger individuals, minimal data are available to determine the best time for screening cessation, according to the task force.

“There are no randomized or observational studies after 2017 that enrolled individuals over age 75 to inform the appropriate time to stop CRC screening,” the authors wrote. “In our search of 37 relevant articles, only one presented primary data for when to stop screening.”

This one available study showed that some individuals older than 74 do in fact gain benefit from screening,

“For example,” Dr. Patel and colleagues wrote, “women without a history of screening and no comorbidities benefitted from annual fecal immunochemical test (FIT) screening until age 90, whereas unscreened men with or without comorbidities benefited from annual FIT screening until age 88. Conversely, screening was not beneficial beyond age 66 in men or women with severe comorbidities.”

The task force therefore recommended personalized screening for individuals 76-85 years of age “based on the balance of benefits and harms and individual patient clinical factors and preferences.”

Screening for individuals 86 years and older, according to the task force, is unnecessary.

The authors disclosed relationships with Olympus America, Bayer Pharmaceuticals, Janssen Pharmaceuticals, and others.

This article was updated on Jan. 3, 2022.

The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) has lowered the recommended age to start CRC screening from 50 to 45 years of age for all average-risk individuals.

Although no studies have directly demonstrated the result of lowering the age of screening, lead author Swati G. Patel, MD, of University of Colorado Anschutz Medical Center, Aurora, and colleagues suggested that the increasing incidence of advanced CRC among younger individuals, coupled with the net benefit of screening, warrant a lower age threshold.

“Recent data ... show that CRC incidence rates in individuals ages 50 to 64 have increased by 1% annually between 2011 and 2016,” the authors wrote in Gastroenterology. “Similarly, CRC incidence and mortality rates in persons under age 50, termed early-age onset CRC (EAO-CRC), are also increasing.”

The task force of nine experts, representing the American Gastroenterological Association, the American College of Gastroenterology, and the American Society for Gastrointestinal Endoscopy, conducted a literature review and generated recommendations using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition to recommending a lower age for initial screening, Dr. Patel and colleagues provided guidance for cessation of screening among older individuals.
 

Guidance for screening initiation

According to the authors, the present risk of CRC among younger individuals mirrors the historical risk for older individuals before screening was prevalent.

“The current CRC incidence rates in individuals ages 45 to 49 are similar to the incidence rates observed in 50-year-olds in 1992, before widespread CRC screening was performed,” they wrote.

Elevated rates among younger people have been disproportionately driven by rectal cancer, according to the authors. From 2006 to 2015, incidence of rectal cancer among Americans under 50 increased 1.7% per year, compared with 0.7% per year for colon cancer, based on data from the North American Association of Central Cancer Registries.

Associated mortality rates also increased, the authors noted. From 1999-2019, mortality from colon cancer among people 45-49 years increased from 6.4 to 6.6 deaths per 100,000 individuals, while deaths from rectal cancer increased from 1.3 to 1.7 per 100,000, according to the CDC. Concurrently, CRC-associated mortality rates among older individuals generally declined.

While these findings suggest a growing disease burden among the under-50-year age group, controlled data demonstrating the effects of earlier screening are lacking, Dr. Patel and colleagues noted. Still, they predicted that expanded screening would generate a net benefit.

“Although there are no CRC screening safety data for average-risk individuals [younger than] 50, there are ample data that colonoscopy for other indications (screening based on family history, symptom evaluation, etc.) is safer when comparing younger versus older individuals,” they wrote.

Supporting this claim, the authors cited three independently generated microsimulation models from the Agency for Healthcare Research and Quality that “showed a favorable balance of life-years gained compared with adverse events,” given 100% compliance.
 

Guidance for screening cessation

Like the situation with younger individuals, minimal data are available to determine the best time for screening cessation, according to the task force.

“There are no randomized or observational studies after 2017 that enrolled individuals over age 75 to inform the appropriate time to stop CRC screening,” the authors wrote. “In our search of 37 relevant articles, only one presented primary data for when to stop screening.”

This one available study showed that some individuals older than 74 do in fact gain benefit from screening,

“For example,” Dr. Patel and colleagues wrote, “women without a history of screening and no comorbidities benefitted from annual fecal immunochemical test (FIT) screening until age 90, whereas unscreened men with or without comorbidities benefited from annual FIT screening until age 88. Conversely, screening was not beneficial beyond age 66 in men or women with severe comorbidities.”

The task force therefore recommended personalized screening for individuals 76-85 years of age “based on the balance of benefits and harms and individual patient clinical factors and preferences.”

Screening for individuals 86 years and older, according to the task force, is unnecessary.

The authors disclosed relationships with Olympus America, Bayer Pharmaceuticals, Janssen Pharmaceuticals, and others.

This article was updated on Jan. 3, 2022.

The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) has lowered the recommended age to start CRC screening from 50 to 45 years of age for all average-risk individuals.

Although no studies have directly demonstrated the result of lowering the age of screening, lead author Swati G. Patel, MD, of University of Colorado Anschutz Medical Center, Aurora, and colleagues suggested that the increasing incidence of advanced CRC among younger individuals, coupled with the net benefit of screening, warrant a lower age threshold.

“Recent data ... show that CRC incidence rates in individuals ages 50 to 64 have increased by 1% annually between 2011 and 2016,” the authors wrote in Gastroenterology. “Similarly, CRC incidence and mortality rates in persons under age 50, termed early-age onset CRC (EAO-CRC), are also increasing.”

The task force of nine experts, representing the American Gastroenterological Association, the American College of Gastroenterology, and the American Society for Gastrointestinal Endoscopy, conducted a literature review and generated recommendations using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition to recommending a lower age for initial screening, Dr. Patel and colleagues provided guidance for cessation of screening among older individuals.
 

Guidance for screening initiation

According to the authors, the present risk of CRC among younger individuals mirrors the historical risk for older individuals before screening was prevalent.

“The current CRC incidence rates in individuals ages 45 to 49 are similar to the incidence rates observed in 50-year-olds in 1992, before widespread CRC screening was performed,” they wrote.

Elevated rates among younger people have been disproportionately driven by rectal cancer, according to the authors. From 2006 to 2015, incidence of rectal cancer among Americans under 50 increased 1.7% per year, compared with 0.7% per year for colon cancer, based on data from the North American Association of Central Cancer Registries.

Associated mortality rates also increased, the authors noted. From 1999-2019, mortality from colon cancer among people 45-49 years increased from 6.4 to 6.6 deaths per 100,000 individuals, while deaths from rectal cancer increased from 1.3 to 1.7 per 100,000, according to the CDC. Concurrently, CRC-associated mortality rates among older individuals generally declined.

While these findings suggest a growing disease burden among the under-50-year age group, controlled data demonstrating the effects of earlier screening are lacking, Dr. Patel and colleagues noted. Still, they predicted that expanded screening would generate a net benefit.

“Although there are no CRC screening safety data for average-risk individuals [younger than] 50, there are ample data that colonoscopy for other indications (screening based on family history, symptom evaluation, etc.) is safer when comparing younger versus older individuals,” they wrote.

Supporting this claim, the authors cited three independently generated microsimulation models from the Agency for Healthcare Research and Quality that “showed a favorable balance of life-years gained compared with adverse events,” given 100% compliance.
 

Guidance for screening cessation

Like the situation with younger individuals, minimal data are available to determine the best time for screening cessation, according to the task force.

“There are no randomized or observational studies after 2017 that enrolled individuals over age 75 to inform the appropriate time to stop CRC screening,” the authors wrote. “In our search of 37 relevant articles, only one presented primary data for when to stop screening.”

This one available study showed that some individuals older than 74 do in fact gain benefit from screening,

“For example,” Dr. Patel and colleagues wrote, “women without a history of screening and no comorbidities benefitted from annual fecal immunochemical test (FIT) screening until age 90, whereas unscreened men with or without comorbidities benefited from annual FIT screening until age 88. Conversely, screening was not beneficial beyond age 66 in men or women with severe comorbidities.”

The task force therefore recommended personalized screening for individuals 76-85 years of age “based on the balance of benefits and harms and individual patient clinical factors and preferences.”

Screening for individuals 86 years and older, according to the task force, is unnecessary.

The authors disclosed relationships with Olympus America, Bayer Pharmaceuticals, Janssen Pharmaceuticals, and others.

This article was updated on Jan. 3, 2022.

The impact of respiratory syncytial virus (RSV)will likely be greater in 2021 and 2022 in the United States than in previous years as a result of the ongoing COVID-19 pandemic, based on data from a simulation-modeling study involving approximately 19 million individuals.

Although RSV usually follows consistent patterns of timing and duration, the disease all but disappeared starting in March 2020 after the introduction of measures to mitigate the spread of COVID-19, Zhe Zheng, MBBS, of Yale University, New Haven, Conn., and colleagues wrote.

However, lifting of mitigation measures has resulted in emergence of RSV in various parts of the world in early 2021, and trends may be similar in the United States, but data are needed to plan for prophylaxis and hospital use, they noted.

In a study published in JAMA Network Open, the researchers developed a simulation model for epidemics of RSV based on historical data. They acquired inpatient records from New York during 2005-2014 and from California during 2003-2011. The primary clinical outcome was the estimated monthly hospitalizations for RSV.

