Clinician Reviews

Losing weight and lowering body mass index may help people slow, delay, or even prevent the structural defects of knee osteoarthritis, especially on the medial side of the knee, results of a prospective multicohort study from Australia suggest.

“We showed that the more weight that is lost, the greater the apparent benefit for delaying or preventing knee joint degradation in osteoarthritis,” senior study author Amanda Sainsbury, PhD, professor of obesity research at the University of Western Australia, Perth, said in an interview. “For example, a person weighing 100 kilograms [220 pounds] who loses 10 kilograms [22 pounds] is likely to have double the benefit compared to losing 5 kilograms [11 pounds].”

wragg/iStockphoto.com

“We showed evidence of association, not causality,” she and her colleagues wrote in Arthritis & Rheumatology. “Future randomized, controlled trials are required to demonstrate causality.”

Dr. Sainsbury and colleagues analyzed radiographs of knees from three independent cohort studies from the United States and the Netherlands – the Osteoarthritis Initiative (OAI), the Multicenter Osteoarthritis Study (MOST), and the Cohort Hip and Cohort Knee (CHECK) study – at baseline and again 4-5 years later.

The authors created two groups of knees at baseline: the “incidence cohort” of 9,683 knees from 5,774 participants without OA structural defects (Kellgren-Lawrence grade 0 or 1) and the “progression cohort” of 6,075 knees from 3,988 participants with OA structural defects (KL grade 2 or higher). After 4-5 years, they determined OA incidence (KL grade 2 or higher in participants without baseline knee OA) and progression (increase of one or more KL grades in those with baseline knee OA).At baseline, the mean patient age in both groups was around 60, and around 60% of participants were female. In the incidence and progression groups, respectively, White patients comprised 87.5% and 80.4% of participants; mean body mass index was 28.2 and 30.4 kg/m²; and 32.6% and 48.4% of participants were obese (BMI, 30 or higher). The authors combined data from the three studies and used logistic regression and generalized estimating equations, with clustering of both knees within individuals. On multivariable analysis, they found that change in BMI 4-5 years post baseline was positively linked with both incidence and progression of knee OA structural defects.

In the incidence group, BMI decreased 1 or more units in 1,101 patients and increased 1 or more units in 1,611. In the progression group, BMI decreased 1 or more units in 798 patients and increased in 1,008.

The adjusted odds ratio for overall structural defects in the incidence group was 1.05 (95% confidence interval, 1.02-1.09) and 1.05 (95% CI, 1.01-1.09) in the progression group was. A 1-unit decrease in BMI was linked with a nearly 5% drop in odds of incidence and progression of knee OA, and a 5-unit decrease was linked with a more than 21% drop in odds of incidence and progression.

In the incidence group, change in BMI was positively linked with medial, but not lateral, joint space degeneration (narrowing; OR, 1.08; 95% CI, 1.04-1.12) and with medial femoral surface degeneration indicated by osteophytes (OR, 1.07; 95% CI, 1.03-1.12).

In the progression group, change in BMI was positively linked with overall structural defects (OR, 1.05; 95% CI, 1.01-1.09) as well as medial, but not lateral, joint space degeneration (OR, 1.08; 95% CI, 1.03-1.12).

“Previous research showed that weight loss helps reduce symptoms of knee osteoarthritis, such as pain and impaired physical function,” said lead study author Zübeyir Salis, BEng, a PhD student in public health at the University of New South Wales, Kensington, Australia. “Weight loss is emerging as a suitable strategy for potentially delaying and preventing osteoarthritic knee joint degeneration.”
 

Two experts not involved in the study welcome its results

Kai Sun, MD, MS, assistant professor of medicine, rheumatology, and immunology at Duke University, Durham, N. C., said it makes mechanical sense that less weight bearing decreases knee damage over time, but she was somewhat surprised that even people who started with normal BMI improved their outcomes by decreasing BMI further.

“Knee osteoarthritis and obesity prevalence are both growing,” Dr. Sun said. “Knee osteoarthritis may one day be considered an obesity-related comorbidity like hypertension and diabetes and be used as additional justification for pharmacologic or nonpharmacologic interventions to treat obesity.”

She noted that the study’s major strengths include its large sample size, long follow-up, and separate inclusion of disease incidence and progression, but also noted some limitations.

“BMI data at only two time points does not consider BMI fluctuations between those times,” she added. “Limited data were presented on physical activity levels, and most participants being White and elderly limited the generalizability of the results.”

Eduardo Grunvald, MD, professor of medicine and medical director of the weight management program at the University of California, San Diego, agreed about the study’s strengths and pointed out its lack of information about the cause of BMI changes.

Dr. Grunvald would like to know whether the BMI changes contributed to the knee changes or vice versa. “An individual’s worsening knee pain could lead to less physical activity and possible increased BMI.

“Long-term weight-loss maintenance is extremely challenging, and for optimal outcomes, medical professionals who treat joint disease should partner with clinicians trained to treat obesity,” he advised.

The authors are planning further related research. “We’re looking forward to running a randomized, controlled clinical weight-loss trial,” Dr. Sainsbury said.The study was supported by scholarship and fellowship funds from the Australian government. Mr. Salis and Dr. Sainsbury each own 50% of shares in a company that provides educational resources and services in adult weight management. Dr. Sainsbury and one coauthor reported relevant financial relationships with various pharmaceutical companies. Dr. Sun and Dr. Grunvald reported no relevant financial relationships.

Losing weight and lowering body mass index may help people slow, delay, or even prevent the structural defects of knee osteoarthritis, especially on the medial side of the knee, results of a prospective multicohort study from Australia suggest.

“We showed that the more weight that is lost, the greater the apparent benefit for delaying or preventing knee joint degradation in osteoarthritis,” senior study author Amanda Sainsbury, PhD, professor of obesity research at the University of Western Australia, Perth, said in an interview. “For example, a person weighing 100 kilograms [220 pounds] who loses 10 kilograms [22 pounds] is likely to have double the benefit compared to losing 5 kilograms [11 pounds].”

wragg/iStockphoto.com

“We showed evidence of association, not causality,” she and her colleagues wrote in Arthritis & Rheumatology. “Future randomized, controlled trials are required to demonstrate causality.”

Dr. Sainsbury and colleagues analyzed radiographs of knees from three independent cohort studies from the United States and the Netherlands – the Osteoarthritis Initiative (OAI), the Multicenter Osteoarthritis Study (MOST), and the Cohort Hip and Cohort Knee (CHECK) study – at baseline and again 4-5 years later.

The authors created two groups of knees at baseline: the “incidence cohort” of 9,683 knees from 5,774 participants without OA structural defects (Kellgren-Lawrence grade 0 or 1) and the “progression cohort” of 6,075 knees from 3,988 participants with OA structural defects (KL grade 2 or higher). After 4-5 years, they determined OA incidence (KL grade 2 or higher in participants without baseline knee OA) and progression (increase of one or more KL grades in those with baseline knee OA).At baseline, the mean patient age in both groups was around 60, and around 60% of participants were female. In the incidence and progression groups, respectively, White patients comprised 87.5% and 80.4% of participants; mean body mass index was 28.2 and 30.4 kg/m²; and 32.6% and 48.4% of participants were obese (BMI, 30 or higher). The authors combined data from the three studies and used logistic regression and generalized estimating equations, with clustering of both knees within individuals. On multivariable analysis, they found that change in BMI 4-5 years post baseline was positively linked with both incidence and progression of knee OA structural defects.

In the incidence group, BMI decreased 1 or more units in 1,101 patients and increased 1 or more units in 1,611. In the progression group, BMI decreased 1 or more units in 798 patients and increased in 1,008.

The adjusted odds ratio for overall structural defects in the incidence group was 1.05 (95% confidence interval, 1.02-1.09) and 1.05 (95% CI, 1.01-1.09) in the progression group was. A 1-unit decrease in BMI was linked with a nearly 5% drop in odds of incidence and progression of knee OA, and a 5-unit decrease was linked with a more than 21% drop in odds of incidence and progression.

In the incidence group, change in BMI was positively linked with medial, but not lateral, joint space degeneration (narrowing; OR, 1.08; 95% CI, 1.04-1.12) and with medial femoral surface degeneration indicated by osteophytes (OR, 1.07; 95% CI, 1.03-1.12).

In the progression group, change in BMI was positively linked with overall structural defects (OR, 1.05; 95% CI, 1.01-1.09) as well as medial, but not lateral, joint space degeneration (OR, 1.08; 95% CI, 1.03-1.12).

“Previous research showed that weight loss helps reduce symptoms of knee osteoarthritis, such as pain and impaired physical function,” said lead study author Zübeyir Salis, BEng, a PhD student in public health at the University of New South Wales, Kensington, Australia. “Weight loss is emerging as a suitable strategy for potentially delaying and preventing osteoarthritic knee joint degeneration.”
 

Two experts not involved in the study welcome its results

Kai Sun, MD, MS, assistant professor of medicine, rheumatology, and immunology at Duke University, Durham, N. C., said it makes mechanical sense that less weight bearing decreases knee damage over time, but she was somewhat surprised that even people who started with normal BMI improved their outcomes by decreasing BMI further.

“Knee osteoarthritis and obesity prevalence are both growing,” Dr. Sun said. “Knee osteoarthritis may one day be considered an obesity-related comorbidity like hypertension and diabetes and be used as additional justification for pharmacologic or nonpharmacologic interventions to treat obesity.”

She noted that the study’s major strengths include its large sample size, long follow-up, and separate inclusion of disease incidence and progression, but also noted some limitations.

“BMI data at only two time points does not consider BMI fluctuations between those times,” she added. “Limited data were presented on physical activity levels, and most participants being White and elderly limited the generalizability of the results.”

Eduardo Grunvald, MD, professor of medicine and medical director of the weight management program at the University of California, San Diego, agreed about the study’s strengths and pointed out its lack of information about the cause of BMI changes.

Dr. Grunvald would like to know whether the BMI changes contributed to the knee changes or vice versa. “An individual’s worsening knee pain could lead to less physical activity and possible increased BMI.

“Long-term weight-loss maintenance is extremely challenging, and for optimal outcomes, medical professionals who treat joint disease should partner with clinicians trained to treat obesity,” he advised.

The authors are planning further related research. “We’re looking forward to running a randomized, controlled clinical weight-loss trial,” Dr. Sainsbury said.The study was supported by scholarship and fellowship funds from the Australian government. Mr. Salis and Dr. Sainsbury each own 50% of shares in a company that provides educational resources and services in adult weight management. Dr. Sainsbury and one coauthor reported relevant financial relationships with various pharmaceutical companies. Dr. Sun and Dr. Grunvald reported no relevant financial relationships.

Losing weight and lowering body mass index may help people slow, delay, or even prevent the structural defects of knee osteoarthritis, especially on the medial side of the knee, results of a prospective multicohort study from Australia suggest.

