Most COVID-19 long-haulers continue to have brain fog, fatigue, and compromised quality of life more than a year after the initial infection, results from the most extensive follow-up to date of a group of long COVID patients show.

Most patients continue to experience debilitating neurologic symptoms an average of 15 months from symptom onset, Igor Koralnik, MD, who oversees the Neuro COVID-19 Clinic at Northwestern Medicine in Chicago, said during a press briefing.

Surprisingly, in some cases, new symptoms appear that didn’t exist before, including variation of heart rate and blood pressure, and gastrointestinal symptoms, indicating there may be a late appearance in dysfunction of the autonomic nervous system in those patients, Dr. Koralnik said.

The study was published online in Annals of Clinical and Translational Neurology.
 

Evolving symptoms

The investigators evaluated the evolution of neurologic symptoms in 52 adults who had mild COVID-19 symptoms and were not admitted to the hospital.

Their mean age was 43 years, 73% were women and 77% had received a COVID-19 vaccine. These patients have now been followed for between 11 and 18 months since their initial infection.

Overall, between first and follow-up evaluations, there was no significant change in the frequency of most neurologic symptoms, including brain fog (81% vs. 71%), numbness/tingling (69% vs. 65%), headache (67% vs. 54%), dizziness (50% vs. 54%), blurred vision (34% vs. 44%), tinnitus (33% vs. 42%), and fatigue (87% vs. 81%).

The only neurologic symptoms that decreased over time were loss of taste (63% vs. 27%) and smell (58% vs. 21%).

Conversely, heart rate and blood pressure variation (35% vs. 56%) and gastrointestinal symptoms (27% vs. 48%; P = .04) increased at follow-up evaluations.

Patients reported subjective improvements in their recovery, cognitive function and fatigue, but quality of life measures remained lower than the average population of the United States.

There was a neutral effect of COVID vaccination on long COVID symptoms – it didn’t cure long COVID or make long COVID worse, which is a reason given by some long-haulers for not getting vaccinated, Dr. Koralnik told the briefing.

Therefore, “we continue to encourage our patients to get vaccinated and boosted according to the Centers for Disease Control and Prevention recommendation,” he said.
 

Escape from the ‘pit of despair’

To date, the Northwestern Medicine Neuro COVID-19 Clinic has treated nearly 1,400 COVID long-haulers from across the United States.

Emily Caffee, a physical therapist from Wheaton, Ill., is one of them.

Speaking at the briefing, the 36-year-old described her saga and roller coaster of recovering from long COVID in three acts: her initial infection, followed by a descent into a pit of physical and emotional despair, followed by her eventual escape from that pit more than two years later.

Following a fairly mild case of COVID, Ms. Caffee said worsening neurologic symptoms forced her to take medical leave from her very physical and cognitively demanding job. 

Ms. Caffee said she experienced crushing fatigue and brain fog, as well as rapid heart rate and blood pressure changes going from sitting to standing position.

She went from being a competitive athlete to someone who could barely get off the couch or empty the dishwasher.

With the ongoing help of her medical team, she slowly returned to daily activities and eventually to work on a limited basis.

Today, Ms. Caffee says she’s 90%-95% better but still she has some lingering symptoms and does not yet feel like her pre-COVID self.

It’s been a very slow climb out of the pit, Ms. Caffee said.

This study has no specific funding. The authors disclosed no relevant conflicts of interest.

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

Most COVID-19 long-haulers continue to have brain fog, fatigue, and compromised quality of life more than a year after the initial infection, results from the most extensive follow-up to date of a group of long COVID patients show.

Most patients continue to experience debilitating neurologic symptoms an average of 15 months from symptom onset, Igor Koralnik, MD, who oversees the Neuro COVID-19 Clinic at Northwestern Medicine in Chicago, said during a press briefing.

Surprisingly, in some cases, new symptoms appear that didn’t exist before, including variation of heart rate and blood pressure, and gastrointestinal symptoms, indicating there may be a late appearance in dysfunction of the autonomic nervous system in those patients, Dr. Koralnik said.

The study was published online in Annals of Clinical and Translational Neurology.
 

Evolving symptoms

The investigators evaluated the evolution of neurologic symptoms in 52 adults who had mild COVID-19 symptoms and were not admitted to the hospital.

Their mean age was 43 years, 73% were women and 77% had received a COVID-19 vaccine. These patients have now been followed for between 11 and 18 months since their initial infection.

Overall, between first and follow-up evaluations, there was no significant change in the frequency of most neurologic symptoms, including brain fog (81% vs. 71%), numbness/tingling (69% vs. 65%), headache (67% vs. 54%), dizziness (50% vs. 54%), blurred vision (34% vs. 44%), tinnitus (33% vs. 42%), and fatigue (87% vs. 81%).

The only neurologic symptoms that decreased over time were loss of taste (63% vs. 27%) and smell (58% vs. 21%).

Conversely, heart rate and blood pressure variation (35% vs. 56%) and gastrointestinal symptoms (27% vs. 48%; P = .04) increased at follow-up evaluations.

Patients reported subjective improvements in their recovery, cognitive function and fatigue, but quality of life measures remained lower than the average population of the United States.

There was a neutral effect of COVID vaccination on long COVID symptoms – it didn’t cure long COVID or make long COVID worse, which is a reason given by some long-haulers for not getting vaccinated, Dr. Koralnik told the briefing.

Therefore, “we continue to encourage our patients to get vaccinated and boosted according to the Centers for Disease Control and Prevention recommendation,” he said.
 

Escape from the ‘pit of despair’

To date, the Northwestern Medicine Neuro COVID-19 Clinic has treated nearly 1,400 COVID long-haulers from across the United States.

Emily Caffee, a physical therapist from Wheaton, Ill., is one of them.

Speaking at the briefing, the 36-year-old described her saga and roller coaster of recovering from long COVID in three acts: her initial infection, followed by a descent into a pit of physical and emotional despair, followed by her eventual escape from that pit more than two years later.

Following a fairly mild case of COVID, Ms. Caffee said worsening neurologic symptoms forced her to take medical leave from her very physical and cognitively demanding job. 

Ms. Caffee said she experienced crushing fatigue and brain fog, as well as rapid heart rate and blood pressure changes going from sitting to standing position.

She went from being a competitive athlete to someone who could barely get off the couch or empty the dishwasher.

With the ongoing help of her medical team, she slowly returned to daily activities and eventually to work on a limited basis.

Today, Ms. Caffee says she’s 90%-95% better but still she has some lingering symptoms and does not yet feel like her pre-COVID self.

It’s been a very slow climb out of the pit, Ms. Caffee said.

This study has no specific funding. The authors disclosed no relevant conflicts of interest.

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

Most COVID-19 long-haulers continue to have brain fog, fatigue, and compromised quality of life more than a year after the initial infection, results from the most extensive follow-up to date of a group of long COVID patients show.

Most patients continue to experience debilitating neurologic symptoms an average of 15 months from symptom onset, Igor Koralnik, MD, who oversees the Neuro COVID-19 Clinic at Northwestern Medicine in Chicago, said during a press briefing.

Surprisingly, in some cases, new symptoms appear that didn’t exist before, including variation of heart rate and blood pressure, and gastrointestinal symptoms, indicating there may be a late appearance in dysfunction of the autonomic nervous system in those patients, Dr. Koralnik said.

The study was published online in Annals of Clinical and Translational Neurology.
 

Evolving symptoms

The investigators evaluated the evolution of neurologic symptoms in 52 adults who had mild COVID-19 symptoms and were not admitted to the hospital.

Their mean age was 43 years, 73% were women and 77% had received a COVID-19 vaccine. These patients have now been followed for between 11 and 18 months since their initial infection.

Overall, between first and follow-up evaluations, there was no significant change in the frequency of most neurologic symptoms, including brain fog (81% vs. 71%), numbness/tingling (69% vs. 65%), headache (67% vs. 54%), dizziness (50% vs. 54%), blurred vision (34% vs. 44%), tinnitus (33% vs. 42%), and fatigue (87% vs. 81%).

The only neurologic symptoms that decreased over time were loss of taste (63% vs. 27%) and smell (58% vs. 21%).

Conversely, heart rate and blood pressure variation (35% vs. 56%) and gastrointestinal symptoms (27% vs. 48%; P = .04) increased at follow-up evaluations.

Patients reported subjective improvements in their recovery, cognitive function and fatigue, but quality of life measures remained lower than the average population of the United States.

There was a neutral effect of COVID vaccination on long COVID symptoms – it didn’t cure long COVID or make long COVID worse, which is a reason given by some long-haulers for not getting vaccinated, Dr. Koralnik told the briefing.

Therefore, “we continue to encourage our patients to get vaccinated and boosted according to the Centers for Disease Control and Prevention recommendation,” he said.
 

Escape from the ‘pit of despair’

To date, the Northwestern Medicine Neuro COVID-19 Clinic has treated nearly 1,400 COVID long-haulers from across the United States.

Emily Caffee, a physical therapist from Wheaton, Ill., is one of them.

Speaking at the briefing, the 36-year-old described her saga and roller coaster of recovering from long COVID in three acts: her initial infection, followed by a descent into a pit of physical and emotional despair, followed by her eventual escape from that pit more than two years later.

Following a fairly mild case of COVID, Ms. Caffee said worsening neurologic symptoms forced her to take medical leave from her very physical and cognitively demanding job. 

Ms. Caffee said she experienced crushing fatigue and brain fog, as well as rapid heart rate and blood pressure changes going from sitting to standing position.

She went from being a competitive athlete to someone who could barely get off the couch or empty the dishwasher.

With the ongoing help of her medical team, she slowly returned to daily activities and eventually to work on a limited basis.

Today, Ms. Caffee says she’s 90%-95% better but still she has some lingering symptoms and does not yet feel like her pre-COVID self.

It’s been a very slow climb out of the pit, Ms. Caffee said.

This study has no specific funding. The authors disclosed no relevant conflicts of interest.

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

SAN DIEGO – Treatments to eradicate Helicobacter pylori (H. pylori) infections do increase the antibiotic resistance of the gut microbiota, but for only a few months, researchers reported at Digestive Disease Week^® (DDW).

The finding applies similarly to levofloxacin quadruple therapy and bismuth quadruple therapy, both of which are equally efficacious as second-line treatments, said Jyh-Ming Liou, MD, PhD, clinical professor of internal medicine at National Taiwan University in Taipei.

This provides some reassurance that increased use of antibiotics to treat these infections won’t cause long-term disruptions to the patients’ microbiomes, said Dr. Liou.

“Maybe if we have indications for antibiotic treatment, then we don’t worry about the emergence of resistance in our bodies,” he said. “But the accumulation of antibodies in the environment may induce bacteria to mutate, so maybe we still need cautious use of antibiotics.”

H. pylori infections are becoming harder to treat as more strains develop resistance to antibiotics, leading physicians to use regimens with multiple agents. This in turn has raised concerns that gut microbiota could be disrupted, with pathogens potentially developing their own resistance.

To explore these risks, Dr. Liou and colleagues recruited adults whose H. pylori infections were not successfully eradicated.

They randomly assigned 280 patients each to one of two second-line therapies, levofloxacin quadruple or bismuth quadruple. At baseline, the researchers could not find any statistically significant differences in the two groups’ demographics, cigarette and alcohol use, or ulcers, as well as antibiotic resistance in patients’ microbiome between the groups.

Levofloxacin quadruple therapy consisted of esomeprazole 40 mg and amoxicillin 1 g for the first 7 days, followed by esomeprazole 40 mg, metronidazole 500 mg, and levofloxacin 250 mg for another 7 days (all twice daily).

Bismuth quadruple therapy consisted of esomeprazole 40 mg twice daily, bismuth tripotassium dicitrate 300 mg four times a day, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day, for 10 days.

The researchers collected stool samples at baseline, week 2, week 8, and 1 year after eradication therapy and analyzed them for microbiota diversity and antibiotic susceptibility.

The H. pylori eradication rates were almost the same in the two second-line therapies: 87.9% for levofloxacin quadruple and 87.5% for bismuth quadruple. When they were used as third-line (rescue) therapies, the success rates were also statistically the same, and the cumulative second-line and third-line eradication rate was 95.6% for levofloxacin quadruple and 96.6% for bismuth quadruple.

The two treatments did differ in adverse events with 48.4% for levofloxacin quadruple and 77.3% for bismuth quadruple, which was statistically significant (P < .0001).

After a year, H. pylori reinfected 2.5% of the levofloxacin group and 3% of the bismuth quadruple group.

The researchers used metagenomic sequencing to examine the bacteria in the patients’ microbiome for antibiotic resistance. Using 16S rRNA sequencing, they found that the proportion of genera and species with significant changes in abundance at 2 weeks after treatment compared with baseline was 52.4% for levofloxacin quadruple therapy versus 45.1% for bismuth quadruple therapy.

However, 8 weeks after treatment, the proportion with significant changes had dropped to 5.8% for the levofloxacin group and 21.5% for the bismuth group. And at the end of a year, they had further dropped to 0.9% for the levofloxacin group and 8.4% for the bismuth group.

“It was generally reassuring that, even after giving these combinations of different antibiotics, eventually it doesn’t seem to affect the resistance pattern in bacteria lower down in the gut,” said session moderator Steven Moss, MD, professor of medicine at Brown University in Providence, R.I.

Still, continuing to pile on more and more antibiotics to treat H. pylori infections won’t work forever because H. pylori strains are themselves developing resistance so rapidly, he said. “We’re certainly going to have worse eradications in the future unless we can come up with new tricks.”

A hopeful development are new techniques to test H. pylori for resistance to specific antibiotics before initiating treatment, said Dr. Moss.

Dr. Moss consults with companies developing H. pylori therapies and diagnostics. Dr. Liou reported no relevant financial interests.

SAN DIEGO – Treatments to eradicate Helicobacter pylori (H. pylori) infections do increase the antibiotic resistance of the gut microbiota, but for only a few months, researchers reported at Digestive Disease Week^® (DDW).

The finding applies similarly to levofloxacin quadruple therapy and bismuth quadruple therapy, both of which are equally efficacious as second-line treatments, said Jyh-Ming Liou, MD, PhD, clinical professor of internal medicine at National Taiwan University in Taipei.

This provides some reassurance that increased use of antibiotics to treat these infections won’t cause long-term disruptions to the patients’ microbiomes, said Dr. Liou.

“Maybe if we have indications for antibiotic treatment, then we don’t worry about the emergence of resistance in our bodies,” he said. “But the accumulation of antibodies in the environment may induce bacteria to mutate, so maybe we still need cautious use of antibiotics.”

H. pylori infections are becoming harder to treat as more strains develop resistance to antibiotics, leading physicians to use regimens with multiple agents. This in turn has raised concerns that gut microbiota could be disrupted, with pathogens potentially developing their own resistance.

To explore these risks, Dr. Liou and colleagues recruited adults whose H. pylori infections were not successfully eradicated.

They randomly assigned 280 patients each to one of two second-line therapies, levofloxacin quadruple or bismuth quadruple. At baseline, the researchers could not find any statistically significant differences in the two groups’ demographics, cigarette and alcohol use, or ulcers, as well as antibiotic resistance in patients’ microbiome between the groups.

Levofloxacin quadruple therapy consisted of esomeprazole 40 mg and amoxicillin 1 g for the first 7 days, followed by esomeprazole 40 mg, metronidazole 500 mg, and levofloxacin 250 mg for another 7 days (all twice daily).

