User login
“Terrific progress”: Adding blinatumomab for infant leukemia
.
Two-year disease-free and overall survival measures, as well as the percentage of children who had complete minimal residual disease (MRD) responses, were substantially higher among the 30 infants in the study than in historical controls treated with the same chemotherapy backbone in an earlier trial, Interfant-06.
“These outcome data are very promising, given the poor survival and lack of improvements in outcomes among infants with KMT2A-rearranged ALL in recent decades,” said the investigators, led by Inge M. van der Sluis, MD, PhD, a hematologist-oncologist at Princess Maxima Center for Pediatric Oncology in Utrecht, the Netherlands.
“The low incidence of relapse after treatment with blinatumomab is remarkable, given that in historical controls relapses occur frequently and early during therapy,” the investigators stated. Although the “follow-up time was relatively short” in the study, “it included the period historically defined” as being at high risk of relapse, they said.
The team suggested that future research should assess whether infants benefit from multiple courses of blinatumomab, rather than the one course used in the study, and whether blinatumomab plus chemotherapy can replace stem cell transplants for high-risk infants.
Pediatric community responds
There was excitement on Twitter about the results; a number of pediatric blood cancer specialists were impressed and posted the study on that platform. Comments included, “Wow! After years of stagnation, a huge step forward for infant leukemia” and “great news for infant lymphoblastic leukemia.”
Akshay Sharma, MBBS, a pediatric bone marrow transplant and cellular therapy specialist at St. Jude Children’s Research Hospital, Memphis, also posted. He said in an interview that the findings are “very exciting.”
The “outcomes of children diagnosed with leukemia in their infancy, particularly if they have a KMT2A rearrangement, have been dismal. This is terrific progress and a testament to the role that immunotherapy and novel agents will be playing in treatment of several malignant diseases in the decade to come,” he said.
Another poster, Pratik “Tik” Patel, MD, a pediatric hematology/oncology fellow at Emory University in Atlanta, told this news organization that the study “is welcome news to pediatric oncologists” and highlights “the success in incorporating newer immune-based therapeutics upfront in treatment rather than in relapsed/refractory settings.”
The National Cancer Institute–funded Children’s Oncology Group is thinking the same way. The group is launching a large, randomized trial to test if adding blinatumomab to chemotherapy upfront for B-cell acute lymphoblastic leukemia and lymphoblastic lymphoma improves outcomes in children and young adults aged 1-31 years. Results are due after 2029.
Study details
Blinatumomab is an expensive “T-cell engager” that helps cytotoxic CD3+T cells link to and destroy leukemic CD19+ B cells. Past studies have shown that it’s safe and works in older children and adults with B-lineage ALL after intensive chemotherapy, but until now the approach hadn’t been tested in infants, the investigators said.
The 30 subjects in the study were under a year old and newly diagnosed with KMT2A-rearranged ALL. They were treated with the Interfant-06 chemotherapy regimen – cytosine arabinoside and other agents – plus one postinduction course of blinatumomab at 15 micrograms/m2 per day as a 4-week continuous infusion. Eight of nine high-risk patients had allogeneic hematopoietic stem cell transplants.
Overall survival was 93.3% over a median follow up of 26.3 months, substantially higher than the 65.8% in the Interfant-06 trial. Two-year disease-free survival was 81.6% versus 49.4% in Interfant-06.
Sixteen patients (53%) were MRD negative after blinatumomab infusion and 12 (40%) had low levels of MRD. All of the children who continued chemotherapy went on to become MRD negative.
There were no permanent blinatumomab discontinuations and no treatment related deaths. Serious toxic effects were consistent with those in older patients and included four fevers, four infections, and one case each of hypertension and vomiting.
There were no cases of severe cytokine release syndrome (CRS) because of the low tumor burden of the subjects. Likewise, there were no obvious neurologic adverse events – like CRS, a particular concern with blinatumomab – but “we cannot rule out underreporting of mild neurologic symptoms that may have been unrecognized in infants,” the investigators said.
Patients who relapsed in the study had CNS involvement at relapse. “This underscores the need for adequate intrathecal chemotherapy during the blinatumomab infusion, because the efficacy of blinatumomab for the treatment of CNS leukemia may be limited,” they said.
The work was supported by Amgen, the maker of blinatumomab, as well as the Princess Maxima Center Foundation, the Danish Childhood Cancer Foundation, and others. Dr. Sluis is a consultant and researcher for Amgen. Five other authors were also consultants/advisers/researchers for the company. Dr. Sharma and Dr. Patel didn’t have any relevant disclosures.
.
Two-year disease-free and overall survival measures, as well as the percentage of children who had complete minimal residual disease (MRD) responses, were substantially higher among the 30 infants in the study than in historical controls treated with the same chemotherapy backbone in an earlier trial, Interfant-06.
“These outcome data are very promising, given the poor survival and lack of improvements in outcomes among infants with KMT2A-rearranged ALL in recent decades,” said the investigators, led by Inge M. van der Sluis, MD, PhD, a hematologist-oncologist at Princess Maxima Center for Pediatric Oncology in Utrecht, the Netherlands.
“The low incidence of relapse after treatment with blinatumomab is remarkable, given that in historical controls relapses occur frequently and early during therapy,” the investigators stated. Although the “follow-up time was relatively short” in the study, “it included the period historically defined” as being at high risk of relapse, they said.
The team suggested that future research should assess whether infants benefit from multiple courses of blinatumomab, rather than the one course used in the study, and whether blinatumomab plus chemotherapy can replace stem cell transplants for high-risk infants.
Pediatric community responds
There was excitement on Twitter about the results; a number of pediatric blood cancer specialists were impressed and posted the study on that platform. Comments included, “Wow! After years of stagnation, a huge step forward for infant leukemia” and “great news for infant lymphoblastic leukemia.”
Akshay Sharma, MBBS, a pediatric bone marrow transplant and cellular therapy specialist at St. Jude Children’s Research Hospital, Memphis, also posted. He said in an interview that the findings are “very exciting.”
The “outcomes of children diagnosed with leukemia in their infancy, particularly if they have a KMT2A rearrangement, have been dismal. This is terrific progress and a testament to the role that immunotherapy and novel agents will be playing in treatment of several malignant diseases in the decade to come,” he said.
Another poster, Pratik “Tik” Patel, MD, a pediatric hematology/oncology fellow at Emory University in Atlanta, told this news organization that the study “is welcome news to pediatric oncologists” and highlights “the success in incorporating newer immune-based therapeutics upfront in treatment rather than in relapsed/refractory settings.”
The National Cancer Institute–funded Children’s Oncology Group is thinking the same way. The group is launching a large, randomized trial to test if adding blinatumomab to chemotherapy upfront for B-cell acute lymphoblastic leukemia and lymphoblastic lymphoma improves outcomes in children and young adults aged 1-31 years. Results are due after 2029.
Study details
Blinatumomab is an expensive “T-cell engager” that helps cytotoxic CD3+T cells link to and destroy leukemic CD19+ B cells. Past studies have shown that it’s safe and works in older children and adults with B-lineage ALL after intensive chemotherapy, but until now the approach hadn’t been tested in infants, the investigators said.
The 30 subjects in the study were under a year old and newly diagnosed with KMT2A-rearranged ALL. They were treated with the Interfant-06 chemotherapy regimen – cytosine arabinoside and other agents – plus one postinduction course of blinatumomab at 15 micrograms/m2 per day as a 4-week continuous infusion. Eight of nine high-risk patients had allogeneic hematopoietic stem cell transplants.
Overall survival was 93.3% over a median follow up of 26.3 months, substantially higher than the 65.8% in the Interfant-06 trial. Two-year disease-free survival was 81.6% versus 49.4% in Interfant-06.
Sixteen patients (53%) were MRD negative after blinatumomab infusion and 12 (40%) had low levels of MRD. All of the children who continued chemotherapy went on to become MRD negative.
There were no permanent blinatumomab discontinuations and no treatment related deaths. Serious toxic effects were consistent with those in older patients and included four fevers, four infections, and one case each of hypertension and vomiting.
There were no cases of severe cytokine release syndrome (CRS) because of the low tumor burden of the subjects. Likewise, there were no obvious neurologic adverse events – like CRS, a particular concern with blinatumomab – but “we cannot rule out underreporting of mild neurologic symptoms that may have been unrecognized in infants,” the investigators said.
Patients who relapsed in the study had CNS involvement at relapse. “This underscores the need for adequate intrathecal chemotherapy during the blinatumomab infusion, because the efficacy of blinatumomab for the treatment of CNS leukemia may be limited,” they said.
The work was supported by Amgen, the maker of blinatumomab, as well as the Princess Maxima Center Foundation, the Danish Childhood Cancer Foundation, and others. Dr. Sluis is a consultant and researcher for Amgen. Five other authors were also consultants/advisers/researchers for the company. Dr. Sharma and Dr. Patel didn’t have any relevant disclosures.
.
Two-year disease-free and overall survival measures, as well as the percentage of children who had complete minimal residual disease (MRD) responses, were substantially higher among the 30 infants in the study than in historical controls treated with the same chemotherapy backbone in an earlier trial, Interfant-06.
“These outcome data are very promising, given the poor survival and lack of improvements in outcomes among infants with KMT2A-rearranged ALL in recent decades,” said the investigators, led by Inge M. van der Sluis, MD, PhD, a hematologist-oncologist at Princess Maxima Center for Pediatric Oncology in Utrecht, the Netherlands.
“The low incidence of relapse after treatment with blinatumomab is remarkable, given that in historical controls relapses occur frequently and early during therapy,” the investigators stated. Although the “follow-up time was relatively short” in the study, “it included the period historically defined” as being at high risk of relapse, they said.
The team suggested that future research should assess whether infants benefit from multiple courses of blinatumomab, rather than the one course used in the study, and whether blinatumomab plus chemotherapy can replace stem cell transplants for high-risk infants.
Pediatric community responds
There was excitement on Twitter about the results; a number of pediatric blood cancer specialists were impressed and posted the study on that platform. Comments included, “Wow! After years of stagnation, a huge step forward for infant leukemia” and “great news for infant lymphoblastic leukemia.”
Akshay Sharma, MBBS, a pediatric bone marrow transplant and cellular therapy specialist at St. Jude Children’s Research Hospital, Memphis, also posted. He said in an interview that the findings are “very exciting.”
The “outcomes of children diagnosed with leukemia in their infancy, particularly if they have a KMT2A rearrangement, have been dismal. This is terrific progress and a testament to the role that immunotherapy and novel agents will be playing in treatment of several malignant diseases in the decade to come,” he said.
Another poster, Pratik “Tik” Patel, MD, a pediatric hematology/oncology fellow at Emory University in Atlanta, told this news organization that the study “is welcome news to pediatric oncologists” and highlights “the success in incorporating newer immune-based therapeutics upfront in treatment rather than in relapsed/refractory settings.”
The National Cancer Institute–funded Children’s Oncology Group is thinking the same way. The group is launching a large, randomized trial to test if adding blinatumomab to chemotherapy upfront for B-cell acute lymphoblastic leukemia and lymphoblastic lymphoma improves outcomes in children and young adults aged 1-31 years. Results are due after 2029.
Study details
Blinatumomab is an expensive “T-cell engager” that helps cytotoxic CD3+T cells link to and destroy leukemic CD19+ B cells. Past studies have shown that it’s safe and works in older children and adults with B-lineage ALL after intensive chemotherapy, but until now the approach hadn’t been tested in infants, the investigators said.
The 30 subjects in the study were under a year old and newly diagnosed with KMT2A-rearranged ALL. They were treated with the Interfant-06 chemotherapy regimen – cytosine arabinoside and other agents – plus one postinduction course of blinatumomab at 15 micrograms/m2 per day as a 4-week continuous infusion. Eight of nine high-risk patients had allogeneic hematopoietic stem cell transplants.
Overall survival was 93.3% over a median follow up of 26.3 months, substantially higher than the 65.8% in the Interfant-06 trial. Two-year disease-free survival was 81.6% versus 49.4% in Interfant-06.
Sixteen patients (53%) were MRD negative after blinatumomab infusion and 12 (40%) had low levels of MRD. All of the children who continued chemotherapy went on to become MRD negative.
There were no permanent blinatumomab discontinuations and no treatment related deaths. Serious toxic effects were consistent with those in older patients and included four fevers, four infections, and one case each of hypertension and vomiting.
There were no cases of severe cytokine release syndrome (CRS) because of the low tumor burden of the subjects. Likewise, there were no obvious neurologic adverse events – like CRS, a particular concern with blinatumomab – but “we cannot rule out underreporting of mild neurologic symptoms that may have been unrecognized in infants,” the investigators said.
Patients who relapsed in the study had CNS involvement at relapse. “This underscores the need for adequate intrathecal chemotherapy during the blinatumomab infusion, because the efficacy of blinatumomab for the treatment of CNS leukemia may be limited,” they said.
The work was supported by Amgen, the maker of blinatumomab, as well as the Princess Maxima Center Foundation, the Danish Childhood Cancer Foundation, and others. Dr. Sluis is a consultant and researcher for Amgen. Five other authors were also consultants/advisers/researchers for the company. Dr. Sharma and Dr. Patel didn’t have any relevant disclosures.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
FDA puts partial hold on investigational alopecia areata drug deuruxolitinib
The in a press release on May 2.
The announcement came after a pulmonary embolism occurred with the 12-mg twice-daily dose in one of the long-term open-label extension (OLE) studies, the company, Sun Pharmaceutical Industries, said.
The company stated that the FDA has placed the Investigational New Drug testing for deuruxolitinib on partial clinical hold, and the agency is requiring that study participants who are currently on the 12-mg twice-daily dose in the OLE studies stop taking that dose. The hold covers only the 12-mg dose.
No hold on 8-mg dose
“There have been no thrombotic events reported to date for the 8-mg b.i.d. dose and U.S. FDA has not placed the 8-mg b.i.d. dose on hold,” the company said in the statement.
The statement added, “We are taking immediate steps to transition the patients in the OLE studies to the 8-mg b.i.d. dose arm in the ongoing studies.”
The company said that no thromboembolic events were observed in the phase 2 or phase 3 trials and said that it will work closely with the FDA to address its concerns. A formal letter detailing the FDA’s concerns is expected within 30 days.
Deuruxolitinib is an investigational oral selective inhibitor of Janus kinase 1 (JAK1) and JAK2 enzymes.
The FDA has granted deuruxolitinib breakthrough therapy designation for the treatment of adult patients with moderate to severe alopecia areata as well as fast-track designation for the treatment of alopecia areata.
In March, this news organization reported from the annual meeting of the American Academy of Dermatology that, based on phase 3 studies that demonstrate robust hair growth in about one-third of patients, deuruxolitinib has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received FDA approval almost 1 year ago.
Also at the AAD annual meeting, this news organization reported that principal investigator Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn., in his presentation on the results of THRIVE-AA2, one of the two phase 3 trials of deuruxolitinib, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.” Dr King also was a principal investigator in studies of baricitinib.
