Low adenoma detection rates (ADRs) were associated with a greater risk of death in colorectal cancer (CRC) patients, especially among those with high-risk adenomas, based on a review of more than 250,000 colonoscopies.

pixologicstudio/Thinkstock

“Both performance quality of the endoscopist as well as specific characteristics of resected adenomas at colonoscopy are associated with colorectal cancer mortality,” but the impact of these combined factors on colorectal cancer mortality has not been examined on a large scale, according to Elisabeth A. Waldmann, MD, of the Medical University of Vienna and colleagues.

In a study published in Clinical Gastroenterology & Hepatology, the researchers reviewed 259,885 colonoscopies performed by 361 endoscopists. Over an average follow-up period of 59 months, 165 CRC-related deaths occurred.

Across all risk groups, CRC mortality was higher among patients whose colonoscopies yielded an ADR of less than 25%, although this was not statistically significant in all groups.

The researchers then stratified patients into those with a negative colonoscopy, those with low-risk adenomas (one to two adenomas less than 10 mm), and those with high-risk adenomas (advanced adenomas or at least three adenomas), with the negative colonoscopy group used as the reference group for comparisons. The average age of the patients was 61 years, and approximately half were women.

Endoscopists were classified as having an ADR of less than 25% or 25% and higher.

Among individuals with low-risk adenomas, CRC mortality was similar whether the ADR on a negative colonoscopy was less than 25% or 25% or higher (adjusted hazard ratios, 1.25 and 1.22, respectively). CRC mortality also remained unaffected by ADR in patients with negatively colonoscopies (aHR, 1.27).

By contrast, individuals with high-risk adenomas had a significantly increased risk of CRC death if their colonoscopy was performed by an endoscopist with an ADR of less than 25%, compared with those whose endoscopists had ADRs of 25% or higher (aHR, 2.25 and 1.35, respectively).

“Our study demonstrated that adding ADR to the risk stratification model improved risk assessment in all risk groups,” the researchers noted. “Importantly, stratification improved most for individuals with high-risk adenomas, the group demanding most resources in health care systems.”

The study findings were limited by several factors including the focus on only screening and surveillance colonoscopies, not including diagnostic colonoscopies, and the inability to adjust for comorbidities and lifestyle factors that might impact CRC mortality, the researchers noted. The 22.4% average ADR in the current study was low, compared with other studies, and could be a limitation as well, although previous guidelines recommend a target ADR of at least 20%.

“Despite the extensive body of literature supporting the importance of ADR in terms of CRC prevention, its implementation into clinical surveillance is challenging,” as physicians under pressure might try to game their ADRs, the researchers wrote.

The findings support the value of mandatory assessment of performance quality, the researchers added. However, “because of the potential possibility of gaming one’s ADR one conclusion drawn by the study results should be that endoscopists’ quality parameters should be monitored and those not meeting the standards trained to improve rather than requiring minimum ADRs as premise for offering screening colonoscopy.”
 

Improve performance, but don’t discount patient factors

The study is important at this time because colorectal cancer is the third-leading cause of cancer death in the United States, Atsushi Sakuraba, MD, of the University of Chicago said in an interview.

“Screening colonoscopy has been shown to decrease CRC mortality, but factors influencing outcomes after screening colonoscopies remain to be determined,” he said.

“It was expected that high-quality colonoscopy performed by an endoscopist with ADR of 25% or greater was associated with a lower risk for CRC death,” Dr. Sakuraba said. “The strength of the study is that the authors demonstrated that high-quality colonoscopy was more important in individuals with high-risk adenomas, such as advanced adenomas or at least three adenomas.”

The study findings have implications for practice in that they show the importance of monitoring performance quality in screening colonoscopy, Dr. Sakuraba said, “especially when patients have high-risk adenomas.” However, “the authors included only age and sex as variables, but the influence of other factors, such as smoking, [body mass index], and race, need to be studied.”

The researchers had no financial conflicts to disclose. Dr. Sakuraba had no financial conflicts to disclose.

Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.

Low adenoma detection rates (ADRs) were associated with a greater risk of death in colorectal cancer (CRC) patients, especially among those with high-risk adenomas, based on a review of more than 250,000 colonoscopies.

pixologicstudio/Thinkstock

“Both performance quality of the endoscopist as well as specific characteristics of resected adenomas at colonoscopy are associated with colorectal cancer mortality,” but the impact of these combined factors on colorectal cancer mortality has not been examined on a large scale, according to Elisabeth A. Waldmann, MD, of the Medical University of Vienna and colleagues.

In a study published in Clinical Gastroenterology & Hepatology, the researchers reviewed 259,885 colonoscopies performed by 361 endoscopists. Over an average follow-up period of 59 months, 165 CRC-related deaths occurred.

Across all risk groups, CRC mortality was higher among patients whose colonoscopies yielded an ADR of less than 25%, although this was not statistically significant in all groups.

The researchers then stratified patients into those with a negative colonoscopy, those with low-risk adenomas (one to two adenomas less than 10 mm), and those with high-risk adenomas (advanced adenomas or at least three adenomas), with the negative colonoscopy group used as the reference group for comparisons. The average age of the patients was 61 years, and approximately half were women.

Endoscopists were classified as having an ADR of less than 25% or 25% and higher.

Among individuals with low-risk adenomas, CRC mortality was similar whether the ADR on a negative colonoscopy was less than 25% or 25% or higher (adjusted hazard ratios, 1.25 and 1.22, respectively). CRC mortality also remained unaffected by ADR in patients with negatively colonoscopies (aHR, 1.27).

By contrast, individuals with high-risk adenomas had a significantly increased risk of CRC death if their colonoscopy was performed by an endoscopist with an ADR of less than 25%, compared with those whose endoscopists had ADRs of 25% or higher (aHR, 2.25 and 1.35, respectively).

“Our study demonstrated that adding ADR to the risk stratification model improved risk assessment in all risk groups,” the researchers noted. “Importantly, stratification improved most for individuals with high-risk adenomas, the group demanding most resources in health care systems.”

The study findings were limited by several factors including the focus on only screening and surveillance colonoscopies, not including diagnostic colonoscopies, and the inability to adjust for comorbidities and lifestyle factors that might impact CRC mortality, the researchers noted. The 22.4% average ADR in the current study was low, compared with other studies, and could be a limitation as well, although previous guidelines recommend a target ADR of at least 20%.

“Despite the extensive body of literature supporting the importance of ADR in terms of CRC prevention, its implementation into clinical surveillance is challenging,” as physicians under pressure might try to game their ADRs, the researchers wrote.

The findings support the value of mandatory assessment of performance quality, the researchers added. However, “because of the potential possibility of gaming one’s ADR one conclusion drawn by the study results should be that endoscopists’ quality parameters should be monitored and those not meeting the standards trained to improve rather than requiring minimum ADRs as premise for offering screening colonoscopy.”
 

Improve performance, but don’t discount patient factors

The study is important at this time because colorectal cancer is the third-leading cause of cancer death in the United States, Atsushi Sakuraba, MD, of the University of Chicago said in an interview.

“Screening colonoscopy has been shown to decrease CRC mortality, but factors influencing outcomes after screening colonoscopies remain to be determined,” he said.

“It was expected that high-quality colonoscopy performed by an endoscopist with ADR of 25% or greater was associated with a lower risk for CRC death,” Dr. Sakuraba said. “The strength of the study is that the authors demonstrated that high-quality colonoscopy was more important in individuals with high-risk adenomas, such as advanced adenomas or at least three adenomas.”

The study findings have implications for practice in that they show the importance of monitoring performance quality in screening colonoscopy, Dr. Sakuraba said, “especially when patients have high-risk adenomas.” However, “the authors included only age and sex as variables, but the influence of other factors, such as smoking, [body mass index], and race, need to be studied.”

The researchers had no financial conflicts to disclose. Dr. Sakuraba had no financial conflicts to disclose.

Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.

Low adenoma detection rates (ADRs) were associated with a greater risk of death in colorectal cancer (CRC) patients, especially among those with high-risk adenomas, based on a review of more than 250,000 colonoscopies.

pixologicstudio/Thinkstock

“Both performance quality of the endoscopist as well as specific characteristics of resected adenomas at colonoscopy are associated with colorectal cancer mortality,” but the impact of these combined factors on colorectal cancer mortality has not been examined on a large scale, according to Elisabeth A. Waldmann, MD, of the Medical University of Vienna and colleagues.

In a study published in Clinical Gastroenterology & Hepatology, the researchers reviewed 259,885 colonoscopies performed by 361 endoscopists. Over an average follow-up period of 59 months, 165 CRC-related deaths occurred.

Across all risk groups, CRC mortality was higher among patients whose colonoscopies yielded an ADR of less than 25%, although this was not statistically significant in all groups.

The researchers then stratified patients into those with a negative colonoscopy, those with low-risk adenomas (one to two adenomas less than 10 mm), and those with high-risk adenomas (advanced adenomas or at least three adenomas), with the negative colonoscopy group used as the reference group for comparisons. The average age of the patients was 61 years, and approximately half were women.

Endoscopists were classified as having an ADR of less than 25% or 25% and higher.

Among individuals with low-risk adenomas, CRC mortality was similar whether the ADR on a negative colonoscopy was less than 25% or 25% or higher (adjusted hazard ratios, 1.25 and 1.22, respectively). CRC mortality also remained unaffected by ADR in patients with negatively colonoscopies (aHR, 1.27).

By contrast, individuals with high-risk adenomas had a significantly increased risk of CRC death if their colonoscopy was performed by an endoscopist with an ADR of less than 25%, compared with those whose endoscopists had ADRs of 25% or higher (aHR, 2.25 and 1.35, respectively).

“Our study demonstrated that adding ADR to the risk stratification model improved risk assessment in all risk groups,” the researchers noted. “Importantly, stratification improved most for individuals with high-risk adenomas, the group demanding most resources in health care systems.”

The study findings were limited by several factors including the focus on only screening and surveillance colonoscopies, not including diagnostic colonoscopies, and the inability to adjust for comorbidities and lifestyle factors that might impact CRC mortality, the researchers noted. The 22.4% average ADR in the current study was low, compared with other studies, and could be a limitation as well, although previous guidelines recommend a target ADR of at least 20%.

“Despite the extensive body of literature supporting the importance of ADR in terms of CRC prevention, its implementation into clinical surveillance is challenging,” as physicians under pressure might try to game their ADRs, the researchers wrote.

The findings support the value of mandatory assessment of performance quality, the researchers added. However, “because of the potential possibility of gaming one’s ADR one conclusion drawn by the study results should be that endoscopists’ quality parameters should be monitored and those not meeting the standards trained to improve rather than requiring minimum ADRs as premise for offering screening colonoscopy.”
 

Improve performance, but don’t discount patient factors

The study is important at this time because colorectal cancer is the third-leading cause of cancer death in the United States, Atsushi Sakuraba, MD, of the University of Chicago said in an interview.

“Screening colonoscopy has been shown to decrease CRC mortality, but factors influencing outcomes after screening colonoscopies remain to be determined,” he said.

“It was expected that high-quality colonoscopy performed by an endoscopist with ADR of 25% or greater was associated with a lower risk for CRC death,” Dr. Sakuraba said. “The strength of the study is that the authors demonstrated that high-quality colonoscopy was more important in individuals with high-risk adenomas, such as advanced adenomas or at least three adenomas.”

The study findings have implications for practice in that they show the importance of monitoring performance quality in screening colonoscopy, Dr. Sakuraba said, “especially when patients have high-risk adenomas.” However, “the authors included only age and sex as variables, but the influence of other factors, such as smoking, [body mass index], and race, need to be studied.”

The researchers had no financial conflicts to disclose. Dr. Sakuraba had no financial conflicts to disclose.

Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.

Hypomethylating agents are generally considered to be agents of choice for older adults with acute myeloid leukemia who cannot tolerate the rigors of more intensive therapies, but HMAs also can serve as a bridge to transplant for children and young adults with relapsed or refractory acute myeloid leukemia.

That’s according to Himalee S. Sabnis, MD, MSc and colleagues at Emory University and the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta.

In a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology, the investigators reported results of a retrospective study of HMA use in patients with relapsed or refractory pediatric AML treated in their center.
 

Curative intent and palliation

They identified 25 patients (15 boys) with a median age of 8.3 years (range 1.4 to 21 years) with relapsed/refractory AML who received HMAs for curative intent prior to hematopoietic stem cell transplant (HSCT), palliation, or in combination with donor leukocyte infusion (DLI).

Of the 21 patients with relapsed disease, 16 were in first relapse and 5 were in second relapse or greater. Four of the patients had primary refractory disease. The cytogenetic and molecular features were KMT2A rearrangements in six patients, monosomy 7/deletion 7 q in four patients, 8;21 translocation in three patients, and FLT3-ITD mutations in four patients.

The patients received a median of 5.3 HMA cycles each. Of the 133 total HMA cycles, 87 were with azacitidine, and 46 were with decitabine.

HMAs were used as monotherapy in 62% of cycles, and in combination with other therapies in 38%. Of the combinations, 16 were with donor leukocyte infusion, and 9 were gemtuzumab ozogamicin (Mylotarg).

Of the 13 patients for whom HMAs were used as part of treatment plan with curative intent, 5 proceeded to HSCT, and 8 did not. Of the 5 patients, 1 died from transplant-related causes, and 4 were alive post transplant. Of the 8 patients who did not undergo transplant, 1 had chimeric antigen receptor T- cell (CAR T) therapy, and 7 experienced disease progression.

The mean duration of palliative care was 144 days, with patients receiving from one to nine cycles with an HMA, and no treatment interruptions due to toxicity.

Of 5 patients who received donor leukocyte infusions, 3 reached minimal residual disease negativity; all 3 of these patients had late relapses but remained long-term survivors, the investigators reported.

They concluded that “hypomethylating agents can be used effectively as a bridge to transplantation in relapsed and refractory AML with gemtuzumab ozogamicin being the most common agent for combination therapy. Palliation with HMAs is associated with low toxicity and high tolerability in relapsed/refractory AML. Use of HMAs with DLI can induce sustained remissions in some patients.”

The authors propose prospective clinical trials using HMAs in the relapsed/refractory pediatric AML setting in combination with gemtuzumab ozogamicin, alternative targeted agents, and chemotherapy.

HMAs in treatment-related AML

Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, has experience administering HMAs primarily in the adolescent and young adult population with AML.

“Azacitidine and decitabine are good for treatment-related leukemias,” she said in an interview. “They can be used otherwise for people who have relapsed disease and are trying to navigate other options.”

Although they are not standard first-line agents in younger patients, HMAs can play a useful role in therapy for relapsed or refractory disease, she said.

The authors and Dr. Shahani reported having no conflicts of interest to disclose.

Hypomethylating agents are generally considered to be agents of choice for older adults with acute myeloid leukemia who cannot tolerate the rigors of more intensive therapies, but HMAs also can serve as a bridge to transplant for children and young adults with relapsed or refractory acute myeloid leukemia.

That’s according to Himalee S. Sabnis, MD, MSc and colleagues at Emory University and the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta.

In a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology, the investigators reported results of a retrospective study of HMA use in patients with relapsed or refractory pediatric AML treated in their center.
 

Curative intent and palliation

They identified 25 patients (15 boys) with a median age of 8.3 years (range 1.4 to 21 years) with relapsed/refractory AML who received HMAs for curative intent prior to hematopoietic stem cell transplant (HSCT), palliation, or in combination with donor leukocyte infusion (DLI).

Of the 21 patients with relapsed disease, 16 were in first relapse and 5 were in second relapse or greater. Four of the patients had primary refractory disease. The cytogenetic and molecular features were KMT2A rearrangements in six patients, monosomy 7/deletion 7 q in four patients, 8;21 translocation in three patients, and FLT3-ITD mutations in four patients.

The patients received a median of 5.3 HMA cycles each. Of the 133 total HMA cycles, 87 were with azacitidine, and 46 were with decitabine.

HMAs were used as monotherapy in 62% of cycles, and in combination with other therapies in 38%. Of the combinations, 16 were with donor leukocyte infusion, and 9 were gemtuzumab ozogamicin (Mylotarg).

Of the 13 patients for whom HMAs were used as part of treatment plan with curative intent, 5 proceeded to HSCT, and 8 did not. Of the 5 patients, 1 died from transplant-related causes, and 4 were alive post transplant. Of the 8 patients who did not undergo transplant, 1 had chimeric antigen receptor T- cell (CAR T) therapy, and 7 experienced disease progression.

The mean duration of palliative care was 144 days, with patients receiving from one to nine cycles with an HMA, and no treatment interruptions due to toxicity.

Of 5 patients who received donor leukocyte infusions, 3 reached minimal residual disease negativity; all 3 of these patients had late relapses but remained long-term survivors, the investigators reported.

They concluded that “hypomethylating agents can be used effectively as a bridge to transplantation in relapsed and refractory AML with gemtuzumab ozogamicin being the most common agent for combination therapy. Palliation with HMAs is associated with low toxicity and high tolerability in relapsed/refractory AML. Use of HMAs with DLI can induce sustained remissions in some patients.”

The authors propose prospective clinical trials using HMAs in the relapsed/refractory pediatric AML setting in combination with gemtuzumab ozogamicin, alternative targeted agents, and chemotherapy.

HMAs in treatment-related AML

Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, has experience administering HMAs primarily in the adolescent and young adult population with AML.

“Azacitidine and decitabine are good for treatment-related leukemias,” she said in an interview. “They can be used otherwise for people who have relapsed disease and are trying to navigate other options.”

Although they are not standard first-line agents in younger patients, HMAs can play a useful role in therapy for relapsed or refractory disease, she said.

The authors and Dr. Shahani reported having no conflicts of interest to disclose.

Hypomethylating agents are generally considered to be agents of choice for older adults with acute myeloid leukemia who cannot tolerate the rigors of more intensive therapies, but HMAs also can serve as a bridge to transplant for children and young adults with relapsed or refractory acute myeloid leukemia.

That’s according to Himalee S. Sabnis, MD, MSc and colleagues at Emory University and the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta.

In a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology, the investigators reported results of a retrospective study of HMA use in patients with relapsed or refractory pediatric AML treated in their center.
 

Curative intent and palliation

They identified 25 patients (15 boys) with a median age of 8.3 years (range 1.4 to 21 years) with relapsed/refractory AML who received HMAs for curative intent prior to hematopoietic stem cell transplant (HSCT), palliation, or in combination with donor leukocyte infusion (DLI).

Of the 21 patients with relapsed disease, 16 were in first relapse and 5 were in second relapse or greater. Four of the patients had primary refractory disease. The cytogenetic and molecular features were KMT2A rearrangements in six patients, monosomy 7/deletion 7 q in four patients, 8;21 translocation in three patients, and FLT3-ITD mutations in four patients.

The patients received a median of 5.3 HMA cycles each. Of the 133 total HMA cycles, 87 were with azacitidine, and 46 were with decitabine.

HMAs were used as monotherapy in 62% of cycles, and in combination with other therapies in 38%. Of the combinations, 16 were with donor leukocyte infusion, and 9 were gemtuzumab ozogamicin (Mylotarg).

Of the 13 patients for whom HMAs were used as part of treatment plan with curative intent, 5 proceeded to HSCT, and 8 did not. Of the 5 patients, 1 died from transplant-related causes, and 4 were alive post transplant. Of the 8 patients who did not undergo transplant, 1 had chimeric antigen receptor T- cell (CAR T) therapy, and 7 experienced disease progression.

The mean duration of palliative care was 144 days, with patients receiving from one to nine cycles with an HMA, and no treatment interruptions due to toxicity.

Of 5 patients who received donor leukocyte infusions, 3 reached minimal residual disease negativity; all 3 of these patients had late relapses but remained long-term survivors, the investigators reported.

They concluded that “hypomethylating agents can be used effectively as a bridge to transplantation in relapsed and refractory AML with gemtuzumab ozogamicin being the most common agent for combination therapy. Palliation with HMAs is associated with low toxicity and high tolerability in relapsed/refractory AML. Use of HMAs with DLI can induce sustained remissions in some patients.”

The authors propose prospective clinical trials using HMAs in the relapsed/refractory pediatric AML setting in combination with gemtuzumab ozogamicin, alternative targeted agents, and chemotherapy.

HMAs in treatment-related AML

Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, has experience administering HMAs primarily in the adolescent and young adult population with AML.

“Azacitidine and decitabine are good for treatment-related leukemias,” she said in an interview. “They can be used otherwise for people who have relapsed disease and are trying to navigate other options.”

Although they are not standard first-line agents in younger patients, HMAs can play a useful role in therapy for relapsed or refractory disease, she said.

The authors and Dr. Shahani reported having no conflicts of interest to disclose.

Key clinical point: High dietary acid load was associated with higher odds of migraine. Restricting dietary acid load could therefore reduce the odds of migraine in susceptible patients.

Major finding: The risk for migraine was higher among individuals in highest vs. lowest tertile of dietary acid load measures, including potential renal acid load (odds ratio [OR], 7.208; 95% confidence interval [95% CI], 3.33-15.55), net endogenous acid production (OR, 4.10; 95% CI, 1.92-8.77) scores, and the protein/potassium ratio (OR, 4.12; 95% CI, 1.93-8.81; all P_trend less than .001).

Study details: Findings are from a case-control study of 1,096 participants including those with migraine (n=514) and healthy volunteers (n=582).

Disclosures: The study was supported by the Iranian Centre of Neurological Research, Neuroscience Institute. All authors declared no conflicts of interest.

Source: Mousavi M et al. Neurol Ther. 2021 Apr 24. doi: 10.1007/s40120-021-00247-2.

Key clinical point: High dietary acid load was associated with higher odds of migraine. Restricting dietary acid load could therefore reduce the odds of migraine in susceptible patients.

Major finding: The risk for migraine was higher among individuals in highest vs. lowest tertile of dietary acid load measures, including potential renal acid load (odds ratio [OR], 7.208; 95% confidence interval [95% CI], 3.33-15.55), net endogenous acid production (OR, 4.10; 95% CI, 1.92-8.77) scores, and the protein/potassium ratio (OR, 4.12; 95% CI, 1.93-8.81; all P_trend less than .001).

Study details: Findings are from a case-control study of 1,096 participants including those with migraine (n=514) and healthy volunteers (n=582).

Disclosures: The study was supported by the Iranian Centre of Neurological Research, Neuroscience Institute. All authors declared no conflicts of interest.

Source: Mousavi M et al. Neurol Ther. 2021 Apr 24. doi: 10.1007/s40120-021-00247-2.

Key clinical point: High dietary acid load was associated with higher odds of migraine. Restricting dietary acid load could therefore reduce the odds of migraine in susceptible patients.

Major finding: The risk for migraine was higher among individuals in highest vs. lowest tertile of dietary acid load measures, including potential renal acid load (odds ratio [OR], 7.208; 95% confidence interval [95% CI], 3.33-15.55), net endogenous acid production (OR, 4.10; 95% CI, 1.92-8.77) scores, and the protein/potassium ratio (OR, 4.12; 95% CI, 1.93-8.81; all P_trend less than .001).