Bismuth quadruple therapy consisted of esomeprazole 40 mg twice daily, bismuth tripotassium dicitrate 300 mg four times a day, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day, for 10 days.

The researchers collected stool samples at baseline, week 2, week 8, and 1 year after eradication therapy and analyzed them for microbiota diversity and antibiotic susceptibility.

The H. pylori eradication rates were almost the same in the two second-line therapies: 87.9% for levofloxacin quadruple and 87.5% for bismuth quadruple. When they were used as third-line (rescue) therapies, the success rates were also statistically the same, and the cumulative second-line and third-line eradication rate was 95.6% for levofloxacin quadruple and 96.6% for bismuth quadruple.

The two treatments did differ in adverse events with 48.4% for levofloxacin quadruple and 77.3% for bismuth quadruple, which was statistically significant (P < .0001).

After a year, H. pylori reinfected 2.5% of the levofloxacin group and 3% of the bismuth quadruple group.

The researchers used metagenomic sequencing to examine the bacteria in the patients’ microbiome for antibiotic resistance. Using 16S rRNA sequencing, they found that the proportion of genera and species with significant changes in abundance at 2 weeks after treatment compared with baseline was 52.4% for levofloxacin quadruple therapy versus 45.1% for bismuth quadruple therapy.

However, 8 weeks after treatment, the proportion with significant changes had dropped to 5.8% for the levofloxacin group and 21.5% for the bismuth group. And at the end of a year, they had further dropped to 0.9% for the levofloxacin group and 8.4% for the bismuth group.

“It was generally reassuring that, even after giving these combinations of different antibiotics, eventually it doesn’t seem to affect the resistance pattern in bacteria lower down in the gut,” said session moderator Steven Moss, MD, professor of medicine at Brown University in Providence, R.I.

Still, continuing to pile on more and more antibiotics to treat H. pylori infections won’t work forever because H. pylori strains are themselves developing resistance so rapidly, he said. “We’re certainly going to have worse eradications in the future unless we can come up with new tricks.”

A hopeful development are new techniques to test H. pylori for resistance to specific antibiotics before initiating treatment, said Dr. Moss.

Dr. Moss consults with companies developing H. pylori therapies and diagnostics. Dr. Liou reported no relevant financial interests.

SAN DIEGO – Treatments to eradicate Helicobacter pylori (H. pylori) infections do increase the antibiotic resistance of the gut microbiota, but for only a few months, researchers reported at Digestive Disease Week^® (DDW).

The finding applies similarly to levofloxacin quadruple therapy and bismuth quadruple therapy, both of which are equally efficacious as second-line treatments, said Jyh-Ming Liou, MD, PhD, clinical professor of internal medicine at National Taiwan University in Taipei.

This provides some reassurance that increased use of antibiotics to treat these infections won’t cause long-term disruptions to the patients’ microbiomes, said Dr. Liou.

“Maybe if we have indications for antibiotic treatment, then we don’t worry about the emergence of resistance in our bodies,” he said. “But the accumulation of antibodies in the environment may induce bacteria to mutate, so maybe we still need cautious use of antibiotics.”

H. pylori infections are becoming harder to treat as more strains develop resistance to antibiotics, leading physicians to use regimens with multiple agents. This in turn has raised concerns that gut microbiota could be disrupted, with pathogens potentially developing their own resistance.

To explore these risks, Dr. Liou and colleagues recruited adults whose H. pylori infections were not successfully eradicated.

They randomly assigned 280 patients each to one of two second-line therapies, levofloxacin quadruple or bismuth quadruple. At baseline, the researchers could not find any statistically significant differences in the two groups’ demographics, cigarette and alcohol use, or ulcers, as well as antibiotic resistance in patients’ microbiome between the groups.

Levofloxacin quadruple therapy consisted of esomeprazole 40 mg and amoxicillin 1 g for the first 7 days, followed by esomeprazole 40 mg, metronidazole 500 mg, and levofloxacin 250 mg for another 7 days (all twice daily).

Bismuth quadruple therapy consisted of esomeprazole 40 mg twice daily, bismuth tripotassium dicitrate 300 mg four times a day, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day, for 10 days.

The researchers collected stool samples at baseline, week 2, week 8, and 1 year after eradication therapy and analyzed them for microbiota diversity and antibiotic susceptibility.

The H. pylori eradication rates were almost the same in the two second-line therapies: 87.9% for levofloxacin quadruple and 87.5% for bismuth quadruple. When they were used as third-line (rescue) therapies, the success rates were also statistically the same, and the cumulative second-line and third-line eradication rate was 95.6% for levofloxacin quadruple and 96.6% for bismuth quadruple.

The two treatments did differ in adverse events with 48.4% for levofloxacin quadruple and 77.3% for bismuth quadruple, which was statistically significant (P < .0001).

After a year, H. pylori reinfected 2.5% of the levofloxacin group and 3% of the bismuth quadruple group.

The researchers used metagenomic sequencing to examine the bacteria in the patients’ microbiome for antibiotic resistance. Using 16S rRNA sequencing, they found that the proportion of genera and species with significant changes in abundance at 2 weeks after treatment compared with baseline was 52.4% for levofloxacin quadruple therapy versus 45.1% for bismuth quadruple therapy.

However, 8 weeks after treatment, the proportion with significant changes had dropped to 5.8% for the levofloxacin group and 21.5% for the bismuth group. And at the end of a year, they had further dropped to 0.9% for the levofloxacin group and 8.4% for the bismuth group.

“It was generally reassuring that, even after giving these combinations of different antibiotics, eventually it doesn’t seem to affect the resistance pattern in bacteria lower down in the gut,” said session moderator Steven Moss, MD, professor of medicine at Brown University in Providence, R.I.

Still, continuing to pile on more and more antibiotics to treat H. pylori infections won’t work forever because H. pylori strains are themselves developing resistance so rapidly, he said. “We’re certainly going to have worse eradications in the future unless we can come up with new tricks.”

A hopeful development are new techniques to test H. pylori for resistance to specific antibiotics before initiating treatment, said Dr. Moss.

Dr. Moss consults with companies developing H. pylori therapies and diagnostics. Dr. Liou reported no relevant financial interests.

INDIANAPOLIS – Recent legislative sessions in state legislative houses across the country have yielded progress toward codifying optimal team practice (OTP) into state law. That’s according to Phil Bongiorno, BA, senior vice president of advocacy and government relations at the American Academy of Physician Associates (AAPA), who spoke at the group’s annual meeting.

OTP refers to the AAPA’s goal of improving patient access to care and lessening administrative obligations by eliminating the legal requirement that there be a specific relationship between a PA, physician, or any other health care provider. This would allow a PA to practice to the full extent of their education, training, and experience, Mr. Bongiorno said.

The second tenet of OTP is to persuade states to create a separate majority PA board to regulate PAs. An alternative to this would be for states to add PAs and physicians who work with PAs to their medical or healing arts boards, he said.

Third, in an OTP environment, each state would authorize PAs to be eligible for direct payment by all public and private insurers. “We have seen that development at the federal level, as far as Medicare is concerned,” Mr. Bongiorno said. “Now, we’re focusing on making that happen in the individual states as well.”

According to Mr. Bongiorno, this year’s state advocacy priorities are to pursue new legislation in additional states, even as efforts continue to persuade state legislatures to act on carryover bills from the previous legislative session.

Mr. Bongiorno briefly summarized what he called “OTP successes” from 2021:

• Federal government: Authorized direct payment to PAs under Medicare
• Arkansas, Delaware, Illinois, Pennsylvania: Added one or more PAs to their medical boards
• Florida, Utah: Approved direct payment to PAs
• Tennessee, Wisconsin: Created a separate PA review board
• Utah, Wisconsin: Removed the relationship/agreement requirement (Wisconsin now requires 10,000 hours of practice to remove the relationship requirement)

North Central region

In Colorado, House Bill 1095 (HB1095) would have removed requirements for a legal relationship between a PA and a physician. Initially that would have happened after 3,000 hours of practice, although changing that to 5,000 hours has been a compromise measure. PAs changing specialties must collaborate for 2,000 hours, now negotiated to 3,000 hours.

HB1095 ultimately was not successful last year or this year, said Erika Miller, director of state advocacy and outreach for the AAPA. “But we do see it as a success, because in the 2022 session, we managed to get it passed in committee by a 10-to-1 vote,” she said. “It then moved to the full house and was not successful there.”

Ms. Miller said that South Dakota Senate Bill 134 would have removed the requirement for a legal PA/physician relationship after 1,040 hours, which is the requirement for nurse practitioners. “South Dakota had introduced similar legislation the year before, but also like Colorado, they went from not getting out of committee last year to making it to the senate floor this time,” she said.

In Wisconsin, the new PA-affiliated credentialing board began on April 1. It gives PAs the authority to license, discipline, and write regulations, Ms. Miller said.
 

South Central region

Arizona Senate Bill 1367 included direct pay, removed the relationship tether with a physician, and made each PA fully responsible for the care they provide. “The bill passed out of committee successfully but did not make it to a vote due to unexpected struggles between the Arizona medical society and PA chapter,” said Shannon Morey, senior director of state advocacy and outreach at the AAPA. “They are ready to go again next year.”

In Louisiana, Senate Bill 158 is a “strong” bill that addressed all the desired aspects of OTP, Ms. Morey said; “The legislation stands subject to call on the Senate floor, but it has been killed by the sponsor.”
 

Northeast region

Massachusetts Senate Bill 740 (S740) would remove the legal tether between PA and physician, said Carson Walker, senior director of state advocacy and outreach at the AAPA. “The committee decided to extend its time in committee until June,” he said. “By next month, we expect that the committee will schedule a hearing that includes S740, and we fully plan on submitting testimony.”

In New York, Senate Bill 9233 (S9233) would remove physician supervision after 3,600 hours of practice.

“Just about 10 days ago, sponsors were able to have S9233 introduced, which is the most succinct and, I think, the most effective OTP bill I have ever seen,” Mr. Walker said.

“S9233 says that after 3,600 hours a PA can practice without the supervision of a physician, and that’s all. There’s not a lot of time left in this session, but we are hopeful that it lays the groundwork for success next year.”

New Hampshire Senate Bill 228 has passed the legislature and is awaiting the governor’s signature. It will allow direct payment, make PAs responsible for the care they provide, and shift the physician-PA relationship from supervision to collaboration, Mr. Walker said.
 

Southeast region

Stephanie Radix, senior director of state advocacy and outreach at the AAPA, discussed North Carolina’s Senate Bill 345, which passed the Senate unanimously in 2021 and has been carried over to this year’s session. The bill defines team-based settings, eliminates the relationship tether, and establishes a supervised career entry interval of 4,000 clinical hours in the state.

The legislature is slated to adjourn June 30, Ms. Radix said: “We are very hopeful that we will get it across the finish line.”

In an interview, Mr. Bongiorno said that the AAPA’s overall advocacy progress is as expected.

“Optimal team practice is about allowing each practice to make that determination on how the team should work as a true collaboration,” he said. “The bottom line is that OTP would allow us to reach more patients, serve the community, and ensure that people are able to get healthcare, especially in underserved areas.”

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

INDIANAPOLIS – Recent legislative sessions in state legislative houses across the country have yielded progress toward codifying optimal team practice (OTP) into state law. That’s according to Phil Bongiorno, BA, senior vice president of advocacy and government relations at the American Academy of Physician Associates (AAPA), who spoke at the group’s annual meeting.

OTP refers to the AAPA’s goal of improving patient access to care and lessening administrative obligations by eliminating the legal requirement that there be a specific relationship between a PA, physician, or any other health care provider. This would allow a PA to practice to the full extent of their education, training, and experience, Mr. Bongiorno said.

The second tenet of OTP is to persuade states to create a separate majority PA board to regulate PAs. An alternative to this would be for states to add PAs and physicians who work with PAs to their medical or healing arts boards, he said.

Third, in an OTP environment, each state would authorize PAs to be eligible for direct payment by all public and private insurers. “We have seen that development at the federal level, as far as Medicare is concerned,” Mr. Bongiorno said. “Now, we’re focusing on making that happen in the individual states as well.”

According to Mr. Bongiorno, this year’s state advocacy priorities are to pursue new legislation in additional states, even as efforts continue to persuade state legislatures to act on carryover bills from the previous legislative session.

Mr. Bongiorno briefly summarized what he called “OTP successes” from 2021:

• Federal government: Authorized direct payment to PAs under Medicare
• Arkansas, Delaware, Illinois, Pennsylvania: Added one or more PAs to their medical boards
• Florida, Utah: Approved direct payment to PAs
• Tennessee, Wisconsin: Created a separate PA review board
• Utah, Wisconsin: Removed the relationship/agreement requirement (Wisconsin now requires 10,000 hours of practice to remove the relationship requirement)

North Central region

In Colorado, House Bill 1095 (HB1095) would have removed requirements for a legal relationship between a PA and a physician. Initially that would have happened after 3,000 hours of practice, although changing that to 5,000 hours has been a compromise measure. PAs changing specialties must collaborate for 2,000 hours, now negotiated to 3,000 hours.

HB1095 ultimately was not successful last year or this year, said Erika Miller, director of state advocacy and outreach for the AAPA. “But we do see it as a success, because in the 2022 session, we managed to get it passed in committee by a 10-to-1 vote,” she said. “It then moved to the full house and was not successful there.”

Ms. Miller said that South Dakota Senate Bill 134 would have removed the requirement for a legal PA/physician relationship after 1,040 hours, which is the requirement for nurse practitioners. “South Dakota had introduced similar legislation the year before, but also like Colorado, they went from not getting out of committee last year to making it to the senate floor this time,” she said.

In Wisconsin, the new PA-affiliated credentialing board began on April 1. It gives PAs the authority to license, discipline, and write regulations, Ms. Miller said.
 

South Central region

Arizona Senate Bill 1367 included direct pay, removed the relationship tether with a physician, and made each PA fully responsible for the care they provide. “The bill passed out of committee successfully but did not make it to a vote due to unexpected struggles between the Arizona medical society and PA chapter,” said Shannon Morey, senior director of state advocacy and outreach at the AAPA. “They are ready to go again next year.”

In Louisiana, Senate Bill 158 is a “strong” bill that addressed all the desired aspects of OTP, Ms. Morey said; “The legislation stands subject to call on the Senate floor, but it has been killed by the sponsor.”
 

Northeast region

Massachusetts Senate Bill 740 (S740) would remove the legal tether between PA and physician, said Carson Walker, senior director of state advocacy and outreach at the AAPA. “The committee decided to extend its time in committee until June,” he said. “By next month, we expect that the committee will schedule a hearing that includes S740, and we fully plan on submitting testimony.”

In New York, Senate Bill 9233 (S9233) would remove physician supervision after 3,600 hours of practice.

“Just about 10 days ago, sponsors were able to have S9233 introduced, which is the most succinct and, I think, the most effective OTP bill I have ever seen,” Mr. Walker said.

“S9233 says that after 3,600 hours a PA can practice without the supervision of a physician, and that’s all. There’s not a lot of time left in this session, but we are hopeful that it lays the groundwork for success next year.”

New Hampshire Senate Bill 228 has passed the legislature and is awaiting the governor’s signature. It will allow direct payment, make PAs responsible for the care they provide, and shift the physician-PA relationship from supervision to collaboration, Mr. Walker said.
 

