Foregoing chemotherapy in favor of cancer immunotherapy (CIT) alone for the first-line treatment of patients with metastatic nonsquamous non–small cell lung cancer (NSCLC) and high programmed death–ligand 1 (PD-L1) expression did not impact survival outcomes in a retrospective cohort of U.S. patients – except in a subgroup of nonsmokers.

Median overall survival was similar at 21.0 months and 22.1 months in 169 patients who received cancer immunotherapy plus chemotherapy and 351 who received cancer immunotherapy monotherapy, respectively (adjusted hazard ratio, 1.03). Median real-world progression-free survival (PFS) was also similar in the two groups (10.8 vs. 11.5 months; aHR, 1.04), Solange Peters, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 17 (abstract VP2_2021).

However, in a small subgroup of 50 never-smokers, CIT plus chemotherapy showed significant and meaningful improvement in both overall survival and real-world progression-free survival, compared with CIT monotherapy, said Dr. Peters, ESMO president and professor and chair of medical oncology at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

The hazard ratios for overall survival and progression-free survival, after adjusting for baseline characteristics, were 0.50 and 0.40 in this subgroup, Dr. Peters said.

She and her colleagues reviewed data from the nationwide Flatiron Health Electronic Health Record–derived deidentified database for patients with metastatic nonsquamous NSCLC with a PD-L1 tumor proportion score at least 50% expression who initiated first-line CIT monotherapy or CIT plus chemotherapy between Oct. 24, 2016, and Feb. 28, 2019.

Median follow-up was 23.5 and 19.9 months in the monotherapy and combination therapy groups, respectively.

The findings are notable because “this is a very important scientific question, which by the way, is a daily question we have,” Dr. Peters said during a plenary debate session at the conference.

“One in four patients [with metastatic nonsquamous NSCLC has] this high PDL expression,” she explained, noting that both treatment approaches are commonly used in the first-line setting in this patient population.

The findings highlight the value of “well-conducted real-world evidence trials” in the absence of randomized trial results, she said.

Invited discussant Marina Chiara Garassino, MBBS, professor of medicine at the University of Chicago, also acknowledged the importance of the findings, noting the “multiple possibilities” for treatment selection in the metastatic nonsquamous NSCLC patient population.

Although patients with PD-L1 expression below 50% derive clear benefit from combination versus single-agent therapy, treatment selection for those with high PD-L1 expression is “very tricky and debatable,” she said.

For those with high PD-L1 expression, the choice is less clear and wrought with uncertainties – particularly for certain subgroups like never-smokers and those with PD-L1 expression over 90%, she said.

The findings reinforce those seen in prior meta-analyses and other clinical trials, particularly with respect to the role of smoking history when making treatment decisions.

“After these results and previous subgroup analyses, in my opinion, in [patients with] PD-L1 expression over 50%, we should consider the combination of chemotherapy and immunotherapy,” she said.

Conversely, findings from this study showing no difference in outcomes between the treatment approaches in patients with brain or liver metastases are based on small numbers and lack power for drawing any conclusions, she said. It also remains unclear whether there is a differential effect for women and those with PD-L1 expression over 90%, high tumor mutation burden, performance score greater than 2, and age over 75 years.

Both Dr. Garassino and Dr. Peters said they are looking to the INSIGNA trial, which is currently recruiting patients in the United States to evaluate the timing of pembrolizumab alone or with chemotherapy as first-line treatment and maintenance in NSCLC, to provide more clarification regarding the best treatment approaches.

This study was funded by F. Hoffmann–La Roche. Dr. Peters and Dr. Garassino each disclosed personal and/or institutional financial relationships with numerous pharmaceutical companies.

[email protected]

Foregoing chemotherapy in favor of cancer immunotherapy (CIT) alone for the first-line treatment of patients with metastatic nonsquamous non–small cell lung cancer (NSCLC) and high programmed death–ligand 1 (PD-L1) expression did not impact survival outcomes in a retrospective cohort of U.S. patients – except in a subgroup of nonsmokers.

Median overall survival was similar at 21.0 months and 22.1 months in 169 patients who received cancer immunotherapy plus chemotherapy and 351 who received cancer immunotherapy monotherapy, respectively (adjusted hazard ratio, 1.03). Median real-world progression-free survival (PFS) was also similar in the two groups (10.8 vs. 11.5 months; aHR, 1.04), Solange Peters, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 17 (abstract VP2_2021).

However, in a small subgroup of 50 never-smokers, CIT plus chemotherapy showed significant and meaningful improvement in both overall survival and real-world progression-free survival, compared with CIT monotherapy, said Dr. Peters, ESMO president and professor and chair of medical oncology at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

The hazard ratios for overall survival and progression-free survival, after adjusting for baseline characteristics, were 0.50 and 0.40 in this subgroup, Dr. Peters said.

She and her colleagues reviewed data from the nationwide Flatiron Health Electronic Health Record–derived deidentified database for patients with metastatic nonsquamous NSCLC with a PD-L1 tumor proportion score at least 50% expression who initiated first-line CIT monotherapy or CIT plus chemotherapy between Oct. 24, 2016, and Feb. 28, 2019.

Median follow-up was 23.5 and 19.9 months in the monotherapy and combination therapy groups, respectively.

The findings are notable because “this is a very important scientific question, which by the way, is a daily question we have,” Dr. Peters said during a plenary debate session at the conference.

“One in four patients [with metastatic nonsquamous NSCLC has] this high PDL expression,” she explained, noting that both treatment approaches are commonly used in the first-line setting in this patient population.

The findings highlight the value of “well-conducted real-world evidence trials” in the absence of randomized trial results, she said.

Invited discussant Marina Chiara Garassino, MBBS, professor of medicine at the University of Chicago, also acknowledged the importance of the findings, noting the “multiple possibilities” for treatment selection in the metastatic nonsquamous NSCLC patient population.

Although patients with PD-L1 expression below 50% derive clear benefit from combination versus single-agent therapy, treatment selection for those with high PD-L1 expression is “very tricky and debatable,” she said.

For those with high PD-L1 expression, the choice is less clear and wrought with uncertainties – particularly for certain subgroups like never-smokers and those with PD-L1 expression over 90%, she said.

The findings reinforce those seen in prior meta-analyses and other clinical trials, particularly with respect to the role of smoking history when making treatment decisions.

“After these results and previous subgroup analyses, in my opinion, in [patients with] PD-L1 expression over 50%, we should consider the combination of chemotherapy and immunotherapy,” she said.

Conversely, findings from this study showing no difference in outcomes between the treatment approaches in patients with brain or liver metastases are based on small numbers and lack power for drawing any conclusions, she said. It also remains unclear whether there is a differential effect for women and those with PD-L1 expression over 90%, high tumor mutation burden, performance score greater than 2, and age over 75 years.

Both Dr. Garassino and Dr. Peters said they are looking to the INSIGNA trial, which is currently recruiting patients in the United States to evaluate the timing of pembrolizumab alone or with chemotherapy as first-line treatment and maintenance in NSCLC, to provide more clarification regarding the best treatment approaches.

This study was funded by F. Hoffmann–La Roche. Dr. Peters and Dr. Garassino each disclosed personal and/or institutional financial relationships with numerous pharmaceutical companies.

[email protected]

Foregoing chemotherapy in favor of cancer immunotherapy (CIT) alone for the first-line treatment of patients with metastatic nonsquamous non–small cell lung cancer (NSCLC) and high programmed death–ligand 1 (PD-L1) expression did not impact survival outcomes in a retrospective cohort of U.S. patients – except in a subgroup of nonsmokers.

Median overall survival was similar at 21.0 months and 22.1 months in 169 patients who received cancer immunotherapy plus chemotherapy and 351 who received cancer immunotherapy monotherapy, respectively (adjusted hazard ratio, 1.03). Median real-world progression-free survival (PFS) was also similar in the two groups (10.8 vs. 11.5 months; aHR, 1.04), Solange Peters, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 17 (abstract VP2_2021).

However, in a small subgroup of 50 never-smokers, CIT plus chemotherapy showed significant and meaningful improvement in both overall survival and real-world progression-free survival, compared with CIT monotherapy, said Dr. Peters, ESMO president and professor and chair of medical oncology at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

The hazard ratios for overall survival and progression-free survival, after adjusting for baseline characteristics, were 0.50 and 0.40 in this subgroup, Dr. Peters said.

She and her colleagues reviewed data from the nationwide Flatiron Health Electronic Health Record–derived deidentified database for patients with metastatic nonsquamous NSCLC with a PD-L1 tumor proportion score at least 50% expression who initiated first-line CIT monotherapy or CIT plus chemotherapy between Oct. 24, 2016, and Feb. 28, 2019.

Median follow-up was 23.5 and 19.9 months in the monotherapy and combination therapy groups, respectively.

The findings are notable because “this is a very important scientific question, which by the way, is a daily question we have,” Dr. Peters said during a plenary debate session at the conference.

“One in four patients [with metastatic nonsquamous NSCLC has] this high PDL expression,” she explained, noting that both treatment approaches are commonly used in the first-line setting in this patient population.

The findings highlight the value of “well-conducted real-world evidence trials” in the absence of randomized trial results, she said.

Invited discussant Marina Chiara Garassino, MBBS, professor of medicine at the University of Chicago, also acknowledged the importance of the findings, noting the “multiple possibilities” for treatment selection in the metastatic nonsquamous NSCLC patient population.

Although patients with PD-L1 expression below 50% derive clear benefit from combination versus single-agent therapy, treatment selection for those with high PD-L1 expression is “very tricky and debatable,” she said.

For those with high PD-L1 expression, the choice is less clear and wrought with uncertainties – particularly for certain subgroups like never-smokers and those with PD-L1 expression over 90%, she said.

The findings reinforce those seen in prior meta-analyses and other clinical trials, particularly with respect to the role of smoking history when making treatment decisions.

“After these results and previous subgroup analyses, in my opinion, in [patients with] PD-L1 expression over 50%, we should consider the combination of chemotherapy and immunotherapy,” she said.

Conversely, findings from this study showing no difference in outcomes between the treatment approaches in patients with brain or liver metastases are based on small numbers and lack power for drawing any conclusions, she said. It also remains unclear whether there is a differential effect for women and those with PD-L1 expression over 90%, high tumor mutation burden, performance score greater than 2, and age over 75 years.

Both Dr. Garassino and Dr. Peters said they are looking to the INSIGNA trial, which is currently recruiting patients in the United States to evaluate the timing of pembrolizumab alone or with chemotherapy as first-line treatment and maintenance in NSCLC, to provide more clarification regarding the best treatment approaches.

This study was funded by F. Hoffmann–La Roche. Dr. Peters and Dr. Garassino each disclosed personal and/or institutional financial relationships with numerous pharmaceutical companies.

[email protected]

PHM 2021 Session

Safe and (Ultra)sound: Why you should use POCUS in your Pediatric Practice

Presenter

Ria Dancel, MD, FAAP, FACP

Session summary

Dr. Ria Dancel and her colleagues from the University of North Carolina at Chapel Hill presented a broad overview of point-of-care ultrasound (POCUS) applications in the field of pediatric hospital medicine. They discussed its advantages and potential uses, ranging from common scenarios to critical care to procedural guidance. Using illustrative scenarios and interactive cases, she discussed the bedside applications to improve care of hospitalized children. The benefits and risks of radiography and POCUS were reviewed.

The session highlighted the use of POCUS in SSTI (skin and soft tissue infection) to help with differentiating cellulitis from abscesses. Use of POCUS for safer incision and drainages and making day-to-day changes in management was discussed. The ease and benefits of performing real-time lung ultrasound in different pathologies (like pneumonia, effusion, COVID-19) was presented. The speakers discussed the use of POCUS in emergency situations like hypotension and different types of shock. The use of ultrasound in common bedside procedures (bladder catheterization, lumbar ultrasound, peripheral IV placement) were also highlighted. Current literature and evidence were reviewed.
 

Key takeaways

• Pediatric POCUS is an extremely valuable bedside tool in pediatric hospital medicine.
• It can be used to guide clinical care for many conditions including SSTI, pneumonia, and shock.
• It can be used for procedural guidance for bladder catheterization, lumbar puncture, and intravenous access.

Dr. Patra is a pediatric hospitalist at West Virginia University Children’s Hospital, Morgantown, and associate professor at West Virginia University School of Medicine. He is interested in medical education, quality improvement and clinical research. He is a member of the Executive Council of the Pediatric Special Interest Group of the Society of Hospital Medicine.

PHM 2021 Session

Safe and (Ultra)sound: Why you should use POCUS in your Pediatric Practice

Presenter

Ria Dancel, MD, FAAP, FACP

Session summary

Dr. Ria Dancel and her colleagues from the University of North Carolina at Chapel Hill presented a broad overview of point-of-care ultrasound (POCUS) applications in the field of pediatric hospital medicine. They discussed its advantages and potential uses, ranging from common scenarios to critical care to procedural guidance. Using illustrative scenarios and interactive cases, she discussed the bedside applications to improve care of hospitalized children. The benefits and risks of radiography and POCUS were reviewed.

The session highlighted the use of POCUS in SSTI (skin and soft tissue infection) to help with differentiating cellulitis from abscesses. Use of POCUS for safer incision and drainages and making day-to-day changes in management was discussed. The ease and benefits of performing real-time lung ultrasound in different pathologies (like pneumonia, effusion, COVID-19) was presented. The speakers discussed the use of POCUS in emergency situations like hypotension and different types of shock. The use of ultrasound in common bedside procedures (bladder catheterization, lumbar ultrasound, peripheral IV placement) were also highlighted. Current literature and evidence were reviewed.
 

Key takeaways

• Pediatric POCUS is an extremely valuable bedside tool in pediatric hospital medicine.
• It can be used to guide clinical care for many conditions including SSTI, pneumonia, and shock.
• It can be used for procedural guidance for bladder catheterization, lumbar puncture, and intravenous access.

Dr. Patra is a pediatric hospitalist at West Virginia University Children’s Hospital, Morgantown, and associate professor at West Virginia University School of Medicine. He is interested in medical education, quality improvement and clinical research. He is a member of the Executive Council of the Pediatric Special Interest Group of the Society of Hospital Medicine.

PHM 2021 Session

Safe and (Ultra)sound: Why you should use POCUS in your Pediatric Practice

Presenter

Ria Dancel, MD, FAAP, FACP

Session summary

Dr. Ria Dancel and her colleagues from the University of North Carolina at Chapel Hill presented a broad overview of point-of-care ultrasound (POCUS) applications in the field of pediatric hospital medicine. They discussed its advantages and potential uses, ranging from common scenarios to critical care to procedural guidance. Using illustrative scenarios and interactive cases, she discussed the bedside applications to improve care of hospitalized children. The benefits and risks of radiography and POCUS were reviewed.

