Federal Practitioner

Long-course radiation therapy for rectal cancer is more likely to spare organs than short-course therapy, including when chemotherapy is provided first as part of a total neoadjuvant therapy (TNT) strategy, shows new research presented at the ASCO Gastrointestinal Cancers Symposium 2023.

“When we looked at the 2-year organ preservation rates, they were numerically higher in the long-course group versus the short-course group,” said study author J. Joshua Smith, MD, PhD,FACS, a colorectal surgeon with Memorial Sloan Kettering Cancer Center, New York. “Our study will be the first, to our knowledge, that examines a significant proportion of patients treated with the induction total neoadjuvant therapy approach – chemo first.”

An ideal outcome in rectal cancer is no need for surgery, Dr. Smith said. “If you can avoid surgery altogether and preserve the organ [the rectum], that’s a big win for the patient as they are usually able to avoid having a permanent or temporary ostomy.”

Long-course and short-course radiation have similar outcomes in terms of patients going on to need surgery, but it’s not clear which is superior in terms of organ sparing, toxicity, and side effects, said Paul Romesser, MD, a radiation oncologist with Memorial Sloan Kettering Cancer Center, New York, who served as first author of the study.

During the early months of the COVID-19 pandemic, the cancer center embraced short-course radiation in rectal cancer, Dr. Romesser said. “Once we emerged from the cloud of COVID, we said: ‘Well, what do we do now? Where do we go? Do we go back to what we did before? Or, do we go stick with the same? And what does that mean for organ preservation?’ ”

The researchers retrospectively identified 563 consecutive patients treated with TNT from 2018 to 2021. They focused on 332 who didn’t have metastatic disease, synchronous/metachronous malignancies, or nonadenocarcinoma histology (long course = 256, short course = 76). The groups had similar high-risk features, and about 82% were clinical stage III).

Patients most commonly received induction chemotherapy followed by consolidative radiation (78% long course, 70% short course).

The 2-year survival rates were similar, but organ preservation was higher in the long-course group versus the short-course group (40%; 95% confidence interval, 35%-47% vs. 29%; 95% CI, 20%-42%). And the 2-year local regrowth rate was also better in the long-course group versus the short-course group (20%; 95% CI, 12%-27% vs. 36%; 95% CI, 16%-52%).

Why might long-course therapy be better? “It’s probably just coming down to the biologically equivalent dose,” which is likely lower in short-course radiation, Dr. Romesser said.

Going forward, Dr. Romesser said he’ll tell patients about the findings of this study and a previous report published in 2022 that determined that “organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME [total mesorectal excision], and postoperative chemotherapy.” Dr. Smith is a coauthor of that study.

“Generally, I’ll steer patients toward long course, assuming all else is equal, and it’s not an undue burden on them financially and socially to come in for 5-6 weeks of chemoradiation,” Dr. Romesser said. He added that, “generally, the insurance companies recognize [short-course and long-course radiation] as both acceptable and standard treatment options for patients. We haven’t found that insurances will approve one, but not the other.”

The study was funded by the National Institutes of Health. Dr. Romesser disclosed consulting/advisory roles (EMD Serono, Faeth, Natera), research funding (XRad), and travel/accommodations/expenses (Elekta). Dr. Smith disclosed consulting/advisory roles (Foundation Medicine, Guardant Health). The other study authors reported no conflicts of interest.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Long-course radiation therapy for rectal cancer is more likely to spare organs than short-course therapy, including when chemotherapy is provided first as part of a total neoadjuvant therapy (TNT) strategy, shows new research presented at the ASCO Gastrointestinal Cancers Symposium 2023.

“When we looked at the 2-year organ preservation rates, they were numerically higher in the long-course group versus the short-course group,” said study author J. Joshua Smith, MD, PhD,FACS, a colorectal surgeon with Memorial Sloan Kettering Cancer Center, New York. “Our study will be the first, to our knowledge, that examines a significant proportion of patients treated with the induction total neoadjuvant therapy approach – chemo first.”

An ideal outcome in rectal cancer is no need for surgery, Dr. Smith said. “If you can avoid surgery altogether and preserve the organ [the rectum], that’s a big win for the patient as they are usually able to avoid having a permanent or temporary ostomy.”

Long-course and short-course radiation have similar outcomes in terms of patients going on to need surgery, but it’s not clear which is superior in terms of organ sparing, toxicity, and side effects, said Paul Romesser, MD, a radiation oncologist with Memorial Sloan Kettering Cancer Center, New York, who served as first author of the study.

During the early months of the COVID-19 pandemic, the cancer center embraced short-course radiation in rectal cancer, Dr. Romesser said. “Once we emerged from the cloud of COVID, we said: ‘Well, what do we do now? Where do we go? Do we go back to what we did before? Or, do we go stick with the same? And what does that mean for organ preservation?’ ”

The researchers retrospectively identified 563 consecutive patients treated with TNT from 2018 to 2021. They focused on 332 who didn’t have metastatic disease, synchronous/metachronous malignancies, or nonadenocarcinoma histology (long course = 256, short course = 76). The groups had similar high-risk features, and about 82% were clinical stage III).

Patients most commonly received induction chemotherapy followed by consolidative radiation (78% long course, 70% short course).

The 2-year survival rates were similar, but organ preservation was higher in the long-course group versus the short-course group (40%; 95% confidence interval, 35%-47% vs. 29%; 95% CI, 20%-42%). And the 2-year local regrowth rate was also better in the long-course group versus the short-course group (20%; 95% CI, 12%-27% vs. 36%; 95% CI, 16%-52%).

Why might long-course therapy be better? “It’s probably just coming down to the biologically equivalent dose,” which is likely lower in short-course radiation, Dr. Romesser said.

Going forward, Dr. Romesser said he’ll tell patients about the findings of this study and a previous report published in 2022 that determined that “organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME [total mesorectal excision], and postoperative chemotherapy.” Dr. Smith is a coauthor of that study.

“Generally, I’ll steer patients toward long course, assuming all else is equal, and it’s not an undue burden on them financially and socially to come in for 5-6 weeks of chemoradiation,” Dr. Romesser said. He added that, “generally, the insurance companies recognize [short-course and long-course radiation] as both acceptable and standard treatment options for patients. We haven’t found that insurances will approve one, but not the other.”

The study was funded by the National Institutes of Health. Dr. Romesser disclosed consulting/advisory roles (EMD Serono, Faeth, Natera), research funding (XRad), and travel/accommodations/expenses (Elekta). Dr. Smith disclosed consulting/advisory roles (Foundation Medicine, Guardant Health). The other study authors reported no conflicts of interest.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Long-course radiation therapy for rectal cancer is more likely to spare organs than short-course therapy, including when chemotherapy is provided first as part of a total neoadjuvant therapy (TNT) strategy, shows new research presented at the ASCO Gastrointestinal Cancers Symposium 2023.

“When we looked at the 2-year organ preservation rates, they were numerically higher in the long-course group versus the short-course group,” said study author J. Joshua Smith, MD, PhD,FACS, a colorectal surgeon with Memorial Sloan Kettering Cancer Center, New York. “Our study will be the first, to our knowledge, that examines a significant proportion of patients treated with the induction total neoadjuvant therapy approach – chemo first.”

An ideal outcome in rectal cancer is no need for surgery, Dr. Smith said. “If you can avoid surgery altogether and preserve the organ [the rectum], that’s a big win for the patient as they are usually able to avoid having a permanent or temporary ostomy.”

Long-course and short-course radiation have similar outcomes in terms of patients going on to need surgery, but it’s not clear which is superior in terms of organ sparing, toxicity, and side effects, said Paul Romesser, MD, a radiation oncologist with Memorial Sloan Kettering Cancer Center, New York, who served as first author of the study.

During the early months of the COVID-19 pandemic, the cancer center embraced short-course radiation in rectal cancer, Dr. Romesser said. “Once we emerged from the cloud of COVID, we said: ‘Well, what do we do now? Where do we go? Do we go back to what we did before? Or, do we go stick with the same? And what does that mean for organ preservation?’ ”

The researchers retrospectively identified 563 consecutive patients treated with TNT from 2018 to 2021. They focused on 332 who didn’t have metastatic disease, synchronous/metachronous malignancies, or nonadenocarcinoma histology (long course = 256, short course = 76). The groups had similar high-risk features, and about 82% were clinical stage III).

Patients most commonly received induction chemotherapy followed by consolidative radiation (78% long course, 70% short course).

The 2-year survival rates were similar, but organ preservation was higher in the long-course group versus the short-course group (40%; 95% confidence interval, 35%-47% vs. 29%; 95% CI, 20%-42%). And the 2-year local regrowth rate was also better in the long-course group versus the short-course group (20%; 95% CI, 12%-27% vs. 36%; 95% CI, 16%-52%).

Why might long-course therapy be better? “It’s probably just coming down to the biologically equivalent dose,” which is likely lower in short-course radiation, Dr. Romesser said.

Going forward, Dr. Romesser said he’ll tell patients about the findings of this study and a previous report published in 2022 that determined that “organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME [total mesorectal excision], and postoperative chemotherapy.” Dr. Smith is a coauthor of that study.

“Generally, I’ll steer patients toward long course, assuming all else is equal, and it’s not an undue burden on them financially and socially to come in for 5-6 weeks of chemoradiation,” Dr. Romesser said. He added that, “generally, the insurance companies recognize [short-course and long-course radiation] as both acceptable and standard treatment options for patients. We haven’t found that insurances will approve one, but not the other.”

The study was funded by the National Institutes of Health. Dr. Romesser disclosed consulting/advisory roles (EMD Serono, Faeth, Natera), research funding (XRad), and travel/accommodations/expenses (Elekta). Dr. Smith disclosed consulting/advisory roles (Foundation Medicine, Guardant Health). The other study authors reported no conflicts of interest.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

In adults with prediabetes, vitamin D helped decrease the risk that these individuals would develop diabetes, suggests a meta-analysis of three trials.

Results of the analysis, led by Anastassios G. Pittas, MD, MS, with the division of endocrinology, diabetes, and metabolism at Tufts Medical Center, in Boston, were published online in Annals of Internal Medicine (2023 Feb 7. doi: 10.7326/M22-3018).

All three eligible trials included in the analysis were randomized, double blinded, and placebo controlled. The three eligible trials tested three oral formulations of Vitamin D: cholecalciferol, 20,000 IU (500 mcg) weekly; cholecalciferol, 4,000 IU (100 mcg) daily; or eldecalcitol, 0.75 mcg daily, against placebos.

The authors of the new paper found that vitamin D reduced the risk for diabetes in people with prediabetes by a statistically significant 15% in adjusted analyses. The 3-year absolute risk reduction was 3.3%.

They found no difference in the rate ratios for adverse events (kidney stones, 1.17, 95% confidence interval, 0.69-1.99; hypercalcemia, 2.34; 95% CI, 0.83-6.66]; hypercalciuria, 1.65; 95% CI, 0.83-3.28]; death, 0.85; 95% CI, 0.31-2.36]) when study participants got vitamin D instead of placebo.

Differences from previous analyses

The relationship between vitamin D levels and risk for type 2 diabetes has been studied in previous trials and results have been mixed.

The authors note that two previous meta-analyses included trials “that had relatively short durations for assessment of diabetes risk (for example, ≤ 1 year), had high risk of bias (for example, open-label trials), or were not specifically designed and conducted for primary prevention of type 2 diabetes, potentially undermining the validity of the results.”

Each of the trials in this meta-analysis had a low risk of bias as determined by the Cochrane risk-of-bias tool, Dr. Pittas and colleagues said.

“The present study does not reach an opposite conclusion from the D2d study,” said Dr. Pittas, who coauthored that paper as well. “Rather, it confirms the results of the D2d study. In D2d and two other similar vitamin D and diabetes prevention trials (one in Norway and one in Japan), vitamin D reduced the rate of progression to diabetes in adults with prediabetes, but the observed differences were not statistically significant because the reported relative risk reductions (10%-13%) were smaller than each trial was powered to detect (25%-36%).”

“Individual participant data meta-analyses increase the statistical power to detect an effect. After combining data, we found that vitamin D reduced the risk of progression from prediabetes to diabetes by 15% and this result was statistically significant. So, the conclusion of the meta-analysis is essentially the same conclusion as in D2d and the other two trials. The difference is that the result is now statistically significant,” Dr. Pittas added.

Small reduction but large population

The authors acknowledged that the absolute risk reduction number is small, especially when compared with the risk reduction seen with intensive lifestyle changes (58%) and metformin (31%), as reported in an article published in the New England of Journal of Medicine (2002 Feb 7;346:393-403). But “extrapolating to the more than 374 million adults worldwide who have prediabetes suggests that inexpensive vitamin D supplementation could delay the development of diabetes in more than 10 million people,” they said.

As for how high vitamin D levels need to be, the authors write that their research indicates that the optimal level of vitamin D in the blood needed to reduce diabetes risk may be higher than an Institute of Medicine committee recommendation in 2011.

“The blood 25-hydroxy vitamin D level needed to optimally reduce diabetes risk may be near and possibly above the range of 125-150 nmol/L (50-60 ng/mL) that the 2011 Institute of Medicine Committee to Review Dietary Reference Intakes for Calcium and Vitamin D provided as the range corresponding to the tolerable upper intake level (UL) of 4,000 IU/d for vitamin D,” the authors of the new paper said.

Editorialists urge caution

In an accompanying editorial also published in the Annals of Internal Medicine, Malachi J. McKenna, MD, with the department of clinical chemistry, at St. Vincent’s University Hospital, and Mary A.T. Flynn, PhD, RD, with the Food Safety Authority of Ireland in Dublin, urge caution regarding vitamin D dosing.