Study details: Findings are from a case-control study of 1,096 participants including those with migraine (n=514) and healthy volunteers (n=582).

Disclosures: The study was supported by the Iranian Centre of Neurological Research, Neuroscience Institute. All authors declared no conflicts of interest.

Source: Mousavi M et al. Neurol Ther. 2021 Apr 24. doi: 10.1007/s40120-021-00247-2.

Key clinical point: Menopausal women with migraine are at a higher risk for incident hypertension.

Major finding: Migraine was associated with an increased risk for incident hypertension (hazard ratio_migraine, 1.29; 95% confidence interval, 1.24-1.35) in menopausal women.

Study details: Findings are from a longitudinal cohort study of 56,202 menopausal women free of hypertension or cardiovascular disease at the age of menopause who participated in the French E3N cohort.

Disclosures: The authors reported no targeted funding. CJ MacDonald and T Kurth received funding and/or honoraria from multiple sources. Other authors had no disclosures relevant to the manuscript.

Source: MacDonald CJ et al. Neurology. 2021 Apr 21. doi: 10.1212/WNL.0000000000011986.

Key clinical point: Menopausal women with migraine are at a higher risk for incident hypertension.

Major finding: Migraine was associated with an increased risk for incident hypertension (hazard ratio_migraine, 1.29; 95% confidence interval, 1.24-1.35) in menopausal women.

Study details: Findings are from a longitudinal cohort study of 56,202 menopausal women free of hypertension or cardiovascular disease at the age of menopause who participated in the French E3N cohort.

Disclosures: The authors reported no targeted funding. CJ MacDonald and T Kurth received funding and/or honoraria from multiple sources. Other authors had no disclosures relevant to the manuscript.

Source: MacDonald CJ et al. Neurology. 2021 Apr 21. doi: 10.1212/WNL.0000000000011986.

Key clinical point: Menopausal women with migraine are at a higher risk for incident hypertension.

Major finding: Migraine was associated with an increased risk for incident hypertension (hazard ratio_migraine, 1.29; 95% confidence interval, 1.24-1.35) in menopausal women.

Study details: Findings are from a longitudinal cohort study of 56,202 menopausal women free of hypertension or cardiovascular disease at the age of menopause who participated in the French E3N cohort.

Disclosures: The authors reported no targeted funding. CJ MacDonald and T Kurth received funding and/or honoraria from multiple sources. Other authors had no disclosures relevant to the manuscript.

Source: MacDonald CJ et al. Neurology. 2021 Apr 21. doi: 10.1212/WNL.0000000000011986.

The early identification of clinical deterioration among adult hospitalized patients remains a challenge.¹ Delayed identification is associated with increased morbidity and mortality, unplanned intensive care unit (ICU) admissions, prolonged hospitalization, and higher costs.^2,3 Earlier detection of deterioration using predictive algorithms of vital sign monitoring might avoid these negative outcomes.⁴ In this scoping review, we summarize current algorithms and their evidence.

Vital signs provide the backbone for detecting clinical deterioration. Early warning scores (EWS) and outreach protocols were developed to bring structure to the assessment of vital signs. Most EWS claim to predict clinical end points such as unplanned ICU admission up to 24 hours in advance.^5,6 Reviews of EWS showed a positive trend toward reduced length of stay and mortality. However, conclusions about general efficacy could not be generated because of case heterogeneity and methodologic shortcomings.^4,7 Continuous automated vital sign monitoring of patients on the general ward can now be accomplished with wearable devices.⁸ The first reports on continuous monitoring showed earlier detection of deterioration but not improved clinical end points.^4,9 Since then, different reports on continuous monitoring have shown positive effects but concluded that unprocessed monitoring data per se falls short of generating actionable alarms.^4,10,11

Predictive algorithms, which often use artificial intelligence (AI), are increasingly employed to recognize complex patterns or abnormalities and support predictions of events in big data sets.^12,13 Especially when combined with continuous vital sign monitoring, predictive algorithms have the potential to expedite detection of clinical deterioration and improve patient outcomes. Predictive algorithms using vital signs in the ICU have shown promising results.¹⁴ The impact of predictive algorithms on the general wards, however, is unclear.

The aims of our scoping review were to explore the extent and range of and evidence for predictive vital signs–based algorithms on the adult general ward; to describe the variety of these algorithms; and to categorize effects, facilitators, and barriers of their implementation.¹⁵

We performed a scoping review to create a summary of the current state of research. We used the five-step method of Levac and followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews guidelines (Appendix 1).^16,17

PubMed, Embase, and CINAHL databases were searched for English-language articles written between January 1, 2010, and November 20, 2020. We developed the search queries with an experienced information scientist, and we used database-specific terms and strategies for input, clinical outcome, method, predictive capability, and population (Appendix 2). Additionally, we searched the references of the selected articles, as well as publications citing these articles.

All studies identified were screened by title and abstract by two researchers (RP and YE). The selected studies were read in their entirety and checked for eligibility using the following inclusion criteria: automated algorithm; vital signs-based; real-time prediction; of clinical deterioration; in an adult, general ward population. In cases where there were successive publications with the same algorithm and population, we selected the most recent study.

For screening and selection, we used the Rayyan QCRI online tool (Qatar Computing Research Institute) and Endnote X9 (Clarivate Analytics). We extracted information using a data extraction form and organized it into descriptive characteristics of the selected studies (Table 1): an input data table showing number of admissions, intermittent or continuous measurements, vital signs measured, laboratory results (Appendix Table 1), a table summarizing study designs and settings (Appendix Table 2), and a prediction performance table (Table 2). We report characteristics of the populations and algorithms, prediction specifications such as area under the receiver operating curve (AUROC), and predictive values. Predictive values are affected by prevalence, which may differ among populations. To compare the algorithms, we calculated an indexed positive predictive value (PPV) and a number needed to evaluate (NNE) using a weighted average prevalence of clinical deterioration of 3.0%.

As shown in the Figure, we found 1741 publications, of which we read the full-text of 109. There were 1632 publications that did not meet the inclusion criteria. The publications by Churpek et al,^20,21 Bartkiowak et al,²² Edelson et al,²³ Escobar et al,^24,25 and Kipnis et al²⁶ reported on the same algorithms or databases but had significantly different approaches. For multiple publications using the same algorithm and population, the most recent was named with inclusion of the earlier findings.^20,21,27-29 The resulting 21 papers are included in this review.

Descriptive characteristics of the studies are summarized in Table 1. Nineteen of the publications were full papers and two were conference abstracts. Most of the studies (n = 18) were from the United States; there was one study from South Korea,³⁰ one study from Portugal,³¹ and one study from the United Kingdom.³² In 15 of the studies, there was a strict focus on general or specific wards; 6 studies also included the ICU and/or emergency departments.

Two of the studies were clinical trials, 2 were prospective observational studies, and 17 were retrospective studies. Five studies reported on an active predictive model during admission. Of these, 3 reported that the model was clinically implemented, using the predictions in their clinical workflow. None of the implemented studies used AI.

All input variables are presented in Appendix Table 1. In 10 of the studies, vital signs were combined with laboratory results; in 13 of the studies, vital signs were combined with patient characteristics. All of the studies used data derived from electronic medical records (EMRs), except for Bai et al³³ and Hu et al,³⁴ who used single-source waveforms directly from the bedside monitor. Three studies focused on continuous vital sign measurements.^27,33,34Most authors reported an AUROC to describe the predictive value of their algorithms. As shown in Table 2, AUROCs varied from 0.65 to 0.95, with indexed PPVs between 0.24 and 0.75. Sensitivity ranged from 7.2% to 52.5% in non-AI models and up to 82.4% in AI models. Prediction definitions, horizons, and the reported metrics differed too much to directly compare studies.

The non-AI algorithm prediction horizons ranged from 4 to 24 hours, with a median of 24 hours (interquartile range [IQR], 12-24 hours). The AI algorithms ranged from 2 to 48 hours and had a median horizon of 14 hours (IQR, 12-24 hours).

We found three studies reporting patient outcomes. The most recent of these was a large multicenter implementation study by Escobar et al²⁵ that included an extensive follow-up response. This study reported a significantly decreased 30-day mortality in the intervention cohort. A smaller randomized controlled trial reported no significant differences in patient outcomes with earlier warning alarms.²⁷ A third study reported more appropriate rapid response team deployment and decreased mortality in a subgroup analysis.³⁵

Effects, Facilitators, and Barriers

As shown in the Appendix Figure and further detailed in Table 3, the described effects were predominantly positive—57 positive effects vs 11 negative effects. These positive effects sorted primarily into the outcome and process domains.

All of the studies that compared their proposed model with one of various warning systems (eg, EWS, National Early Warning Score [NEWS], Modified Early Warning Score [MEWS]) showed superior performance (based on AUROC and reported predictive values). In 17 studies, the authors reported their model as more useful or superior to the EWS.^{20-23,26-28,34,36-41} Four studies reported real-time detection of deterioration before regular EWS,^20,26,42 and three studies reported positive effects on patient-related outcomes.^26,35 Four negative effects were noted on the controllability, validity, and potential limitations.^27,42

There were 26 positive effects on the clinical process mentioned, 7 of which pointed out the effects of earlier, predictive alarming. Algorithms with higher PPVs reported greater rates of actionable alarms, less alarm fatigue, and improved workflow.^{21,22,24-27,30,32,33,35-38,40} Potential alarm fatigue was named as a barrier.^27,42 Smoother scoring instead of binned categories was mentioned positively.^24,26In the infrastructure domain, very few items were reported. The increased need for education on the used techniques was reported once as a negative effect.³⁴ One of the positive infrastructural effects noted was more efficient planning and use of resources.^24,37,40We identified 57 facilitators and 48 barriers for the clinical implementation and use of real-time predictive analytics (Appendix Figure). In the Technology domain, there were 18 facilitators and 20 barriers cited, and in the Organization domain, 25 and 14, respectively. They were equally present in the Professional and Physiology domains (6 vs 5, 8 vs 9).

Of the 38 remarks in the Technology domain, difficulty with implementation in daily practice was a commonly cited barrier.^22,24,40,42 Difficulties included creating real-time data feeds out of the EMR, though there were mentions of some successful examples.^25,27,36 Difficulty in the interpretability of AI was also considered a potential barrier.^{30,32,33,35,39,41} There were remarks as to the applicability of the prolonged prediction horizon because of the associated decoupling from the clinical view.^39,42

Conservative attitudes toward new technologies and inadequate knowledge were mentioned as barriers.³⁹ Repeated remarks were made on the difficulty of interpreting and responding to a predicted escalation, as the clinical pattern might not be recognizable at such an early stage. On the other hand, it is expected that less invasive countermeasures would be adequate to avert further escalation. Earlier recognition of possible escalations also raised potential ethical questions, such as when to discuss palliative care.²⁴

The heterogeneity of the general ward population and the relatively low prevalence of deterioration were mentioned as barriers.^24,30,38,41 There were also concerns that not all escalations are preventable and that some patient outcomes may not be modifiable.^24,38

Many investigators expected reductions in false alarms and associated alarm fatigue (reflected as higher PPVs). Furthermore, they expected workflow to improve and workload to decrease.^{21,23,27,31,33,35,38,41} Despite the capacity of modern EMRs to store large amounts of patient data, some investigators felt improvements to real-time access, data quality and validity, and data density are needed to ensure valid associated predictions.^{21,22,24,32,37}

As the complexity and comorbidity of hospitalized adults grow, predicting clinical deterioration is becoming more important. With an ever-increasing amount of available patient data, real-time algorithms can predict the patient’s clinical course with increasing accuracy, positively affecting outcomes.^4,21,25,43 The studies identified in this scoping review, as measured by higher AUROC scores and improved PPVs, show that predictive algorithms can outperform more conventional EWS, enable earlier and more efficient alarming, and be successfully implemented on the general wards. However, formal meta-analysis was made infeasible by differences in populations, use of different endpoint definitions, cut-off points, time-horizons to prediction, and other methodologic heterogeneity.

There are several important limitations across these studies. In a clinical setting, these models would function as a screening test. Almost all studies report an AUROC; however, sensitivity and PPV or NNE (defined as 1/PPV) may be more useful than AUROC when predicting low-frequency events with high-potential clinical impact.⁴⁴ Assessing the NNE is especially relevant because of its relation to alarm fatigue and responsiveness of clinicians.⁴³ Alarm fatigue and lack of adequate response to alarms were repeatedly cited as potential barriers for application of automated scores. A more useful metric might be NNE over a certain timeframe and across a specified number of patients to more clearly reflect associated workload. Future studies should include these metrics as indicators of the usability and clinical impact of predictive models. This review could not assess PPV or NNE systematically due to inconsistencies in the reporting of these metrics.

Although the results of our scoping review are promising, there are limited data on clinical outcomes using these algorithms. Only three of five algorithms were used to guide clinical decision-making.^25,27,35 Kollef et al²⁷ showed shorter hospitalizations and Evans et al³⁵ found decreased mortality rates in a multimorbid subgroup. Escobar et al²⁵ found an overall and consistent decrease in mortality in a large, heterogenic population of inpatients across 21 hospitals. While Escobar et al’s findings provide strong evidence that predictive algorithms and structured follow-up on alarms can improve patient outcomes, it recognizes that not all facilities will have the resources to implement them.²⁵ Dedicated round-the-clock follow-up of alarms has yet to be proven feasible for smaller institutions, and leaner solutions must be explored. The example set by Escobar et al²⁵ should be translated into various settings to prove its reproducibility and to substantiate the clinical impact of predictive models and structured follow-up.

According to expert opinion, the use of high-frequency or continuous monitoring at low-acuity wards and AI algorithms to detect trends and patterns will reduce failure-to-rescue rates.^4,9,43 However, most studies in our review focused on periodic spot-checked vital signs, and none of the AI algorithms were implemented in clinical care (Appendix Table 1). A significant barrier to implementation was uncertainty surrounding how to react to generated alarms.^9,45 As algorithms become more complex and predict earlier, interpretability and causality in general can diminish, and the response to this type of alarm will be different from that of an acute warning from an EWS.

The assessment of predictive algorithm protocols must include their impact on clinical workflow, workload, and resource utilization. Earlier detection of deterioration can potentially allow coordinated alarm follow-up and lead to more efficient use of resources.^{20,21,31,43,46,47}

Greater numbers of variables do not always improve the quality of monitoring. For example, in one study, an algorithm combining only heart rate, respiration rate, and age outperformed an EWS that tracked six vital sign measures.²³ Algorithms using fewer variables may facilitate more frequent and less complex error-sensitive monitoring. Leaner measurements may also lead to higher patient and clinician acceptance.^43,45The end goal of implementing predictive algorithms on the general ward is to provide timely, reliable, and actionable clinical decision support.⁴³ As shown in a recent study by Blackwell et al,⁴⁸ multiple prediction models for specific clinical events may increase interpretability and performance. Disease-specific algorithms may complement general algorithms for clinical deterioration and enhance overall performance.

STRENGTHS AND LIMITATIONS

We performed a comprehensive review of the current literature using a clear and reproducible methodology to minimize the risk of missing relevant publications. The identified research is mainly limited to large US centers and consists of mostly retrospective studies. Heterogeneity among inputs, endpoints, time horizons, and evaluation metrics make comparisons challenging. Comments on facilitators, barriers, and effects were limited. Positive publication bias may have led to overrepresentation of models showing clinical benefit.

RECOMMENDATIONS FOR FUTURE RESEARCH

Artificial intelligence and the use of continuous monitoring hold great promise in creating optimal predictive algorithms. Future studies should directly compare AI- and non-AI-based algorithms using continuous monitoring to determine predictive accuracy, feasibility, costs, and outcomes. A consensus on endpoint definitions, input variables, methodology, and reporting is needed to enhance reproducibility, comparability, and generalizability of future research. The current research is limited to a few research groups, predominantly in the United States. More international research could enhance validity and increase applicability across varying populations and settings. Greater collaboration would accelerate research and enhance short-cycled continuous improvements. Sharing databases with different populations, variables, and outcomes, such as the Medical Information Mart for Intensive Care database,⁴⁹ could help develop, test, and compare models and contribute to consensus in data standardization and consistent reporting of results. Studies should be designed to determine clinical, societal, and economic effects in accordance with the Quadruple Aim principle.⁵⁰ Successful implementation will depend not only on improved patient outcomes but also on cost-effectiveness, robust statistics, and end-user acceptance. Follow-up protocols and workflows also should be studied and optimized.

Predictive analytics based on vital sign monitoring can identify clinical deterioration at an earlier stage and can do so more accurately than conventional EWS. Implementation of such monitoring can simultaneously decrease alarm-related workload and enhance the efficiency of follow-up. While there is also emerging evidence of associated mortality reduction, it may be too soon to know how representative these findings are. The current literature is limited by heterogeneity across populations studied, monitoring frequency, definitions of deterioration, and clinical outcomes. Consensus is therefore needed to better compare tools and harmonize results. Artificial intelligence and continuous monitoring show great promise in advancing the field; however, additional studies to assess cost, actionability of results, and end-user acceptance are required.

The early identification of clinical deterioration among adult hospitalized patients remains a challenge.¹ Delayed identification is associated with increased morbidity and mortality, unplanned intensive care unit (ICU) admissions, prolonged hospitalization, and higher costs.^2,3 Earlier detection of deterioration using predictive algorithms of vital sign monitoring might avoid these negative outcomes.⁴ In this scoping review, we summarize current algorithms and their evidence.

Vital signs provide the backbone for detecting clinical deterioration. Early warning scores (EWS) and outreach protocols were developed to bring structure to the assessment of vital signs. Most EWS claim to predict clinical end points such as unplanned ICU admission up to 24 hours in advance.^5,6 Reviews of EWS showed a positive trend toward reduced length of stay and mortality. However, conclusions about general efficacy could not be generated because of case heterogeneity and methodologic shortcomings.^4,7 Continuous automated vital sign monitoring of patients on the general ward can now be accomplished with wearable devices.⁸ The first reports on continuous monitoring showed earlier detection of deterioration but not improved clinical end points.^4,9 Since then, different reports on continuous monitoring have shown positive effects but concluded that unprocessed monitoring data per se falls short of generating actionable alarms.^4,10,11

Predictive algorithms, which often use artificial intelligence (AI), are increasingly employed to recognize complex patterns or abnormalities and support predictions of events in big data sets.^12,13 Especially when combined with continuous vital sign monitoring, predictive algorithms have the potential to expedite detection of clinical deterioration and improve patient outcomes. Predictive algorithms using vital signs in the ICU have shown promising results.¹⁴ The impact of predictive algorithms on the general wards, however, is unclear.

The aims of our scoping review were to explore the extent and range of and evidence for predictive vital signs–based algorithms on the adult general ward; to describe the variety of these algorithms; and to categorize effects, facilitators, and barriers of their implementation.¹⁵

We performed a scoping review to create a summary of the current state of research. We used the five-step method of Levac and followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews guidelines (Appendix 1).^16,17

PubMed, Embase, and CINAHL databases were searched for English-language articles written between January 1, 2010, and November 20, 2020. We developed the search queries with an experienced information scientist, and we used database-specific terms and strategies for input, clinical outcome, method, predictive capability, and population (Appendix 2). Additionally, we searched the references of the selected articles, as well as publications citing these articles.

All studies identified were screened by title and abstract by two researchers (RP and YE). The selected studies were read in their entirety and checked for eligibility using the following inclusion criteria: automated algorithm; vital signs-based; real-time prediction; of clinical deterioration; in an adult, general ward population. In cases where there were successive publications with the same algorithm and population, we selected the most recent study.

For screening and selection, we used the Rayyan QCRI online tool (Qatar Computing Research Institute) and Endnote X9 (Clarivate Analytics). We extracted information using a data extraction form and organized it into descriptive characteristics of the selected studies (Table 1): an input data table showing number of admissions, intermittent or continuous measurements, vital signs measured, laboratory results (Appendix Table 1), a table summarizing study designs and settings (Appendix Table 2), and a prediction performance table (Table 2). We report characteristics of the populations and algorithms, prediction specifications such as area under the receiver operating curve (AUROC), and predictive values. Predictive values are affected by prevalence, which may differ among populations. To compare the algorithms, we calculated an indexed positive predictive value (PPV) and a number needed to evaluate (NNE) using a weighted average prevalence of clinical deterioration of 3.0%.

As shown in the Figure, we found 1741 publications, of which we read the full-text of 109. There were 1632 publications that did not meet the inclusion criteria. The publications by Churpek et al,^20,21 Bartkiowak et al,²² Edelson et al,²³ Escobar et al,^24,25 and Kipnis et al²⁶ reported on the same algorithms or databases but had significantly different approaches. For multiple publications using the same algorithm and population, the most recent was named with inclusion of the earlier findings.^20,21,27-29 The resulting 21 papers are included in this review.

Descriptive characteristics of the studies are summarized in Table 1. Nineteen of the publications were full papers and two were conference abstracts. Most of the studies (n = 18) were from the United States; there was one study from South Korea,³⁰ one study from Portugal,³¹ and one study from the United Kingdom.³² In 15 of the studies, there was a strict focus on general or specific wards; 6 studies also included the ICU and/or emergency departments.

Two of the studies were clinical trials, 2 were prospective observational studies, and 17 were retrospective studies. Five studies reported on an active predictive model during admission. Of these, 3 reported that the model was clinically implemented, using the predictions in their clinical workflow. None of the implemented studies used AI.

All input variables are presented in Appendix Table 1. In 10 of the studies, vital signs were combined with laboratory results; in 13 of the studies, vital signs were combined with patient characteristics. All of the studies used data derived from electronic medical records (EMRs), except for Bai et al³³ and Hu et al,³⁴ who used single-source waveforms directly from the bedside monitor. Three studies focused on continuous vital sign measurements.^27,33,34Most authors reported an AUROC to describe the predictive value of their algorithms. As shown in Table 2, AUROCs varied from 0.65 to 0.95, with indexed PPVs between 0.24 and 0.75. Sensitivity ranged from 7.2% to 52.5% in non-AI models and up to 82.4% in AI models. Prediction definitions, horizons, and the reported metrics differed too much to directly compare studies.

The non-AI algorithm prediction horizons ranged from 4 to 24 hours, with a median of 24 hours (interquartile range [IQR], 12-24 hours). The AI algorithms ranged from 2 to 48 hours and had a median horizon of 14 hours (IQR, 12-24 hours).

We found three studies reporting patient outcomes. The most recent of these was a large multicenter implementation study by Escobar et al²⁵ that included an extensive follow-up response. This study reported a significantly decreased 30-day mortality in the intervention cohort. A smaller randomized controlled trial reported no significant differences in patient outcomes with earlier warning alarms.²⁷ A third study reported more appropriate rapid response team deployment and decreased mortality in a subgroup analysis.³⁵

Effects, Facilitators, and Barriers

As shown in the Appendix Figure and further detailed in Table 3, the described effects were predominantly positive—57 positive effects vs 11 negative effects. These positive effects sorted primarily into the outcome and process domains.

