Once-daily monotherapy with elagolix significantly reduced heavy menstrual bleeding in women with uterine leiomyomas compared to a placebo, based on data from 82 individuals.

Uterine leiomyomas are common in premenopausal women, and 60% experience heavy menstrual bleeding, but nonsurgical options as an alternative to hysterectomy are limited, wrote Eric Brown, MD, of Gyn-Care, Atlanta, Georgia, and colleagues.

Elagolix sodium, an oral, short-acting nonpeptide, gonadotropin-releasing hormone antagonist, has been approved by the Food and Drug Administration at a dose of 300 mg twice daily with add-back therapy for up to 24 months of use. However, this treatment protocol is contraindicated or not preferable for some patients, the researchers said.

In a study published in Obstetrics & Gynecology , the researchers randomized 54 women to 150 mg of oral elagolix once daily, and 28 to a placebo for 6 months to investigate the safety and efficacy of the lower dose. The study population included women aged 18-51 years with a history of heavy menstrual bleeding association with uterine leiomyomas. Approximately two-thirds (65.9%) were Black.

The primary endpoint was the proportion of patients who met the criteria of menstrual blood loss volume less than 80 mL during the final month of treatment and menstrual blood loss volume reduction of 50% or more from baseline to the final month of treatment.

After 6 months, nearly half (49.4%) of the elagolix group met the study endpoint compared with 23.3% of the placebo group (P = .035).

Elagolix patients showed significantly greater reductions in both mean and median menstrual blood loss volumes compared with the placebo patients over the study period, and significant differences between the groups in the mean reduction of menstrual blood loss were evident after 1 month of treatment (P < .05 for months 1, 2, 3, and 5).

Results were similar in a further sensitivity analysis in which patients with incomplete final month data were considered nonresponders; 44.4% of elagolix patients and 21.4% of patients met the primary endpoint.

Overall, 51.9% of elagolix patients and 39.3% of placebo patients reported adverse events; the most common were headache and hot flush. Three patients (5.6%) in the elagolix group discontinued the drug because of adverse events. No serious or severe adverse events were reported in the elagolix group; both cases of reported serious adverse events (COVID-19 and an enlarged uvula) occurred in placebo patients.

Patient-reported outcomes were significantly greater in the elagolix patients, based on symptom severity score, 5 of 6 Uterine Fibroid Symptom and Quality of Life (UFS-QOL) health-related quality of life subscales, and the HRQOL total score at the end of the study.

The findings were limited by several factors including the small study population and lenient eligibility criteria that may have led to a higher placebo response rate, and the study did not monitor bone mineral density, the researchers noted.

However, the results suggest that elagolix at a 150-mg dose was well tolerated, with a safety profile similar to that seen in women who took the drug for endometriosis pain, and may be an option for women with contraindications to other therapy or for those who prefer once-daily dosing, they concluded.

The study was funded by AbbVie. Lead author Dr. Brown had no additional financial conflicts to disclose, but several coauthors disclosed relationships with AbbVie and other companies.

Once-daily monotherapy with elagolix significantly reduced heavy menstrual bleeding in women with uterine leiomyomas compared to a placebo, based on data from 82 individuals.

Uterine leiomyomas are common in premenopausal women, and 60% experience heavy menstrual bleeding, but nonsurgical options as an alternative to hysterectomy are limited, wrote Eric Brown, MD, of Gyn-Care, Atlanta, Georgia, and colleagues.

Elagolix sodium, an oral, short-acting nonpeptide, gonadotropin-releasing hormone antagonist, has been approved by the Food and Drug Administration at a dose of 300 mg twice daily with add-back therapy for up to 24 months of use. However, this treatment protocol is contraindicated or not preferable for some patients, the researchers said.

In a study published in Obstetrics & Gynecology , the researchers randomized 54 women to 150 mg of oral elagolix once daily, and 28 to a placebo for 6 months to investigate the safety and efficacy of the lower dose. The study population included women aged 18-51 years with a history of heavy menstrual bleeding association with uterine leiomyomas. Approximately two-thirds (65.9%) were Black.

The primary endpoint was the proportion of patients who met the criteria of menstrual blood loss volume less than 80 mL during the final month of treatment and menstrual blood loss volume reduction of 50% or more from baseline to the final month of treatment.

After 6 months, nearly half (49.4%) of the elagolix group met the study endpoint compared with 23.3% of the placebo group (P = .035).

Elagolix patients showed significantly greater reductions in both mean and median menstrual blood loss volumes compared with the placebo patients over the study period, and significant differences between the groups in the mean reduction of menstrual blood loss were evident after 1 month of treatment (P < .05 for months 1, 2, 3, and 5).

Results were similar in a further sensitivity analysis in which patients with incomplete final month data were considered nonresponders; 44.4% of elagolix patients and 21.4% of patients met the primary endpoint.

Overall, 51.9% of elagolix patients and 39.3% of placebo patients reported adverse events; the most common were headache and hot flush. Three patients (5.6%) in the elagolix group discontinued the drug because of adverse events. No serious or severe adverse events were reported in the elagolix group; both cases of reported serious adverse events (COVID-19 and an enlarged uvula) occurred in placebo patients.

Patient-reported outcomes were significantly greater in the elagolix patients, based on symptom severity score, 5 of 6 Uterine Fibroid Symptom and Quality of Life (UFS-QOL) health-related quality of life subscales, and the HRQOL total score at the end of the study.

The findings were limited by several factors including the small study population and lenient eligibility criteria that may have led to a higher placebo response rate, and the study did not monitor bone mineral density, the researchers noted.

However, the results suggest that elagolix at a 150-mg dose was well tolerated, with a safety profile similar to that seen in women who took the drug for endometriosis pain, and may be an option for women with contraindications to other therapy or for those who prefer once-daily dosing, they concluded.

The study was funded by AbbVie. Lead author Dr. Brown had no additional financial conflicts to disclose, but several coauthors disclosed relationships with AbbVie and other companies.

Once-daily monotherapy with elagolix significantly reduced heavy menstrual bleeding in women with uterine leiomyomas compared to a placebo, based on data from 82 individuals.

Uterine leiomyomas are common in premenopausal women, and 60% experience heavy menstrual bleeding, but nonsurgical options as an alternative to hysterectomy are limited, wrote Eric Brown, MD, of Gyn-Care, Atlanta, Georgia, and colleagues.

Elagolix sodium, an oral, short-acting nonpeptide, gonadotropin-releasing hormone antagonist, has been approved by the Food and Drug Administration at a dose of 300 mg twice daily with add-back therapy for up to 24 months of use. However, this treatment protocol is contraindicated or not preferable for some patients, the researchers said.

In a study published in Obstetrics & Gynecology , the researchers randomized 54 women to 150 mg of oral elagolix once daily, and 28 to a placebo for 6 months to investigate the safety and efficacy of the lower dose. The study population included women aged 18-51 years with a history of heavy menstrual bleeding association with uterine leiomyomas. Approximately two-thirds (65.9%) were Black.

The primary endpoint was the proportion of patients who met the criteria of menstrual blood loss volume less than 80 mL during the final month of treatment and menstrual blood loss volume reduction of 50% or more from baseline to the final month of treatment.

After 6 months, nearly half (49.4%) of the elagolix group met the study endpoint compared with 23.3% of the placebo group (P = .035).

Elagolix patients showed significantly greater reductions in both mean and median menstrual blood loss volumes compared with the placebo patients over the study period, and significant differences between the groups in the mean reduction of menstrual blood loss were evident after 1 month of treatment (P < .05 for months 1, 2, 3, and 5).

Results were similar in a further sensitivity analysis in which patients with incomplete final month data were considered nonresponders; 44.4% of elagolix patients and 21.4% of patients met the primary endpoint.

Overall, 51.9% of elagolix patients and 39.3% of placebo patients reported adverse events; the most common were headache and hot flush. Three patients (5.6%) in the elagolix group discontinued the drug because of adverse events. No serious or severe adverse events were reported in the elagolix group; both cases of reported serious adverse events (COVID-19 and an enlarged uvula) occurred in placebo patients.

Patient-reported outcomes were significantly greater in the elagolix patients, based on symptom severity score, 5 of 6 Uterine Fibroid Symptom and Quality of Life (UFS-QOL) health-related quality of life subscales, and the HRQOL total score at the end of the study.

The findings were limited by several factors including the small study population and lenient eligibility criteria that may have led to a higher placebo response rate, and the study did not monitor bone mineral density, the researchers noted.

However, the results suggest that elagolix at a 150-mg dose was well tolerated, with a safety profile similar to that seen in women who took the drug for endometriosis pain, and may be an option for women with contraindications to other therapy or for those who prefer once-daily dosing, they concluded.

The study was funded by AbbVie. Lead author Dr. Brown had no additional financial conflicts to disclose, but several coauthors disclosed relationships with AbbVie and other companies.

Artificial intelligence technologies significantly improved detection of precancerous polyps during colonoscopy, according to results from a large meta-analysis of randomized controlled trials.

But while adenoma detection rates increased by nearly 25%, compared with conventional care, the AI-guided procedures were also associated with an increase in unnecessary removal of non-neoplastic polyps. Little effect was seen on the detection of larger, advanced lesions.

The findings, published in Annals of Internal Medicine, are likely to change clinical guidelines in favor of AI-assisted procedures, said Cesare Hassan, MD, PhD, of Humanitas Research Hospital and University in Milan, Italy.

For their research, Dr. Hassan and his colleagues looked at results from 21 trials randomizing more than 18,000 patients to colonoscopy with computer-aided detection (CADe) or standard colonoscopy. Colonoscopy could be carried out for screening, surveillance, or diagnostic purposes. The included trials, which were all published in 2019 or later, took place in Asia, North America, and Europe. In most of the studies endoscopists were not blinded to treatment allocation.

The adenoma detection rate, or the proportion of individuals undergoing colonoscopy who had at least one adenoma detected and removed, was 44% in the CADe arms, compared with 35.9% assigned to standard care (relative risk [RR], 1.24; 95% CI, 1.16-1.33). The CADe patients also saw more non-neoplastic polyps removed: 0.52 per colonoscopy, compared with 0.34 for standard care. The increased adenoma detection rate appeared to be driven by a 55% decrease in the error or miss rate of adenomas at per-polyp analysis, the investigators wrote in their paper.

CADe did not increase the number of advanced adenomas (defined as greater than 10 mm, with high-grade dysplasia and villous histology) detected per colonoscopy. Rather, the benefit was “mainly limited to increased detection of diminutive (≤5 mm) adenomas,” the investigators wrote. Dr. Hassan commented that the lack of benefit for detecting larger adenomas was expected, as these are easier for endoscopists to identify visually.

The key limitation of the meta-analysis, Dr. Hassan said, was the fact that endoscopists in the studies could not be blinded. “We can assume there is a risk of bias in our estimates — that is why we describe the quality of evidence as low or moderate, never high. Through randomization we can control other aspects, especially the prevalence of disease, which avoids a scenario in which the endoscopist opts to treat riskier patients with CADe.” But the possibility of a change in the endoscopist’s performance when using these systems cannot be excluded.

Dr. Hassan commented that quantifying the risks, and costs, of overtreatment linked to CADe would require more investigation. “Any time I remove a polyp there’s a risk of perforation and bleeding,” he noted, though most of the unnecessary resections seen in the meta-analysis were of small hyperplastic polyps considered to be low risk for complications. Use of CADe was associated with only slight increases in procedure time, the investigators found.

In a multicenter Spanish study also published in Annals of Internal Medicine, Carolina Mangas-Sanjuan, MD, PhD, of the Hospital General Universitario Dr. Balmis, Alicante, Spain, and her colleagues looked at computer-aided detection of advanced colorectal neoplasias in a higher-risk cohort and saw little advantage over standard colonoscopy.

This study, which randomized 3,213 subjects, is the largest to date aimed at learning whether AI can improve the detection of advanced lesions. As in Dr. Hassan’s meta-analysis, the researchers did not see significant differences in the rates of detection for these larger lesions. Nor, in this study, did CADe did improve the global adenoma detection rate among the FIT positive individuals undergoing screening.

The detection rate of advanced colorectal neoplasias (advanced adenoma or advanced serrated polyp) was 34.8% with CADe (95% CI, 32.5%-37.2%) and 34.6% for standard colonoscopy (95% CI, 32.2%-36.9%); adjusted risk ratio, 1.01 [95% CI, 0.92-1.10]. The mean number of advanced colorectal neoplasias detected per colonoscopy was 0.54 for the intervention group, compared with 0.52 for standard care. For all adenomas, the detection rate was 64.2% with CADe vs 62% for controls.

Dr. Rodrigo Jover of the Hospital General Universitario Dr. Balmis, the study’s corresponding author, commented to this news organization that “while CADe systems are able to improve detection of small low-risk lesions, these devices are not yet able to detect more significant high-risk lesions. Therefore, there is still room for improvement if these systems are adequately trained with datasets of large, difficult-to-detect lesions.”

In an editorial comment on the Spanish and Italian studies Dennis Shung, MD, PhD of Yale University in New Haven, Connecticut, concluded that “this recent evidence suggests that CADe systems do not meaningfully improve the detection of larger (≥10 mm) clinically significant polyps. This tempers enthusiasm for CADe but does not negate the clear performance benefit for detecting adenomas of all sizes.”

How to integrate the AI systems into real-world practice is the real challenge ahead, Dr. Shung argued, noting that, in contrast to randomized trials, “several recent real-world studies have found no improvement in [adenoma detection rate] when CADe is deployed.” Lower trust in the systems can result in their underutilization, Dr. Shung argued, while higher trust can lead to overreliance. “How lgorithmic systems partner with clinicians and how these should be designed and refined across heterogeneous systems and contexts are necessary questions that must be explored to minimize disruption and lead to real-world effectiveness.”

Dr. Mangas-Sanjuan’s study was funded by a grant from Medtronic; Part of Dr. Hassan’s meta-analysis was supported by a European Commission grant to one co-author. Drs. Shung, Hassan, Manguas-Sanjuan, and Jover declared no financial conflicts of interest.

Artificial intelligence technologies significantly improved detection of precancerous polyps during colonoscopy, according to results from a large meta-analysis of randomized controlled trials.

But while adenoma detection rates increased by nearly 25%, compared with conventional care, the AI-guided procedures were also associated with an increase in unnecessary removal of non-neoplastic polyps. Little effect was seen on the detection of larger, advanced lesions.

The findings, published in Annals of Internal Medicine, are likely to change clinical guidelines in favor of AI-assisted procedures, said Cesare Hassan, MD, PhD, of Humanitas Research Hospital and University in Milan, Italy.

For their research, Dr. Hassan and his colleagues looked at results from 21 trials randomizing more than 18,000 patients to colonoscopy with computer-aided detection (CADe) or standard colonoscopy. Colonoscopy could be carried out for screening, surveillance, or diagnostic purposes. The included trials, which were all published in 2019 or later, took place in Asia, North America, and Europe. In most of the studies endoscopists were not blinded to treatment allocation.

The adenoma detection rate, or the proportion of individuals undergoing colonoscopy who had at least one adenoma detected and removed, was 44% in the CADe arms, compared with 35.9% assigned to standard care (relative risk [RR], 1.24; 95% CI, 1.16-1.33). The CADe patients also saw more non-neoplastic polyps removed: 0.52 per colonoscopy, compared with 0.34 for standard care. The increased adenoma detection rate appeared to be driven by a 55% decrease in the error or miss rate of adenomas at per-polyp analysis, the investigators wrote in their paper.

CADe did not increase the number of advanced adenomas (defined as greater than 10 mm, with high-grade dysplasia and villous histology) detected per colonoscopy. Rather, the benefit was “mainly limited to increased detection of diminutive (≤5 mm) adenomas,” the investigators wrote. Dr. Hassan commented that the lack of benefit for detecting larger adenomas was expected, as these are easier for endoscopists to identify visually.

The key limitation of the meta-analysis, Dr. Hassan said, was the fact that endoscopists in the studies could not be blinded. “We can assume there is a risk of bias in our estimates — that is why we describe the quality of evidence as low or moderate, never high. Through randomization we can control other aspects, especially the prevalence of disease, which avoids a scenario in which the endoscopist opts to treat riskier patients with CADe.” But the possibility of a change in the endoscopist’s performance when using these systems cannot be excluded.

Dr. Hassan commented that quantifying the risks, and costs, of overtreatment linked to CADe would require more investigation. “Any time I remove a polyp there’s a risk of perforation and bleeding,” he noted, though most of the unnecessary resections seen in the meta-analysis were of small hyperplastic polyps considered to be low risk for complications. Use of CADe was associated with only slight increases in procedure time, the investigators found.

