The FP used a dermatoscope to get a better look at the lesion and recognized this as a halo nevus, which is characterized by a central nevus with a halo of depigmentation around it (arrow) and sometimes depigmentation within the nevus itself.

The halo is caused when, occasionally, the body develops an immune reaction to a nevus and its melanocytes. As cytotoxic T cells target those melanocytes, there is loss of pigment to the tissue surrounding the nevus.¹

The appearance of the central nevus, rather than the hypopigmentation, determines management strategies. A globular or homogeneous pattern seen on dermoscopy is typically indicative of a benign lesion.² An atypical pigment network or other melanoma specific structures should raise your suspicions for melanoma or atypical nevus and prompt a deep shave excision sent for pathology to rule out melanoma. A nevus without suspicious features, other than the surrounding hypopigmentation, can be managed conservatively with self-monitoring and re-evaluation.

In this case, the lesion displayed a homogeneous pattern, and the FP advised the patient to self-monitor.

‌

Images and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque, NM.

The FP used a dermatoscope to get a better look at the lesion and recognized this as a halo nevus, which is characterized by a central nevus with a halo of depigmentation around it (arrow) and sometimes depigmentation within the nevus itself.

The halo is caused when, occasionally, the body develops an immune reaction to a nevus and its melanocytes. As cytotoxic T cells target those melanocytes, there is loss of pigment to the tissue surrounding the nevus.¹

The appearance of the central nevus, rather than the hypopigmentation, determines management strategies. A globular or homogeneous pattern seen on dermoscopy is typically indicative of a benign lesion.² An atypical pigment network or other melanoma specific structures should raise your suspicions for melanoma or atypical nevus and prompt a deep shave excision sent for pathology to rule out melanoma. A nevus without suspicious features, other than the surrounding hypopigmentation, can be managed conservatively with self-monitoring and re-evaluation.

In this case, the lesion displayed a homogeneous pattern, and the FP advised the patient to self-monitor.

‌

Images and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque, NM.

The FP used a dermatoscope to get a better look at the lesion and recognized this as a halo nevus, which is characterized by a central nevus with a halo of depigmentation around it (arrow) and sometimes depigmentation within the nevus itself.

The halo is caused when, occasionally, the body develops an immune reaction to a nevus and its melanocytes. As cytotoxic T cells target those melanocytes, there is loss of pigment to the tissue surrounding the nevus.¹

The appearance of the central nevus, rather than the hypopigmentation, determines management strategies. A globular or homogeneous pattern seen on dermoscopy is typically indicative of a benign lesion.² An atypical pigment network or other melanoma specific structures should raise your suspicions for melanoma or atypical nevus and prompt a deep shave excision sent for pathology to rule out melanoma. A nevus without suspicious features, other than the surrounding hypopigmentation, can be managed conservatively with self-monitoring and re-evaluation.

In this case, the lesion displayed a homogeneous pattern, and the FP advised the patient to self-monitor.

‌

Images and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque, NM.

About 20% of patients who receive tablets containing 50 mg or 100 mg of ubrogepant for the acute treatment of migraine are pain free 2 hours later, compared with 12% of patients who receive placebo, according to phase 3 trial results published Dec. 4 in the New England Journal of Medicine. In addition, about 38% of patients who receive ubrogepant no longer have their most bothersome migraine-associated symptom, such as photophobia, phonophobia, or nausea, at 2 hours, compared with 28% of patients who receive placebo, said David W. Dodick, MD, and colleagues.

Dr. Dodick, professor of neurology at the Mayo Clinic in Phoenix, and his coauthors described efficacy and safety results from the ACHIEVE I trial. Another phase 3 study of ubrogepant, ACHIEVE II, was published in JAMA in November. That trial evaluated 25- and 50-mg doses of ubrogepant versus placebo and found rates of pain freedom and absence of the most bothersome symptom in the placebo and active treatment arms that were similar to those in ACHIEVE I.

Assessing a gepant for acute migraine treatment

Ubrogepant is an oral calcitonin gene–related peptide (CGRP) receptor antagonist. Allergan, the company developing the drug, has said it expects the Food and Drug Administration to decide in December whether to approve the drug.

To compare ubrogepant 50 mg, ubrogepant 100 mg, and placebo for the acute treatment of migraine, investigators conducted the randomized ACHIEVE I trial. Researchers enrolled 1,672 adults with migraine with or without aura. They excluded patients with clinically significant cardiovascular or cerebrovascular disease. During the trial, patients treated a single migraine attack, and they had the option to take a second dose. In all, 1,436 participants took an initial dose. Patients had an average age of 40.5 years, about 88% were women, and 82% were white.

In ACHIEVE I, the most common adverse events within 48 hours of treatment were nausea, somnolence, and dry mouth, and these events occurred more frequently in the 100-mg–dose group, Dr. Dodick and colleagues reported. Among patients who received ubrogepant, serious adverse events more than 48 hours after treatment but within 30 days of treatment included appendicitis, spontaneous abortion, pericardial effusion, and seizure. No serious adverse events occurred in the placebo group.

The authors noted that, “there was no active comparator and no evaluation of consistency of effect across multiple migraine attacks; therefore it is not possible to determine whether the drug is more or less effective than standard therapies or consistently effective with repeated use.” In addition, “safety and side-effect data from this trial were based on evaluation of a single attack, and therefore safety after repeated use cannot be inferred; an extension trial has assessed the long-term safety of ubrogepant,” they said.

The present trial was performed well, commented Alan M. Rapoport, MD. “The coprimary endpoints of pain freedom and most bothersome symptom freedom, both at 2 hours after dosing, were statistically superior for both doses of ubrogepant versus placebo,” he said. “Some of the secondary endpoints, such as pain relief at 2 hours post dose and sustained pain relief from 2 to 24 hours, were statistically better than placebo.”

“Based on this data, I suspect that the FDA would approve this gepant after appropriate safety data,” said Dr. Rapoport, clinical professor of neurology at the University of California, Los Angeles and editor-in-chief of Neurology Reviews. “Many more patients need to take this drug before we can be sure it is safe and effective.”

The CGRP therapeutic landscape

“Other gepants have been shown to be effective, although some have caused a degree of liver toxicity,” said Dr. Rapoport. “Blocking the effect of CGRP on the migraine peripheral nervous system, in this case by preventing the ligand from docking at its receptor by administering an oral CGRP receptor blocker, appears to be effective.” Researchers are studying another oral gepant for similar approval, he added.

Ubrogepant stands to join other treatments targeting CGRP.

“There are currently three, and soon to be four, injectable monoclonal antibodies against CGRP functionality, which are preventive, not acute-care drugs,” Dr. Rapoport said. “The first released was a subcutaneous injection of a CGRP receptor blocker, and the other two are subcutaneous injections of CGRP ligand blockers. The last drug will be an intravenous infusion of a ligand blocker. These recently approved migraine treatments have greatly improved the lives of many of our patients, even when other preventives have failed. I expect ubrogepant and other gepants will do the same for the acute care of migraine.”

Allergan funded the trials of ubrogepant, and some of the authors are Allergan employees and stockholders. Dr. Dodick reported consulting fees and advisory board fees from Allergan and various pharmaceutical companies.

[email protected]

SOURCE: Dodick DW et al. N Engl J Med. 2019;381(23):2230-41. doi: 10.1056/NEJMoa1813049.

About 20% of patients who receive tablets containing 50 mg or 100 mg of ubrogepant for the acute treatment of migraine are pain free 2 hours later, compared with 12% of patients who receive placebo, according to phase 3 trial results published Dec. 4 in the New England Journal of Medicine. In addition, about 38% of patients who receive ubrogepant no longer have their most bothersome migraine-associated symptom, such as photophobia, phonophobia, or nausea, at 2 hours, compared with 28% of patients who receive placebo, said David W. Dodick, MD, and colleagues.

Dr. Dodick, professor of neurology at the Mayo Clinic in Phoenix, and his coauthors described efficacy and safety results from the ACHIEVE I trial. Another phase 3 study of ubrogepant, ACHIEVE II, was published in JAMA in November. That trial evaluated 25- and 50-mg doses of ubrogepant versus placebo and found rates of pain freedom and absence of the most bothersome symptom in the placebo and active treatment arms that were similar to those in ACHIEVE I.

Assessing a gepant for acute migraine treatment

Ubrogepant is an oral calcitonin gene–related peptide (CGRP) receptor antagonist. Allergan, the company developing the drug, has said it expects the Food and Drug Administration to decide in December whether to approve the drug.

To compare ubrogepant 50 mg, ubrogepant 100 mg, and placebo for the acute treatment of migraine, investigators conducted the randomized ACHIEVE I trial. Researchers enrolled 1,672 adults with migraine with or without aura. They excluded patients with clinically significant cardiovascular or cerebrovascular disease. During the trial, patients treated a single migraine attack, and they had the option to take a second dose. In all, 1,436 participants took an initial dose. Patients had an average age of 40.5 years, about 88% were women, and 82% were white.

In ACHIEVE I, the most common adverse events within 48 hours of treatment were nausea, somnolence, and dry mouth, and these events occurred more frequently in the 100-mg–dose group, Dr. Dodick and colleagues reported. Among patients who received ubrogepant, serious adverse events more than 48 hours after treatment but within 30 days of treatment included appendicitis, spontaneous abortion, pericardial effusion, and seizure. No serious adverse events occurred in the placebo group.

The authors noted that, “there was no active comparator and no evaluation of consistency of effect across multiple migraine attacks; therefore it is not possible to determine whether the drug is more or less effective than standard therapies or consistently effective with repeated use.” In addition, “safety and side-effect data from this trial were based on evaluation of a single attack, and therefore safety after repeated use cannot be inferred; an extension trial has assessed the long-term safety of ubrogepant,” they said.

The present trial was performed well, commented Alan M. Rapoport, MD. “The coprimary endpoints of pain freedom and most bothersome symptom freedom, both at 2 hours after dosing, were statistically superior for both doses of ubrogepant versus placebo,” he said. “Some of the secondary endpoints, such as pain relief at 2 hours post dose and sustained pain relief from 2 to 24 hours, were statistically better than placebo.”

“Based on this data, I suspect that the FDA would approve this gepant after appropriate safety data,” said Dr. Rapoport, clinical professor of neurology at the University of California, Los Angeles and editor-in-chief of Neurology Reviews. “Many more patients need to take this drug before we can be sure it is safe and effective.”

The CGRP therapeutic landscape

“Other gepants have been shown to be effective, although some have caused a degree of liver toxicity,” said Dr. Rapoport. “Blocking the effect of CGRP on the migraine peripheral nervous system, in this case by preventing the ligand from docking at its receptor by administering an oral CGRP receptor blocker, appears to be effective.” Researchers are studying another oral gepant for similar approval, he added.