They write that there are important distinctions between vitamin D supplements and vitamin D therapy, and the potential harms of high-dose vitamin D are still unclear.

“Vitamin D supplementation of 10 to 20 mcg (400 to 800 IU) daily can be applied safely at the population level to prevent skeletal and possibly nonskeletal disease. Very-high-dose vitamin D therapy might prevent type 2 diabetes in some patients but may also cause harm,” they note.

Dr. Pittas said in an interview that there have been some studies with high-dose vitamin D (up to 500,000 IU a year in one study) that reported an increased fall risk in older adults who had high fall risk. “However, these findings are not generalizable to other populations that are younger and at low or average fall risk, such as the prediabetes population to which the results of this meta-analysis apply,” he noted.

“The benefit-to-risk ratio for vitamin D depends on the target population and medical condition,” Dr. Pittas said. “The editorial refers to the NAM (National Academy of Medicine) vitamin D guidelines for the general, healthy population to promote bone health. The guidelines should not be extrapolated to specific populations, for example [patients with] prediabetes,” where the vitamin D benefit-to-risk ratio would be different from that in the general population.

Dr. Pittas and colleagues caution that the people studied in this meta-analysis were at high risk for type 2 diabetes, so these results do not apply to the general healthy population. The results also should not be extrapolated to people at average risk for any type of diabetes, they add.

Several physicians either declined to comment or did not respond to requests for comment on this research.

Dr. Pittas reports the National Institutes of Health and the American Diabetes Association made payments to his institution to conduct Vitamin D-related research. He is an unpaid cochair of the Endocrine Society’s Evaluation, Treatment and Prevention of Vitamin D Deficiency Clinical Practice Guideline team.

Coauthor Dr. Jorde reports grants from Novo Nordisk Foundation, North Norwegian Regional Health Authorities, and the Research Council of Norway.

Dr. Dawson-Hughes reports she is on the DSMB for AgNovos Healthcare. AgNovos is developing a bone implant to reduce hip fracture risk and she gets a stipend from the company. She reports Helsinn Therapeutics provided anamorelin and matching placebo for an NIH-funded clinical trial.

Dr. Trikalinos was supported by the D2d study. He is a technical methodological consultant to Latham and Watkins, who is retained by Pacira Pharmaceuticals.

Dr. Angellotti has been employed by Takeda and owns stock in the company.

The editorialists report no relevant financial relationships.

In adults with prediabetes, vitamin D helped decrease the risk that these individuals would develop diabetes, suggests a meta-analysis of three trials.

Results of the analysis, led by Anastassios G. Pittas, MD, MS, with the division of endocrinology, diabetes, and metabolism at Tufts Medical Center, in Boston, were published online in Annals of Internal Medicine (2023 Feb 7. doi: 10.7326/M22-3018).

All three eligible trials included in the analysis were randomized, double blinded, and placebo controlled. The three eligible trials tested three oral formulations of Vitamin D: cholecalciferol, 20,000 IU (500 mcg) weekly; cholecalciferol, 4,000 IU (100 mcg) daily; or eldecalcitol, 0.75 mcg daily, against placebos.

The authors of the new paper found that vitamin D reduced the risk for diabetes in people with prediabetes by a statistically significant 15% in adjusted analyses. The 3-year absolute risk reduction was 3.3%.

They found no difference in the rate ratios for adverse events (kidney stones, 1.17, 95% confidence interval, 0.69-1.99; hypercalcemia, 2.34; 95% CI, 0.83-6.66]; hypercalciuria, 1.65; 95% CI, 0.83-3.28]; death, 0.85; 95% CI, 0.31-2.36]) when study participants got vitamin D instead of placebo.

Differences from previous analyses

The relationship between vitamin D levels and risk for type 2 diabetes has been studied in previous trials and results have been mixed.

The authors note that two previous meta-analyses included trials “that had relatively short durations for assessment of diabetes risk (for example, ≤ 1 year), had high risk of bias (for example, open-label trials), or were not specifically designed and conducted for primary prevention of type 2 diabetes, potentially undermining the validity of the results.”

Each of the trials in this meta-analysis had a low risk of bias as determined by the Cochrane risk-of-bias tool, Dr. Pittas and colleagues said.

“The present study does not reach an opposite conclusion from the D2d study,” said Dr. Pittas, who coauthored that paper as well. “Rather, it confirms the results of the D2d study. In D2d and two other similar vitamin D and diabetes prevention trials (one in Norway and one in Japan), vitamin D reduced the rate of progression to diabetes in adults with prediabetes, but the observed differences were not statistically significant because the reported relative risk reductions (10%-13%) were smaller than each trial was powered to detect (25%-36%).”

“Individual participant data meta-analyses increase the statistical power to detect an effect. After combining data, we found that vitamin D reduced the risk of progression from prediabetes to diabetes by 15% and this result was statistically significant. So, the conclusion of the meta-analysis is essentially the same conclusion as in D2d and the other two trials. The difference is that the result is now statistically significant,” Dr. Pittas added.

Small reduction but large population

The authors acknowledged that the absolute risk reduction number is small, especially when compared with the risk reduction seen with intensive lifestyle changes (58%) and metformin (31%), as reported in an article published in the New England of Journal of Medicine (2002 Feb 7;346:393-403). But “extrapolating to the more than 374 million adults worldwide who have prediabetes suggests that inexpensive vitamin D supplementation could delay the development of diabetes in more than 10 million people,” they said.

As for how high vitamin D levels need to be, the authors write that their research indicates that the optimal level of vitamin D in the blood needed to reduce diabetes risk may be higher than an Institute of Medicine committee recommendation in 2011.

“The blood 25-hydroxy vitamin D level needed to optimally reduce diabetes risk may be near and possibly above the range of 125-150 nmol/L (50-60 ng/mL) that the 2011 Institute of Medicine Committee to Review Dietary Reference Intakes for Calcium and Vitamin D provided as the range corresponding to the tolerable upper intake level (UL) of 4,000 IU/d for vitamin D,” the authors of the new paper said.

Editorialists urge caution

In an accompanying editorial also published in the Annals of Internal Medicine, Malachi J. McKenna, MD, with the department of clinical chemistry, at St. Vincent’s University Hospital, and Mary A.T. Flynn, PhD, RD, with the Food Safety Authority of Ireland in Dublin, urge caution regarding vitamin D dosing.

They write that there are important distinctions between vitamin D supplements and vitamin D therapy, and the potential harms of high-dose vitamin D are still unclear.

“Vitamin D supplementation of 10 to 20 mcg (400 to 800 IU) daily can be applied safely at the population level to prevent skeletal and possibly nonskeletal disease. Very-high-dose vitamin D therapy might prevent type 2 diabetes in some patients but may also cause harm,” they note.

Dr. Pittas said in an interview that there have been some studies with high-dose vitamin D (up to 500,000 IU a year in one study) that reported an increased fall risk in older adults who had high fall risk. “However, these findings are not generalizable to other populations that are younger and at low or average fall risk, such as the prediabetes population to which the results of this meta-analysis apply,” he noted.

“The benefit-to-risk ratio for vitamin D depends on the target population and medical condition,” Dr. Pittas said. “The editorial refers to the NAM (National Academy of Medicine) vitamin D guidelines for the general, healthy population to promote bone health. The guidelines should not be extrapolated to specific populations, for example [patients with] prediabetes,” where the vitamin D benefit-to-risk ratio would be different from that in the general population.

Dr. Pittas and colleagues caution that the people studied in this meta-analysis were at high risk for type 2 diabetes, so these results do not apply to the general healthy population. The results also should not be extrapolated to people at average risk for any type of diabetes, they add.

Several physicians either declined to comment or did not respond to requests for comment on this research.

Dr. Pittas reports the National Institutes of Health and the American Diabetes Association made payments to his institution to conduct Vitamin D-related research. He is an unpaid cochair of the Endocrine Society’s Evaluation, Treatment and Prevention of Vitamin D Deficiency Clinical Practice Guideline team.

Coauthor Dr. Jorde reports grants from Novo Nordisk Foundation, North Norwegian Regional Health Authorities, and the Research Council of Norway.

Dr. Dawson-Hughes reports she is on the DSMB for AgNovos Healthcare. AgNovos is developing a bone implant to reduce hip fracture risk and she gets a stipend from the company. She reports Helsinn Therapeutics provided anamorelin and matching placebo for an NIH-funded clinical trial.

Dr. Trikalinos was supported by the D2d study. He is a technical methodological consultant to Latham and Watkins, who is retained by Pacira Pharmaceuticals.

Dr. Angellotti has been employed by Takeda and owns stock in the company.

The editorialists report no relevant financial relationships.

In adults with prediabetes, vitamin D helped decrease the risk that these individuals would develop diabetes, suggests a meta-analysis of three trials.

Results of the analysis, led by Anastassios G. Pittas, MD, MS, with the division of endocrinology, diabetes, and metabolism at Tufts Medical Center, in Boston, were published online in Annals of Internal Medicine (2023 Feb 7. doi: 10.7326/M22-3018).

All three eligible trials included in the analysis were randomized, double blinded, and placebo controlled. The three eligible trials tested three oral formulations of Vitamin D: cholecalciferol, 20,000 IU (500 mcg) weekly; cholecalciferol, 4,000 IU (100 mcg) daily; or eldecalcitol, 0.75 mcg daily, against placebos.

The authors of the new paper found that vitamin D reduced the risk for diabetes in people with prediabetes by a statistically significant 15% in adjusted analyses. The 3-year absolute risk reduction was 3.3%.

They found no difference in the rate ratios for adverse events (kidney stones, 1.17, 95% confidence interval, 0.69-1.99; hypercalcemia, 2.34; 95% CI, 0.83-6.66]; hypercalciuria, 1.65; 95% CI, 0.83-3.28]; death, 0.85; 95% CI, 0.31-2.36]) when study participants got vitamin D instead of placebo.

Differences from previous analyses

The relationship between vitamin D levels and risk for type 2 diabetes has been studied in previous trials and results have been mixed.

The authors note that two previous meta-analyses included trials “that had relatively short durations for assessment of diabetes risk (for example, ≤ 1 year), had high risk of bias (for example, open-label trials), or were not specifically designed and conducted for primary prevention of type 2 diabetes, potentially undermining the validity of the results.”

Each of the trials in this meta-analysis had a low risk of bias as determined by the Cochrane risk-of-bias tool, Dr. Pittas and colleagues said.

“The present study does not reach an opposite conclusion from the D2d study,” said Dr. Pittas, who coauthored that paper as well. “Rather, it confirms the results of the D2d study. In D2d and two other similar vitamin D and diabetes prevention trials (one in Norway and one in Japan), vitamin D reduced the rate of progression to diabetes in adults with prediabetes, but the observed differences were not statistically significant because the reported relative risk reductions (10%-13%) were smaller than each trial was powered to detect (25%-36%).”

“Individual participant data meta-analyses increase the statistical power to detect an effect. After combining data, we found that vitamin D reduced the risk of progression from prediabetes to diabetes by 15% and this result was statistically significant. So, the conclusion of the meta-analysis is essentially the same conclusion as in D2d and the other two trials. The difference is that the result is now statistically significant,” Dr. Pittas added.

Small reduction but large population

The authors acknowledged that the absolute risk reduction number is small, especially when compared with the risk reduction seen with intensive lifestyle changes (58%) and metformin (31%), as reported in an article published in the New England of Journal of Medicine (2002 Feb 7;346:393-403). But “extrapolating to the more than 374 million adults worldwide who have prediabetes suggests that inexpensive vitamin D supplementation could delay the development of diabetes in more than 10 million people,” they said.

As for how high vitamin D levels need to be, the authors write that their research indicates that the optimal level of vitamin D in the blood needed to reduce diabetes risk may be higher than an Institute of Medicine committee recommendation in 2011.

“The blood 25-hydroxy vitamin D level needed to optimally reduce diabetes risk may be near and possibly above the range of 125-150 nmol/L (50-60 ng/mL) that the 2011 Institute of Medicine Committee to Review Dietary Reference Intakes for Calcium and Vitamin D provided as the range corresponding to the tolerable upper intake level (UL) of 4,000 IU/d for vitamin D,” the authors of the new paper said.

Editorialists urge caution

In an accompanying editorial also published in the Annals of Internal Medicine, Malachi J. McKenna, MD, with the department of clinical chemistry, at St. Vincent’s University Hospital, and Mary A.T. Flynn, PhD, RD, with the Food Safety Authority of Ireland in Dublin, urge caution regarding vitamin D dosing.

They write that there are important distinctions between vitamin D supplements and vitamin D therapy, and the potential harms of high-dose vitamin D are still unclear.

“Vitamin D supplementation of 10 to 20 mcg (400 to 800 IU) daily can be applied safely at the population level to prevent skeletal and possibly nonskeletal disease. Very-high-dose vitamin D therapy might prevent type 2 diabetes in some patients but may also cause harm,” they note.

Dr. Pittas said in an interview that there have been some studies with high-dose vitamin D (up to 500,000 IU a year in one study) that reported an increased fall risk in older adults who had high fall risk. “However, these findings are not generalizable to other populations that are younger and at low or average fall risk, such as the prediabetes population to which the results of this meta-analysis apply,” he noted.

“The benefit-to-risk ratio for vitamin D depends on the target population and medical condition,” Dr. Pittas said. “The editorial refers to the NAM (National Academy of Medicine) vitamin D guidelines for the general, healthy population to promote bone health. The guidelines should not be extrapolated to specific populations, for example [patients with] prediabetes,” where the vitamin D benefit-to-risk ratio would be different from that in the general population.

