Diabetes mellitus is prevalent in our society; 1 in 10 Americans has the condition and > 1 in 3 has prediabetes.¹ Due to the widespread comorbidities and complications of this disease, the American Diabetes Association (ADA) recommends that diabetes management focus on evaluation and treatment of complications.² Diabetes-related complications can be life-altering and challenging for patients because their quality of life suffers.

For providers, there are several evidence-based screening tools and preventive practices (in and beyond glycemic control) that reduce diabetes complications such as congestive heart failure, kidney failure, lower extremity amputation, and stroke.³ We as providers can treat patients by implementing appropriate goal-directed therapy.^4-6

In this 5-part series, I will explore the evidence and recommendations for a multimodal approach in a patient with type 2 diabetes. Here—in Part 1—I explore the self-care behaviors our patients can adopt to improve their symptoms of diabetes.

Case Report

Mr. W is an overweight 64-year-old man with hypertension, hyperlipidemia, and type 2 diabetes mellitus. He visits the clinic for his yearly physical exam. He is concerned because his father, who had diabetes, developed renal failure and had multiple amputations near the end of his life. He is worried that he might face the same outcomes and asks you what he can do to avoid his father’s fate.

Advising Your Patient on Self-care

The cornerstone of diabetes management is appropriate self-care. Both the ADA and the American Association of Clinical Endocrinologists (AACE) recommend that treatment plans should encourage the patient to adopt healthy lifestyle behaviors, including a healthy diet, regular exercise, weight control, and avoidance of tobacco.^2,7,8 These interventions have positive effects on blood pressure, glucose control, and lipid levels. They can also reduce the risk for diabetic complications, including atherosclerotic cardiovascular disease (ASCVD), which is the foremost cause of death among patients with diabetes. During a patient visit, clinicians can suggest the following self-care interventions for improving long-term outcomes.

Education sessions. The ADA recommends that individuals with diabetes participate in diabetes self-management education and support (DSMES) sessions.² In these sessions, patients with diabetes are instructed on a variety of self-care behaviors, including lifestyle interventions, medication management, self-monitoring, and problem-solving.⁹ These programs—often paid for in part by health insurance—are taught by health care professionals such as registered dieticians, nutritionists, or certified diabetes educators.^9,10 Evidence suggests DSMES increases patients’ sense of self-efficacy and may improve blood sugar management.¹⁰ Clinicians can help guide their patients through the Association of Diabetes Care & Education Specialists’ online database to identify a DSMES program near them (see www.diabeteseducator.org/living-with-diabetes/find-an-education-program).¹¹

Diet. The AACE recommends a plant-based diet high in polyunsaturated and monounsaturated fatty acids and limited in trans fatty acids and saturated fats.⁷ Evidence strongly suggests that a Mediterranean diet with high vegetable intake and decreased saturated fats helps to reduce the risk for major cardiovascular events (myocardial infarction and stroke).¹²

Continue to: Exercise

Exercise. Both the ADA and AACE recommend that most adults with diabetes engage in at least 150 min/week of moderate-to-vigorous aerobic and strength-training exercises.^2,7 Clinicians should evaluate patients with sedentary lifestyles prior to them engaging in vigorous physical activity beyond simple walking.² The ADA also recommends that patients should avoid sitting for long periods of time by engaging in physical activity at least every 30 minutes.² For adults who may not be able to participate in moderate-to-vigorous exercise, recommend alternative flexibility and balance-training activities, such as yoga or tai chi, 2 to 3 times per week.²

Weight management—a combined effort of diet, exercise, and behavioral therapy—is pivotal in the management of type 2 diabetes due to the potential benefits in insulin resistance, blood pressure, hyperlipidemia, and other factors.² Weight loss may also improve glycemic control and reduce the need for glucose-lowering medications.² For patients who struggle with weight loss, consider prescribing FDA-approved weight-loss medications (phentermine, orlistat, lorcaserin, naltrexone/bupropion, liraglutide) or, in some cases, referring for bariatric surgery.^2,7

Sleep hygiene is an important element in any preventive treatment plan. This includes interventions as simple as going to bed at the same time every night, sleeping in a dark room, sleeping for at least 7 hours, and removing electronic devices from the bedroom.13 Patients should avoid alcohol, caffeine, and large meals before bedtime.¹³

Additionally, obstructive sleep apnea (OSA) is often underdiagnosed in patients with diabetes and contributes to insulin resistance, inflammation, and elevated blood pressure.^7,14 For early identification of OSA, order a sleep study when appropriate and refer patients to sleep specialists if needed. Patients who are recommended for treatment should be monitored for increasing compliance with care and to ensure benefit from treatment.

In Part 2, we’ll check in with Mr. W as I discuss the role of blood pressure monitoring and antihypertensive medications in reducing cardiovascular risks in patients with diabetes.

Diabetes mellitus is prevalent in our society; 1 in 10 Americans has the condition and > 1 in 3 has prediabetes.¹ Due to the widespread comorbidities and complications of this disease, the American Diabetes Association (ADA) recommends that diabetes management focus on evaluation and treatment of complications.² Diabetes-related complications can be life-altering and challenging for patients because their quality of life suffers.

For providers, there are several evidence-based screening tools and preventive practices (in and beyond glycemic control) that reduce diabetes complications such as congestive heart failure, kidney failure, lower extremity amputation, and stroke.³ We as providers can treat patients by implementing appropriate goal-directed therapy.^4-6

In this 5-part series, I will explore the evidence and recommendations for a multimodal approach in a patient with type 2 diabetes. Here—in Part 1—I explore the self-care behaviors our patients can adopt to improve their symptoms of diabetes.

Case Report

Mr. W is an overweight 64-year-old man with hypertension, hyperlipidemia, and type 2 diabetes mellitus. He visits the clinic for his yearly physical exam. He is concerned because his father, who had diabetes, developed renal failure and had multiple amputations near the end of his life. He is worried that he might face the same outcomes and asks you what he can do to avoid his father’s fate.

Advising Your Patient on Self-care

The cornerstone of diabetes management is appropriate self-care. Both the ADA and the American Association of Clinical Endocrinologists (AACE) recommend that treatment plans should encourage the patient to adopt healthy lifestyle behaviors, including a healthy diet, regular exercise, weight control, and avoidance of tobacco.^2,7,8 These interventions have positive effects on blood pressure, glucose control, and lipid levels. They can also reduce the risk for diabetic complications, including atherosclerotic cardiovascular disease (ASCVD), which is the foremost cause of death among patients with diabetes. During a patient visit, clinicians can suggest the following self-care interventions for improving long-term outcomes.

Education sessions. The ADA recommends that individuals with diabetes participate in diabetes self-management education and support (DSMES) sessions.² In these sessions, patients with diabetes are instructed on a variety of self-care behaviors, including lifestyle interventions, medication management, self-monitoring, and problem-solving.⁹ These programs—often paid for in part by health insurance—are taught by health care professionals such as registered dieticians, nutritionists, or certified diabetes educators.^9,10 Evidence suggests DSMES increases patients’ sense of self-efficacy and may improve blood sugar management.¹⁰ Clinicians can help guide their patients through the Association of Diabetes Care & Education Specialists’ online database to identify a DSMES program near them (see www.diabeteseducator.org/living-with-diabetes/find-an-education-program).¹¹

Diet. The AACE recommends a plant-based diet high in polyunsaturated and monounsaturated fatty acids and limited in trans fatty acids and saturated fats.⁷ Evidence strongly suggests that a Mediterranean diet with high vegetable intake and decreased saturated fats helps to reduce the risk for major cardiovascular events (myocardial infarction and stroke).¹²

Continue to: Exercise

Exercise. Both the ADA and AACE recommend that most adults with diabetes engage in at least 150 min/week of moderate-to-vigorous aerobic and strength-training exercises.^2,7 Clinicians should evaluate patients with sedentary lifestyles prior to them engaging in vigorous physical activity beyond simple walking.² The ADA also recommends that patients should avoid sitting for long periods of time by engaging in physical activity at least every 30 minutes.² For adults who may not be able to participate in moderate-to-vigorous exercise, recommend alternative flexibility and balance-training activities, such as yoga or tai chi, 2 to 3 times per week.²

Weight management—a combined effort of diet, exercise, and behavioral therapy—is pivotal in the management of type 2 diabetes due to the potential benefits in insulin resistance, blood pressure, hyperlipidemia, and other factors.² Weight loss may also improve glycemic control and reduce the need for glucose-lowering medications.² For patients who struggle with weight loss, consider prescribing FDA-approved weight-loss medications (phentermine, orlistat, lorcaserin, naltrexone/bupropion, liraglutide) or, in some cases, referring for bariatric surgery.^2,7

Sleep hygiene is an important element in any preventive treatment plan. This includes interventions as simple as going to bed at the same time every night, sleeping in a dark room, sleeping for at least 7 hours, and removing electronic devices from the bedroom.13 Patients should avoid alcohol, caffeine, and large meals before bedtime.¹³

Additionally, obstructive sleep apnea (OSA) is often underdiagnosed in patients with diabetes and contributes to insulin resistance, inflammation, and elevated blood pressure.^7,14 For early identification of OSA, order a sleep study when appropriate and refer patients to sleep specialists if needed. Patients who are recommended for treatment should be monitored for increasing compliance with care and to ensure benefit from treatment.

In Part 2, we’ll check in with Mr. W as I discuss the role of blood pressure monitoring and antihypertensive medications in reducing cardiovascular risks in patients with diabetes.

Diabetes mellitus is prevalent in our society; 1 in 10 Americans has the condition and > 1 in 3 has prediabetes.¹ Due to the widespread comorbidities and complications of this disease, the American Diabetes Association (ADA) recommends that diabetes management focus on evaluation and treatment of complications.² Diabetes-related complications can be life-altering and challenging for patients because their quality of life suffers.

For providers, there are several evidence-based screening tools and preventive practices (in and beyond glycemic control) that reduce diabetes complications such as congestive heart failure, kidney failure, lower extremity amputation, and stroke.³ We as providers can treat patients by implementing appropriate goal-directed therapy.^4-6

In this 5-part series, I will explore the evidence and recommendations for a multimodal approach in a patient with type 2 diabetes. Here—in Part 1—I explore the self-care behaviors our patients can adopt to improve their symptoms of diabetes.

Case Report

Mr. W is an overweight 64-year-old man with hypertension, hyperlipidemia, and type 2 diabetes mellitus. He visits the clinic for his yearly physical exam. He is concerned because his father, who had diabetes, developed renal failure and had multiple amputations near the end of his life. He is worried that he might face the same outcomes and asks you what he can do to avoid his father’s fate.

Advising Your Patient on Self-care

The cornerstone of diabetes management is appropriate self-care. Both the ADA and the American Association of Clinical Endocrinologists (AACE) recommend that treatment plans should encourage the patient to adopt healthy lifestyle behaviors, including a healthy diet, regular exercise, weight control, and avoidance of tobacco.^2,7,8 These interventions have positive effects on blood pressure, glucose control, and lipid levels. They can also reduce the risk for diabetic complications, including atherosclerotic cardiovascular disease (ASCVD), which is the foremost cause of death among patients with diabetes. During a patient visit, clinicians can suggest the following self-care interventions for improving long-term outcomes.