The session highlighted the use of POCUS in SSTI (skin and soft tissue infection) to help with differentiating cellulitis from abscesses. Use of POCUS for safer incision and drainages and making day-to-day changes in management was discussed. The ease and benefits of performing real-time lung ultrasound in different pathologies (like pneumonia, effusion, COVID-19) was presented. The speakers discussed the use of POCUS in emergency situations like hypotension and different types of shock. The use of ultrasound in common bedside procedures (bladder catheterization, lumbar ultrasound, peripheral IV placement) were also highlighted. Current literature and evidence were reviewed.
 

Key takeaways

• Pediatric POCUS is an extremely valuable bedside tool in pediatric hospital medicine.
• It can be used to guide clinical care for many conditions including SSTI, pneumonia, and shock.
• It can be used for procedural guidance for bladder catheterization, lumbar puncture, and intravenous access.

Dr. Patra is a pediatric hospitalist at West Virginia University Children’s Hospital, Morgantown, and associate professor at West Virginia University School of Medicine. He is interested in medical education, quality improvement and clinical research. He is a member of the Executive Council of the Pediatric Special Interest Group of the Society of Hospital Medicine.

The observed rates of intracranial hemorrhaging (ICH) in patients with hemophilia were higher compared to the general populations among all age groups examined, according to a meta-analysis of studies reported online ahead of print in Blood.

As previously reported, the risk seemed higher in the group of infants and toddlers, and neonates with hemophilia showed a 33-fold higher risk of ICH than newborns in the general population, in the current study.

The researchers performed a literature review and assessed 45 studies that represented 54,470 patients, 809,151 person-years and 5,326 live births of patients with hemophilia. Pooled ICH incidence and mortality were calculated for three age groups: persons of all ages with hemophilia; children and young adults below 25 years of age with hemophilia; and neonates with hemophilia.
 

Overall results

Among the persons of all ages, the pooled ICH incidence and mortality rates were 2.3 (95% confidence interval, 1.2-4.8) and 0.8 (95% CI, 0.5-1.2) per 1,000 person-years, respectively, according to the authors. They found that in children and young adults, the pooled ICH incidence and mortality rates were 7.4 (95% CI, 4.9-11.1) and 0.5 (95% CI, 0.3-0.9) per 1,000 person-years, respectively. In neonates, the pooled cumulative ICH incidence was 2.1% (95% CI, 1.5-2.8) per 100 live births and the pooled ICH cumulative mortality was 0.2% (95% CI, 0.0-1.2) per 100 live births.

Overall, the occurrence of ICH was classified as spontaneous in 35%-58% of cases.
 

Neonates at risk

The observed ICH rates in hemophilia were higher compared to the general populations among the age groups assessed. Neonates showed the highest risk of ICH, which is confirmed by other studies in severe hemophilia demonstrating that neonates were at 11.2 times higher risk for ICH compared with 1- to 12-month-old children, and is also strongly increased compared to neonates in the general populations, the researchers stated.

A previous large study of term infants reported 361 intracranial bleeding episodes per 583,340 live births (0.062% per 100 live births), and comparing this to the current pooled estimate of 2.1% per 100 live births, neonates with hemophilia showed a 33-fold higher risk of ICH than newborns in the general population, according to the researchers.
 

Monitoring and follow-up

“Our findings suggest that adequate follow-up and monitoring of patients is warranted among all ages, especially in the presence of risk factors. Prophylaxis seems to halve ICH risk in children and adults with severe hemophilia, which supports existing recommendations encouraging early initiation of prophylactic treatment,” the authors advised.

Accurate capture of the true frequency of ICH is challenged by considerable clinical heterogeneity, limiting the precision and generalizability of the pooled estimates, leading to the likelihood that ICH and mortality were underdiagnosed in this analysis, according to the authors.

“We found high ICH incidence and mortality rates in patients with hemophilia. Our findings suggest that ICH is still an important problem in hemophilia requiring adequate counseling of patients of all ages,” the researchers concluded.

This work was supported by a grant from Sobi. Some of the authors reported research, consulting or lecturing fees from a variety of pharmaceutical companies, including Sobi.

[email protected]

The observed rates of intracranial hemorrhaging (ICH) in patients with hemophilia were higher compared to the general populations among all age groups examined, according to a meta-analysis of studies reported online ahead of print in Blood.

As previously reported, the risk seemed higher in the group of infants and toddlers, and neonates with hemophilia showed a 33-fold higher risk of ICH than newborns in the general population, in the current study.

The researchers performed a literature review and assessed 45 studies that represented 54,470 patients, 809,151 person-years and 5,326 live births of patients with hemophilia. Pooled ICH incidence and mortality were calculated for three age groups: persons of all ages with hemophilia; children and young adults below 25 years of age with hemophilia; and neonates with hemophilia.
 

Overall results

Among the persons of all ages, the pooled ICH incidence and mortality rates were 2.3 (95% confidence interval, 1.2-4.8) and 0.8 (95% CI, 0.5-1.2) per 1,000 person-years, respectively, according to the authors. They found that in children and young adults, the pooled ICH incidence and mortality rates were 7.4 (95% CI, 4.9-11.1) and 0.5 (95% CI, 0.3-0.9) per 1,000 person-years, respectively. In neonates, the pooled cumulative ICH incidence was 2.1% (95% CI, 1.5-2.8) per 100 live births and the pooled ICH cumulative mortality was 0.2% (95% CI, 0.0-1.2) per 100 live births.

Overall, the occurrence of ICH was classified as spontaneous in 35%-58% of cases.
 

Neonates at risk

The observed ICH rates in hemophilia were higher compared to the general populations among the age groups assessed. Neonates showed the highest risk of ICH, which is confirmed by other studies in severe hemophilia demonstrating that neonates were at 11.2 times higher risk for ICH compared with 1- to 12-month-old children, and is also strongly increased compared to neonates in the general populations, the researchers stated.

A previous large study of term infants reported 361 intracranial bleeding episodes per 583,340 live births (0.062% per 100 live births), and comparing this to the current pooled estimate of 2.1% per 100 live births, neonates with hemophilia showed a 33-fold higher risk of ICH than newborns in the general population, according to the researchers.
 

Monitoring and follow-up

“Our findings suggest that adequate follow-up and monitoring of patients is warranted among all ages, especially in the presence of risk factors. Prophylaxis seems to halve ICH risk in children and adults with severe hemophilia, which supports existing recommendations encouraging early initiation of prophylactic treatment,” the authors advised.

Accurate capture of the true frequency of ICH is challenged by considerable clinical heterogeneity, limiting the precision and generalizability of the pooled estimates, leading to the likelihood that ICH and mortality were underdiagnosed in this analysis, according to the authors.

“We found high ICH incidence and mortality rates in patients with hemophilia. Our findings suggest that ICH is still an important problem in hemophilia requiring adequate counseling of patients of all ages,” the researchers concluded.

This work was supported by a grant from Sobi. Some of the authors reported research, consulting or lecturing fees from a variety of pharmaceutical companies, including Sobi.

[email protected]

The observed rates of intracranial hemorrhaging (ICH) in patients with hemophilia were higher compared to the general populations among all age groups examined, according to a meta-analysis of studies reported online ahead of print in Blood.

As previously reported, the risk seemed higher in the group of infants and toddlers, and neonates with hemophilia showed a 33-fold higher risk of ICH than newborns in the general population, in the current study.

The researchers performed a literature review and assessed 45 studies that represented 54,470 patients, 809,151 person-years and 5,326 live births of patients with hemophilia. Pooled ICH incidence and mortality were calculated for three age groups: persons of all ages with hemophilia; children and young adults below 25 years of age with hemophilia; and neonates with hemophilia.
 

Overall results

Among the persons of all ages, the pooled ICH incidence and mortality rates were 2.3 (95% confidence interval, 1.2-4.8) and 0.8 (95% CI, 0.5-1.2) per 1,000 person-years, respectively, according to the authors. They found that in children and young adults, the pooled ICH incidence and mortality rates were 7.4 (95% CI, 4.9-11.1) and 0.5 (95% CI, 0.3-0.9) per 1,000 person-years, respectively. In neonates, the pooled cumulative ICH incidence was 2.1% (95% CI, 1.5-2.8) per 100 live births and the pooled ICH cumulative mortality was 0.2% (95% CI, 0.0-1.2) per 100 live births.

Overall, the occurrence of ICH was classified as spontaneous in 35%-58% of cases.
 

Neonates at risk

The observed ICH rates in hemophilia were higher compared to the general populations among the age groups assessed. Neonates showed the highest risk of ICH, which is confirmed by other studies in severe hemophilia demonstrating that neonates were at 11.2 times higher risk for ICH compared with 1- to 12-month-old children, and is also strongly increased compared to neonates in the general populations, the researchers stated.

A previous large study of term infants reported 361 intracranial bleeding episodes per 583,340 live births (0.062% per 100 live births), and comparing this to the current pooled estimate of 2.1% per 100 live births, neonates with hemophilia showed a 33-fold higher risk of ICH than newborns in the general population, according to the researchers.
 

Monitoring and follow-up

“Our findings suggest that adequate follow-up and monitoring of patients is warranted among all ages, especially in the presence of risk factors. Prophylaxis seems to halve ICH risk in children and adults with severe hemophilia, which supports existing recommendations encouraging early initiation of prophylactic treatment,” the authors advised.

Accurate capture of the true frequency of ICH is challenged by considerable clinical heterogeneity, limiting the precision and generalizability of the pooled estimates, leading to the likelihood that ICH and mortality were underdiagnosed in this analysis, according to the authors.

“We found high ICH incidence and mortality rates in patients with hemophilia. Our findings suggest that ICH is still an important problem in hemophilia requiring adequate counseling of patients of all ages,” the researchers concluded.

This work was supported by a grant from Sobi. Some of the authors reported research, consulting or lecturing fees from a variety of pharmaceutical companies, including Sobi.

[email protected]

The Diagnosis: Nodular Hidradenoma

A biopsy of the nodule showed a large, fungating, well-circumscribed, multilobulated neoplasm composed of primarily monotonous eosinophilic cells in a background of keloidal stroma (Figure). There was a minority population of small, monotonous, clear cells within the lobules, and no glandular structures were noted. Neither cytological nor architectural atypia were evident. MART-1/Melan-A and S-100 stains were negative, consistent with a diagnosis of benign nodular hidradenoma.

Nodular hidradenoma (also known as acrospiroma, solid-cystic hidradenoma, clear cell hidradenoma, and eccrine sweat gland adenoma) is a benign adnexal tumor of the apocrine or eccrine glands.^1,2 Nodular hidradenoma can arise at any cutaneous site but most commonly arises on the head and anterior portion of the trunk and rarely on the extremities.² It presents as a solitary nodular, cystic, or pedunculated mass that can reach up to several centimeters in diameter.^2,3 Nodular hidradenoma more commonly affects women compared to men with a ratio of 1.7 to 1 and commonly presents between the third and fifth decades of life, with an average age at presentation of 37.2 years.^2,4 There can be associated skin changes, including smoothening, thickening, ulceration, and bluish discoloration. Dermoscopy commonly shows a pinkish homogenous area that extends throughout the entire lesion. This homogenous area less commonly can be bluish, brownish, or pink-blue. Most nodular hidradenomas also can exhibit vascularization, with arborizing telangiectases, polymorphous atypical vessels, and linear irregular vessels being most common; however, this is not specific to nodular hidradenoma.3 Occasionally, tumors can drain serous or hemorrhagic fluid. Nodular hidradenoma commonly is a slow-growing tumor.⁵ Rapid increase in tumor size can be indicative of malignant transformation, hemorrhage into the tumor, or trauma to the area.²

Histologically, nodular hidradenoma consists of a circumscribed, nonencapsulated, multilobular tumor commonly found in the dermis and sometimes extending into the subcutaneous tissue. There usually is no epidermal attachment, and the overlying epidermis largely is normal. The tumor consists of large multilobulated areas of epithelial cells, tubular lamina, and large cystic areas filled with homogenous eosinophilic material.¹ It notably is composed of 2 epithelial cell types: (1) fusiform cells with elongated vesicular nuclei and basophilic cytoplasm, and (2) large polygonal cells with round eccentric nuclei and eosinophilic, periodic acid–Schiff–positive cytoplasm that washes away during fixation, giving the appearance of clear cells.⁵ Both types of cells are small, monotonous, and void of mitosis or dyskeratosis. Although there can be ducts with apocrine secretion present within the lobulated tumor, they are not consistently found. Due to the varying features that are neither mandatory nor consistent to arrive at this diagnosis, some dermatopathologists view the term hidradenoma as a catch-all term that includes several different types of benign sweat gland tumors. Some authors divide the terminology into apocrine hidradenoma and eccrine hidradenoma based on whether the tumor is composed of solely clear mucinous cells, or poroid and cuticular cells, respectively.

Although nodular hidradenoma classically is a benign tumor, total surgical excision is recommended due to the rare risk for malignant transformation. Rarely, longstanding hidradenomas can metastasize to lymph nodes, bone, or viscera; in these instances, metastatic hidradenoma has a 5-year survival rate of 30%. Recurrence may occur in tumors that are inadequately excised, and the rate of recurrence is estimated to be approximately 10% of surgically excised tumors.⁵ However, utilization of Mohs micrographic surgery for excision of nodular hidradenoma is associated with a reduced recurrence rate.⁶

Keloids present as painful, sometimes pruritic, raised scars that extend beyond the boundary of the initial injury, commonly arising on the shoulder, upper arm, and chest. Histopathology reveals nodules of thick hyalinized collagen bundles, keloidal collagen with mucinous ground substance, and few fibroblasts.⁷

Metastatic renal cell carcinoma to the skin most commonly presents on the face and scalp as a nodular, rapidly growing, round to oval lesion that is flesh colored to reddish purple in a patient with history of renal cell carcinoma.⁸ Histopathology shows clusters of atypical, nucleated clear cells surrounded by chicken wire vasculature.^8,9

Verruca vulgaris is caused by human papillomavirus and most commonly occurs on the hands and feet. It presents as a pink to white, sessile lesion with a verrucous surface and exophytic growths. Histopathology shows acanthosis; hypergranulosis; exophytic projections with a fibrovascular core; inward cupping of the rete ridges; and koilocytes, which are cells with an eccentric, raisinlike nucleus and vacuolated cytoplasm in the granular layer of the epidermis.¹⁰

Similar to nodular hidradenoma, nodular melanoma most commonly presents on the head and neck as a symmetric, elevated, amelanotic nodule, but in contrast to nodular hidradenoma, it typically is confined to a smaller diameter.¹¹ Histologically, it is characterized by sheets of atypical, commonly epithelioid melanocytes with a lack of maturation and brisk mitotic activity extending through the epidermis and dermis with lateral extension limited to less than 3 rete ridges.¹²

The Diagnosis: Nodular Hidradenoma

A biopsy of the nodule showed a large, fungating, well-circumscribed, multilobulated neoplasm composed of primarily monotonous eosinophilic cells in a background of keloidal stroma (Figure). There was a minority population of small, monotonous, clear cells within the lobules, and no glandular structures were noted. Neither cytological nor architectural atypia were evident. MART-1/Melan-A and S-100 stains were negative, consistent with a diagnosis of benign nodular hidradenoma.