In a multicenter Spanish study also published in Annals of Internal Medicine, Carolina Mangas-Sanjuan, MD, PhD, of the Hospital General Universitario Dr. Balmis, Alicante, Spain, and her colleagues looked at computer-aided detection of advanced colorectal neoplasias in a higher-risk cohort and saw little advantage over standard colonoscopy.

This study, which randomized 3,213 subjects, is the largest to date aimed at learning whether AI can improve the detection of advanced lesions. As in Dr. Hassan’s meta-analysis, the researchers did not see significant differences in the rates of detection for these larger lesions. Nor, in this study, did CADe did improve the global adenoma detection rate among the FIT positive individuals undergoing screening.

The detection rate of advanced colorectal neoplasias (advanced adenoma or advanced serrated polyp) was 34.8% with CADe (95% CI, 32.5%-37.2%) and 34.6% for standard colonoscopy (95% CI, 32.2%-36.9%); adjusted risk ratio, 1.01 [95% CI, 0.92-1.10]. The mean number of advanced colorectal neoplasias detected per colonoscopy was 0.54 for the intervention group, compared with 0.52 for standard care. For all adenomas, the detection rate was 64.2% with CADe vs 62% for controls.

Dr. Rodrigo Jover of the Hospital General Universitario Dr. Balmis, the study’s corresponding author, commented to this news organization that “while CADe systems are able to improve detection of small low-risk lesions, these devices are not yet able to detect more significant high-risk lesions. Therefore, there is still room for improvement if these systems are adequately trained with datasets of large, difficult-to-detect lesions.”

In an editorial comment on the Spanish and Italian studies Dennis Shung, MD, PhD of Yale University in New Haven, Connecticut, concluded that “this recent evidence suggests that CADe systems do not meaningfully improve the detection of larger (≥10 mm) clinically significant polyps. This tempers enthusiasm for CADe but does not negate the clear performance benefit for detecting adenomas of all sizes.”

How to integrate the AI systems into real-world practice is the real challenge ahead, Dr. Shung argued, noting that, in contrast to randomized trials, “several recent real-world studies have found no improvement in [adenoma detection rate] when CADe is deployed.” Lower trust in the systems can result in their underutilization, Dr. Shung argued, while higher trust can lead to overreliance. “How lgorithmic systems partner with clinicians and how these should be designed and refined across heterogeneous systems and contexts are necessary questions that must be explored to minimize disruption and lead to real-world effectiveness.”

Dr. Mangas-Sanjuan’s study was funded by a grant from Medtronic; Part of Dr. Hassan’s meta-analysis was supported by a European Commission grant to one co-author. Drs. Shung, Hassan, Manguas-Sanjuan, and Jover declared no financial conflicts of interest.

Artificial intelligence technologies significantly improved detection of precancerous polyps during colonoscopy, according to results from a large meta-analysis of randomized controlled trials.

But while adenoma detection rates increased by nearly 25%, compared with conventional care, the AI-guided procedures were also associated with an increase in unnecessary removal of non-neoplastic polyps. Little effect was seen on the detection of larger, advanced lesions.

The findings, published in Annals of Internal Medicine, are likely to change clinical guidelines in favor of AI-assisted procedures, said Cesare Hassan, MD, PhD, of Humanitas Research Hospital and University in Milan, Italy.

For their research, Dr. Hassan and his colleagues looked at results from 21 trials randomizing more than 18,000 patients to colonoscopy with computer-aided detection (CADe) or standard colonoscopy. Colonoscopy could be carried out for screening, surveillance, or diagnostic purposes. The included trials, which were all published in 2019 or later, took place in Asia, North America, and Europe. In most of the studies endoscopists were not blinded to treatment allocation.

The adenoma detection rate, or the proportion of individuals undergoing colonoscopy who had at least one adenoma detected and removed, was 44% in the CADe arms, compared with 35.9% assigned to standard care (relative risk [RR], 1.24; 95% CI, 1.16-1.33). The CADe patients also saw more non-neoplastic polyps removed: 0.52 per colonoscopy, compared with 0.34 for standard care. The increased adenoma detection rate appeared to be driven by a 55% decrease in the error or miss rate of adenomas at per-polyp analysis, the investigators wrote in their paper.

CADe did not increase the number of advanced adenomas (defined as greater than 10 mm, with high-grade dysplasia and villous histology) detected per colonoscopy. Rather, the benefit was “mainly limited to increased detection of diminutive (≤5 mm) adenomas,” the investigators wrote. Dr. Hassan commented that the lack of benefit for detecting larger adenomas was expected, as these are easier for endoscopists to identify visually.

The key limitation of the meta-analysis, Dr. Hassan said, was the fact that endoscopists in the studies could not be blinded. “We can assume there is a risk of bias in our estimates — that is why we describe the quality of evidence as low or moderate, never high. Through randomization we can control other aspects, especially the prevalence of disease, which avoids a scenario in which the endoscopist opts to treat riskier patients with CADe.” But the possibility of a change in the endoscopist’s performance when using these systems cannot be excluded.

Dr. Hassan commented that quantifying the risks, and costs, of overtreatment linked to CADe would require more investigation. “Any time I remove a polyp there’s a risk of perforation and bleeding,” he noted, though most of the unnecessary resections seen in the meta-analysis were of small hyperplastic polyps considered to be low risk for complications. Use of CADe was associated with only slight increases in procedure time, the investigators found.

In a multicenter Spanish study also published in Annals of Internal Medicine, Carolina Mangas-Sanjuan, MD, PhD, of the Hospital General Universitario Dr. Balmis, Alicante, Spain, and her colleagues looked at computer-aided detection of advanced colorectal neoplasias in a higher-risk cohort and saw little advantage over standard colonoscopy.

This study, which randomized 3,213 subjects, is the largest to date aimed at learning whether AI can improve the detection of advanced lesions. As in Dr. Hassan’s meta-analysis, the researchers did not see significant differences in the rates of detection for these larger lesions. Nor, in this study, did CADe did improve the global adenoma detection rate among the FIT positive individuals undergoing screening.

The detection rate of advanced colorectal neoplasias (advanced adenoma or advanced serrated polyp) was 34.8% with CADe (95% CI, 32.5%-37.2%) and 34.6% for standard colonoscopy (95% CI, 32.2%-36.9%); adjusted risk ratio, 1.01 [95% CI, 0.92-1.10]. The mean number of advanced colorectal neoplasias detected per colonoscopy was 0.54 for the intervention group, compared with 0.52 for standard care. For all adenomas, the detection rate was 64.2% with CADe vs 62% for controls.

Dr. Rodrigo Jover of the Hospital General Universitario Dr. Balmis, the study’s corresponding author, commented to this news organization that “while CADe systems are able to improve detection of small low-risk lesions, these devices are not yet able to detect more significant high-risk lesions. Therefore, there is still room for improvement if these systems are adequately trained with datasets of large, difficult-to-detect lesions.”

In an editorial comment on the Spanish and Italian studies Dennis Shung, MD, PhD of Yale University in New Haven, Connecticut, concluded that “this recent evidence suggests that CADe systems do not meaningfully improve the detection of larger (≥10 mm) clinically significant polyps. This tempers enthusiasm for CADe but does not negate the clear performance benefit for detecting adenomas of all sizes.”

How to integrate the AI systems into real-world practice is the real challenge ahead, Dr. Shung argued, noting that, in contrast to randomized trials, “several recent real-world studies have found no improvement in [adenoma detection rate] when CADe is deployed.” Lower trust in the systems can result in their underutilization, Dr. Shung argued, while higher trust can lead to overreliance. “How lgorithmic systems partner with clinicians and how these should be designed and refined across heterogeneous systems and contexts are necessary questions that must be explored to minimize disruption and lead to real-world effectiveness.”

Dr. Mangas-Sanjuan’s study was funded by a grant from Medtronic; Part of Dr. Hassan’s meta-analysis was supported by a European Commission grant to one co-author. Drs. Shung, Hassan, Manguas-Sanjuan, and Jover declared no financial conflicts of interest.

The current conflict in Israel and Gaza has evoked more questions than answers, existentially and professionally, for mental health professionals.

In the realm of clinical psychology and psychiatry, our primary duty and commitment is (and should be) to the well-being of our patients. Yet, as we find ourselves in an era marked by escalating geopolitical conflict, such as the Israel-Hamas war, probably more aptly titled the Israeli-Hamas-Hezbollah-Houthi war (a clarification that elucidates a later point), clinicians are increasingly confronted with ethical dilemmas that extend far beyond what is outlined in our code of ethics.

Dr. Feldman

These challenges are not only impacting us on a personal level but are also spilling over into our professional lives, creating a divisive and non-collegial environment within the healthcare community. We commit to “do no harm” when delivering care and yet we are doing harm to one another as colleagues.

We are no strangers to the complexities of human behavior and the intricate tapestry of emotions that are involved with our professional work. However, the current geopolitical landscape has added an extra layer of difficulty to our already taxing professional lives. We are, after all, human first with unconscious drives that govern how we negotiate cognitive dissonance and our need for the illusion of absolute justice as Yuval Noah Harari explains in a recent podcast.

Humans are notoriously bad at holding the multiplicity of experience in mind and various (often competing narratives) that impede the capacity for nuanced thinking. We would like to believe we are better and more capable than the average person in doing so, but divisiveness in our profession has become disturbingly pronounced, making it essential for us to carve out reflective space, more than ever.
 

The personal and professional divide

Geopolitical conflicts like the current war have a unique capacity to ignite strong emotions and deeply held convictions. It’s not hard to quickly become embroiled in passionate and engaged debate.

While discussion and discourse are healthy, these are bleeding into professional spheres, creating rifts within our clinical communities and contributing to a culture where not everyone feels safe. Look at any professional listserv in medicine or psychology and you will find the evidence. It should be an immediate call to action that we need to be fostering a different type of environment.

The impact of divisiveness is profound, hindering opportunities for collaboration, mentorship, and the free exchange of ideas among clinicians. It may lead to misunderstandings, mistrust, and an erosion of the support systems we rely on, ultimately diverting energy away from the pursuit of providing quality patient-care.
 

Balancing obligations and limits

Because of the inherent power differential that accompanies being in a provider role (physician and psychologist alike), we have a social and moral responsibility to be mindful of what we share – for the sake of humanity. There is an implicit assumption that a provider’s guidance should be adhered to and respected. In other words, words carry tremendous weight and deeply matter, and people in the general public ascribe significant meaning to messages put out by professionals.

When providers steer from their lanes of professional expertise to provide the general public with opinions or recommendations on nonmedical topics, problematic precedents can be set. We may be doing people a disservice.

Unfortunately, I have heard several anecdotes about clinicians who spend their patient’s time in session pushing their own ideological agendas. The patient-provider relationship is founded on principles of trust, empathy, and collaboration, with the primary goal of improving overall well-being and addressing a specific presenting problem. Of course, issues emerge that need to be addressed outside of the initial scope of treatment, an inherent part of the process. However, a grave concern emerges when clinicians initiate dialogue that is not meaningful to a patient, disclose and discuss their personal ideologies, or put pressure on patients to explain their beliefs in an attempt to change the patients’ minds.

Clinicians pushing their own agenda during patient sessions is antithetical to the objectives of psychotherapy and compromises the therapeutic alliance by diverting the focus of care in a way that serves the clinician rather than the client. It is quite the opposite of the patient-centered care that we strive for in training and practice.

Even within one’s theoretical professional scope of competence, I have seen the impact of emotions running high during this conflict, and have witnessed trained professionals making light of, or even mocking, hostages and their behavior upon release. These are care providers who could elucidate the complexities of captor-captive dynamics and the impact of trauma for the general public, yet they are contributing to dangerous perceptions and divisiveness.

I have also seen providers justify sexual violence, diminishing survivor and witness testimony due to ideological differences and strong personal beliefs. This is harmful to those impacted and does a disservice to our profession at large. In a helping profession we should strive to support and advocate for anyone who has been maltreated or experienced any form of victimization, violence, or abuse. This should be a professional standard.

As clinicians, we have an ethical obligation to uphold the well-being, autonomy, and dignity of our patients — and humanity. It is crucial to recognize the limits of our expertise and the ethical concerns that can arise in light of geopolitical conflict. How can we balance our duty to provide psychological support while also being cautious about delving into the realms of political analysis, foreign policy, or international relations?

The pitfalls of well-intentioned speaking out

In the age of social media and instant communication, a critical aspect to consider is the role of speaking out. The point I made above, in naming all partaking in the current conflict, speaks to this issue.

As providers and programs, we must be mindful of the inadvertent harm that can arise from making brief, underdeveloped, uninformed, or emotionally charged statements. Expressing opinions without a solid understanding of the historical, cultural, and political nuances of a conflict can contribute to misinformation and further polarization.

Anecdotally, there appears to be some significant degree of bias emerging within professional fields (e.g., psychology, medicine) and an innate calling for providers to “weigh in” as the war continues. Obviously, physicians and psychologists are trained to provide care and to be humanistic and empathic, but the majority do not have expertise in geopolitics or a nuanced awareness of the complexities of the conflict in the Middle East.

While hearts may be in the right place, issuing statements on complicated humanitarian/political situations can inadvertently have unintended and harmful consequences (in terms of antisemitism and islamophobia, increased incidence of hate crimes, and colleagues not feeling safe within professional societies or member organizations).

Unsophisticated, overly simplistic, and reductionistic statements that do not adequately convey nuance will not reflect the range of experience reflected by providers in the field (or the patients we treat). It is essential for clinicians and institutions putting out public statements to engage in deep reflection and utilize discernment. We must recognize that our words carry weight, given our position of influence as treatment providers. To minimize harm, we should seek to provide information that is fair, vetted, and balanced, and encourage open, respectful dialogue rather than asserting definitive positions.

Ultimately, as providers we must strive to seek unity and inclusivity amidst the current challenges. It is important for us to embody a spirit of collaboration during a time demarcated by deep fragmentation.

By acknowledging our limitations, promoting informed discussion, and avoiding the pitfalls of uninformed advocacy, we can contribute to a more compassionate and understanding world, even in the face of the most divisive geopolitical conflicts. We have an obligation to uphold when it comes to ourselves as professionals, and we need to foster healthy, respectful dialogue while maintaining an awareness of our blind spots.

Dr. Feldman is a licensed clinical psychologist in private practice in Miami. She is an adjunct professor in the College of Psychology at Nova Southeastern University, Fort Lauderdale, Fla., where she teaches clinical psychology doctoral students. She is an affiliate of Baptist West Kendall Hospital/FIU Family Medicine Residency Program and serves as president on the board of directors of The Southeast Florida Association for Psychoanalytic Psychology. The opinions expressed by Dr. Feldman are her own and do not represent the institutions with which she is affiliated. She has no disclosures.

The current conflict in Israel and Gaza has evoked more questions than answers, existentially and professionally, for mental health professionals.

In the realm of clinical psychology and psychiatry, our primary duty and commitment is (and should be) to the well-being of our patients. Yet, as we find ourselves in an era marked by escalating geopolitical conflict, such as the Israel-Hamas war, probably more aptly titled the Israeli-Hamas-Hezbollah-Houthi war (a clarification that elucidates a later point), clinicians are increasingly confronted with ethical dilemmas that extend far beyond what is outlined in our code of ethics.

Dr. Feldman

These challenges are not only impacting us on a personal level but are also spilling over into our professional lives, creating a divisive and non-collegial environment within the healthcare community. We commit to “do no harm” when delivering care and yet we are doing harm to one another as colleagues.

We are no strangers to the complexities of human behavior and the intricate tapestry of emotions that are involved with our professional work. However, the current geopolitical landscape has added an extra layer of difficulty to our already taxing professional lives. We are, after all, human first with unconscious drives that govern how we negotiate cognitive dissonance and our need for the illusion of absolute justice as Yuval Noah Harari explains in a recent podcast.

Humans are notoriously bad at holding the multiplicity of experience in mind and various (often competing narratives) that impede the capacity for nuanced thinking. We would like to believe we are better and more capable than the average person in doing so, but divisiveness in our profession has become disturbingly pronounced, making it essential for us to carve out reflective space, more than ever.
 

The personal and professional divide

Geopolitical conflicts like the current war have a unique capacity to ignite strong emotions and deeply held convictions. It’s not hard to quickly become embroiled in passionate and engaged debate.

While discussion and discourse are healthy, these are bleeding into professional spheres, creating rifts within our clinical communities and contributing to a culture where not everyone feels safe. Look at any professional listserv in medicine or psychology and you will find the evidence. It should be an immediate call to action that we need to be fostering a different type of environment.

The impact of divisiveness is profound, hindering opportunities for collaboration, mentorship, and the free exchange of ideas among clinicians. It may lead to misunderstandings, mistrust, and an erosion of the support systems we rely on, ultimately diverting energy away from the pursuit of providing quality patient-care.
 