Southeast region

Stephanie Radix, senior director of state advocacy and outreach at the AAPA, discussed North Carolina’s Senate Bill 345, which passed the Senate unanimously in 2021 and has been carried over to this year’s session. The bill defines team-based settings, eliminates the relationship tether, and establishes a supervised career entry interval of 4,000 clinical hours in the state.

The legislature is slated to adjourn June 30, Ms. Radix said: “We are very hopeful that we will get it across the finish line.”

In an interview, Mr. Bongiorno said that the AAPA’s overall advocacy progress is as expected.

“Optimal team practice is about allowing each practice to make that determination on how the team should work as a true collaboration,” he said. “The bottom line is that OTP would allow us to reach more patients, serve the community, and ensure that people are able to get healthcare, especially in underserved areas.”

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

INDIANAPOLIS – Recent legislative sessions in state legislative houses across the country have yielded progress toward codifying optimal team practice (OTP) into state law. That’s according to Phil Bongiorno, BA, senior vice president of advocacy and government relations at the American Academy of Physician Associates (AAPA), who spoke at the group’s annual meeting.

OTP refers to the AAPA’s goal of improving patient access to care and lessening administrative obligations by eliminating the legal requirement that there be a specific relationship between a PA, physician, or any other health care provider. This would allow a PA to practice to the full extent of their education, training, and experience, Mr. Bongiorno said.

The second tenet of OTP is to persuade states to create a separate majority PA board to regulate PAs. An alternative to this would be for states to add PAs and physicians who work with PAs to their medical or healing arts boards, he said.

Third, in an OTP environment, each state would authorize PAs to be eligible for direct payment by all public and private insurers. “We have seen that development at the federal level, as far as Medicare is concerned,” Mr. Bongiorno said. “Now, we’re focusing on making that happen in the individual states as well.”

According to Mr. Bongiorno, this year’s state advocacy priorities are to pursue new legislation in additional states, even as efforts continue to persuade state legislatures to act on carryover bills from the previous legislative session.

Mr. Bongiorno briefly summarized what he called “OTP successes” from 2021:

• Federal government: Authorized direct payment to PAs under Medicare
• Arkansas, Delaware, Illinois, Pennsylvania: Added one or more PAs to their medical boards
• Florida, Utah: Approved direct payment to PAs
• Tennessee, Wisconsin: Created a separate PA review board
• Utah, Wisconsin: Removed the relationship/agreement requirement (Wisconsin now requires 10,000 hours of practice to remove the relationship requirement)

North Central region

In Colorado, House Bill 1095 (HB1095) would have removed requirements for a legal relationship between a PA and a physician. Initially that would have happened after 3,000 hours of practice, although changing that to 5,000 hours has been a compromise measure. PAs changing specialties must collaborate for 2,000 hours, now negotiated to 3,000 hours.

HB1095 ultimately was not successful last year or this year, said Erika Miller, director of state advocacy and outreach for the AAPA. “But we do see it as a success, because in the 2022 session, we managed to get it passed in committee by a 10-to-1 vote,” she said. “It then moved to the full house and was not successful there.”

Ms. Miller said that South Dakota Senate Bill 134 would have removed the requirement for a legal PA/physician relationship after 1,040 hours, which is the requirement for nurse practitioners. “South Dakota had introduced similar legislation the year before, but also like Colorado, they went from not getting out of committee last year to making it to the senate floor this time,” she said.

In Wisconsin, the new PA-affiliated credentialing board began on April 1. It gives PAs the authority to license, discipline, and write regulations, Ms. Miller said.
 

South Central region

Arizona Senate Bill 1367 included direct pay, removed the relationship tether with a physician, and made each PA fully responsible for the care they provide. “The bill passed out of committee successfully but did not make it to a vote due to unexpected struggles between the Arizona medical society and PA chapter,” said Shannon Morey, senior director of state advocacy and outreach at the AAPA. “They are ready to go again next year.”

In Louisiana, Senate Bill 158 is a “strong” bill that addressed all the desired aspects of OTP, Ms. Morey said; “The legislation stands subject to call on the Senate floor, but it has been killed by the sponsor.”
 

Northeast region

Massachusetts Senate Bill 740 (S740) would remove the legal tether between PA and physician, said Carson Walker, senior director of state advocacy and outreach at the AAPA. “The committee decided to extend its time in committee until June,” he said. “By next month, we expect that the committee will schedule a hearing that includes S740, and we fully plan on submitting testimony.”

In New York, Senate Bill 9233 (S9233) would remove physician supervision after 3,600 hours of practice.

“Just about 10 days ago, sponsors were able to have S9233 introduced, which is the most succinct and, I think, the most effective OTP bill I have ever seen,” Mr. Walker said.

“S9233 says that after 3,600 hours a PA can practice without the supervision of a physician, and that’s all. There’s not a lot of time left in this session, but we are hopeful that it lays the groundwork for success next year.”

New Hampshire Senate Bill 228 has passed the legislature and is awaiting the governor’s signature. It will allow direct payment, make PAs responsible for the care they provide, and shift the physician-PA relationship from supervision to collaboration, Mr. Walker said.
 

Southeast region

Stephanie Radix, senior director of state advocacy and outreach at the AAPA, discussed North Carolina’s Senate Bill 345, which passed the Senate unanimously in 2021 and has been carried over to this year’s session. The bill defines team-based settings, eliminates the relationship tether, and establishes a supervised career entry interval of 4,000 clinical hours in the state.

The legislature is slated to adjourn June 30, Ms. Radix said: “We are very hopeful that we will get it across the finish line.”

In an interview, Mr. Bongiorno said that the AAPA’s overall advocacy progress is as expected.

“Optimal team practice is about allowing each practice to make that determination on how the team should work as a true collaboration,” he said. “The bottom line is that OTP would allow us to reach more patients, serve the community, and ensure that people are able to get healthcare, especially in underserved areas.”

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

Yet another study has found that vitamin D supplementation doesn’t reduce the risk of developing type 2 diabetes in the general population with prediabetes, but it does leave the door open for benefit in those with low insulin secretion.

The new findings come from the prospective Diabetes Prevention With Active Vitamin D (DPVD) trial of more than 1,200 Japanese participants with impaired glucose tolerance.

The data were published online in The BMJ by Tetsuya Kawahara, MD, PhD, of Shin Komonji Hospital, Kitakyushu, Japan, and colleagues.

Treatment with 0.75 μg/day of eldecalcitol, an active vitamin D analogue, for 3 years did not prevent progression from prediabetes to type 2 diabetes, nor did it improve the rate of regression to normoglycemia, compared with placebo.

However, “we showed a preventive effect of eldecalcitol after adjusting for covariables ... The preventive effect of eldecalcitol on development of type 2 diabetes in a prediabetic population was seen especially among participants with insulin insufficiency,” wrote Dr. Kawahara and colleagues.
 

‘Remarkably similar’ results in several trials

The new trial is “well conducted, with rigorously defined and tested diagnostic criteria, and of sufficient duration, but it may have been underpowered to detect a small effect,” Tatiana Christides, MD, PhD, of Queen Mary University of London, wrote in an accompanying editorial.

Dr. Christides notes that a recent meta-analysis of intervention trials did find a significant 10% reduction in risk of type 2 diabetes with vitamin D supplementation, “a difference too small to be detected by the new trial ... Although a 10% risk reduction is modest, it may be valuable at the population level and justifies further study.”

The new finding, a nonsignificant 13% relative reduction in risk, is similar to the 13% relative risk reduction found in the Vitamin D and Type 2 Diabetes (D2d) trial reported in 2019.

But in that study as in this one, there was a suggested benefit in a subset of people. In D2d, it was in those who were vitamin D deficient.  

Asked to comment, D2d lead investigator Anastassios G. Pittas, MD, chief of the division of diabetes, endocrinology, and metabolism at Tufts University, Boston, pointed out that the results were also “remarkably similar” to those of a third study from Norway published in 2014, which also found a 13% relative risk reduction.

“The nearly identical results from the three trials that were specifically designed and conducted to test whether vitamin D supplementation lowers diabetes clearly points to a beneficial effect of vitamin D for diabetes risk reduction. However, the overall effect in people not selected for vitamin D insufficiency seems to be less than hypothesized in each trial,” Dr. Pittas said in an interview.  

He added, “there will be no more specific vitamin D and diabetes prevention trials, so we need to continue gaining insights from these three trials.”

Some patients with prediabetes may benefit from vitamin D

Dr. Pittas advised that although the overall effect is modest in people with prediabetes who aren’t selected for vitamin D deficiency, “given how prevalent prediabetes and type 2 diabetes are, clinicians and patients should consider vitamin D supplementation as an adjunct to weight loss for diabetes prevention. Based on analyses from the D2d study, people with prediabetes who have low levels of vitamin D and are nonobese derive the most benefit.”

He noted that secondary analyses from D2d also suggest greater benefit among those achieving higher blood levels of vitamin D, but that high supplemental doses could cause adverse musculoskeletal outcomes in older adults, “so the benefit–harm ratio needs to be ascertained individually.”

Dr. Christides advised, “Until further data are available from high-quality randomized trials, health care professionals should continue to discuss with patients the musculoskeletal health benefits of vitamin D and support them to achieve and maintain lifestyle changes that, although challenging to sustain, are known to decrease development of [type 2 diabetes].”
 

DPVD: Hint of benefit in those with greater insulin resistance

The double-blind, multicenter, randomized, placebo-controlled DPVD trial took place from June 1, 2013, through Aug. 31, 2015, and involved 1,256 participants with impaired glucose tolerance (with or without impaired fasting glucose) from 32 institutions in Japan. They were randomized 1:1 to receive eldecalcitol or placebo for 3 years.

During the 3-year period, 12.5% of the 630 patients in the eldecalcitol group and 14.2% of the 626 patients in the placebo group developed diabetes. The difference was not significant, with a hazard ratio (HR) of 0.87 (P = .39). There was no difference in regression to normoglycemia, which had occurred in 23.0% with eldecalcitol versus 20.1% with placebo by the end of the study (P = .21).

However, eldecalcitol was effective for preventing the development of type 2 diabetes after adjustment for prespecified variables, including age, sex, hypertension, body mass index, family history of diabetes, 2-hour plasma glucose, 25-hydroxyvitamin D, and insulin resistance (HR, 0.69; P = .02).

In a post hoc analysis, eldecalcitol significantly prevented the development of type 2 diabetes among those with the lowest divisions of homeostatic model assessment (HOMA)-β (HR, 0.35; P < .001), HOMA-insulin resistance (HR, 0.37; P = .001), and fasting immunoreactive insulin (HR, 0.41; P = .001).

“These results indicate that eldecalcitol had a beneficial effect on insufficient basal insulin secretion,” Dr. Kawahara and colleagues wrote.

Discontinuations due to adverse events occurred in 4.1% with eldecalcitol and 3.4% in the placebo group (HR, 1.23; P = .47). Rates and types of adverse events didn’t differ significantly between the two groups.

The study was supported by a grant from the Kitakyushu Medical Association. The authors had no further disclosures. Dr. Christides had no disclosures. Dr. Pittas has reported receiving funding from the National Institutes of Health.

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

Yet another study has found that vitamin D supplementation doesn’t reduce the risk of developing type 2 diabetes in the general population with prediabetes, but it does leave the door open for benefit in those with low insulin secretion.

The new findings come from the prospective Diabetes Prevention With Active Vitamin D (DPVD) trial of more than 1,200 Japanese participants with impaired glucose tolerance.

The data were published online in The BMJ by Tetsuya Kawahara, MD, PhD, of Shin Komonji Hospital, Kitakyushu, Japan, and colleagues.

Treatment with 0.75 μg/day of eldecalcitol, an active vitamin D analogue, for 3 years did not prevent progression from prediabetes to type 2 diabetes, nor did it improve the rate of regression to normoglycemia, compared with placebo.

However, “we showed a preventive effect of eldecalcitol after adjusting for covariables ... The preventive effect of eldecalcitol on development of type 2 diabetes in a prediabetic population was seen especially among participants with insulin insufficiency,” wrote Dr. Kawahara and colleagues.
 

‘Remarkably similar’ results in several trials

The new trial is “well conducted, with rigorously defined and tested diagnostic criteria, and of sufficient duration, but it may have been underpowered to detect a small effect,” Tatiana Christides, MD, PhD, of Queen Mary University of London, wrote in an accompanying editorial.

Dr. Christides notes that a recent meta-analysis of intervention trials did find a significant 10% reduction in risk of type 2 diabetes with vitamin D supplementation, “a difference too small to be detected by the new trial ... Although a 10% risk reduction is modest, it may be valuable at the population level and justifies further study.”

The new finding, a nonsignificant 13% relative reduction in risk, is similar to the 13% relative risk reduction found in the Vitamin D and Type 2 Diabetes (D2d) trial reported in 2019.

But in that study as in this one, there was a suggested benefit in a subset of people. In D2d, it was in those who were vitamin D deficient.  

Asked to comment, D2d lead investigator Anastassios G. Pittas, MD, chief of the division of diabetes, endocrinology, and metabolism at Tufts University, Boston, pointed out that the results were also “remarkably similar” to those of a third study from Norway published in 2014, which also found a 13% relative risk reduction.

“The nearly identical results from the three trials that were specifically designed and conducted to test whether vitamin D supplementation lowers diabetes clearly points to a beneficial effect of vitamin D for diabetes risk reduction. However, the overall effect in people not selected for vitamin D insufficiency seems to be less than hypothesized in each trial,” Dr. Pittas said in an interview.  

He added, “there will be no more specific vitamin D and diabetes prevention trials, so we need to continue gaining insights from these three trials.”

Some patients with prediabetes may benefit from vitamin D

Dr. Pittas advised that although the overall effect is modest in people with prediabetes who aren’t selected for vitamin D deficiency, “given how prevalent prediabetes and type 2 diabetes are, clinicians and patients should consider vitamin D supplementation as an adjunct to weight loss for diabetes prevention. Based on analyses from the D2d study, people with prediabetes who have low levels of vitamin D and are nonobese derive the most benefit.”

He noted that secondary analyses from D2d also suggest greater benefit among those achieving higher blood levels of vitamin D, but that high supplemental doses could cause adverse musculoskeletal outcomes in older adults, “so the benefit–harm ratio needs to be ascertained individually.”

Dr. Christides advised, “Until further data are available from high-quality randomized trials, health care professionals should continue to discuss with patients the musculoskeletal health benefits of vitamin D and support them to achieve and maintain lifestyle changes that, although challenging to sustain, are known to decrease development of [type 2 diabetes].”
 

DPVD: Hint of benefit in those with greater insulin resistance

The double-blind, multicenter, randomized, placebo-controlled DPVD trial took place from June 1, 2013, through Aug. 31, 2015, and involved 1,256 participants with impaired glucose tolerance (with or without impaired fasting glucose) from 32 institutions in Japan. They were randomized 1:1 to receive eldecalcitol or placebo for 3 years.

During the 3-year period, 12.5% of the 630 patients in the eldecalcitol group and 14.2% of the 626 patients in the placebo group developed diabetes. The difference was not significant, with a hazard ratio (HR) of 0.87 (P = .39). There was no difference in regression to normoglycemia, which had occurred in 23.0% with eldecalcitol versus 20.1% with placebo by the end of the study (P = .21).