The simulated study population was 19.45 million individuals. After evaluating several scenarios including continued low transmission associated with social distancing and other mitigation measures, the researchers focused on the likely scenario that introduction of RSV from other regions would likely spark RSV epidemics in the United States.

They determined that spring and summer 2021 would show an increase in hospitalizations for RSV. Overall, higher rates of virus introduction from other regions were associated with more intense spring and summer RSV epidemics, with the trade-off of smaller winter epidemics. In the model, the expected RSV epidemic in spring and summer 2021 in New York was small, with a peak incidence of 419 hospitalizations per 100,000 people in April; by contrast, for states with less seasonal variability, such as Florida, the model predicted a larger summer epidemic.

In the model, the mean age of hospitalization for children younger than 5 years for January 2022 was expected to be 1.17 years, compared with 0.84 years in January 2019, the researchers noted.

Across all age groups, the greatest relative increase in the incidence of RSV infection was predicted for children aged 1-4 years (ranging from 82% to 86%), as were lower respiratory infections (87%-101%) and hospitalization (99%-119%), compared with prepandemic levels.

Hospitalizations for children aged 1 year were predicted to double compared with prepandemic seasons; 707 per 100,000 children per year for 2021 and 2022 versus 355 per 100,000 children per year in a typical prepandemic season. However, the largest incidence of lower respiratory infections (30,075 per 100,000) was predicted for infants aged 3-5 months, and the largest incidence of hospitalizations (3,116 per 100,000) was predicted for infants younger than 3 months.

“Without virus importation, the risk of RSV infections across all age groups in the winter of 2021 and 2022 would be greater, as more susceptible individuals were spared from infections in the absence of summer epidemics,” the researchers noted.

The older mean hospitalization age seen in the model was similar to the reported median patient age in Australia both before the pandemic and during the reemergent RSV epidemic.

“This makes intuitive sense, since many children born in 2020 were spared from RSV infection due to the low virus activity; these children will be older when they get infected for the first time during the reemergent epidemics,” the researchers wrote. “Consequently, stakeholders should consider modifying prophylaxis guidelines to include high-risk infants less than 2 years of age for the 2021-2022 season.”

The study findings were limited by several factors including the lack of data on level of virus introduction or on the impact of lack of boosting on infants with only transplacentally acquired RSV antibodies, the researchers noted. Other limitations include the use of historical data and the lack of data on values outside those included in the model, as well as the inability to control for other factors that could influence RSV, such as vaccines or long-lasting antibodies.

However, the results suggest that the rate of imported infections is associated with RSV hospitalizations, and the model effectively captured the RSV epidemics in the United States in spring and summer 2021.

Models can guide clinical preparations

“Health care simulation modeling is a growing field, with very exciting implications,” Lenore Jarvis, MD, of George Washington University, Washington, said in an interview. The field has the potential ability to influence health care in a data-driven way, including, but not limited to, staffing and other hospital operations, as well as patient care decision-making. “In short, accurate modeling and predictions can help us to make informed health care decisions that can lead to increased quality of care, potential cost savings, and even to help save lives,” she said.

Although the details of transmission modeling were not mentioned in the study, the authors evaluated the performances of several models and scenarios. “Scenario 4, for example, was focused on in particular because it best captured the observed dynamics [for RSV] that emerged during the spring and summer of 2021,” Dr. Jarvis said.

“Pediatricians can speak to these trends firsthand. A decrease in expected RSV infections and hospitalizations in 2020, followed by an unprecedented and early increase in RSV infections and severity in 2021, and the factors that the authors account for make sense, such as reintroduction of RSV from other regions and low immunity in the population,” she said. “It also makes sense that, in these transmission modeling scenarios, the expected mean age of hospitalization because of RSV increased with a temporary (hopefully) increase in RSV hospitalizations in the 2021 season, and potentially the 2022 RSV season.”

As for additional research, Dr. Jarvis said she would like to see follow-up data on the RSV transmission modeling. “For example, with scenario 4, does this scenario continue to perform well in other time periods, such as the winter? If the modeling continues to be accurate during other periods of evaluation and reevaluation, this modeling could be very useful in helping pediatric clinics and hospitals to prepare for RSV care and hospital capacity management.”

The study was supported by grants to various researchers from the National Institute of Allergy and Infectious Diseases/National Institutes of Health, the National Center for Advancing Translational Science at the National Institutes of Health, and NIH Roadmap for Medical Research. Lead author Ms. Zheng had no financial conflicts to disclose. Her study coauthors disclosed relationships with companies including AbbVie, Merck, Pfizer, GlaxoSmithKline, MedImmune, and Janssen. Dr. Jarvis had no financial conflicts to disclose and serves on the Pediatric News editorial advisory board.

The impact of respiratory syncytial virus (RSV)will likely be greater in 2021 and 2022 in the United States than in previous years as a result of the ongoing COVID-19 pandemic, based on data from a simulation-modeling study involving approximately 19 million individuals.

Although RSV usually follows consistent patterns of timing and duration, the disease all but disappeared starting in March 2020 after the introduction of measures to mitigate the spread of COVID-19, Zhe Zheng, MBBS, of Yale University, New Haven, Conn., and colleagues wrote.

However, lifting of mitigation measures has resulted in emergence of RSV in various parts of the world in early 2021, and trends may be similar in the United States, but data are needed to plan for prophylaxis and hospital use, they noted.

In a study published in JAMA Network Open, the researchers developed a simulation model for epidemics of RSV based on historical data. They acquired inpatient records from New York during 2005-2014 and from California during 2003-2011. The primary clinical outcome was the estimated monthly hospitalizations for RSV.

The simulated study population was 19.45 million individuals. After evaluating several scenarios including continued low transmission associated with social distancing and other mitigation measures, the researchers focused on the likely scenario that introduction of RSV from other regions would likely spark RSV epidemics in the United States.

They determined that spring and summer 2021 would show an increase in hospitalizations for RSV. Overall, higher rates of virus introduction from other regions were associated with more intense spring and summer RSV epidemics, with the trade-off of smaller winter epidemics. In the model, the expected RSV epidemic in spring and summer 2021 in New York was small, with a peak incidence of 419 hospitalizations per 100,000 people in April; by contrast, for states with less seasonal variability, such as Florida, the model predicted a larger summer epidemic.

In the model, the mean age of hospitalization for children younger than 5 years for January 2022 was expected to be 1.17 years, compared with 0.84 years in January 2019, the researchers noted.

Across all age groups, the greatest relative increase in the incidence of RSV infection was predicted for children aged 1-4 years (ranging from 82% to 86%), as were lower respiratory infections (87%-101%) and hospitalization (99%-119%), compared with prepandemic levels.

Hospitalizations for children aged 1 year were predicted to double compared with prepandemic seasons; 707 per 100,000 children per year for 2021 and 2022 versus 355 per 100,000 children per year in a typical prepandemic season. However, the largest incidence of lower respiratory infections (30,075 per 100,000) was predicted for infants aged 3-5 months, and the largest incidence of hospitalizations (3,116 per 100,000) was predicted for infants younger than 3 months.

“Without virus importation, the risk of RSV infections across all age groups in the winter of 2021 and 2022 would be greater, as more susceptible individuals were spared from infections in the absence of summer epidemics,” the researchers noted.

The older mean hospitalization age seen in the model was similar to the reported median patient age in Australia both before the pandemic and during the reemergent RSV epidemic.

“This makes intuitive sense, since many children born in 2020 were spared from RSV infection due to the low virus activity; these children will be older when they get infected for the first time during the reemergent epidemics,” the researchers wrote. “Consequently, stakeholders should consider modifying prophylaxis guidelines to include high-risk infants less than 2 years of age for the 2021-2022 season.”

The study findings were limited by several factors including the lack of data on level of virus introduction or on the impact of lack of boosting on infants with only transplacentally acquired RSV antibodies, the researchers noted. Other limitations include the use of historical data and the lack of data on values outside those included in the model, as well as the inability to control for other factors that could influence RSV, such as vaccines or long-lasting antibodies.

However, the results suggest that the rate of imported infections is associated with RSV hospitalizations, and the model effectively captured the RSV epidemics in the United States in spring and summer 2021.

Models can guide clinical preparations

“Health care simulation modeling is a growing field, with very exciting implications,” Lenore Jarvis, MD, of George Washington University, Washington, said in an interview. The field has the potential ability to influence health care in a data-driven way, including, but not limited to, staffing and other hospital operations, as well as patient care decision-making. “In short, accurate modeling and predictions can help us to make informed health care decisions that can lead to increased quality of care, potential cost savings, and even to help save lives,” she said.

Although the details of transmission modeling were not mentioned in the study, the authors evaluated the performances of several models and scenarios. “Scenario 4, for example, was focused on in particular because it best captured the observed dynamics [for RSV] that emerged during the spring and summer of 2021,” Dr. Jarvis said.