Balancing obligations and limits

Because of the inherent power differential that accompanies being in a provider role (physician and psychologist alike), we have a social and moral responsibility to be mindful of what we share – for the sake of humanity. There is an implicit assumption that a provider’s guidance should be adhered to and respected. In other words, words carry tremendous weight and deeply matter, and people in the general public ascribe significant meaning to messages put out by professionals.

When providers steer from their lanes of professional expertise to provide the general public with opinions or recommendations on nonmedical topics, problematic precedents can be set. We may be doing people a disservice.

Unfortunately, I have heard several anecdotes about clinicians who spend their patient’s time in session pushing their own ideological agendas. The patient-provider relationship is founded on principles of trust, empathy, and collaboration, with the primary goal of improving overall well-being and addressing a specific presenting problem. Of course, issues emerge that need to be addressed outside of the initial scope of treatment, an inherent part of the process. However, a grave concern emerges when clinicians initiate dialogue that is not meaningful to a patient, disclose and discuss their personal ideologies, or put pressure on patients to explain their beliefs in an attempt to change the patients’ minds.

Clinicians pushing their own agenda during patient sessions is antithetical to the objectives of psychotherapy and compromises the therapeutic alliance by diverting the focus of care in a way that serves the clinician rather than the client. It is quite the opposite of the patient-centered care that we strive for in training and practice.

Even within one’s theoretical professional scope of competence, I have seen the impact of emotions running high during this conflict, and have witnessed trained professionals making light of, or even mocking, hostages and their behavior upon release. These are care providers who could elucidate the complexities of captor-captive dynamics and the impact of trauma for the general public, yet they are contributing to dangerous perceptions and divisiveness.

I have also seen providers justify sexual violence, diminishing survivor and witness testimony due to ideological differences and strong personal beliefs. This is harmful to those impacted and does a disservice to our profession at large. In a helping profession we should strive to support and advocate for anyone who has been maltreated or experienced any form of victimization, violence, or abuse. This should be a professional standard.

As clinicians, we have an ethical obligation to uphold the well-being, autonomy, and dignity of our patients — and humanity. It is crucial to recognize the limits of our expertise and the ethical concerns that can arise in light of geopolitical conflict. How can we balance our duty to provide psychological support while also being cautious about delving into the realms of political analysis, foreign policy, or international relations?

The pitfalls of well-intentioned speaking out

In the age of social media and instant communication, a critical aspect to consider is the role of speaking out. The point I made above, in naming all partaking in the current conflict, speaks to this issue.

As providers and programs, we must be mindful of the inadvertent harm that can arise from making brief, underdeveloped, uninformed, or emotionally charged statements. Expressing opinions without a solid understanding of the historical, cultural, and political nuances of a conflict can contribute to misinformation and further polarization.

Anecdotally, there appears to be some significant degree of bias emerging within professional fields (e.g., psychology, medicine) and an innate calling for providers to “weigh in” as the war continues. Obviously, physicians and psychologists are trained to provide care and to be humanistic and empathic, but the majority do not have expertise in geopolitics or a nuanced awareness of the complexities of the conflict in the Middle East.

While hearts may be in the right place, issuing statements on complicated humanitarian/political situations can inadvertently have unintended and harmful consequences (in terms of antisemitism and islamophobia, increased incidence of hate crimes, and colleagues not feeling safe within professional societies or member organizations).

Unsophisticated, overly simplistic, and reductionistic statements that do not adequately convey nuance will not reflect the range of experience reflected by providers in the field (or the patients we treat). It is essential for clinicians and institutions putting out public statements to engage in deep reflection and utilize discernment. We must recognize that our words carry weight, given our position of influence as treatment providers. To minimize harm, we should seek to provide information that is fair, vetted, and balanced, and encourage open, respectful dialogue rather than asserting definitive positions.

Ultimately, as providers we must strive to seek unity and inclusivity amidst the current challenges. It is important for us to embody a spirit of collaboration during a time demarcated by deep fragmentation.

By acknowledging our limitations, promoting informed discussion, and avoiding the pitfalls of uninformed advocacy, we can contribute to a more compassionate and understanding world, even in the face of the most divisive geopolitical conflicts. We have an obligation to uphold when it comes to ourselves as professionals, and we need to foster healthy, respectful dialogue while maintaining an awareness of our blind spots.

Dr. Feldman is a licensed clinical psychologist in private practice in Miami. She is an adjunct professor in the College of Psychology at Nova Southeastern University, Fort Lauderdale, Fla., where she teaches clinical psychology doctoral students. She is an affiliate of Baptist West Kendall Hospital/FIU Family Medicine Residency Program and serves as president on the board of directors of The Southeast Florida Association for Psychoanalytic Psychology. The opinions expressed by Dr. Feldman are her own and do not represent the institutions with which she is affiliated. She has no disclosures.

The current conflict in Israel and Gaza has evoked more questions than answers, existentially and professionally, for mental health professionals.

In the realm of clinical psychology and psychiatry, our primary duty and commitment is (and should be) to the well-being of our patients. Yet, as we find ourselves in an era marked by escalating geopolitical conflict, such as the Israel-Hamas war, probably more aptly titled the Israeli-Hamas-Hezbollah-Houthi war (a clarification that elucidates a later point), clinicians are increasingly confronted with ethical dilemmas that extend far beyond what is outlined in our code of ethics.

Dr. Feldman

These challenges are not only impacting us on a personal level but are also spilling over into our professional lives, creating a divisive and non-collegial environment within the healthcare community. We commit to “do no harm” when delivering care and yet we are doing harm to one another as colleagues.

We are no strangers to the complexities of human behavior and the intricate tapestry of emotions that are involved with our professional work. However, the current geopolitical landscape has added an extra layer of difficulty to our already taxing professional lives. We are, after all, human first with unconscious drives that govern how we negotiate cognitive dissonance and our need for the illusion of absolute justice as Yuval Noah Harari explains in a recent podcast.

Humans are notoriously bad at holding the multiplicity of experience in mind and various (often competing narratives) that impede the capacity for nuanced thinking. We would like to believe we are better and more capable than the average person in doing so, but divisiveness in our profession has become disturbingly pronounced, making it essential for us to carve out reflective space, more than ever.
 

The personal and professional divide

Geopolitical conflicts like the current war have a unique capacity to ignite strong emotions and deeply held convictions. It’s not hard to quickly become embroiled in passionate and engaged debate.

While discussion and discourse are healthy, these are bleeding into professional spheres, creating rifts within our clinical communities and contributing to a culture where not everyone feels safe. Look at any professional listserv in medicine or psychology and you will find the evidence. It should be an immediate call to action that we need to be fostering a different type of environment.

The impact of divisiveness is profound, hindering opportunities for collaboration, mentorship, and the free exchange of ideas among clinicians. It may lead to misunderstandings, mistrust, and an erosion of the support systems we rely on, ultimately diverting energy away from the pursuit of providing quality patient-care.
 

Balancing obligations and limits

Because of the inherent power differential that accompanies being in a provider role (physician and psychologist alike), we have a social and moral responsibility to be mindful of what we share – for the sake of humanity. There is an implicit assumption that a provider’s guidance should be adhered to and respected. In other words, words carry tremendous weight and deeply matter, and people in the general public ascribe significant meaning to messages put out by professionals.

When providers steer from their lanes of professional expertise to provide the general public with opinions or recommendations on nonmedical topics, problematic precedents can be set. We may be doing people a disservice.

Unfortunately, I have heard several anecdotes about clinicians who spend their patient’s time in session pushing their own ideological agendas. The patient-provider relationship is founded on principles of trust, empathy, and collaboration, with the primary goal of improving overall well-being and addressing a specific presenting problem. Of course, issues emerge that need to be addressed outside of the initial scope of treatment, an inherent part of the process. However, a grave concern emerges when clinicians initiate dialogue that is not meaningful to a patient, disclose and discuss their personal ideologies, or put pressure on patients to explain their beliefs in an attempt to change the patients’ minds.

Clinicians pushing their own agenda during patient sessions is antithetical to the objectives of psychotherapy and compromises the therapeutic alliance by diverting the focus of care in a way that serves the clinician rather than the client. It is quite the opposite of the patient-centered care that we strive for in training and practice.

Even within one’s theoretical professional scope of competence, I have seen the impact of emotions running high during this conflict, and have witnessed trained professionals making light of, or even mocking, hostages and their behavior upon release. These are care providers who could elucidate the complexities of captor-captive dynamics and the impact of trauma for the general public, yet they are contributing to dangerous perceptions and divisiveness.

I have also seen providers justify sexual violence, diminishing survivor and witness testimony due to ideological differences and strong personal beliefs. This is harmful to those impacted and does a disservice to our profession at large. In a helping profession we should strive to support and advocate for anyone who has been maltreated or experienced any form of victimization, violence, or abuse. This should be a professional standard.

As clinicians, we have an ethical obligation to uphold the well-being, autonomy, and dignity of our patients — and humanity. It is crucial to recognize the limits of our expertise and the ethical concerns that can arise in light of geopolitical conflict. How can we balance our duty to provide psychological support while also being cautious about delving into the realms of political analysis, foreign policy, or international relations?

The pitfalls of well-intentioned speaking out

In the age of social media and instant communication, a critical aspect to consider is the role of speaking out. The point I made above, in naming all partaking in the current conflict, speaks to this issue.

As providers and programs, we must be mindful of the inadvertent harm that can arise from making brief, underdeveloped, uninformed, or emotionally charged statements. Expressing opinions without a solid understanding of the historical, cultural, and political nuances of a conflict can contribute to misinformation and further polarization.

Anecdotally, there appears to be some significant degree of bias emerging within professional fields (e.g., psychology, medicine) and an innate calling for providers to “weigh in” as the war continues. Obviously, physicians and psychologists are trained to provide care and to be humanistic and empathic, but the majority do not have expertise in geopolitics or a nuanced awareness of the complexities of the conflict in the Middle East.

While hearts may be in the right place, issuing statements on complicated humanitarian/political situations can inadvertently have unintended and harmful consequences (in terms of antisemitism and islamophobia, increased incidence of hate crimes, and colleagues not feeling safe within professional societies or member organizations).

Unsophisticated, overly simplistic, and reductionistic statements that do not adequately convey nuance will not reflect the range of experience reflected by providers in the field (or the patients we treat). It is essential for clinicians and institutions putting out public statements to engage in deep reflection and utilize discernment. We must recognize that our words carry weight, given our position of influence as treatment providers. To minimize harm, we should seek to provide information that is fair, vetted, and balanced, and encourage open, respectful dialogue rather than asserting definitive positions.

Ultimately, as providers we must strive to seek unity and inclusivity amidst the current challenges. It is important for us to embody a spirit of collaboration during a time demarcated by deep fragmentation.

By acknowledging our limitations, promoting informed discussion, and avoiding the pitfalls of uninformed advocacy, we can contribute to a more compassionate and understanding world, even in the face of the most divisive geopolitical conflicts. We have an obligation to uphold when it comes to ourselves as professionals, and we need to foster healthy, respectful dialogue while maintaining an awareness of our blind spots.

Dr. Feldman is a licensed clinical psychologist in private practice in Miami. She is an adjunct professor in the College of Psychology at Nova Southeastern University, Fort Lauderdale, Fla., where she teaches clinical psychology doctoral students. She is an affiliate of Baptist West Kendall Hospital/FIU Family Medicine Residency Program and serves as president on the board of directors of The Southeast Florida Association for Psychoanalytic Psychology. The opinions expressed by Dr. Feldman are her own and do not represent the institutions with which she is affiliated. She has no disclosures.

SAN ANTONIO — There’s a long-standing debate in breast oncology about what to do when positive axillary lymph nodes turn negative after neoadjuvant chemotherapy.

Do patients still need regional nodal irradiation or can they skip it? 

Currently, it’s about a 50/50 split among oncologists, according to breast cancer surgeon Eleftherios P. Mamounas, MD, medical director of the Comprehensive Breast Program at the Orlando Health Cancer Institute in Florida.

Until now, Dr. Mamounas’s own institution has opted for regional irradiation just to be on the safe side, but he said that’s going to change in the wake of a multicenter trial he presented at the San Antonio Breast Cancer Symposium. 

Dr. Mamounas led a team that randomized 1556 women equally to either regional nodal irradiation or no nodal irradiation following surgery, which was lumpectomy in just over half the subjects and mastectomy in the rest. 

Women were a median of 52 years old. Almost 60% had T2 disease and the rest were split about evenly between T1 and T3 disease. Nearly a quarter of the tumors were triple-negative, and over half were HER2 positive.

In the regional nodal irradiation arm, women who had mastectomies had chest wall irradiation in addition to regional nodal irradiation, while women who underwent lumpectomies had whole breast irradiation with regional nodal irradiation. In the no-irradiation group, mastectomies were followed by observation and lumpectomies by whole breast irradiation alone. 

All the women had positive axillary lymph nodes (N1) on needle biopsies at baseline that were found to be free of cancer at surgery (ypN0) following neoadjuvant chemotherapy. Neoadjuvant therapy consisted of at least 8 weeks of chemotherapy plus anti-HER2 therapy for HER2-positive patients. 

Dr. Mamounas and colleagues observed no meaningful differences in outcomes between the two groups: 92.7% of women in the nodal irradiation arm and 91.8% in the no-irradiation arm were free from invasive recurrences 5 years after surgery.

Patients in both groups demonstrated similar 5-year disease-free survival and overall survival. The 5-year disease-free survival was 88.5% without and 88.3% with regional nodal irradiation and 5-year overall survival was 94% without and 93.6% with regional nodal irradiation.

The team did not observe study-related deaths or unexpected toxicities. Overall, 6.5% of patients without regional nodal irradiation developed grade 3 toxicity vs. 10% of patients with irradiation. Grade 4 toxicity was rare, occurring in 0.1% of patients in the no-irradiation group vs. 0.5% in the irradiation group.

The trial answers “a very important question,” according to Kate Lathrop, MD, a breast medical oncologist at UT Health San Antonio, who moderated the presentation. 

The trial results were “highly awaited” because “we didn’t have the data to make these” decisions, Dr. Lathrop said. 

Knowing these patients do just as well without regional nodal irradiation is “going to change a lot of opinions,” said Dr. Lathrop, because we can avoid subjecting patients to unnecessary toxicity, including lymphedema with regional nodal irradiation as well as problems with breast reconstruction after mastectomy.

Because recurrences can still occur after 5 years, Dr. Mamounas’s team will continue to follow the women, but he believes “it’s very unlikely that long-term distant disease-free survival will change.” 

Based on the study, “we will omit” regional nodal irradiation for women who fit the study criteria, Dr. Mamounas said.

When asked if women should ask their doctors about skipping regional nodal irradiation, Dr. Mamounas said “absolutely.” 

“I think it requires a discussion at this point,” he explained. “Based on the data, it’s a reasonable conclusion that radiotherapy can be avoided” in many cases, such as in lower-stage women with one initially positive node. 

Dr. Mamounas said he thinks patients will be interested in the approach “because they are really looking to avoid radiotherapy” if they can. 

The work was funded by the National Cancer Institute. Dr. Mamounas has been a consultant and speaker for Genentech, Merck, and an adviser for TerSera Therapeutics, Biotheranostics Inc., and Sanofi. He owns stock in Moderna. Dr. Lathrop is a consultant for Pfizer, GE Healthcare, and Biotheranostics, and a speaker for Biotheranostics.
 

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

SAN ANTONIO — There’s a long-standing debate in breast oncology about what to do when positive axillary lymph nodes turn negative after neoadjuvant chemotherapy.

Do patients still need regional nodal irradiation or can they skip it? 

Currently, it’s about a 50/50 split among oncologists, according to breast cancer surgeon Eleftherios P. Mamounas, MD, medical director of the Comprehensive Breast Program at the Orlando Health Cancer Institute in Florida.

Until now, Dr. Mamounas’s own institution has opted for regional irradiation just to be on the safe side, but he said that’s going to change in the wake of a multicenter trial he presented at the San Antonio Breast Cancer Symposium. 

Dr. Mamounas led a team that randomized 1556 women equally to either regional nodal irradiation or no nodal irradiation following surgery, which was lumpectomy in just over half the subjects and mastectomy in the rest. 

Women were a median of 52 years old. Almost 60% had T2 disease and the rest were split about evenly between T1 and T3 disease. Nearly a quarter of the tumors were triple-negative, and over half were HER2 positive.

In the regional nodal irradiation arm, women who had mastectomies had chest wall irradiation in addition to regional nodal irradiation, while women who underwent lumpectomies had whole breast irradiation with regional nodal irradiation. In the no-irradiation group, mastectomies were followed by observation and lumpectomies by whole breast irradiation alone. 