“We showed that the more weight that is lost, the greater the apparent benefit for delaying or preventing knee joint degradation in osteoarthritis,” senior study author Amanda Sainsbury, PhD, professor of obesity research at the University of Western Australia, Perth, said in an interview. “For example, a person weighing 100 kilograms [220 pounds] who loses 10 kilograms [22 pounds] is likely to have double the benefit compared to losing 5 kilograms [11 pounds].”

wragg/iStockphoto.com

“We showed evidence of association, not causality,” she and her colleagues wrote in Arthritis & Rheumatology. “Future randomized, controlled trials are required to demonstrate causality.”

Dr. Sainsbury and colleagues analyzed radiographs of knees from three independent cohort studies from the United States and the Netherlands – the Osteoarthritis Initiative (OAI), the Multicenter Osteoarthritis Study (MOST), and the Cohort Hip and Cohort Knee (CHECK) study – at baseline and again 4-5 years later.

The authors created two groups of knees at baseline: the “incidence cohort” of 9,683 knees from 5,774 participants without OA structural defects (Kellgren-Lawrence grade 0 or 1) and the “progression cohort” of 6,075 knees from 3,988 participants with OA structural defects (KL grade 2 or higher). After 4-5 years, they determined OA incidence (KL grade 2 or higher in participants without baseline knee OA) and progression (increase of one or more KL grades in those with baseline knee OA).At baseline, the mean patient age in both groups was around 60, and around 60% of participants were female. In the incidence and progression groups, respectively, White patients comprised 87.5% and 80.4% of participants; mean body mass index was 28.2 and 30.4 kg/m²; and 32.6% and 48.4% of participants were obese (BMI, 30 or higher). The authors combined data from the three studies and used logistic regression and generalized estimating equations, with clustering of both knees within individuals. On multivariable analysis, they found that change in BMI 4-5 years post baseline was positively linked with both incidence and progression of knee OA structural defects.

In the incidence group, BMI decreased 1 or more units in 1,101 patients and increased 1 or more units in 1,611. In the progression group, BMI decreased 1 or more units in 798 patients and increased in 1,008.

The adjusted odds ratio for overall structural defects in the incidence group was 1.05 (95% confidence interval, 1.02-1.09) and 1.05 (95% CI, 1.01-1.09) in the progression group was. A 1-unit decrease in BMI was linked with a nearly 5% drop in odds of incidence and progression of knee OA, and a 5-unit decrease was linked with a more than 21% drop in odds of incidence and progression.

In the incidence group, change in BMI was positively linked with medial, but not lateral, joint space degeneration (narrowing; OR, 1.08; 95% CI, 1.04-1.12) and with medial femoral surface degeneration indicated by osteophytes (OR, 1.07; 95% CI, 1.03-1.12).

In the progression group, change in BMI was positively linked with overall structural defects (OR, 1.05; 95% CI, 1.01-1.09) as well as medial, but not lateral, joint space degeneration (OR, 1.08; 95% CI, 1.03-1.12).

“Previous research showed that weight loss helps reduce symptoms of knee osteoarthritis, such as pain and impaired physical function,” said lead study author Zübeyir Salis, BEng, a PhD student in public health at the University of New South Wales, Kensington, Australia. “Weight loss is emerging as a suitable strategy for potentially delaying and preventing osteoarthritic knee joint degeneration.”
 

Two experts not involved in the study welcome its results

Kai Sun, MD, MS, assistant professor of medicine, rheumatology, and immunology at Duke University, Durham, N. C., said it makes mechanical sense that less weight bearing decreases knee damage over time, but she was somewhat surprised that even people who started with normal BMI improved their outcomes by decreasing BMI further.

“Knee osteoarthritis and obesity prevalence are both growing,” Dr. Sun said. “Knee osteoarthritis may one day be considered an obesity-related comorbidity like hypertension and diabetes and be used as additional justification for pharmacologic or nonpharmacologic interventions to treat obesity.”

She noted that the study’s major strengths include its large sample size, long follow-up, and separate inclusion of disease incidence and progression, but also noted some limitations.

“BMI data at only two time points does not consider BMI fluctuations between those times,” she added. “Limited data were presented on physical activity levels, and most participants being White and elderly limited the generalizability of the results.”

Eduardo Grunvald, MD, professor of medicine and medical director of the weight management program at the University of California, San Diego, agreed about the study’s strengths and pointed out its lack of information about the cause of BMI changes.

Dr. Grunvald would like to know whether the BMI changes contributed to the knee changes or vice versa. “An individual’s worsening knee pain could lead to less physical activity and possible increased BMI.

“Long-term weight-loss maintenance is extremely challenging, and for optimal outcomes, medical professionals who treat joint disease should partner with clinicians trained to treat obesity,” he advised.

The authors are planning further related research. “We’re looking forward to running a randomized, controlled clinical weight-loss trial,” Dr. Sainsbury said.The study was supported by scholarship and fellowship funds from the Australian government. Mr. Salis and Dr. Sainsbury each own 50% of shares in a company that provides educational resources and services in adult weight management. Dr. Sainsbury and one coauthor reported relevant financial relationships with various pharmaceutical companies. Dr. Sun and Dr. Grunvald reported no relevant financial relationships.

Ketamine infusions can help reduce symptoms of suicidal ideation, depression, and anxiety in patients with treatment-resistant depression (TRD), new research suggests.

MindPeace Clinics

Results from a retrospective chart review analysis, which included more than 400 participants with TRD, illustrate that ketamine is a safe and rapid treatment in a real-world patient population, lead author Patrick A. Oliver, MD, founder and medical director, MindPeace Clinics, Richmond, Va., told this news organization.

The effect was perhaps most notable for reducing suicidal ideation, he said.

“In 2 weeks, we can take somebody from being suicidal to nonsuicidal. It’s a total game changer,” Dr. Oliver added.

Every year in the United States, about 12 million individuals think about suicide, 3.2 million make a plan to kill themselves, and more than 46,000 succeed, the investigators note.

The findings were published online in the Journal of Clinical Psychiatry.
 

Molecule mixture

Primarily used as an anesthetic in hospitals, ketamine is also taken illegally as a recreational drug. Users may aim for an intense high or feeling of dissociation, or an out-of-body–type experience.

Ketamine is a mixture of two mirror-image molecules. An intranasal version of one of these molecules (esketamine) is approved by the U.S. Food and Drug Administration for TRD. Both esketamine and ketamine are believed to increase neurotrophic signaling that affects synaptic function.

The study included 424 patients (mean age, 41.7 years) with major depressive disorder or another mood disorder and who received at least one ketamine infusion at a specialty clinic. Most participants had failed prior medication trials.

Patients in the study were typically started on 0.5 mg/kg of ketamine, with the dose titrated to achieve symptoms of partial dissociation. The median dose administered after titration was 0.93 mg/kg over 40 minutes.

The main treatment course of at least six infusions within 21 days was completed by 70% of the patients.

At each clinic visit, all participants completed the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7).

The primary outcome was PHQ-9 total scores, for which researchers looked at seven time periods: 1 week, 2-3 weeks, 4-6 weeks, 7-12 weeks, 13-24 weeks, 25-51 weeks, and 52+ weeks.
 

‘Blows it out of the water’

Results showed PHQ-9 total scores declined by 50% throughout the course of treatment, with much of the improvement gained within 4-6 weeks. There was a significant difference between week 1 and all later time periods (all P values < .001) and between weeks 2 and 3 and all later periods (all P values < .001).

Other measures included treatment response, defined as at least a 50% improvement on the PHQ-9, and depression remission, defined as a PHQ-9 score of less than 5. After three infusions, 14% of the patients responded and 7% were in remission. After 10 infusions, 72% responded and 38% were in remission.

These results compare favorably to other depression treatments, said Dr. Oliver. “Truthfully, with the exception of ECT [electroconvulsive therapy], this blows it all out of the water,” he added.

Dr. Oliver noted that the success rate for repetitive transcranial magnetic stimulation is 40%-60% depending on the modality; and for selective serotonin reuptake inhibitors, the success rate “is somewhere between the mid-20s and low-30s percent range.”

Another outcome measure was the self-harm/suicidal ideation item of the PHQ-9 questionnaire, which asks about “thoughts that you would be better off dead, or of hurting yourself in some way.” About 22% of the study participants no longer reported suicidal ideation after 3 infusions, 50% by 6 infusions, and 75% by 10 infusions.

By 15 infusions, 85% no longer reported these thoughts. “Nothing else has shown that, ever,” said Dr. Oliver.

Symptoms of generalized anxiety were also substantially improved. There was about a 30% reduction in the GAD-7 score during treatment and, again, most of the response occurred by 4-6 weeks.
 

Study limitations

Sex, age, and other demographic characteristics did not predict response or remission, but suicide planning trended toward higher response rates (P = .083). This suggests that a more depressed subgroup can achieve greater benefit from the treatment than can less symptomatic patients, the investigators note.

A history of psychosis also trended toward better response to treatment (P = .086) but not remission.

The researchers note that study limitations include that it was retrospective, lacked a control group, and did not require patients to be hospitalized – so the study sample may have been less severely ill than in other studies.

In addition, most patients paid out of pocket for the treatment at $495 per infusion, and they self-reported their symptoms.

As well, the researchers did not assess adverse events, although nurses made follow-up calls to patients. Dr. Oliver noted the most common side effects of ketamine are nausea, vomiting, and anxiety.

Previous research has suggested that ketamine therapy is not linked to long-term side effects, such as sexual dysfunction, weight gain, lethargy, or cognitive issues, said Dr. Oliver.

The investigators point out another study limitation was lack of detailed demographic information, such as race, income, and education, which might affect its generalizability.
 

Concerns and questions

Pouya Movahed Rad, MD, PhD, senior consultant and researcher in psychiatry, Lund (Sweden) University, noted several concerns, including that the clinics treating the study participants with ketamine profited from it.

He also speculated about who can afford the treatment because only a few patients in the study were reimbursed through insurance.

Dr. Movahed Rad was not involved with the current research but was principal investigator for a recent study  that compared intravenous ketamine to ECT.

He questioned whether the patient population in the new study really was “real world.” Well-designed randomized controlled trials have been carried out in a “naturalistic setting, [which] get closer to real-life patients,” he said.

He also noted that the median dose after clinician titration (0.93 mg/kg over 40 minutes) “may be considered very high.”

With regard to doses being titrated to achieve symptoms of partial dissociation, “there is no obvious evidence to my knowledge that patients need to develop dissociative symptoms in order to have antidepressant effect,” said Dr. Movahed Rad.

Finally, he noted that the finding that 28% of the participants were using illegal drugs “is worrying” and wondered what drugs they were taking; he also questioned why 81% of the study population needed to take antidepressants.

The study did not receive outside funding. Dr. Oliver is the founder of MindPeace Clinics, which specialize in ketamine therapeutics. Dr. Movahed Rad has reported no relevant financial relationships.

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

Ketamine infusions can help reduce symptoms of suicidal ideation, depression, and anxiety in patients with treatment-resistant depression (TRD), new research suggests.

