Federal Practitioner

Immune checkpoint inhibitors (ICIs) are at least as effective in patients with advanced non–small cell lung cancer (NSCLC) and mild preexisting interstitial lung disease (ILD) as in those without ILD. However, the risk of checkpoint inhibitor pneumonitis (CIP) is higher in patients with the dual diagnoses and they need careful monitoring when introducing an ICI, a systematic review and meta-analysis indicated.

“Patients with preexisting ILD, especially symptomatic ILD, are frequently excluded from clinical trials so almost all the patients [we analyzed] were diagnosed with mild preexisting ILD,” said Yuan Cheng, MD, Peking University First Hospital, Beijing, China.

“At this stage, we think that mild ILD is not a contraindication to the use of anti-programmed death-1 (PD-1) and anti-programmed death-ligand 1 (PD-L1) treatment for patients with NSCLC but whether ICIs can be used in patients with moderate to severe ILD needs further study,” she added.

The study was published online Jan. 10 in the journal CHEST.
 

Ten studies

A total of 179 patients from 10 studies were included in the review and meta-analysis. Among these, six were retrospective case-control studies, one was a retrospective noncontrolled study and three were prospective, noncontrolled clinical trials. “All the included studies were from East Asian countries,” the authors noted.

Preexisting ILD was diagnosed by use of CT or high-resolution CT. The mean age of patients was 71 years (range, 33-85 years), 87% were male and 96% of the cohort had a history of smoking. Approximately one-quarter of patients with ILD had usual interstitial pneumonitis (UIP); about the same percentage had possible UIP; one-third were diagnosed with inconsistent UIP; 14% had nonspecific interstitial pneumonia (NSIP); and 6% had indeterminate UIP.

Patients received ICIs either as first-, second-, or third-line or higher therapy and all were treated with ICI monotherapy by way of either nivolumab (Opdivo), pembrolizumab (Keytruda), or atezolizumab (Tecentriq). About 10% of patients had a PD-L1 tumor proportion score (TPS) of less than 1%, one-quarter had a PD-L1 TPS of 1%-49%, and approximately two-thirds had a TPS of 50% or greater.
 

Objective response rates

Some 35% of patients with both NSCLC and preexisting ILD achieved an objective response rate (ORR) to ICI therapy and almost two-thirds of patients achieved disease control. However, there was considerable heterogeneity in ORRs between the studies where it ranged from 5.9% to 70%, the authors cautioned.

On meta-analysis, the pooled ORR was 34% (95% confidence interval, 20%-47%) but again, with significant heterogeneity (I2 = 75.9%). However, on meta-analysis of eligible studies, patients with NSCLC who had preexisting ILD were 99% more likely to achieve an ORR compared to those without ILD (odds ratio, 1.99; 95% CI, 1.31-3.00), the investigators pointed out.

The disease control rate (DCR) also varied considerably between studies from a low of 33.3% to a high of 100%, they added. On meta-analysis, the pooled DCR was 66% (95% CI, 56%-75%). “Meanwhile, in patients without preexisting ILD, the crude ORR and pooled ORR were 24.3% and 24% (95% CI, 17%-31%), respectively” – again with significant heterogeneity between studies (I2 = 87.4%).

In contrast to the ORR, there was no difference in the DCR between the two groups, with no evidence of heterogeneity. There were no significant differences between the two groups in either median progression-free survival (PFS) or overall survival (OS). In patients with NSCLC and preexisting ILD, median PFS ranged from 1.4 to 8 months whereas median OS ranged from 15.6 to 27.8 months.

For those without preexisting ILD, the median PFS ranged from 2.3 to 8.1 months while median OS ranged from 17.4 to 25.5 months.
 

ICI safety

In patients with NSCLC and preexisting ILD, the incidence of immune-related adverse events (irAes) of any grade was 56.7%, whereas the incidence of irAEs grade 3 and higher was 27.7%. “Among the 179 patients included in the studies, 45 developed any grade of CIP, corresponding to a crude incidence of 25.1%,” the authors noted – very similar to the pooled incidence of 27% on meta-analysis.

The pooled incidence of grade 3 and higher CIP in the same group of patients was 15%. The median time from initiation of ICIs to the development of CIP ranged from 31 to 74 days, but 88% of patients who developed CIP improved with appropriate treatment. In patients with NSCLC who did not have ILD, the pooled incidence of CIP was 10% (95% CI, 6%-13%), again with significant heterogeneity between studies (I2 = 78.8%). “Generally, CIP can be managed through ICI discontinuation with or without steroid administration,” the authors noted.

However, even if most CIP can be easily managed, “the incidence of severe CIP is higher [in NSCLC patients with preexisting ILD] than in other populations,” Dr. Chen observed. “So patients with preexisting ILD should be closely monitored during ICI therapy,” she added.

Indeed, compared with patients without preexisting ILD, grade 3 or higher CIP in patients with the dual diagnosis was significantly higher at an OR of 3.23 (95%, 2.06-5.06), the investigators emphasized.

A limitation to the review and systematic meta-analysis included the fact that none of the studies analyzed were randomized clinical trials and most of the studies were retrospective and had several other shortcomings.
 

Umbrella diagnosis

Asked to comment on the review, Karthik Suresh, MD, associate professor of medicine, Johns Hopkins University, Baltimore, pointed out that ILD is really an “umbrella” diagnosis that a few hundred diseases fit under, so the first question he and members of his multidisciplinary team ask is: What is the nature of the ILD in this patient? What is the actual underlying etiology?

It could, for example, be that the patient has undergone prior chemotherapy or radiation therapy and has developed ILD as a result, as Dr. Suresh and his coauthor, Jarushka Naidoo, MD, Sidney Kimmel Comprehensive Cancer Center, Baltimore, pointed out in their paper on how to approach patients with preexisting lung disease to avoid ICI toxicities. “We’ll go back to their prior CT scans and can see the ILD has been there for years – it’s stable and the patient’s lung function is not changing,” Dr. Suresh related to this news organization.

“That’s a very different story from a [patients] whom there are new interstitial changes, who are progressing and who are symptomatic,” he noted. Essentially, what Dr. Suresh and his team members want to know is: What is the specific subdiagnosis of this disease, how severe is it, and is it progressing? Then they need to take the tumor itself into consideration.

“Some tumors have high PD-L1 expression, others have low PD-L1 expression so response to immunotherapy is usually very different based on tumor histology,” Dr. Suresh pointed out. Thus, the next question that needs to be addressed is: What is the expected response of the tumor to ICI therapy? If a tumor is exquisitely sensitive to immunotherapy, “that changes the game,” Dr. Suresh said, “whereas with other tumors, the oncologist might say there may be some benefit but it won’t be dramatic.”

The third risk factor for ICI toxicity that needs to be evaluated is the patient’s general cardiopulmonary status – for example, if a patient has mild, even moderate, ILD but is still walking 3 miles a day, has no heart problems, and is doing fine. Another patient with the same severity of disease in turn may have mild heart failure, be relatively debilitated, and sedentary: “Performance status also plays a big role in determining treatment,” Dr. Suresh emphasized.

The presence of other pulmonary conditions such as chronic obstructive pulmonary disease – common in patients with NSCLC – has to be taken into account, too. Lastly, clinicians need to ask themselves if there are any alternative therapies that might work just as well if not better than ICI therapy for this particular patient. If the patient has had genomic testing, results might indicate that the tumor has a mutation that may respond well to targeted therapies. “We put all these factors out on the table,” Dr. Suresh said.

“And you obviously have to involve the patient, too, so they understand the risks of ICI therapy and together we decide, ‘Yes, this patient with ILD should get immunotherapy or no, they should not,’ “ he said.  

The study had no specific funding. The study authors and Dr. Suresh have disclosed no relevant financial relationships.

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

Immune checkpoint inhibitors (ICIs) are at least as effective in patients with advanced non–small cell lung cancer (NSCLC) and mild preexisting interstitial lung disease (ILD) as in those without ILD. However, the risk of checkpoint inhibitor pneumonitis (CIP) is higher in patients with the dual diagnoses and they need careful monitoring when introducing an ICI, a systematic review and meta-analysis indicated.

“Patients with preexisting ILD, especially symptomatic ILD, are frequently excluded from clinical trials so almost all the patients [we analyzed] were diagnosed with mild preexisting ILD,” said Yuan Cheng, MD, Peking University First Hospital, Beijing, China.

“At this stage, we think that mild ILD is not a contraindication to the use of anti-programmed death-1 (PD-1) and anti-programmed death-ligand 1 (PD-L1) treatment for patients with NSCLC but whether ICIs can be used in patients with moderate to severe ILD needs further study,” she added.

The study was published online Jan. 10 in the journal CHEST.
 

Ten studies

A total of 179 patients from 10 studies were included in the review and meta-analysis. Among these, six were retrospective case-control studies, one was a retrospective noncontrolled study and three were prospective, noncontrolled clinical trials. “All the included studies were from East Asian countries,” the authors noted.

Preexisting ILD was diagnosed by use of CT or high-resolution CT. The mean age of patients was 71 years (range, 33-85 years), 87% were male and 96% of the cohort had a history of smoking. Approximately one-quarter of patients with ILD had usual interstitial pneumonitis (UIP); about the same percentage had possible UIP; one-third were diagnosed with inconsistent UIP; 14% had nonspecific interstitial pneumonia (NSIP); and 6% had indeterminate UIP.

Patients received ICIs either as first-, second-, or third-line or higher therapy and all were treated with ICI monotherapy by way of either nivolumab (Opdivo), pembrolizumab (Keytruda), or atezolizumab (Tecentriq). About 10% of patients had a PD-L1 tumor proportion score (TPS) of less than 1%, one-quarter had a PD-L1 TPS of 1%-49%, and approximately two-thirds had a TPS of 50% or greater.
 

Objective response rates

Some 35% of patients with both NSCLC and preexisting ILD achieved an objective response rate (ORR) to ICI therapy and almost two-thirds of patients achieved disease control. However, there was considerable heterogeneity in ORRs between the studies where it ranged from 5.9% to 70%, the authors cautioned.

On meta-analysis, the pooled ORR was 34% (95% confidence interval, 20%-47%) but again, with significant heterogeneity (I2 = 75.9%). However, on meta-analysis of eligible studies, patients with NSCLC who had preexisting ILD were 99% more likely to achieve an ORR compared to those without ILD (odds ratio, 1.99; 95% CI, 1.31-3.00), the investigators pointed out.

The disease control rate (DCR) also varied considerably between studies from a low of 33.3% to a high of 100%, they added. On meta-analysis, the pooled DCR was 66% (95% CI, 56%-75%). “Meanwhile, in patients without preexisting ILD, the crude ORR and pooled ORR were 24.3% and 24% (95% CI, 17%-31%), respectively” – again with significant heterogeneity between studies (I2 = 87.4%).

In contrast to the ORR, there was no difference in the DCR between the two groups, with no evidence of heterogeneity. There were no significant differences between the two groups in either median progression-free survival (PFS) or overall survival (OS). In patients with NSCLC and preexisting ILD, median PFS ranged from 1.4 to 8 months whereas median OS ranged from 15.6 to 27.8 months.

For those without preexisting ILD, the median PFS ranged from 2.3 to 8.1 months while median OS ranged from 17.4 to 25.5 months.
 

ICI safety

In patients with NSCLC and preexisting ILD, the incidence of immune-related adverse events (irAes) of any grade was 56.7%, whereas the incidence of irAEs grade 3 and higher was 27.7%. “Among the 179 patients included in the studies, 45 developed any grade of CIP, corresponding to a crude incidence of 25.1%,” the authors noted – very similar to the pooled incidence of 27% on meta-analysis.

The pooled incidence of grade 3 and higher CIP in the same group of patients was 15%. The median time from initiation of ICIs to the development of CIP ranged from 31 to 74 days, but 88% of patients who developed CIP improved with appropriate treatment. In patients with NSCLC who did not have ILD, the pooled incidence of CIP was 10% (95% CI, 6%-13%), again with significant heterogeneity between studies (I2 = 78.8%). “Generally, CIP can be managed through ICI discontinuation with or without steroid administration,” the authors noted.

However, even if most CIP can be easily managed, “the incidence of severe CIP is higher [in NSCLC patients with preexisting ILD] than in other populations,” Dr. Chen observed. “So patients with preexisting ILD should be closely monitored during ICI therapy,” she added.

Indeed, compared with patients without preexisting ILD, grade 3 or higher CIP in patients with the dual diagnosis was significantly higher at an OR of 3.23 (95%, 2.06-5.06), the investigators emphasized.

A limitation to the review and systematic meta-analysis included the fact that none of the studies analyzed were randomized clinical trials and most of the studies were retrospective and had several other shortcomings.
 

Umbrella diagnosis

Asked to comment on the review, Karthik Suresh, MD, associate professor of medicine, Johns Hopkins University, Baltimore, pointed out that ILD is really an “umbrella” diagnosis that a few hundred diseases fit under, so the first question he and members of his multidisciplinary team ask is: What is the nature of the ILD in this patient? What is the actual underlying etiology?

It could, for example, be that the patient has undergone prior chemotherapy or radiation therapy and has developed ILD as a result, as Dr. Suresh and his coauthor, Jarushka Naidoo, MD, Sidney Kimmel Comprehensive Cancer Center, Baltimore, pointed out in their paper on how to approach patients with preexisting lung disease to avoid ICI toxicities. “We’ll go back to their prior CT scans and can see the ILD has been there for years – it’s stable and the patient’s lung function is not changing,” Dr. Suresh related to this news organization.

“That’s a very different story from a [patients] whom there are new interstitial changes, who are progressing and who are symptomatic,” he noted. Essentially, what Dr. Suresh and his team members want to know is: What is the specific subdiagnosis of this disease, how severe is it, and is it progressing? Then they need to take the tumor itself into consideration.

“Some tumors have high PD-L1 expression, others have low PD-L1 expression so response to immunotherapy is usually very different based on tumor histology,” Dr. Suresh pointed out. Thus, the next question that needs to be addressed is: What is the expected response of the tumor to ICI therapy? If a tumor is exquisitely sensitive to immunotherapy, “that changes the game,” Dr. Suresh said, “whereas with other tumors, the oncologist might say there may be some benefit but it won’t be dramatic.”

The third risk factor for ICI toxicity that needs to be evaluated is the patient’s general cardiopulmonary status – for example, if a patient has mild, even moderate, ILD but is still walking 3 miles a day, has no heart problems, and is doing fine. Another patient with the same severity of disease in turn may have mild heart failure, be relatively debilitated, and sedentary: “Performance status also plays a big role in determining treatment,” Dr. Suresh emphasized.

The presence of other pulmonary conditions such as chronic obstructive pulmonary disease – common in patients with NSCLC – has to be taken into account, too. Lastly, clinicians need to ask themselves if there are any alternative therapies that might work just as well if not better than ICI therapy for this particular patient. If the patient has had genomic testing, results might indicate that the tumor has a mutation that may respond well to targeted therapies. “We put all these factors out on the table,” Dr. Suresh said.