Nodular hidradenoma (also known as acrospiroma, solid-cystic hidradenoma, clear cell hidradenoma, and eccrine sweat gland adenoma) is a benign adnexal tumor of the apocrine or eccrine glands.^1,2 Nodular hidradenoma can arise at any cutaneous site but most commonly arises on the head and anterior portion of the trunk and rarely on the extremities.² It presents as a solitary nodular, cystic, or pedunculated mass that can reach up to several centimeters in diameter.^2,3 Nodular hidradenoma more commonly affects women compared to men with a ratio of 1.7 to 1 and commonly presents between the third and fifth decades of life, with an average age at presentation of 37.2 years.^2,4 There can be associated skin changes, including smoothening, thickening, ulceration, and bluish discoloration. Dermoscopy commonly shows a pinkish homogenous area that extends throughout the entire lesion. This homogenous area less commonly can be bluish, brownish, or pink-blue. Most nodular hidradenomas also can exhibit vascularization, with arborizing telangiectases, polymorphous atypical vessels, and linear irregular vessels being most common; however, this is not specific to nodular hidradenoma.3 Occasionally, tumors can drain serous or hemorrhagic fluid. Nodular hidradenoma commonly is a slow-growing tumor.⁵ Rapid increase in tumor size can be indicative of malignant transformation, hemorrhage into the tumor, or trauma to the area.²

Histologically, nodular hidradenoma consists of a circumscribed, nonencapsulated, multilobular tumor commonly found in the dermis and sometimes extending into the subcutaneous tissue. There usually is no epidermal attachment, and the overlying epidermis largely is normal. The tumor consists of large multilobulated areas of epithelial cells, tubular lamina, and large cystic areas filled with homogenous eosinophilic material.¹ It notably is composed of 2 epithelial cell types: (1) fusiform cells with elongated vesicular nuclei and basophilic cytoplasm, and (2) large polygonal cells with round eccentric nuclei and eosinophilic, periodic acid–Schiff–positive cytoplasm that washes away during fixation, giving the appearance of clear cells.⁵ Both types of cells are small, monotonous, and void of mitosis or dyskeratosis. Although there can be ducts with apocrine secretion present within the lobulated tumor, they are not consistently found. Due to the varying features that are neither mandatory nor consistent to arrive at this diagnosis, some dermatopathologists view the term hidradenoma as a catch-all term that includes several different types of benign sweat gland tumors. Some authors divide the terminology into apocrine hidradenoma and eccrine hidradenoma based on whether the tumor is composed of solely clear mucinous cells, or poroid and cuticular cells, respectively.

Although nodular hidradenoma classically is a benign tumor, total surgical excision is recommended due to the rare risk for malignant transformation. Rarely, longstanding hidradenomas can metastasize to lymph nodes, bone, or viscera; in these instances, metastatic hidradenoma has a 5-year survival rate of 30%. Recurrence may occur in tumors that are inadequately excised, and the rate of recurrence is estimated to be approximately 10% of surgically excised tumors.⁵ However, utilization of Mohs micrographic surgery for excision of nodular hidradenoma is associated with a reduced recurrence rate.⁶

Keloids present as painful, sometimes pruritic, raised scars that extend beyond the boundary of the initial injury, commonly arising on the shoulder, upper arm, and chest. Histopathology reveals nodules of thick hyalinized collagen bundles, keloidal collagen with mucinous ground substance, and few fibroblasts.⁷

Metastatic renal cell carcinoma to the skin most commonly presents on the face and scalp as a nodular, rapidly growing, round to oval lesion that is flesh colored to reddish purple in a patient with history of renal cell carcinoma.⁸ Histopathology shows clusters of atypical, nucleated clear cells surrounded by chicken wire vasculature.^8,9

Verruca vulgaris is caused by human papillomavirus and most commonly occurs on the hands and feet. It presents as a pink to white, sessile lesion with a verrucous surface and exophytic growths. Histopathology shows acanthosis; hypergranulosis; exophytic projections with a fibrovascular core; inward cupping of the rete ridges; and koilocytes, which are cells with an eccentric, raisinlike nucleus and vacuolated cytoplasm in the granular layer of the epidermis.¹⁰

Similar to nodular hidradenoma, nodular melanoma most commonly presents on the head and neck as a symmetric, elevated, amelanotic nodule, but in contrast to nodular hidradenoma, it typically is confined to a smaller diameter.¹¹ Histologically, it is characterized by sheets of atypical, commonly epithelioid melanocytes with a lack of maturation and brisk mitotic activity extending through the epidermis and dermis with lateral extension limited to less than 3 rete ridges.¹²

The Diagnosis: Nodular Hidradenoma

A biopsy of the nodule showed a large, fungating, well-circumscribed, multilobulated neoplasm composed of primarily monotonous eosinophilic cells in a background of keloidal stroma (Figure). There was a minority population of small, monotonous, clear cells within the lobules, and no glandular structures were noted. Neither cytological nor architectural atypia were evident. MART-1/Melan-A and S-100 stains were negative, consistent with a diagnosis of benign nodular hidradenoma.

Nodular hidradenoma (also known as acrospiroma, solid-cystic hidradenoma, clear cell hidradenoma, and eccrine sweat gland adenoma) is a benign adnexal tumor of the apocrine or eccrine glands.^1,2 Nodular hidradenoma can arise at any cutaneous site but most commonly arises on the head and anterior portion of the trunk and rarely on the extremities.² It presents as a solitary nodular, cystic, or pedunculated mass that can reach up to several centimeters in diameter.^2,3 Nodular hidradenoma more commonly affects women compared to men with a ratio of 1.7 to 1 and commonly presents between the third and fifth decades of life, with an average age at presentation of 37.2 years.^2,4 There can be associated skin changes, including smoothening, thickening, ulceration, and bluish discoloration. Dermoscopy commonly shows a pinkish homogenous area that extends throughout the entire lesion. This homogenous area less commonly can be bluish, brownish, or pink-blue. Most nodular hidradenomas also can exhibit vascularization, with arborizing telangiectases, polymorphous atypical vessels, and linear irregular vessels being most common; however, this is not specific to nodular hidradenoma.3 Occasionally, tumors can drain serous or hemorrhagic fluid. Nodular hidradenoma commonly is a slow-growing tumor.⁵ Rapid increase in tumor size can be indicative of malignant transformation, hemorrhage into the tumor, or trauma to the area.²

Histologically, nodular hidradenoma consists of a circumscribed, nonencapsulated, multilobular tumor commonly found in the dermis and sometimes extending into the subcutaneous tissue. There usually is no epidermal attachment, and the overlying epidermis largely is normal. The tumor consists of large multilobulated areas of epithelial cells, tubular lamina, and large cystic areas filled with homogenous eosinophilic material.¹ It notably is composed of 2 epithelial cell types: (1) fusiform cells with elongated vesicular nuclei and basophilic cytoplasm, and (2) large polygonal cells with round eccentric nuclei and eosinophilic, periodic acid–Schiff–positive cytoplasm that washes away during fixation, giving the appearance of clear cells.⁵ Both types of cells are small, monotonous, and void of mitosis or dyskeratosis. Although there can be ducts with apocrine secretion present within the lobulated tumor, they are not consistently found. Due to the varying features that are neither mandatory nor consistent to arrive at this diagnosis, some dermatopathologists view the term hidradenoma as a catch-all term that includes several different types of benign sweat gland tumors. Some authors divide the terminology into apocrine hidradenoma and eccrine hidradenoma based on whether the tumor is composed of solely clear mucinous cells, or poroid and cuticular cells, respectively.

Although nodular hidradenoma classically is a benign tumor, total surgical excision is recommended due to the rare risk for malignant transformation. Rarely, longstanding hidradenomas can metastasize to lymph nodes, bone, or viscera; in these instances, metastatic hidradenoma has a 5-year survival rate of 30%. Recurrence may occur in tumors that are inadequately excised, and the rate of recurrence is estimated to be approximately 10% of surgically excised tumors.⁵ However, utilization of Mohs micrographic surgery for excision of nodular hidradenoma is associated with a reduced recurrence rate.⁶

Keloids present as painful, sometimes pruritic, raised scars that extend beyond the boundary of the initial injury, commonly arising on the shoulder, upper arm, and chest. Histopathology reveals nodules of thick hyalinized collagen bundles, keloidal collagen with mucinous ground substance, and few fibroblasts.⁷

Metastatic renal cell carcinoma to the skin most commonly presents on the face and scalp as a nodular, rapidly growing, round to oval lesion that is flesh colored to reddish purple in a patient with history of renal cell carcinoma.⁸ Histopathology shows clusters of atypical, nucleated clear cells surrounded by chicken wire vasculature.^8,9

Verruca vulgaris is caused by human papillomavirus and most commonly occurs on the hands and feet. It presents as a pink to white, sessile lesion with a verrucous surface and exophytic growths. Histopathology shows acanthosis; hypergranulosis; exophytic projections with a fibrovascular core; inward cupping of the rete ridges; and koilocytes, which are cells with an eccentric, raisinlike nucleus and vacuolated cytoplasm in the granular layer of the epidermis.¹⁰

Similar to nodular hidradenoma, nodular melanoma most commonly presents on the head and neck as a symmetric, elevated, amelanotic nodule, but in contrast to nodular hidradenoma, it typically is confined to a smaller diameter.¹¹ Histologically, it is characterized by sheets of atypical, commonly epithelioid melanocytes with a lack of maturation and brisk mitotic activity extending through the epidermis and dermis with lateral extension limited to less than 3 rete ridges.¹²

Cigarette smoking is a well-known modifiable risk factor for the development of rheumatoid arthritis (RA). Studies have suggested not only an elevated risk but possible pathogenetic role in the development of autoantibodies, as well as effects on disease outcomes. Passive cigarette smoking has also been proposed as a potential risk factor for RA, though studies are harder to evaluate. This review of prospective data from the Nurses Health Study (NHS) by Yoshida et al looks at incident RA among women enrolled in the study and the influence of in utero, childhood, and adulthood exposure to cigarettes. Childhood exposure to parental smoking was associated with seropositive RA (hazard ratio 1.75) even after controlling for adult personal smoking, and maternal smoking during pregnancy was associated with RA, though the latter effect was not seen after controlling for subsequent smoking exposure. As the authors point out, verifiable prospective data is difficult to obtain regarding exposure to smoking in utero or in childhood and recall bias is possible in obtaining historical information in this prospective study given the use of questionnaires, though it remains plausible given prior studies on the association of personal smoking with RA.

The involvement of gut microbiota in development of autoimmunity has also been postulated but not well-explained. Several recent studies have examined the impact of antibiotic use on the development of RA, including a recent large UK-based case-control study suggesting an increase in RA incidence in people with antibiotic exposure. While a systematic review is ongoing, this prospective cohort study by Liu et al also examines data from NHSI and NHSII and RA risk in patients exposed to antibiotics, stratified by duration of use (none, ≤14 days, ≥15 days). It is reassuring that in this study neither short term (≤14 days) nor long term (≥15 days) antibiotic use was associated with RA risk. Comparison with prior studies with prescription data, however, is limited given the use of questionnaires to establish duration of recent antibiotic exposure.

Fatigue is a common symptom of RA and has a high impact on quality of life in terms of function. The study by Holten et al examines data from the ARCTIC trial in terms of associations between disease activity and fatigue in early RA, as well as change in fatigue with therapy for RA. Fatigue was measured via a visual analog scale (VAS) and did decrease with therapy from baseline; 80% of patients in the study had moderate or high disease activity based on disease activity score (DAS) at baseline and 69% of patients reported fatigue, while 9% of patients had moderate or high disease activity based on DAS at  24 months and 38% reported fatigue. Interestingly, patients who were in remission (per DAS) at 6 months had a reduced risk of fatigue at 24 months. It is hard to interpret this information in a granular way as fatigue is not measured in a standardized way across clinical studies and the only instrument of measure in the ARCTIC trial was the VAS. An alternate view, for example examining the impact of baseline fatigue on response to therapy, may also be reasonable, or fatigue may be a residual symptom similar to chronic myofascial or “non-inflammatory” pain not responsive to treatment in RA.

Finally, another associated extra-articular manifestation of RA is bronchiectasis. Martin et al performed a systematic review and meta-analysis of the literature and found that the prevalence of bronchiectasis was about 18% in RA patients, suggesting that it is more common than previously thought. However, inclusion of CT imaging may detect subclinical bronchiectasis and other secondary causes were not determined. Still, given the effects on quality of life and mortality, further research into causes and risk factors for bronchiectasis in RA is warranted.

Cigarette smoking is a well-known modifiable risk factor for the development of rheumatoid arthritis (RA). Studies have suggested not only an elevated risk but possible pathogenetic role in the development of autoantibodies, as well as effects on disease outcomes. Passive cigarette smoking has also been proposed as a potential risk factor for RA, though studies are harder to evaluate. This review of prospective data from the Nurses Health Study (NHS) by Yoshida et al looks at incident RA among women enrolled in the study and the influence of in utero, childhood, and adulthood exposure to cigarettes. Childhood exposure to parental smoking was associated with seropositive RA (hazard ratio 1.75) even after controlling for adult personal smoking, and maternal smoking during pregnancy was associated with RA, though the latter effect was not seen after controlling for subsequent smoking exposure. As the authors point out, verifiable prospective data is difficult to obtain regarding exposure to smoking in utero or in childhood and recall bias is possible in obtaining historical information in this prospective study given the use of questionnaires, though it remains plausible given prior studies on the association of personal smoking with RA.

The involvement of gut microbiota in development of autoimmunity has also been postulated but not well-explained. Several recent studies have examined the impact of antibiotic use on the development of RA, including a recent large UK-based case-control study suggesting an increase in RA incidence in people with antibiotic exposure. While a systematic review is ongoing, this prospective cohort study by Liu et al also examines data from NHSI and NHSII and RA risk in patients exposed to antibiotics, stratified by duration of use (none, ≤14 days, ≥15 days). It is reassuring that in this study neither short term (≤14 days) nor long term (≥15 days) antibiotic use was associated with RA risk. Comparison with prior studies with prescription data, however, is limited given the use of questionnaires to establish duration of recent antibiotic exposure.

Fatigue is a common symptom of RA and has a high impact on quality of life in terms of function. The study by Holten et al examines data from the ARCTIC trial in terms of associations between disease activity and fatigue in early RA, as well as change in fatigue with therapy for RA. Fatigue was measured via a visual analog scale (VAS) and did decrease with therapy from baseline; 80% of patients in the study had moderate or high disease activity based on disease activity score (DAS) at baseline and 69% of patients reported fatigue, while 9% of patients had moderate or high disease activity based on DAS at  24 months and 38% reported fatigue. Interestingly, patients who were in remission (per DAS) at 6 months had a reduced risk of fatigue at 24 months. It is hard to interpret this information in a granular way as fatigue is not measured in a standardized way across clinical studies and the only instrument of measure in the ARCTIC trial was the VAS. An alternate view, for example examining the impact of baseline fatigue on response to therapy, may also be reasonable, or fatigue may be a residual symptom similar to chronic myofascial or “non-inflammatory” pain not responsive to treatment in RA.