All of the studies that compared their proposed model with one of various warning systems (eg, EWS, National Early Warning Score [NEWS], Modified Early Warning Score [MEWS]) showed superior performance (based on AUROC and reported predictive values). In 17 studies, the authors reported their model as more useful or superior to the EWS.^{20-23,26-28,34,36-41} Four studies reported real-time detection of deterioration before regular EWS,^20,26,42 and three studies reported positive effects on patient-related outcomes.^26,35 Four negative effects were noted on the controllability, validity, and potential limitations.^27,42

There were 26 positive effects on the clinical process mentioned, 7 of which pointed out the effects of earlier, predictive alarming. Algorithms with higher PPVs reported greater rates of actionable alarms, less alarm fatigue, and improved workflow.^{21,22,24-27,30,32,33,35-38,40} Potential alarm fatigue was named as a barrier.^27,42 Smoother scoring instead of binned categories was mentioned positively.^24,26In the infrastructure domain, very few items were reported. The increased need for education on the used techniques was reported once as a negative effect.³⁴ One of the positive infrastructural effects noted was more efficient planning and use of resources.^24,37,40We identified 57 facilitators and 48 barriers for the clinical implementation and use of real-time predictive analytics (Appendix Figure). In the Technology domain, there were 18 facilitators and 20 barriers cited, and in the Organization domain, 25 and 14, respectively. They were equally present in the Professional and Physiology domains (6 vs 5, 8 vs 9).

Of the 38 remarks in the Technology domain, difficulty with implementation in daily practice was a commonly cited barrier.^22,24,40,42 Difficulties included creating real-time data feeds out of the EMR, though there were mentions of some successful examples.^25,27,36 Difficulty in the interpretability of AI was also considered a potential barrier.^{30,32,33,35,39,41} There were remarks as to the applicability of the prolonged prediction horizon because of the associated decoupling from the clinical view.^39,42

Conservative attitudes toward new technologies and inadequate knowledge were mentioned as barriers.³⁹ Repeated remarks were made on the difficulty of interpreting and responding to a predicted escalation, as the clinical pattern might not be recognizable at such an early stage. On the other hand, it is expected that less invasive countermeasures would be adequate to avert further escalation. Earlier recognition of possible escalations also raised potential ethical questions, such as when to discuss palliative care.²⁴

The heterogeneity of the general ward population and the relatively low prevalence of deterioration were mentioned as barriers.^24,30,38,41 There were also concerns that not all escalations are preventable and that some patient outcomes may not be modifiable.^24,38

Many investigators expected reductions in false alarms and associated alarm fatigue (reflected as higher PPVs). Furthermore, they expected workflow to improve and workload to decrease.^{21,23,27,31,33,35,38,41} Despite the capacity of modern EMRs to store large amounts of patient data, some investigators felt improvements to real-time access, data quality and validity, and data density are needed to ensure valid associated predictions.^{21,22,24,32,37}

As the complexity and comorbidity of hospitalized adults grow, predicting clinical deterioration is becoming more important. With an ever-increasing amount of available patient data, real-time algorithms can predict the patient’s clinical course with increasing accuracy, positively affecting outcomes.^4,21,25,43 The studies identified in this scoping review, as measured by higher AUROC scores and improved PPVs, show that predictive algorithms can outperform more conventional EWS, enable earlier and more efficient alarming, and be successfully implemented on the general wards. However, formal meta-analysis was made infeasible by differences in populations, use of different endpoint definitions, cut-off points, time-horizons to prediction, and other methodologic heterogeneity.

There are several important limitations across these studies. In a clinical setting, these models would function as a screening test. Almost all studies report an AUROC; however, sensitivity and PPV or NNE (defined as 1/PPV) may be more useful than AUROC when predicting low-frequency events with high-potential clinical impact.⁴⁴ Assessing the NNE is especially relevant because of its relation to alarm fatigue and responsiveness of clinicians.⁴³ Alarm fatigue and lack of adequate response to alarms were repeatedly cited as potential barriers for application of automated scores. A more useful metric might be NNE over a certain timeframe and across a specified number of patients to more clearly reflect associated workload. Future studies should include these metrics as indicators of the usability and clinical impact of predictive models. This review could not assess PPV or NNE systematically due to inconsistencies in the reporting of these metrics.

Although the results of our scoping review are promising, there are limited data on clinical outcomes using these algorithms. Only three of five algorithms were used to guide clinical decision-making.^25,27,35 Kollef et al²⁷ showed shorter hospitalizations and Evans et al³⁵ found decreased mortality rates in a multimorbid subgroup. Escobar et al²⁵ found an overall and consistent decrease in mortality in a large, heterogenic population of inpatients across 21 hospitals. While Escobar et al’s findings provide strong evidence that predictive algorithms and structured follow-up on alarms can improve patient outcomes, it recognizes that not all facilities will have the resources to implement them.²⁵ Dedicated round-the-clock follow-up of alarms has yet to be proven feasible for smaller institutions, and leaner solutions must be explored. The example set by Escobar et al²⁵ should be translated into various settings to prove its reproducibility and to substantiate the clinical impact of predictive models and structured follow-up.

According to expert opinion, the use of high-frequency or continuous monitoring at low-acuity wards and AI algorithms to detect trends and patterns will reduce failure-to-rescue rates.^4,9,43 However, most studies in our review focused on periodic spot-checked vital signs, and none of the AI algorithms were implemented in clinical care (Appendix Table 1). A significant barrier to implementation was uncertainty surrounding how to react to generated alarms.^9,45 As algorithms become more complex and predict earlier, interpretability and causality in general can diminish, and the response to this type of alarm will be different from that of an acute warning from an EWS.

The assessment of predictive algorithm protocols must include their impact on clinical workflow, workload, and resource utilization. Earlier detection of deterioration can potentially allow coordinated alarm follow-up and lead to more efficient use of resources.^{20,21,31,43,46,47}

Greater numbers of variables do not always improve the quality of monitoring. For example, in one study, an algorithm combining only heart rate, respiration rate, and age outperformed an EWS that tracked six vital sign measures.²³ Algorithms using fewer variables may facilitate more frequent and less complex error-sensitive monitoring. Leaner measurements may also lead to higher patient and clinician acceptance.^43,45The end goal of implementing predictive algorithms on the general ward is to provide timely, reliable, and actionable clinical decision support.⁴³ As shown in a recent study by Blackwell et al,⁴⁸ multiple prediction models for specific clinical events may increase interpretability and performance. Disease-specific algorithms may complement general algorithms for clinical deterioration and enhance overall performance.

STRENGTHS AND LIMITATIONS

We performed a comprehensive review of the current literature using a clear and reproducible methodology to minimize the risk of missing relevant publications. The identified research is mainly limited to large US centers and consists of mostly retrospective studies. Heterogeneity among inputs, endpoints, time horizons, and evaluation metrics make comparisons challenging. Comments on facilitators, barriers, and effects were limited. Positive publication bias may have led to overrepresentation of models showing clinical benefit.

RECOMMENDATIONS FOR FUTURE RESEARCH

Artificial intelligence and the use of continuous monitoring hold great promise in creating optimal predictive algorithms. Future studies should directly compare AI- and non-AI-based algorithms using continuous monitoring to determine predictive accuracy, feasibility, costs, and outcomes. A consensus on endpoint definitions, input variables, methodology, and reporting is needed to enhance reproducibility, comparability, and generalizability of future research. The current research is limited to a few research groups, predominantly in the United States. More international research could enhance validity and increase applicability across varying populations and settings. Greater collaboration would accelerate research and enhance short-cycled continuous improvements. Sharing databases with different populations, variables, and outcomes, such as the Medical Information Mart for Intensive Care database,⁴⁹ could help develop, test, and compare models and contribute to consensus in data standardization and consistent reporting of results. Studies should be designed to determine clinical, societal, and economic effects in accordance with the Quadruple Aim principle.⁵⁰ Successful implementation will depend not only on improved patient outcomes but also on cost-effectiveness, robust statistics, and end-user acceptance. Follow-up protocols and workflows also should be studied and optimized.

Predictive analytics based on vital sign monitoring can identify clinical deterioration at an earlier stage and can do so more accurately than conventional EWS. Implementation of such monitoring can simultaneously decrease alarm-related workload and enhance the efficiency of follow-up. While there is also emerging evidence of associated mortality reduction, it may be too soon to know how representative these findings are. The current literature is limited by heterogeneity across populations studied, monitoring frequency, definitions of deterioration, and clinical outcomes. Consensus is therefore needed to better compare tools and harmonize results. Artificial intelligence and continuous monitoring show great promise in advancing the field; however, additional studies to assess cost, actionability of results, and end-user acceptance are required.

The early identification of clinical deterioration among adult hospitalized patients remains a challenge.¹ Delayed identification is associated with increased morbidity and mortality, unplanned intensive care unit (ICU) admissions, prolonged hospitalization, and higher costs.^2,3 Earlier detection of deterioration using predictive algorithms of vital sign monitoring might avoid these negative outcomes.⁴ In this scoping review, we summarize current algorithms and their evidence.

Vital signs provide the backbone for detecting clinical deterioration. Early warning scores (EWS) and outreach protocols were developed to bring structure to the assessment of vital signs. Most EWS claim to predict clinical end points such as unplanned ICU admission up to 24 hours in advance.^5,6 Reviews of EWS showed a positive trend toward reduced length of stay and mortality. However, conclusions about general efficacy could not be generated because of case heterogeneity and methodologic shortcomings.^4,7 Continuous automated vital sign monitoring of patients on the general ward can now be accomplished with wearable devices.⁸ The first reports on continuous monitoring showed earlier detection of deterioration but not improved clinical end points.^4,9 Since then, different reports on continuous monitoring have shown positive effects but concluded that unprocessed monitoring data per se falls short of generating actionable alarms.^4,10,11

Predictive algorithms, which often use artificial intelligence (AI), are increasingly employed to recognize complex patterns or abnormalities and support predictions of events in big data sets.^12,13 Especially when combined with continuous vital sign monitoring, predictive algorithms have the potential to expedite detection of clinical deterioration and improve patient outcomes. Predictive algorithms using vital signs in the ICU have shown promising results.¹⁴ The impact of predictive algorithms on the general wards, however, is unclear.

The aims of our scoping review were to explore the extent and range of and evidence for predictive vital signs–based algorithms on the adult general ward; to describe the variety of these algorithms; and to categorize effects, facilitators, and barriers of their implementation.¹⁵

We performed a scoping review to create a summary of the current state of research. We used the five-step method of Levac and followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews guidelines (Appendix 1).^16,17

PubMed, Embase, and CINAHL databases were searched for English-language articles written between January 1, 2010, and November 20, 2020. We developed the search queries with an experienced information scientist, and we used database-specific terms and strategies for input, clinical outcome, method, predictive capability, and population (Appendix 2). Additionally, we searched the references of the selected articles, as well as publications citing these articles.

All studies identified were screened by title and abstract by two researchers (RP and YE). The selected studies were read in their entirety and checked for eligibility using the following inclusion criteria: automated algorithm; vital signs-based; real-time prediction; of clinical deterioration; in an adult, general ward population. In cases where there were successive publications with the same algorithm and population, we selected the most recent study.

For screening and selection, we used the Rayyan QCRI online tool (Qatar Computing Research Institute) and Endnote X9 (Clarivate Analytics). We extracted information using a data extraction form and organized it into descriptive characteristics of the selected studies (Table 1): an input data table showing number of admissions, intermittent or continuous measurements, vital signs measured, laboratory results (Appendix Table 1), a table summarizing study designs and settings (Appendix Table 2), and a prediction performance table (Table 2). We report characteristics of the populations and algorithms, prediction specifications such as area under the receiver operating curve (AUROC), and predictive values. Predictive values are affected by prevalence, which may differ among populations. To compare the algorithms, we calculated an indexed positive predictive value (PPV) and a number needed to evaluate (NNE) using a weighted average prevalence of clinical deterioration of 3.0%.

As shown in the Figure, we found 1741 publications, of which we read the full-text of 109. There were 1632 publications that did not meet the inclusion criteria. The publications by Churpek et al,^20,21 Bartkiowak et al,²² Edelson et al,²³ Escobar et al,^24,25 and Kipnis et al²⁶ reported on the same algorithms or databases but had significantly different approaches. For multiple publications using the same algorithm and population, the most recent was named with inclusion of the earlier findings.^20,21,27-29 The resulting 21 papers are included in this review.

Descriptive characteristics of the studies are summarized in Table 1. Nineteen of the publications were full papers and two were conference abstracts. Most of the studies (n = 18) were from the United States; there was one study from South Korea,³⁰ one study from Portugal,³¹ and one study from the United Kingdom.³² In 15 of the studies, there was a strict focus on general or specific wards; 6 studies also included the ICU and/or emergency departments.

Two of the studies were clinical trials, 2 were prospective observational studies, and 17 were retrospective studies. Five studies reported on an active predictive model during admission. Of these, 3 reported that the model was clinically implemented, using the predictions in their clinical workflow. None of the implemented studies used AI.

All input variables are presented in Appendix Table 1. In 10 of the studies, vital signs were combined with laboratory results; in 13 of the studies, vital signs were combined with patient characteristics. All of the studies used data derived from electronic medical records (EMRs), except for Bai et al³³ and Hu et al,³⁴ who used single-source waveforms directly from the bedside monitor. Three studies focused on continuous vital sign measurements.^27,33,34Most authors reported an AUROC to describe the predictive value of their algorithms. As shown in Table 2, AUROCs varied from 0.65 to 0.95, with indexed PPVs between 0.24 and 0.75. Sensitivity ranged from 7.2% to 52.5% in non-AI models and up to 82.4% in AI models. Prediction definitions, horizons, and the reported metrics differed too much to directly compare studies.

The non-AI algorithm prediction horizons ranged from 4 to 24 hours, with a median of 24 hours (interquartile range [IQR], 12-24 hours). The AI algorithms ranged from 2 to 48 hours and had a median horizon of 14 hours (IQR, 12-24 hours).

We found three studies reporting patient outcomes. The most recent of these was a large multicenter implementation study by Escobar et al²⁵ that included an extensive follow-up response. This study reported a significantly decreased 30-day mortality in the intervention cohort. A smaller randomized controlled trial reported no significant differences in patient outcomes with earlier warning alarms.²⁷ A third study reported more appropriate rapid response team deployment and decreased mortality in a subgroup analysis.³⁵

Effects, Facilitators, and Barriers

As shown in the Appendix Figure and further detailed in Table 3, the described effects were predominantly positive—57 positive effects vs 11 negative effects. These positive effects sorted primarily into the outcome and process domains.

All of the studies that compared their proposed model with one of various warning systems (eg, EWS, National Early Warning Score [NEWS], Modified Early Warning Score [MEWS]) showed superior performance (based on AUROC and reported predictive values). In 17 studies, the authors reported their model as more useful or superior to the EWS.^{20-23,26-28,34,36-41} Four studies reported real-time detection of deterioration before regular EWS,^20,26,42 and three studies reported positive effects on patient-related outcomes.^26,35 Four negative effects were noted on the controllability, validity, and potential limitations.^27,42

There were 26 positive effects on the clinical process mentioned, 7 of which pointed out the effects of earlier, predictive alarming. Algorithms with higher PPVs reported greater rates of actionable alarms, less alarm fatigue, and improved workflow.^{21,22,24-27,30,32,33,35-38,40} Potential alarm fatigue was named as a barrier.^27,42 Smoother scoring instead of binned categories was mentioned positively.^24,26In the infrastructure domain, very few items were reported. The increased need for education on the used techniques was reported once as a negative effect.³⁴ One of the positive infrastructural effects noted was more efficient planning and use of resources.^24,37,40We identified 57 facilitators and 48 barriers for the clinical implementation and use of real-time predictive analytics (Appendix Figure). In the Technology domain, there were 18 facilitators and 20 barriers cited, and in the Organization domain, 25 and 14, respectively. They were equally present in the Professional and Physiology domains (6 vs 5, 8 vs 9).

Of the 38 remarks in the Technology domain, difficulty with implementation in daily practice was a commonly cited barrier.^22,24,40,42 Difficulties included creating real-time data feeds out of the EMR, though there were mentions of some successful examples.^25,27,36 Difficulty in the interpretability of AI was also considered a potential barrier.^{30,32,33,35,39,41} There were remarks as to the applicability of the prolonged prediction horizon because of the associated decoupling from the clinical view.^39,42

Conservative attitudes toward new technologies and inadequate knowledge were mentioned as barriers.³⁹ Repeated remarks were made on the difficulty of interpreting and responding to a predicted escalation, as the clinical pattern might not be recognizable at such an early stage. On the other hand, it is expected that less invasive countermeasures would be adequate to avert further escalation. Earlier recognition of possible escalations also raised potential ethical questions, such as when to discuss palliative care.²⁴

The heterogeneity of the general ward population and the relatively low prevalence of deterioration were mentioned as barriers.^24,30,38,41 There were also concerns that not all escalations are preventable and that some patient outcomes may not be modifiable.^24,38

Many investigators expected reductions in false alarms and associated alarm fatigue (reflected as higher PPVs). Furthermore, they expected workflow to improve and workload to decrease.^{21,23,27,31,33,35,38,41} Despite the capacity of modern EMRs to store large amounts of patient data, some investigators felt improvements to real-time access, data quality and validity, and data density are needed to ensure valid associated predictions.^{21,22,24,32,37}

As the complexity and comorbidity of hospitalized adults grow, predicting clinical deterioration is becoming more important. With an ever-increasing amount of available patient data, real-time algorithms can predict the patient’s clinical course with increasing accuracy, positively affecting outcomes.^4,21,25,43 The studies identified in this scoping review, as measured by higher AUROC scores and improved PPVs, show that predictive algorithms can outperform more conventional EWS, enable earlier and more efficient alarming, and be successfully implemented on the general wards. However, formal meta-analysis was made infeasible by differences in populations, use of different endpoint definitions, cut-off points, time-horizons to prediction, and other methodologic heterogeneity.

There are several important limitations across these studies. In a clinical setting, these models would function as a screening test. Almost all studies report an AUROC; however, sensitivity and PPV or NNE (defined as 1/PPV) may be more useful than AUROC when predicting low-frequency events with high-potential clinical impact.⁴⁴ Assessing the NNE is especially relevant because of its relation to alarm fatigue and responsiveness of clinicians.⁴³ Alarm fatigue and lack of adequate response to alarms were repeatedly cited as potential barriers for application of automated scores. A more useful metric might be NNE over a certain timeframe and across a specified number of patients to more clearly reflect associated workload. Future studies should include these metrics as indicators of the usability and clinical impact of predictive models. This review could not assess PPV or NNE systematically due to inconsistencies in the reporting of these metrics.

Although the results of our scoping review are promising, there are limited data on clinical outcomes using these algorithms. Only three of five algorithms were used to guide clinical decision-making.^25,27,35 Kollef et al²⁷ showed shorter hospitalizations and Evans et al³⁵ found decreased mortality rates in a multimorbid subgroup. Escobar et al²⁵ found an overall and consistent decrease in mortality in a large, heterogenic population of inpatients across 21 hospitals. While Escobar et al’s findings provide strong evidence that predictive algorithms and structured follow-up on alarms can improve patient outcomes, it recognizes that not all facilities will have the resources to implement them.²⁵ Dedicated round-the-clock follow-up of alarms has yet to be proven feasible for smaller institutions, and leaner solutions must be explored. The example set by Escobar et al²⁵ should be translated into various settings to prove its reproducibility and to substantiate the clinical impact of predictive models and structured follow-up.

According to expert opinion, the use of high-frequency or continuous monitoring at low-acuity wards and AI algorithms to detect trends and patterns will reduce failure-to-rescue rates.^4,9,43 However, most studies in our review focused on periodic spot-checked vital signs, and none of the AI algorithms were implemented in clinical care (Appendix Table 1). A significant barrier to implementation was uncertainty surrounding how to react to generated alarms.^9,45 As algorithms become more complex and predict earlier, interpretability and causality in general can diminish, and the response to this type of alarm will be different from that of an acute warning from an EWS.

The assessment of predictive algorithm protocols must include their impact on clinical workflow, workload, and resource utilization. Earlier detection of deterioration can potentially allow coordinated alarm follow-up and lead to more efficient use of resources.^{20,21,31,43,46,47}

Greater numbers of variables do not always improve the quality of monitoring. For example, in one study, an algorithm combining only heart rate, respiration rate, and age outperformed an EWS that tracked six vital sign measures.²³ Algorithms using fewer variables may facilitate more frequent and less complex error-sensitive monitoring. Leaner measurements may also lead to higher patient and clinician acceptance.^43,45The end goal of implementing predictive algorithms on the general ward is to provide timely, reliable, and actionable clinical decision support.⁴³ As shown in a recent study by Blackwell et al,⁴⁸ multiple prediction models for specific clinical events may increase interpretability and performance. Disease-specific algorithms may complement general algorithms for clinical deterioration and enhance overall performance.

STRENGTHS AND LIMITATIONS

We performed a comprehensive review of the current literature using a clear and reproducible methodology to minimize the risk of missing relevant publications. The identified research is mainly limited to large US centers and consists of mostly retrospective studies. Heterogeneity among inputs, endpoints, time horizons, and evaluation metrics make comparisons challenging. Comments on facilitators, barriers, and effects were limited. Positive publication bias may have led to overrepresentation of models showing clinical benefit.

RECOMMENDATIONS FOR FUTURE RESEARCH

Artificial intelligence and the use of continuous monitoring hold great promise in creating optimal predictive algorithms. Future studies should directly compare AI- and non-AI-based algorithms using continuous monitoring to determine predictive accuracy, feasibility, costs, and outcomes. A consensus on endpoint definitions, input variables, methodology, and reporting is needed to enhance reproducibility, comparability, and generalizability of future research. The current research is limited to a few research groups, predominantly in the United States. More international research could enhance validity and increase applicability across varying populations and settings. Greater collaboration would accelerate research and enhance short-cycled continuous improvements. Sharing databases with different populations, variables, and outcomes, such as the Medical Information Mart for Intensive Care database,⁴⁹ could help develop, test, and compare models and contribute to consensus in data standardization and consistent reporting of results. Studies should be designed to determine clinical, societal, and economic effects in accordance with the Quadruple Aim principle.⁵⁰ Successful implementation will depend not only on improved patient outcomes but also on cost-effectiveness, robust statistics, and end-user acceptance. Follow-up protocols and workflows also should be studied and optimized.