However, eldecalcitol was effective for preventing the development of type 2 diabetes after adjustment for prespecified variables, including age, sex, hypertension, body mass index, family history of diabetes, 2-hour plasma glucose, 25-hydroxyvitamin D, and insulin resistance (HR, 0.69; P = .02).

In a post hoc analysis, eldecalcitol significantly prevented the development of type 2 diabetes among those with the lowest divisions of homeostatic model assessment (HOMA)-β (HR, 0.35; P < .001), HOMA-insulin resistance (HR, 0.37; P = .001), and fasting immunoreactive insulin (HR, 0.41; P = .001).

“These results indicate that eldecalcitol had a beneficial effect on insufficient basal insulin secretion,” Dr. Kawahara and colleagues wrote.

Discontinuations due to adverse events occurred in 4.1% with eldecalcitol and 3.4% in the placebo group (HR, 1.23; P = .47). Rates and types of adverse events didn’t differ significantly between the two groups.

The study was supported by a grant from the Kitakyushu Medical Association. The authors had no further disclosures. Dr. Christides had no disclosures. Dr. Pittas has reported receiving funding from the National Institutes of Health.

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

Yet another study has found that vitamin D supplementation doesn’t reduce the risk of developing type 2 diabetes in the general population with prediabetes, but it does leave the door open for benefit in those with low insulin secretion.

The new findings come from the prospective Diabetes Prevention With Active Vitamin D (DPVD) trial of more than 1,200 Japanese participants with impaired glucose tolerance.

The data were published online in The BMJ by Tetsuya Kawahara, MD, PhD, of Shin Komonji Hospital, Kitakyushu, Japan, and colleagues.

Treatment with 0.75 μg/day of eldecalcitol, an active vitamin D analogue, for 3 years did not prevent progression from prediabetes to type 2 diabetes, nor did it improve the rate of regression to normoglycemia, compared with placebo.

However, “we showed a preventive effect of eldecalcitol after adjusting for covariables ... The preventive effect of eldecalcitol on development of type 2 diabetes in a prediabetic population was seen especially among participants with insulin insufficiency,” wrote Dr. Kawahara and colleagues.
 

‘Remarkably similar’ results in several trials

The new trial is “well conducted, with rigorously defined and tested diagnostic criteria, and of sufficient duration, but it may have been underpowered to detect a small effect,” Tatiana Christides, MD, PhD, of Queen Mary University of London, wrote in an accompanying editorial.

Dr. Christides notes that a recent meta-analysis of intervention trials did find a significant 10% reduction in risk of type 2 diabetes with vitamin D supplementation, “a difference too small to be detected by the new trial ... Although a 10% risk reduction is modest, it may be valuable at the population level and justifies further study.”

The new finding, a nonsignificant 13% relative reduction in risk, is similar to the 13% relative risk reduction found in the Vitamin D and Type 2 Diabetes (D2d) trial reported in 2019.

But in that study as in this one, there was a suggested benefit in a subset of people. In D2d, it was in those who were vitamin D deficient.  

Asked to comment, D2d lead investigator Anastassios G. Pittas, MD, chief of the division of diabetes, endocrinology, and metabolism at Tufts University, Boston, pointed out that the results were also “remarkably similar” to those of a third study from Norway published in 2014, which also found a 13% relative risk reduction.

“The nearly identical results from the three trials that were specifically designed and conducted to test whether vitamin D supplementation lowers diabetes clearly points to a beneficial effect of vitamin D for diabetes risk reduction. However, the overall effect in people not selected for vitamin D insufficiency seems to be less than hypothesized in each trial,” Dr. Pittas said in an interview.  

He added, “there will be no more specific vitamin D and diabetes prevention trials, so we need to continue gaining insights from these three trials.”

Some patients with prediabetes may benefit from vitamin D

Dr. Pittas advised that although the overall effect is modest in people with prediabetes who aren’t selected for vitamin D deficiency, “given how prevalent prediabetes and type 2 diabetes are, clinicians and patients should consider vitamin D supplementation as an adjunct to weight loss for diabetes prevention. Based on analyses from the D2d study, people with prediabetes who have low levels of vitamin D and are nonobese derive the most benefit.”

He noted that secondary analyses from D2d also suggest greater benefit among those achieving higher blood levels of vitamin D, but that high supplemental doses could cause adverse musculoskeletal outcomes in older adults, “so the benefit–harm ratio needs to be ascertained individually.”

Dr. Christides advised, “Until further data are available from high-quality randomized trials, health care professionals should continue to discuss with patients the musculoskeletal health benefits of vitamin D and support them to achieve and maintain lifestyle changes that, although challenging to sustain, are known to decrease development of [type 2 diabetes].”
 

DPVD: Hint of benefit in those with greater insulin resistance

The double-blind, multicenter, randomized, placebo-controlled DPVD trial took place from June 1, 2013, through Aug. 31, 2015, and involved 1,256 participants with impaired glucose tolerance (with or without impaired fasting glucose) from 32 institutions in Japan. They were randomized 1:1 to receive eldecalcitol or placebo for 3 years.

During the 3-year period, 12.5% of the 630 patients in the eldecalcitol group and 14.2% of the 626 patients in the placebo group developed diabetes. The difference was not significant, with a hazard ratio (HR) of 0.87 (P = .39). There was no difference in regression to normoglycemia, which had occurred in 23.0% with eldecalcitol versus 20.1% with placebo by the end of the study (P = .21).

However, eldecalcitol was effective for preventing the development of type 2 diabetes after adjustment for prespecified variables, including age, sex, hypertension, body mass index, family history of diabetes, 2-hour plasma glucose, 25-hydroxyvitamin D, and insulin resistance (HR, 0.69; P = .02).

In a post hoc analysis, eldecalcitol significantly prevented the development of type 2 diabetes among those with the lowest divisions of homeostatic model assessment (HOMA)-β (HR, 0.35; P < .001), HOMA-insulin resistance (HR, 0.37; P = .001), and fasting immunoreactive insulin (HR, 0.41; P = .001).

“These results indicate that eldecalcitol had a beneficial effect on insufficient basal insulin secretion,” Dr. Kawahara and colleagues wrote.

Discontinuations due to adverse events occurred in 4.1% with eldecalcitol and 3.4% in the placebo group (HR, 1.23; P = .47). Rates and types of adverse events didn’t differ significantly between the two groups.

The study was supported by a grant from the Kitakyushu Medical Association. The authors had no further disclosures. Dr. Christides had no disclosures. Dr. Pittas has reported receiving funding from the National Institutes of Health.

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

The Catholic University of Louvain (Belgium) announced that its researchers have managed to identify the key that allows the COVID-19 virus to attack cells. What’s more, they have succeeded in closing the lock to block the virus and prevent it from interacting with the cell, thereby preventing infection.

UCLouvain emphasized that this discovery, which was published in Nature Communications, is sparking hope that an aerosol antiviral therapy can be developed that would eradicate the virus in the case of an infection or a high-risk contact.

For 2 years, the team under David Alsteens, PhD, a researcher at the UCLouvain Institute of Biomolecular Science and Technology, has been working hard to understand the precise molecular mechanisms the virus uses to infect a cell. They investigated the interaction between sialic acids, a kind of sugar residue present on the surface of cells, and the SARS-CoV-2 spike (S) protein to clarify its role in the infection process.

It was already known that the function of the sugar residues that coat the cells is to promote cell recognition, thus enabling, in particular, viruses to identify their targets more easily, but also to provide them with a point of attachment and to facilitate infection of the cells.

The researchers have now revealed a variant of these sugars that interacts more strongly with the S protein than other sugars do.

In other words, the university explained, they found the set of keys that allows the virus to open the cell door. So, the researchers decided to catch the virus in its own trap, by preventing it from attaching to its host cell. To do this, they blocked the S protein’s points of attachment, thus suppressing any interaction with the cell surface, as if a padlock had been placed on the lock on the cell’s entry door.

Th researchers added that the advantage of this discovery is that it acts on the virus, irrespective of mutations.

The team of researchers will now conduct tests on mice to apply this blocking of virus binding sites and observe whether it works on the body. The results should make it possible to develop an antiviral therapy administered by aerosol in the case of infection or at-risk contact.

This discovery is also of interest for the future to counter other viruses with similar attachment factors.

This article was translated from MediQuality; a version appeared on Medscape.com.

The Catholic University of Louvain (Belgium) announced that its researchers have managed to identify the key that allows the COVID-19 virus to attack cells. What’s more, they have succeeded in closing the lock to block the virus and prevent it from interacting with the cell, thereby preventing infection.

UCLouvain emphasized that this discovery, which was published in Nature Communications, is sparking hope that an aerosol antiviral therapy can be developed that would eradicate the virus in the case of an infection or a high-risk contact.

For 2 years, the team under David Alsteens, PhD, a researcher at the UCLouvain Institute of Biomolecular Science and Technology, has been working hard to understand the precise molecular mechanisms the virus uses to infect a cell. They investigated the interaction between sialic acids, a kind of sugar residue present on the surface of cells, and the SARS-CoV-2 spike (S) protein to clarify its role in the infection process.

It was already known that the function of the sugar residues that coat the cells is to promote cell recognition, thus enabling, in particular, viruses to identify their targets more easily, but also to provide them with a point of attachment and to facilitate infection of the cells.

The researchers have now revealed a variant of these sugars that interacts more strongly with the S protein than other sugars do.

In other words, the university explained, they found the set of keys that allows the virus to open the cell door. So, the researchers decided to catch the virus in its own trap, by preventing it from attaching to its host cell. To do this, they blocked the S protein’s points of attachment, thus suppressing any interaction with the cell surface, as if a padlock had been placed on the lock on the cell’s entry door.

Th researchers added that the advantage of this discovery is that it acts on the virus, irrespective of mutations.

The team of researchers will now conduct tests on mice to apply this blocking of virus binding sites and observe whether it works on the body. The results should make it possible to develop an antiviral therapy administered by aerosol in the case of infection or at-risk contact.

This discovery is also of interest for the future to counter other viruses with similar attachment factors.

This article was translated from MediQuality; a version appeared on Medscape.com.

The Catholic University of Louvain (Belgium) announced that its researchers have managed to identify the key that allows the COVID-19 virus to attack cells. What’s more, they have succeeded in closing the lock to block the virus and prevent it from interacting with the cell, thereby preventing infection.

UCLouvain emphasized that this discovery, which was published in Nature Communications, is sparking hope that an aerosol antiviral therapy can be developed that would eradicate the virus in the case of an infection or a high-risk contact.

For 2 years, the team under David Alsteens, PhD, a researcher at the UCLouvain Institute of Biomolecular Science and Technology, has been working hard to understand the precise molecular mechanisms the virus uses to infect a cell. They investigated the interaction between sialic acids, a kind of sugar residue present on the surface of cells, and the SARS-CoV-2 spike (S) protein to clarify its role in the infection process.

It was already known that the function of the sugar residues that coat the cells is to promote cell recognition, thus enabling, in particular, viruses to identify their targets more easily, but also to provide them with a point of attachment and to facilitate infection of the cells.

The researchers have now revealed a variant of these sugars that interacts more strongly with the S protein than other sugars do.

In other words, the university explained, they found the set of keys that allows the virus to open the cell door. So, the researchers decided to catch the virus in its own trap, by preventing it from attaching to its host cell. To do this, they blocked the S protein’s points of attachment, thus suppressing any interaction with the cell surface, as if a padlock had been placed on the lock on the cell’s entry door.

Th researchers added that the advantage of this discovery is that it acts on the virus, irrespective of mutations.

The team of researchers will now conduct tests on mice to apply this blocking of virus binding sites and observe whether it works on the body. The results should make it possible to develop an antiviral therapy administered by aerosol in the case of infection or at-risk contact.

This discovery is also of interest for the future to counter other viruses with similar attachment factors.

This article was translated from MediQuality; a version appeared on Medscape.com.

Sildenafil (Viagra, Pfizer), a phosphodieterase-5 (PDE-5) inhibitor and a pulmonary-selective vasodilator, may reduce mortality in patients with idiopathic pulmonary fibrosis (IPF), compared with placebo or standard of care but it does not reduce hospitalizations or acute exacerbations from the disorder, a small meta-analysis suggests.

“There have only been four trials investigating sildenafil [in IPF] and the results were very close to being statistically significant so the addition of a few events would cause that to be true,” Tyler Pitre, MD, McMaster University, Hamilton, Ont., and Dena Zeraatkar, PhD, Harvard Medical School, Boston, told this news organization in a joint email.

“So lack of statistical significance does not preclude benefit,” they added, “and we think these results warrant additional trials and, if results remain consistent, [we] suspect the next update of the analysis may demonstrate statistical significance.”

The study was published online in Pulmonary Pharmacology & Therapeutics.
 

Reanalysis necessary

As the investigators pointed out, the most recent international guidelines have a conditional recommendation against the use of sildenafil in IPF patients so reanalysis of the data was felt to be necessary in order to inform upcoming guidelines. The purpose of the review was to provide an update of the evidence as to whether sildenafil not only provides mortality benefit in this patient population but also whether it improves overall lung function, reduces exacerbations and hospitalizations along with adverse events (AEs) leading to drug discontinuation.

The four studies included in the meta-analysis were all randomized, controlled trials in which either standalone PDE-5 inhibitors were compared with placebo or with standard IPF care with either pirfenidone (Esbroef ) or nintedanib (Ofev). The age of participants across the trials ranged from 68.6 years to 70.4 years and participants were predominantly male.

Follow-up ranged from just 12 weeks to 52 weeks. “Four trials including 659 patients and 88 deaths, reported on mortality,” the investigators noted. At a relative risk reduction of 0.73 (95% confidence interval, 0.51-1.04), the investigators concluded with moderate certainty that sildenafil probably reduces mortality in IPF patients.

Four trials including 659 patients reported on acute exacerbations and hospitalizations. At a RR of 1.10 (95% CI, 0.61-1.67), pooled results showed sildenafil may not reduce hospitalizations or acute exacerbations, compared with controls, although this conclusion was reached with low certainty. Four trials containing slightly more patients at 661 participants reported on AEs leading to drug discontinuation.

Again with moderate certainty, the authors concluded there is probably no difference in drug discontinuation rates because of AEs when comparing sildenafil to controls, at a RR of 0.79 (95% CI, 0.56-1.10). Four trials including 602 patients reported on lung function changes while diffusion capacity of carbon monoxide (DLCO) results were available for 487 patients. Based on these four trials, sildenafil may not change the decline of forced vital capacity (FVC) at a mean difference of 0.61% (95% CI, –0.29 to 1.59), compared with standard of care or placebo.

Nor may it change the rate of DLCO decline at a MD of 0.97 (95% CI, 0.04-1.90), both outcomes again being rated with moderate certainty. Asked if the combination of either nintedanib plus sildenafil or pirfenidone plus sildenafil led to a mortality benefit in IPF patients, Dr. Pitre and Dr. Zeraatkar noted that there was no mortality benefit in either the INSTAGE trial or in another recent study published in Lancet Respiratory Medicine.

“However, both of these trials were quite small and therefore unlikely to detect a mortality benefit,” Dr. Pitre and Dr. Zeraatkar noted. Indeed, the benefit of doing a systematic review is the ability to pool event rates across trials to see if a benefit emerges as well as to evaluate the consistency of the direction of these effects.

“Our review presented the most up-to-date and comprehensive summary of the evidence on sildenafil therapy for IPF patients,” the authors stated.