Finally, another associated extra-articular manifestation of RA is bronchiectasis. Martin et al performed a systematic review and meta-analysis of the literature and found that the prevalence of bronchiectasis was about 18% in RA patients, suggesting that it is more common than previously thought. However, inclusion of CT imaging may detect subclinical bronchiectasis and other secondary causes were not determined. Still, given the effects on quality of life and mortality, further research into causes and risk factors for bronchiectasis in RA is warranted.

Cigarette smoking is a well-known modifiable risk factor for the development of rheumatoid arthritis (RA). Studies have suggested not only an elevated risk but possible pathogenetic role in the development of autoantibodies, as well as effects on disease outcomes. Passive cigarette smoking has also been proposed as a potential risk factor for RA, though studies are harder to evaluate. This review of prospective data from the Nurses Health Study (NHS) by Yoshida et al looks at incident RA among women enrolled in the study and the influence of in utero, childhood, and adulthood exposure to cigarettes. Childhood exposure to parental smoking was associated with seropositive RA (hazard ratio 1.75) even after controlling for adult personal smoking, and maternal smoking during pregnancy was associated with RA, though the latter effect was not seen after controlling for subsequent smoking exposure. As the authors point out, verifiable prospective data is difficult to obtain regarding exposure to smoking in utero or in childhood and recall bias is possible in obtaining historical information in this prospective study given the use of questionnaires, though it remains plausible given prior studies on the association of personal smoking with RA.

The involvement of gut microbiota in development of autoimmunity has also been postulated but not well-explained. Several recent studies have examined the impact of antibiotic use on the development of RA, including a recent large UK-based case-control study suggesting an increase in RA incidence in people with antibiotic exposure. While a systematic review is ongoing, this prospective cohort study by Liu et al also examines data from NHSI and NHSII and RA risk in patients exposed to antibiotics, stratified by duration of use (none, ≤14 days, ≥15 days). It is reassuring that in this study neither short term (≤14 days) nor long term (≥15 days) antibiotic use was associated with RA risk. Comparison with prior studies with prescription data, however, is limited given the use of questionnaires to establish duration of recent antibiotic exposure.

Fatigue is a common symptom of RA and has a high impact on quality of life in terms of function. The study by Holten et al examines data from the ARCTIC trial in terms of associations between disease activity and fatigue in early RA, as well as change in fatigue with therapy for RA. Fatigue was measured via a visual analog scale (VAS) and did decrease with therapy from baseline; 80% of patients in the study had moderate or high disease activity based on disease activity score (DAS) at baseline and 69% of patients reported fatigue, while 9% of patients had moderate or high disease activity based on DAS at  24 months and 38% reported fatigue. Interestingly, patients who were in remission (per DAS) at 6 months had a reduced risk of fatigue at 24 months. It is hard to interpret this information in a granular way as fatigue is not measured in a standardized way across clinical studies and the only instrument of measure in the ARCTIC trial was the VAS. An alternate view, for example examining the impact of baseline fatigue on response to therapy, may also be reasonable, or fatigue may be a residual symptom similar to chronic myofascial or “non-inflammatory” pain not responsive to treatment in RA.

Finally, another associated extra-articular manifestation of RA is bronchiectasis. Martin et al performed a systematic review and meta-analysis of the literature and found that the prevalence of bronchiectasis was about 18% in RA patients, suggesting that it is more common than previously thought. However, inclusion of CT imaging may detect subclinical bronchiectasis and other secondary causes were not determined. Still, given the effects on quality of life and mortality, further research into causes and risk factors for bronchiectasis in RA is warranted.

Good nutrition has long been linked to better behavior and academic performance in schoolchildren, as longstanding breakfast and lunch programs in U.S. schools attest. Now British researchers report that nutrition, a modifiable risk factor that can adversely impact mental health, should be part of public health strategies to boost children’s psychological wellness.

In a cross-sectional study published online Sept. 27 in BMJ Nutrition, Prevention & Health, a team from the University of East Anglia in Norwich, England, found a nutritious breakfast and lunch were linked to emotional well-being in schoolchildren of both primary and secondary school age. They also found that some school kids ate neither breakfast nor lunch.

In particular, eating more fruits and vegetables was significantly associated with better mental health in secondary schoolchildren, while a nutritious breakfast and lunch were linked to emotional well-being in students across the age spectrum, according to senior lecturer Richard P. Hayhoe, PhD, of East Anglia University and Anglia Ruskin University in Norwich and colleagues.

They found that primary school pupils who ate only a snack for breakfast had mental well-being scores 5.50 units lower than those eating a substantial breakfast, while having no lunch was tied to scores more than 6 units lower.

“The importance of good-quality nutrition for childhood growth and development is well established,” the authors wrote. “As a potentially modifiable factor, both at an individual and societal level, nutrition may therefore represent an important public health target for strategies to address childhood mental well-being.”

Their current analysis examined data on 7,570 secondary and 1,253 primary school children from 50 schools participating in the Norfolk Children and Young People Health and Well-being Survey 2017.

Multivariable linear regression measured the association between nutritional factors and mental well-being assessed by the Warwick-Edinburgh Mental Well-being Scale for secondary school pupils or by the Stirling Children’s Well-being Scale for primary school pupils. All analyses were adjusted for covariates including demographic, health variables, living/home situations, and adverse experiences.

“The 2017 survey provided a means for Norfolk children and young people to share their feelings on topics such as healthy lifestyles and nutrition, relationships, school experiences, bullying, and their mental well-being,” Dr. Hayhoe said in an interview. “Initial analysis of the data suggested an association between nutrition and well-being and so we decided to investigate this further.”

Dr. Hayhoe added that, as in the United States, youngsters in England get a high proportion of their daily calories from ultraprocessed convenience foods of lesser nutritional value.

“But what we didn’t know was whether the dietary habits of children in our survey had any association with their mental well-being,” he said. “Our current findings suggest that increasing fruit and vegetable consumption and ensuring all schoolchildren eat a nutritional breakfast and lunch may be of benefit to their mental well-being.”

His group cautions, however, that this is an observational study that cannot establish direct causation.

“This study provides the first insights into how fruit and vegetable intake affects children’s mental health, and contributes to the emerging evidence around ‘food and mood,’ ” said Sumantra Ray, MD, executive director of the NNEdPro Global Centre for Nutrition and Health in Cambridge, England.

“The findings are timely, not only because of the impact the pandemic has had on mental well-being, food security, and diet quality, especially in school children, but also in light of the recently published National Food Strategy for England, which highlighted gaps in school meal provision,” added Dr. Ray, who was not involved in the study.
 

Study results

In total, 10,853 schoolchildren completed the survey: 9% of Norfolk primary school children aged 9-11 and 22% of secondary school students, with approximately 6% of these in the 17- and 18-year-old age bracket. Comprehensive dietary questions explored fruit and vegetable intake, as well as type of breakfast and lunch eaten, alcohol intake, eligibility for free school meals, and satisfaction with weight.

The survey also gathered information on parameters ranging from having one’s own bedroom and bed and exposure to violence or discord in the home.

“Some of these were found to be associated with lower mental well-being scores, but we did not specifically investigate the interaction between these factors and the nutritional factors,” Dr. Hayhoe said. However, the difference in mental well-being between children who ate the most fruit and vegetables and those who ate the least was on a similar scale to those reporting daily, or almost daily, arguing or violence at home, he said.

Average mental health was assessed using validated age-appropriate measures. The mean mental health score of participants was 46.6 out of 70 for secondary school students and 46 out of 60 for primary school pupils.

Among the survey findings were:

• Just 25% of secondary school participants and 28.5% of primary school pupils reported eating the recommended five portions of fruits and vegetables a day, with 10% and 9%, respectively, eating none.
• 21% of secondary and 12% of primary school pupils consumed only a non–energy drink or nothing for breakfast, while 11.5% of secondary schoolchildren ate no lunch. In one high school class of 30, for example, four had nothing to eat or drink before starting classes in the morning, and three had nothing to eat or drink before starting classes in the afternoon.
• Higher combined fruit and vegetable intake was significantly associated in dose-related fashion with higher mental health scores: 3.73 (95% confidence interval, 2.94- 4.53) units higher in those consuming five or more fruits and vegetables (P < .001), compared with none.
• Breakfast or lunch type also correlated with significant differences in well-being scores. Compared with children consuming a conventional breakfast (porridge, toast, cereal, yogurt, fruit, or a cooked meal), those eating no breakfast had mean well-being scores that were 2.73 (95% CI, 2.11-3.35) units lower (P < .001). Those consuming only an energy drink scored even worse: 3.14 (95% CI, 1.20- 5.09) units lower (P = .002).
• Skipping lunch resulted in a 2.95-unit drop in well-being score (95% CI, 2.22-3.68, P < .001), compared with consuming a packed lunch.

In terms of the amounts of fruits and vegetables consumed, one or two daily portions were associated with a score 1.42 units higher, while three or four portions correlated with a score 2.34 units higher. Those eating five or more portions scored 3.73 units higher.

• For primary school pupils, eating only a snack for breakfast was associated with a score 5.50 units lower, and consuming only a non–energy drink was tied to a score 2.67 units lower than eating a conventional breakfast. Not eating any breakfast was associated with a score 3.62 units lower.
• Eating school food versus a packed lunch was associated with a score 1.27 units lower, although this wasn’t statistically significant. Having no lunch was associated with a score 6.08 units lower, although only a few children fell into this group.

“As a potentially modifiable factor, both at an individual and societal level, nutrition may therefore represent an important public health target for strategies to address childhood mental well-being,” the authors wrote, calling for further investigation of the association between nutrition and mental well-being.

This study was commissioned by Norfolk County Council Public Health and the Norfolk Safeguarding Children Board. The University of East Anglia and Social Care Partners provided funding to support Dr. Hayhoe’s work on this project.

Some coauthors are employed by the Norfolk County Council that commissioned the survey.
 

Good nutrition has long been linked to better behavior and academic performance in schoolchildren, as longstanding breakfast and lunch programs in U.S. schools attest. Now British researchers report that nutrition, a modifiable risk factor that can adversely impact mental health, should be part of public health strategies to boost children’s psychological wellness.

In a cross-sectional study published online Sept. 27 in BMJ Nutrition, Prevention & Health, a team from the University of East Anglia in Norwich, England, found a nutritious breakfast and lunch were linked to emotional well-being in schoolchildren of both primary and secondary school age. They also found that some school kids ate neither breakfast nor lunch.

In particular, eating more fruits and vegetables was significantly associated with better mental health in secondary schoolchildren, while a nutritious breakfast and lunch were linked to emotional well-being in students across the age spectrum, according to senior lecturer Richard P. Hayhoe, PhD, of East Anglia University and Anglia Ruskin University in Norwich and colleagues.

They found that primary school pupils who ate only a snack for breakfast had mental well-being scores 5.50 units lower than those eating a substantial breakfast, while having no lunch was tied to scores more than 6 units lower.

“The importance of good-quality nutrition for childhood growth and development is well established,” the authors wrote. “As a potentially modifiable factor, both at an individual and societal level, nutrition may therefore represent an important public health target for strategies to address childhood mental well-being.”

Their current analysis examined data on 7,570 secondary and 1,253 primary school children from 50 schools participating in the Norfolk Children and Young People Health and Well-being Survey 2017.

Multivariable linear regression measured the association between nutritional factors and mental well-being assessed by the Warwick-Edinburgh Mental Well-being Scale for secondary school pupils or by the Stirling Children’s Well-being Scale for primary school pupils. All analyses were adjusted for covariates including demographic, health variables, living/home situations, and adverse experiences.

“The 2017 survey provided a means for Norfolk children and young people to share their feelings on topics such as healthy lifestyles and nutrition, relationships, school experiences, bullying, and their mental well-being,” Dr. Hayhoe said in an interview. “Initial analysis of the data suggested an association between nutrition and well-being and so we decided to investigate this further.”

Dr. Hayhoe added that, as in the United States, youngsters in England get a high proportion of their daily calories from ultraprocessed convenience foods of lesser nutritional value.

“But what we didn’t know was whether the dietary habits of children in our survey had any association with their mental well-being,” he said. “Our current findings suggest that increasing fruit and vegetable consumption and ensuring all schoolchildren eat a nutritional breakfast and lunch may be of benefit to their mental well-being.”

His group cautions, however, that this is an observational study that cannot establish direct causation.

“This study provides the first insights into how fruit and vegetable intake affects children’s mental health, and contributes to the emerging evidence around ‘food and mood,’ ” said Sumantra Ray, MD, executive director of the NNEdPro Global Centre for Nutrition and Health in Cambridge, England.

“The findings are timely, not only because of the impact the pandemic has had on mental well-being, food security, and diet quality, especially in school children, but also in light of the recently published National Food Strategy for England, which highlighted gaps in school meal provision,” added Dr. Ray, who was not involved in the study.
 

Study results

In total, 10,853 schoolchildren completed the survey: 9% of Norfolk primary school children aged 9-11 and 22% of secondary school students, with approximately 6% of these in the 17- and 18-year-old age bracket. Comprehensive dietary questions explored fruit and vegetable intake, as well as type of breakfast and lunch eaten, alcohol intake, eligibility for free school meals, and satisfaction with weight.

The survey also gathered information on parameters ranging from having one’s own bedroom and bed and exposure to violence or discord in the home.

“Some of these were found to be associated with lower mental well-being scores, but we did not specifically investigate the interaction between these factors and the nutritional factors,” Dr. Hayhoe said. However, the difference in mental well-being between children who ate the most fruit and vegetables and those who ate the least was on a similar scale to those reporting daily, or almost daily, arguing or violence at home, he said.

Average mental health was assessed using validated age-appropriate measures. The mean mental health score of participants was 46.6 out of 70 for secondary school students and 46 out of 60 for primary school pupils.

Among the survey findings were:

• Just 25% of secondary school participants and 28.5% of primary school pupils reported eating the recommended five portions of fruits and vegetables a day, with 10% and 9%, respectively, eating none.
• 21% of secondary and 12% of primary school pupils consumed only a non–energy drink or nothing for breakfast, while 11.5% of secondary schoolchildren ate no lunch. In one high school class of 30, for example, four had nothing to eat or drink before starting classes in the morning, and three had nothing to eat or drink before starting classes in the afternoon.
• Higher combined fruit and vegetable intake was significantly associated in dose-related fashion with higher mental health scores: 3.73 (95% confidence interval, 2.94- 4.53) units higher in those consuming five or more fruits and vegetables (P < .001), compared with none.
• Breakfast or lunch type also correlated with significant differences in well-being scores. Compared with children consuming a conventional breakfast (porridge, toast, cereal, yogurt, fruit, or a cooked meal), those eating no breakfast had mean well-being scores that were 2.73 (95% CI, 2.11-3.35) units lower (P < .001). Those consuming only an energy drink scored even worse: 3.14 (95% CI, 1.20- 5.09) units lower (P = .002).
• Skipping lunch resulted in a 2.95-unit drop in well-being score (95% CI, 2.22-3.68, P < .001), compared with consuming a packed lunch.