Dr. Pittas and colleagues caution that the people studied in this meta-analysis were at high risk for type 2 diabetes, so these results do not apply to the general healthy population. The results also should not be extrapolated to people at average risk for any type of diabetes, they add.

Several physicians either declined to comment or did not respond to requests for comment on this research.

Dr. Pittas reports the National Institutes of Health and the American Diabetes Association made payments to his institution to conduct Vitamin D-related research. He is an unpaid cochair of the Endocrine Society’s Evaluation, Treatment and Prevention of Vitamin D Deficiency Clinical Practice Guideline team.

Coauthor Dr. Jorde reports grants from Novo Nordisk Foundation, North Norwegian Regional Health Authorities, and the Research Council of Norway.

Dr. Dawson-Hughes reports she is on the DSMB for AgNovos Healthcare. AgNovos is developing a bone implant to reduce hip fracture risk and she gets a stipend from the company. She reports Helsinn Therapeutics provided anamorelin and matching placebo for an NIH-funded clinical trial.

Dr. Trikalinos was supported by the D2d study. He is a technical methodological consultant to Latham and Watkins, who is retained by Pacira Pharmaceuticals.

Dr. Angellotti has been employed by Takeda and owns stock in the company.

The editorialists report no relevant financial relationships.

A pair of new studies suggest limitations of adjuvant chemotherapy among older adults with stage 3 colorectal cancer. A phase 2, multi-institutional feasibility study found a completion rate of 67.3%, while a prospective study found that completion was associated with improved disease-free survival.

Both studies were presented in January at the ASCO Gastrointestinal Cancers Symposium 2023.

In HiSCO-04, Japanese researchers found that of 64 older patients with stage 3A colorectal cancer who underwent adjuvant chemotherapy, 53% completed the treatment with an improvement in disease-free survival. Patients who completed adjuvant chemotherapy had better disease-free survival (P = .03), while the survival was lower among those who did not receive adjuvant chemotherapy, and lowest among those who discontinued adjuvant chemotherapy.

“The results showed that adjuvant chemotherapy is not always recommended for elderly patients, and that patients who are able to complete treatment may have a better prognosis for survival. However, the results do not indicate which patients are unable to complete chemotherapy, and it will be necessary to identify patients who are intolerant of chemotherapy,” said the study’s lead author Manabu Shimomura, MD, PhD, an assistant professor of gastroenterological and transplant surgery at the Hiroshima University Graduate School of Biomedical and Health Sciences in Japan.

The study, which was conducted between 2013 and 2021, enrolled 214 patients (99 men, 115 women, 80-101 years old) who were in stage 3 cancer (27 cases 3A, 158 cases 3B, and 29 cases 3C). A total of 41 patients were ineligible for chemotherapy. Of the remaining patients, 65 received adjuvant chemotherapy and 108 did not receive adjuvant chemotherapy.

The 3-year disease-free survival was 63.6%, the 3-year overall survival was 76.9%, and the 3-year relapse-free survival was 63.1%. Thirty-six patients died because of colorectal cancer, and 30 patients died of other causes. There was recurrence in 58 cases and secondary cancers were observed in 17 cases during the 42.5 months–long follow-up period.

There were few reports of serious adverse events, but some cases of treatment discontinuation were because of adverse events.

In a second study presented by Dr. Shimomura’s group, called HiSCO-03, 65 patients (33 female) underwent curative resection and received five courses of uracil-tegafur and leucovorin (UFT/LV).

The completion rate of 67.3% had a 95% lower bound of 54.9%, which were lower than the predefined thresholds of 75% completion and a lower bound of 60%. “Based on the results of a previous (ACTS-CC phase III) study, we set the expected value of UFT/LV therapy in patients over 80 years of age at 75% and the threshold at 60%. Since the target age group of previous study was 75 years or younger, we concluded from the results of the current study that UFT/LV therapy is less well tolerated in patients 80 years of age and older than in patients 75 years of age and younger,” Dr. Shimomura said.

The treatment completion rate trended higher in males than females (77.6% versus 57.2%; P = .06) and performance status of 0 versus 1 or 2 (74.3% versus 58.9%; P = .10). The most common adverse events were anorexia (33.8%), diarrhea (30.8%), and anemia (24.6%). The median relative dose intensity was 84% for UFT and 100% for LV.

The challenges of treating older patients

If and how older patients with colorectal cancer should be treated is not clear cut. While 20% of patients in the United States who have colorectal cancer are over 80 years old, each case should be evaluated individually, experts say.

Writing in a 2015 review of colorectal cancer treatment in older adults, Monica Millan, MD, PhD, of Joan XXIII University Hospital, Tarragona, Spain, and colleagues, wrote that physiological heterogeneity and coexisting medical conditions make treating older patients with colorectal cancer challenging.

“Age in itself should not be an exclusion criterion for radical treatment, but there will be many elderly patients that will not tolerate or respond well to standard therapies. These patients need to be properly assessed before proposing treatment, and a tailored, individualized approach should be offered in a multidisciplinary setting,” wrote Dr. Millan, who is a colorectal surgeon.

The authors suggest that older patients who are fit could be treated similarly to younger patients, but there remain uncertainties about how to proceed in frail older adults with comorbidities.

“Most elderly patients with cancer will have priorities besides simply prolonging their lives. Surveys have found that their top concerns include avoiding suffering, strengthening relationships with family and friends, being mentally aware, not being a burden on others, and achieving a sense that their life is complete. The treatment plan should be comprehensive: cancer-specific treatment, symptom-specific treatment, supportive treatment modalities, and end-of-life care,” they wrote.

The U.S. Preventive Services Task Force recommends colorectal cancer screening for men and women who are between 45 and 75 years old; however, screening for patients between 76 and 85 years old should be done on a case-by-case basis based on a patient’s overall health, screening history, and the patient’s preferences.

Colorectal cancer incidence rates have been declining since the mid-1980s because of an increase in screening among adults 50 years and older, according to the American Cancer Society. Likewise, mortality rates have dropped from 29.2% in 1970 to 12.6% in 2020 – mostly because of screening.

Dr. Shimomura has no relevant financial disclosures.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

A pair of new studies suggest limitations of adjuvant chemotherapy among older adults with stage 3 colorectal cancer. A phase 2, multi-institutional feasibility study found a completion rate of 67.3%, while a prospective study found that completion was associated with improved disease-free survival.

Both studies were presented in January at the ASCO Gastrointestinal Cancers Symposium 2023.

In HiSCO-04, Japanese researchers found that of 64 older patients with stage 3A colorectal cancer who underwent adjuvant chemotherapy, 53% completed the treatment with an improvement in disease-free survival. Patients who completed adjuvant chemotherapy had better disease-free survival (P = .03), while the survival was lower among those who did not receive adjuvant chemotherapy, and lowest among those who discontinued adjuvant chemotherapy.

“The results showed that adjuvant chemotherapy is not always recommended for elderly patients, and that patients who are able to complete treatment may have a better prognosis for survival. However, the results do not indicate which patients are unable to complete chemotherapy, and it will be necessary to identify patients who are intolerant of chemotherapy,” said the study’s lead author Manabu Shimomura, MD, PhD, an assistant professor of gastroenterological and transplant surgery at the Hiroshima University Graduate School of Biomedical and Health Sciences in Japan.

The study, which was conducted between 2013 and 2021, enrolled 214 patients (99 men, 115 women, 80-101 years old) who were in stage 3 cancer (27 cases 3A, 158 cases 3B, and 29 cases 3C). A total of 41 patients were ineligible for chemotherapy. Of the remaining patients, 65 received adjuvant chemotherapy and 108 did not receive adjuvant chemotherapy.

The 3-year disease-free survival was 63.6%, the 3-year overall survival was 76.9%, and the 3-year relapse-free survival was 63.1%. Thirty-six patients died because of colorectal cancer, and 30 patients died of other causes. There was recurrence in 58 cases and secondary cancers were observed in 17 cases during the 42.5 months–long follow-up period.

There were few reports of serious adverse events, but some cases of treatment discontinuation were because of adverse events.

In a second study presented by Dr. Shimomura’s group, called HiSCO-03, 65 patients (33 female) underwent curative resection and received five courses of uracil-tegafur and leucovorin (UFT/LV).

The completion rate of 67.3% had a 95% lower bound of 54.9%, which were lower than the predefined thresholds of 75% completion and a lower bound of 60%. “Based on the results of a previous (ACTS-CC phase III) study, we set the expected value of UFT/LV therapy in patients over 80 years of age at 75% and the threshold at 60%. Since the target age group of previous study was 75 years or younger, we concluded from the results of the current study that UFT/LV therapy is less well tolerated in patients 80 years of age and older than in patients 75 years of age and younger,” Dr. Shimomura said.

The treatment completion rate trended higher in males than females (77.6% versus 57.2%; P = .06) and performance status of 0 versus 1 or 2 (74.3% versus 58.9%; P = .10). The most common adverse events were anorexia (33.8%), diarrhea (30.8%), and anemia (24.6%). The median relative dose intensity was 84% for UFT and 100% for LV.

The challenges of treating older patients

If and how older patients with colorectal cancer should be treated is not clear cut. While 20% of patients in the United States who have colorectal cancer are over 80 years old, each case should be evaluated individually, experts say.

Writing in a 2015 review of colorectal cancer treatment in older adults, Monica Millan, MD, PhD, of Joan XXIII University Hospital, Tarragona, Spain, and colleagues, wrote that physiological heterogeneity and coexisting medical conditions make treating older patients with colorectal cancer challenging.

“Age in itself should not be an exclusion criterion for radical treatment, but there will be many elderly patients that will not tolerate or respond well to standard therapies. These patients need to be properly assessed before proposing treatment, and a tailored, individualized approach should be offered in a multidisciplinary setting,” wrote Dr. Millan, who is a colorectal surgeon.

The authors suggest that older patients who are fit could be treated similarly to younger patients, but there remain uncertainties about how to proceed in frail older adults with comorbidities.

“Most elderly patients with cancer will have priorities besides simply prolonging their lives. Surveys have found that their top concerns include avoiding suffering, strengthening relationships with family and friends, being mentally aware, not being a burden on others, and achieving a sense that their life is complete. The treatment plan should be comprehensive: cancer-specific treatment, symptom-specific treatment, supportive treatment modalities, and end-of-life care,” they wrote.

The U.S. Preventive Services Task Force recommends colorectal cancer screening for men and women who are between 45 and 75 years old; however, screening for patients between 76 and 85 years old should be done on a case-by-case basis based on a patient’s overall health, screening history, and the patient’s preferences.

Colorectal cancer incidence rates have been declining since the mid-1980s because of an increase in screening among adults 50 years and older, according to the American Cancer Society. Likewise, mortality rates have dropped from 29.2% in 1970 to 12.6% in 2020 – mostly because of screening.

Dr. Shimomura has no relevant financial disclosures.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

A pair of new studies suggest limitations of adjuvant chemotherapy among older adults with stage 3 colorectal cancer. A phase 2, multi-institutional feasibility study found a completion rate of 67.3%, while a prospective study found that completion was associated with improved disease-free survival.

Both studies were presented in January at the ASCO Gastrointestinal Cancers Symposium 2023.

In HiSCO-04, Japanese researchers found that of 64 older patients with stage 3A colorectal cancer who underwent adjuvant chemotherapy, 53% completed the treatment with an improvement in disease-free survival. Patients who completed adjuvant chemotherapy had better disease-free survival (P = .03), while the survival was lower among those who did not receive adjuvant chemotherapy, and lowest among those who discontinued adjuvant chemotherapy.

“The results showed that adjuvant chemotherapy is not always recommended for elderly patients, and that patients who are able to complete treatment may have a better prognosis for survival. However, the results do not indicate which patients are unable to complete chemotherapy, and it will be necessary to identify patients who are intolerant of chemotherapy,” said the study’s lead author Manabu Shimomura, MD, PhD, an assistant professor of gastroenterological and transplant surgery at the Hiroshima University Graduate School of Biomedical and Health Sciences in Japan.

The study, which was conducted between 2013 and 2021, enrolled 214 patients (99 men, 115 women, 80-101 years old) who were in stage 3 cancer (27 cases 3A, 158 cases 3B, and 29 cases 3C). A total of 41 patients were ineligible for chemotherapy. Of the remaining patients, 65 received adjuvant chemotherapy and 108 did not receive adjuvant chemotherapy.

The 3-year disease-free survival was 63.6%, the 3-year overall survival was 76.9%, and the 3-year relapse-free survival was 63.1%. Thirty-six patients died because of colorectal cancer, and 30 patients died of other causes. There was recurrence in 58 cases and secondary cancers were observed in 17 cases during the 42.5 months–long follow-up period.

There were few reports of serious adverse events, but some cases of treatment discontinuation were because of adverse events.

In a second study presented by Dr. Shimomura’s group, called HiSCO-03, 65 patients (33 female) underwent curative resection and received five courses of uracil-tegafur and leucovorin (UFT/LV).

The completion rate of 67.3% had a 95% lower bound of 54.9%, which were lower than the predefined thresholds of 75% completion and a lower bound of 60%. “Based on the results of a previous (ACTS-CC phase III) study, we set the expected value of UFT/LV therapy in patients over 80 years of age at 75% and the threshold at 60%. Since the target age group of previous study was 75 years or younger, we concluded from the results of the current study that UFT/LV therapy is less well tolerated in patients 80 years of age and older than in patients 75 years of age and younger,” Dr. Shimomura said.

The treatment completion rate trended higher in males than females (77.6% versus 57.2%; P = .06) and performance status of 0 versus 1 or 2 (74.3% versus 58.9%; P = .10). The most common adverse events were anorexia (33.8%), diarrhea (30.8%), and anemia (24.6%). The median relative dose intensity was 84% for UFT and 100% for LV.