“And you obviously have to involve the patient, too, so they understand the risks of ICI therapy and together we decide, ‘Yes, this patient with ILD should get immunotherapy or no, they should not,’ “ he said.  

The study had no specific funding. The study authors and Dr. Suresh have disclosed no relevant financial relationships.

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

Immune checkpoint inhibitors (ICIs) are at least as effective in patients with advanced non–small cell lung cancer (NSCLC) and mild preexisting interstitial lung disease (ILD) as in those without ILD. However, the risk of checkpoint inhibitor pneumonitis (CIP) is higher in patients with the dual diagnoses and they need careful monitoring when introducing an ICI, a systematic review and meta-analysis indicated.

“Patients with preexisting ILD, especially symptomatic ILD, are frequently excluded from clinical trials so almost all the patients [we analyzed] were diagnosed with mild preexisting ILD,” said Yuan Cheng, MD, Peking University First Hospital, Beijing, China.

“At this stage, we think that mild ILD is not a contraindication to the use of anti-programmed death-1 (PD-1) and anti-programmed death-ligand 1 (PD-L1) treatment for patients with NSCLC but whether ICIs can be used in patients with moderate to severe ILD needs further study,” she added.

The study was published online Jan. 10 in the journal CHEST.
 

Ten studies

A total of 179 patients from 10 studies were included in the review and meta-analysis. Among these, six were retrospective case-control studies, one was a retrospective noncontrolled study and three were prospective, noncontrolled clinical trials. “All the included studies were from East Asian countries,” the authors noted.

Preexisting ILD was diagnosed by use of CT or high-resolution CT. The mean age of patients was 71 years (range, 33-85 years), 87% were male and 96% of the cohort had a history of smoking. Approximately one-quarter of patients with ILD had usual interstitial pneumonitis (UIP); about the same percentage had possible UIP; one-third were diagnosed with inconsistent UIP; 14% had nonspecific interstitial pneumonia (NSIP); and 6% had indeterminate UIP.

Patients received ICIs either as first-, second-, or third-line or higher therapy and all were treated with ICI monotherapy by way of either nivolumab (Opdivo), pembrolizumab (Keytruda), or atezolizumab (Tecentriq). About 10% of patients had a PD-L1 tumor proportion score (TPS) of less than 1%, one-quarter had a PD-L1 TPS of 1%-49%, and approximately two-thirds had a TPS of 50% or greater.
 

Objective response rates

Some 35% of patients with both NSCLC and preexisting ILD achieved an objective response rate (ORR) to ICI therapy and almost two-thirds of patients achieved disease control. However, there was considerable heterogeneity in ORRs between the studies where it ranged from 5.9% to 70%, the authors cautioned.

On meta-analysis, the pooled ORR was 34% (95% confidence interval, 20%-47%) but again, with significant heterogeneity (I2 = 75.9%). However, on meta-analysis of eligible studies, patients with NSCLC who had preexisting ILD were 99% more likely to achieve an ORR compared to those without ILD (odds ratio, 1.99; 95% CI, 1.31-3.00), the investigators pointed out.

The disease control rate (DCR) also varied considerably between studies from a low of 33.3% to a high of 100%, they added. On meta-analysis, the pooled DCR was 66% (95% CI, 56%-75%). “Meanwhile, in patients without preexisting ILD, the crude ORR and pooled ORR were 24.3% and 24% (95% CI, 17%-31%), respectively” – again with significant heterogeneity between studies (I2 = 87.4%).

In contrast to the ORR, there was no difference in the DCR between the two groups, with no evidence of heterogeneity. There were no significant differences between the two groups in either median progression-free survival (PFS) or overall survival (OS). In patients with NSCLC and preexisting ILD, median PFS ranged from 1.4 to 8 months whereas median OS ranged from 15.6 to 27.8 months.

For those without preexisting ILD, the median PFS ranged from 2.3 to 8.1 months while median OS ranged from 17.4 to 25.5 months.
 

ICI safety

In patients with NSCLC and preexisting ILD, the incidence of immune-related adverse events (irAes) of any grade was 56.7%, whereas the incidence of irAEs grade 3 and higher was 27.7%. “Among the 179 patients included in the studies, 45 developed any grade of CIP, corresponding to a crude incidence of 25.1%,” the authors noted – very similar to the pooled incidence of 27% on meta-analysis.

The pooled incidence of grade 3 and higher CIP in the same group of patients was 15%. The median time from initiation of ICIs to the development of CIP ranged from 31 to 74 days, but 88% of patients who developed CIP improved with appropriate treatment. In patients with NSCLC who did not have ILD, the pooled incidence of CIP was 10% (95% CI, 6%-13%), again with significant heterogeneity between studies (I2 = 78.8%). “Generally, CIP can be managed through ICI discontinuation with or without steroid administration,” the authors noted.

However, even if most CIP can be easily managed, “the incidence of severe CIP is higher [in NSCLC patients with preexisting ILD] than in other populations,” Dr. Chen observed. “So patients with preexisting ILD should be closely monitored during ICI therapy,” she added.

Indeed, compared with patients without preexisting ILD, grade 3 or higher CIP in patients with the dual diagnosis was significantly higher at an OR of 3.23 (95%, 2.06-5.06), the investigators emphasized.

A limitation to the review and systematic meta-analysis included the fact that none of the studies analyzed were randomized clinical trials and most of the studies were retrospective and had several other shortcomings.
 

Umbrella diagnosis

Asked to comment on the review, Karthik Suresh, MD, associate professor of medicine, Johns Hopkins University, Baltimore, pointed out that ILD is really an “umbrella” diagnosis that a few hundred diseases fit under, so the first question he and members of his multidisciplinary team ask is: What is the nature of the ILD in this patient? What is the actual underlying etiology?

It could, for example, be that the patient has undergone prior chemotherapy or radiation therapy and has developed ILD as a result, as Dr. Suresh and his coauthor, Jarushka Naidoo, MD, Sidney Kimmel Comprehensive Cancer Center, Baltimore, pointed out in their paper on how to approach patients with preexisting lung disease to avoid ICI toxicities. “We’ll go back to their prior CT scans and can see the ILD has been there for years – it’s stable and the patient’s lung function is not changing,” Dr. Suresh related to this news organization.

“That’s a very different story from a [patients] whom there are new interstitial changes, who are progressing and who are symptomatic,” he noted. Essentially, what Dr. Suresh and his team members want to know is: What is the specific subdiagnosis of this disease, how severe is it, and is it progressing? Then they need to take the tumor itself into consideration.

“Some tumors have high PD-L1 expression, others have low PD-L1 expression so response to immunotherapy is usually very different based on tumor histology,” Dr. Suresh pointed out. Thus, the next question that needs to be addressed is: What is the expected response of the tumor to ICI therapy? If a tumor is exquisitely sensitive to immunotherapy, “that changes the game,” Dr. Suresh said, “whereas with other tumors, the oncologist might say there may be some benefit but it won’t be dramatic.”

The third risk factor for ICI toxicity that needs to be evaluated is the patient’s general cardiopulmonary status – for example, if a patient has mild, even moderate, ILD but is still walking 3 miles a day, has no heart problems, and is doing fine. Another patient with the same severity of disease in turn may have mild heart failure, be relatively debilitated, and sedentary: “Performance status also plays a big role in determining treatment,” Dr. Suresh emphasized.

The presence of other pulmonary conditions such as chronic obstructive pulmonary disease – common in patients with NSCLC – has to be taken into account, too. Lastly, clinicians need to ask themselves if there are any alternative therapies that might work just as well if not better than ICI therapy for this particular patient. If the patient has had genomic testing, results might indicate that the tumor has a mutation that may respond well to targeted therapies. “We put all these factors out on the table,” Dr. Suresh said.

“And you obviously have to involve the patient, too, so they understand the risks of ICI therapy and together we decide, ‘Yes, this patient with ILD should get immunotherapy or no, they should not,’ “ he said.  

The study had no specific funding. The study authors and Dr. Suresh have disclosed no relevant financial relationships.

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

Intravenous ketamine is effective for treating depression but is inferior to electroconvulsive therapy (ECT), new research suggests.

In the first head-to-head trial, ECT was more effective than intravenous ketamine in hospitalized patients with severe depression, with higher remission rates and a greater reduction in symptoms.

However, ketamine led to remission in nearly half of participants and is a “valuable” option for treating severe depression, particularly in younger patients, the investigators noted.

The high rate of remission for ketamine infusion “indicates that it definitely can be used in a clinical setting, but it is more probable that a patient will achieve remission with ECT compared to ketamine,” principal investigator Pouya Movahed Rad, MD, PhD (pharmacology), senior consultant and researcher in psychiatry, Lund (Sweden) University, said in an interview.

Results of the KetECT study were recently published online in the International Journal of Neuropsychopharmacology.
 

Primary focus on remission

The parallel, open-label, noninferiority study included 186 patients aged 18-85 years who were hospitalized with severe unipolar depression and had a score of at least 20 on the Montgomery-Åsberg Depression Rating Scale (MADRS).

Participants were randomly allocated (1:1) to thrice-weekly infusions of racemic ketamine (0.5 mg/kg over 40 minutes) or ECT. All patients continued to take their antidepressant medication during the study. The primary outcome was remission, defined as a MADRS score of 10 or less.  

Results showed the remission rate was significantly higher in the ECT group than in the ketamine group (63% vs. 46%, respectively; P = .026). The 95% confidence interval of the difference in remission rates was estimated between 2% and 30%. 

Both ketamine and ECT required a median of six treatment sessions to induce remission.

Post-hoc analysis indicated that age was a factor in the findings. In the ECT group, remission was significantly more likely in older patients (51-85 years), compared with younger patients (18-50 years), with remission rates of 77% and 50%, respectively.

But the opposite was true in the ketamine group, with significantly higher remission rates in younger versus older patients (61% vs. 37%).

The study results also support the safety and efficacy of ketamine in patients with psychotic depression, which was present in 15% of patients in the ECT group and 18% of those in the ketamine group.

In this subgroup, half of patients with psychotic depression remitted after ketamine, with no indications of adverse reactions particular for these patients. The remission rate with ECT was 79%.

During the 12-month follow-up period, rate of relapse among remitters was similar at 64% in the ECT group and 70% in the ketamine group (log rank P = .44).
 

Let the patient decide

As expected, ECT and ketamine had distinct side effect profiles. Subjectively reported prolonged amnesia was more common with ECT and reports of dissociative side effects, anxiety, blurred vision, euphoria, vertigo, and diplopia (double vision) were more common with ketamine. 

“Dissociative symptoms were, as expected, observed during treatment with ketamine, but they were brief and in the majority of cases mild and tolerable,” Dr. Movahed Rad said.

The investigators noted that participating study sites all had long-time experience with ECT but no experience administering ketamine.

“Staffs, and some patients, were familiar with side effects common to ECT but were less prepared for the adverse psychological effects of ketamine. This, and knowing ECT was available after the study, probably contributed to the higher dropout rate in the ketamine group,” they wrote.

If both ECT and ketamine are available, “the patient’s preference should, of course, be taken in account when choosing treatment,” said Dr. Movahed Rad.

“Ketamine should be offered if ECT is not available, or cannot be given due to excessive risks with anesthesia or other somatic risk factor. Patients who have not responded to ECT or have had unacceptable side effects should be offered ketamine infusion and vice versa,” he added.

A good alternative

Commenting on the findings, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said the data confirm ECT is highly effective for treatment-resistant depression and show that “newcomer” intravenous ketamine also performs “exceptionally well.”

“This is an extremely important study that really establishes the efficacy of ketamine in a very difficult to treat population,” added Dr. McIntyre, who was not involved in the research.

He added that this “rigorous, well-designed study addresses a critical question” about the comparative efficacy of ECT and intravenous ketamine. It also makes “quite a strong statement about the efficacy of ketamine in younger people.”

He cautioned, however, that this study represents the “first data point and, of course, is not the final word on the topic. There are other studies currently still ongoing that are also comparing ECT to IV ketamine and we’ll look forward to seeing the results.”

The fact that 15%-20% of the study patients had psychotic depression is also noteworthy, said Dr. McIntyre.

“We’ve been hesitant to use ketamine in these patients, I think for obvious reasons, but we recently published a paper showing that it is safe and very effective in these patients,” he said.

Having ketamine as a treatment option is important because the majority of patients who could benefit from ECT decline it, often because of the stigma associated with the procedure, which is often portrayed negatively in films and other media.

“I have been recommending ECT almost every day of my professional life and 98 times out of 100 people say: ‘Thanks but no thanks.’ That’s a problem because ECT is so effective,” Dr. McIntyre said.

The study was funded by the Swedish Research Council, Crafoord Foundation, Skåne Regional Council, Königska Foundation, Lions Forskningsfond Skåne, and the OM Perssons donation foundation. Dr. Movahed Rad has received lecturer honoraria from Lundbeck. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, and other companies. McIntyre is also CEO of AltMed.

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

Intravenous ketamine is effective for treating depression but is inferior to electroconvulsive therapy (ECT), new research suggests.

In the first head-to-head trial, ECT was more effective than intravenous ketamine in hospitalized patients with severe depression, with higher remission rates and a greater reduction in symptoms.

However, ketamine led to remission in nearly half of participants and is a “valuable” option for treating severe depression, particularly in younger patients, the investigators noted.

The high rate of remission for ketamine infusion “indicates that it definitely can be used in a clinical setting, but it is more probable that a patient will achieve remission with ECT compared to ketamine,” principal investigator Pouya Movahed Rad, MD, PhD (pharmacology), senior consultant and researcher in psychiatry, Lund (Sweden) University, said in an interview.

Results of the KetECT study were recently published online in the International Journal of Neuropsychopharmacology.
 

Primary focus on remission

The parallel, open-label, noninferiority study included 186 patients aged 18-85 years who were hospitalized with severe unipolar depression and had a score of at least 20 on the Montgomery-Åsberg Depression Rating Scale (MADRS).

Participants were randomly allocated (1:1) to thrice-weekly infusions of racemic ketamine (0.5 mg/kg over 40 minutes) or ECT. All patients continued to take their antidepressant medication during the study. The primary outcome was remission, defined as a MADRS score of 10 or less.  

Results showed the remission rate was significantly higher in the ECT group than in the ketamine group (63% vs. 46%, respectively; P = .026). The 95% confidence interval of the difference in remission rates was estimated between 2% and 30%. 

Both ketamine and ECT required a median of six treatment sessions to induce remission.

Post-hoc analysis indicated that age was a factor in the findings. In the ECT group, remission was significantly more likely in older patients (51-85 years), compared with younger patients (18-50 years), with remission rates of 77% and 50%, respectively.

But the opposite was true in the ketamine group, with significantly higher remission rates in younger versus older patients (61% vs. 37%).

The study results also support the safety and efficacy of ketamine in patients with psychotic depression, which was present in 15% of patients in the ECT group and 18% of those in the ketamine group.