Ubrogepant stands to join other treatments targeting CGRP.

“There are currently three, and soon to be four, injectable monoclonal antibodies against CGRP functionality, which are preventive, not acute-care drugs,” Dr. Rapoport said. “The first released was a subcutaneous injection of a CGRP receptor blocker, and the other two are subcutaneous injections of CGRP ligand blockers. The last drug will be an intravenous infusion of a ligand blocker. These recently approved migraine treatments have greatly improved the lives of many of our patients, even when other preventives have failed. I expect ubrogepant and other gepants will do the same for the acute care of migraine.”

Allergan funded the trials of ubrogepant, and some of the authors are Allergan employees and stockholders. Dr. Dodick reported consulting fees and advisory board fees from Allergan and various pharmaceutical companies.

[email protected]

SOURCE: Dodick DW et al. N Engl J Med. 2019;381(23):2230-41. doi: 10.1056/NEJMoa1813049.

About 20% of patients who receive tablets containing 50 mg or 100 mg of ubrogepant for the acute treatment of migraine are pain free 2 hours later, compared with 12% of patients who receive placebo, according to phase 3 trial results published Dec. 4 in the New England Journal of Medicine. In addition, about 38% of patients who receive ubrogepant no longer have their most bothersome migraine-associated symptom, such as photophobia, phonophobia, or nausea, at 2 hours, compared with 28% of patients who receive placebo, said David W. Dodick, MD, and colleagues.

Dr. Dodick, professor of neurology at the Mayo Clinic in Phoenix, and his coauthors described efficacy and safety results from the ACHIEVE I trial. Another phase 3 study of ubrogepant, ACHIEVE II, was published in JAMA in November. That trial evaluated 25- and 50-mg doses of ubrogepant versus placebo and found rates of pain freedom and absence of the most bothersome symptom in the placebo and active treatment arms that were similar to those in ACHIEVE I.

Assessing a gepant for acute migraine treatment

Ubrogepant is an oral calcitonin gene–related peptide (CGRP) receptor antagonist. Allergan, the company developing the drug, has said it expects the Food and Drug Administration to decide in December whether to approve the drug.

To compare ubrogepant 50 mg, ubrogepant 100 mg, and placebo for the acute treatment of migraine, investigators conducted the randomized ACHIEVE I trial. Researchers enrolled 1,672 adults with migraine with or without aura. They excluded patients with clinically significant cardiovascular or cerebrovascular disease. During the trial, patients treated a single migraine attack, and they had the option to take a second dose. In all, 1,436 participants took an initial dose. Patients had an average age of 40.5 years, about 88% were women, and 82% were white.

In ACHIEVE I, the most common adverse events within 48 hours of treatment were nausea, somnolence, and dry mouth, and these events occurred more frequently in the 100-mg–dose group, Dr. Dodick and colleagues reported. Among patients who received ubrogepant, serious adverse events more than 48 hours after treatment but within 30 days of treatment included appendicitis, spontaneous abortion, pericardial effusion, and seizure. No serious adverse events occurred in the placebo group.

The authors noted that, “there was no active comparator and no evaluation of consistency of effect across multiple migraine attacks; therefore it is not possible to determine whether the drug is more or less effective than standard therapies or consistently effective with repeated use.” In addition, “safety and side-effect data from this trial were based on evaluation of a single attack, and therefore safety after repeated use cannot be inferred; an extension trial has assessed the long-term safety of ubrogepant,” they said.

The present trial was performed well, commented Alan M. Rapoport, MD. “The coprimary endpoints of pain freedom and most bothersome symptom freedom, both at 2 hours after dosing, were statistically superior for both doses of ubrogepant versus placebo,” he said. “Some of the secondary endpoints, such as pain relief at 2 hours post dose and sustained pain relief from 2 to 24 hours, were statistically better than placebo.”

“Based on this data, I suspect that the FDA would approve this gepant after appropriate safety data,” said Dr. Rapoport, clinical professor of neurology at the University of California, Los Angeles and editor-in-chief of Neurology Reviews. “Many more patients need to take this drug before we can be sure it is safe and effective.”

The CGRP therapeutic landscape

“Other gepants have been shown to be effective, although some have caused a degree of liver toxicity,” said Dr. Rapoport. “Blocking the effect of CGRP on the migraine peripheral nervous system, in this case by preventing the ligand from docking at its receptor by administering an oral CGRP receptor blocker, appears to be effective.” Researchers are studying another oral gepant for similar approval, he added.

Ubrogepant stands to join other treatments targeting CGRP.

“There are currently three, and soon to be four, injectable monoclonal antibodies against CGRP functionality, which are preventive, not acute-care drugs,” Dr. Rapoport said. “The first released was a subcutaneous injection of a CGRP receptor blocker, and the other two are subcutaneous injections of CGRP ligand blockers. The last drug will be an intravenous infusion of a ligand blocker. These recently approved migraine treatments have greatly improved the lives of many of our patients, even when other preventives have failed. I expect ubrogepant and other gepants will do the same for the acute care of migraine.”

Allergan funded the trials of ubrogepant, and some of the authors are Allergan employees and stockholders. Dr. Dodick reported consulting fees and advisory board fees from Allergan and various pharmaceutical companies.

[email protected]

SOURCE: Dodick DW et al. N Engl J Med. 2019;381(23):2230-41. doi: 10.1056/NEJMoa1813049.

Childproof your study protocols

Childproof caps on medicine bottles. Like a bank vault lock to third-rate thieves, they’re an impregnable line of defense between inquisitive little hands and heavy-duty pharmaceuticals.

miflippo/Getty Images

So, you can imagine the delight with which parents learned that their children’s education at an Illinois elementary school included a test of their ability to spring drugs from their fortress-like bottling.

In a quest to advance scientific understanding, a junior high student recruited some of the school’s kindergartners and first graders as participants in a science fair experiment. The hypothesis: “Childproof” medicine bottles were anything but.

The junior high scientist collected data on how quickly the study subjects could defeat assorted bottles. And, being a kindly soul, the adolescent researcher demonstrated techniques for achieving a state of, ahem, pharmaceutical openness.

While teachers were present during the experiment, parental permission slips were not. As any principal or institutional review board knows, informed consent is kind of a big deal.

Surprised parents learned of the experiment only when their kids deftly demonstrated their newfound pill skills. One shocked parent even shared a video of his daughter defeating a childproof lid.

Pharmacies, of course, would remind us all that their bottles are at best “child resistant,” not childproof. It’s a distinction lost on us here at the Bureau of LOTME, however. We’re desperately viewing that how-to video for tips on liberating our statins from the “child resistant” bottle our millennial pharmacist clearly superglued the cap onto.

What’s the deal with airline food?

You probably thought Jerry Seinfeld’s immortal query was rhetorical. No one actually knows what the deal is with airline food, right?

ThamKC/Getty Images

Enter Charles Platkin, PhD, JD, MPH, executive director of the Hunter College NYC Food Policy Center, and editor of DietDetective.com. Not only does he know the deal, he publishes a study detailing the healthiness of the food offered by 11 airlines every year, based on criteria such as healthy nutrients and calorie levels of meals, level of transparency, improvement and maintenance of healthy offerings, and water health.

For the 2018-2019 edition, there’s a tie at the top between Alaska Airlines and Air Canada, both scoring 4 out of 5 on Dr. Platkin’s “Health Score,” both well ahead of Delta and JetBlue in second place with a score of 2.9.

At the bottom? Southwest Airlines, with a paltry 1.7, edging out Spirit and Hawaiian Airlines.

Our personal favorite tidbit from the study has to be the poor scores in water health. Spirit managed to score a measly 1 out of 5 in the water health subscore, and several airlines were below 2. An actual quote from the study: “The quality of drinking water varies by airline, and many have provided passengers with unhealthy water. In general, it’s probably best to avoid drinking coffee and tea on board since they are made with galley water.”

While Hawaiian can take some comfort because they didn’t finish dead last, Dr. Platkin did award them his special “Shame on You” award for not providing all their nutritional information. You can try to hide, Hawaiian Airlines, but Dr. Platkin will find you.

Use the Force, Jack Nicklaus

We here at LOTME usually strive to provide an insightful and up-to-date wrap-up of the latest news on cutting-edge research, clinical breakthroughs, and impolite bodily functions. But right now, we want to talk about something really important: your golf game.

jacoblund/Getty Images

There’s an old saying in golf: Drive for show, putt for dough. That cliché may need a bit of updating, though, now that investigators in Ireland (where they are pretty serious about their golf) have brought science to the party.

Their research indicates that it may be possible for golfers to improve their putting without practicing. Without physically practicing, that is. Without going to the golf course. Just think about it: Golfers can putt better by, you know … just thinking about it.

Imagining the feel of an action without actually performing it is known as kinesthetic imagery ability, and it just might have an effect on putting, researchers from the physical education and sports sciences department at the University of Limerick and Lero, the Science Foundation Ireland Research Centre for Software, reported in Psychology of Sport and Exercise.

In a group of 44 skilled golfers, half watched video of an expert golfer putting in a lab environment “while listening to a motor imagery script consisting of short sentences describing key visual and kinesthetic feelings associated with performing the putting.” Then all the golfers took 40 putts from 15 feet in the lab.

The good kinesthetic imagers in the bunch improved their putting consistency more than subjects with poorer kinesthetic imagery ability and subjects from the nonintervention group.

So, here’s the new and improved old saying for golfers: Drive for show, use your kinesthetic imagery ability for dough. Yup, that’ll definitely catch on.

Childproof your study protocols

Childproof caps on medicine bottles. Like a bank vault lock to third-rate thieves, they’re an impregnable line of defense between inquisitive little hands and heavy-duty pharmaceuticals.

miflippo/Getty Images

So, you can imagine the delight with which parents learned that their children’s education at an Illinois elementary school included a test of their ability to spring drugs from their fortress-like bottling.

In a quest to advance scientific understanding, a junior high student recruited some of the school’s kindergartners and first graders as participants in a science fair experiment. The hypothesis: “Childproof” medicine bottles were anything but.

The junior high scientist collected data on how quickly the study subjects could defeat assorted bottles. And, being a kindly soul, the adolescent researcher demonstrated techniques for achieving a state of, ahem, pharmaceutical openness.

While teachers were present during the experiment, parental permission slips were not. As any principal or institutional review board knows, informed consent is kind of a big deal.

Surprised parents learned of the experiment only when their kids deftly demonstrated their newfound pill skills. One shocked parent even shared a video of his daughter defeating a childproof lid.

Pharmacies, of course, would remind us all that their bottles are at best “child resistant,” not childproof. It’s a distinction lost on us here at the Bureau of LOTME, however. We’re desperately viewing that how-to video for tips on liberating our statins from the “child resistant” bottle our millennial pharmacist clearly superglued the cap onto.