Education sessions. The ADA recommends that individuals with diabetes participate in diabetes self-management education and support (DSMES) sessions.² In these sessions, patients with diabetes are instructed on a variety of self-care behaviors, including lifestyle interventions, medication management, self-monitoring, and problem-solving.⁹ These programs—often paid for in part by health insurance—are taught by health care professionals such as registered dieticians, nutritionists, or certified diabetes educators.^9,10 Evidence suggests DSMES increases patients’ sense of self-efficacy and may improve blood sugar management.¹⁰ Clinicians can help guide their patients through the Association of Diabetes Care & Education Specialists’ online database to identify a DSMES program near them (see www.diabeteseducator.org/living-with-diabetes/find-an-education-program).¹¹

Diet. The AACE recommends a plant-based diet high in polyunsaturated and monounsaturated fatty acids and limited in trans fatty acids and saturated fats.⁷ Evidence strongly suggests that a Mediterranean diet with high vegetable intake and decreased saturated fats helps to reduce the risk for major cardiovascular events (myocardial infarction and stroke).¹²

Continue to: Exercise

Exercise. Both the ADA and AACE recommend that most adults with diabetes engage in at least 150 min/week of moderate-to-vigorous aerobic and strength-training exercises.^2,7 Clinicians should evaluate patients with sedentary lifestyles prior to them engaging in vigorous physical activity beyond simple walking.² The ADA also recommends that patients should avoid sitting for long periods of time by engaging in physical activity at least every 30 minutes.² For adults who may not be able to participate in moderate-to-vigorous exercise, recommend alternative flexibility and balance-training activities, such as yoga or tai chi, 2 to 3 times per week.²

Weight management—a combined effort of diet, exercise, and behavioral therapy—is pivotal in the management of type 2 diabetes due to the potential benefits in insulin resistance, blood pressure, hyperlipidemia, and other factors.² Weight loss may also improve glycemic control and reduce the need for glucose-lowering medications.² For patients who struggle with weight loss, consider prescribing FDA-approved weight-loss medications (phentermine, orlistat, lorcaserin, naltrexone/bupropion, liraglutide) or, in some cases, referring for bariatric surgery.^2,7

Sleep hygiene is an important element in any preventive treatment plan. This includes interventions as simple as going to bed at the same time every night, sleeping in a dark room, sleeping for at least 7 hours, and removing electronic devices from the bedroom.13 Patients should avoid alcohol, caffeine, and large meals before bedtime.¹³

Additionally, obstructive sleep apnea (OSA) is often underdiagnosed in patients with diabetes and contributes to insulin resistance, inflammation, and elevated blood pressure.^7,14 For early identification of OSA, order a sleep study when appropriate and refer patients to sleep specialists if needed. Patients who are recommended for treatment should be monitored for increasing compliance with care and to ensure benefit from treatment.

In Part 2, we’ll check in with Mr. W as I discuss the role of blood pressure monitoring and antihypertensive medications in reducing cardiovascular risks in patients with diabetes.

A large proportion of results from heart failure trials registered with clinicaltrials.gov are published a year or more after completion or not at all, which violates the U.S. FDA Amendments Act (FDAAA), according to a detailed analysis of the interventional and observational trials in this database.

Of the 1,429 heart failure trials identified, 75% of which were randomized interventional studies and the remainder of which were observational, fewer than 20% met the FDAAA 1-year reporting requirement, and 44% have yet to be published at all, reported a team of collaborative investigators led by cardiologists from the Inova Heart and Vascular Institute (IHVI), Falls Church, Va.

“I believe the critical issue is that the FDAAA has thus far never been enforced,” reported Christopher M. O’Connor, MD, a cardiologist and president of IHVI. He was the senior author of the study, reported in the Journal of the American College of Cardiology.

To improve systematic reporting of clinical trials, including negative results, clinicaltrials.gov was created in 2000. In 2007, the FDAAA enacted rules to broaden the requirements for reporting and to make timely reporting of results mandatory.

Ten years later, the FDA was finally authorized to issue a penalty of $10,000 for failure to release results in a timely fashion, a provision of the 2007 amendment but not confirmed at that time, the investigators reported. In the majority of cases, timely reporting was defined as within 12 months of completion of the trial.

The new study shows that reporting of completed trials, timely or otherwise, remains low. Of the 1,243 trials completed after 2007, the proportion meeting the 1-year reporting requirement was just 20%. Although a significant improvement over the 13% reporting in this time frame before 2007, more than 80% of findings are not being released in a timely manner more than 10 years after this was made mandatory.

There are a number of reasons to consider this to be a serious issue, according to Mandeep R. Mehra, MD, of Brigham and Women’s Hospital, Boston. One of the authors of an accompanying editorial regarding this analysis, Dr. Mehra called underreporting “a public health matter because it is an impediment to medical discovery and poses plausible threats to patient safety.”

Among studies registered after 2007, publication rates were higher for trials funded by the National Institutes of Health (71%) relative to industry (49%) or the U.S. Veterans Affairs (45%).

Publication rates were also higher among interventional relative to observational trials (59% vs. 46%) and trials that enrolled more than 1,000 patients relative to those enrolling fewer than 150 (77% vs. 51%), although trial size was not a significant predictor of publication on multivariate analysis. Clinical endpoints, such as death or hospitalization, were also associated with a greater likelihood of publication relative to nonclinical endpoints.

Of the 251 trials terminated before completion, findings were published within 1 year in only 6%. Two years after completion, only 20% were published at all.

Results consistent with the primary hypothesis did not predict timely publication, but only 39% of the studies listed a primary hypothesis. Since 2017, this is another violation of the FDAAA, according to Dr. O’Connor.

The problem is not unique to heart failure trials, according to the authors who cited numerous studies showing low rates of timely publication in other therapeutic areas. Heart failure was selected for evaluation in this study mainly to keep the analysis feasible, although the authors contend this is an area with an urgent need for better treatments.

The problem needs to be fixed, according to Dr. Mehra. In his editorial, he called for rules to be “transitioned to regulations and action taken for underreporting.” Dr. O’Connor agreed.

“A combination of carrots and sticks might be needed to achieve sufficient result sharing,” Dr. O’Connor said. He suggested that stakeholders, such as investigators, sponsors, regulators, and journal editors, should collaborate to address the problem.

So far, the FDA has never levied a fine for lack of reporting or for failure to report in a timely manner. Routine imposition of large fines might not be viable, given the complex reasons that delay or inhibit publication of trial findings, but it would be a large source of revenue.

“According to the FDAAA TrialsTracker, a live tool that tracks FDAAA compliance and promotes trial transparency, the U.S. government could already have imposed more than $2.8 billion in fines for trials due after January 2018,” Dr. O’Connor reported.

The first and senior authors are among those who report financial relationships with pharmaceutical companies.

SOURCE: Psotka MA et al. J Am Coll Cardiol. 2020;75:3151-61.

A large proportion of results from heart failure trials registered with clinicaltrials.gov are published a year or more after completion or not at all, which violates the U.S. FDA Amendments Act (FDAAA), according to a detailed analysis of the interventional and observational trials in this database.

Of the 1,429 heart failure trials identified, 75% of which were randomized interventional studies and the remainder of which were observational, fewer than 20% met the FDAAA 1-year reporting requirement, and 44% have yet to be published at all, reported a team of collaborative investigators led by cardiologists from the Inova Heart and Vascular Institute (IHVI), Falls Church, Va.

“I believe the critical issue is that the FDAAA has thus far never been enforced,” reported Christopher M. O’Connor, MD, a cardiologist and president of IHVI. He was the senior author of the study, reported in the Journal of the American College of Cardiology.

To improve systematic reporting of clinical trials, including negative results, clinicaltrials.gov was created in 2000. In 2007, the FDAAA enacted rules to broaden the requirements for reporting and to make timely reporting of results mandatory.

Ten years later, the FDA was finally authorized to issue a penalty of $10,000 for failure to release results in a timely fashion, a provision of the 2007 amendment but not confirmed at that time, the investigators reported. In the majority of cases, timely reporting was defined as within 12 months of completion of the trial.

The new study shows that reporting of completed trials, timely or otherwise, remains low. Of the 1,243 trials completed after 2007, the proportion meeting the 1-year reporting requirement was just 20%. Although a significant improvement over the 13% reporting in this time frame before 2007, more than 80% of findings are not being released in a timely manner more than 10 years after this was made mandatory.

There are a number of reasons to consider this to be a serious issue, according to Mandeep R. Mehra, MD, of Brigham and Women’s Hospital, Boston. One of the authors of an accompanying editorial regarding this analysis, Dr. Mehra called underreporting “a public health matter because it is an impediment to medical discovery and poses plausible threats to patient safety.”

Among studies registered after 2007, publication rates were higher for trials funded by the National Institutes of Health (71%) relative to industry (49%) or the U.S. Veterans Affairs (45%).

Publication rates were also higher among interventional relative to observational trials (59% vs. 46%) and trials that enrolled more than 1,000 patients relative to those enrolling fewer than 150 (77% vs. 51%), although trial size was not a significant predictor of publication on multivariate analysis. Clinical endpoints, such as death or hospitalization, were also associated with a greater likelihood of publication relative to nonclinical endpoints.

Of the 251 trials terminated before completion, findings were published within 1 year in only 6%. Two years after completion, only 20% were published at all.

Results consistent with the primary hypothesis did not predict timely publication, but only 39% of the studies listed a primary hypothesis. Since 2017, this is another violation of the FDAAA, according to Dr. O’Connor.

The problem is not unique to heart failure trials, according to the authors who cited numerous studies showing low rates of timely publication in other therapeutic areas. Heart failure was selected for evaluation in this study mainly to keep the analysis feasible, although the authors contend this is an area with an urgent need for better treatments.

The problem needs to be fixed, according to Dr. Mehra. In his editorial, he called for rules to be “transitioned to regulations and action taken for underreporting.” Dr. O’Connor agreed.

“A combination of carrots and sticks might be needed to achieve sufficient result sharing,” Dr. O’Connor said. He suggested that stakeholders, such as investigators, sponsors, regulators, and journal editors, should collaborate to address the problem.

So far, the FDA has never levied a fine for lack of reporting or for failure to report in a timely manner. Routine imposition of large fines might not be viable, given the complex reasons that delay or inhibit publication of trial findings, but it would be a large source of revenue.

“According to the FDAAA TrialsTracker, a live tool that tracks FDAAA compliance and promotes trial transparency, the U.S. government could already have imposed more than $2.8 billion in fines for trials due after January 2018,” Dr. O’Connor reported.

The first and senior authors are among those who report financial relationships with pharmaceutical companies.

SOURCE: Psotka MA et al. J Am Coll Cardiol. 2020;75:3151-61.

A large proportion of results from heart failure trials registered with clinicaltrials.gov are published a year or more after completion or not at all, which violates the U.S. FDA Amendments Act (FDAAA), according to a detailed analysis of the interventional and observational trials in this database.

Of the 1,429 heart failure trials identified, 75% of which were randomized interventional studies and the remainder of which were observational, fewer than 20% met the FDAAA 1-year reporting requirement, and 44% have yet to be published at all, reported a team of collaborative investigators led by cardiologists from the Inova Heart and Vascular Institute (IHVI), Falls Church, Va.