MindPeace Clinics

Results from a retrospective chart review analysis, which included more than 400 participants with TRD, illustrate that ketamine is a safe and rapid treatment in a real-world patient population, lead author Patrick A. Oliver, MD, founder and medical director, MindPeace Clinics, Richmond, Va., told this news organization.

The effect was perhaps most notable for reducing suicidal ideation, he said.

“In 2 weeks, we can take somebody from being suicidal to nonsuicidal. It’s a total game changer,” Dr. Oliver added.

Every year in the United States, about 12 million individuals think about suicide, 3.2 million make a plan to kill themselves, and more than 46,000 succeed, the investigators note.

The findings were published online in the Journal of Clinical Psychiatry.
 

Molecule mixture

Primarily used as an anesthetic in hospitals, ketamine is also taken illegally as a recreational drug. Users may aim for an intense high or feeling of dissociation, or an out-of-body–type experience.

Ketamine is a mixture of two mirror-image molecules. An intranasal version of one of these molecules (esketamine) is approved by the U.S. Food and Drug Administration for TRD. Both esketamine and ketamine are believed to increase neurotrophic signaling that affects synaptic function.

The study included 424 patients (mean age, 41.7 years) with major depressive disorder or another mood disorder and who received at least one ketamine infusion at a specialty clinic. Most participants had failed prior medication trials.

Patients in the study were typically started on 0.5 mg/kg of ketamine, with the dose titrated to achieve symptoms of partial dissociation. The median dose administered after titration was 0.93 mg/kg over 40 minutes.

The main treatment course of at least six infusions within 21 days was completed by 70% of the patients.

At each clinic visit, all participants completed the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7).

The primary outcome was PHQ-9 total scores, for which researchers looked at seven time periods: 1 week, 2-3 weeks, 4-6 weeks, 7-12 weeks, 13-24 weeks, 25-51 weeks, and 52+ weeks.
 

‘Blows it out of the water’

Results showed PHQ-9 total scores declined by 50% throughout the course of treatment, with much of the improvement gained within 4-6 weeks. There was a significant difference between week 1 and all later time periods (all P values < .001) and between weeks 2 and 3 and all later periods (all P values < .001).

Other measures included treatment response, defined as at least a 50% improvement on the PHQ-9, and depression remission, defined as a PHQ-9 score of less than 5. After three infusions, 14% of the patients responded and 7% were in remission. After 10 infusions, 72% responded and 38% were in remission.

These results compare favorably to other depression treatments, said Dr. Oliver. “Truthfully, with the exception of ECT [electroconvulsive therapy], this blows it all out of the water,” he added.

Dr. Oliver noted that the success rate for repetitive transcranial magnetic stimulation is 40%-60% depending on the modality; and for selective serotonin reuptake inhibitors, the success rate “is somewhere between the mid-20s and low-30s percent range.”

Another outcome measure was the self-harm/suicidal ideation item of the PHQ-9 questionnaire, which asks about “thoughts that you would be better off dead, or of hurting yourself in some way.” About 22% of the study participants no longer reported suicidal ideation after 3 infusions, 50% by 6 infusions, and 75% by 10 infusions.

By 15 infusions, 85% no longer reported these thoughts. “Nothing else has shown that, ever,” said Dr. Oliver.

Symptoms of generalized anxiety were also substantially improved. There was about a 30% reduction in the GAD-7 score during treatment and, again, most of the response occurred by 4-6 weeks.
 

Study limitations

Sex, age, and other demographic characteristics did not predict response or remission, but suicide planning trended toward higher response rates (P = .083). This suggests that a more depressed subgroup can achieve greater benefit from the treatment than can less symptomatic patients, the investigators note.

A history of psychosis also trended toward better response to treatment (P = .086) but not remission.

The researchers note that study limitations include that it was retrospective, lacked a control group, and did not require patients to be hospitalized – so the study sample may have been less severely ill than in other studies.

In addition, most patients paid out of pocket for the treatment at $495 per infusion, and they self-reported their symptoms.

As well, the researchers did not assess adverse events, although nurses made follow-up calls to patients. Dr. Oliver noted the most common side effects of ketamine are nausea, vomiting, and anxiety.

Previous research has suggested that ketamine therapy is not linked to long-term side effects, such as sexual dysfunction, weight gain, lethargy, or cognitive issues, said Dr. Oliver.

The investigators point out another study limitation was lack of detailed demographic information, such as race, income, and education, which might affect its generalizability.
 

Concerns and questions

Pouya Movahed Rad, MD, PhD, senior consultant and researcher in psychiatry, Lund (Sweden) University, noted several concerns, including that the clinics treating the study participants with ketamine profited from it.

He also speculated about who can afford the treatment because only a few patients in the study were reimbursed through insurance.

Dr. Movahed Rad was not involved with the current research but was principal investigator for a recent study  that compared intravenous ketamine to ECT.

He questioned whether the patient population in the new study really was “real world.” Well-designed randomized controlled trials have been carried out in a “naturalistic setting, [which] get closer to real-life patients,” he said.

He also noted that the median dose after clinician titration (0.93 mg/kg over 40 minutes) “may be considered very high.”

With regard to doses being titrated to achieve symptoms of partial dissociation, “there is no obvious evidence to my knowledge that patients need to develop dissociative symptoms in order to have antidepressant effect,” said Dr. Movahed Rad.

Finally, he noted that the finding that 28% of the participants were using illegal drugs “is worrying” and wondered what drugs they were taking; he also questioned why 81% of the study population needed to take antidepressants.

The study did not receive outside funding. Dr. Oliver is the founder of MindPeace Clinics, which specialize in ketamine therapeutics. Dr. Movahed Rad has reported no relevant financial relationships.

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

Ketamine infusions can help reduce symptoms of suicidal ideation, depression, and anxiety in patients with treatment-resistant depression (TRD), new research suggests.

MindPeace Clinics

Results from a retrospective chart review analysis, which included more than 400 participants with TRD, illustrate that ketamine is a safe and rapid treatment in a real-world patient population, lead author Patrick A. Oliver, MD, founder and medical director, MindPeace Clinics, Richmond, Va., told this news organization.

The effect was perhaps most notable for reducing suicidal ideation, he said.

“In 2 weeks, we can take somebody from being suicidal to nonsuicidal. It’s a total game changer,” Dr. Oliver added.

Every year in the United States, about 12 million individuals think about suicide, 3.2 million make a plan to kill themselves, and more than 46,000 succeed, the investigators note.

The findings were published online in the Journal of Clinical Psychiatry.
 

Molecule mixture

Primarily used as an anesthetic in hospitals, ketamine is also taken illegally as a recreational drug. Users may aim for an intense high or feeling of dissociation, or an out-of-body–type experience.

Ketamine is a mixture of two mirror-image molecules. An intranasal version of one of these molecules (esketamine) is approved by the U.S. Food and Drug Administration for TRD. Both esketamine and ketamine are believed to increase neurotrophic signaling that affects synaptic function.

The study included 424 patients (mean age, 41.7 years) with major depressive disorder or another mood disorder and who received at least one ketamine infusion at a specialty clinic. Most participants had failed prior medication trials.

Patients in the study were typically started on 0.5 mg/kg of ketamine, with the dose titrated to achieve symptoms of partial dissociation. The median dose administered after titration was 0.93 mg/kg over 40 minutes.

The main treatment course of at least six infusions within 21 days was completed by 70% of the patients.

At each clinic visit, all participants completed the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7).

The primary outcome was PHQ-9 total scores, for which researchers looked at seven time periods: 1 week, 2-3 weeks, 4-6 weeks, 7-12 weeks, 13-24 weeks, 25-51 weeks, and 52+ weeks.
 

‘Blows it out of the water’

Results showed PHQ-9 total scores declined by 50% throughout the course of treatment, with much of the improvement gained within 4-6 weeks. There was a significant difference between week 1 and all later time periods (all P values < .001) and between weeks 2 and 3 and all later periods (all P values < .001).

Other measures included treatment response, defined as at least a 50% improvement on the PHQ-9, and depression remission, defined as a PHQ-9 score of less than 5. After three infusions, 14% of the patients responded and 7% were in remission. After 10 infusions, 72% responded and 38% were in remission.

These results compare favorably to other depression treatments, said Dr. Oliver. “Truthfully, with the exception of ECT [electroconvulsive therapy], this blows it all out of the water,” he added.

Dr. Oliver noted that the success rate for repetitive transcranial magnetic stimulation is 40%-60% depending on the modality; and for selective serotonin reuptake inhibitors, the success rate “is somewhere between the mid-20s and low-30s percent range.”

Another outcome measure was the self-harm/suicidal ideation item of the PHQ-9 questionnaire, which asks about “thoughts that you would be better off dead, or of hurting yourself in some way.” About 22% of the study participants no longer reported suicidal ideation after 3 infusions, 50% by 6 infusions, and 75% by 10 infusions.

By 15 infusions, 85% no longer reported these thoughts. “Nothing else has shown that, ever,” said Dr. Oliver.

Symptoms of generalized anxiety were also substantially improved. There was about a 30% reduction in the GAD-7 score during treatment and, again, most of the response occurred by 4-6 weeks.
 

Study limitations

Sex, age, and other demographic characteristics did not predict response or remission, but suicide planning trended toward higher response rates (P = .083). This suggests that a more depressed subgroup can achieve greater benefit from the treatment than can less symptomatic patients, the investigators note.

A history of psychosis also trended toward better response to treatment (P = .086) but not remission.

The researchers note that study limitations include that it was retrospective, lacked a control group, and did not require patients to be hospitalized – so the study sample may have been less severely ill than in other studies.

In addition, most patients paid out of pocket for the treatment at $495 per infusion, and they self-reported their symptoms.

As well, the researchers did not assess adverse events, although nurses made follow-up calls to patients. Dr. Oliver noted the most common side effects of ketamine are nausea, vomiting, and anxiety.

Previous research has suggested that ketamine therapy is not linked to long-term side effects, such as sexual dysfunction, weight gain, lethargy, or cognitive issues, said Dr. Oliver.

The investigators point out another study limitation was lack of detailed demographic information, such as race, income, and education, which might affect its generalizability.
 

Concerns and questions

Pouya Movahed Rad, MD, PhD, senior consultant and researcher in psychiatry, Lund (Sweden) University, noted several concerns, including that the clinics treating the study participants with ketamine profited from it.

He also speculated about who can afford the treatment because only a few patients in the study were reimbursed through insurance.

Dr. Movahed Rad was not involved with the current research but was principal investigator for a recent study  that compared intravenous ketamine to ECT.

He questioned whether the patient population in the new study really was “real world.” Well-designed randomized controlled trials have been carried out in a “naturalistic setting, [which] get closer to real-life patients,” he said.

He also noted that the median dose after clinician titration (0.93 mg/kg over 40 minutes) “may be considered very high.”

With regard to doses being titrated to achieve symptoms of partial dissociation, “there is no obvious evidence to my knowledge that patients need to develop dissociative symptoms in order to have antidepressant effect,” said Dr. Movahed Rad.