All the women had positive axillary lymph nodes (N1) on needle biopsies at baseline that were found to be free of cancer at surgery (ypN0) following neoadjuvant chemotherapy. Neoadjuvant therapy consisted of at least 8 weeks of chemotherapy plus anti-HER2 therapy for HER2-positive patients. 

Dr. Mamounas and colleagues observed no meaningful differences in outcomes between the two groups: 92.7% of women in the nodal irradiation arm and 91.8% in the no-irradiation arm were free from invasive recurrences 5 years after surgery.

Patients in both groups demonstrated similar 5-year disease-free survival and overall survival. The 5-year disease-free survival was 88.5% without and 88.3% with regional nodal irradiation and 5-year overall survival was 94% without and 93.6% with regional nodal irradiation.

The team did not observe study-related deaths or unexpected toxicities. Overall, 6.5% of patients without regional nodal irradiation developed grade 3 toxicity vs. 10% of patients with irradiation. Grade 4 toxicity was rare, occurring in 0.1% of patients in the no-irradiation group vs. 0.5% in the irradiation group.

The trial answers “a very important question,” according to Kate Lathrop, MD, a breast medical oncologist at UT Health San Antonio, who moderated the presentation. 

The trial results were “highly awaited” because “we didn’t have the data to make these” decisions, Dr. Lathrop said. 

Knowing these patients do just as well without regional nodal irradiation is “going to change a lot of opinions,” said Dr. Lathrop, because we can avoid subjecting patients to unnecessary toxicity, including lymphedema with regional nodal irradiation as well as problems with breast reconstruction after mastectomy.

Because recurrences can still occur after 5 years, Dr. Mamounas’s team will continue to follow the women, but he believes “it’s very unlikely that long-term distant disease-free survival will change.” 

Based on the study, “we will omit” regional nodal irradiation for women who fit the study criteria, Dr. Mamounas said.

When asked if women should ask their doctors about skipping regional nodal irradiation, Dr. Mamounas said “absolutely.” 

“I think it requires a discussion at this point,” he explained. “Based on the data, it’s a reasonable conclusion that radiotherapy can be avoided” in many cases, such as in lower-stage women with one initially positive node. 

Dr. Mamounas said he thinks patients will be interested in the approach “because they are really looking to avoid radiotherapy” if they can. 

The work was funded by the National Cancer Institute. Dr. Mamounas has been a consultant and speaker for Genentech, Merck, and an adviser for TerSera Therapeutics, Biotheranostics Inc., and Sanofi. He owns stock in Moderna. Dr. Lathrop is a consultant for Pfizer, GE Healthcare, and Biotheranostics, and a speaker for Biotheranostics.
 

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

SAN ANTONIO — There’s a long-standing debate in breast oncology about what to do when positive axillary lymph nodes turn negative after neoadjuvant chemotherapy.

Do patients still need regional nodal irradiation or can they skip it? 

Currently, it’s about a 50/50 split among oncologists, according to breast cancer surgeon Eleftherios P. Mamounas, MD, medical director of the Comprehensive Breast Program at the Orlando Health Cancer Institute in Florida.

Until now, Dr. Mamounas’s own institution has opted for regional irradiation just to be on the safe side, but he said that’s going to change in the wake of a multicenter trial he presented at the San Antonio Breast Cancer Symposium. 

Dr. Mamounas led a team that randomized 1556 women equally to either regional nodal irradiation or no nodal irradiation following surgery, which was lumpectomy in just over half the subjects and mastectomy in the rest. 

Women were a median of 52 years old. Almost 60% had T2 disease and the rest were split about evenly between T1 and T3 disease. Nearly a quarter of the tumors were triple-negative, and over half were HER2 positive.

In the regional nodal irradiation arm, women who had mastectomies had chest wall irradiation in addition to regional nodal irradiation, while women who underwent lumpectomies had whole breast irradiation with regional nodal irradiation. In the no-irradiation group, mastectomies were followed by observation and lumpectomies by whole breast irradiation alone. 

All the women had positive axillary lymph nodes (N1) on needle biopsies at baseline that were found to be free of cancer at surgery (ypN0) following neoadjuvant chemotherapy. Neoadjuvant therapy consisted of at least 8 weeks of chemotherapy plus anti-HER2 therapy for HER2-positive patients. 

Dr. Mamounas and colleagues observed no meaningful differences in outcomes between the two groups: 92.7% of women in the nodal irradiation arm and 91.8% in the no-irradiation arm were free from invasive recurrences 5 years after surgery.

Patients in both groups demonstrated similar 5-year disease-free survival and overall survival. The 5-year disease-free survival was 88.5% without and 88.3% with regional nodal irradiation and 5-year overall survival was 94% without and 93.6% with regional nodal irradiation.

The team did not observe study-related deaths or unexpected toxicities. Overall, 6.5% of patients without regional nodal irradiation developed grade 3 toxicity vs. 10% of patients with irradiation. Grade 4 toxicity was rare, occurring in 0.1% of patients in the no-irradiation group vs. 0.5% in the irradiation group.

The trial answers “a very important question,” according to Kate Lathrop, MD, a breast medical oncologist at UT Health San Antonio, who moderated the presentation. 

The trial results were “highly awaited” because “we didn’t have the data to make these” decisions, Dr. Lathrop said. 

Knowing these patients do just as well without regional nodal irradiation is “going to change a lot of opinions,” said Dr. Lathrop, because we can avoid subjecting patients to unnecessary toxicity, including lymphedema with regional nodal irradiation as well as problems with breast reconstruction after mastectomy.

Because recurrences can still occur after 5 years, Dr. Mamounas’s team will continue to follow the women, but he believes “it’s very unlikely that long-term distant disease-free survival will change.” 

Based on the study, “we will omit” regional nodal irradiation for women who fit the study criteria, Dr. Mamounas said.

When asked if women should ask their doctors about skipping regional nodal irradiation, Dr. Mamounas said “absolutely.” 

“I think it requires a discussion at this point,” he explained. “Based on the data, it’s a reasonable conclusion that radiotherapy can be avoided” in many cases, such as in lower-stage women with one initially positive node. 

Dr. Mamounas said he thinks patients will be interested in the approach “because they are really looking to avoid radiotherapy” if they can. 

The work was funded by the National Cancer Institute. Dr. Mamounas has been a consultant and speaker for Genentech, Merck, and an adviser for TerSera Therapeutics, Biotheranostics Inc., and Sanofi. He owns stock in Moderna. Dr. Lathrop is a consultant for Pfizer, GE Healthcare, and Biotheranostics, and a speaker for Biotheranostics.
 

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

SAN ANTONIO — Breast cancer care can cause significant financial stress for patients, but certain interventions may help patients cope with these financial burdens, new survey findings show. 

Almost half of patients surveyed reported a “significant” or “catastrophic” financial burden related to their breast cancer care. But patients also found a range of resources helpful for minimizing this burden, including direct assistance programs that reduce the cost of medications, grants from nonprofits that can cover cancer-related expenses, as well as programs that offer free or low-cost transportation to medical appointments. 

Financial toxicity remains a “pervasive problem in the breast cancer community and we really need to go to the next step, which is designing patient-centered, patient-facing interventions to make improvements,” Fumiko Chino, MD, with Memorial Sloan Kettering Cancer Center in New York City, said when presenting the survey results at the San Antonio Breast Cancer Symposium. 

A growing body of evidence shows that cancer care, especially for breast cancer, can take a heavy financial toll on patients. However, routine screening for financial toxicity is not necessarily a routine part of clinical care, and providers may not know the types of financial assistance patients value most, Dr. Chino explained.

Dr. Chino and colleagues surveyed 1437 women with breast cancer about their level of financial distress as well as the specific interventions or education initiatives they found most helpful.

Most patients (60%) were White, 27% were Hispanic, and 8% Black. Three quarters of patients were on active treatments, 89% had nonmetastatic disease, and 11% had metastatic disease.

Overall, 47% of patients reported a significant or catastrophic financial burden related to their breast cancer diagnosis and care. This burden was higher for those with metastatic disease (61% vs 45%).

Patients assessed 10 strategies for coping with the financial burdens of care. The top-rated interventions included patient assistance programs offered by pharmaceutical or medical test companies, rated highly by 32% of respondents, and grants from nonprofits, rated highly by 31% of respondents. Patients also found financial assistance departments at cancer centers or hospitals helpful (29%); coupons and savings cards to reduce the cost of prescription drugs (28%); and programs that provide free or low-cost transportation to medical appointments (28%).

In terms of education, respondents said having a checklist of questions to ask their oncology team as well as a list of breast cancer-specific financial grants to apply for would be especially helpful when navigating the financial burdens of breast cancer care.

These preferences, however, did vary by race/ethnicity and disease status. Hispanic patients, for instance, found patient assistance programs offered by companies and cancer centers as well as transportation assistance more helpful than other groups. 

Patients with metastatic disease found patient assistance programs offered by medical companies particularly helpful compared with patients with nonmetastatic disease. And compared with patients with metastatic disease, those with nonmetastatic breast cancer found assistance through clinical trials and professional medical billing advocates helpful.

This study confirms the high rates of financial burden in women with breast cancer and clearly demonstrates that intervention preferences vary by sociodemographic and clinical characteristics, study discussant Claire C. Conley, PhD, from Georgetown University, Washington, DC, commented.

“This highlights that one size really doesn’t fit all when it comes to those financial burden interventions,” Dr. Conley said. “We need to think about factors at the patient level, the organizational level, and the environment level.”

The study had no commercial funding. Dr. Chino and Dr. Conley have disclosed no relevant financial relationships.

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

SAN ANTONIO — Breast cancer care can cause significant financial stress for patients, but certain interventions may help patients cope with these financial burdens, new survey findings show. 

Almost half of patients surveyed reported a “significant” or “catastrophic” financial burden related to their breast cancer care. But patients also found a range of resources helpful for minimizing this burden, including direct assistance programs that reduce the cost of medications, grants from nonprofits that can cover cancer-related expenses, as well as programs that offer free or low-cost transportation to medical appointments. 

Financial toxicity remains a “pervasive problem in the breast cancer community and we really need to go to the next step, which is designing patient-centered, patient-facing interventions to make improvements,” Fumiko Chino, MD, with Memorial Sloan Kettering Cancer Center in New York City, said when presenting the survey results at the San Antonio Breast Cancer Symposium. 

A growing body of evidence shows that cancer care, especially for breast cancer, can take a heavy financial toll on patients. However, routine screening for financial toxicity is not necessarily a routine part of clinical care, and providers may not know the types of financial assistance patients value most, Dr. Chino explained.

Dr. Chino and colleagues surveyed 1437 women with breast cancer about their level of financial distress as well as the specific interventions or education initiatives they found most helpful.

Most patients (60%) were White, 27% were Hispanic, and 8% Black. Three quarters of patients were on active treatments, 89% had nonmetastatic disease, and 11% had metastatic disease.

Overall, 47% of patients reported a significant or catastrophic financial burden related to their breast cancer diagnosis and care. This burden was higher for those with metastatic disease (61% vs 45%).

Patients assessed 10 strategies for coping with the financial burdens of care. The top-rated interventions included patient assistance programs offered by pharmaceutical or medical test companies, rated highly by 32% of respondents, and grants from nonprofits, rated highly by 31% of respondents. Patients also found financial assistance departments at cancer centers or hospitals helpful (29%); coupons and savings cards to reduce the cost of prescription drugs (28%); and programs that provide free or low-cost transportation to medical appointments (28%).

In terms of education, respondents said having a checklist of questions to ask their oncology team as well as a list of breast cancer-specific financial grants to apply for would be especially helpful when navigating the financial burdens of breast cancer care.

These preferences, however, did vary by race/ethnicity and disease status. Hispanic patients, for instance, found patient assistance programs offered by companies and cancer centers as well as transportation assistance more helpful than other groups. 

Patients with metastatic disease found patient assistance programs offered by medical companies particularly helpful compared with patients with nonmetastatic disease. And compared with patients with metastatic disease, those with nonmetastatic breast cancer found assistance through clinical trials and professional medical billing advocates helpful.

This study confirms the high rates of financial burden in women with breast cancer and clearly demonstrates that intervention preferences vary by sociodemographic and clinical characteristics, study discussant Claire C. Conley, PhD, from Georgetown University, Washington, DC, commented.

“This highlights that one size really doesn’t fit all when it comes to those financial burden interventions,” Dr. Conley said. “We need to think about factors at the patient level, the organizational level, and the environment level.”

The study had no commercial funding. Dr. Chino and Dr. Conley have disclosed no relevant financial relationships.

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

SAN ANTONIO — Breast cancer care can cause significant financial stress for patients, but certain interventions may help patients cope with these financial burdens, new survey findings show. 

Almost half of patients surveyed reported a “significant” or “catastrophic” financial burden related to their breast cancer care. But patients also found a range of resources helpful for minimizing this burden, including direct assistance programs that reduce the cost of medications, grants from nonprofits that can cover cancer-related expenses, as well as programs that offer free or low-cost transportation to medical appointments. 

Financial toxicity remains a “pervasive problem in the breast cancer community and we really need to go to the next step, which is designing patient-centered, patient-facing interventions to make improvements,” Fumiko Chino, MD, with Memorial Sloan Kettering Cancer Center in New York City, said when presenting the survey results at the San Antonio Breast Cancer Symposium. 

A growing body of evidence shows that cancer care, especially for breast cancer, can take a heavy financial toll on patients. However, routine screening for financial toxicity is not necessarily a routine part of clinical care, and providers may not know the types of financial assistance patients value most, Dr. Chino explained.

Dr. Chino and colleagues surveyed 1437 women with breast cancer about their level of financial distress as well as the specific interventions or education initiatives they found most helpful.

Most patients (60%) were White, 27% were Hispanic, and 8% Black. Three quarters of patients were on active treatments, 89% had nonmetastatic disease, and 11% had metastatic disease.

Overall, 47% of patients reported a significant or catastrophic financial burden related to their breast cancer diagnosis and care. This burden was higher for those with metastatic disease (61% vs 45%).

Patients assessed 10 strategies for coping with the financial burdens of care. The top-rated interventions included patient assistance programs offered by pharmaceutical or medical test companies, rated highly by 32% of respondents, and grants from nonprofits, rated highly by 31% of respondents. Patients also found financial assistance departments at cancer centers or hospitals helpful (29%); coupons and savings cards to reduce the cost of prescription drugs (28%); and programs that provide free or low-cost transportation to medical appointments (28%).

In terms of education, respondents said having a checklist of questions to ask their oncology team as well as a list of breast cancer-specific financial grants to apply for would be especially helpful when navigating the financial burdens of breast cancer care.

These preferences, however, did vary by race/ethnicity and disease status. Hispanic patients, for instance, found patient assistance programs offered by companies and cancer centers as well as transportation assistance more helpful than other groups. 

Patients with metastatic disease found patient assistance programs offered by medical companies particularly helpful compared with patients with nonmetastatic disease. And compared with patients with metastatic disease, those with nonmetastatic breast cancer found assistance through clinical trials and professional medical billing advocates helpful.

This study confirms the high rates of financial burden in women with breast cancer and clearly demonstrates that intervention preferences vary by sociodemographic and clinical characteristics, study discussant Claire C. Conley, PhD, from Georgetown University, Washington, DC, commented.

“This highlights that one size really doesn’t fit all when it comes to those financial burden interventions,” Dr. Conley said. “We need to think about factors at the patient level, the organizational level, and the environment level.”

The study had no commercial funding. Dr. Chino and Dr. Conley have disclosed no relevant financial relationships.

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

Long-term data showed negligible differences in mortality among hypertensive adults treated with thiazide-type diuretics, calcium channel blockers, or angiotensin-converting enzyme inhibitors in a review of nearly 33,000 individuals published in JAMA Network Open.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study was designed to compare initial antihypertensive treatments with a calcium channel blocker (CCB; amlodipine), an angiotensin-converting enzyme (ACE) inhibitor (lisinopril) or an alpha-blocker (doxazosin), and a thiazide-type diuretic (chlorthalidone).

The composite primary outcome was fatal coronary heart disease (CHD) or nonfatal myocardial infarction (MI), but long-term data were lacking, wrote Jose-Miguel Yamal, PhD, of University of Texas Health Science Center at Houston, and colleagues. A previous study with 8-13 years of follow-up showed no significant differences in mortality between the treatment groups, the researchers noted.

In the current study, a prespecified secondary analysis of ALLHAT, the researchers added 11 more years of data for a total of 19-24 years of follow-up after randomization.

In the original ALLHAT, 32,804 adults aged 55 years and older with a diagnosis of hypertension and at least one additional coronary heart disease risk factor were followed for 4-8 years for all-cause mortality. A subgroup of 22,754 were followed for fatal or nonfatal cardiovascular disease (CVD) for a mean of 13.7 years, with a maximum of 23.9 years.