“I believe the critical issue is that the FDAAA has thus far never been enforced,” reported Christopher M. O’Connor, MD, a cardiologist and president of IHVI. He was the senior author of the study, reported in the Journal of the American College of Cardiology.

To improve systematic reporting of clinical trials, including negative results, clinicaltrials.gov was created in 2000. In 2007, the FDAAA enacted rules to broaden the requirements for reporting and to make timely reporting of results mandatory.

Ten years later, the FDA was finally authorized to issue a penalty of $10,000 for failure to release results in a timely fashion, a provision of the 2007 amendment but not confirmed at that time, the investigators reported. In the majority of cases, timely reporting was defined as within 12 months of completion of the trial.

The new study shows that reporting of completed trials, timely or otherwise, remains low. Of the 1,243 trials completed after 2007, the proportion meeting the 1-year reporting requirement was just 20%. Although a significant improvement over the 13% reporting in this time frame before 2007, more than 80% of findings are not being released in a timely manner more than 10 years after this was made mandatory.

There are a number of reasons to consider this to be a serious issue, according to Mandeep R. Mehra, MD, of Brigham and Women’s Hospital, Boston. One of the authors of an accompanying editorial regarding this analysis, Dr. Mehra called underreporting “a public health matter because it is an impediment to medical discovery and poses plausible threats to patient safety.”

Among studies registered after 2007, publication rates were higher for trials funded by the National Institutes of Health (71%) relative to industry (49%) or the U.S. Veterans Affairs (45%).

Publication rates were also higher among interventional relative to observational trials (59% vs. 46%) and trials that enrolled more than 1,000 patients relative to those enrolling fewer than 150 (77% vs. 51%), although trial size was not a significant predictor of publication on multivariate analysis. Clinical endpoints, such as death or hospitalization, were also associated with a greater likelihood of publication relative to nonclinical endpoints.

Of the 251 trials terminated before completion, findings were published within 1 year in only 6%. Two years after completion, only 20% were published at all.

Results consistent with the primary hypothesis did not predict timely publication, but only 39% of the studies listed a primary hypothesis. Since 2017, this is another violation of the FDAAA, according to Dr. O’Connor.

The problem is not unique to heart failure trials, according to the authors who cited numerous studies showing low rates of timely publication in other therapeutic areas. Heart failure was selected for evaluation in this study mainly to keep the analysis feasible, although the authors contend this is an area with an urgent need for better treatments.

The problem needs to be fixed, according to Dr. Mehra. In his editorial, he called for rules to be “transitioned to regulations and action taken for underreporting.” Dr. O’Connor agreed.

“A combination of carrots and sticks might be needed to achieve sufficient result sharing,” Dr. O’Connor said. He suggested that stakeholders, such as investigators, sponsors, regulators, and journal editors, should collaborate to address the problem.

So far, the FDA has never levied a fine for lack of reporting or for failure to report in a timely manner. Routine imposition of large fines might not be viable, given the complex reasons that delay or inhibit publication of trial findings, but it would be a large source of revenue.

“According to the FDAAA TrialsTracker, a live tool that tracks FDAAA compliance and promotes trial transparency, the U.S. government could already have imposed more than $2.8 billion in fines for trials due after January 2018,” Dr. O’Connor reported.

The first and senior authors are among those who report financial relationships with pharmaceutical companies.

SOURCE: Psotka MA et al. J Am Coll Cardiol. 2020;75:3151-61.

Patients with Philadelphia chromosome–positive acute lymphoblastic or chronic myeloid leukemias in lymphoid blast phase may have longer event-free and overall survival with a combination of inotuzumab ozogamicin (Besponsa) and bosutinib (Bosulif) than with standard chemotherapy combined with a targeted agent, investigators in a phase 1/2 study reported.

Among patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) or chronic myeloid leukemia (Ph+ CML) in lymphoid blast phase treated with inotuzumab ozogamicin (Besponsa) and bosutinib (Bosulif), the median overall survival was 15.4 months. In contrast, median overall survival for similar patients treated with chemotherapy and a tyrosine kinase inhibitor (TKI) was less than 6 months, reported Nitin Jain, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston.

The study was presented in a scientific poster session as part of the virtual annual congress of the European Hematology Association.

“Patients with relapsed/refractory Philadelphia chromosome–positive ALL/CML in lymphoid blast crisis are also best managed with a TKI targeting the constitutively active ABL kinase with the TKI selected based on presence of ABL kinase mutations and prior TKI history,” commented Marlise R. Luskin, MD, a leukemia specialist at the Dana-Farber Cancer Institute in Boston.

“A critical question for this patient population is whether these two approaches [TKI and inotuzumab ozogamicin] can be administered safely in combination. I congratulate MD Anderson for completion of this Phase I trial which demonstrates that inotuzumab and bosutinib can be safely combined with identification of a maximum tolerated dose of bosutinib 400 mg daily when administered in combination. I look forward to further studies that explore the efficacy of combination versus the approved single-agent regimen,” she said in an interview.
 

Study details

To see whether they could improve the dismal outcomes for patients with Ph+ ALL or Ph+ CML in lymphoid blast phase, they studied the combination of inotuzumab ozogamicin, an anti-CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin, and bosutinib, an inhibitor of the ABL kinase. Inotuzumab is approved in the United States for treatment of adults with relapsed or refractory B-cell precursor ALL, bosutinib is approved for the treatment of patients with newly-diagnosed chronic phase Ph+ CML and for adults with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy.

The investigators enrolled 16 patients with Ph+ ALL and 2 with Ph+ CML with bone marrow blasts greater than 5%, CD22 expressed on at least 20% of blasts, and good to fair performance status. The patients also had adequate organ function as measured by liver enzyme, total bilirubin, and serum creatinine levels. Patients with the T315I mutation, prior anti-CD22 therapy, active graft-versus-host disease, or liver disease were excluded.

The patients received inotuzumab 0.8 mg/m² intravenously on day 1, they received 0.5 mg/m² on days 8 and 15 of cycle 1, and they received 0.5 mg/m² on days 1, 8, and 15 of cycles 2 through 6. Each cycle was 4 weeks. Patients who had a complete remission (CR), had complete cytogenetic remission (CCyR), or became negative for minimal residual disease (MRD) continued on 1 mg/m² every 4 weeks. Bosutinib was dosed continuously day starting on the first day of cycle 1 and continued until disease progression or toxicity.

After a median follow-up of 36.7 months, 11 of the 18 patients had CRs, and 4 had CRs with incomplete recovery of hematologic counts. In addition, 13 of 16 patients with without diploid cytogenetics at the start of the study had CCyr; 14 patients had major molecular remission; 10 had complete molecular remission, and 11 were negative by flow cytometry.

As noted before, the median overall survival was 15.4 months. Event-free survival – time to lack of response, relapse, MRD relapse requiring therapy, or death – was 8 months. The event-free survival data were not censored for allogeneic stem cell transplant. Six patients underwent transplant while in remission.

The primary objective of the phase 1 trial was to evaluate safety of the combination and determine the maximum tolerated dose of bosutinib, which was determined to be 400 mg daily. At this dose level, one patient had a dose-limiting toxicity in the form of a grade 3 skin rash.

The most frequent adverse events were diarrhea and rash, in 50% of patients each, and nausea in 39% of patients. Grade 3 adverse events included were rash in three patients and reversible alanine aminotransferase and hyponatremia in one patient each. No patients developed veno-occlusive disease, and there no deaths within 30 days of the start of therapy.

Dr. Jain disclosed consultancy, honoraria, advisory board/committee activity, and research funding from Pfizer, maker of inotuzumab ozogamicin and bosutinib. Dr. Luskin reported no relevant disclosures.

SOURCE: Jain N et al. EHA25, Abstract EP396.

Patients with Philadelphia chromosome–positive acute lymphoblastic or chronic myeloid leukemias in lymphoid blast phase may have longer event-free and overall survival with a combination of inotuzumab ozogamicin (Besponsa) and bosutinib (Bosulif) than with standard chemotherapy combined with a targeted agent, investigators in a phase 1/2 study reported.

Among patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) or chronic myeloid leukemia (Ph+ CML) in lymphoid blast phase treated with inotuzumab ozogamicin (Besponsa) and bosutinib (Bosulif), the median overall survival was 15.4 months. In contrast, median overall survival for similar patients treated with chemotherapy and a tyrosine kinase inhibitor (TKI) was less than 6 months, reported Nitin Jain, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston.

The study was presented in a scientific poster session as part of the virtual annual congress of the European Hematology Association.

“Patients with relapsed/refractory Philadelphia chromosome–positive ALL/CML in lymphoid blast crisis are also best managed with a TKI targeting the constitutively active ABL kinase with the TKI selected based on presence of ABL kinase mutations and prior TKI history,” commented Marlise R. Luskin, MD, a leukemia specialist at the Dana-Farber Cancer Institute in Boston.

“A critical question for this patient population is whether these two approaches [TKI and inotuzumab ozogamicin] can be administered safely in combination. I congratulate MD Anderson for completion of this Phase I trial which demonstrates that inotuzumab and bosutinib can be safely combined with identification of a maximum tolerated dose of bosutinib 400 mg daily when administered in combination. I look forward to further studies that explore the efficacy of combination versus the approved single-agent regimen,” she said in an interview.
 

Study details

To see whether they could improve the dismal outcomes for patients with Ph+ ALL or Ph+ CML in lymphoid blast phase, they studied the combination of inotuzumab ozogamicin, an anti-CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin, and bosutinib, an inhibitor of the ABL kinase. Inotuzumab is approved in the United States for treatment of adults with relapsed or refractory B-cell precursor ALL, bosutinib is approved for the treatment of patients with newly-diagnosed chronic phase Ph+ CML and for adults with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy.

The investigators enrolled 16 patients with Ph+ ALL and 2 with Ph+ CML with bone marrow blasts greater than 5%, CD22 expressed on at least 20% of blasts, and good to fair performance status. The patients also had adequate organ function as measured by liver enzyme, total bilirubin, and serum creatinine levels. Patients with the T315I mutation, prior anti-CD22 therapy, active graft-versus-host disease, or liver disease were excluded.

The patients received inotuzumab 0.8 mg/m² intravenously on day 1, they received 0.5 mg/m² on days 8 and 15 of cycle 1, and they received 0.5 mg/m² on days 1, 8, and 15 of cycles 2 through 6. Each cycle was 4 weeks. Patients who had a complete remission (CR), had complete cytogenetic remission (CCyR), or became negative for minimal residual disease (MRD) continued on 1 mg/m² every 4 weeks. Bosutinib was dosed continuously day starting on the first day of cycle 1 and continued until disease progression or toxicity.

After a median follow-up of 36.7 months, 11 of the 18 patients had CRs, and 4 had CRs with incomplete recovery of hematologic counts. In addition, 13 of 16 patients with without diploid cytogenetics at the start of the study had CCyr; 14 patients had major molecular remission; 10 had complete molecular remission, and 11 were negative by flow cytometry.

As noted before, the median overall survival was 15.4 months. Event-free survival – time to lack of response, relapse, MRD relapse requiring therapy, or death – was 8 months. The event-free survival data were not censored for allogeneic stem cell transplant. Six patients underwent transplant while in remission.