The challenges of treating older patients

If and how older patients with colorectal cancer should be treated is not clear cut. While 20% of patients in the United States who have colorectal cancer are over 80 years old, each case should be evaluated individually, experts say.

Writing in a 2015 review of colorectal cancer treatment in older adults, Monica Millan, MD, PhD, of Joan XXIII University Hospital, Tarragona, Spain, and colleagues, wrote that physiological heterogeneity and coexisting medical conditions make treating older patients with colorectal cancer challenging.

“Age in itself should not be an exclusion criterion for radical treatment, but there will be many elderly patients that will not tolerate or respond well to standard therapies. These patients need to be properly assessed before proposing treatment, and a tailored, individualized approach should be offered in a multidisciplinary setting,” wrote Dr. Millan, who is a colorectal surgeon.

The authors suggest that older patients who are fit could be treated similarly to younger patients, but there remain uncertainties about how to proceed in frail older adults with comorbidities.

“Most elderly patients with cancer will have priorities besides simply prolonging their lives. Surveys have found that their top concerns include avoiding suffering, strengthening relationships with family and friends, being mentally aware, not being a burden on others, and achieving a sense that their life is complete. The treatment plan should be comprehensive: cancer-specific treatment, symptom-specific treatment, supportive treatment modalities, and end-of-life care,” they wrote.

The U.S. Preventive Services Task Force recommends colorectal cancer screening for men and women who are between 45 and 75 years old; however, screening for patients between 76 and 85 years old should be done on a case-by-case basis based on a patient’s overall health, screening history, and the patient’s preferences.

Colorectal cancer incidence rates have been declining since the mid-1980s because of an increase in screening among adults 50 years and older, according to the American Cancer Society. Likewise, mortality rates have dropped from 29.2% in 1970 to 12.6% in 2020 – mostly because of screening.

Dr. Shimomura has no relevant financial disclosures.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

The Food and Drug Administration approved a new indication for sacituzumab govitecan (Trodelvy, Gilead Sciences) on Feb. 3 for patients with unresectable, locally advanced or metastatic hormone receptor (HR)–positive, HER2-negative breast cancer after endocrine-based therapy and at least two additional systemic therapies for metastatic disease.

Label expansion for the Trop-2–directed antibody-drug conjugate was based on the TROPICS-02 trial, which randomized 543 adults 1:1 to either sacituzumab govitecan 10 mg/kg IV on days 1 and 8 of a 21-day cycle or single agent chemotherapy, most often eribulin but also vinorelbine, gemcitabine, or capecitabine.

Median progression free survival was 5.5 months with sacituzumab govitecan versus 4 months with single agent chemotherapy (hazard ratio, 0.66; P = .0003). Median overall survival was 14.4 months in the sacituzumab govitecan group versus 11.2 months with chemotherapy (HR, 0.79), according to an FDA press release announcing the approval.

In a Gilead press release, Hope Rugo, MD, a breast cancer specialist at the University of California, San Francisco, and principal investigator for TROPICS-02, said the approval “is significant for the breast cancer community. We have had limited options to offer patients after endocrine-based therapy and chemotherapy, and to see a clinically meaningful survival benefit of more than 3 months with a quality-of-life benefit for these women is exceptional.”

The most common adverse events associated with sacituzumab govitecan in the trial, occurring in a quarter or more of participants, were decreased leukocyte count, decreased neutrophil count, decreased hemoglobin, decreased lymphocyte count, diarrhea, fatigue, nausea, alopecia, glucose elevation, constipation, and decreased albumin.

Labeling for the agent carries a boxedwarning of severe or life-threatening neutropenia and severe diarrhea.

The recommended dose is the trial dose: 10 mg/kg IV on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity.

Sacituzumab govitecan was previously approved for unresectable, locally advanced or metastatic triple-negative breast cancer after two or more prior systemic therapies and locally advanced or metastatic urothelial cancer after platinum-based chemotherapy and either a PD-1 or PD-L1 inhibitor.

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

The Food and Drug Administration approved a new indication for sacituzumab govitecan (Trodelvy, Gilead Sciences) on Feb. 3 for patients with unresectable, locally advanced or metastatic hormone receptor (HR)–positive, HER2-negative breast cancer after endocrine-based therapy and at least two additional systemic therapies for metastatic disease.

Label expansion for the Trop-2–directed antibody-drug conjugate was based on the TROPICS-02 trial, which randomized 543 adults 1:1 to either sacituzumab govitecan 10 mg/kg IV on days 1 and 8 of a 21-day cycle or single agent chemotherapy, most often eribulin but also vinorelbine, gemcitabine, or capecitabine.

Median progression free survival was 5.5 months with sacituzumab govitecan versus 4 months with single agent chemotherapy (hazard ratio, 0.66; P = .0003). Median overall survival was 14.4 months in the sacituzumab govitecan group versus 11.2 months with chemotherapy (HR, 0.79), according to an FDA press release announcing the approval.

In a Gilead press release, Hope Rugo, MD, a breast cancer specialist at the University of California, San Francisco, and principal investigator for TROPICS-02, said the approval “is significant for the breast cancer community. We have had limited options to offer patients after endocrine-based therapy and chemotherapy, and to see a clinically meaningful survival benefit of more than 3 months with a quality-of-life benefit for these women is exceptional.”

The most common adverse events associated with sacituzumab govitecan in the trial, occurring in a quarter or more of participants, were decreased leukocyte count, decreased neutrophil count, decreased hemoglobin, decreased lymphocyte count, diarrhea, fatigue, nausea, alopecia, glucose elevation, constipation, and decreased albumin.

Labeling for the agent carries a boxedwarning of severe or life-threatening neutropenia and severe diarrhea.

The recommended dose is the trial dose: 10 mg/kg IV on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity.

Sacituzumab govitecan was previously approved for unresectable, locally advanced or metastatic triple-negative breast cancer after two or more prior systemic therapies and locally advanced or metastatic urothelial cancer after platinum-based chemotherapy and either a PD-1 or PD-L1 inhibitor.

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

The Food and Drug Administration approved a new indication for sacituzumab govitecan (Trodelvy, Gilead Sciences) on Feb. 3 for patients with unresectable, locally advanced or metastatic hormone receptor (HR)–positive, HER2-negative breast cancer after endocrine-based therapy and at least two additional systemic therapies for metastatic disease.

Label expansion for the Trop-2–directed antibody-drug conjugate was based on the TROPICS-02 trial, which randomized 543 adults 1:1 to either sacituzumab govitecan 10 mg/kg IV on days 1 and 8 of a 21-day cycle or single agent chemotherapy, most often eribulin but also vinorelbine, gemcitabine, or capecitabine.

Median progression free survival was 5.5 months with sacituzumab govitecan versus 4 months with single agent chemotherapy (hazard ratio, 0.66; P = .0003). Median overall survival was 14.4 months in the sacituzumab govitecan group versus 11.2 months with chemotherapy (HR, 0.79), according to an FDA press release announcing the approval.

In a Gilead press release, Hope Rugo, MD, a breast cancer specialist at the University of California, San Francisco, and principal investigator for TROPICS-02, said the approval “is significant for the breast cancer community. We have had limited options to offer patients after endocrine-based therapy and chemotherapy, and to see a clinically meaningful survival benefit of more than 3 months with a quality-of-life benefit for these women is exceptional.”

The most common adverse events associated with sacituzumab govitecan in the trial, occurring in a quarter or more of participants, were decreased leukocyte count, decreased neutrophil count, decreased hemoglobin, decreased lymphocyte count, diarrhea, fatigue, nausea, alopecia, glucose elevation, constipation, and decreased albumin.

Labeling for the agent carries a boxedwarning of severe or life-threatening neutropenia and severe diarrhea.

The recommended dose is the trial dose: 10 mg/kg IV on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity.

Sacituzumab govitecan was previously approved for unresectable, locally advanced or metastatic triple-negative breast cancer after two or more prior systemic therapies and locally advanced or metastatic urothelial cancer after platinum-based chemotherapy and either a PD-1 or PD-L1 inhibitor.

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

Both race and place of residence affect how soon a woman in North Carolina receives treatment for breast cancer, suggesting the need to target high-risk geographic regions and patient groups to ensure timely care, new research suggests.

Among nearly 33,000 women from North Carolina with stage I-III breast cancer, Black patients were nearly twice as likely has non-Black patients to experience treatment delays of more than 60 days, researchers found.

“Our findings suggest that treatment delays are alarmingly common in patients at high risk for breast cancer death, including young Black women and patients with stage III disease,” the authors note in their article, which was published online in Cancer.

Research shows that breast cancer treatment delays of 30-60 days can lower survival, and Black patients face a “disproportionate risk of treatment delays across the breast cancer care delivery spectrum,” the authors explain.

However, studies exploring whether or how racial disparities in treatment delays relate to geography are more limited.

In the current analysis, researchers amassed a retrospective cohort of all patients with stage I-III breast cancer between 2004 and 2015 in the North Carolina Central Cancer Registry and explored the risk of treatment delay by race and geographic subregion.

The cohort included 32,626 women, 6,190 (19.0%) of whom were Black. Counties were divided into the nine Area Health Education Center regions for North Carolina.

Compared with non‐Black patients, Black patients were more likely to have stage III disease (15.2% vs. 9.3%), hormone receptor–negative tumors (29.3% vs. 15.6%), Medicaid insurance (46.7% vs. 14.9%), and to live within 5 miles of their treatment site (30.6% vs. 25.2%).

Overall, Black patients were almost two times more likely to experience a treatment delay of more than 60 days (15% vs. 8%).

On average, about one in seven Black women experienced a lengthy delay, but the risk varied depending on geographic location. Patients living in certain regions of the state were more likely to experience delays; those in the highest-risk region were about twice as likely to experience a delay as those in the lowest-risk region (relative risk, 2.1 among Black patients; and RR, 1.9 among non-Black patients).

The magnitude of the racial gap in treatment delay varied by region – from 0% to 9.4%. But overall, of patients who experienced treatment delays, a significantly greater proportion were Black patients in every region except region 2, where only 2.7% (93 of 3,362) of patients were Black.

Notably, two regions with the greatest disparities in treatment delay, as well as the highest absolute risk of treatment delay for Black patients, surround large cities.

“These delays weren’t explained by the patients’ distance from cancer treatment facilities, their specific stage of cancer or type of treatment, or what insurance they had,” lead author Katherine Reeder-Hayes, MD, with the University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, said in a news release.

Instead, Dr. Reeder-Hayes said, the findings suggest that the structure of local health care systems, rather than patient characteristics, may better explain why some patients experience treatment delays.

In other words, “if cancer care teams in certain areas say, ‘Oh, it’s particularly hard to treat breast cancer in our area because people are poor or have really advanced stages of cancer when they come in,’ our research does not bear out that explanation,” Dr. Reeder-Hayes said in email to this news organization.

This study “highlights the persistent disparities in treatment delays Black women encounter, which often lead to worse outcomes,” said Kathie-Ann Joseph, MD, MPH, who was not involved in the research.

“Interestingly, the authors could not attribute these delays in treatment to patient-level factors,” said Dr. Joseph, a breast cancer surgeon at NYU Langone Perlmutter Cancer Center, New York. But the authors “did find substantial geographic variation, which suggests the need to address structural barriers contributing to treatment delays in Black women.”

Sara P. Cate, MD, who was not involved with the research, also noted that the study highlights a known issue – “that racial minorities have longer delays in cancer treatment.” And notably, she said, the findings reveal that this disparity persists in areas where access to care is better and more robust.

“The nuances of the delays to care are multifactorial,” said Dr. Cate, a breast cancer surgeon and director of the Breast Surgery Quality Program at Mount Sinai in New York. “We need to do better with this population, and it is a multilevel solution of financial assistance, social work, and patient navigation.”

The study was supported in part by grants from the Susan G. Komen Foundation and the NC State Employees’ Credit Union. Dr. Reeder-Hayes, Dr. Cate, and Dr. Joseph have disclosed no relevant financial relationships.

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

Both race and place of residence affect how soon a woman in North Carolina receives treatment for breast cancer, suggesting the need to target high-risk geographic regions and patient groups to ensure timely care, new research suggests.

Among nearly 33,000 women from North Carolina with stage I-III breast cancer, Black patients were nearly twice as likely has non-Black patients to experience treatment delays of more than 60 days, researchers found.

“Our findings suggest that treatment delays are alarmingly common in patients at high risk for breast cancer death, including young Black women and patients with stage III disease,” the authors note in their article, which was published online in Cancer.

Research shows that breast cancer treatment delays of 30-60 days can lower survival, and Black patients face a “disproportionate risk of treatment delays across the breast cancer care delivery spectrum,” the authors explain.

However, studies exploring whether or how racial disparities in treatment delays relate to geography are more limited.

In the current analysis, researchers amassed a retrospective cohort of all patients with stage I-III breast cancer between 2004 and 2015 in the North Carolina Central Cancer Registry and explored the risk of treatment delay by race and geographic subregion.

The cohort included 32,626 women, 6,190 (19.0%) of whom were Black. Counties were divided into the nine Area Health Education Center regions for North Carolina.

Compared with non‐Black patients, Black patients were more likely to have stage III disease (15.2% vs. 9.3%), hormone receptor–negative tumors (29.3% vs. 15.6%), Medicaid insurance (46.7% vs. 14.9%), and to live within 5 miles of their treatment site (30.6% vs. 25.2%).

Overall, Black patients were almost two times more likely to experience a treatment delay of more than 60 days (15% vs. 8%).

On average, about one in seven Black women experienced a lengthy delay, but the risk varied depending on geographic location. Patients living in certain regions of the state were more likely to experience delays; those in the highest-risk region were about twice as likely to experience a delay as those in the lowest-risk region (relative risk, 2.1 among Black patients; and RR, 1.9 among non-Black patients).