In terms of the amounts of fruits and vegetables consumed, one or two daily portions were associated with a score 1.42 units higher, while three or four portions correlated with a score 2.34 units higher. Those eating five or more portions scored 3.73 units higher.

• For primary school pupils, eating only a snack for breakfast was associated with a score 5.50 units lower, and consuming only a non–energy drink was tied to a score 2.67 units lower than eating a conventional breakfast. Not eating any breakfast was associated with a score 3.62 units lower.
• Eating school food versus a packed lunch was associated with a score 1.27 units lower, although this wasn’t statistically significant. Having no lunch was associated with a score 6.08 units lower, although only a few children fell into this group.

“As a potentially modifiable factor, both at an individual and societal level, nutrition may therefore represent an important public health target for strategies to address childhood mental well-being,” the authors wrote, calling for further investigation of the association between nutrition and mental well-being.

This study was commissioned by Norfolk County Council Public Health and the Norfolk Safeguarding Children Board. The University of East Anglia and Social Care Partners provided funding to support Dr. Hayhoe’s work on this project.

Some coauthors are employed by the Norfolk County Council that commissioned the survey.
 

Good nutrition has long been linked to better behavior and academic performance in schoolchildren, as longstanding breakfast and lunch programs in U.S. schools attest. Now British researchers report that nutrition, a modifiable risk factor that can adversely impact mental health, should be part of public health strategies to boost children’s psychological wellness.

In a cross-sectional study published online Sept. 27 in BMJ Nutrition, Prevention & Health, a team from the University of East Anglia in Norwich, England, found a nutritious breakfast and lunch were linked to emotional well-being in schoolchildren of both primary and secondary school age. They also found that some school kids ate neither breakfast nor lunch.

In particular, eating more fruits and vegetables was significantly associated with better mental health in secondary schoolchildren, while a nutritious breakfast and lunch were linked to emotional well-being in students across the age spectrum, according to senior lecturer Richard P. Hayhoe, PhD, of East Anglia University and Anglia Ruskin University in Norwich and colleagues.

They found that primary school pupils who ate only a snack for breakfast had mental well-being scores 5.50 units lower than those eating a substantial breakfast, while having no lunch was tied to scores more than 6 units lower.

“The importance of good-quality nutrition for childhood growth and development is well established,” the authors wrote. “As a potentially modifiable factor, both at an individual and societal level, nutrition may therefore represent an important public health target for strategies to address childhood mental well-being.”

Their current analysis examined data on 7,570 secondary and 1,253 primary school children from 50 schools participating in the Norfolk Children and Young People Health and Well-being Survey 2017.

Multivariable linear regression measured the association between nutritional factors and mental well-being assessed by the Warwick-Edinburgh Mental Well-being Scale for secondary school pupils or by the Stirling Children’s Well-being Scale for primary school pupils. All analyses were adjusted for covariates including demographic, health variables, living/home situations, and adverse experiences.

“The 2017 survey provided a means for Norfolk children and young people to share their feelings on topics such as healthy lifestyles and nutrition, relationships, school experiences, bullying, and their mental well-being,” Dr. Hayhoe said in an interview. “Initial analysis of the data suggested an association between nutrition and well-being and so we decided to investigate this further.”

Dr. Hayhoe added that, as in the United States, youngsters in England get a high proportion of their daily calories from ultraprocessed convenience foods of lesser nutritional value.

“But what we didn’t know was whether the dietary habits of children in our survey had any association with their mental well-being,” he said. “Our current findings suggest that increasing fruit and vegetable consumption and ensuring all schoolchildren eat a nutritional breakfast and lunch may be of benefit to their mental well-being.”

His group cautions, however, that this is an observational study that cannot establish direct causation.

“This study provides the first insights into how fruit and vegetable intake affects children’s mental health, and contributes to the emerging evidence around ‘food and mood,’ ” said Sumantra Ray, MD, executive director of the NNEdPro Global Centre for Nutrition and Health in Cambridge, England.

“The findings are timely, not only because of the impact the pandemic has had on mental well-being, food security, and diet quality, especially in school children, but also in light of the recently published National Food Strategy for England, which highlighted gaps in school meal provision,” added Dr. Ray, who was not involved in the study.
 

Study results

In total, 10,853 schoolchildren completed the survey: 9% of Norfolk primary school children aged 9-11 and 22% of secondary school students, with approximately 6% of these in the 17- and 18-year-old age bracket. Comprehensive dietary questions explored fruit and vegetable intake, as well as type of breakfast and lunch eaten, alcohol intake, eligibility for free school meals, and satisfaction with weight.

The survey also gathered information on parameters ranging from having one’s own bedroom and bed and exposure to violence or discord in the home.

“Some of these were found to be associated with lower mental well-being scores, but we did not specifically investigate the interaction between these factors and the nutritional factors,” Dr. Hayhoe said. However, the difference in mental well-being between children who ate the most fruit and vegetables and those who ate the least was on a similar scale to those reporting daily, or almost daily, arguing or violence at home, he said.

Average mental health was assessed using validated age-appropriate measures. The mean mental health score of participants was 46.6 out of 70 for secondary school students and 46 out of 60 for primary school pupils.

Among the survey findings were:

• Just 25% of secondary school participants and 28.5% of primary school pupils reported eating the recommended five portions of fruits and vegetables a day, with 10% and 9%, respectively, eating none.
• 21% of secondary and 12% of primary school pupils consumed only a non–energy drink or nothing for breakfast, while 11.5% of secondary schoolchildren ate no lunch. In one high school class of 30, for example, four had nothing to eat or drink before starting classes in the morning, and three had nothing to eat or drink before starting classes in the afternoon.
• Higher combined fruit and vegetable intake was significantly associated in dose-related fashion with higher mental health scores: 3.73 (95% confidence interval, 2.94- 4.53) units higher in those consuming five or more fruits and vegetables (P < .001), compared with none.
• Breakfast or lunch type also correlated with significant differences in well-being scores. Compared with children consuming a conventional breakfast (porridge, toast, cereal, yogurt, fruit, or a cooked meal), those eating no breakfast had mean well-being scores that were 2.73 (95% CI, 2.11-3.35) units lower (P < .001). Those consuming only an energy drink scored even worse: 3.14 (95% CI, 1.20- 5.09) units lower (P = .002).
• Skipping lunch resulted in a 2.95-unit drop in well-being score (95% CI, 2.22-3.68, P < .001), compared with consuming a packed lunch.

In terms of the amounts of fruits and vegetables consumed, one or two daily portions were associated with a score 1.42 units higher, while three or four portions correlated with a score 2.34 units higher. Those eating five or more portions scored 3.73 units higher.

• For primary school pupils, eating only a snack for breakfast was associated with a score 5.50 units lower, and consuming only a non–energy drink was tied to a score 2.67 units lower than eating a conventional breakfast. Not eating any breakfast was associated with a score 3.62 units lower.
• Eating school food versus a packed lunch was associated with a score 1.27 units lower, although this wasn’t statistically significant. Having no lunch was associated with a score 6.08 units lower, although only a few children fell into this group.

“As a potentially modifiable factor, both at an individual and societal level, nutrition may therefore represent an important public health target for strategies to address childhood mental well-being,” the authors wrote, calling for further investigation of the association between nutrition and mental well-being.

This study was commissioned by Norfolk County Council Public Health and the Norfolk Safeguarding Children Board. The University of East Anglia and Social Care Partners provided funding to support Dr. Hayhoe’s work on this project.

Some coauthors are employed by the Norfolk County Council that commissioned the survey.
 

The U.S. Drug Enforcement Administration has issued a public safety alert over an “alarming” increase in fake prescription pills laced with the synthetic opioid fentanyl or the stimulant methamphetamine.

“The United States is facing an unprecedented crisis of overdose deaths fueled by illegally manufactured fentanyl and methamphetamine,” DEA Administrator Anne Milgram said in the alert.

“Counterfeit pills that contain these dangerous and extremely addictive drugs are more lethal and more accessible than ever before. DEA is focusing resources on taking down the violent drug traffickers causing the greatest harm and posing the greatest threat to the safety and health of Americans,” Ms. Milgram said.

Criminal drug networks are mass-producing fake fentanyl- and methamphetamine-laced pills and deceptively marketing them as legitimate prescription pills, the DEA warns.

These lethal counterfeit pills are made to look like legitimate prescription opioid medications such as oxycodone (Oxycontin, Percocet), hydrocodone (Vicodin), and alprazolam (Xanax); or stimulants like amphetamines (Adderall).

The agency has seized fake pills in every U.S. state. More than 9.5 million fake pills have been seized so far this year – more than the last 2 years combined.

The number of seized counterfeit pills with fentanyl has jumped nearly 430% since 2019. DEA lab tests reveal that two out of every five pills with fentanyl contain a potentially lethal dose.

These deadly pills are widely accessible and often sold on social media and e-commerce platforms – making them available to anyone with a smartphone, including minors, the DEA warns.

More than 93,000 people died of a drug overdose in the United States last year, according to federal statistics, and fentanyl is the primary driver of this alarming increase in overdose deaths, the DEA says.

The agency has launched a “One Pill Can Kill” public awareness campaign to educate the public of the dangers of counterfeit pills purchased outside of a licensed pharmacy. These pills are “illegal, dangerous, and potentially lethal,” the DEA warns.

This alert does not apply to legitimate pharmaceutical medications prescribed by doctors and dispensed by licensed pharmacists, the DEA says.

“The legitimate prescription supply chain is not impacted. Anyone filling a prescription at a licensed pharmacy can be confident that the medications they receive are safe when taken as directed by a medical professional,” the agency says.

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

The U.S. Drug Enforcement Administration has issued a public safety alert over an “alarming” increase in fake prescription pills laced with the synthetic opioid fentanyl or the stimulant methamphetamine.

“The United States is facing an unprecedented crisis of overdose deaths fueled by illegally manufactured fentanyl and methamphetamine,” DEA Administrator Anne Milgram said in the alert.

“Counterfeit pills that contain these dangerous and extremely addictive drugs are more lethal and more accessible than ever before. DEA is focusing resources on taking down the violent drug traffickers causing the greatest harm and posing the greatest threat to the safety and health of Americans,” Ms. Milgram said.

Criminal drug networks are mass-producing fake fentanyl- and methamphetamine-laced pills and deceptively marketing them as legitimate prescription pills, the DEA warns.

These lethal counterfeit pills are made to look like legitimate prescription opioid medications such as oxycodone (Oxycontin, Percocet), hydrocodone (Vicodin), and alprazolam (Xanax); or stimulants like amphetamines (Adderall).

The agency has seized fake pills in every U.S. state. More than 9.5 million fake pills have been seized so far this year – more than the last 2 years combined.

The number of seized counterfeit pills with fentanyl has jumped nearly 430% since 2019. DEA lab tests reveal that two out of every five pills with fentanyl contain a potentially lethal dose.

These deadly pills are widely accessible and often sold on social media and e-commerce platforms – making them available to anyone with a smartphone, including minors, the DEA warns.

More than 93,000 people died of a drug overdose in the United States last year, according to federal statistics, and fentanyl is the primary driver of this alarming increase in overdose deaths, the DEA says.

The agency has launched a “One Pill Can Kill” public awareness campaign to educate the public of the dangers of counterfeit pills purchased outside of a licensed pharmacy. These pills are “illegal, dangerous, and potentially lethal,” the DEA warns.

This alert does not apply to legitimate pharmaceutical medications prescribed by doctors and dispensed by licensed pharmacists, the DEA says.

“The legitimate prescription supply chain is not impacted. Anyone filling a prescription at a licensed pharmacy can be confident that the medications they receive are safe when taken as directed by a medical professional,” the agency says.

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

The U.S. Drug Enforcement Administration has issued a public safety alert over an “alarming” increase in fake prescription pills laced with the synthetic opioid fentanyl or the stimulant methamphetamine.

“The United States is facing an unprecedented crisis of overdose deaths fueled by illegally manufactured fentanyl and methamphetamine,” DEA Administrator Anne Milgram said in the alert.

“Counterfeit pills that contain these dangerous and extremely addictive drugs are more lethal and more accessible than ever before. DEA is focusing resources on taking down the violent drug traffickers causing the greatest harm and posing the greatest threat to the safety and health of Americans,” Ms. Milgram said.

Criminal drug networks are mass-producing fake fentanyl- and methamphetamine-laced pills and deceptively marketing them as legitimate prescription pills, the DEA warns.

These lethal counterfeit pills are made to look like legitimate prescription opioid medications such as oxycodone (Oxycontin, Percocet), hydrocodone (Vicodin), and alprazolam (Xanax); or stimulants like amphetamines (Adderall).

The agency has seized fake pills in every U.S. state. More than 9.5 million fake pills have been seized so far this year – more than the last 2 years combined.

The number of seized counterfeit pills with fentanyl has jumped nearly 430% since 2019. DEA lab tests reveal that two out of every five pills with fentanyl contain a potentially lethal dose.

These deadly pills are widely accessible and often sold on social media and e-commerce platforms – making them available to anyone with a smartphone, including minors, the DEA warns.

More than 93,000 people died of a drug overdose in the United States last year, according to federal statistics, and fentanyl is the primary driver of this alarming increase in overdose deaths, the DEA says.

The agency has launched a “One Pill Can Kill” public awareness campaign to educate the public of the dangers of counterfeit pills purchased outside of a licensed pharmacy. These pills are “illegal, dangerous, and potentially lethal,” the DEA warns.

This alert does not apply to legitimate pharmaceutical medications prescribed by doctors and dispensed by licensed pharmacists, the DEA says.

“The legitimate prescription supply chain is not impacted. Anyone filling a prescription at a licensed pharmacy can be confident that the medications they receive are safe when taken as directed by a medical professional,” the agency says.

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

When it comes to protecting diabetic hearts, sodium-glucose cotransporter-2 (SGLT2) inhibitors may have a slight edge over glucagonlike peptide-1 receptor agonists (GLP-1 RAs) according to the results of large, population-based, observational cohort study.

Around a 30% reduction in the risk for being hospitalized for heart failure was achieved in people with type 2 diabetes who were treated with a SGLT2 inhibitor over a GLP-1 RA regardless of whether the patients had a preexisting heart condition.

The findings, published in the Annals of Internal Medicine, also showed a 10% lower risk for myocardial infarction or stroke among those treated with a SGLT2 inhibitor who had preexisting cardiovascular disease (CVD), although there was no difference in risk between the two classes of drugs in those without preexisting CVD.

“These findings are important as they suggest that SGLT2 [inhibitors] and GLP-1 RA offer similar benefits in preventing myocardial infarction and stroke in patients with diabetes,” said study investigator Elisabetta Patorno, MD, DrPH, of Brigham and Women’s Hospital and Harvard Medical School in Boston, in an interview.