With one exception, labeling for baricitinib and other JAK inhibitors with dermatologic indications includes a boxed warning listing serious adverse events including the risk for major adverse cardiac events and thrombosis, including pulmonary embolism, based on the risks in a rheumatoid arthritis study.
A version of this article first appeared on Medscape.com.
The in a press release on May 2.
The announcement came after a pulmonary embolism occurred with the 12-mg twice-daily dose in one of the long-term open-label extension (OLE) studies, the company, Sun Pharmaceutical Industries, said.
The company stated that the FDA has placed the Investigational New Drug testing for deuruxolitinib on partial clinical hold, and the agency is requiring that study participants who are currently on the 12-mg twice-daily dose in the OLE studies stop taking that dose. The hold covers only the 12-mg dose.
No hold on 8-mg dose
“There have been no thrombotic events reported to date for the 8-mg b.i.d. dose and U.S. FDA has not placed the 8-mg b.i.d. dose on hold,” the company said in the statement.
The statement added, “We are taking immediate steps to transition the patients in the OLE studies to the 8-mg b.i.d. dose arm in the ongoing studies.”
The company said that no thromboembolic events were observed in the phase 2 or phase 3 trials and said that it will work closely with the FDA to address its concerns. A formal letter detailing the FDA’s concerns is expected within 30 days.
Deuruxolitinib is an investigational oral selective inhibitor of Janus kinase 1 (JAK1) and JAK2 enzymes.
The FDA has granted deuruxolitinib breakthrough therapy designation for the treatment of adult patients with moderate to severe alopecia areata as well as fast-track designation for the treatment of alopecia areata.
In March, this news organization reported from the annual meeting of the American Academy of Dermatology that, based on phase 3 studies that demonstrate robust hair growth in about one-third of patients, deuruxolitinib has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received FDA approval almost 1 year ago.
Also at the AAD annual meeting, this news organization reported that principal investigator Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn., in his presentation on the results of THRIVE-AA2, one of the two phase 3 trials of deuruxolitinib, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.” Dr King also was a principal investigator in studies of baricitinib.
With one exception, labeling for baricitinib and other JAK inhibitors with dermatologic indications includes a boxed warning listing serious adverse events including the risk for major adverse cardiac events and thrombosis, including pulmonary embolism, based on the risks in a rheumatoid arthritis study.
A version of this article first appeared on Medscape.com.
The in a press release on May 2.
The announcement came after a pulmonary embolism occurred with the 12-mg twice-daily dose in one of the long-term open-label extension (OLE) studies, the company, Sun Pharmaceutical Industries, said.
The company stated that the FDA has placed the Investigational New Drug testing for deuruxolitinib on partial clinical hold, and the agency is requiring that study participants who are currently on the 12-mg twice-daily dose in the OLE studies stop taking that dose. The hold covers only the 12-mg dose.
No hold on 8-mg dose
“There have been no thrombotic events reported to date for the 8-mg b.i.d. dose and U.S. FDA has not placed the 8-mg b.i.d. dose on hold,” the company said in the statement.
The statement added, “We are taking immediate steps to transition the patients in the OLE studies to the 8-mg b.i.d. dose arm in the ongoing studies.”
The company said that no thromboembolic events were observed in the phase 2 or phase 3 trials and said that it will work closely with the FDA to address its concerns. A formal letter detailing the FDA’s concerns is expected within 30 days.
Deuruxolitinib is an investigational oral selective inhibitor of Janus kinase 1 (JAK1) and JAK2 enzymes.
The FDA has granted deuruxolitinib breakthrough therapy designation for the treatment of adult patients with moderate to severe alopecia areata as well as fast-track designation for the treatment of alopecia areata.
In March, this news organization reported from the annual meeting of the American Academy of Dermatology that, based on phase 3 studies that demonstrate robust hair growth in about one-third of patients, deuruxolitinib has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received FDA approval almost 1 year ago.
Also at the AAD annual meeting, this news organization reported that principal investigator Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn., in his presentation on the results of THRIVE-AA2, one of the two phase 3 trials of deuruxolitinib, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.” Dr King also was a principal investigator in studies of baricitinib.
With one exception, labeling for baricitinib and other JAK inhibitors with dermatologic indications includes a boxed warning listing serious adverse events including the risk for major adverse cardiac events and thrombosis, including pulmonary embolism, based on the risks in a rheumatoid arthritis study.
A version of this article first appeared on Medscape.com.
Should CGM be used for those without diabetes?
Dallas Waldon doesn’t have diabetes, but she says she benefits from continuous glucose monitoring (CGM). “I’m a huge fan of CGMs and used them before, during, and after my pregnancy, [up to] 6 months postpartum, I’m down 11 pounds from my prepregnancy weight,” said Ms. Waldon, a manager for a land-buying company who lives in El Dorado, Calif.
“CGMs bring a certain level of accountability to what you’re eating. You can’t pretend you didn’t eat that cookie while making the kids’ lunch, or that the latte you had was ‘just coffee,’ ” she said. “You have the hard numbers to answer to, and that makes you think twice before putting anything in your mouth.”
Ms. Waldon is not alone. Although CGMs are typically used by people with type 1 diabetes, and increasingly those with type 2 diabetes, some endocrinologists say they are seeing an increased demand for CGM use from individuals who don’t have diabetes.
This allows users to monitor the glucose level and see how eating and exercise affects it. The companies claim that CGM use will help motivate individuals to eat better and maximize their exercise, and therefore consequently lose weight.
These lifestyle programs typically offer users the FreeStyle Libre (Abbott Laboratories). It uses a coin-sized sensor, generally worn on the upper arm, which lasts 14 days and measures glucose in the interstitial fluid. Users can read their glucose levels via an app on their smartphones as many times a day as they want. The FreeStyle Libre is worn by many people with diabetes and is a simple CGM to use, said Anne Peters, MD, professor of clinical medicine, University of Southern California, Los Angeles.
This growing demand for CGM use among healthy people is driven by an increasing “fascination” for monitoring every bodily function, as can be seen by the popularity of smart devices such as Fitbits and Apple watches, Dr. Peters added. These devices allow users to see their heart rates, review their sleep patterns, and monitor their pulses in real time; a CGM is an extension of that by providing up-to-the-minute glucose monitoring.
‘Everyone wants a CGM’
“Everyone wants a CGM,” Dr. Peters said, noting that even family members of her patients with diabetes are asking for them. She admits that their use can be effective for those who are prediabetic so they can see their glycemic responses to food. For instance, someone who typically eats oatmeal for breakfast may see their blood glucose increase, meaning they might want to lower their carbs.
David Klonoff, MD, medical director of the Diabetes Research Institute, Mills-Peninsula Medical Center, San Mateo, Calif., agrees that there has been an increase in use by people who don’t have diabetes as CGMs offer information they wouldn’t otherwise have access to “without having to prick themselves many times.”
People are using CGMs to monitor how high their blood glucose rises after eating certain foods, the length of time it takes to reach peak levels, and how quickly levels drop, he added. Elite athletes are using CGMs to ensure that they are consuming enough calories to avoid hypoglycemia, Dr. Klonoff said.
David T. Ahn, MD, program director at the Mary & Dick Allen Diabetes Center at Hoag Hospital in Newport Beach, Calif., also believes that the devices can provide useful information. “I find that CGM helps people learn a lot about nutrition and how lifestyle choices like food, activity, and stress impact their own physiology,” he stated.
“For example, comparing glucose spikes after different [types of] meals can deepen people’s understanding of carbohydrates vs. protein, or high glycemic index foods vs. low glycemic index foods,” he continued. “In addition, if a patient chooses to follow a very low-carbohydrate diet and/or an intermittent fasting diet, a CGM can be a powerful tool to measure consistency with that lifestyle choice.”
And for a person without diabetes, wearing a CGM provides a way to have personalized information on other physiologic measures, part of the quantified self movement where users log and track their blood pressure, urine output, and oxygen saturation, among other things, Dr. Klonoff said.
But does knowing all this result in behavioral changes?
Dr. Ahn isn’t sure. “For many people, being able to see glucose excursions throughout the day and after meals can be extremely educational and motivating. But much like the Fitbit or Apple Watch, simply wearing [a CGM] ... does not translate to behavior change. The CGM data patterns in someone without diabetes can start to become predictable over time, leading to a drop-off in utility/adherence after the initial education period,” he said.
Dr. Peters said she too isn’t convinced about the long-term worth of CGM in promoting or sustaining behavioral change, as the “novelty” of tracking may wear off after a few months.
And there’s no scientific proof that CGM use in those without diabetes has any impact.
“While there are many programs that offer coaching with CGM data, we need more studies to determine if this leads to improved outcomes like weight loss and prevention, or delay in the development of diabetes,” said Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES, FADCES, FCCP, director of education and training in diabetes technology at Cleveland Clinic Diabetes Center.
A 2019 study published in the Journal of Clinical Endocrinology and Metabolism found that the blood glucose of individuals without diabetes using a CGM was in the “ideal” range between 70 mg/dL and 140 mg/dL 96% of the time. “Their glucose was beautifully controlled,” said Dr. Peters, who was one of the study authors.
Currently there aren’t any studies evaluating patterns among healthy individuals wearing CGMs, Dr. Klonoff noted, but he predicts that those studies will be done in the future to examine metabolic patterns that might contribute to someone developing prediabetes or diabetes.
“More data are needed from studies that focus on individuals at risk for diabetes to better understand the role of CGM in these cases, and how to best interpret and utilize the results,” said Fida Bacha, MD, a diabetes and endocrinology specialist and associate professor of pediatrics at Baylor College of Medicine in Houston.
“If clear metrics are identified to predict the progression to diabetes, then this would be worthwhile for early detection and prevention of the disease,” Dr. Bacha said.
Are CGMs too expensive, and can the information overwhelm some?
The biggest obstacle to many people using CGM is cost. “The main downside of using a CGM without diabetes is cost, since insurance won’t usually cover a CGM if the patient does not have diabetes,” said Marilyn Tan, MD, FACE, chief of the Endocrine Clinic, Stanford Health Clinic, Palo Alto, Calif. “Even for patients with diabetes but not on insulin, CGM coverage can be challenging, as out-of-pocket costs for CGM are variable.”
The lifestyle companies mentioned above charge $139-$399 per month, which covers two CGM sensors, each one good for 14 days. Users need to subscribe to a plan for service and delivery. Additional services such as nutrition counseling may be available at an additional cost. Because CGMs in the United States require a prescription, these companies offer web screening and access to a web-based provider.
If healthy patients feel that the informational value of CGMs is worth the money, then they shouldn’t be discouraged, the experts believe.
“There’s little risk of harm with wearing a CGM,” Dr. Tan said, although she acknowledges that “[t]oo much information can also be overwhelming for some individuals.”
Users need to consult with their clinicians to ensure they understand the readings, Dr. Peters said. “You have to tell them not to overreact if the device reads low [glucose] or not to freak out if they get an alarm.” A high glucose reading, indicating hyperglycemia, can be caused by a steroid injection, or older people may experience a postprandial high after eating, she added. “They need to talk to their healthcare provider to interpret the data especially if they are out of [the ideal glucose] range.”
Dr. Klonoff agreed that there is a risk of people trying to “medicalize” too much information. “If you have a fever, you don’t have to go to a doctor to know you have an infection,” he said.
And the point, he added, is not to obsess over the individual numbers but to look for patterns particularly as predictors of metabolic syndrome. If a patient’s glucose is primarily in range, he or she wouldn’t necessarily worry about diabetes. But if it’s out of range more than 10% of the time, it might mean that patient is at risk for diabetes. “It might be time to counsel the patient to eat healthier and exercise more,” he said. “It’s never wrong to steer people to a healthier lifestyle.”
But another issue is whether the numbers from CGMs are entirely accurate in people without diabetes. A 2020 study published in the American Journal of Clinical Nutrition had 16 adults without diabetes wear both the Dexcom G4 Platinum CGM and Abbott FreeStyle Libre Pro for 28 days.
Researchers found that mean postprandial glucose was higher with the Dexcom than with the Abbott system, suggesting that “postprandial glycemic excursions were somewhat inconsistent between the CGMs.” The authors concluded that it may be too early to personalize meal recommendations via CGM.
Dr. Isaacs said perhaps the happy medium is for those without diabetes to just use CGMs occasionally. “It’s ... unclear [if] the right [use] of CGM needs to be continuous or if periodic use, such as once every 3 months, is enough for benefits,” she concluded.
A version of this article first appeared on Medscape.com.
Dallas Waldon doesn’t have diabetes, but she says she benefits from continuous glucose monitoring (CGM). “I’m a huge fan of CGMs and used them before, during, and after my pregnancy, [up to] 6 months postpartum, I’m down 11 pounds from my prepregnancy weight,” said Ms. Waldon, a manager for a land-buying company who lives in El Dorado, Calif.
“CGMs bring a certain level of accountability to what you’re eating. You can’t pretend you didn’t eat that cookie while making the kids’ lunch, or that the latte you had was ‘just coffee,’ ” she said. “You have the hard numbers to answer to, and that makes you think twice before putting anything in your mouth.”
Ms. Waldon is not alone. Although CGMs are typically used by people with type 1 diabetes, and increasingly those with type 2 diabetes, some endocrinologists say they are seeing an increased demand for CGM use from individuals who don’t have diabetes.
This allows users to monitor the glucose level and see how eating and exercise affects it. The companies claim that CGM use will help motivate individuals to eat better and maximize their exercise, and therefore consequently lose weight.
These lifestyle programs typically offer users the FreeStyle Libre (Abbott Laboratories). It uses a coin-sized sensor, generally worn on the upper arm, which lasts 14 days and measures glucose in the interstitial fluid. Users can read their glucose levels via an app on their smartphones as many times a day as they want. The FreeStyle Libre is worn by many people with diabetes and is a simple CGM to use, said Anne Peters, MD, professor of clinical medicine, University of Southern California, Los Angeles.
This growing demand for CGM use among healthy people is driven by an increasing “fascination” for monitoring every bodily function, as can be seen by the popularity of smart devices such as Fitbits and Apple watches, Dr. Peters added. These devices allow users to see their heart rates, review their sleep patterns, and monitor their pulses in real time; a CGM is an extension of that by providing up-to-the-minute glucose monitoring.
‘Everyone wants a CGM’
“Everyone wants a CGM,” Dr. Peters said, noting that even family members of her patients with diabetes are asking for them. She admits that their use can be effective for those who are prediabetic so they can see their glycemic responses to food. For instance, someone who typically eats oatmeal for breakfast may see their blood glucose increase, meaning they might want to lower their carbs.
David Klonoff, MD, medical director of the Diabetes Research Institute, Mills-Peninsula Medical Center, San Mateo, Calif., agrees that there has been an increase in use by people who don’t have diabetes as CGMs offer information they wouldn’t otherwise have access to “without having to prick themselves many times.”
People are using CGMs to monitor how high their blood glucose rises after eating certain foods, the length of time it takes to reach peak levels, and how quickly levels drop, he added. Elite athletes are using CGMs to ensure that they are consuming enough calories to avoid hypoglycemia, Dr. Klonoff said.