The magnitude of the racial gap in treatment delay varied by region – from 0% to 9.4%. But overall, of patients who experienced treatment delays, a significantly greater proportion were Black patients in every region except region 2, where only 2.7% (93 of 3,362) of patients were Black.

Notably, two regions with the greatest disparities in treatment delay, as well as the highest absolute risk of treatment delay for Black patients, surround large cities.

“These delays weren’t explained by the patients’ distance from cancer treatment facilities, their specific stage of cancer or type of treatment, or what insurance they had,” lead author Katherine Reeder-Hayes, MD, with the University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, said in a news release.

Instead, Dr. Reeder-Hayes said, the findings suggest that the structure of local health care systems, rather than patient characteristics, may better explain why some patients experience treatment delays.

In other words, “if cancer care teams in certain areas say, ‘Oh, it’s particularly hard to treat breast cancer in our area because people are poor or have really advanced stages of cancer when they come in,’ our research does not bear out that explanation,” Dr. Reeder-Hayes said in email to this news organization.

This study “highlights the persistent disparities in treatment delays Black women encounter, which often lead to worse outcomes,” said Kathie-Ann Joseph, MD, MPH, who was not involved in the research.

“Interestingly, the authors could not attribute these delays in treatment to patient-level factors,” said Dr. Joseph, a breast cancer surgeon at NYU Langone Perlmutter Cancer Center, New York. But the authors “did find substantial geographic variation, which suggests the need to address structural barriers contributing to treatment delays in Black women.”

Sara P. Cate, MD, who was not involved with the research, also noted that the study highlights a known issue – “that racial minorities have longer delays in cancer treatment.” And notably, she said, the findings reveal that this disparity persists in areas where access to care is better and more robust.

“The nuances of the delays to care are multifactorial,” said Dr. Cate, a breast cancer surgeon and director of the Breast Surgery Quality Program at Mount Sinai in New York. “We need to do better with this population, and it is a multilevel solution of financial assistance, social work, and patient navigation.”

The study was supported in part by grants from the Susan G. Komen Foundation and the NC State Employees’ Credit Union. Dr. Reeder-Hayes, Dr. Cate, and Dr. Joseph have disclosed no relevant financial relationships.

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

Both race and place of residence affect how soon a woman in North Carolina receives treatment for breast cancer, suggesting the need to target high-risk geographic regions and patient groups to ensure timely care, new research suggests.

Among nearly 33,000 women from North Carolina with stage I-III breast cancer, Black patients were nearly twice as likely has non-Black patients to experience treatment delays of more than 60 days, researchers found.

“Our findings suggest that treatment delays are alarmingly common in patients at high risk for breast cancer death, including young Black women and patients with stage III disease,” the authors note in their article, which was published online in Cancer.

Research shows that breast cancer treatment delays of 30-60 days can lower survival, and Black patients face a “disproportionate risk of treatment delays across the breast cancer care delivery spectrum,” the authors explain.

However, studies exploring whether or how racial disparities in treatment delays relate to geography are more limited.

In the current analysis, researchers amassed a retrospective cohort of all patients with stage I-III breast cancer between 2004 and 2015 in the North Carolina Central Cancer Registry and explored the risk of treatment delay by race and geographic subregion.

The cohort included 32,626 women, 6,190 (19.0%) of whom were Black. Counties were divided into the nine Area Health Education Center regions for North Carolina.

Compared with non‐Black patients, Black patients were more likely to have stage III disease (15.2% vs. 9.3%), hormone receptor–negative tumors (29.3% vs. 15.6%), Medicaid insurance (46.7% vs. 14.9%), and to live within 5 miles of their treatment site (30.6% vs. 25.2%).

Overall, Black patients were almost two times more likely to experience a treatment delay of more than 60 days (15% vs. 8%).

On average, about one in seven Black women experienced a lengthy delay, but the risk varied depending on geographic location. Patients living in certain regions of the state were more likely to experience delays; those in the highest-risk region were about twice as likely to experience a delay as those in the lowest-risk region (relative risk, 2.1 among Black patients; and RR, 1.9 among non-Black patients).

The magnitude of the racial gap in treatment delay varied by region – from 0% to 9.4%. But overall, of patients who experienced treatment delays, a significantly greater proportion were Black patients in every region except region 2, where only 2.7% (93 of 3,362) of patients were Black.

Notably, two regions with the greatest disparities in treatment delay, as well as the highest absolute risk of treatment delay for Black patients, surround large cities.

“These delays weren’t explained by the patients’ distance from cancer treatment facilities, their specific stage of cancer or type of treatment, or what insurance they had,” lead author Katherine Reeder-Hayes, MD, with the University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, said in a news release.

Instead, Dr. Reeder-Hayes said, the findings suggest that the structure of local health care systems, rather than patient characteristics, may better explain why some patients experience treatment delays.

In other words, “if cancer care teams in certain areas say, ‘Oh, it’s particularly hard to treat breast cancer in our area because people are poor or have really advanced stages of cancer when they come in,’ our research does not bear out that explanation,” Dr. Reeder-Hayes said in email to this news organization.

This study “highlights the persistent disparities in treatment delays Black women encounter, which often lead to worse outcomes,” said Kathie-Ann Joseph, MD, MPH, who was not involved in the research.

“Interestingly, the authors could not attribute these delays in treatment to patient-level factors,” said Dr. Joseph, a breast cancer surgeon at NYU Langone Perlmutter Cancer Center, New York. But the authors “did find substantial geographic variation, which suggests the need to address structural barriers contributing to treatment delays in Black women.”

Sara P. Cate, MD, who was not involved with the research, also noted that the study highlights a known issue – “that racial minorities have longer delays in cancer treatment.” And notably, she said, the findings reveal that this disparity persists in areas where access to care is better and more robust.

“The nuances of the delays to care are multifactorial,” said Dr. Cate, a breast cancer surgeon and director of the Breast Surgery Quality Program at Mount Sinai in New York. “We need to do better with this population, and it is a multilevel solution of financial assistance, social work, and patient navigation.”

The study was supported in part by grants from the Susan G. Komen Foundation and the NC State Employees’ Credit Union. Dr. Reeder-Hayes, Dr. Cate, and Dr. Joseph have disclosed no relevant financial relationships.

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

While it’s well known that COVID-19 vaccines are less effective in patients with chronic lymphocytic leukemia (CLL) who take immunity-lowering drugs, a new study offers fresh insight into what’s happening inside the body. In these patients, the vaccines often don’t boost B cells, which produce antibodies, but they do strengthen T cells, potentially providing crucial protection against severe illness and death.

These findings don’t reveal whether the T-cell boost actually provides extra protection against COVID-19. Still, the study suggests that patients with CLL should be vaccinated no matter which medications they’re taking, coauthor and hematologist/oncologist Clemens-Martin Wendtner, MD, of the Munich (Germany) Clinic, said in an interview.

“Do not defer or pause treatment,” said Dr. Wendtner, whose study was published in Blood Advances.

Patients with CLL appear to have among the weakest responses to the COVID-19 vaccine among people with various types of blood cancer. A meta-analysis published in 2022 found that seropositivity rates following vaccination were just 51% in patients with CLL, compared with 80%-90% in those with acute leukemia and 76%-80% of those with myeloma.

“Usually, the response rate to vaccination among the nonimmunocompromised would be 95%,” Dr. Wendtner said.

Research has also suggested that patients treated with B-cell pathway inhibitors and anti-CD20 antibodies are especially likely to have poorer responses to COVID-19 vaccines, no surprise considering that their job is to dampen the immune system. But there’s an unanswered question, according to Dr. Wendtner: Does “just measuring B-cell response tell us everything about the immune response?”

The new prospective, single-institution study aims to answer that question in patients who each received two types of vaccines. Researchers compared peripheral blood mononuclear cell transcriptional response with antibody and T-cell response rates in 15 patients with CLL/small lymphocytic lymphoma following vaccination with both the Pfizer-BioNTech and AstraZeneca vaccines.

The average antibody response was limited. “Overall, 7/15 of patients failed to mount a humoral response even after three-dose vaccination,” the researchers reported. All of the patients were “heavily pretreated” with CLL medications such as venetoclax, an anti-CD20 monoclonal antibody.

By contrast, the T-cell response was much stronger: 80% of patients (12/15) had a robust response, a number that grew to 90% (14/15) after a booster. This response is “almost ideal” considering that the response in a nonimmunocompromised person would be about 99%, Dr. Wendtner said.

The study also revealed that vaccine responses were weaker in patients who took a combination of a Bruton tyrosine kinase inhibitor and venetoclax within a year.

Four patients developed COVID-19 infections with the Omicron variant about 6 months after vaccination. All had mild symptoms. A lone patient had a history of COVID-19 infection prior to vaccination.

The researchers noted that the study had several limitations, including its small size, its reliance on a single institution, and the differences in treatments and vaccination protocols among the patient population.

Broadly speaking, the study showed that “a vaccine is not in vain” in patients with CLL, “although the doctor might not detect an antibody response,” Dr. Wendtner said. He added that mixing vaccine types should provide more protection. Start with a viral vector vaccine followed by an mRNA vaccine or vice versa, he suggested.

In an interview, infectious disease physician Joshua A. Hill, MD, from Fred Hutchinson Cancer Center, Seattle, who wasn’t involved with the study, said it makes “important and interesting observations to reinforce other studies with similar findings.”

Specifically, Dr. Hill said, “despite the absence of a robust antibody response some of these patients who are on active treatment, patients can still generate robust cellular immune responses in the form of T-cell immunity. Our understanding is that having T cell immunity will provide important additional protection for developing severe disease, although is less easily tested.”

As for the best vaccination strategies, Dr. Hill said “patients should get vaccinated as soon as they are eligible, according to standard guidelines. If patients have not yet started therapy, they should get their indicated vaccines before starting treatment whenever possible.”

The German study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Bavarian State Ministry of Science and Art. Dr. Wendtner disclosed consultant fees from AstraZeneca and BioNTech, and another author disclosed consultant fees from AstraZeneca. The other authors reported no disclosures. Dr. Hill disclosed consultant fees from Moderna, Pfizer, and Gilead.

While it’s well known that COVID-19 vaccines are less effective in patients with chronic lymphocytic leukemia (CLL) who take immunity-lowering drugs, a new study offers fresh insight into what’s happening inside the body. In these patients, the vaccines often don’t boost B cells, which produce antibodies, but they do strengthen T cells, potentially providing crucial protection against severe illness and death.

These findings don’t reveal whether the T-cell boost actually provides extra protection against COVID-19. Still, the study suggests that patients with CLL should be vaccinated no matter which medications they’re taking, coauthor and hematologist/oncologist Clemens-Martin Wendtner, MD, of the Munich (Germany) Clinic, said in an interview.

“Do not defer or pause treatment,” said Dr. Wendtner, whose study was published in Blood Advances.

Patients with CLL appear to have among the weakest responses to the COVID-19 vaccine among people with various types of blood cancer. A meta-analysis published in 2022 found that seropositivity rates following vaccination were just 51% in patients with CLL, compared with 80%-90% in those with acute leukemia and 76%-80% of those with myeloma.

“Usually, the response rate to vaccination among the nonimmunocompromised would be 95%,” Dr. Wendtner said.

Research has also suggested that patients treated with B-cell pathway inhibitors and anti-CD20 antibodies are especially likely to have poorer responses to COVID-19 vaccines, no surprise considering that their job is to dampen the immune system. But there’s an unanswered question, according to Dr. Wendtner: Does “just measuring B-cell response tell us everything about the immune response?”

The new prospective, single-institution study aims to answer that question in patients who each received two types of vaccines. Researchers compared peripheral blood mononuclear cell transcriptional response with antibody and T-cell response rates in 15 patients with CLL/small lymphocytic lymphoma following vaccination with both the Pfizer-BioNTech and AstraZeneca vaccines.

The average antibody response was limited. “Overall, 7/15 of patients failed to mount a humoral response even after three-dose vaccination,” the researchers reported. All of the patients were “heavily pretreated” with CLL medications such as venetoclax, an anti-CD20 monoclonal antibody.

By contrast, the T-cell response was much stronger: 80% of patients (12/15) had a robust response, a number that grew to 90% (14/15) after a booster. This response is “almost ideal” considering that the response in a nonimmunocompromised person would be about 99%, Dr. Wendtner said.

The study also revealed that vaccine responses were weaker in patients who took a combination of a Bruton tyrosine kinase inhibitor and venetoclax within a year.

Four patients developed COVID-19 infections with the Omicron variant about 6 months after vaccination. All had mild symptoms. A lone patient had a history of COVID-19 infection prior to vaccination.

The researchers noted that the study had several limitations, including its small size, its reliance on a single institution, and the differences in treatments and vaccination protocols among the patient population.

Broadly speaking, the study showed that “a vaccine is not in vain” in patients with CLL, “although the doctor might not detect an antibody response,” Dr. Wendtner said. He added that mixing vaccine types should provide more protection. Start with a viral vector vaccine followed by an mRNA vaccine or vice versa, he suggested.

In an interview, infectious disease physician Joshua A. Hill, MD, from Fred Hutchinson Cancer Center, Seattle, who wasn’t involved with the study, said it makes “important and interesting observations to reinforce other studies with similar findings.”

Specifically, Dr. Hill said, “despite the absence of a robust antibody response some of these patients who are on active treatment, patients can still generate robust cellular immune responses in the form of T-cell immunity. Our understanding is that having T cell immunity will provide important additional protection for developing severe disease, although is less easily tested.”