In this subgroup, half of patients with psychotic depression remitted after ketamine, with no indications of adverse reactions particular for these patients. The remission rate with ECT was 79%.

During the 12-month follow-up period, rate of relapse among remitters was similar at 64% in the ECT group and 70% in the ketamine group (log rank P = .44).
 

Let the patient decide

As expected, ECT and ketamine had distinct side effect profiles. Subjectively reported prolonged amnesia was more common with ECT and reports of dissociative side effects, anxiety, blurred vision, euphoria, vertigo, and diplopia (double vision) were more common with ketamine. 

“Dissociative symptoms were, as expected, observed during treatment with ketamine, but they were brief and in the majority of cases mild and tolerable,” Dr. Movahed Rad said.

The investigators noted that participating study sites all had long-time experience with ECT but no experience administering ketamine.

“Staffs, and some patients, were familiar with side effects common to ECT but were less prepared for the adverse psychological effects of ketamine. This, and knowing ECT was available after the study, probably contributed to the higher dropout rate in the ketamine group,” they wrote.

If both ECT and ketamine are available, “the patient’s preference should, of course, be taken in account when choosing treatment,” said Dr. Movahed Rad.

“Ketamine should be offered if ECT is not available, or cannot be given due to excessive risks with anesthesia or other somatic risk factor. Patients who have not responded to ECT or have had unacceptable side effects should be offered ketamine infusion and vice versa,” he added.

A good alternative

Commenting on the findings, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said the data confirm ECT is highly effective for treatment-resistant depression and show that “newcomer” intravenous ketamine also performs “exceptionally well.”

“This is an extremely important study that really establishes the efficacy of ketamine in a very difficult to treat population,” added Dr. McIntyre, who was not involved in the research.

He added that this “rigorous, well-designed study addresses a critical question” about the comparative efficacy of ECT and intravenous ketamine. It also makes “quite a strong statement about the efficacy of ketamine in younger people.”

He cautioned, however, that this study represents the “first data point and, of course, is not the final word on the topic. There are other studies currently still ongoing that are also comparing ECT to IV ketamine and we’ll look forward to seeing the results.”

The fact that 15%-20% of the study patients had psychotic depression is also noteworthy, said Dr. McIntyre.

“We’ve been hesitant to use ketamine in these patients, I think for obvious reasons, but we recently published a paper showing that it is safe and very effective in these patients,” he said.

Having ketamine as a treatment option is important because the majority of patients who could benefit from ECT decline it, often because of the stigma associated with the procedure, which is often portrayed negatively in films and other media.

“I have been recommending ECT almost every day of my professional life and 98 times out of 100 people say: ‘Thanks but no thanks.’ That’s a problem because ECT is so effective,” Dr. McIntyre said.

The study was funded by the Swedish Research Council, Crafoord Foundation, Skåne Regional Council, Königska Foundation, Lions Forskningsfond Skåne, and the OM Perssons donation foundation. Dr. Movahed Rad has received lecturer honoraria from Lundbeck. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, and other companies. McIntyre is also CEO of AltMed.

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

Intravenous ketamine is effective for treating depression but is inferior to electroconvulsive therapy (ECT), new research suggests.

In the first head-to-head trial, ECT was more effective than intravenous ketamine in hospitalized patients with severe depression, with higher remission rates and a greater reduction in symptoms.

However, ketamine led to remission in nearly half of participants and is a “valuable” option for treating severe depression, particularly in younger patients, the investigators noted.

The high rate of remission for ketamine infusion “indicates that it definitely can be used in a clinical setting, but it is more probable that a patient will achieve remission with ECT compared to ketamine,” principal investigator Pouya Movahed Rad, MD, PhD (pharmacology), senior consultant and researcher in psychiatry, Lund (Sweden) University, said in an interview.

Results of the KetECT study were recently published online in the International Journal of Neuropsychopharmacology.
 

Primary focus on remission

The parallel, open-label, noninferiority study included 186 patients aged 18-85 years who were hospitalized with severe unipolar depression and had a score of at least 20 on the Montgomery-Åsberg Depression Rating Scale (MADRS).

Participants were randomly allocated (1:1) to thrice-weekly infusions of racemic ketamine (0.5 mg/kg over 40 minutes) or ECT. All patients continued to take their antidepressant medication during the study. The primary outcome was remission, defined as a MADRS score of 10 or less.  

Results showed the remission rate was significantly higher in the ECT group than in the ketamine group (63% vs. 46%, respectively; P = .026). The 95% confidence interval of the difference in remission rates was estimated between 2% and 30%. 

Both ketamine and ECT required a median of six treatment sessions to induce remission.

Post-hoc analysis indicated that age was a factor in the findings. In the ECT group, remission was significantly more likely in older patients (51-85 years), compared with younger patients (18-50 years), with remission rates of 77% and 50%, respectively.

But the opposite was true in the ketamine group, with significantly higher remission rates in younger versus older patients (61% vs. 37%).

The study results also support the safety and efficacy of ketamine in patients with psychotic depression, which was present in 15% of patients in the ECT group and 18% of those in the ketamine group.

In this subgroup, half of patients with psychotic depression remitted after ketamine, with no indications of adverse reactions particular for these patients. The remission rate with ECT was 79%.

During the 12-month follow-up period, rate of relapse among remitters was similar at 64% in the ECT group and 70% in the ketamine group (log rank P = .44).
 

Let the patient decide

As expected, ECT and ketamine had distinct side effect profiles. Subjectively reported prolonged amnesia was more common with ECT and reports of dissociative side effects, anxiety, blurred vision, euphoria, vertigo, and diplopia (double vision) were more common with ketamine. 

“Dissociative symptoms were, as expected, observed during treatment with ketamine, but they were brief and in the majority of cases mild and tolerable,” Dr. Movahed Rad said.

The investigators noted that participating study sites all had long-time experience with ECT but no experience administering ketamine.

“Staffs, and some patients, were familiar with side effects common to ECT but were less prepared for the adverse psychological effects of ketamine. This, and knowing ECT was available after the study, probably contributed to the higher dropout rate in the ketamine group,” they wrote.

If both ECT and ketamine are available, “the patient’s preference should, of course, be taken in account when choosing treatment,” said Dr. Movahed Rad.

“Ketamine should be offered if ECT is not available, or cannot be given due to excessive risks with anesthesia or other somatic risk factor. Patients who have not responded to ECT or have had unacceptable side effects should be offered ketamine infusion and vice versa,” he added.

A good alternative

Commenting on the findings, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said the data confirm ECT is highly effective for treatment-resistant depression and show that “newcomer” intravenous ketamine also performs “exceptionally well.”

“This is an extremely important study that really establishes the efficacy of ketamine in a very difficult to treat population,” added Dr. McIntyre, who was not involved in the research.

He added that this “rigorous, well-designed study addresses a critical question” about the comparative efficacy of ECT and intravenous ketamine. It also makes “quite a strong statement about the efficacy of ketamine in younger people.”

He cautioned, however, that this study represents the “first data point and, of course, is not the final word on the topic. There are other studies currently still ongoing that are also comparing ECT to IV ketamine and we’ll look forward to seeing the results.”

The fact that 15%-20% of the study patients had psychotic depression is also noteworthy, said Dr. McIntyre.

“We’ve been hesitant to use ketamine in these patients, I think for obvious reasons, but we recently published a paper showing that it is safe and very effective in these patients,” he said.

Having ketamine as a treatment option is important because the majority of patients who could benefit from ECT decline it, often because of the stigma associated with the procedure, which is often portrayed negatively in films and other media.

“I have been recommending ECT almost every day of my professional life and 98 times out of 100 people say: ‘Thanks but no thanks.’ That’s a problem because ECT is so effective,” Dr. McIntyre said.

The study was funded by the Swedish Research Council, Crafoord Foundation, Skåne Regional Council, Königska Foundation, Lions Forskningsfond Skåne, and the OM Perssons donation foundation. Dr. Movahed Rad has received lecturer honoraria from Lundbeck. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, and other companies. McIntyre is also CEO of AltMed.

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

Regular practice of a specific yoga maneuver appears to reduce susceptibility to reflex vasovagal syncope, a new study suggests.

The tadasana exercise – a movement-based contemplative practice that gradually corrects orthostatic imbalance by strengthening protective neuromuscular reflexes – practiced for just 15 minutes twice a day, was associated with the complete elimination of episodes of vasovagal syncope for many patients.

“These exercises are very easy to perform, inexpensive, and very effective. This is a very easy fix for a scary and potentially dangerous condition,” lead author Hygriv Rao, MD, said in an interview. “We are excited about these results. We thought it would work, but we did not expect it to be so effective. It seems to work for almost all patients.

“We found that, with the tadasana maneuver, episodes of full syncope, where the patient actually loses consciousness, ceased completely, and episodes of near-syncope, where the patient feels faint but does not completely pass out, were greatly reduced,” Dr. Rao added. “The actual loss of consciousness, which is the most dangerous part, is practically gone. This gives a lot of confidence to patients and their families.”

The researchers reported their initial results from a pilot study of the technique in a letter to JACC: Clinical Electrophysiology that was published online Jan. 26, 2022.

Dr. Rao, a cardiologist at the KIMS Hospitals, Hyderabad, India, explained that vasovagal syncope is a brief loss of consciousness caused by a neurologically induced drop in blood pressure caused by faulty neuromuscular reflexes.

It is typically triggered by emotional stress, prolonged standing, or getting up from a sitting position too quickly.

Very few treatments have been shown effective, with current management approaches involving avoiding triggers, increasing fluids, and if the individual feels an episode coming on, they can take steps to stop it by lying down, raising their legs, or lowering their head to increase blood flow to the brain.

“Recently, there has been a lot of interest in yoga as a preventative therapy for vasovagal syncope,” Dr. Rao noted. “We considered various yoga positions and we chose the tadasana maneuver to study in this context as it resembles exercises sometimes given to patients with vasovagal syncope but with some differences including the addition of synchronized breathing, which may help stabilize autonomic tone.”

For the tadasana maneuver, the individual stands straight with their feet together, arms by their side (against a wall if they need support), and alternatively lift the front and back part of their feet.

They first lift their toes with their weight resting on the ball of their feet, then after a few seconds they raise their heels with their weight on the front of the foot. Then after a few more seconds they lift their arms over their shoulders, stretching upward while standing on their toes.

These movements are synchronized with breathing exercises, with the individual taking a deep breath in as they lift their arms and breathing out again on lowering the arms.

“Each movement takes a few seconds, and each cycle of movements takes about 2 minutes. If this is performed 8 times, then this would take about 15 minutes. We recommend this 15-minute routine twice a day,” Dr. Rao said.

For the current study, 113 patients diagnosed with recurrent vasovagal disorder were counseled to practice standard physical maneuvers and maintain adequate hydration. Medications were prescribed at the discretion of the treating physician.

Of these, 61 patients were additionally trained to practice the tadasana maneuver and asked to practice the movement for 15 minutes twice a day. The mean durations of symptoms and follow-up in the two groups were similar. The average follow-up was about 20 months.

Results showed that episodes of both near-syncope and syncope decreased in both groups but there was a much larger reduction in the patients practicing the tadasana maneuver.

Before treatment, the 52 patients in the conventional group experienced 163 syncope or near-syncope events. At follow-up, 22 symptom recurrences occurred in 12 patients (23%). Total mean events per patient declined from 3 to 0.4.

Full syncope events in this group declined from 65 in 32 patients to 2 in 2 patients (mean per patient, 1.3 to 1), and near-syncope events fell from 98 in 34 patients to 20 in 10 patients (mean per patient, 2.0 to 0.4).

In the tadasana group, 61 patients had 378 syncope/near-syncope events before treatment; at follow-up, only 6 events occurred in 5 patients (8%). Per patient, total events declined from a mean of 6 to 0.1.

Full syncope events fell from 108 in 48 patients to 0 (mean per patient, 1.8 to 0), and near-syncope events declined from 269 in 33 patients to 6 in 5 patients (mean per patient, 4.4 to 0.1).

“This combination of exercise and breathing influences the neuromuscular reflex malfunction that occurs in vasovagal syncope,” Dr. Rao noted. “The movements focus on strengthening neuromuscular reflexes in the quadriceps and the calf muscles, which can increase the blood circulation and venous return, thus preventing blood pooling in the lower body.”

The researchers said this pilot study offers three main findings. First, both conventional therapy and conventional plus tadasana therapy appeared to benefit patients, compared with their respective baseline symptom burden. Second, application of tadasana as an adjunctive treatment was associated with fewer total event recurrences (that is, syncope and near-syncope combined), and third, tadasana was well tolerated, with no adverse events reported.

“The reduction in total events (i.e., syncope and near-syncope events), compared with pretreatment numbers, was substantial and most tadasana patients were managed without any pharmacotherapy,” the authors reported.

Dr. Rao noted that at baseline almost all patients in both groups were taking medications for the condition, but during the study these medications were reduced as fewer episodes occurred. At the end of the follow-up, 80% of the conventional group were still taking medication, compared with just 14% of those in the tadasana group.

Patients had an initial training session in person with a yoga instructor and then received follow-on training by video online. Dr. Rao said there was a very high rate of compliance, “almost 100%.”

He reports that a total of 200 patients have now been treated with this approach at his hospital with very similar results to those seen in the initial study.

This work was supported in part by a grant from the Dr Earl E. Bakken Family in support of heart-brain research. Dr. Rao disclosed no relevant financial relationships.

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

Regular practice of a specific yoga maneuver appears to reduce susceptibility to reflex vasovagal syncope, a new study suggests.

The tadasana exercise – a movement-based contemplative practice that gradually corrects orthostatic imbalance by strengthening protective neuromuscular reflexes – practiced for just 15 minutes twice a day, was associated with the complete elimination of episodes of vasovagal syncope for many patients.

“These exercises are very easy to perform, inexpensive, and very effective. This is a very easy fix for a scary and potentially dangerous condition,” lead author Hygriv Rao, MD, said in an interview. “We are excited about these results. We thought it would work, but we did not expect it to be so effective. It seems to work for almost all patients.

“We found that, with the tadasana maneuver, episodes of full syncope, where the patient actually loses consciousness, ceased completely, and episodes of near-syncope, where the patient feels faint but does not completely pass out, were greatly reduced,” Dr. Rao added. “The actual loss of consciousness, which is the most dangerous part, is practically gone. This gives a lot of confidence to patients and their families.”

The researchers reported their initial results from a pilot study of the technique in a letter to JACC: Clinical Electrophysiology that was published online Jan. 26, 2022.

Dr. Rao, a cardiologist at the KIMS Hospitals, Hyderabad, India, explained that vasovagal syncope is a brief loss of consciousness caused by a neurologically induced drop in blood pressure caused by faulty neuromuscular reflexes.

It is typically triggered by emotional stress, prolonged standing, or getting up from a sitting position too quickly.

Very few treatments have been shown effective, with current management approaches involving avoiding triggers, increasing fluids, and if the individual feels an episode coming on, they can take steps to stop it by lying down, raising their legs, or lowering their head to increase blood flow to the brain.