While they did acknowledge that the mortality benefit seen with sildenafil over placebo or standard of care did not reach statistical significance, this was likely because of too few patients and events. For example, in a systematic review published in the New England Journal of Medicine in 1988, the authors were able to show a statistically significant benefit on 5-year mortality risk with the combination of tamoxifen and cytotoxic therapy whereas none of the individual trials analyzed were able to detect a mortality benefit because they were underpowered.

“Similarly, we suggest that something like this is possible with sildenafil, as the three major trials addressing sildenafil show the same direction toward benefit with little inconsistency,” Dr. Pitre and Dr. Zeraatkar noted.

“We should not exclude benefits based on P values alone,” they said, adding: “Clearly out systematic review is not going to change clinical practice given the uncertainty of the results but I do think that in a disease such as IPF, further research is warranted in targeted patient populations [and] for clinicians, we suggest they keep an open mind to sildenafil.”

Commentary

Asked to comment on the findings, Krishna Thavarajah, MD, director of the interstitial lung disease program at Henry Ford Hospital and clinical assistant professor at Wayne State University, both in Detroit, agreed with the authors that the lack of a statistically significant mortality benefit seen in the meta-analysis does not necessarily translate into a lack of benefit from the use of sildenafil in IPF patients. “As the authors point out, there are simply not enough data available to know if there is a mortality benefit, limited by the variable follow-up times and IPF patients targeted with or without pulmonary hypertension.”

Indeed, Dr. Thavarajah felt that a mortality benefit might be difficult to show in IPF patients, especially those on antifibrotics, given the duration of the studies analyzed and the number of patients needed to be able to show a statistically significant difference. “I myself have not prescribed sildenafil for IPF patients given the lack of clear data,” Dr. Thavarajah acknowledged.

“[But] the meta-analysis shows that sildenafil could have a mortality benefit in IPF patients without evidence of a benefit in FVC, DLCO, or acute exacerbations,” she confirmed, agreeing that further study would be helpful in assessing the potential for sildenafil to provide a mortality benefit in IPF patients.

No funding for the study was reported. Neither the authors nor Dr. Thavarajah had any conflicts of interest to declare.

Sildenafil (Viagra, Pfizer), a phosphodieterase-5 (PDE-5) inhibitor and a pulmonary-selective vasodilator, may reduce mortality in patients with idiopathic pulmonary fibrosis (IPF), compared with placebo or standard of care but it does not reduce hospitalizations or acute exacerbations from the disorder, a small meta-analysis suggests.

“There have only been four trials investigating sildenafil [in IPF] and the results were very close to being statistically significant so the addition of a few events would cause that to be true,” Tyler Pitre, MD, McMaster University, Hamilton, Ont., and Dena Zeraatkar, PhD, Harvard Medical School, Boston, told this news organization in a joint email.

“So lack of statistical significance does not preclude benefit,” they added, “and we think these results warrant additional trials and, if results remain consistent, [we] suspect the next update of the analysis may demonstrate statistical significance.”

The study was published online in Pulmonary Pharmacology & Therapeutics.
 

Reanalysis necessary

As the investigators pointed out, the most recent international guidelines have a conditional recommendation against the use of sildenafil in IPF patients so reanalysis of the data was felt to be necessary in order to inform upcoming guidelines. The purpose of the review was to provide an update of the evidence as to whether sildenafil not only provides mortality benefit in this patient population but also whether it improves overall lung function, reduces exacerbations and hospitalizations along with adverse events (AEs) leading to drug discontinuation.

The four studies included in the meta-analysis were all randomized, controlled trials in which either standalone PDE-5 inhibitors were compared with placebo or with standard IPF care with either pirfenidone (Esbroef ) or nintedanib (Ofev). The age of participants across the trials ranged from 68.6 years to 70.4 years and participants were predominantly male.

Follow-up ranged from just 12 weeks to 52 weeks. “Four trials including 659 patients and 88 deaths, reported on mortality,” the investigators noted. At a relative risk reduction of 0.73 (95% confidence interval, 0.51-1.04), the investigators concluded with moderate certainty that sildenafil probably reduces mortality in IPF patients.

Four trials including 659 patients reported on acute exacerbations and hospitalizations. At a RR of 1.10 (95% CI, 0.61-1.67), pooled results showed sildenafil may not reduce hospitalizations or acute exacerbations, compared with controls, although this conclusion was reached with low certainty. Four trials containing slightly more patients at 661 participants reported on AEs leading to drug discontinuation.

Again with moderate certainty, the authors concluded there is probably no difference in drug discontinuation rates because of AEs when comparing sildenafil to controls, at a RR of 0.79 (95% CI, 0.56-1.10). Four trials including 602 patients reported on lung function changes while diffusion capacity of carbon monoxide (DLCO) results were available for 487 patients. Based on these four trials, sildenafil may not change the decline of forced vital capacity (FVC) at a mean difference of 0.61% (95% CI, –0.29 to 1.59), compared with standard of care or placebo.

Nor may it change the rate of DLCO decline at a MD of 0.97 (95% CI, 0.04-1.90), both outcomes again being rated with moderate certainty. Asked if the combination of either nintedanib plus sildenafil or pirfenidone plus sildenafil led to a mortality benefit in IPF patients, Dr. Pitre and Dr. Zeraatkar noted that there was no mortality benefit in either the INSTAGE trial or in another recent study published in Lancet Respiratory Medicine.

“However, both of these trials were quite small and therefore unlikely to detect a mortality benefit,” Dr. Pitre and Dr. Zeraatkar noted. Indeed, the benefit of doing a systematic review is the ability to pool event rates across trials to see if a benefit emerges as well as to evaluate the consistency of the direction of these effects.

“Our review presented the most up-to-date and comprehensive summary of the evidence on sildenafil therapy for IPF patients,” the authors stated.

While they did acknowledge that the mortality benefit seen with sildenafil over placebo or standard of care did not reach statistical significance, this was likely because of too few patients and events. For example, in a systematic review published in the New England Journal of Medicine in 1988, the authors were able to show a statistically significant benefit on 5-year mortality risk with the combination of tamoxifen and cytotoxic therapy whereas none of the individual trials analyzed were able to detect a mortality benefit because they were underpowered.

“Similarly, we suggest that something like this is possible with sildenafil, as the three major trials addressing sildenafil show the same direction toward benefit with little inconsistency,” Dr. Pitre and Dr. Zeraatkar noted.

“We should not exclude benefits based on P values alone,” they said, adding: “Clearly out systematic review is not going to change clinical practice given the uncertainty of the results but I do think that in a disease such as IPF, further research is warranted in targeted patient populations [and] for clinicians, we suggest they keep an open mind to sildenafil.”

Commentary

Asked to comment on the findings, Krishna Thavarajah, MD, director of the interstitial lung disease program at Henry Ford Hospital and clinical assistant professor at Wayne State University, both in Detroit, agreed with the authors that the lack of a statistically significant mortality benefit seen in the meta-analysis does not necessarily translate into a lack of benefit from the use of sildenafil in IPF patients. “As the authors point out, there are simply not enough data available to know if there is a mortality benefit, limited by the variable follow-up times and IPF patients targeted with or without pulmonary hypertension.”

Indeed, Dr. Thavarajah felt that a mortality benefit might be difficult to show in IPF patients, especially those on antifibrotics, given the duration of the studies analyzed and the number of patients needed to be able to show a statistically significant difference. “I myself have not prescribed sildenafil for IPF patients given the lack of clear data,” Dr. Thavarajah acknowledged.

“[But] the meta-analysis shows that sildenafil could have a mortality benefit in IPF patients without evidence of a benefit in FVC, DLCO, or acute exacerbations,” she confirmed, agreeing that further study would be helpful in assessing the potential for sildenafil to provide a mortality benefit in IPF patients.

No funding for the study was reported. Neither the authors nor Dr. Thavarajah had any conflicts of interest to declare.

Sildenafil (Viagra, Pfizer), a phosphodieterase-5 (PDE-5) inhibitor and a pulmonary-selective vasodilator, may reduce mortality in patients with idiopathic pulmonary fibrosis (IPF), compared with placebo or standard of care but it does not reduce hospitalizations or acute exacerbations from the disorder, a small meta-analysis suggests.

“There have only been four trials investigating sildenafil [in IPF] and the results were very close to being statistically significant so the addition of a few events would cause that to be true,” Tyler Pitre, MD, McMaster University, Hamilton, Ont., and Dena Zeraatkar, PhD, Harvard Medical School, Boston, told this news organization in a joint email.

“So lack of statistical significance does not preclude benefit,” they added, “and we think these results warrant additional trials and, if results remain consistent, [we] suspect the next update of the analysis may demonstrate statistical significance.”

The study was published online in Pulmonary Pharmacology & Therapeutics.
 

Reanalysis necessary

As the investigators pointed out, the most recent international guidelines have a conditional recommendation against the use of sildenafil in IPF patients so reanalysis of the data was felt to be necessary in order to inform upcoming guidelines. The purpose of the review was to provide an update of the evidence as to whether sildenafil not only provides mortality benefit in this patient population but also whether it improves overall lung function, reduces exacerbations and hospitalizations along with adverse events (AEs) leading to drug discontinuation.

The four studies included in the meta-analysis were all randomized, controlled trials in which either standalone PDE-5 inhibitors were compared with placebo or with standard IPF care with either pirfenidone (Esbroef ) or nintedanib (Ofev). The age of participants across the trials ranged from 68.6 years to 70.4 years and participants were predominantly male.

Follow-up ranged from just 12 weeks to 52 weeks. “Four trials including 659 patients and 88 deaths, reported on mortality,” the investigators noted. At a relative risk reduction of 0.73 (95% confidence interval, 0.51-1.04), the investigators concluded with moderate certainty that sildenafil probably reduces mortality in IPF patients.

Four trials including 659 patients reported on acute exacerbations and hospitalizations. At a RR of 1.10 (95% CI, 0.61-1.67), pooled results showed sildenafil may not reduce hospitalizations or acute exacerbations, compared with controls, although this conclusion was reached with low certainty. Four trials containing slightly more patients at 661 participants reported on AEs leading to drug discontinuation.

Again with moderate certainty, the authors concluded there is probably no difference in drug discontinuation rates because of AEs when comparing sildenafil to controls, at a RR of 0.79 (95% CI, 0.56-1.10). Four trials including 602 patients reported on lung function changes while diffusion capacity of carbon monoxide (DLCO) results were available for 487 patients. Based on these four trials, sildenafil may not change the decline of forced vital capacity (FVC) at a mean difference of 0.61% (95% CI, –0.29 to 1.59), compared with standard of care or placebo.

Nor may it change the rate of DLCO decline at a MD of 0.97 (95% CI, 0.04-1.90), both outcomes again being rated with moderate certainty. Asked if the combination of either nintedanib plus sildenafil or pirfenidone plus sildenafil led to a mortality benefit in IPF patients, Dr. Pitre and Dr. Zeraatkar noted that there was no mortality benefit in either the INSTAGE trial or in another recent study published in Lancet Respiratory Medicine.

“However, both of these trials were quite small and therefore unlikely to detect a mortality benefit,” Dr. Pitre and Dr. Zeraatkar noted. Indeed, the benefit of doing a systematic review is the ability to pool event rates across trials to see if a benefit emerges as well as to evaluate the consistency of the direction of these effects.

“Our review presented the most up-to-date and comprehensive summary of the evidence on sildenafil therapy for IPF patients,” the authors stated.

While they did acknowledge that the mortality benefit seen with sildenafil over placebo or standard of care did not reach statistical significance, this was likely because of too few patients and events. For example, in a systematic review published in the New England Journal of Medicine in 1988, the authors were able to show a statistically significant benefit on 5-year mortality risk with the combination of tamoxifen and cytotoxic therapy whereas none of the individual trials analyzed were able to detect a mortality benefit because they were underpowered.

“Similarly, we suggest that something like this is possible with sildenafil, as the three major trials addressing sildenafil show the same direction toward benefit with little inconsistency,” Dr. Pitre and Dr. Zeraatkar noted.

“We should not exclude benefits based on P values alone,” they said, adding: “Clearly out systematic review is not going to change clinical practice given the uncertainty of the results but I do think that in a disease such as IPF, further research is warranted in targeted patient populations [and] for clinicians, we suggest they keep an open mind to sildenafil.”

Commentary

Asked to comment on the findings, Krishna Thavarajah, MD, director of the interstitial lung disease program at Henry Ford Hospital and clinical assistant professor at Wayne State University, both in Detroit, agreed with the authors that the lack of a statistically significant mortality benefit seen in the meta-analysis does not necessarily translate into a lack of benefit from the use of sildenafil in IPF patients. “As the authors point out, there are simply not enough data available to know if there is a mortality benefit, limited by the variable follow-up times and IPF patients targeted with or without pulmonary hypertension.”

Indeed, Dr. Thavarajah felt that a mortality benefit might be difficult to show in IPF patients, especially those on antifibrotics, given the duration of the studies analyzed and the number of patients needed to be able to show a statistically significant difference. “I myself have not prescribed sildenafil for IPF patients given the lack of clear data,” Dr. Thavarajah acknowledged.

“[But] the meta-analysis shows that sildenafil could have a mortality benefit in IPF patients without evidence of a benefit in FVC, DLCO, or acute exacerbations,” she confirmed, agreeing that further study would be helpful in assessing the potential for sildenafil to provide a mortality benefit in IPF patients.

No funding for the study was reported. Neither the authors nor Dr. Thavarajah had any conflicts of interest to declare.

NEW ORLEANS – Research into video game addiction is turning up new insights, and some treatments seem to make a difference, according to addiction psychiatry experts speaking at the annual meeting of the American Psychiatric Association. Still, understanding remains limited amid a general lack of clarity about definitions, measurements, and the most effective treatment strategies.

“Video games have the potential to be uniquely addictive, and it’s difficult to come up with treatment modalities that you can use for kids who have access to these things 24/7 on their mobile phones or laptops,” psychiatrist James C. Sherer, MD, of NYU Langone Health, said during the May 22 session, “Internet Gaming Disorder: From Harmless Fun to Dependence,” at the meeting. “It makes treating this a really complicated endeavor.”

iStock/Getty Images

The number of people with so-called Internet gaming disorder is unknown, but video games remain wildly popular among adults and children of all genders. According to a 2021 survey by Common Sense Media, U.S. individuals aged 8-12 and 13-18 spent an average of 1:27 hours and 1:46 hours per day, respectively, playing video games.

“Video games are an extremely important part of normal social networking among kids, and there’s a huge amount of social pressure to be good,” Dr. Sherer said. “If you’re in a particularly affluent neighborhood, it’s not unheard of for a parent to hire a coach to make their kid good at a game like Fortnite so they impress the other kids.”

The 2013 edition of the DSM-5 doesn’t list Internet gaming disorder as a mental illness but suggests that the topic warrants more research and evaluation, Dr. Sherer said.

Why are video games so addicting? According to Dr. Sherer, they’re simply designed that way. Game manufacturers “employ psychologists and behaviorists whose only job is to look at the game and determine what colors and what sounds are most likely to make you spend a little bit extra.” And with the help of the Internet, video games have evolved over the past 40 years to encourage users to make multiple purchases on single games such as Candy Crush instead of simply buying, say, a single 1980s-style Atari cartridge.