The study occurred from Feb. 23, 1994, to Dec. 31, 2017. The participants were randomized to receive a thiazide-type diuretic (15,002 patients), a CCB (8,898 patients), or an ACE inhibitor (8,904 patients).

The primary outcome was CVD mortality; secondary outcomes included all-cause mortality, combined fatal and nonfatal CVD (CVD morbidity), and both morbidity and mortality for coronary heart disease, stroke, heart failure, end-stage renal disease, and cancer.

At 23 years, CVD mortality rates per 100 persons were 23.7, 21.6, and 23.8 in the diuretic, CCB, and ACE inhibitor groups, respectively. The adjusted hazard ratios were 0.97 for CCB vs. diuretics and 1.06 for ACE inhibitors vs. diuretics.

Although the risk of stroke mortality and of combined fatal and nonfatal hospitalized stroke was higher in the ACE inhibitor group compared with the diuretic group (adjusted hazard ratios 1.19 and 1.11, respectively), this increase was no longer significant after adjustment for multiple comparisons. “In contrast to the in-trial and 8-year to 13-year analyses, we now observed that the lisinopril group had an increased risk of kidney disease mortality that emerged after approximately 13 years after randomization, but this effect was attenuated after adjustment for baseline variables,” the researchers wrote in their discussion.

The findings were limited by several factors including the potential effect of unblinding if participants stopped the randomized drug, and by the lack of morbidity and mortality data on Canadian participants, Veterans Affairs participants, and those with no Medicare number, the researchers noted. Other limitations included the lack of data on posttrial medication use, blood pressure, and laboratory findings, they said.

However, the results over the follow-up period of up to 23 years supported those of the larger ALLHAT study, with similar outcomes among the drugs, and with 11 years of passive follow-up, “the results for lisinopril vs. chlorthalidone for stroke and stroke mortality are almost the same,” they concluded.
 

Findings support current practice, but new drug data are needed

The current study was important to determine whether there was a significant difference in long-term morbidity and mortality between patients treated with thiazide diuretics, calcium channel blockers and ACE inhibitors, Noel Deep, MD, said in an interview.

“Previously reported data had indicated no significant differences between patients randomized to one of these three classes of antihypertensive medications during the trial period or at 8-13 years post trial,” said Dr. Deep, a general internist in private practice in Antigo, Wisc., who was not involved in the study. Dr. Deep is chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

“This study reinforces the previously noted benefits of the three classes of antihypertensive medications, as well as the higher rates of cardiovascular disease and stroke in the ACE inhibitor arm,” he said.

In clinical practice, the results suggest that thiazide diuretics should be considered first-line agents for management of hypertension based on their noninferiority compared with ACE inhibitors and CCBs, and lower risk of stroke compared with ACE inhibitors, Dr. Deep said in an interview. “All three classes of antihypertensive medications are equally efficacious in blood pressure control and preventing all-cause mortality,” he said.

More research is needed in the wake of the introduction of other classes of antihypertensives since the original ALLHAT trial, Dr. Deep said. “It would be beneficial to assess the relative benefit/risks of those medications compared to the thiazide diuretics, and I would also look at studies comparing beta blockers to the thiazide diuretics,” he said. The question remains as to whether outcomes were affected by patients’ use of other classes of antihypertensives after the trial period, he said.

The study was supported by the National Institute on Aging of the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose and serves on the editorial advisory board of Internal Medicine News.

Long-term data showed negligible differences in mortality among hypertensive adults treated with thiazide-type diuretics, calcium channel blockers, or angiotensin-converting enzyme inhibitors in a review of nearly 33,000 individuals published in JAMA Network Open.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study was designed to compare initial antihypertensive treatments with a calcium channel blocker (CCB; amlodipine), an angiotensin-converting enzyme (ACE) inhibitor (lisinopril) or an alpha-blocker (doxazosin), and a thiazide-type diuretic (chlorthalidone).

The composite primary outcome was fatal coronary heart disease (CHD) or nonfatal myocardial infarction (MI), but long-term data were lacking, wrote Jose-Miguel Yamal, PhD, of University of Texas Health Science Center at Houston, and colleagues. A previous study with 8-13 years of follow-up showed no significant differences in mortality between the treatment groups, the researchers noted.

In the current study, a prespecified secondary analysis of ALLHAT, the researchers added 11 more years of data for a total of 19-24 years of follow-up after randomization.

In the original ALLHAT, 32,804 adults aged 55 years and older with a diagnosis of hypertension and at least one additional coronary heart disease risk factor were followed for 4-8 years for all-cause mortality. A subgroup of 22,754 were followed for fatal or nonfatal cardiovascular disease (CVD) for a mean of 13.7 years, with a maximum of 23.9 years.

The study occurred from Feb. 23, 1994, to Dec. 31, 2017. The participants were randomized to receive a thiazide-type diuretic (15,002 patients), a CCB (8,898 patients), or an ACE inhibitor (8,904 patients).

The primary outcome was CVD mortality; secondary outcomes included all-cause mortality, combined fatal and nonfatal CVD (CVD morbidity), and both morbidity and mortality for coronary heart disease, stroke, heart failure, end-stage renal disease, and cancer.

At 23 years, CVD mortality rates per 100 persons were 23.7, 21.6, and 23.8 in the diuretic, CCB, and ACE inhibitor groups, respectively. The adjusted hazard ratios were 0.97 for CCB vs. diuretics and 1.06 for ACE inhibitors vs. diuretics.

Although the risk of stroke mortality and of combined fatal and nonfatal hospitalized stroke was higher in the ACE inhibitor group compared with the diuretic group (adjusted hazard ratios 1.19 and 1.11, respectively), this increase was no longer significant after adjustment for multiple comparisons. “In contrast to the in-trial and 8-year to 13-year analyses, we now observed that the lisinopril group had an increased risk of kidney disease mortality that emerged after approximately 13 years after randomization, but this effect was attenuated after adjustment for baseline variables,” the researchers wrote in their discussion.

The findings were limited by several factors including the potential effect of unblinding if participants stopped the randomized drug, and by the lack of morbidity and mortality data on Canadian participants, Veterans Affairs participants, and those with no Medicare number, the researchers noted. Other limitations included the lack of data on posttrial medication use, blood pressure, and laboratory findings, they said.

However, the results over the follow-up period of up to 23 years supported those of the larger ALLHAT study, with similar outcomes among the drugs, and with 11 years of passive follow-up, “the results for lisinopril vs. chlorthalidone for stroke and stroke mortality are almost the same,” they concluded.
 

Findings support current practice, but new drug data are needed

The current study was important to determine whether there was a significant difference in long-term morbidity and mortality between patients treated with thiazide diuretics, calcium channel blockers and ACE inhibitors, Noel Deep, MD, said in an interview.

“Previously reported data had indicated no significant differences between patients randomized to one of these three classes of antihypertensive medications during the trial period or at 8-13 years post trial,” said Dr. Deep, a general internist in private practice in Antigo, Wisc., who was not involved in the study. Dr. Deep is chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

“This study reinforces the previously noted benefits of the three classes of antihypertensive medications, as well as the higher rates of cardiovascular disease and stroke in the ACE inhibitor arm,” he said.

In clinical practice, the results suggest that thiazide diuretics should be considered first-line agents for management of hypertension based on their noninferiority compared with ACE inhibitors and CCBs, and lower risk of stroke compared with ACE inhibitors, Dr. Deep said in an interview. “All three classes of antihypertensive medications are equally efficacious in blood pressure control and preventing all-cause mortality,” he said.

More research is needed in the wake of the introduction of other classes of antihypertensives since the original ALLHAT trial, Dr. Deep said. “It would be beneficial to assess the relative benefit/risks of those medications compared to the thiazide diuretics, and I would also look at studies comparing beta blockers to the thiazide diuretics,” he said. The question remains as to whether outcomes were affected by patients’ use of other classes of antihypertensives after the trial period, he said.

The study was supported by the National Institute on Aging of the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose and serves on the editorial advisory board of Internal Medicine News.

Long-term data showed negligible differences in mortality among hypertensive adults treated with thiazide-type diuretics, calcium channel blockers, or angiotensin-converting enzyme inhibitors in a review of nearly 33,000 individuals published in JAMA Network Open.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study was designed to compare initial antihypertensive treatments with a calcium channel blocker (CCB; amlodipine), an angiotensin-converting enzyme (ACE) inhibitor (lisinopril) or an alpha-blocker (doxazosin), and a thiazide-type diuretic (chlorthalidone).

The composite primary outcome was fatal coronary heart disease (CHD) or nonfatal myocardial infarction (MI), but long-term data were lacking, wrote Jose-Miguel Yamal, PhD, of University of Texas Health Science Center at Houston, and colleagues. A previous study with 8-13 years of follow-up showed no significant differences in mortality between the treatment groups, the researchers noted.

In the current study, a prespecified secondary analysis of ALLHAT, the researchers added 11 more years of data for a total of 19-24 years of follow-up after randomization.

In the original ALLHAT, 32,804 adults aged 55 years and older with a diagnosis of hypertension and at least one additional coronary heart disease risk factor were followed for 4-8 years for all-cause mortality. A subgroup of 22,754 were followed for fatal or nonfatal cardiovascular disease (CVD) for a mean of 13.7 years, with a maximum of 23.9 years.

The study occurred from Feb. 23, 1994, to Dec. 31, 2017. The participants were randomized to receive a thiazide-type diuretic (15,002 patients), a CCB (8,898 patients), or an ACE inhibitor (8,904 patients).

The primary outcome was CVD mortality; secondary outcomes included all-cause mortality, combined fatal and nonfatal CVD (CVD morbidity), and both morbidity and mortality for coronary heart disease, stroke, heart failure, end-stage renal disease, and cancer.

At 23 years, CVD mortality rates per 100 persons were 23.7, 21.6, and 23.8 in the diuretic, CCB, and ACE inhibitor groups, respectively. The adjusted hazard ratios were 0.97 for CCB vs. diuretics and 1.06 for ACE inhibitors vs. diuretics.

Although the risk of stroke mortality and of combined fatal and nonfatal hospitalized stroke was higher in the ACE inhibitor group compared with the diuretic group (adjusted hazard ratios 1.19 and 1.11, respectively), this increase was no longer significant after adjustment for multiple comparisons. “In contrast to the in-trial and 8-year to 13-year analyses, we now observed that the lisinopril group had an increased risk of kidney disease mortality that emerged after approximately 13 years after randomization, but this effect was attenuated after adjustment for baseline variables,” the researchers wrote in their discussion.

The findings were limited by several factors including the potential effect of unblinding if participants stopped the randomized drug, and by the lack of morbidity and mortality data on Canadian participants, Veterans Affairs participants, and those with no Medicare number, the researchers noted. Other limitations included the lack of data on posttrial medication use, blood pressure, and laboratory findings, they said.

However, the results over the follow-up period of up to 23 years supported those of the larger ALLHAT study, with similar outcomes among the drugs, and with 11 years of passive follow-up, “the results for lisinopril vs. chlorthalidone for stroke and stroke mortality are almost the same,” they concluded.
 

Findings support current practice, but new drug data are needed

The current study was important to determine whether there was a significant difference in long-term morbidity and mortality between patients treated with thiazide diuretics, calcium channel blockers and ACE inhibitors, Noel Deep, MD, said in an interview.

“Previously reported data had indicated no significant differences between patients randomized to one of these three classes of antihypertensive medications during the trial period or at 8-13 years post trial,” said Dr. Deep, a general internist in private practice in Antigo, Wisc., who was not involved in the study. Dr. Deep is chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

“This study reinforces the previously noted benefits of the three classes of antihypertensive medications, as well as the higher rates of cardiovascular disease and stroke in the ACE inhibitor arm,” he said.

In clinical practice, the results suggest that thiazide diuretics should be considered first-line agents for management of hypertension based on their noninferiority compared with ACE inhibitors and CCBs, and lower risk of stroke compared with ACE inhibitors, Dr. Deep said in an interview. “All three classes of antihypertensive medications are equally efficacious in blood pressure control and preventing all-cause mortality,” he said.

More research is needed in the wake of the introduction of other classes of antihypertensives since the original ALLHAT trial, Dr. Deep said. “It would be beneficial to assess the relative benefit/risks of those medications compared to the thiazide diuretics, and I would also look at studies comparing beta blockers to the thiazide diuretics,” he said. The question remains as to whether outcomes were affected by patients’ use of other classes of antihypertensives after the trial period, he said.

The study was supported by the National Institute on Aging of the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose and serves on the editorial advisory board of Internal Medicine News.

ORLANDO — Older people with epilepsy who live in deprived neighborhoods with lower socioeconomic status, fewer educational opportunities, and less access to health care have poorer memory, executive function, and processing speed than those living in more affluent areas, early research suggests.

Seniors with epilepsy present with multiple comorbidities, including, for example, hypertension and diabetes, and they are at increased risk of developing dementia, said study investigator Anny Reyes, PhD, a postdoctoral scholar at the University of California at San Diego.

Past research has shown neighborhood disadvantage is associated with numerous adverse health outcomes, including an increased risk for developing Alzheimer’s disease and related dementias (ADRD).

“We already know epilepsy on its own increases risks for dementia, and when you add disadvantaged to that, it’s going to increase the risk even more,” said Dr. Reyes.

Neurologists should ask their older patients with epilepsy, many of whom live alone, about food insecurity and access to resources “not just within the hospital system but also within their community,” she said.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Proxy Measure of Disadvantage

The incidence and prevalence of epilepsy increases with age. Older adults represent the fastest growing segment of individuals with epilepsy, said Dr. Reyes.

The new study included 40 patients with focal epilepsy, average age 67 years, from three areas: San Diego, California; Madison, Wisconsin; and Cleveland, Ohio.

Researchers collected clinical and sociodemographic information as well as vascular biomarkers. They also gathered individual-level data, including income, parental education levels, details on childhood upbringing, etc.

Using residential addresses, investigators determined the area deprivation index (ADI) value for study participants. The ADI is a proxy measure for neighborhood-level socioeconomic disadvantage that captures factors such a poverty, employment, housing, and education opportunities.

ADI values range from 1 to 10, with a higher number indicating greater neighborhood disadvantage. About 30% of the cohort had an ADI decile greater than 6.

Researchers divided subjects into Most Disadvantaged (ADI greater than 7) and Least Disadvantaged (AD 7 or less). The two groups were similar with regard to age, education level, and race/ethnicity.

But those from the most disadvantaged areas were younger, taking more antiseizure medications, had fewer years of education, lower levels of father’s education, less personal and family income, and were less likely to be diagnosed with hypertension.

Study subjects completed neuropsychological testing, including:

• Measures of learning (Rey Auditory Verbal Learning Test [RAVLT] Learning Over Trials; Wechsler Memory Scale 4th Edition [WMS-4] Logical Memory [LM] Story B immediate; and WMS-4 Visual Reproduction [VR] immediate)
• Memory (RAVLT delayed recall, WMS-4 LM delayed recall, and WMS-4 VR delayed recall)
• Language (Multilingual Naming Test, Auditory Naming Test, and animal fluency)
• Executive function/processing speed (Letter fluency and Trail-Making Test Parts A and B)

The study found a correlation between higher ADI (most disadvantaged) and poorer performance on learning (Spearman rho: -0.433; 95% CI -0.664 to -0.126; P = .006), memory (r = -0.496; 95% CI -0.707 to -0.205; P = .001), and executive function/processes speed (r = -0.315; 95% CI -0.577 to 0.006; P = .048), but no significant association with language.

Looking at individual-level data, the study found memory and processing speed “were driving the relationship, and again, patients had worse performance when they were coming from the most disadvantaged neighborhoods,” said Dr. Reyes.

The investigators also examined mood, including depression and anxiety, and subjective complaints of cognitive problems. “We found those patients residing in the most disadvantaged neighborhoods complained more about memory problems,” she said.

The results underscore the need for community-level interventions “that could provide resources in support of these older adults and their families and connect them to services we know are good for brain health,” said Dr. Reyes.

Alzheimer’s disease experts “have done a really good job of this, but this is new for epilepsy,” she added. “This gives us a great opportunity to kind of bridge the worlds of dementia and epilepsy.”
 

Novel Research

Commenting on the research, Rani Sarkis, MD, assistant professor of neurology, Brigham and Women’s Hospital, Boston, said the study is “very useful” as it ties social determinants of health to cognition.

“We have not been doing that” in people with epilepsy, he said.

The study, one of the first to look at the link between disadvantaged neighborhoods and cognitive impairment, “has very important” public health implications, including the need to consider access to activities that promote cognitive resilience and other brain health initiatives, said Dr. Sarkis.