“Recently, there has been a lot of interest in yoga as a preventative therapy for vasovagal syncope,” Dr. Rao noted. “We considered various yoga positions and we chose the tadasana maneuver to study in this context as it resembles exercises sometimes given to patients with vasovagal syncope but with some differences including the addition of synchronized breathing, which may help stabilize autonomic tone.”

For the tadasana maneuver, the individual stands straight with their feet together, arms by their side (against a wall if they need support), and alternatively lift the front and back part of their feet.

They first lift their toes with their weight resting on the ball of their feet, then after a few seconds they raise their heels with their weight on the front of the foot. Then after a few more seconds they lift their arms over their shoulders, stretching upward while standing on their toes.

These movements are synchronized with breathing exercises, with the individual taking a deep breath in as they lift their arms and breathing out again on lowering the arms.

“Each movement takes a few seconds, and each cycle of movements takes about 2 minutes. If this is performed 8 times, then this would take about 15 minutes. We recommend this 15-minute routine twice a day,” Dr. Rao said.

For the current study, 113 patients diagnosed with recurrent vasovagal disorder were counseled to practice standard physical maneuvers and maintain adequate hydration. Medications were prescribed at the discretion of the treating physician.

Of these, 61 patients were additionally trained to practice the tadasana maneuver and asked to practice the movement for 15 minutes twice a day. The mean durations of symptoms and follow-up in the two groups were similar. The average follow-up was about 20 months.

Results showed that episodes of both near-syncope and syncope decreased in both groups but there was a much larger reduction in the patients practicing the tadasana maneuver.

Before treatment, the 52 patients in the conventional group experienced 163 syncope or near-syncope events. At follow-up, 22 symptom recurrences occurred in 12 patients (23%). Total mean events per patient declined from 3 to 0.4.

Full syncope events in this group declined from 65 in 32 patients to 2 in 2 patients (mean per patient, 1.3 to 1), and near-syncope events fell from 98 in 34 patients to 20 in 10 patients (mean per patient, 2.0 to 0.4).

In the tadasana group, 61 patients had 378 syncope/near-syncope events before treatment; at follow-up, only 6 events occurred in 5 patients (8%). Per patient, total events declined from a mean of 6 to 0.1.

Full syncope events fell from 108 in 48 patients to 0 (mean per patient, 1.8 to 0), and near-syncope events declined from 269 in 33 patients to 6 in 5 patients (mean per patient, 4.4 to 0.1).

“This combination of exercise and breathing influences the neuromuscular reflex malfunction that occurs in vasovagal syncope,” Dr. Rao noted. “The movements focus on strengthening neuromuscular reflexes in the quadriceps and the calf muscles, which can increase the blood circulation and venous return, thus preventing blood pooling in the lower body.”

The researchers said this pilot study offers three main findings. First, both conventional therapy and conventional plus tadasana therapy appeared to benefit patients, compared with their respective baseline symptom burden. Second, application of tadasana as an adjunctive treatment was associated with fewer total event recurrences (that is, syncope and near-syncope combined), and third, tadasana was well tolerated, with no adverse events reported.

“The reduction in total events (i.e., syncope and near-syncope events), compared with pretreatment numbers, was substantial and most tadasana patients were managed without any pharmacotherapy,” the authors reported.

Dr. Rao noted that at baseline almost all patients in both groups were taking medications for the condition, but during the study these medications were reduced as fewer episodes occurred. At the end of the follow-up, 80% of the conventional group were still taking medication, compared with just 14% of those in the tadasana group.

Patients had an initial training session in person with a yoga instructor and then received follow-on training by video online. Dr. Rao said there was a very high rate of compliance, “almost 100%.”

He reports that a total of 200 patients have now been treated with this approach at his hospital with very similar results to those seen in the initial study.

This work was supported in part by a grant from the Dr Earl E. Bakken Family in support of heart-brain research. Dr. Rao disclosed no relevant financial relationships.

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

Regular practice of a specific yoga maneuver appears to reduce susceptibility to reflex vasovagal syncope, a new study suggests.

The tadasana exercise – a movement-based contemplative practice that gradually corrects orthostatic imbalance by strengthening protective neuromuscular reflexes – practiced for just 15 minutes twice a day, was associated with the complete elimination of episodes of vasovagal syncope for many patients.

“These exercises are very easy to perform, inexpensive, and very effective. This is a very easy fix for a scary and potentially dangerous condition,” lead author Hygriv Rao, MD, said in an interview. “We are excited about these results. We thought it would work, but we did not expect it to be so effective. It seems to work for almost all patients.

“We found that, with the tadasana maneuver, episodes of full syncope, where the patient actually loses consciousness, ceased completely, and episodes of near-syncope, where the patient feels faint but does not completely pass out, were greatly reduced,” Dr. Rao added. “The actual loss of consciousness, which is the most dangerous part, is practically gone. This gives a lot of confidence to patients and their families.”

The researchers reported their initial results from a pilot study of the technique in a letter to JACC: Clinical Electrophysiology that was published online Jan. 26, 2022.

Dr. Rao, a cardiologist at the KIMS Hospitals, Hyderabad, India, explained that vasovagal syncope is a brief loss of consciousness caused by a neurologically induced drop in blood pressure caused by faulty neuromuscular reflexes.

It is typically triggered by emotional stress, prolonged standing, or getting up from a sitting position too quickly.

Very few treatments have been shown effective, with current management approaches involving avoiding triggers, increasing fluids, and if the individual feels an episode coming on, they can take steps to stop it by lying down, raising their legs, or lowering their head to increase blood flow to the brain.

“Recently, there has been a lot of interest in yoga as a preventative therapy for vasovagal syncope,” Dr. Rao noted. “We considered various yoga positions and we chose the tadasana maneuver to study in this context as it resembles exercises sometimes given to patients with vasovagal syncope but with some differences including the addition of synchronized breathing, which may help stabilize autonomic tone.”

For the tadasana maneuver, the individual stands straight with their feet together, arms by their side (against a wall if they need support), and alternatively lift the front and back part of their feet.

They first lift their toes with their weight resting on the ball of their feet, then after a few seconds they raise their heels with their weight on the front of the foot. Then after a few more seconds they lift their arms over their shoulders, stretching upward while standing on their toes.

These movements are synchronized with breathing exercises, with the individual taking a deep breath in as they lift their arms and breathing out again on lowering the arms.

“Each movement takes a few seconds, and each cycle of movements takes about 2 minutes. If this is performed 8 times, then this would take about 15 minutes. We recommend this 15-minute routine twice a day,” Dr. Rao said.

For the current study, 113 patients diagnosed with recurrent vasovagal disorder were counseled to practice standard physical maneuvers and maintain adequate hydration. Medications were prescribed at the discretion of the treating physician.

Of these, 61 patients were additionally trained to practice the tadasana maneuver and asked to practice the movement for 15 minutes twice a day. The mean durations of symptoms and follow-up in the two groups were similar. The average follow-up was about 20 months.

Results showed that episodes of both near-syncope and syncope decreased in both groups but there was a much larger reduction in the patients practicing the tadasana maneuver.

Before treatment, the 52 patients in the conventional group experienced 163 syncope or near-syncope events. At follow-up, 22 symptom recurrences occurred in 12 patients (23%). Total mean events per patient declined from 3 to 0.4.

Full syncope events in this group declined from 65 in 32 patients to 2 in 2 patients (mean per patient, 1.3 to 1), and near-syncope events fell from 98 in 34 patients to 20 in 10 patients (mean per patient, 2.0 to 0.4).

In the tadasana group, 61 patients had 378 syncope/near-syncope events before treatment; at follow-up, only 6 events occurred in 5 patients (8%). Per patient, total events declined from a mean of 6 to 0.1.

Full syncope events fell from 108 in 48 patients to 0 (mean per patient, 1.8 to 0), and near-syncope events declined from 269 in 33 patients to 6 in 5 patients (mean per patient, 4.4 to 0.1).

“This combination of exercise and breathing influences the neuromuscular reflex malfunction that occurs in vasovagal syncope,” Dr. Rao noted. “The movements focus on strengthening neuromuscular reflexes in the quadriceps and the calf muscles, which can increase the blood circulation and venous return, thus preventing blood pooling in the lower body.”

The researchers said this pilot study offers three main findings. First, both conventional therapy and conventional plus tadasana therapy appeared to benefit patients, compared with their respective baseline symptom burden. Second, application of tadasana as an adjunctive treatment was associated with fewer total event recurrences (that is, syncope and near-syncope combined), and third, tadasana was well tolerated, with no adverse events reported.

“The reduction in total events (i.e., syncope and near-syncope events), compared with pretreatment numbers, was substantial and most tadasana patients were managed without any pharmacotherapy,” the authors reported.

Dr. Rao noted that at baseline almost all patients in both groups were taking medications for the condition, but during the study these medications were reduced as fewer episodes occurred. At the end of the follow-up, 80% of the conventional group were still taking medication, compared with just 14% of those in the tadasana group.

Patients had an initial training session in person with a yoga instructor and then received follow-on training by video online. Dr. Rao said there was a very high rate of compliance, “almost 100%.”

He reports that a total of 200 patients have now been treated with this approach at his hospital with very similar results to those seen in the initial study.

This work was supported in part by a grant from the Dr Earl E. Bakken Family in support of heart-brain research. Dr. Rao disclosed no relevant financial relationships.

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

Takayama et al evaluated 301 Japanese HCC patients who had a Child-Pugh score ≤ 7, no more than 3 HCC nodules (none more than 3 cm in greatest diameter), who were then randomly assigned to undergo either surgery (n=150) or RFA (n=151). The authors reported that though the median procedure duration was longer in the surgery group than in the RFA group (274 versus 40 minutes, P < 0.01) as was the median duration of hospital stay (17 days versus 10 days, P < 0.01), recurrence free survival (RFS) did not differ significantly between the groups. The median RFS was 3.5 years (95% confidence interval [CI], 2.6–5.1) in the surgery group and 3.0 years (95% CI, 2.4–5.6) in the RFA group (hazard ratio, 0.92; 95% CI, 0.67–1.25; P = 0.58). The overall survival (OS) data for this study are not yet mature.

Cao et al looked at outcomes of patients with periportal HCCs who were treated with RFA. They evaluated 233 patients who had a single nodular HCC that was ≤ 5 cm in greatest diameter who underwent RFA with or without transarterial chemoembolization (TACE) as first-line therapy. In that group, 56 patients had a periportal HCC. The authors reported that patients with periportal HCCs had worse outcomes. Local recurrence rates at 1, 3, and 5 years were significantly higher with periportal HCCs than with nonperiportal HCCs (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year OS rates with periportal HCCs were significantly worse than with nonperiportal HCCs (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P < 0.0001). In the subgroup of HCC ≤ 3 cm, patients with periportal HCCs showed significantly higher local recurrence rates (P = 0.0006) and OS (P < 0.0001) after RFA than patients with single nonperiportal HCCs. Subgroup analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. The authors concluded that periportal HCCs have a worse prognosis, and need better treatment options than are currently available.

Lee at al report a retrospective evaluation of Korean patients with HCC who were either treated with RFA or microwave ablation (MWA). Of 150 HCC patients (100 in the RFA group and 50 in the MWA group), the complete response rate, two-year survival rate, and complication rate were similar between the two groups. However, the MWA group had better one- and two-year disease-free survival than the RFA group (P = 0.035 and P = 0.032, respectively). In addition, there were fewer major complications in the MWA group (P = 0.043). In a subgroup analysis, patients with perivascular tumors, high risk of recurrence, and small tumor size (≤3 cm) were more suitable for MWA than RFA. The authors concluded that in patients with HCC, initial treatment with microwave ablation leads to better 1- and 2-year disease-free survival and a lower risk of major complications than RFA.

Takayama et al evaluated 301 Japanese HCC patients who had a Child-Pugh score ≤ 7, no more than 3 HCC nodules (none more than 3 cm in greatest diameter), who were then randomly assigned to undergo either surgery (n=150) or RFA (n=151). The authors reported that though the median procedure duration was longer in the surgery group than in the RFA group (274 versus 40 minutes, P < 0.01) as was the median duration of hospital stay (17 days versus 10 days, P < 0.01), recurrence free survival (RFS) did not differ significantly between the groups. The median RFS was 3.5 years (95% confidence interval [CI], 2.6–5.1) in the surgery group and 3.0 years (95% CI, 2.4–5.6) in the RFA group (hazard ratio, 0.92; 95% CI, 0.67–1.25; P = 0.58). The overall survival (OS) data for this study are not yet mature.

Cao et al looked at outcomes of patients with periportal HCCs who were treated with RFA. They evaluated 233 patients who had a single nodular HCC that was ≤ 5 cm in greatest diameter who underwent RFA with or without transarterial chemoembolization (TACE) as first-line therapy. In that group, 56 patients had a periportal HCC. The authors reported that patients with periportal HCCs had worse outcomes. Local recurrence rates at 1, 3, and 5 years were significantly higher with periportal HCCs than with nonperiportal HCCs (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year OS rates with periportal HCCs were significantly worse than with nonperiportal HCCs (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P < 0.0001). In the subgroup of HCC ≤ 3 cm, patients with periportal HCCs showed significantly higher local recurrence rates (P = 0.0006) and OS (P < 0.0001) after RFA than patients with single nonperiportal HCCs. Subgroup analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. The authors concluded that periportal HCCs have a worse prognosis, and need better treatment options than are currently available.

Lee at al report a retrospective evaluation of Korean patients with HCC who were either treated with RFA or microwave ablation (MWA). Of 150 HCC patients (100 in the RFA group and 50 in the MWA group), the complete response rate, two-year survival rate, and complication rate were similar between the two groups. However, the MWA group had better one- and two-year disease-free survival than the RFA group (P = 0.035 and P = 0.032, respectively). In addition, there were fewer major complications in the MWA group (P = 0.043). In a subgroup analysis, patients with perivascular tumors, high risk of recurrence, and small tumor size (≤3 cm) were more suitable for MWA than RFA. The authors concluded that in patients with HCC, initial treatment with microwave ablation leads to better 1- and 2-year disease-free survival and a lower risk of major complications than RFA.

Takayama et al evaluated 301 Japanese HCC patients who had a Child-Pugh score ≤ 7, no more than 3 HCC nodules (none more than 3 cm in greatest diameter), who were then randomly assigned to undergo either surgery (n=150) or RFA (n=151). The authors reported that though the median procedure duration was longer in the surgery group than in the RFA group (274 versus 40 minutes, P < 0.01) as was the median duration of hospital stay (17 days versus 10 days, P < 0.01), recurrence free survival (RFS) did not differ significantly between the groups. The median RFS was 3.5 years (95% confidence interval [CI], 2.6–5.1) in the surgery group and 3.0 years (95% CI, 2.4–5.6) in the RFA group (hazard ratio, 0.92; 95% CI, 0.67–1.25; P = 0.58). The overall survival (OS) data for this study are not yet mature.