The primary objective of the phase 1 trial was to evaluate safety of the combination and determine the maximum tolerated dose of bosutinib, which was determined to be 400 mg daily. At this dose level, one patient had a dose-limiting toxicity in the form of a grade 3 skin rash.

The most frequent adverse events were diarrhea and rash, in 50% of patients each, and nausea in 39% of patients. Grade 3 adverse events included were rash in three patients and reversible alanine aminotransferase and hyponatremia in one patient each. No patients developed veno-occlusive disease, and there no deaths within 30 days of the start of therapy.

Dr. Jain disclosed consultancy, honoraria, advisory board/committee activity, and research funding from Pfizer, maker of inotuzumab ozogamicin and bosutinib. Dr. Luskin reported no relevant disclosures.

SOURCE: Jain N et al. EHA25, Abstract EP396.

Patients with Philadelphia chromosome–positive acute lymphoblastic or chronic myeloid leukemias in lymphoid blast phase may have longer event-free and overall survival with a combination of inotuzumab ozogamicin (Besponsa) and bosutinib (Bosulif) than with standard chemotherapy combined with a targeted agent, investigators in a phase 1/2 study reported.

Among patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) or chronic myeloid leukemia (Ph+ CML) in lymphoid blast phase treated with inotuzumab ozogamicin (Besponsa) and bosutinib (Bosulif), the median overall survival was 15.4 months. In contrast, median overall survival for similar patients treated with chemotherapy and a tyrosine kinase inhibitor (TKI) was less than 6 months, reported Nitin Jain, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston.

The study was presented in a scientific poster session as part of the virtual annual congress of the European Hematology Association.

“Patients with relapsed/refractory Philadelphia chromosome–positive ALL/CML in lymphoid blast crisis are also best managed with a TKI targeting the constitutively active ABL kinase with the TKI selected based on presence of ABL kinase mutations and prior TKI history,” commented Marlise R. Luskin, MD, a leukemia specialist at the Dana-Farber Cancer Institute in Boston.

“A critical question for this patient population is whether these two approaches [TKI and inotuzumab ozogamicin] can be administered safely in combination. I congratulate MD Anderson for completion of this Phase I trial which demonstrates that inotuzumab and bosutinib can be safely combined with identification of a maximum tolerated dose of bosutinib 400 mg daily when administered in combination. I look forward to further studies that explore the efficacy of combination versus the approved single-agent regimen,” she said in an interview.
 

Study details

To see whether they could improve the dismal outcomes for patients with Ph+ ALL or Ph+ CML in lymphoid blast phase, they studied the combination of inotuzumab ozogamicin, an anti-CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin, and bosutinib, an inhibitor of the ABL kinase. Inotuzumab is approved in the United States for treatment of adults with relapsed or refractory B-cell precursor ALL, bosutinib is approved for the treatment of patients with newly-diagnosed chronic phase Ph+ CML and for adults with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy.

The investigators enrolled 16 patients with Ph+ ALL and 2 with Ph+ CML with bone marrow blasts greater than 5%, CD22 expressed on at least 20% of blasts, and good to fair performance status. The patients also had adequate organ function as measured by liver enzyme, total bilirubin, and serum creatinine levels. Patients with the T315I mutation, prior anti-CD22 therapy, active graft-versus-host disease, or liver disease were excluded.

The patients received inotuzumab 0.8 mg/m² intravenously on day 1, they received 0.5 mg/m² on days 8 and 15 of cycle 1, and they received 0.5 mg/m² on days 1, 8, and 15 of cycles 2 through 6. Each cycle was 4 weeks. Patients who had a complete remission (CR), had complete cytogenetic remission (CCyR), or became negative for minimal residual disease (MRD) continued on 1 mg/m² every 4 weeks. Bosutinib was dosed continuously day starting on the first day of cycle 1 and continued until disease progression or toxicity.

After a median follow-up of 36.7 months, 11 of the 18 patients had CRs, and 4 had CRs with incomplete recovery of hematologic counts. In addition, 13 of 16 patients with without diploid cytogenetics at the start of the study had CCyr; 14 patients had major molecular remission; 10 had complete molecular remission, and 11 were negative by flow cytometry.

As noted before, the median overall survival was 15.4 months. Event-free survival – time to lack of response, relapse, MRD relapse requiring therapy, or death – was 8 months. The event-free survival data were not censored for allogeneic stem cell transplant. Six patients underwent transplant while in remission.

The primary objective of the phase 1 trial was to evaluate safety of the combination and determine the maximum tolerated dose of bosutinib, which was determined to be 400 mg daily. At this dose level, one patient had a dose-limiting toxicity in the form of a grade 3 skin rash.

The most frequent adverse events were diarrhea and rash, in 50% of patients each, and nausea in 39% of patients. Grade 3 adverse events included were rash in three patients and reversible alanine aminotransferase and hyponatremia in one patient each. No patients developed veno-occlusive disease, and there no deaths within 30 days of the start of therapy.

Dr. Jain disclosed consultancy, honoraria, advisory board/committee activity, and research funding from Pfizer, maker of inotuzumab ozogamicin and bosutinib. Dr. Luskin reported no relevant disclosures.

SOURCE: Jain N et al. EHA25, Abstract EP396.

Past treatment may affect the risk of death among patients with thoracic malignancies who develop COVID-19, according to data from the TERAVOLT registry.

Prior treatment with steroids, anticoagulants, chemotherapy alone, or chemotherapy plus immunotherapy were all associated with an increased risk of death, but prior treatment with tyrosine kinase inhibitors or immunotherapy alone were not.

At the same time, there were no COVID-19–directed treatments that seemed to affect the risk of death.

“When we look at therapies administered to treat COVID-19 … including anticoagulation, antibiotics, antivirals, hydroxychloroquine, we found that no particular therapy was associated with increased chance of recovery from COVID-19,” said Leora Horn, MD, of Vanderbilt-Ingram Cancer Center in Nashville, Tenn.

Dr. Horn presented these findings as part of the American Society of Clinical Oncology virtual scientific program.
 

About TERAVOLT

The TERAVOLT registry is the brainchild of Marina Garassino, MD, of the National Cancer Institute of Milan. On March 15, Dr. Garassino emailed colleagues around the world with the idea of starting the registry. Within 5 days, the final protocol was approved, and the first patient was entered onto TERAVOLT.

In creating a registry, Dr. Garassino and colleagues wanted to “determine the demographic factors, comorbidities, cancer characteristics, and therapies that place patients with thoracic malignancies who develop COVID-19 most at risk for hospitalization and death,” Dr. Horn said.

Other goals of the registry are “to understand the clinical course of patients with thoracic malignancies who are infected by SARS-CoV-2, to provide practitioners with real-time data on therapeutic strategies that may impact survival, [and] to evaluate the long-term impact on cancer outcomes related to care adjustments and delays in patients with thoracic malignancies,” she added.

Dr. Garassino presented the first analysis of TERAVOLT data at the AACR virtual meeting I in April. Results were recently published in The Lancet Oncology as well. That analysis included 200 patients, 98% of whom were from Europe, and the median follow-up was 15 days.

Baseline characteristics and outcomes

Dr. Horn’s updated analysis included 400 patients with a median follow-up of 33 days from COVID-19 diagnosis. The data encompassed patients from North and South America, Europe, Africa, Asia, and Australia.

Of the 400 patients, 169 had recovered, 141 had died, and 118 were still in the hospital at the time of analysis. In all, 334 patients (78.3%) required a hospital admission, and 33 (8.3%) were admitted to the ICU. The median length of hospitalization was 10 days.

Across the three outcome groups (recovered, died, ongoing), the median age was 67-70 years. Most patients had non–small cell lung cancer (74.5%-81.9%), and most had stage IV disease (61.4%-76.8%).

A majority of patients were male (63.3%-70.2%), and most were current or former smokers (77.5%-86.9%). The median body mass index was 24-25 kg/m², and 35%-46.4% of patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0.

Most patients (82.2%-90.7%) had COVID-19 diagnosed via real-time polymerase chain reaction, although some patients were diagnosed via clinical findings alone (3.1%-5%).

“[R]egardless of outcome, the most common presenting symptom was fever, cough, or dyspnea,” Dr. Horn noted.

As for complications of COVID-19, 71% of patients who died had pneumonitis/pneumonia, 49.6% had acute respiratory distress syndrome, 14.9% had multiorgan failure, 12.1% had sepsis, and 5.7% had coagulopathy.

Among recovered patients, 59% had pneumonitis/pneumonia, 4.1% had acute respiratory distress syndrome, 3% had coagulopathy, 0.6% had sepsis, and none had multiorgan failure.

Patients who recovered were more likely to have no comorbidities at baseline, and 31.2% of patients who died had at least one comorbidity. The most frequent comorbidities were hypertension, chronic obstructive pulmonary disease, vascular disease, diabetes, and renal insufficiencies.
 

Prior treatments and COVID therapy

Among patients who died, 33.4% were on ACE inhibitors or angiotensin II receptor blockers, 27% were on anticoagulants, and 23.4% were on steroids (the equivalent of at least 10 mg of prednisone per day) at the time of COVID-19 diagnosis.

Among recovered patients, 20.7% were on ACE inhibitors or angiotensin II receptor blockers, 18.3% were on anticoagulants, and 14.2% were on steroids at the time of COVID-19 diagnosis.

“When we look at cancer therapy in the last 3 months, we can see that, regardless of outcome, the majority of patients had either not been treated or were on first-line therapy at the time of their COVID-19 diagnosis,” Dr. Horn noted.

Among patients who died, 46.8% had received chemotherapy, 22% had received immunotherapy, 12.8% had received targeted therapy, and 9.2% had received radiotherapy.

Among recovered patients, 33.7% had received chemotherapy, 26.6% had received immunotherapy, 19.5% had received targeted therapy, and 14.2% had received radiotherapy.

COVID-19–directed treatments included anticoagulation, antibiotics, antivirals, antifungals, steroids, interleukin-6 inhibitors, and hydroxychloroquine. Use of these therapies was similar among patients who recovered and patients who died.
 

Factors associated with death

In all, 79.4% of deaths were attributed to COVID-19, 10.6% were attributed to cancer, 8.5% were attributed to cancer and COVID-19, and 1.4% of deaths had an unknown cause.

In a univariate analysis, baseline characteristics associated with an increased risk of death were age of 65 years or older (P = .0033), one or more comorbidity (P = .0351), and ECOG performance status of 1 (P < .0001). Therapies associated with an increased risk of death in a univariate analysis included steroids (P = .0186), anticoagulation (P = .0562), and either chemotherapy alone or chemotherapy plus immunotherapy (P = .0256).

In a multivariate analysis, age over 65 years (P = .018), ECOG performance status of 1 (P < .001), prior use of steroids (P = .052), and receipt of chemotherapy alone or in combination with immunotherapy (P = .025) were all associated with an increased risk of death.

“There is no impact of gender [sex], body mass index, smoking status, stage, or type of cancer on risk of death,” Dr. Horn said. “Therapy administered to treat COVID-19 is not significantly associated with outcome.”