They also show “that SGLT2 [inhibitors] offer greater efficacy in preventing heart failure, which supports the existing guidelines,” she added.

Paul S. Jellinger, MD, MACE, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., said these data were likely to be “additive to guidelines but not transformative.” The overall analysis results were “not surprising.” It was not unexpected that SGLT2 inhibitors provided a robust chronic heart failure (CHF) benefit, particularly in individuals with history of CVD, he said.

Dr. Jellinger, a clinical endocrinologist and professor of clinical medicine on the voluntary faculty at the University of Miami, observed, however, that “the similar CVD benefit in both drug classes in patients without known CVD adds to our knowledge in this somewhat controversial area and may be useful to the clinician in evaluating therapy in a diabetic individual without evidence of or at high risk for CHF.”

Furthermore, “the study also reminds us that, as demonstrated in published meta-analysis, there is also a modest CHF benefit associated with GLP-1 RA treatment particularly in patients with a history of CVD.”
 

Addressing the knowledge gap

Thanks to the results of many large-scale, prospective, cardiovascular outcomes studies, both SGLT2 inhibitors and GLP1 RA have been recommended as treatment for people with diabetes who have established CVD. But with no direct head-to-head trials having been conducted, there is a gap in knowledge and there is currently little guidance for physicians on which drug class to choose for an individual patient.

To try to clarify things, Dr. Patorno and associates looked at data from more than 370,000 people with type 2 diabetes who had been treated between April 2013 and December 2017 with either a SGLT2 inhibitor (canagliflozin, dapagliflozin, or empagliflozin) or GLP-1 RA (albiglutide, dulaglutide, exenatide, or liraglutide).

One-to-one propensity score matching was used to create the study groups: participants were first grouped according to their history of CVD, and then by the class of drug they had been prescribed. The primary outcomes were hospitalization for MI, stroke, or heart failure.

Comparing the initiation of a SGLT2 inhibitor with GLP-1 RA therapy, the hazard ratios (HRs) for MI or stroke in patients with and without a history of CVD were a respective 0.90 (95% CI, 0.82 to 0.98) and 1.07 (0.97 to 1.18).

The corresponding hazard ratios for heart failure hospitalizations were 0.71 (0.64 to 0.79) and 0.69 (0.56 to 0.85).
 

Real-world studies are of ‘increasing value’

“As in other not-randomized studies based on real-world data, residual confounding cannot be completely ruled out,” Dr. Patorno acknowledged. She added, however that “state-of-the-art methodological strategies were implemented to minimize this possibility.”

Limitations notwithstanding, “real world studies are demonstrating increasing value,” observed Dr. Jellinger. Further large-scale cardiovascular outcomes trials that directly compare these two drug classes “are unlikely given the depth of information available now,” Dr. Jellinger suggested.

“This head-to-head retrospective study may be as close as we get and does represent the first effort at a comparison of these two classes.”

Dr. Patorno said of the potential clinical implications: “Because the two classes are equally effective for stroke and myocardial infarction, but the SGLT2 inhibitors are superior for heart failure, when considered in aggregate, SGLT2 inhibitors are likely to prevent more of these adverse cardiovascular events than GLP-1 RA.”

The study received no commercial funding and was supported by the Brigham and Women’s Hospital and Harvard Medical School Division of Pharmacoepidemiology and Pharmacoeconomics.

Dr. Patorno reported no conflicts of interest. Dr. Jellinger is on the speaker’s bureau for Astra Zeneca, Amgen, and Esperion, and has served on advisory boards for Corcept and Regeneron.

When it comes to protecting diabetic hearts, sodium-glucose cotransporter-2 (SGLT2) inhibitors may have a slight edge over glucagonlike peptide-1 receptor agonists (GLP-1 RAs) according to the results of large, population-based, observational cohort study.

Around a 30% reduction in the risk for being hospitalized for heart failure was achieved in people with type 2 diabetes who were treated with a SGLT2 inhibitor over a GLP-1 RA regardless of whether the patients had a preexisting heart condition.

The findings, published in the Annals of Internal Medicine, also showed a 10% lower risk for myocardial infarction or stroke among those treated with a SGLT2 inhibitor who had preexisting cardiovascular disease (CVD), although there was no difference in risk between the two classes of drugs in those without preexisting CVD.

“These findings are important as they suggest that SGLT2 [inhibitors] and GLP-1 RA offer similar benefits in preventing myocardial infarction and stroke in patients with diabetes,” said study investigator Elisabetta Patorno, MD, DrPH, of Brigham and Women’s Hospital and Harvard Medical School in Boston, in an interview.

They also show “that SGLT2 [inhibitors] offer greater efficacy in preventing heart failure, which supports the existing guidelines,” she added.

Paul S. Jellinger, MD, MACE, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., said these data were likely to be “additive to guidelines but not transformative.” The overall analysis results were “not surprising.” It was not unexpected that SGLT2 inhibitors provided a robust chronic heart failure (CHF) benefit, particularly in individuals with history of CVD, he said.

Dr. Jellinger, a clinical endocrinologist and professor of clinical medicine on the voluntary faculty at the University of Miami, observed, however, that “the similar CVD benefit in both drug classes in patients without known CVD adds to our knowledge in this somewhat controversial area and may be useful to the clinician in evaluating therapy in a diabetic individual without evidence of or at high risk for CHF.”

Furthermore, “the study also reminds us that, as demonstrated in published meta-analysis, there is also a modest CHF benefit associated with GLP-1 RA treatment particularly in patients with a history of CVD.”
 

Addressing the knowledge gap

Thanks to the results of many large-scale, prospective, cardiovascular outcomes studies, both SGLT2 inhibitors and GLP1 RA have been recommended as treatment for people with diabetes who have established CVD. But with no direct head-to-head trials having been conducted, there is a gap in knowledge and there is currently little guidance for physicians on which drug class to choose for an individual patient.

To try to clarify things, Dr. Patorno and associates looked at data from more than 370,000 people with type 2 diabetes who had been treated between April 2013 and December 2017 with either a SGLT2 inhibitor (canagliflozin, dapagliflozin, or empagliflozin) or GLP-1 RA (albiglutide, dulaglutide, exenatide, or liraglutide).

One-to-one propensity score matching was used to create the study groups: participants were first grouped according to their history of CVD, and then by the class of drug they had been prescribed. The primary outcomes were hospitalization for MI, stroke, or heart failure.

Comparing the initiation of a SGLT2 inhibitor with GLP-1 RA therapy, the hazard ratios (HRs) for MI or stroke in patients with and without a history of CVD were a respective 0.90 (95% CI, 0.82 to 0.98) and 1.07 (0.97 to 1.18).

The corresponding hazard ratios for heart failure hospitalizations were 0.71 (0.64 to 0.79) and 0.69 (0.56 to 0.85).
 

Real-world studies are of ‘increasing value’

“As in other not-randomized studies based on real-world data, residual confounding cannot be completely ruled out,” Dr. Patorno acknowledged. She added, however that “state-of-the-art methodological strategies were implemented to minimize this possibility.”

Limitations notwithstanding, “real world studies are demonstrating increasing value,” observed Dr. Jellinger. Further large-scale cardiovascular outcomes trials that directly compare these two drug classes “are unlikely given the depth of information available now,” Dr. Jellinger suggested.

“This head-to-head retrospective study may be as close as we get and does represent the first effort at a comparison of these two classes.”

Dr. Patorno said of the potential clinical implications: “Because the two classes are equally effective for stroke and myocardial infarction, but the SGLT2 inhibitors are superior for heart failure, when considered in aggregate, SGLT2 inhibitors are likely to prevent more of these adverse cardiovascular events than GLP-1 RA.”

The study received no commercial funding and was supported by the Brigham and Women’s Hospital and Harvard Medical School Division of Pharmacoepidemiology and Pharmacoeconomics.

Dr. Patorno reported no conflicts of interest. Dr. Jellinger is on the speaker’s bureau for Astra Zeneca, Amgen, and Esperion, and has served on advisory boards for Corcept and Regeneron.

When it comes to protecting diabetic hearts, sodium-glucose cotransporter-2 (SGLT2) inhibitors may have a slight edge over glucagonlike peptide-1 receptor agonists (GLP-1 RAs) according to the results of large, population-based, observational cohort study.

Around a 30% reduction in the risk for being hospitalized for heart failure was achieved in people with type 2 diabetes who were treated with a SGLT2 inhibitor over a GLP-1 RA regardless of whether the patients had a preexisting heart condition.

The findings, published in the Annals of Internal Medicine, also showed a 10% lower risk for myocardial infarction or stroke among those treated with a SGLT2 inhibitor who had preexisting cardiovascular disease (CVD), although there was no difference in risk between the two classes of drugs in those without preexisting CVD.

“These findings are important as they suggest that SGLT2 [inhibitors] and GLP-1 RA offer similar benefits in preventing myocardial infarction and stroke in patients with diabetes,” said study investigator Elisabetta Patorno, MD, DrPH, of Brigham and Women’s Hospital and Harvard Medical School in Boston, in an interview.

They also show “that SGLT2 [inhibitors] offer greater efficacy in preventing heart failure, which supports the existing guidelines,” she added.

Paul S. Jellinger, MD, MACE, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., said these data were likely to be “additive to guidelines but not transformative.” The overall analysis results were “not surprising.” It was not unexpected that SGLT2 inhibitors provided a robust chronic heart failure (CHF) benefit, particularly in individuals with history of CVD, he said.

Dr. Jellinger, a clinical endocrinologist and professor of clinical medicine on the voluntary faculty at the University of Miami, observed, however, that “the similar CVD benefit in both drug classes in patients without known CVD adds to our knowledge in this somewhat controversial area and may be useful to the clinician in evaluating therapy in a diabetic individual without evidence of or at high risk for CHF.”

Furthermore, “the study also reminds us that, as demonstrated in published meta-analysis, there is also a modest CHF benefit associated with GLP-1 RA treatment particularly in patients with a history of CVD.”
 

Addressing the knowledge gap

Thanks to the results of many large-scale, prospective, cardiovascular outcomes studies, both SGLT2 inhibitors and GLP1 RA have been recommended as treatment for people with diabetes who have established CVD. But with no direct head-to-head trials having been conducted, there is a gap in knowledge and there is currently little guidance for physicians on which drug class to choose for an individual patient.

To try to clarify things, Dr. Patorno and associates looked at data from more than 370,000 people with type 2 diabetes who had been treated between April 2013 and December 2017 with either a SGLT2 inhibitor (canagliflozin, dapagliflozin, or empagliflozin) or GLP-1 RA (albiglutide, dulaglutide, exenatide, or liraglutide).

One-to-one propensity score matching was used to create the study groups: participants were first grouped according to their history of CVD, and then by the class of drug they had been prescribed. The primary outcomes were hospitalization for MI, stroke, or heart failure.

Comparing the initiation of a SGLT2 inhibitor with GLP-1 RA therapy, the hazard ratios (HRs) for MI or stroke in patients with and without a history of CVD were a respective 0.90 (95% CI, 0.82 to 0.98) and 1.07 (0.97 to 1.18).

The corresponding hazard ratios for heart failure hospitalizations were 0.71 (0.64 to 0.79) and 0.69 (0.56 to 0.85).
 

Real-world studies are of ‘increasing value’

“As in other not-randomized studies based on real-world data, residual confounding cannot be completely ruled out,” Dr. Patorno acknowledged. She added, however that “state-of-the-art methodological strategies were implemented to minimize this possibility.”

Limitations notwithstanding, “real world studies are demonstrating increasing value,” observed Dr. Jellinger. Further large-scale cardiovascular outcomes trials that directly compare these two drug classes “are unlikely given the depth of information available now,” Dr. Jellinger suggested.

“This head-to-head retrospective study may be as close as we get and does represent the first effort at a comparison of these two classes.”

Dr. Patorno said of the potential clinical implications: “Because the two classes are equally effective for stroke and myocardial infarction, but the SGLT2 inhibitors are superior for heart failure, when considered in aggregate, SGLT2 inhibitors are likely to prevent more of these adverse cardiovascular events than GLP-1 RA.”

The study received no commercial funding and was supported by the Brigham and Women’s Hospital and Harvard Medical School Division of Pharmacoepidemiology and Pharmacoeconomics.

Dr. Patorno reported no conflicts of interest. Dr. Jellinger is on the speaker’s bureau for Astra Zeneca, Amgen, and Esperion, and has served on advisory boards for Corcept and Regeneron.

Physical activity, long recommended by health experts to reduce risk for obesity, heart disease, type 2 diabetes, high blood pressure, hypercholesterolemia, and other cardiovascular disease risk factors, is also associated with increases in the amount of calcium deposited in the coronary arteries, new observational data suggest.

In a prospective cohort study of Korean men and women 18 years and older, participants who were the most physically active had the fastest progression of their coronary artery calcium (CAC) scores at 5 years, compared with those who were the least physically active.

“People who exercise may have an increase in their coronary calcium levels, but this is not necessarily bad news. This may mean that atherosclerotic lesions in the coronary arteries are becoming more stable and less dangerous, but we need additional research to understand these changes,” Eliseo Guallar, MD, PhD, professor, Johns Hopkins Bloomberg School of Public Health, Baltimore, the study’s corresponding author, said in an interview.

This paradoxical effect notwithstanding, doctors should continue to advise their patients to follow the physical activity guidelines for Americans that were published in 2018, Dr. Guallar said.

“Physical activity is a key component of a healthy lifestyle. Our analysis can be useful, however, if someone starts exercising and sees that his or her coronary calcium score goes up,” he said.

The study is published online September 20 in Heart.

The degree of build-up of calcium deposits in the coronary arteries is used to determine future cardiovascular disease risk and to guide treatment to prevent myocardial infarction and stroke. A CAC score of at least 100 Agatston units indicates that treatment with statins is warranted, the researchers write.

In the current study, investigators — led by Ki-Chul Sung, MD, Sungkyunkwan University School of Medicine, Seoul, Korea, and Yun Soo Hong, MD, Johns Hopkins Bloomberg School of Public Health, Baltimore — explored the link between different degrees of physical activity and the progression of CAC scores in healthy adults.

“While physical activity improves a wide array of cardiovascular and metabolic biomarkers, endurance athletes were more likely to have a coronary artery calcium (CAC) score >300 Agatston units or coronary plaques compared with sedentary men with a similar risk profile. It is not clear if exercise may itself be associated with calcification of the arteries,” the authors write.

The researchers studied 25,485 participants (22,741 men and 2,744 women) who were part of the Kangbuk Samsung Health Study. All were free of cardiovascular disease at study entry and underwent comprehensive health screening exams at one of two major health centers in Seoul and Suwon, South Korea, between March 1, 2011, and December 31, 2017.

At each exam, participants filled out a questionnaire that included questions on medical and family history, smoking habits, alcohol intake, and education level.