Cao et al looked at outcomes of patients with periportal HCCs who were treated with RFA. They evaluated 233 patients who had a single nodular HCC that was ≤ 5 cm in greatest diameter who underwent RFA with or without transarterial chemoembolization (TACE) as first-line therapy. In that group, 56 patients had a periportal HCC. The authors reported that patients with periportal HCCs had worse outcomes. Local recurrence rates at 1, 3, and 5 years were significantly higher with periportal HCCs than with nonperiportal HCCs (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year OS rates with periportal HCCs were significantly worse than with nonperiportal HCCs (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P < 0.0001). In the subgroup of HCC ≤ 3 cm, patients with periportal HCCs showed significantly higher local recurrence rates (P = 0.0006) and OS (P < 0.0001) after RFA than patients with single nonperiportal HCCs. Subgroup analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. The authors concluded that periportal HCCs have a worse prognosis, and need better treatment options than are currently available.

Lee at al report a retrospective evaluation of Korean patients with HCC who were either treated with RFA or microwave ablation (MWA). Of 150 HCC patients (100 in the RFA group and 50 in the MWA group), the complete response rate, two-year survival rate, and complication rate were similar between the two groups. However, the MWA group had better one- and two-year disease-free survival than the RFA group (P = 0.035 and P = 0.032, respectively). In addition, there were fewer major complications in the MWA group (P = 0.043). In a subgroup analysis, patients with perivascular tumors, high risk of recurrence, and small tumor size (≤3 cm) were more suitable for MWA than RFA. The authors concluded that in patients with HCC, initial treatment with microwave ablation leads to better 1- and 2-year disease-free survival and a lower risk of major complications than RFA.

A new study of thousands of women has found that sticking to recommended healthy dietary patterns can lessen the risk of new-onset gout.

“The identification of multiple patterns of eating that can similarly reduce a woman’s risk of incident gout in our study allows more choice for potential personalization of dietary recommendations according to culinary traditions and personal preferences to enhance adherence,” Chio Yokose, MD, of Harvard Medical School, Boston, and coauthors wrote. The study was published Jan. 31, 2022, in JAMA Internal Medicine.

OksanaKiian/Getty Images

To determine whether consistent healthy eating plays a role in preventing gout in women, the authors launched a prospective cohort study tied to the Nurses’ Health Study, an ongoing endeavor that has been questioning its participants’ food and beverage intake since 1984. Based on the 2020 to 2025 Dietary Guidelines for Americans, four healthy eating patterns were identified for assessment: the Dietary Approaches to Stop Hypertension (DASH), the Mediterranean diet, the Alternative Healthy Eating Index, and the Prudent diet, as well as the unhealthy Western dietary pattern for comparison.

Over 34 years of follow-up, the researchers identified 3,890 cases of gout among 80,039 women with an average age of 50.5 and an average body mass index (BMI) of 25.0 kg/m². Women who strongly adhered to either of the four healthy dietary patterns had a significantly lower risk of gout, especially those who stuck to DASH (multivariable hazard ratio, 0.68; 95% confidence interval, 0.61-0.76) and Prudent (HR, 0.75; 95% CI, 0.73-0.90). In contrast, women with high Western diet scores had a 49% increased risk of gout (HR, 1.49; 95% CI, 1.33-1.68), compared with those who had low scores.

After additional analysis that factored in variables like diuretic use, alcohol use, and obesity, the associations between each diet and their risk of gout persisted in almost every instance. In particular, the most DASH-adherent women with normal BMI had a 68% lower risk of gout (HR, 0.32; 95% CI, 0.26-0.38), compared with the least-adherent women who were overweight or obese. Strong DASH adherence and no diuretic use also led to a 65% gout risk reduction (HR, 0.35; 95% CI, 0.30-0.41).
 

Healthy eating offers broad benefits for gout patients

“These results are consistent with a lot of the conversations we have on a day-to-day basis with patients,” Ted Mikuls, MD, of the University of Nebraska Medical Center, Omaha, said in an interview. “But I will say, I don’t get a lot of patients coming in saying: ‘Hey, what can I do to prevent gout?’ You’re usually seeing them after the fact.”

“These results shouldn’t be confused with that,” he said. “In other words, I wouldn’t want people interpreting this study to mean diet is always a satisfactory treatment for someone with established gout. The fact of the matter is, often it’s not. We need medication to effectively treat gout. I think this and other studies like it call for future research that can look at these dietary interventions as either standalone or probably adjuvant therapies in gout treatment.”

But, he added, that doesn’t mean conversations about diet aren’t of the utmost importance for gout patients.

“That shouldn’t stop clinicians from talking to patients about dietary changes that holistically are going to have positive benefits,” he said. “By the time you meet them, gout patients often already have other health conditions: high blood pressure, diabetes, obesity. The dietary changes that these authors studied are going to have a holistic benefit that goes well beyond gout risk, and that’s important. That’s a conversation that physicians and health care providers can and should be having right now with their patients.”

The authors acknowledged their study’s limitations, including the unmeasured or residual confounding that could come with any observational study as well as these rates of gout and these dietary patterns not necessarily being representative of a random sample of American women. “Future research could examine the population contributions of diets and other risk factors for incident female gout, as done in men.”

The study was funded by the National Institutes of Health. The authors reported several potential conflicts of interest, including receiving grants from the NIH and grants and personal fees from other organizations and pharmaceutical companies. Dr. Mikuls reported receiving past funding from Horizon Therapeutics and serving for them in a consulting capacity.

A new study of thousands of women has found that sticking to recommended healthy dietary patterns can lessen the risk of new-onset gout.

“The identification of multiple patterns of eating that can similarly reduce a woman’s risk of incident gout in our study allows more choice for potential personalization of dietary recommendations according to culinary traditions and personal preferences to enhance adherence,” Chio Yokose, MD, of Harvard Medical School, Boston, and coauthors wrote. The study was published Jan. 31, 2022, in JAMA Internal Medicine.

OksanaKiian/Getty Images

To determine whether consistent healthy eating plays a role in preventing gout in women, the authors launched a prospective cohort study tied to the Nurses’ Health Study, an ongoing endeavor that has been questioning its participants’ food and beverage intake since 1984. Based on the 2020 to 2025 Dietary Guidelines for Americans, four healthy eating patterns were identified for assessment: the Dietary Approaches to Stop Hypertension (DASH), the Mediterranean diet, the Alternative Healthy Eating Index, and the Prudent diet, as well as the unhealthy Western dietary pattern for comparison.

Over 34 years of follow-up, the researchers identified 3,890 cases of gout among 80,039 women with an average age of 50.5 and an average body mass index (BMI) of 25.0 kg/m². Women who strongly adhered to either of the four healthy dietary patterns had a significantly lower risk of gout, especially those who stuck to DASH (multivariable hazard ratio, 0.68; 95% confidence interval, 0.61-0.76) and Prudent (HR, 0.75; 95% CI, 0.73-0.90). In contrast, women with high Western diet scores had a 49% increased risk of gout (HR, 1.49; 95% CI, 1.33-1.68), compared with those who had low scores.

After additional analysis that factored in variables like diuretic use, alcohol use, and obesity, the associations between each diet and their risk of gout persisted in almost every instance. In particular, the most DASH-adherent women with normal BMI had a 68% lower risk of gout (HR, 0.32; 95% CI, 0.26-0.38), compared with the least-adherent women who were overweight or obese. Strong DASH adherence and no diuretic use also led to a 65% gout risk reduction (HR, 0.35; 95% CI, 0.30-0.41).
 

Healthy eating offers broad benefits for gout patients

“These results are consistent with a lot of the conversations we have on a day-to-day basis with patients,” Ted Mikuls, MD, of the University of Nebraska Medical Center, Omaha, said in an interview. “But I will say, I don’t get a lot of patients coming in saying: ‘Hey, what can I do to prevent gout?’ You’re usually seeing them after the fact.”

“These results shouldn’t be confused with that,” he said. “In other words, I wouldn’t want people interpreting this study to mean diet is always a satisfactory treatment for someone with established gout. The fact of the matter is, often it’s not. We need medication to effectively treat gout. I think this and other studies like it call for future research that can look at these dietary interventions as either standalone or probably adjuvant therapies in gout treatment.”

But, he added, that doesn’t mean conversations about diet aren’t of the utmost importance for gout patients.

“That shouldn’t stop clinicians from talking to patients about dietary changes that holistically are going to have positive benefits,” he said. “By the time you meet them, gout patients often already have other health conditions: high blood pressure, diabetes, obesity. The dietary changes that these authors studied are going to have a holistic benefit that goes well beyond gout risk, and that’s important. That’s a conversation that physicians and health care providers can and should be having right now with their patients.”

The authors acknowledged their study’s limitations, including the unmeasured or residual confounding that could come with any observational study as well as these rates of gout and these dietary patterns not necessarily being representative of a random sample of American women. “Future research could examine the population contributions of diets and other risk factors for incident female gout, as done in men.”

The study was funded by the National Institutes of Health. The authors reported several potential conflicts of interest, including receiving grants from the NIH and grants and personal fees from other organizations and pharmaceutical companies. Dr. Mikuls reported receiving past funding from Horizon Therapeutics and serving for them in a consulting capacity.

A new study of thousands of women has found that sticking to recommended healthy dietary patterns can lessen the risk of new-onset gout.

“The identification of multiple patterns of eating that can similarly reduce a woman’s risk of incident gout in our study allows more choice for potential personalization of dietary recommendations according to culinary traditions and personal preferences to enhance adherence,” Chio Yokose, MD, of Harvard Medical School, Boston, and coauthors wrote. The study was published Jan. 31, 2022, in JAMA Internal Medicine.

OksanaKiian/Getty Images

To determine whether consistent healthy eating plays a role in preventing gout in women, the authors launched a prospective cohort study tied to the Nurses’ Health Study, an ongoing endeavor that has been questioning its participants’ food and beverage intake since 1984. Based on the 2020 to 2025 Dietary Guidelines for Americans, four healthy eating patterns were identified for assessment: the Dietary Approaches to Stop Hypertension (DASH), the Mediterranean diet, the Alternative Healthy Eating Index, and the Prudent diet, as well as the unhealthy Western dietary pattern for comparison.

Over 34 years of follow-up, the researchers identified 3,890 cases of gout among 80,039 women with an average age of 50.5 and an average body mass index (BMI) of 25.0 kg/m². Women who strongly adhered to either of the four healthy dietary patterns had a significantly lower risk of gout, especially those who stuck to DASH (multivariable hazard ratio, 0.68; 95% confidence interval, 0.61-0.76) and Prudent (HR, 0.75; 95% CI, 0.73-0.90). In contrast, women with high Western diet scores had a 49% increased risk of gout (HR, 1.49; 95% CI, 1.33-1.68), compared with those who had low scores.

After additional analysis that factored in variables like diuretic use, alcohol use, and obesity, the associations between each diet and their risk of gout persisted in almost every instance. In particular, the most DASH-adherent women with normal BMI had a 68% lower risk of gout (HR, 0.32; 95% CI, 0.26-0.38), compared with the least-adherent women who were overweight or obese. Strong DASH adherence and no diuretic use also led to a 65% gout risk reduction (HR, 0.35; 95% CI, 0.30-0.41).
 

Healthy eating offers broad benefits for gout patients

“These results are consistent with a lot of the conversations we have on a day-to-day basis with patients,” Ted Mikuls, MD, of the University of Nebraska Medical Center, Omaha, said in an interview. “But I will say, I don’t get a lot of patients coming in saying: ‘Hey, what can I do to prevent gout?’ You’re usually seeing them after the fact.”

“These results shouldn’t be confused with that,” he said. “In other words, I wouldn’t want people interpreting this study to mean diet is always a satisfactory treatment for someone with established gout. The fact of the matter is, often it’s not. We need medication to effectively treat gout. I think this and other studies like it call for future research that can look at these dietary interventions as either standalone or probably adjuvant therapies in gout treatment.”

But, he added, that doesn’t mean conversations about diet aren’t of the utmost importance for gout patients.

“That shouldn’t stop clinicians from talking to patients about dietary changes that holistically are going to have positive benefits,” he said. “By the time you meet them, gout patients often already have other health conditions: high blood pressure, diabetes, obesity. The dietary changes that these authors studied are going to have a holistic benefit that goes well beyond gout risk, and that’s important. That’s a conversation that physicians and health care providers can and should be having right now with their patients.”

The authors acknowledged their study’s limitations, including the unmeasured or residual confounding that could come with any observational study as well as these rates of gout and these dietary patterns not necessarily being representative of a random sample of American women. “Future research could examine the population contributions of diets and other risk factors for incident female gout, as done in men.”

The study was funded by the National Institutes of Health. The authors reported several potential conflicts of interest, including receiving grants from the NIH and grants and personal fees from other organizations and pharmaceutical companies. Dr. Mikuls reported receiving past funding from Horizon Therapeutics and serving for them in a consulting capacity.

Metabolic adaptation – slowing of metabolism in response to weight loss – increases the length of time needed to achieve a target lower weight, a new study of premenopausal women with overweight reports.

All of the 65 sedentary young and middle-aged women with overweight who were on a low-calorie diet (800 calories/day) attained their target lower weight – corresponding to a body mass index (BMI) of 25 kg/m² or less – after 66-252 days.

But a woman with the largest metabolic adaptation needed to stay on the diet for an extra 70 days, compared with a woman with no metabolic adaptation, to reach the target BMI, after adjusting for dietary adherence.

The study by Catia Martins, PhD, and colleagues was published Jan. 27, 2022, in Obesity.

“Even though adherence to the diet is clearly the most important determinant of time to reach weight loss goals,” wrote Dr. Martins and colleagues, “the present findings are of great clinical relevance as they mean that individuals who are struggling to achieve weight-loss goals, despite assuring compliance with the diet, may indeed be ‘suffering’ from metabolic adaptation during active weight loss.”

Therefore, “clinicians need to consider metabolic adaptation when assessing resistance to weight loss,” they concluded.
 

Good news: Metabolic adaption ceases when weight stabilizes

“This study shows that a longer than expected duration of intervention to achieve weight loss targets might be due to metabolic adaptation, even after controlling for adherence to the diet,” Dr. Martins said in an interview.

Metabolic adaptation while on a diet makes it harder to lose the last pound than to lose the first pound because as weight loss progresses metabolic adaptation increases, she noted.

However, “the good news is that this mechanism disappears once weight is stabilized (a new energy balance is established), and it is not a predictor of weight regain in the long term,” noted Dr. Martins, associate professor, nutrition sciences research, University of Alabama at Birmingham.

The group published a study in 2020 showing that metabolic adaptation does not predict weight regain at 1 year, and another study, published a few months earlier, showed it is not a barrier to weight-loss maintenance.

The current study findings “provide further evidence of the ways that physiology fights back when people are trying to lose weight,” David B. Sarwer, PhD, who was not involved with this research, said in a press release from the Obesity Society.