“Pediatricians can speak to these trends firsthand. A decrease in expected RSV infections and hospitalizations in 2020, followed by an unprecedented and early increase in RSV infections and severity in 2021, and the factors that the authors account for make sense, such as reintroduction of RSV from other regions and low immunity in the population,” she said. “It also makes sense that, in these transmission modeling scenarios, the expected mean age of hospitalization because of RSV increased with a temporary (hopefully) increase in RSV hospitalizations in the 2021 season, and potentially the 2022 RSV season.”

As for additional research, Dr. Jarvis said she would like to see follow-up data on the RSV transmission modeling. “For example, with scenario 4, does this scenario continue to perform well in other time periods, such as the winter? If the modeling continues to be accurate during other periods of evaluation and reevaluation, this modeling could be very useful in helping pediatric clinics and hospitals to prepare for RSV care and hospital capacity management.”

The study was supported by grants to various researchers from the National Institute of Allergy and Infectious Diseases/National Institutes of Health, the National Center for Advancing Translational Science at the National Institutes of Health, and NIH Roadmap for Medical Research. Lead author Ms. Zheng had no financial conflicts to disclose. Her study coauthors disclosed relationships with companies including AbbVie, Merck, Pfizer, GlaxoSmithKline, MedImmune, and Janssen. Dr. Jarvis had no financial conflicts to disclose and serves on the Pediatric News editorial advisory board.

The impact of respiratory syncytial virus (RSV)will likely be greater in 2021 and 2022 in the United States than in previous years as a result of the ongoing COVID-19 pandemic, based on data from a simulation-modeling study involving approximately 19 million individuals.

Although RSV usually follows consistent patterns of timing and duration, the disease all but disappeared starting in March 2020 after the introduction of measures to mitigate the spread of COVID-19, Zhe Zheng, MBBS, of Yale University, New Haven, Conn., and colleagues wrote.

However, lifting of mitigation measures has resulted in emergence of RSV in various parts of the world in early 2021, and trends may be similar in the United States, but data are needed to plan for prophylaxis and hospital use, they noted.

In a study published in JAMA Network Open, the researchers developed a simulation model for epidemics of RSV based on historical data. They acquired inpatient records from New York during 2005-2014 and from California during 2003-2011. The primary clinical outcome was the estimated monthly hospitalizations for RSV.

The simulated study population was 19.45 million individuals. After evaluating several scenarios including continued low transmission associated with social distancing and other mitigation measures, the researchers focused on the likely scenario that introduction of RSV from other regions would likely spark RSV epidemics in the United States.

They determined that spring and summer 2021 would show an increase in hospitalizations for RSV. Overall, higher rates of virus introduction from other regions were associated with more intense spring and summer RSV epidemics, with the trade-off of smaller winter epidemics. In the model, the expected RSV epidemic in spring and summer 2021 in New York was small, with a peak incidence of 419 hospitalizations per 100,000 people in April; by contrast, for states with less seasonal variability, such as Florida, the model predicted a larger summer epidemic.

In the model, the mean age of hospitalization for children younger than 5 years for January 2022 was expected to be 1.17 years, compared with 0.84 years in January 2019, the researchers noted.

Across all age groups, the greatest relative increase in the incidence of RSV infection was predicted for children aged 1-4 years (ranging from 82% to 86%), as were lower respiratory infections (87%-101%) and hospitalization (99%-119%), compared with prepandemic levels.

Hospitalizations for children aged 1 year were predicted to double compared with prepandemic seasons; 707 per 100,000 children per year for 2021 and 2022 versus 355 per 100,000 children per year in a typical prepandemic season. However, the largest incidence of lower respiratory infections (30,075 per 100,000) was predicted for infants aged 3-5 months, and the largest incidence of hospitalizations (3,116 per 100,000) was predicted for infants younger than 3 months.

“Without virus importation, the risk of RSV infections across all age groups in the winter of 2021 and 2022 would be greater, as more susceptible individuals were spared from infections in the absence of summer epidemics,” the researchers noted.

The older mean hospitalization age seen in the model was similar to the reported median patient age in Australia both before the pandemic and during the reemergent RSV epidemic.

“This makes intuitive sense, since many children born in 2020 were spared from RSV infection due to the low virus activity; these children will be older when they get infected for the first time during the reemergent epidemics,” the researchers wrote. “Consequently, stakeholders should consider modifying prophylaxis guidelines to include high-risk infants less than 2 years of age for the 2021-2022 season.”

The study findings were limited by several factors including the lack of data on level of virus introduction or on the impact of lack of boosting on infants with only transplacentally acquired RSV antibodies, the researchers noted. Other limitations include the use of historical data and the lack of data on values outside those included in the model, as well as the inability to control for other factors that could influence RSV, such as vaccines or long-lasting antibodies.

However, the results suggest that the rate of imported infections is associated with RSV hospitalizations, and the model effectively captured the RSV epidemics in the United States in spring and summer 2021.

Models can guide clinical preparations

“Health care simulation modeling is a growing field, with very exciting implications,” Lenore Jarvis, MD, of George Washington University, Washington, said in an interview. The field has the potential ability to influence health care in a data-driven way, including, but not limited to, staffing and other hospital operations, as well as patient care decision-making. “In short, accurate modeling and predictions can help us to make informed health care decisions that can lead to increased quality of care, potential cost savings, and even to help save lives,” she said.

Although the details of transmission modeling were not mentioned in the study, the authors evaluated the performances of several models and scenarios. “Scenario 4, for example, was focused on in particular because it best captured the observed dynamics [for RSV] that emerged during the spring and summer of 2021,” Dr. Jarvis said.

“Pediatricians can speak to these trends firsthand. A decrease in expected RSV infections and hospitalizations in 2020, followed by an unprecedented and early increase in RSV infections and severity in 2021, and the factors that the authors account for make sense, such as reintroduction of RSV from other regions and low immunity in the population,” she said. “It also makes sense that, in these transmission modeling scenarios, the expected mean age of hospitalization because of RSV increased with a temporary (hopefully) increase in RSV hospitalizations in the 2021 season, and potentially the 2022 RSV season.”

As for additional research, Dr. Jarvis said she would like to see follow-up data on the RSV transmission modeling. “For example, with scenario 4, does this scenario continue to perform well in other time periods, such as the winter? If the modeling continues to be accurate during other periods of evaluation and reevaluation, this modeling could be very useful in helping pediatric clinics and hospitals to prepare for RSV care and hospital capacity management.”

The study was supported by grants to various researchers from the National Institute of Allergy and Infectious Diseases/National Institutes of Health, the National Center for Advancing Translational Science at the National Institutes of Health, and NIH Roadmap for Medical Research. Lead author Ms. Zheng had no financial conflicts to disclose. Her study coauthors disclosed relationships with companies including AbbVie, Merck, Pfizer, GlaxoSmithKline, MedImmune, and Janssen. Dr. Jarvis had no financial conflicts to disclose and serves on the Pediatric News editorial advisory board.

SILVER SPRING, MD – The FDA issued approval for long-acting, injectable cabotegravir (CAB-LA) on Dec. 21, providing an alternative to daily oral tenofovir disoproxil fumarate-emtricitabine (TDC-FTC) for pre-exposure prophylaxis (PrEP) against HIV acquisition.

The priority review approval was based on phase 2b-3 clinical trial data submitted to the agency this past August, after the study was stopped early due to encouraging efficacy results of the first pre-planned interim end-point analysis.

“Although TDF-FTC PrEP could be almost astoundingly effective in preventing HIV acquisition across populations and risk exposures, the adherence to the daily protocols was really challenging and difficult to attain initially and to maintain for some of our most vulnerable populations,” Raphael Landovitz, MD, MDC, lead study investigator and co-director of The Center for HIV Identification, Prevention, and Treatment Services at UCLA, Los Angeles, told this news organization.

Dr. Landovitz noted that population level benefits observed with PrEP were limited to people who were highly engaged in health care and well resourced, but the same benefits were not observed in the most vulnerable, highest-risk populations. 

“The idea was, is there anything that we can do to improve ... choices for different options, some of which – like long-acting agents – would remove the obligation to adhere to daily prescribing or a post-coital and be more discreet,” he said.
 

Data demonstrated superiority versus TDF-FTC

Details of the prospective, phase 2b-3 randomized, double-blind, double-dummy, active-controlled trial among 4,566 cisgender MSM (men who have sex with men) and transgender women highlighted the superiority of CAB 600 mg intramuscularly versus placebo or active TDF-FTC (300 mg/200 mg), with CAB-LA reducing HIV infection risk by 66%. These results were published August 11 in the New England Journal of Medicine and previously reported by this news organization.

Investigators identified HIV infections in 57 participants (including 52 who acquired HIV infections after enrollment). The hazard ratio for incident HIV infection versus TDG-FTC was 0.34, P < .001. Notably, effects were consistent across prespecified subgroups and populations. 

Additionally, integrase strand-transfer inhibitor (INSTI) resistance mutations were detected in 1 of 4 of baseline HIV infection cases among CAB participants, while 2 of 39 incident infections in TDF-FTC participants occurred despite drug concentrations indicating good PrEP adherence. 
 