According to Dr. Sherer, research suggests that video games place users into something called the “flow state,” which a recent review article published in Frontiers in Psychology describes as “a state of full task engagement that is accompanied with low-levels of self-referential thinking” and “highly relevant for human performance and well-being.”
 

Diagnosing gaming addiction

How can psychiatrists diagnose video gaming addiction? Dr. Sherer, who is himself a devoted gamer, advised against focusing too much on time spent gaming in determining whether a patient has a problem. Instead, keep in mind that excessive gaming can displace exercise and normal socialization, he said, and lead to worsening mood.

Rober Aziz, MD, also of NYU Langone Health, suggested asking these questions: What types of games do you play? How long do you spend playing? What’s your reason for playing? What’s the meaning of your character choices? Does this game interfere with school or work? Have you neglected your self-care to play more?

He recommends other questions, too: Have you tried to limit your play time without success? How uncomfortable do you get if you must stop in the middle of playing? Do you get agitated if servers go down unexpectedly?

“There’s actually a lot of parallel here to other addictions that we’re very familiar with,” he said.

According to Dr. Sherer, it’s helpful to know that children who have attention-deficit/hyperactivity disorder tend to struggle with gaming addiction the most. He highlighted a brain-scan study in the Journal of Attention Disorders that found that patients with gaming addiction and ADHD had less functional connectivity from the cortex to the subcortex compared to matched controls. But treatment helped increase connectivity in those with good prognoses.

The findings are “heartening,” he said. “Basically, if you’re treating ADHD, you’re treating Internet gaming disorder. And if you’re treating Internet gaming disorder, you’re treating ADHD.”

As for treatments, the speakers agreed that there is little research to point in the right direction regarding gaming addiction specifically.

According to Dr. Aziz, research has suggested that bupropion, methylphenidate, and escitalopram can be helpful. In terms of nondrug approaches, he recommends directing patients toward games that have distinct beginnings, middles, and ends instead of endlessly providing rewards. One such game is “Legend of Zelda: Breath of the Wild” on the Nintendo Switch platform, he said.

On the psychotherapy front, Dr. Aziz said, “reducing use rather than abstinence should be the treatment goal.” Research suggests that cognitive behavioral therapy may not help patients in the long term, he said. Other strategies, he said, include specific approaches known as “CBT for Internet addiction” and “motivational interviewing for Internet gaming disorder.”

Gaming addiction treatment centers have also popped up in the U.S., he said, and there’s now an organization called Gaming Addicts Anonymous.

The good news is that “there is a lot of active research that’s being done” into treating video game addiction, said psychiatrist Anil Thomas, MD, program director of the addiction psychiatry fellowship at NYU Langone Health and moderator of the APA session. “We just have to wait to see what the results are.”

NEW ORLEANS – Research into video game addiction is turning up new insights, and some treatments seem to make a difference, according to addiction psychiatry experts speaking at the annual meeting of the American Psychiatric Association. Still, understanding remains limited amid a general lack of clarity about definitions, measurements, and the most effective treatment strategies.

“Video games have the potential to be uniquely addictive, and it’s difficult to come up with treatment modalities that you can use for kids who have access to these things 24/7 on their mobile phones or laptops,” psychiatrist James C. Sherer, MD, of NYU Langone Health, said during the May 22 session, “Internet Gaming Disorder: From Harmless Fun to Dependence,” at the meeting. “It makes treating this a really complicated endeavor.”

iStock/Getty Images

The number of people with so-called Internet gaming disorder is unknown, but video games remain wildly popular among adults and children of all genders. According to a 2021 survey by Common Sense Media, U.S. individuals aged 8-12 and 13-18 spent an average of 1:27 hours and 1:46 hours per day, respectively, playing video games.

“Video games are an extremely important part of normal social networking among kids, and there’s a huge amount of social pressure to be good,” Dr. Sherer said. “If you’re in a particularly affluent neighborhood, it’s not unheard of for a parent to hire a coach to make their kid good at a game like Fortnite so they impress the other kids.”

The 2013 edition of the DSM-5 doesn’t list Internet gaming disorder as a mental illness but suggests that the topic warrants more research and evaluation, Dr. Sherer said.

Why are video games so addicting? According to Dr. Sherer, they’re simply designed that way. Game manufacturers “employ psychologists and behaviorists whose only job is to look at the game and determine what colors and what sounds are most likely to make you spend a little bit extra.” And with the help of the Internet, video games have evolved over the past 40 years to encourage users to make multiple purchases on single games such as Candy Crush instead of simply buying, say, a single 1980s-style Atari cartridge.

According to Dr. Sherer, research suggests that video games place users into something called the “flow state,” which a recent review article published in Frontiers in Psychology describes as “a state of full task engagement that is accompanied with low-levels of self-referential thinking” and “highly relevant for human performance and well-being.”
 

Diagnosing gaming addiction

How can psychiatrists diagnose video gaming addiction? Dr. Sherer, who is himself a devoted gamer, advised against focusing too much on time spent gaming in determining whether a patient has a problem. Instead, keep in mind that excessive gaming can displace exercise and normal socialization, he said, and lead to worsening mood.

Rober Aziz, MD, also of NYU Langone Health, suggested asking these questions: What types of games do you play? How long do you spend playing? What’s your reason for playing? What’s the meaning of your character choices? Does this game interfere with school or work? Have you neglected your self-care to play more?

He recommends other questions, too: Have you tried to limit your play time without success? How uncomfortable do you get if you must stop in the middle of playing? Do you get agitated if servers go down unexpectedly?

“There’s actually a lot of parallel here to other addictions that we’re very familiar with,” he said.

According to Dr. Sherer, it’s helpful to know that children who have attention-deficit/hyperactivity disorder tend to struggle with gaming addiction the most. He highlighted a brain-scan study in the Journal of Attention Disorders that found that patients with gaming addiction and ADHD had less functional connectivity from the cortex to the subcortex compared to matched controls. But treatment helped increase connectivity in those with good prognoses.

The findings are “heartening,” he said. “Basically, if you’re treating ADHD, you’re treating Internet gaming disorder. And if you’re treating Internet gaming disorder, you’re treating ADHD.”

As for treatments, the speakers agreed that there is little research to point in the right direction regarding gaming addiction specifically.

According to Dr. Aziz, research has suggested that bupropion, methylphenidate, and escitalopram can be helpful. In terms of nondrug approaches, he recommends directing patients toward games that have distinct beginnings, middles, and ends instead of endlessly providing rewards. One such game is “Legend of Zelda: Breath of the Wild” on the Nintendo Switch platform, he said.

On the psychotherapy front, Dr. Aziz said, “reducing use rather than abstinence should be the treatment goal.” Research suggests that cognitive behavioral therapy may not help patients in the long term, he said. Other strategies, he said, include specific approaches known as “CBT for Internet addiction” and “motivational interviewing for Internet gaming disorder.”

Gaming addiction treatment centers have also popped up in the U.S., he said, and there’s now an organization called Gaming Addicts Anonymous.

The good news is that “there is a lot of active research that’s being done” into treating video game addiction, said psychiatrist Anil Thomas, MD, program director of the addiction psychiatry fellowship at NYU Langone Health and moderator of the APA session. “We just have to wait to see what the results are.”

NEW ORLEANS – Research into video game addiction is turning up new insights, and some treatments seem to make a difference, according to addiction psychiatry experts speaking at the annual meeting of the American Psychiatric Association. Still, understanding remains limited amid a general lack of clarity about definitions, measurements, and the most effective treatment strategies.

“Video games have the potential to be uniquely addictive, and it’s difficult to come up with treatment modalities that you can use for kids who have access to these things 24/7 on their mobile phones or laptops,” psychiatrist James C. Sherer, MD, of NYU Langone Health, said during the May 22 session, “Internet Gaming Disorder: From Harmless Fun to Dependence,” at the meeting. “It makes treating this a really complicated endeavor.”

iStock/Getty Images

The number of people with so-called Internet gaming disorder is unknown, but video games remain wildly popular among adults and children of all genders. According to a 2021 survey by Common Sense Media, U.S. individuals aged 8-12 and 13-18 spent an average of 1:27 hours and 1:46 hours per day, respectively, playing video games.

“Video games are an extremely important part of normal social networking among kids, and there’s a huge amount of social pressure to be good,” Dr. Sherer said. “If you’re in a particularly affluent neighborhood, it’s not unheard of for a parent to hire a coach to make their kid good at a game like Fortnite so they impress the other kids.”

The 2013 edition of the DSM-5 doesn’t list Internet gaming disorder as a mental illness but suggests that the topic warrants more research and evaluation, Dr. Sherer said.

Why are video games so addicting? According to Dr. Sherer, they’re simply designed that way. Game manufacturers “employ psychologists and behaviorists whose only job is to look at the game and determine what colors and what sounds are most likely to make you spend a little bit extra.” And with the help of the Internet, video games have evolved over the past 40 years to encourage users to make multiple purchases on single games such as Candy Crush instead of simply buying, say, a single 1980s-style Atari cartridge.

According to Dr. Sherer, research suggests that video games place users into something called the “flow state,” which a recent review article published in Frontiers in Psychology describes as “a state of full task engagement that is accompanied with low-levels of self-referential thinking” and “highly relevant for human performance and well-being.”
 

Diagnosing gaming addiction

How can psychiatrists diagnose video gaming addiction? Dr. Sherer, who is himself a devoted gamer, advised against focusing too much on time spent gaming in determining whether a patient has a problem. Instead, keep in mind that excessive gaming can displace exercise and normal socialization, he said, and lead to worsening mood.

Rober Aziz, MD, also of NYU Langone Health, suggested asking these questions: What types of games do you play? How long do you spend playing? What’s your reason for playing? What’s the meaning of your character choices? Does this game interfere with school or work? Have you neglected your self-care to play more?

He recommends other questions, too: Have you tried to limit your play time without success? How uncomfortable do you get if you must stop in the middle of playing? Do you get agitated if servers go down unexpectedly?

“There’s actually a lot of parallel here to other addictions that we’re very familiar with,” he said.

According to Dr. Sherer, it’s helpful to know that children who have attention-deficit/hyperactivity disorder tend to struggle with gaming addiction the most. He highlighted a brain-scan study in the Journal of Attention Disorders that found that patients with gaming addiction and ADHD had less functional connectivity from the cortex to the subcortex compared to matched controls. But treatment helped increase connectivity in those with good prognoses.

The findings are “heartening,” he said. “Basically, if you’re treating ADHD, you’re treating Internet gaming disorder. And if you’re treating Internet gaming disorder, you’re treating ADHD.”

As for treatments, the speakers agreed that there is little research to point in the right direction regarding gaming addiction specifically.

According to Dr. Aziz, research has suggested that bupropion, methylphenidate, and escitalopram can be helpful. In terms of nondrug approaches, he recommends directing patients toward games that have distinct beginnings, middles, and ends instead of endlessly providing rewards. One such game is “Legend of Zelda: Breath of the Wild” on the Nintendo Switch platform, he said.

On the psychotherapy front, Dr. Aziz said, “reducing use rather than abstinence should be the treatment goal.” Research suggests that cognitive behavioral therapy may not help patients in the long term, he said. Other strategies, he said, include specific approaches known as “CBT for Internet addiction” and “motivational interviewing for Internet gaming disorder.”

Gaming addiction treatment centers have also popped up in the U.S., he said, and there’s now an organization called Gaming Addicts Anonymous.

The good news is that “there is a lot of active research that’s being done” into treating video game addiction, said psychiatrist Anil Thomas, MD, program director of the addiction psychiatry fellowship at NYU Langone Health and moderator of the APA session. “We just have to wait to see what the results are.”

SAN DIEGO – During her third year in the combined Harvard/Massachusetts General Hospital dermatology residency program in 2011, Lilit Garibyan, MD, PhD, attended a lecture presented by R. Rox Anderson, MD, director of the Wellman Center for Photomedicine at MGH. He described the concept of selective cryolipolysis – the method of removing fat by topical cooling that eventually led to the development of the CoolSculpting device.

“He was saying that this is such a great noninvasive technology for fat removal and that patients love it,” Dr. Garibyan recalled at the annual meeting of the American Society for Laser Medicine and Surgery. “But one of the most common side effects after cryolipolysis that is long-lasting, but completely reversible, is hypoesthesia. I was intrigued by this because even as a dermatology resident, I had seen how pain and itch symptoms are present in many dermatologic diseases, and we don’t have great treatments for them. I thought to myself, if we can figure out the mechanism of how this topical cooling is affecting the nerves for such a long time, then maybe we could develop therapies where we could selectively target just the nerves,” not the fat.

courtesy Dr. Lilit Garibyan

Following Dr. Anderson’s lecture, Dr. Garibyan asked him if anyone knew the mechanism of action or if anyone was working to find out. He did not, but Dr. Anderson invited her to join his lab to investigate. “I didn’t have a background in lasers or energy devices, but I thought this was such a great opportunity” and addressed an unmet need, she said at the meeting.

Dr. Garibyan then led a clinical trial to characterize the effect of a single cryolipolysis treatment in 11 healthy people and to quantitatively analyze what sensory functions change with treatment over a period of 56 days. Skin biopsies revealed that cryolipolysis mainly decreased myelinated dermal nerve fiber density, which persisted throughout the study.

“The conclusion was that yes, controlled topical cooling does lead to significant and long-lasting but reversible reduction of sensory function, including pain,” said Dr. Garibyan, who is now an assistant professor of dermatology at Harvard Medical School, Boston, and director of the Magic Wand Initiative at the Wellman Center.

Ice slurry injections

Enter ice slurry, a chilly mix of ice, saline, and glycol that can be directly injected into adipose tissue. In a swine study published online in January 2020, Dr. Garibyan and colleagues at the Wellman Center injected ice slurry into the flanks of swine and followed them for up to 8 weeks, using ultrasound imaging to quantify and show the location of fat loss. The researchers observed about 40%-50% loss of fat in the treated area, compared with a 60% increase of fat in controls. “On histology, this was very selective,” she said. “Only adipose tissue was affected. There was no damage to the underlying muscle or to the dermis or epidermis.”

In 2021, researchers tested the injection of ice slurry in 12 humans for the first time, injected into tissue, and followed them for 12 weeks. As observed by thermal imaging, ultrasound, and tissue histology, they concluded that ice slurry injection was feasible and safe as a way of inducing cryolipolysis, and was well tolerated by patients.

“This can become a promising treatment for a precise, effective, and customizable way of removing unwanted fat for aesthetic application,” Dr. Garibyan said. However, she added, it is not approved by the Food and Drug Administration and more studies are needed, “but it’s promising and encouraging to see this move forward in patients.”
 

Potential nonaesthetic uses

The potential applications of injectable ice slurry extend well beyond cosmetic dermatology, she continued, noting that it is being explored as a treatment for many medical conditions including obstructive sleep apnea (OSA). At the University of Pennsylvania, Philadelphia, researchers used MRI to image the tongue fat in a case-control study of 31 obese patients without OSA and 90 obese patients with OSA. They found that patients with OSA had increased deposition of fat at the base of their tongue, which can lead to airway obstruction in this subset of patients with OSA, pointed out Dr. Garibyan, who was not involved with the study. “This also gave us a hint. If we can remove that tongue fat, we could potentially help reduce severity or even cure OSA in this population of patients. This points to tongue fat as a therapeutic target.”