Another larger study that looked at neighborhood deprivation and cognition in epilepsy was also presented at the AES meeting and published earlier this year in the journal Neurology.

That study included 800 patients with pharmaco-resistant temporal lobe epilepsy being evaluated for surgery at the Cleveland Clinic, mean age about 38 years. It examined numerous cognitive domains as well as depression and anxiety in relation to ADI generated by patient addresses and split into quintiles from least to most disadvantaged.

After controlling for covariants, the study found scores for all cognitive domains were significantly worse in the most disadvantaged quintile except for executive function, which was close to reaching significance (P = .052), said lead author Robyn M. Busch, PhD, a clinical neuropsychologist in the Epilepsy Center, Department of Neurology, Cleveland Clinic.

The study also found people in the most disadvantaged areas had more symptoms of depression and anxiety compared with people in the least disadvantaged areas, said Busch.
 

A Complex Issue

Although the exact mechanism tying disadvantaged areas to cognition in epilepsy isn’t fully understood, having less access to health care and educational opportunities, poor nutrition, and being under chronic stress “are all things that affect the brain,” said Dr. Busch.

“This is super complex and it’s going to be really difficult to tease apart, but we’d like to look at imaging data to see if it’s something structural, if there are functional changes in the brain or something that might help us understand this better.”

But it’s also possible that having epilepsy “might be pushing people into environments” that offer fewer employment and educational opportunities and less access to resources, she said.

The study authors and Dr. Sarkis report no relevant financial relationships.

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

ORLANDO — Older people with epilepsy who live in deprived neighborhoods with lower socioeconomic status, fewer educational opportunities, and less access to health care have poorer memory, executive function, and processing speed than those living in more affluent areas, early research suggests.

Seniors with epilepsy present with multiple comorbidities, including, for example, hypertension and diabetes, and they are at increased risk of developing dementia, said study investigator Anny Reyes, PhD, a postdoctoral scholar at the University of California at San Diego.

Past research has shown neighborhood disadvantage is associated with numerous adverse health outcomes, including an increased risk for developing Alzheimer’s disease and related dementias (ADRD).

“We already know epilepsy on its own increases risks for dementia, and when you add disadvantaged to that, it’s going to increase the risk even more,” said Dr. Reyes.

Neurologists should ask their older patients with epilepsy, many of whom live alone, about food insecurity and access to resources “not just within the hospital system but also within their community,” she said.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Proxy Measure of Disadvantage

The incidence and prevalence of epilepsy increases with age. Older adults represent the fastest growing segment of individuals with epilepsy, said Dr. Reyes.

The new study included 40 patients with focal epilepsy, average age 67 years, from three areas: San Diego, California; Madison, Wisconsin; and Cleveland, Ohio.

Researchers collected clinical and sociodemographic information as well as vascular biomarkers. They also gathered individual-level data, including income, parental education levels, details on childhood upbringing, etc.

Using residential addresses, investigators determined the area deprivation index (ADI) value for study participants. The ADI is a proxy measure for neighborhood-level socioeconomic disadvantage that captures factors such a poverty, employment, housing, and education opportunities.

ADI values range from 1 to 10, with a higher number indicating greater neighborhood disadvantage. About 30% of the cohort had an ADI decile greater than 6.

Researchers divided subjects into Most Disadvantaged (ADI greater than 7) and Least Disadvantaged (AD 7 or less). The two groups were similar with regard to age, education level, and race/ethnicity.

But those from the most disadvantaged areas were younger, taking more antiseizure medications, had fewer years of education, lower levels of father’s education, less personal and family income, and were less likely to be diagnosed with hypertension.

Study subjects completed neuropsychological testing, including:

• Measures of learning (Rey Auditory Verbal Learning Test [RAVLT] Learning Over Trials; Wechsler Memory Scale 4th Edition [WMS-4] Logical Memory [LM] Story B immediate; and WMS-4 Visual Reproduction [VR] immediate)
• Memory (RAVLT delayed recall, WMS-4 LM delayed recall, and WMS-4 VR delayed recall)
• Language (Multilingual Naming Test, Auditory Naming Test, and animal fluency)
• Executive function/processing speed (Letter fluency and Trail-Making Test Parts A and B)

The study found a correlation between higher ADI (most disadvantaged) and poorer performance on learning (Spearman rho: -0.433; 95% CI -0.664 to -0.126; P = .006), memory (r = -0.496; 95% CI -0.707 to -0.205; P = .001), and executive function/processes speed (r = -0.315; 95% CI -0.577 to 0.006; P = .048), but no significant association with language.

Looking at individual-level data, the study found memory and processing speed “were driving the relationship, and again, patients had worse performance when they were coming from the most disadvantaged neighborhoods,” said Dr. Reyes.

The investigators also examined mood, including depression and anxiety, and subjective complaints of cognitive problems. “We found those patients residing in the most disadvantaged neighborhoods complained more about memory problems,” she said.

The results underscore the need for community-level interventions “that could provide resources in support of these older adults and their families and connect them to services we know are good for brain health,” said Dr. Reyes.

Alzheimer’s disease experts “have done a really good job of this, but this is new for epilepsy,” she added. “This gives us a great opportunity to kind of bridge the worlds of dementia and epilepsy.”
 

Novel Research

Commenting on the research, Rani Sarkis, MD, assistant professor of neurology, Brigham and Women’s Hospital, Boston, said the study is “very useful” as it ties social determinants of health to cognition.

“We have not been doing that” in people with epilepsy, he said.

The study, one of the first to look at the link between disadvantaged neighborhoods and cognitive impairment, “has very important” public health implications, including the need to consider access to activities that promote cognitive resilience and other brain health initiatives, said Dr. Sarkis.

Another larger study that looked at neighborhood deprivation and cognition in epilepsy was also presented at the AES meeting and published earlier this year in the journal Neurology.

That study included 800 patients with pharmaco-resistant temporal lobe epilepsy being evaluated for surgery at the Cleveland Clinic, mean age about 38 years. It examined numerous cognitive domains as well as depression and anxiety in relation to ADI generated by patient addresses and split into quintiles from least to most disadvantaged.

After controlling for covariants, the study found scores for all cognitive domains were significantly worse in the most disadvantaged quintile except for executive function, which was close to reaching significance (P = .052), said lead author Robyn M. Busch, PhD, a clinical neuropsychologist in the Epilepsy Center, Department of Neurology, Cleveland Clinic.

The study also found people in the most disadvantaged areas had more symptoms of depression and anxiety compared with people in the least disadvantaged areas, said Busch.
 

A Complex Issue

Although the exact mechanism tying disadvantaged areas to cognition in epilepsy isn’t fully understood, having less access to health care and educational opportunities, poor nutrition, and being under chronic stress “are all things that affect the brain,” said Dr. Busch.

“This is super complex and it’s going to be really difficult to tease apart, but we’d like to look at imaging data to see if it’s something structural, if there are functional changes in the brain or something that might help us understand this better.”

But it’s also possible that having epilepsy “might be pushing people into environments” that offer fewer employment and educational opportunities and less access to resources, she said.

The study authors and Dr. Sarkis report no relevant financial relationships.

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

ORLANDO — Older people with epilepsy who live in deprived neighborhoods with lower socioeconomic status, fewer educational opportunities, and less access to health care have poorer memory, executive function, and processing speed than those living in more affluent areas, early research suggests.

Seniors with epilepsy present with multiple comorbidities, including, for example, hypertension and diabetes, and they are at increased risk of developing dementia, said study investigator Anny Reyes, PhD, a postdoctoral scholar at the University of California at San Diego.

Past research has shown neighborhood disadvantage is associated with numerous adverse health outcomes, including an increased risk for developing Alzheimer’s disease and related dementias (ADRD).

“We already know epilepsy on its own increases risks for dementia, and when you add disadvantaged to that, it’s going to increase the risk even more,” said Dr. Reyes.

Neurologists should ask their older patients with epilepsy, many of whom live alone, about food insecurity and access to resources “not just within the hospital system but also within their community,” she said.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Proxy Measure of Disadvantage

The incidence and prevalence of epilepsy increases with age. Older adults represent the fastest growing segment of individuals with epilepsy, said Dr. Reyes.

The new study included 40 patients with focal epilepsy, average age 67 years, from three areas: San Diego, California; Madison, Wisconsin; and Cleveland, Ohio.

Researchers collected clinical and sociodemographic information as well as vascular biomarkers. They also gathered individual-level data, including income, parental education levels, details on childhood upbringing, etc.

Using residential addresses, investigators determined the area deprivation index (ADI) value for study participants. The ADI is a proxy measure for neighborhood-level socioeconomic disadvantage that captures factors such a poverty, employment, housing, and education opportunities.

ADI values range from 1 to 10, with a higher number indicating greater neighborhood disadvantage. About 30% of the cohort had an ADI decile greater than 6.

Researchers divided subjects into Most Disadvantaged (ADI greater than 7) and Least Disadvantaged (AD 7 or less). The two groups were similar with regard to age, education level, and race/ethnicity.

But those from the most disadvantaged areas were younger, taking more antiseizure medications, had fewer years of education, lower levels of father’s education, less personal and family income, and were less likely to be diagnosed with hypertension.

Study subjects completed neuropsychological testing, including:

• Measures of learning (Rey Auditory Verbal Learning Test [RAVLT] Learning Over Trials; Wechsler Memory Scale 4th Edition [WMS-4] Logical Memory [LM] Story B immediate; and WMS-4 Visual Reproduction [VR] immediate)
• Memory (RAVLT delayed recall, WMS-4 LM delayed recall, and WMS-4 VR delayed recall)
• Language (Multilingual Naming Test, Auditory Naming Test, and animal fluency)
• Executive function/processing speed (Letter fluency and Trail-Making Test Parts A and B)

The study found a correlation between higher ADI (most disadvantaged) and poorer performance on learning (Spearman rho: -0.433; 95% CI -0.664 to -0.126; P = .006), memory (r = -0.496; 95% CI -0.707 to -0.205; P = .001), and executive function/processes speed (r = -0.315; 95% CI -0.577 to 0.006; P = .048), but no significant association with language.

Looking at individual-level data, the study found memory and processing speed “were driving the relationship, and again, patients had worse performance when they were coming from the most disadvantaged neighborhoods,” said Dr. Reyes.

The investigators also examined mood, including depression and anxiety, and subjective complaints of cognitive problems. “We found those patients residing in the most disadvantaged neighborhoods complained more about memory problems,” she said.

The results underscore the need for community-level interventions “that could provide resources in support of these older adults and their families and connect them to services we know are good for brain health,” said Dr. Reyes.

Alzheimer’s disease experts “have done a really good job of this, but this is new for epilepsy,” she added. “This gives us a great opportunity to kind of bridge the worlds of dementia and epilepsy.”
 

Novel Research

Commenting on the research, Rani Sarkis, MD, assistant professor of neurology, Brigham and Women’s Hospital, Boston, said the study is “very useful” as it ties social determinants of health to cognition.

“We have not been doing that” in people with epilepsy, he said.

The study, one of the first to look at the link between disadvantaged neighborhoods and cognitive impairment, “has very important” public health implications, including the need to consider access to activities that promote cognitive resilience and other brain health initiatives, said Dr. Sarkis.

Another larger study that looked at neighborhood deprivation and cognition in epilepsy was also presented at the AES meeting and published earlier this year in the journal Neurology.

That study included 800 patients with pharmaco-resistant temporal lobe epilepsy being evaluated for surgery at the Cleveland Clinic, mean age about 38 years. It examined numerous cognitive domains as well as depression and anxiety in relation to ADI generated by patient addresses and split into quintiles from least to most disadvantaged.

After controlling for covariants, the study found scores for all cognitive domains were significantly worse in the most disadvantaged quintile except for executive function, which was close to reaching significance (P = .052), said lead author Robyn M. Busch, PhD, a clinical neuropsychologist in the Epilepsy Center, Department of Neurology, Cleveland Clinic.

The study also found people in the most disadvantaged areas had more symptoms of depression and anxiety compared with people in the least disadvantaged areas, said Busch.
 

A Complex Issue

Although the exact mechanism tying disadvantaged areas to cognition in epilepsy isn’t fully understood, having less access to health care and educational opportunities, poor nutrition, and being under chronic stress “are all things that affect the brain,” said Dr. Busch.

“This is super complex and it’s going to be really difficult to tease apart, but we’d like to look at imaging data to see if it’s something structural, if there are functional changes in the brain or something that might help us understand this better.”

But it’s also possible that having epilepsy “might be pushing people into environments” that offer fewer employment and educational opportunities and less access to resources, she said.

The study authors and Dr. Sarkis report no relevant financial relationships.

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

Patients receiving semaglutide for weight loss show a significantly higher rate of continuing the medication at 1 year compared with less effective anti-obesity drugs. However, even among those patients, continuation declines to fewer than half of patients.

“We now have effective US Food and Drug Administration–approved anti-obesity medications; [however], this study shows that in a real-world setting, the vast majority of patients discontinued their prescription fills within the first year,” said first author Hamlet Gasoyan, PhD, lead author of the study and a researcher with Cleveland Clinic’s Center for Value-Based Care Research, said in a press statement.

The study was published online in the journal Obesity.

While breakthrough drugs such as glucagon-like peptide-1 (GLP-1) receptor agonists have shown high efficacy in achieving weight loss while providing a host of other health benefits, their discontinuation has been shown to potentially result in a rapid regaining of weight that was lost, as well as a reversal of the other health benefits, such as cardiometabolic improvements, the study authors wrote.

To evaluate rates of persistence with those along with other weight loss medications and factors associated with discontinuation, Dr. Gasoyan and colleagues conducted a retrospective cohort study, identifying 1911 patients with obesity, who had an initial anti-obesity medication prescription filled between 2015 and 2022 at Cleveland Clinic centers in Ohio and Florida. 

Over the study period, 25% of patients filled a prescription for semaglutide, 34% for naltrexone-bupropion, 26% for phentermine-topiramate, 14% for liraglutide, and 0.9% for orlistat.

The patients had a median baseline BMI of 38, with obesity defined as a BMI of 30 or higher.
 

Medication Continuation Drops After 3 Months

With a median follow-up time of 2.4 years, the rate of persistence to the medications overall dropped from 44% at 3 months to 33% at 6 months and just 19% at 12 months. 

In a multivariate analysis, semaglutide was associated with the highest odds of 1-year persistence (adjusted odds ratio [AOR], 4.26), while naltrexone-bupropion had the lowest odds (AOR, 0.68), compared with phentermine-topiramate. The other agents did not have significantly different odds of persistence.

Semaglutide and liraglutide also had the highest persistence rates overall, including at 3 months (63% and 52%, respectively) and 6 months (56% and 37%, respectively).

Those with higher weight loss at 6 months had a higher likelihood of remaining on the weight loss medication at 1 year, with a 1% increase in weight loss at 6 months associated with 6% increased odds of still being persistent at year 1 (adjusted odds ratio, 1.06).

Those who did continue medications at 1 year had a mean of 10% weight loss at 12 months compared with just 2% among individuals who were not persistent (P <.001).

Most patients (84%) in the study were privately insured, and weight loss drug adherence varied significantly based on the insurance carrier. 

Studies demonstrating the effects of discontinuing treatment with semaglutide include the STEP 1 trial extension, which showed that 1 year after discontinuation of treatment and lifestyle intervention, participants regained two thirds of their lost weight on average, and the cardiometabolic improvements with the weight loss were reversed.

In light of those findings, “the current scientific knowledge favors using anti-obesity medications longer term for weight loss maintenance if they are well-tolerated and have resulted in clinically meaningful weight loss,” Dr. Gasoyan told this news organization. 

Paradoxically, the possible regaining of weight could be a factor in some insurers denying longer-term coverage, he noted.
 

Discontinuing Medications Means Regaining Appetite

Anne Peters, MD, a professor of medicine at USC’s Keck School of Medicine in Los Angeles and director of the USC Clinical Diabetes Programs, underscored that the possibility of regaining weight with discontinuation of GLP-1 receptor agonists is indeed “a big concern because your appetite comes back in spades when you take away the effect of these hormones,” she told this news organization. “For that reason, I don’t ever tell people to stop cold turkey.”

Regarding the question of how long patients should remain on the medications, Peters said the scenario might be compared to the need for patients with type 1 diabetes to be on insulin, which is a gut hormone.

“These medications are also gut hormones, and some patients may need to also be on them for life to maintain the benefits,” she said. 

“If a patient for some reason wishes to come off of the medication, for instance in order to be on less medicine, I have them titrate down and usually there will be a dose where they actually need only a small dose.

“I even have some patients who just take semaglutide once a month who are able to manage to maintain their weight loss,” Dr. Peters noted. 