Adverse events, breakthrough infections, and other important considerations

Because the trial was halted early, long-term safety data were lacking, thereby prompting investigators to launch an ongoing, open-label extension. In the initial trial, injection site reactions were reported in 81.4% (1,724) of CAB participants, most beginning a median of 1 day (IQR 0-2 days) post-injection, mild to moderate in severity (60.8% pain, 23.7% tenderness), and lasting a median of 3 days (IQR 2-6 days). In comparison, injection site reactions were reported in 31.3% of TDF-FTC participants (who, incidentally, received at least one placebo injection).

Severe adverse events (grade 3 or higher) were similar between CAB and TDF-FTC groups, They consisted mostly of an increase in creatine kinase level (14.2% with CAB vs. 13.5% with TDF-FTC) and a decrease in creatinine clearance (7.0% with CAB vs. 8.3% with TDF-FTC).

Although weight gain was higher among CAB participants (1.23 kg/year vs. 0.37 kg/year, TDF-FTC participants), most of the differences were observed during the first 40 weeks and were driven by weight loss in the TDF-FDC group. Weight changes were similar (~1 kg/year) thereafter.

Importantly, study participants assigned CAB underwent an oral-tablet, 5-week lead-in phase, which might have contributed to eventual treatment failure.

In a companion piece published Nov. 1 in the Journal of Infectious Diseases, investigators noted that adherence to the oral lead-in was poor in roughly one-third of participants with incident, breakthrough infections. They wrote that the barriers to adherence with daily oral PrEP regimens coupled with the favorable CAB-LA safety profile suggested that “the oral phase before CAB-LA initiation might not be necessary or desirable.”

The question remains as to whether or not strategies entailing viral load or other RNA screening tests at follow-up clinic visits might be warranted. 

“It’s one of the biggest sort of ‘what’s next’ questions that’s come out of this study,” Dr. Landovitz said. “We’re now testing the strategy of using viral load or RNA screening at every visit to see if, in fact, we can catch these breakthrough infections earlier and potentially avoid resistance,” he added.

Until more data are available, Dr. Landovitz said that “the guidance for the clinician would be that until you have resistance testing back on someone who breaks through cabotegravir PrEP to use a protease inhibitor-based treatment regimen, at least initially.”

Institutional changes to ensure delivery of injections, tracking, and follow-up to ensure optimal use of long-acting PrEP agents are likely to challenge already overburdened health care systems and may require additional strategies for implementation (for example, pharmacy or at-home administration). Despite these factors, CAB-LA approval is welcome news to clinicians and patients alike.

“We’re constantly searching for new drugs to expand our repertoire of what we can provide patients,” Lina Rosengren-Hovee, MD, MPH, assistant professor of medicine and infectious disease specialist at UNC Health, Chapel Hill, N.C., said in an interview. Dr. Rosengren-Hovee was not involved in the study.

“For folks under 30, the sexual and gender minority, Black, and Latino, they are the ones with the highest need for PrEP, that are in a position that places them at higher risk for HIV. Being able to offer an injectable option is ... a game changer,” she said.

Dr. Rosengren-Hovee reports no relevant financial relationships. Dr. Landovitz has consulting relationships with Gilead, Janssen, Roche, and Cepheus.

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

SILVER SPRING, MD – The FDA issued approval for long-acting, injectable cabotegravir (CAB-LA) on Dec. 21, providing an alternative to daily oral tenofovir disoproxil fumarate-emtricitabine (TDC-FTC) for pre-exposure prophylaxis (PrEP) against HIV acquisition.

The priority review approval was based on phase 2b-3 clinical trial data submitted to the agency this past August, after the study was stopped early due to encouraging efficacy results of the first pre-planned interim end-point analysis.

“Although TDF-FTC PrEP could be almost astoundingly effective in preventing HIV acquisition across populations and risk exposures, the adherence to the daily protocols was really challenging and difficult to attain initially and to maintain for some of our most vulnerable populations,” Raphael Landovitz, MD, MDC, lead study investigator and co-director of The Center for HIV Identification, Prevention, and Treatment Services at UCLA, Los Angeles, told this news organization.

Dr. Landovitz noted that population level benefits observed with PrEP were limited to people who were highly engaged in health care and well resourced, but the same benefits were not observed in the most vulnerable, highest-risk populations. 

“The idea was, is there anything that we can do to improve ... choices for different options, some of which – like long-acting agents – would remove the obligation to adhere to daily prescribing or a post-coital and be more discreet,” he said.
 

Data demonstrated superiority versus TDF-FTC

Details of the prospective, phase 2b-3 randomized, double-blind, double-dummy, active-controlled trial among 4,566 cisgender MSM (men who have sex with men) and transgender women highlighted the superiority of CAB 600 mg intramuscularly versus placebo or active TDF-FTC (300 mg/200 mg), with CAB-LA reducing HIV infection risk by 66%. These results were published August 11 in the New England Journal of Medicine and previously reported by this news organization.

Investigators identified HIV infections in 57 participants (including 52 who acquired HIV infections after enrollment). The hazard ratio for incident HIV infection versus TDG-FTC was 0.34, P < .001. Notably, effects were consistent across prespecified subgroups and populations. 

Additionally, integrase strand-transfer inhibitor (INSTI) resistance mutations were detected in 1 of 4 of baseline HIV infection cases among CAB participants, while 2 of 39 incident infections in TDF-FTC participants occurred despite drug concentrations indicating good PrEP adherence. 
 

Adverse events, breakthrough infections, and other important considerations

Because the trial was halted early, long-term safety data were lacking, thereby prompting investigators to launch an ongoing, open-label extension. In the initial trial, injection site reactions were reported in 81.4% (1,724) of CAB participants, most beginning a median of 1 day (IQR 0-2 days) post-injection, mild to moderate in severity (60.8% pain, 23.7% tenderness), and lasting a median of 3 days (IQR 2-6 days). In comparison, injection site reactions were reported in 31.3% of TDF-FTC participants (who, incidentally, received at least one placebo injection).

Severe adverse events (grade 3 or higher) were similar between CAB and TDF-FTC groups, They consisted mostly of an increase in creatine kinase level (14.2% with CAB vs. 13.5% with TDF-FTC) and a decrease in creatinine clearance (7.0% with CAB vs. 8.3% with TDF-FTC).

Although weight gain was higher among CAB participants (1.23 kg/year vs. 0.37 kg/year, TDF-FTC participants), most of the differences were observed during the first 40 weeks and were driven by weight loss in the TDF-FDC group. Weight changes were similar (~1 kg/year) thereafter.

Importantly, study participants assigned CAB underwent an oral-tablet, 5-week lead-in phase, which might have contributed to eventual treatment failure.

In a companion piece published Nov. 1 in the Journal of Infectious Diseases, investigators noted that adherence to the oral lead-in was poor in roughly one-third of participants with incident, breakthrough infections. They wrote that the barriers to adherence with daily oral PrEP regimens coupled with the favorable CAB-LA safety profile suggested that “the oral phase before CAB-LA initiation might not be necessary or desirable.”

The question remains as to whether or not strategies entailing viral load or other RNA screening tests at follow-up clinic visits might be warranted. 

“It’s one of the biggest sort of ‘what’s next’ questions that’s come out of this study,” Dr. Landovitz said. “We’re now testing the strategy of using viral load or RNA screening at every visit to see if, in fact, we can catch these breakthrough infections earlier and potentially avoid resistance,” he added.

Until more data are available, Dr. Landovitz said that “the guidance for the clinician would be that until you have resistance testing back on someone who breaks through cabotegravir PrEP to use a protease inhibitor-based treatment regimen, at least initially.”

Institutional changes to ensure delivery of injections, tracking, and follow-up to ensure optimal use of long-acting PrEP agents are likely to challenge already overburdened health care systems and may require additional strategies for implementation (for example, pharmacy or at-home administration). Despite these factors, CAB-LA approval is welcome news to clinicians and patients alike.

“We’re constantly searching for new drugs to expand our repertoire of what we can provide patients,” Lina Rosengren-Hovee, MD, MPH, assistant professor of medicine and infectious disease specialist at UNC Health, Chapel Hill, N.C., said in an interview. Dr. Rosengren-Hovee was not involved in the study.

“For folks under 30, the sexual and gender minority, Black, and Latino, they are the ones with the highest need for PrEP, that are in a position that places them at higher risk for HIV. Being able to offer an injectable option is ... a game changer,” she said.

Dr. Rosengren-Hovee reports no relevant financial relationships. Dr. Landovitz has consulting relationships with Gilead, Janssen, Roche, and Cepheus.

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

SILVER SPRING, MD – The FDA issued approval for long-acting, injectable cabotegravir (CAB-LA) on Dec. 21, providing an alternative to daily oral tenofovir disoproxil fumarate-emtricitabine (TDC-FTC) for pre-exposure prophylaxis (PrEP) against HIV acquisition.

The priority review approval was based on phase 2b-3 clinical trial data submitted to the agency this past August, after the study was stopped early due to encouraging efficacy results of the first pre-planned interim end-point analysis.

“Although TDF-FTC PrEP could be almost astoundingly effective in preventing HIV acquisition across populations and risk exposures, the adherence to the daily protocols was really challenging and difficult to attain initially and to maintain for some of our most vulnerable populations,” Raphael Landovitz, MD, MDC, lead study investigator and co-director of The Center for HIV Identification, Prevention, and Treatment Services at UCLA, Los Angeles, told this news organization.