With help from researchers at Uniformed Services University of the Health Sciences, Bethesda, Md., she and her Wellman Center colleagues recently completed a swine study that showed the safety and feasibility of injecting the base of the tongue with ice slurry, targeting adipose tissue. The work has been submitted for publication in a journal, but at the meeting, she said that, 8 weeks after injecting the ice slurry, there were no changes to any tongue tissue other than fat.

“On histology, we only see selective damage to the adipose tissue,” she said. “It is very promising that it’s safe in animal models and we’re hoping to conduct a human trial later this year to test the ability of this injectable ice slurry to remove fat at the base of the tongue with the hope that this will treat OSA.”

Another potential application of this technology is in the cardiology field. Dr. Garibyan is part of a multidisciplinary team at MGH that includes cardiac surgeons, cardiologists, and imaging experts who plan to investigate whether injecting ice slurry into fat around the heart can modify heart disease in humans. “Visceral fat around the heart – pericardial fat and epicardial fat – is involved in cardiovascular disease, arrhythmias, and many other unwanted effects on the heart,” she said. “Imagine if you could inject this around the heart, ablate the fat, and halt cardiovascular disease?”

She led a study that examined the effect of injecting ice slurry into swine with significant amounts of adipose tissue around their hearts, based on baseline CT scans. She and her coinvestigators observed a significant loss of that fat tissue on follow-up CT scans 8 weeks later. “On average, there was about a 30% reduction of this pericardial adipose tissue after a single injection,” and the procedure “was safe and well tolerated by the animals,” she added.

Ice slurry could also play a role in managing pain by targeting peripheral nerves. Peripheral nerves are composed of 75%-80% lipids, such as the myelin sheaths around the nerves, she noted. “That’s lipid-rich tissue. We think that by targeting that we’re able to block pain.”

She led a study that showed that a single injection of ice slurry around the sciatic nerve in rats served as a sustained anesthetic by blocking mechanical pain sensation for up to 56 days. They imaged the peripheral nerves in the rats and showed that the mechanism involved was loss of the lipid-rich myelin tissue around the nerves, which blocks the signaling of the nerve, she said.

Dr. Garibyan disclosed that she is a member of the advisory board for Brixton Biosciences, Vyome Therapeutics, and Aegle Therapeutics. She is also a consultant for Aegle Therapeutics and Blossom Innovations and holds equity in Brixton Biosciences and EyeCool Therapeutics.

SAN DIEGO – During her third year in the combined Harvard/Massachusetts General Hospital dermatology residency program in 2011, Lilit Garibyan, MD, PhD, attended a lecture presented by R. Rox Anderson, MD, director of the Wellman Center for Photomedicine at MGH. He described the concept of selective cryolipolysis – the method of removing fat by topical cooling that eventually led to the development of the CoolSculpting device.

“He was saying that this is such a great noninvasive technology for fat removal and that patients love it,” Dr. Garibyan recalled at the annual meeting of the American Society for Laser Medicine and Surgery. “But one of the most common side effects after cryolipolysis that is long-lasting, but completely reversible, is hypoesthesia. I was intrigued by this because even as a dermatology resident, I had seen how pain and itch symptoms are present in many dermatologic diseases, and we don’t have great treatments for them. I thought to myself, if we can figure out the mechanism of how this topical cooling is affecting the nerves for such a long time, then maybe we could develop therapies where we could selectively target just the nerves,” not the fat.

courtesy Dr. Lilit Garibyan

Following Dr. Anderson’s lecture, Dr. Garibyan asked him if anyone knew the mechanism of action or if anyone was working to find out. He did not, but Dr. Anderson invited her to join his lab to investigate. “I didn’t have a background in lasers or energy devices, but I thought this was such a great opportunity” and addressed an unmet need, she said at the meeting.

Dr. Garibyan then led a clinical trial to characterize the effect of a single cryolipolysis treatment in 11 healthy people and to quantitatively analyze what sensory functions change with treatment over a period of 56 days. Skin biopsies revealed that cryolipolysis mainly decreased myelinated dermal nerve fiber density, which persisted throughout the study.

“The conclusion was that yes, controlled topical cooling does lead to significant and long-lasting but reversible reduction of sensory function, including pain,” said Dr. Garibyan, who is now an assistant professor of dermatology at Harvard Medical School, Boston, and director of the Magic Wand Initiative at the Wellman Center.

Ice slurry injections

Enter ice slurry, a chilly mix of ice, saline, and glycol that can be directly injected into adipose tissue. In a swine study published online in January 2020, Dr. Garibyan and colleagues at the Wellman Center injected ice slurry into the flanks of swine and followed them for up to 8 weeks, using ultrasound imaging to quantify and show the location of fat loss. The researchers observed about 40%-50% loss of fat in the treated area, compared with a 60% increase of fat in controls. “On histology, this was very selective,” she said. “Only adipose tissue was affected. There was no damage to the underlying muscle or to the dermis or epidermis.”

In 2021, researchers tested the injection of ice slurry in 12 humans for the first time, injected into tissue, and followed them for 12 weeks. As observed by thermal imaging, ultrasound, and tissue histology, they concluded that ice slurry injection was feasible and safe as a way of inducing cryolipolysis, and was well tolerated by patients.

“This can become a promising treatment for a precise, effective, and customizable way of removing unwanted fat for aesthetic application,” Dr. Garibyan said. However, she added, it is not approved by the Food and Drug Administration and more studies are needed, “but it’s promising and encouraging to see this move forward in patients.”
 

Potential nonaesthetic uses

The potential applications of injectable ice slurry extend well beyond cosmetic dermatology, she continued, noting that it is being explored as a treatment for many medical conditions including obstructive sleep apnea (OSA). At the University of Pennsylvania, Philadelphia, researchers used MRI to image the tongue fat in a case-control study of 31 obese patients without OSA and 90 obese patients with OSA. They found that patients with OSA had increased deposition of fat at the base of their tongue, which can lead to airway obstruction in this subset of patients with OSA, pointed out Dr. Garibyan, who was not involved with the study. “This also gave us a hint. If we can remove that tongue fat, we could potentially help reduce severity or even cure OSA in this population of patients. This points to tongue fat as a therapeutic target.”

With help from researchers at Uniformed Services University of the Health Sciences, Bethesda, Md., she and her Wellman Center colleagues recently completed a swine study that showed the safety and feasibility of injecting the base of the tongue with ice slurry, targeting adipose tissue. The work has been submitted for publication in a journal, but at the meeting, she said that, 8 weeks after injecting the ice slurry, there were no changes to any tongue tissue other than fat.

“On histology, we only see selective damage to the adipose tissue,” she said. “It is very promising that it’s safe in animal models and we’re hoping to conduct a human trial later this year to test the ability of this injectable ice slurry to remove fat at the base of the tongue with the hope that this will treat OSA.”

Another potential application of this technology is in the cardiology field. Dr. Garibyan is part of a multidisciplinary team at MGH that includes cardiac surgeons, cardiologists, and imaging experts who plan to investigate whether injecting ice slurry into fat around the heart can modify heart disease in humans. “Visceral fat around the heart – pericardial fat and epicardial fat – is involved in cardiovascular disease, arrhythmias, and many other unwanted effects on the heart,” she said. “Imagine if you could inject this around the heart, ablate the fat, and halt cardiovascular disease?”

She led a study that examined the effect of injecting ice slurry into swine with significant amounts of adipose tissue around their hearts, based on baseline CT scans. She and her coinvestigators observed a significant loss of that fat tissue on follow-up CT scans 8 weeks later. “On average, there was about a 30% reduction of this pericardial adipose tissue after a single injection,” and the procedure “was safe and well tolerated by the animals,” she added.

Ice slurry could also play a role in managing pain by targeting peripheral nerves. Peripheral nerves are composed of 75%-80% lipids, such as the myelin sheaths around the nerves, she noted. “That’s lipid-rich tissue. We think that by targeting that we’re able to block pain.”

She led a study that showed that a single injection of ice slurry around the sciatic nerve in rats served as a sustained anesthetic by blocking mechanical pain sensation for up to 56 days. They imaged the peripheral nerves in the rats and showed that the mechanism involved was loss of the lipid-rich myelin tissue around the nerves, which blocks the signaling of the nerve, she said.

Dr. Garibyan disclosed that she is a member of the advisory board for Brixton Biosciences, Vyome Therapeutics, and Aegle Therapeutics. She is also a consultant for Aegle Therapeutics and Blossom Innovations and holds equity in Brixton Biosciences and EyeCool Therapeutics.

SAN DIEGO – During her third year in the combined Harvard/Massachusetts General Hospital dermatology residency program in 2011, Lilit Garibyan, MD, PhD, attended a lecture presented by R. Rox Anderson, MD, director of the Wellman Center for Photomedicine at MGH. He described the concept of selective cryolipolysis – the method of removing fat by topical cooling that eventually led to the development of the CoolSculpting device.

“He was saying that this is such a great noninvasive technology for fat removal and that patients love it,” Dr. Garibyan recalled at the annual meeting of the American Society for Laser Medicine and Surgery. “But one of the most common side effects after cryolipolysis that is long-lasting, but completely reversible, is hypoesthesia. I was intrigued by this because even as a dermatology resident, I had seen how pain and itch symptoms are present in many dermatologic diseases, and we don’t have great treatments for them. I thought to myself, if we can figure out the mechanism of how this topical cooling is affecting the nerves for such a long time, then maybe we could develop therapies where we could selectively target just the nerves,” not the fat.

courtesy Dr. Lilit Garibyan

Following Dr. Anderson’s lecture, Dr. Garibyan asked him if anyone knew the mechanism of action or if anyone was working to find out. He did not, but Dr. Anderson invited her to join his lab to investigate. “I didn’t have a background in lasers or energy devices, but I thought this was such a great opportunity” and addressed an unmet need, she said at the meeting.

Dr. Garibyan then led a clinical trial to characterize the effect of a single cryolipolysis treatment in 11 healthy people and to quantitatively analyze what sensory functions change with treatment over a period of 56 days. Skin biopsies revealed that cryolipolysis mainly decreased myelinated dermal nerve fiber density, which persisted throughout the study.

“The conclusion was that yes, controlled topical cooling does lead to significant and long-lasting but reversible reduction of sensory function, including pain,” said Dr. Garibyan, who is now an assistant professor of dermatology at Harvard Medical School, Boston, and director of the Magic Wand Initiative at the Wellman Center.

Ice slurry injections

Enter ice slurry, a chilly mix of ice, saline, and glycol that can be directly injected into adipose tissue. In a swine study published online in January 2020, Dr. Garibyan and colleagues at the Wellman Center injected ice slurry into the flanks of swine and followed them for up to 8 weeks, using ultrasound imaging to quantify and show the location of fat loss. The researchers observed about 40%-50% loss of fat in the treated area, compared with a 60% increase of fat in controls. “On histology, this was very selective,” she said. “Only adipose tissue was affected. There was no damage to the underlying muscle or to the dermis or epidermis.”

In 2021, researchers tested the injection of ice slurry in 12 humans for the first time, injected into tissue, and followed them for 12 weeks. As observed by thermal imaging, ultrasound, and tissue histology, they concluded that ice slurry injection was feasible and safe as a way of inducing cryolipolysis, and was well tolerated by patients.

“This can become a promising treatment for a precise, effective, and customizable way of removing unwanted fat for aesthetic application,” Dr. Garibyan said. However, she added, it is not approved by the Food and Drug Administration and more studies are needed, “but it’s promising and encouraging to see this move forward in patients.”
 

Potential nonaesthetic uses

The potential applications of injectable ice slurry extend well beyond cosmetic dermatology, she continued, noting that it is being explored as a treatment for many medical conditions including obstructive sleep apnea (OSA). At the University of Pennsylvania, Philadelphia, researchers used MRI to image the tongue fat in a case-control study of 31 obese patients without OSA and 90 obese patients with OSA. They found that patients with OSA had increased deposition of fat at the base of their tongue, which can lead to airway obstruction in this subset of patients with OSA, pointed out Dr. Garibyan, who was not involved with the study. “This also gave us a hint. If we can remove that tongue fat, we could potentially help reduce severity or even cure OSA in this population of patients. This points to tongue fat as a therapeutic target.”

With help from researchers at Uniformed Services University of the Health Sciences, Bethesda, Md., she and her Wellman Center colleagues recently completed a swine study that showed the safety and feasibility of injecting the base of the tongue with ice slurry, targeting adipose tissue. The work has been submitted for publication in a journal, but at the meeting, she said that, 8 weeks after injecting the ice slurry, there were no changes to any tongue tissue other than fat.

“On histology, we only see selective damage to the adipose tissue,” she said. “It is very promising that it’s safe in animal models and we’re hoping to conduct a human trial later this year to test the ability of this injectable ice slurry to remove fat at the base of the tongue with the hope that this will treat OSA.”

Another potential application of this technology is in the cardiology field. Dr. Garibyan is part of a multidisciplinary team at MGH that includes cardiac surgeons, cardiologists, and imaging experts who plan to investigate whether injecting ice slurry into fat around the heart can modify heart disease in humans. “Visceral fat around the heart – pericardial fat and epicardial fat – is involved in cardiovascular disease, arrhythmias, and many other unwanted effects on the heart,” she said. “Imagine if you could inject this around the heart, ablate the fat, and halt cardiovascular disease?”

She led a study that examined the effect of injecting ice slurry into swine with significant amounts of adipose tissue around their hearts, based on baseline CT scans. She and her coinvestigators observed a significant loss of that fat tissue on follow-up CT scans 8 weeks later. “On average, there was about a 30% reduction of this pericardial adipose tissue after a single injection,” and the procedure “was safe and well tolerated by the animals,” she added.

Ice slurry could also play a role in managing pain by targeting peripheral nerves. Peripheral nerves are composed of 75%-80% lipids, such as the myelin sheaths around the nerves, she noted. “That’s lipid-rich tissue. We think that by targeting that we’re able to block pain.”

She led a study that showed that a single injection of ice slurry around the sciatic nerve in rats served as a sustained anesthetic by blocking mechanical pain sensation for up to 56 days. They imaged the peripheral nerves in the rats and showed that the mechanism involved was loss of the lipid-rich myelin tissue around the nerves, which blocks the signaling of the nerve, she said.

Dr. Garibyan disclosed that she is a member of the advisory board for Brixton Biosciences, Vyome Therapeutics, and Aegle Therapeutics. She is also a consultant for Aegle Therapeutics and Blossom Innovations and holds equity in Brixton Biosciences and EyeCool Therapeutics.

Fidaxomicin (Fificid) emerged favorable to vancomycin for the treatment of both initial and recurrent Clostridioides difficile infections in a Medicare population, according to a new retrospective study.

Although fidaxomicin was about 14% more effective than vancomycin in treating the initial infection, a larger difference of 30% was found among people with recurrent C. diff. infections.

Lead investigator Erik Dubberke, MD, professor of infectious diseases at the University of Washington, St. Louis, and colleagues noted that this real-world evidence of the two agents used to treat C. diff. was “strikingly similar” to clinical trial data.

They said that their findings support the 2021 change in clinical guidelines from the Infectious Diseases Society of America recommending fidaxomicin over vancomycin.

The study was presented at Digestive Disease Week^® (DDW) 2022, which was held virtually and in San Diego.
 