What’s the deal with airline food?

You probably thought Jerry Seinfeld’s immortal query was rhetorical. No one actually knows what the deal is with airline food, right?

ThamKC/Getty Images

Enter Charles Platkin, PhD, JD, MPH, executive director of the Hunter College NYC Food Policy Center, and editor of DietDetective.com. Not only does he know the deal, he publishes a study detailing the healthiness of the food offered by 11 airlines every year, based on criteria such as healthy nutrients and calorie levels of meals, level of transparency, improvement and maintenance of healthy offerings, and water health.

For the 2018-2019 edition, there’s a tie at the top between Alaska Airlines and Air Canada, both scoring 4 out of 5 on Dr. Platkin’s “Health Score,” both well ahead of Delta and JetBlue in second place with a score of 2.9.

At the bottom? Southwest Airlines, with a paltry 1.7, edging out Spirit and Hawaiian Airlines.

Our personal favorite tidbit from the study has to be the poor scores in water health. Spirit managed to score a measly 1 out of 5 in the water health subscore, and several airlines were below 2. An actual quote from the study: “The quality of drinking water varies by airline, and many have provided passengers with unhealthy water. In general, it’s probably best to avoid drinking coffee and tea on board since they are made with galley water.”

While Hawaiian can take some comfort because they didn’t finish dead last, Dr. Platkin did award them his special “Shame on You” award for not providing all their nutritional information. You can try to hide, Hawaiian Airlines, but Dr. Platkin will find you.

Use the Force, Jack Nicklaus

We here at LOTME usually strive to provide an insightful and up-to-date wrap-up of the latest news on cutting-edge research, clinical breakthroughs, and impolite bodily functions. But right now, we want to talk about something really important: your golf game.

jacoblund/Getty Images

There’s an old saying in golf: Drive for show, putt for dough. That cliché may need a bit of updating, though, now that investigators in Ireland (where they are pretty serious about their golf) have brought science to the party.

Their research indicates that it may be possible for golfers to improve their putting without practicing. Without physically practicing, that is. Without going to the golf course. Just think about it: Golfers can putt better by, you know … just thinking about it.

Imagining the feel of an action without actually performing it is known as kinesthetic imagery ability, and it just might have an effect on putting, researchers from the physical education and sports sciences department at the University of Limerick and Lero, the Science Foundation Ireland Research Centre for Software, reported in Psychology of Sport and Exercise.

In a group of 44 skilled golfers, half watched video of an expert golfer putting in a lab environment “while listening to a motor imagery script consisting of short sentences describing key visual and kinesthetic feelings associated with performing the putting.” Then all the golfers took 40 putts from 15 feet in the lab.

The good kinesthetic imagers in the bunch improved their putting consistency more than subjects with poorer kinesthetic imagery ability and subjects from the nonintervention group.

So, here’s the new and improved old saying for golfers: Drive for show, use your kinesthetic imagery ability for dough. Yup, that’ll definitely catch on.

Childproof your study protocols

Childproof caps on medicine bottles. Like a bank vault lock to third-rate thieves, they’re an impregnable line of defense between inquisitive little hands and heavy-duty pharmaceuticals.

miflippo/Getty Images

So, you can imagine the delight with which parents learned that their children’s education at an Illinois elementary school included a test of their ability to spring drugs from their fortress-like bottling.

In a quest to advance scientific understanding, a junior high student recruited some of the school’s kindergartners and first graders as participants in a science fair experiment. The hypothesis: “Childproof” medicine bottles were anything but.

The junior high scientist collected data on how quickly the study subjects could defeat assorted bottles. And, being a kindly soul, the adolescent researcher demonstrated techniques for achieving a state of, ahem, pharmaceutical openness.

While teachers were present during the experiment, parental permission slips were not. As any principal or institutional review board knows, informed consent is kind of a big deal.

Surprised parents learned of the experiment only when their kids deftly demonstrated their newfound pill skills. One shocked parent even shared a video of his daughter defeating a childproof lid.

Pharmacies, of course, would remind us all that their bottles are at best “child resistant,” not childproof. It’s a distinction lost on us here at the Bureau of LOTME, however. We’re desperately viewing that how-to video for tips on liberating our statins from the “child resistant” bottle our millennial pharmacist clearly superglued the cap onto.

What’s the deal with airline food?

You probably thought Jerry Seinfeld’s immortal query was rhetorical. No one actually knows what the deal is with airline food, right?

ThamKC/Getty Images

Enter Charles Platkin, PhD, JD, MPH, executive director of the Hunter College NYC Food Policy Center, and editor of DietDetective.com. Not only does he know the deal, he publishes a study detailing the healthiness of the food offered by 11 airlines every year, based on criteria such as healthy nutrients and calorie levels of meals, level of transparency, improvement and maintenance of healthy offerings, and water health.

For the 2018-2019 edition, there’s a tie at the top between Alaska Airlines and Air Canada, both scoring 4 out of 5 on Dr. Platkin’s “Health Score,” both well ahead of Delta and JetBlue in second place with a score of 2.9.

At the bottom? Southwest Airlines, with a paltry 1.7, edging out Spirit and Hawaiian Airlines.

Our personal favorite tidbit from the study has to be the poor scores in water health. Spirit managed to score a measly 1 out of 5 in the water health subscore, and several airlines were below 2. An actual quote from the study: “The quality of drinking water varies by airline, and many have provided passengers with unhealthy water. In general, it’s probably best to avoid drinking coffee and tea on board since they are made with galley water.”

While Hawaiian can take some comfort because they didn’t finish dead last, Dr. Platkin did award them his special “Shame on You” award for not providing all their nutritional information. You can try to hide, Hawaiian Airlines, but Dr. Platkin will find you.

Use the Force, Jack Nicklaus

We here at LOTME usually strive to provide an insightful and up-to-date wrap-up of the latest news on cutting-edge research, clinical breakthroughs, and impolite bodily functions. But right now, we want to talk about something really important: your golf game.

jacoblund/Getty Images

There’s an old saying in golf: Drive for show, putt for dough. That cliché may need a bit of updating, though, now that investigators in Ireland (where they are pretty serious about their golf) have brought science to the party.

Their research indicates that it may be possible for golfers to improve their putting without practicing. Without physically practicing, that is. Without going to the golf course. Just think about it: Golfers can putt better by, you know … just thinking about it.

Imagining the feel of an action without actually performing it is known as kinesthetic imagery ability, and it just might have an effect on putting, researchers from the physical education and sports sciences department at the University of Limerick and Lero, the Science Foundation Ireland Research Centre for Software, reported in Psychology of Sport and Exercise.

In a group of 44 skilled golfers, half watched video of an expert golfer putting in a lab environment “while listening to a motor imagery script consisting of short sentences describing key visual and kinesthetic feelings associated with performing the putting.” Then all the golfers took 40 putts from 15 feet in the lab.

The good kinesthetic imagers in the bunch improved their putting consistency more than subjects with poorer kinesthetic imagery ability and subjects from the nonintervention group.

So, here’s the new and improved old saying for golfers: Drive for show, use your kinesthetic imagery ability for dough. Yup, that’ll definitely catch on.

Whether patients aged 50 years and older with a displaced femoral neck fracture underwent total hip arthroplasty or hemiarthroplasty had no significant influence on the risk of unplanned secondary hip procedures over 2 years of follow-up. In addition, while functional outcomes modestly favored total hip arthroplasty, the rates of mortality and serious adverse events were similar between the two treatment groups.

Those are key findings from a randomized, multicenter trial of the two procedures that was carried out in 10 countries.

“The American Academy of Orthopedic Surgeons and National Institute for Health and Care Excellence guidelines recommend total hip arthroplasty in all patients with displaced femoral neck fractures who are able to ambulate independently,” a team of investigators led by Mohit Bhandari, MD, and P.J. Devereaux, MD, both from McMaster University, Hamilton, Ont., wrote in a study published in the New England Journal of Medicine. “Our findings suggest that the advantages of total hip arthroplasty may not be compelling. The limited advantages of total hip arthroplasty, as well as the possible higher risk of complications, may be particularly important in regions of the world where total hip arthroplasty is not easily accessible or is cost prohibitive.”

In the Hip Fracture Evaluation With Alternative of Total Hip Arthroplasty Versus Hemiarthroplasty (HEALTH) trial, the researchers randomly assigned 1,495 patients aged 50 years and older who had a displaced femoral neck fracture to undergo either total hip arthroplasty or hemiarthroplasty. They were eligible for the trial only if they had been able to ambulate without the assistance of another person before the hip fracture occurred. The primary endpoint was any unplanned secondary hip procedure within 24 months after the initial surgery. Secondary endpoints included death, serious adverse events, hip-related complications, health-related quality of life, function, and overall health measures. Assessments included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score, pain score, stiffness score, and function score; the European Quality of Life–5 Dimensions utility index score and visual analogue scale; the 12-Item Short Form General Health Survey physical and mental component summary scores; and the Timed Up and Go scores.

The researchers found that the primary endpoint occurred in 7.9% of patients who had been randomly assigned to total hip arthroplasty and in 8.3% of those who had been randomly assigned to hemiarthroplasty (hazard ratio, 0.95; P = .79). As for secondary endpoints, mortality did not differ significantly between the two treatment groups (14.3% in the total hip arthroplasty group vs. 13.1% in the hemiarthroplasty group; P = .48), while serious adverse events occurred in 41.8% of patients in the total hip arthroplasty group versus 36.7% of those in the hemiarthroplasty group (HR, 1.16; P = .13).

In other findings, hip instability or dislocation occurred in 4.7% of patients who were assigned to total hip arthroplasty, compared with 2.4% of those who were assigned to hemiarthroplasty (HR, 2.00), while patients who underwent total hip arthroplasty had superior function as measured by the WOMAC total score, pain score, stiffness score, and function score. “These differences between the treatment groups fell below the threshold for a minimal clinically important difference for WOMAC,” the researchers wrote.

They acknowledged certain limitations of the study, including the fact that patients and endpoint assessors were unblinded in the assessments of function, “which left a possibility of bias.” In addition, 14.9% of patients were lost to follow-up for analysis of the primary endpoint.

In an accompanying editorial, Jan-Erik Gjertsen, MD, wrote that one implication of the HEALTH trial is that hemiarthroplasty may provide a satisfactory results for the majority of elderly patients with hip fractures. “Considering the nearly equal risk of secondary surgical procedures and the modest benefit in functional outcome, should we abandon the use of total hip arthroplasty in the treatment of hip fractures?” asked Dr. Gjertsen, of the department of orthopedic surgery at Haukeland University Hospital in Bergen, Norway (N Engl J Med. 2019 Dec 4. doi:10.1056/NEJMe1913800). “Even if the benefits seem smaller than we previously thought, patients with high physical demands and a long remaining life expectancy should probably still be considered for treatment with total hip arthroplasty. Yet the expected remaining lifetime of those patients who potentially could benefit most from a total hip arthroplasty is much longer than the 2-year follow-up period used in the HEALTH trial. However, the number of secondary procedures after hemiarthroplasty may increase with longer follow-up. Therefore, one hopes that the HEALTH investigators will be able to provide long-term results from their trial in the future.”