David T. Ahn, MD, program director at the Mary & Dick Allen Diabetes Center at Hoag Hospital in Newport Beach, Calif., also believes that the devices can provide useful information. “I find that CGM helps people learn a lot about nutrition and how lifestyle choices like food, activity, and stress impact their own physiology,” he stated.
“For example, comparing glucose spikes after different [types of] meals can deepen people’s understanding of carbohydrates vs. protein, or high glycemic index foods vs. low glycemic index foods,” he continued. “In addition, if a patient chooses to follow a very low-carbohydrate diet and/or an intermittent fasting diet, a CGM can be a powerful tool to measure consistency with that lifestyle choice.”
And for a person without diabetes, wearing a CGM provides a way to have personalized information on other physiologic measures, part of the quantified self movement where users log and track their blood pressure, urine output, and oxygen saturation, among other things, Dr. Klonoff said.
But does knowing all this result in behavioral changes?
Dr. Ahn isn’t sure. “For many people, being able to see glucose excursions throughout the day and after meals can be extremely educational and motivating. But much like the Fitbit or Apple Watch, simply wearing [a CGM] ... does not translate to behavior change. The CGM data patterns in someone without diabetes can start to become predictable over time, leading to a drop-off in utility/adherence after the initial education period,” he said.
Dr. Peters said she too isn’t convinced about the long-term worth of CGM in promoting or sustaining behavioral change, as the “novelty” of tracking may wear off after a few months.
And there’s no scientific proof that CGM use in those without diabetes has any impact.
“While there are many programs that offer coaching with CGM data, we need more studies to determine if this leads to improved outcomes like weight loss and prevention, or delay in the development of diabetes,” said Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES, FADCES, FCCP, director of education and training in diabetes technology at Cleveland Clinic Diabetes Center.
A 2019 study published in the Journal of Clinical Endocrinology and Metabolism found that the blood glucose of individuals without diabetes using a CGM was in the “ideal” range between 70 mg/dL and 140 mg/dL 96% of the time. “Their glucose was beautifully controlled,” said Dr. Peters, who was one of the study authors.
Currently there aren’t any studies evaluating patterns among healthy individuals wearing CGMs, Dr. Klonoff noted, but he predicts that those studies will be done in the future to examine metabolic patterns that might contribute to someone developing prediabetes or diabetes.
“More data are needed from studies that focus on individuals at risk for diabetes to better understand the role of CGM in these cases, and how to best interpret and utilize the results,” said Fida Bacha, MD, a diabetes and endocrinology specialist and associate professor of pediatrics at Baylor College of Medicine in Houston.
“If clear metrics are identified to predict the progression to diabetes, then this would be worthwhile for early detection and prevention of the disease,” Dr. Bacha said.
Are CGMs too expensive, and can the information overwhelm some?
The biggest obstacle to many people using CGM is cost. “The main downside of using a CGM without diabetes is cost, since insurance won’t usually cover a CGM if the patient does not have diabetes,” said Marilyn Tan, MD, FACE, chief of the Endocrine Clinic, Stanford Health Clinic, Palo Alto, Calif. “Even for patients with diabetes but not on insulin, CGM coverage can be challenging, as out-of-pocket costs for CGM are variable.”
The lifestyle companies mentioned above charge $139-$399 per month, which covers two CGM sensors, each one good for 14 days. Users need to subscribe to a plan for service and delivery. Additional services such as nutrition counseling may be available at an additional cost. Because CGMs in the United States require a prescription, these companies offer web screening and access to a web-based provider.
If healthy patients feel that the informational value of CGMs is worth the money, then they shouldn’t be discouraged, the experts believe.
“There’s little risk of harm with wearing a CGM,” Dr. Tan said, although she acknowledges that “[t]oo much information can also be overwhelming for some individuals.”
Users need to consult with their clinicians to ensure they understand the readings, Dr. Peters said. “You have to tell them not to overreact if the device reads low [glucose] or not to freak out if they get an alarm.” A high glucose reading, indicating hyperglycemia, can be caused by a steroid injection, or older people may experience a postprandial high after eating, she added. “They need to talk to their healthcare provider to interpret the data especially if they are out of [the ideal glucose] range.”
Dr. Klonoff agreed that there is a risk of people trying to “medicalize” too much information. “If you have a fever, you don’t have to go to a doctor to know you have an infection,” he said.
And the point, he added, is not to obsess over the individual numbers but to look for patterns particularly as predictors of metabolic syndrome. If a patient’s glucose is primarily in range, he or she wouldn’t necessarily worry about diabetes. But if it’s out of range more than 10% of the time, it might mean that patient is at risk for diabetes. “It might be time to counsel the patient to eat healthier and exercise more,” he said. “It’s never wrong to steer people to a healthier lifestyle.”
But another issue is whether the numbers from CGMs are entirely accurate in people without diabetes. A 2020 study published in the American Journal of Clinical Nutrition had 16 adults without diabetes wear both the Dexcom G4 Platinum CGM and Abbott FreeStyle Libre Pro for 28 days.
Researchers found that mean postprandial glucose was higher with the Dexcom than with the Abbott system, suggesting that “postprandial glycemic excursions were somewhat inconsistent between the CGMs.” The authors concluded that it may be too early to personalize meal recommendations via CGM.
Dr. Isaacs said perhaps the happy medium is for those without diabetes to just use CGMs occasionally. “It’s ... unclear [if] the right [use] of CGM needs to be continuous or if periodic use, such as once every 3 months, is enough for benefits,” she concluded.
A version of this article first appeared on Medscape.com.
Dallas Waldon doesn’t have diabetes, but she says she benefits from continuous glucose monitoring (CGM). “I’m a huge fan of CGMs and used them before, during, and after my pregnancy, [up to] 6 months postpartum, I’m down 11 pounds from my prepregnancy weight,” said Ms. Waldon, a manager for a land-buying company who lives in El Dorado, Calif.
“CGMs bring a certain level of accountability to what you’re eating. You can’t pretend you didn’t eat that cookie while making the kids’ lunch, or that the latte you had was ‘just coffee,’ ” she said. “You have the hard numbers to answer to, and that makes you think twice before putting anything in your mouth.”
Ms. Waldon is not alone. Although CGMs are typically used by people with type 1 diabetes, and increasingly those with type 2 diabetes, some endocrinologists say they are seeing an increased demand for CGM use from individuals who don’t have diabetes.
This allows users to monitor the glucose level and see how eating and exercise affects it. The companies claim that CGM use will help motivate individuals to eat better and maximize their exercise, and therefore consequently lose weight.
These lifestyle programs typically offer users the FreeStyle Libre (Abbott Laboratories). It uses a coin-sized sensor, generally worn on the upper arm, which lasts 14 days and measures glucose in the interstitial fluid. Users can read their glucose levels via an app on their smartphones as many times a day as they want. The FreeStyle Libre is worn by many people with diabetes and is a simple CGM to use, said Anne Peters, MD, professor of clinical medicine, University of Southern California, Los Angeles.
This growing demand for CGM use among healthy people is driven by an increasing “fascination” for monitoring every bodily function, as can be seen by the popularity of smart devices such as Fitbits and Apple watches, Dr. Peters added. These devices allow users to see their heart rates, review their sleep patterns, and monitor their pulses in real time; a CGM is an extension of that by providing up-to-the-minute glucose monitoring.
‘Everyone wants a CGM’
“Everyone wants a CGM,” Dr. Peters said, noting that even family members of her patients with diabetes are asking for them. She admits that their use can be effective for those who are prediabetic so they can see their glycemic responses to food. For instance, someone who typically eats oatmeal for breakfast may see their blood glucose increase, meaning they might want to lower their carbs.
David Klonoff, MD, medical director of the Diabetes Research Institute, Mills-Peninsula Medical Center, San Mateo, Calif., agrees that there has been an increase in use by people who don’t have diabetes as CGMs offer information they wouldn’t otherwise have access to “without having to prick themselves many times.”
People are using CGMs to monitor how high their blood glucose rises after eating certain foods, the length of time it takes to reach peak levels, and how quickly levels drop, he added. Elite athletes are using CGMs to ensure that they are consuming enough calories to avoid hypoglycemia, Dr. Klonoff said.
David T. Ahn, MD, program director at the Mary & Dick Allen Diabetes Center at Hoag Hospital in Newport Beach, Calif., also believes that the devices can provide useful information. “I find that CGM helps people learn a lot about nutrition and how lifestyle choices like food, activity, and stress impact their own physiology,” he stated.
“For example, comparing glucose spikes after different [types of] meals can deepen people’s understanding of carbohydrates vs. protein, or high glycemic index foods vs. low glycemic index foods,” he continued. “In addition, if a patient chooses to follow a very low-carbohydrate diet and/or an intermittent fasting diet, a CGM can be a powerful tool to measure consistency with that lifestyle choice.”
And for a person without diabetes, wearing a CGM provides a way to have personalized information on other physiologic measures, part of the quantified self movement where users log and track their blood pressure, urine output, and oxygen saturation, among other things, Dr. Klonoff said.
But does knowing all this result in behavioral changes?
Dr. Ahn isn’t sure. “For many people, being able to see glucose excursions throughout the day and after meals can be extremely educational and motivating. But much like the Fitbit or Apple Watch, simply wearing [a CGM] ... does not translate to behavior change. The CGM data patterns in someone without diabetes can start to become predictable over time, leading to a drop-off in utility/adherence after the initial education period,” he said.
Dr. Peters said she too isn’t convinced about the long-term worth of CGM in promoting or sustaining behavioral change, as the “novelty” of tracking may wear off after a few months.
And there’s no scientific proof that CGM use in those without diabetes has any impact.
“While there are many programs that offer coaching with CGM data, we need more studies to determine if this leads to improved outcomes like weight loss and prevention, or delay in the development of diabetes,” said Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES, FADCES, FCCP, director of education and training in diabetes technology at Cleveland Clinic Diabetes Center.
A 2019 study published in the Journal of Clinical Endocrinology and Metabolism found that the blood glucose of individuals without diabetes using a CGM was in the “ideal” range between 70 mg/dL and 140 mg/dL 96% of the time. “Their glucose was beautifully controlled,” said Dr. Peters, who was one of the study authors.
Currently there aren’t any studies evaluating patterns among healthy individuals wearing CGMs, Dr. Klonoff noted, but he predicts that those studies will be done in the future to examine metabolic patterns that might contribute to someone developing prediabetes or diabetes.
“More data are needed from studies that focus on individuals at risk for diabetes to better understand the role of CGM in these cases, and how to best interpret and utilize the results,” said Fida Bacha, MD, a diabetes and endocrinology specialist and associate professor of pediatrics at Baylor College of Medicine in Houston.
“If clear metrics are identified to predict the progression to diabetes, then this would be worthwhile for early detection and prevention of the disease,” Dr. Bacha said.
Are CGMs too expensive, and can the information overwhelm some?
The biggest obstacle to many people using CGM is cost. “The main downside of using a CGM without diabetes is cost, since insurance won’t usually cover a CGM if the patient does not have diabetes,” said Marilyn Tan, MD, FACE, chief of the Endocrine Clinic, Stanford Health Clinic, Palo Alto, Calif. “Even for patients with diabetes but not on insulin, CGM coverage can be challenging, as out-of-pocket costs for CGM are variable.”
The lifestyle companies mentioned above charge $139-$399 per month, which covers two CGM sensors, each one good for 14 days. Users need to subscribe to a plan for service and delivery. Additional services such as nutrition counseling may be available at an additional cost. Because CGMs in the United States require a prescription, these companies offer web screening and access to a web-based provider.
If healthy patients feel that the informational value of CGMs is worth the money, then they shouldn’t be discouraged, the experts believe.
“There’s little risk of harm with wearing a CGM,” Dr. Tan said, although she acknowledges that “[t]oo much information can also be overwhelming for some individuals.”
Users need to consult with their clinicians to ensure they understand the readings, Dr. Peters said. “You have to tell them not to overreact if the device reads low [glucose] or not to freak out if they get an alarm.” A high glucose reading, indicating hyperglycemia, can be caused by a steroid injection, or older people may experience a postprandial high after eating, she added. “They need to talk to their healthcare provider to interpret the data especially if they are out of [the ideal glucose] range.”
Dr. Klonoff agreed that there is a risk of people trying to “medicalize” too much information. “If you have a fever, you don’t have to go to a doctor to know you have an infection,” he said.
And the point, he added, is not to obsess over the individual numbers but to look for patterns particularly as predictors of metabolic syndrome. If a patient’s glucose is primarily in range, he or she wouldn’t necessarily worry about diabetes. But if it’s out of range more than 10% of the time, it might mean that patient is at risk for diabetes. “It might be time to counsel the patient to eat healthier and exercise more,” he said. “It’s never wrong to steer people to a healthier lifestyle.”
But another issue is whether the numbers from CGMs are entirely accurate in people without diabetes. A 2020 study published in the American Journal of Clinical Nutrition had 16 adults without diabetes wear both the Dexcom G4 Platinum CGM and Abbott FreeStyle Libre Pro for 28 days.
Researchers found that mean postprandial glucose was higher with the Dexcom than with the Abbott system, suggesting that “postprandial glycemic excursions were somewhat inconsistent between the CGMs.” The authors concluded that it may be too early to personalize meal recommendations via CGM.
Dr. Isaacs said perhaps the happy medium is for those without diabetes to just use CGMs occasionally. “It’s ... unclear [if] the right [use] of CGM needs to be continuous or if periodic use, such as once every 3 months, is enough for benefits,” she concluded.
A version of this article first appeared on Medscape.com.
ASCO updates treatment guidelines for anxiety and depression
Since the last guidelines, published in 2014, screening and assessment for depression and anxiety have improved, and a large new evidence base has emerged. To ensure the most up-to-date recommendations, a group of experts spanning psychology, psychiatry, medical and surgical oncology, internal medicine, and nursing convened to review the current literature on managing depression and anxiety. The review included 61 studies – 16 meta-analyses, 44 randomized controlled trials, and one systematic review – published between 2013 and 2021.
“The purpose of this guideline update is to gather and examine the evidence published since the 2014 guideline ... [with a] focus on management and treatment only.” The overall goal is to provide “the most effective and least resource-intensive intervention based on symptom severity” for patients with cancer, the experts write.
The new clinical practice guideline addresses the following question: What are the recommended treatment approaches in the management of anxiety and/or depression in survivors of adult cancer?
After an extensive literature search and analysis, the study was published online in the Journal of Clinical Oncology.
The expert panel’s recommendations fell into three broad categories – general management principles, treatment and care options for depressive symptoms, and treatment and care options for anxiety symptoms – with the guidelines for managing depression and anxiety largely mirroring each other.
The authors caution, however, that the guidelines “were developed in the context of mental health care being available and may not be applicable within other resource settings.”
General management principals
All patients with cancer, along with their caregivers, family members, or trusted confidants, should be offered information and resources on depression and anxiety. The panel gave this a “strong” recommendation but provided the caveat that the “information should be culturally informed and linguistically appropriate and can include a conversation between clinician and patient.”
