Liam Davenport

Patients with inflammatory bowel disease (IBD) can safely take tumor necrosis factor inhibitors (TNFi) prior to abdominal surgery, a prospective, multicenter, observational study confirms.

The researchers found that exposure to TNFi in the 12 weeks prior to surgery was not associated with an increased risk of either overall infections or surgical site infections (SSI).

The findings should be “very reassuring” for clinicians, lead author Benjamin L. Cohen, MD, Cleveland Clinic Foundation, told this news organization. “In the past, when clinicians were unsure about the safety of using these drugs in the perioperative period, they may have delayed surgeries or stopped medications unnecessarily.”

“For me, the key take-home point of this study is that we need to plan the timing and management of medications around surgery based on factors other than the use of tumor necrosis factor inhibitors in most patients,” Dr. Cohen continued.

Ultimately, “we will help change practice in how we manage patients with IBD having surgery,” he said.

The research was published online in Gastroenterology.
 

No increased postop infection risk

The Prospective Cohort of Ulcerative Colitis and Crohn’s Disease Patients Undergoing Surgery to Identify Risk Factors for Post-Operative Infection I (PUCCINI) trial enrolled patients with IBD from 17 sites participating in the Crohn’s and Colitis Foundation Clinical Research Alliance between September 2014 and June 2017.

Patients had Crohn’s disease, ulcerative colitis, or indeterminate colitis, as determined by standard criteria, and planned to undergo intra-abdominal surgery or had undergone intra-abdominal surgery in the preceding 4 days.

Among the 947 patients enrolled, 47.8% were women. All were aged 18 years or older. The median disease duration was 10 years; 34.4% of patients had undergone prior bowel resection, and a further 17.5% had undergone other abdominal surgery.

Systemic corticosteroid use within 2 weeks of surgery was reported by 40.9% of patients, and 42.3% had used antibiotics.

TNFi exposure within the 12 weeks prior to surgery was reported by 40.3% of patients. Adalimumab and infliximab were the most commonly used drugs. Among those who had not used TNFi prior to surgery, 23.7% were TNFi-naive, and 36.0% had used them in the past.

The researchers report that there was no significant difference in the rate of postoperative infections between patients who reported using TNFi in the 12 weeks prior to surgery and those who did not (18.1% vs. 20.2%; P = .469). There was also no difference in SSI, as defined using the Centers for Disease Control and Prevention criteria, between the two groups (12.0% vs 12.6%; P = .889).

Multivariate analysis revealed that current TNFi exposure was not associated with any infection, at an odds ratio versus no exposure of 1.050 (P = .80), or with SSI, at an odds ratio of 1.249 (P = .34).

In contrast, preoperative corticosteroid exposure, prior bowel resection, and current smoking were associated with any infection and with SSI.

Approached for comment, Stephen B. Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, said that the current findings are consistent with those of previous studies and that their relevance extends beyond abdominal surgery.

In the past, when surgeons were “confronted with a patient on a TNF blocker, even if it’s orthopedic or plastic surgery, they recommended against using a TNF blocker or operating at the end of the cycle when the drug levels are low,” he told this news organization.

Dr. Hanauer said such practice gets clinicians into a “bind because you’ve got a patient, for instance, who’s got a blockage with Crohn’s disease ... but the only way you could manage them when the TNFi was out of their system was with steroids, which is worse” in terms of postoperative infection risk, he explained.
 

Prospective studies important

The researchers note that up to 50% of patients with IBD are exposed to TNFi prior to their first surgery. They also note that there is concern that preoperative treatment with these and other immunosuppressive medications may increase the risk of postoperative infections.

However, the evidence is inconsistent, they write, so whether to continue or stop the drugs prior to surgery remains controversial.

“A lot of the initial studies in the perioperative population were single-center and retrospective for the most part,” Dr. Cohen said, adding that the studies used different modes of assessment and followed different time frames.

“So, there’s a lot of heterogeneity,” he said.

In addition, early studies of TNFi were often conducted with patients who were very ill and who had started receiving the drug right before surgery, and they sometimes had a complication Dr. Cohen said. “But you don’t know if that’s because of the drug itself or because of many other factors associated with them being very sick, such as being on steroids, being very malnourished, or having other complications of disease.”

It is difficult to control for such risk factors in retrospective analyses because the information is not always available from medical records, he said. “That’s why it’s so important to study clinical questions like this in a prospective manner.”

Dr. Cohen added that it is important that studies such as theirs continue to be undertaken as new drugs become available.

“We’re entering an era of rapidly expanding drug discovery, so we’re going to have new medications available for use in our patients with IBD,” he explained. “It’s important that we continue to build prospective cohorts to look at questions such as the safety of medications in the perioperative period, rather than solely relying on retrospective data.”

The study was funded by a Crohn’s & Colitis Foundation Senior Research Award. Dr. Cohen reports relationships with AbbVie, Celgene, Bristol-Myers Squibb, Pfizer, Sublimity Therapeutics, Target RWE, Janssen, Ferring, AlphaSigma, and Takeda. Other authors report numerous financial relationships. Dr. Hanauer reports relationships with Janssen, AbbVie, Pfizer, Amgen, Genentech, and Merck.

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

Patients with inflammatory bowel disease (IBD) can safely take tumor necrosis factor inhibitors (TNFi) prior to abdominal surgery, a prospective, multicenter, observational study confirms.

The researchers found that exposure to TNFi in the 12 weeks prior to surgery was not associated with an increased risk of either overall infections or surgical site infections (SSI).

The findings should be “very reassuring” for clinicians, lead author Benjamin L. Cohen, MD, Cleveland Clinic Foundation, told this news organization. “In the past, when clinicians were unsure about the safety of using these drugs in the perioperative period, they may have delayed surgeries or stopped medications unnecessarily.”

“For me, the key take-home point of this study is that we need to plan the timing and management of medications around surgery based on factors other than the use of tumor necrosis factor inhibitors in most patients,” Dr. Cohen continued.

Ultimately, “we will help change practice in how we manage patients with IBD having surgery,” he said.

The research was published online in Gastroenterology.
 

No increased postop infection risk

The Prospective Cohort of Ulcerative Colitis and Crohn’s Disease Patients Undergoing Surgery to Identify Risk Factors for Post-Operative Infection I (PUCCINI) trial enrolled patients with IBD from 17 sites participating in the Crohn’s and Colitis Foundation Clinical Research Alliance between September 2014 and June 2017.

Patients had Crohn’s disease, ulcerative colitis, or indeterminate colitis, as determined by standard criteria, and planned to undergo intra-abdominal surgery or had undergone intra-abdominal surgery in the preceding 4 days.

Among the 947 patients enrolled, 47.8% were women. All were aged 18 years or older. The median disease duration was 10 years; 34.4% of patients had undergone prior bowel resection, and a further 17.5% had undergone other abdominal surgery.

Systemic corticosteroid use within 2 weeks of surgery was reported by 40.9% of patients, and 42.3% had used antibiotics.

TNFi exposure within the 12 weeks prior to surgery was reported by 40.3% of patients. Adalimumab and infliximab were the most commonly used drugs. Among those who had not used TNFi prior to surgery, 23.7% were TNFi-naive, and 36.0% had used them in the past.

The researchers report that there was no significant difference in the rate of postoperative infections between patients who reported using TNFi in the 12 weeks prior to surgery and those who did not (18.1% vs. 20.2%; P = .469). There was also no difference in SSI, as defined using the Centers for Disease Control and Prevention criteria, between the two groups (12.0% vs 12.6%; P = .889).

Multivariate analysis revealed that current TNFi exposure was not associated with any infection, at an odds ratio versus no exposure of 1.050 (P = .80), or with SSI, at an odds ratio of 1.249 (P = .34).

In contrast, preoperative corticosteroid exposure, prior bowel resection, and current smoking were associated with any infection and with SSI.

Approached for comment, Stephen B. Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, said that the current findings are consistent with those of previous studies and that their relevance extends beyond abdominal surgery.

In the past, when surgeons were “confronted with a patient on a TNF blocker, even if it’s orthopedic or plastic surgery, they recommended against using a TNF blocker or operating at the end of the cycle when the drug levels are low,” he told this news organization.

Dr. Hanauer said such practice gets clinicians into a “bind because you’ve got a patient, for instance, who’s got a blockage with Crohn’s disease ... but the only way you could manage them when the TNFi was out of their system was with steroids, which is worse” in terms of postoperative infection risk, he explained.
 

Prospective studies important

The researchers note that up to 50% of patients with IBD are exposed to TNFi prior to their first surgery. They also note that there is concern that preoperative treatment with these and other immunosuppressive medications may increase the risk of postoperative infections.

However, the evidence is inconsistent, they write, so whether to continue or stop the drugs prior to surgery remains controversial.

“A lot of the initial studies in the perioperative population were single-center and retrospective for the most part,” Dr. Cohen said, adding that the studies used different modes of assessment and followed different time frames.

“So, there’s a lot of heterogeneity,” he said.

In addition, early studies of TNFi were often conducted with patients who were very ill and who had started receiving the drug right before surgery, and they sometimes had a complication Dr. Cohen said. “But you don’t know if that’s because of the drug itself or because of many other factors associated with them being very sick, such as being on steroids, being very malnourished, or having other complications of disease.”

It is difficult to control for such risk factors in retrospective analyses because the information is not always available from medical records, he said. “That’s why it’s so important to study clinical questions like this in a prospective manner.”

Dr. Cohen added that it is important that studies such as theirs continue to be undertaken as new drugs become available.

“We’re entering an era of rapidly expanding drug discovery, so we’re going to have new medications available for use in our patients with IBD,” he explained. “It’s important that we continue to build prospective cohorts to look at questions such as the safety of medications in the perioperative period, rather than solely relying on retrospective data.”

The study was funded by a Crohn’s & Colitis Foundation Senior Research Award. Dr. Cohen reports relationships with AbbVie, Celgene, Bristol-Myers Squibb, Pfizer, Sublimity Therapeutics, Target RWE, Janssen, Ferring, AlphaSigma, and Takeda. Other authors report numerous financial relationships. Dr. Hanauer reports relationships with Janssen, AbbVie, Pfizer, Amgen, Genentech, and Merck.

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

Patients with inflammatory bowel disease (IBD) can safely take tumor necrosis factor inhibitors (TNFi) prior to abdominal surgery, a prospective, multicenter, observational study confirms.

The researchers found that exposure to TNFi in the 12 weeks prior to surgery was not associated with an increased risk of either overall infections or surgical site infections (SSI).

The findings should be “very reassuring” for clinicians, lead author Benjamin L. Cohen, MD, Cleveland Clinic Foundation, told this news organization. “In the past, when clinicians were unsure about the safety of using these drugs in the perioperative period, they may have delayed surgeries or stopped medications unnecessarily.”

“For me, the key take-home point of this study is that we need to plan the timing and management of medications around surgery based on factors other than the use of tumor necrosis factor inhibitors in most patients,” Dr. Cohen continued.

Ultimately, “we will help change practice in how we manage patients with IBD having surgery,” he said.

The research was published online in Gastroenterology.
 

No increased postop infection risk

The Prospective Cohort of Ulcerative Colitis and Crohn’s Disease Patients Undergoing Surgery to Identify Risk Factors for Post-Operative Infection I (PUCCINI) trial enrolled patients with IBD from 17 sites participating in the Crohn’s and Colitis Foundation Clinical Research Alliance between September 2014 and June 2017.

Patients had Crohn’s disease, ulcerative colitis, or indeterminate colitis, as determined by standard criteria, and planned to undergo intra-abdominal surgery or had undergone intra-abdominal surgery in the preceding 4 days.

Among the 947 patients enrolled, 47.8% were women. All were aged 18 years or older. The median disease duration was 10 years; 34.4% of patients had undergone prior bowel resection, and a further 17.5% had undergone other abdominal surgery.

Systemic corticosteroid use within 2 weeks of surgery was reported by 40.9% of patients, and 42.3% had used antibiotics.

TNFi exposure within the 12 weeks prior to surgery was reported by 40.3% of patients. Adalimumab and infliximab were the most commonly used drugs. Among those who had not used TNFi prior to surgery, 23.7% were TNFi-naive, and 36.0% had used them in the past.

The researchers report that there was no significant difference in the rate of postoperative infections between patients who reported using TNFi in the 12 weeks prior to surgery and those who did not (18.1% vs. 20.2%; P = .469). There was also no difference in SSI, as defined using the Centers for Disease Control and Prevention criteria, between the two groups (12.0% vs 12.6%; P = .889).

Multivariate analysis revealed that current TNFi exposure was not associated with any infection, at an odds ratio versus no exposure of 1.050 (P = .80), or with SSI, at an odds ratio of 1.249 (P = .34).

In contrast, preoperative corticosteroid exposure, prior bowel resection, and current smoking were associated with any infection and with SSI.

Approached for comment, Stephen B. Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, said that the current findings are consistent with those of previous studies and that their relevance extends beyond abdominal surgery.

In the past, when surgeons were “confronted with a patient on a TNF blocker, even if it’s orthopedic or plastic surgery, they recommended against using a TNF blocker or operating at the end of the cycle when the drug levels are low,” he told this news organization.

Dr. Hanauer said such practice gets clinicians into a “bind because you’ve got a patient, for instance, who’s got a blockage with Crohn’s disease ... but the only way you could manage them when the TNFi was out of their system was with steroids, which is worse” in terms of postoperative infection risk, he explained.
 

Prospective studies important

The researchers note that up to 50% of patients with IBD are exposed to TNFi prior to their first surgery. They also note that there is concern that preoperative treatment with these and other immunosuppressive medications may increase the risk of postoperative infections.

However, the evidence is inconsistent, they write, so whether to continue or stop the drugs prior to surgery remains controversial.

“A lot of the initial studies in the perioperative population were single-center and retrospective for the most part,” Dr. Cohen said, adding that the studies used different modes of assessment and followed different time frames.

“So, there’s a lot of heterogeneity,” he said.

In addition, early studies of TNFi were often conducted with patients who were very ill and who had started receiving the drug right before surgery, and they sometimes had a complication Dr. Cohen said. “But you don’t know if that’s because of the drug itself or because of many other factors associated with them being very sick, such as being on steroids, being very malnourished, or having other complications of disease.”

It is difficult to control for such risk factors in retrospective analyses because the information is not always available from medical records, he said. “That’s why it’s so important to study clinical questions like this in a prospective manner.”

Dr. Cohen added that it is important that studies such as theirs continue to be undertaken as new drugs become available.

“We’re entering an era of rapidly expanding drug discovery, so we’re going to have new medications available for use in our patients with IBD,” he explained. “It’s important that we continue to build prospective cohorts to look at questions such as the safety of medications in the perioperative period, rather than solely relying on retrospective data.”

The study was funded by a Crohn’s & Colitis Foundation Senior Research Award. Dr. Cohen reports relationships with AbbVie, Celgene, Bristol-Myers Squibb, Pfizer, Sublimity Therapeutics, Target RWE, Janssen, Ferring, AlphaSigma, and Takeda. Other authors report numerous financial relationships. Dr. Hanauer reports relationships with Janssen, AbbVie, Pfizer, Amgen, Genentech, and Merck.

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

MANCHESTER, ENGLAND – A new treatment option may soon be available for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

Zanubrutinib (Brukinsa), an irreversible, next-generation Bruton tyrosine kinase (BTK) inhibitor, is designed to minimize the off-target cardiovascular toxicities, such as atrial fibrillation and hypertension, seen with the first-generation ibrutinib (Imbruvica).

Zanubrutinib is already approved for use in mantle cell and marginal zone lymphomas and Waldenström’s macroglobulinemia.

Now it has also shown efficacy in CLL. In two phase 3 clinical trials, zanubrutinib has shown improved outcomes and reduced toxicity when compared with more established treatments in patients with relapsed/refractory and untreated CLL and SLL.

However, experts question whether the drug will find its place in an increasingly crowded space for the management of CLL.
 

Data from two phase 3 trials

The new data from two phase 3 clinical trials were presented recently at the British Society for Haematology 62nd annual scientific meeting, held in Manchester, England.

The ALPINE trial compared zanubrutinib with ibrutinib in 415 patients with CLL/SLL and showed that the novel drug was associated with a significant improvement in overall response rate, at 78% versus 63%.

This first interim analysis also showed that there was an increase in progression-free survival (PFS) with zanubrutinib, and crucially, it was associated with a lower atrial fibrillation/flutter rate than ibrutinib.

“These data support that more selective BTK inhibition, with more complete and sustained BTK occupancy, results in improved efficacy and safety outcomes,” said lead author Peter Hillmen, MBChB, FRCP, PhD, St. James’s University Hospital, Leeds, England.

The SEQUOIA study looked at zanubrutinib versus bendamustine plus rituximab in patients with untreated CLL/SLL with a 17p deletion and showed that PFS was improved with zanubrutinib by 58%.

Zanubrutinib was also associated with improved overall response rates and was well tolerated.

The results therefore “support the potential utility of zanubrutinib in the frontline management of patients with previously untreated CLL/SLL,” said lead author Talha Munir, MBBS, also of St. James’s University Hospital.
 

Improvement over ibrutinib

Ibrutinib, the first BTK inhibitor, “truly revolutionized the way we treat CLL,” commented Renata Walewska, MRCP, PhD, consultant hematologist at the Royal Bournemouth (England) Hospital and chair of the UKCLL Forum.

“But it has got quite a lot of, especially cardiac, problems, with atrial fibrillation and hypertension,” she said in an interview. The problem is that it acts not only as an inhibitor of Bruton kinase, but also affects other kinases, she explained.

Zanubrutinib is “much cleaner,” continued Dr. Walewska, who was lead author of the recently published British Society of Haematology guideline for the treatment of CLL.

However, the drug “is not that groundbreaking,” she commented, as acalabrutinib (Calquence), another next-generation BTK inhibitor, is already available for use in the clinic.

“We’re really lucky in CLL,” Dr. Walewska said, “we’ve got so many new drugs available, and it’s getting quite crowded. Trying to find a place for zanubrutinib is going be tricky.”

Lee Greenberger, PhD, chief scientific officer at the Leukemia & Lymphoma Society, commented that he “gives a lot of credit” to BeiGene, the company behind zanubrutinib, for “taking on these big studies.”

He said that, with the improvements in PFS and reduced atrial fibrillation with the drug, “there will be many clinicians paying attention to this and zanubrutinib could be preferred over conventional options.”

However, he agreed that it will have to compete with acalabrutinib, adding that, beyond BTK inhibitors, there are “a lot of options” for patients with CLL.

“That makes it very difficult for physicians to figure out what is the best type of therapy” to use in these patients, he added.

Dr. Greenberger told this news organization that further studies will need to demonstrate that zanubrutinib is associated with extended survival, which is “just not possible to show” at the moment with the current follow-up period.