The HEALTH trial was supported by grants from the Canadian Institutes of Health, the National Institutes of Health, ZorgOnderzoek Nederland/Medische Wetenschappen, the Sophies Minde Foundation for Orthopedic Research, McMaster Surgical Associates, and Stryker Orthopedics. Dr. Bhandari reported receiving grant support and lecture fees from Sanofi, lecture fees from Pendopharm, and grant support from Acumed and Aphria. Dr. Devereaux reported receiving grant support from Abbott Diagnostics, Boehringer Ingelheim, Philips Healthcare, Roche Diagnostics, and Siemens.

[email protected]

SOURCE: Bhandari M et al. N Engl J Med. 2019 Dec 4. doi: 10.1056/NEJMoa1906190.

Whether patients aged 50 years and older with a displaced femoral neck fracture underwent total hip arthroplasty or hemiarthroplasty had no significant influence on the risk of unplanned secondary hip procedures over 2 years of follow-up. In addition, while functional outcomes modestly favored total hip arthroplasty, the rates of mortality and serious adverse events were similar between the two treatment groups.

Those are key findings from a randomized, multicenter trial of the two procedures that was carried out in 10 countries.

“The American Academy of Orthopedic Surgeons and National Institute for Health and Care Excellence guidelines recommend total hip arthroplasty in all patients with displaced femoral neck fractures who are able to ambulate independently,” a team of investigators led by Mohit Bhandari, MD, and P.J. Devereaux, MD, both from McMaster University, Hamilton, Ont., wrote in a study published in the New England Journal of Medicine. “Our findings suggest that the advantages of total hip arthroplasty may not be compelling. The limited advantages of total hip arthroplasty, as well as the possible higher risk of complications, may be particularly important in regions of the world where total hip arthroplasty is not easily accessible or is cost prohibitive.”

In the Hip Fracture Evaluation With Alternative of Total Hip Arthroplasty Versus Hemiarthroplasty (HEALTH) trial, the researchers randomly assigned 1,495 patients aged 50 years and older who had a displaced femoral neck fracture to undergo either total hip arthroplasty or hemiarthroplasty. They were eligible for the trial only if they had been able to ambulate without the assistance of another person before the hip fracture occurred. The primary endpoint was any unplanned secondary hip procedure within 24 months after the initial surgery. Secondary endpoints included death, serious adverse events, hip-related complications, health-related quality of life, function, and overall health measures. Assessments included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score, pain score, stiffness score, and function score; the European Quality of Life–5 Dimensions utility index score and visual analogue scale; the 12-Item Short Form General Health Survey physical and mental component summary scores; and the Timed Up and Go scores.

The researchers found that the primary endpoint occurred in 7.9% of patients who had been randomly assigned to total hip arthroplasty and in 8.3% of those who had been randomly assigned to hemiarthroplasty (hazard ratio, 0.95; P = .79). As for secondary endpoints, mortality did not differ significantly between the two treatment groups (14.3% in the total hip arthroplasty group vs. 13.1% in the hemiarthroplasty group; P = .48), while serious adverse events occurred in 41.8% of patients in the total hip arthroplasty group versus 36.7% of those in the hemiarthroplasty group (HR, 1.16; P = .13).

In other findings, hip instability or dislocation occurred in 4.7% of patients who were assigned to total hip arthroplasty, compared with 2.4% of those who were assigned to hemiarthroplasty (HR, 2.00), while patients who underwent total hip arthroplasty had superior function as measured by the WOMAC total score, pain score, stiffness score, and function score. “These differences between the treatment groups fell below the threshold for a minimal clinically important difference for WOMAC,” the researchers wrote.

They acknowledged certain limitations of the study, including the fact that patients and endpoint assessors were unblinded in the assessments of function, “which left a possibility of bias.” In addition, 14.9% of patients were lost to follow-up for analysis of the primary endpoint.

In an accompanying editorial, Jan-Erik Gjertsen, MD, wrote that one implication of the HEALTH trial is that hemiarthroplasty may provide a satisfactory results for the majority of elderly patients with hip fractures. “Considering the nearly equal risk of secondary surgical procedures and the modest benefit in functional outcome, should we abandon the use of total hip arthroplasty in the treatment of hip fractures?” asked Dr. Gjertsen, of the department of orthopedic surgery at Haukeland University Hospital in Bergen, Norway (N Engl J Med. 2019 Dec 4. doi:10.1056/NEJMe1913800). “Even if the benefits seem smaller than we previously thought, patients with high physical demands and a long remaining life expectancy should probably still be considered for treatment with total hip arthroplasty. Yet the expected remaining lifetime of those patients who potentially could benefit most from a total hip arthroplasty is much longer than the 2-year follow-up period used in the HEALTH trial. However, the number of secondary procedures after hemiarthroplasty may increase with longer follow-up. Therefore, one hopes that the HEALTH investigators will be able to provide long-term results from their trial in the future.”

The HEALTH trial was supported by grants from the Canadian Institutes of Health, the National Institutes of Health, ZorgOnderzoek Nederland/Medische Wetenschappen, the Sophies Minde Foundation for Orthopedic Research, McMaster Surgical Associates, and Stryker Orthopedics. Dr. Bhandari reported receiving grant support and lecture fees from Sanofi, lecture fees from Pendopharm, and grant support from Acumed and Aphria. Dr. Devereaux reported receiving grant support from Abbott Diagnostics, Boehringer Ingelheim, Philips Healthcare, Roche Diagnostics, and Siemens.

[email protected]

SOURCE: Bhandari M et al. N Engl J Med. 2019 Dec 4. doi: 10.1056/NEJMoa1906190.

Whether patients aged 50 years and older with a displaced femoral neck fracture underwent total hip arthroplasty or hemiarthroplasty had no significant influence on the risk of unplanned secondary hip procedures over 2 years of follow-up. In addition, while functional outcomes modestly favored total hip arthroplasty, the rates of mortality and serious adverse events were similar between the two treatment groups.

Those are key findings from a randomized, multicenter trial of the two procedures that was carried out in 10 countries.

“The American Academy of Orthopedic Surgeons and National Institute for Health and Care Excellence guidelines recommend total hip arthroplasty in all patients with displaced femoral neck fractures who are able to ambulate independently,” a team of investigators led by Mohit Bhandari, MD, and P.J. Devereaux, MD, both from McMaster University, Hamilton, Ont., wrote in a study published in the New England Journal of Medicine. “Our findings suggest that the advantages of total hip arthroplasty may not be compelling. The limited advantages of total hip arthroplasty, as well as the possible higher risk of complications, may be particularly important in regions of the world where total hip arthroplasty is not easily accessible or is cost prohibitive.”

In the Hip Fracture Evaluation With Alternative of Total Hip Arthroplasty Versus Hemiarthroplasty (HEALTH) trial, the researchers randomly assigned 1,495 patients aged 50 years and older who had a displaced femoral neck fracture to undergo either total hip arthroplasty or hemiarthroplasty. They were eligible for the trial only if they had been able to ambulate without the assistance of another person before the hip fracture occurred. The primary endpoint was any unplanned secondary hip procedure within 24 months after the initial surgery. Secondary endpoints included death, serious adverse events, hip-related complications, health-related quality of life, function, and overall health measures. Assessments included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score, pain score, stiffness score, and function score; the European Quality of Life–5 Dimensions utility index score and visual analogue scale; the 12-Item Short Form General Health Survey physical and mental component summary scores; and the Timed Up and Go scores.

The researchers found that the primary endpoint occurred in 7.9% of patients who had been randomly assigned to total hip arthroplasty and in 8.3% of those who had been randomly assigned to hemiarthroplasty (hazard ratio, 0.95; P = .79). As for secondary endpoints, mortality did not differ significantly between the two treatment groups (14.3% in the total hip arthroplasty group vs. 13.1% in the hemiarthroplasty group; P = .48), while serious adverse events occurred in 41.8% of patients in the total hip arthroplasty group versus 36.7% of those in the hemiarthroplasty group (HR, 1.16; P = .13).

In other findings, hip instability or dislocation occurred in 4.7% of patients who were assigned to total hip arthroplasty, compared with 2.4% of those who were assigned to hemiarthroplasty (HR, 2.00), while patients who underwent total hip arthroplasty had superior function as measured by the WOMAC total score, pain score, stiffness score, and function score. “These differences between the treatment groups fell below the threshold for a minimal clinically important difference for WOMAC,” the researchers wrote.

They acknowledged certain limitations of the study, including the fact that patients and endpoint assessors were unblinded in the assessments of function, “which left a possibility of bias.” In addition, 14.9% of patients were lost to follow-up for analysis of the primary endpoint.

In an accompanying editorial, Jan-Erik Gjertsen, MD, wrote that one implication of the HEALTH trial is that hemiarthroplasty may provide a satisfactory results for the majority of elderly patients with hip fractures. “Considering the nearly equal risk of secondary surgical procedures and the modest benefit in functional outcome, should we abandon the use of total hip arthroplasty in the treatment of hip fractures?” asked Dr. Gjertsen, of the department of orthopedic surgery at Haukeland University Hospital in Bergen, Norway (N Engl J Med. 2019 Dec 4. doi:10.1056/NEJMe1913800). “Even if the benefits seem smaller than we previously thought, patients with high physical demands and a long remaining life expectancy should probably still be considered for treatment with total hip arthroplasty. Yet the expected remaining lifetime of those patients who potentially could benefit most from a total hip arthroplasty is much longer than the 2-year follow-up period used in the HEALTH trial. However, the number of secondary procedures after hemiarthroplasty may increase with longer follow-up. Therefore, one hopes that the HEALTH investigators will be able to provide long-term results from their trial in the future.”

The HEALTH trial was supported by grants from the Canadian Institutes of Health, the National Institutes of Health, ZorgOnderzoek Nederland/Medische Wetenschappen, the Sophies Minde Foundation for Orthopedic Research, McMaster Surgical Associates, and Stryker Orthopedics. Dr. Bhandari reported receiving grant support and lecture fees from Sanofi, lecture fees from Pendopharm, and grant support from Acumed and Aphria. Dr. Devereaux reported receiving grant support from Abbott Diagnostics, Boehringer Ingelheim, Philips Healthcare, Roche Diagnostics, and Siemens.

[email protected]

SOURCE: Bhandari M et al. N Engl J Med. 2019 Dec 4. doi: 10.1056/NEJMoa1906190.