Dr. Landovitz noted that population level benefits observed with PrEP were limited to people who were highly engaged in health care and well resourced, but the same benefits were not observed in the most vulnerable, highest-risk populations. 

“The idea was, is there anything that we can do to improve ... choices for different options, some of which – like long-acting agents – would remove the obligation to adhere to daily prescribing or a post-coital and be more discreet,” he said.
 

Data demonstrated superiority versus TDF-FTC

Details of the prospective, phase 2b-3 randomized, double-blind, double-dummy, active-controlled trial among 4,566 cisgender MSM (men who have sex with men) and transgender women highlighted the superiority of CAB 600 mg intramuscularly versus placebo or active TDF-FTC (300 mg/200 mg), with CAB-LA reducing HIV infection risk by 66%. These results were published August 11 in the New England Journal of Medicine and previously reported by this news organization.

Investigators identified HIV infections in 57 participants (including 52 who acquired HIV infections after enrollment). The hazard ratio for incident HIV infection versus TDG-FTC was 0.34, P < .001. Notably, effects were consistent across prespecified subgroups and populations. 

Additionally, integrase strand-transfer inhibitor (INSTI) resistance mutations were detected in 1 of 4 of baseline HIV infection cases among CAB participants, while 2 of 39 incident infections in TDF-FTC participants occurred despite drug concentrations indicating good PrEP adherence. 
 

Adverse events, breakthrough infections, and other important considerations

Because the trial was halted early, long-term safety data were lacking, thereby prompting investigators to launch an ongoing, open-label extension. In the initial trial, injection site reactions were reported in 81.4% (1,724) of CAB participants, most beginning a median of 1 day (IQR 0-2 days) post-injection, mild to moderate in severity (60.8% pain, 23.7% tenderness), and lasting a median of 3 days (IQR 2-6 days). In comparison, injection site reactions were reported in 31.3% of TDF-FTC participants (who, incidentally, received at least one placebo injection).

Severe adverse events (grade 3 or higher) were similar between CAB and TDF-FTC groups, They consisted mostly of an increase in creatine kinase level (14.2% with CAB vs. 13.5% with TDF-FTC) and a decrease in creatinine clearance (7.0% with CAB vs. 8.3% with TDF-FTC).

Although weight gain was higher among CAB participants (1.23 kg/year vs. 0.37 kg/year, TDF-FTC participants), most of the differences were observed during the first 40 weeks and were driven by weight loss in the TDF-FDC group. Weight changes were similar (~1 kg/year) thereafter.

Importantly, study participants assigned CAB underwent an oral-tablet, 5-week lead-in phase, which might have contributed to eventual treatment failure.

In a companion piece published Nov. 1 in the Journal of Infectious Diseases, investigators noted that adherence to the oral lead-in was poor in roughly one-third of participants with incident, breakthrough infections. They wrote that the barriers to adherence with daily oral PrEP regimens coupled with the favorable CAB-LA safety profile suggested that “the oral phase before CAB-LA initiation might not be necessary or desirable.”

The question remains as to whether or not strategies entailing viral load or other RNA screening tests at follow-up clinic visits might be warranted. 

“It’s one of the biggest sort of ‘what’s next’ questions that’s come out of this study,” Dr. Landovitz said. “We’re now testing the strategy of using viral load or RNA screening at every visit to see if, in fact, we can catch these breakthrough infections earlier and potentially avoid resistance,” he added.

Until more data are available, Dr. Landovitz said that “the guidance for the clinician would be that until you have resistance testing back on someone who breaks through cabotegravir PrEP to use a protease inhibitor-based treatment regimen, at least initially.”

Institutional changes to ensure delivery of injections, tracking, and follow-up to ensure optimal use of long-acting PrEP agents are likely to challenge already overburdened health care systems and may require additional strategies for implementation (for example, pharmacy or at-home administration). Despite these factors, CAB-LA approval is welcome news to clinicians and patients alike.

“We’re constantly searching for new drugs to expand our repertoire of what we can provide patients,” Lina Rosengren-Hovee, MD, MPH, assistant professor of medicine and infectious disease specialist at UNC Health, Chapel Hill, N.C., said in an interview. Dr. Rosengren-Hovee was not involved in the study.

“For folks under 30, the sexual and gender minority, Black, and Latino, they are the ones with the highest need for PrEP, that are in a position that places them at higher risk for HIV. Being able to offer an injectable option is ... a game changer,” she said.

Dr. Rosengren-Hovee reports no relevant financial relationships. Dr. Landovitz has consulting relationships with Gilead, Janssen, Roche, and Cepheus.

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

The ophthalmologist credited with developing botulinum toxin (Botox) for medical use has died at the age of 89, his family confirmed to National Public Radio.

Four decades ago, Alan Brown Scott, MD, a native of Berkeley, Calif., turned the drug, once a deadly poison, into a revolutionary treatment for obscure eye diseases. It later became a well-known blockbuster treatment for reducing the appearance of wrinkles and treating hyperhidrosis (excessive sweating). Other approved medical uses include treatment of overactive bladder and urinary incontinence.

According to the American Society of Plastic Surgeons, its popularity for cosmetic use was boosted further during the pandemic and it was the No. 1 minimally invasive cosmetic procedure performed in 2020. Among the 13.3 million procedures, 4.4 million involved Botox.

According to Bloomberg Businessweek, Ed Schantz, who was working in the military’s biological weapons program, was the one to first send the toxin to Dr. Scott, who wanted to explore its properties for medical use.

The same Bloomberg article also noted that the original botulinum toxin itself “is so powerful that a tiny amount can suffocate a person by paralyzing the muscles used for breathing.”

Dr. Scott was looking for a way to help his patients avoid extensive surgeries.

“Specifically, he was aiming to treat people with strabismus, or cross-eyes, and blepharospasm, which is an uncontrollable closure of eyes. Today, it’s also used as a treatment to help with migraines, hair loss, and drooling,” NPR reported.

The New York Times once described Botox as “medicine’s answer to duct tape.”

Dr. Scott was the executive director of the Smith-Kettlewell Eye Research Institute in San Francisco when he did his pioneering research with botulinum toxin in the 1970s and 1980s, according to a 2002 article in SFGate.

In 1991, Dr. Scott sold the drug to Allergan, when it was called Oculinum. The next year, the name was officially changed to Botox.

In 2002, Dr. Scott told SFGate, when asked about the more popular use for the drug, “I think that’s a charming, slightly frivolous use,” adding, “but it’s not along the lines of what I was into, applications for serious disorders.”

According to Scientific American in 2016, Dr. Scott, then age 83, kept working on the noncosmetic benefits of botulism-toxin injections for eye-related disorders at the Strabismus Research Foundation,

He told Scientific American he was proud that his efforts “are directly helpful to people.”

“There are interesting and difficult problems still to be solved, and I’m a practicing physician and I see them every day,” he said.

Dr. Scott’s daughter, Ann Scott, told NPR: “He definitely loved his work and he was also a really great father.” She said her dad involved his children in his research and work.

She added, “He was a really calm, more of a quiet reserved person,” and said he was committed to teaching his students, many of them international students.

“That was what he really loved,” she said.

Dr. Scott, who died Dec. 16, was in intensive care for the last 10 days from an unspecified illness, his daughter told NPR.

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

The ophthalmologist credited with developing botulinum toxin (Botox) for medical use has died at the age of 89, his family confirmed to National Public Radio.

Four decades ago, Alan Brown Scott, MD, a native of Berkeley, Calif., turned the drug, once a deadly poison, into a revolutionary treatment for obscure eye diseases. It later became a well-known blockbuster treatment for reducing the appearance of wrinkles and treating hyperhidrosis (excessive sweating). Other approved medical uses include treatment of overactive bladder and urinary incontinence.

According to the American Society of Plastic Surgeons, its popularity for cosmetic use was boosted further during the pandemic and it was the No. 1 minimally invasive cosmetic procedure performed in 2020. Among the 13.3 million procedures, 4.4 million involved Botox.

According to Bloomberg Businessweek, Ed Schantz, who was working in the military’s biological weapons program, was the one to first send the toxin to Dr. Scott, who wanted to explore its properties for medical use.

The same Bloomberg article also noted that the original botulinum toxin itself “is so powerful that a tiny amount can suffocate a person by paralyzing the muscles used for breathing.”

Dr. Scott was looking for a way to help his patients avoid extensive surgeries.

“Specifically, he was aiming to treat people with strabismus, or cross-eyes, and blepharospasm, which is an uncontrollable closure of eyes. Today, it’s also used as a treatment to help with migraines, hair loss, and drooling,” NPR reported.

The New York Times once described Botox as “medicine’s answer to duct tape.”

Dr. Scott was the executive director of the Smith-Kettlewell Eye Research Institute in San Francisco when he did his pioneering research with botulinum toxin in the 1970s and 1980s, according to a 2002 article in SFGate.

In 1991, Dr. Scott sold the drug to Allergan, when it was called Oculinum. The next year, the name was officially changed to Botox.