Predictive analytics based on vital sign monitoring can identify clinical deterioration at an earlier stage and can do so more accurately than conventional EWS. Implementation of such monitoring can simultaneously decrease alarm-related workload and enhance the efficiency of follow-up. While there is also emerging evidence of associated mortality reduction, it may be too soon to know how representative these findings are. The current literature is limited by heterogeneity across populations studied, monitoring frequency, definitions of deterioration, and clinical outcomes. Consensus is therefore needed to better compare tools and harmonize results. Artificial intelligence and continuous monitoring show great promise in advancing the field; however, additional studies to assess cost, actionability of results, and end-user acceptance are required.

Pregnant women with migraine are at increased risk for more obstetric and postpartum complications and should be considered “high risk,” new research suggests. Although pregnancy is generally considered a “safe period” for women with migraine, “we actually found they have more diabetes, more hypertension, more blood clots, more complications during their delivery, and more postpartum complications,” said study investigator Nirit Lev, MD, PhD, head, department of neurology, Meir Medical Center, Kfar Saba Sackler Faculty of Medicine, Tel Aviv University.

The results highlight the need for clinicians “to take people with migraines seriously” and reinforce the idea that migraine is not “just a headache,” said Dr. Lev.

Pregnant women with migraine should be considered high risk and have specialized neurologic follow-up during pregnancy and the postpartum period, she added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

Prevalent, disabling

Migraine is one of the most prevalent and disabling neurologic disorders. Such disorders are major causes of death and disability.

In childhood, there’s no difference between the sexes in terms of migraine prevalence, but after puberty, migraine is about three times more common in women than men. Fluctuating levels of estrogen and progesterone likely explain these differences, said Dr. Lev.

The prevalence of migraine among females peaks during their reproductive years. Most female migraine patients report an improvement in headache symptoms during pregnancy, with some experiencing a “complete remission.” However, a minority report worsening of migraine when expecting a child, said Dr. Lev.

Some patients have their first aura during pregnancy. The most common migraine aura is visual, a problem with the visual field that can affect motor and sensory functioning, said Dr. Lev.

Managing migraine during pregnancy is “very complicated,” said Dr. Lev. She said the first-line treatment is paracetamol (acetaminophen) and stressed that taking opioids should be avoided.
 

Retrospective database study

For the study, the researchers retrospectively reviewed pregnancy and delivery records from a database of Clalit Medical Services, which has more than 4.5 million members and is the largest such database in Israel. They collected demographic data and information on mode of delivery, medical and obstetric complications, hospitalizations, emergency department visits, use of medications, laboratory reports, and medical consultations.

The study included 145,102 women who gave birth from 2014 to 2020.

Of these, 10,646 had migraine without aura, and 1,576 had migraine with aura. The migraine diagnoses, which were based on International Headache Society criteria and diagnostic codes, were made prior to pregnancy.

Dr. Lev noted that the number of patients with migraine is likely an underestimation because migraine is “not always diagnosed.”

Results showed that the risk for obstetric complications was higher among pregnant women with migraine, especially those with aura, in comparison with women without migraine. About 6.9% of patients with migraine without aura were admitted to high-risk hospital departments, compared with 6% of pregnant control patients who did not have migraine (P < .0001). For patients with migraine with aura, the risk for admissions was even higher (8.7%; P < .0001 vs. control patients and P < .03 vs. patients with migraine without aura) and was “very highly statistically significant,” said Dr. Lev.

Pregnant women with migraine were at significantly increased risk for gestational diabetes, hyperlipidemia, and being diagnosed with a psychiatric disorder (all P < .0001). These women were also more likely to experience preeclampsia and blood clots (P < .0001).
 

Unexpected finding

The finding that the risk for diabetes was higher was “unexpected,” inasmuch as older women with migraine are typically at increased risk for metabolic syndrome and higher body mass index, said Dr. Lev.

Migraine patients had significantly more consultations with family physicians, gynecologists, and neurologists (P < .0001). In addition, they were more likely to utilize emergency services; take more medications, mostly analgesics; and undergo more laboratory studies and brain imaging.

Those with aura had significantly more specialist consultations and took more medications compared with migraine patients without aura.

There was a statistically significant increase in the use of epidural anesthesia for migraine patients (40.5% of women without migraine; 45.7% of those with migraine accompanied by aura; and 47.5% of migraine patients without aura).

This was an “interesting” finding, said Dr. Lev. “We didn’t know what to expect; people with migraine are used to pain, so the question was, will they tolerate pain better or be more afraid of pain?”

Women with migraine also experienced more assisted deliveries with increased use of vacuums and forceps.

During the 3-month postpartum period, women with migraine sought more medical consultations and used more medications compared with control patients. They also underwent more lab examinations and more brain imaging during this period.

Dr. Lev noted that some of these evaluations may have been postponed because of the pregnancy.

Women with migraine also had a greater risk for postpartum depression, which Dr. Lev found “concerning.” She noted that depression is often underreported but is treatable. Women with migraine should be monitored for depression post partum, she said.

It’s unclear which factors contribute to the increased risk for pregnancy complications in women with migraine. Dr. Lev said she doesn’t believe it’s drug related.

“Although they’re taking more medications than people who don’t have migraine, we still are giving very low doses and only safe medicines, so I don’t think these increased risks are side effects,” she said.

She noted that women with migraine have more cardiovascular complications, including stroke and myocardial infarction, although these generally affect older patients.

Dr. Lev also noted that pain, especially chronic pain, can cause depression. “We know that people with migraine have more depression and anxiety, so maybe that also affects them during their pregnancy and after,” she said.

She suggested that pregnant women with migraine be considered high risk and be managed via specialized clinics.
 

Room for improvement

Commenting on the research, Lauren Doyle Strauss, DO, associate professor of neurology, Wake Forest University, Winston-Salem, N.C., who has written about the management of migraine during pregnancy, said studies such as this help raise awareness about pregnancy risks in migraine patients. Dr. Strauss did not attend the live presentation but is aware of the findings.

The increased use of epidurals during delivery among migraine patients in the study makes some sense, said Dr. Strauss. “It kind of shows a comfort level with medicines.”

She expressed concern that such research may be “skewed” because it includes patients with more severe migraine. If less severe cases were included in this research, “maybe there would still be higher risks, but not as high as what we have been finding in some of our studies,” she said.

Dr. Strauss said she feels the medical community should do a better job of identifying and diagnosing migraine. She said she would like to see migraine screening become a routine part of obstetric/gynecologic care. Doctors should counsel migraine patients who wish to become pregnant about potential risks, said Dr. Strauss. “We need to be up front in telling them when to seek care and when to report symptoms and not to wait for it to become super severe,” she said.

She also believes doctors should be “proactive” in helping patients develop a treatment plan before becoming pregnant, because the limited pain control options available for pregnant patients can take time to have an effect.

Also commenting on the study findings, Nina Riggins, MD, PhD, clinical associate professor of neurology at the University of California, San Francisco, said the study raises “important questions” and has “important aims.”

She believes the study reinforces the importance of collaboration between experts in primary care, obstetrics/gynecology, and neurology. However, she was surprised at some of the investigators’ assertions that there are no differences in migraine among prepubertal children and that the course of migraine for men is stable throughout their life span.

“There is literature that supports the view that the prevalence in boys is higher in prepuberty, and studies do show that migraine prevalence decreases in older adults – men and women,” she said.

There is still not enough evidence to determine that antiemetics and triptans are safe during pregnancy or that pregnant women with migraine should be taking acetylsalicylic acid, said Dr. Riggins.

The investigators, Dr. Strauss, and Dr. Riggins have disclosed no relevant financial relationships.

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

Pregnant women with migraine are at increased risk for more obstetric and postpartum complications and should be considered “high risk,” new research suggests. Although pregnancy is generally considered a “safe period” for women with migraine, “we actually found they have more diabetes, more hypertension, more blood clots, more complications during their delivery, and more postpartum complications,” said study investigator Nirit Lev, MD, PhD, head, department of neurology, Meir Medical Center, Kfar Saba Sackler Faculty of Medicine, Tel Aviv University.

The results highlight the need for clinicians “to take people with migraines seriously” and reinforce the idea that migraine is not “just a headache,” said Dr. Lev.

Pregnant women with migraine should be considered high risk and have specialized neurologic follow-up during pregnancy and the postpartum period, she added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

Prevalent, disabling

Migraine is one of the most prevalent and disabling neurologic disorders. Such disorders are major causes of death and disability.

In childhood, there’s no difference between the sexes in terms of migraine prevalence, but after puberty, migraine is about three times more common in women than men. Fluctuating levels of estrogen and progesterone likely explain these differences, said Dr. Lev.

The prevalence of migraine among females peaks during their reproductive years. Most female migraine patients report an improvement in headache symptoms during pregnancy, with some experiencing a “complete remission.” However, a minority report worsening of migraine when expecting a child, said Dr. Lev.

Some patients have their first aura during pregnancy. The most common migraine aura is visual, a problem with the visual field that can affect motor and sensory functioning, said Dr. Lev.

Managing migraine during pregnancy is “very complicated,” said Dr. Lev. She said the first-line treatment is paracetamol (acetaminophen) and stressed that taking opioids should be avoided.
 

Retrospective database study

For the study, the researchers retrospectively reviewed pregnancy and delivery records from a database of Clalit Medical Services, which has more than 4.5 million members and is the largest such database in Israel. They collected demographic data and information on mode of delivery, medical and obstetric complications, hospitalizations, emergency department visits, use of medications, laboratory reports, and medical consultations.

The study included 145,102 women who gave birth from 2014 to 2020.

Of these, 10,646 had migraine without aura, and 1,576 had migraine with aura. The migraine diagnoses, which were based on International Headache Society criteria and diagnostic codes, were made prior to pregnancy.

Dr. Lev noted that the number of patients with migraine is likely an underestimation because migraine is “not always diagnosed.”

Results showed that the risk for obstetric complications was higher among pregnant women with migraine, especially those with aura, in comparison with women without migraine. About 6.9% of patients with migraine without aura were admitted to high-risk hospital departments, compared with 6% of pregnant control patients who did not have migraine (P < .0001). For patients with migraine with aura, the risk for admissions was even higher (8.7%; P < .0001 vs. control patients and P < .03 vs. patients with migraine without aura) and was “very highly statistically significant,” said Dr. Lev.

Pregnant women with migraine were at significantly increased risk for gestational diabetes, hyperlipidemia, and being diagnosed with a psychiatric disorder (all P < .0001). These women were also more likely to experience preeclampsia and blood clots (P < .0001).
 

Unexpected finding

The finding that the risk for diabetes was higher was “unexpected,” inasmuch as older women with migraine are typically at increased risk for metabolic syndrome and higher body mass index, said Dr. Lev.

Migraine patients had significantly more consultations with family physicians, gynecologists, and neurologists (P < .0001). In addition, they were more likely to utilize emergency services; take more medications, mostly analgesics; and undergo more laboratory studies and brain imaging.

Those with aura had significantly more specialist consultations and took more medications compared with migraine patients without aura.

There was a statistically significant increase in the use of epidural anesthesia for migraine patients (40.5% of women without migraine; 45.7% of those with migraine accompanied by aura; and 47.5% of migraine patients without aura).

This was an “interesting” finding, said Dr. Lev. “We didn’t know what to expect; people with migraine are used to pain, so the question was, will they tolerate pain better or be more afraid of pain?”

Women with migraine also experienced more assisted deliveries with increased use of vacuums and forceps.

During the 3-month postpartum period, women with migraine sought more medical consultations and used more medications compared with control patients. They also underwent more lab examinations and more brain imaging during this period.

Dr. Lev noted that some of these evaluations may have been postponed because of the pregnancy.

Women with migraine also had a greater risk for postpartum depression, which Dr. Lev found “concerning.” She noted that depression is often underreported but is treatable. Women with migraine should be monitored for depression post partum, she said.

It’s unclear which factors contribute to the increased risk for pregnancy complications in women with migraine. Dr. Lev said she doesn’t believe it’s drug related.

“Although they’re taking more medications than people who don’t have migraine, we still are giving very low doses and only safe medicines, so I don’t think these increased risks are side effects,” she said.

She noted that women with migraine have more cardiovascular complications, including stroke and myocardial infarction, although these generally affect older patients.

Dr. Lev also noted that pain, especially chronic pain, can cause depression. “We know that people with migraine have more depression and anxiety, so maybe that also affects them during their pregnancy and after,” she said.

She suggested that pregnant women with migraine be considered high risk and be managed via specialized clinics.
 

Room for improvement

Commenting on the research, Lauren Doyle Strauss, DO, associate professor of neurology, Wake Forest University, Winston-Salem, N.C., who has written about the management of migraine during pregnancy, said studies such as this help raise awareness about pregnancy risks in migraine patients. Dr. Strauss did not attend the live presentation but is aware of the findings.

The increased use of epidurals during delivery among migraine patients in the study makes some sense, said Dr. Strauss. “It kind of shows a comfort level with medicines.”

She expressed concern that such research may be “skewed” because it includes patients with more severe migraine. If less severe cases were included in this research, “maybe there would still be higher risks, but not as high as what we have been finding in some of our studies,” she said.

Dr. Strauss said she feels the medical community should do a better job of identifying and diagnosing migraine. She said she would like to see migraine screening become a routine part of obstetric/gynecologic care. Doctors should counsel migraine patients who wish to become pregnant about potential risks, said Dr. Strauss. “We need to be up front in telling them when to seek care and when to report symptoms and not to wait for it to become super severe,” she said.

She also believes doctors should be “proactive” in helping patients develop a treatment plan before becoming pregnant, because the limited pain control options available for pregnant patients can take time to have an effect.

Also commenting on the study findings, Nina Riggins, MD, PhD, clinical associate professor of neurology at the University of California, San Francisco, said the study raises “important questions” and has “important aims.”

She believes the study reinforces the importance of collaboration between experts in primary care, obstetrics/gynecology, and neurology. However, she was surprised at some of the investigators’ assertions that there are no differences in migraine among prepubertal children and that the course of migraine for men is stable throughout their life span.

“There is literature that supports the view that the prevalence in boys is higher in prepuberty, and studies do show that migraine prevalence decreases in older adults – men and women,” she said.

There is still not enough evidence to determine that antiemetics and triptans are safe during pregnancy or that pregnant women with migraine should be taking acetylsalicylic acid, said Dr. Riggins.

The investigators, Dr. Strauss, and Dr. Riggins have disclosed no relevant financial relationships.

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

Pregnant women with migraine are at increased risk for more obstetric and postpartum complications and should be considered “high risk,” new research suggests. Although pregnancy is generally considered a “safe period” for women with migraine, “we actually found they have more diabetes, more hypertension, more blood clots, more complications during their delivery, and more postpartum complications,” said study investigator Nirit Lev, MD, PhD, head, department of neurology, Meir Medical Center, Kfar Saba Sackler Faculty of Medicine, Tel Aviv University.

The results highlight the need for clinicians “to take people with migraines seriously” and reinforce the idea that migraine is not “just a headache,” said Dr. Lev.

Pregnant women with migraine should be considered high risk and have specialized neurologic follow-up during pregnancy and the postpartum period, she added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

Prevalent, disabling

Migraine is one of the most prevalent and disabling neurologic disorders. Such disorders are major causes of death and disability.

In childhood, there’s no difference between the sexes in terms of migraine prevalence, but after puberty, migraine is about three times more common in women than men. Fluctuating levels of estrogen and progesterone likely explain these differences, said Dr. Lev.

The prevalence of migraine among females peaks during their reproductive years. Most female migraine patients report an improvement in headache symptoms during pregnancy, with some experiencing a “complete remission.” However, a minority report worsening of migraine when expecting a child, said Dr. Lev.

Some patients have their first aura during pregnancy. The most common migraine aura is visual, a problem with the visual field that can affect motor and sensory functioning, said Dr. Lev.

Managing migraine during pregnancy is “very complicated,” said Dr. Lev. She said the first-line treatment is paracetamol (acetaminophen) and stressed that taking opioids should be avoided.
 

Retrospective database study

For the study, the researchers retrospectively reviewed pregnancy and delivery records from a database of Clalit Medical Services, which has more than 4.5 million members and is the largest such database in Israel. They collected demographic data and information on mode of delivery, medical and obstetric complications, hospitalizations, emergency department visits, use of medications, laboratory reports, and medical consultations.

The study included 145,102 women who gave birth from 2014 to 2020.

Of these, 10,646 had migraine without aura, and 1,576 had migraine with aura. The migraine diagnoses, which were based on International Headache Society criteria and diagnostic codes, were made prior to pregnancy.

Dr. Lev noted that the number of patients with migraine is likely an underestimation because migraine is “not always diagnosed.”

Results showed that the risk for obstetric complications was higher among pregnant women with migraine, especially those with aura, in comparison with women without migraine. About 6.9% of patients with migraine without aura were admitted to high-risk hospital departments, compared with 6% of pregnant control patients who did not have migraine (P < .0001). For patients with migraine with aura, the risk for admissions was even higher (8.7%; P < .0001 vs. control patients and P < .03 vs. patients with migraine without aura) and was “very highly statistically significant,” said Dr. Lev.

Pregnant women with migraine were at significantly increased risk for gestational diabetes, hyperlipidemia, and being diagnosed with a psychiatric disorder (all P < .0001). These women were also more likely to experience preeclampsia and blood clots (P < .0001).
 

Unexpected finding

The finding that the risk for diabetes was higher was “unexpected,” inasmuch as older women with migraine are typically at increased risk for metabolic syndrome and higher body mass index, said Dr. Lev.

Migraine patients had significantly more consultations with family physicians, gynecologists, and neurologists (P < .0001). In addition, they were more likely to utilize emergency services; take more medications, mostly analgesics; and undergo more laboratory studies and brain imaging.

Those with aura had significantly more specialist consultations and took more medications compared with migraine patients without aura.

There was a statistically significant increase in the use of epidural anesthesia for migraine patients (40.5% of women without migraine; 45.7% of those with migraine accompanied by aura; and 47.5% of migraine patients without aura).

This was an “interesting” finding, said Dr. Lev. “We didn’t know what to expect; people with migraine are used to pain, so the question was, will they tolerate pain better or be more afraid of pain?”

Women with migraine also experienced more assisted deliveries with increased use of vacuums and forceps.

During the 3-month postpartum period, women with migraine sought more medical consultations and used more medications compared with control patients. They also underwent more lab examinations and more brain imaging during this period.

Dr. Lev noted that some of these evaluations may have been postponed because of the pregnancy.

Women with migraine also had a greater risk for postpartum depression, which Dr. Lev found “concerning.” She noted that depression is often underreported but is treatable. Women with migraine should be monitored for depression post partum, she said.

It’s unclear which factors contribute to the increased risk for pregnancy complications in women with migraine. Dr. Lev said she doesn’t believe it’s drug related.

“Although they’re taking more medications than people who don’t have migraine, we still are giving very low doses and only safe medicines, so I don’t think these increased risks are side effects,” she said.

She noted that women with migraine have more cardiovascular complications, including stroke and myocardial infarction, although these generally affect older patients.

Dr. Lev also noted that pain, especially chronic pain, can cause depression. “We know that people with migraine have more depression and anxiety, so maybe that also affects them during their pregnancy and after,” she said.

She suggested that pregnant women with migraine be considered high risk and be managed via specialized clinics.
 

Room for improvement

Commenting on the research, Lauren Doyle Strauss, DO, associate professor of neurology, Wake Forest University, Winston-Salem, N.C., who has written about the management of migraine during pregnancy, said studies such as this help raise awareness about pregnancy risks in migraine patients. Dr. Strauss did not attend the live presentation but is aware of the findings.

The increased use of epidurals during delivery among migraine patients in the study makes some sense, said Dr. Strauss. “It kind of shows a comfort level with medicines.”

She expressed concern that such research may be “skewed” because it includes patients with more severe migraine. If less severe cases were included in this research, “maybe there would still be higher risks, but not as high as what we have been finding in some of our studies,” she said.

Dr. Strauss said she feels the medical community should do a better job of identifying and diagnosing migraine. She said she would like to see migraine screening become a routine part of obstetric/gynecologic care. Doctors should counsel migraine patients who wish to become pregnant about potential risks, said Dr. Strauss. “We need to be up front in telling them when to seek care and when to report symptoms and not to wait for it to become super severe,” she said.

She also believes doctors should be “proactive” in helping patients develop a treatment plan before becoming pregnant, because the limited pain control options available for pregnant patients can take time to have an effect.

Also commenting on the study findings, Nina Riggins, MD, PhD, clinical associate professor of neurology at the University of California, San Francisco, said the study raises “important questions” and has “important aims.”

She believes the study reinforces the importance of collaboration between experts in primary care, obstetrics/gynecology, and neurology. However, she was surprised at some of the investigators’ assertions that there are no differences in migraine among prepubertal children and that the course of migraine for men is stable throughout their life span.

“There is literature that supports the view that the prevalence in boys is higher in prepuberty, and studies do show that migraine prevalence decreases in older adults – men and women,” she said.

There is still not enough evidence to determine that antiemetics and triptans are safe during pregnancy or that pregnant women with migraine should be taking acetylsalicylic acid, said Dr. Riggins.

The investigators, Dr. Strauss, and Dr. Riggins have disclosed no relevant financial relationships.

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

A large retrospective U.S. study published June 23 in JAMA Dermatology finds that chilblains, an inflammatory skin condition marked by erythema and also known as ‘COVID toes,’ is likely not associated with a COVID-19 diagnosis, despite an unprecedented number of new chilblain cases reported in 2020.

This study follows a report published almost 2 weeks earlier, of 17 adolescents in Italy with chilblain lesions of the toes. That report indicated that the lesions were not related to current or past infections, and that lifestyle changes may have been a contributing factor .

Early last year, clinicians in Europe and the United States began reporting an unusually high number of chilblain cases, but few of the patients described in the cases were positive for SARS-CoV-2 or its antibodies. The possible connection was explored in studies and featured extensively in the lay press. After all, viral infections, including SARS-CoV-2, are known to be associated with skin rashes. Plus, SARS-CoV-2 infections are known to exhibit a number of dermatological manifestations, such as urticarial and morbilliform eruptions, and vesicular eruptions. More than 150 papers have been published on the spectrum of cutaneous reactions to this virus.

In the new study, led by Patrick E. McCleskey, MD, a dermatologist with Kaiser Permanente Oakland (Calif.) Medical Center, a review of chilblain cases from six Bay Area counties in Northern California found a weak correlation confirming 2% of chilblain cases as potentially secondary to COVID-19.

“While chilblains do seem to follow COVID-19 infection in some cases, most cases of chilblains in our study were not shown to be related to SARS-CoV-2 infection,” Dr. McCleskey said in an interview.

“We think the increase in cases probably had more to do with changes in behavior as children and adults were at home instead of work and school. The highest incidence in chilblains were seen in children ages 13-19, who were staying home from school. Only 6% in our study said they wear shoes at home, and half of our patients don’t have home heating in northern California,” he said.

The condition of chilblains primarily affects the dorsal feet or hands and is almost uniquely associated with spending an inordinate amount of time in damp and cold conditions. There are some medical conditions associated with chilblains, such as Raynaud’s disease, systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, hyperhidrosis, and lymphomas and leukemias. And, as with COVID-19, chilblains affect more women than men.