Mitchel L. Zoler’s article on Abstract A105, presented at Obesity Week 2019, addresses an important health concern and is timely.

Over the past 4 decades we have seen a rise in the prevalence of obesity and associated health complications, not just in the United States but across the world. The incidence of obesity (having a BMI greater than 30) was 35% for women and 31% for men in the United States, and associated deaths and disability were primarily attributed to diabetes and cardiovascular disease resulting from obesity.

This article references the benefits of bariatric/metabolic surgery in individuals with class 1 obesity. In the United States, more than half of those who meet the criteria for obesity come under the class 1 category (BMI, 30-34.9). Those in this class of obesity are at increased risk of developing diabetes, hypertension, hyperlipidemia, coronary artery disease, cerebrovascular disease, obstructive sleep apnea, polycystic ovarian syndrome, and bone and joint disorders.

There are several studies that document the significant reduction in incidence of the above cardiometabolic risks with sustained weight loss. Nonsurgical interventions in individuals with class 1 obesity through lifestyle modifications and pharmacotherapy have not demonstrated success in providing persistent weight loss or metabolic benefits. The data presented in this article are of great significance to patients and physicians alike as they highlight the long-term benefits and reversal of metabolic disorders.

Current guidelines for bariatric surgery for individuals with a BMI greater than 35 were published in 1991. Since then several safe surgical options including laparoscopic procedures, sleeve gastrectomy, and adjustable gastric banding have been developed with decreased surgical risks, morbidity, and mortality.

The International Federation for the Surgery of Obesity and Metabolic Disorders, the International Diabetes Federation, and the National Institute for Health and Care Excellence of the United Kingdom, have supported the option of bariatric surgery in class 1 obese individuals with metabolic disorders.

While lifestyle modifications with medications should be the first-line treatment for class 1 obesity, as a primary care physician I believe that, given the major changes in the surgical options, the proven long-term benefits, and the rising incidences of obesity and metabolic syndrome, it is time for the health care community, insurers, patients, and all other stakeholders to consider bariatric surgery in class 1 obese individuals as a potential and viable option.

Noel N. Deep, MD, is a general internist in a multispecialty group practice with Aspirus Antigo (Wis.) Clinic and the chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo. He is also assistant clinical professor at the Medical College of Wisconsin, Central Wisconsin Campus, Wausau, and the governor of the Wisconsin chapter of the American College of Physicians. Dr. Deep serves on the editorial advisory board of Internal Medicine News.

He made these comments in response to questions from MDedge and had no relevant disclosures.

Mitchel L. Zoler’s article on Abstract A105, presented at Obesity Week 2019, addresses an important health concern and is timely.

Over the past 4 decades we have seen a rise in the prevalence of obesity and associated health complications, not just in the United States but across the world. The incidence of obesity (having a BMI greater than 30) was 35% for women and 31% for men in the United States, and associated deaths and disability were primarily attributed to diabetes and cardiovascular disease resulting from obesity.

This article references the benefits of bariatric/metabolic surgery in individuals with class 1 obesity. In the United States, more than half of those who meet the criteria for obesity come under the class 1 category (BMI, 30-34.9). Those in this class of obesity are at increased risk of developing diabetes, hypertension, hyperlipidemia, coronary artery disease, cerebrovascular disease, obstructive sleep apnea, polycystic ovarian syndrome, and bone and joint disorders.

There are several studies that document the significant reduction in incidence of the above cardiometabolic risks with sustained weight loss. Nonsurgical interventions in individuals with class 1 obesity through lifestyle modifications and pharmacotherapy have not demonstrated success in providing persistent weight loss or metabolic benefits. The data presented in this article are of great significance to patients and physicians alike as they highlight the long-term benefits and reversal of metabolic disorders.

Current guidelines for bariatric surgery for individuals with a BMI greater than 35 were published in 1991. Since then several safe surgical options including laparoscopic procedures, sleeve gastrectomy, and adjustable gastric banding have been developed with decreased surgical risks, morbidity, and mortality.

The International Federation for the Surgery of Obesity and Metabolic Disorders, the International Diabetes Federation, and the National Institute for Health and Care Excellence of the United Kingdom, have supported the option of bariatric surgery in class 1 obese individuals with metabolic disorders.

While lifestyle modifications with medications should be the first-line treatment for class 1 obesity, as a primary care physician I believe that, given the major changes in the surgical options, the proven long-term benefits, and the rising incidences of obesity and metabolic syndrome, it is time for the health care community, insurers, patients, and all other stakeholders to consider bariatric surgery in class 1 obese individuals as a potential and viable option.

Noel N. Deep, MD, is a general internist in a multispecialty group practice with Aspirus Antigo (Wis.) Clinic and the chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo. He is also assistant clinical professor at the Medical College of Wisconsin, Central Wisconsin Campus, Wausau, and the governor of the Wisconsin chapter of the American College of Physicians. Dr. Deep serves on the editorial advisory board of Internal Medicine News.

He made these comments in response to questions from MDedge and had no relevant disclosures.

Mitchel L. Zoler’s article on Abstract A105, presented at Obesity Week 2019, addresses an important health concern and is timely.

Over the past 4 decades we have seen a rise in the prevalence of obesity and associated health complications, not just in the United States but across the world. The incidence of obesity (having a BMI greater than 30) was 35% for women and 31% for men in the United States, and associated deaths and disability were primarily attributed to diabetes and cardiovascular disease resulting from obesity.

This article references the benefits of bariatric/metabolic surgery in individuals with class 1 obesity. In the United States, more than half of those who meet the criteria for obesity come under the class 1 category (BMI, 30-34.9). Those in this class of obesity are at increased risk of developing diabetes, hypertension, hyperlipidemia, coronary artery disease, cerebrovascular disease, obstructive sleep apnea, polycystic ovarian syndrome, and bone and joint disorders.

There are several studies that document the significant reduction in incidence of the above cardiometabolic risks with sustained weight loss. Nonsurgical interventions in individuals with class 1 obesity through lifestyle modifications and pharmacotherapy have not demonstrated success in providing persistent weight loss or metabolic benefits. The data presented in this article are of great significance to patients and physicians alike as they highlight the long-term benefits and reversal of metabolic disorders.

Current guidelines for bariatric surgery for individuals with a BMI greater than 35 were published in 1991. Since then several safe surgical options including laparoscopic procedures, sleeve gastrectomy, and adjustable gastric banding have been developed with decreased surgical risks, morbidity, and mortality.

The International Federation for the Surgery of Obesity and Metabolic Disorders, the International Diabetes Federation, and the National Institute for Health and Care Excellence of the United Kingdom, have supported the option of bariatric surgery in class 1 obese individuals with metabolic disorders.

While lifestyle modifications with medications should be the first-line treatment for class 1 obesity, as a primary care physician I believe that, given the major changes in the surgical options, the proven long-term benefits, and the rising incidences of obesity and metabolic syndrome, it is time for the health care community, insurers, patients, and all other stakeholders to consider bariatric surgery in class 1 obese individuals as a potential and viable option.

Noel N. Deep, MD, is a general internist in a multispecialty group practice with Aspirus Antigo (Wis.) Clinic and the chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo. He is also assistant clinical professor at the Medical College of Wisconsin, Central Wisconsin Campus, Wausau, and the governor of the Wisconsin chapter of the American College of Physicians. Dr. Deep serves on the editorial advisory board of Internal Medicine News.

He made these comments in response to questions from MDedge and had no relevant disclosures.

Preterm birth (PTB) remains a significant public health concern and a major cause of newborn morbidity and mortality. In the United States, 1 in 10 babies are born preterm (< 37 weeks), and this rate has changed little in 30 years.¹ 

In 2011, the US Food and Drug Administration (FDA) approved progesterone supplementation—specifically, α-hydroxyprogesterone caproate (17P) injection (Makena)—to prevent recurrent PTB in women with a singleton pregnancy at high risk by virtue of a prior spontaneous PTB.² This was the first-ever FDA-approved drug for PTB prevention, and it was the first drug approved by the FDA for use in pregnancy in more than 15 years. The approval of 17P utilized the FDA's Subpart H Accelerated Approval Pathway, which applies to therapies that: 1) treat serious conditions with unmet need, and 2) demonstrate safety and efficacy on surrogate end points reasonably likely to predict clinical benefit.³ 

By voting their approval of 17P in 2011, the FDA affirmed that PTB was a serious condition with unmet need, that birth < 37 weeks was an accepted surrogate end point, and that there was compelling evidence of safety and benefit. The compelling evidence presented was a single, randomized, vehicle-controlled clinical trial conducted by the Maternal-Fetal Medicine Units (MFMU) Network, which showed significant reduction in recurrent PTB < 37 weeks (from 54.9% in the placebo group to 36.3% in the 17P group; P<.001; relative risk [RR], 0.66; 95% confidence interval [CI], 0.54-0.81).⁴ 

In 2017, the Society for Maternal-Fetal Medicine (SMFM) reaffirmed the use of 17P to prevent recurrent PTB and, that same year, it was estimated that 75% of eligible patients received 17P.^5,6 Importantly, Subpart H approval requires one or more follow-up clinical trials confirming safety and efficacy. And the FDA has the right—the responsibility—to revisit approval if such trials are either not performed or are unfavorable. 

The recently published PROLONG study by Blackwell and colleagues is this required postapproval confirmatory trial conducted to verify the clinical benefit of 17P supplementation.⁷ 

Continue to: Study design, and stunning results...

Study design, and stunning results 

PROLONG (Progestin's Role in Optimizing Neonatal Gestation) was a randomized (2:1), double-blind, vehicle-controlled, multicenter international trial (2009-2018) conducted to assess the safety and efficacy of 17P injection in 1,708 women with a singleton pregnancy and one or more prior spontaneous PTBs.⁷ Women in the active treatment group (n = 1,130) received weekly intramuscular injections of 17P, while those in the control group (n = 578) received weekly injections of inert oil vehicle. 

Results of the trial showed no significant reduction in the co-primary end points, which were PTB < 35 weeks (11.0% in the 17P group vs 11.5% in the placebo group; RR, 0.95; 95% CI, 0.71-1.26) and neonatal morbidity index (5.6% in the 17P group vs 5.0% in the placebo group; RR, 1.12; 95% CI, 0.68-1.61). There was no evidence of benefit for any subpopulation (geographic region, race, or other PTB risk factor). Maternal outcomes also were similar between the groups. No significant safety concerns were identified. 

Important differences between MFMU and PROLONG trials 

Strengths of the PROLONG trial include its randomized, placebo-controlled design, excellent follow-up rate, and use of a protocol that mirrored that of the MFMU trial. The primary limitation of PROLONG is that participants experienced a lower rate of PTB compared with those in the MFMU trial. The rate of PTB < 37 weeks was 54.9% in the control group of the MFMU trial compared with 21.9% in PROLONG. 