He also noted that, in 10 years, ibrutinib will be off-patent, but zanubrutinib will not, at which point the “substantial” cost of the medication, which is a source of “hardship to patients,” will be increasingly relevant.
 

Study details

The phase 3 ALPINE study involved 415 adults with CLL/SLL refractory to one or more prior systemic therapies and measurable lymphadenopathy on imaging.  

They were randomized 1:1 to zanubrutinib or ibrutinib until disease progression or withdrawal from the study.

Most patients had Binet stage A/B or Ann Arbor stage I/II disease, and 7.3% of patients treated with zanubrutinib and 10.1% of those assigned to ibrutinib had received more than three prior lines of therapy.

Over 60% of patients were aged 65 years or older and around 70% were men, with no significant differences between treatment groups.

Patients were randomized 1:1 to zanubrutinib or ibrutinib until disease progression or study withdrawal.

After a median follow-up of 15 months, the overall response rate was significantly higher with zanubrutinib than ibrutinib, at 78.3% versus 62.5% (P = .0006).

Subgroup analysis confirmed that the effect was seen regardless of age, sex, disease stage, number of prior lines of therapy, mutation status, or bulky disease.

Over a median follow-up of 14 months, the investigator-assessed 12-month PFS was 94.9% for zanubrutinib and 84.0% for ibrutinib (P = .0007). Overall survival at 12 months was 97% versus 92.7%, but the difference was not significant (P = .1081).

Patients treated with zanubrutinib experienced more grade 3 or higher adverse events than those given ibrutinib, at 55.9% versus 51.2%, although they had fewer adverse events leading to treatment discontinuation, at 7.8% versus 13.0%.

More importantly, there were fewer cardiac disorders of any grade with zanubrutinib versus ibrutinib, and any-grade atrial fibrillation was significantly less common, at 2.5% versus 10.1% (P = .0014).

Rates of hypertension and hemorrhage were similar between the two treatments, while rates of neutropenia were higher with zanubrutinib versus ibrutinib, at 28.4% versus 21.7%.

The phase 3 SEQUOIA study looked at an earlier stage of disease and included patients with previously untreated CLL/SLL (without 17p depletion) who were unsuitable for treatment with fludarabine, cyclophosphamide, and rituximab.

This trial involved 479 patients randomized to zanubrutinib or bendamustine (days 1 and 2) plus rituximab for six cycles of 28 days each (B+R).

The median age of patients was 70 years, and approximately 80% were at least 65 years old. Just over 60% were men and most (over 70%) were from Europe.

After a median of 26.2 months, independent review committee–assessed PFS was significantly longer with zanubrutinib versus B+R (hazard ratio, 0.42; P < .0001), with an estimated 24-month PFS of 85.5% versus 69.5%.

These results held whether patients were stratified by age, Binet stage, bulky disease, or 11q deletion status, and for patients with an unmutated, but not mutated, immunoglobulin heavy chain gene.

The overall response rate with zanubrutinib was 94.6% versus 85.3% with B+R, and estimated 24-month overall survival was 94.3% versus 94.6%.

Rates of adverse events of any grade were similar between the two treatment groups, although B+R was associated with a higher (grade ≥ 3) adverse event rate, at 79.7%, versus 52.5% for zanubrutinib, and a higher rate of treatment discontinuation because of adverse events, at 13.7% versus 8.3%.

Interestingly, any-grade hypertension was more common with zanubrutinib versus B+R, at 14.2% versus 10.6%, but much lower rates of neutropenia were more common with zanubrutinib, at 15.8% versus 56.8%.

The studies were sponsored by BeiGene. Dr. Hillmen has reported relationships with Janssen, AbbVie, Pharmacyclics, Roche, Gilead, AstraZeneca, SOBI, and BeiGene. Dr. Munir has reported relationships with AbbVie, AstraZeneca, Roche, Alexion, Janssen, MorphoSys, and SOBI. Other authors have also declared numerous relationships.

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

MANCHESTER, ENGLAND – A new treatment option may soon be available for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

Zanubrutinib (Brukinsa), an irreversible, next-generation Bruton tyrosine kinase (BTK) inhibitor, is designed to minimize the off-target cardiovascular toxicities, such as atrial fibrillation and hypertension, seen with the first-generation ibrutinib (Imbruvica).

Zanubrutinib is already approved for use in mantle cell and marginal zone lymphomas and Waldenström’s macroglobulinemia.

Now it has also shown efficacy in CLL. In two phase 3 clinical trials, zanubrutinib has shown improved outcomes and reduced toxicity when compared with more established treatments in patients with relapsed/refractory and untreated CLL and SLL.

However, experts question whether the drug will find its place in an increasingly crowded space for the management of CLL.
 

Data from two phase 3 trials

The new data from two phase 3 clinical trials were presented recently at the British Society for Haematology 62nd annual scientific meeting, held in Manchester, England.

The ALPINE trial compared zanubrutinib with ibrutinib in 415 patients with CLL/SLL and showed that the novel drug was associated with a significant improvement in overall response rate, at 78% versus 63%.

This first interim analysis also showed that there was an increase in progression-free survival (PFS) with zanubrutinib, and crucially, it was associated with a lower atrial fibrillation/flutter rate than ibrutinib.

“These data support that more selective BTK inhibition, with more complete and sustained BTK occupancy, results in improved efficacy and safety outcomes,” said lead author Peter Hillmen, MBChB, FRCP, PhD, St. James’s University Hospital, Leeds, England.

The SEQUOIA study looked at zanubrutinib versus bendamustine plus rituximab in patients with untreated CLL/SLL with a 17p deletion and showed that PFS was improved with zanubrutinib by 58%.

Zanubrutinib was also associated with improved overall response rates and was well tolerated.

The results therefore “support the potential utility of zanubrutinib in the frontline management of patients with previously untreated CLL/SLL,” said lead author Talha Munir, MBBS, also of St. James’s University Hospital.
 

Improvement over ibrutinib

Ibrutinib, the first BTK inhibitor, “truly revolutionized the way we treat CLL,” commented Renata Walewska, MRCP, PhD, consultant hematologist at the Royal Bournemouth (England) Hospital and chair of the UKCLL Forum.

“But it has got quite a lot of, especially cardiac, problems, with atrial fibrillation and hypertension,” she said in an interview. The problem is that it acts not only as an inhibitor of Bruton kinase, but also affects other kinases, she explained.

Zanubrutinib is “much cleaner,” continued Dr. Walewska, who was lead author of the recently published British Society of Haematology guideline for the treatment of CLL.

However, the drug “is not that groundbreaking,” she commented, as acalabrutinib (Calquence), another next-generation BTK inhibitor, is already available for use in the clinic.

“We’re really lucky in CLL,” Dr. Walewska said, “we’ve got so many new drugs available, and it’s getting quite crowded. Trying to find a place for zanubrutinib is going be tricky.”

Lee Greenberger, PhD, chief scientific officer at the Leukemia & Lymphoma Society, commented that he “gives a lot of credit” to BeiGene, the company behind zanubrutinib, for “taking on these big studies.”

He said that, with the improvements in PFS and reduced atrial fibrillation with the drug, “there will be many clinicians paying attention to this and zanubrutinib could be preferred over conventional options.”

However, he agreed that it will have to compete with acalabrutinib, adding that, beyond BTK inhibitors, there are “a lot of options” for patients with CLL.

“That makes it very difficult for physicians to figure out what is the best type of therapy” to use in these patients, he added.

Dr. Greenberger told this news organization that further studies will need to demonstrate that zanubrutinib is associated with extended survival, which is “just not possible to show” at the moment with the current follow-up period.

He also noted that, in 10 years, ibrutinib will be off-patent, but zanubrutinib will not, at which point the “substantial” cost of the medication, which is a source of “hardship to patients,” will be increasingly relevant.
 

Study details

The phase 3 ALPINE study involved 415 adults with CLL/SLL refractory to one or more prior systemic therapies and measurable lymphadenopathy on imaging.  

They were randomized 1:1 to zanubrutinib or ibrutinib until disease progression or withdrawal from the study.

Most patients had Binet stage A/B or Ann Arbor stage I/II disease, and 7.3% of patients treated with zanubrutinib and 10.1% of those assigned to ibrutinib had received more than three prior lines of therapy.

Over 60% of patients were aged 65 years or older and around 70% were men, with no significant differences between treatment groups.

Patients were randomized 1:1 to zanubrutinib or ibrutinib until disease progression or study withdrawal.

After a median follow-up of 15 months, the overall response rate was significantly higher with zanubrutinib than ibrutinib, at 78.3% versus 62.5% (P = .0006).

Subgroup analysis confirmed that the effect was seen regardless of age, sex, disease stage, number of prior lines of therapy, mutation status, or bulky disease.

Over a median follow-up of 14 months, the investigator-assessed 12-month PFS was 94.9% for zanubrutinib and 84.0% for ibrutinib (P = .0007). Overall survival at 12 months was 97% versus 92.7%, but the difference was not significant (P = .1081).

Patients treated with zanubrutinib experienced more grade 3 or higher adverse events than those given ibrutinib, at 55.9% versus 51.2%, although they had fewer adverse events leading to treatment discontinuation, at 7.8% versus 13.0%.

More importantly, there were fewer cardiac disorders of any grade with zanubrutinib versus ibrutinib, and any-grade atrial fibrillation was significantly less common, at 2.5% versus 10.1% (P = .0014).

Rates of hypertension and hemorrhage were similar between the two treatments, while rates of neutropenia were higher with zanubrutinib versus ibrutinib, at 28.4% versus 21.7%.

The phase 3 SEQUOIA study looked at an earlier stage of disease and included patients with previously untreated CLL/SLL (without 17p depletion) who were unsuitable for treatment with fludarabine, cyclophosphamide, and rituximab.

This trial involved 479 patients randomized to zanubrutinib or bendamustine (days 1 and 2) plus rituximab for six cycles of 28 days each (B+R).

The median age of patients was 70 years, and approximately 80% were at least 65 years old. Just over 60% were men and most (over 70%) were from Europe.

After a median of 26.2 months, independent review committee–assessed PFS was significantly longer with zanubrutinib versus B+R (hazard ratio, 0.42; P < .0001), with an estimated 24-month PFS of 85.5% versus 69.5%.

These results held whether patients were stratified by age, Binet stage, bulky disease, or 11q deletion status, and for patients with an unmutated, but not mutated, immunoglobulin heavy chain gene.

The overall response rate with zanubrutinib was 94.6% versus 85.3% with B+R, and estimated 24-month overall survival was 94.3% versus 94.6%.

Rates of adverse events of any grade were similar between the two treatment groups, although B+R was associated with a higher (grade ≥ 3) adverse event rate, at 79.7%, versus 52.5% for zanubrutinib, and a higher rate of treatment discontinuation because of adverse events, at 13.7% versus 8.3%.

Interestingly, any-grade hypertension was more common with zanubrutinib versus B+R, at 14.2% versus 10.6%, but much lower rates of neutropenia were more common with zanubrutinib, at 15.8% versus 56.8%.

The studies were sponsored by BeiGene. Dr. Hillmen has reported relationships with Janssen, AbbVie, Pharmacyclics, Roche, Gilead, AstraZeneca, SOBI, and BeiGene. Dr. Munir has reported relationships with AbbVie, AstraZeneca, Roche, Alexion, Janssen, MorphoSys, and SOBI. Other authors have also declared numerous relationships.

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

MANCHESTER, ENGLAND – A new treatment option may soon be available for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

Zanubrutinib (Brukinsa), an irreversible, next-generation Bruton tyrosine kinase (BTK) inhibitor, is designed to minimize the off-target cardiovascular toxicities, such as atrial fibrillation and hypertension, seen with the first-generation ibrutinib (Imbruvica).

Zanubrutinib is already approved for use in mantle cell and marginal zone lymphomas and Waldenström’s macroglobulinemia.

Now it has also shown efficacy in CLL. In two phase 3 clinical trials, zanubrutinib has shown improved outcomes and reduced toxicity when compared with more established treatments in patients with relapsed/refractory and untreated CLL and SLL.

However, experts question whether the drug will find its place in an increasingly crowded space for the management of CLL.
 

Data from two phase 3 trials

The new data from two phase 3 clinical trials were presented recently at the British Society for Haematology 62nd annual scientific meeting, held in Manchester, England.

The ALPINE trial compared zanubrutinib with ibrutinib in 415 patients with CLL/SLL and showed that the novel drug was associated with a significant improvement in overall response rate, at 78% versus 63%.

This first interim analysis also showed that there was an increase in progression-free survival (PFS) with zanubrutinib, and crucially, it was associated with a lower atrial fibrillation/flutter rate than ibrutinib.

“These data support that more selective BTK inhibition, with more complete and sustained BTK occupancy, results in improved efficacy and safety outcomes,” said lead author Peter Hillmen, MBChB, FRCP, PhD, St. James’s University Hospital, Leeds, England.

The SEQUOIA study looked at zanubrutinib versus bendamustine plus rituximab in patients with untreated CLL/SLL with a 17p deletion and showed that PFS was improved with zanubrutinib by 58%.

Zanubrutinib was also associated with improved overall response rates and was well tolerated.

The results therefore “support the potential utility of zanubrutinib in the frontline management of patients with previously untreated CLL/SLL,” said lead author Talha Munir, MBBS, also of St. James’s University Hospital.
 

Improvement over ibrutinib

Ibrutinib, the first BTK inhibitor, “truly revolutionized the way we treat CLL,” commented Renata Walewska, MRCP, PhD, consultant hematologist at the Royal Bournemouth (England) Hospital and chair of the UKCLL Forum.

“But it has got quite a lot of, especially cardiac, problems, with atrial fibrillation and hypertension,” she said in an interview. The problem is that it acts not only as an inhibitor of Bruton kinase, but also affects other kinases, she explained.

Zanubrutinib is “much cleaner,” continued Dr. Walewska, who was lead author of the recently published British Society of Haematology guideline for the treatment of CLL.

However, the drug “is not that groundbreaking,” she commented, as acalabrutinib (Calquence), another next-generation BTK inhibitor, is already available for use in the clinic.

“We’re really lucky in CLL,” Dr. Walewska said, “we’ve got so many new drugs available, and it’s getting quite crowded. Trying to find a place for zanubrutinib is going be tricky.”

Lee Greenberger, PhD, chief scientific officer at the Leukemia & Lymphoma Society, commented that he “gives a lot of credit” to BeiGene, the company behind zanubrutinib, for “taking on these big studies.”

He said that, with the improvements in PFS and reduced atrial fibrillation with the drug, “there will be many clinicians paying attention to this and zanubrutinib could be preferred over conventional options.”

However, he agreed that it will have to compete with acalabrutinib, adding that, beyond BTK inhibitors, there are “a lot of options” for patients with CLL.

“That makes it very difficult for physicians to figure out what is the best type of therapy” to use in these patients, he added.

Dr. Greenberger told this news organization that further studies will need to demonstrate that zanubrutinib is associated with extended survival, which is “just not possible to show” at the moment with the current follow-up period.

He also noted that, in 10 years, ibrutinib will be off-patent, but zanubrutinib will not, at which point the “substantial” cost of the medication, which is a source of “hardship to patients,” will be increasingly relevant.
 

Study details

The phase 3 ALPINE study involved 415 adults with CLL/SLL refractory to one or more prior systemic therapies and measurable lymphadenopathy on imaging.  

They were randomized 1:1 to zanubrutinib or ibrutinib until disease progression or withdrawal from the study.

Most patients had Binet stage A/B or Ann Arbor stage I/II disease, and 7.3% of patients treated with zanubrutinib and 10.1% of those assigned to ibrutinib had received more than three prior lines of therapy.

Over 60% of patients were aged 65 years or older and around 70% were men, with no significant differences between treatment groups.

Patients were randomized 1:1 to zanubrutinib or ibrutinib until disease progression or study withdrawal.

After a median follow-up of 15 months, the overall response rate was significantly higher with zanubrutinib than ibrutinib, at 78.3% versus 62.5% (P = .0006).

Subgroup analysis confirmed that the effect was seen regardless of age, sex, disease stage, number of prior lines of therapy, mutation status, or bulky disease.

Over a median follow-up of 14 months, the investigator-assessed 12-month PFS was 94.9% for zanubrutinib and 84.0% for ibrutinib (P = .0007). Overall survival at 12 months was 97% versus 92.7%, but the difference was not significant (P = .1081).

Patients treated with zanubrutinib experienced more grade 3 or higher adverse events than those given ibrutinib, at 55.9% versus 51.2%, although they had fewer adverse events leading to treatment discontinuation, at 7.8% versus 13.0%.

More importantly, there were fewer cardiac disorders of any grade with zanubrutinib versus ibrutinib, and any-grade atrial fibrillation was significantly less common, at 2.5% versus 10.1% (P = .0014).

Rates of hypertension and hemorrhage were similar between the two treatments, while rates of neutropenia were higher with zanubrutinib versus ibrutinib, at 28.4% versus 21.7%.

The phase 3 SEQUOIA study looked at an earlier stage of disease and included patients with previously untreated CLL/SLL (without 17p depletion) who were unsuitable for treatment with fludarabine, cyclophosphamide, and rituximab.

This trial involved 479 patients randomized to zanubrutinib or bendamustine (days 1 and 2) plus rituximab for six cycles of 28 days each (B+R).

The median age of patients was 70 years, and approximately 80% were at least 65 years old. Just over 60% were men and most (over 70%) were from Europe.

After a median of 26.2 months, independent review committee–assessed PFS was significantly longer with zanubrutinib versus B+R (hazard ratio, 0.42; P < .0001), with an estimated 24-month PFS of 85.5% versus 69.5%.

These results held whether patients were stratified by age, Binet stage, bulky disease, or 11q deletion status, and for patients with an unmutated, but not mutated, immunoglobulin heavy chain gene.

The overall response rate with zanubrutinib was 94.6% versus 85.3% with B+R, and estimated 24-month overall survival was 94.3% versus 94.6%.

Rates of adverse events of any grade were similar between the two treatment groups, although B+R was associated with a higher (grade ≥ 3) adverse event rate, at 79.7%, versus 52.5% for zanubrutinib, and a higher rate of treatment discontinuation because of adverse events, at 13.7% versus 8.3%.

Interestingly, any-grade hypertension was more common with zanubrutinib versus B+R, at 14.2% versus 10.6%, but much lower rates of neutropenia were more common with zanubrutinib, at 15.8% versus 56.8%.

The studies were sponsored by BeiGene. Dr. Hillmen has reported relationships with Janssen, AbbVie, Pharmacyclics, Roche, Gilead, AstraZeneca, SOBI, and BeiGene. Dr. Munir has reported relationships with AbbVie, AstraZeneca, Roche, Alexion, Janssen, MorphoSys, and SOBI. Other authors have also declared numerous relationships.