“The impact of COVID-19 infection on cancer management and outcomes must be evaluated,” she added. “Data collection is ongoing, with additional analysis and studies planned to look at patient and provider perception of COVID-19 and the impact it has had on cancer care.”

Strengths and limitations

There are several limitations to findings from the TERAVOLT registry, according to invited discussant Giuseppe Curigliano, MD, PhD, of the University of Milan.

He said the results are limited by the differences in triage decisions between European and other centers, the fact that most patients in TERAVOLT were hospitalized, the high proportion of patients with stage IV non–small cell lung cancer, and methods of data collection and analysis.

“There is no real-time data capture, no auditing, no standardized outcome definitions, and CRFs [case report forms] had a lot of limitations,” Dr. Curigliano said. “We have multiple biases, including selection bias, recall bias, confounding by indication, and changes in practice or disease evolution.”

Dr. Curigliano noted, however, that TERAVOLT is the largest real-world dataset of patients with COVID-19 and thoracic malignancies.

Furthermore, results from TERAVOLT correspond to results from the CCC-19 registry. Data from both registries suggest that older age, the presence of comorbidities, higher ECOG performances status, and chemotherapy alone or in combination with other therapies are associated with increased mortality among patients with cancer and COVID-19.

The TERAVOLT registry is funded, in part, by the International Association for the Study of Lung Cancer. Dr. Horn disclosed relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, and other pharmaceutical companies. Dr. Curigliano disclosed relationships with AstraZeneca, Boehringer Ingelheim, Ellipses Pharma, and other pharmaceutical companies.
 

[email protected]

SOURCE: Horn L et al. ASCO 2020, Abstract LBA111.

Past treatment may affect the risk of death among patients with thoracic malignancies who develop COVID-19, according to data from the TERAVOLT registry.

Prior treatment with steroids, anticoagulants, chemotherapy alone, or chemotherapy plus immunotherapy were all associated with an increased risk of death, but prior treatment with tyrosine kinase inhibitors or immunotherapy alone were not.

At the same time, there were no COVID-19–directed treatments that seemed to affect the risk of death.

“When we look at therapies administered to treat COVID-19 … including anticoagulation, antibiotics, antivirals, hydroxychloroquine, we found that no particular therapy was associated with increased chance of recovery from COVID-19,” said Leora Horn, MD, of Vanderbilt-Ingram Cancer Center in Nashville, Tenn.

Dr. Horn presented these findings as part of the American Society of Clinical Oncology virtual scientific program.
 

About TERAVOLT

The TERAVOLT registry is the brainchild of Marina Garassino, MD, of the National Cancer Institute of Milan. On March 15, Dr. Garassino emailed colleagues around the world with the idea of starting the registry. Within 5 days, the final protocol was approved, and the first patient was entered onto TERAVOLT.

In creating a registry, Dr. Garassino and colleagues wanted to “determine the demographic factors, comorbidities, cancer characteristics, and therapies that place patients with thoracic malignancies who develop COVID-19 most at risk for hospitalization and death,” Dr. Horn said.

Other goals of the registry are “to understand the clinical course of patients with thoracic malignancies who are infected by SARS-CoV-2, to provide practitioners with real-time data on therapeutic strategies that may impact survival, [and] to evaluate the long-term impact on cancer outcomes related to care adjustments and delays in patients with thoracic malignancies,” she added.

Dr. Garassino presented the first analysis of TERAVOLT data at the AACR virtual meeting I in April. Results were recently published in The Lancet Oncology as well. That analysis included 200 patients, 98% of whom were from Europe, and the median follow-up was 15 days.

Baseline characteristics and outcomes

Dr. Horn’s updated analysis included 400 patients with a median follow-up of 33 days from COVID-19 diagnosis. The data encompassed patients from North and South America, Europe, Africa, Asia, and Australia.

Of the 400 patients, 169 had recovered, 141 had died, and 118 were still in the hospital at the time of analysis. In all, 334 patients (78.3%) required a hospital admission, and 33 (8.3%) were admitted to the ICU. The median length of hospitalization was 10 days.

Across the three outcome groups (recovered, died, ongoing), the median age was 67-70 years. Most patients had non–small cell lung cancer (74.5%-81.9%), and most had stage IV disease (61.4%-76.8%).

A majority of patients were male (63.3%-70.2%), and most were current or former smokers (77.5%-86.9%). The median body mass index was 24-25 kg/m², and 35%-46.4% of patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0.

Most patients (82.2%-90.7%) had COVID-19 diagnosed via real-time polymerase chain reaction, although some patients were diagnosed via clinical findings alone (3.1%-5%).

“[R]egardless of outcome, the most common presenting symptom was fever, cough, or dyspnea,” Dr. Horn noted.

As for complications of COVID-19, 71% of patients who died had pneumonitis/pneumonia, 49.6% had acute respiratory distress syndrome, 14.9% had multiorgan failure, 12.1% had sepsis, and 5.7% had coagulopathy.

Among recovered patients, 59% had pneumonitis/pneumonia, 4.1% had acute respiratory distress syndrome, 3% had coagulopathy, 0.6% had sepsis, and none had multiorgan failure.

Patients who recovered were more likely to have no comorbidities at baseline, and 31.2% of patients who died had at least one comorbidity. The most frequent comorbidities were hypertension, chronic obstructive pulmonary disease, vascular disease, diabetes, and renal insufficiencies.
 

Prior treatments and COVID therapy

Among patients who died, 33.4% were on ACE inhibitors or angiotensin II receptor blockers, 27% were on anticoagulants, and 23.4% were on steroids (the equivalent of at least 10 mg of prednisone per day) at the time of COVID-19 diagnosis.

Among recovered patients, 20.7% were on ACE inhibitors or angiotensin II receptor blockers, 18.3% were on anticoagulants, and 14.2% were on steroids at the time of COVID-19 diagnosis.

“When we look at cancer therapy in the last 3 months, we can see that, regardless of outcome, the majority of patients had either not been treated or were on first-line therapy at the time of their COVID-19 diagnosis,” Dr. Horn noted.

Among patients who died, 46.8% had received chemotherapy, 22% had received immunotherapy, 12.8% had received targeted therapy, and 9.2% had received radiotherapy.

Among recovered patients, 33.7% had received chemotherapy, 26.6% had received immunotherapy, 19.5% had received targeted therapy, and 14.2% had received radiotherapy.

COVID-19–directed treatments included anticoagulation, antibiotics, antivirals, antifungals, steroids, interleukin-6 inhibitors, and hydroxychloroquine. Use of these therapies was similar among patients who recovered and patients who died.
 

Factors associated with death

In all, 79.4% of deaths were attributed to COVID-19, 10.6% were attributed to cancer, 8.5% were attributed to cancer and COVID-19, and 1.4% of deaths had an unknown cause.

In a univariate analysis, baseline characteristics associated with an increased risk of death were age of 65 years or older (P = .0033), one or more comorbidity (P = .0351), and ECOG performance status of 1 (P < .0001). Therapies associated with an increased risk of death in a univariate analysis included steroids (P = .0186), anticoagulation (P = .0562), and either chemotherapy alone or chemotherapy plus immunotherapy (P = .0256).

In a multivariate analysis, age over 65 years (P = .018), ECOG performance status of 1 (P < .001), prior use of steroids (P = .052), and receipt of chemotherapy alone or in combination with immunotherapy (P = .025) were all associated with an increased risk of death.

“There is no impact of gender [sex], body mass index, smoking status, stage, or type of cancer on risk of death,” Dr. Horn said. “Therapy administered to treat COVID-19 is not significantly associated with outcome.”

“The impact of COVID-19 infection on cancer management and outcomes must be evaluated,” she added. “Data collection is ongoing, with additional analysis and studies planned to look at patient and provider perception of COVID-19 and the impact it has had on cancer care.”

Strengths and limitations

There are several limitations to findings from the TERAVOLT registry, according to invited discussant Giuseppe Curigliano, MD, PhD, of the University of Milan.

He said the results are limited by the differences in triage decisions between European and other centers, the fact that most patients in TERAVOLT were hospitalized, the high proportion of patients with stage IV non–small cell lung cancer, and methods of data collection and analysis.

“There is no real-time data capture, no auditing, no standardized outcome definitions, and CRFs [case report forms] had a lot of limitations,” Dr. Curigliano said. “We have multiple biases, including selection bias, recall bias, confounding by indication, and changes in practice or disease evolution.”

Dr. Curigliano noted, however, that TERAVOLT is the largest real-world dataset of patients with COVID-19 and thoracic malignancies.

Furthermore, results from TERAVOLT correspond to results from the CCC-19 registry. Data from both registries suggest that older age, the presence of comorbidities, higher ECOG performances status, and chemotherapy alone or in combination with other therapies are associated with increased mortality among patients with cancer and COVID-19.

The TERAVOLT registry is funded, in part, by the International Association for the Study of Lung Cancer. Dr. Horn disclosed relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, and other pharmaceutical companies. Dr. Curigliano disclosed relationships with AstraZeneca, Boehringer Ingelheim, Ellipses Pharma, and other pharmaceutical companies.
 

[email protected]

SOURCE: Horn L et al. ASCO 2020, Abstract LBA111.

Past treatment may affect the risk of death among patients with thoracic malignancies who develop COVID-19, according to data from the TERAVOLT registry.

Prior treatment with steroids, anticoagulants, chemotherapy alone, or chemotherapy plus immunotherapy were all associated with an increased risk of death, but prior treatment with tyrosine kinase inhibitors or immunotherapy alone were not.

At the same time, there were no COVID-19–directed treatments that seemed to affect the risk of death.

“When we look at therapies administered to treat COVID-19 … including anticoagulation, antibiotics, antivirals, hydroxychloroquine, we found that no particular therapy was associated with increased chance of recovery from COVID-19,” said Leora Horn, MD, of Vanderbilt-Ingram Cancer Center in Nashville, Tenn.

Dr. Horn presented these findings as part of the American Society of Clinical Oncology virtual scientific program.
 

About TERAVOLT

The TERAVOLT registry is the brainchild of Marina Garassino, MD, of the National Cancer Institute of Milan. On March 15, Dr. Garassino emailed colleagues around the world with the idea of starting the registry. Within 5 days, the final protocol was approved, and the first patient was entered onto TERAVOLT.

In creating a registry, Dr. Garassino and colleagues wanted to “determine the demographic factors, comorbidities, cancer characteristics, and therapies that place patients with thoracic malignancies who develop COVID-19 most at risk for hospitalization and death,” Dr. Horn said.

Other goals of the registry are “to understand the clinical course of patients with thoracic malignancies who are infected by SARS-CoV-2, to provide practitioners with real-time data on therapeutic strategies that may impact survival, [and] to evaluate the long-term impact on cancer outcomes related to care adjustments and delays in patients with thoracic malignancies,” she added.

Dr. Garassino presented the first analysis of TERAVOLT data at the AACR virtual meeting I in April. Results were recently published in The Lancet Oncology as well. That analysis included 200 patients, 98% of whom were from Europe, and the median follow-up was 15 days.

Baseline characteristics and outcomes

Dr. Horn’s updated analysis included 400 patients with a median follow-up of 33 days from COVID-19 diagnosis. The data encompassed patients from North and South America, Europe, Africa, Asia, and Australia.