“A countless number of environmental variables and other social determinants of health also make weight loss and maintenance challenging for many individuals,” added Dr. Sarwer, director of the Center for Obesity Research and Education at Temple University, Philadelphia.

“Nevertheless, it is import to remember that even a modest weight loss of 5% of initial body weight – much smaller than seen in this study – is associated with clinically significant improvements in weight-related health issues for many individuals,” he stressed.
 

16% weight loss at 5 weeks with 800-calorie/day diet

It is unclear whether metabolic adaptation contributes to resistance to weight loss by increasing the time necessary to achieve weight-loss goals.

To investigate this, Dr. Martins and associates analyzed data from 36 White women and 29 Black women, aged 20-41 years (mean age, 36), who had a mean BMI of 28.6 and had participated in the diet arms of two studies (ROMEO and JULIET) conducted at Martins’ institution.

Participants received food containing 20% to 22% fat, 20% to 22% protein, and 56% to 58% carbohydrate provided by the center’s research kitchen.

On average, the women were 64% compliant with the diet and lost 12.5 kg (27.6 pounds), a 16% weight loss, over 155 days.

Metabolic adaption was measured 4 weeks after weight stabilization after reaching the weight-loss target.

On average, participants’ resting metabolic rate after weight loss was 46 kcal lower than what would be expected for their lower body weight.  

Metabolic adaptation after weight loss was a significant predictor of time to reach the weight-loss goal, after adjusting for target weight loss, energy deficit, and adherence to the diet (R2 adjusted, 0.63; P < .001).

The study findings may not be generalizable to men, older patients, or people with a higher BMI, so further research is needed in a broader population, the researchers concluded.

The research was supported by National Institutes of Health grants. Dr. Martins was supported by a sabbatical grant from the Liaison Committee for Education, Research, and Innovation in Central Norway and the Norwegian University of Science and Technology. The researchers have no relevant financial disclosures.

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

Metabolic adaptation – slowing of metabolism in response to weight loss – increases the length of time needed to achieve a target lower weight, a new study of premenopausal women with overweight reports.

All of the 65 sedentary young and middle-aged women with overweight who were on a low-calorie diet (800 calories/day) attained their target lower weight – corresponding to a body mass index (BMI) of 25 kg/m² or less – after 66-252 days.

But a woman with the largest metabolic adaptation needed to stay on the diet for an extra 70 days, compared with a woman with no metabolic adaptation, to reach the target BMI, after adjusting for dietary adherence.

The study by Catia Martins, PhD, and colleagues was published Jan. 27, 2022, in Obesity.

“Even though adherence to the diet is clearly the most important determinant of time to reach weight loss goals,” wrote Dr. Martins and colleagues, “the present findings are of great clinical relevance as they mean that individuals who are struggling to achieve weight-loss goals, despite assuring compliance with the diet, may indeed be ‘suffering’ from metabolic adaptation during active weight loss.”

Therefore, “clinicians need to consider metabolic adaptation when assessing resistance to weight loss,” they concluded.
 

Good news: Metabolic adaption ceases when weight stabilizes

“This study shows that a longer than expected duration of intervention to achieve weight loss targets might be due to metabolic adaptation, even after controlling for adherence to the diet,” Dr. Martins said in an interview.

Metabolic adaptation while on a diet makes it harder to lose the last pound than to lose the first pound because as weight loss progresses metabolic adaptation increases, she noted.

However, “the good news is that this mechanism disappears once weight is stabilized (a new energy balance is established), and it is not a predictor of weight regain in the long term,” noted Dr. Martins, associate professor, nutrition sciences research, University of Alabama at Birmingham.

The group published a study in 2020 showing that metabolic adaptation does not predict weight regain at 1 year, and another study, published a few months earlier, showed it is not a barrier to weight-loss maintenance.

The current study findings “provide further evidence of the ways that physiology fights back when people are trying to lose weight,” David B. Sarwer, PhD, who was not involved with this research, said in a press release from the Obesity Society.

“A countless number of environmental variables and other social determinants of health also make weight loss and maintenance challenging for many individuals,” added Dr. Sarwer, director of the Center for Obesity Research and Education at Temple University, Philadelphia.

“Nevertheless, it is import to remember that even a modest weight loss of 5% of initial body weight – much smaller than seen in this study – is associated with clinically significant improvements in weight-related health issues for many individuals,” he stressed.
 

16% weight loss at 5 weeks with 800-calorie/day diet

It is unclear whether metabolic adaptation contributes to resistance to weight loss by increasing the time necessary to achieve weight-loss goals.

To investigate this, Dr. Martins and associates analyzed data from 36 White women and 29 Black women, aged 20-41 years (mean age, 36), who had a mean BMI of 28.6 and had participated in the diet arms of two studies (ROMEO and JULIET) conducted at Martins’ institution.

Participants received food containing 20% to 22% fat, 20% to 22% protein, and 56% to 58% carbohydrate provided by the center’s research kitchen.

On average, the women were 64% compliant with the diet and lost 12.5 kg (27.6 pounds), a 16% weight loss, over 155 days.

Metabolic adaption was measured 4 weeks after weight stabilization after reaching the weight-loss target.

On average, participants’ resting metabolic rate after weight loss was 46 kcal lower than what would be expected for their lower body weight.  

Metabolic adaptation after weight loss was a significant predictor of time to reach the weight-loss goal, after adjusting for target weight loss, energy deficit, and adherence to the diet (R2 adjusted, 0.63; P < .001).

The study findings may not be generalizable to men, older patients, or people with a higher BMI, so further research is needed in a broader population, the researchers concluded.

The research was supported by National Institutes of Health grants. Dr. Martins was supported by a sabbatical grant from the Liaison Committee for Education, Research, and Innovation in Central Norway and the Norwegian University of Science and Technology. The researchers have no relevant financial disclosures.

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

Metabolic adaptation – slowing of metabolism in response to weight loss – increases the length of time needed to achieve a target lower weight, a new study of premenopausal women with overweight reports.

All of the 65 sedentary young and middle-aged women with overweight who were on a low-calorie diet (800 calories/day) attained their target lower weight – corresponding to a body mass index (BMI) of 25 kg/m² or less – after 66-252 days.

But a woman with the largest metabolic adaptation needed to stay on the diet for an extra 70 days, compared with a woman with no metabolic adaptation, to reach the target BMI, after adjusting for dietary adherence.

The study by Catia Martins, PhD, and colleagues was published Jan. 27, 2022, in Obesity.

“Even though adherence to the diet is clearly the most important determinant of time to reach weight loss goals,” wrote Dr. Martins and colleagues, “the present findings are of great clinical relevance as they mean that individuals who are struggling to achieve weight-loss goals, despite assuring compliance with the diet, may indeed be ‘suffering’ from metabolic adaptation during active weight loss.”

Therefore, “clinicians need to consider metabolic adaptation when assessing resistance to weight loss,” they concluded.
 

Good news: Metabolic adaption ceases when weight stabilizes

“This study shows that a longer than expected duration of intervention to achieve weight loss targets might be due to metabolic adaptation, even after controlling for adherence to the diet,” Dr. Martins said in an interview.

Metabolic adaptation while on a diet makes it harder to lose the last pound than to lose the first pound because as weight loss progresses metabolic adaptation increases, she noted.

However, “the good news is that this mechanism disappears once weight is stabilized (a new energy balance is established), and it is not a predictor of weight regain in the long term,” noted Dr. Martins, associate professor, nutrition sciences research, University of Alabama at Birmingham.

The group published a study in 2020 showing that metabolic adaptation does not predict weight regain at 1 year, and another study, published a few months earlier, showed it is not a barrier to weight-loss maintenance.

The current study findings “provide further evidence of the ways that physiology fights back when people are trying to lose weight,” David B. Sarwer, PhD, who was not involved with this research, said in a press release from the Obesity Society.

“A countless number of environmental variables and other social determinants of health also make weight loss and maintenance challenging for many individuals,” added Dr. Sarwer, director of the Center for Obesity Research and Education at Temple University, Philadelphia.

“Nevertheless, it is import to remember that even a modest weight loss of 5% of initial body weight – much smaller than seen in this study – is associated with clinically significant improvements in weight-related health issues for many individuals,” he stressed.
 

16% weight loss at 5 weeks with 800-calorie/day diet

It is unclear whether metabolic adaptation contributes to resistance to weight loss by increasing the time necessary to achieve weight-loss goals.

To investigate this, Dr. Martins and associates analyzed data from 36 White women and 29 Black women, aged 20-41 years (mean age, 36), who had a mean BMI of 28.6 and had participated in the diet arms of two studies (ROMEO and JULIET) conducted at Martins’ institution.

Participants received food containing 20% to 22% fat, 20% to 22% protein, and 56% to 58% carbohydrate provided by the center’s research kitchen.

On average, the women were 64% compliant with the diet and lost 12.5 kg (27.6 pounds), a 16% weight loss, over 155 days.

Metabolic adaption was measured 4 weeks after weight stabilization after reaching the weight-loss target.

On average, participants’ resting metabolic rate after weight loss was 46 kcal lower than what would be expected for their lower body weight.  

Metabolic adaptation after weight loss was a significant predictor of time to reach the weight-loss goal, after adjusting for target weight loss, energy deficit, and adherence to the diet (R2 adjusted, 0.63; P < .001).

The study findings may not be generalizable to men, older patients, or people with a higher BMI, so further research is needed in a broader population, the researchers concluded.

The research was supported by National Institutes of Health grants. Dr. Martins was supported by a sabbatical grant from the Liaison Committee for Education, Research, and Innovation in Central Norway and the Norwegian University of Science and Technology. The researchers have no relevant financial disclosures.

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

Long story short, we still have a lot to learn about long COVID-19.

But it is a real phenomenon with real long-term health effects for people recovering from coronavirus infections. And diagnosing and managing it can get tricky, as some symptoms of long COVID-19 overlap with those of other conditions – and what many people have as they recover from any challenging stay in the ICU.

Risk factors remain largely unknown as well: What makes one person more likely to have symptoms like fatigue, “brain fog,” or headaches versus someone else? Researchers are just starting to offer some intriguing answers, but the evidence is preliminary at this point, experts said at a media briefing sponsored by the Infectious Diseases Society of America.

Unanswered questions include: Does an autoimmune reaction drive long COVID? Does the coronavirus linger in reservoirs within the body and reactivate later? What protection against long COVID do vaccines and treatments offer, if any?

To get a handle on these and other questions, nailing down a standard definition of long COVID would be a good start.

“Studies so far have used different definitions of long COVID,” Nahid Bhadelia, MD, founding director of the Boston University Center for Emerging Infectious Diseases Policy and Research, said during the briefing.

Fatigue is the most commonly symptom of long COVID in research so far, said Dr. Bhadelia, who is also an associate professor of medicine at Boston University.

“What’s difficult in this situation is it’s been 2 years in a global pandemic. We’re all fatigued. How do you tease this apart?” she asked.

Other common symptoms are a hard time thinking quickly – also known as “brain fog” – and the feeling that, despite normal oxygen levels, breathing is difficult, said Kathleen Bell, MD.

Headache, joint and muscle pain, and persistent loss of smell and taste are also widely reported, said Dr. Bell, a professor and chair of the department of physical medicine and rehabilitation at the University of Texas Southwestern Medical Center in Dallas.

Not all the symptoms are physical either.

“Pretty prominent things that we’re seeing are very high levels of anxiety, depression, and insomnia,” Dr. Bell said. These “actually seem to be associated independently with the virus as opposed to just being a completely reactive component.”

More research will be needed to distinguish the causes of these conditions.
 

A difficult diagnosis

Without a standard definition, the wide range of symptoms, and the lack of specific guidance on how to manage them, contribute to making it more challenging to distinguish long COVID from other conditions, the experts said.

“We are starting to see some interesting features of inaccurate attributions to COVID, both on the part of perhaps the person with long COVID symptoms and health care providers,” Dr. Bell said.“It’s sometimes a little difficult to sort it out.”

Dr. Bell said she was not suggesting misdiagnoses are common, “but it is difficult for physicians that don’t see a lot of people with long COVID.”

The advice is to consider other conditions. “You can have both a long COVID syndrome and other syndromes as well,” she said. “As one of my teachers used to say: ‘You can have both ticks and fleas.’ ”
 

Predicting long COVID

In a study getting attention, researchers identified four early things linked to greater chances that someone with COVID-19 will have long-term effects: type 2 diabetes at the time of diagnosis, the presence of specific autoantibodies, unusual levels of SARS-CoV-2 RNA in the blood, and signs of the Epstein-Barr virus in the blood.

The study, published in Cell, followed 309 people 2-3 months after COVID-19.

“That’s important work, but it’s early work,” Dr. Bhadelia said. “I think we still have a while to go in terms of understanding the mechanism of long COVID.”
 

Unexpected patients getting long COVID care

“We are seeing different populations than we all expected to see when this pandemic first started,” Dr. Bell said.

Instead of seeing primarily patients who had severe COVID-19, “the preponderance of people that we’re seeing in long COVID clinics are people who are enabled, were never hospitalized, and have what people might call mild to moderate cases of coronavirus infection,” she said.

Also, instead of just older patients, people of all ages are seeking long COVID care.

One thing that appears more certain is a lack of diversity in people seeking care at long COVID clinics nationwide.

“Many of us who have long COVID specialty clinics will tell you that we are tending to see fairly educated, socioeconomically stable population in these clinics,” Dr. Bell said. “We know that based on the early statistics of who’s getting COVID and having significant COVID that we may not be seeing those populations for follow-up.”
 

Is an autoinflammatory process to blame?

It remains unclear if a hyperinflammatory response is driving persistent post–COVID-19 symptoms. Children and some adults have developed multisystem inflammatory conditions associated with COVID-19, for example.

There is a signal, and “I think there is enough data now to show something does happen,” Dr. Bhadelia said. “The question is, how often does it happen?”

Spending time in critical care, even without COVID-19, can result in persistent symptoms after a hospital stay, such as acute respiratory distress syndrome. Recovery can take time because being in an ICU is “basically the physiologically equivalent of a car crash,” Dr. Bhadelia said. “So you’re recovering from that, too.”

Dr. Bell agreed. “You’re not only recovering from the virus itself, you’re recovering from intubation, secondary infections, secondary lung conditions, perhaps other organ failure, and prolonged bed rest. There are so many things that go into that, that it’s a little bit hard to sort that out from what long COVID is and what the direct effects of the virus are.”
 

Also a research opportunity

“I hate to call it this, but we’ve never had an opportunity [where] we have so many people in such a short amount of time with the same viral disorder,” Dr. Bell said. “We also have the technology to investigate it. This has never happened.

“SARS-CoV-2 is not the only virus. This is just the only one we’ve gotten whacked with in such a huge quantity at one time,” she said.

What researchers learn now about COVID-19 and long COVID “is a model that’s going to be able to be applied in the future to infectious diseases in general,” Dr. Bell predicted.
 

How long will long COVID last?

The vast majority of people with long COVID will get better over time, given enough support and relief of their symptoms, Dr. Bell said.