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

Patients with first-episode psychosis (FEP) show altered speech patterns and content that could pinpoint symptom severity – and help predict future relapse, two new studies suggest.

In the first study, an algorithm was created to analyze speech patterns and semantic content to create novel “speech networks.” Compared with their healthy peers, patients with FEP had smaller and more fragmented networks. At-risk individuals had fragmented values that were in between those of the FEP and healthy control groups.

“This suggests that semantic speech networks can enable deeper phenotyping of formal thought disorder and psychosis,” said lead author Caroline Nettekoven, PhD, department of psychiatry, University of Cambridge, England.

In the second study, Janna N. de Boer, MD, University of Groningen, the Netherlands, and colleagues examined patients with FEP who did and did not experience relapse after 24 months of follow-up.

An algorithm based on natural language processing (NLP) of speech recordings predicted the relapses with an accuracy of more than 80%.

NLP “is a powerful tool with high potential for clinical application and diagnosis and differentiation, given its ease in acquirement, low cost, and naturally low patient burden,” said de Boer.

The findings for both studies were presented at the annual congress of the Schizophrenia International Research Society.
 

Fragmented networks

Dr. Nettekoven noted that previous research has shown “mapping the speech of a psychosis patient as a network and analyzing the network using graph theory is useful for understanding formal thought disorder.”

However, these tools ignore the semantic content of speech, which is a “key feature” that is altered in psychotic language, she added.

The researchers therefore proposed a “novel type of network to map the content of speech.”

For example, if someone said, “I see a man,” a semantic speech network developed from this sentence would have the first and last words connected by “the edge” to the word “see,” Dr. Nettekoven explained.

To explore further, the investigators developed an algorithm known as “netts” that automatically creates semantic speech networks from transcribed speech.

They first applied the algorithm to transcribed speech from a general population sample of 436 individuals and then to a clinical sample (n = 53) comprising patients with FEP, those at clinical high risk for psychosis, and a healthy control group.

Comparing the general population sample with randomly generated semantic speech networks, the investigators found that networks from the general population had fewer but larger connected components, which “reflects the nonrandom nature of speech,” said Dr. Nettekoven.

In the clinical sample, networks from the FEP group had a significantly higher number of connected components compared with the healthy control group (P = .05) and a significantly smaller median connected-component size (P < .01).

“So patients’ mental speech networks are more fragmented than those from controls,” said Dr. Nettekoven. She added that the networks from clinically high-risk individuals “showed fragmentation values in between [those of] patients and controls.”

A further clustering analysis suggested the semantic speech networks “capture a novel signal that is not already described” by other NLP measures, Dr. Nettekoven said. In addition, the network features were related to negative symptom scores and scores on the Thought and Language Index.

However, Dr. Nettekoven noted that these relationships “did not survive correcting for multiple comparisons.”
 

Relapse predictor

During her presentation of the second study, Dr. de Boer said that “predicting relapse remains challenging” in FEP.

However, she noted that recent developments in NLP have proved to be effective in a “range of applications,” including early symptom recognition and differential diagnosis in psychosis.

To determine whether NLP could help predict relapse, the study included 104 patients aged 16-55 years with FEP whose conditions had been in remission for 3-6 months. Speech recordings were made at baseline and after 3 and 6 months and were analyzed via OpenSMILE software.

After a follow-up of 24 months, 24 of the patients remaining in the study had not experienced relapse, while 21 patients had experienced relapse. There were no significant age, education, or gender differences between those who did and those who did not experience relapse.

On the basis of speech analysis, the investigators identified a machine learning classifier, which showed an accuracy of 80.8% in predicting relapse 3 months in advance of the occurrence.
 

‘Valid and informative’

Commenting on the studies, Eric J. Tan, PhD, Centre for Mental Health, Swinburne University of Technology, Melbourne, said they are “but two of a variety of ways in which speech can be analyzed and are both equally valid and informative.”

The key takeaway “is that both studies are examples of the ways in which speech can be used clinically, such as for predicting relapse and for the potential proxy measure for the assessment of symptom severity,” said Dr. Tan, who was not involved with the research.

The studies also show that “speech is sensitive to different stages of the disorder, as well as its individual symptoms,” he added.

However, Dr. Tan noted that although “speech may be more of a sign of an underlying pathology or dysfunction, given that it waxes and wanes with illness severity, more analyses are needed before drawing definitive conclusions.” This is especially needed “given the relative infancy of quantitative speech analysis,” he said.

“It would also be useful to conduct these analyses across a variety of different languages to look for commonalities and differences that will help shed light on the variables most closely linked to the disorder,” Dr. Tan concluded.

The investigators have reported no relevant financial relationships. Dr. Tan has received an Early Career Research Fellowship from the National Health and Medical Research Council of Australia.

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

Patients with first-episode psychosis (FEP) show altered speech patterns and content that could pinpoint symptom severity – and help predict future relapse, two new studies suggest.

In the first study, an algorithm was created to analyze speech patterns and semantic content to create novel “speech networks.” Compared with their healthy peers, patients with FEP had smaller and more fragmented networks. At-risk individuals had fragmented values that were in between those of the FEP and healthy control groups.

“This suggests that semantic speech networks can enable deeper phenotyping of formal thought disorder and psychosis,” said lead author Caroline Nettekoven, PhD, department of psychiatry, University of Cambridge, England.

In the second study, Janna N. de Boer, MD, University of Groningen, the Netherlands, and colleagues examined patients with FEP who did and did not experience relapse after 24 months of follow-up.

An algorithm based on natural language processing (NLP) of speech recordings predicted the relapses with an accuracy of more than 80%.

NLP “is a powerful tool with high potential for clinical application and diagnosis and differentiation, given its ease in acquirement, low cost, and naturally low patient burden,” said de Boer.

The findings for both studies were presented at the annual congress of the Schizophrenia International Research Society.
 

Fragmented networks

Dr. Nettekoven noted that previous research has shown “mapping the speech of a psychosis patient as a network and analyzing the network using graph theory is useful for understanding formal thought disorder.”

However, these tools ignore the semantic content of speech, which is a “key feature” that is altered in psychotic language, she added.

The researchers therefore proposed a “novel type of network to map the content of speech.”

For example, if someone said, “I see a man,” a semantic speech network developed from this sentence would have the first and last words connected by “the edge” to the word “see,” Dr. Nettekoven explained.

To explore further, the investigators developed an algorithm known as “netts” that automatically creates semantic speech networks from transcribed speech.

They first applied the algorithm to transcribed speech from a general population sample of 436 individuals and then to a clinical sample (n = 53) comprising patients with FEP, those at clinical high risk for psychosis, and a healthy control group.

Comparing the general population sample with randomly generated semantic speech networks, the investigators found that networks from the general population had fewer but larger connected components, which “reflects the nonrandom nature of speech,” said Dr. Nettekoven.

In the clinical sample, networks from the FEP group had a significantly higher number of connected components compared with the healthy control group (P = .05) and a significantly smaller median connected-component size (P < .01).

“So patients’ mental speech networks are more fragmented than those from controls,” said Dr. Nettekoven. She added that the networks from clinically high-risk individuals “showed fragmentation values in between [those of] patients and controls.”

A further clustering analysis suggested the semantic speech networks “capture a novel signal that is not already described” by other NLP measures, Dr. Nettekoven said. In addition, the network features were related to negative symptom scores and scores on the Thought and Language Index.

However, Dr. Nettekoven noted that these relationships “did not survive correcting for multiple comparisons.”
 

Relapse predictor

During her presentation of the second study, Dr. de Boer said that “predicting relapse remains challenging” in FEP.

However, she noted that recent developments in NLP have proved to be effective in a “range of applications,” including early symptom recognition and differential diagnosis in psychosis.

To determine whether NLP could help predict relapse, the study included 104 patients aged 16-55 years with FEP whose conditions had been in remission for 3-6 months. Speech recordings were made at baseline and after 3 and 6 months and were analyzed via OpenSMILE software.

After a follow-up of 24 months, 24 of the patients remaining in the study had not experienced relapse, while 21 patients had experienced relapse. There were no significant age, education, or gender differences between those who did and those who did not experience relapse.

On the basis of speech analysis, the investigators identified a machine learning classifier, which showed an accuracy of 80.8% in predicting relapse 3 months in advance of the occurrence.
 

‘Valid and informative’

Commenting on the studies, Eric J. Tan, PhD, Centre for Mental Health, Swinburne University of Technology, Melbourne, said they are “but two of a variety of ways in which speech can be analyzed and are both equally valid and informative.”

The key takeaway “is that both studies are examples of the ways in which speech can be used clinically, such as for predicting relapse and for the potential proxy measure for the assessment of symptom severity,” said Dr. Tan, who was not involved with the research.

The studies also show that “speech is sensitive to different stages of the disorder, as well as its individual symptoms,” he added.

However, Dr. Tan noted that although “speech may be more of a sign of an underlying pathology or dysfunction, given that it waxes and wanes with illness severity, more analyses are needed before drawing definitive conclusions.” This is especially needed “given the relative infancy of quantitative speech analysis,” he said.

“It would also be useful to conduct these analyses across a variety of different languages to look for commonalities and differences that will help shed light on the variables most closely linked to the disorder,” Dr. Tan concluded.

The investigators have reported no relevant financial relationships. Dr. Tan has received an Early Career Research Fellowship from the National Health and Medical Research Council of Australia.

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

Patients with first-episode psychosis (FEP) show altered speech patterns and content that could pinpoint symptom severity – and help predict future relapse, two new studies suggest.

In the first study, an algorithm was created to analyze speech patterns and semantic content to create novel “speech networks.” Compared with their healthy peers, patients with FEP had smaller and more fragmented networks. At-risk individuals had fragmented values that were in between those of the FEP and healthy control groups.

“This suggests that semantic speech networks can enable deeper phenotyping of formal thought disorder and psychosis,” said lead author Caroline Nettekoven, PhD, department of psychiatry, University of Cambridge, England.

In the second study, Janna N. de Boer, MD, University of Groningen, the Netherlands, and colleagues examined patients with FEP who did and did not experience relapse after 24 months of follow-up.

An algorithm based on natural language processing (NLP) of speech recordings predicted the relapses with an accuracy of more than 80%.

NLP “is a powerful tool with high potential for clinical application and diagnosis and differentiation, given its ease in acquirement, low cost, and naturally low patient burden,” said de Boer.

The findings for both studies were presented at the annual congress of the Schizophrenia International Research Society.
 

Fragmented networks

Dr. Nettekoven noted that previous research has shown “mapping the speech of a psychosis patient as a network and analyzing the network using graph theory is useful for understanding formal thought disorder.”

However, these tools ignore the semantic content of speech, which is a “key feature” that is altered in psychotic language, she added.

The researchers therefore proposed a “novel type of network to map the content of speech.”

For example, if someone said, “I see a man,” a semantic speech network developed from this sentence would have the first and last words connected by “the edge” to the word “see,” Dr. Nettekoven explained.

To explore further, the investigators developed an algorithm known as “netts” that automatically creates semantic speech networks from transcribed speech.

They first applied the algorithm to transcribed speech from a general population sample of 436 individuals and then to a clinical sample (n = 53) comprising patients with FEP, those at clinical high risk for psychosis, and a healthy control group.

Comparing the general population sample with randomly generated semantic speech networks, the investigators found that networks from the general population had fewer but larger connected components, which “reflects the nonrandom nature of speech,” said Dr. Nettekoven.

In the clinical sample, networks from the FEP group had a significantly higher number of connected components compared with the healthy control group (P = .05) and a significantly smaller median connected-component size (P < .01).

“So patients’ mental speech networks are more fragmented than those from controls,” said Dr. Nettekoven. She added that the networks from clinically high-risk individuals “showed fragmentation values in between [those of] patients and controls.”

A further clustering analysis suggested the semantic speech networks “capture a novel signal that is not already described” by other NLP measures, Dr. Nettekoven said. In addition, the network features were related to negative symptom scores and scores on the Thought and Language Index.

However, Dr. Nettekoven noted that these relationships “did not survive correcting for multiple comparisons.”
 

Relapse predictor

During her presentation of the second study, Dr. de Boer said that “predicting relapse remains challenging” in FEP.

However, she noted that recent developments in NLP have proved to be effective in a “range of applications,” including early symptom recognition and differential diagnosis in psychosis.

To determine whether NLP could help predict relapse, the study included 104 patients aged 16-55 years with FEP whose conditions had been in remission for 3-6 months. Speech recordings were made at baseline and after 3 and 6 months and were analyzed via OpenSMILE software.

After a follow-up of 24 months, 24 of the patients remaining in the study had not experienced relapse, while 21 patients had experienced relapse. There were no significant age, education, or gender differences between those who did and those who did not experience relapse.

On the basis of speech analysis, the investigators identified a machine learning classifier, which showed an accuracy of 80.8% in predicting relapse 3 months in advance of the occurrence.
 

‘Valid and informative’

Commenting on the studies, Eric J. Tan, PhD, Centre for Mental Health, Swinburne University of Technology, Melbourne, said they are “but two of a variety of ways in which speech can be analyzed and are both equally valid and informative.”

The key takeaway “is that both studies are examples of the ways in which speech can be used clinically, such as for predicting relapse and for the potential proxy measure for the assessment of symptom severity,” said Dr. Tan, who was not involved with the research.

The studies also show that “speech is sensitive to different stages of the disorder, as well as its individual symptoms,” he added.

However, Dr. Tan noted that although “speech may be more of a sign of an underlying pathology or dysfunction, given that it waxes and wanes with illness severity, more analyses are needed before drawing definitive conclusions.” This is especially needed “given the relative infancy of quantitative speech analysis,” he said.

“It would also be useful to conduct these analyses across a variety of different languages to look for commonalities and differences that will help shed light on the variables most closely linked to the disorder,” Dr. Tan concluded.

The investigators have reported no relevant financial relationships. Dr. Tan has received an Early Career Research Fellowship from the National Health and Medical Research Council of Australia.

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

A long-acting subcutaneous antipsychotic (LASCA) suspension that combines risperidone with a novel copolymer substantially reduces risk for relapse and prolongs time to impending relapse for patients with schizophrenia, new research suggests.

In the phase 3 Risperidone Subcutaneous Extended-Release (RISE) trial, which included more than 500 patients with schizophrenia, those who received the novel combination treatment, known as TV-46000, had relapse reduced by 80% with monthly administration and by 63.5% with the bimonthly dose.

“Long-acting injectable medications are grossly underutilized,” study investigator John M. Kane, MD, Hofstra University, Hempstead, N.Y., told this news organization.

The attributes of TV-46000, which include its subcutaneous delivery rather than intramuscular injections, its being active within 24 hours of first treatment, and its being administered monthly or bimonthly, “might be advantageous for some patients,” Dr. Kane noted.

Because it is also effective in reducing risk for relapse, TV-46000 is “another alternative when people are looking at the possibility of using a long-acting injectable formulation,” he added.

The findings were presented at the annual congress of the Schizophrenia International Research Society.
 

Time to relapse

To examine the efficacy and safety of monthly and bimonthly doses of the drug, the researchers recruited patients aged 13-65 years who were diagnosed with schizophrenia more than a year previously and who had experienced at least one relapse in the previous 24 months.

After a screening period of up to 4 weeks, participants entered a 12-week pretreatment phase, during which their condition was stabilized on oral risperidone. During this period, the patients’ conditions had to remain stable for at least 4 consecutive weeks.

Patients were then randomly assigned in a 1:1:1 ratio to receive TV-46000 monthly, TV-46000 every 2 months, or matching placebo. All doses were given as subcutaneous injections.

Treatment was continued until participants experienced a relapse event, met at least one criteria for study withdrawal, or the study recorded a total of 90 or more relapse events.

Of 1,267 patients screened, 863 were enrolled in the study, and 544 underwent randomization. The median age of the patients who underwent randomization was 52 years; 61% were male; and the majority (59%) were Black.

In addition, the average length of time with the disease was 20.8 years, and the average time since the most recent relapse was 10.2 months.

The primary endpoint was time to impending relapse, the criteria for which included the following:

• Increases in Positive and Negative Syndrome Scale (PANSS) scores from randomization.
• Hospitalization because of worsening psychotic symptoms.
• Violent behavior resulting in clinically significant injury or damage.

Well tolerated?

In the intent-to-treat population, which comprised all adults who underwent randomization, monthly TV-46000 was associated with a fivefold prolongation of time to impending relapse in comparison with placebo; TV-46000 given every 2 months prolonged the time 2.7-fold.

This translated into a significant benefit vs. placebo for both TV-46000 monthly (hazard ratio for impending relapse, 0.2) and TV-46000 every 2 months (HR, 0.375; P < .0001 for both comparisons).

At the trial’s endpoint, impending relapse rates were 29% in the placebo group vs. 7% in the TV-46000 monthly group and 13% in the group that received TV-46000 every 2 months (P < .0001 for both).

While more patients in the two active-treatment groups met the strict criteria for remission, which included no relapse during the study and PANSS scores of 3 or less for at least 6 months prior to the study endpoint, the differences were not significant.

Treatment-related adverse events (AEs) were experienced by 39%-42% of the TV-46000 groups and by 26% of the placebo group. Serious AEs were experienced by 4%-6% of the TV-46000 groups and by 8% of the placebo group.

The investigators note that TV-46000 was “well tolerated” and that there were no new safety signals in comparison with what is already known about risperidone and “other long-acting risperidone formulations.”

Expanding on the reasons why long-acting antipsychotics are underprescribed, Dr. Kane said that “doctors often overestimate how adherent their patients are.”

He added that doctors may worry they are “insulting” their patient by suggesting they receive injections in order to increase adherence and that doctors are “not very good” at having these types of conversation with their patients.

“We did a study where we trained the clinical staff on how to have those conversations, and the result was the uptake [in patients switching to long-acting antipsychotics] was very high,” Dr. Kane said.

The personnel who received training included all of the medical team, therapists, who spend “much more time” with the patient than does the prescriber, and also social workers, case managers, and rehabilitation counselors, who are typically “not very familiar” with the idea of long-acting medications, he added.
 

‘Highly desirable’ option

Commenting on the study, Stephen R. Saklad, PharmD, director of the psychiatric pharmacy program, University of Texas Health Science Center at San Antonio, said that to call TV-46000 a LASCA rather than a depot injection is merely a “change in nomenclature.”

However, compared with a once-monthly subcutaneous injection of risperidone (Perseris), which was approved by the U.S. Food and Drug Administration in 2018 for the treatment of schizophrenia, the new drug has fewer injection site reactions, said Dr. Saklad, who was not involved with the current research.