Participants were also quizzed at baseline about their physical activity, using the Korean version of the International Physical Activity Questionnaire Short Form (IPAQ-SF).

On the basis of that, they were categorized into one of three categories: inactive; moderately active, defined as at least 3 days of vigorous-intensity activity for at least 20 min/day or at least 5 days of moderate-intensity activity or walking for at least 30 min/ day or at least 5 days of any combination of walking and moderate- or vigorous-intensity activities, attaining at least 600 MET-min/week; or health-enhancing physically active (HEPA), defined as at least 3 days of vigorous-intensity activity, attaining at least 1,500 MET-min/week or 7 days of any combination of walking or moderate- or vigorous-intensity activities, attaining at least 3000 MET-min/week.  

Of the study participants, 47% were classified as inactive, 38% as moderately active, and 15% as HEPA.

Those who were more physically active tended to be older and less likely to smoke than less physically active participants. They also had lower total cholesterol, more hypertension, and existing evidence of calcium deposits in their coronary arteries.

A graded association between physical activity level and the prevalence and progression of coronary artery calcification was seen, irrespective of CAC scores at the start of monitoring.

At baseline, the estimated adjusted average baseline CAC scores in inactive participants was 9.45 (95% CI, 8.76 - 10.14), in moderately active participants was 10.20 (95% CI, 9.40 - 11.00), and in HEPA participants was 12.04 (95% CI, 10.81 - 13.26).

Compared with the least active participants, the estimated adjusted 5-year average increases in CAC was 3.20 (95% CI, 0.72 - 5.69) in moderately active participants and 8.16 (95% CI, 4.80 - 11.53) in HEPA participants.

A higher level of physical activity was associated with faster progression of CAC scores, both in participants with CAC score of 0 at baseline and in those with prevalent CAC.

The authors note there are several limitations to consider when interpreting their findings. These include the absence of an objective assessment of physical activity, the inability to evaluate the association between physical activity and CAC levels with incident cardiovascular events because of a lack of data, and the lack of information on incident myocardial infarction, stroke, CAC density, or volume.

Physical activity might increase coronary atherosclerosis through mechanical stress and vessel wall injury of coronary arteries; physiologic responses during exercise, such as increased blood pressure; increased parathyroid hormone levels; and changes in coronary hemodynamics and inflammation. “In addition, other factors, such as diet, vitamins, and minerals, may change with physical activity,” the authors write.

“The second possibility is that physical activity may increase CAC scores without increasing cardiovascular disease risk,” they write.

“The cardiovascular benefits of physical activity are unquestionable,” the authors emphasize, adding that the national guidelines recommend at least 150 to 300 minutes per week of moderate-intensity or 75 to 150 minutes per week of vigorous-intensity aerobic physical activity.

“Patients and physicians, however, need to consider that engaging in physical activity may accelerate the progression of coronary calcium, possibly due to plaque healing, stabilization and calcification,” they conclude.

Dr. Guallar added: “We would like to link our research to clinical outcomes, so that we can really be sure that the increase in coronary calcium scores does not imply an increase in risk.”

“Do these findings mean that we should stop using coronary artery calcium scores to assess coronary artery disease?” ask Gaurav Gulsin, MD, and Alastair James Moss, MD, University of Leicester, United Kingdom, in an accompanying editorial.

The study highlights the complexity of interpreting CAC scores in patients who have implemented recommendations for physical activity or started statin therapy, they note.

“While proponents would argue that it is an effective tool to screen for subclinical atherosclerosis in asymptomatic individuals, clinicians should be cautious regarding the overuse of this test in otherwise healthy individuals. The coronary artery calcium paradox should not result in paradoxical care for our patients,” Dr. Gulsin and Dr. Moss conclude.

Dr. Sung, Dr. Hong, and the other study authors report no relevant financial relationships. The British Heart Foundation provides funding support for Dr. Gulsin and Dr. Moss.

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

Physical activity, long recommended by health experts to reduce risk for obesity, heart disease, type 2 diabetes, high blood pressure, hypercholesterolemia, and other cardiovascular disease risk factors, is also associated with increases in the amount of calcium deposited in the coronary arteries, new observational data suggest.

In a prospective cohort study of Korean men and women 18 years and older, participants who were the most physically active had the fastest progression of their coronary artery calcium (CAC) scores at 5 years, compared with those who were the least physically active.

“People who exercise may have an increase in their coronary calcium levels, but this is not necessarily bad news. This may mean that atherosclerotic lesions in the coronary arteries are becoming more stable and less dangerous, but we need additional research to understand these changes,” Eliseo Guallar, MD, PhD, professor, Johns Hopkins Bloomberg School of Public Health, Baltimore, the study’s corresponding author, said in an interview.

This paradoxical effect notwithstanding, doctors should continue to advise their patients to follow the physical activity guidelines for Americans that were published in 2018, Dr. Guallar said.

“Physical activity is a key component of a healthy lifestyle. Our analysis can be useful, however, if someone starts exercising and sees that his or her coronary calcium score goes up,” he said.

The study is published online September 20 in Heart.

The degree of build-up of calcium deposits in the coronary arteries is used to determine future cardiovascular disease risk and to guide treatment to prevent myocardial infarction and stroke. A CAC score of at least 100 Agatston units indicates that treatment with statins is warranted, the researchers write.

In the current study, investigators — led by Ki-Chul Sung, MD, Sungkyunkwan University School of Medicine, Seoul, Korea, and Yun Soo Hong, MD, Johns Hopkins Bloomberg School of Public Health, Baltimore — explored the link between different degrees of physical activity and the progression of CAC scores in healthy adults.

“While physical activity improves a wide array of cardiovascular and metabolic biomarkers, endurance athletes were more likely to have a coronary artery calcium (CAC) score >300 Agatston units or coronary plaques compared with sedentary men with a similar risk profile. It is not clear if exercise may itself be associated with calcification of the arteries,” the authors write.

The researchers studied 25,485 participants (22,741 men and 2,744 women) who were part of the Kangbuk Samsung Health Study. All were free of cardiovascular disease at study entry and underwent comprehensive health screening exams at one of two major health centers in Seoul and Suwon, South Korea, between March 1, 2011, and December 31, 2017.

At each exam, participants filled out a questionnaire that included questions on medical and family history, smoking habits, alcohol intake, and education level.

Participants were also quizzed at baseline about their physical activity, using the Korean version of the International Physical Activity Questionnaire Short Form (IPAQ-SF).

On the basis of that, they were categorized into one of three categories: inactive; moderately active, defined as at least 3 days of vigorous-intensity activity for at least 20 min/day or at least 5 days of moderate-intensity activity or walking for at least 30 min/ day or at least 5 days of any combination of walking and moderate- or vigorous-intensity activities, attaining at least 600 MET-min/week; or health-enhancing physically active (HEPA), defined as at least 3 days of vigorous-intensity activity, attaining at least 1,500 MET-min/week or 7 days of any combination of walking or moderate- or vigorous-intensity activities, attaining at least 3000 MET-min/week.  

Of the study participants, 47% were classified as inactive, 38% as moderately active, and 15% as HEPA.

Those who were more physically active tended to be older and less likely to smoke than less physically active participants. They also had lower total cholesterol, more hypertension, and existing evidence of calcium deposits in their coronary arteries.

A graded association between physical activity level and the prevalence and progression of coronary artery calcification was seen, irrespective of CAC scores at the start of monitoring.

At baseline, the estimated adjusted average baseline CAC scores in inactive participants was 9.45 (95% CI, 8.76 - 10.14), in moderately active participants was 10.20 (95% CI, 9.40 - 11.00), and in HEPA participants was 12.04 (95% CI, 10.81 - 13.26).

Compared with the least active participants, the estimated adjusted 5-year average increases in CAC was 3.20 (95% CI, 0.72 - 5.69) in moderately active participants and 8.16 (95% CI, 4.80 - 11.53) in HEPA participants.

A higher level of physical activity was associated with faster progression of CAC scores, both in participants with CAC score of 0 at baseline and in those with prevalent CAC.

The authors note there are several limitations to consider when interpreting their findings. These include the absence of an objective assessment of physical activity, the inability to evaluate the association between physical activity and CAC levels with incident cardiovascular events because of a lack of data, and the lack of information on incident myocardial infarction, stroke, CAC density, or volume.

Physical activity might increase coronary atherosclerosis through mechanical stress and vessel wall injury of coronary arteries; physiologic responses during exercise, such as increased blood pressure; increased parathyroid hormone levels; and changes in coronary hemodynamics and inflammation. “In addition, other factors, such as diet, vitamins, and minerals, may change with physical activity,” the authors write.

“The second possibility is that physical activity may increase CAC scores without increasing cardiovascular disease risk,” they write.

“The cardiovascular benefits of physical activity are unquestionable,” the authors emphasize, adding that the national guidelines recommend at least 150 to 300 minutes per week of moderate-intensity or 75 to 150 minutes per week of vigorous-intensity aerobic physical activity.

“Patients and physicians, however, need to consider that engaging in physical activity may accelerate the progression of coronary calcium, possibly due to plaque healing, stabilization and calcification,” they conclude.

Dr. Guallar added: “We would like to link our research to clinical outcomes, so that we can really be sure that the increase in coronary calcium scores does not imply an increase in risk.”

“Do these findings mean that we should stop using coronary artery calcium scores to assess coronary artery disease?” ask Gaurav Gulsin, MD, and Alastair James Moss, MD, University of Leicester, United Kingdom, in an accompanying editorial.

The study highlights the complexity of interpreting CAC scores in patients who have implemented recommendations for physical activity or started statin therapy, they note.

“While proponents would argue that it is an effective tool to screen for subclinical atherosclerosis in asymptomatic individuals, clinicians should be cautious regarding the overuse of this test in otherwise healthy individuals. The coronary artery calcium paradox should not result in paradoxical care for our patients,” Dr. Gulsin and Dr. Moss conclude.

Dr. Sung, Dr. Hong, and the other study authors report no relevant financial relationships. The British Heart Foundation provides funding support for Dr. Gulsin and Dr. Moss.

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

Physical activity, long recommended by health experts to reduce risk for obesity, heart disease, type 2 diabetes, high blood pressure, hypercholesterolemia, and other cardiovascular disease risk factors, is also associated with increases in the amount of calcium deposited in the coronary arteries, new observational data suggest.

In a prospective cohort study of Korean men and women 18 years and older, participants who were the most physically active had the fastest progression of their coronary artery calcium (CAC) scores at 5 years, compared with those who were the least physically active.

“People who exercise may have an increase in their coronary calcium levels, but this is not necessarily bad news. This may mean that atherosclerotic lesions in the coronary arteries are becoming more stable and less dangerous, but we need additional research to understand these changes,” Eliseo Guallar, MD, PhD, professor, Johns Hopkins Bloomberg School of Public Health, Baltimore, the study’s corresponding author, said in an interview.

This paradoxical effect notwithstanding, doctors should continue to advise their patients to follow the physical activity guidelines for Americans that were published in 2018, Dr. Guallar said.

“Physical activity is a key component of a healthy lifestyle. Our analysis can be useful, however, if someone starts exercising and sees that his or her coronary calcium score goes up,” he said.

The study is published online September 20 in Heart.

The degree of build-up of calcium deposits in the coronary arteries is used to determine future cardiovascular disease risk and to guide treatment to prevent myocardial infarction and stroke. A CAC score of at least 100 Agatston units indicates that treatment with statins is warranted, the researchers write.

In the current study, investigators — led by Ki-Chul Sung, MD, Sungkyunkwan University School of Medicine, Seoul, Korea, and Yun Soo Hong, MD, Johns Hopkins Bloomberg School of Public Health, Baltimore — explored the link between different degrees of physical activity and the progression of CAC scores in healthy adults.

“While physical activity improves a wide array of cardiovascular and metabolic biomarkers, endurance athletes were more likely to have a coronary artery calcium (CAC) score >300 Agatston units or coronary plaques compared with sedentary men with a similar risk profile. It is not clear if exercise may itself be associated with calcification of the arteries,” the authors write.

The researchers studied 25,485 participants (22,741 men and 2,744 women) who were part of the Kangbuk Samsung Health Study. All were free of cardiovascular disease at study entry and underwent comprehensive health screening exams at one of two major health centers in Seoul and Suwon, South Korea, between March 1, 2011, and December 31, 2017.

At each exam, participants filled out a questionnaire that included questions on medical and family history, smoking habits, alcohol intake, and education level.

Participants were also quizzed at baseline about their physical activity, using the Korean version of the International Physical Activity Questionnaire Short Form (IPAQ-SF).

On the basis of that, they were categorized into one of three categories: inactive; moderately active, defined as at least 3 days of vigorous-intensity activity for at least 20 min/day or at least 5 days of moderate-intensity activity or walking for at least 30 min/ day or at least 5 days of any combination of walking and moderate- or vigorous-intensity activities, attaining at least 600 MET-min/week; or health-enhancing physically active (HEPA), defined as at least 3 days of vigorous-intensity activity, attaining at least 1,500 MET-min/week or 7 days of any combination of walking or moderate- or vigorous-intensity activities, attaining at least 3000 MET-min/week.  

Of the study participants, 47% were classified as inactive, 38% as moderately active, and 15% as HEPA.

Those who were more physically active tended to be older and less likely to smoke than less physically active participants. They also had lower total cholesterol, more hypertension, and existing evidence of calcium deposits in their coronary arteries.

A graded association between physical activity level and the prevalence and progression of coronary artery calcification was seen, irrespective of CAC scores at the start of monitoring.

At baseline, the estimated adjusted average baseline CAC scores in inactive participants was 9.45 (95% CI, 8.76 - 10.14), in moderately active participants was 10.20 (95% CI, 9.40 - 11.00), and in HEPA participants was 12.04 (95% CI, 10.81 - 13.26).

Compared with the least active participants, the estimated adjusted 5-year average increases in CAC was 3.20 (95% CI, 0.72 - 5.69) in moderately active participants and 8.16 (95% CI, 4.80 - 11.53) in HEPA participants.

A higher level of physical activity was associated with faster progression of CAC scores, both in participants with CAC score of 0 at baseline and in those with prevalent CAC.

The authors note there are several limitations to consider when interpreting their findings. These include the absence of an objective assessment of physical activity, the inability to evaluate the association between physical activity and CAC levels with incident cardiovascular events because of a lack of data, and the lack of information on incident myocardial infarction, stroke, CAC density, or volume.

Physical activity might increase coronary atherosclerosis through mechanical stress and vessel wall injury of coronary arteries; physiologic responses during exercise, such as increased blood pressure; increased parathyroid hormone levels; and changes in coronary hemodynamics and inflammation. “In addition, other factors, such as diet, vitamins, and minerals, may change with physical activity,” the authors write.

“The second possibility is that physical activity may increase CAC scores without increasing cardiovascular disease risk,” they write.

“The cardiovascular benefits of physical activity are unquestionable,” the authors emphasize, adding that the national guidelines recommend at least 150 to 300 minutes per week of moderate-intensity or 75 to 150 minutes per week of vigorous-intensity aerobic physical activity.