Finally, he noted that the finding that 28% of the participants were using illegal drugs “is worrying” and wondered what drugs they were taking; he also questioned why 81% of the study population needed to take antidepressants.

The study did not receive outside funding. Dr. Oliver is the founder of MindPeace Clinics, which specialize in ketamine therapeutics. Dr. Movahed Rad has reported no relevant financial relationships.

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

Following an online yoga program improves physical function in patients with knee osteoarthritis, according to the results of a new randomized control trial.

Although pain did not significantly improve in the yoga group, participants only completed about two-thirds of the recommended sessions, suggesting that more benefit may be possible with greater adherence, wrote lead author Kim L. Bennell, PhD, of the University of Melbourne, and colleagues in the Annals of Internal Medicine.

“To date, an online yoga program specifically for people with knee osteoarthritis has not been investigated,” the investigators said. “The need for such evidence-based packaged online exercise programs is highlighted in the 2020 U.S. National Public Health Agenda for Osteoarthritis.”
 

Methods and results

The trial involved 212 adults aged 45 years or older with symptomatic knee osteoarthritis. All patients had access to online educational materials about managing osteoarthritis.

Half of the participants were randomized into the 12-week online yoga program. This self-directed, unsupervised course consisted of 12 prerecorded 30-minute instructional yoga sessions, each with a unique sequence of poses to be completed three times in one week before moving on to the next class the following week. After 12 weeks, these participants could choose to continue doing yoga via the online program for 12 additional weeks, if desired.

The primary outcomes were knee pain and physical function, gauged by a 10-point numerical rating scale and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), respectively. Adherence was defined as completion of at least 2 yoga sessions within the preceding week.

At the 12-week mark, the yoga group did not show any significant improvement in knee pain (–0.6; 95% confidence interval, –1.2 to 0.1), but they did achieve a mean 4-point reduction in WOMAC, suggesting significant improvement in knee function (­–4.0; 95% CI, –6.8 to –1.3). Of note, however, this improvement was not enough to meet the threshold for minimal clinically important difference. At 24 weeks, the yoga group no longer showed significant improvement in knee function versus baseline.

“I don’t think a longer program would necessarily reduce knee pain, as benefits from a whole range of different types of exercise for knee osteoarthritis generally can show benefits within 8 weeks,” Dr. Bennell said in an interview.

Still, she noted that the average outcome in the trial may not represent what is possible if a patient commits to a regular yoga routine.

“I think it relates more to adherence [than duration], and I think benefits for knee pain would have been seen if a greater number of people had fully adhered to the program three times a week,” she said.

At 12 weeks, 68.8% of those in the yoga group were adherent, while just 28.4% were still adherent at week 24 after the optional extension period.

“As this was a self-directed program, adherence might be expected to be less than that of a supervised program,” Dr. Bennell noted.

Referring to unpublished data, Dr. Bennell said a sensitivity analysis showed that participants in the yoga group who completed yoga at least twice a week did show greater improvements in function and pain than those who did yoga less than twice per week.

“So it does suggest that adherence is important, as we might expect,” she said.
 

Another tool in the OA toolbox

Nick Trasolini, MD, of Wake Forest University School of Medicine, Winston-Salem, N.C., described the benefits in the trial as “modest” and noted that the improvement in function did not meet the threshold for minimal clinically important difference.

“Nevertheless,” he said in a written comment, “the [yoga] program was safe and associated with high participant satisfaction [mean satisfaction, 8 out of 10]. While this may not be the ‘silver bullet,’ it is another tool that we can offer to sufficiently motivated patients seeking non-operative solutions for knee osteoarthritis.”

Unfortunately, these tools remain “fraught with challenges,” Dr. Trasolini added.

“While multiple injection options are available (including corticosteroid, hyaluronic acid viscosupplementation, and biologic injections), the benefits of these injections can be short-lived,” he said. “This is frustrating to patients and physicians alike. Physical therapy is beneficial for knee osteoarthritis when deconditioning has led to decreased knee, hip, and core stability. However, physical therapy can be time consuming, painful, and cost prohibitive.”

In the present study, participants in the yoga group were somewhat willing (mean willingness, 5 out of 10) to pay for their 12-week yoga program. They reported that they would pay approximately $80 U.S. dollars for chance to do it all again.

The study was supported by grants from the National Health and Medical Research Council Program and the Centres of Research Excellence. The investigators disclosed additional relationships with Pfizer, Lilly, TLCBio, and others. Dr. Trasolini disclosed no relevant conflicts of interest.

Following an online yoga program improves physical function in patients with knee osteoarthritis, according to the results of a new randomized control trial.

Although pain did not significantly improve in the yoga group, participants only completed about two-thirds of the recommended sessions, suggesting that more benefit may be possible with greater adherence, wrote lead author Kim L. Bennell, PhD, of the University of Melbourne, and colleagues in the Annals of Internal Medicine.

“To date, an online yoga program specifically for people with knee osteoarthritis has not been investigated,” the investigators said. “The need for such evidence-based packaged online exercise programs is highlighted in the 2020 U.S. National Public Health Agenda for Osteoarthritis.”
 

Methods and results

The trial involved 212 adults aged 45 years or older with symptomatic knee osteoarthritis. All patients had access to online educational materials about managing osteoarthritis.

Half of the participants were randomized into the 12-week online yoga program. This self-directed, unsupervised course consisted of 12 prerecorded 30-minute instructional yoga sessions, each with a unique sequence of poses to be completed three times in one week before moving on to the next class the following week. After 12 weeks, these participants could choose to continue doing yoga via the online program for 12 additional weeks, if desired.

The primary outcomes were knee pain and physical function, gauged by a 10-point numerical rating scale and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), respectively. Adherence was defined as completion of at least 2 yoga sessions within the preceding week.

At the 12-week mark, the yoga group did not show any significant improvement in knee pain (–0.6; 95% confidence interval, –1.2 to 0.1), but they did achieve a mean 4-point reduction in WOMAC, suggesting significant improvement in knee function (­–4.0; 95% CI, –6.8 to –1.3). Of note, however, this improvement was not enough to meet the threshold for minimal clinically important difference. At 24 weeks, the yoga group no longer showed significant improvement in knee function versus baseline.

“I don’t think a longer program would necessarily reduce knee pain, as benefits from a whole range of different types of exercise for knee osteoarthritis generally can show benefits within 8 weeks,” Dr. Bennell said in an interview.

Still, she noted that the average outcome in the trial may not represent what is possible if a patient commits to a regular yoga routine.

“I think it relates more to adherence [than duration], and I think benefits for knee pain would have been seen if a greater number of people had fully adhered to the program three times a week,” she said.

At 12 weeks, 68.8% of those in the yoga group were adherent, while just 28.4% were still adherent at week 24 after the optional extension period.

“As this was a self-directed program, adherence might be expected to be less than that of a supervised program,” Dr. Bennell noted.

Referring to unpublished data, Dr. Bennell said a sensitivity analysis showed that participants in the yoga group who completed yoga at least twice a week did show greater improvements in function and pain than those who did yoga less than twice per week.

“So it does suggest that adherence is important, as we might expect,” she said.
 

Another tool in the OA toolbox

Nick Trasolini, MD, of Wake Forest University School of Medicine, Winston-Salem, N.C., described the benefits in the trial as “modest” and noted that the improvement in function did not meet the threshold for minimal clinically important difference.

“Nevertheless,” he said in a written comment, “the [yoga] program was safe and associated with high participant satisfaction [mean satisfaction, 8 out of 10]. While this may not be the ‘silver bullet,’ it is another tool that we can offer to sufficiently motivated patients seeking non-operative solutions for knee osteoarthritis.”

Unfortunately, these tools remain “fraught with challenges,” Dr. Trasolini added.

“While multiple injection options are available (including corticosteroid, hyaluronic acid viscosupplementation, and biologic injections), the benefits of these injections can be short-lived,” he said. “This is frustrating to patients and physicians alike. Physical therapy is beneficial for knee osteoarthritis when deconditioning has led to decreased knee, hip, and core stability. However, physical therapy can be time consuming, painful, and cost prohibitive.”

In the present study, participants in the yoga group were somewhat willing (mean willingness, 5 out of 10) to pay for their 12-week yoga program. They reported that they would pay approximately $80 U.S. dollars for chance to do it all again.

The study was supported by grants from the National Health and Medical Research Council Program and the Centres of Research Excellence. The investigators disclosed additional relationships with Pfizer, Lilly, TLCBio, and others. Dr. Trasolini disclosed no relevant conflicts of interest.

Following an online yoga program improves physical function in patients with knee osteoarthritis, according to the results of a new randomized control trial.

Although pain did not significantly improve in the yoga group, participants only completed about two-thirds of the recommended sessions, suggesting that more benefit may be possible with greater adherence, wrote lead author Kim L. Bennell, PhD, of the University of Melbourne, and colleagues in the Annals of Internal Medicine.

“To date, an online yoga program specifically for people with knee osteoarthritis has not been investigated,” the investigators said. “The need for such evidence-based packaged online exercise programs is highlighted in the 2020 U.S. National Public Health Agenda for Osteoarthritis.”
 

Methods and results

The trial involved 212 adults aged 45 years or older with symptomatic knee osteoarthritis. All patients had access to online educational materials about managing osteoarthritis.

Half of the participants were randomized into the 12-week online yoga program. This self-directed, unsupervised course consisted of 12 prerecorded 30-minute instructional yoga sessions, each with a unique sequence of poses to be completed three times in one week before moving on to the next class the following week. After 12 weeks, these participants could choose to continue doing yoga via the online program for 12 additional weeks, if desired.

The primary outcomes were knee pain and physical function, gauged by a 10-point numerical rating scale and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), respectively. Adherence was defined as completion of at least 2 yoga sessions within the preceding week.

At the 12-week mark, the yoga group did not show any significant improvement in knee pain (–0.6; 95% confidence interval, –1.2 to 0.1), but they did achieve a mean 4-point reduction in WOMAC, suggesting significant improvement in knee function (­–4.0; 95% CI, –6.8 to –1.3). Of note, however, this improvement was not enough to meet the threshold for minimal clinically important difference. At 24 weeks, the yoga group no longer showed significant improvement in knee function versus baseline.

“I don’t think a longer program would necessarily reduce knee pain, as benefits from a whole range of different types of exercise for knee osteoarthritis generally can show benefits within 8 weeks,” Dr. Bennell said in an interview.

Still, she noted that the average outcome in the trial may not represent what is possible if a patient commits to a regular yoga routine.

“I think it relates more to adherence [than duration], and I think benefits for knee pain would have been seen if a greater number of people had fully adhered to the program three times a week,” she said.

At 12 weeks, 68.8% of those in the yoga group were adherent, while just 28.4% were still adherent at week 24 after the optional extension period.

“As this was a self-directed program, adherence might be expected to be less than that of a supervised program,” Dr. Bennell noted.