That benefit plus having efficacy similar to that of oral risperidone and having the “more patient- and clinician-desirable administration location” of the upper arm as well as the abdomen means the option to switch a risperidone-stabilized patient directly to TV-46000 monthly or bimonthly is “highly desirable,” he added.

Dr. Saklad also noted the reduction in the likelihood of impending relapse with TV-46000 over placebo is a relatively large effect size “and shows the value toward improving the care of these patients.”

In addition, he agreed with Dr. Kane that the uptake of long-acting antipsychotics is “deplorably low.”

“This is due to a number of factors that include patient reluctance to get a ‘shot’ or ‘jab,’ clinician inexperience with LAIs during training, and the incorrect presentation of LAIs as a punishment paradigm for ‘bad’ patients,” Dr. Saklad said.

He added that “everyone tires of taking their medication or just forgets to take a dose,” and most patients with other disorders will resume their medication the next day.

However, patients with schizophrenia have a “specific cognitive difficulty” in making the connection between stopping their medication and a later relapse. If they miss a dose, they will “incorrectly conclude that they are now ‘well’ and don’t need the medication any longer,” he said.

Dr. Saklad stressed that for a patient with schizophrenia a relapse can mean substantial loss of function and of assets such as housing or support networks, and many “will complete suicide.”

The study was supported by Teva Branded Pharmaceutical Products R&D. Dr. Kane reported relationships with Alkermes, Allergan, Dainioppon Sumitomo, H. Lundbeck, Indivior, Intracellular Therapies, Janssen, Janssen Pharmaceuticals, Johnson & Johnson, LB Pharmaceuticals, Merck, Neurocine, North Shore Therapeutics, Novartis Pharmaceutical, Otsuka, Reviva, Roche, Saladex, Sunovion, Takeda, Teva, Otsuka, Lundbeck, Sunovion, UptoDate, and Vanguard Research Group.

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

A long-acting subcutaneous antipsychotic (LASCA) suspension that combines risperidone with a novel copolymer substantially reduces risk for relapse and prolongs time to impending relapse for patients with schizophrenia, new research suggests.

In the phase 3 Risperidone Subcutaneous Extended-Release (RISE) trial, which included more than 500 patients with schizophrenia, those who received the novel combination treatment, known as TV-46000, had relapse reduced by 80% with monthly administration and by 63.5% with the bimonthly dose.

“Long-acting injectable medications are grossly underutilized,” study investigator John M. Kane, MD, Hofstra University, Hempstead, N.Y., told this news organization.

The attributes of TV-46000, which include its subcutaneous delivery rather than intramuscular injections, its being active within 24 hours of first treatment, and its being administered monthly or bimonthly, “might be advantageous for some patients,” Dr. Kane noted.

Because it is also effective in reducing risk for relapse, TV-46000 is “another alternative when people are looking at the possibility of using a long-acting injectable formulation,” he added.

The findings were presented at the annual congress of the Schizophrenia International Research Society.
 

Time to relapse

To examine the efficacy and safety of monthly and bimonthly doses of the drug, the researchers recruited patients aged 13-65 years who were diagnosed with schizophrenia more than a year previously and who had experienced at least one relapse in the previous 24 months.

After a screening period of up to 4 weeks, participants entered a 12-week pretreatment phase, during which their condition was stabilized on oral risperidone. During this period, the patients’ conditions had to remain stable for at least 4 consecutive weeks.

Patients were then randomly assigned in a 1:1:1 ratio to receive TV-46000 monthly, TV-46000 every 2 months, or matching placebo. All doses were given as subcutaneous injections.

Treatment was continued until participants experienced a relapse event, met at least one criteria for study withdrawal, or the study recorded a total of 90 or more relapse events.

Of 1,267 patients screened, 863 were enrolled in the study, and 544 underwent randomization. The median age of the patients who underwent randomization was 52 years; 61% were male; and the majority (59%) were Black.

In addition, the average length of time with the disease was 20.8 years, and the average time since the most recent relapse was 10.2 months.

The primary endpoint was time to impending relapse, the criteria for which included the following:

• Increases in Positive and Negative Syndrome Scale (PANSS) scores from randomization.
• Hospitalization because of worsening psychotic symptoms.
• Violent behavior resulting in clinically significant injury or damage.

Well tolerated?

In the intent-to-treat population, which comprised all adults who underwent randomization, monthly TV-46000 was associated with a fivefold prolongation of time to impending relapse in comparison with placebo; TV-46000 given every 2 months prolonged the time 2.7-fold.

This translated into a significant benefit vs. placebo for both TV-46000 monthly (hazard ratio for impending relapse, 0.2) and TV-46000 every 2 months (HR, 0.375; P < .0001 for both comparisons).

At the trial’s endpoint, impending relapse rates were 29% in the placebo group vs. 7% in the TV-46000 monthly group and 13% in the group that received TV-46000 every 2 months (P < .0001 for both).

While more patients in the two active-treatment groups met the strict criteria for remission, which included no relapse during the study and PANSS scores of 3 or less for at least 6 months prior to the study endpoint, the differences were not significant.

Treatment-related adverse events (AEs) were experienced by 39%-42% of the TV-46000 groups and by 26% of the placebo group. Serious AEs were experienced by 4%-6% of the TV-46000 groups and by 8% of the placebo group.

The investigators note that TV-46000 was “well tolerated” and that there were no new safety signals in comparison with what is already known about risperidone and “other long-acting risperidone formulations.”

Expanding on the reasons why long-acting antipsychotics are underprescribed, Dr. Kane said that “doctors often overestimate how adherent their patients are.”

He added that doctors may worry they are “insulting” their patient by suggesting they receive injections in order to increase adherence and that doctors are “not very good” at having these types of conversation with their patients.

“We did a study where we trained the clinical staff on how to have those conversations, and the result was the uptake [in patients switching to long-acting antipsychotics] was very high,” Dr. Kane said.

The personnel who received training included all of the medical team, therapists, who spend “much more time” with the patient than does the prescriber, and also social workers, case managers, and rehabilitation counselors, who are typically “not very familiar” with the idea of long-acting medications, he added.
 

‘Highly desirable’ option

Commenting on the study, Stephen R. Saklad, PharmD, director of the psychiatric pharmacy program, University of Texas Health Science Center at San Antonio, said that to call TV-46000 a LASCA rather than a depot injection is merely a “change in nomenclature.”

However, compared with a once-monthly subcutaneous injection of risperidone (Perseris), which was approved by the U.S. Food and Drug Administration in 2018 for the treatment of schizophrenia, the new drug has fewer injection site reactions, said Dr. Saklad, who was not involved with the current research.

That benefit plus having efficacy similar to that of oral risperidone and having the “more patient- and clinician-desirable administration location” of the upper arm as well as the abdomen means the option to switch a risperidone-stabilized patient directly to TV-46000 monthly or bimonthly is “highly desirable,” he added.

Dr. Saklad also noted the reduction in the likelihood of impending relapse with TV-46000 over placebo is a relatively large effect size “and shows the value toward improving the care of these patients.”

In addition, he agreed with Dr. Kane that the uptake of long-acting antipsychotics is “deplorably low.”

“This is due to a number of factors that include patient reluctance to get a ‘shot’ or ‘jab,’ clinician inexperience with LAIs during training, and the incorrect presentation of LAIs as a punishment paradigm for ‘bad’ patients,” Dr. Saklad said.

He added that “everyone tires of taking their medication or just forgets to take a dose,” and most patients with other disorders will resume their medication the next day.

However, patients with schizophrenia have a “specific cognitive difficulty” in making the connection between stopping their medication and a later relapse. If they miss a dose, they will “incorrectly conclude that they are now ‘well’ and don’t need the medication any longer,” he said.

Dr. Saklad stressed that for a patient with schizophrenia a relapse can mean substantial loss of function and of assets such as housing or support networks, and many “will complete suicide.”

The study was supported by Teva Branded Pharmaceutical Products R&D. Dr. Kane reported relationships with Alkermes, Allergan, Dainioppon Sumitomo, H. Lundbeck, Indivior, Intracellular Therapies, Janssen, Janssen Pharmaceuticals, Johnson & Johnson, LB Pharmaceuticals, Merck, Neurocine, North Shore Therapeutics, Novartis Pharmaceutical, Otsuka, Reviva, Roche, Saladex, Sunovion, Takeda, Teva, Otsuka, Lundbeck, Sunovion, UptoDate, and Vanguard Research Group.

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

A long-acting subcutaneous antipsychotic (LASCA) suspension that combines risperidone with a novel copolymer substantially reduces risk for relapse and prolongs time to impending relapse for patients with schizophrenia, new research suggests.

In the phase 3 Risperidone Subcutaneous Extended-Release (RISE) trial, which included more than 500 patients with schizophrenia, those who received the novel combination treatment, known as TV-46000, had relapse reduced by 80% with monthly administration and by 63.5% with the bimonthly dose.

“Long-acting injectable medications are grossly underutilized,” study investigator John M. Kane, MD, Hofstra University, Hempstead, N.Y., told this news organization.

The attributes of TV-46000, which include its subcutaneous delivery rather than intramuscular injections, its being active within 24 hours of first treatment, and its being administered monthly or bimonthly, “might be advantageous for some patients,” Dr. Kane noted.

Because it is also effective in reducing risk for relapse, TV-46000 is “another alternative when people are looking at the possibility of using a long-acting injectable formulation,” he added.

The findings were presented at the annual congress of the Schizophrenia International Research Society.
 

Time to relapse

To examine the efficacy and safety of monthly and bimonthly doses of the drug, the researchers recruited patients aged 13-65 years who were diagnosed with schizophrenia more than a year previously and who had experienced at least one relapse in the previous 24 months.

After a screening period of up to 4 weeks, participants entered a 12-week pretreatment phase, during which their condition was stabilized on oral risperidone. During this period, the patients’ conditions had to remain stable for at least 4 consecutive weeks.

Patients were then randomly assigned in a 1:1:1 ratio to receive TV-46000 monthly, TV-46000 every 2 months, or matching placebo. All doses were given as subcutaneous injections.

Treatment was continued until participants experienced a relapse event, met at least one criteria for study withdrawal, or the study recorded a total of 90 or more relapse events.

Of 1,267 patients screened, 863 were enrolled in the study, and 544 underwent randomization. The median age of the patients who underwent randomization was 52 years; 61% were male; and the majority (59%) were Black.

In addition, the average length of time with the disease was 20.8 years, and the average time since the most recent relapse was 10.2 months.

The primary endpoint was time to impending relapse, the criteria for which included the following:

• Increases in Positive and Negative Syndrome Scale (PANSS) scores from randomization.
• Hospitalization because of worsening psychotic symptoms.
• Violent behavior resulting in clinically significant injury or damage.

Well tolerated?

In the intent-to-treat population, which comprised all adults who underwent randomization, monthly TV-46000 was associated with a fivefold prolongation of time to impending relapse in comparison with placebo; TV-46000 given every 2 months prolonged the time 2.7-fold.

This translated into a significant benefit vs. placebo for both TV-46000 monthly (hazard ratio for impending relapse, 0.2) and TV-46000 every 2 months (HR, 0.375; P < .0001 for both comparisons).

At the trial’s endpoint, impending relapse rates were 29% in the placebo group vs. 7% in the TV-46000 monthly group and 13% in the group that received TV-46000 every 2 months (P < .0001 for both).

While more patients in the two active-treatment groups met the strict criteria for remission, which included no relapse during the study and PANSS scores of 3 or less for at least 6 months prior to the study endpoint, the differences were not significant.

Treatment-related adverse events (AEs) were experienced by 39%-42% of the TV-46000 groups and by 26% of the placebo group. Serious AEs were experienced by 4%-6% of the TV-46000 groups and by 8% of the placebo group.

The investigators note that TV-46000 was “well tolerated” and that there were no new safety signals in comparison with what is already known about risperidone and “other long-acting risperidone formulations.”

Expanding on the reasons why long-acting antipsychotics are underprescribed, Dr. Kane said that “doctors often overestimate how adherent their patients are.”

He added that doctors may worry they are “insulting” their patient by suggesting they receive injections in order to increase adherence and that doctors are “not very good” at having these types of conversation with their patients.

“We did a study where we trained the clinical staff on how to have those conversations, and the result was the uptake [in patients switching to long-acting antipsychotics] was very high,” Dr. Kane said.

The personnel who received training included all of the medical team, therapists, who spend “much more time” with the patient than does the prescriber, and also social workers, case managers, and rehabilitation counselors, who are typically “not very familiar” with the idea of long-acting medications, he added.
 

‘Highly desirable’ option

Commenting on the study, Stephen R. Saklad, PharmD, director of the psychiatric pharmacy program, University of Texas Health Science Center at San Antonio, said that to call TV-46000 a LASCA rather than a depot injection is merely a “change in nomenclature.”

However, compared with a once-monthly subcutaneous injection of risperidone (Perseris), which was approved by the U.S. Food and Drug Administration in 2018 for the treatment of schizophrenia, the new drug has fewer injection site reactions, said Dr. Saklad, who was not involved with the current research.

That benefit plus having efficacy similar to that of oral risperidone and having the “more patient- and clinician-desirable administration location” of the upper arm as well as the abdomen means the option to switch a risperidone-stabilized patient directly to TV-46000 monthly or bimonthly is “highly desirable,” he added.

Dr. Saklad also noted the reduction in the likelihood of impending relapse with TV-46000 over placebo is a relatively large effect size “and shows the value toward improving the care of these patients.”

In addition, he agreed with Dr. Kane that the uptake of long-acting antipsychotics is “deplorably low.”

“This is due to a number of factors that include patient reluctance to get a ‘shot’ or ‘jab,’ clinician inexperience with LAIs during training, and the incorrect presentation of LAIs as a punishment paradigm for ‘bad’ patients,” Dr. Saklad said.

He added that “everyone tires of taking their medication or just forgets to take a dose,” and most patients with other disorders will resume their medication the next day.

However, patients with schizophrenia have a “specific cognitive difficulty” in making the connection between stopping their medication and a later relapse. If they miss a dose, they will “incorrectly conclude that they are now ‘well’ and don’t need the medication any longer,” he said.

Dr. Saklad stressed that for a patient with schizophrenia a relapse can mean substantial loss of function and of assets such as housing or support networks, and many “will complete suicide.”

The study was supported by Teva Branded Pharmaceutical Products R&D. Dr. Kane reported relationships with Alkermes, Allergan, Dainioppon Sumitomo, H. Lundbeck, Indivior, Intracellular Therapies, Janssen, Janssen Pharmaceuticals, Johnson & Johnson, LB Pharmaceuticals, Merck, Neurocine, North Shore Therapeutics, Novartis Pharmaceutical, Otsuka, Reviva, Roche, Saladex, Sunovion, Takeda, Teva, Otsuka, Lundbeck, Sunovion, UptoDate, and Vanguard Research Group.

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

AUT00206, a novel compound that targets potassium channels in brain interneurons, not only improves gamma oscillations in patients with schizophrenia, it also improves their symptoms, new randomized trial data suggest.

In a randomized, double-blind study that included two dozen men with schizophrenia, AUT00206, compared with placebo, increased the power of gamma oscillations, which were in turn associated with positive symptom scores.

The investigators note that targeting a potassium channel linked to brain gamma oscillations may offer a novel way to treat schizophrenia.

In addition, lead author Charles Large, PhD, chief executive officer, Autifony Therapeutics, Stevenage, United Kingdom, told this news organization that it may be “important” to study patients relatively early in their disease course. Participants in the current study were diagnosed less than 5 years previously.

Many previous trials in this area have failed, “and some of the questions were maybe the patients were sort of beyond the point in which you can actually make a difference,” Dr. Large said.

The findings were presented at the Congress of the Schizophrenia International Research Society (SIRS) 2022.
 

‘Opportunity to intervene’

Dr. Large noted that patients with chronic, long-term symptoms of schizophrenia have been treated with antipsychotics for decades, “and the pathology of that stage is then different.”

For the current study, the investigators hypothesized that the brain may be more “plastic” earlier on in the disease course, and so “maybe there’s an opportunity to intervene and make a change,” said Dr. Large.

In addition, patients with schizophrenia have abnormalities in both their resting state and induced and evolved gamma oscillations, which can include increased resting state power – and reduced power and “phase locking” to cyclical stimuli – the researchers note.

Previous studies have suggested such abnormalities are associated with dysfunction in parvalbumin-expressing interneurons (PVINs) found in cortical and subcortical circuits.

Moreover, Kv3.1 potassium channels expressed on PVINs are integral to establishing and maintaining fast-firing activity and to network synchronization across the brain. They may, therefore, offer a “potential therapeutic approach” for countering PVIN dysfunction, the investigators write.

To examine the impact of AUT00206, a novel Kv3.1/Kv3.2 positive neuromodulator, on resting state and induced gamma oscillations, they conducted a randomized, double-blind study in 24 men with schizophrenia who were aged 18-50 years.

Participants had been diagnosed less than 5 years previously and were stable on a maximum of two antipsychotic medications. They were randomly assigned 2:1 to a loading 2,000-mg dose of AUT00206 on day 1 and then 800 mg twice daily for 27 days or to placebo.

At baseline/day 1, and on a further 3 days over the treatment period, the men underwent resting-state electroencephalography, 40-Hz auditory steady-state response stimulation, and deviant and standard stimulation in an auditory oddball paradigm to assess resting state, induced, and evoked oscillations, respectively.
 

Positive associations

Results showed that early auditory gamma responses were increased at day 28 in patients who received AUT00206 but not in those who received placebo. The active drug was also associated with increases in the power of gamma oscillations from Day 5 in response to stimuli but not in phase locking.

There was also a significant positive association between frontal resting gamma power and baseline Positive and Negative Syndrome Scale (PANSS) positive symptom severity scores (r = 0.675; P < .001).

Moreover, changes in PANSS positive scores were significantly correlated with a decrease in frontal resting gamma power in patients treated with AUT00206 (r = 0.532; P = .05).

While a similar correlation was not found with placebo, the investigators note this “may be in part due to the low number” of individuals in the group.

They add that a larger study is now needed to confirm their findings and to “explore efficacy versus clinical symptoms.”

However, Dr. Large noted that participants in their next study will have fragile X syndrome.

He added the reason for this is “not because we’ve given up on schizophrenia – we feel that schizophrenia is a massive opportunity.”

Patients with schizophrenia are heterogeneous, both in terms of their clinical course and prior treatment. So it is “impossible” for a company of their size to take all of that into account in a single study, Dr. Large said.

In contrast, fragile X is “genetically homogenous,” and so it is possible to focus on the deficit and then translate the findings out into a “broader population.”
 

Preliminary but worth pursuing?