In 2002, Dr. Scott told SFGate, when asked about the more popular use for the drug, “I think that’s a charming, slightly frivolous use,” adding, “but it’s not along the lines of what I was into, applications for serious disorders.”

According to Scientific American in 2016, Dr. Scott, then age 83, kept working on the noncosmetic benefits of botulism-toxin injections for eye-related disorders at the Strabismus Research Foundation,

He told Scientific American he was proud that his efforts “are directly helpful to people.”

“There are interesting and difficult problems still to be solved, and I’m a practicing physician and I see them every day,” he said.

Dr. Scott’s daughter, Ann Scott, told NPR: “He definitely loved his work and he was also a really great father.” She said her dad involved his children in his research and work.

She added, “He was a really calm, more of a quiet reserved person,” and said he was committed to teaching his students, many of them international students.

“That was what he really loved,” she said.

Dr. Scott, who died Dec. 16, was in intensive care for the last 10 days from an unspecified illness, his daughter told NPR.

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

The ophthalmologist credited with developing botulinum toxin (Botox) for medical use has died at the age of 89, his family confirmed to National Public Radio.

Four decades ago, Alan Brown Scott, MD, a native of Berkeley, Calif., turned the drug, once a deadly poison, into a revolutionary treatment for obscure eye diseases. It later became a well-known blockbuster treatment for reducing the appearance of wrinkles and treating hyperhidrosis (excessive sweating). Other approved medical uses include treatment of overactive bladder and urinary incontinence.

According to the American Society of Plastic Surgeons, its popularity for cosmetic use was boosted further during the pandemic and it was the No. 1 minimally invasive cosmetic procedure performed in 2020. Among the 13.3 million procedures, 4.4 million involved Botox.

According to Bloomberg Businessweek, Ed Schantz, who was working in the military’s biological weapons program, was the one to first send the toxin to Dr. Scott, who wanted to explore its properties for medical use.

The same Bloomberg article also noted that the original botulinum toxin itself “is so powerful that a tiny amount can suffocate a person by paralyzing the muscles used for breathing.”

Dr. Scott was looking for a way to help his patients avoid extensive surgeries.

“Specifically, he was aiming to treat people with strabismus, or cross-eyes, and blepharospasm, which is an uncontrollable closure of eyes. Today, it’s also used as a treatment to help with migraines, hair loss, and drooling,” NPR reported.

The New York Times once described Botox as “medicine’s answer to duct tape.”

Dr. Scott was the executive director of the Smith-Kettlewell Eye Research Institute in San Francisco when he did his pioneering research with botulinum toxin in the 1970s and 1980s, according to a 2002 article in SFGate.

In 1991, Dr. Scott sold the drug to Allergan, when it was called Oculinum. The next year, the name was officially changed to Botox.

In 2002, Dr. Scott told SFGate, when asked about the more popular use for the drug, “I think that’s a charming, slightly frivolous use,” adding, “but it’s not along the lines of what I was into, applications for serious disorders.”

According to Scientific American in 2016, Dr. Scott, then age 83, kept working on the noncosmetic benefits of botulism-toxin injections for eye-related disorders at the Strabismus Research Foundation,

He told Scientific American he was proud that his efforts “are directly helpful to people.”

“There are interesting and difficult problems still to be solved, and I’m a practicing physician and I see them every day,” he said.

Dr. Scott’s daughter, Ann Scott, told NPR: “He definitely loved his work and he was also a really great father.” She said her dad involved his children in his research and work.

She added, “He was a really calm, more of a quiet reserved person,” and said he was committed to teaching his students, many of them international students.

“That was what he really loved,” she said.

Dr. Scott, who died Dec. 16, was in intensive care for the last 10 days from an unspecified illness, his daughter told NPR.

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

In HER2-positive gastric cancer, the addition of pembrolizumab (Keytruda, Merck) to trastuzumab (Herceptin, Roche) and platinum-based chemotherapy led to a significant improvement in overall response rate, according to results from the first interim analysis of the KEYNOTE-811 phase 3, randomized clinical trial.

The results of the trial, initially presented at the 2021 annual meeting of the American Society of Clinical Oncology and now published in Nature, were instrumental in the May 2021 FDA approval of pembrolizumab plus trastuzumab along with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma.

Pembrolizumab is an anti–programmed death–ligand 1 (PD-L1) antibody, which blocks a key immune escape mechanism employed by cancer cells. Trastuzumab causes an immune response that leads to HER2 internalization and cellular recycling, as well as stimulating HER2-specific T cells. Death of cancer cells from platinum-containing chemotherapy stimulates dendritic cells, which in turn promote tumor-specific T cells.

In her studies of immunotherapy and gastric cancer, lead author Yelena Janjigian, MD, chief of the gastrointestinal oncology service at Memorial Sloan Kettering Cancer Center, New York, noticed a trend in HER2-positive patients. “PD-L1 overexpression actually can occur and continue to increase while the patient is on trastuzumab as a mode of resistance,” Dr. Janjigian said in an interview.

That observation prompted the idea to combine a PD-L1 inhibitor in a phase 3 clinical trial. The results were striking. “I’ve never seen such depth of response. You could see responses as early as week 3 – after just one dose – and no one’s ever shown that before,” Dr. Janjigian said.

The new study randomized 264 patients to receive pembrolizumab or placebo in combination with trastuzumab plus fluoropyrimidine- and platinum-containing chemotherapy. In the intention-to-treat population, 81.3% of the population was male, and the primary tumor site was the stomach in 68.4%. The pembrolizumab group had a significantly higher objective response rate than the placebo group (74.4% vs. 51.9%; P = .00006).

The median decrease in lesion size was 65% in the pembrolizumab group and 49% in the placebo group. 32.3% of the pembrolizumab group had at least an 80% decrease in lesion size, versus 14.8% in the placebo group. The pembrolizumab group had more complete responses (11.3% vs. 3.1%).

The message from this is that biomarkers are critical, even if actionable ones are rare, Dr. Janjigian said. “Even though it feels like it’s only 10% or 5% of population, you start chipping away at it. How do we cure cancer? We cure it one percentage at a time through biomarker testing.”

Writing in a commentary published with the study, Myriam Chalabi, MD, a physician specializing in gastrointestinal oncology with the Netherlands Cancer Institute, Amsterdam, described the findings as “impressive in terms of the tumor responses.” But she was cautious saying data on progression-free survival and overall survival are needed to understand how well the proposed treatment would work long term.

“Given that PD-1 blockade seems to complement trastuzumab and chemotherapy for the treatment of HER2-positive gastric cancers, Janjigian and colleagues’ study has moved the field forward, and their findings could be the next, long-awaited development in the treatment of these cancers,” she wrote.

A key limitation is that the study looked at overall response rate, rather than the overall survival. The latter results should come within a year, Dr. Janjigian said.

The study was funded by Merck. Dr. Janjigian has received research funding from Merck, Rgenix, Bayer, Genentech/Roche, Bristol-Myers Squibb, and Eli Lilly, and has served on advisory boards for Rgenix, Merck Serono, Bristol-Myers Squibb, Eli Lilly, Pfizer, Bayer, Imugene, Merck Sharp & Dohme, Daiichi-Sankyo, Zymeworks, SeaGen, Basilea Pharmaceutical, and AstraZeneca. She has equity in Rgenix.

In HER2-positive gastric cancer, the addition of pembrolizumab (Keytruda, Merck) to trastuzumab (Herceptin, Roche) and platinum-based chemotherapy led to a significant improvement in overall response rate, according to results from the first interim analysis of the KEYNOTE-811 phase 3, randomized clinical trial.

The results of the trial, initially presented at the 2021 annual meeting of the American Society of Clinical Oncology and now published in Nature, were instrumental in the May 2021 FDA approval of pembrolizumab plus trastuzumab along with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma.

Pembrolizumab is an anti–programmed death–ligand 1 (PD-L1) antibody, which blocks a key immune escape mechanism employed by cancer cells. Trastuzumab causes an immune response that leads to HER2 internalization and cellular recycling, as well as stimulating HER2-specific T cells. Death of cancer cells from platinum-containing chemotherapy stimulates dendritic cells, which in turn promote tumor-specific T cells.

In her studies of immunotherapy and gastric cancer, lead author Yelena Janjigian, MD, chief of the gastrointestinal oncology service at Memorial Sloan Kettering Cancer Center, New York, noticed a trend in HER2-positive patients. “PD-L1 overexpression actually can occur and continue to increase while the patient is on trastuzumab as a mode of resistance,” Dr. Janjigian said in an interview.

That observation prompted the idea to combine a PD-L1 inhibitor in a phase 3 clinical trial. The results were striking. “I’ve never seen such depth of response. You could see responses as early as week 3 – after just one dose – and no one’s ever shown that before,” Dr. Janjigian said.

The new study randomized 264 patients to receive pembrolizumab or placebo in combination with trastuzumab plus fluoropyrimidine- and platinum-containing chemotherapy. In the intention-to-treat population, 81.3% of the population was male, and the primary tumor site was the stomach in 68.4%. The pembrolizumab group had a significantly higher objective response rate than the placebo group (74.4% vs. 51.9%; P = .00006).