Type 2 diabetes, preexisting pulmonary disease, and other things could affect how long it takes to recover from long COVID, she said, although more evidence is needed.

“I don’t think at this point that anyone can say how long this long COVID will last because there are a variety of factors,” Dr. Bell said.

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

Long story short, we still have a lot to learn about long COVID-19.

But it is a real phenomenon with real long-term health effects for people recovering from coronavirus infections. And diagnosing and managing it can get tricky, as some symptoms of long COVID-19 overlap with those of other conditions – and what many people have as they recover from any challenging stay in the ICU.

Risk factors remain largely unknown as well: What makes one person more likely to have symptoms like fatigue, “brain fog,” or headaches versus someone else? Researchers are just starting to offer some intriguing answers, but the evidence is preliminary at this point, experts said at a media briefing sponsored by the Infectious Diseases Society of America.

Unanswered questions include: Does an autoimmune reaction drive long COVID? Does the coronavirus linger in reservoirs within the body and reactivate later? What protection against long COVID do vaccines and treatments offer, if any?

To get a handle on these and other questions, nailing down a standard definition of long COVID would be a good start.

“Studies so far have used different definitions of long COVID,” Nahid Bhadelia, MD, founding director of the Boston University Center for Emerging Infectious Diseases Policy and Research, said during the briefing.

Fatigue is the most commonly symptom of long COVID in research so far, said Dr. Bhadelia, who is also an associate professor of medicine at Boston University.

“What’s difficult in this situation is it’s been 2 years in a global pandemic. We’re all fatigued. How do you tease this apart?” she asked.

Other common symptoms are a hard time thinking quickly – also known as “brain fog” – and the feeling that, despite normal oxygen levels, breathing is difficult, said Kathleen Bell, MD.

Headache, joint and muscle pain, and persistent loss of smell and taste are also widely reported, said Dr. Bell, a professor and chair of the department of physical medicine and rehabilitation at the University of Texas Southwestern Medical Center in Dallas.

Not all the symptoms are physical either.

“Pretty prominent things that we’re seeing are very high levels of anxiety, depression, and insomnia,” Dr. Bell said. These “actually seem to be associated independently with the virus as opposed to just being a completely reactive component.”

More research will be needed to distinguish the causes of these conditions.
 

A difficult diagnosis

Without a standard definition, the wide range of symptoms, and the lack of specific guidance on how to manage them, contribute to making it more challenging to distinguish long COVID from other conditions, the experts said.

“We are starting to see some interesting features of inaccurate attributions to COVID, both on the part of perhaps the person with long COVID symptoms and health care providers,” Dr. Bell said.“It’s sometimes a little difficult to sort it out.”

Dr. Bell said she was not suggesting misdiagnoses are common, “but it is difficult for physicians that don’t see a lot of people with long COVID.”

The advice is to consider other conditions. “You can have both a long COVID syndrome and other syndromes as well,” she said. “As one of my teachers used to say: ‘You can have both ticks and fleas.’ ”
 

Predicting long COVID

In a study getting attention, researchers identified four early things linked to greater chances that someone with COVID-19 will have long-term effects: type 2 diabetes at the time of diagnosis, the presence of specific autoantibodies, unusual levels of SARS-CoV-2 RNA in the blood, and signs of the Epstein-Barr virus in the blood.

The study, published in Cell, followed 309 people 2-3 months after COVID-19.

“That’s important work, but it’s early work,” Dr. Bhadelia said. “I think we still have a while to go in terms of understanding the mechanism of long COVID.”
 

Unexpected patients getting long COVID care

“We are seeing different populations than we all expected to see when this pandemic first started,” Dr. Bell said.

Instead of seeing primarily patients who had severe COVID-19, “the preponderance of people that we’re seeing in long COVID clinics are people who are enabled, were never hospitalized, and have what people might call mild to moderate cases of coronavirus infection,” she said.

Also, instead of just older patients, people of all ages are seeking long COVID care.

One thing that appears more certain is a lack of diversity in people seeking care at long COVID clinics nationwide.

“Many of us who have long COVID specialty clinics will tell you that we are tending to see fairly educated, socioeconomically stable population in these clinics,” Dr. Bell said. “We know that based on the early statistics of who’s getting COVID and having significant COVID that we may not be seeing those populations for follow-up.”
 

Is an autoinflammatory process to blame?

It remains unclear if a hyperinflammatory response is driving persistent post–COVID-19 symptoms. Children and some adults have developed multisystem inflammatory conditions associated with COVID-19, for example.

There is a signal, and “I think there is enough data now to show something does happen,” Dr. Bhadelia said. “The question is, how often does it happen?”

Spending time in critical care, even without COVID-19, can result in persistent symptoms after a hospital stay, such as acute respiratory distress syndrome. Recovery can take time because being in an ICU is “basically the physiologically equivalent of a car crash,” Dr. Bhadelia said. “So you’re recovering from that, too.”

Dr. Bell agreed. “You’re not only recovering from the virus itself, you’re recovering from intubation, secondary infections, secondary lung conditions, perhaps other organ failure, and prolonged bed rest. There are so many things that go into that, that it’s a little bit hard to sort that out from what long COVID is and what the direct effects of the virus are.”
 

Also a research opportunity

“I hate to call it this, but we’ve never had an opportunity [where] we have so many people in such a short amount of time with the same viral disorder,” Dr. Bell said. “We also have the technology to investigate it. This has never happened.

“SARS-CoV-2 is not the only virus. This is just the only one we’ve gotten whacked with in such a huge quantity at one time,” she said.

What researchers learn now about COVID-19 and long COVID “is a model that’s going to be able to be applied in the future to infectious diseases in general,” Dr. Bell predicted.
 

How long will long COVID last?

The vast majority of people with long COVID will get better over time, given enough support and relief of their symptoms, Dr. Bell said.

Type 2 diabetes, preexisting pulmonary disease, and other things could affect how long it takes to recover from long COVID, she said, although more evidence is needed.

“I don’t think at this point that anyone can say how long this long COVID will last because there are a variety of factors,” Dr. Bell said.

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

Long story short, we still have a lot to learn about long COVID-19.

But it is a real phenomenon with real long-term health effects for people recovering from coronavirus infections. And diagnosing and managing it can get tricky, as some symptoms of long COVID-19 overlap with those of other conditions – and what many people have as they recover from any challenging stay in the ICU.

Risk factors remain largely unknown as well: What makes one person more likely to have symptoms like fatigue, “brain fog,” or headaches versus someone else? Researchers are just starting to offer some intriguing answers, but the evidence is preliminary at this point, experts said at a media briefing sponsored by the Infectious Diseases Society of America.

Unanswered questions include: Does an autoimmune reaction drive long COVID? Does the coronavirus linger in reservoirs within the body and reactivate later? What protection against long COVID do vaccines and treatments offer, if any?

To get a handle on these and other questions, nailing down a standard definition of long COVID would be a good start.

“Studies so far have used different definitions of long COVID,” Nahid Bhadelia, MD, founding director of the Boston University Center for Emerging Infectious Diseases Policy and Research, said during the briefing.

Fatigue is the most commonly symptom of long COVID in research so far, said Dr. Bhadelia, who is also an associate professor of medicine at Boston University.

“What’s difficult in this situation is it’s been 2 years in a global pandemic. We’re all fatigued. How do you tease this apart?” she asked.

Other common symptoms are a hard time thinking quickly – also known as “brain fog” – and the feeling that, despite normal oxygen levels, breathing is difficult, said Kathleen Bell, MD.

Headache, joint and muscle pain, and persistent loss of smell and taste are also widely reported, said Dr. Bell, a professor and chair of the department of physical medicine and rehabilitation at the University of Texas Southwestern Medical Center in Dallas.

Not all the symptoms are physical either.

“Pretty prominent things that we’re seeing are very high levels of anxiety, depression, and insomnia,” Dr. Bell said. These “actually seem to be associated independently with the virus as opposed to just being a completely reactive component.”

More research will be needed to distinguish the causes of these conditions.
 

A difficult diagnosis

Without a standard definition, the wide range of symptoms, and the lack of specific guidance on how to manage them, contribute to making it more challenging to distinguish long COVID from other conditions, the experts said.

“We are starting to see some interesting features of inaccurate attributions to COVID, both on the part of perhaps the person with long COVID symptoms and health care providers,” Dr. Bell said.“It’s sometimes a little difficult to sort it out.”

Dr. Bell said she was not suggesting misdiagnoses are common, “but it is difficult for physicians that don’t see a lot of people with long COVID.”

The advice is to consider other conditions. “You can have both a long COVID syndrome and other syndromes as well,” she said. “As one of my teachers used to say: ‘You can have both ticks and fleas.’ ”
 

Predicting long COVID

In a study getting attention, researchers identified four early things linked to greater chances that someone with COVID-19 will have long-term effects: type 2 diabetes at the time of diagnosis, the presence of specific autoantibodies, unusual levels of SARS-CoV-2 RNA in the blood, and signs of the Epstein-Barr virus in the blood.

The study, published in Cell, followed 309 people 2-3 months after COVID-19.

“That’s important work, but it’s early work,” Dr. Bhadelia said. “I think we still have a while to go in terms of understanding the mechanism of long COVID.”
 

Unexpected patients getting long COVID care

“We are seeing different populations than we all expected to see when this pandemic first started,” Dr. Bell said.

Instead of seeing primarily patients who had severe COVID-19, “the preponderance of people that we’re seeing in long COVID clinics are people who are enabled, were never hospitalized, and have what people might call mild to moderate cases of coronavirus infection,” she said.

Also, instead of just older patients, people of all ages are seeking long COVID care.

One thing that appears more certain is a lack of diversity in people seeking care at long COVID clinics nationwide.

“Many of us who have long COVID specialty clinics will tell you that we are tending to see fairly educated, socioeconomically stable population in these clinics,” Dr. Bell said. “We know that based on the early statistics of who’s getting COVID and having significant COVID that we may not be seeing those populations for follow-up.”
 

Is an autoinflammatory process to blame?

It remains unclear if a hyperinflammatory response is driving persistent post–COVID-19 symptoms. Children and some adults have developed multisystem inflammatory conditions associated with COVID-19, for example.

There is a signal, and “I think there is enough data now to show something does happen,” Dr. Bhadelia said. “The question is, how often does it happen?”

Spending time in critical care, even without COVID-19, can result in persistent symptoms after a hospital stay, such as acute respiratory distress syndrome. Recovery can take time because being in an ICU is “basically the physiologically equivalent of a car crash,” Dr. Bhadelia said. “So you’re recovering from that, too.”

Dr. Bell agreed. “You’re not only recovering from the virus itself, you’re recovering from intubation, secondary infections, secondary lung conditions, perhaps other organ failure, and prolonged bed rest. There are so many things that go into that, that it’s a little bit hard to sort that out from what long COVID is and what the direct effects of the virus are.”
 

Also a research opportunity

“I hate to call it this, but we’ve never had an opportunity [where] we have so many people in such a short amount of time with the same viral disorder,” Dr. Bell said. “We also have the technology to investigate it. This has never happened.

“SARS-CoV-2 is not the only virus. This is just the only one we’ve gotten whacked with in such a huge quantity at one time,” she said.

What researchers learn now about COVID-19 and long COVID “is a model that’s going to be able to be applied in the future to infectious diseases in general,” Dr. Bell predicted.
 

How long will long COVID last?

The vast majority of people with long COVID will get better over time, given enough support and relief of their symptoms, Dr. Bell said.

Type 2 diabetes, preexisting pulmonary disease, and other things could affect how long it takes to recover from long COVID, she said, although more evidence is needed.

“I don’t think at this point that anyone can say how long this long COVID will last because there are a variety of factors,” Dr. Bell said.

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

The STAMPEDE platform included a multiple arm and multiple stage protocol to evaluate abiraterone and enzalutamide in high risk non-metastatic and metastatic disease in separate trials. In the accompanying article by Attard et. al, a meta-analysis of two separate trials conducted as part of the STAMPEDE platform was undertaken. In the first trial, patients with high-risk localized prostate cancer were randomized to androgen deprivation therapy (ADT) with or without abiraterone. In the second trial, similar patients were randomized to ADT versus ADT plus abiraterone plus enzalutamide. The primary outcome of metastasis-free survival and secondary outcome of overall survival [OS] were significantly longer for the treatment arms over ADT; however, the addition of enzalutamide to abiraterone did not result in additional benefit. In appropriately selected patients with high risk localized prostate cancer, abiraterone is a reasonable option to consider in appropriately selected patients.

While bone is the most frequent site of metastasis in men with prostate cancer, visceral metastases (predominantly liver or lung) has been associated with worse outcomes. However, lower incidence of visceral metastases makes conduct of studies focused on visceral disease challenging. Baciarello et al conducted a post-hoc analysis of the LATITUDE study (where men with metastatic castrate-sensitive disease were treated with ADT plus abiraterone or ADT alone) in participants with visceral disease. Overall, patients with visceral metastases derived OS benefit (55.4 versus 33 months). Patients with lung metastases had similar OS to the entire cohort; however, those with liver metastases still derived benefit but had lower OS (36.8 versus 25.6 months). These post-hoc findings suggest that liver metastases present unique challenges compare to other metastatic disease sites, but further study is needed.

In the ENZAMET trial, enzalutamide plus ADT was compared to ADT alone in patients with metastatic castrate-sensitive disease, and enzalutamide treatment was associated with improved OS. In the report by Stockler et al, quality of life metrics as assessed by periodic evaluation utilizing standard questionnaires were reported. Patients who received enzalutamide reported more fatigue and lower cognitive and physical function than those receiving placebo. However, the overall quality of life did not decrease. These important quality of life findings, which are increasingly being reported in similar studies, support the overall net benefit of utilization of enzalutamide in patients with metastatic castrate-sensitive disease.

The STAMPEDE platform included a multiple arm and multiple stage protocol to evaluate abiraterone and enzalutamide in high risk non-metastatic and metastatic disease in separate trials. In the accompanying article by Attard et. al, a meta-analysis of two separate trials conducted as part of the STAMPEDE platform was undertaken. In the first trial, patients with high-risk localized prostate cancer were randomized to androgen deprivation therapy (ADT) with or without abiraterone. In the second trial, similar patients were randomized to ADT versus ADT plus abiraterone plus enzalutamide. The primary outcome of metastasis-free survival and secondary outcome of overall survival [OS] were significantly longer for the treatment arms over ADT; however, the addition of enzalutamide to abiraterone did not result in additional benefit. In appropriately selected patients with high risk localized prostate cancer, abiraterone is a reasonable option to consider in appropriately selected patients.