Evaluating a high-risk population

Because few real-world data exist that compare these two agents for C. diff., “particularly in a high-risk, high-prevalence population like Medicare,” the researchers evaluated Medicare Parts A, B, and D claims from 2016 to 2018 and included patients who had received fidaxomicin or vancomycin for an initial episode of C. diff. and for any recurrent episodes.

The researchers compared sustained response and recurrence of C. diff. within 4 weeks and 8 weeks after initial treatment with fidaxomicin or vancomycin. Treatment was considered successful if clinical resolution occurred 1 day after finishing therapy and there was no evidence of C. diff. recurrence.

Recurrence of C. diff. was defined as any evidence of new treatment or hospitalization for the infection within 4 or 8 weeks of when a patient filled the prescription for fidaxomicin or vancomycin.

The treatment groups were similar in age and race. However, the fidaxomicin group was at higher risk for recurrence, owing to risk factors such as history of C. diff. infection and compromised immunity. To reduce bias in comparing the groups, Dr. Dubberke and colleagues used propensity score matching. This approach yielded 190 matched pairs in the initial C. diff. episode sample and 67 matched pairs in the recurrent episode sample.

Among patients with their first C. diff. infection, fidaxomicin had a 13.5% higher rate of 4-week sustained response, compared with vancomycin (71.7% vs. 58.2%; P = .0058). There was also a 13.2% higher rate for 8-week sustained response with fidaxomicin (63.2% vs. 50.0%; P = .0114).

Sustained response at 4 weeks and 8 weeks among the patients who experienced a recurrent episode of C. diff. favored fidaxomicin over vancomycin by 30.1% (P = .0002) and 27.6% (P = .0012), respectively.

The rates of C. diff. recurrence in patients who experienced their first C. diff. infection or who experienced a recurrent bout were lower with fidaxomicin than vancomycin, but the differences were not statistically significant.
 

A costly edge

When asked to comment, Colleen Kelly, MD, a gastroenterologist and associate professor of medicine at Brown University, Providence, R.I., said that the study was “worthwhile” and added that “Eric Dubberke has done a lot of work in this area.”

The study “gives more evidence that fidaxomicin does have a bit of an edge in people who have already had a bout of C. diff.,” she said.

Dr. Kelly added that the cost needs to be considered. Fidaxomicin “is about 30 times more expensive than vancomycin,” she said.

In part because of the cost difference, the American College of Gastroenterology (ACG) 2021 guidelines, which Dr. Kelly helped create, recommend that fidaxomicin be held as a second-line agent. The ACG guidance reserved fidaxomicin for people with C. diff. for whom initial treatment with vancomycin failed.

“The fidaxomicin question is going to get a lot easier once the cost of the drug comes down,” Dr. Kelly said.

The study was funded by Merck. Dr. Dubberke is a consultant for Merck. Dr. Kelly reports no relevant financial relationships.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

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

Fidaxomicin (Fificid) emerged favorable to vancomycin for the treatment of both initial and recurrent Clostridioides difficile infections in a Medicare population, according to a new retrospective study.

Although fidaxomicin was about 14% more effective than vancomycin in treating the initial infection, a larger difference of 30% was found among people with recurrent C. diff. infections.

Lead investigator Erik Dubberke, MD, professor of infectious diseases at the University of Washington, St. Louis, and colleagues noted that this real-world evidence of the two agents used to treat C. diff. was “strikingly similar” to clinical trial data.

They said that their findings support the 2021 change in clinical guidelines from the Infectious Diseases Society of America recommending fidaxomicin over vancomycin.

The study was presented at Digestive Disease Week^® (DDW) 2022, which was held virtually and in San Diego.
 

Evaluating a high-risk population

Because few real-world data exist that compare these two agents for C. diff., “particularly in a high-risk, high-prevalence population like Medicare,” the researchers evaluated Medicare Parts A, B, and D claims from 2016 to 2018 and included patients who had received fidaxomicin or vancomycin for an initial episode of C. diff. and for any recurrent episodes.

The researchers compared sustained response and recurrence of C. diff. within 4 weeks and 8 weeks after initial treatment with fidaxomicin or vancomycin. Treatment was considered successful if clinical resolution occurred 1 day after finishing therapy and there was no evidence of C. diff. recurrence.

Recurrence of C. diff. was defined as any evidence of new treatment or hospitalization for the infection within 4 or 8 weeks of when a patient filled the prescription for fidaxomicin or vancomycin.

The treatment groups were similar in age and race. However, the fidaxomicin group was at higher risk for recurrence, owing to risk factors such as history of C. diff. infection and compromised immunity. To reduce bias in comparing the groups, Dr. Dubberke and colleagues used propensity score matching. This approach yielded 190 matched pairs in the initial C. diff. episode sample and 67 matched pairs in the recurrent episode sample.

Among patients with their first C. diff. infection, fidaxomicin had a 13.5% higher rate of 4-week sustained response, compared with vancomycin (71.7% vs. 58.2%; P = .0058). There was also a 13.2% higher rate for 8-week sustained response with fidaxomicin (63.2% vs. 50.0%; P = .0114).

Sustained response at 4 weeks and 8 weeks among the patients who experienced a recurrent episode of C. diff. favored fidaxomicin over vancomycin by 30.1% (P = .0002) and 27.6% (P = .0012), respectively.

The rates of C. diff. recurrence in patients who experienced their first C. diff. infection or who experienced a recurrent bout were lower with fidaxomicin than vancomycin, but the differences were not statistically significant.
 

A costly edge

When asked to comment, Colleen Kelly, MD, a gastroenterologist and associate professor of medicine at Brown University, Providence, R.I., said that the study was “worthwhile” and added that “Eric Dubberke has done a lot of work in this area.”

The study “gives more evidence that fidaxomicin does have a bit of an edge in people who have already had a bout of C. diff.,” she said.

Dr. Kelly added that the cost needs to be considered. Fidaxomicin “is about 30 times more expensive than vancomycin,” she said.

In part because of the cost difference, the American College of Gastroenterology (ACG) 2021 guidelines, which Dr. Kelly helped create, recommend that fidaxomicin be held as a second-line agent. The ACG guidance reserved fidaxomicin for people with C. diff. for whom initial treatment with vancomycin failed.

“The fidaxomicin question is going to get a lot easier once the cost of the drug comes down,” Dr. Kelly said.

The study was funded by Merck. Dr. Dubberke is a consultant for Merck. Dr. Kelly reports no relevant financial relationships.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

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

Fidaxomicin (Fificid) emerged favorable to vancomycin for the treatment of both initial and recurrent Clostridioides difficile infections in a Medicare population, according to a new retrospective study.

Although fidaxomicin was about 14% more effective than vancomycin in treating the initial infection, a larger difference of 30% was found among people with recurrent C. diff. infections.

Lead investigator Erik Dubberke, MD, professor of infectious diseases at the University of Washington, St. Louis, and colleagues noted that this real-world evidence of the two agents used to treat C. diff. was “strikingly similar” to clinical trial data.

They said that their findings support the 2021 change in clinical guidelines from the Infectious Diseases Society of America recommending fidaxomicin over vancomycin.

The study was presented at Digestive Disease Week^® (DDW) 2022, which was held virtually and in San Diego.
 

Evaluating a high-risk population

Because few real-world data exist that compare these two agents for C. diff., “particularly in a high-risk, high-prevalence population like Medicare,” the researchers evaluated Medicare Parts A, B, and D claims from 2016 to 2018 and included patients who had received fidaxomicin or vancomycin for an initial episode of C. diff. and for any recurrent episodes.

The researchers compared sustained response and recurrence of C. diff. within 4 weeks and 8 weeks after initial treatment with fidaxomicin or vancomycin. Treatment was considered successful if clinical resolution occurred 1 day after finishing therapy and there was no evidence of C. diff. recurrence.

Recurrence of C. diff. was defined as any evidence of new treatment or hospitalization for the infection within 4 or 8 weeks of when a patient filled the prescription for fidaxomicin or vancomycin.

The treatment groups were similar in age and race. However, the fidaxomicin group was at higher risk for recurrence, owing to risk factors such as history of C. diff. infection and compromised immunity. To reduce bias in comparing the groups, Dr. Dubberke and colleagues used propensity score matching. This approach yielded 190 matched pairs in the initial C. diff. episode sample and 67 matched pairs in the recurrent episode sample.

Among patients with their first C. diff. infection, fidaxomicin had a 13.5% higher rate of 4-week sustained response, compared with vancomycin (71.7% vs. 58.2%; P = .0058). There was also a 13.2% higher rate for 8-week sustained response with fidaxomicin (63.2% vs. 50.0%; P = .0114).

Sustained response at 4 weeks and 8 weeks among the patients who experienced a recurrent episode of C. diff. favored fidaxomicin over vancomycin by 30.1% (P = .0002) and 27.6% (P = .0012), respectively.

The rates of C. diff. recurrence in patients who experienced their first C. diff. infection or who experienced a recurrent bout were lower with fidaxomicin than vancomycin, but the differences were not statistically significant.
 

A costly edge

When asked to comment, Colleen Kelly, MD, a gastroenterologist and associate professor of medicine at Brown University, Providence, R.I., said that the study was “worthwhile” and added that “Eric Dubberke has done a lot of work in this area.”

The study “gives more evidence that fidaxomicin does have a bit of an edge in people who have already had a bout of C. diff.,” she said.

Dr. Kelly added that the cost needs to be considered. Fidaxomicin “is about 30 times more expensive than vancomycin,” she said.

In part because of the cost difference, the American College of Gastroenterology (ACG) 2021 guidelines, which Dr. Kelly helped create, recommend that fidaxomicin be held as a second-line agent. The ACG guidance reserved fidaxomicin for people with C. diff. for whom initial treatment with vancomycin failed.

“The fidaxomicin question is going to get a lot easier once the cost of the drug comes down,” Dr. Kelly said.

The study was funded by Merck. Dr. Dubberke is a consultant for Merck. Dr. Kelly reports no relevant financial relationships.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

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

Self-management of gout using a smartphone app to record self-test urate levels and flares, and communicate those results to clinicians, could see more patients reaching target urate levels and even reducing flare frequency, a study has found.

Writing in The Lancet Rheumatology, Philip Riches, PhD, of the rheumatic disease unit at Western General Hospital in Edinburgh, and coauthors presented the findings of their randomized, controlled feasibility study of a new gout self-management approach aimed at helping patients treat to target.

Patients in the intervention group also had fewer flares, experiencing a mean of 2.03 flares in the first 24 weeks, compared with a mean of 3 among the control group, although the study didn’t report any difference in the rates of tophaceous disease.

Those in the self-management group had fewer medical appointments, but were prescribed higher doses of allopurinol at the 24- and 52-week visits.

“Qualitative feedback suggests that the self-monitoring approach was accepted by most participants and was enthusiastically endorsed by many,” the authors wrote. “The approach empowers patients and provides feedback on the effect of medication.”

It will be important to determine if the success of this self-management intervention can be replicated in an even broader patient population, Lisa K. Stamp, MBChB, PhD, of University of Otago, Christchurch, New Zealand, and Angelo L. Gaffo, MD, of University of Alabama at Birmingham, noted in an accompanying editorial. They wrote it was encouraging that only 7% of the 92 people screened for the trial did not have a smartphone and that it the patient sample had a mean age of 53 years. However, the trial did not include people with chronic kidney disease who make up nearly a quarter of all people with gout.

“It remains unknown whether the characteristics of those who did not reach target urate are the same or different as those who did, and a head-to-head comparison of these interventions would be of interest,” Dr. Stamp and Dr. Gaffo wrote. “A key challenge in managing gout is to determine which treatment strategy will be best suited to an individual with gout and to identify those for whom more support might be required.”

This study was supported by the University of Edinburgh and funded by NHS Lothian Health Foundation. No conflicts of interest were declared.

Self-management of gout using a smartphone app to record self-test urate levels and flares, and communicate those results to clinicians, could see more patients reaching target urate levels and even reducing flare frequency, a study has found.

Writing in The Lancet Rheumatology, Philip Riches, PhD, of the rheumatic disease unit at Western General Hospital in Edinburgh, and coauthors presented the findings of their randomized, controlled feasibility study of a new gout self-management approach aimed at helping patients treat to target.

Patients in the intervention group also had fewer flares, experiencing a mean of 2.03 flares in the first 24 weeks, compared with a mean of 3 among the control group, although the study didn’t report any difference in the rates of tophaceous disease.

Those in the self-management group had fewer medical appointments, but were prescribed higher doses of allopurinol at the 24- and 52-week visits.

“Qualitative feedback suggests that the self-monitoring approach was accepted by most participants and was enthusiastically endorsed by many,” the authors wrote. “The approach empowers patients and provides feedback on the effect of medication.”

It will be important to determine if the success of this self-management intervention can be replicated in an even broader patient population, Lisa K. Stamp, MBChB, PhD, of University of Otago, Christchurch, New Zealand, and Angelo L. Gaffo, MD, of University of Alabama at Birmingham, noted in an accompanying editorial. They wrote it was encouraging that only 7% of the 92 people screened for the trial did not have a smartphone and that it the patient sample had a mean age of 53 years. However, the trial did not include people with chronic kidney disease who make up nearly a quarter of all people with gout.

“It remains unknown whether the characteristics of those who did not reach target urate are the same or different as those who did, and a head-to-head comparison of these interventions would be of interest,” Dr. Stamp and Dr. Gaffo wrote. “A key challenge in managing gout is to determine which treatment strategy will be best suited to an individual with gout and to identify those for whom more support might be required.”

This study was supported by the University of Edinburgh and funded by NHS Lothian Health Foundation. No conflicts of interest were declared.

Self-management of gout using a smartphone app to record self-test urate levels and flares, and communicate those results to clinicians, could see more patients reaching target urate levels and even reducing flare frequency, a study has found.

Writing in The Lancet Rheumatology, Philip Riches, PhD, of the rheumatic disease unit at Western General Hospital in Edinburgh, and coauthors presented the findings of their randomized, controlled feasibility study of a new gout self-management approach aimed at helping patients treat to target.

Patients in the intervention group also had fewer flares, experiencing a mean of 2.03 flares in the first 24 weeks, compared with a mean of 3 among the control group, although the study didn’t report any difference in the rates of tophaceous disease.

Those in the self-management group had fewer medical appointments, but were prescribed higher doses of allopurinol at the 24- and 52-week visits.

“Qualitative feedback suggests that the self-monitoring approach was accepted by most participants and was enthusiastically endorsed by many,” the authors wrote. “The approach empowers patients and provides feedback on the effect of medication.”

It will be important to determine if the success of this self-management intervention can be replicated in an even broader patient population, Lisa K. Stamp, MBChB, PhD, of University of Otago, Christchurch, New Zealand, and Angelo L. Gaffo, MD, of University of Alabama at Birmingham, noted in an accompanying editorial. They wrote it was encouraging that only 7% of the 92 people screened for the trial did not have a smartphone and that it the patient sample had a mean age of 53 years. However, the trial did not include people with chronic kidney disease who make up nearly a quarter of all people with gout.

“It remains unknown whether the characteristics of those who did not reach target urate are the same or different as those who did, and a head-to-head comparison of these interventions would be of interest,” Dr. Stamp and Dr. Gaffo wrote. “A key challenge in managing gout is to determine which treatment strategy will be best suited to an individual with gout and to identify those for whom more support might be required.”

This study was supported by the University of Edinburgh and funded by NHS Lothian Health Foundation. No conflicts of interest were declared.