As for the best vaccination strategies, Dr. Hill said “patients should get vaccinated as soon as they are eligible, according to standard guidelines. If patients have not yet started therapy, they should get their indicated vaccines before starting treatment whenever possible.”

The German study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Bavarian State Ministry of Science and Art. Dr. Wendtner disclosed consultant fees from AstraZeneca and BioNTech, and another author disclosed consultant fees from AstraZeneca. The other authors reported no disclosures. Dr. Hill disclosed consultant fees from Moderna, Pfizer, and Gilead.

While it’s well known that COVID-19 vaccines are less effective in patients with chronic lymphocytic leukemia (CLL) who take immunity-lowering drugs, a new study offers fresh insight into what’s happening inside the body. In these patients, the vaccines often don’t boost B cells, which produce antibodies, but they do strengthen T cells, potentially providing crucial protection against severe illness and death.

These findings don’t reveal whether the T-cell boost actually provides extra protection against COVID-19. Still, the study suggests that patients with CLL should be vaccinated no matter which medications they’re taking, coauthor and hematologist/oncologist Clemens-Martin Wendtner, MD, of the Munich (Germany) Clinic, said in an interview.

“Do not defer or pause treatment,” said Dr. Wendtner, whose study was published in Blood Advances.

Patients with CLL appear to have among the weakest responses to the COVID-19 vaccine among people with various types of blood cancer. A meta-analysis published in 2022 found that seropositivity rates following vaccination were just 51% in patients with CLL, compared with 80%-90% in those with acute leukemia and 76%-80% of those with myeloma.

“Usually, the response rate to vaccination among the nonimmunocompromised would be 95%,” Dr. Wendtner said.

Research has also suggested that patients treated with B-cell pathway inhibitors and anti-CD20 antibodies are especially likely to have poorer responses to COVID-19 vaccines, no surprise considering that their job is to dampen the immune system. But there’s an unanswered question, according to Dr. Wendtner: Does “just measuring B-cell response tell us everything about the immune response?”

The new prospective, single-institution study aims to answer that question in patients who each received two types of vaccines. Researchers compared peripheral blood mononuclear cell transcriptional response with antibody and T-cell response rates in 15 patients with CLL/small lymphocytic lymphoma following vaccination with both the Pfizer-BioNTech and AstraZeneca vaccines.

The average antibody response was limited. “Overall, 7/15 of patients failed to mount a humoral response even after three-dose vaccination,” the researchers reported. All of the patients were “heavily pretreated” with CLL medications such as venetoclax, an anti-CD20 monoclonal antibody.

By contrast, the T-cell response was much stronger: 80% of patients (12/15) had a robust response, a number that grew to 90% (14/15) after a booster. This response is “almost ideal” considering that the response in a nonimmunocompromised person would be about 99%, Dr. Wendtner said.

The study also revealed that vaccine responses were weaker in patients who took a combination of a Bruton tyrosine kinase inhibitor and venetoclax within a year.

Four patients developed COVID-19 infections with the Omicron variant about 6 months after vaccination. All had mild symptoms. A lone patient had a history of COVID-19 infection prior to vaccination.

The researchers noted that the study had several limitations, including its small size, its reliance on a single institution, and the differences in treatments and vaccination protocols among the patient population.

Broadly speaking, the study showed that “a vaccine is not in vain” in patients with CLL, “although the doctor might not detect an antibody response,” Dr. Wendtner said. He added that mixing vaccine types should provide more protection. Start with a viral vector vaccine followed by an mRNA vaccine or vice versa, he suggested.

In an interview, infectious disease physician Joshua A. Hill, MD, from Fred Hutchinson Cancer Center, Seattle, who wasn’t involved with the study, said it makes “important and interesting observations to reinforce other studies with similar findings.”

Specifically, Dr. Hill said, “despite the absence of a robust antibody response some of these patients who are on active treatment, patients can still generate robust cellular immune responses in the form of T-cell immunity. Our understanding is that having T cell immunity will provide important additional protection for developing severe disease, although is less easily tested.”

As for the best vaccination strategies, Dr. Hill said “patients should get vaccinated as soon as they are eligible, according to standard guidelines. If patients have not yet started therapy, they should get their indicated vaccines before starting treatment whenever possible.”

The German study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Bavarian State Ministry of Science and Art. Dr. Wendtner disclosed consultant fees from AstraZeneca and BioNTech, and another author disclosed consultant fees from AstraZeneca. The other authors reported no disclosures. Dr. Hill disclosed consultant fees from Moderna, Pfizer, and Gilead.

Montrouge, France – Four in five women will be infected by one or more human papillomavirus (HPV) strains during their lifetimes. For most of these women, the HPV will be cleared from the body, but 5% of them will develop precancerous lesions in the cervix. The role of vaginal flora in persistent HPV has been brought into focus by research studies carried out over the past few years.

At a press conference ahead of the 46th meeting of the French Colposcopy and Cervical and Vaginal Diseases Society, Julia Maruani, MD, a medical gynecologist in Marseille, France, took the opportunity to discuss the importance of vaginal flora and the need to treat cases of bacterial vaginosis.
 

Striking a balance

Essential for reducing the risk of sexually transmitted infections, a healthy vaginal flora is made up of millions of microorganisms, mainly lactobacilli, as well as other bacteria (Gardnerella vaginalis, Atopobium vaginae, Prevotella, streptococcus, gonococcus), HPV, and fungi.

Lactobacilli produce lactic acid, which reduces the vagina’s pH, as well as hydrogen peroxide, which is toxic to the other bacteria.

Different factors, such as alcohol, a diet rich in polyunsaturated fatty acids and sugar, and especially smoking, can lead to an imbalance of the bacteria in the vaginal flora and thus result in vaginosis. What occurs is an abnormal multiplication of different types of anaerobic bacteria that are normally present in much lower numbers. There is a relative reduction in lactobacilli, which results in an increased vaginal pH, a greater risk of contracting an STI, and reduced clearance of the HPV infection. “Women who smoke probably experience persistent HPV infections due to an imbalance in vaginal flora,” said Dr. Maruani.
 

Vaginosis and HPV

When there are fewer lactobacilli than there should be, these bacteria can no longer protect the vaginal mucosa, which is disrupted by other bacteria. “HPV then has access to the basal cells,” said Dr. Maruani, acknowledging that the relationship between bacterial vaginosis and persistent HPV infections has been the subject of numerous research studies over the past decade or so. “For years, I would see this same link in my patients. Those with persistent vaginosis were also the ones with persistent HPV. And I’m not the only one to notice this. Studies have also been carried out investigating this exact correlation,” she added.

These studies have shown that HPV infections persist in cases of vaginosis, resulting in the appearance of epithelial lesions. Additionally, the lesions are more severe when dysbiosis is more severe.

What about probiotics? Can they treat dysbiosis and an HPV infection at the same time? “Probiotics work very well for vaginosis, provided they are used for a long time. We know that they lessen HPV infections and low-grade lesions,” said Dr. Maruani, although no randomized studies support this conclusion. “It’s not a one size fits all. We aren’t about to treat patients with precancerous lesions with probiotics.” There are currently no data concerning the efficacy of probiotics on high-grade lesions. These days, Dr. Maruani has been thinking about a new issue: the benefit of diagnosing cases of asymptomatic vaginosis – because treating them would reduce the risk of persistent HPV infection.

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Montrouge, France – Four in five women will be infected by one or more human papillomavirus (HPV) strains during their lifetimes. For most of these women, the HPV will be cleared from the body, but 5% of them will develop precancerous lesions in the cervix. The role of vaginal flora in persistent HPV has been brought into focus by research studies carried out over the past few years.

At a press conference ahead of the 46th meeting of the French Colposcopy and Cervical and Vaginal Diseases Society, Julia Maruani, MD, a medical gynecologist in Marseille, France, took the opportunity to discuss the importance of vaginal flora and the need to treat cases of bacterial vaginosis.
 

Striking a balance

Essential for reducing the risk of sexually transmitted infections, a healthy vaginal flora is made up of millions of microorganisms, mainly lactobacilli, as well as other bacteria (Gardnerella vaginalis, Atopobium vaginae, Prevotella, streptococcus, gonococcus), HPV, and fungi.

Lactobacilli produce lactic acid, which reduces the vagina’s pH, as well as hydrogen peroxide, which is toxic to the other bacteria.

Different factors, such as alcohol, a diet rich in polyunsaturated fatty acids and sugar, and especially smoking, can lead to an imbalance of the bacteria in the vaginal flora and thus result in vaginosis. What occurs is an abnormal multiplication of different types of anaerobic bacteria that are normally present in much lower numbers. There is a relative reduction in lactobacilli, which results in an increased vaginal pH, a greater risk of contracting an STI, and reduced clearance of the HPV infection. “Women who smoke probably experience persistent HPV infections due to an imbalance in vaginal flora,” said Dr. Maruani.
 

Vaginosis and HPV

When there are fewer lactobacilli than there should be, these bacteria can no longer protect the vaginal mucosa, which is disrupted by other bacteria. “HPV then has access to the basal cells,” said Dr. Maruani, acknowledging that the relationship between bacterial vaginosis and persistent HPV infections has been the subject of numerous research studies over the past decade or so. “For years, I would see this same link in my patients. Those with persistent vaginosis were also the ones with persistent HPV. And I’m not the only one to notice this. Studies have also been carried out investigating this exact correlation,” she added.

These studies have shown that HPV infections persist in cases of vaginosis, resulting in the appearance of epithelial lesions. Additionally, the lesions are more severe when dysbiosis is more severe.

What about probiotics? Can they treat dysbiosis and an HPV infection at the same time? “Probiotics work very well for vaginosis, provided they are used for a long time. We know that they lessen HPV infections and low-grade lesions,” said Dr. Maruani, although no randomized studies support this conclusion. “It’s not a one size fits all. We aren’t about to treat patients with precancerous lesions with probiotics.” There are currently no data concerning the efficacy of probiotics on high-grade lesions. These days, Dr. Maruani has been thinking about a new issue: the benefit of diagnosing cases of asymptomatic vaginosis – because treating them would reduce the risk of persistent HPV infection.

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Montrouge, France – Four in five women will be infected by one or more human papillomavirus (HPV) strains during their lifetimes. For most of these women, the HPV will be cleared from the body, but 5% of them will develop precancerous lesions in the cervix. The role of vaginal flora in persistent HPV has been brought into focus by research studies carried out over the past few years.

At a press conference ahead of the 46th meeting of the French Colposcopy and Cervical and Vaginal Diseases Society, Julia Maruani, MD, a medical gynecologist in Marseille, France, took the opportunity to discuss the importance of vaginal flora and the need to treat cases of bacterial vaginosis.
 

Striking a balance

Essential for reducing the risk of sexually transmitted infections, a healthy vaginal flora is made up of millions of microorganisms, mainly lactobacilli, as well as other bacteria (Gardnerella vaginalis, Atopobium vaginae, Prevotella, streptococcus, gonococcus), HPV, and fungi.

Lactobacilli produce lactic acid, which reduces the vagina’s pH, as well as hydrogen peroxide, which is toxic to the other bacteria.

Different factors, such as alcohol, a diet rich in polyunsaturated fatty acids and sugar, and especially smoking, can lead to an imbalance of the bacteria in the vaginal flora and thus result in vaginosis. What occurs is an abnormal multiplication of different types of anaerobic bacteria that are normally present in much lower numbers. There is a relative reduction in lactobacilli, which results in an increased vaginal pH, a greater risk of contracting an STI, and reduced clearance of the HPV infection. “Women who smoke probably experience persistent HPV infections due to an imbalance in vaginal flora,” said Dr. Maruani.
 

Vaginosis and HPV

When there are fewer lactobacilli than there should be, these bacteria can no longer protect the vaginal mucosa, which is disrupted by other bacteria. “HPV then has access to the basal cells,” said Dr. Maruani, acknowledging that the relationship between bacterial vaginosis and persistent HPV infections has been the subject of numerous research studies over the past decade or so. “For years, I would see this same link in my patients. Those with persistent vaginosis were also the ones with persistent HPV. And I’m not the only one to notice this. Studies have also been carried out investigating this exact correlation,” she added.

These studies have shown that HPV infections persist in cases of vaginosis, resulting in the appearance of epithelial lesions. Additionally, the lesions are more severe when dysbiosis is more severe.

What about probiotics? Can they treat dysbiosis and an HPV infection at the same time? “Probiotics work very well for vaginosis, provided they are used for a long time. We know that they lessen HPV infections and low-grade lesions,” said Dr. Maruani, although no randomized studies support this conclusion. “It’s not a one size fits all. We aren’t about to treat patients with precancerous lesions with probiotics.” There are currently no data concerning the efficacy of probiotics on high-grade lesions. These days, Dr. Maruani has been thinking about a new issue: the benefit of diagnosing cases of asymptomatic vaginosis – because treating them would reduce the risk of persistent HPV infection.

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Last week, a number of patients emailed me regarding their concerns about this phenomenon known as Ozempic face. I went on to read about what this meant. I live in Los Angeles, where most people appear to be on semaglutide (Ozempic). It’s the phenomenon where people lose weight relatively rapidly, making their faces thin out. Then what happens, apparently, is they look older because their face is more wrinkled and baggier. They might have to have further plastic surgery. I say that with slight sarcasm because of where I live.

I want to talk about what I think about this, living here where there’s a great pressure to prescribe semaglutide off label, and what I think about it for my patients with diabetes.

Historically, we haven’t had much in terms of effective medication for treating obesity, and frankly, now we do. We now have agents that are effective, that have relatively few side effects, and that have become part of what’s out there. People now want to use these agents, semaglutide, and there’s been a great need for these agents.