“But the whole goal in people who are overweight or obese is to establish a new set point and maintain whatever that new target weight is.”

Dr. Peters agreed that the loss of insurance coverage for the medications can throw a big wrench into that maintenance, presenting adverse effects of its own by causing a lack of treatment continuity. 

“When you lose weight, you lose lean body mass and fat mass, but when you regain, it’s primary fat mass, so if you go on and off these drugs, it can contribute to a loss of lean mass. Therefore, these drugs should not be taken if someone is going to go on and off them repeatedly.” 

The study received funding from the National Cancer Institute. Dr. Peters has consulted for Eli Lilly in the past.

A version of this article appeared on Medscape.com.

Patients receiving semaglutide for weight loss show a significantly higher rate of continuing the medication at 1 year compared with less effective anti-obesity drugs. However, even among those patients, continuation declines to fewer than half of patients.

“We now have effective US Food and Drug Administration–approved anti-obesity medications; [however], this study shows that in a real-world setting, the vast majority of patients discontinued their prescription fills within the first year,” said first author Hamlet Gasoyan, PhD, lead author of the study and a researcher with Cleveland Clinic’s Center for Value-Based Care Research, said in a press statement.

The study was published online in the journal Obesity.

While breakthrough drugs such as glucagon-like peptide-1 (GLP-1) receptor agonists have shown high efficacy in achieving weight loss while providing a host of other health benefits, their discontinuation has been shown to potentially result in a rapid regaining of weight that was lost, as well as a reversal of the other health benefits, such as cardiometabolic improvements, the study authors wrote.

To evaluate rates of persistence with those along with other weight loss medications and factors associated with discontinuation, Dr. Gasoyan and colleagues conducted a retrospective cohort study, identifying 1911 patients with obesity, who had an initial anti-obesity medication prescription filled between 2015 and 2022 at Cleveland Clinic centers in Ohio and Florida. 

Over the study period, 25% of patients filled a prescription for semaglutide, 34% for naltrexone-bupropion, 26% for phentermine-topiramate, 14% for liraglutide, and 0.9% for orlistat.

The patients had a median baseline BMI of 38, with obesity defined as a BMI of 30 or higher.
 

Medication Continuation Drops After 3 Months

With a median follow-up time of 2.4 years, the rate of persistence to the medications overall dropped from 44% at 3 months to 33% at 6 months and just 19% at 12 months. 

In a multivariate analysis, semaglutide was associated with the highest odds of 1-year persistence (adjusted odds ratio [AOR], 4.26), while naltrexone-bupropion had the lowest odds (AOR, 0.68), compared with phentermine-topiramate. The other agents did not have significantly different odds of persistence.

Semaglutide and liraglutide also had the highest persistence rates overall, including at 3 months (63% and 52%, respectively) and 6 months (56% and 37%, respectively).

Those with higher weight loss at 6 months had a higher likelihood of remaining on the weight loss medication at 1 year, with a 1% increase in weight loss at 6 months associated with 6% increased odds of still being persistent at year 1 (adjusted odds ratio, 1.06).

Those who did continue medications at 1 year had a mean of 10% weight loss at 12 months compared with just 2% among individuals who were not persistent (P <.001).

Most patients (84%) in the study were privately insured, and weight loss drug adherence varied significantly based on the insurance carrier. 

Studies demonstrating the effects of discontinuing treatment with semaglutide include the STEP 1 trial extension, which showed that 1 year after discontinuation of treatment and lifestyle intervention, participants regained two thirds of their lost weight on average, and the cardiometabolic improvements with the weight loss were reversed.

In light of those findings, “the current scientific knowledge favors using anti-obesity medications longer term for weight loss maintenance if they are well-tolerated and have resulted in clinically meaningful weight loss,” Dr. Gasoyan told this news organization. 

Paradoxically, the possible regaining of weight could be a factor in some insurers denying longer-term coverage, he noted.
 

Discontinuing Medications Means Regaining Appetite

Anne Peters, MD, a professor of medicine at USC’s Keck School of Medicine in Los Angeles and director of the USC Clinical Diabetes Programs, underscored that the possibility of regaining weight with discontinuation of GLP-1 receptor agonists is indeed “a big concern because your appetite comes back in spades when you take away the effect of these hormones,” she told this news organization. “For that reason, I don’t ever tell people to stop cold turkey.”

Regarding the question of how long patients should remain on the medications, Peters said the scenario might be compared to the need for patients with type 1 diabetes to be on insulin, which is a gut hormone.

“These medications are also gut hormones, and some patients may need to also be on them for life to maintain the benefits,” she said. 

“If a patient for some reason wishes to come off of the medication, for instance in order to be on less medicine, I have them titrate down and usually there will be a dose where they actually need only a small dose.

“I even have some patients who just take semaglutide once a month who are able to manage to maintain their weight loss,” Dr. Peters noted. 

“But the whole goal in people who are overweight or obese is to establish a new set point and maintain whatever that new target weight is.”

Dr. Peters agreed that the loss of insurance coverage for the medications can throw a big wrench into that maintenance, presenting adverse effects of its own by causing a lack of treatment continuity. 

“When you lose weight, you lose lean body mass and fat mass, but when you regain, it’s primary fat mass, so if you go on and off these drugs, it can contribute to a loss of lean mass. Therefore, these drugs should not be taken if someone is going to go on and off them repeatedly.” 

The study received funding from the National Cancer Institute. Dr. Peters has consulted for Eli Lilly in the past.

A version of this article appeared on Medscape.com.

Patients receiving semaglutide for weight loss show a significantly higher rate of continuing the medication at 1 year compared with less effective anti-obesity drugs. However, even among those patients, continuation declines to fewer than half of patients.

“We now have effective US Food and Drug Administration–approved anti-obesity medications; [however], this study shows that in a real-world setting, the vast majority of patients discontinued their prescription fills within the first year,” said first author Hamlet Gasoyan, PhD, lead author of the study and a researcher with Cleveland Clinic’s Center for Value-Based Care Research, said in a press statement.

The study was published online in the journal Obesity.

While breakthrough drugs such as glucagon-like peptide-1 (GLP-1) receptor agonists have shown high efficacy in achieving weight loss while providing a host of other health benefits, their discontinuation has been shown to potentially result in a rapid regaining of weight that was lost, as well as a reversal of the other health benefits, such as cardiometabolic improvements, the study authors wrote.

To evaluate rates of persistence with those along with other weight loss medications and factors associated with discontinuation, Dr. Gasoyan and colleagues conducted a retrospective cohort study, identifying 1911 patients with obesity, who had an initial anti-obesity medication prescription filled between 2015 and 2022 at Cleveland Clinic centers in Ohio and Florida. 

Over the study period, 25% of patients filled a prescription for semaglutide, 34% for naltrexone-bupropion, 26% for phentermine-topiramate, 14% for liraglutide, and 0.9% for orlistat.

The patients had a median baseline BMI of 38, with obesity defined as a BMI of 30 or higher.
 

Medication Continuation Drops After 3 Months

With a median follow-up time of 2.4 years, the rate of persistence to the medications overall dropped from 44% at 3 months to 33% at 6 months and just 19% at 12 months. 

In a multivariate analysis, semaglutide was associated with the highest odds of 1-year persistence (adjusted odds ratio [AOR], 4.26), while naltrexone-bupropion had the lowest odds (AOR, 0.68), compared with phentermine-topiramate. The other agents did not have significantly different odds of persistence.

Semaglutide and liraglutide also had the highest persistence rates overall, including at 3 months (63% and 52%, respectively) and 6 months (56% and 37%, respectively).

Those with higher weight loss at 6 months had a higher likelihood of remaining on the weight loss medication at 1 year, with a 1% increase in weight loss at 6 months associated with 6% increased odds of still being persistent at year 1 (adjusted odds ratio, 1.06).

Those who did continue medications at 1 year had a mean of 10% weight loss at 12 months compared with just 2% among individuals who were not persistent (P <.001).

Most patients (84%) in the study were privately insured, and weight loss drug adherence varied significantly based on the insurance carrier. 

Studies demonstrating the effects of discontinuing treatment with semaglutide include the STEP 1 trial extension, which showed that 1 year after discontinuation of treatment and lifestyle intervention, participants regained two thirds of their lost weight on average, and the cardiometabolic improvements with the weight loss were reversed.

In light of those findings, “the current scientific knowledge favors using anti-obesity medications longer term for weight loss maintenance if they are well-tolerated and have resulted in clinically meaningful weight loss,” Dr. Gasoyan told this news organization. 

Paradoxically, the possible regaining of weight could be a factor in some insurers denying longer-term coverage, he noted.
 

Discontinuing Medications Means Regaining Appetite

Anne Peters, MD, a professor of medicine at USC’s Keck School of Medicine in Los Angeles and director of the USC Clinical Diabetes Programs, underscored that the possibility of regaining weight with discontinuation of GLP-1 receptor agonists is indeed “a big concern because your appetite comes back in spades when you take away the effect of these hormones,” she told this news organization. “For that reason, I don’t ever tell people to stop cold turkey.”

Regarding the question of how long patients should remain on the medications, Peters said the scenario might be compared to the need for patients with type 1 diabetes to be on insulin, which is a gut hormone.

“These medications are also gut hormones, and some patients may need to also be on them for life to maintain the benefits,” she said. 

“If a patient for some reason wishes to come off of the medication, for instance in order to be on less medicine, I have them titrate down and usually there will be a dose where they actually need only a small dose.

“I even have some patients who just take semaglutide once a month who are able to manage to maintain their weight loss,” Dr. Peters noted. 

“But the whole goal in people who are overweight or obese is to establish a new set point and maintain whatever that new target weight is.”

Dr. Peters agreed that the loss of insurance coverage for the medications can throw a big wrench into that maintenance, presenting adverse effects of its own by causing a lack of treatment continuity. 

“When you lose weight, you lose lean body mass and fat mass, but when you regain, it’s primary fat mass, so if you go on and off these drugs, it can contribute to a loss of lean mass. Therefore, these drugs should not be taken if someone is going to go on and off them repeatedly.” 

The study received funding from the National Cancer Institute. Dr. Peters has consulted for Eli Lilly in the past.

A version of this article appeared on Medscape.com.

ORLANDO — Genetic testing is warranted in patients with epilepsy of unknown origin, new research suggests. Investigators found that pathogenic genetic variants were identified in over 40% of patients with epilepsy of unknown cause who underwent genetic testing.

Such testing is particularly beneficial for those with early-onset epilepsy and those with comorbid developmental delay, said study investigator Yi Li, MD, PhD, clinical assistant professor, Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, California. 

But every patient with epilepsy of unknown etiology needs to consider genetic testing as part of their standard workup.

Dr. Li noted research showing that a diagnosis of a genetic epilepsy leads to alteration of treatment in about 20% of cases — for example, starting a specific antiseizure medication or avoiding a treatment such as a sodium channel blocker in patients diagnosed with Dravet syndrome. A genetic diagnosis also may make patients eligible for clinical trials investigating gene therapies. 

Genetic testing results may end a long and exhausting “diagnostic odyssey” that families have been on, she said. Patients often wait more than a decade to get genetic testing, the study found.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Major Delays

About 20%-30% of epilepsy is caused by acquired conditions such as stroke, tumor, or head injury. The remaining 70%-80% is believed to be due to one or more genetic factors.

Genetic testing has become standard for children with early-onset epilepsy, but it’s not common practice among adults with the condition — at least not yet.

The retrospective study involved a chart review of patient electronic health records from 2018-2023. Researchers used the Stanford electronic health record Cohort Discovery tool (STARR) database to identify 286 patients over age 16 years with epilepsy who had records of genetic testing.

Of the 286 patients, 148 were male and 138 female, and mean age was approximately 30 years. Among those with known epilepsy types, 53.6% had focal epilepsy and 28.8% had generalized epilpesy.

The mean age of seizure onset was 11.9 years, but the mean age at genetic testing was 25.1 years. “There’s a gap of about 13 or 14 years for genetic workup after a patient has a first seizure,” said Dr. Li.

Such a “huge delay” means patients may miss out on “potential precision treatment choices,” she said.

And having a diagnosis can connect patients to others with the same condition as well as to related organizations and communities that offer support, she added.

Types of genetic testing identified in the study included panel testing, which looks at the genes associated with epilepsy; whole exome sequencing (WES), which includes all 20,000 genes in one test; and microarray testing, which assesses missing sections of chromosomes. WES had the highest diagnostic yield (48%), followed by genetic panel testing (32.7%) and microarray testing (20.9%).

These tests collectively identified pathogenic variants in 40.9% of patients. In addition, test results showed that 53.10% of patients had variants of uncertain significance.

In the full cohort, the most commonly identified variants were mutations in TSC1 (which causes tuberous sclerosis, SCN1A (which causes Dravet syndrome), and MECP2. Among patients with seizure onset after age 1 year, MECP2 and DEPDC5 were the two most commonly identified pathogenic variants.

Researchers examined factors possibly associated with a higher risk for genetic epilepsy, including family history, comorbid developmental delay, febrile seizures, status epilepticus, perinatal injury, and seizure onset age. In an adjusted analysis, comorbid developmental delay (estimate 2.338; 95% confidence interval [CI], 1.402-3.900; P =.001) and seizure onset before 1 year (estimate 2.365; 95% CI, 1.282-4.366; P =.006) predicted higher yield of pathogenic variants related to epilepsy.

Dr. Li noted that study participants with a family history of epilepsy were not more likely to test positive for a genetic link, so doctors shouldn’t rule out testing in patients if there’s no family history.

Both the International League Against Epilepsy (ILAE) and the National Society of Genetic Counselors (NSGC) recommend genetic testing in adult epilepsy patients, with the AES endorsing the NSGC guideline.

Although testing is becoming increasingly accessible, insurance companies don’t always cover the cost.

Dr. Li said she hopes her research raises awareness among clinicians that there’s more they can do to improve care for epilepsy patients. “We should offer patients genetic testing if we don’t have a clear etiology.”
 

Valuable Evidence

Commenting on the research findings, Annapurna Poduri, MD, MPH, director, Epilepsy Genetics Program, Boston Children’s Hospital, Boston, Massachusetts, said this research “is incredibly important.”

“What’s really telling about this study and others that have come up over the last few years is they’re real-world retrospective studies, so they’re looking back at patients who have been seen over many, many years.”

The research provides clinicians, insurance companies, and others with evidence that genetic testing is “valuable and can actually improve outcomes,” said Dr. Poduri.

She noted that 20 years ago, there were only a handful of genes identified as being involved with epilepsy, most related to sodium or potassium channels. But since then, “the technology has just raced ahead” to the point where now “dozens of genes” have been identified.

Not only does knowing the genetic basis of epilepsy improve management, but it offers families some peace of mind. “They blame themselves” for their loved one’s condition, said Dr. Poduri. “They may worry it was something they did in pregnancy; for example, maybe it was because [they] didn’t take that vitamin one day.”

Diagnostic certainty also means that patients “don’t have to do more tests which might be invasive” and unnecessarily costly.

Drs. Li and Poduri report no relevant conflicts of interest.

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

ORLANDO — Genetic testing is warranted in patients with epilepsy of unknown origin, new research suggests. Investigators found that pathogenic genetic variants were identified in over 40% of patients with epilepsy of unknown cause who underwent genetic testing.

Such testing is particularly beneficial for those with early-onset epilepsy and those with comorbid developmental delay, said study investigator Yi Li, MD, PhD, clinical assistant professor, Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, California. 

But every patient with epilepsy of unknown etiology needs to consider genetic testing as part of their standard workup.

Dr. Li noted research showing that a diagnosis of a genetic epilepsy leads to alteration of treatment in about 20% of cases — for example, starting a specific antiseizure medication or avoiding a treatment such as a sodium channel blocker in patients diagnosed with Dravet syndrome. A genetic diagnosis also may make patients eligible for clinical trials investigating gene therapies. 

Genetic testing results may end a long and exhausting “diagnostic odyssey” that families have been on, she said. Patients often wait more than a decade to get genetic testing, the study found.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Major Delays

About 20%-30% of epilepsy is caused by acquired conditions such as stroke, tumor, or head injury. The remaining 70%-80% is believed to be due to one or more genetic factors.

Genetic testing has become standard for children with early-onset epilepsy, but it’s not common practice among adults with the condition — at least not yet.

The retrospective study involved a chart review of patient electronic health records from 2018-2023. Researchers used the Stanford electronic health record Cohort Discovery tool (STARR) database to identify 286 patients over age 16 years with epilepsy who had records of genetic testing.

Of the 286 patients, 148 were male and 138 female, and mean age was approximately 30 years. Among those with known epilepsy types, 53.6% had focal epilepsy and 28.8% had generalized epilpesy.