Given the low rate of PTB in PROLONG, the study was underpowered for the co-primary outcomes. In addition, lower rates of PTB in PROLONG compared with in the MFMU trial likely reflected different patient populations.⁸ Moreover, PROLONG was an international trial. Of the 1,708 participants, most were recruited in Russia (36%) and Ukraine (25%); only 23% were from the United States. By contrast, participants in the MFMU trial were recruited from US academic medical centers. Also, participants in the MFMU trial were significantly more likely to have a short cervix, to have a history of more than one PTB, and to be African American.

Discrepant trial results create clinical quandary 

In October 2019, the FDA's Bone, Reproductive and Urologic Drugs Advisory Committee voted 9-7 to withdraw approval for 17P. Committee members struggled with the conflicting data between the 2 trials and hesitated to remove a medication whose use has become standard practice. Ultimately, however, it was lack of substantial evidence of effectiveness of 17P that swayed the committee's vote. While the FDA generally follows the recommendation of an advisory committee, it is not bound to do so. 

Societies' perspectives 

So what are physicians and patients to do? It is possible that a small subgroup of women at extremely high risk for early PTB may benefit from 17P administration. SMFM stated: "...it is reasonable for providers to use 17-OHPC [17P] in women with a profile more representative of the very high-risk population reported in the Meis [MFMU] trial."⁸ Further, the American College of Obstetricians and Gynecologists (ACOG) stated in a Practice Advisory dated October 25, 2019, that "ACOG is not changing our clinical recommendations at this time... [We] will be reviewing subsequent forthcoming analyses and will issue updated clinical guidance as appropriate."⁹ 

Where we stand on 17P use going forward 

17P should be available to women who previously may have benefited from its use. However, 17P should not be recommended routinely to prevent recurrent spontaneous PTB in women with one prior PTB and no other risk factors. Of note, the PROLONG trial does not change recommendations for cervical length screening. Women with a history of a prior spontaneous PTB should undergo cervical length screening to identify those individuals who may benefit from an ultrasound-indicated cerclage.  

Preterm birth (PTB) remains a significant public health concern and a major cause of newborn morbidity and mortality. In the United States, 1 in 10 babies are born preterm (< 37 weeks), and this rate has changed little in 30 years.¹ 

In 2011, the US Food and Drug Administration (FDA) approved progesterone supplementation—specifically, α-hydroxyprogesterone caproate (17P) injection (Makena)—to prevent recurrent PTB in women with a singleton pregnancy at high risk by virtue of a prior spontaneous PTB.² This was the first-ever FDA-approved drug for PTB prevention, and it was the first drug approved by the FDA for use in pregnancy in more than 15 years. The approval of 17P utilized the FDA's Subpart H Accelerated Approval Pathway, which applies to therapies that: 1) treat serious conditions with unmet need, and 2) demonstrate safety and efficacy on surrogate end points reasonably likely to predict clinical benefit.³ 

By voting their approval of 17P in 2011, the FDA affirmed that PTB was a serious condition with unmet need, that birth < 37 weeks was an accepted surrogate end point, and that there was compelling evidence of safety and benefit. The compelling evidence presented was a single, randomized, vehicle-controlled clinical trial conducted by the Maternal-Fetal Medicine Units (MFMU) Network, which showed significant reduction in recurrent PTB < 37 weeks (from 54.9% in the placebo group to 36.3% in the 17P group; P<.001; relative risk [RR], 0.66; 95% confidence interval [CI], 0.54-0.81).⁴ 

In 2017, the Society for Maternal-Fetal Medicine (SMFM) reaffirmed the use of 17P to prevent recurrent PTB and, that same year, it was estimated that 75% of eligible patients received 17P.^5,6 Importantly, Subpart H approval requires one or more follow-up clinical trials confirming safety and efficacy. And the FDA has the right—the responsibility—to revisit approval if such trials are either not performed or are unfavorable. 

The recently published PROLONG study by Blackwell and colleagues is this required postapproval confirmatory trial conducted to verify the clinical benefit of 17P supplementation.⁷ 

Continue to: Study design, and stunning results...

Study design, and stunning results 

PROLONG (Progestin's Role in Optimizing Neonatal Gestation) was a randomized (2:1), double-blind, vehicle-controlled, multicenter international trial (2009-2018) conducted to assess the safety and efficacy of 17P injection in 1,708 women with a singleton pregnancy and one or more prior spontaneous PTBs.⁷ Women in the active treatment group (n = 1,130) received weekly intramuscular injections of 17P, while those in the control group (n = 578) received weekly injections of inert oil vehicle. 

Results of the trial showed no significant reduction in the co-primary end points, which were PTB < 35 weeks (11.0% in the 17P group vs 11.5% in the placebo group; RR, 0.95; 95% CI, 0.71-1.26) and neonatal morbidity index (5.6% in the 17P group vs 5.0% in the placebo group; RR, 1.12; 95% CI, 0.68-1.61). There was no evidence of benefit for any subpopulation (geographic region, race, or other PTB risk factor). Maternal outcomes also were similar between the groups. No significant safety concerns were identified. 

Important differences between MFMU and PROLONG trials 

Strengths of the PROLONG trial include its randomized, placebo-controlled design, excellent follow-up rate, and use of a protocol that mirrored that of the MFMU trial. The primary limitation of PROLONG is that participants experienced a lower rate of PTB compared with those in the MFMU trial. The rate of PTB < 37 weeks was 54.9% in the control group of the MFMU trial compared with 21.9% in PROLONG. 

Given the low rate of PTB in PROLONG, the study was underpowered for the co-primary outcomes. In addition, lower rates of PTB in PROLONG compared with in the MFMU trial likely reflected different patient populations.⁸ Moreover, PROLONG was an international trial. Of the 1,708 participants, most were recruited in Russia (36%) and Ukraine (25%); only 23% were from the United States. By contrast, participants in the MFMU trial were recruited from US academic medical centers. Also, participants in the MFMU trial were significantly more likely to have a short cervix, to have a history of more than one PTB, and to be African American.

Discrepant trial results create clinical quandary 

In October 2019, the FDA's Bone, Reproductive and Urologic Drugs Advisory Committee voted 9-7 to withdraw approval for 17P. Committee members struggled with the conflicting data between the 2 trials and hesitated to remove a medication whose use has become standard practice. Ultimately, however, it was lack of substantial evidence of effectiveness of 17P that swayed the committee's vote. While the FDA generally follows the recommendation of an advisory committee, it is not bound to do so. 

Societies' perspectives 

So what are physicians and patients to do? It is possible that a small subgroup of women at extremely high risk for early PTB may benefit from 17P administration. SMFM stated: "...it is reasonable for providers to use 17-OHPC [17P] in women with a profile more representative of the very high-risk population reported in the Meis [MFMU] trial."⁸ Further, the American College of Obstetricians and Gynecologists (ACOG) stated in a Practice Advisory dated October 25, 2019, that "ACOG is not changing our clinical recommendations at this time... [We] will be reviewing subsequent forthcoming analyses and will issue updated clinical guidance as appropriate."⁹ 

Where we stand on 17P use going forward 

17P should be available to women who previously may have benefited from its use. However, 17P should not be recommended routinely to prevent recurrent spontaneous PTB in women with one prior PTB and no other risk factors. Of note, the PROLONG trial does not change recommendations for cervical length screening. Women with a history of a prior spontaneous PTB should undergo cervical length screening to identify those individuals who may benefit from an ultrasound-indicated cerclage.  

Preterm birth (PTB) remains a significant public health concern and a major cause of newborn morbidity and mortality. In the United States, 1 in 10 babies are born preterm (< 37 weeks), and this rate has changed little in 30 years.¹ 

In 2011, the US Food and Drug Administration (FDA) approved progesterone supplementation—specifically, α-hydroxyprogesterone caproate (17P) injection (Makena)—to prevent recurrent PTB in women with a singleton pregnancy at high risk by virtue of a prior spontaneous PTB.² This was the first-ever FDA-approved drug for PTB prevention, and it was the first drug approved by the FDA for use in pregnancy in more than 15 years. The approval of 17P utilized the FDA's Subpart H Accelerated Approval Pathway, which applies to therapies that: 1) treat serious conditions with unmet need, and 2) demonstrate safety and efficacy on surrogate end points reasonably likely to predict clinical benefit.³ 

By voting their approval of 17P in 2011, the FDA affirmed that PTB was a serious condition with unmet need, that birth < 37 weeks was an accepted surrogate end point, and that there was compelling evidence of safety and benefit. The compelling evidence presented was a single, randomized, vehicle-controlled clinical trial conducted by the Maternal-Fetal Medicine Units (MFMU) Network, which showed significant reduction in recurrent PTB < 37 weeks (from 54.9% in the placebo group to 36.3% in the 17P group; P<.001; relative risk [RR], 0.66; 95% confidence interval [CI], 0.54-0.81).⁴ 

In 2017, the Society for Maternal-Fetal Medicine (SMFM) reaffirmed the use of 17P to prevent recurrent PTB and, that same year, it was estimated that 75% of eligible patients received 17P.^5,6 Importantly, Subpart H approval requires one or more follow-up clinical trials confirming safety and efficacy. And the FDA has the right—the responsibility—to revisit approval if such trials are either not performed or are unfavorable. 

The recently published PROLONG study by Blackwell and colleagues is this required postapproval confirmatory trial conducted to verify the clinical benefit of 17P supplementation.⁷ 

Continue to: Study design, and stunning results...

Study design, and stunning results 

PROLONG (Progestin's Role in Optimizing Neonatal Gestation) was a randomized (2:1), double-blind, vehicle-controlled, multicenter international trial (2009-2018) conducted to assess the safety and efficacy of 17P injection in 1,708 women with a singleton pregnancy and one or more prior spontaneous PTBs.⁷ Women in the active treatment group (n = 1,130) received weekly intramuscular injections of 17P, while those in the control group (n = 578) received weekly injections of inert oil vehicle. 

Results of the trial showed no significant reduction in the co-primary end points, which were PTB < 35 weeks (11.0% in the 17P group vs 11.5% in the placebo group; RR, 0.95; 95% CI, 0.71-1.26) and neonatal morbidity index (5.6% in the 17P group vs 5.0% in the placebo group; RR, 1.12; 95% CI, 0.68-1.61). There was no evidence of benefit for any subpopulation (geographic region, race, or other PTB risk factor). Maternal outcomes also were similar between the groups. No significant safety concerns were identified. 