Commenting on the study, James M. McNally, PhD, assistant professor of psychiatry, Harvard Medical School, Boston, said the findings are “quite preliminary” and that the investigators provided “limited information as to how their findings were derived.”

Nevertheless, it is “nice to see that they observed a significant correlation between resting gamma and positive symptom severity at baseline [and] that the observed change in gamma correlates with change in PANSS scores,” said Dr. McNally, who was not involved with the research.

He added that the “idea of targeting Kv3.1 function to restore PV neuron/gamma activity is very interesting and worth pursuing.”

The study was funded by Autifony Therapeutics, of which Dr. Large is an employee.

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

AUT00206, a novel compound that targets potassium channels in brain interneurons, not only improves gamma oscillations in patients with schizophrenia, it also improves their symptoms, new randomized trial data suggest.

In a randomized, double-blind study that included two dozen men with schizophrenia, AUT00206, compared with placebo, increased the power of gamma oscillations, which were in turn associated with positive symptom scores.

The investigators note that targeting a potassium channel linked to brain gamma oscillations may offer a novel way to treat schizophrenia.

In addition, lead author Charles Large, PhD, chief executive officer, Autifony Therapeutics, Stevenage, United Kingdom, told this news organization that it may be “important” to study patients relatively early in their disease course. Participants in the current study were diagnosed less than 5 years previously.

Many previous trials in this area have failed, “and some of the questions were maybe the patients were sort of beyond the point in which you can actually make a difference,” Dr. Large said.

The findings were presented at the Congress of the Schizophrenia International Research Society (SIRS) 2022.
 

‘Opportunity to intervene’

Dr. Large noted that patients with chronic, long-term symptoms of schizophrenia have been treated with antipsychotics for decades, “and the pathology of that stage is then different.”

For the current study, the investigators hypothesized that the brain may be more “plastic” earlier on in the disease course, and so “maybe there’s an opportunity to intervene and make a change,” said Dr. Large.

In addition, patients with schizophrenia have abnormalities in both their resting state and induced and evolved gamma oscillations, which can include increased resting state power – and reduced power and “phase locking” to cyclical stimuli – the researchers note.

Previous studies have suggested such abnormalities are associated with dysfunction in parvalbumin-expressing interneurons (PVINs) found in cortical and subcortical circuits.

Moreover, Kv3.1 potassium channels expressed on PVINs are integral to establishing and maintaining fast-firing activity and to network synchronization across the brain. They may, therefore, offer a “potential therapeutic approach” for countering PVIN dysfunction, the investigators write.

To examine the impact of AUT00206, a novel Kv3.1/Kv3.2 positive neuromodulator, on resting state and induced gamma oscillations, they conducted a randomized, double-blind study in 24 men with schizophrenia who were aged 18-50 years.

Participants had been diagnosed less than 5 years previously and were stable on a maximum of two antipsychotic medications. They were randomly assigned 2:1 to a loading 2,000-mg dose of AUT00206 on day 1 and then 800 mg twice daily for 27 days or to placebo.

At baseline/day 1, and on a further 3 days over the treatment period, the men underwent resting-state electroencephalography, 40-Hz auditory steady-state response stimulation, and deviant and standard stimulation in an auditory oddball paradigm to assess resting state, induced, and evoked oscillations, respectively.
 

Positive associations

Results showed that early auditory gamma responses were increased at day 28 in patients who received AUT00206 but not in those who received placebo. The active drug was also associated with increases in the power of gamma oscillations from Day 5 in response to stimuli but not in phase locking.

There was also a significant positive association between frontal resting gamma power and baseline Positive and Negative Syndrome Scale (PANSS) positive symptom severity scores (r = 0.675; P < .001).

Moreover, changes in PANSS positive scores were significantly correlated with a decrease in frontal resting gamma power in patients treated with AUT00206 (r = 0.532; P = .05).

While a similar correlation was not found with placebo, the investigators note this “may be in part due to the low number” of individuals in the group.

They add that a larger study is now needed to confirm their findings and to “explore efficacy versus clinical symptoms.”

However, Dr. Large noted that participants in their next study will have fragile X syndrome.

He added the reason for this is “not because we’ve given up on schizophrenia – we feel that schizophrenia is a massive opportunity.”

Patients with schizophrenia are heterogeneous, both in terms of their clinical course and prior treatment. So it is “impossible” for a company of their size to take all of that into account in a single study, Dr. Large said.

In contrast, fragile X is “genetically homogenous,” and so it is possible to focus on the deficit and then translate the findings out into a “broader population.”
 

Preliminary but worth pursuing?

Commenting on the study, James M. McNally, PhD, assistant professor of psychiatry, Harvard Medical School, Boston, said the findings are “quite preliminary” and that the investigators provided “limited information as to how their findings were derived.”

Nevertheless, it is “nice to see that they observed a significant correlation between resting gamma and positive symptom severity at baseline [and] that the observed change in gamma correlates with change in PANSS scores,” said Dr. McNally, who was not involved with the research.

He added that the “idea of targeting Kv3.1 function to restore PV neuron/gamma activity is very interesting and worth pursuing.”

The study was funded by Autifony Therapeutics, of which Dr. Large is an employee.

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

AUT00206, a novel compound that targets potassium channels in brain interneurons, not only improves gamma oscillations in patients with schizophrenia, it also improves their symptoms, new randomized trial data suggest.

In a randomized, double-blind study that included two dozen men with schizophrenia, AUT00206, compared with placebo, increased the power of gamma oscillations, which were in turn associated with positive symptom scores.

The investigators note that targeting a potassium channel linked to brain gamma oscillations may offer a novel way to treat schizophrenia.

In addition, lead author Charles Large, PhD, chief executive officer, Autifony Therapeutics, Stevenage, United Kingdom, told this news organization that it may be “important” to study patients relatively early in their disease course. Participants in the current study were diagnosed less than 5 years previously.

Many previous trials in this area have failed, “and some of the questions were maybe the patients were sort of beyond the point in which you can actually make a difference,” Dr. Large said.

The findings were presented at the Congress of the Schizophrenia International Research Society (SIRS) 2022.
 

‘Opportunity to intervene’

Dr. Large noted that patients with chronic, long-term symptoms of schizophrenia have been treated with antipsychotics for decades, “and the pathology of that stage is then different.”

For the current study, the investigators hypothesized that the brain may be more “plastic” earlier on in the disease course, and so “maybe there’s an opportunity to intervene and make a change,” said Dr. Large.

In addition, patients with schizophrenia have abnormalities in both their resting state and induced and evolved gamma oscillations, which can include increased resting state power – and reduced power and “phase locking” to cyclical stimuli – the researchers note.

Previous studies have suggested such abnormalities are associated with dysfunction in parvalbumin-expressing interneurons (PVINs) found in cortical and subcortical circuits.

Moreover, Kv3.1 potassium channels expressed on PVINs are integral to establishing and maintaining fast-firing activity and to network synchronization across the brain. They may, therefore, offer a “potential therapeutic approach” for countering PVIN dysfunction, the investigators write.

To examine the impact of AUT00206, a novel Kv3.1/Kv3.2 positive neuromodulator, on resting state and induced gamma oscillations, they conducted a randomized, double-blind study in 24 men with schizophrenia who were aged 18-50 years.

Participants had been diagnosed less than 5 years previously and were stable on a maximum of two antipsychotic medications. They were randomly assigned 2:1 to a loading 2,000-mg dose of AUT00206 on day 1 and then 800 mg twice daily for 27 days or to placebo.

At baseline/day 1, and on a further 3 days over the treatment period, the men underwent resting-state electroencephalography, 40-Hz auditory steady-state response stimulation, and deviant and standard stimulation in an auditory oddball paradigm to assess resting state, induced, and evoked oscillations, respectively.
 

Positive associations

Results showed that early auditory gamma responses were increased at day 28 in patients who received AUT00206 but not in those who received placebo. The active drug was also associated with increases in the power of gamma oscillations from Day 5 in response to stimuli but not in phase locking.

There was also a significant positive association between frontal resting gamma power and baseline Positive and Negative Syndrome Scale (PANSS) positive symptom severity scores (r = 0.675; P < .001).

Moreover, changes in PANSS positive scores were significantly correlated with a decrease in frontal resting gamma power in patients treated with AUT00206 (r = 0.532; P = .05).

While a similar correlation was not found with placebo, the investigators note this “may be in part due to the low number” of individuals in the group.

They add that a larger study is now needed to confirm their findings and to “explore efficacy versus clinical symptoms.”

However, Dr. Large noted that participants in their next study will have fragile X syndrome.

He added the reason for this is “not because we’ve given up on schizophrenia – we feel that schizophrenia is a massive opportunity.”

Patients with schizophrenia are heterogeneous, both in terms of their clinical course and prior treatment. So it is “impossible” for a company of their size to take all of that into account in a single study, Dr. Large said.

In contrast, fragile X is “genetically homogenous,” and so it is possible to focus on the deficit and then translate the findings out into a “broader population.”
 

Preliminary but worth pursuing?

Commenting on the study, James M. McNally, PhD, assistant professor of psychiatry, Harvard Medical School, Boston, said the findings are “quite preliminary” and that the investigators provided “limited information as to how their findings were derived.”

Nevertheless, it is “nice to see that they observed a significant correlation between resting gamma and positive symptom severity at baseline [and] that the observed change in gamma correlates with change in PANSS scores,” said Dr. McNally, who was not involved with the research.

He added that the “idea of targeting Kv3.1 function to restore PV neuron/gamma activity is very interesting and worth pursuing.”

The study was funded by Autifony Therapeutics, of which Dr. Large is an employee.

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

MANCHESTER, ENGLAND – About one-third of patients who are scheduled for major surgery are anemic. This issue is underrecognized and requires the involvement of all health care professionals to work together to optimize care and maximize outcomes, state the first U.K. guidelines for perioperative anemia.

Anemia management may include dietary changes, iron supplementation, blood transfusion, perioperative physiological optimization, delay or review of the surgical plan, medication reviews, and greater intraoperative care.

It is quite clear that patients have a better experience if management covers the whole pathway, said lead author of the guidelines, Scarlett McNally, MD, PhD, East Sussex Healthcare NHS Trust, Eastbourne, England.

It’s much better for the patient “if every individual member of staff knows what’s supposed to happen, not just for their bit, but the whole way along,” she said. “Otherwise things go wrong, and people don’t anticipate things early enough.” 

The new guidelines, to be published in full later this year by the Centre for Perioperative Care, cover emergency and elective surgery for all ages.

It follows the 2021 publication of a guideline for perioperative diabetes management, and a previous document that covered frailty.

Dr. McNally was presenting the new guidelines on perioperative anemia at the British Society for Haematology 62nd Annual Scientific Meeting.

Although perioperative anemia is a “big issue” in clinical management, “some health care professionals know a lot about one area,” but tend to work in “silos,” Dr. McNally said.

The result is clinicians believe that all other areas are “complex” and opaque, and they “don’t make the simple decisions” that could have a big impact on patient care.

As an example, she said there are already some excellent guidelines out there, but they are not widely read.

One example of a comprehensive guideline, Dr. McNally said, is that issued by the British Society of Gastroenterology. This guideline notes that in cases where a man or a postmenopausal woman has anemia of unknown cause, about 30% of those cases end up having a gastrointestinal cause, and so gastroenterologists are happy to have those patients referred to them.

But Dr. McNally said that she personally, as an orthopedic surgeon, wouldn’t have known what to do with such a patient, and may have referred that person back to primary care to be investigated.

The new guidelines contain algorithms to help staff plan care. Without those, she said, “a lot is resting on the preassessment nurses, but they are having to think about everything else.”

The guidance suggests proactive measures to identify and manage anemia. These include testing for anemia while assessing renal function ahead of a CT scan, or asking patients about their nutrition.

For low-risk patients, it may be enough to give general advice about a good diet and exercise to try to get them through the operation.

However, patients who are high risk (defined as likely to lose > 500 mL or > 10% of blood volume during surgery) need to be identified as such early on, so that early measures can be put in place, as well as a senior review of their care plan.

The guidelines also recommend that operating room staff consider tranexamic acid and other bloodless minimization strategies, and that senior staff give clinical input in cases of functional iron deficiency, a marker of ill health.

To maximize postoperative outcomes, it is suggested that staff work with prehabilitation services and mobilize patients, as symptoms allow.

More importantly, they emphasize the need for shared decision-making about potential surgery, ensuring that the patients understand “Benefits, Risks, Alternatives, and what if we do Nothing (BRAN).”

No funding was declared. One study author declared relationships with the National Institute for Health Research and Pfizer.

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

MANCHESTER, ENGLAND – About one-third of patients who are scheduled for major surgery are anemic. This issue is underrecognized and requires the involvement of all health care professionals to work together to optimize care and maximize outcomes, state the first U.K. guidelines for perioperative anemia.

Anemia management may include dietary changes, iron supplementation, blood transfusion, perioperative physiological optimization, delay or review of the surgical plan, medication reviews, and greater intraoperative care.

It is quite clear that patients have a better experience if management covers the whole pathway, said lead author of the guidelines, Scarlett McNally, MD, PhD, East Sussex Healthcare NHS Trust, Eastbourne, England.

It’s much better for the patient “if every individual member of staff knows what’s supposed to happen, not just for their bit, but the whole way along,” she said. “Otherwise things go wrong, and people don’t anticipate things early enough.” 

The new guidelines, to be published in full later this year by the Centre for Perioperative Care, cover emergency and elective surgery for all ages.

It follows the 2021 publication of a guideline for perioperative diabetes management, and a previous document that covered frailty.

Dr. McNally was presenting the new guidelines on perioperative anemia at the British Society for Haematology 62nd Annual Scientific Meeting.

Although perioperative anemia is a “big issue” in clinical management, “some health care professionals know a lot about one area,” but tend to work in “silos,” Dr. McNally said.

The result is clinicians believe that all other areas are “complex” and opaque, and they “don’t make the simple decisions” that could have a big impact on patient care.

As an example, she said there are already some excellent guidelines out there, but they are not widely read.

One example of a comprehensive guideline, Dr. McNally said, is that issued by the British Society of Gastroenterology. This guideline notes that in cases where a man or a postmenopausal woman has anemia of unknown cause, about 30% of those cases end up having a gastrointestinal cause, and so gastroenterologists are happy to have those patients referred to them.

But Dr. McNally said that she personally, as an orthopedic surgeon, wouldn’t have known what to do with such a patient, and may have referred that person back to primary care to be investigated.

The new guidelines contain algorithms to help staff plan care. Without those, she said, “a lot is resting on the preassessment nurses, but they are having to think about everything else.”

The guidance suggests proactive measures to identify and manage anemia. These include testing for anemia while assessing renal function ahead of a CT scan, or asking patients about their nutrition.

For low-risk patients, it may be enough to give general advice about a good diet and exercise to try to get them through the operation.

However, patients who are high risk (defined as likely to lose > 500 mL or > 10% of blood volume during surgery) need to be identified as such early on, so that early measures can be put in place, as well as a senior review of their care plan.

The guidelines also recommend that operating room staff consider tranexamic acid and other bloodless minimization strategies, and that senior staff give clinical input in cases of functional iron deficiency, a marker of ill health.

To maximize postoperative outcomes, it is suggested that staff work with prehabilitation services and mobilize patients, as symptoms allow.

More importantly, they emphasize the need for shared decision-making about potential surgery, ensuring that the patients understand “Benefits, Risks, Alternatives, and what if we do Nothing (BRAN).”

No funding was declared. One study author declared relationships with the National Institute for Health Research and Pfizer.

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

MANCHESTER, ENGLAND – About one-third of patients who are scheduled for major surgery are anemic. This issue is underrecognized and requires the involvement of all health care professionals to work together to optimize care and maximize outcomes, state the first U.K. guidelines for perioperative anemia.

Anemia management may include dietary changes, iron supplementation, blood transfusion, perioperative physiological optimization, delay or review of the surgical plan, medication reviews, and greater intraoperative care.

It is quite clear that patients have a better experience if management covers the whole pathway, said lead author of the guidelines, Scarlett McNally, MD, PhD, East Sussex Healthcare NHS Trust, Eastbourne, England.

It’s much better for the patient “if every individual member of staff knows what’s supposed to happen, not just for their bit, but the whole way along,” she said. “Otherwise things go wrong, and people don’t anticipate things early enough.” 

The new guidelines, to be published in full later this year by the Centre for Perioperative Care, cover emergency and elective surgery for all ages.

It follows the 2021 publication of a guideline for perioperative diabetes management, and a previous document that covered frailty.

Dr. McNally was presenting the new guidelines on perioperative anemia at the British Society for Haematology 62nd Annual Scientific Meeting.

Although perioperative anemia is a “big issue” in clinical management, “some health care professionals know a lot about one area,” but tend to work in “silos,” Dr. McNally said.

The result is clinicians believe that all other areas are “complex” and opaque, and they “don’t make the simple decisions” that could have a big impact on patient care.

As an example, she said there are already some excellent guidelines out there, but they are not widely read.

One example of a comprehensive guideline, Dr. McNally said, is that issued by the British Society of Gastroenterology. This guideline notes that in cases where a man or a postmenopausal woman has anemia of unknown cause, about 30% of those cases end up having a gastrointestinal cause, and so gastroenterologists are happy to have those patients referred to them.

But Dr. McNally said that she personally, as an orthopedic surgeon, wouldn’t have known what to do with such a patient, and may have referred that person back to primary care to be investigated.

The new guidelines contain algorithms to help staff plan care. Without those, she said, “a lot is resting on the preassessment nurses, but they are having to think about everything else.”

The guidance suggests proactive measures to identify and manage anemia. These include testing for anemia while assessing renal function ahead of a CT scan, or asking patients about their nutrition.

For low-risk patients, it may be enough to give general advice about a good diet and exercise to try to get them through the operation.

However, patients who are high risk (defined as likely to lose > 500 mL or > 10% of blood volume during surgery) need to be identified as such early on, so that early measures can be put in place, as well as a senior review of their care plan.

The guidelines also recommend that operating room staff consider tranexamic acid and other bloodless minimization strategies, and that senior staff give clinical input in cases of functional iron deficiency, a marker of ill health.

To maximize postoperative outcomes, it is suggested that staff work with prehabilitation services and mobilize patients, as symptoms allow.

More importantly, they emphasize the need for shared decision-making about potential surgery, ensuring that the patients understand “Benefits, Risks, Alternatives, and what if we do Nothing (BRAN).”

No funding was declared. One study author declared relationships with the National Institute for Health Research and Pfizer.

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

MANCHESTER, ENGLAND – A London-based rapper known for his gospel-inspired music has now given a voice to patients with sickle cell disease. He is using one of his music videos to raise awareness and educate health care professionals about living with the condition.