Referring to unpublished data, Dr. Bennell said a sensitivity analysis showed that participants in the yoga group who completed yoga at least twice a week did show greater improvements in function and pain than those who did yoga less than twice per week.

“So it does suggest that adherence is important, as we might expect,” she said.
 

Another tool in the OA toolbox

Nick Trasolini, MD, of Wake Forest University School of Medicine, Winston-Salem, N.C., described the benefits in the trial as “modest” and noted that the improvement in function did not meet the threshold for minimal clinically important difference.

“Nevertheless,” he said in a written comment, “the [yoga] program was safe and associated with high participant satisfaction [mean satisfaction, 8 out of 10]. While this may not be the ‘silver bullet,’ it is another tool that we can offer to sufficiently motivated patients seeking non-operative solutions for knee osteoarthritis.”

Unfortunately, these tools remain “fraught with challenges,” Dr. Trasolini added.

“While multiple injection options are available (including corticosteroid, hyaluronic acid viscosupplementation, and biologic injections), the benefits of these injections can be short-lived,” he said. “This is frustrating to patients and physicians alike. Physical therapy is beneficial for knee osteoarthritis when deconditioning has led to decreased knee, hip, and core stability. However, physical therapy can be time consuming, painful, and cost prohibitive.”

In the present study, participants in the yoga group were somewhat willing (mean willingness, 5 out of 10) to pay for their 12-week yoga program. They reported that they would pay approximately $80 U.S. dollars for chance to do it all again.

The study was supported by grants from the National Health and Medical Research Council Program and the Centres of Research Excellence. The investigators disclosed additional relationships with Pfizer, Lilly, TLCBio, and others. Dr. Trasolini disclosed no relevant conflicts of interest.

New research calls into question the assumption that acetaminophen is safer than NSAIDs for patients with known cardiovascular disease (CVD) or CVD risk factors.

The analysis found a significant correlation between the use of acetaminophen and elevated systolic blood pressure.

While acetaminophen may still be safer than NSAIDs from a bleeding risk standpoint, or in patients with known kidney disease, “the gap may not be as large as once thought,” Rahul Gupta, MD, cardiologist with Lehigh Valley Health Network, Allentown, Pa., said in an interview.

ironstealth/Thinkstock

Subgroup analysis of the effect on hypertensive patients showed significant change in systolic blood pressure as well (SMD = 0.38; 95% CI, 0.05-0.71; P = .02).

“Interestingly, there was no significant difference in the effect on diastolic blood pressure,” Dr. Gupta commented.

Reached for comment, Timothy S. Anderson, MD, clinical investigator in the Division of General Medicine at Beth Israel Deaconess Medical Center and assistant professor of medicine at the Harvard Medical School, both in Boston, said this is “an interesting and not particularly well-known issue.”

“However, most of the trials look at very high doses of acetaminophen use (for example, six to eight of the 500 mg pills each day) so we don’t really know whether the more common patterns of using one to two acetaminophen pills every once in a while is problematic,” Dr. Anderson told this news organization.

“We also don’t have data showing a direct harm from these medications with regards to strokes or heart attacks or other downstream consequences of high blood pressure. Ideally we would need a head-to-head trial comparing ibuprofen-type medications to acetaminophen-type medications,” Dr. Anderson said.

The study had no specific funding. Dr. Gupta and Dr. Anderson reported no relevant disclosures.

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

New research calls into question the assumption that acetaminophen is safer than NSAIDs for patients with known cardiovascular disease (CVD) or CVD risk factors.

The analysis found a significant correlation between the use of acetaminophen and elevated systolic blood pressure.

While acetaminophen may still be safer than NSAIDs from a bleeding risk standpoint, or in patients with known kidney disease, “the gap may not be as large as once thought,” Rahul Gupta, MD, cardiologist with Lehigh Valley Health Network, Allentown, Pa., said in an interview.

ironstealth/Thinkstock

Subgroup analysis of the effect on hypertensive patients showed significant change in systolic blood pressure as well (SMD = 0.38; 95% CI, 0.05-0.71; P = .02).

“Interestingly, there was no significant difference in the effect on diastolic blood pressure,” Dr. Gupta commented.

Reached for comment, Timothy S. Anderson, MD, clinical investigator in the Division of General Medicine at Beth Israel Deaconess Medical Center and assistant professor of medicine at the Harvard Medical School, both in Boston, said this is “an interesting and not particularly well-known issue.”

“However, most of the trials look at very high doses of acetaminophen use (for example, six to eight of the 500 mg pills each day) so we don’t really know whether the more common patterns of using one to two acetaminophen pills every once in a while is problematic,” Dr. Anderson told this news organization.

“We also don’t have data showing a direct harm from these medications with regards to strokes or heart attacks or other downstream consequences of high blood pressure. Ideally we would need a head-to-head trial comparing ibuprofen-type medications to acetaminophen-type medications,” Dr. Anderson said.

The study had no specific funding. Dr. Gupta and Dr. Anderson reported no relevant disclosures.

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

New research calls into question the assumption that acetaminophen is safer than NSAIDs for patients with known cardiovascular disease (CVD) or CVD risk factors.

The analysis found a significant correlation between the use of acetaminophen and elevated systolic blood pressure.

While acetaminophen may still be safer than NSAIDs from a bleeding risk standpoint, or in patients with known kidney disease, “the gap may not be as large as once thought,” Rahul Gupta, MD, cardiologist with Lehigh Valley Health Network, Allentown, Pa., said in an interview.

ironstealth/Thinkstock

Subgroup analysis of the effect on hypertensive patients showed significant change in systolic blood pressure as well (SMD = 0.38; 95% CI, 0.05-0.71; P = .02).

“Interestingly, there was no significant difference in the effect on diastolic blood pressure,” Dr. Gupta commented.

Reached for comment, Timothy S. Anderson, MD, clinical investigator in the Division of General Medicine at Beth Israel Deaconess Medical Center and assistant professor of medicine at the Harvard Medical School, both in Boston, said this is “an interesting and not particularly well-known issue.”

“However, most of the trials look at very high doses of acetaminophen use (for example, six to eight of the 500 mg pills each day) so we don’t really know whether the more common patterns of using one to two acetaminophen pills every once in a while is problematic,” Dr. Anderson told this news organization.

“We also don’t have data showing a direct harm from these medications with regards to strokes or heart attacks or other downstream consequences of high blood pressure. Ideally we would need a head-to-head trial comparing ibuprofen-type medications to acetaminophen-type medications,” Dr. Anderson said.

The study had no specific funding. Dr. Gupta and Dr. Anderson reported no relevant disclosures.

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

Treatment of people with obesity but without diabetes with the glucagon-like peptide-1 (GLP-1) agonist semaglutide (Wegovy) – hailed at its approval in 2021 as a “game changer” for the treatment of obesity – led to beneficial changes in body mass index (BMI), glycemic control, and other clinical measures.

This collectively cut the calculated risk for possible future development of type 2 diabetes in study participants by more than half, based on post-hoc analysis of data from two pivotal trials that compared semaglutide with placebo.

The findings “suggest that semaglutide could help prevent type 2 diabetes in people with overweight or obesity,” said W. Timothy Garvey, MD, in a presentation at the annual meeting of the European Association for the Study of Diabetes.

Asked to comment, Rodolfo J. Galindo, MD, said: “We devote a significant amount of effort to treating people with diabetes but very little effort for diabetes prevention. We hope that further scientific findings showing the benefits of weight loss, as illustrated by [Dr.] Garvey [and colleagues], for diabetes prevention will change the pandemic of adiposity-based chronic disease.”
 

GLP-1 agonists as complication-reducing agents

Finding a link between treatment with semaglutide and a reduced future risk of developing type 2 diabetes is important because it shows that this regimen is not just a BMI-centric approach to treating people with obesity but is also a way to potentially reduce complications of obesity such as diabetes onset, explained Dr. Garvey, a professor and director of the Diabetes Research Center at the University of Alabama at Birmingham.

Recent obesity-management recommendations have focused on interventions aimed at avoiding complications, as in 2016 guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology, he noted.

Having evidence that treatment with a GLP-1 agonist such as semaglutide can reduce the incidence of diabetes in people with obesity might also help convince payers to more uniformly reimburse for this type of obesity intervention, which up to now has commonly faced coverage limitations, especially in the United States, he said in an interview.

Dr. Garvey added that evidence for a reduction in the incidence of cardiovascular disease complications such as myocardial infarction and stroke may need to join diabetes prevention as proven effects from obesity intervention before coverage decisions change.

He cited the SELECT trial, which is testing the hypothesis that semaglutide treatment of people with overweight or obesity can reduce the incidence of cardiovascular events in about 17,500 participants and with expected completion toward the end of 2023.

“A complication-centric approach to management of people with obesity needs prediction tools that allow a focus on prevention strategies for people with obesity who are at increased risk of developing diabetes,” commented Dr. Galindo, an endocrinologist at Emory University, Atlanta, in an interview.
 

Combined analysis of STEP 1 and STEP 4 data

The analysis conducted by Dr. Garvey and colleagues used data from the STEP 1 trial, which compared semaglutide 2.4 mg subcutaneous once weekly with placebo for weight loss in more than 1,500 people predominantly with obesity (about 6% were overweight) and showed that after 68 weeks semaglutide cut the calculated risk of developing type 2 diabetes over the subsequent 10 years from 18% at baseline to 7%, compared with a drop from 18% at baseline to 16% among those who received placebo.

A second, similar analysis of data from people predominantly with obesity in the STEP 4 trial – which treated around 800 people with semaglutide 2.4 mg for 20 weeks and then randomized them to placebo or continued semaglutide treatment – showed that semaglutide treatment cut their calculated 10-year risk for incident type 2 diabetes from 20% at baseline to about 11% after 20 weeks. The risk rebounded in the study participants who then switched from semaglutide to placebo. Among those randomized to remain on semaglutide for a total of 68 weeks, the 10-year risk fell further to 8%.

Dr. Garvey and associates used a validated prognostic formula, the cardiometabolic disease staging (CMDS) tool, they had previously developed and reported to calculate 10-year risk for development of type 2 diabetes based on three unmodifiable factors (age, sex, and race) and five modifiable factors (BMI, blood pressure, glucose level, HDL cholesterol, and triglycerides). They applied the analysis to data from 1,561 of the STEP 1 participants and 766 participants in the STEP 4 study.

“There is no better tool I know of to predict diabetes incidence,” commented Michael A. Nauck, MD, professor and chief of clinical research, diabetes division, St. Josef Hospital, Bochum, Germany.

In his opinion, the CMDS tool is appropriate for estimating the risk of developing incident type 2 diabetes in populations but not in specific individuals.

The new analyses also showed that, in STEP 1, the impact of semaglutide on reducing future risk of developing type 2 diabetes was roughly the same regardless of whether participants entered the study with prediabetes or were normoglycemic at entry.