The problem, however, is twofold. One, as we all know, is that it has basically caused a shortage of medication for treating our patients who actually have type 2 diabetes and really need these medications to manage their disease. Then we have people who want these medications who can’t pay for them. Insurance doesn’t cover obesity medications, which is problematic and actually quite frustrating for people who, I think, really would benefit from using these medications.

What I tell people, frankly, is that until I have enough supply for my patients with type 2 diabetes, who need these agents to control their blood sugars, I want to keep this class of drugs available to them. I also hope we’re able to expand it more and more with improving insurance coverage – and that’s a big if, if you ask me – both for people who have prediabetes and for patients who are overweight and obese, because I think it’s really hard for people to lose weight.

It’s frustrating, and for many people, being overweight and obese causes all sorts of other health issues, not only diabetes. I believe that these drugs are both safe and effective and should be more available. I do think we need to be careful in terms of who we prescribe them to, at least at the moment. Hopefully, we’ll be able to expand their use.

Anything that can encourage our population to lose weight and maintain that weight loss is very important. We need to couple weight loss medications with lifestyle interventions. I think people can out-eat any medication; therefore, it’s very important to encourage our patients to eat better, to exercise more, and to do all the other things they need to do to reduce their risks for other comorbidities.

I am incredibly happy to have these newer agents on the market. I tell my patients – at least those who have diabetes – that they have to accept looking a little bit too thin for the benefits that we can see in using these medications.

Thank you.

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations. She has ties with Abbott Diabetes Care, AstraZeneca Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen. A version of this article originally appeared on Medscape.com.

This transcript has been edited for clarity.

Last week, a number of patients emailed me regarding their concerns about this phenomenon known as Ozempic face. I went on to read about what this meant. I live in Los Angeles, where most people appear to be on semaglutide (Ozempic). It’s the phenomenon where people lose weight relatively rapidly, making their faces thin out. Then what happens, apparently, is they look older because their face is more wrinkled and baggier. They might have to have further plastic surgery. I say that with slight sarcasm because of where I live.

I want to talk about what I think about this, living here where there’s a great pressure to prescribe semaglutide off label, and what I think about it for my patients with diabetes.

Historically, we haven’t had much in terms of effective medication for treating obesity, and frankly, now we do. We now have agents that are effective, that have relatively few side effects, and that have become part of what’s out there. People now want to use these agents, semaglutide, and there’s been a great need for these agents.

The problem, however, is twofold. One, as we all know, is that it has basically caused a shortage of medication for treating our patients who actually have type 2 diabetes and really need these medications to manage their disease. Then we have people who want these medications who can’t pay for them. Insurance doesn’t cover obesity medications, which is problematic and actually quite frustrating for people who, I think, really would benefit from using these medications.

What I tell people, frankly, is that until I have enough supply for my patients with type 2 diabetes, who need these agents to control their blood sugars, I want to keep this class of drugs available to them. I also hope we’re able to expand it more and more with improving insurance coverage – and that’s a big if, if you ask me – both for people who have prediabetes and for patients who are overweight and obese, because I think it’s really hard for people to lose weight.

It’s frustrating, and for many people, being overweight and obese causes all sorts of other health issues, not only diabetes. I believe that these drugs are both safe and effective and should be more available. I do think we need to be careful in terms of who we prescribe them to, at least at the moment. Hopefully, we’ll be able to expand their use.

Anything that can encourage our population to lose weight and maintain that weight loss is very important. We need to couple weight loss medications with lifestyle interventions. I think people can out-eat any medication; therefore, it’s very important to encourage our patients to eat better, to exercise more, and to do all the other things they need to do to reduce their risks for other comorbidities.

I am incredibly happy to have these newer agents on the market. I tell my patients – at least those who have diabetes – that they have to accept looking a little bit too thin for the benefits that we can see in using these medications.

Thank you.

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations. She has ties with Abbott Diabetes Care, AstraZeneca Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen. A version of this article originally appeared on Medscape.com.

This transcript has been edited for clarity.

Last week, a number of patients emailed me regarding their concerns about this phenomenon known as Ozempic face. I went on to read about what this meant. I live in Los Angeles, where most people appear to be on semaglutide (Ozempic). It’s the phenomenon where people lose weight relatively rapidly, making their faces thin out. Then what happens, apparently, is they look older because their face is more wrinkled and baggier. They might have to have further plastic surgery. I say that with slight sarcasm because of where I live.

I want to talk about what I think about this, living here where there’s a great pressure to prescribe semaglutide off label, and what I think about it for my patients with diabetes.

Historically, we haven’t had much in terms of effective medication for treating obesity, and frankly, now we do. We now have agents that are effective, that have relatively few side effects, and that have become part of what’s out there. People now want to use these agents, semaglutide, and there’s been a great need for these agents.

The problem, however, is twofold. One, as we all know, is that it has basically caused a shortage of medication for treating our patients who actually have type 2 diabetes and really need these medications to manage their disease. Then we have people who want these medications who can’t pay for them. Insurance doesn’t cover obesity medications, which is problematic and actually quite frustrating for people who, I think, really would benefit from using these medications.

What I tell people, frankly, is that until I have enough supply for my patients with type 2 diabetes, who need these agents to control their blood sugars, I want to keep this class of drugs available to them. I also hope we’re able to expand it more and more with improving insurance coverage – and that’s a big if, if you ask me – both for people who have prediabetes and for patients who are overweight and obese, because I think it’s really hard for people to lose weight.

It’s frustrating, and for many people, being overweight and obese causes all sorts of other health issues, not only diabetes. I believe that these drugs are both safe and effective and should be more available. I do think we need to be careful in terms of who we prescribe them to, at least at the moment. Hopefully, we’ll be able to expand their use.

Anything that can encourage our population to lose weight and maintain that weight loss is very important. We need to couple weight loss medications with lifestyle interventions. I think people can out-eat any medication; therefore, it’s very important to encourage our patients to eat better, to exercise more, and to do all the other things they need to do to reduce their risks for other comorbidities.

I am incredibly happy to have these newer agents on the market. I tell my patients – at least those who have diabetes – that they have to accept looking a little bit too thin for the benefits that we can see in using these medications.

Thank you.

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations. She has ties with Abbott Diabetes Care, AstraZeneca Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen. A version of this article originally appeared on Medscape.com.

The longer people had diabetes, the greater their rate of incident heart failure, suggests a recently published review of prospectively collected observational data from nearly 24,000 people with diabetes in the UK Biobank.

The findings “add to the growing body of evidence suggesting that duration of diabetes is an important and independent determinant of heart failure among patients with diabetes,” comments Justin B. Echouffo-Tcheugui, MD, PhD, in an accompanying editorial.

Collectively, the new UK Biobank results and prior findings, “provide additional persuasive evidence that the link between duration of diabetes and heart failure is real,” although the physiological mechanisms behind the relationship remain incompletely understood, wrote Dr. Echouffo-Tcheugui, an endocrinologist at Johns Hopkins Medicine, Baltimore.

“The duration of diabetes may reflect cumulative effects of various adverse processes in the setting of diabetes” that result in “intrinsic myocardial lesions,” he suggested. These adverse processes might include not only hyperglycemia, but also glucotoxicity, lipotoxicity, hyperinsulinemia, advanced glycosylation end products, oxidative stress, mitochondrial dysfunction, cardiac autonomic neuropathy, and coronary microvascular dysfunction. Long-duration diabetes may also contribute to declining kidney function, which can further worsen heart failure risk.

The upshot is that clinicians may need to consider more systematically the duration of diabetes when assessing people with diabetes for heart failure.

Existing risk-assessment tools for predicting heart failure in people with diabetes “have not always accounted for diabetes duration,” Dr. Echouffo-Tcheugui noted.
 

Intensify heart failure detection with longer diabetes duration

“Active heart failure detection should perhaps be intensified with increased diabetes duration,” Dr. Echouffo-Tcheugui suggested in his editorial. He noted that a 2022 consensus report by the American Diabetes Association recommends clinicians measure natriuretic peptide or high-sensitivity cardiac troponin in all people with diabetes “on at least a yearly basis to identify the earliest heart failure stages and implement strategies to prevent transition to symptomatic heart failure.”

The UK Biobank study was run by investigators primarily based in China and included data from 23,754 people with type 1 or type 2 diabetes and no heart failure at baseline. The prospectively collected data allowed for a median follow-up of 11.7 years, during which time 2,081 people developed incident heart failure.

In an analysis that divided participants into four categories of diabetes duration (< 5 years, 5-9 years, 10-14 years, and ≥ 15 years) and adjusted for potential confounders, heart failure incidence showed a significant 32% increased incidence among those with diabetes for at least 15 years, compared with those with diabetes for less than 5 years. People with a diabetes duration of 5-14 years showed a trend toward having more incident heart failure, compared with those with diabetes for less than 5 years, but the difference was not significant. 

An adjusted analysis also showed poor glycemic control at baseline (hemoglobin A1c ≥ 8.0%) significantly linked with a 46% increased incidence of heart failure, compared with those with baseline A1c less than 7.0%.
 

Additive effect?

When the authors analyzed the effect of both these variables, they saw a roughly additive effect.

Patients with diabetes for at least 15 years and a baseline A1c of at least 8.0% had a 98% increased incidence of heart failure, compared with those who had diabetes for less than 5 years and a baseline A1c less than 7.0%, after adjustment. This association was independent of age, sex, and race.

These findings “highlight the paramount role of the duration of diabetes and its interaction with glycemic control in the development of heart failure,” the authors concluded. “Long duration of diabetes and poor glycemic control may result in structural and functional changes in the myocardium, which is likely to underlie the pathogenesis of heart failure among individuals with diabetes.”

In his editorial, Dr. Echouffo-Tcheugui lauded the report for its “robust” analyses that included a large sample and accounted for key confounders, such as glycemic control. However, he also cited eight “shortcomings” of the study, including its sole reliance on A1c levels to identify diabetes, a likely underestimation of diabetes duration, the lumping together of people with type 1 and type 2 diabetes, and lack of a subanalysis of incident heart failure in those with preserved or reduced left ventricular ejection fraction.

Among prior reports of evidence also suggesting an effect of diabetes duration on incident heart failure, Dr. Echouffo-Tcheugui cited a study he led, published in 2021, that analyzed prospective, longitudinal, observational data from 9,734 adults enrolled in the Atherosclerosis Risk in Communities study. The results showed that, compared with those without diabetes, the incidence of heart failure rose with longer diabetes duration, with the highest risk among those with diabetes for at least 15 years, who had a 2.8-fold increase in heart failure versus the reference group. Each 5-year increase in diabetes duration was associated with a significant 17% relative increase in heart failure incidence.

The study received no commercial funding. The authors and editorialist reported no relevant financial relationships.

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

The longer people had diabetes, the greater their rate of incident heart failure, suggests a recently published review of prospectively collected observational data from nearly 24,000 people with diabetes in the UK Biobank.

The findings “add to the growing body of evidence suggesting that duration of diabetes is an important and independent determinant of heart failure among patients with diabetes,” comments Justin B. Echouffo-Tcheugui, MD, PhD, in an accompanying editorial.

Collectively, the new UK Biobank results and prior findings, “provide additional persuasive evidence that the link between duration of diabetes and heart failure is real,” although the physiological mechanisms behind the relationship remain incompletely understood, wrote Dr. Echouffo-Tcheugui, an endocrinologist at Johns Hopkins Medicine, Baltimore.

“The duration of diabetes may reflect cumulative effects of various adverse processes in the setting of diabetes” that result in “intrinsic myocardial lesions,” he suggested. These adverse processes might include not only hyperglycemia, but also glucotoxicity, lipotoxicity, hyperinsulinemia, advanced glycosylation end products, oxidative stress, mitochondrial dysfunction, cardiac autonomic neuropathy, and coronary microvascular dysfunction. Long-duration diabetes may also contribute to declining kidney function, which can further worsen heart failure risk.

The upshot is that clinicians may need to consider more systematically the duration of diabetes when assessing people with diabetes for heart failure.

Existing risk-assessment tools for predicting heart failure in people with diabetes “have not always accounted for diabetes duration,” Dr. Echouffo-Tcheugui noted.
 

Intensify heart failure detection with longer diabetes duration

“Active heart failure detection should perhaps be intensified with increased diabetes duration,” Dr. Echouffo-Tcheugui suggested in his editorial. He noted that a 2022 consensus report by the American Diabetes Association recommends clinicians measure natriuretic peptide or high-sensitivity cardiac troponin in all people with diabetes “on at least a yearly basis to identify the earliest heart failure stages and implement strategies to prevent transition to symptomatic heart failure.”

The UK Biobank study was run by investigators primarily based in China and included data from 23,754 people with type 1 or type 2 diabetes and no heart failure at baseline. The prospectively collected data allowed for a median follow-up of 11.7 years, during which time 2,081 people developed incident heart failure.

In an analysis that divided participants into four categories of diabetes duration (< 5 years, 5-9 years, 10-14 years, and ≥ 15 years) and adjusted for potential confounders, heart failure incidence showed a significant 32% increased incidence among those with diabetes for at least 15 years, compared with those with diabetes for less than 5 years. People with a diabetes duration of 5-14 years showed a trend toward having more incident heart failure, compared with those with diabetes for less than 5 years, but the difference was not significant. 

An adjusted analysis also showed poor glycemic control at baseline (hemoglobin A1c ≥ 8.0%) significantly linked with a 46% increased incidence of heart failure, compared with those with baseline A1c less than 7.0%.
 

Additive effect?

When the authors analyzed the effect of both these variables, they saw a roughly additive effect.

Patients with diabetes for at least 15 years and a baseline A1c of at least 8.0% had a 98% increased incidence of heart failure, compared with those who had diabetes for less than 5 years and a baseline A1c less than 7.0%, after adjustment. This association was independent of age, sex, and race.