Clinicians should select the most effective and least intensive intervention based on symptom severity when selecting treatment – what the panelists referred to as a stepped-care model. History of psychiatric diagnoses or substance use as well as prior responses to mental health treatment are some of the factors that may inform treatment choice.
For patients experiencing both depression and anxiety symptoms, treatment of depressive symptoms should be prioritized.
When referring a patient for further evaluation or care, clinicians “should make every effort to reduce barriers and facilitate patient follow-through,” the authors write. And health care professionals should regularly assess the treatment responses for patients receiving psychological or pharmacological interventions.
Overall, the treatments should be “supervised by a psychiatrist, and primary care or oncology providers work collaboratively with a nurse care manager to provide psychological interventions and monitor treatment compliance and outcomes,” the panelists write. “This type of collaborative care is found to be superior to usual care and is more cost-effective than face-to-face and pharmacologic treatment for depression.”
Treatment and care options for depressive and anxiety symptoms
For patients with moderate to severe depression symptoms, the panelists again stressed that clinicians should provide “culturally informed and linguistically appropriate information.” This information may include the frequency and symptoms of depression as well as signs these symptoms may be getting worse, with contact information for the medical team provided.
Among patients with moderate symptoms, clinicians can offer patients a range of individual or group therapy options, including cognitive-behavioral therapy (CBT), behavioral activation, mindfulness-based stress reduction, or structured physical activity and exercise. For patients with severe symptoms of depression, clinicians should offer individual therapy with one of these four treatment options: CBT, behavioral activation, mindfulness-based stress reduction, or interpersonal therapy.
The panelists offered almost identical recommendations for patients with anxiety, except mindfulness-based stress reduction was an option for patients with severe symptoms.
Clinicians can also provide pharmacologic options to treat depression or anxiety in certain patients, though the panelists provided the caveat that evidence for pharmacologic management is weak.
“These guidelines make no recommendations about any specific pharmacologic regimen being better than another,” the experts wrote. And “patients should be warned of potential harm or adverse effects.”
Overall, the panelists noted that, as highlighted in the 2014 ASCO guideline, the updated version continues to stress the importance of providing education on coping with stress, anxiety, and depression.
And “for individuals with elevated symptoms, validation and normalizing patients’ experiences is crucial,” the panelists write.
Although the timing of screening is not the focus of this updated review, the experts recognized that “how and when patients with cancer and survivors are screened are important determinants of timely management of anxiety and depression.”
And unlike the prior guideline, “pharmacotherapy is not recommended as a first-line treatment, neither alone nor in combination,” the authors say.
Overall, the panelists emphasize how widespread the mental health care crisis is and that problems accessing mental health care remain. “The choice of intervention to offer patients facing such obstacles should be based on shared decision-making, taking into account availability, accessibility, patient preference, likelihood of adverse events, adherence, and cost,” the experts conclude.
A version of this article first appeared on Medscape.com.
Since the last guidelines, published in 2014, screening and assessment for depression and anxiety have improved, and a large new evidence base has emerged. To ensure the most up-to-date recommendations, a group of experts spanning psychology, psychiatry, medical and surgical oncology, internal medicine, and nursing convened to review the current literature on managing depression and anxiety. The review included 61 studies – 16 meta-analyses, 44 randomized controlled trials, and one systematic review – published between 2013 and 2021.
“The purpose of this guideline update is to gather and examine the evidence published since the 2014 guideline ... [with a] focus on management and treatment only.” The overall goal is to provide “the most effective and least resource-intensive intervention based on symptom severity” for patients with cancer, the experts write.
The new clinical practice guideline addresses the following question: What are the recommended treatment approaches in the management of anxiety and/or depression in survivors of adult cancer?
After an extensive literature search and analysis, the study was published online in the Journal of Clinical Oncology.
The expert panel’s recommendations fell into three broad categories – general management principles, treatment and care options for depressive symptoms, and treatment and care options for anxiety symptoms – with the guidelines for managing depression and anxiety largely mirroring each other.
The authors caution, however, that the guidelines “were developed in the context of mental health care being available and may not be applicable within other resource settings.”
General management principals
All patients with cancer, along with their caregivers, family members, or trusted confidants, should be offered information and resources on depression and anxiety. The panel gave this a “strong” recommendation but provided the caveat that the “information should be culturally informed and linguistically appropriate and can include a conversation between clinician and patient.”
Clinicians should select the most effective and least intensive intervention based on symptom severity when selecting treatment – what the panelists referred to as a stepped-care model. History of psychiatric diagnoses or substance use as well as prior responses to mental health treatment are some of the factors that may inform treatment choice.
For patients experiencing both depression and anxiety symptoms, treatment of depressive symptoms should be prioritized.
When referring a patient for further evaluation or care, clinicians “should make every effort to reduce barriers and facilitate patient follow-through,” the authors write. And health care professionals should regularly assess the treatment responses for patients receiving psychological or pharmacological interventions.
Overall, the treatments should be “supervised by a psychiatrist, and primary care or oncology providers work collaboratively with a nurse care manager to provide psychological interventions and monitor treatment compliance and outcomes,” the panelists write. “This type of collaborative care is found to be superior to usual care and is more cost-effective than face-to-face and pharmacologic treatment for depression.”
Treatment and care options for depressive and anxiety symptoms
For patients with moderate to severe depression symptoms, the panelists again stressed that clinicians should provide “culturally informed and linguistically appropriate information.” This information may include the frequency and symptoms of depression as well as signs these symptoms may be getting worse, with contact information for the medical team provided.
Among patients with moderate symptoms, clinicians can offer patients a range of individual or group therapy options, including cognitive-behavioral therapy (CBT), behavioral activation, mindfulness-based stress reduction, or structured physical activity and exercise. For patients with severe symptoms of depression, clinicians should offer individual therapy with one of these four treatment options: CBT, behavioral activation, mindfulness-based stress reduction, or interpersonal therapy.
The panelists offered almost identical recommendations for patients with anxiety, except mindfulness-based stress reduction was an option for patients with severe symptoms.
Clinicians can also provide pharmacologic options to treat depression or anxiety in certain patients, though the panelists provided the caveat that evidence for pharmacologic management is weak.
“These guidelines make no recommendations about any specific pharmacologic regimen being better than another,” the experts wrote. And “patients should be warned of potential harm or adverse effects.”
Overall, the panelists noted that, as highlighted in the 2014 ASCO guideline, the updated version continues to stress the importance of providing education on coping with stress, anxiety, and depression.
And “for individuals with elevated symptoms, validation and normalizing patients’ experiences is crucial,” the panelists write.
Although the timing of screening is not the focus of this updated review, the experts recognized that “how and when patients with cancer and survivors are screened are important determinants of timely management of anxiety and depression.”
And unlike the prior guideline, “pharmacotherapy is not recommended as a first-line treatment, neither alone nor in combination,” the authors say.
Overall, the panelists emphasize how widespread the mental health care crisis is and that problems accessing mental health care remain. “The choice of intervention to offer patients facing such obstacles should be based on shared decision-making, taking into account availability, accessibility, patient preference, likelihood of adverse events, adherence, and cost,” the experts conclude.
A version of this article first appeared on Medscape.com.
Since the last guidelines, published in 2014, screening and assessment for depression and anxiety have improved, and a large new evidence base has emerged. To ensure the most up-to-date recommendations, a group of experts spanning psychology, psychiatry, medical and surgical oncology, internal medicine, and nursing convened to review the current literature on managing depression and anxiety. The review included 61 studies – 16 meta-analyses, 44 randomized controlled trials, and one systematic review – published between 2013 and 2021.
“The purpose of this guideline update is to gather and examine the evidence published since the 2014 guideline ... [with a] focus on management and treatment only.” The overall goal is to provide “the most effective and least resource-intensive intervention based on symptom severity” for patients with cancer, the experts write.
The new clinical practice guideline addresses the following question: What are the recommended treatment approaches in the management of anxiety and/or depression in survivors of adult cancer?
After an extensive literature search and analysis, the study was published online in the Journal of Clinical Oncology.
The expert panel’s recommendations fell into three broad categories – general management principles, treatment and care options for depressive symptoms, and treatment and care options for anxiety symptoms – with the guidelines for managing depression and anxiety largely mirroring each other.
The authors caution, however, that the guidelines “were developed in the context of mental health care being available and may not be applicable within other resource settings.”
General management principals
All patients with cancer, along with their caregivers, family members, or trusted confidants, should be offered information and resources on depression and anxiety. The panel gave this a “strong” recommendation but provided the caveat that the “information should be culturally informed and linguistically appropriate and can include a conversation between clinician and patient.”
Clinicians should select the most effective and least intensive intervention based on symptom severity when selecting treatment – what the panelists referred to as a stepped-care model. History of psychiatric diagnoses or substance use as well as prior responses to mental health treatment are some of the factors that may inform treatment choice.
For patients experiencing both depression and anxiety symptoms, treatment of depressive symptoms should be prioritized.
When referring a patient for further evaluation or care, clinicians “should make every effort to reduce barriers and facilitate patient follow-through,” the authors write. And health care professionals should regularly assess the treatment responses for patients receiving psychological or pharmacological interventions.
Overall, the treatments should be “supervised by a psychiatrist, and primary care or oncology providers work collaboratively with a nurse care manager to provide psychological interventions and monitor treatment compliance and outcomes,” the panelists write. “This type of collaborative care is found to be superior to usual care and is more cost-effective than face-to-face and pharmacologic treatment for depression.”
Treatment and care options for depressive and anxiety symptoms
For patients with moderate to severe depression symptoms, the panelists again stressed that clinicians should provide “culturally informed and linguistically appropriate information.” This information may include the frequency and symptoms of depression as well as signs these symptoms may be getting worse, with contact information for the medical team provided.
Among patients with moderate symptoms, clinicians can offer patients a range of individual or group therapy options, including cognitive-behavioral therapy (CBT), behavioral activation, mindfulness-based stress reduction, or structured physical activity and exercise. For patients with severe symptoms of depression, clinicians should offer individual therapy with one of these four treatment options: CBT, behavioral activation, mindfulness-based stress reduction, or interpersonal therapy.
The panelists offered almost identical recommendations for patients with anxiety, except mindfulness-based stress reduction was an option for patients with severe symptoms.
Clinicians can also provide pharmacologic options to treat depression or anxiety in certain patients, though the panelists provided the caveat that evidence for pharmacologic management is weak.
“These guidelines make no recommendations about any specific pharmacologic regimen being better than another,” the experts wrote. And “patients should be warned of potential harm or adverse effects.”
Overall, the panelists noted that, as highlighted in the 2014 ASCO guideline, the updated version continues to stress the importance of providing education on coping with stress, anxiety, and depression.
And “for individuals with elevated symptoms, validation and normalizing patients’ experiences is crucial,” the panelists write.
Although the timing of screening is not the focus of this updated review, the experts recognized that “how and when patients with cancer and survivors are screened are important determinants of timely management of anxiety and depression.”
And unlike the prior guideline, “pharmacotherapy is not recommended as a first-line treatment, neither alone nor in combination,” the authors say.
Overall, the panelists emphasize how widespread the mental health care crisis is and that problems accessing mental health care remain. “The choice of intervention to offer patients facing such obstacles should be based on shared decision-making, taking into account availability, accessibility, patient preference, likelihood of adverse events, adherence, and cost,” the experts conclude.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Federal rules don’t require period product ingredients on packaging labels. States are stepping in.
Tens of millions of Americans use menstrual products, and while manufacturers contend they are safe, most disclose little about the chemicals they contain. Now, amid calls for more disclosure and research into the health effects of these products, some states require more transparency.
The manufacture and sale of period and related products is a big business, with revenue expected to top $4.5 billion in the United States this year. On average, a person uses up to 17,000 tampons or pads in their lifetime, and they might also use rubber or silicone cups, or absorbent period underwear.
The FDA regulates and classifies menstrual products as medical devices, meaning they are not subject to the same labeling laws as other consumer items. But companies can voluntarily disclose what’s in their products.
Now, some states are stepping into the breach. In 2021, New York became the first state to enact a menstrual product disclosure law requiring companies to list all intentionally added ingredients on packaging. California’s governor signed a similar law that took effect this year, but it gives manufacturers trade secret protections, so not all ingredients are necessarily disclosed. At least six other states have introduced legislation to address safety and disclosure of ingredients in these products.
Shruthi Mahalingaiah, an assistant professor of environmental, reproductive, and women’s health at Harvard University, Boston, evaluates endocrine disruptors in personal care products and studies menstrual health. She said the health risk depends on the dose, duration, and sensitivity of a person to the ingredients and their mixtures.
Harmful chemicals could come from manufacturing processes, through materials and shipping, from equipment cleaners, from contact with contaminants, or from companies adding them intentionally, said Alexandra Scranton, director of science and research for Women’s Voices for the Earth, a Montana-based nonprofit focused on eliminating toxic chemicals that affect women’s health.
Vaginal and vulvar tissues are capable of absorbing fluids at a higher rate than skin, which can lead to rapid chemical exposure. Ms. Scranton said scarcity of clinical studies and funding for vaginal health research limits understanding about the long-term effects of the ingredients and additives in period products.
“We think manufacturers should do better and be more careful with the ingredients they choose to use,” Ms. Scranton said. “The presence of toxic and hormone-disrupting chemicals in menstrual products is unsettling. We know that chemicals can cause disease, and exposures do add up over time.”
Ms. Scranton’s organization advocates for labels to include the chemical name of the ingredient, the component in which the ingredient is used, and the function of the ingredient.
K. Malaika Walton, operations director for the Center for Baby and Adult Hygiene Products, a trade industry group, said in an email, “BAHP supports accurate and transparent information for users of period products and many of our member companies list ingredients on their packages and websites.”
In a written statement, Procter & Gamble, a major manufacturer of menstrual products, said that ingredients it uses go through rigorous safety evaluations and are continuously tested, and that all fragrance components are added at levels the industry considers safe.
Even though manufacturing of scented tampons for the U.S. market has mostly stopped, companies still use fragrances in other menstrual products. Laws protecting trade secrets keep details about fragrances in pads and tampons confidential so competitors can’t copy the formulas. The Children’s Environmental Health Network lists phthalates, a group of chemicals commonly called plasticizers, that are suspected hormone disruptors, as an ingredient found in fragrances.
Manufacturers follow regulatory guidance issued in 2005 by registering with the Food and Drug Administration and submitting a detailed risk assessment of their products’ components and design, and a safety profile, before being cleared to sell in the United States.
Pads and menstrual cups are considered exempt from regulatory guidance and do not require premarket review, according to FDA spokesperson Carly Kempler. While tampons do require review, the FDA “does not clear or approve individual materials that are used in the fabrication of medical devices.”