Blood glucose changes confer the biggest effect

The biggest contributor among the five modifiable components of the CMDS tool for altering the predicted risk for incident diabetes was the reduction in blood glucose produced by semaglutide treatment, which influenced just under half of the change in predicted risk, Dr. Garvey said. The four other modifiable components had roughly similar individual effects on predicted risk, with change in BMI influencing about 15% of the observed effect.

“Our analysis shows that semaglutide treatment is preventing diabetes via several mechanisms. It’s not just a reduction in glucose,” Dr. Garvey said.

Dr. Nauck cautioned, however, that it is hard to judge the efficacy of an intervention like semaglutide for preventing incident diabetes when one of its effects is to dampen down hyperglycemia, the signal indicator of diabetes onset.

Indeed, semaglutide was first approved as a treatment for type 2 diabetes (known as Ozempic, Novo Nordisk) at slightly lower doses than it is approved for obesity. It is also available as an oral agent to treat diabetes (Rybelsus).  

Dr. Nauck also noted that the results from at least one previously reported study had already shown the same relationship between treatment with the GLP-1 agonist liraglutide as an anti-obesity agent (3.0 mg dose daily, known as Saxenda) and a reduced subsequent incidence of type 2 diabetes but using actual clinical outcomes during 3 years of follow-up rather than a calculated projection of diabetes likelihood.

The SCALE Obesity and Prediabetes trial randomized 2,254 people with prediabetes and overweight or obesity to weekly treatment with 3.0 mg of liraglutide or placebo. After 160 weeks on treatment, the cumulative incidence of type 2 diabetes was 2% in those who received liraglutide and 6% among those on placebo, with a significant hazard ratio reduction of 79% in the incidence of diabetes on liraglutide treatment.

The STEP 1 and STEP 4 trials were sponsored by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Garvey has reported serving as an advisor without compensation to Novo Nordisk as well as Boehringer Ingelheim, Eli Lilly, Jazz, and Pfizer. He is also a site principal investigator for multicentered clinical trials sponsored by the University of Alabama at Birmingham and funded by Novo Nordisk, Eli Lilly, Epitomee, and Pfizer. Dr .Galindo has reported being a consultant or advisor for Boehringer Ingelheim, Eli Lilly, Pfizer, Sanofi, and Weight Watchers and receiving research funding from Dexcom, Eli Lilly, and Novo Nordisk. Dr. Nauck has reported being an advisor or consultant to Novo Nordisk as well as to Boehringer Ingelheim, Eli Lilly, Menarini/Berlin Chemie, MSD, Regor, and ShouTi/Gasherbrum, receiving research funding from MSD, being a member of a data monitoring and safety board for Inventiva, and being a speaker on behalf of Novo Nordisk as well as for Eli Lilly, Menarini/Berlin Chemie, MSD, and Sun Pharmaceuticals.

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

Treatment of people with obesity but without diabetes with the glucagon-like peptide-1 (GLP-1) agonist semaglutide (Wegovy) – hailed at its approval in 2021 as a “game changer” for the treatment of obesity – led to beneficial changes in body mass index (BMI), glycemic control, and other clinical measures.

This collectively cut the calculated risk for possible future development of type 2 diabetes in study participants by more than half, based on post-hoc analysis of data from two pivotal trials that compared semaglutide with placebo.

The findings “suggest that semaglutide could help prevent type 2 diabetes in people with overweight or obesity,” said W. Timothy Garvey, MD, in a presentation at the annual meeting of the European Association for the Study of Diabetes.

Asked to comment, Rodolfo J. Galindo, MD, said: “We devote a significant amount of effort to treating people with diabetes but very little effort for diabetes prevention. We hope that further scientific findings showing the benefits of weight loss, as illustrated by [Dr.] Garvey [and colleagues], for diabetes prevention will change the pandemic of adiposity-based chronic disease.”
 

GLP-1 agonists as complication-reducing agents

Finding a link between treatment with semaglutide and a reduced future risk of developing type 2 diabetes is important because it shows that this regimen is not just a BMI-centric approach to treating people with obesity but is also a way to potentially reduce complications of obesity such as diabetes onset, explained Dr. Garvey, a professor and director of the Diabetes Research Center at the University of Alabama at Birmingham.

Recent obesity-management recommendations have focused on interventions aimed at avoiding complications, as in 2016 guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology, he noted.

Having evidence that treatment with a GLP-1 agonist such as semaglutide can reduce the incidence of diabetes in people with obesity might also help convince payers to more uniformly reimburse for this type of obesity intervention, which up to now has commonly faced coverage limitations, especially in the United States, he said in an interview.

Dr. Garvey added that evidence for a reduction in the incidence of cardiovascular disease complications such as myocardial infarction and stroke may need to join diabetes prevention as proven effects from obesity intervention before coverage decisions change.

He cited the SELECT trial, which is testing the hypothesis that semaglutide treatment of people with overweight or obesity can reduce the incidence of cardiovascular events in about 17,500 participants and with expected completion toward the end of 2023.

“A complication-centric approach to management of people with obesity needs prediction tools that allow a focus on prevention strategies for people with obesity who are at increased risk of developing diabetes,” commented Dr. Galindo, an endocrinologist at Emory University, Atlanta, in an interview.
 

Combined analysis of STEP 1 and STEP 4 data

The analysis conducted by Dr. Garvey and colleagues used data from the STEP 1 trial, which compared semaglutide 2.4 mg subcutaneous once weekly with placebo for weight loss in more than 1,500 people predominantly with obesity (about 6% were overweight) and showed that after 68 weeks semaglutide cut the calculated risk of developing type 2 diabetes over the subsequent 10 years from 18% at baseline to 7%, compared with a drop from 18% at baseline to 16% among those who received placebo.

A second, similar analysis of data from people predominantly with obesity in the STEP 4 trial – which treated around 800 people with semaglutide 2.4 mg for 20 weeks and then randomized them to placebo or continued semaglutide treatment – showed that semaglutide treatment cut their calculated 10-year risk for incident type 2 diabetes from 20% at baseline to about 11% after 20 weeks. The risk rebounded in the study participants who then switched from semaglutide to placebo. Among those randomized to remain on semaglutide for a total of 68 weeks, the 10-year risk fell further to 8%.

Dr. Garvey and associates used a validated prognostic formula, the cardiometabolic disease staging (CMDS) tool, they had previously developed and reported to calculate 10-year risk for development of type 2 diabetes based on three unmodifiable factors (age, sex, and race) and five modifiable factors (BMI, blood pressure, glucose level, HDL cholesterol, and triglycerides). They applied the analysis to data from 1,561 of the STEP 1 participants and 766 participants in the STEP 4 study.

“There is no better tool I know of to predict diabetes incidence,” commented Michael A. Nauck, MD, professor and chief of clinical research, diabetes division, St. Josef Hospital, Bochum, Germany.

In his opinion, the CMDS tool is appropriate for estimating the risk of developing incident type 2 diabetes in populations but not in specific individuals.

The new analyses also showed that, in STEP 1, the impact of semaglutide on reducing future risk of developing type 2 diabetes was roughly the same regardless of whether participants entered the study with prediabetes or were normoglycemic at entry.

Blood glucose changes confer the biggest effect

The biggest contributor among the five modifiable components of the CMDS tool for altering the predicted risk for incident diabetes was the reduction in blood glucose produced by semaglutide treatment, which influenced just under half of the change in predicted risk, Dr. Garvey said. The four other modifiable components had roughly similar individual effects on predicted risk, with change in BMI influencing about 15% of the observed effect.

“Our analysis shows that semaglutide treatment is preventing diabetes via several mechanisms. It’s not just a reduction in glucose,” Dr. Garvey said.

Dr. Nauck cautioned, however, that it is hard to judge the efficacy of an intervention like semaglutide for preventing incident diabetes when one of its effects is to dampen down hyperglycemia, the signal indicator of diabetes onset.

Indeed, semaglutide was first approved as a treatment for type 2 diabetes (known as Ozempic, Novo Nordisk) at slightly lower doses than it is approved for obesity. It is also available as an oral agent to treat diabetes (Rybelsus).  

Dr. Nauck also noted that the results from at least one previously reported study had already shown the same relationship between treatment with the GLP-1 agonist liraglutide as an anti-obesity agent (3.0 mg dose daily, known as Saxenda) and a reduced subsequent incidence of type 2 diabetes but using actual clinical outcomes during 3 years of follow-up rather than a calculated projection of diabetes likelihood.

The SCALE Obesity and Prediabetes trial randomized 2,254 people with prediabetes and overweight or obesity to weekly treatment with 3.0 mg of liraglutide or placebo. After 160 weeks on treatment, the cumulative incidence of type 2 diabetes was 2% in those who received liraglutide and 6% among those on placebo, with a significant hazard ratio reduction of 79% in the incidence of diabetes on liraglutide treatment.

The STEP 1 and STEP 4 trials were sponsored by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Garvey has reported serving as an advisor without compensation to Novo Nordisk as well as Boehringer Ingelheim, Eli Lilly, Jazz, and Pfizer. He is also a site principal investigator for multicentered clinical trials sponsored by the University of Alabama at Birmingham and funded by Novo Nordisk, Eli Lilly, Epitomee, and Pfizer. Dr .Galindo has reported being a consultant or advisor for Boehringer Ingelheim, Eli Lilly, Pfizer, Sanofi, and Weight Watchers and receiving research funding from Dexcom, Eli Lilly, and Novo Nordisk. Dr. Nauck has reported being an advisor or consultant to Novo Nordisk as well as to Boehringer Ingelheim, Eli Lilly, Menarini/Berlin Chemie, MSD, Regor, and ShouTi/Gasherbrum, receiving research funding from MSD, being a member of a data monitoring and safety board for Inventiva, and being a speaker on behalf of Novo Nordisk as well as for Eli Lilly, Menarini/Berlin Chemie, MSD, and Sun Pharmaceuticals.

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

Treatment of people with obesity but without diabetes with the glucagon-like peptide-1 (GLP-1) agonist semaglutide (Wegovy) – hailed at its approval in 2021 as a “game changer” for the treatment of obesity – led to beneficial changes in body mass index (BMI), glycemic control, and other clinical measures.

This collectively cut the calculated risk for possible future development of type 2 diabetes in study participants by more than half, based on post-hoc analysis of data from two pivotal trials that compared semaglutide with placebo.

The findings “suggest that semaglutide could help prevent type 2 diabetes in people with overweight or obesity,” said W. Timothy Garvey, MD, in a presentation at the annual meeting of the European Association for the Study of Diabetes.

Asked to comment, Rodolfo J. Galindo, MD, said: “We devote a significant amount of effort to treating people with diabetes but very little effort for diabetes prevention. We hope that further scientific findings showing the benefits of weight loss, as illustrated by [Dr.] Garvey [and colleagues], for diabetes prevention will change the pandemic of adiposity-based chronic disease.”
 