These findings “highlight the paramount role of the duration of diabetes and its interaction with glycemic control in the development of heart failure,” the authors concluded. “Long duration of diabetes and poor glycemic control may result in structural and functional changes in the myocardium, which is likely to underlie the pathogenesis of heart failure among individuals with diabetes.”

In his editorial, Dr. Echouffo-Tcheugui lauded the report for its “robust” analyses that included a large sample and accounted for key confounders, such as glycemic control. However, he also cited eight “shortcomings” of the study, including its sole reliance on A1c levels to identify diabetes, a likely underestimation of diabetes duration, the lumping together of people with type 1 and type 2 diabetes, and lack of a subanalysis of incident heart failure in those with preserved or reduced left ventricular ejection fraction.

Among prior reports of evidence also suggesting an effect of diabetes duration on incident heart failure, Dr. Echouffo-Tcheugui cited a study he led, published in 2021, that analyzed prospective, longitudinal, observational data from 9,734 adults enrolled in the Atherosclerosis Risk in Communities study. The results showed that, compared with those without diabetes, the incidence of heart failure rose with longer diabetes duration, with the highest risk among those with diabetes for at least 15 years, who had a 2.8-fold increase in heart failure versus the reference group. Each 5-year increase in diabetes duration was associated with a significant 17% relative increase in heart failure incidence.

The study received no commercial funding. The authors and editorialist reported no relevant financial relationships.

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

The longer people had diabetes, the greater their rate of incident heart failure, suggests a recently published review of prospectively collected observational data from nearly 24,000 people with diabetes in the UK Biobank.

The findings “add to the growing body of evidence suggesting that duration of diabetes is an important and independent determinant of heart failure among patients with diabetes,” comments Justin B. Echouffo-Tcheugui, MD, PhD, in an accompanying editorial.

Collectively, the new UK Biobank results and prior findings, “provide additional persuasive evidence that the link between duration of diabetes and heart failure is real,” although the physiological mechanisms behind the relationship remain incompletely understood, wrote Dr. Echouffo-Tcheugui, an endocrinologist at Johns Hopkins Medicine, Baltimore.

“The duration of diabetes may reflect cumulative effects of various adverse processes in the setting of diabetes” that result in “intrinsic myocardial lesions,” he suggested. These adverse processes might include not only hyperglycemia, but also glucotoxicity, lipotoxicity, hyperinsulinemia, advanced glycosylation end products, oxidative stress, mitochondrial dysfunction, cardiac autonomic neuropathy, and coronary microvascular dysfunction. Long-duration diabetes may also contribute to declining kidney function, which can further worsen heart failure risk.

The upshot is that clinicians may need to consider more systematically the duration of diabetes when assessing people with diabetes for heart failure.

Existing risk-assessment tools for predicting heart failure in people with diabetes “have not always accounted for diabetes duration,” Dr. Echouffo-Tcheugui noted.
 

Intensify heart failure detection with longer diabetes duration

“Active heart failure detection should perhaps be intensified with increased diabetes duration,” Dr. Echouffo-Tcheugui suggested in his editorial. He noted that a 2022 consensus report by the American Diabetes Association recommends clinicians measure natriuretic peptide or high-sensitivity cardiac troponin in all people with diabetes “on at least a yearly basis to identify the earliest heart failure stages and implement strategies to prevent transition to symptomatic heart failure.”

The UK Biobank study was run by investigators primarily based in China and included data from 23,754 people with type 1 or type 2 diabetes and no heart failure at baseline. The prospectively collected data allowed for a median follow-up of 11.7 years, during which time 2,081 people developed incident heart failure.

In an analysis that divided participants into four categories of diabetes duration (< 5 years, 5-9 years, 10-14 years, and ≥ 15 years) and adjusted for potential confounders, heart failure incidence showed a significant 32% increased incidence among those with diabetes for at least 15 years, compared with those with diabetes for less than 5 years. People with a diabetes duration of 5-14 years showed a trend toward having more incident heart failure, compared with those with diabetes for less than 5 years, but the difference was not significant. 

An adjusted analysis also showed poor glycemic control at baseline (hemoglobin A1c ≥ 8.0%) significantly linked with a 46% increased incidence of heart failure, compared with those with baseline A1c less than 7.0%.
 

Additive effect?

When the authors analyzed the effect of both these variables, they saw a roughly additive effect.

Patients with diabetes for at least 15 years and a baseline A1c of at least 8.0% had a 98% increased incidence of heart failure, compared with those who had diabetes for less than 5 years and a baseline A1c less than 7.0%, after adjustment. This association was independent of age, sex, and race.

These findings “highlight the paramount role of the duration of diabetes and its interaction with glycemic control in the development of heart failure,” the authors concluded. “Long duration of diabetes and poor glycemic control may result in structural and functional changes in the myocardium, which is likely to underlie the pathogenesis of heart failure among individuals with diabetes.”

In his editorial, Dr. Echouffo-Tcheugui lauded the report for its “robust” analyses that included a large sample and accounted for key confounders, such as glycemic control. However, he also cited eight “shortcomings” of the study, including its sole reliance on A1c levels to identify diabetes, a likely underestimation of diabetes duration, the lumping together of people with type 1 and type 2 diabetes, and lack of a subanalysis of incident heart failure in those with preserved or reduced left ventricular ejection fraction.

Among prior reports of evidence also suggesting an effect of diabetes duration on incident heart failure, Dr. Echouffo-Tcheugui cited a study he led, published in 2021, that analyzed prospective, longitudinal, observational data from 9,734 adults enrolled in the Atherosclerosis Risk in Communities study. The results showed that, compared with those without diabetes, the incidence of heart failure rose with longer diabetes duration, with the highest risk among those with diabetes for at least 15 years, who had a 2.8-fold increase in heart failure versus the reference group. Each 5-year increase in diabetes duration was associated with a significant 17% relative increase in heart failure incidence.

The study received no commercial funding. The authors and editorialist reported no relevant financial relationships.

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

Frequent visits to green spaces such as parks and community gardens are associated with a reduced use of certain prescription medications among city dwellers, a new analysis suggests.

In a cross-sectional cohort study, frequent green space visits were associated with less frequent use of psychotropic, antihypertensive, and asthma medications in urban environments.

Viewing green or so called “blue” spaces (views of lakes, rivers, or other water views) from the home was not associated with reduced medication use.

Flickr-Rickr [CC BY-SA 2.0](http://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons

Nature exposure a timely topic

Exposure to natural environments is thought to be beneficial for human health, but the evidence is inconsistent, Dr. Turunen said.

“The potential health benefits of nature exposure is a very timely topic in environmental epidemiology. Scientific evidence indicates that residential exposure to greenery and water bodies might be beneficial, especially for mental, cardiovascular, and respiratory health, but the findings are partly inconsistent and thus, more detailed information is needed,” she said.

In the current cross-sectional study, the investigators surveyed 16,000 residents of three urban areas in Finland – Helsinki, Espoo, and Vantaa – over the period of 12 months from 2015 to 2016, about their exposure to green and blue spaces.

Of this number, 43% responded, resulting in 7,321 participants.

In the questionnaire, green areas were defined as forests, parks, fields, meadows, boglands, and rocks, as well as any playgrounds or playing fields within those areas, and blue areas were defined as sea, lakes, and rivers. 

Residents were asked about their use of anxiolytics, hypnotics, antidepressants, antihypertensives, and asthma medication within the past 7 to 52 weeks.

They were also asked if they had any green and blue views from any of the windows of their home, and if so, how often did they look out of those windows, selecting “seldom” to “often.”

They were also asked about how much time they spent outdoors in green spaces during the months of May and September. If so, did they spend any of that time exercising? Options ranged from never to five or more times a week.

In addition, amounts of residential green and blue spaces located within a 1 km radius of the respondents’ homes were assessed from land use and land cover data.

Covariates included health behaviors, outdoor air pollution and noise, and socioeconomic status, including household income and educational attainment.

Results showed that the presence of green and blue spaces at home, and the amount of time spent viewing them, had no association with the use of the prescribed medicines.

However, greater frequency of green space visits was associated with lower odds of using the medications surveyed.

For psychotropic medications, the odds ratios were 0.67 (95% confidence interval, 0.55-0.82) for 3-4 times per week and 0.78 (95% CI, 0.63-0.96) for 5 or more times per week.

For antihypertensive meds, the ORs were 0.64 (95% CI, 0.52-0.78) for 3-4 times per week and 0.59 (95% CI, 0.48-0.74) for 5 or more times per week.

For asthma medications, the ORs were 0.74 (95% CI, 0.58-0.94) for 3-4 times per week and 0.76 (95% CI, 0.59-0.99) for 5 or more times per week.

The observed associations were attenuated by body mass index.

“We observed that those who reported visiting green spaces often had a slightly lower BMI than those who visited green spaces less often,” Dr. Turunen said. However, no consistent interactions with socioeconomic status indicators were observed.

“We are hoping to see new results from different countries and different settings,” she noted. “Longitudinal studies, especially, are needed. In epidemiology, a large body of consistent evidence is needed to draw strong conclusions and to make recommendations.”
 

Evidence mounts on the benefits of nature

There is growing evidence that exposure to nature could benefit human health, especially mental and cardiovascular health, says Jochem Klompmaker, PhD, a postdoctoral researcher in the department of environmental health at the Harvard T.H. Chan School of Public Health, Boston.

Dr. Klompmaker has researched the association between exposure to green spaces and health outcomes related to neurological diseases.

In a study recently published in JAMA Network Open, and reported by this news organization, Dr. Klompmaker and his team found that among a large cohort of about 6.7 million fee-for-service Medicare beneficiaries in the United States aged 65 or older, living in areas rich with greenery, parks, and waterways was associated with fewer hospitalizations for certain neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and related dementias.

Commenting on the current study, Dr. Klompmaker noted its strengths.

“A particular strength of this study is that they used data about the amount of green and blue spaces around the residential addresses of the participants, data about green space visit frequency, and data about green and blue views from home. Most other studies only have data about the amount of green and blue spaces in general,” he said.

“The strong protective associations of frequency of green space visits make sense to me and indicate the importance of one’s actual nature exposure,” he added. “Like the results of our study, these results provide clinicians with more evidence of the importance of being close to nature and of encouraging patients to take more walks. If they live near a park, that could be a good place to be more physically active and reduce stress levels.”

The study was supported by the Academy of Finland and the Ministry of the Environment. Dr. Turunen and Dr. Klompmaker report no relevant financial relationships.

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

Frequent visits to green spaces such as parks and community gardens are associated with a reduced use of certain prescription medications among city dwellers, a new analysis suggests.

In a cross-sectional cohort study, frequent green space visits were associated with less frequent use of psychotropic, antihypertensive, and asthma medications in urban environments.

Viewing green or so called “blue” spaces (views of lakes, rivers, or other water views) from the home was not associated with reduced medication use.

Flickr-Rickr [CC BY-SA 2.0](http://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons

Nature exposure a timely topic

Exposure to natural environments is thought to be beneficial for human health, but the evidence is inconsistent, Dr. Turunen said.

“The potential health benefits of nature exposure is a very timely topic in environmental epidemiology. Scientific evidence indicates that residential exposure to greenery and water bodies might be beneficial, especially for mental, cardiovascular, and respiratory health, but the findings are partly inconsistent and thus, more detailed information is needed,” she said.

In the current cross-sectional study, the investigators surveyed 16,000 residents of three urban areas in Finland – Helsinki, Espoo, and Vantaa – over the period of 12 months from 2015 to 2016, about their exposure to green and blue spaces.

Of this number, 43% responded, resulting in 7,321 participants.

In the questionnaire, green areas were defined as forests, parks, fields, meadows, boglands, and rocks, as well as any playgrounds or playing fields within those areas, and blue areas were defined as sea, lakes, and rivers. 

Residents were asked about their use of anxiolytics, hypnotics, antidepressants, antihypertensives, and asthma medication within the past 7 to 52 weeks.

They were also asked if they had any green and blue views from any of the windows of their home, and if so, how often did they look out of those windows, selecting “seldom” to “often.”

They were also asked about how much time they spent outdoors in green spaces during the months of May and September. If so, did they spend any of that time exercising? Options ranged from never to five or more times a week.

In addition, amounts of residential green and blue spaces located within a 1 km radius of the respondents’ homes were assessed from land use and land cover data.

Covariates included health behaviors, outdoor air pollution and noise, and socioeconomic status, including household income and educational attainment.

Results showed that the presence of green and blue spaces at home, and the amount of time spent viewing them, had no association with the use of the prescribed medicines.

However, greater frequency of green space visits was associated with lower odds of using the medications surveyed.

For psychotropic medications, the odds ratios were 0.67 (95% confidence interval, 0.55-0.82) for 3-4 times per week and 0.78 (95% CI, 0.63-0.96) for 5 or more times per week.

For antihypertensive meds, the ORs were 0.64 (95% CI, 0.52-0.78) for 3-4 times per week and 0.59 (95% CI, 0.48-0.74) for 5 or more times per week.

For asthma medications, the ORs were 0.74 (95% CI, 0.58-0.94) for 3-4 times per week and 0.76 (95% CI, 0.59-0.99) for 5 or more times per week.

The observed associations were attenuated by body mass index.

“We observed that those who reported visiting green spaces often had a slightly lower BMI than those who visited green spaces less often,” Dr. Turunen said. However, no consistent interactions with socioeconomic status indicators were observed.

“We are hoping to see new results from different countries and different settings,” she noted. “Longitudinal studies, especially, are needed. In epidemiology, a large body of consistent evidence is needed to draw strong conclusions and to make recommendations.”