Of the 400 patients, 169 had recovered, 141 had died, and 118 were still in the hospital at the time of analysis. In all, 334 patients (78.3%) required a hospital admission, and 33 (8.3%) were admitted to the ICU. The median length of hospitalization was 10 days.

Across the three outcome groups (recovered, died, ongoing), the median age was 67-70 years. Most patients had non–small cell lung cancer (74.5%-81.9%), and most had stage IV disease (61.4%-76.8%).

A majority of patients were male (63.3%-70.2%), and most were current or former smokers (77.5%-86.9%). The median body mass index was 24-25 kg/m², and 35%-46.4% of patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0.

Most patients (82.2%-90.7%) had COVID-19 diagnosed via real-time polymerase chain reaction, although some patients were diagnosed via clinical findings alone (3.1%-5%).

“[R]egardless of outcome, the most common presenting symptom was fever, cough, or dyspnea,” Dr. Horn noted.

As for complications of COVID-19, 71% of patients who died had pneumonitis/pneumonia, 49.6% had acute respiratory distress syndrome, 14.9% had multiorgan failure, 12.1% had sepsis, and 5.7% had coagulopathy.

Among recovered patients, 59% had pneumonitis/pneumonia, 4.1% had acute respiratory distress syndrome, 3% had coagulopathy, 0.6% had sepsis, and none had multiorgan failure.

Patients who recovered were more likely to have no comorbidities at baseline, and 31.2% of patients who died had at least one comorbidity. The most frequent comorbidities were hypertension, chronic obstructive pulmonary disease, vascular disease, diabetes, and renal insufficiencies.
 

Prior treatments and COVID therapy

Among patients who died, 33.4% were on ACE inhibitors or angiotensin II receptor blockers, 27% were on anticoagulants, and 23.4% were on steroids (the equivalent of at least 10 mg of prednisone per day) at the time of COVID-19 diagnosis.

Among recovered patients, 20.7% were on ACE inhibitors or angiotensin II receptor blockers, 18.3% were on anticoagulants, and 14.2% were on steroids at the time of COVID-19 diagnosis.

“When we look at cancer therapy in the last 3 months, we can see that, regardless of outcome, the majority of patients had either not been treated or were on first-line therapy at the time of their COVID-19 diagnosis,” Dr. Horn noted.

Among patients who died, 46.8% had received chemotherapy, 22% had received immunotherapy, 12.8% had received targeted therapy, and 9.2% had received radiotherapy.

Among recovered patients, 33.7% had received chemotherapy, 26.6% had received immunotherapy, 19.5% had received targeted therapy, and 14.2% had received radiotherapy.

COVID-19–directed treatments included anticoagulation, antibiotics, antivirals, antifungals, steroids, interleukin-6 inhibitors, and hydroxychloroquine. Use of these therapies was similar among patients who recovered and patients who died.
 

Factors associated with death

In all, 79.4% of deaths were attributed to COVID-19, 10.6% were attributed to cancer, 8.5% were attributed to cancer and COVID-19, and 1.4% of deaths had an unknown cause.

In a univariate analysis, baseline characteristics associated with an increased risk of death were age of 65 years or older (P = .0033), one or more comorbidity (P = .0351), and ECOG performance status of 1 (P < .0001). Therapies associated with an increased risk of death in a univariate analysis included steroids (P = .0186), anticoagulation (P = .0562), and either chemotherapy alone or chemotherapy plus immunotherapy (P = .0256).

In a multivariate analysis, age over 65 years (P = .018), ECOG performance status of 1 (P < .001), prior use of steroids (P = .052), and receipt of chemotherapy alone or in combination with immunotherapy (P = .025) were all associated with an increased risk of death.

“There is no impact of gender [sex], body mass index, smoking status, stage, or type of cancer on risk of death,” Dr. Horn said. “Therapy administered to treat COVID-19 is not significantly associated with outcome.”

“The impact of COVID-19 infection on cancer management and outcomes must be evaluated,” she added. “Data collection is ongoing, with additional analysis and studies planned to look at patient and provider perception of COVID-19 and the impact it has had on cancer care.”

Strengths and limitations

There are several limitations to findings from the TERAVOLT registry, according to invited discussant Giuseppe Curigliano, MD, PhD, of the University of Milan.

He said the results are limited by the differences in triage decisions between European and other centers, the fact that most patients in TERAVOLT were hospitalized, the high proportion of patients with stage IV non–small cell lung cancer, and methods of data collection and analysis.

“There is no real-time data capture, no auditing, no standardized outcome definitions, and CRFs [case report forms] had a lot of limitations,” Dr. Curigliano said. “We have multiple biases, including selection bias, recall bias, confounding by indication, and changes in practice or disease evolution.”

Dr. Curigliano noted, however, that TERAVOLT is the largest real-world dataset of patients with COVID-19 and thoracic malignancies.

Furthermore, results from TERAVOLT correspond to results from the CCC-19 registry. Data from both registries suggest that older age, the presence of comorbidities, higher ECOG performances status, and chemotherapy alone or in combination with other therapies are associated with increased mortality among patients with cancer and COVID-19.

The TERAVOLT registry is funded, in part, by the International Association for the Study of Lung Cancer. Dr. Horn disclosed relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, and other pharmaceutical companies. Dr. Curigliano disclosed relationships with AstraZeneca, Boehringer Ingelheim, Ellipses Pharma, and other pharmaceutical companies.
 

[email protected]

SOURCE: Horn L et al. ASCO 2020, Abstract LBA111.

Bariatric surgery may yield increases in muscle mass from baseline among older adults, findings from a small study suggest.

Although bariatric surgery can be used to treat obesity and related comorbidities in older adults, “here are concerns of excess loss of muscle mass after bariatric surgery, especially in elderly patients whose muscle tends to be less, compared to younger patients, at baseline,” wrote Moiz Dawood, MD, of Banner Gateway Medical Center, Gilbert, Ariz., and colleagues.

In a study presented in a poster at the virtual Annual Minimally Invasive Surgery Symposium sponsored by Global Academy for Medical Education, the researchers reviewed data from 89 adults older than 65 years (74% women) who underwent either laparoscopic sleeve gastrectomy (87 patients) or Roux-en-Y gastric bypass (2 patients) between May 2015 and March 2017.

At baseline, the average total body weight was 251 pounds and the average muscle mass percent was 50%. At 12 months after surgery, the average weight of the patients decreased to 197 pounds and the percentage of muscle mass increased to 55% (P < .001 for both).

The study findings were limited by the small sample size and retrospective design. However, the results support the benefits of bariatric surgery for older adults, not only with reductions in total body weight loss, but also increasing the total percentage of muscle mass, the researchers said.

The study is important in light of the ongoing discussion regarding the age limit for bariatric surgery, Dr. Dawood said in an interview. “Currently there is no upper age cutoff for patients who undergo bariatric surgery, and understanding the relationship between muscle mass and bariatric surgery would help in determining if there was a negative relationship,” he said.

“The results definitely point toward evidence that suggests that elderly patients do not lose muscle mass to a significant degree,” Dr. Dawood noted. “Muscle mass definitions and calculations also include variables such as weight and fat content. With the additional loss in weight after surgery, it was expected that the muscle mass composition would be affected,” he explained. “However, the results clearly show that even up to 1 year after surgery, older patients who lose weight do not lose significant weight from their muscle mass,” he noted.

The take-home message for clinicians, said Dr. Dawood, is “to understand that metabolic and bariatric surgery, when performed cohesively in a unified program that focuses on lifestyle and dietary changes, is the best way to achieve sustained weight loss.” He added, “this study indicates that physiologic changes that occur after weight loss surgery are not detrimental in the elderly population.”

Next steps for research include further studies in the elderly population to examine the physiologic changes that occur after weight loss surgery, said Dr. Dawood. “Being able to characterize the metabolic changes will help in answering the question of whether there is an upper age cut-off for patients undergoing bariatric surgery.”

Global Academy for Medical Education and this news organization are owned by the same parent company. The researchers had no relevant financial conflicts to disclose.

Bariatric surgery may yield increases in muscle mass from baseline among older adults, findings from a small study suggest.

Although bariatric surgery can be used to treat obesity and related comorbidities in older adults, “here are concerns of excess loss of muscle mass after bariatric surgery, especially in elderly patients whose muscle tends to be less, compared to younger patients, at baseline,” wrote Moiz Dawood, MD, of Banner Gateway Medical Center, Gilbert, Ariz., and colleagues.

In a study presented in a poster at the virtual Annual Minimally Invasive Surgery Symposium sponsored by Global Academy for Medical Education, the researchers reviewed data from 89 adults older than 65 years (74% women) who underwent either laparoscopic sleeve gastrectomy (87 patients) or Roux-en-Y gastric bypass (2 patients) between May 2015 and March 2017.

At baseline, the average total body weight was 251 pounds and the average muscle mass percent was 50%. At 12 months after surgery, the average weight of the patients decreased to 197 pounds and the percentage of muscle mass increased to 55% (P < .001 for both).

The study findings were limited by the small sample size and retrospective design. However, the results support the benefits of bariatric surgery for older adults, not only with reductions in total body weight loss, but also increasing the total percentage of muscle mass, the researchers said.

The study is important in light of the ongoing discussion regarding the age limit for bariatric surgery, Dr. Dawood said in an interview. “Currently there is no upper age cutoff for patients who undergo bariatric surgery, and understanding the relationship between muscle mass and bariatric surgery would help in determining if there was a negative relationship,” he said.

“The results definitely point toward evidence that suggests that elderly patients do not lose muscle mass to a significant degree,” Dr. Dawood noted. “Muscle mass definitions and calculations also include variables such as weight and fat content. With the additional loss in weight after surgery, it was expected that the muscle mass composition would be affected,” he explained. “However, the results clearly show that even up to 1 year after surgery, older patients who lose weight do not lose significant weight from their muscle mass,” he noted.

The take-home message for clinicians, said Dr. Dawood, is “to understand that metabolic and bariatric surgery, when performed cohesively in a unified program that focuses on lifestyle and dietary changes, is the best way to achieve sustained weight loss.” He added, “this study indicates that physiologic changes that occur after weight loss surgery are not detrimental in the elderly population.”

Next steps for research include further studies in the elderly population to examine the physiologic changes that occur after weight loss surgery, said Dr. Dawood. “Being able to characterize the metabolic changes will help in answering the question of whether there is an upper age cut-off for patients undergoing bariatric surgery.”

Global Academy for Medical Education and this news organization are owned by the same parent company. The researchers had no relevant financial conflicts to disclose.

Bariatric surgery may yield increases in muscle mass from baseline among older adults, findings from a small study suggest.

Although bariatric surgery can be used to treat obesity and related comorbidities in older adults, “here are concerns of excess loss of muscle mass after bariatric surgery, especially in elderly patients whose muscle tends to be less, compared to younger patients, at baseline,” wrote Moiz Dawood, MD, of Banner Gateway Medical Center, Gilbert, Ariz., and colleagues.

In a study presented in a poster at the virtual Annual Minimally Invasive Surgery Symposium sponsored by Global Academy for Medical Education, the researchers reviewed data from 89 adults older than 65 years (74% women) who underwent either laparoscopic sleeve gastrectomy (87 patients) or Roux-en-Y gastric bypass (2 patients) between May 2015 and March 2017.