Northern California study

The retrospective cohort study evaluated 780 patients (464 female; mean age 36.8 years) from six Bay Area counties in Northern California, who were treated for chilblains between April and December 2020 when stay-at-home orders were in effect in California. Of the 780 patients, 456 were tested for SARS-CoV-2, and 17 patients (3.7%) tested positive for the virus. In nine patients (2%), a COVID-19 infection was preceded by 6 weeks of chilblains. By September, testing for the COVID-19 virus was more reliable. Testing showed that of 97 chilblains cases, 1% were positive for the virus.

“The finding that some patients with COVID-19 developed chilblains at the same time, or subsequent to the infection, is suggestive of secondary chilblains due to COVID-19,” Dr. McCleskey said.

The 2020 cases were compared with 539 patients (mean age 44.7 years) with chilblains who were treated during the same period in 2016, 2017, 2018 and 2019. During these years, the annual incidence of chilblains was 5.2 (95% confidence interval, 4.8-5.6) per 100,000 person years, compared with 28.6 (95% CI, 26.8-30.4) in 2020, during the pandemic.
 

Possible explanations

The authors suggest there are several explanations for the increased reports of chilblains in 2020. First, the lack of shoes: During the pandemic, children between the ages of 13 and 19 years had more cases of chilblains than any other age group despite the fact that teenagers have a low-risk of contracting SARS-CoV-2. Six percent of teenagers with newly diagnosed chilblains wore shoes at home during the study period in 2020.

Chilblains was almost three times more common in Asian American (42.5; 95% CI, 37.7-47.8) and White individuals (35.7; 95% CI, 32.6-39.1), compared with Black (11.6; 95% CI, 7.8-17.3) and Latinx (12.5; 95% CI, 10.1-15.4) individuals. But the authors noted that the Latinx community had the highest number of COVID-19 cases (62.5; 95% CI, 61.9-63.1), three times more than Asian Americans (19.0; 95% CI, 18.6-19.3) and White individuals (17.9; 95% CI, 17.7-18.2) and two times more than in Black individuals (29.2; 95% CI, 28.4-29.9).

“Latinx patients had the highest rates of COVID-19 infections in our population, but the lowest rates of chilblains. Groups in Northern California who were more likely to stay home during the pandemic because they could work from home – White and Asian American and White patients – had much higher rates of chilblains than groups who were more likely to have to work outside the home – Latinx and African American patients,” Dr. McCleskey said.

A report by the Bay Area Council in December 2020 found that Asian Americans and Whites were more likely to work from home during the pandemic (52% and 50% respectively) compared with Black and Latinx workers (33% and 30% respectively). While Latinx individuals made up 46% of all COVID-19 cases, they accounted for 9% of chilblain cases in 2020 (but cases may have been underreported), the authors wrote.

And while there may have been more cases of chilblains during the pandemic in 2020, they did not occur in cities with higher rates of COVID-19. “If chilblains were occurring in the same communities where COVID-19 cases were occurring, the Spearman coefficient would be closer to 1,” wrote the authors, referring to the measure used to rank correlation in the study. In this case, the Spearman coefficient was 0.18.

Another explanation for the increase in chilblain cases could be that more patients sought care in response to news reports about ‘COVID toes.’

“The exact cause of chilblains is still elusive. Some publications coming out of the pandemic suggest an interferon response is part of the pathophysiology of chilblains, but this was not the focus of our research,” Dr. McCleskey said.

The authors hypothesized that in affected individuals, particularly younger patients, the immune response to SARS-CoV-2 contributed to chilblains in asymptomatic individuals. “It is possible that some patients with chilblains were exposed to SARS-CoV-2 but produced such a robust innate immune response that it was later difficult to find any evidence of infection,” they wrote.

They suggested that better testing may help identify past exposure to SARS-CoV-2 and secondary chilblains.

The strengths of this study included its size, community base, a control group dating back to 2016, validation by medical records review, and the ability to control for geographic variation allowing investigators to track weather, which can be a factor in chilblain cases. The authors noted several limitations to the study, including the lack of reliable antibody testing early in the year and the lack of IgA antibody testing.

The authors had no disclosures. The study was funded by The Permanente Medical Group Delivery Science and Applied Research initiative.

A large retrospective U.S. study published June 23 in JAMA Dermatology finds that chilblains, an inflammatory skin condition marked by erythema and also known as ‘COVID toes,’ is likely not associated with a COVID-19 diagnosis, despite an unprecedented number of new chilblain cases reported in 2020.

This study follows a report published almost 2 weeks earlier, of 17 adolescents in Italy with chilblain lesions of the toes. That report indicated that the lesions were not related to current or past infections, and that lifestyle changes may have been a contributing factor .

Early last year, clinicians in Europe and the United States began reporting an unusually high number of chilblain cases, but few of the patients described in the cases were positive for SARS-CoV-2 or its antibodies. The possible connection was explored in studies and featured extensively in the lay press. After all, viral infections, including SARS-CoV-2, are known to be associated with skin rashes. Plus, SARS-CoV-2 infections are known to exhibit a number of dermatological manifestations, such as urticarial and morbilliform eruptions, and vesicular eruptions. More than 150 papers have been published on the spectrum of cutaneous reactions to this virus.

In the new study, led by Patrick E. McCleskey, MD, a dermatologist with Kaiser Permanente Oakland (Calif.) Medical Center, a review of chilblain cases from six Bay Area counties in Northern California found a weak correlation confirming 2% of chilblain cases as potentially secondary to COVID-19.

“While chilblains do seem to follow COVID-19 infection in some cases, most cases of chilblains in our study were not shown to be related to SARS-CoV-2 infection,” Dr. McCleskey said in an interview.

“We think the increase in cases probably had more to do with changes in behavior as children and adults were at home instead of work and school. The highest incidence in chilblains were seen in children ages 13-19, who were staying home from school. Only 6% in our study said they wear shoes at home, and half of our patients don’t have home heating in northern California,” he said.

The condition of chilblains primarily affects the dorsal feet or hands and is almost uniquely associated with spending an inordinate amount of time in damp and cold conditions. There are some medical conditions associated with chilblains, such as Raynaud’s disease, systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, hyperhidrosis, and lymphomas and leukemias. And, as with COVID-19, chilblains affect more women than men.

Northern California study

The retrospective cohort study evaluated 780 patients (464 female; mean age 36.8 years) from six Bay Area counties in Northern California, who were treated for chilblains between April and December 2020 when stay-at-home orders were in effect in California. Of the 780 patients, 456 were tested for SARS-CoV-2, and 17 patients (3.7%) tested positive for the virus. In nine patients (2%), a COVID-19 infection was preceded by 6 weeks of chilblains. By September, testing for the COVID-19 virus was more reliable. Testing showed that of 97 chilblains cases, 1% were positive for the virus.

“The finding that some patients with COVID-19 developed chilblains at the same time, or subsequent to the infection, is suggestive of secondary chilblains due to COVID-19,” Dr. McCleskey said.

The 2020 cases were compared with 539 patients (mean age 44.7 years) with chilblains who were treated during the same period in 2016, 2017, 2018 and 2019. During these years, the annual incidence of chilblains was 5.2 (95% confidence interval, 4.8-5.6) per 100,000 person years, compared with 28.6 (95% CI, 26.8-30.4) in 2020, during the pandemic.
 

Possible explanations

The authors suggest there are several explanations for the increased reports of chilblains in 2020. First, the lack of shoes: During the pandemic, children between the ages of 13 and 19 years had more cases of chilblains than any other age group despite the fact that teenagers have a low-risk of contracting SARS-CoV-2. Six percent of teenagers with newly diagnosed chilblains wore shoes at home during the study period in 2020.

Chilblains was almost three times more common in Asian American (42.5; 95% CI, 37.7-47.8) and White individuals (35.7; 95% CI, 32.6-39.1), compared with Black (11.6; 95% CI, 7.8-17.3) and Latinx (12.5; 95% CI, 10.1-15.4) individuals. But the authors noted that the Latinx community had the highest number of COVID-19 cases (62.5; 95% CI, 61.9-63.1), three times more than Asian Americans (19.0; 95% CI, 18.6-19.3) and White individuals (17.9; 95% CI, 17.7-18.2) and two times more than in Black individuals (29.2; 95% CI, 28.4-29.9).

“Latinx patients had the highest rates of COVID-19 infections in our population, but the lowest rates of chilblains. Groups in Northern California who were more likely to stay home during the pandemic because they could work from home – White and Asian American and White patients – had much higher rates of chilblains than groups who were more likely to have to work outside the home – Latinx and African American patients,” Dr. McCleskey said.

A report by the Bay Area Council in December 2020 found that Asian Americans and Whites were more likely to work from home during the pandemic (52% and 50% respectively) compared with Black and Latinx workers (33% and 30% respectively). While Latinx individuals made up 46% of all COVID-19 cases, they accounted for 9% of chilblain cases in 2020 (but cases may have been underreported), the authors wrote.

And while there may have been more cases of chilblains during the pandemic in 2020, they did not occur in cities with higher rates of COVID-19. “If chilblains were occurring in the same communities where COVID-19 cases were occurring, the Spearman coefficient would be closer to 1,” wrote the authors, referring to the measure used to rank correlation in the study. In this case, the Spearman coefficient was 0.18.

Another explanation for the increase in chilblain cases could be that more patients sought care in response to news reports about ‘COVID toes.’

“The exact cause of chilblains is still elusive. Some publications coming out of the pandemic suggest an interferon response is part of the pathophysiology of chilblains, but this was not the focus of our research,” Dr. McCleskey said.

The authors hypothesized that in affected individuals, particularly younger patients, the immune response to SARS-CoV-2 contributed to chilblains in asymptomatic individuals. “It is possible that some patients with chilblains were exposed to SARS-CoV-2 but produced such a robust innate immune response that it was later difficult to find any evidence of infection,” they wrote.

They suggested that better testing may help identify past exposure to SARS-CoV-2 and secondary chilblains.

The strengths of this study included its size, community base, a control group dating back to 2016, validation by medical records review, and the ability to control for geographic variation allowing investigators to track weather, which can be a factor in chilblain cases. The authors noted several limitations to the study, including the lack of reliable antibody testing early in the year and the lack of IgA antibody testing.

The authors had no disclosures. The study was funded by The Permanente Medical Group Delivery Science and Applied Research initiative.

A large retrospective U.S. study published June 23 in JAMA Dermatology finds that chilblains, an inflammatory skin condition marked by erythema and also known as ‘COVID toes,’ is likely not associated with a COVID-19 diagnosis, despite an unprecedented number of new chilblain cases reported in 2020.

This study follows a report published almost 2 weeks earlier, of 17 adolescents in Italy with chilblain lesions of the toes. That report indicated that the lesions were not related to current or past infections, and that lifestyle changes may have been a contributing factor .

Early last year, clinicians in Europe and the United States began reporting an unusually high number of chilblain cases, but few of the patients described in the cases were positive for SARS-CoV-2 or its antibodies. The possible connection was explored in studies and featured extensively in the lay press. After all, viral infections, including SARS-CoV-2, are known to be associated with skin rashes. Plus, SARS-CoV-2 infections are known to exhibit a number of dermatological manifestations, such as urticarial and morbilliform eruptions, and vesicular eruptions. More than 150 papers have been published on the spectrum of cutaneous reactions to this virus.

In the new study, led by Patrick E. McCleskey, MD, a dermatologist with Kaiser Permanente Oakland (Calif.) Medical Center, a review of chilblain cases from six Bay Area counties in Northern California found a weak correlation confirming 2% of chilblain cases as potentially secondary to COVID-19.

“While chilblains do seem to follow COVID-19 infection in some cases, most cases of chilblains in our study were not shown to be related to SARS-CoV-2 infection,” Dr. McCleskey said in an interview.

“We think the increase in cases probably had more to do with changes in behavior as children and adults were at home instead of work and school. The highest incidence in chilblains were seen in children ages 13-19, who were staying home from school. Only 6% in our study said they wear shoes at home, and half of our patients don’t have home heating in northern California,” he said.

The condition of chilblains primarily affects the dorsal feet or hands and is almost uniquely associated with spending an inordinate amount of time in damp and cold conditions. There are some medical conditions associated with chilblains, such as Raynaud’s disease, systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, hyperhidrosis, and lymphomas and leukemias. And, as with COVID-19, chilblains affect more women than men.

Northern California study

The retrospective cohort study evaluated 780 patients (464 female; mean age 36.8 years) from six Bay Area counties in Northern California, who were treated for chilblains between April and December 2020 when stay-at-home orders were in effect in California. Of the 780 patients, 456 were tested for SARS-CoV-2, and 17 patients (3.7%) tested positive for the virus. In nine patients (2%), a COVID-19 infection was preceded by 6 weeks of chilblains. By September, testing for the COVID-19 virus was more reliable. Testing showed that of 97 chilblains cases, 1% were positive for the virus.

“The finding that some patients with COVID-19 developed chilblains at the same time, or subsequent to the infection, is suggestive of secondary chilblains due to COVID-19,” Dr. McCleskey said.

The 2020 cases were compared with 539 patients (mean age 44.7 years) with chilblains who were treated during the same period in 2016, 2017, 2018 and 2019. During these years, the annual incidence of chilblains was 5.2 (95% confidence interval, 4.8-5.6) per 100,000 person years, compared with 28.6 (95% CI, 26.8-30.4) in 2020, during the pandemic.
 

Possible explanations

The authors suggest there are several explanations for the increased reports of chilblains in 2020. First, the lack of shoes: During the pandemic, children between the ages of 13 and 19 years had more cases of chilblains than any other age group despite the fact that teenagers have a low-risk of contracting SARS-CoV-2. Six percent of teenagers with newly diagnosed chilblains wore shoes at home during the study period in 2020.

Chilblains was almost three times more common in Asian American (42.5; 95% CI, 37.7-47.8) and White individuals (35.7; 95% CI, 32.6-39.1), compared with Black (11.6; 95% CI, 7.8-17.3) and Latinx (12.5; 95% CI, 10.1-15.4) individuals. But the authors noted that the Latinx community had the highest number of COVID-19 cases (62.5; 95% CI, 61.9-63.1), three times more than Asian Americans (19.0; 95% CI, 18.6-19.3) and White individuals (17.9; 95% CI, 17.7-18.2) and two times more than in Black individuals (29.2; 95% CI, 28.4-29.9).

“Latinx patients had the highest rates of COVID-19 infections in our population, but the lowest rates of chilblains. Groups in Northern California who were more likely to stay home during the pandemic because they could work from home – White and Asian American and White patients – had much higher rates of chilblains than groups who were more likely to have to work outside the home – Latinx and African American patients,” Dr. McCleskey said.

A report by the Bay Area Council in December 2020 found that Asian Americans and Whites were more likely to work from home during the pandemic (52% and 50% respectively) compared with Black and Latinx workers (33% and 30% respectively). While Latinx individuals made up 46% of all COVID-19 cases, they accounted for 9% of chilblain cases in 2020 (but cases may have been underreported), the authors wrote.

And while there may have been more cases of chilblains during the pandemic in 2020, they did not occur in cities with higher rates of COVID-19. “If chilblains were occurring in the same communities where COVID-19 cases were occurring, the Spearman coefficient would be closer to 1,” wrote the authors, referring to the measure used to rank correlation in the study. In this case, the Spearman coefficient was 0.18.

Another explanation for the increase in chilblain cases could be that more patients sought care in response to news reports about ‘COVID toes.’

“The exact cause of chilblains is still elusive. Some publications coming out of the pandemic suggest an interferon response is part of the pathophysiology of chilblains, but this was not the focus of our research,” Dr. McCleskey said.

The authors hypothesized that in affected individuals, particularly younger patients, the immune response to SARS-CoV-2 contributed to chilblains in asymptomatic individuals. “It is possible that some patients with chilblains were exposed to SARS-CoV-2 but produced such a robust innate immune response that it was later difficult to find any evidence of infection,” they wrote.

They suggested that better testing may help identify past exposure to SARS-CoV-2 and secondary chilblains.

The strengths of this study included its size, community base, a control group dating back to 2016, validation by medical records review, and the ability to control for geographic variation allowing investigators to track weather, which can be a factor in chilblain cases. The authors noted several limitations to the study, including the lack of reliable antibody testing early in the year and the lack of IgA antibody testing.

The authors had no disclosures. The study was funded by The Permanente Medical Group Delivery Science and Applied Research initiative.

Long-awaited twincretin data, a study to inform prescribing in type 2 diabetes, COVID-19 and diabetes, and new guidance for treating type 1 diabetes in adults will be among the hot topics at the annual scientific sessions of the American Diabetes Association.

The meeting, to be held virtually for a second year, will take place June 25-29. As usual, the sessions will cover a wide range of basic, translational, and clinical material pertaining to type 1 and type 2 diabetes, complications, related subjects such as obesity and cardiovascular disease, and health care delivery.

New to this year’s agenda is COVID-19 and the many ways it has affected people with diabetes and health care delivery. And, more than in the past, the meeting will focus on ethnic and racial disparities in the delivery of care to people with diabetes.

And of course, there will be a tribute to another special aspect of 2021: the 100th anniversary of the discovery of insulin.

“I think there will undoubtedly be several things that will come out of this meeting that will change practice, and it will be important for clinicians to be aware of those, whether that’s groundbreaking trials or interpretation of data that will help us understand the interrelation between diabetes and COVID-19, which is still with us,” ADA chief scientific and medical officer Robert A. Gabbay, MD, PhD, said in an interview.

And ADA president of medicine and science Ruth S. Weinstock, MD, PhD, said in an interview: “I think there are many exciting sessions at this year’s meeting. ...I hope that it will help [clinicians] take better care of their patients with diabetes.

”

Will the twincretin tirzepatide live up to the hype?

Between December 2020 and May 2021, Eli Lilly issued a series of four press releases touting positive top-line results from a series of phase 3 studies on its novel agent tirzepatide, dubbed a twincretin for its dual actions as an agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagonlike peptide-1 receptors.  

Detailed results from those four trials, SURPASS-1, -2, -3, and -5, will be presented in a symposium on Tuesday, June 29. Results from SURPASS-4 will be presented at the annual meeting of the European Association for the Study of Diabetes in September 2021.

According to the company, the drug met its phase 3 primary efficacy endpoints for both hemoglobin A1c reduction and weight loss.

“At least the buzz on it has been good, but now we want to see the real data,” Dr. Gabbay said, noting that “the early data on weight loss in particular were quite good. So then the question would be: Do you go to a GLP-1 [agonist] or a dual agonist? There will be studies to tease that out.”

Regarding tirzepatide, Dr. Weinstock said: “Hopefully, more people with type 2 diabetes could achieve their glycemic goals, and those who would benefit from weight loss could have better weight loss. I haven’t seen the data, but if the addition of GIP can further improve glucose lowering as well as weight loss that would be great.”
 

How far will GRADE go in answering the second-drug question?

On Monday, June 28, results will be presented from the long-awaited Glycemia Reduction Approaches in Diabetes – A Comparative Effectiveness (GRADE) study.

Launched in 2013, the trial is funded by the National Institutes of Health and several pharmaceutical company partners. Over 5,000 patients diagnosed with type 2 diabetes within the prior 10 years and already taking metformin were randomized to one of four commonly used second-line glucose-lowering agents: glimepiride, sitagliptin, liraglutide, and basal insulin glargine. The aim was to determine which combination produced the best glycemic control with the fewest side effects.

Dr. Weinstock said: “Clinicians now have increasing numbers of medications to choose from when treating hyperglycemia in type 2 diabetes, and a common dilemma is which one to select. The results of GRADE should be informative for people taking care of type 2 diabetes in different populations.”

However, she also pointed out that GRADE does not include a group with a sodium-glucose transporter 2 inhibitor, as the trial was designed prior to the availability of the drug class. Now, SGLT2 inhibitors are widely used and recommended for cardiovascular and kidney benefit as well as glucose lowering.

“I believe the future is really precision medicine where we individualize treatment. So, for someone with heart failure you might choose an SGLT2 inhibitor, but there are plenty of other subpopulations. They are going to be looking at different subpopulations. I think we’re all very interested in seeing what the results are, but it’s not the end of the story. We will still have to individualize therapy and keep in mind their kidney, heart, heart failure status, and other factors,” she said.

Dr. Gabbay pointed out that GRADE is important because it’s one of the few comparative effectiveness trials conducted in diabetes. “I think it will be very rich [data] that will impact practice in a variety of ways. On the one hand, it doesn’t do everything we’d want it to do, but on the other hand, if you think of the number of comparative effectiveness trials in diabetes, there are not a lot ... I think it will be big.”
 

COVID-19 and diabetes: A lot to discuss  

In contrast to the ADA scientific sessions in 2020, which took place too soon after the start of the COVID-19 pandemic to include much material about it, this year’s meeting will address many different aspects of the novel coronavirus.

Sessions will cover minimizing risk in people with diabetes during the pandemic, the latest data on whether COVID-19 triggers diabetes, and if so, by what mechanism, mental health issues related to COVID-19, as well as the management of foot care, pregnancy, and the pediatric population during the pandemic.

On Sunday, June 27, a symposium will be devoted to results of the DARE-19 trial, which explored the effects of the SGLT2 inhibitor dapagliflozin in more than 1200 patients hospitalized with COVID-19. The overall results, presented in May 2021 at the scientific sessions of the American College of Cardiology, showed a nonsignificant trend for benefit in time to organ failure or death compared with placebo. At ADA, separate efficacy and safety results for patients with and without diabetes will be presented.

According to Dr. Weinstock, “We know that in nonhospitalized patients with type 2 diabetes the SGLT2 inhibitors can help preserve kidney function and reduce heart failure. But we also know there can be diabetic ketoacidosis and genital infections and other side effects, so it’s been unclear up till now in type 2 diabetes whether they are safe and effective in people hospitalized in respiratory failure with COVID-19. And, given that people with type 2 diabetes and COVID-19 are more likely to require mechanical ventilation and are at greater risk of mortality, we’re anxious to see what these results are.”

Dr. Gabbay commented that, when the DARE study was initiated in April 2020, there were concerns about whether it was safe. And even now, “we’re still not sure about whether SGLT2 inhibitors should be stopped in hospitalized patients. The recommendations say to stop. I think this will be interesting.”

Also to be addressed in several meeting sessions are related issues the pandemic has brought forth, such as the use of telehealth for routine diabetes management, inpatient use of continuous glucose monitoring, and, of course, health care disparities.

“A lot of important issues related to COVID-19 of great interest will be discussed in a variety of sessions,” Dr. Weinstock said.
 

Type 1 diabetes in adults: It’s not just a pediatric disease  

On Monday, June 28, a draft of the first-ever ADA/EASD consensus report on the management of type 1 diabetes in adults will be presented, with the final version slated for the annual meeting of the EASD in September 2021.