Alidor Gaspar, also known as A Star, composed the song Hidden Pain about his experience of living with sickle cell disease, and he created a video posted on YouTube that shows him in a hospital bed, writhing in pain.

One important aim of the video, he says, is to help educate health care professionals, some of whom have not come across this condition, he explained at a session during the annual meeting of the British Society for Haematology, held recently in Manchester, England.

“It’s kind of frustrating to feel like your safe space, when you’re in front of doctors and nurses and paramedics who are supposed to know what it is and react with treatment, [and they] don’t know what it is,” Mr. Gaspar said.

He recalled an occasion in which he was experiencing a crisis, and his wife called for an ambulance. The paramedics arrived and his wife asked them for “gas and air and morphine, and they were, like, no, we don’t want to give that to him.” She tried to explain that he has sickle cell disease, but the paramedics had not heard of the condition and were suspicious that the request for morphine was a sign of drug addiction.

Mr. Gaspar expressed his frustration over “constantly having to prove that you have something serious enough to need the treatment you are asking for.”

At the meeting, Mr. Gaspar was talking on the stage with hematologist Dr. Stephen Hibbs from Barts Health NHS Trust, London.

Mr. Gaspar explained that it took years before he eventually reached “a point where I understood that it’s something that affects me and affects many other people, and I didn’t want to hide it any more.”

Sickle cell disease, which occurs primarily in people of Afro-Caribbean background, is a taboo subject in his community, Mr. Gaspar elaborated in an interview.

The condition has been associated with a great deal of stigma, with young sufferers traditionally seen as “demonically possessed,” he commented.

“So there was always a shameful aspect around it when it came to African families speaking about it, especially back in Africa.”

But after his parents came to the United Kingdom, he was able to “do his research and understand that it’s just genetics.”

This knowledge, Mr. Gaspar said, “takes away the spiritual aspect” and allows people to “have the conversation about sickle cell with potential partners” and ask them to find out their genotype, which in turn helps to “break down the barriers and the stigma.”

Mr. Gaspar emphasizes that there is much more work still to do.

In the video, he appeals to the Black community to make blood donations.

He said that something that “haunts” him is that currently, only 1% of Black people in the United Kingdom give blood, “so I really want the song to move my community to take a step forward and make that difference.”

He has been in contact with NHS Blood and Transplant, which provides blood and transplantation service to the National Health Service. They “really liked” the song, Mr. Gaspar said, and helped him get access to a hospital ward in University College Hospital, London, for the video.

“I really wanted to make a video that made people uncomfortable when watching it,” he said. It shows him hospitalized for pain and breathlessness and recalling having to use a Zimmer frame at the age of 25.

“This is a side of sickle cell that normally people don’t know,” he said.

Since releasing the song and the video, Mr. Gaspar says he has been contacted by many fellow patients. They have told him that he is now their “voice”; when they are asked how the condition affects them, “they can show someone the Hidden Pain video and say: This is how it feels.”

Clinicians have also approached him, asking if they can show his video to illustrate to patients and their families how having the condition may affect their lives.
 

Preventable deaths

At the meeting, Dr. Hibbs highlighted the 2021 report No One’s Listening, which was issued by the Sickle Cell Society following an inquiry into avoidable deaths and failures of care for sickle cell patients.

The inquiry, published by an All-Party Parliamentary group, found “serious care failings” in acute services and evidence of attitudes underpinned by racism. There was evidence of substandard care for sickle cell patients who were admitted to general wards or to hospital accident and emergency departments, as well as low awareness of the condition among health care professionals.

The report noted that the care failings have led to patient deaths, some which could have been prevented, and that there have been many “near misses.”

Many patients with sickle cell disease said they are “not being listened to” or are not being understood, especially during that vulnerable period when they are “in a crisis.”

Mr. Gaspar said that the report, and also the deaths, really struck a chord with him and many in his community. “We felt like that was us. ... We’ve all been in that same position where we’ve been misunderstood and not heard by nurses, doctors, or paramedics.”

He emphasized the need for awareness of the condition and the need for timely treatment. Just 3 weeks ago, Mr. Gaspar attended the funeral of one of his friends who is in the Hidden Pain video, a fellow sickle cell disease patient, who died at 30 years of age.
 

Ignorance about the condition ‘all too common’

The lack of awareness about sickle cell disease, even among health care professionals, is “all too common,” says Dr. Subarna Chakravorty, consultant pediatric hematologist, King’s College Hospital, London.

Even in London, where there is a large Black community and the teaching hospitals have world-class expertise, patients with sickle cell disease are “still facing a lot of problems with knowledge” among health care professionals, she said in an interview.

“Often people are having to speak for their own condition; which is fine, except that sometimes they are not believed,” she commented.

“On the one hand, you rely on the patient to provide information about their disease, and then when you receive it, you don’t do anything about it. So [they’re] between a rock and a hard place.”
 

Why are sickle cell patients treated in this way?

For Dr. Chakravorty, there is “a lot to be said about racism and disparities” in treating patients “as morphine-seekers, opiate addicts, even in children.”

“So we really need to improve the knowledge and perceptions among nonspecialist staff,” she said, “and even among specialists.”

Mr. Gaspar aims to help with this effort and hopes that his song and video will be useful to health care professionals. Sickle cell disease “needs to be spoken about,” and more doctors and nurses need to “know what it is,” he said.

He said it is a relief to encounter health care professionals who are knowledgeable about his condition. There have been times when he has been “having a crisis at home, calling the ambulance, and the paramedic comes and says: ‘Mr. Gaspar, you have sickle cell...we believe that you usually have gas and air and morphine, is that correct?’”

“That gives me a sense of peace, to know that I don’t have to fight my case or convince someone I have sickle cell, and I need to start treatment. They already know.”

No relevant financial relationships have been disclosed.

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

MANCHESTER, ENGLAND – A London-based rapper known for his gospel-inspired music has now given a voice to patients with sickle cell disease. He is using one of his music videos to raise awareness and educate health care professionals about living with the condition.

Alidor Gaspar, also known as A Star, composed the song Hidden Pain about his experience of living with sickle cell disease, and he created a video posted on YouTube that shows him in a hospital bed, writhing in pain.

One important aim of the video, he says, is to help educate health care professionals, some of whom have not come across this condition, he explained at a session during the annual meeting of the British Society for Haematology, held recently in Manchester, England.

“It’s kind of frustrating to feel like your safe space, when you’re in front of doctors and nurses and paramedics who are supposed to know what it is and react with treatment, [and they] don’t know what it is,” Mr. Gaspar said.

He recalled an occasion in which he was experiencing a crisis, and his wife called for an ambulance. The paramedics arrived and his wife asked them for “gas and air and morphine, and they were, like, no, we don’t want to give that to him.” She tried to explain that he has sickle cell disease, but the paramedics had not heard of the condition and were suspicious that the request for morphine was a sign of drug addiction.

Mr. Gaspar expressed his frustration over “constantly having to prove that you have something serious enough to need the treatment you are asking for.”

At the meeting, Mr. Gaspar was talking on the stage with hematologist Dr. Stephen Hibbs from Barts Health NHS Trust, London.

Mr. Gaspar explained that it took years before he eventually reached “a point where I understood that it’s something that affects me and affects many other people, and I didn’t want to hide it any more.”

Sickle cell disease, which occurs primarily in people of Afro-Caribbean background, is a taboo subject in his community, Mr. Gaspar elaborated in an interview.

The condition has been associated with a great deal of stigma, with young sufferers traditionally seen as “demonically possessed,” he commented.

“So there was always a shameful aspect around it when it came to African families speaking about it, especially back in Africa.”

But after his parents came to the United Kingdom, he was able to “do his research and understand that it’s just genetics.”

This knowledge, Mr. Gaspar said, “takes away the spiritual aspect” and allows people to “have the conversation about sickle cell with potential partners” and ask them to find out their genotype, which in turn helps to “break down the barriers and the stigma.”

Mr. Gaspar emphasizes that there is much more work still to do.

In the video, he appeals to the Black community to make blood donations.

He said that something that “haunts” him is that currently, only 1% of Black people in the United Kingdom give blood, “so I really want the song to move my community to take a step forward and make that difference.”

He has been in contact with NHS Blood and Transplant, which provides blood and transplantation service to the National Health Service. They “really liked” the song, Mr. Gaspar said, and helped him get access to a hospital ward in University College Hospital, London, for the video.

“I really wanted to make a video that made people uncomfortable when watching it,” he said. It shows him hospitalized for pain and breathlessness and recalling having to use a Zimmer frame at the age of 25.

“This is a side of sickle cell that normally people don’t know,” he said.

Since releasing the song and the video, Mr. Gaspar says he has been contacted by many fellow patients. They have told him that he is now their “voice”; when they are asked how the condition affects them, “they can show someone the Hidden Pain video and say: This is how it feels.”

Clinicians have also approached him, asking if they can show his video to illustrate to patients and their families how having the condition may affect their lives.
 

Preventable deaths

At the meeting, Dr. Hibbs highlighted the 2021 report No One’s Listening, which was issued by the Sickle Cell Society following an inquiry into avoidable deaths and failures of care for sickle cell patients.

The inquiry, published by an All-Party Parliamentary group, found “serious care failings” in acute services and evidence of attitudes underpinned by racism. There was evidence of substandard care for sickle cell patients who were admitted to general wards or to hospital accident and emergency departments, as well as low awareness of the condition among health care professionals.

The report noted that the care failings have led to patient deaths, some which could have been prevented, and that there have been many “near misses.”

Many patients with sickle cell disease said they are “not being listened to” or are not being understood, especially during that vulnerable period when they are “in a crisis.”

Mr. Gaspar said that the report, and also the deaths, really struck a chord with him and many in his community. “We felt like that was us. ... We’ve all been in that same position where we’ve been misunderstood and not heard by nurses, doctors, or paramedics.”

He emphasized the need for awareness of the condition and the need for timely treatment. Just 3 weeks ago, Mr. Gaspar attended the funeral of one of his friends who is in the Hidden Pain video, a fellow sickle cell disease patient, who died at 30 years of age.
 

Ignorance about the condition ‘all too common’

The lack of awareness about sickle cell disease, even among health care professionals, is “all too common,” says Dr. Subarna Chakravorty, consultant pediatric hematologist, King’s College Hospital, London.

Even in London, where there is a large Black community and the teaching hospitals have world-class expertise, patients with sickle cell disease are “still facing a lot of problems with knowledge” among health care professionals, she said in an interview.

“Often people are having to speak for their own condition; which is fine, except that sometimes they are not believed,” she commented.

“On the one hand, you rely on the patient to provide information about their disease, and then when you receive it, you don’t do anything about it. So [they’re] between a rock and a hard place.”
 

Why are sickle cell patients treated in this way?

For Dr. Chakravorty, there is “a lot to be said about racism and disparities” in treating patients “as morphine-seekers, opiate addicts, even in children.”

“So we really need to improve the knowledge and perceptions among nonspecialist staff,” she said, “and even among specialists.”

Mr. Gaspar aims to help with this effort and hopes that his song and video will be useful to health care professionals. Sickle cell disease “needs to be spoken about,” and more doctors and nurses need to “know what it is,” he said.

He said it is a relief to encounter health care professionals who are knowledgeable about his condition. There have been times when he has been “having a crisis at home, calling the ambulance, and the paramedic comes and says: ‘Mr. Gaspar, you have sickle cell...we believe that you usually have gas and air and morphine, is that correct?’”

“That gives me a sense of peace, to know that I don’t have to fight my case or convince someone I have sickle cell, and I need to start treatment. They already know.”

No relevant financial relationships have been disclosed.

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

MANCHESTER, ENGLAND – A London-based rapper known for his gospel-inspired music has now given a voice to patients with sickle cell disease. He is using one of his music videos to raise awareness and educate health care professionals about living with the condition.

Alidor Gaspar, also known as A Star, composed the song Hidden Pain about his experience of living with sickle cell disease, and he created a video posted on YouTube that shows him in a hospital bed, writhing in pain.

One important aim of the video, he says, is to help educate health care professionals, some of whom have not come across this condition, he explained at a session during the annual meeting of the British Society for Haematology, held recently in Manchester, England.

“It’s kind of frustrating to feel like your safe space, when you’re in front of doctors and nurses and paramedics who are supposed to know what it is and react with treatment, [and they] don’t know what it is,” Mr. Gaspar said.

He recalled an occasion in which he was experiencing a crisis, and his wife called for an ambulance. The paramedics arrived and his wife asked them for “gas and air and morphine, and they were, like, no, we don’t want to give that to him.” She tried to explain that he has sickle cell disease, but the paramedics had not heard of the condition and were suspicious that the request for morphine was a sign of drug addiction.

Mr. Gaspar expressed his frustration over “constantly having to prove that you have something serious enough to need the treatment you are asking for.”

At the meeting, Mr. Gaspar was talking on the stage with hematologist Dr. Stephen Hibbs from Barts Health NHS Trust, London.

Mr. Gaspar explained that it took years before he eventually reached “a point where I understood that it’s something that affects me and affects many other people, and I didn’t want to hide it any more.”

Sickle cell disease, which occurs primarily in people of Afro-Caribbean background, is a taboo subject in his community, Mr. Gaspar elaborated in an interview.

The condition has been associated with a great deal of stigma, with young sufferers traditionally seen as “demonically possessed,” he commented.

“So there was always a shameful aspect around it when it came to African families speaking about it, especially back in Africa.”

But after his parents came to the United Kingdom, he was able to “do his research and understand that it’s just genetics.”

This knowledge, Mr. Gaspar said, “takes away the spiritual aspect” and allows people to “have the conversation about sickle cell with potential partners” and ask them to find out their genotype, which in turn helps to “break down the barriers and the stigma.”

Mr. Gaspar emphasizes that there is much more work still to do.

In the video, he appeals to the Black community to make blood donations.

He said that something that “haunts” him is that currently, only 1% of Black people in the United Kingdom give blood, “so I really want the song to move my community to take a step forward and make that difference.”

He has been in contact with NHS Blood and Transplant, which provides blood and transplantation service to the National Health Service. They “really liked” the song, Mr. Gaspar said, and helped him get access to a hospital ward in University College Hospital, London, for the video.

“I really wanted to make a video that made people uncomfortable when watching it,” he said. It shows him hospitalized for pain and breathlessness and recalling having to use a Zimmer frame at the age of 25.

“This is a side of sickle cell that normally people don’t know,” he said.

Since releasing the song and the video, Mr. Gaspar says he has been contacted by many fellow patients. They have told him that he is now their “voice”; when they are asked how the condition affects them, “they can show someone the Hidden Pain video and say: This is how it feels.”

Clinicians have also approached him, asking if they can show his video to illustrate to patients and their families how having the condition may affect their lives.
 

Preventable deaths

At the meeting, Dr. Hibbs highlighted the 2021 report No One’s Listening, which was issued by the Sickle Cell Society following an inquiry into avoidable deaths and failures of care for sickle cell patients.

The inquiry, published by an All-Party Parliamentary group, found “serious care failings” in acute services and evidence of attitudes underpinned by racism. There was evidence of substandard care for sickle cell patients who were admitted to general wards or to hospital accident and emergency departments, as well as low awareness of the condition among health care professionals.

The report noted that the care failings have led to patient deaths, some which could have been prevented, and that there have been many “near misses.”

Many patients with sickle cell disease said they are “not being listened to” or are not being understood, especially during that vulnerable period when they are “in a crisis.”

Mr. Gaspar said that the report, and also the deaths, really struck a chord with him and many in his community. “We felt like that was us. ... We’ve all been in that same position where we’ve been misunderstood and not heard by nurses, doctors, or paramedics.”

He emphasized the need for awareness of the condition and the need for timely treatment. Just 3 weeks ago, Mr. Gaspar attended the funeral of one of his friends who is in the Hidden Pain video, a fellow sickle cell disease patient, who died at 30 years of age.
 

Ignorance about the condition ‘all too common’

The lack of awareness about sickle cell disease, even among health care professionals, is “all too common,” says Dr. Subarna Chakravorty, consultant pediatric hematologist, King’s College Hospital, London.

Even in London, where there is a large Black community and the teaching hospitals have world-class expertise, patients with sickle cell disease are “still facing a lot of problems with knowledge” among health care professionals, she said in an interview.

“Often people are having to speak for their own condition; which is fine, except that sometimes they are not believed,” she commented.

“On the one hand, you rely on the patient to provide information about their disease, and then when you receive it, you don’t do anything about it. So [they’re] between a rock and a hard place.”
 

Why are sickle cell patients treated in this way?

For Dr. Chakravorty, there is “a lot to be said about racism and disparities” in treating patients “as morphine-seekers, opiate addicts, even in children.”

“So we really need to improve the knowledge and perceptions among nonspecialist staff,” she said, “and even among specialists.”

Mr. Gaspar aims to help with this effort and hopes that his song and video will be useful to health care professionals. Sickle cell disease “needs to be spoken about,” and more doctors and nurses need to “know what it is,” he said.

He said it is a relief to encounter health care professionals who are knowledgeable about his condition. There have been times when he has been “having a crisis at home, calling the ambulance, and the paramedic comes and says: ‘Mr. Gaspar, you have sickle cell...we believe that you usually have gas and air and morphine, is that correct?’”

“That gives me a sense of peace, to know that I don’t have to fight my case or convince someone I have sickle cell, and I need to start treatment. They already know.”

No relevant financial relationships have been disclosed.

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

A weight-loss program can lead to type 2 diabetes remission, even in individuals with a normal body mass index (BMI), via loss of body fat, particularly in the liver and pancreas, shows a U.K. study.

The ReTUNE trial, funded by Diabetes UK, involved 20 people with type 2 diabetes of less than 6 year’s duration and a BMI of 27 kg/m² or lower.

Joel Austell/MDedge News

After 1 year, participants had lost 9% of their body weight.

Their body fat decreased significantly, to the same level as controls without type 2 diabetes, and they experienced decreases in liver fat, total triglycerides, and pancreatic fat.

The research, presented at the 2022 Diabetes UK Professional Conference, also showed this was accompanied by increases in insulin secretion and reductions in hemoglobin A1c and fasting plasma glucose levels.

Lead author Roy Taylor, MD, PhD, professor of medicine and metabolism, Newcastle University, Newcastle upon Tyne, England, said the findings indicate that the “etiology and pathophysiology of type 2 diabetes is the same whether BMI is normal or raised.”

This information should make a profound difference in what doctors advise their patients, Dr. Taylor added.

“One of the dramatic things about dealing with people in this group,” he said, “is they feel very resentful that healthcare professionals tell them not to lose weight.”

Based on the current results, Dr. Taylor believes this is “inappropriate advice, and it’s that personal advice that I think that this study points a way towards.”
 