At baseline, the average total body weight was 251 pounds and the average muscle mass percent was 50%. At 12 months after surgery, the average weight of the patients decreased to 197 pounds and the percentage of muscle mass increased to 55% (P < .001 for both).

The study findings were limited by the small sample size and retrospective design. However, the results support the benefits of bariatric surgery for older adults, not only with reductions in total body weight loss, but also increasing the total percentage of muscle mass, the researchers said.

The study is important in light of the ongoing discussion regarding the age limit for bariatric surgery, Dr. Dawood said in an interview. “Currently there is no upper age cutoff for patients who undergo bariatric surgery, and understanding the relationship between muscle mass and bariatric surgery would help in determining if there was a negative relationship,” he said.

“The results definitely point toward evidence that suggests that elderly patients do not lose muscle mass to a significant degree,” Dr. Dawood noted. “Muscle mass definitions and calculations also include variables such as weight and fat content. With the additional loss in weight after surgery, it was expected that the muscle mass composition would be affected,” he explained. “However, the results clearly show that even up to 1 year after surgery, older patients who lose weight do not lose significant weight from their muscle mass,” he noted.

The take-home message for clinicians, said Dr. Dawood, is “to understand that metabolic and bariatric surgery, when performed cohesively in a unified program that focuses on lifestyle and dietary changes, is the best way to achieve sustained weight loss.” He added, “this study indicates that physiologic changes that occur after weight loss surgery are not detrimental in the elderly population.”

Next steps for research include further studies in the elderly population to examine the physiologic changes that occur after weight loss surgery, said Dr. Dawood. “Being able to characterize the metabolic changes will help in answering the question of whether there is an upper age cut-off for patients undergoing bariatric surgery.”

Global Academy for Medical Education and this news organization are owned by the same parent company. The researchers had no relevant financial conflicts to disclose.

The first validated classification criteria for discoid lupus erythematosus has a sensitivity that ranges between 73.9% and 84.1% and a specificity that ranges between 75.9% and 92.9%.

M. Alexander Otto/MDedge News

“Discoid lupus erythematosus [DLE] is the most common type of chronic cutaneous lupus,” lead study author Scott A. Elman, MD, said during the virtual annual meeting of the American Academy of Dermatology. “It’s one of the most potentially disfiguring forms of cutaneous lupus erythematosus [CLE], which can lead to scarring, hair loss, and dyspigmentation if not treated early or promptly. It has a significant impact on patient quality of life and there are currently no classification criteria for DLE, which has led to problematic heterogeneity in observational and interventional research efforts. As there is increasing interest in drug development programs for CLE and DLE, there is a need to develop classification criteria.”

Dr. Elman, of the Harvard combined medicine-dermatology training program at Brigham and Women’s Hospital, Boston, pointed out that classification criteria are the standard definitions that are primarily intended to enroll uniform cohorts for research. “These emphasize high specificity, whereas diagnostic criteria reflect a more broad and variable set of features of a given disease, and therefore require a higher sensitivity,” he explained. “While classification criteria are not synonymous with diagnostic criteria, they typically mirror the list of criteria that are used for diagnosis.”

In 2017, Dr. Elman and colleagues generated an item list of 12 potential classification criteria using an international Delphi consensus process: 5 criteria represented disease morphology, 2 represented discoid lupus location, and 5 represented histopathology (J Am Acad Dermatol. 2017 Aug 1;77[2]:261-7). The purpose of the current study, which was presented as a late-breaking abstract, was to validate the proposed classification criteria in a multicenter, international trial. “The point is to be able to differentiate between discoid lupus and its disease mimickers, which could be confused in enrollment in clinical trials,” he said.

At nine participating sites, patients were identified at clinical visits as having either DLE or a DLE mimicker. After each visit, dermatologists determined if morphological features were present. One dermatopathologist at each site reviewed pathology, if available, to see if the histopathologic features were present. Diagnosis by clinical features and dermatopathology were tabulated and presented as counts and percentages. Clinical features among those with and without DLE were calculated and compared with chi-square or Fisher’s exact tests. The researchers used best subsets logistic regression analysis to identify candidate models.

A total of 215 patients were enrolled: 94 that were consistent with DLE and 121 that were consistent with a DLE mimicker. Most cases (83%) were from North America, 11% were from Asia, and 6% were from Europe. Only 86 cases (40%) had biopsies for dermatopathology review.

The following clinical features were found to be more commonly associated with DLE, compared with DLE mimickers: atrophic scarring (83% vs. 24%; P < .001), dyspigmentation (84% vs. 55%; P < .001), follicular hyperkeratosis/plugging (43% vs. 11%; P < .001), scarring alopecia (61% vs. 21%; P < .001), location in the conchal bowl (49% vs. 10%; P < .001), preference for the head and neck (87% vs. 49%; P < .001), and erythematous to violaceous in color (93% vs. 85%, a nonsignificant difference; P = .09).

When histopathological items were assessed, the following features were found to be more commonly associated with DLE, compared with DLE mimickers: interface/vacuolar dermatitis (83% vs. 53%; P = .004), perivascular and/or periappendageal lymphohistiocytic infiltrate (95% vs. 84%, a nonsignificant difference; P = .18), follicular keratin plugs (57% vs. 20%; P < .001), mucin deposition (73% vs. 39%; P = .002), and basement membrane thickening (57% vs. 14%; P < .001).

“There was good agreement between the diagnoses made by dermatologists and dermatopathologists, with a Cohen’s kappa statistic of 0.83,” Dr. Elman added. “Similarly, in many of the cases, the dermatopathologists and the dermatologists felt confident in their diagnosis.”

For the final model, the researchers excluded patients who had any missing data as well as those who had a diagnosis that was uncertain. This left 200 cases in the final model. Clinical variables associated with DLE were: atrophic scarring (odds ratio, 8.70; P < .001), location in the conchal bowl (OR, 6.80; P < .001), preference for head and neck (OR, 9.41; P < .001), dyspigmentation (OR, 3.23; P = .020), follicular hyperkeratosis/plugging (OR, 2.94; P = .054), and erythematous to violaceous in color (OR, 3.44; P = .056). The area under the curve for the model was 0.91.

According to Dr. Elman, the final model is a points-based model with 3 points assigned to atrophic scarring, 2 points assigned to location in the conchal bowl, 2 points assigned to preference for head and neck, 1 point assigned to dyspigmentation, 1 point assigned to follicular hyperkeratosis/plugging, and 1 point assigned to erythematous to violaceous in color. A score of 5 or greater yields a classification as DLE with 84.1% sensitivity and 75.9% specificity, while a score of 7 or greater yields a 73.9% sensitivity and 92.9% specificity.

Dr. Elman acknowledged certain limitations of the study, including the fact that information related to histopathology was not included in the final model. “This was a result of having only 40% of cases with relevant dermatopathology,” he said. “This limited our ability to meaningfully incorporate these items into a classification criteria set. However, with the data we’ve collected, efforts are under way to make a DLE-specific histopathology classification criteria.”

Another limitation is that the researchers relied on expert diagnosis as the preferred option. “Similarly, many of the cases came from large referral centers, and no demographic data were obtained, so this limits the generalizability of our study,” he said.

Dr. Elman reported having no financial disclosures.

[email protected]

The first validated classification criteria for discoid lupus erythematosus has a sensitivity that ranges between 73.9% and 84.1% and a specificity that ranges between 75.9% and 92.9%.

M. Alexander Otto/MDedge News

“Discoid lupus erythematosus [DLE] is the most common type of chronic cutaneous lupus,” lead study author Scott A. Elman, MD, said during the virtual annual meeting of the American Academy of Dermatology. “It’s one of the most potentially disfiguring forms of cutaneous lupus erythematosus [CLE], which can lead to scarring, hair loss, and dyspigmentation if not treated early or promptly. It has a significant impact on patient quality of life and there are currently no classification criteria for DLE, which has led to problematic heterogeneity in observational and interventional research efforts. As there is increasing interest in drug development programs for CLE and DLE, there is a need to develop classification criteria.”

Dr. Elman, of the Harvard combined medicine-dermatology training program at Brigham and Women’s Hospital, Boston, pointed out that classification criteria are the standard definitions that are primarily intended to enroll uniform cohorts for research. “These emphasize high specificity, whereas diagnostic criteria reflect a more broad and variable set of features of a given disease, and therefore require a higher sensitivity,” he explained. “While classification criteria are not synonymous with diagnostic criteria, they typically mirror the list of criteria that are used for diagnosis.”

In 2017, Dr. Elman and colleagues generated an item list of 12 potential classification criteria using an international Delphi consensus process: 5 criteria represented disease morphology, 2 represented discoid lupus location, and 5 represented histopathology (J Am Acad Dermatol. 2017 Aug 1;77[2]:261-7). The purpose of the current study, which was presented as a late-breaking abstract, was to validate the proposed classification criteria in a multicenter, international trial. “The point is to be able to differentiate between discoid lupus and its disease mimickers, which could be confused in enrollment in clinical trials,” he said.

At nine participating sites, patients were identified at clinical visits as having either DLE or a DLE mimicker. After each visit, dermatologists determined if morphological features were present. One dermatopathologist at each site reviewed pathology, if available, to see if the histopathologic features were present. Diagnosis by clinical features and dermatopathology were tabulated and presented as counts and percentages. Clinical features among those with and without DLE were calculated and compared with chi-square or Fisher’s exact tests. The researchers used best subsets logistic regression analysis to identify candidate models.

A total of 215 patients were enrolled: 94 that were consistent with DLE and 121 that were consistent with a DLE mimicker. Most cases (83%) were from North America, 11% were from Asia, and 6% were from Europe. Only 86 cases (40%) had biopsies for dermatopathology review.

The following clinical features were found to be more commonly associated with DLE, compared with DLE mimickers: atrophic scarring (83% vs. 24%; P < .001), dyspigmentation (84% vs. 55%; P < .001), follicular hyperkeratosis/plugging (43% vs. 11%; P < .001), scarring alopecia (61% vs. 21%; P < .001), location in the conchal bowl (49% vs. 10%; P < .001), preference for the head and neck (87% vs. 49%; P < .001), and erythematous to violaceous in color (93% vs. 85%, a nonsignificant difference; P = .09).

When histopathological items were assessed, the following features were found to be more commonly associated with DLE, compared with DLE mimickers: interface/vacuolar dermatitis (83% vs. 53%; P = .004), perivascular and/or periappendageal lymphohistiocytic infiltrate (95% vs. 84%, a nonsignificant difference; P = .18), follicular keratin plugs (57% vs. 20%; P < .001), mucin deposition (73% vs. 39%; P = .002), and basement membrane thickening (57% vs. 14%; P < .001).

“There was good agreement between the diagnoses made by dermatologists and dermatopathologists, with a Cohen’s kappa statistic of 0.83,” Dr. Elman added. “Similarly, in many of the cases, the dermatopathologists and the dermatologists felt confident in their diagnosis.”