“There’s an understanding that the FDA is regulating these products, and they are; it’s just not very adequate,” said Laura Strausfeld, an attorney and a cofounder of Period Law, an organization working to advance state and federal period-equity policies that would stop taxation of products and make them freely available in places like schools and prisons. “The consumer is supposed to trust that when these products are put on shelves they’ve been vetted by the government. But it’s basically a rubber stamp.”
In a 2022 report, a congressional committee directed the FDA to update its guidance for menstrual products to recommend that labels disclose intentionally added ingredients, such as fragrances, and test for contaminants. The FDA is reviewing the directives outlined by the House Appropriations Committee and will update the 2005 guidance as soon as possible, Ms. Kempler said. “We will share additional details when we are able to.”
At least one period product company makes disclosure of its ingredients a selling point. Alex Friedman, cofounder of Lola, said a lack of knowledge is a problem, and more action and awareness are needed to keep people safe.
“The hardest part to swallow is why this is even up for debate. We should all know what’s in these products,” Ms. Friedman said.
New York’s law requires companies to disclose all intentionally added ingredients no matter how much is used, with no trade secret protections for fragrances. Though it applies only to products sold in that state, similar detailed labeling is appearing elsewhere, advocates said.
“We’re also seeing similar or identical disclosure on packaging in other states outside of New York, which is a testament to the power of the law,” said Jamie McConnell, deputy director of Women’s Voices for the Earth.
Manufacturers have 18 months from the passage of the New York law to comply, and some products on shelves in New York still list few ingredients other than “absorbent material,” “surfactant,” “ink,” and “adhesive.”
“We’re like, ‘OK, what is that exactly?’ ” Ms. McConnell said.
Her organization is calling for a federal law at least as strong as New York’s. Previous federal legislation failed to advance, including the most recent, the Menstrual Products Right to Know Act, introduced in 2022.
BAHP, the trade group, supported the federal legislation and the California law. Ms. McConnell said she opposed both bills because they didn’t require companies to list all fragrance ingredients.
“I think what it boiled down to at the federal level was the support of corporate interests over public health,” she said.
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.
Tens of millions of Americans use menstrual products, and while manufacturers contend they are safe, most disclose little about the chemicals they contain. Now, amid calls for more disclosure and research into the health effects of these products, some states require more transparency.
The manufacture and sale of period and related products is a big business, with revenue expected to top $4.5 billion in the United States this year. On average, a person uses up to 17,000 tampons or pads in their lifetime, and they might also use rubber or silicone cups, or absorbent period underwear.
The FDA regulates and classifies menstrual products as medical devices, meaning they are not subject to the same labeling laws as other consumer items. But companies can voluntarily disclose what’s in their products.
Now, some states are stepping into the breach. In 2021, New York became the first state to enact a menstrual product disclosure law requiring companies to list all intentionally added ingredients on packaging. California’s governor signed a similar law that took effect this year, but it gives manufacturers trade secret protections, so not all ingredients are necessarily disclosed. At least six other states have introduced legislation to address safety and disclosure of ingredients in these products.
Shruthi Mahalingaiah, an assistant professor of environmental, reproductive, and women’s health at Harvard University, Boston, evaluates endocrine disruptors in personal care products and studies menstrual health. She said the health risk depends on the dose, duration, and sensitivity of a person to the ingredients and their mixtures.
Harmful chemicals could come from manufacturing processes, through materials and shipping, from equipment cleaners, from contact with contaminants, or from companies adding them intentionally, said Alexandra Scranton, director of science and research for Women’s Voices for the Earth, a Montana-based nonprofit focused on eliminating toxic chemicals that affect women’s health.
Vaginal and vulvar tissues are capable of absorbing fluids at a higher rate than skin, which can lead to rapid chemical exposure. Ms. Scranton said scarcity of clinical studies and funding for vaginal health research limits understanding about the long-term effects of the ingredients and additives in period products.
“We think manufacturers should do better and be more careful with the ingredients they choose to use,” Ms. Scranton said. “The presence of toxic and hormone-disrupting chemicals in menstrual products is unsettling. We know that chemicals can cause disease, and exposures do add up over time.”
Ms. Scranton’s organization advocates for labels to include the chemical name of the ingredient, the component in which the ingredient is used, and the function of the ingredient.
K. Malaika Walton, operations director for the Center for Baby and Adult Hygiene Products, a trade industry group, said in an email, “BAHP supports accurate and transparent information for users of period products and many of our member companies list ingredients on their packages and websites.”
In a written statement, Procter & Gamble, a major manufacturer of menstrual products, said that ingredients it uses go through rigorous safety evaluations and are continuously tested, and that all fragrance components are added at levels the industry considers safe.
Even though manufacturing of scented tampons for the U.S. market has mostly stopped, companies still use fragrances in other menstrual products. Laws protecting trade secrets keep details about fragrances in pads and tampons confidential so competitors can’t copy the formulas. The Children’s Environmental Health Network lists phthalates, a group of chemicals commonly called plasticizers, that are suspected hormone disruptors, as an ingredient found in fragrances.
Manufacturers follow regulatory guidance issued in 2005 by registering with the Food and Drug Administration and submitting a detailed risk assessment of their products’ components and design, and a safety profile, before being cleared to sell in the United States.
Pads and menstrual cups are considered exempt from regulatory guidance and do not require premarket review, according to FDA spokesperson Carly Kempler. While tampons do require review, the FDA “does not clear or approve individual materials that are used in the fabrication of medical devices.”
“There’s an understanding that the FDA is regulating these products, and they are; it’s just not very adequate,” said Laura Strausfeld, an attorney and a cofounder of Period Law, an organization working to advance state and federal period-equity policies that would stop taxation of products and make them freely available in places like schools and prisons. “The consumer is supposed to trust that when these products are put on shelves they’ve been vetted by the government. But it’s basically a rubber stamp.”
In a 2022 report, a congressional committee directed the FDA to update its guidance for menstrual products to recommend that labels disclose intentionally added ingredients, such as fragrances, and test for contaminants. The FDA is reviewing the directives outlined by the House Appropriations Committee and will update the 2005 guidance as soon as possible, Ms. Kempler said. “We will share additional details when we are able to.”
At least one period product company makes disclosure of its ingredients a selling point. Alex Friedman, cofounder of Lola, said a lack of knowledge is a problem, and more action and awareness are needed to keep people safe.
“The hardest part to swallow is why this is even up for debate. We should all know what’s in these products,” Ms. Friedman said.
New York’s law requires companies to disclose all intentionally added ingredients no matter how much is used, with no trade secret protections for fragrances. Though it applies only to products sold in that state, similar detailed labeling is appearing elsewhere, advocates said.
“We’re also seeing similar or identical disclosure on packaging in other states outside of New York, which is a testament to the power of the law,” said Jamie McConnell, deputy director of Women’s Voices for the Earth.
Manufacturers have 18 months from the passage of the New York law to comply, and some products on shelves in New York still list few ingredients other than “absorbent material,” “surfactant,” “ink,” and “adhesive.”
“We’re like, ‘OK, what is that exactly?’ ” Ms. McConnell said.
Her organization is calling for a federal law at least as strong as New York’s. Previous federal legislation failed to advance, including the most recent, the Menstrual Products Right to Know Act, introduced in 2022.
BAHP, the trade group, supported the federal legislation and the California law. Ms. McConnell said she opposed both bills because they didn’t require companies to list all fragrance ingredients.
“I think what it boiled down to at the federal level was the support of corporate interests over public health,” she said.
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.
Tens of millions of Americans use menstrual products, and while manufacturers contend they are safe, most disclose little about the chemicals they contain. Now, amid calls for more disclosure and research into the health effects of these products, some states require more transparency.
The manufacture and sale of period and related products is a big business, with revenue expected to top $4.5 billion in the United States this year. On average, a person uses up to 17,000 tampons or pads in their lifetime, and they might also use rubber or silicone cups, or absorbent period underwear.
The FDA regulates and classifies menstrual products as medical devices, meaning they are not subject to the same labeling laws as other consumer items. But companies can voluntarily disclose what’s in their products.
Now, some states are stepping into the breach. In 2021, New York became the first state to enact a menstrual product disclosure law requiring companies to list all intentionally added ingredients on packaging. California’s governor signed a similar law that took effect this year, but it gives manufacturers trade secret protections, so not all ingredients are necessarily disclosed. At least six other states have introduced legislation to address safety and disclosure of ingredients in these products.
Shruthi Mahalingaiah, an assistant professor of environmental, reproductive, and women’s health at Harvard University, Boston, evaluates endocrine disruptors in personal care products and studies menstrual health. She said the health risk depends on the dose, duration, and sensitivity of a person to the ingredients and their mixtures.
Harmful chemicals could come from manufacturing processes, through materials and shipping, from equipment cleaners, from contact with contaminants, or from companies adding them intentionally, said Alexandra Scranton, director of science and research for Women’s Voices for the Earth, a Montana-based nonprofit focused on eliminating toxic chemicals that affect women’s health.
Vaginal and vulvar tissues are capable of absorbing fluids at a higher rate than skin, which can lead to rapid chemical exposure. Ms. Scranton said scarcity of clinical studies and funding for vaginal health research limits understanding about the long-term effects of the ingredients and additives in period products.
“We think manufacturers should do better and be more careful with the ingredients they choose to use,” Ms. Scranton said. “The presence of toxic and hormone-disrupting chemicals in menstrual products is unsettling. We know that chemicals can cause disease, and exposures do add up over time.”
Ms. Scranton’s organization advocates for labels to include the chemical name of the ingredient, the component in which the ingredient is used, and the function of the ingredient.
K. Malaika Walton, operations director for the Center for Baby and Adult Hygiene Products, a trade industry group, said in an email, “BAHP supports accurate and transparent information for users of period products and many of our member companies list ingredients on their packages and websites.”
In a written statement, Procter & Gamble, a major manufacturer of menstrual products, said that ingredients it uses go through rigorous safety evaluations and are continuously tested, and that all fragrance components are added at levels the industry considers safe.
Even though manufacturing of scented tampons for the U.S. market has mostly stopped, companies still use fragrances in other menstrual products. Laws protecting trade secrets keep details about fragrances in pads and tampons confidential so competitors can’t copy the formulas. The Children’s Environmental Health Network lists phthalates, a group of chemicals commonly called plasticizers, that are suspected hormone disruptors, as an ingredient found in fragrances.
Manufacturers follow regulatory guidance issued in 2005 by registering with the Food and Drug Administration and submitting a detailed risk assessment of their products’ components and design, and a safety profile, before being cleared to sell in the United States.
Pads and menstrual cups are considered exempt from regulatory guidance and do not require premarket review, according to FDA spokesperson Carly Kempler. While tampons do require review, the FDA “does not clear or approve individual materials that are used in the fabrication of medical devices.”
“There’s an understanding that the FDA is regulating these products, and they are; it’s just not very adequate,” said Laura Strausfeld, an attorney and a cofounder of Period Law, an organization working to advance state and federal period-equity policies that would stop taxation of products and make them freely available in places like schools and prisons. “The consumer is supposed to trust that when these products are put on shelves they’ve been vetted by the government. But it’s basically a rubber stamp.”
In a 2022 report, a congressional committee directed the FDA to update its guidance for menstrual products to recommend that labels disclose intentionally added ingredients, such as fragrances, and test for contaminants. The FDA is reviewing the directives outlined by the House Appropriations Committee and will update the 2005 guidance as soon as possible, Ms. Kempler said. “We will share additional details when we are able to.”
At least one period product company makes disclosure of its ingredients a selling point. Alex Friedman, cofounder of Lola, said a lack of knowledge is a problem, and more action and awareness are needed to keep people safe.
“The hardest part to swallow is why this is even up for debate. We should all know what’s in these products,” Ms. Friedman said.
New York’s law requires companies to disclose all intentionally added ingredients no matter how much is used, with no trade secret protections for fragrances. Though it applies only to products sold in that state, similar detailed labeling is appearing elsewhere, advocates said.
“We’re also seeing similar or identical disclosure on packaging in other states outside of New York, which is a testament to the power of the law,” said Jamie McConnell, deputy director of Women’s Voices for the Earth.
Manufacturers have 18 months from the passage of the New York law to comply, and some products on shelves in New York still list few ingredients other than “absorbent material,” “surfactant,” “ink,” and “adhesive.”
“We’re like, ‘OK, what is that exactly?’ ” Ms. McConnell said.
Her organization is calling for a federal law at least as strong as New York’s. Previous federal legislation failed to advance, including the most recent, the Menstrual Products Right to Know Act, introduced in 2022.
BAHP, the trade group, supported the federal legislation and the California law. Ms. McConnell said she opposed both bills because they didn’t require companies to list all fragrance ingredients.
“I think what it boiled down to at the federal level was the support of corporate interests over public health,” she said.
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.
Transcranial magnetic stimulation during pregnancy: An alternative to antidepressant treatment?
A growing number of women ask about nonpharmacologic approaches for either the treatment of acute perinatal depression or for relapse prevention during pregnancy.
The last several decades have brought an increasing level of comfort with respect to antidepressant use during pregnancy, which derives from several factors.
First, it’s been well described that there’s an increased risk of relapse and morbidity associated with discontinuation of antidepressants proximate to pregnancy, particularly in women with histories of recurrent disease (JAMA Psychiatry. 2023;80[5]:441-50 and JAMA. 2006;295[5]:499-507).
Second, there’s an obvious increased confidence about using antidepressants during pregnancy given the robust reproductive safety data about antidepressants with respect to both teratogenesis and risk for organ malformation. Other studies also fail to demonstrate a relationship between fetal exposure to antidepressants and risk for subsequent development of attention-deficit/hyperactivity disorder (ADHD) and autism. These latter studies have been reviewed extensively in systematic reviews of meta-analyses addressing this question.
However, there are women who, as they approach the question of antidepressant use during pregnancy, would prefer a nonpharmacologic approach to managing depression in the setting of either a planned pregnancy, or sometimes in the setting of acute onset of depressive symptoms during pregnancy. Other women are more comfortable with the data in hand regarding the reproductive safety of antidepressants and continue antidepressants that have afforded emotional well-being, particularly if the road to well-being or euthymia has been a long one.
Still, we at Massachusetts General Hospital (MGH) Center for Women’s Mental Health along with multidisciplinary colleagues with whom we engage during our weekly Virtual Rounds community have observed a growing number of women asking about nonpharmacologic approaches for either the treatment of acute perinatal depression or for relapse prevention during pregnancy. They ask about these options for personal reasons, regardless of what we may know (and what we may not know) about existing pharmacologic interventions. In these scenarios, it is important to keep in mind that it is not about what we as clinicians necessarily know about these medicines per se that drives treatment, but rather about the private calculus that women and their partners apply about risk and benefit of pharmacologic treatment during pregnancy.
Nonpharmacologic treatment options
Mindfulness-based cognitive therapy (MBCT), cognitive behavioral therapy (CBT), and behavioral activation are therapies all of which have an evidence base with respect to their effectiveness for either the acute treatment of both depression (and perinatal depression specifically) or for mitigating risk for depressive relapse (MBCT). Several investigations are underway evaluating digital apps that utilize MBCT and CBT in these patient populations as well.