Weight loss ‘first line of treatment’

These findings support the theory of a personal fat threshold, above which “type 2 diabetes occurs,” said Dr. Taylor. “Weight loss is the first-line treatment for all with type 2 diabetes, irrespective of BMI.”

Dr. Taylor already showed in the DiRECT trial that a calorie-restricted liquid diet followed by gradual food reintroduction and a weight-loss maintenance program can achieve and sustain type 2 diabetes remission at 2 years in people who are overweight or obese.

As reported this news organization, 36% of 300 patients enrolled in the trial attained diabetes remission and maintained it out to 24 months, compared with negligible changes in the control group.

Inspired by the results of DiRECT and the DROPLET study, the National Health Service has been rolling out a low calorie–diet treatment program for people who are overweight and living with diabetes.

Asked during the postpresentation discussion whether the current results could have implications for the NHS program, Dr. Taylor said it remains, in effect, a study and will not change things for now.

Chris Askew, chief executive of Diabetes UK, said in a release: “This game-changing study ... advances our understanding of why type 2 diabetes develops and what can be done to treat it.

“Our ambition is for as many people as possible to have the chance to put their type 2 diabetes into remission and live well for longer.”

Mr. Askew continued: “The findings of ReTUNE potentially take us a significant step closer to achieving this goal by showing that remission isn’t only possible for people of certain body weights.”
 

Weight and body fat decrease led to remission

For ReTUNE, the team recruited 20 individuals with type 2 diabetes of less than 6 year’s duration who had a BMI of 21-27 and compared them with 20 matched controls, with a follow-up of 52 weeks. 

Patients were an average age of 59.0 years, 13 were women, mean BMI was 24.8, and average duration of diabetes was 2.8 years. Mean A1c was 54 mmol/mol.

Fourteen of the patients were taking metformin at enrollment and two were being treated with gliclazide. These medications were stopped when the individuals with type 2 diabetes entered a weight-loss program incremented in 5% steps, followed by 6 weeks of weight stability.

Overall, weight decreased by an average of 9%, while body fat decreased from 32% at baseline to 28% at 1 year (P < .001), the same percentage as that seen in the controls.

Liver fats also decreased significantly from baseline (P < .001) down to approximately the same level as controls at 1 year, a pattern also seen with very low-density lipoprotein cholesterol and triglyceride levels.

Pancreatic fat decreased steadily and significantly over the course of the 52-week follow-up (P < .05), although remained above the level seen in controls.

Insulin secretion increased significantly over the course of the study (P = .005) to finish just over the threshold for the lower range of normal at 52 weeks.

This, Dr. Taylor showed, was enough for the 14 patients who achieved type 2 diabetes remission to see their A1c levels fall significantly during follow-up (P < .001), alongside fasting plasma glucose levels (P < .001).

ReTUNE is funded by Diabetes UK. The authors reported no relevant financial relationships.

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

A weight-loss program can lead to type 2 diabetes remission, even in individuals with a normal body mass index (BMI), via loss of body fat, particularly in the liver and pancreas, shows a U.K. study.

The ReTUNE trial, funded by Diabetes UK, involved 20 people with type 2 diabetes of less than 6 year’s duration and a BMI of 27 kg/m² or lower.

Joel Austell/MDedge News

After 1 year, participants had lost 9% of their body weight.

Their body fat decreased significantly, to the same level as controls without type 2 diabetes, and they experienced decreases in liver fat, total triglycerides, and pancreatic fat.

The research, presented at the 2022 Diabetes UK Professional Conference, also showed this was accompanied by increases in insulin secretion and reductions in hemoglobin A1c and fasting plasma glucose levels.

Lead author Roy Taylor, MD, PhD, professor of medicine and metabolism, Newcastle University, Newcastle upon Tyne, England, said the findings indicate that the “etiology and pathophysiology of type 2 diabetes is the same whether BMI is normal or raised.”

This information should make a profound difference in what doctors advise their patients, Dr. Taylor added.

“One of the dramatic things about dealing with people in this group,” he said, “is they feel very resentful that healthcare professionals tell them not to lose weight.”

Based on the current results, Dr. Taylor believes this is “inappropriate advice, and it’s that personal advice that I think that this study points a way towards.”
 

Weight loss ‘first line of treatment’

These findings support the theory of a personal fat threshold, above which “type 2 diabetes occurs,” said Dr. Taylor. “Weight loss is the first-line treatment for all with type 2 diabetes, irrespective of BMI.”

Dr. Taylor already showed in the DiRECT trial that a calorie-restricted liquid diet followed by gradual food reintroduction and a weight-loss maintenance program can achieve and sustain type 2 diabetes remission at 2 years in people who are overweight or obese.

As reported this news organization, 36% of 300 patients enrolled in the trial attained diabetes remission and maintained it out to 24 months, compared with negligible changes in the control group.

Inspired by the results of DiRECT and the DROPLET study, the National Health Service has been rolling out a low calorie–diet treatment program for people who are overweight and living with diabetes.

Asked during the postpresentation discussion whether the current results could have implications for the NHS program, Dr. Taylor said it remains, in effect, a study and will not change things for now.

Chris Askew, chief executive of Diabetes UK, said in a release: “This game-changing study ... advances our understanding of why type 2 diabetes develops and what can be done to treat it.

“Our ambition is for as many people as possible to have the chance to put their type 2 diabetes into remission and live well for longer.”

Mr. Askew continued: “The findings of ReTUNE potentially take us a significant step closer to achieving this goal by showing that remission isn’t only possible for people of certain body weights.”
 

Weight and body fat decrease led to remission

For ReTUNE, the team recruited 20 individuals with type 2 diabetes of less than 6 year’s duration who had a BMI of 21-27 and compared them with 20 matched controls, with a follow-up of 52 weeks. 

Patients were an average age of 59.0 years, 13 were women, mean BMI was 24.8, and average duration of diabetes was 2.8 years. Mean A1c was 54 mmol/mol.

Fourteen of the patients were taking metformin at enrollment and two were being treated with gliclazide. These medications were stopped when the individuals with type 2 diabetes entered a weight-loss program incremented in 5% steps, followed by 6 weeks of weight stability.

Overall, weight decreased by an average of 9%, while body fat decreased from 32% at baseline to 28% at 1 year (P < .001), the same percentage as that seen in the controls.

Liver fats also decreased significantly from baseline (P < .001) down to approximately the same level as controls at 1 year, a pattern also seen with very low-density lipoprotein cholesterol and triglyceride levels.

Pancreatic fat decreased steadily and significantly over the course of the 52-week follow-up (P < .05), although remained above the level seen in controls.

Insulin secretion increased significantly over the course of the study (P = .005) to finish just over the threshold for the lower range of normal at 52 weeks.

This, Dr. Taylor showed, was enough for the 14 patients who achieved type 2 diabetes remission to see their A1c levels fall significantly during follow-up (P < .001), alongside fasting plasma glucose levels (P < .001).

ReTUNE is funded by Diabetes UK. The authors reported no relevant financial relationships.

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

A weight-loss program can lead to type 2 diabetes remission, even in individuals with a normal body mass index (BMI), via loss of body fat, particularly in the liver and pancreas, shows a U.K. study.

The ReTUNE trial, funded by Diabetes UK, involved 20 people with type 2 diabetes of less than 6 year’s duration and a BMI of 27 kg/m² or lower.

Joel Austell/MDedge News

After 1 year, participants had lost 9% of their body weight.

Their body fat decreased significantly, to the same level as controls without type 2 diabetes, and they experienced decreases in liver fat, total triglycerides, and pancreatic fat.

The research, presented at the 2022 Diabetes UK Professional Conference, also showed this was accompanied by increases in insulin secretion and reductions in hemoglobin A1c and fasting plasma glucose levels.

Lead author Roy Taylor, MD, PhD, professor of medicine and metabolism, Newcastle University, Newcastle upon Tyne, England, said the findings indicate that the “etiology and pathophysiology of type 2 diabetes is the same whether BMI is normal or raised.”

This information should make a profound difference in what doctors advise their patients, Dr. Taylor added.

“One of the dramatic things about dealing with people in this group,” he said, “is they feel very resentful that healthcare professionals tell them not to lose weight.”

Based on the current results, Dr. Taylor believes this is “inappropriate advice, and it’s that personal advice that I think that this study points a way towards.”
 

Weight loss ‘first line of treatment’

These findings support the theory of a personal fat threshold, above which “type 2 diabetes occurs,” said Dr. Taylor. “Weight loss is the first-line treatment for all with type 2 diabetes, irrespective of BMI.”

Dr. Taylor already showed in the DiRECT trial that a calorie-restricted liquid diet followed by gradual food reintroduction and a weight-loss maintenance program can achieve and sustain type 2 diabetes remission at 2 years in people who are overweight or obese.

As reported this news organization, 36% of 300 patients enrolled in the trial attained diabetes remission and maintained it out to 24 months, compared with negligible changes in the control group.

Inspired by the results of DiRECT and the DROPLET study, the National Health Service has been rolling out a low calorie–diet treatment program for people who are overweight and living with diabetes.

Asked during the postpresentation discussion whether the current results could have implications for the NHS program, Dr. Taylor said it remains, in effect, a study and will not change things for now.

Chris Askew, chief executive of Diabetes UK, said in a release: “This game-changing study ... advances our understanding of why type 2 diabetes develops and what can be done to treat it.

“Our ambition is for as many people as possible to have the chance to put their type 2 diabetes into remission and live well for longer.”

Mr. Askew continued: “The findings of ReTUNE potentially take us a significant step closer to achieving this goal by showing that remission isn’t only possible for people of certain body weights.”
 

Weight and body fat decrease led to remission

For ReTUNE, the team recruited 20 individuals with type 2 diabetes of less than 6 year’s duration who had a BMI of 21-27 and compared them with 20 matched controls, with a follow-up of 52 weeks. 

Patients were an average age of 59.0 years, 13 were women, mean BMI was 24.8, and average duration of diabetes was 2.8 years. Mean A1c was 54 mmol/mol.

Fourteen of the patients were taking metformin at enrollment and two were being treated with gliclazide. These medications were stopped when the individuals with type 2 diabetes entered a weight-loss program incremented in 5% steps, followed by 6 weeks of weight stability.

Overall, weight decreased by an average of 9%, while body fat decreased from 32% at baseline to 28% at 1 year (P < .001), the same percentage as that seen in the controls.

Liver fats also decreased significantly from baseline (P < .001) down to approximately the same level as controls at 1 year, a pattern also seen with very low-density lipoprotein cholesterol and triglyceride levels.

Pancreatic fat decreased steadily and significantly over the course of the 52-week follow-up (P < .05), although remained above the level seen in controls.

Insulin secretion increased significantly over the course of the study (P = .005) to finish just over the threshold for the lower range of normal at 52 weeks.

This, Dr. Taylor showed, was enough for the 14 patients who achieved type 2 diabetes remission to see their A1c levels fall significantly during follow-up (P < .001), alongside fasting plasma glucose levels (P < .001).

ReTUNE is funded by Diabetes UK. The authors reported no relevant financial relationships.

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

An artificial intelligence (AI)–based predictive tool may be able to identify type 1 diabetes in children earlier, before they are diagnosed as a result of potentially fatal diabetic ketoacidosis (DKA), suggests a new U.K. study.

The tool was developed by Julia Townson, PhD, senior trial manager in children and young people at Cardiff University, U.K., and colleagues.

Her team had previously shown that children who develop type 1 diabetes have a different pattern of contact with primary care in the 6 months leading up to their diagnosis.

Symptoms of type 1 diabetes include going to the toilet more and being thirsty, tired, and thin, but GPs can still miss these signs.

So they tested different combinations of factors from GP records – such as urinary tract infections or bedwetting, being prescribed antibiotics or family history of type 1 diabetes – in approximately 1 million children in Wales, more than 2,000 of whom had been diagnosed with type 1 diabetes, to train the predictive tool.

In a separate study of around 1.5 million children in England, they found that the algorithm could identify type 1 diabetes in 75% of affected children 11 days earlier than without the tool, if it was set up as an alert at every one in 10 general practice consultations.

Dr. Townson presented her research at the recent Diabetes UK Professional Conference 2022.
 

One-quarter of kids diagnosed with type 1 diabetes are in DKA

During her presentation, Dr. Townson explained that, in the U.K., approximately 25% of children with type 1 diabetes are diagnosed while they are in DKA, a figure that has remained unchanged for 25 years.

“We know that delayed- and misdiagnosis are the most common reasons for a child presenting in DKA at diagnosis,” she said. “And of course, the reason why it’s so important to prevent presentation in DKA is because of the considerable morbidity and potentially mortality associated with it.”

Indeed, with a simple internet search, Dr. Townson was able to identify four children who lost their lives to DKA in the past 8 years in the U.K.

“It’s encouraging to see that this research could save many families a potentially traumatic trip to the hospital by helping family doctors diagnose type 1 diabetes more rapidly,” Conor McKeever, research communications manager at the type 1 diabetes charity JDRF, told this news organization.

“This approach could go hand-in-hand with population screening, which has the potential to identify people at high risk of developing type 1 diabetes before they experience any symptoms,” he added. The hope is that “far fewer families experience DKA at the start of their type 1 diabetes journey.”

“Finding a way to catch the condition and treat it early could help to avoid emergency hospital treatment and save lives,” agreed Lucy Chambers, PhD, head of research communications at Diabetes UK, which funded the research.
 

How to integrate tool into GP systems

“We are now looking to see how this tool might work with primary care computer systems,” Dr. Townson said. She said in an interview that they are exploring “how it could be ‘bolted’ on to the GP’s software system.”

“It works on many different levels, but one level is frequency of consultations in relation to the frequency of previous consultations, so it needs to be able to ‘look’ through the electronic health records, at the time of the consultation, to come up with a predictive score.”

Dr. Townson said it is not clear how “easy it will be to integrate it into current systems, and I do not know of any other machine learning applications which have been used like this in primary care.”

“But we are hopeful, and we have started to contact companies who are involved in providing these systems.”

The research was funded by Diabetes UK, and the Clinical Trials Unit was funded by Health and Care Research Wales. No relevant financial relationships were declared.

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

An artificial intelligence (AI)–based predictive tool may be able to identify type 1 diabetes in children earlier, before they are diagnosed as a result of potentially fatal diabetic ketoacidosis (DKA), suggests a new U.K. study.

The tool was developed by Julia Townson, PhD, senior trial manager in children and young people at Cardiff University, U.K., and colleagues.

Her team had previously shown that children who develop type 1 diabetes have a different pattern of contact with primary care in the 6 months leading up to their diagnosis.

Symptoms of type 1 diabetes include going to the toilet more and being thirsty, tired, and thin, but GPs can still miss these signs.

So they tested different combinations of factors from GP records – such as urinary tract infections or bedwetting, being prescribed antibiotics or family history of type 1 diabetes – in approximately 1 million children in Wales, more than 2,000 of whom had been diagnosed with type 1 diabetes, to train the predictive tool.

In a separate study of around 1.5 million children in England, they found that the algorithm could identify type 1 diabetes in 75% of affected children 11 days earlier than without the tool, if it was set up as an alert at every one in 10 general practice consultations.

Dr. Townson presented her research at the recent Diabetes UK Professional Conference 2022.
 

One-quarter of kids diagnosed with type 1 diabetes are in DKA

During her presentation, Dr. Townson explained that, in the U.K., approximately 25% of children with type 1 diabetes are diagnosed while they are in DKA, a figure that has remained unchanged for 25 years.

“We know that delayed- and misdiagnosis are the most common reasons for a child presenting in DKA at diagnosis,” she said. “And of course, the reason why it’s so important to prevent presentation in DKA is because of the considerable morbidity and potentially mortality associated with it.”

Indeed, with a simple internet search, Dr. Townson was able to identify four children who lost their lives to DKA in the past 8 years in the U.K.

“It’s encouraging to see that this research could save many families a potentially traumatic trip to the hospital by helping family doctors diagnose type 1 diabetes more rapidly,” Conor McKeever, research communications manager at the type 1 diabetes charity JDRF, told this news organization.

“This approach could go hand-in-hand with population screening, which has the potential to identify people at high risk of developing type 1 diabetes before they experience any symptoms,” he added. The hope is that “far fewer families experience DKA at the start of their type 1 diabetes journey.”

“Finding a way to catch the condition and treat it early could help to avoid emergency hospital treatment and save lives,” agreed Lucy Chambers, PhD, head of research communications at Diabetes UK, which funded the research.
 

How to integrate tool into GP systems

“We are now looking to see how this tool might work with primary care computer systems,” Dr. Townson said. She said in an interview that they are exploring “how it could be ‘bolted’ on to the GP’s software system.”

“It works on many different levels, but one level is frequency of consultations in relation to the frequency of previous consultations, so it needs to be able to ‘look’ through the electronic health records, at the time of the consultation, to come up with a predictive score.”

Dr. Townson said it is not clear how “easy it will be to integrate it into current systems, and I do not know of any other machine learning applications which have been used like this in primary care.”

“But we are hopeful, and we have started to contact companies who are involved in providing these systems.”

The research was funded by Diabetes UK, and the Clinical Trials Unit was funded by Health and Care Research Wales. No relevant financial relationships were declared.

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

An artificial intelligence (AI)–based predictive tool may be able to identify type 1 diabetes in children earlier, before they are diagnosed as a result of potentially fatal diabetic ketoacidosis (DKA), suggests a new U.K. study.

The tool was developed by Julia Townson, PhD, senior trial manager in children and young people at Cardiff University, U.K., and colleagues.

Her team had previously shown that children who develop type 1 diabetes have a different pattern of contact with primary care in the 6 months leading up to their diagnosis.

Symptoms of type 1 diabetes include going to the toilet more and being thirsty, tired, and thin, but GPs can still miss these signs.

So they tested different combinations of factors from GP records – such as urinary tract infections or bedwetting, being prescribed antibiotics or family history of type 1 diabetes – in approximately 1 million children in Wales, more than 2,000 of whom had been diagnosed with type 1 diabetes, to train the predictive tool.

In a separate study of around 1.5 million children in England, they found that the algorithm could identify type 1 diabetes in 75% of affected children 11 days earlier than without the tool, if it was set up as an alert at every one in 10 general practice consultations.

Dr. Townson presented her research at the recent Diabetes UK Professional Conference 2022.
 

One-quarter of kids diagnosed with type 1 diabetes are in DKA

During her presentation, Dr. Townson explained that, in the U.K., approximately 25% of children with type 1 diabetes are diagnosed while they are in DKA, a figure that has remained unchanged for 25 years.

“We know that delayed- and misdiagnosis are the most common reasons for a child presenting in DKA at diagnosis,” she said. “And of course, the reason why it’s so important to prevent presentation in DKA is because of the considerable morbidity and potentially mortality associated with it.”