While bone is the most frequent site of metastasis in men with prostate cancer, visceral metastases (predominantly liver or lung) has been associated with worse outcomes. However, lower incidence of visceral metastases makes conduct of studies focused on visceral disease challenging. Baciarello et al conducted a post-hoc analysis of the LATITUDE study (where men with metastatic castrate-sensitive disease were treated with ADT plus abiraterone or ADT alone) in participants with visceral disease. Overall, patients with visceral metastases derived OS benefit (55.4 versus 33 months). Patients with lung metastases had similar OS to the entire cohort; however, those with liver metastases still derived benefit but had lower OS (36.8 versus 25.6 months). These post-hoc findings suggest that liver metastases present unique challenges compare to other metastatic disease sites, but further study is needed.

In the ENZAMET trial, enzalutamide plus ADT was compared to ADT alone in patients with metastatic castrate-sensitive disease, and enzalutamide treatment was associated with improved OS. In the report by Stockler et al, quality of life metrics as assessed by periodic evaluation utilizing standard questionnaires were reported. Patients who received enzalutamide reported more fatigue and lower cognitive and physical function than those receiving placebo. However, the overall quality of life did not decrease. These important quality of life findings, which are increasingly being reported in similar studies, support the overall net benefit of utilization of enzalutamide in patients with metastatic castrate-sensitive disease.

The STAMPEDE platform included a multiple arm and multiple stage protocol to evaluate abiraterone and enzalutamide in high risk non-metastatic and metastatic disease in separate trials. In the accompanying article by Attard et. al, a meta-analysis of two separate trials conducted as part of the STAMPEDE platform was undertaken. In the first trial, patients with high-risk localized prostate cancer were randomized to androgen deprivation therapy (ADT) with or without abiraterone. In the second trial, similar patients were randomized to ADT versus ADT plus abiraterone plus enzalutamide. The primary outcome of metastasis-free survival and secondary outcome of overall survival [OS] were significantly longer for the treatment arms over ADT; however, the addition of enzalutamide to abiraterone did not result in additional benefit. In appropriately selected patients with high risk localized prostate cancer, abiraterone is a reasonable option to consider in appropriately selected patients.

While bone is the most frequent site of metastasis in men with prostate cancer, visceral metastases (predominantly liver or lung) has been associated with worse outcomes. However, lower incidence of visceral metastases makes conduct of studies focused on visceral disease challenging. Baciarello et al conducted a post-hoc analysis of the LATITUDE study (where men with metastatic castrate-sensitive disease were treated with ADT plus abiraterone or ADT alone) in participants with visceral disease. Overall, patients with visceral metastases derived OS benefit (55.4 versus 33 months). Patients with lung metastases had similar OS to the entire cohort; however, those with liver metastases still derived benefit but had lower OS (36.8 versus 25.6 months). These post-hoc findings suggest that liver metastases present unique challenges compare to other metastatic disease sites, but further study is needed.

In the ENZAMET trial, enzalutamide plus ADT was compared to ADT alone in patients with metastatic castrate-sensitive disease, and enzalutamide treatment was associated with improved OS. In the report by Stockler et al, quality of life metrics as assessed by periodic evaluation utilizing standard questionnaires were reported. Patients who received enzalutamide reported more fatigue and lower cognitive and physical function than those receiving placebo. However, the overall quality of life did not decrease. These important quality of life findings, which are increasingly being reported in similar studies, support the overall net benefit of utilization of enzalutamide in patients with metastatic castrate-sensitive disease.

Subclinical changes in cardiac structure and diastolic function in early adulthood may serve as risk markers for cognitive decline in midlife, new research suggests.

Cardiovascular disease risk factors such as high blood pressure, high cholesterol, and diabetes have been associated with an increased risk for cognitive impairment, but much less is known about heart structure and function and the risks for cognition.

“We showed for the first time that, even before the occurrence of cardiovascular disease, people with abnormalities in cardiac structure and function as early as in young adulthood have lower midlife cognition,” investigators Laure Rouch, PharmD, PhD, and Kristine Yaffe, MD, both with the department of psychiatry, University of California, San Francisco, said in a joint email.

“This study reminds us that heart health is key to brain health and that the overlap and interplay between the two is not limited to patients with end-stage heart disease,” Dr. Rouch and Dr. Yaffe said.

The findings were published online Jan. 26, 2022, in Neurology.
 

Heart/brain connection

The analysis included 2,653 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Echocardiograms were obtained at year 5, 25, and 30 study visits – at mean ages of 30, 50, and 55 years, respectively. At year 30, participants underwent a standard battery of tests measuring global cognition, processing speed, executive function, delayed verbal memory, and verbal fluency.

Over 25 years, there was an average increase in left ventricular mass of 0.27 g/m2 per year – from a mean of 80.5 g/m² in year 5 to 86.0 g/m² in year 30.

Left atrial volume increased by an average of 0.42 mL/m2 per year, from 16 mL/m² in year 5 to 26 mL/m² in year 30.

Left ventricular ejection fraction (LVEF) decreased by 0.11% per year, from 63.3% in year 5 to 59.7% in year 30.

After adjustment for demographics and education, an increase in left ventricular mass of at least 1 standard deviation over 25 years was associated with lower cognition on most tests (P ≤ .02).

An increase in left atrial volume over the study period was associated with lower global cognition (P = .04), whereas a decrease in LVEF was not associated with cognition. Further adjustment for cardiovascular risk factors yielded similar results.

“A more effective collaboration is needed between cardiologists and neurologists to promote healthy brain aging,” Dr. Rouch and Dr. Yaffe said.

“Echocardiography is a widely available, relatively inexpensive, and noninvasive imaging method that could be integrated into a risk assessment for cognitive impairment,” they added.

Looking ahead, the investigators noted there is a need for further research to determine whether interventions to improve cardiac structure and diastolic function could also benefit brain health.

They should also investigate the role of arterial stiffness and cerebral small vessel disease in the relationship between cardiac structure, function, and cognition, the researchers added.
 

First structural biomarker

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Mass., said the study is important because, “thus far, the connections have really been physiological parameters,” such as blood pressure and cognitive health.

“This is really strong evidence of a structural cardiac biomarker that can be measured before and independent of changes in physiology or diseased state,” said Dr. Lakhan, who was not involved with the research.

As more and more interventions are being introduced for addressing disorders of cognition, “this potential structural finding may serve as a solid biomarker to determine” what lifestyle or drug therapy should be taken, he added.

Also weighing in on the findings, Pierre Fayad, MD, professor in the department of neurological sciences and director of the Nebraska Stroke Center, University of Nebraska Medical Center, Omaha, said CARDIA is “an important study” providing “precious data.”

The reported changes in cardiac structure and function “precede the clinical symptomatology, as the follow-up stops before they enter into later adulthood, where the risk of clinical events dramatically rises. Meaning these patients still have not had stroke, congestive heart failure, heart attack or dementia, but some of them could be on that trajectory later in their life,” Dr. Fayad told this news organization.

Documenting such changes over time is “valuable to give an insight into what leads us to such progression,” he noted.

How reliably predictive the findings are for eventual clinical cognitive impairment “will need to be confirmed and verified” in future studies, he added.

“If verified, it could be helpful to provide interventions to those with the left atrial volume enlargement marker and see their effectiveness at preventing eventual clinical cognitive impairment,” said Dr. Fayad.

The CARDIA study is supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Rouch, Lakhan, and Dr. Fayad have disclosed no relevant financial relationships.

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

Subclinical changes in cardiac structure and diastolic function in early adulthood may serve as risk markers for cognitive decline in midlife, new research suggests.

Cardiovascular disease risk factors such as high blood pressure, high cholesterol, and diabetes have been associated with an increased risk for cognitive impairment, but much less is known about heart structure and function and the risks for cognition.

“We showed for the first time that, even before the occurrence of cardiovascular disease, people with abnormalities in cardiac structure and function as early as in young adulthood have lower midlife cognition,” investigators Laure Rouch, PharmD, PhD, and Kristine Yaffe, MD, both with the department of psychiatry, University of California, San Francisco, said in a joint email.

“This study reminds us that heart health is key to brain health and that the overlap and interplay between the two is not limited to patients with end-stage heart disease,” Dr. Rouch and Dr. Yaffe said.

The findings were published online Jan. 26, 2022, in Neurology.
 

Heart/brain connection

The analysis included 2,653 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Echocardiograms were obtained at year 5, 25, and 30 study visits – at mean ages of 30, 50, and 55 years, respectively. At year 30, participants underwent a standard battery of tests measuring global cognition, processing speed, executive function, delayed verbal memory, and verbal fluency.

Over 25 years, there was an average increase in left ventricular mass of 0.27 g/m2 per year – from a mean of 80.5 g/m² in year 5 to 86.0 g/m² in year 30.

Left atrial volume increased by an average of 0.42 mL/m2 per year, from 16 mL/m² in year 5 to 26 mL/m² in year 30.

Left ventricular ejection fraction (LVEF) decreased by 0.11% per year, from 63.3% in year 5 to 59.7% in year 30.

After adjustment for demographics and education, an increase in left ventricular mass of at least 1 standard deviation over 25 years was associated with lower cognition on most tests (P ≤ .02).

An increase in left atrial volume over the study period was associated with lower global cognition (P = .04), whereas a decrease in LVEF was not associated with cognition. Further adjustment for cardiovascular risk factors yielded similar results.

“A more effective collaboration is needed between cardiologists and neurologists to promote healthy brain aging,” Dr. Rouch and Dr. Yaffe said.

“Echocardiography is a widely available, relatively inexpensive, and noninvasive imaging method that could be integrated into a risk assessment for cognitive impairment,” they added.

Looking ahead, the investigators noted there is a need for further research to determine whether interventions to improve cardiac structure and diastolic function could also benefit brain health.

They should also investigate the role of arterial stiffness and cerebral small vessel disease in the relationship between cardiac structure, function, and cognition, the researchers added.
 

First structural biomarker

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Mass., said the study is important because, “thus far, the connections have really been physiological parameters,” such as blood pressure and cognitive health.

“This is really strong evidence of a structural cardiac biomarker that can be measured before and independent of changes in physiology or diseased state,” said Dr. Lakhan, who was not involved with the research.

As more and more interventions are being introduced for addressing disorders of cognition, “this potential structural finding may serve as a solid biomarker to determine” what lifestyle or drug therapy should be taken, he added.

Also weighing in on the findings, Pierre Fayad, MD, professor in the department of neurological sciences and director of the Nebraska Stroke Center, University of Nebraska Medical Center, Omaha, said CARDIA is “an important study” providing “precious data.”

The reported changes in cardiac structure and function “precede the clinical symptomatology, as the follow-up stops before they enter into later adulthood, where the risk of clinical events dramatically rises. Meaning these patients still have not had stroke, congestive heart failure, heart attack or dementia, but some of them could be on that trajectory later in their life,” Dr. Fayad told this news organization.

Documenting such changes over time is “valuable to give an insight into what leads us to such progression,” he noted.

How reliably predictive the findings are for eventual clinical cognitive impairment “will need to be confirmed and verified” in future studies, he added.

“If verified, it could be helpful to provide interventions to those with the left atrial volume enlargement marker and see their effectiveness at preventing eventual clinical cognitive impairment,” said Dr. Fayad.

The CARDIA study is supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Rouch, Lakhan, and Dr. Fayad have disclosed no relevant financial relationships.

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

Subclinical changes in cardiac structure and diastolic function in early adulthood may serve as risk markers for cognitive decline in midlife, new research suggests.

Cardiovascular disease risk factors such as high blood pressure, high cholesterol, and diabetes have been associated with an increased risk for cognitive impairment, but much less is known about heart structure and function and the risks for cognition.

“We showed for the first time that, even before the occurrence of cardiovascular disease, people with abnormalities in cardiac structure and function as early as in young adulthood have lower midlife cognition,” investigators Laure Rouch, PharmD, PhD, and Kristine Yaffe, MD, both with the department of psychiatry, University of California, San Francisco, said in a joint email.

“This study reminds us that heart health is key to brain health and that the overlap and interplay between the two is not limited to patients with end-stage heart disease,” Dr. Rouch and Dr. Yaffe said.

The findings were published online Jan. 26, 2022, in Neurology.
 

Heart/brain connection

The analysis included 2,653 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Echocardiograms were obtained at year 5, 25, and 30 study visits – at mean ages of 30, 50, and 55 years, respectively. At year 30, participants underwent a standard battery of tests measuring global cognition, processing speed, executive function, delayed verbal memory, and verbal fluency.

Over 25 years, there was an average increase in left ventricular mass of 0.27 g/m2 per year – from a mean of 80.5 g/m² in year 5 to 86.0 g/m² in year 30.

Left atrial volume increased by an average of 0.42 mL/m2 per year, from 16 mL/m² in year 5 to 26 mL/m² in year 30.

Left ventricular ejection fraction (LVEF) decreased by 0.11% per year, from 63.3% in year 5 to 59.7% in year 30.

After adjustment for demographics and education, an increase in left ventricular mass of at least 1 standard deviation over 25 years was associated with lower cognition on most tests (P ≤ .02).

An increase in left atrial volume over the study period was associated with lower global cognition (P = .04), whereas a decrease in LVEF was not associated with cognition. Further adjustment for cardiovascular risk factors yielded similar results.

“A more effective collaboration is needed between cardiologists and neurologists to promote healthy brain aging,” Dr. Rouch and Dr. Yaffe said.

“Echocardiography is a widely available, relatively inexpensive, and noninvasive imaging method that could be integrated into a risk assessment for cognitive impairment,” they added.

Looking ahead, the investigators noted there is a need for further research to determine whether interventions to improve cardiac structure and diastolic function could also benefit brain health.

They should also investigate the role of arterial stiffness and cerebral small vessel disease in the relationship between cardiac structure, function, and cognition, the researchers added.
 

First structural biomarker

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Mass., said the study is important because, “thus far, the connections have really been physiological parameters,” such as blood pressure and cognitive health.

“This is really strong evidence of a structural cardiac biomarker that can be measured before and independent of changes in physiology or diseased state,” said Dr. Lakhan, who was not involved with the research.

As more and more interventions are being introduced for addressing disorders of cognition, “this potential structural finding may serve as a solid biomarker to determine” what lifestyle or drug therapy should be taken, he added.

Also weighing in on the findings, Pierre Fayad, MD, professor in the department of neurological sciences and director of the Nebraska Stroke Center, University of Nebraska Medical Center, Omaha, said CARDIA is “an important study” providing “precious data.”

The reported changes in cardiac structure and function “precede the clinical symptomatology, as the follow-up stops before they enter into later adulthood, where the risk of clinical events dramatically rises. Meaning these patients still have not had stroke, congestive heart failure, heart attack or dementia, but some of them could be on that trajectory later in their life,” Dr. Fayad told this news organization.

Documenting such changes over time is “valuable to give an insight into what leads us to such progression,” he noted.

How reliably predictive the findings are for eventual clinical cognitive impairment “will need to be confirmed and verified” in future studies, he added.

“If verified, it could be helpful to provide interventions to those with the left atrial volume enlargement marker and see their effectiveness at preventing eventual clinical cognitive impairment,” said Dr. Fayad.

The CARDIA study is supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Rouch, Lakhan, and Dr. Fayad have disclosed no relevant financial relationships.

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