The median decrease in lesion size was 65% in the pembrolizumab group and 49% in the placebo group. 32.3% of the pembrolizumab group had at least an 80% decrease in lesion size, versus 14.8% in the placebo group. The pembrolizumab group had more complete responses (11.3% vs. 3.1%).

The message from this is that biomarkers are critical, even if actionable ones are rare, Dr. Janjigian said. “Even though it feels like it’s only 10% or 5% of population, you start chipping away at it. How do we cure cancer? We cure it one percentage at a time through biomarker testing.”

Writing in a commentary published with the study, Myriam Chalabi, MD, a physician specializing in gastrointestinal oncology with the Netherlands Cancer Institute, Amsterdam, described the findings as “impressive in terms of the tumor responses.” But she was cautious saying data on progression-free survival and overall survival are needed to understand how well the proposed treatment would work long term.

“Given that PD-1 blockade seems to complement trastuzumab and chemotherapy for the treatment of HER2-positive gastric cancers, Janjigian and colleagues’ study has moved the field forward, and their findings could be the next, long-awaited development in the treatment of these cancers,” she wrote.

A key limitation is that the study looked at overall response rate, rather than the overall survival. The latter results should come within a year, Dr. Janjigian said.

The study was funded by Merck. Dr. Janjigian has received research funding from Merck, Rgenix, Bayer, Genentech/Roche, Bristol-Myers Squibb, and Eli Lilly, and has served on advisory boards for Rgenix, Merck Serono, Bristol-Myers Squibb, Eli Lilly, Pfizer, Bayer, Imugene, Merck Sharp & Dohme, Daiichi-Sankyo, Zymeworks, SeaGen, Basilea Pharmaceutical, and AstraZeneca. She has equity in Rgenix.

In HER2-positive gastric cancer, the addition of pembrolizumab (Keytruda, Merck) to trastuzumab (Herceptin, Roche) and platinum-based chemotherapy led to a significant improvement in overall response rate, according to results from the first interim analysis of the KEYNOTE-811 phase 3, randomized clinical trial.

The results of the trial, initially presented at the 2021 annual meeting of the American Society of Clinical Oncology and now published in Nature, were instrumental in the May 2021 FDA approval of pembrolizumab plus trastuzumab along with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma.

Pembrolizumab is an anti–programmed death–ligand 1 (PD-L1) antibody, which blocks a key immune escape mechanism employed by cancer cells. Trastuzumab causes an immune response that leads to HER2 internalization and cellular recycling, as well as stimulating HER2-specific T cells. Death of cancer cells from platinum-containing chemotherapy stimulates dendritic cells, which in turn promote tumor-specific T cells.

In her studies of immunotherapy and gastric cancer, lead author Yelena Janjigian, MD, chief of the gastrointestinal oncology service at Memorial Sloan Kettering Cancer Center, New York, noticed a trend in HER2-positive patients. “PD-L1 overexpression actually can occur and continue to increase while the patient is on trastuzumab as a mode of resistance,” Dr. Janjigian said in an interview.

That observation prompted the idea to combine a PD-L1 inhibitor in a phase 3 clinical trial. The results were striking. “I’ve never seen such depth of response. You could see responses as early as week 3 – after just one dose – and no one’s ever shown that before,” Dr. Janjigian said.

The new study randomized 264 patients to receive pembrolizumab or placebo in combination with trastuzumab plus fluoropyrimidine- and platinum-containing chemotherapy. In the intention-to-treat population, 81.3% of the population was male, and the primary tumor site was the stomach in 68.4%. The pembrolizumab group had a significantly higher objective response rate than the placebo group (74.4% vs. 51.9%; P = .00006).

The median decrease in lesion size was 65% in the pembrolizumab group and 49% in the placebo group. 32.3% of the pembrolizumab group had at least an 80% decrease in lesion size, versus 14.8% in the placebo group. The pembrolizumab group had more complete responses (11.3% vs. 3.1%).

The message from this is that biomarkers are critical, even if actionable ones are rare, Dr. Janjigian said. “Even though it feels like it’s only 10% or 5% of population, you start chipping away at it. How do we cure cancer? We cure it one percentage at a time through biomarker testing.”

Writing in a commentary published with the study, Myriam Chalabi, MD, a physician specializing in gastrointestinal oncology with the Netherlands Cancer Institute, Amsterdam, described the findings as “impressive in terms of the tumor responses.” But she was cautious saying data on progression-free survival and overall survival are needed to understand how well the proposed treatment would work long term.

“Given that PD-1 blockade seems to complement trastuzumab and chemotherapy for the treatment of HER2-positive gastric cancers, Janjigian and colleagues’ study has moved the field forward, and their findings could be the next, long-awaited development in the treatment of these cancers,” she wrote.

A key limitation is that the study looked at overall response rate, rather than the overall survival. The latter results should come within a year, Dr. Janjigian said.

The study was funded by Merck. Dr. Janjigian has received research funding from Merck, Rgenix, Bayer, Genentech/Roche, Bristol-Myers Squibb, and Eli Lilly, and has served on advisory boards for Rgenix, Merck Serono, Bristol-Myers Squibb, Eli Lilly, Pfizer, Bayer, Imugene, Merck Sharp & Dohme, Daiichi-Sankyo, Zymeworks, SeaGen, Basilea Pharmaceutical, and AstraZeneca. She has equity in Rgenix.

Editors at the BMJ have released an urgent request to Facebook’s Mark Zuckerberg and parent company Meta regarding a recent “fact-check” on the medical trade journal’s article about questionable Pfizer vaccine trial practices.

According to an open letter written by outgoing BMJ editor-in-chief Fiona Godlee, MD, and incoming editor-in-chief Kamran Abbasi, MD, Facebook hired a third-party contractor to evaluate the article’s findings. This resulted in “inaccurate, incompetent, and irresponsible” conclusions that “should be of concern to anyone who values and relies on sources such as the BMJ for reliable medical information.”

The article in question investigated data integrity concerns at Pfizer vaccine clinical trial sites. In September 2020, the letter states, a former employee of the research group involved in Pfizer’s main vaccine trials, Ventavia, reached out to the BMJ and “began providing ... dozens of internal company documents, photos, audio recordings, and emails.” According to the company’s website, Ventavia “played a significant part in [COVID-19 clinical trial] recruitment” and “has received recognition by Pfizer for their contribution to vaccine trials.”

It was previously reported that the whistle-blower is a former regional director who was involved in Pfizer’s vaccine trials in Texas during the fall of 2020. She alleges “the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer’s pivotal phase 3 trial.”

The images provided to the BMJ “showed needles discarded in a plastic biohazard bag instead of a sharps container box” and another displayed “vaccine packaging materials with trial participants’ identification numbers written on them left out in the open, potentially unblinding participants.”

Despite informing Ventavia, the director’s concerns went unaddressed. She then filed a complaint with the Food and Drug Administration and was subsequently fired the same day. The FDA did not investigate the director’s allegations, said Dr. Godlee and Dr. Abbasi, even though the evidence “revealed a host of poor clinical trial research practices occurring at Ventavia that could impact data integrity and patient safety.”
 

Article labeled as ‘hoax,’ without pointing out errors

The BMJ hired an investigative reporter to follow up on the clinical trial claims. The findings were published in an article on Nov. 2, 2021, after the article “went through ... the usual high-level legal and editorial oversight and peer review,” according to the journal.

However, by Nov. 10, the journal began receiving complaints from readers unable to share the article on social media. Others had their posts flagged with warnings, such as “missing context ... independent fact-checkers say this information could mislead people.” Administrators of various Facebook groups were notified that posts containing the article were “partly false.”

Readers were informed that Facebook contractor Lead Stories performed the article’s “fact check.” Lead Stories is “an award-winning innovative fact checking and debunking website” and “an active part of Facebook’s partnership with third-party fact checkers” – with the latter granting them “access to listings of content that has been flagged as potentially false by Facebook’s systems or its users.” The company said they “decide independently if we want to fact check it or not.”

Lead Stories stated that they “can enter our fact checks into a tool provided by Facebook and Facebook then uses our data to help slow down the spread of false information on its platform.” Although the contractor is compensated, Lead Stories claims they have “no say or influence over what we fact check or what our conclusions are.”

Both editors question the validity of the fact check performed by Lead Stories, as it failed to provide any “assertions of fact” as to what the BMJ got wrong. Moreover, the editors take issue with Lead Stories referring to the journal as a “news blog” and using the phrase “hoax-alert” in the URL when publishing the story on its site.

The BMJ has reached out to Lead Stories and Facebook, said the letter, but Lead Stories refuses to “change anything about their article or actions that have led to Facebook flagging our article.” Requests for Facebook to remove the “fact-checking” label and allow “readers to freely share the article on [Facebook’s] platform” have been unfruitful.

Dr. Godlee and Dr. Abbasi expressed concern that other “high quality information provider[s] have been affected by the incompetence of Meta’s fact checking regime.” In November, Instagram censored Cochrane, an international provider of independent systematic medical reviews. Instagram, also owned by Meta, prohibited users from tagging Cochrane because the organization “repeatedly posted ... false content about COVID-19 or vaccines.” Cochrane refuted the allegations.