A previous ADA position statement had addressed management of type 1 diabetes across all age groups, but this will be the first to focus on adults. This is important, given that type 1 diabetes was formerly called juvenile diabetes and is still often perceived as a childhood disease. Adults who develop it are commonly misdiagnosed as having type 2 diabetes, Dr. Gabbay noted.

“A big-time issue is recognition of type 1 in adults. We often see patients come in who were misdiagnosed, on metformin, and not given insulin. Often they go for a while and get sicker and sicker.” Or, he said, sometimes they’re prescribed insulin but not the intensive regimens that are required for adequate glycemic control in type 1 diabetes. “They can be suboptimally treated and it can take years to get the right therapy. ... It’s unfortunate that they have to experience that.”

Dr. Weinstock, one of the authors of the statement, said it will cover a range of issues, including care schedules, therapies, psychosocial issues, and social determinants of health. “We tried to be comprehensive in this in terms of glycemic management. It doesn’t include a discussion of complications or their management. It really focuses on diagnosis and glycemic management.”
 

Dealing with disparities: ADA has taken several steps

A priority of the ADA is addressing disparities in the delivery of health care to people with diabetes, both Dr. Weinstock and Dr. Gabbay stressed. Quite a few sessions at the meeting will touch on various aspects, including sessions on Friday afternoon on “Health Care as a Social Justice Issue in the Diagnosis and Management of Diabetes,” and separate sessions on “Challenges and Successes With Health Inequities and Health Disparities in Diabetes” in adult and pediatric populations.

“For us at ADA, addressing health disparities is extremely important and we have a number of new programs this year to address this very important issue,” Dr. Weinstock said.

In August 2020, the ADA issued a Health Equity Bill of Rights, which includes access to insulin and other medications, affordable health care, and freedom from stigma and discrimination. The Association has also requested applications from researchers studying disparities in diabetes care.
 

Celebrating 100 years of lifesaving medication

Of course, the ADA will be celebrating the 100th anniversary of the discovery of insulin. A session on Saturday afternoon, entitled, “Insulin at Its 100th Birthday,” will cover the history of the landmark discovery, as well as insulin biosynthesis and mechanisms of action, and “the future of insulin as a therapy.”

Dr. Weinstock noted: “The discovery of insulin was an incredible achievement that, of course, saved the lives of many millions of children and adults. Before insulin became available, children and adults only survived for days or at most a few years after diagnosis. We will commemorate this anniversary.”
 

The virtual platform: Like last year, only better

Dr. Gabbay said in an interview that the virtual setup will be similar to last year’s in that talks will be prerecorded to ensure there are no technical glitches, but for many, presenters will be available afterward for live question and answers.

This year, though, the chat functionality will be enhanced to allow for discussion during the presentation, separate from the scientific question and answers. And, he noted, the virtual exhibit hall will be “bigger and better.”

Despite these improvements, Dr. Gabbay said, the plan is to go back to an in-person meeting in 2022 in New Orleans.

Dr. Weinstock’s institution receives research grants from Medtronic, Insulet, Lilly, Novo Nordisk, and Boehringer Ingelheim. Dr. Gabbay reported no relevant financial relationships.

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

Long-awaited twincretin data, a study to inform prescribing in type 2 diabetes, COVID-19 and diabetes, and new guidance for treating type 1 diabetes in adults will be among the hot topics at the annual scientific sessions of the American Diabetes Association.

The meeting, to be held virtually for a second year, will take place June 25-29. As usual, the sessions will cover a wide range of basic, translational, and clinical material pertaining to type 1 and type 2 diabetes, complications, related subjects such as obesity and cardiovascular disease, and health care delivery.

New to this year’s agenda is COVID-19 and the many ways it has affected people with diabetes and health care delivery. And, more than in the past, the meeting will focus on ethnic and racial disparities in the delivery of care to people with diabetes.

And of course, there will be a tribute to another special aspect of 2021: the 100th anniversary of the discovery of insulin.

“I think there will undoubtedly be several things that will come out of this meeting that will change practice, and it will be important for clinicians to be aware of those, whether that’s groundbreaking trials or interpretation of data that will help us understand the interrelation between diabetes and COVID-19, which is still with us,” ADA chief scientific and medical officer Robert A. Gabbay, MD, PhD, said in an interview.

And ADA president of medicine and science Ruth S. Weinstock, MD, PhD, said in an interview: “I think there are many exciting sessions at this year’s meeting. ...I hope that it will help [clinicians] take better care of their patients with diabetes.

”

Will the twincretin tirzepatide live up to the hype?

Between December 2020 and May 2021, Eli Lilly issued a series of four press releases touting positive top-line results from a series of phase 3 studies on its novel agent tirzepatide, dubbed a twincretin for its dual actions as an agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagonlike peptide-1 receptors.  

Detailed results from those four trials, SURPASS-1, -2, -3, and -5, will be presented in a symposium on Tuesday, June 29. Results from SURPASS-4 will be presented at the annual meeting of the European Association for the Study of Diabetes in September 2021.

According to the company, the drug met its phase 3 primary efficacy endpoints for both hemoglobin A1c reduction and weight loss.

“At least the buzz on it has been good, but now we want to see the real data,” Dr. Gabbay said, noting that “the early data on weight loss in particular were quite good. So then the question would be: Do you go to a GLP-1 [agonist] or a dual agonist? There will be studies to tease that out.”

Regarding tirzepatide, Dr. Weinstock said: “Hopefully, more people with type 2 diabetes could achieve their glycemic goals, and those who would benefit from weight loss could have better weight loss. I haven’t seen the data, but if the addition of GIP can further improve glucose lowering as well as weight loss that would be great.”
 

How far will GRADE go in answering the second-drug question?

On Monday, June 28, results will be presented from the long-awaited Glycemia Reduction Approaches in Diabetes – A Comparative Effectiveness (GRADE) study.

Launched in 2013, the trial is funded by the National Institutes of Health and several pharmaceutical company partners. Over 5,000 patients diagnosed with type 2 diabetes within the prior 10 years and already taking metformin were randomized to one of four commonly used second-line glucose-lowering agents: glimepiride, sitagliptin, liraglutide, and basal insulin glargine. The aim was to determine which combination produced the best glycemic control with the fewest side effects.

Dr. Weinstock said: “Clinicians now have increasing numbers of medications to choose from when treating hyperglycemia in type 2 diabetes, and a common dilemma is which one to select. The results of GRADE should be informative for people taking care of type 2 diabetes in different populations.”

However, she also pointed out that GRADE does not include a group with a sodium-glucose transporter 2 inhibitor, as the trial was designed prior to the availability of the drug class. Now, SGLT2 inhibitors are widely used and recommended for cardiovascular and kidney benefit as well as glucose lowering.

“I believe the future is really precision medicine where we individualize treatment. So, for someone with heart failure you might choose an SGLT2 inhibitor, but there are plenty of other subpopulations. They are going to be looking at different subpopulations. I think we’re all very interested in seeing what the results are, but it’s not the end of the story. We will still have to individualize therapy and keep in mind their kidney, heart, heart failure status, and other factors,” she said.

Dr. Gabbay pointed out that GRADE is important because it’s one of the few comparative effectiveness trials conducted in diabetes. “I think it will be very rich [data] that will impact practice in a variety of ways. On the one hand, it doesn’t do everything we’d want it to do, but on the other hand, if you think of the number of comparative effectiveness trials in diabetes, there are not a lot ... I think it will be big.”
 

COVID-19 and diabetes: A lot to discuss  

In contrast to the ADA scientific sessions in 2020, which took place too soon after the start of the COVID-19 pandemic to include much material about it, this year’s meeting will address many different aspects of the novel coronavirus.

Sessions will cover minimizing risk in people with diabetes during the pandemic, the latest data on whether COVID-19 triggers diabetes, and if so, by what mechanism, mental health issues related to COVID-19, as well as the management of foot care, pregnancy, and the pediatric population during the pandemic.

On Sunday, June 27, a symposium will be devoted to results of the DARE-19 trial, which explored the effects of the SGLT2 inhibitor dapagliflozin in more than 1200 patients hospitalized with COVID-19. The overall results, presented in May 2021 at the scientific sessions of the American College of Cardiology, showed a nonsignificant trend for benefit in time to organ failure or death compared with placebo. At ADA, separate efficacy and safety results for patients with and without diabetes will be presented.

According to Dr. Weinstock, “We know that in nonhospitalized patients with type 2 diabetes the SGLT2 inhibitors can help preserve kidney function and reduce heart failure. But we also know there can be diabetic ketoacidosis and genital infections and other side effects, so it’s been unclear up till now in type 2 diabetes whether they are safe and effective in people hospitalized in respiratory failure with COVID-19. And, given that people with type 2 diabetes and COVID-19 are more likely to require mechanical ventilation and are at greater risk of mortality, we’re anxious to see what these results are.”

Dr. Gabbay commented that, when the DARE study was initiated in April 2020, there were concerns about whether it was safe. And even now, “we’re still not sure about whether SGLT2 inhibitors should be stopped in hospitalized patients. The recommendations say to stop. I think this will be interesting.”

Also to be addressed in several meeting sessions are related issues the pandemic has brought forth, such as the use of telehealth for routine diabetes management, inpatient use of continuous glucose monitoring, and, of course, health care disparities.

“A lot of important issues related to COVID-19 of great interest will be discussed in a variety of sessions,” Dr. Weinstock said.
 

Type 1 diabetes in adults: It’s not just a pediatric disease  

On Monday, June 28, a draft of the first-ever ADA/EASD consensus report on the management of type 1 diabetes in adults will be presented, with the final version slated for the annual meeting of the EASD in September 2021.

A previous ADA position statement had addressed management of type 1 diabetes across all age groups, but this will be the first to focus on adults. This is important, given that type 1 diabetes was formerly called juvenile diabetes and is still often perceived as a childhood disease. Adults who develop it are commonly misdiagnosed as having type 2 diabetes, Dr. Gabbay noted.

“A big-time issue is recognition of type 1 in adults. We often see patients come in who were misdiagnosed, on metformin, and not given insulin. Often they go for a while and get sicker and sicker.” Or, he said, sometimes they’re prescribed insulin but not the intensive regimens that are required for adequate glycemic control in type 1 diabetes. “They can be suboptimally treated and it can take years to get the right therapy. ... It’s unfortunate that they have to experience that.”

Dr. Weinstock, one of the authors of the statement, said it will cover a range of issues, including care schedules, therapies, psychosocial issues, and social determinants of health. “We tried to be comprehensive in this in terms of glycemic management. It doesn’t include a discussion of complications or their management. It really focuses on diagnosis and glycemic management.”
 

Dealing with disparities: ADA has taken several steps

A priority of the ADA is addressing disparities in the delivery of health care to people with diabetes, both Dr. Weinstock and Dr. Gabbay stressed. Quite a few sessions at the meeting will touch on various aspects, including sessions on Friday afternoon on “Health Care as a Social Justice Issue in the Diagnosis and Management of Diabetes,” and separate sessions on “Challenges and Successes With Health Inequities and Health Disparities in Diabetes” in adult and pediatric populations.

“For us at ADA, addressing health disparities is extremely important and we have a number of new programs this year to address this very important issue,” Dr. Weinstock said.

In August 2020, the ADA issued a Health Equity Bill of Rights, which includes access to insulin and other medications, affordable health care, and freedom from stigma and discrimination. The Association has also requested applications from researchers studying disparities in diabetes care.
 

Celebrating 100 years of lifesaving medication

Of course, the ADA will be celebrating the 100th anniversary of the discovery of insulin. A session on Saturday afternoon, entitled, “Insulin at Its 100th Birthday,” will cover the history of the landmark discovery, as well as insulin biosynthesis and mechanisms of action, and “the future of insulin as a therapy.”

Dr. Weinstock noted: “The discovery of insulin was an incredible achievement that, of course, saved the lives of many millions of children and adults. Before insulin became available, children and adults only survived for days or at most a few years after diagnosis. We will commemorate this anniversary.”
 

The virtual platform: Like last year, only better

Dr. Gabbay said in an interview that the virtual setup will be similar to last year’s in that talks will be prerecorded to ensure there are no technical glitches, but for many, presenters will be available afterward for live question and answers.

This year, though, the chat functionality will be enhanced to allow for discussion during the presentation, separate from the scientific question and answers. And, he noted, the virtual exhibit hall will be “bigger and better.”

Despite these improvements, Dr. Gabbay said, the plan is to go back to an in-person meeting in 2022 in New Orleans.

Dr. Weinstock’s institution receives research grants from Medtronic, Insulet, Lilly, Novo Nordisk, and Boehringer Ingelheim. Dr. Gabbay reported no relevant financial relationships.

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

Long-awaited twincretin data, a study to inform prescribing in type 2 diabetes, COVID-19 and diabetes, and new guidance for treating type 1 diabetes in adults will be among the hot topics at the annual scientific sessions of the American Diabetes Association.

The meeting, to be held virtually for a second year, will take place June 25-29. As usual, the sessions will cover a wide range of basic, translational, and clinical material pertaining to type 1 and type 2 diabetes, complications, related subjects such as obesity and cardiovascular disease, and health care delivery.

New to this year’s agenda is COVID-19 and the many ways it has affected people with diabetes and health care delivery. And, more than in the past, the meeting will focus on ethnic and racial disparities in the delivery of care to people with diabetes.

And of course, there will be a tribute to another special aspect of 2021: the 100th anniversary of the discovery of insulin.

“I think there will undoubtedly be several things that will come out of this meeting that will change practice, and it will be important for clinicians to be aware of those, whether that’s groundbreaking trials or interpretation of data that will help us understand the interrelation between diabetes and COVID-19, which is still with us,” ADA chief scientific and medical officer Robert A. Gabbay, MD, PhD, said in an interview.

And ADA president of medicine and science Ruth S. Weinstock, MD, PhD, said in an interview: “I think there are many exciting sessions at this year’s meeting. ...I hope that it will help [clinicians] take better care of their patients with diabetes.

”

Will the twincretin tirzepatide live up to the hype?

Between December 2020 and May 2021, Eli Lilly issued a series of four press releases touting positive top-line results from a series of phase 3 studies on its novel agent tirzepatide, dubbed a twincretin for its dual actions as an agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagonlike peptide-1 receptors.  

Detailed results from those four trials, SURPASS-1, -2, -3, and -5, will be presented in a symposium on Tuesday, June 29. Results from SURPASS-4 will be presented at the annual meeting of the European Association for the Study of Diabetes in September 2021.

According to the company, the drug met its phase 3 primary efficacy endpoints for both hemoglobin A1c reduction and weight loss.

“At least the buzz on it has been good, but now we want to see the real data,” Dr. Gabbay said, noting that “the early data on weight loss in particular were quite good. So then the question would be: Do you go to a GLP-1 [agonist] or a dual agonist? There will be studies to tease that out.”

Regarding tirzepatide, Dr. Weinstock said: “Hopefully, more people with type 2 diabetes could achieve their glycemic goals, and those who would benefit from weight loss could have better weight loss. I haven’t seen the data, but if the addition of GIP can further improve glucose lowering as well as weight loss that would be great.”
 

How far will GRADE go in answering the second-drug question?

On Monday, June 28, results will be presented from the long-awaited Glycemia Reduction Approaches in Diabetes – A Comparative Effectiveness (GRADE) study.

Launched in 2013, the trial is funded by the National Institutes of Health and several pharmaceutical company partners. Over 5,000 patients diagnosed with type 2 diabetes within the prior 10 years and already taking metformin were randomized to one of four commonly used second-line glucose-lowering agents: glimepiride, sitagliptin, liraglutide, and basal insulin glargine. The aim was to determine which combination produced the best glycemic control with the fewest side effects.

Dr. Weinstock said: “Clinicians now have increasing numbers of medications to choose from when treating hyperglycemia in type 2 diabetes, and a common dilemma is which one to select. The results of GRADE should be informative for people taking care of type 2 diabetes in different populations.”

However, she also pointed out that GRADE does not include a group with a sodium-glucose transporter 2 inhibitor, as the trial was designed prior to the availability of the drug class. Now, SGLT2 inhibitors are widely used and recommended for cardiovascular and kidney benefit as well as glucose lowering.

“I believe the future is really precision medicine where we individualize treatment. So, for someone with heart failure you might choose an SGLT2 inhibitor, but there are plenty of other subpopulations. They are going to be looking at different subpopulations. I think we’re all very interested in seeing what the results are, but it’s not the end of the story. We will still have to individualize therapy and keep in mind their kidney, heart, heart failure status, and other factors,” she said.

Dr. Gabbay pointed out that GRADE is important because it’s one of the few comparative effectiveness trials conducted in diabetes. “I think it will be very rich [data] that will impact practice in a variety of ways. On the one hand, it doesn’t do everything we’d want it to do, but on the other hand, if you think of the number of comparative effectiveness trials in diabetes, there are not a lot ... I think it will be big.”
 

COVID-19 and diabetes: A lot to discuss  

In contrast to the ADA scientific sessions in 2020, which took place too soon after the start of the COVID-19 pandemic to include much material about it, this year’s meeting will address many different aspects of the novel coronavirus.

Sessions will cover minimizing risk in people with diabetes during the pandemic, the latest data on whether COVID-19 triggers diabetes, and if so, by what mechanism, mental health issues related to COVID-19, as well as the management of foot care, pregnancy, and the pediatric population during the pandemic.

On Sunday, June 27, a symposium will be devoted to results of the DARE-19 trial, which explored the effects of the SGLT2 inhibitor dapagliflozin in more than 1200 patients hospitalized with COVID-19. The overall results, presented in May 2021 at the scientific sessions of the American College of Cardiology, showed a nonsignificant trend for benefit in time to organ failure or death compared with placebo. At ADA, separate efficacy and safety results for patients with and without diabetes will be presented.

According to Dr. Weinstock, “We know that in nonhospitalized patients with type 2 diabetes the SGLT2 inhibitors can help preserve kidney function and reduce heart failure. But we also know there can be diabetic ketoacidosis and genital infections and other side effects, so it’s been unclear up till now in type 2 diabetes whether they are safe and effective in people hospitalized in respiratory failure with COVID-19. And, given that people with type 2 diabetes and COVID-19 are more likely to require mechanical ventilation and are at greater risk of mortality, we’re anxious to see what these results are.”

Dr. Gabbay commented that, when the DARE study was initiated in April 2020, there were concerns about whether it was safe. And even now, “we’re still not sure about whether SGLT2 inhibitors should be stopped in hospitalized patients. The recommendations say to stop. I think this will be interesting.”

Also to be addressed in several meeting sessions are related issues the pandemic has brought forth, such as the use of telehealth for routine diabetes management, inpatient use of continuous glucose monitoring, and, of course, health care disparities.

“A lot of important issues related to COVID-19 of great interest will be discussed in a variety of sessions,” Dr. Weinstock said.
 

Type 1 diabetes in adults: It’s not just a pediatric disease  

On Monday, June 28, a draft of the first-ever ADA/EASD consensus report on the management of type 1 diabetes in adults will be presented, with the final version slated for the annual meeting of the EASD in September 2021.

A previous ADA position statement had addressed management of type 1 diabetes across all age groups, but this will be the first to focus on adults. This is important, given that type 1 diabetes was formerly called juvenile diabetes and is still often perceived as a childhood disease. Adults who develop it are commonly misdiagnosed as having type 2 diabetes, Dr. Gabbay noted.

“A big-time issue is recognition of type 1 in adults. We often see patients come in who were misdiagnosed, on metformin, and not given insulin. Often they go for a while and get sicker and sicker.” Or, he said, sometimes they’re prescribed insulin but not the intensive regimens that are required for adequate glycemic control in type 1 diabetes. “They can be suboptimally treated and it can take years to get the right therapy. ... It’s unfortunate that they have to experience that.”

Dr. Weinstock, one of the authors of the statement, said it will cover a range of issues, including care schedules, therapies, psychosocial issues, and social determinants of health. “We tried to be comprehensive in this in terms of glycemic management. It doesn’t include a discussion of complications or their management. It really focuses on diagnosis and glycemic management.”
 

Dealing with disparities: ADA has taken several steps

A priority of the ADA is addressing disparities in the delivery of health care to people with diabetes, both Dr. Weinstock and Dr. Gabbay stressed. Quite a few sessions at the meeting will touch on various aspects, including sessions on Friday afternoon on “Health Care as a Social Justice Issue in the Diagnosis and Management of Diabetes,” and separate sessions on “Challenges and Successes With Health Inequities and Health Disparities in Diabetes” in adult and pediatric populations.

“For us at ADA, addressing health disparities is extremely important and we have a number of new programs this year to address this very important issue,” Dr. Weinstock said.

In August 2020, the ADA issued a Health Equity Bill of Rights, which includes access to insulin and other medications, affordable health care, and freedom from stigma and discrimination. The Association has also requested applications from researchers studying disparities in diabetes care.
 

Celebrating 100 years of lifesaving medication

Of course, the ADA will be celebrating the 100th anniversary of the discovery of insulin. A session on Saturday afternoon, entitled, “Insulin at Its 100th Birthday,” will cover the history of the landmark discovery, as well as insulin biosynthesis and mechanisms of action, and “the future of insulin as a therapy.”

Dr. Weinstock noted: “The discovery of insulin was an incredible achievement that, of course, saved the lives of many millions of children and adults. Before insulin became available, children and adults only survived for days or at most a few years after diagnosis. We will commemorate this anniversary.”
 

The virtual platform: Like last year, only better

Dr. Gabbay said in an interview that the virtual setup will be similar to last year’s in that talks will be prerecorded to ensure there are no technical glitches, but for many, presenters will be available afterward for live question and answers.

This year, though, the chat functionality will be enhanced to allow for discussion during the presentation, separate from the scientific question and answers. And, he noted, the virtual exhibit hall will be “bigger and better.”

Despite these improvements, Dr. Gabbay said, the plan is to go back to an in-person meeting in 2022 in New Orleans.

Dr. Weinstock’s institution receives research grants from Medtronic, Insulet, Lilly, Novo Nordisk, and Boehringer Ingelheim. Dr. Gabbay reported no relevant financial relationships.

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

For well over a year, the COVID-19 pandemic has been the biggest story in the world, costing millions of lives, impacting a presidential election, and quaking economies around the world.

But as vaccination rates increase and restrictions relax across the United States, relief is beginning to mix with reflection. Part of that contemplation means grappling with how the media depicted the crisis – in ways that were helpful, harmful, and somewhere in between.

“This story was so overwhelming, and the amount of journalism done about it was also overwhelming, and it’s going to be a while before we can do any kind of comprehensive overview of how journalism really performed,” said Maryn McKenna, an independent journalist and journalism professor at Emory University, Atlanta, who specializes in public and global health.
 

Some ‘heroically good’ reporting

The pandemic hit at a time when journalism was under a lot of pressure from external forces – undermined by politics, swimming through a sea of misinformation, and pressed by financial pressure to produce more stories more quickly, said Emily Bell, founding director of the Tow Center for Digital Journalism at Columbia University, New York.