GLP-1 agonists as complication-reducing agents

Finding a link between treatment with semaglutide and a reduced future risk of developing type 2 diabetes is important because it shows that this regimen is not just a BMI-centric approach to treating people with obesity but is also a way to potentially reduce complications of obesity such as diabetes onset, explained Dr. Garvey, a professor and director of the Diabetes Research Center at the University of Alabama at Birmingham.

Recent obesity-management recommendations have focused on interventions aimed at avoiding complications, as in 2016 guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology, he noted.

Having evidence that treatment with a GLP-1 agonist such as semaglutide can reduce the incidence of diabetes in people with obesity might also help convince payers to more uniformly reimburse for this type of obesity intervention, which up to now has commonly faced coverage limitations, especially in the United States, he said in an interview.

Dr. Garvey added that evidence for a reduction in the incidence of cardiovascular disease complications such as myocardial infarction and stroke may need to join diabetes prevention as proven effects from obesity intervention before coverage decisions change.

He cited the SELECT trial, which is testing the hypothesis that semaglutide treatment of people with overweight or obesity can reduce the incidence of cardiovascular events in about 17,500 participants and with expected completion toward the end of 2023.

“A complication-centric approach to management of people with obesity needs prediction tools that allow a focus on prevention strategies for people with obesity who are at increased risk of developing diabetes,” commented Dr. Galindo, an endocrinologist at Emory University, Atlanta, in an interview.
 

Combined analysis of STEP 1 and STEP 4 data

The analysis conducted by Dr. Garvey and colleagues used data from the STEP 1 trial, which compared semaglutide 2.4 mg subcutaneous once weekly with placebo for weight loss in more than 1,500 people predominantly with obesity (about 6% were overweight) and showed that after 68 weeks semaglutide cut the calculated risk of developing type 2 diabetes over the subsequent 10 years from 18% at baseline to 7%, compared with a drop from 18% at baseline to 16% among those who received placebo.

A second, similar analysis of data from people predominantly with obesity in the STEP 4 trial – which treated around 800 people with semaglutide 2.4 mg for 20 weeks and then randomized them to placebo or continued semaglutide treatment – showed that semaglutide treatment cut their calculated 10-year risk for incident type 2 diabetes from 20% at baseline to about 11% after 20 weeks. The risk rebounded in the study participants who then switched from semaglutide to placebo. Among those randomized to remain on semaglutide for a total of 68 weeks, the 10-year risk fell further to 8%.

Dr. Garvey and associates used a validated prognostic formula, the cardiometabolic disease staging (CMDS) tool, they had previously developed and reported to calculate 10-year risk for development of type 2 diabetes based on three unmodifiable factors (age, sex, and race) and five modifiable factors (BMI, blood pressure, glucose level, HDL cholesterol, and triglycerides). They applied the analysis to data from 1,561 of the STEP 1 participants and 766 participants in the STEP 4 study.

“There is no better tool I know of to predict diabetes incidence,” commented Michael A. Nauck, MD, professor and chief of clinical research, diabetes division, St. Josef Hospital, Bochum, Germany.

In his opinion, the CMDS tool is appropriate for estimating the risk of developing incident type 2 diabetes in populations but not in specific individuals.

The new analyses also showed that, in STEP 1, the impact of semaglutide on reducing future risk of developing type 2 diabetes was roughly the same regardless of whether participants entered the study with prediabetes or were normoglycemic at entry.

Blood glucose changes confer the biggest effect

The biggest contributor among the five modifiable components of the CMDS tool for altering the predicted risk for incident diabetes was the reduction in blood glucose produced by semaglutide treatment, which influenced just under half of the change in predicted risk, Dr. Garvey said. The four other modifiable components had roughly similar individual effects on predicted risk, with change in BMI influencing about 15% of the observed effect.

“Our analysis shows that semaglutide treatment is preventing diabetes via several mechanisms. It’s not just a reduction in glucose,” Dr. Garvey said.

Dr. Nauck cautioned, however, that it is hard to judge the efficacy of an intervention like semaglutide for preventing incident diabetes when one of its effects is to dampen down hyperglycemia, the signal indicator of diabetes onset.

Indeed, semaglutide was first approved as a treatment for type 2 diabetes (known as Ozempic, Novo Nordisk) at slightly lower doses than it is approved for obesity. It is also available as an oral agent to treat diabetes (Rybelsus).  

Dr. Nauck also noted that the results from at least one previously reported study had already shown the same relationship between treatment with the GLP-1 agonist liraglutide as an anti-obesity agent (3.0 mg dose daily, known as Saxenda) and a reduced subsequent incidence of type 2 diabetes but using actual clinical outcomes during 3 years of follow-up rather than a calculated projection of diabetes likelihood.

The SCALE Obesity and Prediabetes trial randomized 2,254 people with prediabetes and overweight or obesity to weekly treatment with 3.0 mg of liraglutide or placebo. After 160 weeks on treatment, the cumulative incidence of type 2 diabetes was 2% in those who received liraglutide and 6% among those on placebo, with a significant hazard ratio reduction of 79% in the incidence of diabetes on liraglutide treatment.

The STEP 1 and STEP 4 trials were sponsored by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Garvey has reported serving as an advisor without compensation to Novo Nordisk as well as Boehringer Ingelheim, Eli Lilly, Jazz, and Pfizer. He is also a site principal investigator for multicentered clinical trials sponsored by the University of Alabama at Birmingham and funded by Novo Nordisk, Eli Lilly, Epitomee, and Pfizer. Dr .Galindo has reported being a consultant or advisor for Boehringer Ingelheim, Eli Lilly, Pfizer, Sanofi, and Weight Watchers and receiving research funding from Dexcom, Eli Lilly, and Novo Nordisk. Dr. Nauck has reported being an advisor or consultant to Novo Nordisk as well as to Boehringer Ingelheim, Eli Lilly, Menarini/Berlin Chemie, MSD, Regor, and ShouTi/Gasherbrum, receiving research funding from MSD, being a member of a data monitoring and safety board for Inventiva, and being a speaker on behalf of Novo Nordisk as well as for Eli Lilly, Menarini/Berlin Chemie, MSD, and Sun Pharmaceuticals.

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

Key clinical point: Pediatric patients with irritable bowel syndrome (IBS) and normal weight had higher levels of fecal calprotectin than those with IBS and obesity, suggesting the role of obesity and intestinal inflammation in the development and manifestations of IBS in children.

Major finding: The mean calprotectin levels were significantly higher in patients with body mass index <85^th vs 85^th to <95^th percentile (P = .028) and ≥95^th percentile (P ≥ .025), with the difference being prominent among children aged between 6 and 12 years (P = .029) but not among adolescents aged between 12 and 18 years (P = .139).

Study details: The data come from a retrospective analysis of 277 pediatric patients with IBS.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Kim JH et al. Association between body mass index and fecal calprotectin levels in children and adolescents with irritable bowel syndrome. Medicine (Baltimore). 2022;101(32):e29968 (Aug 12). Doi: 10.1097/MD.0000000000029968.

Key clinical point: Pediatric patients with irritable bowel syndrome (IBS) and normal weight had higher levels of fecal calprotectin than those with IBS and obesity, suggesting the role of obesity and intestinal inflammation in the development and manifestations of IBS in children.

Major finding: The mean calprotectin levels were significantly higher in patients with body mass index <85^th vs 85^th to <95^th percentile (P = .028) and ≥95^th percentile (P ≥ .025), with the difference being prominent among children aged between 6 and 12 years (P = .029) but not among adolescents aged between 12 and 18 years (P = .139).

Study details: The data come from a retrospective analysis of 277 pediatric patients with IBS.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Kim JH et al. Association between body mass index and fecal calprotectin levels in children and adolescents with irritable bowel syndrome. Medicine (Baltimore). 2022;101(32):e29968 (Aug 12). Doi: 10.1097/MD.0000000000029968.

Key clinical point: Pediatric patients with irritable bowel syndrome (IBS) and normal weight had higher levels of fecal calprotectin than those with IBS and obesity, suggesting the role of obesity and intestinal inflammation in the development and manifestations of IBS in children.

Major finding: The mean calprotectin levels were significantly higher in patients with body mass index <85^th vs 85^th to <95^th percentile (P = .028) and ≥95^th percentile (P ≥ .025), with the difference being prominent among children aged between 6 and 12 years (P = .029) but not among adolescents aged between 12 and 18 years (P = .139).

Study details: The data come from a retrospective analysis of 277 pediatric patients with IBS.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Kim JH et al. Association between body mass index and fecal calprotectin levels in children and adolescents with irritable bowel syndrome. Medicine (Baltimore). 2022;101(32):e29968 (Aug 12). Doi: 10.1097/MD.0000000000029968.

Key clinical point: Meta-analysis indicated a relatively higher but nonsignificantly increased risk for Helicobacter pylori infection (HPI) in patients with irritable bowel syndrome (IBS) vs non-IBS participants; however, the association between IBS and HPI could be an underestimation, with a positive association persisting between HPI and diarrhea-type IBS (IBS-D).

Major finding: A nonsignificant positive association was observed between HPI and IBS (odds ratio [OR], 1.03 ;lt; P = .84); however, the association was significant after excluding studies with defined confounding factors (adjusted OR, 1.29; P = .03), indicating an underestimation. The positive association of HPI persisted with IBS-D (OR, 1.54; P = .0003) but not with IBS-C (P = .17) or IBS-M (P = .33).

Study details: Findings are from a systematic review and meta-analysis of 13 studies including 1,403 patients with IBS and 11,770 non-IBS participants.

Disclosures: This research was funded by the National Natural Science Foundation of China and the Natural Science Foundation of Guangdong Province. The authors declared no conflicts of interest.

Source: Wang Z et al. Helicobacterpylori infection-A risk factor for irritable bowel syndrome? An updated systematic review and meta-analysis. Medicina (Kaunas). 2022;58(8):1035 (Aug 2). Doi: 10.3390/medicina58081035.

Key clinical point: Meta-analysis indicated a relatively higher but nonsignificantly increased risk for Helicobacter pylori infection (HPI) in patients with irritable bowel syndrome (IBS) vs non-IBS participants; however, the association between IBS and HPI could be an underestimation, with a positive association persisting between HPI and diarrhea-type IBS (IBS-D).

Major finding: A nonsignificant positive association was observed between HPI and IBS (odds ratio [OR], 1.03 ;lt; P = .84); however, the association was significant after excluding studies with defined confounding factors (adjusted OR, 1.29; P = .03), indicating an underestimation. The positive association of HPI persisted with IBS-D (OR, 1.54; P = .0003) but not with IBS-C (P = .17) or IBS-M (P = .33).

Study details: Findings are from a systematic review and meta-analysis of 13 studies including 1,403 patients with IBS and 11,770 non-IBS participants.

Disclosures: This research was funded by the National Natural Science Foundation of China and the Natural Science Foundation of Guangdong Province. The authors declared no conflicts of interest.

Source: Wang Z et al. Helicobacterpylori infection-A risk factor for irritable bowel syndrome? An updated systematic review and meta-analysis. Medicina (Kaunas). 2022;58(8):1035 (Aug 2). Doi: 10.3390/medicina58081035.