Indeed, with a simple internet search, Dr. Townson was able to identify four children who lost their lives to DKA in the past 8 years in the U.K.

“It’s encouraging to see that this research could save many families a potentially traumatic trip to the hospital by helping family doctors diagnose type 1 diabetes more rapidly,” Conor McKeever, research communications manager at the type 1 diabetes charity JDRF, told this news organization.

“This approach could go hand-in-hand with population screening, which has the potential to identify people at high risk of developing type 1 diabetes before they experience any symptoms,” he added. The hope is that “far fewer families experience DKA at the start of their type 1 diabetes journey.”

“Finding a way to catch the condition and treat it early could help to avoid emergency hospital treatment and save lives,” agreed Lucy Chambers, PhD, head of research communications at Diabetes UK, which funded the research.
 

How to integrate tool into GP systems

“We are now looking to see how this tool might work with primary care computer systems,” Dr. Townson said. She said in an interview that they are exploring “how it could be ‘bolted’ on to the GP’s software system.”

“It works on many different levels, but one level is frequency of consultations in relation to the frequency of previous consultations, so it needs to be able to ‘look’ through the electronic health records, at the time of the consultation, to come up with a predictive score.”

Dr. Townson said it is not clear how “easy it will be to integrate it into current systems, and I do not know of any other machine learning applications which have been used like this in primary care.”

“But we are hopeful, and we have started to contact companies who are involved in providing these systems.”

The research was funded by Diabetes UK, and the Clinical Trials Unit was funded by Health and Care Research Wales. No relevant financial relationships were declared.

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

The link between obesity and cancer has increasingly been emphasized in public health messages, but is the current message correct?

“Being overweight or having obesity increases your risk of getting cancer,” warns the U.S. Centers for Disease Control and Prevention. It warns that overweight/obesity is “linked with a higher risk of getting 13 types of cancer ... [which] make up 40% of all cancers diagnosed in the United States each year.”

But that message, which is also promulgated by many cancer organizations, is based on data from observational studies, which have many limitations.

A new study based on Mendelian randomization studies has come to a slightly different conclusion and has found a potential causal association with just six cancers.

In addition, it found an inverse relationship for breast cancer, in which early-life obesity was associated with a reduced risk of breast cancer, and the relationship with obesity was “complicated” for lung and prostate cancer.

The study, headed by Zhe Fang, MBBS, Harvard T. H. Chan School of Public Health, Boston, Mass., was published in the Journal of the National Cancer Institute

“For a seemingly straightforward question of whether excessive body fatness causes cancer, the answer may not be straightforward after all,” writes Song Yao, PhD, professor of oncology, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., in an accompanying editorial

“How to craft a simple public health message to convey the complexity and nuances of the relationships may be a challenge to be grappled with going forward,” he added.

In an interview, Dr. Yao said that it “really depends on what kind of message you want to get out.”

“If you want to talk about cancer overall, as one disease, we all know that a clear association with obesity does not exist,” he said. “It’s not that simple.”

“You really cannot say that obesity increases cancer risk overall,” he said.

For some cancers included in the study, Dr. Yao continued, it was “very clear that obesity increased the risk ... but for some other cancer types, we either don’t have enough data yet or the association is not as consistent.”

This, he said, is especially the case for prostate and lung cancer.

All of this indicates that there is a complex relationship between obesity and cancer risk, he maintains.

“We always think obesity is bad, not only for cancer but also for more common conditions, like hypertension, diabetes, and cardiovascular disease,” Dr. Yao noted. This points to the link between obesity and chronic inflammation, he added.

However, there are also other hypotheses, including synthesis of estrogen in adipose tissue, which may explain the link between obesity and breast cancer risk in older women.

However, in younger women, obesity protects against breast cancer, and “we really don’t know why,” Dr. Yao said.

The new study used Mendelian randomization to examine these relationships. This is a “new tool that we have developed over the past 20 years or so, largely because there is so much data coming from genome-wide association studies,” Dr. Yao explained.

It has “advantages” over other methods, including observational studies. One of its strengths is that it is “not impacted by reverse causality,” because genetic risk does not change over time.

However, he said, it is “quite straightforward to think that the genetics do not change, but at the same time, the environment we live in throughout our life course changes,” and the impact of genetic variants may be “washed out.”

How genetics influences cancer risk may therefore change over time, and it is a “dynamic process,” Dr. Yao commented.

In addition, this approach has its own limitations, he said, because it depends on how much of the variation in a given measure can be attributed to genetic factors.
 

New conclusions

In their study, Dr. Fang and colleagues reviewed 204 meta-analyses of 2,179 individual estimates from 507 cohort or case-control studies. They found “strong evidence” that supports the association between obesity and 11 cancers.

These are esophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract system, pancreas, breast, endometrium, ovary, and kidney.

They note, however, that the associations “may be causal for some malignancies” but that the co-occurrence of obesity with various cancer risk factors means that others may be “susceptible to potential confounding bias.”

To overcome some of these limitations, the team looked to Mendelian randomization studies that examined the association between genetic variants linked to body mass index (BMI), indicating lifetime risk of high BMI, and cancer risk for a range of cancer types.

These Mendelian randomization studies were then compared with the results of large-scale conventional observational studies, as well as with evidence in reports from the International Agency for Research on Cancer and the World Cancer Research Fund–American Institute of Cancer Research, which also include experimental studies.

The researchers say that, overall, the Mendelian randomization studies “further establish the causality of obesity” with six cancer types: colorectal, endometrial, ovarian, kidney, and pancreatic cancer, and esophageal adenocarcinoma.

In addition, these studies further establish the inverse relationship of early-life obesity with breast cancer.

However, the approach could not confirm a positive association between obesity and gallbladder and gastric cardia cancer, as well as multiple myeloma.

“This could be due to low power,” the team suggests, “and larger studies are required.”

With respect to lung cancer, the Mendelian randomization identified a positive association with obesity that supports the inverse association identified in observational studies, that is, that obesity may reduce the risk for lung cancer.

The researchers suggest this may reflect reverse causality related to the loss of lean body mass before diagnosis, as well as confounding by smoking.

For prostate cancer, the evidence was “conflicting” and “implies a complicated role of obesity,” Dr. Zhang and colleagues comment.

The link between obesity and lower prostate-specific antigen levels, they suggest, may result in a detection bias by masking the presence of prostate cancer, or it “could be biological” in origin, owing to reduced androgen levels.

For six cancer types for which a causal relationship with obesity could be established, the effect estimates from the Mendelian randomization studies were stronger than those seen in conventional studies, with the magnitude of risk ranging from 1.14-fold for early-life obesity and breast cancer to 1.37-fold for adult obesity and esophageal adenocarcinoma.

In another editorial accompanying the new study, Graham A. Colditz, MD, DrPH, from Washington University School of Medicine, St. Louis, underlined that childhood and adolescent obesity and their contribution to cancer risk need further attention.

“To reap the reward from past research, we must act to implement effective strategies to reduce childhood and adolescent adiposity, reduce excess weight gain in adult years, and maintain a healthy weight,” he writes.

“This will require us to change the way we live, but COVID-19 has shown we can make changes to how we live and work. Let us keep the changes we have already made, or take on new ones, that will cut our collective cancer toll,” he implores.

No funding for the study was described. Dr. Colditz is supported by the Breast Cancer Research Foundation. No other relevant financial relationships were described.

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

The link between obesity and cancer has increasingly been emphasized in public health messages, but is the current message correct?

“Being overweight or having obesity increases your risk of getting cancer,” warns the U.S. Centers for Disease Control and Prevention. It warns that overweight/obesity is “linked with a higher risk of getting 13 types of cancer ... [which] make up 40% of all cancers diagnosed in the United States each year.”

But that message, which is also promulgated by many cancer organizations, is based on data from observational studies, which have many limitations.

A new study based on Mendelian randomization studies has come to a slightly different conclusion and has found a potential causal association with just six cancers.

In addition, it found an inverse relationship for breast cancer, in which early-life obesity was associated with a reduced risk of breast cancer, and the relationship with obesity was “complicated” for lung and prostate cancer.

The study, headed by Zhe Fang, MBBS, Harvard T. H. Chan School of Public Health, Boston, Mass., was published in the Journal of the National Cancer Institute

“For a seemingly straightforward question of whether excessive body fatness causes cancer, the answer may not be straightforward after all,” writes Song Yao, PhD, professor of oncology, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., in an accompanying editorial

“How to craft a simple public health message to convey the complexity and nuances of the relationships may be a challenge to be grappled with going forward,” he added.

In an interview, Dr. Yao said that it “really depends on what kind of message you want to get out.”

“If you want to talk about cancer overall, as one disease, we all know that a clear association with obesity does not exist,” he said. “It’s not that simple.”

“You really cannot say that obesity increases cancer risk overall,” he said.

For some cancers included in the study, Dr. Yao continued, it was “very clear that obesity increased the risk ... but for some other cancer types, we either don’t have enough data yet or the association is not as consistent.”

This, he said, is especially the case for prostate and lung cancer.

All of this indicates that there is a complex relationship between obesity and cancer risk, he maintains.

“We always think obesity is bad, not only for cancer but also for more common conditions, like hypertension, diabetes, and cardiovascular disease,” Dr. Yao noted. This points to the link between obesity and chronic inflammation, he added.

However, there are also other hypotheses, including synthesis of estrogen in adipose tissue, which may explain the link between obesity and breast cancer risk in older women.

However, in younger women, obesity protects against breast cancer, and “we really don’t know why,” Dr. Yao said.

The new study used Mendelian randomization to examine these relationships. This is a “new tool that we have developed over the past 20 years or so, largely because there is so much data coming from genome-wide association studies,” Dr. Yao explained.

It has “advantages” over other methods, including observational studies. One of its strengths is that it is “not impacted by reverse causality,” because genetic risk does not change over time.

However, he said, it is “quite straightforward to think that the genetics do not change, but at the same time, the environment we live in throughout our life course changes,” and the impact of genetic variants may be “washed out.”

How genetics influences cancer risk may therefore change over time, and it is a “dynamic process,” Dr. Yao commented.

In addition, this approach has its own limitations, he said, because it depends on how much of the variation in a given measure can be attributed to genetic factors.
 

New conclusions

In their study, Dr. Fang and colleagues reviewed 204 meta-analyses of 2,179 individual estimates from 507 cohort or case-control studies. They found “strong evidence” that supports the association between obesity and 11 cancers.

These are esophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract system, pancreas, breast, endometrium, ovary, and kidney.

They note, however, that the associations “may be causal for some malignancies” but that the co-occurrence of obesity with various cancer risk factors means that others may be “susceptible to potential confounding bias.”

To overcome some of these limitations, the team looked to Mendelian randomization studies that examined the association between genetic variants linked to body mass index (BMI), indicating lifetime risk of high BMI, and cancer risk for a range of cancer types.

These Mendelian randomization studies were then compared with the results of large-scale conventional observational studies, as well as with evidence in reports from the International Agency for Research on Cancer and the World Cancer Research Fund–American Institute of Cancer Research, which also include experimental studies.

The researchers say that, overall, the Mendelian randomization studies “further establish the causality of obesity” with six cancer types: colorectal, endometrial, ovarian, kidney, and pancreatic cancer, and esophageal adenocarcinoma.

In addition, these studies further establish the inverse relationship of early-life obesity with breast cancer.

However, the approach could not confirm a positive association between obesity and gallbladder and gastric cardia cancer, as well as multiple myeloma.

“This could be due to low power,” the team suggests, “and larger studies are required.”

With respect to lung cancer, the Mendelian randomization identified a positive association with obesity that supports the inverse association identified in observational studies, that is, that obesity may reduce the risk for lung cancer.

The researchers suggest this may reflect reverse causality related to the loss of lean body mass before diagnosis, as well as confounding by smoking.

For prostate cancer, the evidence was “conflicting” and “implies a complicated role of obesity,” Dr. Zhang and colleagues comment.

The link between obesity and lower prostate-specific antigen levels, they suggest, may result in a detection bias by masking the presence of prostate cancer, or it “could be biological” in origin, owing to reduced androgen levels.

For six cancer types for which a causal relationship with obesity could be established, the effect estimates from the Mendelian randomization studies were stronger than those seen in conventional studies, with the magnitude of risk ranging from 1.14-fold for early-life obesity and breast cancer to 1.37-fold for adult obesity and esophageal adenocarcinoma.

In another editorial accompanying the new study, Graham A. Colditz, MD, DrPH, from Washington University School of Medicine, St. Louis, underlined that childhood and adolescent obesity and their contribution to cancer risk need further attention.

“To reap the reward from past research, we must act to implement effective strategies to reduce childhood and adolescent adiposity, reduce excess weight gain in adult years, and maintain a healthy weight,” he writes.

“This will require us to change the way we live, but COVID-19 has shown we can make changes to how we live and work. Let us keep the changes we have already made, or take on new ones, that will cut our collective cancer toll,” he implores.

No funding for the study was described. Dr. Colditz is supported by the Breast Cancer Research Foundation. No other relevant financial relationships were described.

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

The link between obesity and cancer has increasingly been emphasized in public health messages, but is the current message correct?

“Being overweight or having obesity increases your risk of getting cancer,” warns the U.S. Centers for Disease Control and Prevention. It warns that overweight/obesity is “linked with a higher risk of getting 13 types of cancer ... [which] make up 40% of all cancers diagnosed in the United States each year.”

But that message, which is also promulgated by many cancer organizations, is based on data from observational studies, which have many limitations.

A new study based on Mendelian randomization studies has come to a slightly different conclusion and has found a potential causal association with just six cancers.

In addition, it found an inverse relationship for breast cancer, in which early-life obesity was associated with a reduced risk of breast cancer, and the relationship with obesity was “complicated” for lung and prostate cancer.

The study, headed by Zhe Fang, MBBS, Harvard T. H. Chan School of Public Health, Boston, Mass., was published in the Journal of the National Cancer Institute

“For a seemingly straightforward question of whether excessive body fatness causes cancer, the answer may not be straightforward after all,” writes Song Yao, PhD, professor of oncology, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., in an accompanying editorial

“How to craft a simple public health message to convey the complexity and nuances of the relationships may be a challenge to be grappled with going forward,” he added.

In an interview, Dr. Yao said that it “really depends on what kind of message you want to get out.”

“If you want to talk about cancer overall, as one disease, we all know that a clear association with obesity does not exist,” he said. “It’s not that simple.”

“You really cannot say that obesity increases cancer risk overall,” he said.

For some cancers included in the study, Dr. Yao continued, it was “very clear that obesity increased the risk ... but for some other cancer types, we either don’t have enough data yet or the association is not as consistent.”

This, he said, is especially the case for prostate and lung cancer.

All of this indicates that there is a complex relationship between obesity and cancer risk, he maintains.

“We always think obesity is bad, not only for cancer but also for more common conditions, like hypertension, diabetes, and cardiovascular disease,” Dr. Yao noted. This points to the link between obesity and chronic inflammation, he added.

However, there are also other hypotheses, including synthesis of estrogen in adipose tissue, which may explain the link between obesity and breast cancer risk in older women.

However, in younger women, obesity protects against breast cancer, and “we really don’t know why,” Dr. Yao said.

The new study used Mendelian randomization to examine these relationships. This is a “new tool that we have developed over the past 20 years or so, largely because there is so much data coming from genome-wide association studies,” Dr. Yao explained.

It has “advantages” over other methods, including observational studies. One of its strengths is that it is “not impacted by reverse causality,” because genetic risk does not change over time.

However, he said, it is “quite straightforward to think that the genetics do not change, but at the same time, the environment we live in throughout our life course changes,” and the impact of genetic variants may be “washed out.”

How genetics influences cancer risk may therefore change over time, and it is a “dynamic process,” Dr. Yao commented.

In addition, this approach has its own limitations, he said, because it depends on how much of the variation in a given measure can be attributed to genetic factors.
 

New conclusions

In their study, Dr. Fang and colleagues reviewed 204 meta-analyses of 2,179 individual estimates from 507 cohort or case-control studies. They found “strong evidence” that supports the association between obesity and 11 cancers.

These are esophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract system, pancreas, breast, endometrium, ovary, and kidney.

They note, however, that the associations “may be causal for some malignancies” but that the co-occurrence of obesity with various cancer risk factors means that others may be “susceptible to potential confounding bias.”

To overcome some of these limitations, the team looked to Mendelian randomization studies that examined the association between genetic variants linked to body mass index (BMI), indicating lifetime risk of high BMI, and cancer risk for a range of cancer types.

These Mendelian randomization studies were then compared with the results of large-scale conventional observational studies, as well as with evidence in reports from the International Agency for Research on Cancer and the World Cancer Research Fund–American Institute of Cancer Research, which also include experimental studies.

The researchers say that, overall, the Mendelian randomization studies “further establish the causality of obesity” with six cancer types: colorectal, endometrial, ovarian, kidney, and pancreatic cancer, and esophageal adenocarcinoma.

In addition, these studies further establish the inverse relationship of early-life obesity with breast cancer.

However, the approach could not confirm a positive association between obesity and gallbladder and gastric cardia cancer, as well as multiple myeloma.

“This could be due to low power,” the team suggests, “and larger studies are required.”

With respect to lung cancer, the Mendelian randomization identified a positive association with obesity that supports the inverse association identified in observational studies, that is, that obesity may reduce the risk for lung cancer.

The researchers suggest this may reflect reverse causality related to the loss of lean body mass before diagnosis, as well as confounding by smoking.

For prostate cancer, the evidence was “conflicting” and “implies a complicated role of obesity,” Dr. Zhang and colleagues comment.

The link between obesity and lower prostate-specific antigen levels, they suggest, may result in a detection bias by masking the presence of prostate cancer, or it “could be biological” in origin, owing to reduced androgen levels.

For six cancer types for which a causal relationship with obesity could be established, the effect estimates from the Mendelian randomization studies were stronger than those seen in conventional studies, with the magnitude of risk ranging from 1.14-fold for early-life obesity and breast cancer to 1.37-fold for adult obesity and esophageal adenocarcinoma.

In another editorial accompanying the new study, Graham A. Colditz, MD, DrPH, from Washington University School of Medicine, St. Louis, underlined that childhood and adolescent obesity and their contribution to cancer risk need further attention.

“To reap the reward from past research, we must act to implement effective strategies to reduce childhood and adolescent adiposity, reduce excess weight gain in adult years, and maintain a healthy weight,” he writes.

“This will require us to change the way we live, but COVID-19 has shown we can make changes to how we live and work. Let us keep the changes we have already made, or take on new ones, that will cut our collective cancer toll,” he implores.

No funding for the study was described. Dr. Colditz is supported by the Breast Cancer Research Foundation. No other relevant financial relationships were described.

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