Important differences between MFMU and PROLONG trials 

Strengths of the PROLONG trial include its randomized, placebo-controlled design, excellent follow-up rate, and use of a protocol that mirrored that of the MFMU trial. The primary limitation of PROLONG is that participants experienced a lower rate of PTB compared with those in the MFMU trial. The rate of PTB < 37 weeks was 54.9% in the control group of the MFMU trial compared with 21.9% in PROLONG. 

Given the low rate of PTB in PROLONG, the study was underpowered for the co-primary outcomes. In addition, lower rates of PTB in PROLONG compared with in the MFMU trial likely reflected different patient populations.⁸ Moreover, PROLONG was an international trial. Of the 1,708 participants, most were recruited in Russia (36%) and Ukraine (25%); only 23% were from the United States. By contrast, participants in the MFMU trial were recruited from US academic medical centers. Also, participants in the MFMU trial were significantly more likely to have a short cervix, to have a history of more than one PTB, and to be African American.

Discrepant trial results create clinical quandary 

In October 2019, the FDA's Bone, Reproductive and Urologic Drugs Advisory Committee voted 9-7 to withdraw approval for 17P. Committee members struggled with the conflicting data between the 2 trials and hesitated to remove a medication whose use has become standard practice. Ultimately, however, it was lack of substantial evidence of effectiveness of 17P that swayed the committee's vote. While the FDA generally follows the recommendation of an advisory committee, it is not bound to do so. 

Societies' perspectives 

So what are physicians and patients to do? It is possible that a small subgroup of women at extremely high risk for early PTB may benefit from 17P administration. SMFM stated: "...it is reasonable for providers to use 17-OHPC [17P] in women with a profile more representative of the very high-risk population reported in the Meis [MFMU] trial."⁸ Further, the American College of Obstetricians and Gynecologists (ACOG) stated in a Practice Advisory dated October 25, 2019, that "ACOG is not changing our clinical recommendations at this time... [We] will be reviewing subsequent forthcoming analyses and will issue updated clinical guidance as appropriate."⁹ 

Where we stand on 17P use going forward 

17P should be available to women who previously may have benefited from its use. However, 17P should not be recommended routinely to prevent recurrent spontaneous PTB in women with one prior PTB and no other risk factors. Of note, the PROLONG trial does not change recommendations for cervical length screening. Women with a history of a prior spontaneous PTB should undergo cervical length screening to identify those individuals who may benefit from an ultrasound-indicated cerclage.  

SOX11 may be an accurate diagnostic marker for mantle cell lymphoma (MCL), allowing clinicians to distinguish it from other lymphoproliferative disorders, according to findings from a meta-analysis of 14 case-control studies.

Gio_tto/Thinkstock

Woojoo Lee, PhD, of Inha University, Incheon, Republic of Korea, and coinvestigators, evaluated the diagnostic accuracy of SOX11 immunohistochemistry for the diagnosis of MCL. The results were published in PLoS One.

The researchers searched major databases for studies that evaluated the use of SOX11 immunohistochemistry in patients with MCL and other lymphoproliferative disorders. After applying the search parameters, the team identified 383 studies, 14 of which were included in the meta-analysis. Various data were extracted from eligible studies, including the type and clonality of anti-SOX11 antibody, number of SOX11-positive lymphomas (MCLs and other lymphoproliferative disorders), specificity, sensitivity, and others. After combining the data, the investigators calculated pooled sensitivity, specificity, and area under the curve. Among the included studies, hairy cell leukemia, Burkitt’s lymphoma, and lymphoblastic lymphoma were common among patient populations. In total, clone MRQ-58 mouse antibodies were used in five study populations.

The researchers found that the pooled specificity was 0.95 (95% CI, 0.9-0.97), and sensitivity was 0.9 (95% CI, 0.86-0.92). There was statistically significant substantial heterogeneity observed for specificity, but not for sensitivity, the investigators reported.

“The results demonstrated that SOX11 was a potential diagnostic marker for MCL,” they wrote. “Meta-regression revealed a significant inverse relationship between specificity and proportions of [Burkitt’s lymphoma, lymphoblastic lymphoma, and hairy cell leukemia].”

With respect to antibody type, the clone MRQ-58 mouse antibody showed consistently high specificity in the clinical setting, despite observed heterogeneity.

“Future studies using MRQ-58 are needed to improve our understanding of the diagnostic accuracy of SOX11 immunohistochemistry for MCL,” the investigators wrote.

The study was funded by the Next-Generation BioGreen 21 program (Republic of Korea). The authors reported having no conflicts of interest.

SOURCE: Lee W et al. PLoS One. 2019 Nov 12. doi: 10.1371/journal.pone.0225096.

SOX11 may be an accurate diagnostic marker for mantle cell lymphoma (MCL), allowing clinicians to distinguish it from other lymphoproliferative disorders, according to findings from a meta-analysis of 14 case-control studies.

Gio_tto/Thinkstock

Woojoo Lee, PhD, of Inha University, Incheon, Republic of Korea, and coinvestigators, evaluated the diagnostic accuracy of SOX11 immunohistochemistry for the diagnosis of MCL. The results were published in PLoS One.

The researchers searched major databases for studies that evaluated the use of SOX11 immunohistochemistry in patients with MCL and other lymphoproliferative disorders. After applying the search parameters, the team identified 383 studies, 14 of which were included in the meta-analysis. Various data were extracted from eligible studies, including the type and clonality of anti-SOX11 antibody, number of SOX11-positive lymphomas (MCLs and other lymphoproliferative disorders), specificity, sensitivity, and others. After combining the data, the investigators calculated pooled sensitivity, specificity, and area under the curve. Among the included studies, hairy cell leukemia, Burkitt’s lymphoma, and lymphoblastic lymphoma were common among patient populations. In total, clone MRQ-58 mouse antibodies were used in five study populations.

The researchers found that the pooled specificity was 0.95 (95% CI, 0.9-0.97), and sensitivity was 0.9 (95% CI, 0.86-0.92). There was statistically significant substantial heterogeneity observed for specificity, but not for sensitivity, the investigators reported.

“The results demonstrated that SOX11 was a potential diagnostic marker for MCL,” they wrote. “Meta-regression revealed a significant inverse relationship between specificity and proportions of [Burkitt’s lymphoma, lymphoblastic lymphoma, and hairy cell leukemia].”

With respect to antibody type, the clone MRQ-58 mouse antibody showed consistently high specificity in the clinical setting, despite observed heterogeneity.

“Future studies using MRQ-58 are needed to improve our understanding of the diagnostic accuracy of SOX11 immunohistochemistry for MCL,” the investigators wrote.

The study was funded by the Next-Generation BioGreen 21 program (Republic of Korea). The authors reported having no conflicts of interest.

SOURCE: Lee W et al. PLoS One. 2019 Nov 12. doi: 10.1371/journal.pone.0225096.

SOX11 may be an accurate diagnostic marker for mantle cell lymphoma (MCL), allowing clinicians to distinguish it from other lymphoproliferative disorders, according to findings from a meta-analysis of 14 case-control studies.

Gio_tto/Thinkstock

Woojoo Lee, PhD, of Inha University, Incheon, Republic of Korea, and coinvestigators, evaluated the diagnostic accuracy of SOX11 immunohistochemistry for the diagnosis of MCL. The results were published in PLoS One.

The researchers searched major databases for studies that evaluated the use of SOX11 immunohistochemistry in patients with MCL and other lymphoproliferative disorders. After applying the search parameters, the team identified 383 studies, 14 of which were included in the meta-analysis. Various data were extracted from eligible studies, including the type and clonality of anti-SOX11 antibody, number of SOX11-positive lymphomas (MCLs and other lymphoproliferative disorders), specificity, sensitivity, and others. After combining the data, the investigators calculated pooled sensitivity, specificity, and area under the curve. Among the included studies, hairy cell leukemia, Burkitt’s lymphoma, and lymphoblastic lymphoma were common among patient populations. In total, clone MRQ-58 mouse antibodies were used in five study populations.

The researchers found that the pooled specificity was 0.95 (95% CI, 0.9-0.97), and sensitivity was 0.9 (95% CI, 0.86-0.92). There was statistically significant substantial heterogeneity observed for specificity, but not for sensitivity, the investigators reported.

“The results demonstrated that SOX11 was a potential diagnostic marker for MCL,” they wrote. “Meta-regression revealed a significant inverse relationship between specificity and proportions of [Burkitt’s lymphoma, lymphoblastic lymphoma, and hairy cell leukemia].”

With respect to antibody type, the clone MRQ-58 mouse antibody showed consistently high specificity in the clinical setting, despite observed heterogeneity.

“Future studies using MRQ-58 are needed to improve our understanding of the diagnostic accuracy of SOX11 immunohistochemistry for MCL,” the investigators wrote.

The study was funded by the Next-Generation BioGreen 21 program (Republic of Korea). The authors reported having no conflicts of interest.

SOURCE: Lee W et al. PLoS One. 2019 Nov 12. doi: 10.1371/journal.pone.0225096.

For patients with relapsed or refractory mantle cell lymphoma (MCL), second generation Bruton’s tyrosine kinase (BTK) inhibitor acalabrutinib may offer increased response rates and better tolerability compared with other single-agent targeted therapies, based on a recent analysis.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

Improved safety could lead to long-term benefits resulting from extended treatment duration, according to lead author Claire Telford, PhD, of AstraZeneca in Gaithersburg, Md., and colleagues. AstraZeneca manufactures acalabrutinib (Calquence).

Currently, treatment for MCL is guided by a number of clinical considerations, the investigators explained in Clinical Therapeutics.

“The type of treatment recommended for relapsed/refractory MCL depends on multiple factors, namely time to the relapse, extent of disease, previous regimens, candidacy for allogeneic stem cell transplantation, and the patient’s overall health,” they wrote.

To determine how acalabrutinib stacks up with other options, the investigators drew data from the phase 2 ACE-LY-004 trial, which tested acalabrutinib in 124 patients with relapsed or refractory MCL. After matching, the investigators compared the ACE-LY-004 outcomes from 12 other trials, in which patients received different targeted therapies.

Results pointed to higher overall response and complete response rates for acalabrutinib, compared with other single-agent targeted therapy. Specifically, acalabrutinib had a higher overall response rate, compared with ibrutinib (9.3% higher), lenalidomide (38.1% higher), temsirolimus (40.7% higher), and bortezomib (50.6% higher). For each of these, complete responses also were higher.

There was no significant difference in overall response or complete response rates between acalabrutinib and rituximab combinations – bendamustine plus rituximab, ibrutinib plus rituximab, and lenalidomide plus rituximab.

The investigators also highlighted a number of safety advantages. Compared with ibrutinib, acalabrutinib was associated with significantly fewer instances of grade 3 or 4 atrial fibrillation. Risk of grade 3 or 4 thrombocytopenia was significantly lower with acalabrutinib than with ibrutinib, bortezomib, lenalidomide, and temsirolimus.