“Patients and physicians, however, need to consider that engaging in physical activity may accelerate the progression of coronary calcium, possibly due to plaque healing, stabilization and calcification,” they conclude.

Dr. Guallar added: “We would like to link our research to clinical outcomes, so that we can really be sure that the increase in coronary calcium scores does not imply an increase in risk.”

“Do these findings mean that we should stop using coronary artery calcium scores to assess coronary artery disease?” ask Gaurav Gulsin, MD, and Alastair James Moss, MD, University of Leicester, United Kingdom, in an accompanying editorial.

The study highlights the complexity of interpreting CAC scores in patients who have implemented recommendations for physical activity or started statin therapy, they note.

“While proponents would argue that it is an effective tool to screen for subclinical atherosclerosis in asymptomatic individuals, clinicians should be cautious regarding the overuse of this test in otherwise healthy individuals. The coronary artery calcium paradox should not result in paradoxical care for our patients,” Dr. Gulsin and Dr. Moss conclude.

Dr. Sung, Dr. Hong, and the other study authors report no relevant financial relationships. The British Heart Foundation provides funding support for Dr. Gulsin and Dr. Moss.

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

A 4-month, structured diet and exercise intervention lowered blood pressure in adults with resistant blood pressure, according to results from a randomized, clinical trial. The program also led to improvements in baroreflex sensitivity, heart rate variability, and flow-mediated dilation, compared with individuals who received only a single education session.

The intervention included instruction from a nutritionist on how to follow the Dietary Approaches to Stop Hypertension (DASH) diet, as well as restricting calories and sodium to less than 2,300 mg/day. It included weekly, 45-minute group counseling sessions, run by a clinical psychiatrist, focusing on eating behaviors. The exercise component included 30- to 45-minute sessions at 70%-85% of initial heart rate reserve, carried out three times per week at a cardiac rehabilitation facility.

“While some individuals can make the lifestyle changes on their own, a structured program of supervised exercise and dietary modification conducted by a multidisciplinary team of physicians, psychologists, nutritionists, and physical therapists/exercise physiologists found in cardiac rehabilitation programs throughout the country is likely to be more effective. There are many cardiac rehabilitation programs throughout the country that are accessible to most patients,” said lead author James Blumenthal, PhD, the J.P. Gibbons Professor in Psychiatry and Behavioral Sciences at Duke University, Durham, N.C.

The study, called Treating Resistant Hypertension Using Lifestyle Modification to Promote Health (TRIUMPH), was published in Circulation. It is one of few that have examined lifestyle interventions in resistant hypertension, defined as systolic blood pressure ≥ 130 mm Hg or diastolic blood pressure ≥ 80 mm Hg after adherence to three or more optimally-dosed antihypertensive medications of three different classes, including one diuretic.

“This is a nice study [that] emphasizes what we often forget: Lifestyle factors, especially salt intake, are important drivers of resistant hypertension. Our own studies have shown that this is predominantly a salt retaining state, and one would expect dietary salt restriction to be particularly effective in this group of patients and that is what this study showed,” said Bryan Williams, MD, who was asked to comment on the study. Dr. Williams is chair of medicine at University College London.

The results should also be reassuring to some who worried that exercise might lead to worsened blood pressure. “This study showed that in patients with resistant hypertension, though not out of control blood pressures, exercise was not only safe, but effective in lowering their blood pressure,” said Deepak L. Bhatt, MD, MPH, who was asked to comment. He is executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, and professor of medicine at Harvard Medical School, both in Boston.

The new research isn’t unique. In August, researchers in Portugal and Brazil showed that a 12-week exercise-only intervention reduced 24-hour and daytime ambulatory systolic and diastolic blood pressure. The two studies communicate the same message. “Lifestyle changes can work for resistant hypertension. So, two independent, modest-sized studies with essentially the same, positive, actionable conclusion,” said Dr. Bhatt, adding that the next step should be a larger, multicenter trial.

In the new study, 90 patients were assigned to the diet and exercise intervention and 50 to the control group. They had a mean age of 63 years, and 48% were women. Participants attended 94% of DASH diet classes and 89% of exercise sessions, and both groups had excellent adherence to medications.

The treatment group had a greater reduction in clinic systolic BP (–12.5 versus –7.1 mm Hg; P = .005) and diastolic BP (–5.9 versus –3.7 mm Hg; P = .034), as well as 24-hour ambulatory systolic BP (–7.0 versus –0.3 mm Hg; P = .001). The treatment group also had more improvement in resting baroreflex sensitivity (2.3 versus –1.1 ms/mm Hg; P = .003), high-frequency heart rate variability (0.4 versus –0.2 ln ms²; P = .025, and flow-mediated dilation (0.3% versus –1.4%, P = .022). The two groups had similar outcomes with respect to pulse wave velocity and left ventricular mass.

“Results of the TRIUMPH study suggest that policymakers should consider resistant hypertension as a new indication for cardiac rehabilitation with appropriate coverage by governmental agencies and private insurers,” Dr. Blumenthal said.

“This is an important new, evidence-based intervention for resistant hypertension. It is safe and relatively inexpensive. It should now be something physicians routinely offer these patients. Hopefully in the future, insurers will cover cardiac rehabilitation for patients with resistant hypertension,” Dr. Bhatt said.

The study also pointed towards an effective approach for patients who may be unable to sustain lifestyle changes. “Of course, not every patient will be able to maintain a healthy diet and an exercise program on their own, thus a cardiac rehabilitation program can be an excellent way to increase the likelihood of successful lifestyle modification,” Dr. Bhatt said.

TRIUMPH was sponsored by grants from the National Heart, Lung, and Blood Institute. None of the authors had disclosures to report. Dr. Bhatt disclosed having financial relationships with more than 40 pharmaceutical companies. Dr. Williams reported having no relevant financial disclosures.
 

A 4-month, structured diet and exercise intervention lowered blood pressure in adults with resistant blood pressure, according to results from a randomized, clinical trial. The program also led to improvements in baroreflex sensitivity, heart rate variability, and flow-mediated dilation, compared with individuals who received only a single education session.

The intervention included instruction from a nutritionist on how to follow the Dietary Approaches to Stop Hypertension (DASH) diet, as well as restricting calories and sodium to less than 2,300 mg/day. It included weekly, 45-minute group counseling sessions, run by a clinical psychiatrist, focusing on eating behaviors. The exercise component included 30- to 45-minute sessions at 70%-85% of initial heart rate reserve, carried out three times per week at a cardiac rehabilitation facility.

“While some individuals can make the lifestyle changes on their own, a structured program of supervised exercise and dietary modification conducted by a multidisciplinary team of physicians, psychologists, nutritionists, and physical therapists/exercise physiologists found in cardiac rehabilitation programs throughout the country is likely to be more effective. There are many cardiac rehabilitation programs throughout the country that are accessible to most patients,” said lead author James Blumenthal, PhD, the J.P. Gibbons Professor in Psychiatry and Behavioral Sciences at Duke University, Durham, N.C.

The study, called Treating Resistant Hypertension Using Lifestyle Modification to Promote Health (TRIUMPH), was published in Circulation. It is one of few that have examined lifestyle interventions in resistant hypertension, defined as systolic blood pressure ≥ 130 mm Hg or diastolic blood pressure ≥ 80 mm Hg after adherence to three or more optimally-dosed antihypertensive medications of three different classes, including one diuretic.

“This is a nice study [that] emphasizes what we often forget: Lifestyle factors, especially salt intake, are important drivers of resistant hypertension. Our own studies have shown that this is predominantly a salt retaining state, and one would expect dietary salt restriction to be particularly effective in this group of patients and that is what this study showed,” said Bryan Williams, MD, who was asked to comment on the study. Dr. Williams is chair of medicine at University College London.

The results should also be reassuring to some who worried that exercise might lead to worsened blood pressure. “This study showed that in patients with resistant hypertension, though not out of control blood pressures, exercise was not only safe, but effective in lowering their blood pressure,” said Deepak L. Bhatt, MD, MPH, who was asked to comment. He is executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, and professor of medicine at Harvard Medical School, both in Boston.

The new research isn’t unique. In August, researchers in Portugal and Brazil showed that a 12-week exercise-only intervention reduced 24-hour and daytime ambulatory systolic and diastolic blood pressure. The two studies communicate the same message. “Lifestyle changes can work for resistant hypertension. So, two independent, modest-sized studies with essentially the same, positive, actionable conclusion,” said Dr. Bhatt, adding that the next step should be a larger, multicenter trial.

In the new study, 90 patients were assigned to the diet and exercise intervention and 50 to the control group. They had a mean age of 63 years, and 48% were women. Participants attended 94% of DASH diet classes and 89% of exercise sessions, and both groups had excellent adherence to medications.

The treatment group had a greater reduction in clinic systolic BP (–12.5 versus –7.1 mm Hg; P = .005) and diastolic BP (–5.9 versus –3.7 mm Hg; P = .034), as well as 24-hour ambulatory systolic BP (–7.0 versus –0.3 mm Hg; P = .001). The treatment group also had more improvement in resting baroreflex sensitivity (2.3 versus –1.1 ms/mm Hg; P = .003), high-frequency heart rate variability (0.4 versus –0.2 ln ms²; P = .025, and flow-mediated dilation (0.3% versus –1.4%, P = .022). The two groups had similar outcomes with respect to pulse wave velocity and left ventricular mass.

“Results of the TRIUMPH study suggest that policymakers should consider resistant hypertension as a new indication for cardiac rehabilitation with appropriate coverage by governmental agencies and private insurers,” Dr. Blumenthal said.

“This is an important new, evidence-based intervention for resistant hypertension. It is safe and relatively inexpensive. It should now be something physicians routinely offer these patients. Hopefully in the future, insurers will cover cardiac rehabilitation for patients with resistant hypertension,” Dr. Bhatt said.

The study also pointed towards an effective approach for patients who may be unable to sustain lifestyle changes. “Of course, not every patient will be able to maintain a healthy diet and an exercise program on their own, thus a cardiac rehabilitation program can be an excellent way to increase the likelihood of successful lifestyle modification,” Dr. Bhatt said.

TRIUMPH was sponsored by grants from the National Heart, Lung, and Blood Institute. None of the authors had disclosures to report. Dr. Bhatt disclosed having financial relationships with more than 40 pharmaceutical companies. Dr. Williams reported having no relevant financial disclosures.
 

A 4-month, structured diet and exercise intervention lowered blood pressure in adults with resistant blood pressure, according to results from a randomized, clinical trial. The program also led to improvements in baroreflex sensitivity, heart rate variability, and flow-mediated dilation, compared with individuals who received only a single education session.

The intervention included instruction from a nutritionist on how to follow the Dietary Approaches to Stop Hypertension (DASH) diet, as well as restricting calories and sodium to less than 2,300 mg/day. It included weekly, 45-minute group counseling sessions, run by a clinical psychiatrist, focusing on eating behaviors. The exercise component included 30- to 45-minute sessions at 70%-85% of initial heart rate reserve, carried out three times per week at a cardiac rehabilitation facility.

“While some individuals can make the lifestyle changes on their own, a structured program of supervised exercise and dietary modification conducted by a multidisciplinary team of physicians, psychologists, nutritionists, and physical therapists/exercise physiologists found in cardiac rehabilitation programs throughout the country is likely to be more effective. There are many cardiac rehabilitation programs throughout the country that are accessible to most patients,” said lead author James Blumenthal, PhD, the J.P. Gibbons Professor in Psychiatry and Behavioral Sciences at Duke University, Durham, N.C.

The study, called Treating Resistant Hypertension Using Lifestyle Modification to Promote Health (TRIUMPH), was published in Circulation. It is one of few that have examined lifestyle interventions in resistant hypertension, defined as systolic blood pressure ≥ 130 mm Hg or diastolic blood pressure ≥ 80 mm Hg after adherence to three or more optimally-dosed antihypertensive medications of three different classes, including one diuretic.

“This is a nice study [that] emphasizes what we often forget: Lifestyle factors, especially salt intake, are important drivers of resistant hypertension. Our own studies have shown that this is predominantly a salt retaining state, and one would expect dietary salt restriction to be particularly effective in this group of patients and that is what this study showed,” said Bryan Williams, MD, who was asked to comment on the study. Dr. Williams is chair of medicine at University College London.

The results should also be reassuring to some who worried that exercise might lead to worsened blood pressure. “This study showed that in patients with resistant hypertension, though not out of control blood pressures, exercise was not only safe, but effective in lowering their blood pressure,” said Deepak L. Bhatt, MD, MPH, who was asked to comment. He is executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, and professor of medicine at Harvard Medical School, both in Boston.

The new research isn’t unique. In August, researchers in Portugal and Brazil showed that a 12-week exercise-only intervention reduced 24-hour and daytime ambulatory systolic and diastolic blood pressure. The two studies communicate the same message. “Lifestyle changes can work for resistant hypertension. So, two independent, modest-sized studies with essentially the same, positive, actionable conclusion,” said Dr. Bhatt, adding that the next step should be a larger, multicenter trial.

In the new study, 90 patients were assigned to the diet and exercise intervention and 50 to the control group. They had a mean age of 63 years, and 48% were women. Participants attended 94% of DASH diet classes and 89% of exercise sessions, and both groups had excellent adherence to medications.

The treatment group had a greater reduction in clinic systolic BP (–12.5 versus –7.1 mm Hg; P = .005) and diastolic BP (–5.9 versus –3.7 mm Hg; P = .034), as well as 24-hour ambulatory systolic BP (–7.0 versus –0.3 mm Hg; P = .001). The treatment group also had more improvement in resting baroreflex sensitivity (2.3 versus –1.1 ms/mm Hg; P = .003), high-frequency heart rate variability (0.4 versus –0.2 ln ms²; P = .025, and flow-mediated dilation (0.3% versus –1.4%, P = .022). The two groups had similar outcomes with respect to pulse wave velocity and left ventricular mass.

“Results of the TRIUMPH study suggest that policymakers should consider resistant hypertension as a new indication for cardiac rehabilitation with appropriate coverage by governmental agencies and private insurers,” Dr. Blumenthal said.

“This is an important new, evidence-based intervention for resistant hypertension. It is safe and relatively inexpensive. It should now be something physicians routinely offer these patients. Hopefully in the future, insurers will cover cardiac rehabilitation for patients with resistant hypertension,” Dr. Bhatt said.

The study also pointed towards an effective approach for patients who may be unable to sustain lifestyle changes. “Of course, not every patient will be able to maintain a healthy diet and an exercise program on their own, thus a cardiac rehabilitation program can be an excellent way to increase the likelihood of successful lifestyle modification,” Dr. Bhatt said.

TRIUMPH was sponsored by grants from the National Heart, Lung, and Blood Institute. None of the authors had disclosures to report. Dr. Bhatt disclosed having financial relationships with more than 40 pharmaceutical companies. Dr. Williams reported having no relevant financial disclosures.