The pandemic drove enormous audiences to news outlets, as people searched for reliable information, and increased the appreciation many people felt for the work of journalists, she said.

“I think there’s been some heroically good reporting and some really empathetic reporting as well,” said Ms. Bell. She cites The New York Times stories honoring the nearly 100,000 people lost to COVID-19 in May 2020 and The Atlantic’s COVID Tracking Project as exceptionally good examples.

Journalism is part of a complex, and evolving, information ecosystem characterized by “traditional” television, radio, and newspapers but also social media, search engine results, niche online news outlets, and clickbait sites.

On the one hand, social media provided a way for physicians, nurses, and scientists to speak directly to the world about their experiences and research. On the other hand, it’s challenging to elevate the really good work of traditional media over all of the bad or unhelpful signals, said Ms. Bell.

But, at the end of the day, much of journalism is a business. There are incentives in the market for tabloids to do sensational coverage and for outlets to push misleading, clickbait headlines, Ms. Bell said.

“Sometimes we’ll criticize journalists for ‘getting it wrong,’ but they might be getting it right in their business model but getting it wrong in terms of what it’s doing for society,” she said.

“We need to do a self-examination, when or if the dust from this ever settles, [on] how much of the past year was viewed as a business opportunity and did that get in the way of informing the public adequately,” Ms. McKenna said.

Digital platforms and journalists also need to reflect on how narratives build on one another, particularly online, said Ms. Bell. If you search for side effects of the Johnson & Johnson vaccine, for example, you will see a list of dozens of headlines that might give you the impression this is a major problem without the context that these effects are exceedingly rare, she notes.

There was also a personnel problem. Shrinking newsrooms over the last decade meant many outlets didn’t have dedicated science and health reporting, or very few staffers, if any. During the pandemic, suddenly general assignment and politics reporters had to be science and health reporters, too.

“You have a hard enough time with these issues if you’re a fairly seasoned science journalist,” said Gary Schwitzer, a former head of the health care news unit for CNN, journalism professor at the University of Minnesota, and founder of the watchdog site HealthNewsReview.org.

And outlets that had the staffing didn’t always put science reporters to full use, Ms. McKenna said. In March and April of 2020, major media outlets should have sent science reporters, not politics reporters, to President Donald Trump’s White House press briefings, which often included incorrect statements about COVID-19 science.

“I just don’t feel that the big outlets understood that that expertise would have made a difference,” she said.
 

New challenges, old problems

Some of the science journalism done during the pandemic has been some of the best ever seen in this country, said Mr. Schwitzer. But between the peaks of excellence, there is “the daily drumbeat coverage of dreck,” he added.

Many of the issues with this dreck coverage aren’t new or unique to the pandemic. For example, over the last year there have been far too many news stories based solely on weak information sources, like a drug company press release or a not-yet-peer-reviewed preprint article that hasn’t been put into proper context, said Mr. Schwitzer.

A quality science story should always include an independent perspective, he said, but many COVID-19 stories missed that perspective. This isn’t a new issue for science coverage – at Health News Review, Mr. Schwitzer and his colleagues saw stories without appropriate independent sources every day for 15 years.

It’s also challenging to write about uncertainty without over- or underselling what scientists know about a particular phenomenon. “We know that the media in general tends to portray science as more certain than it is,” said Dominique Brossard, PhD, professor and department chair at the University of Wisconsin–Madison and an expert on the intersection between science, media, and policy. This can lead to confusion when the science, and the advice based on that science, changes.

“The public has a really difficult time understanding what uncertainty means within science,” said Todd P. Newman, PhD, assistant professor at the University of Wisconsin–Madison who studies strategic communication within the context of science, technology, and the environment.

“I think the media generally has been good on the subject,” said Paul Offit, MD, director of the Vaccine Education Center, attending physician in the Division of Infectious Diseases at the Children’s Hospital of Philadelphia, and a prominent expert voice throughout the pandemic. “I think where they’ve been imperfect is they tend to be a little more dramatic in terms of how we’re doing.”

Dr. Offit isn’t the only expert to point to the drama of COVID-19 coverage. A study published in March 2021 by the National Bureau of Economic Research found 87% of stories by major U.S. media outlets leaned negative in the tone of their COVID-19 reporting, compared with 50% of stories from non-U.S. major outlets and 64% of articles in scientific journals. The negative emphasis persists even around positive developments, like vaccine trials and school re-openings.

John Whyte, MD, chief medical officer for WebMD, said he is very proud of the way WebMD and Medscape ramped up production of video series and other content to give health care providers the most up-to-date guidance on a rapidly evolving medical situation.

“But I think as [we] started to make progress – especially in the last 6 months – the coverage was never balanced enough; any positive news was immediately proceeded by negative,” he said.

“You want to be honest, but you also don’t want to be alarmist – and that’s where I think the challenge is at times in the media,” said Dr. Whyte. “We didn’t put enough optimism in at times, especially in recent months.”

“Any good coverage on vaccines immediately [was] covered by ‘[we] might need boosters in the fall.’ Why can’t [we] have an opportunity to breathe for a little while and see the good news?” he asked.
 

Variants or scariants?

Negativity and fear shaped much of the coverage around variants and vaccines earlier this year. In February 2021, Zeynep Tufekci, PhD, a sociologist at the University of North Carolina at Chapel Hill school of information and library science, wrote in The Atlantic about how much reporting has not reflected “the truly amazing reality of these vaccines,” and has instead highlighted “a chorus of relentless pessimism.”

This felt especially true earlier in 2021, when lots of coverage repeatedly emphasized what vaccinated people still could not do.

Eric Topol, MD, editor-in-chief of Medscape and executive vice president of Scripps Research in La Jolla, California, said New York Times editors told him earlier in the pandemic that he couldn’t use the word “scariant” in an opinion piece about the media’s overly fearful and sometimes inaccurate reporting around COVID-19 variants because they worried it would seem like the Times was coming after other media outlets.

“A variant is innocent until proven guilty,” said Dr. Topol. Had journalists approached the subject from that point of view, he said we would have seen “much more faithful reporting.”

Dr. Brossard and Dr. Newman worry that focusing on uncommon negative behavior, like people who break social distancing and mask rules by gathering at the beach or the bar, makes those actions seem more common than they actually are.

The evidence suggests that “if you show these kinds of things to people, you encourage them to do the same behavior,” said Dr. Brossard.

There have been other mistakes along the way, too. Early in the pandemic, many outlets pointed viewers to official government sources of information, some of which, like the White House press briefings in March and April of 2020, ended up being some of the most virulent spreaders of misinformation, said Ms. Bell.

Before that, a handful of journalists like Roxanne Khamsi were the few pushing back against the dominant media narrative in early 2020 that the novel coronavirus was less concerning than the seasonal flu.

“Science journalists have always been writing about studies that sometimes contradict each other, and what’s happened is that has only been condensed in time,” said Ms. Khamsi, a health care reporter for outlets like WIRED magazine and The New York Times and a former chief news editor for Nature Medicine.
 

Politics and misinformation

It’s impossible to talk about media coverage of COVID-19 without touching on politics and misinformation.

Coverage of the pandemic was politicized and polarized from the very beginning, said Sedona Chinn, PhD, an assistant professor at the University of Wisconsin–Madison who researches the prevalence and effects of scientific disagreements in media.

By looking at network news transcripts and articles from national outlets like the Washington Post and The New York Times, Dr. Chinn and her colleagues were able to determine politicization of coverage by counting the mentions of politicians versus scientists in COVID-19 coverage and polarization by looking at how different or similar the language was surrounding mentions of Republicans and Democrats.

If the two parties were working together or on the same page, they reasoned, the language would be similar.

From mid-March through May 2020, Dr. Chinn and fellow researchers found politicians were featured more often than scientists in newspaper coverage and as frequently as scientists in network news coverage. They also found polarized language around Republicans and Democrats, particularly in stories describing duels between the (at the time) Republican national government and Democratic state and local leaders.

It’s possible that polarization in news coverage helped contribute to polarized attitudes around the virus, the authors write in the study, which was published in August 2020 in the journal Science Communication.

The politicization and polarization of the issue is mirrored in our fractured media environment, where people tend to read, listen, and watch outlets that align with their political leanings. If that trusted outlet features misinformation, the people who follow it are more likely to accept that false information as truth, said Matt Motta, PhD, a political scientist at Oklahoma State University whose research includes public opinion and science communication.

This is true across the political spectrum, he said. When it comes to COVID-19, however, right-wing media outlets like Fox News and Breitbart are more likely to promote conspiratorial tropes and misinformation about the pandemic, according to Dr. Motta and his collaborator Dominik Stecula, PhD, a political scientist at Colorado State University who studies the news media environment and its effects on society.

Across the media ecosystem, reporting on the “infodemic” accompanying the pandemic – the rapid spread of misinformation and disinformation about the virus – has been a major challenge. Outlets may not be creating the misinformation, but they are the ones choosing to give it a platform, said Dr. Motta.

By repeating a false idea, even with the goal of debunking it, you can unintentionally cause the information to stick in people’s minds, said Dr. Brossard.

“Just because something is controversial doesn’t mean it’s worth covering,” said Dr. Motta. Using vaccines as an example, he said many reporters and scientists alike assume that if people have all the facts, they’ll land on the side of science.

“That is just fundamentally not how people think about the decision to get vaccinated,” he said. Instead, the choice is wrapped up with cultural factors, religious beliefs, political identity, and more.

The factors and challenges that shaped the media’s coverage of the pandemic aren’t going anywhere. Improving science and medical coverage in the future is a collective project for journalists, scientists, and everyone in between, said Dr. Newman.

“I call on scientists, too, to think really deeply about how they’re communicating – and especially how they’re communicating what they know and don’t know,” he said.

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

For well over a year, the COVID-19 pandemic has been the biggest story in the world, costing millions of lives, impacting a presidential election, and quaking economies around the world.

But as vaccination rates increase and restrictions relax across the United States, relief is beginning to mix with reflection. Part of that contemplation means grappling with how the media depicted the crisis – in ways that were helpful, harmful, and somewhere in between.

“This story was so overwhelming, and the amount of journalism done about it was also overwhelming, and it’s going to be a while before we can do any kind of comprehensive overview of how journalism really performed,” said Maryn McKenna, an independent journalist and journalism professor at Emory University, Atlanta, who specializes in public and global health.
 

Some ‘heroically good’ reporting

The pandemic hit at a time when journalism was under a lot of pressure from external forces – undermined by politics, swimming through a sea of misinformation, and pressed by financial pressure to produce more stories more quickly, said Emily Bell, founding director of the Tow Center for Digital Journalism at Columbia University, New York.

The pandemic drove enormous audiences to news outlets, as people searched for reliable information, and increased the appreciation many people felt for the work of journalists, she said.

“I think there’s been some heroically good reporting and some really empathetic reporting as well,” said Ms. Bell. She cites The New York Times stories honoring the nearly 100,000 people lost to COVID-19 in May 2020 and The Atlantic’s COVID Tracking Project as exceptionally good examples.

Journalism is part of a complex, and evolving, information ecosystem characterized by “traditional” television, radio, and newspapers but also social media, search engine results, niche online news outlets, and clickbait sites.

On the one hand, social media provided a way for physicians, nurses, and scientists to speak directly to the world about their experiences and research. On the other hand, it’s challenging to elevate the really good work of traditional media over all of the bad or unhelpful signals, said Ms. Bell.

But, at the end of the day, much of journalism is a business. There are incentives in the market for tabloids to do sensational coverage and for outlets to push misleading, clickbait headlines, Ms. Bell said.

“Sometimes we’ll criticize journalists for ‘getting it wrong,’ but they might be getting it right in their business model but getting it wrong in terms of what it’s doing for society,” she said.

“We need to do a self-examination, when or if the dust from this ever settles, [on] how much of the past year was viewed as a business opportunity and did that get in the way of informing the public adequately,” Ms. McKenna said.

Digital platforms and journalists also need to reflect on how narratives build on one another, particularly online, said Ms. Bell. If you search for side effects of the Johnson & Johnson vaccine, for example, you will see a list of dozens of headlines that might give you the impression this is a major problem without the context that these effects are exceedingly rare, she notes.

There was also a personnel problem. Shrinking newsrooms over the last decade meant many outlets didn’t have dedicated science and health reporting, or very few staffers, if any. During the pandemic, suddenly general assignment and politics reporters had to be science and health reporters, too.

“You have a hard enough time with these issues if you’re a fairly seasoned science journalist,” said Gary Schwitzer, a former head of the health care news unit for CNN, journalism professor at the University of Minnesota, and founder of the watchdog site HealthNewsReview.org.

And outlets that had the staffing didn’t always put science reporters to full use, Ms. McKenna said. In March and April of 2020, major media outlets should have sent science reporters, not politics reporters, to President Donald Trump’s White House press briefings, which often included incorrect statements about COVID-19 science.

“I just don’t feel that the big outlets understood that that expertise would have made a difference,” she said.
 

New challenges, old problems

Some of the science journalism done during the pandemic has been some of the best ever seen in this country, said Mr. Schwitzer. But between the peaks of excellence, there is “the daily drumbeat coverage of dreck,” he added.

Many of the issues with this dreck coverage aren’t new or unique to the pandemic. For example, over the last year there have been far too many news stories based solely on weak information sources, like a drug company press release or a not-yet-peer-reviewed preprint article that hasn’t been put into proper context, said Mr. Schwitzer.

A quality science story should always include an independent perspective, he said, but many COVID-19 stories missed that perspective. This isn’t a new issue for science coverage – at Health News Review, Mr. Schwitzer and his colleagues saw stories without appropriate independent sources every day for 15 years.

It’s also challenging to write about uncertainty without over- or underselling what scientists know about a particular phenomenon. “We know that the media in general tends to portray science as more certain than it is,” said Dominique Brossard, PhD, professor and department chair at the University of Wisconsin–Madison and an expert on the intersection between science, media, and policy. This can lead to confusion when the science, and the advice based on that science, changes.

“The public has a really difficult time understanding what uncertainty means within science,” said Todd P. Newman, PhD, assistant professor at the University of Wisconsin–Madison who studies strategic communication within the context of science, technology, and the environment.

“I think the media generally has been good on the subject,” said Paul Offit, MD, director of the Vaccine Education Center, attending physician in the Division of Infectious Diseases at the Children’s Hospital of Philadelphia, and a prominent expert voice throughout the pandemic. “I think where they’ve been imperfect is they tend to be a little more dramatic in terms of how we’re doing.”

Dr. Offit isn’t the only expert to point to the drama of COVID-19 coverage. A study published in March 2021 by the National Bureau of Economic Research found 87% of stories by major U.S. media outlets leaned negative in the tone of their COVID-19 reporting, compared with 50% of stories from non-U.S. major outlets and 64% of articles in scientific journals. The negative emphasis persists even around positive developments, like vaccine trials and school re-openings.

John Whyte, MD, chief medical officer for WebMD, said he is very proud of the way WebMD and Medscape ramped up production of video series and other content to give health care providers the most up-to-date guidance on a rapidly evolving medical situation.

“But I think as [we] started to make progress – especially in the last 6 months – the coverage was never balanced enough; any positive news was immediately proceeded by negative,” he said.

“You want to be honest, but you also don’t want to be alarmist – and that’s where I think the challenge is at times in the media,” said Dr. Whyte. “We didn’t put enough optimism in at times, especially in recent months.”

“Any good coverage on vaccines immediately [was] covered by ‘[we] might need boosters in the fall.’ Why can’t [we] have an opportunity to breathe for a little while and see the good news?” he asked.
 

Variants or scariants?

Negativity and fear shaped much of the coverage around variants and vaccines earlier this year. In February 2021, Zeynep Tufekci, PhD, a sociologist at the University of North Carolina at Chapel Hill school of information and library science, wrote in The Atlantic about how much reporting has not reflected “the truly amazing reality of these vaccines,” and has instead highlighted “a chorus of relentless pessimism.”

This felt especially true earlier in 2021, when lots of coverage repeatedly emphasized what vaccinated people still could not do.

Eric Topol, MD, editor-in-chief of Medscape and executive vice president of Scripps Research in La Jolla, California, said New York Times editors told him earlier in the pandemic that he couldn’t use the word “scariant” in an opinion piece about the media’s overly fearful and sometimes inaccurate reporting around COVID-19 variants because they worried it would seem like the Times was coming after other media outlets.

“A variant is innocent until proven guilty,” said Dr. Topol. Had journalists approached the subject from that point of view, he said we would have seen “much more faithful reporting.”

Dr. Brossard and Dr. Newman worry that focusing on uncommon negative behavior, like people who break social distancing and mask rules by gathering at the beach or the bar, makes those actions seem more common than they actually are.

The evidence suggests that “if you show these kinds of things to people, you encourage them to do the same behavior,” said Dr. Brossard.

There have been other mistakes along the way, too. Early in the pandemic, many outlets pointed viewers to official government sources of information, some of which, like the White House press briefings in March and April of 2020, ended up being some of the most virulent spreaders of misinformation, said Ms. Bell.

Before that, a handful of journalists like Roxanne Khamsi were the few pushing back against the dominant media narrative in early 2020 that the novel coronavirus was less concerning than the seasonal flu.

“Science journalists have always been writing about studies that sometimes contradict each other, and what’s happened is that has only been condensed in time,” said Ms. Khamsi, a health care reporter for outlets like WIRED magazine and The New York Times and a former chief news editor for Nature Medicine.
 

Politics and misinformation

It’s impossible to talk about media coverage of COVID-19 without touching on politics and misinformation.

Coverage of the pandemic was politicized and polarized from the very beginning, said Sedona Chinn, PhD, an assistant professor at the University of Wisconsin–Madison who researches the prevalence and effects of scientific disagreements in media.

By looking at network news transcripts and articles from national outlets like the Washington Post and The New York Times, Dr. Chinn and her colleagues were able to determine politicization of coverage by counting the mentions of politicians versus scientists in COVID-19 coverage and polarization by looking at how different or similar the language was surrounding mentions of Republicans and Democrats.

If the two parties were working together or on the same page, they reasoned, the language would be similar.

From mid-March through May 2020, Dr. Chinn and fellow researchers found politicians were featured more often than scientists in newspaper coverage and as frequently as scientists in network news coverage. They also found polarized language around Republicans and Democrats, particularly in stories describing duels between the (at the time) Republican national government and Democratic state and local leaders.

It’s possible that polarization in news coverage helped contribute to polarized attitudes around the virus, the authors write in the study, which was published in August 2020 in the journal Science Communication.

The politicization and polarization of the issue is mirrored in our fractured media environment, where people tend to read, listen, and watch outlets that align with their political leanings. If that trusted outlet features misinformation, the people who follow it are more likely to accept that false information as truth, said Matt Motta, PhD, a political scientist at Oklahoma State University whose research includes public opinion and science communication.

This is true across the political spectrum, he said. When it comes to COVID-19, however, right-wing media outlets like Fox News and Breitbart are more likely to promote conspiratorial tropes and misinformation about the pandemic, according to Dr. Motta and his collaborator Dominik Stecula, PhD, a political scientist at Colorado State University who studies the news media environment and its effects on society.

Across the media ecosystem, reporting on the “infodemic” accompanying the pandemic – the rapid spread of misinformation and disinformation about the virus – has been a major challenge. Outlets may not be creating the misinformation, but they are the ones choosing to give it a platform, said Dr. Motta.

By repeating a false idea, even with the goal of debunking it, you can unintentionally cause the information to stick in people’s minds, said Dr. Brossard.

“Just because something is controversial doesn’t mean it’s worth covering,” said Dr. Motta. Using vaccines as an example, he said many reporters and scientists alike assume that if people have all the facts, they’ll land on the side of science.

“That is just fundamentally not how people think about the decision to get vaccinated,” he said. Instead, the choice is wrapped up with cultural factors, religious beliefs, political identity, and more.

The factors and challenges that shaped the media’s coverage of the pandemic aren’t going anywhere. Improving science and medical coverage in the future is a collective project for journalists, scientists, and everyone in between, said Dr. Newman.

“I call on scientists, too, to think really deeply about how they’re communicating – and especially how they’re communicating what they know and don’t know,” he said.

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

For well over a year, the COVID-19 pandemic has been the biggest story in the world, costing millions of lives, impacting a presidential election, and quaking economies around the world.

But as vaccination rates increase and restrictions relax across the United States, relief is beginning to mix with reflection. Part of that contemplation means grappling with how the media depicted the crisis – in ways that were helpful, harmful, and somewhere in between.

“This story was so overwhelming, and the amount of journalism done about it was also overwhelming, and it’s going to be a while before we can do any kind of comprehensive overview of how journalism really performed,” said Maryn McKenna, an independent journalist and journalism professor at Emory University, Atlanta, who specializes in public and global health.
 

Some ‘heroically good’ reporting

The pandemic hit at a time when journalism was under a lot of pressure from external forces – undermined by politics, swimming through a sea of misinformation, and pressed by financial pressure to produce more stories more quickly, said Emily Bell, founding director of the Tow Center for Digital Journalism at Columbia University, New York.

The pandemic drove enormous audiences to news outlets, as people searched for reliable information, and increased the appreciation many people felt for the work of journalists, she said.

“I think there’s been some heroically good reporting and some really empathetic reporting as well,” said Ms. Bell. She cites The New York Times stories honoring the nearly 100,000 people lost to COVID-19 in May 2020 and The Atlantic’s COVID Tracking Project as exceptionally good examples.

Journalism is part of a complex, and evolving, information ecosystem characterized by “traditional” television, radio, and newspapers but also social media, search engine results, niche online news outlets, and clickbait sites.

On the one hand, social media provided a way for physicians, nurses, and scientists to speak directly to the world about their experiences and research. On the other hand, it’s challenging to elevate the really good work of traditional media over all of the bad or unhelpful signals, said Ms. Bell.

But, at the end of the day, much of journalism is a business. There are incentives in the market for tabloids to do sensational coverage and for outlets to push misleading, clickbait headlines, Ms. Bell said.

“Sometimes we’ll criticize journalists for ‘getting it wrong,’ but they might be getting it right in their business model but getting it wrong in terms of what it’s doing for society,” she said.

“We need to do a self-examination, when or if the dust from this ever settles, [on] how much of the past year was viewed as a business opportunity and did that get in the way of informing the public adequately,” Ms. McKenna said.

Digital platforms and journalists also need to reflect on how narratives build on one another, particularly online, said Ms. Bell. If you search for side effects of the Johnson & Johnson vaccine, for example, you will see a list of dozens of headlines that might give you the impression this is a major problem without the context that these effects are exceedingly rare, she notes.

There was also a personnel problem. Shrinking newsrooms over the last decade meant many outlets didn’t have dedicated science and health reporting, or very few staffers, if any. During the pandemic, suddenly general assignment and politics reporters had to be science and health reporters, too.

“You have a hard enough time with these issues if you’re a fairly seasoned science journalist,” said Gary Schwitzer, a former head of the health care news unit for CNN, journalism professor at the University of Minnesota, and founder of the watchdog site HealthNewsReview.org.