While “fact checking has been a staple of good journalism for decades,” said the editors, Meta has “apparently delegated responsibility to people incompetent in carrying out this crucial task.” They urged the company to reconsider its fact-checking strategy and review the issues that contributed to the error.

This news organization reached out to Meta for comment but did not receive a response at press time.

Lead Stories has posted a reply (Lead Stories’ Response To BMJ Open Letter Objecting To A Lead Stories Fact Check) to the BMJ’s complaint on its website.

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

Editors at the BMJ have released an urgent request to Facebook’s Mark Zuckerberg and parent company Meta regarding a recent “fact-check” on the medical trade journal’s article about questionable Pfizer vaccine trial practices.

According to an open letter written by outgoing BMJ editor-in-chief Fiona Godlee, MD, and incoming editor-in-chief Kamran Abbasi, MD, Facebook hired a third-party contractor to evaluate the article’s findings. This resulted in “inaccurate, incompetent, and irresponsible” conclusions that “should be of concern to anyone who values and relies on sources such as the BMJ for reliable medical information.”

The article in question investigated data integrity concerns at Pfizer vaccine clinical trial sites. In September 2020, the letter states, a former employee of the research group involved in Pfizer’s main vaccine trials, Ventavia, reached out to the BMJ and “began providing ... dozens of internal company documents, photos, audio recordings, and emails.” According to the company’s website, Ventavia “played a significant part in [COVID-19 clinical trial] recruitment” and “has received recognition by Pfizer for their contribution to vaccine trials.”

It was previously reported that the whistle-blower is a former regional director who was involved in Pfizer’s vaccine trials in Texas during the fall of 2020. She alleges “the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer’s pivotal phase 3 trial.”

The images provided to the BMJ “showed needles discarded in a plastic biohazard bag instead of a sharps container box” and another displayed “vaccine packaging materials with trial participants’ identification numbers written on them left out in the open, potentially unblinding participants.”

Despite informing Ventavia, the director’s concerns went unaddressed. She then filed a complaint with the Food and Drug Administration and was subsequently fired the same day. The FDA did not investigate the director’s allegations, said Dr. Godlee and Dr. Abbasi, even though the evidence “revealed a host of poor clinical trial research practices occurring at Ventavia that could impact data integrity and patient safety.”
 

Article labeled as ‘hoax,’ without pointing out errors

The BMJ hired an investigative reporter to follow up on the clinical trial claims. The findings were published in an article on Nov. 2, 2021, after the article “went through ... the usual high-level legal and editorial oversight and peer review,” according to the journal.

However, by Nov. 10, the journal began receiving complaints from readers unable to share the article on social media. Others had their posts flagged with warnings, such as “missing context ... independent fact-checkers say this information could mislead people.” Administrators of various Facebook groups were notified that posts containing the article were “partly false.”

Readers were informed that Facebook contractor Lead Stories performed the article’s “fact check.” Lead Stories is “an award-winning innovative fact checking and debunking website” and “an active part of Facebook’s partnership with third-party fact checkers” – with the latter granting them “access to listings of content that has been flagged as potentially false by Facebook’s systems or its users.” The company said they “decide independently if we want to fact check it or not.”

Lead Stories stated that they “can enter our fact checks into a tool provided by Facebook and Facebook then uses our data to help slow down the spread of false information on its platform.” Although the contractor is compensated, Lead Stories claims they have “no say or influence over what we fact check or what our conclusions are.”

Both editors question the validity of the fact check performed by Lead Stories, as it failed to provide any “assertions of fact” as to what the BMJ got wrong. Moreover, the editors take issue with Lead Stories referring to the journal as a “news blog” and using the phrase “hoax-alert” in the URL when publishing the story on its site.

The BMJ has reached out to Lead Stories and Facebook, said the letter, but Lead Stories refuses to “change anything about their article or actions that have led to Facebook flagging our article.” Requests for Facebook to remove the “fact-checking” label and allow “readers to freely share the article on [Facebook’s] platform” have been unfruitful.

Dr. Godlee and Dr. Abbasi expressed concern that other “high quality information provider[s] have been affected by the incompetence of Meta’s fact checking regime.” In November, Instagram censored Cochrane, an international provider of independent systematic medical reviews. Instagram, also owned by Meta, prohibited users from tagging Cochrane because the organization “repeatedly posted ... false content about COVID-19 or vaccines.” Cochrane refuted the allegations.

While “fact checking has been a staple of good journalism for decades,” said the editors, Meta has “apparently delegated responsibility to people incompetent in carrying out this crucial task.” They urged the company to reconsider its fact-checking strategy and review the issues that contributed to the error.

This news organization reached out to Meta for comment but did not receive a response at press time.

Lead Stories has posted a reply (Lead Stories’ Response To BMJ Open Letter Objecting To A Lead Stories Fact Check) to the BMJ’s complaint on its website.

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

Editors at the BMJ have released an urgent request to Facebook’s Mark Zuckerberg and parent company Meta regarding a recent “fact-check” on the medical trade journal’s article about questionable Pfizer vaccine trial practices.

According to an open letter written by outgoing BMJ editor-in-chief Fiona Godlee, MD, and incoming editor-in-chief Kamran Abbasi, MD, Facebook hired a third-party contractor to evaluate the article’s findings. This resulted in “inaccurate, incompetent, and irresponsible” conclusions that “should be of concern to anyone who values and relies on sources such as the BMJ for reliable medical information.”

The article in question investigated data integrity concerns at Pfizer vaccine clinical trial sites. In September 2020, the letter states, a former employee of the research group involved in Pfizer’s main vaccine trials, Ventavia, reached out to the BMJ and “began providing ... dozens of internal company documents, photos, audio recordings, and emails.” According to the company’s website, Ventavia “played a significant part in [COVID-19 clinical trial] recruitment” and “has received recognition by Pfizer for their contribution to vaccine trials.”

It was previously reported that the whistle-blower is a former regional director who was involved in Pfizer’s vaccine trials in Texas during the fall of 2020. She alleges “the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer’s pivotal phase 3 trial.”

The images provided to the BMJ “showed needles discarded in a plastic biohazard bag instead of a sharps container box” and another displayed “vaccine packaging materials with trial participants’ identification numbers written on them left out in the open, potentially unblinding participants.”

Despite informing Ventavia, the director’s concerns went unaddressed. She then filed a complaint with the Food and Drug Administration and was subsequently fired the same day. The FDA did not investigate the director’s allegations, said Dr. Godlee and Dr. Abbasi, even though the evidence “revealed a host of poor clinical trial research practices occurring at Ventavia that could impact data integrity and patient safety.”
 

Article labeled as ‘hoax,’ without pointing out errors

The BMJ hired an investigative reporter to follow up on the clinical trial claims. The findings were published in an article on Nov. 2, 2021, after the article “went through ... the usual high-level legal and editorial oversight and peer review,” according to the journal.

However, by Nov. 10, the journal began receiving complaints from readers unable to share the article on social media. Others had their posts flagged with warnings, such as “missing context ... independent fact-checkers say this information could mislead people.” Administrators of various Facebook groups were notified that posts containing the article were “partly false.”

Readers were informed that Facebook contractor Lead Stories performed the article’s “fact check.” Lead Stories is “an award-winning innovative fact checking and debunking website” and “an active part of Facebook’s partnership with third-party fact checkers” – with the latter granting them “access to listings of content that has been flagged as potentially false by Facebook’s systems or its users.” The company said they “decide independently if we want to fact check it or not.”

Lead Stories stated that they “can enter our fact checks into a tool provided by Facebook and Facebook then uses our data to help slow down the spread of false information on its platform.” Although the contractor is compensated, Lead Stories claims they have “no say or influence over what we fact check or what our conclusions are.”

Both editors question the validity of the fact check performed by Lead Stories, as it failed to provide any “assertions of fact” as to what the BMJ got wrong. Moreover, the editors take issue with Lead Stories referring to the journal as a “news blog” and using the phrase “hoax-alert” in the URL when publishing the story on its site.

The BMJ has reached out to Lead Stories and Facebook, said the letter, but Lead Stories refuses to “change anything about their article or actions that have led to Facebook flagging our article.” Requests for Facebook to remove the “fact-checking” label and allow “readers to freely share the article on [Facebook’s] platform” have been unfruitful.

Dr. Godlee and Dr. Abbasi expressed concern that other “high quality information provider[s] have been affected by the incompetence of Meta’s fact checking regime.” In November, Instagram censored Cochrane, an international provider of independent systematic medical reviews. Instagram, also owned by Meta, prohibited users from tagging Cochrane because the organization “repeatedly posted ... false content about COVID-19 or vaccines.” Cochrane refuted the allegations.

While “fact checking has been a staple of good journalism for decades,” said the editors, Meta has “apparently delegated responsibility to people incompetent in carrying out this crucial task.” They urged the company to reconsider its fact-checking strategy and review the issues that contributed to the error.

This news organization reached out to Meta for comment but did not receive a response at press time.

Lead Stories has posted a reply (Lead Stories’ Response To BMJ Open Letter Objecting To A Lead Stories Fact Check) to the BMJ’s complaint on its website.

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