Key clinical point: Meta-analysis indicated a relatively higher but nonsignificantly increased risk for Helicobacter pylori infection (HPI) in patients with irritable bowel syndrome (IBS) vs non-IBS participants; however, the association between IBS and HPI could be an underestimation, with a positive association persisting between HPI and diarrhea-type IBS (IBS-D).

Major finding: A nonsignificant positive association was observed between HPI and IBS (odds ratio [OR], 1.03 ;lt; P = .84); however, the association was significant after excluding studies with defined confounding factors (adjusted OR, 1.29; P = .03), indicating an underestimation. The positive association of HPI persisted with IBS-D (OR, 1.54; P = .0003) but not with IBS-C (P = .17) or IBS-M (P = .33).

Study details: Findings are from a systematic review and meta-analysis of 13 studies including 1,403 patients with IBS and 11,770 non-IBS participants.

Disclosures: This research was funded by the National Natural Science Foundation of China and the Natural Science Foundation of Guangdong Province. The authors declared no conflicts of interest.

Source: Wang Z et al. Helicobacterpylori infection-A risk factor for irritable bowel syndrome? An updated systematic review and meta-analysis. Medicina (Kaunas). 2022;58(8):1035 (Aug 2). Doi: 10.3390/medicina58081035.

Key clinical point: Irritable bowel syndrome (IBS) is prevalent among veterans and is associated with significant psychological comorbidities.

Major finding: Overall, 28.4% of veterans met Rome IV IBS criteria, and significant associations of IBS with anxiety (adjusted odds ratio [aOR], 3.47; P < .001), depression (aOR, 2.88; P < .001), post-traumatic stress disorder (aOR, 3.09; P < .001), prior infectious enteritis (aOR, 4.44; P < .001), and a history of bowel problems after antibiotics (aOR, 1.84; P = .005) were observed.

Study details: The data come from a cross-sectional survey including 858 veteran respondents (mean age, 53.6 years), of whom 244 had IBS.

Disclosures: The authors declared no conflicts of interest.

Source: Shin A et al. The prevalence, humanistic burden, and healthcare impact of irritable bowel syndrome (IBS) among United States veterans. Clin Gastroenterol Hepatol. 2022 (Aug 11). Doi: 10.1016/j.cgh.2022.08.005.

Key clinical point: Irritable bowel syndrome (IBS) is prevalent among veterans and is associated with significant psychological comorbidities.

Major finding: Overall, 28.4% of veterans met Rome IV IBS criteria, and significant associations of IBS with anxiety (adjusted odds ratio [aOR], 3.47; P < .001), depression (aOR, 2.88; P < .001), post-traumatic stress disorder (aOR, 3.09; P < .001), prior infectious enteritis (aOR, 4.44; P < .001), and a history of bowel problems after antibiotics (aOR, 1.84; P = .005) were observed.

Study details: The data come from a cross-sectional survey including 858 veteran respondents (mean age, 53.6 years), of whom 244 had IBS.

Disclosures: The authors declared no conflicts of interest.

Source: Shin A et al. The prevalence, humanistic burden, and healthcare impact of irritable bowel syndrome (IBS) among United States veterans. Clin Gastroenterol Hepatol. 2022 (Aug 11). Doi: 10.1016/j.cgh.2022.08.005.

Key clinical point: Irritable bowel syndrome (IBS) is prevalent among veterans and is associated with significant psychological comorbidities.

Major finding: Overall, 28.4% of veterans met Rome IV IBS criteria, and significant associations of IBS with anxiety (adjusted odds ratio [aOR], 3.47; P < .001), depression (aOR, 2.88; P < .001), post-traumatic stress disorder (aOR, 3.09; P < .001), prior infectious enteritis (aOR, 4.44; P < .001), and a history of bowel problems after antibiotics (aOR, 1.84; P = .005) were observed.

Study details: The data come from a cross-sectional survey including 858 veteran respondents (mean age, 53.6 years), of whom 244 had IBS.

Disclosures: The authors declared no conflicts of interest.

Source: Shin A et al. The prevalence, humanistic burden, and healthcare impact of irritable bowel syndrome (IBS) among United States veterans. Clin Gastroenterol Hepatol. 2022 (Aug 11). Doi: 10.1016/j.cgh.2022.08.005.

Key clinical point: Somatization and celiac disease are the primary risk factors associated with irritable bowel syndrome (IBS) in both men and women.

Major finding: The risk for IBS was almost 4-fold higher in men (adjusted odds ratio [aOR] 4.786; 95% CI 4.544-5.041) and women (aOR 5.326; 95% CI 4.863-5.832) experiencing somatization, with the second important influencing factor being celiac disease (men: aOR 4.107; 95% CI 3.132-5.385; women: aOR 3.783; 95% CI 3.310-4.323).

Study details: This study included 31,918 participants who met the Rome III criteria for IBS and completed the Digestive Health Questionnaire.

Disclosures: This study was supported by QW of the National Natural Science Foundation of China and the National Office for Philosophy and Social Sciences. The authors declared no potential conflicts of interest.

Source: Wang K et al. Factors related to irritable bowel syndrome and differences among subtypes: A cross-sectional study in the UK Biobank. Front Pharmacol. 2022;13:905564 (Aug 26). Doi: 10.3389/fphar.2022.905564

Key clinical point: Somatization and celiac disease are the primary risk factors associated with irritable bowel syndrome (IBS) in both men and women.

Major finding: The risk for IBS was almost 4-fold higher in men (adjusted odds ratio [aOR] 4.786; 95% CI 4.544-5.041) and women (aOR 5.326; 95% CI 4.863-5.832) experiencing somatization, with the second important influencing factor being celiac disease (men: aOR 4.107; 95% CI 3.132-5.385; women: aOR 3.783; 95% CI 3.310-4.323).

Study details: This study included 31,918 participants who met the Rome III criteria for IBS and completed the Digestive Health Questionnaire.

Disclosures: This study was supported by QW of the National Natural Science Foundation of China and the National Office for Philosophy and Social Sciences. The authors declared no potential conflicts of interest.

Source: Wang K et al. Factors related to irritable bowel syndrome and differences among subtypes: A cross-sectional study in the UK Biobank. Front Pharmacol. 2022;13:905564 (Aug 26). Doi: 10.3389/fphar.2022.905564

Key clinical point: Somatization and celiac disease are the primary risk factors associated with irritable bowel syndrome (IBS) in both men and women.

Major finding: The risk for IBS was almost 4-fold higher in men (adjusted odds ratio [aOR] 4.786; 95% CI 4.544-5.041) and women (aOR 5.326; 95% CI 4.863-5.832) experiencing somatization, with the second important influencing factor being celiac disease (men: aOR 4.107; 95% CI 3.132-5.385; women: aOR 3.783; 95% CI 3.310-4.323).

Study details: This study included 31,918 participants who met the Rome III criteria for IBS and completed the Digestive Health Questionnaire.

Disclosures: This study was supported by QW of the National Natural Science Foundation of China and the National Office for Philosophy and Social Sciences. The authors declared no potential conflicts of interest.

Source: Wang K et al. Factors related to irritable bowel syndrome and differences among subtypes: A cross-sectional study in the UK Biobank. Front Pharmacol. 2022;13:905564 (Aug 26). Doi: 10.3389/fphar.2022.905564

Key clinical point: Supplementation with a multistrain probiotic for 30 days improved intestinal permeability, stool consistency, and health-related quality-of-life (QoL) in a considerable proportion of patients with diarrhea-predominant irritable bowel syndrome (IBS-D).

Major finding: On day 30, the intestinal permeability improved or normalized in 81.5% of patients, with the intestinal permeability decreasing by 3.4 units (P = .0005), the Bristol Stool Scale score decreasing by 0.9 units (P = .0057), and the IBS-QoL total score increasing by 8.0 points (95% CI 3.0-12.9). The multistrain probiotic was well tolerated.

Study details: The data come from a pilot, open-label, prospective, phase 4 study including 30 patients with IBS-D and leaky gut who received 2 capsules of multistrain probiotic daily for 30 days.

Disclosures: This study was sponsored by PiLeJe Laboratoire. SA Abdellah and C Gal declared being employees of PiLeJe Laboratoire. L Laterza and A Gasbarrini reported ties with various sources.

Source: Ait Abdellah S et al. Effect of a multistrain probiotic on leaky gut in patients with diarrhea-predominant irritable bowel syndrome (IBS-D): A pilot study. Dig Dis. 2022 (Aug 25). Doi: 10.1159/000526712

Key clinical point: Supplementation with a multistrain probiotic for 30 days improved intestinal permeability, stool consistency, and health-related quality-of-life (QoL) in a considerable proportion of patients with diarrhea-predominant irritable bowel syndrome (IBS-D).

Major finding: On day 30, the intestinal permeability improved or normalized in 81.5% of patients, with the intestinal permeability decreasing by 3.4 units (P = .0005), the Bristol Stool Scale score decreasing by 0.9 units (P = .0057), and the IBS-QoL total score increasing by 8.0 points (95% CI 3.0-12.9). The multistrain probiotic was well tolerated.

Study details: The data come from a pilot, open-label, prospective, phase 4 study including 30 patients with IBS-D and leaky gut who received 2 capsules of multistrain probiotic daily for 30 days.

Disclosures: This study was sponsored by PiLeJe Laboratoire. SA Abdellah and C Gal declared being employees of PiLeJe Laboratoire. L Laterza and A Gasbarrini reported ties with various sources.

Source: Ait Abdellah S et al. Effect of a multistrain probiotic on leaky gut in patients with diarrhea-predominant irritable bowel syndrome (IBS-D): A pilot study. Dig Dis. 2022 (Aug 25). Doi: 10.1159/000526712

Key clinical point: Supplementation with a multistrain probiotic for 30 days improved intestinal permeability, stool consistency, and health-related quality-of-life (QoL) in a considerable proportion of patients with diarrhea-predominant irritable bowel syndrome (IBS-D).

Major finding: On day 30, the intestinal permeability improved or normalized in 81.5% of patients, with the intestinal permeability decreasing by 3.4 units (P = .0005), the Bristol Stool Scale score decreasing by 0.9 units (P = .0057), and the IBS-QoL total score increasing by 8.0 points (95% CI 3.0-12.9). The multistrain probiotic was well tolerated.

Study details: The data come from a pilot, open-label, prospective, phase 4 study including 30 patients with IBS-D and leaky gut who received 2 capsules of multistrain probiotic daily for 30 days.

Disclosures: This study was sponsored by PiLeJe Laboratoire. SA Abdellah and C Gal declared being employees of PiLeJe Laboratoire. L Laterza and A Gasbarrini reported ties with various sources.

Source: Ait Abdellah S et al. Effect of a multistrain probiotic on leaky gut in patients with diarrhea-predominant irritable bowel syndrome (IBS-D): A pilot study. Dig Dis. 2022 (Aug 25). Doi: 10.1159/000526712