Still, in some instances, acalabrutinib was comparatively less tolerable. It was associated with a higher risk of grade 3 or 4 infections than bendamustine plus rituximab; and anemia was more common among patients receiving acalabrutinib than among those who had lenalidomide plus rituximab or ibrutinib plus rituximab.

“This comparison of targeted therapies used in the treatment of relapsed/refractory MCL has shown that acalabrutinib has the potential to provide higher response rates, with trends for longer [progression-free survival] and [overall survival], and an improved safety profile,” the investigators wrote.

The study was funded by AstraZeneca. Dr. Telford is an employee of AstraZeneca and other authors reported financial relationships with the company.

SOURCE: Telford C et al. Clin Ther. 2019 Nov 4. doi: 10.1016/j.clinthera.2019.09.012 .

For patients with relapsed or refractory mantle cell lymphoma (MCL), second generation Bruton’s tyrosine kinase (BTK) inhibitor acalabrutinib may offer increased response rates and better tolerability compared with other single-agent targeted therapies, based on a recent analysis.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

Improved safety could lead to long-term benefits resulting from extended treatment duration, according to lead author Claire Telford, PhD, of AstraZeneca in Gaithersburg, Md., and colleagues. AstraZeneca manufactures acalabrutinib (Calquence).

Currently, treatment for MCL is guided by a number of clinical considerations, the investigators explained in Clinical Therapeutics.

“The type of treatment recommended for relapsed/refractory MCL depends on multiple factors, namely time to the relapse, extent of disease, previous regimens, candidacy for allogeneic stem cell transplantation, and the patient’s overall health,” they wrote.

To determine how acalabrutinib stacks up with other options, the investigators drew data from the phase 2 ACE-LY-004 trial, which tested acalabrutinib in 124 patients with relapsed or refractory MCL. After matching, the investigators compared the ACE-LY-004 outcomes from 12 other trials, in which patients received different targeted therapies.

Results pointed to higher overall response and complete response rates for acalabrutinib, compared with other single-agent targeted therapy. Specifically, acalabrutinib had a higher overall response rate, compared with ibrutinib (9.3% higher), lenalidomide (38.1% higher), temsirolimus (40.7% higher), and bortezomib (50.6% higher). For each of these, complete responses also were higher.

There was no significant difference in overall response or complete response rates between acalabrutinib and rituximab combinations – bendamustine plus rituximab, ibrutinib plus rituximab, and lenalidomide plus rituximab.

The investigators also highlighted a number of safety advantages. Compared with ibrutinib, acalabrutinib was associated with significantly fewer instances of grade 3 or 4 atrial fibrillation. Risk of grade 3 or 4 thrombocytopenia was significantly lower with acalabrutinib than with ibrutinib, bortezomib, lenalidomide, and temsirolimus.

Still, in some instances, acalabrutinib was comparatively less tolerable. It was associated with a higher risk of grade 3 or 4 infections than bendamustine plus rituximab; and anemia was more common among patients receiving acalabrutinib than among those who had lenalidomide plus rituximab or ibrutinib plus rituximab.

“This comparison of targeted therapies used in the treatment of relapsed/refractory MCL has shown that acalabrutinib has the potential to provide higher response rates, with trends for longer [progression-free survival] and [overall survival], and an improved safety profile,” the investigators wrote.

The study was funded by AstraZeneca. Dr. Telford is an employee of AstraZeneca and other authors reported financial relationships with the company.

SOURCE: Telford C et al. Clin Ther. 2019 Nov 4. doi: 10.1016/j.clinthera.2019.09.012 .

For patients with relapsed or refractory mantle cell lymphoma (MCL), second generation Bruton’s tyrosine kinase (BTK) inhibitor acalabrutinib may offer increased response rates and better tolerability compared with other single-agent targeted therapies, based on a recent analysis.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

Improved safety could lead to long-term benefits resulting from extended treatment duration, according to lead author Claire Telford, PhD, of AstraZeneca in Gaithersburg, Md., and colleagues. AstraZeneca manufactures acalabrutinib (Calquence).

Currently, treatment for MCL is guided by a number of clinical considerations, the investigators explained in Clinical Therapeutics.

“The type of treatment recommended for relapsed/refractory MCL depends on multiple factors, namely time to the relapse, extent of disease, previous regimens, candidacy for allogeneic stem cell transplantation, and the patient’s overall health,” they wrote.

To determine how acalabrutinib stacks up with other options, the investigators drew data from the phase 2 ACE-LY-004 trial, which tested acalabrutinib in 124 patients with relapsed or refractory MCL. After matching, the investigators compared the ACE-LY-004 outcomes from 12 other trials, in which patients received different targeted therapies.

Results pointed to higher overall response and complete response rates for acalabrutinib, compared with other single-agent targeted therapy. Specifically, acalabrutinib had a higher overall response rate, compared with ibrutinib (9.3% higher), lenalidomide (38.1% higher), temsirolimus (40.7% higher), and bortezomib (50.6% higher). For each of these, complete responses also were higher.

There was no significant difference in overall response or complete response rates between acalabrutinib and rituximab combinations – bendamustine plus rituximab, ibrutinib plus rituximab, and lenalidomide plus rituximab.

The investigators also highlighted a number of safety advantages. Compared with ibrutinib, acalabrutinib was associated with significantly fewer instances of grade 3 or 4 atrial fibrillation. Risk of grade 3 or 4 thrombocytopenia was significantly lower with acalabrutinib than with ibrutinib, bortezomib, lenalidomide, and temsirolimus.

Still, in some instances, acalabrutinib was comparatively less tolerable. It was associated with a higher risk of grade 3 or 4 infections than bendamustine plus rituximab; and anemia was more common among patients receiving acalabrutinib than among those who had lenalidomide plus rituximab or ibrutinib plus rituximab.

“This comparison of targeted therapies used in the treatment of relapsed/refractory MCL has shown that acalabrutinib has the potential to provide higher response rates, with trends for longer [progression-free survival] and [overall survival], and an improved safety profile,” the investigators wrote.

The study was funded by AstraZeneca. Dr. Telford is an employee of AstraZeneca and other authors reported financial relationships with the company.

SOURCE: Telford C et al. Clin Ther. 2019 Nov 4. doi: 10.1016/j.clinthera.2019.09.012 .

The Food and Drug Administration has approved atezolizumab (Tecentriq) in combination with paclitaxel and carboplatin chemotherapy for first-line treatment of adults with metastatic, nonsquamous non–small cell lung cancer (NSCLC) with no EGFR or ALK genomic tumor aberrations.

Atezolizumab has been previously approved in combination with bevacizumab, paclitaxel, and carboplatin for the first-line treatment of adults with metastatic NSCLC with no EGFR or ALK genomic tumor aberrations. The monoclonal antibody is also approved to treat adults with metastatic NSCLC who have disease progression during or following chemotherapy, and for those with extensive-stage SCLC.

The current approval was based on a demonstrated improvement in overall survival in the phase 3 IMpower130 trial (NCT02367781). Median overall survival for advanced NSCLC patients who received atezolizumab in combination with chemotherapy was 18.6 months, compared with 13.9 months for patients who received chemotherapy alone (hazard ratio, 0.80; 95% confidence interval, 0.64-0.99; P = .0384) in the intention-to-treat wild-type population of 681 patients.

Grade 3-4 treatment-related adverse events were reported in 73.2% of people receiving atezolizumab plus chemotherapy, compared with 60.3% of people receiving chemotherapy alone, according to the company press release.

[email protected]

The Food and Drug Administration has approved atezolizumab (Tecentriq) in combination with paclitaxel and carboplatin chemotherapy for first-line treatment of adults with metastatic, nonsquamous non–small cell lung cancer (NSCLC) with no EGFR or ALK genomic tumor aberrations.

Atezolizumab has been previously approved in combination with bevacizumab, paclitaxel, and carboplatin for the first-line treatment of adults with metastatic NSCLC with no EGFR or ALK genomic tumor aberrations. The monoclonal antibody is also approved to treat adults with metastatic NSCLC who have disease progression during or following chemotherapy, and for those with extensive-stage SCLC.

The current approval was based on a demonstrated improvement in overall survival in the phase 3 IMpower130 trial (NCT02367781). Median overall survival for advanced NSCLC patients who received atezolizumab in combination with chemotherapy was 18.6 months, compared with 13.9 months for patients who received chemotherapy alone (hazard ratio, 0.80; 95% confidence interval, 0.64-0.99; P = .0384) in the intention-to-treat wild-type population of 681 patients.

Grade 3-4 treatment-related adverse events were reported in 73.2% of people receiving atezolizumab plus chemotherapy, compared with 60.3% of people receiving chemotherapy alone, according to the company press release.

[email protected]

The Food and Drug Administration has approved atezolizumab (Tecentriq) in combination with paclitaxel and carboplatin chemotherapy for first-line treatment of adults with metastatic, nonsquamous non–small cell lung cancer (NSCLC) with no EGFR or ALK genomic tumor aberrations.

Atezolizumab has been previously approved in combination with bevacizumab, paclitaxel, and carboplatin for the first-line treatment of adults with metastatic NSCLC with no EGFR or ALK genomic tumor aberrations. The monoclonal antibody is also approved to treat adults with metastatic NSCLC who have disease progression during or following chemotherapy, and for those with extensive-stage SCLC.

The current approval was based on a demonstrated improvement in overall survival in the phase 3 IMpower130 trial (NCT02367781). Median overall survival for advanced NSCLC patients who received atezolizumab in combination with chemotherapy was 18.6 months, compared with 13.9 months for patients who received chemotherapy alone (hazard ratio, 0.80; 95% confidence interval, 0.64-0.99; P = .0384) in the intention-to-treat wild-type population of 681 patients.

Grade 3-4 treatment-related adverse events were reported in 73.2% of people receiving atezolizumab plus chemotherapy, compared with 60.3% of people receiving chemotherapy alone, according to the company press release.

[email protected]

The ideas and opinions expressed in Best of 2019 – The RA Report: Top News Highlights do not necessarily reflect those of the publisher. Frontline Medical Communications will not assume responsibility for damages, loss, or claims of any kind arising from or related to the information contained in this publication, including any claims related to the products, drugs, or services mentioned herein.

The ideas and opinions expressed in Best of 2019 – The RA Report: Top News Highlights do not necessarily reflect those of the publisher. Frontline Medical Communications will not assume responsibility for damages, loss, or claims of any kind arising from or related to the information contained in this publication, including any claims related to the products, drugs, or services mentioned herein.

The ideas and opinions expressed in Best of 2019 – The RA Report: Top News Highlights do not necessarily reflect those of the publisher. Frontline Medical Communications will not assume responsibility for damages, loss, or claims of any kind arising from or related to the information contained in this publication, including any claims related to the products, drugs, or services mentioned herein.