New treatments for which we have none or exceedingly sparse data to support use during pregnancy are neurosteroids. We are asked all the time about the use of neurosteroids such as brexanolone or zuranolone during pregnancy. Given the data on effectiveness of these agents for treatment of postpartum depression, the question about use during pregnancy is intuitive. But at this point in time, absent data, their use during pregnancy cannot be recommended.
With respect to newer nonpharmacologic approaches that have been looked at for treatment of major depressive disorder, the Food and Drug Administration has approved transcranial magnetic stimulation (TMS), a noninvasive form of neuromodulating therapy that use magnetic pulses to stimulate specific regions of the brain that have been implicated in psychiatric illness.
While there are no safety concerns that have been noted about use of TMS, the data regarding its use during pregnancy are still relatively limited, but it has been used to treat certain neurologic conditions during pregnancy. We now have a small randomized controlled study using TMS during pregnancy and multiple small case series suggesting a signal of efficacy in women with perinatal major depressive disorder. Side effects of TMS use during pregnancy have included hypotension, which has sometimes required repositioning of subjects, particularly later in pregnancy. Unlike electroconvulsive therapy, (ECT), often used when clinicians have exhausted other treatment options, TMS has no risk of seizure associated with its use.
TMS is now entering into the clinical arena in a more robust way. In certain settings, insurance companies are reimbursing for TMS treatment more often than was the case previously, making it a more viable option for a larger number of patients. There are also several exciting newer protocols, including theta burst stimulation, a new form of TMS treatment with less of a time commitment, and which may be more cost effective. However, data on this modality of treatment remain limited.
Where TMS fits in treating depression during pregnancy
The real question we are getting asked in clinic, both in person and during virtual rounds with multidisciplinary colleagues from across the world, is where TMS might fit into the algorithm for treating of depression during pregnancy. Where is it appropriate to be thinking about TMS in pregnancy, and where should it perhaps be deferred at this moment (and where is it not appropriate)?
It is probably of limited value (and possibly of potential harm) to switch to TMS in patients who have severe recurrent major depression and who are on maintenance antidepressant, and who believe that a switch to TMS will be effective for relapse prevention; there are simply no data currently suggesting that TMS can be used as a relapse prevention tool, unlike certain other nonpharmacologic interventions.
What about managing relapse of major depressive disorder during pregnancy in a patient who had responded to an antidepressant? We have seen patients with histories of severe recurrent disease who are managed well on antidepressants during pregnancy who then have breakthrough symptoms and inquire about using TMS as an augmentation strategy. Although we don’t have clear data supporting the use of TMS as an adjunct in that setting, in those patients, one could argue that a trial of TMS may be appropriate – as opposed to introducing multiple medicines to recapture euthymia during pregnancy where the benefit is unclear and where more exposure is implied by having to do potentially multiple trials.
Other patients with new onset of depression during pregnancy who, for personal reasons, will not take an antidepressant or pursue other nonpharmacologic interventions will frequently ask about TMS. and the increased availability of TMS in the community in various centers – as opposed to previously where it was more restricted to large academic medical centers.
I think it is a time of excitement in reproductive psychiatry where we have a growing number of tools to treat perinatal depression – from medications to digital tools. These tools – either alone or in combination with medicines that we’ve been using for years – are able to afford women a greater number of choices with respect to the treatment of perinatal depression than was available even 5 years ago. That takes us closer to an ability to use interventions that truly combine patient wishes and “precision perinatal psychiatry,” where we can match effective therapies with the individual clinical presentations and wishes with which patients come to us.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].
A growing number of women ask about nonpharmacologic approaches for either the treatment of acute perinatal depression or for relapse prevention during pregnancy.
The last several decades have brought an increasing level of comfort with respect to antidepressant use during pregnancy, which derives from several factors.
First, it’s been well described that there’s an increased risk of relapse and morbidity associated with discontinuation of antidepressants proximate to pregnancy, particularly in women with histories of recurrent disease (JAMA Psychiatry. 2023;80[5]:441-50 and JAMA. 2006;295[5]:499-507).
Second, there’s an obvious increased confidence about using antidepressants during pregnancy given the robust reproductive safety data about antidepressants with respect to both teratogenesis and risk for organ malformation. Other studies also fail to demonstrate a relationship between fetal exposure to antidepressants and risk for subsequent development of attention-deficit/hyperactivity disorder (ADHD) and autism. These latter studies have been reviewed extensively in systematic reviews of meta-analyses addressing this question.
However, there are women who, as they approach the question of antidepressant use during pregnancy, would prefer a nonpharmacologic approach to managing depression in the setting of either a planned pregnancy, or sometimes in the setting of acute onset of depressive symptoms during pregnancy. Other women are more comfortable with the data in hand regarding the reproductive safety of antidepressants and continue antidepressants that have afforded emotional well-being, particularly if the road to well-being or euthymia has been a long one.
Still, we at Massachusetts General Hospital (MGH) Center for Women’s Mental Health along with multidisciplinary colleagues with whom we engage during our weekly Virtual Rounds community have observed a growing number of women asking about nonpharmacologic approaches for either the treatment of acute perinatal depression or for relapse prevention during pregnancy. They ask about these options for personal reasons, regardless of what we may know (and what we may not know) about existing pharmacologic interventions. In these scenarios, it is important to keep in mind that it is not about what we as clinicians necessarily know about these medicines per se that drives treatment, but rather about the private calculus that women and their partners apply about risk and benefit of pharmacologic treatment during pregnancy.
Nonpharmacologic treatment options
Mindfulness-based cognitive therapy (MBCT), cognitive behavioral therapy (CBT), and behavioral activation are therapies all of which have an evidence base with respect to their effectiveness for either the acute treatment of both depression (and perinatal depression specifically) or for mitigating risk for depressive relapse (MBCT). Several investigations are underway evaluating digital apps that utilize MBCT and CBT in these patient populations as well.
New treatments for which we have none or exceedingly sparse data to support use during pregnancy are neurosteroids. We are asked all the time about the use of neurosteroids such as brexanolone or zuranolone during pregnancy. Given the data on effectiveness of these agents for treatment of postpartum depression, the question about use during pregnancy is intuitive. But at this point in time, absent data, their use during pregnancy cannot be recommended.
With respect to newer nonpharmacologic approaches that have been looked at for treatment of major depressive disorder, the Food and Drug Administration has approved transcranial magnetic stimulation (TMS), a noninvasive form of neuromodulating therapy that use magnetic pulses to stimulate specific regions of the brain that have been implicated in psychiatric illness.
While there are no safety concerns that have been noted about use of TMS, the data regarding its use during pregnancy are still relatively limited, but it has been used to treat certain neurologic conditions during pregnancy. We now have a small randomized controlled study using TMS during pregnancy and multiple small case series suggesting a signal of efficacy in women with perinatal major depressive disorder. Side effects of TMS use during pregnancy have included hypotension, which has sometimes required repositioning of subjects, particularly later in pregnancy. Unlike electroconvulsive therapy, (ECT), often used when clinicians have exhausted other treatment options, TMS has no risk of seizure associated with its use.
TMS is now entering into the clinical arena in a more robust way. In certain settings, insurance companies are reimbursing for TMS treatment more often than was the case previously, making it a more viable option for a larger number of patients. There are also several exciting newer protocols, including theta burst stimulation, a new form of TMS treatment with less of a time commitment, and which may be more cost effective. However, data on this modality of treatment remain limited.
Where TMS fits in treating depression during pregnancy
The real question we are getting asked in clinic, both in person and during virtual rounds with multidisciplinary colleagues from across the world, is where TMS might fit into the algorithm for treating of depression during pregnancy. Where is it appropriate to be thinking about TMS in pregnancy, and where should it perhaps be deferred at this moment (and where is it not appropriate)?
It is probably of limited value (and possibly of potential harm) to switch to TMS in patients who have severe recurrent major depression and who are on maintenance antidepressant, and who believe that a switch to TMS will be effective for relapse prevention; there are simply no data currently suggesting that TMS can be used as a relapse prevention tool, unlike certain other nonpharmacologic interventions.
What about managing relapse of major depressive disorder during pregnancy in a patient who had responded to an antidepressant? We have seen patients with histories of severe recurrent disease who are managed well on antidepressants during pregnancy who then have breakthrough symptoms and inquire about using TMS as an augmentation strategy. Although we don’t have clear data supporting the use of TMS as an adjunct in that setting, in those patients, one could argue that a trial of TMS may be appropriate – as opposed to introducing multiple medicines to recapture euthymia during pregnancy where the benefit is unclear and where more exposure is implied by having to do potentially multiple trials.
Other patients with new onset of depression during pregnancy who, for personal reasons, will not take an antidepressant or pursue other nonpharmacologic interventions will frequently ask about TMS. and the increased availability of TMS in the community in various centers – as opposed to previously where it was more restricted to large academic medical centers.
I think it is a time of excitement in reproductive psychiatry where we have a growing number of tools to treat perinatal depression – from medications to digital tools. These tools – either alone or in combination with medicines that we’ve been using for years – are able to afford women a greater number of choices with respect to the treatment of perinatal depression than was available even 5 years ago. That takes us closer to an ability to use interventions that truly combine patient wishes and “precision perinatal psychiatry,” where we can match effective therapies with the individual clinical presentations and wishes with which patients come to us.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].
A growing number of women ask about nonpharmacologic approaches for either the treatment of acute perinatal depression or for relapse prevention during pregnancy.
The last several decades have brought an increasing level of comfort with respect to antidepressant use during pregnancy, which derives from several factors.
First, it’s been well described that there’s an increased risk of relapse and morbidity associated with discontinuation of antidepressants proximate to pregnancy, particularly in women with histories of recurrent disease (JAMA Psychiatry. 2023;80[5]:441-50 and JAMA. 2006;295[5]:499-507).
Second, there’s an obvious increased confidence about using antidepressants during pregnancy given the robust reproductive safety data about antidepressants with respect to both teratogenesis and risk for organ malformation. Other studies also fail to demonstrate a relationship between fetal exposure to antidepressants and risk for subsequent development of attention-deficit/hyperactivity disorder (ADHD) and autism. These latter studies have been reviewed extensively in systematic reviews of meta-analyses addressing this question.
However, there are women who, as they approach the question of antidepressant use during pregnancy, would prefer a nonpharmacologic approach to managing depression in the setting of either a planned pregnancy, or sometimes in the setting of acute onset of depressive symptoms during pregnancy. Other women are more comfortable with the data in hand regarding the reproductive safety of antidepressants and continue antidepressants that have afforded emotional well-being, particularly if the road to well-being or euthymia has been a long one.
Still, we at Massachusetts General Hospital (MGH) Center for Women’s Mental Health along with multidisciplinary colleagues with whom we engage during our weekly Virtual Rounds community have observed a growing number of women asking about nonpharmacologic approaches for either the treatment of acute perinatal depression or for relapse prevention during pregnancy. They ask about these options for personal reasons, regardless of what we may know (and what we may not know) about existing pharmacologic interventions. In these scenarios, it is important to keep in mind that it is not about what we as clinicians necessarily know about these medicines per se that drives treatment, but rather about the private calculus that women and their partners apply about risk and benefit of pharmacologic treatment during pregnancy.
Nonpharmacologic treatment options
Mindfulness-based cognitive therapy (MBCT), cognitive behavioral therapy (CBT), and behavioral activation are therapies all of which have an evidence base with respect to their effectiveness for either the acute treatment of both depression (and perinatal depression specifically) or for mitigating risk for depressive relapse (MBCT). Several investigations are underway evaluating digital apps that utilize MBCT and CBT in these patient populations as well.
New treatments for which we have none or exceedingly sparse data to support use during pregnancy are neurosteroids. We are asked all the time about the use of neurosteroids such as brexanolone or zuranolone during pregnancy. Given the data on effectiveness of these agents for treatment of postpartum depression, the question about use during pregnancy is intuitive. But at this point in time, absent data, their use during pregnancy cannot be recommended.
With respect to newer nonpharmacologic approaches that have been looked at for treatment of major depressive disorder, the Food and Drug Administration has approved transcranial magnetic stimulation (TMS), a noninvasive form of neuromodulating therapy that use magnetic pulses to stimulate specific regions of the brain that have been implicated in psychiatric illness.
While there are no safety concerns that have been noted about use of TMS, the data regarding its use during pregnancy are still relatively limited, but it has been used to treat certain neurologic conditions during pregnancy. We now have a small randomized controlled study using TMS during pregnancy and multiple small case series suggesting a signal of efficacy in women with perinatal major depressive disorder. Side effects of TMS use during pregnancy have included hypotension, which has sometimes required repositioning of subjects, particularly later in pregnancy. Unlike electroconvulsive therapy, (ECT), often used when clinicians have exhausted other treatment options, TMS has no risk of seizure associated with its use.
TMS is now entering into the clinical arena in a more robust way. In certain settings, insurance companies are reimbursing for TMS treatment more often than was the case previously, making it a more viable option for a larger number of patients. There are also several exciting newer protocols, including theta burst stimulation, a new form of TMS treatment with less of a time commitment, and which may be more cost effective. However, data on this modality of treatment remain limited.
Where TMS fits in treating depression during pregnancy
The real question we are getting asked in clinic, both in person and during virtual rounds with multidisciplinary colleagues from across the world, is where TMS might fit into the algorithm for treating of depression during pregnancy. Where is it appropriate to be thinking about TMS in pregnancy, and where should it perhaps be deferred at this moment (and where is it not appropriate)?
It is probably of limited value (and possibly of potential harm) to switch to TMS in patients who have severe recurrent major depression and who are on maintenance antidepressant, and who believe that a switch to TMS will be effective for relapse prevention; there are simply no data currently suggesting that TMS can be used as a relapse prevention tool, unlike certain other nonpharmacologic interventions.
What about managing relapse of major depressive disorder during pregnancy in a patient who had responded to an antidepressant? We have seen patients with histories of severe recurrent disease who are managed well on antidepressants during pregnancy who then have breakthrough symptoms and inquire about using TMS as an augmentation strategy. Although we don’t have clear data supporting the use of TMS as an adjunct in that setting, in those patients, one could argue that a trial of TMS may be appropriate – as opposed to introducing multiple medicines to recapture euthymia during pregnancy where the benefit is unclear and where more exposure is implied by having to do potentially multiple trials.
Other patients with new onset of depression during pregnancy who, for personal reasons, will not take an antidepressant or pursue other nonpharmacologic interventions will frequently ask about TMS. and the increased availability of TMS in the community in various centers – as opposed to previously where it was more restricted to large academic medical centers.
I think it is a time of excitement in reproductive psychiatry where we have a growing number of tools to treat perinatal depression – from medications to digital tools. These tools – either alone or in combination with medicines that we’ve been using for years – are able to afford women a greater number of choices with respect to the treatment of perinatal depression than was available even 5 years ago. That takes us closer to an ability to use interventions that truly combine patient wishes and “precision perinatal psychiatry,” where we can match effective therapies with the individual clinical presentations and wishes with which patients come to us.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].