And outlets that had the staffing didn’t always put science reporters to full use, Ms. McKenna said. In March and April of 2020, major media outlets should have sent science reporters, not politics reporters, to President Donald Trump’s White House press briefings, which often included incorrect statements about COVID-19 science.

“I just don’t feel that the big outlets understood that that expertise would have made a difference,” she said.
 

New challenges, old problems

Some of the science journalism done during the pandemic has been some of the best ever seen in this country, said Mr. Schwitzer. But between the peaks of excellence, there is “the daily drumbeat coverage of dreck,” he added.

Many of the issues with this dreck coverage aren’t new or unique to the pandemic. For example, over the last year there have been far too many news stories based solely on weak information sources, like a drug company press release or a not-yet-peer-reviewed preprint article that hasn’t been put into proper context, said Mr. Schwitzer.

A quality science story should always include an independent perspective, he said, but many COVID-19 stories missed that perspective. This isn’t a new issue for science coverage – at Health News Review, Mr. Schwitzer and his colleagues saw stories without appropriate independent sources every day for 15 years.

It’s also challenging to write about uncertainty without over- or underselling what scientists know about a particular phenomenon. “We know that the media in general tends to portray science as more certain than it is,” said Dominique Brossard, PhD, professor and department chair at the University of Wisconsin–Madison and an expert on the intersection between science, media, and policy. This can lead to confusion when the science, and the advice based on that science, changes.

“The public has a really difficult time understanding what uncertainty means within science,” said Todd P. Newman, PhD, assistant professor at the University of Wisconsin–Madison who studies strategic communication within the context of science, technology, and the environment.

“I think the media generally has been good on the subject,” said Paul Offit, MD, director of the Vaccine Education Center, attending physician in the Division of Infectious Diseases at the Children’s Hospital of Philadelphia, and a prominent expert voice throughout the pandemic. “I think where they’ve been imperfect is they tend to be a little more dramatic in terms of how we’re doing.”

Dr. Offit isn’t the only expert to point to the drama of COVID-19 coverage. A study published in March 2021 by the National Bureau of Economic Research found 87% of stories by major U.S. media outlets leaned negative in the tone of their COVID-19 reporting, compared with 50% of stories from non-U.S. major outlets and 64% of articles in scientific journals. The negative emphasis persists even around positive developments, like vaccine trials and school re-openings.

John Whyte, MD, chief medical officer for WebMD, said he is very proud of the way WebMD and Medscape ramped up production of video series and other content to give health care providers the most up-to-date guidance on a rapidly evolving medical situation.

“But I think as [we] started to make progress – especially in the last 6 months – the coverage was never balanced enough; any positive news was immediately proceeded by negative,” he said.

“You want to be honest, but you also don’t want to be alarmist – and that’s where I think the challenge is at times in the media,” said Dr. Whyte. “We didn’t put enough optimism in at times, especially in recent months.”

“Any good coverage on vaccines immediately [was] covered by ‘[we] might need boosters in the fall.’ Why can’t [we] have an opportunity to breathe for a little while and see the good news?” he asked.
 

Variants or scariants?

Negativity and fear shaped much of the coverage around variants and vaccines earlier this year. In February 2021, Zeynep Tufekci, PhD, a sociologist at the University of North Carolina at Chapel Hill school of information and library science, wrote in The Atlantic about how much reporting has not reflected “the truly amazing reality of these vaccines,” and has instead highlighted “a chorus of relentless pessimism.”

This felt especially true earlier in 2021, when lots of coverage repeatedly emphasized what vaccinated people still could not do.

Eric Topol, MD, editor-in-chief of Medscape and executive vice president of Scripps Research in La Jolla, California, said New York Times editors told him earlier in the pandemic that he couldn’t use the word “scariant” in an opinion piece about the media’s overly fearful and sometimes inaccurate reporting around COVID-19 variants because they worried it would seem like the Times was coming after other media outlets.

“A variant is innocent until proven guilty,” said Dr. Topol. Had journalists approached the subject from that point of view, he said we would have seen “much more faithful reporting.”

Dr. Brossard and Dr. Newman worry that focusing on uncommon negative behavior, like people who break social distancing and mask rules by gathering at the beach or the bar, makes those actions seem more common than they actually are.

The evidence suggests that “if you show these kinds of things to people, you encourage them to do the same behavior,” said Dr. Brossard.

There have been other mistakes along the way, too. Early in the pandemic, many outlets pointed viewers to official government sources of information, some of which, like the White House press briefings in March and April of 2020, ended up being some of the most virulent spreaders of misinformation, said Ms. Bell.

Before that, a handful of journalists like Roxanne Khamsi were the few pushing back against the dominant media narrative in early 2020 that the novel coronavirus was less concerning than the seasonal flu.

“Science journalists have always been writing about studies that sometimes contradict each other, and what’s happened is that has only been condensed in time,” said Ms. Khamsi, a health care reporter for outlets like WIRED magazine and The New York Times and a former chief news editor for Nature Medicine.
 

Politics and misinformation

It’s impossible to talk about media coverage of COVID-19 without touching on politics and misinformation.

Coverage of the pandemic was politicized and polarized from the very beginning, said Sedona Chinn, PhD, an assistant professor at the University of Wisconsin–Madison who researches the prevalence and effects of scientific disagreements in media.

By looking at network news transcripts and articles from national outlets like the Washington Post and The New York Times, Dr. Chinn and her colleagues were able to determine politicization of coverage by counting the mentions of politicians versus scientists in COVID-19 coverage and polarization by looking at how different or similar the language was surrounding mentions of Republicans and Democrats.

If the two parties were working together or on the same page, they reasoned, the language would be similar.

From mid-March through May 2020, Dr. Chinn and fellow researchers found politicians were featured more often than scientists in newspaper coverage and as frequently as scientists in network news coverage. They also found polarized language around Republicans and Democrats, particularly in stories describing duels between the (at the time) Republican national government and Democratic state and local leaders.

It’s possible that polarization in news coverage helped contribute to polarized attitudes around the virus, the authors write in the study, which was published in August 2020 in the journal Science Communication.

The politicization and polarization of the issue is mirrored in our fractured media environment, where people tend to read, listen, and watch outlets that align with their political leanings. If that trusted outlet features misinformation, the people who follow it are more likely to accept that false information as truth, said Matt Motta, PhD, a political scientist at Oklahoma State University whose research includes public opinion and science communication.

This is true across the political spectrum, he said. When it comes to COVID-19, however, right-wing media outlets like Fox News and Breitbart are more likely to promote conspiratorial tropes and misinformation about the pandemic, according to Dr. Motta and his collaborator Dominik Stecula, PhD, a political scientist at Colorado State University who studies the news media environment and its effects on society.

Across the media ecosystem, reporting on the “infodemic” accompanying the pandemic – the rapid spread of misinformation and disinformation about the virus – has been a major challenge. Outlets may not be creating the misinformation, but they are the ones choosing to give it a platform, said Dr. Motta.

By repeating a false idea, even with the goal of debunking it, you can unintentionally cause the information to stick in people’s minds, said Dr. Brossard.

“Just because something is controversial doesn’t mean it’s worth covering,” said Dr. Motta. Using vaccines as an example, he said many reporters and scientists alike assume that if people have all the facts, they’ll land on the side of science.

“That is just fundamentally not how people think about the decision to get vaccinated,” he said. Instead, the choice is wrapped up with cultural factors, religious beliefs, political identity, and more.

The factors and challenges that shaped the media’s coverage of the pandemic aren’t going anywhere. Improving science and medical coverage in the future is a collective project for journalists, scientists, and everyone in between, said Dr. Newman.

“I call on scientists, too, to think really deeply about how they’re communicating – and especially how they’re communicating what they know and don’t know,” he said.

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

Among patients with atherosclerotic cardiovascular disease (ASCVD), 2 years after release of treat-to-target guidelines from the American Heart Association and the European Society of Cardiology and European Atherosclerosis Society, most patients with LDL cholesterol higher than 70 mg/dL did not receive intensification of therapy, and two-thirds continued to have LDL levels above that level, according to a prospective registry study.

Both guidelines recommend driving LDL-C levels to 50% or below of baseline levels; results from the Getting to an Improved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management (GOULD) registry suggest this is rarely achieved. “Unfortunately it’s not a total surprise, but it’s disappointing,” said Christopher Cannon, MD, the study’s lead author.

“Therapeutic inertia seems to be the rule in clinical practice,” said Jennifer G. Robinson, MD, MPH, who was asked to comment on the study. Dr. Robinson is professor epidemiology and cardiology at the University of Iowa, Iowa City.

Patients hesitant

Changes in practice following guidelines can often be slow, but in this case may have been complicated by the fact that statins have a reputation for causing side effects, so some patients may be refusing treatment based on what they’ve seen on the Internet. Even though the study looked at all lipid-lowering agents, the misinformation around statins may be spilling over, according to Dr. Cannon. “There’s in general so much misinformation around COVID and every other topic in the world. That makes people question what is real [about] anything,” said Dr. Cannon, a cardiologist at Brigham and Women’s hospital and professor of medicine at Harvard Medical School, both in Boston.

Patient characteristics may partly explain slow uptake. “Clinicians may not think further LDL-C lowering is a high enough priority in terms of potential benefit for a given patient in light of the effort being expended to take care of all their other issues and chronic health problems. If the clinician does bring it up to the patient, there may be barriers in terms of additional medication burden, cost, or acquisition issues,” said Dr. Robinson.

The answer may be better evidence and a more personalized approach. Clinical trials that explore defined patient populations could convince patients of a benefit, and payers to reimburse, according to Dr. Robinson.
 

Changing guidance

Another complication is that both the guidelines and the field are rapidly changing. The 2013 AHA guidelines did not include a treatment to goal and focused instead on use of high-dose statins. But the 2018 update reversed course after randomized studies demonstrated a benefit to treating to target. The researchers found no increase in the frequency of treating to target after the release of the 2018 guidelines. “Publication and announcement of guidelines doesn’t mean that people are getting treated better. We really have to implement them,” said Dr. Cannon.

On a positive note, the GOULD researchers found high acceptance of the new proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) inhibitors, with over 90% of patients continuing those medications after 2 years. “That’s nice and high. If people do get onto the very intensive lipid-lowing therapies, they tend to stay on them,” said Dr. Cannon.
 

What’s next

Still, the lack of intensification is concerning, and the findings led to some consternation in Twitter exchanges, said Dr. Cannon. “People posted ‘Well, what do we do now?’ ” Dr. Cannon’s team is addressing the issue with an algorithm-based risk management program with prospective enrollment. They have conducted educational webinars and provided site-specific reports on LDL status among patients at each center compared to others, and hope that information will improve compliance. In 2020, the group published an interim analysis of the first 5,000 enrollees, and Dr. Cannon expects to finish that study by the end of the year.

Dr. Navar agreed that physicians need to do a better job of testing LDL-C levels after treatment to identify patients who require more aggressive therapy. That can be deferred in some primary prevention patients with high LDL-C but normal particle numbers as measured with ApoB. “But in those at high risk for disease and those with established CVD who are not at goal, as long as they don’t have a life-limiting condition, we should always up-titrate therapy. It’s one of the safest, most effective ways to lower cardiovascular risk,” said Dr. Navar.

Key study results

The prospective study included 5,006 patients at 119 centers with a mean age of 68 years. About 40% were women, and 86.1% were White. All had ASCVD and LDL levels of at least 70 mg/dL. After 2 years, 17% had undergone intensification of lipid-lowering therapy (LLT). Among patients with LDL-C levels ≥ 100 mg/dL, 22% underwent LLT intensification, compared with 14% of patients with LDL-C levels of 70-99 mg/dL.

The vast majority, 92%, of patients who underwent LLT via addition of PCSK9 inhibitors were still taking the drug after 2 years.

Three-quarters (3,768) had lipid level measurements at least once during follow-up, and median LDL-C levels dropped from 120 to 95 mg/dL in the ≥100-mg/dL cohort (P < .001), and from 82 to 77 mg/dL in the 70- to 99-mg/dL cohort (P <. 001). There was no significant difference in the median values in the patients on PCSK9 inhibitors.

In all, 21% of the ≥100-mg/dL cohort achieved LDL-C levels <70 mg/dL at 2 years, versus 34% in the 77- to 99-mg/dL cohort and 52% of patients taking PCSK9 inhibitors.

Patients seen at teaching hospitals were more likely to undergo LLT intensification compared to nonteaching hospitals (25% versus 17%; P < .001), as were those where lipid protocols were in place (22% versus 15%; P < .001), and those treated in cardiology (22%) compared to treatment in internal or family medicine (12%; P <.001). The study was published online June 16 in JAMA Cardiology.

Dr. Cannon, Dr. Navar, and Dr. Robinson disclosed ties with Amgen, which funded the study, and other companies.

Among patients with atherosclerotic cardiovascular disease (ASCVD), 2 years after release of treat-to-target guidelines from the American Heart Association and the European Society of Cardiology and European Atherosclerosis Society, most patients with LDL cholesterol higher than 70 mg/dL did not receive intensification of therapy, and two-thirds continued to have LDL levels above that level, according to a prospective registry study.

Both guidelines recommend driving LDL-C levels to 50% or below of baseline levels; results from the Getting to an Improved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management (GOULD) registry suggest this is rarely achieved. “Unfortunately it’s not a total surprise, but it’s disappointing,” said Christopher Cannon, MD, the study’s lead author.

“Therapeutic inertia seems to be the rule in clinical practice,” said Jennifer G. Robinson, MD, MPH, who was asked to comment on the study. Dr. Robinson is professor epidemiology and cardiology at the University of Iowa, Iowa City.

Patients hesitant

Changes in practice following guidelines can often be slow, but in this case may have been complicated by the fact that statins have a reputation for causing side effects, so some patients may be refusing treatment based on what they’ve seen on the Internet. Even though the study looked at all lipid-lowering agents, the misinformation around statins may be spilling over, according to Dr. Cannon. “There’s in general so much misinformation around COVID and every other topic in the world. That makes people question what is real [about] anything,” said Dr. Cannon, a cardiologist at Brigham and Women’s hospital and professor of medicine at Harvard Medical School, both in Boston.

Patient characteristics may partly explain slow uptake. “Clinicians may not think further LDL-C lowering is a high enough priority in terms of potential benefit for a given patient in light of the effort being expended to take care of all their other issues and chronic health problems. If the clinician does bring it up to the patient, there may be barriers in terms of additional medication burden, cost, or acquisition issues,” said Dr. Robinson.

The answer may be better evidence and a more personalized approach. Clinical trials that explore defined patient populations could convince patients of a benefit, and payers to reimburse, according to Dr. Robinson.
 

Changing guidance

Another complication is that both the guidelines and the field are rapidly changing. The 2013 AHA guidelines did not include a treatment to goal and focused instead on use of high-dose statins. But the 2018 update reversed course after randomized studies demonstrated a benefit to treating to target. The researchers found no increase in the frequency of treating to target after the release of the 2018 guidelines. “Publication and announcement of guidelines doesn’t mean that people are getting treated better. We really have to implement them,” said Dr. Cannon.

On a positive note, the GOULD researchers found high acceptance of the new proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) inhibitors, with over 90% of patients continuing those medications after 2 years. “That’s nice and high. If people do get onto the very intensive lipid-lowing therapies, they tend to stay on them,” said Dr. Cannon.
 

What’s next

Still, the lack of intensification is concerning, and the findings led to some consternation in Twitter exchanges, said Dr. Cannon. “People posted ‘Well, what do we do now?’ ” Dr. Cannon’s team is addressing the issue with an algorithm-based risk management program with prospective enrollment. They have conducted educational webinars and provided site-specific reports on LDL status among patients at each center compared to others, and hope that information will improve compliance. In 2020, the group published an interim analysis of the first 5,000 enrollees, and Dr. Cannon expects to finish that study by the end of the year.

Dr. Navar agreed that physicians need to do a better job of testing LDL-C levels after treatment to identify patients who require more aggressive therapy. That can be deferred in some primary prevention patients with high LDL-C but normal particle numbers as measured with ApoB. “But in those at high risk for disease and those with established CVD who are not at goal, as long as they don’t have a life-limiting condition, we should always up-titrate therapy. It’s one of the safest, most effective ways to lower cardiovascular risk,” said Dr. Navar.

Key study results

The prospective study included 5,006 patients at 119 centers with a mean age of 68 years. About 40% were women, and 86.1% were White. All had ASCVD and LDL levels of at least 70 mg/dL. After 2 years, 17% had undergone intensification of lipid-lowering therapy (LLT). Among patients with LDL-C levels ≥ 100 mg/dL, 22% underwent LLT intensification, compared with 14% of patients with LDL-C levels of 70-99 mg/dL.

The vast majority, 92%, of patients who underwent LLT via addition of PCSK9 inhibitors were still taking the drug after 2 years.

Three-quarters (3,768) had lipid level measurements at least once during follow-up, and median LDL-C levels dropped from 120 to 95 mg/dL in the ≥100-mg/dL cohort (P < .001), and from 82 to 77 mg/dL in the 70- to 99-mg/dL cohort (P <. 001). There was no significant difference in the median values in the patients on PCSK9 inhibitors.

In all, 21% of the ≥100-mg/dL cohort achieved LDL-C levels <70 mg/dL at 2 years, versus 34% in the 77- to 99-mg/dL cohort and 52% of patients taking PCSK9 inhibitors.

Patients seen at teaching hospitals were more likely to undergo LLT intensification compared to nonteaching hospitals (25% versus 17%; P < .001), as were those where lipid protocols were in place (22% versus 15%; P < .001), and those treated in cardiology (22%) compared to treatment in internal or family medicine (12%; P <.001). The study was published online June 16 in JAMA Cardiology.

Dr. Cannon, Dr. Navar, and Dr. Robinson disclosed ties with Amgen, which funded the study, and other companies.

Among patients with atherosclerotic cardiovascular disease (ASCVD), 2 years after release of treat-to-target guidelines from the American Heart Association and the European Society of Cardiology and European Atherosclerosis Society, most patients with LDL cholesterol higher than 70 mg/dL did not receive intensification of therapy, and two-thirds continued to have LDL levels above that level, according to a prospective registry study.

Both guidelines recommend driving LDL-C levels to 50% or below of baseline levels; results from the Getting to an Improved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management (GOULD) registry suggest this is rarely achieved. “Unfortunately it’s not a total surprise, but it’s disappointing,” said Christopher Cannon, MD, the study’s lead author.

“Therapeutic inertia seems to be the rule in clinical practice,” said Jennifer G. Robinson, MD, MPH, who was asked to comment on the study. Dr. Robinson is professor epidemiology and cardiology at the University of Iowa, Iowa City.

Patients hesitant

Changes in practice following guidelines can often be slow, but in this case may have been complicated by the fact that statins have a reputation for causing side effects, so some patients may be refusing treatment based on what they’ve seen on the Internet. Even though the study looked at all lipid-lowering agents, the misinformation around statins may be spilling over, according to Dr. Cannon. “There’s in general so much misinformation around COVID and every other topic in the world. That makes people question what is real [about] anything,” said Dr. Cannon, a cardiologist at Brigham and Women’s hospital and professor of medicine at Harvard Medical School, both in Boston.

Patient characteristics may partly explain slow uptake. “Clinicians may not think further LDL-C lowering is a high enough priority in terms of potential benefit for a given patient in light of the effort being expended to take care of all their other issues and chronic health problems. If the clinician does bring it up to the patient, there may be barriers in terms of additional medication burden, cost, or acquisition issues,” said Dr. Robinson.

The answer may be better evidence and a more personalized approach. Clinical trials that explore defined patient populations could convince patients of a benefit, and payers to reimburse, according to Dr. Robinson.
 

Changing guidance

Another complication is that both the guidelines and the field are rapidly changing. The 2013 AHA guidelines did not include a treatment to goal and focused instead on use of high-dose statins. But the 2018 update reversed course after randomized studies demonstrated a benefit to treating to target. The researchers found no increase in the frequency of treating to target after the release of the 2018 guidelines. “Publication and announcement of guidelines doesn’t mean that people are getting treated better. We really have to implement them,” said Dr. Cannon.

On a positive note, the GOULD researchers found high acceptance of the new proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) inhibitors, with over 90% of patients continuing those medications after 2 years. “That’s nice and high. If people do get onto the very intensive lipid-lowing therapies, they tend to stay on them,” said Dr. Cannon.
 

What’s next

Still, the lack of intensification is concerning, and the findings led to some consternation in Twitter exchanges, said Dr. Cannon. “People posted ‘Well, what do we do now?’ ” Dr. Cannon’s team is addressing the issue with an algorithm-based risk management program with prospective enrollment. They have conducted educational webinars and provided site-specific reports on LDL status among patients at each center compared to others, and hope that information will improve compliance. In 2020, the group published an interim analysis of the first 5,000 enrollees, and Dr. Cannon expects to finish that study by the end of the year.

Dr. Navar agreed that physicians need to do a better job of testing LDL-C levels after treatment to identify patients who require more aggressive therapy. That can be deferred in some primary prevention patients with high LDL-C but normal particle numbers as measured with ApoB. “But in those at high risk for disease and those with established CVD who are not at goal, as long as they don’t have a life-limiting condition, we should always up-titrate therapy. It’s one of the safest, most effective ways to lower cardiovascular risk,” said Dr. Navar.

Key study results

The prospective study included 5,006 patients at 119 centers with a mean age of 68 years. About 40% were women, and 86.1% were White. All had ASCVD and LDL levels of at least 70 mg/dL. After 2 years, 17% had undergone intensification of lipid-lowering therapy (LLT). Among patients with LDL-C levels ≥ 100 mg/dL, 22% underwent LLT intensification, compared with 14% of patients with LDL-C levels of 70-99 mg/dL.

The vast majority, 92%, of patients who underwent LLT via addition of PCSK9 inhibitors were still taking the drug after 2 years.

Three-quarters (3,768) had lipid level measurements at least once during follow-up, and median LDL-C levels dropped from 120 to 95 mg/dL in the ≥100-mg/dL cohort (P < .001), and from 82 to 77 mg/dL in the 70- to 99-mg/dL cohort (P <. 001). There was no significant difference in the median values in the patients on PCSK9 inhibitors.

In all, 21% of the ≥100-mg/dL cohort achieved LDL-C levels <70 mg/dL at 2 years, versus 34% in the 77- to 99-mg/dL cohort and 52% of patients taking PCSK9 inhibitors.

Patients seen at teaching hospitals were more likely to undergo LLT intensification compared to nonteaching hospitals (25% versus 17%; P < .001), as were those where lipid protocols were in place (22% versus 15%; P < .001), and those treated in cardiology (22%) compared to treatment in internal or family medicine (12%; P <.001). The study was published online June 16 in JAMA Cardiology.

Dr. Cannon, Dr. Navar, and Dr. Robinson disclosed ties with Amgen, which funded the study, and other companies.