The mean age of seizure onset was 11.9 years, but the mean age at genetic testing was 25.1 years. “There’s a gap of about 13 or 14 years for genetic workup after a patient has a first seizure,” said Dr. Li.

Such a “huge delay” means patients may miss out on “potential precision treatment choices,” she said.

And having a diagnosis can connect patients to others with the same condition as well as to related organizations and communities that offer support, she added.

Types of genetic testing identified in the study included panel testing, which looks at the genes associated with epilepsy; whole exome sequencing (WES), which includes all 20,000 genes in one test; and microarray testing, which assesses missing sections of chromosomes. WES had the highest diagnostic yield (48%), followed by genetic panel testing (32.7%) and microarray testing (20.9%).

These tests collectively identified pathogenic variants in 40.9% of patients. In addition, test results showed that 53.10% of patients had variants of uncertain significance.

In the full cohort, the most commonly identified variants were mutations in TSC1 (which causes tuberous sclerosis, SCN1A (which causes Dravet syndrome), and MECP2. Among patients with seizure onset after age 1 year, MECP2 and DEPDC5 were the two most commonly identified pathogenic variants.

Researchers examined factors possibly associated with a higher risk for genetic epilepsy, including family history, comorbid developmental delay, febrile seizures, status epilepticus, perinatal injury, and seizure onset age. In an adjusted analysis, comorbid developmental delay (estimate 2.338; 95% confidence interval [CI], 1.402-3.900; P =.001) and seizure onset before 1 year (estimate 2.365; 95% CI, 1.282-4.366; P =.006) predicted higher yield of pathogenic variants related to epilepsy.

Dr. Li noted that study participants with a family history of epilepsy were not more likely to test positive for a genetic link, so doctors shouldn’t rule out testing in patients if there’s no family history.

Both the International League Against Epilepsy (ILAE) and the National Society of Genetic Counselors (NSGC) recommend genetic testing in adult epilepsy patients, with the AES endorsing the NSGC guideline.

Although testing is becoming increasingly accessible, insurance companies don’t always cover the cost.

Dr. Li said she hopes her research raises awareness among clinicians that there’s more they can do to improve care for epilepsy patients. “We should offer patients genetic testing if we don’t have a clear etiology.”
 

Valuable Evidence

Commenting on the research findings, Annapurna Poduri, MD, MPH, director, Epilepsy Genetics Program, Boston Children’s Hospital, Boston, Massachusetts, said this research “is incredibly important.”

“What’s really telling about this study and others that have come up over the last few years is they’re real-world retrospective studies, so they’re looking back at patients who have been seen over many, many years.”

The research provides clinicians, insurance companies, and others with evidence that genetic testing is “valuable and can actually improve outcomes,” said Dr. Poduri.

She noted that 20 years ago, there were only a handful of genes identified as being involved with epilepsy, most related to sodium or potassium channels. But since then, “the technology has just raced ahead” to the point where now “dozens of genes” have been identified.

Not only does knowing the genetic basis of epilepsy improve management, but it offers families some peace of mind. “They blame themselves” for their loved one’s condition, said Dr. Poduri. “They may worry it was something they did in pregnancy; for example, maybe it was because [they] didn’t take that vitamin one day.”

Diagnostic certainty also means that patients “don’t have to do more tests which might be invasive” and unnecessarily costly.

Drs. Li and Poduri report no relevant conflicts of interest.

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

ORLANDO — Genetic testing is warranted in patients with epilepsy of unknown origin, new research suggests. Investigators found that pathogenic genetic variants were identified in over 40% of patients with epilepsy of unknown cause who underwent genetic testing.

Such testing is particularly beneficial for those with early-onset epilepsy and those with comorbid developmental delay, said study investigator Yi Li, MD, PhD, clinical assistant professor, Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, California. 

But every patient with epilepsy of unknown etiology needs to consider genetic testing as part of their standard workup.

Dr. Li noted research showing that a diagnosis of a genetic epilepsy leads to alteration of treatment in about 20% of cases — for example, starting a specific antiseizure medication or avoiding a treatment such as a sodium channel blocker in patients diagnosed with Dravet syndrome. A genetic diagnosis also may make patients eligible for clinical trials investigating gene therapies. 

Genetic testing results may end a long and exhausting “diagnostic odyssey” that families have been on, she said. Patients often wait more than a decade to get genetic testing, the study found.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Major Delays

About 20%-30% of epilepsy is caused by acquired conditions such as stroke, tumor, or head injury. The remaining 70%-80% is believed to be due to one or more genetic factors.

Genetic testing has become standard for children with early-onset epilepsy, but it’s not common practice among adults with the condition — at least not yet.

The retrospective study involved a chart review of patient electronic health records from 2018-2023. Researchers used the Stanford electronic health record Cohort Discovery tool (STARR) database to identify 286 patients over age 16 years with epilepsy who had records of genetic testing.

Of the 286 patients, 148 were male and 138 female, and mean age was approximately 30 years. Among those with known epilepsy types, 53.6% had focal epilepsy and 28.8% had generalized epilpesy.

The mean age of seizure onset was 11.9 years, but the mean age at genetic testing was 25.1 years. “There’s a gap of about 13 or 14 years for genetic workup after a patient has a first seizure,” said Dr. Li.

Such a “huge delay” means patients may miss out on “potential precision treatment choices,” she said.

And having a diagnosis can connect patients to others with the same condition as well as to related organizations and communities that offer support, she added.

Types of genetic testing identified in the study included panel testing, which looks at the genes associated with epilepsy; whole exome sequencing (WES), which includes all 20,000 genes in one test; and microarray testing, which assesses missing sections of chromosomes. WES had the highest diagnostic yield (48%), followed by genetic panel testing (32.7%) and microarray testing (20.9%).

These tests collectively identified pathogenic variants in 40.9% of patients. In addition, test results showed that 53.10% of patients had variants of uncertain significance.

In the full cohort, the most commonly identified variants were mutations in TSC1 (which causes tuberous sclerosis, SCN1A (which causes Dravet syndrome), and MECP2. Among patients with seizure onset after age 1 year, MECP2 and DEPDC5 were the two most commonly identified pathogenic variants.

Researchers examined factors possibly associated with a higher risk for genetic epilepsy, including family history, comorbid developmental delay, febrile seizures, status epilepticus, perinatal injury, and seizure onset age. In an adjusted analysis, comorbid developmental delay (estimate 2.338; 95% confidence interval [CI], 1.402-3.900; P =.001) and seizure onset before 1 year (estimate 2.365; 95% CI, 1.282-4.366; P =.006) predicted higher yield of pathogenic variants related to epilepsy.

Dr. Li noted that study participants with a family history of epilepsy were not more likely to test positive for a genetic link, so doctors shouldn’t rule out testing in patients if there’s no family history.

Both the International League Against Epilepsy (ILAE) and the National Society of Genetic Counselors (NSGC) recommend genetic testing in adult epilepsy patients, with the AES endorsing the NSGC guideline.

Although testing is becoming increasingly accessible, insurance companies don’t always cover the cost.

Dr. Li said she hopes her research raises awareness among clinicians that there’s more they can do to improve care for epilepsy patients. “We should offer patients genetic testing if we don’t have a clear etiology.”
 

Valuable Evidence

Commenting on the research findings, Annapurna Poduri, MD, MPH, director, Epilepsy Genetics Program, Boston Children’s Hospital, Boston, Massachusetts, said this research “is incredibly important.”

“What’s really telling about this study and others that have come up over the last few years is they’re real-world retrospective studies, so they’re looking back at patients who have been seen over many, many years.”

The research provides clinicians, insurance companies, and others with evidence that genetic testing is “valuable and can actually improve outcomes,” said Dr. Poduri.

She noted that 20 years ago, there were only a handful of genes identified as being involved with epilepsy, most related to sodium or potassium channels. But since then, “the technology has just raced ahead” to the point where now “dozens of genes” have been identified.

Not only does knowing the genetic basis of epilepsy improve management, but it offers families some peace of mind. “They blame themselves” for their loved one’s condition, said Dr. Poduri. “They may worry it was something they did in pregnancy; for example, maybe it was because [they] didn’t take that vitamin one day.”

Diagnostic certainty also means that patients “don’t have to do more tests which might be invasive” and unnecessarily costly.

Drs. Li and Poduri report no relevant conflicts of interest.

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

For patients with chronic migraine, combination therapy with anti-CGRP monoclonal antibodies and onabotulinumtoxinA may be more effective than monotherapy, possibly owing to the synergistic mechanism of action of the two agents, a new study suggests.

“People with chronic migraine may be the toughest to treat. They have the greatest disability, and often insurance companies would prefer monotherapy, but in these patients, sometimes using a multifaceted approach and using different drugs that target different pathophysiologies of migraine can probably provide greater benefit in terms of reducing the frequency and severity of the headaches,” study investigator MaryAnn Mays, MD, staff neurologist at the Headache and Facial Pain Clinic in the Neurologic Institute, Cleveland Clinic, Cleveland, Ohio, said in an interview.

The findings were presented at the annual meeting of the American Headache Society.
 

Fewer Migraine Days

OnabotulinumtodxinA (onabot) has been shown to selectively inhibit unmyelinated C-fibers but not A-delta-meningeal nociceptors. Anti-CGRP mAb therapies have been shown to prevent the activation of A-delta-fibers but not C-fibers, said Dr. Mays.

For the study, the investigators reviewed the electronic medical records of 194 patients who had been concurrently treated with anti-CGRP mAbs and onabot. Most (86.6%) were women; ages ranged from 36 to 65 years, and at baseline, they had been having an average of 28 (+4.6) monthly migraine days (MMDs).

The number of MMDs were assessed at two periods: 3 months after monotherapy with an anti-CGRP mAb or onabot injections, and 3 months after combined therapy.

Monotherapy reduced the average number of MMDs from 28 to 18.6, for a reduction of 9.4 days (P > .0001).

After initiation of combined therapy, the average number of MMDs decreased further, from 18.6 MMDs to 12.1 MMDs (P > .0001).

In all, the combination of onabot and anti-CGRP mAbs resulted in a total MMD reduction of 15.8 (P > .0001).

In addition, most patients (68%) reported a 50% or greater reduction in MMDs, and 46.4% reported a 75% or greater reduction.
 

Great News for Patients

Commenting for this article, Rashmi B. Halker Singh, MD, associate professor of neurology at Mayo Clinic, Scottsdale, Arizona, said the study findings “support what we see in clinical practice and what we suspected from preclinical data.”

Single-agent treatment is not sufficient for many patients. Data confirming the benefit of dual therapy will provide more evidence to insurance companies of the need for coverage.

“We have lots of individuals for whom single treatment is not sufficient and who need this combination of treatment, and it is often denied by insurance. There are preclinical data suggesting synergy, but insurance says it is experimental, so the claims get denied. This leaves patients having to choose which drug they want to continue with, and that’s really heartbreaking,” Dr. Halker Singh said.

The importance of this study is that it adds more data to support evidence-based therapies for migraine and to help patients get the treatment they need, she added.

Dr. Mays reports financial relationships with AbbVie, Amgen, and Teva. Dr. Halker Singh reports no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

For patients with chronic migraine, combination therapy with anti-CGRP monoclonal antibodies and onabotulinumtoxinA may be more effective than monotherapy, possibly owing to the synergistic mechanism of action of the two agents, a new study suggests.

“People with chronic migraine may be the toughest to treat. They have the greatest disability, and often insurance companies would prefer monotherapy, but in these patients, sometimes using a multifaceted approach and using different drugs that target different pathophysiologies of migraine can probably provide greater benefit in terms of reducing the frequency and severity of the headaches,” study investigator MaryAnn Mays, MD, staff neurologist at the Headache and Facial Pain Clinic in the Neurologic Institute, Cleveland Clinic, Cleveland, Ohio, said in an interview.

The findings were presented at the annual meeting of the American Headache Society.
 

Fewer Migraine Days

OnabotulinumtodxinA (onabot) has been shown to selectively inhibit unmyelinated C-fibers but not A-delta-meningeal nociceptors. Anti-CGRP mAb therapies have been shown to prevent the activation of A-delta-fibers but not C-fibers, said Dr. Mays.

For the study, the investigators reviewed the electronic medical records of 194 patients who had been concurrently treated with anti-CGRP mAbs and onabot. Most (86.6%) were women; ages ranged from 36 to 65 years, and at baseline, they had been having an average of 28 (+4.6) monthly migraine days (MMDs).

The number of MMDs were assessed at two periods: 3 months after monotherapy with an anti-CGRP mAb or onabot injections, and 3 months after combined therapy.

Monotherapy reduced the average number of MMDs from 28 to 18.6, for a reduction of 9.4 days (P > .0001).

After initiation of combined therapy, the average number of MMDs decreased further, from 18.6 MMDs to 12.1 MMDs (P > .0001).

In all, the combination of onabot and anti-CGRP mAbs resulted in a total MMD reduction of 15.8 (P > .0001).

In addition, most patients (68%) reported a 50% or greater reduction in MMDs, and 46.4% reported a 75% or greater reduction.
 

Great News for Patients

Commenting for this article, Rashmi B. Halker Singh, MD, associate professor of neurology at Mayo Clinic, Scottsdale, Arizona, said the study findings “support what we see in clinical practice and what we suspected from preclinical data.”

Single-agent treatment is not sufficient for many patients. Data confirming the benefit of dual therapy will provide more evidence to insurance companies of the need for coverage.

“We have lots of individuals for whom single treatment is not sufficient and who need this combination of treatment, and it is often denied by insurance. There are preclinical data suggesting synergy, but insurance says it is experimental, so the claims get denied. This leaves patients having to choose which drug they want to continue with, and that’s really heartbreaking,” Dr. Halker Singh said.

The importance of this study is that it adds more data to support evidence-based therapies for migraine and to help patients get the treatment they need, she added.

Dr. Mays reports financial relationships with AbbVie, Amgen, and Teva. Dr. Halker Singh reports no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

For patients with chronic migraine, combination therapy with anti-CGRP monoclonal antibodies and onabotulinumtoxinA may be more effective than monotherapy, possibly owing to the synergistic mechanism of action of the two agents, a new study suggests.

“People with chronic migraine may be the toughest to treat. They have the greatest disability, and often insurance companies would prefer monotherapy, but in these patients, sometimes using a multifaceted approach and using different drugs that target different pathophysiologies of migraine can probably provide greater benefit in terms of reducing the frequency and severity of the headaches,” study investigator MaryAnn Mays, MD, staff neurologist at the Headache and Facial Pain Clinic in the Neurologic Institute, Cleveland Clinic, Cleveland, Ohio, said in an interview.

The findings were presented at the annual meeting of the American Headache Society.
 

Fewer Migraine Days

OnabotulinumtodxinA (onabot) has been shown to selectively inhibit unmyelinated C-fibers but not A-delta-meningeal nociceptors. Anti-CGRP mAb therapies have been shown to prevent the activation of A-delta-fibers but not C-fibers, said Dr. Mays.

For the study, the investigators reviewed the electronic medical records of 194 patients who had been concurrently treated with anti-CGRP mAbs and onabot. Most (86.6%) were women; ages ranged from 36 to 65 years, and at baseline, they had been having an average of 28 (+4.6) monthly migraine days (MMDs).

The number of MMDs were assessed at two periods: 3 months after monotherapy with an anti-CGRP mAb or onabot injections, and 3 months after combined therapy.

Monotherapy reduced the average number of MMDs from 28 to 18.6, for a reduction of 9.4 days (P > .0001).

After initiation of combined therapy, the average number of MMDs decreased further, from 18.6 MMDs to 12.1 MMDs (P > .0001).

In all, the combination of onabot and anti-CGRP mAbs resulted in a total MMD reduction of 15.8 (P > .0001).

In addition, most patients (68%) reported a 50% or greater reduction in MMDs, and 46.4% reported a 75% or greater reduction.
 

Great News for Patients

Commenting for this article, Rashmi B. Halker Singh, MD, associate professor of neurology at Mayo Clinic, Scottsdale, Arizona, said the study findings “support what we see in clinical practice and what we suspected from preclinical data.”

Single-agent treatment is not sufficient for many patients. Data confirming the benefit of dual therapy will provide more evidence to insurance companies of the need for coverage.

“We have lots of individuals for whom single treatment is not sufficient and who need this combination of treatment, and it is often denied by insurance. There are preclinical data suggesting synergy, but insurance says it is experimental, so the claims get denied. This leaves patients having to choose which drug they want to continue with, and that’s really heartbreaking,” Dr. Halker Singh said.

The importance of this study is that it adds more data to support evidence-based therapies for migraine and to help patients get the treatment they need, she added.

Dr. Mays reports financial relationships with AbbVie, Amgen, and Teva. Dr. Halker Singh reports no relevant financial relationships.
 

A version of this article appeared on Medscape.com.