Statins tied to lower stroke risk in atrial fibrillation
Among patients with atrial fibrillation (AFib), initiation of statins soon after diagnosis was protective against stroke and related vascular events, and longer duration of use was associated with greater protection, a new cohort study shows.
Statin use was associated with lower risks of ischemic stroke or systemic embolism, hemorrhagic stroke, and transient ischemic attack (TIA), regardless of whether patients were also taking anticoagulant medications.
Lead author Jiayi Huang, a PhD student at Hong Kong University at Shenzhen (China) Hospital, concluded that the study’s findings support the use of statins to prevent stroke for patients with new-onset AFib.
“The findings have important clinical implications, particularly given that in atrial fibrillation, patients’ ischemic strokes are often fatal or disabling and have a high risk of recurrence,” she said.
The results were presented in a moderated poster session at the European Heart Rhythm Association 2023 Congress.
Widely prescribed
Anticoagulant drugs are prescribed to lower the fivefold increased risk of stroke among individuals with AFib, compared with those without AFib, but the therapy does not eliminate the higher risk, Ms. Huang explained. And although statins are widely prescribed to reduce the likelihood of myocardial infarction and stroke, “the benefit of statins for stroke prevention in patients with atrial fibrillation has been unclear.”
Ms. Huang and colleagues analyzed data from 51,472 patients newly diagnosed with AFib between 2010 and 2018. The population was divided into statin users (n = 11,866), defined as patients who had taken statins for at least 19 consecutive days in the first year after AFib diagnosis, and statin nonusers (n = 39,606), based on whether they were prescribed statin therapy after their first diagnosis of AFib.
The median age of the cohort was 74.9 years, and 47.7% were women. The investigators used statistical methods to balance baseline covariates between the two groups.
The primary outcomes were ischemic stroke or systemic embolism, hemorrhagic stroke, and TIA. Median follow-up was 5.1 years.
Statin use was associated with a significantly lower risk of all outcomes, compared with nonuse. Statin users had a 17% reduced risk of ischemic stroke or systemic embolism, a 7% reduced risk of hemorrhagic stroke, and a 15% rate of reduced risk of TIA, Ms. Huang reported.
“We also found long-term statin use was associated with greater protection than short-term use,” she said. For statin use of 6 years or longer, in comparison with use of 3 months to 2 years, the risk of ischemic stroke or systemic embolism was lowered by 43%; for hemorrhagic stroke, it was lowered by 44%, and for TIA, it was lowered by 42%.
These associations were consistent regardless of whether patients used anticoagulant medications or the type of anticoagulant.
Oussama Wazni, MD, MBA, section head of cardiac electrophysiology and pacing at the Cleveland Clinic, was a moderator of the poster session at which Ms. Huang presented her study. In an interview, he called the study “very important.”
“The message should be that all patients who have atrial fibrillation should be checked for cholesterol levels, and we should consider placing them on statins,” he said. “Is there an opportunity? Probably there is, and that’s why we’re seeing this effect in this group of patients.”
When asked about a possible mechanism by which statins produced the effects seen in the study, he pointed to LDL cholesterol lowering and possibly an effect on inflammation. “If a patient had a carotid atheroma, for example, maybe it helped with that,” he said. Previous work has shown that inflammation is related to or is associated with higher risk of thrombogenic effects, including MI or stroke.
It may be a bit less clear how statins reduced the incidence of hemorrhagic strokes, but Dr. Wazni proposed that some strokes could have started as an ischemic stroke “and then had hemorrhagic conversion, so we don’t have the granularity in here to know whether that was the case or not.”
Given the fact that the effect was stronger the longer a patient had been taking a statin, Dr. Wazni said that if a patient is tolerating the drug well, there should be no reason to discontinue it, regardless of age.
He said the study provides “welcome data and evidence because it’s pointing in the right direction,” but prospective studies would be useful “so that we can see what is driving what. Otherwise, this is just an association.”
The study was supported by Sanming Project Shenzhen. Ms. Huang and Dr. Wazni disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Among patients with atrial fibrillation (AFib), initiation of statins soon after diagnosis was protective against stroke and related vascular events, and longer duration of use was associated with greater protection, a new cohort study shows.
Statin use was associated with lower risks of ischemic stroke or systemic embolism, hemorrhagic stroke, and transient ischemic attack (TIA), regardless of whether patients were also taking anticoagulant medications.
Lead author Jiayi Huang, a PhD student at Hong Kong University at Shenzhen (China) Hospital, concluded that the study’s findings support the use of statins to prevent stroke for patients with new-onset AFib.
“The findings have important clinical implications, particularly given that in atrial fibrillation, patients’ ischemic strokes are often fatal or disabling and have a high risk of recurrence,” she said.
The results were presented in a moderated poster session at the European Heart Rhythm Association 2023 Congress.
Widely prescribed
Anticoagulant drugs are prescribed to lower the fivefold increased risk of stroke among individuals with AFib, compared with those without AFib, but the therapy does not eliminate the higher risk, Ms. Huang explained. And although statins are widely prescribed to reduce the likelihood of myocardial infarction and stroke, “the benefit of statins for stroke prevention in patients with atrial fibrillation has been unclear.”
Ms. Huang and colleagues analyzed data from 51,472 patients newly diagnosed with AFib between 2010 and 2018. The population was divided into statin users (n = 11,866), defined as patients who had taken statins for at least 19 consecutive days in the first year after AFib diagnosis, and statin nonusers (n = 39,606), based on whether they were prescribed statin therapy after their first diagnosis of AFib.
The median age of the cohort was 74.9 years, and 47.7% were women. The investigators used statistical methods to balance baseline covariates between the two groups.
The primary outcomes were ischemic stroke or systemic embolism, hemorrhagic stroke, and TIA. Median follow-up was 5.1 years.
Statin use was associated with a significantly lower risk of all outcomes, compared with nonuse. Statin users had a 17% reduced risk of ischemic stroke or systemic embolism, a 7% reduced risk of hemorrhagic stroke, and a 15% rate of reduced risk of TIA, Ms. Huang reported.
“We also found long-term statin use was associated with greater protection than short-term use,” she said. For statin use of 6 years or longer, in comparison with use of 3 months to 2 years, the risk of ischemic stroke or systemic embolism was lowered by 43%; for hemorrhagic stroke, it was lowered by 44%, and for TIA, it was lowered by 42%.
These associations were consistent regardless of whether patients used anticoagulant medications or the type of anticoagulant.
Oussama Wazni, MD, MBA, section head of cardiac electrophysiology and pacing at the Cleveland Clinic, was a moderator of the poster session at which Ms. Huang presented her study. In an interview, he called the study “very important.”
“The message should be that all patients who have atrial fibrillation should be checked for cholesterol levels, and we should consider placing them on statins,” he said. “Is there an opportunity? Probably there is, and that’s why we’re seeing this effect in this group of patients.”
When asked about a possible mechanism by which statins produced the effects seen in the study, he pointed to LDL cholesterol lowering and possibly an effect on inflammation. “If a patient had a carotid atheroma, for example, maybe it helped with that,” he said. Previous work has shown that inflammation is related to or is associated with higher risk of thrombogenic effects, including MI or stroke.
It may be a bit less clear how statins reduced the incidence of hemorrhagic strokes, but Dr. Wazni proposed that some strokes could have started as an ischemic stroke “and then had hemorrhagic conversion, so we don’t have the granularity in here to know whether that was the case or not.”
Given the fact that the effect was stronger the longer a patient had been taking a statin, Dr. Wazni said that if a patient is tolerating the drug well, there should be no reason to discontinue it, regardless of age.
He said the study provides “welcome data and evidence because it’s pointing in the right direction,” but prospective studies would be useful “so that we can see what is driving what. Otherwise, this is just an association.”
The study was supported by Sanming Project Shenzhen. Ms. Huang and Dr. Wazni disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Among patients with atrial fibrillation (AFib), initiation of statins soon after diagnosis was protective against stroke and related vascular events, and longer duration of use was associated with greater protection, a new cohort study shows.
Statin use was associated with lower risks of ischemic stroke or systemic embolism, hemorrhagic stroke, and transient ischemic attack (TIA), regardless of whether patients were also taking anticoagulant medications.
Lead author Jiayi Huang, a PhD student at Hong Kong University at Shenzhen (China) Hospital, concluded that the study’s findings support the use of statins to prevent stroke for patients with new-onset AFib.
“The findings have important clinical implications, particularly given that in atrial fibrillation, patients’ ischemic strokes are often fatal or disabling and have a high risk of recurrence,” she said.
The results were presented in a moderated poster session at the European Heart Rhythm Association 2023 Congress.
Widely prescribed
Anticoagulant drugs are prescribed to lower the fivefold increased risk of stroke among individuals with AFib, compared with those without AFib, but the therapy does not eliminate the higher risk, Ms. Huang explained. And although statins are widely prescribed to reduce the likelihood of myocardial infarction and stroke, “the benefit of statins for stroke prevention in patients with atrial fibrillation has been unclear.”
Ms. Huang and colleagues analyzed data from 51,472 patients newly diagnosed with AFib between 2010 and 2018. The population was divided into statin users (n = 11,866), defined as patients who had taken statins for at least 19 consecutive days in the first year after AFib diagnosis, and statin nonusers (n = 39,606), based on whether they were prescribed statin therapy after their first diagnosis of AFib.
The median age of the cohort was 74.9 years, and 47.7% were women. The investigators used statistical methods to balance baseline covariates between the two groups.
The primary outcomes were ischemic stroke or systemic embolism, hemorrhagic stroke, and TIA. Median follow-up was 5.1 years.
Statin use was associated with a significantly lower risk of all outcomes, compared with nonuse. Statin users had a 17% reduced risk of ischemic stroke or systemic embolism, a 7% reduced risk of hemorrhagic stroke, and a 15% rate of reduced risk of TIA, Ms. Huang reported.
“We also found long-term statin use was associated with greater protection than short-term use,” she said. For statin use of 6 years or longer, in comparison with use of 3 months to 2 years, the risk of ischemic stroke or systemic embolism was lowered by 43%; for hemorrhagic stroke, it was lowered by 44%, and for TIA, it was lowered by 42%.
These associations were consistent regardless of whether patients used anticoagulant medications or the type of anticoagulant.
Oussama Wazni, MD, MBA, section head of cardiac electrophysiology and pacing at the Cleveland Clinic, was a moderator of the poster session at which Ms. Huang presented her study. In an interview, he called the study “very important.”
“The message should be that all patients who have atrial fibrillation should be checked for cholesterol levels, and we should consider placing them on statins,” he said. “Is there an opportunity? Probably there is, and that’s why we’re seeing this effect in this group of patients.”
When asked about a possible mechanism by which statins produced the effects seen in the study, he pointed to LDL cholesterol lowering and possibly an effect on inflammation. “If a patient had a carotid atheroma, for example, maybe it helped with that,” he said. Previous work has shown that inflammation is related to or is associated with higher risk of thrombogenic effects, including MI or stroke.
It may be a bit less clear how statins reduced the incidence of hemorrhagic strokes, but Dr. Wazni proposed that some strokes could have started as an ischemic stroke “and then had hemorrhagic conversion, so we don’t have the granularity in here to know whether that was the case or not.”
Given the fact that the effect was stronger the longer a patient had been taking a statin, Dr. Wazni said that if a patient is tolerating the drug well, there should be no reason to discontinue it, regardless of age.
He said the study provides “welcome data and evidence because it’s pointing in the right direction,” but prospective studies would be useful “so that we can see what is driving what. Otherwise, this is just an association.”
The study was supported by Sanming Project Shenzhen. Ms. Huang and Dr. Wazni disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM EHRA 2023
Advances in Breast Cancer From AACR 2023
Notable advances in breast cancer, presented at the American Association for Cancer Research Annual Meeting 2023, are discussed by Dr Kathy Miller, Ballvé Lantero Professor of Oncology at Indiana University Health, Indianapolis.
She begins with two studies looking at PARP inhibitors in combination with immune checkpoint inhibitors.
The TALAVE study suggested that talazoparib induction followed by talazoparib plus avelumab could enhance the benefits of PARP inhibition. In contrast, a study of olaparib vs olaparib plus atezolizumab suggested that the combination offered few clinical improvements at the cost of additional toxicities.
Dr Miller next discusses the combination of olaparib and the novel agent sapacitabine in BRCA-mutated breast cancer. Although hematologic toxicities were an issue in this small trial, some patients experienced prolonged benefits.
Finally, she presents early results with a whole tumor cell therapeutic vaccine, before examining some of the future challenges around antibody-drug conjugates.
--
Ballvé Lantero Professor of Oncology, Indiana University Health, Indianapolis, Indiana
Kathy D. Miller, MD, has disclosed the following relevant financial relationships:
Serves on independent Data Monitoring Committees for ongoing trials for: Merck; Genentech/Roche; AstraZeneca; Celcuity
Notable advances in breast cancer, presented at the American Association for Cancer Research Annual Meeting 2023, are discussed by Dr Kathy Miller, Ballvé Lantero Professor of Oncology at Indiana University Health, Indianapolis.
She begins with two studies looking at PARP inhibitors in combination with immune checkpoint inhibitors.
The TALAVE study suggested that talazoparib induction followed by talazoparib plus avelumab could enhance the benefits of PARP inhibition. In contrast, a study of olaparib vs olaparib plus atezolizumab suggested that the combination offered few clinical improvements at the cost of additional toxicities.
Dr Miller next discusses the combination of olaparib and the novel agent sapacitabine in BRCA-mutated breast cancer. Although hematologic toxicities were an issue in this small trial, some patients experienced prolonged benefits.
Finally, she presents early results with a whole tumor cell therapeutic vaccine, before examining some of the future challenges around antibody-drug conjugates.
--
Ballvé Lantero Professor of Oncology, Indiana University Health, Indianapolis, Indiana
Kathy D. Miller, MD, has disclosed the following relevant financial relationships:
Serves on independent Data Monitoring Committees for ongoing trials for: Merck; Genentech/Roche; AstraZeneca; Celcuity
Notable advances in breast cancer, presented at the American Association for Cancer Research Annual Meeting 2023, are discussed by Dr Kathy Miller, Ballvé Lantero Professor of Oncology at Indiana University Health, Indianapolis.
She begins with two studies looking at PARP inhibitors in combination with immune checkpoint inhibitors.
The TALAVE study suggested that talazoparib induction followed by talazoparib plus avelumab could enhance the benefits of PARP inhibition. In contrast, a study of olaparib vs olaparib plus atezolizumab suggested that the combination offered few clinical improvements at the cost of additional toxicities.
Dr Miller next discusses the combination of olaparib and the novel agent sapacitabine in BRCA-mutated breast cancer. Although hematologic toxicities were an issue in this small trial, some patients experienced prolonged benefits.
Finally, she presents early results with a whole tumor cell therapeutic vaccine, before examining some of the future challenges around antibody-drug conjugates.
--
Ballvé Lantero Professor of Oncology, Indiana University Health, Indianapolis, Indiana
Kathy D. Miller, MD, has disclosed the following relevant financial relationships:
Serves on independent Data Monitoring Committees for ongoing trials for: Merck; Genentech/Roche; AstraZeneca; Celcuity
Key Takeaways in Early Breast Cancer From AACR 2023
Dr Kathy Miller of Indiana University Health in Indianapolis discusses key takeaways in early breast cancer from the American Association for Cancer Research (AACR) Annual Meeting 2023.
She begins with a novel imaging agent that allows surgeons to visualize residual disease during lumpectomy and reduce the risk for positive margins. It is now being investigated in patients who undergo neoadjuvant therapy.
Next, Dr Miller focuses on a study of skin toxicity in patients undergoing fractionated radiotherapy, which found that rates varied widely by race/ethnicity.
She also examines the implications of these findings and other research presented at AACR addressing the effect of genetic ancestry on the biology of breast cancers.
Finally, Dr Miller looks at a study of disease progression in ductal carcinoma in situ (DCIS), which found that 80% of cases were the result of clonal recurrences of residual cells left behind at the time of treatment.
--
Kathy D. Miller, MD, Ballvé Lantero Professor of Oncology, Indiana University Health, Indianapolis, Indiana
Kathy D. Miller, MD, has disclosed the following relevant financial relationships:
Serve on independent Data Monitoring Committees for ongoing trials for: Merck; Genentech/Roche; AstraZeneca; Celcuity
Dr Kathy Miller of Indiana University Health in Indianapolis discusses key takeaways in early breast cancer from the American Association for Cancer Research (AACR) Annual Meeting 2023.
She begins with a novel imaging agent that allows surgeons to visualize residual disease during lumpectomy and reduce the risk for positive margins. It is now being investigated in patients who undergo neoadjuvant therapy.
Next, Dr Miller focuses on a study of skin toxicity in patients undergoing fractionated radiotherapy, which found that rates varied widely by race/ethnicity.
She also examines the implications of these findings and other research presented at AACR addressing the effect of genetic ancestry on the biology of breast cancers.
Finally, Dr Miller looks at a study of disease progression in ductal carcinoma in situ (DCIS), which found that 80% of cases were the result of clonal recurrences of residual cells left behind at the time of treatment.
--
Kathy D. Miller, MD, Ballvé Lantero Professor of Oncology, Indiana University Health, Indianapolis, Indiana
Kathy D. Miller, MD, has disclosed the following relevant financial relationships:
Serve on independent Data Monitoring Committees for ongoing trials for: Merck; Genentech/Roche; AstraZeneca; Celcuity
Dr Kathy Miller of Indiana University Health in Indianapolis discusses key takeaways in early breast cancer from the American Association for Cancer Research (AACR) Annual Meeting 2023.
She begins with a novel imaging agent that allows surgeons to visualize residual disease during lumpectomy and reduce the risk for positive margins. It is now being investigated in patients who undergo neoadjuvant therapy.
Next, Dr Miller focuses on a study of skin toxicity in patients undergoing fractionated radiotherapy, which found that rates varied widely by race/ethnicity.
She also examines the implications of these findings and other research presented at AACR addressing the effect of genetic ancestry on the biology of breast cancers.
Finally, Dr Miller looks at a study of disease progression in ductal carcinoma in situ (DCIS), which found that 80% of cases were the result of clonal recurrences of residual cells left behind at the time of treatment.
--
Kathy D. Miller, MD, Ballvé Lantero Professor of Oncology, Indiana University Health, Indianapolis, Indiana
Kathy D. Miller, MD, has disclosed the following relevant financial relationships:
Serve on independent Data Monitoring Committees for ongoing trials for: Merck; Genentech/Roche; AstraZeneca; Celcuity
New clues to how air pollution fuels lung cancer in nonsmokers
“This work adds to our understanding of the mechanism by which air pollutants promote the earliest stages of lung cancer, particularly in people who have never smoked,” William Hill, PhD, co–first author and postdoctoral researcher at the Francis Crick Institute, London, told this news organization.
The study, which assessed human lung samples and mouse cancer models, was published online in Nature.
Although smoking remains the chief risk factor for lung cancer, outdoor air pollution causes roughly 1 in 10 cases of lung cancer in the United Kingdom, according to Cancer Research UK. In 2019, about 300,000 lung cancer deaths around the world were attributed to exposure to ambient particulate matter measuring ≤ 2.5 mcm (PM2.5).
While the link between air pollution and lung cancer is well known, the mechanism that explains this link has been harder to pinpoint.
One theory is that environmental carcinogens such as tobacco smoke and UV light cause mutations by damaging DNA directly. However, recent data have hinted that that may not be the case.
In the current study, Dr. Hill and colleagues proposed that, rather than act on DNA directly, air pollutants might promote inflammatory changes in the lung tissue that wake up inactive cancer-causing mutations, which accumulate naturally in these cells as people age. This idea lines up with a decades-old theory of cancer promotion, according to which tumorigenesis is a two-step process: The initial step induces mutations in healthy cells, after which a promoter step triggers cancer development.
The study team focused on epidermal growth factor receptor (EGFR)–driven lung cancer, which is more common in never-smokers and light smokers, and on environmental particulate matter measuring ≤ 2.5 mcm (PM2.5), which is fine enough to travel into the lungs and is associated with lung cancer risk.
Dr. Hill and colleagues analyzed data from over 400,000 people in three countries. They compared rates of EGFR-mutant lung cancer cases in areas with different levels of PM2.5 pollution. The team found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in England, South Korea, and Taiwan.
The researchers then studied genetically engineered mouse models of lung adenocarcinoma to determine whether particulate matter exposure could trigger the development of lung tumors. In these functional mouse models, air pollutants led to an influx of macrophages in the lung and the release of interleukin-1beta, a key mediator of the inflammatory response.
This process ultimately “fuels tumorigenesis,” the study team concluded.
The team also found that treatment with an anti-interleukin-1beta antibody during PM2.5 exposure reduced lung cancer promotion by air pollutants.
A detailed mutational profiling of histologically normal lung tissue from 295 individuals revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively.
Overall, “our data suggest a mechanistic and causative link between air pollutants and lung cancer,” the study team wrote.
The study demonstrates that air pollution rouses cells in the lung that carry cancer-causing mutations, “encouraging them to grow and potentially form tumors,” Dr. Hill said. “Understanding the biology could help identify high-risk individuals and, in the future, may open avenues to prevent cancer caused by breathing polluted air.”
In a related article in Nature, Allan Balmain, PhD, of the University of California, San Francisco, said these results have “major implications for how to think about cancer prevention.”
“There is presently nothing that can be done to remove the mutated cells that accumulate in normal tissues, but if there is a promotion stage that influences the rate of cancer development, then inhibition of this stage might be an effective way to prevent cancer,” Dr. Balmain said.
Another prevention option, Dr. Hill noted, is to reduce the levels of air pollution. “Our study provides a mandate for the reduction of PM2.5 emissions globally,” he said.
Dr. Hill also believes the findings may extend beyond lung cancer.
“It’s possible that this inflammatory pathway could be involved in other types of cancer and that it could be triggered by other environmental carcinogens,” he said. “But further research is needed to find out which other environmental carcinogens might trigger this pathway, as well as which other parts of the body this may occur in.”
Funding for the study was provided by Cancer Research UK, the European Research Council, the Francis Crick Institute, the Mark Foundation, the Lung Cancer Research Foundation, Rosetrees Trust, and the Ruth Strauss Foundation. A complete list of author disclosures is available with the original article. Dr. Balmain has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“This work adds to our understanding of the mechanism by which air pollutants promote the earliest stages of lung cancer, particularly in people who have never smoked,” William Hill, PhD, co–first author and postdoctoral researcher at the Francis Crick Institute, London, told this news organization.
The study, which assessed human lung samples and mouse cancer models, was published online in Nature.
Although smoking remains the chief risk factor for lung cancer, outdoor air pollution causes roughly 1 in 10 cases of lung cancer in the United Kingdom, according to Cancer Research UK. In 2019, about 300,000 lung cancer deaths around the world were attributed to exposure to ambient particulate matter measuring ≤ 2.5 mcm (PM2.5).
While the link between air pollution and lung cancer is well known, the mechanism that explains this link has been harder to pinpoint.
One theory is that environmental carcinogens such as tobacco smoke and UV light cause mutations by damaging DNA directly. However, recent data have hinted that that may not be the case.
In the current study, Dr. Hill and colleagues proposed that, rather than act on DNA directly, air pollutants might promote inflammatory changes in the lung tissue that wake up inactive cancer-causing mutations, which accumulate naturally in these cells as people age. This idea lines up with a decades-old theory of cancer promotion, according to which tumorigenesis is a two-step process: The initial step induces mutations in healthy cells, after which a promoter step triggers cancer development.
The study team focused on epidermal growth factor receptor (EGFR)–driven lung cancer, which is more common in never-smokers and light smokers, and on environmental particulate matter measuring ≤ 2.5 mcm (PM2.5), which is fine enough to travel into the lungs and is associated with lung cancer risk.
Dr. Hill and colleagues analyzed data from over 400,000 people in three countries. They compared rates of EGFR-mutant lung cancer cases in areas with different levels of PM2.5 pollution. The team found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in England, South Korea, and Taiwan.
The researchers then studied genetically engineered mouse models of lung adenocarcinoma to determine whether particulate matter exposure could trigger the development of lung tumors. In these functional mouse models, air pollutants led to an influx of macrophages in the lung and the release of interleukin-1beta, a key mediator of the inflammatory response.
This process ultimately “fuels tumorigenesis,” the study team concluded.
The team also found that treatment with an anti-interleukin-1beta antibody during PM2.5 exposure reduced lung cancer promotion by air pollutants.
A detailed mutational profiling of histologically normal lung tissue from 295 individuals revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively.
Overall, “our data suggest a mechanistic and causative link between air pollutants and lung cancer,” the study team wrote.
The study demonstrates that air pollution rouses cells in the lung that carry cancer-causing mutations, “encouraging them to grow and potentially form tumors,” Dr. Hill said. “Understanding the biology could help identify high-risk individuals and, in the future, may open avenues to prevent cancer caused by breathing polluted air.”
In a related article in Nature, Allan Balmain, PhD, of the University of California, San Francisco, said these results have “major implications for how to think about cancer prevention.”
“There is presently nothing that can be done to remove the mutated cells that accumulate in normal tissues, but if there is a promotion stage that influences the rate of cancer development, then inhibition of this stage might be an effective way to prevent cancer,” Dr. Balmain said.
Another prevention option, Dr. Hill noted, is to reduce the levels of air pollution. “Our study provides a mandate for the reduction of PM2.5 emissions globally,” he said.
Dr. Hill also believes the findings may extend beyond lung cancer.
“It’s possible that this inflammatory pathway could be involved in other types of cancer and that it could be triggered by other environmental carcinogens,” he said. “But further research is needed to find out which other environmental carcinogens might trigger this pathway, as well as which other parts of the body this may occur in.”
Funding for the study was provided by Cancer Research UK, the European Research Council, the Francis Crick Institute, the Mark Foundation, the Lung Cancer Research Foundation, Rosetrees Trust, and the Ruth Strauss Foundation. A complete list of author disclosures is available with the original article. Dr. Balmain has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“This work adds to our understanding of the mechanism by which air pollutants promote the earliest stages of lung cancer, particularly in people who have never smoked,” William Hill, PhD, co–first author and postdoctoral researcher at the Francis Crick Institute, London, told this news organization.
The study, which assessed human lung samples and mouse cancer models, was published online in Nature.
Although smoking remains the chief risk factor for lung cancer, outdoor air pollution causes roughly 1 in 10 cases of lung cancer in the United Kingdom, according to Cancer Research UK. In 2019, about 300,000 lung cancer deaths around the world were attributed to exposure to ambient particulate matter measuring ≤ 2.5 mcm (PM2.5).
While the link between air pollution and lung cancer is well known, the mechanism that explains this link has been harder to pinpoint.
One theory is that environmental carcinogens such as tobacco smoke and UV light cause mutations by damaging DNA directly. However, recent data have hinted that that may not be the case.
In the current study, Dr. Hill and colleagues proposed that, rather than act on DNA directly, air pollutants might promote inflammatory changes in the lung tissue that wake up inactive cancer-causing mutations, which accumulate naturally in these cells as people age. This idea lines up with a decades-old theory of cancer promotion, according to which tumorigenesis is a two-step process: The initial step induces mutations in healthy cells, after which a promoter step triggers cancer development.
The study team focused on epidermal growth factor receptor (EGFR)–driven lung cancer, which is more common in never-smokers and light smokers, and on environmental particulate matter measuring ≤ 2.5 mcm (PM2.5), which is fine enough to travel into the lungs and is associated with lung cancer risk.
Dr. Hill and colleagues analyzed data from over 400,000 people in three countries. They compared rates of EGFR-mutant lung cancer cases in areas with different levels of PM2.5 pollution. The team found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in England, South Korea, and Taiwan.
The researchers then studied genetically engineered mouse models of lung adenocarcinoma to determine whether particulate matter exposure could trigger the development of lung tumors. In these functional mouse models, air pollutants led to an influx of macrophages in the lung and the release of interleukin-1beta, a key mediator of the inflammatory response.
This process ultimately “fuels tumorigenesis,” the study team concluded.
The team also found that treatment with an anti-interleukin-1beta antibody during PM2.5 exposure reduced lung cancer promotion by air pollutants.
A detailed mutational profiling of histologically normal lung tissue from 295 individuals revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively.
Overall, “our data suggest a mechanistic and causative link between air pollutants and lung cancer,” the study team wrote.
The study demonstrates that air pollution rouses cells in the lung that carry cancer-causing mutations, “encouraging them to grow and potentially form tumors,” Dr. Hill said. “Understanding the biology could help identify high-risk individuals and, in the future, may open avenues to prevent cancer caused by breathing polluted air.”
In a related article in Nature, Allan Balmain, PhD, of the University of California, San Francisco, said these results have “major implications for how to think about cancer prevention.”
“There is presently nothing that can be done to remove the mutated cells that accumulate in normal tissues, but if there is a promotion stage that influences the rate of cancer development, then inhibition of this stage might be an effective way to prevent cancer,” Dr. Balmain said.
Another prevention option, Dr. Hill noted, is to reduce the levels of air pollution. “Our study provides a mandate for the reduction of PM2.5 emissions globally,” he said.
Dr. Hill also believes the findings may extend beyond lung cancer.
“It’s possible that this inflammatory pathway could be involved in other types of cancer and that it could be triggered by other environmental carcinogens,” he said. “But further research is needed to find out which other environmental carcinogens might trigger this pathway, as well as which other parts of the body this may occur in.”
Funding for the study was provided by Cancer Research UK, the European Research Council, the Francis Crick Institute, the Mark Foundation, the Lung Cancer Research Foundation, Rosetrees Trust, and the Ruth Strauss Foundation. A complete list of author disclosures is available with the original article. Dr. Balmain has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.