For the final model, the researchers excluded patients who had any missing data as well as those who had a diagnosis that was uncertain. This left 200 cases in the final model. Clinical variables associated with DLE were: atrophic scarring (odds ratio, 8.70; P < .001), location in the conchal bowl (OR, 6.80; P < .001), preference for head and neck (OR, 9.41; P < .001), dyspigmentation (OR, 3.23; P = .020), follicular hyperkeratosis/plugging (OR, 2.94; P = .054), and erythematous to violaceous in color (OR, 3.44; P = .056). The area under the curve for the model was 0.91.

According to Dr. Elman, the final model is a points-based model with 3 points assigned to atrophic scarring, 2 points assigned to location in the conchal bowl, 2 points assigned to preference for head and neck, 1 point assigned to dyspigmentation, 1 point assigned to follicular hyperkeratosis/plugging, and 1 point assigned to erythematous to violaceous in color. A score of 5 or greater yields a classification as DLE with 84.1% sensitivity and 75.9% specificity, while a score of 7 or greater yields a 73.9% sensitivity and 92.9% specificity.

Dr. Elman acknowledged certain limitations of the study, including the fact that information related to histopathology was not included in the final model. “This was a result of having only 40% of cases with relevant dermatopathology,” he said. “This limited our ability to meaningfully incorporate these items into a classification criteria set. However, with the data we’ve collected, efforts are under way to make a DLE-specific histopathology classification criteria.”

Another limitation is that the researchers relied on expert diagnosis as the preferred option. “Similarly, many of the cases came from large referral centers, and no demographic data were obtained, so this limits the generalizability of our study,” he said.

Dr. Elman reported having no financial disclosures.

[email protected]

The first validated classification criteria for discoid lupus erythematosus has a sensitivity that ranges between 73.9% and 84.1% and a specificity that ranges between 75.9% and 92.9%.

M. Alexander Otto/MDedge News

“Discoid lupus erythematosus [DLE] is the most common type of chronic cutaneous lupus,” lead study author Scott A. Elman, MD, said during the virtual annual meeting of the American Academy of Dermatology. “It’s one of the most potentially disfiguring forms of cutaneous lupus erythematosus [CLE], which can lead to scarring, hair loss, and dyspigmentation if not treated early or promptly. It has a significant impact on patient quality of life and there are currently no classification criteria for DLE, which has led to problematic heterogeneity in observational and interventional research efforts. As there is increasing interest in drug development programs for CLE and DLE, there is a need to develop classification criteria.”

Dr. Elman, of the Harvard combined medicine-dermatology training program at Brigham and Women’s Hospital, Boston, pointed out that classification criteria are the standard definitions that are primarily intended to enroll uniform cohorts for research. “These emphasize high specificity, whereas diagnostic criteria reflect a more broad and variable set of features of a given disease, and therefore require a higher sensitivity,” he explained. “While classification criteria are not synonymous with diagnostic criteria, they typically mirror the list of criteria that are used for diagnosis.”

In 2017, Dr. Elman and colleagues generated an item list of 12 potential classification criteria using an international Delphi consensus process: 5 criteria represented disease morphology, 2 represented discoid lupus location, and 5 represented histopathology (J Am Acad Dermatol. 2017 Aug 1;77[2]:261-7). The purpose of the current study, which was presented as a late-breaking abstract, was to validate the proposed classification criteria in a multicenter, international trial. “The point is to be able to differentiate between discoid lupus and its disease mimickers, which could be confused in enrollment in clinical trials,” he said.

At nine participating sites, patients were identified at clinical visits as having either DLE or a DLE mimicker. After each visit, dermatologists determined if morphological features were present. One dermatopathologist at each site reviewed pathology, if available, to see if the histopathologic features were present. Diagnosis by clinical features and dermatopathology were tabulated and presented as counts and percentages. Clinical features among those with and without DLE were calculated and compared with chi-square or Fisher’s exact tests. The researchers used best subsets logistic regression analysis to identify candidate models.

A total of 215 patients were enrolled: 94 that were consistent with DLE and 121 that were consistent with a DLE mimicker. Most cases (83%) were from North America, 11% were from Asia, and 6% were from Europe. Only 86 cases (40%) had biopsies for dermatopathology review.

The following clinical features were found to be more commonly associated with DLE, compared with DLE mimickers: atrophic scarring (83% vs. 24%; P < .001), dyspigmentation (84% vs. 55%; P < .001), follicular hyperkeratosis/plugging (43% vs. 11%; P < .001), scarring alopecia (61% vs. 21%; P < .001), location in the conchal bowl (49% vs. 10%; P < .001), preference for the head and neck (87% vs. 49%; P < .001), and erythematous to violaceous in color (93% vs. 85%, a nonsignificant difference; P = .09).

When histopathological items were assessed, the following features were found to be more commonly associated with DLE, compared with DLE mimickers: interface/vacuolar dermatitis (83% vs. 53%; P = .004), perivascular and/or periappendageal lymphohistiocytic infiltrate (95% vs. 84%, a nonsignificant difference; P = .18), follicular keratin plugs (57% vs. 20%; P < .001), mucin deposition (73% vs. 39%; P = .002), and basement membrane thickening (57% vs. 14%; P < .001).

“There was good agreement between the diagnoses made by dermatologists and dermatopathologists, with a Cohen’s kappa statistic of 0.83,” Dr. Elman added. “Similarly, in many of the cases, the dermatopathologists and the dermatologists felt confident in their diagnosis.”

For the final model, the researchers excluded patients who had any missing data as well as those who had a diagnosis that was uncertain. This left 200 cases in the final model. Clinical variables associated with DLE were: atrophic scarring (odds ratio, 8.70; P < .001), location in the conchal bowl (OR, 6.80; P < .001), preference for head and neck (OR, 9.41; P < .001), dyspigmentation (OR, 3.23; P = .020), follicular hyperkeratosis/plugging (OR, 2.94; P = .054), and erythematous to violaceous in color (OR, 3.44; P = .056). The area under the curve for the model was 0.91.

According to Dr. Elman, the final model is a points-based model with 3 points assigned to atrophic scarring, 2 points assigned to location in the conchal bowl, 2 points assigned to preference for head and neck, 1 point assigned to dyspigmentation, 1 point assigned to follicular hyperkeratosis/plugging, and 1 point assigned to erythematous to violaceous in color. A score of 5 or greater yields a classification as DLE with 84.1% sensitivity and 75.9% specificity, while a score of 7 or greater yields a 73.9% sensitivity and 92.9% specificity.

Dr. Elman acknowledged certain limitations of the study, including the fact that information related to histopathology was not included in the final model. “This was a result of having only 40% of cases with relevant dermatopathology,” he said. “This limited our ability to meaningfully incorporate these items into a classification criteria set. However, with the data we’ve collected, efforts are under way to make a DLE-specific histopathology classification criteria.”

Another limitation is that the researchers relied on expert diagnosis as the preferred option. “Similarly, many of the cases came from large referral centers, and no demographic data were obtained, so this limits the generalizability of our study,” he said.

Dr. Elman reported having no financial disclosures.

[email protected]

The famous quote from the German philosopher Friedrich Nietzsche, “That which does not kill us makes us stronger,” may not be true after all – at least when it comes to mental health.

Results of a new study show that individuals who have a history of a stressful life events are more likely to develop posttraumatic stress disorder (PTSD) and/or major depressive disorder (MDD) following a major natural disaster than their counterparts who do not have such a history.

The investigation of more than a thousand Chilean residents – all of whom experienced one of the most powerful earthquakes in the country’s history – showed that the odds of developing postdisaster PTSD or MDD increased according to the number of predisaster stressors participants had experienced.

“We’ve learned that Nietzsche was wrong in this case and that the people who have had prior stressful and traumatic histories were more likely to develop PTSD and depression than those with fewer, study investigator Stephen L. Buka, PhD, professor of epidemiology at Brown University, Providence, Rhode Island, said in an interview.

The study was published online June 11 in the British Journal of Psychiatry.

Stress inoculation hypothesis

The so-called stress inoculation hypothesis proposes that individuals who experience manageable stressors may be able to better cope with subsequent stressors, inasmuch as such experience affords them opportunities to practice effective coping skills and develop a sense of mastery over stressors.

It’s unclear whether the theory is true for individuals who are exposed to subsequent trauma, particularly with respect to such common mental health disorders as MDD and PTSD. Although less severe day-to-day stressors may be easier to cope with, major trauma can overwhelm an individual’s coping mechanisms.

Findings from previous research have been mixed. Some studiessuggest that prior stressors can increase the risk of developing later psychiatric disorders. On the other hand, previous research has also shown that exposure to prior trauma alone does not predict subsequent PTSD.

Given these contradictions, the investigators wanted to determine whether a history of prior stressors was associated with psychiatric resilience among individuals who had no psychiatric history of MDD or PTSD.

“Only a small minority of people who have experienced a traumatic event go on to develop PTSD or MDD,” said lead author Cristina Fernandez, PhD, a psychiatric epidemiologist at the PAHO/WHO Collaborating Center for Research on Psychiatric Epidemiology and Mental Health, Brown University, Providence, R.I.

“So most people are resilient and move on without developing these disorders. But what is unique about this minority of individuals that makes them more susceptible to developing these disorders?” she continued. “It’s one of the most significant questions in the PTSD literature,” she added.

The analysis included data from 10 sites in the Chilean cities of Concepción and Talcahuano that had participated in the PREDICT investigation, a prospective cohort study that sought to predict mental health outcomes among primary care patients.

While the PREDICT study was being conducted, in February 2010, a major earthquake struck the coast of central Chile, killing more than 500 people and displacing 800,000. Concepción and Talcahuano experienced the most damage from the earthquake and its subsequent effects, including a tsunami that ravaged Talcahuano.

Dose-dependent effect

At baseline and 1 year after the disaster, all participants completed the Composite International Diagnostic Interview, which assesses for the presence of PTSD and/or MDD. Participants also completed the List of Threatening Experiences, a 12-item questionnaire that measures major stressful life events.

Of 3,000 participants who initially agreed to take part in the trial, 1708 completed both the predisaster assessment in 2003 and the postdisaster assessment in 2011, 1 year after the earthquake and tsunami occurred. After excluding for a variety other criteria, 1,160 individuals were included in the final analysis.

“As it turns out, it was a very natural experiment,” said Dr. Buka. “We had a group of people whose past traumatic experiences we knew about, and then they were all subjected to this terrible earthquake, and then we were able to look forward into time and see who did and didn’t develop PTSD and MDD.”

When the study began in 2003, none of the 1,160 participants had a history of PTSD or MDD. After the 2010 earthquake, 9.1% of the survivors (n = 106) were diagnosed with PTSD, and 14.4% were diagnosed with MDD (n = 167).

Further analyses showed that prior disaster exposure was not a significant predictor of postdisaster PTSD. Nevertheless, for every unit increase in prior nondisaster stressors, the odds of developing postdisaster PTSD increased (odds ratio, 1.21; 95% confidence interval, 1.08-1.37; P = .001).

When categorizing predisaster stressors, the investigators found that individuals who had four or more predisaster stressors had a significantly greater chance of developing postdisaster PTSD than those with no predisaster stressors (OR, 2.77; 95% CI, 1.52 – 5.04).

Similar logistic regression analyses were performed for MDD, with comparable results. Although prior disaster exposure was not a significant predictor of postdisaster MDD, each one-unit increase in prior nondisaster stressors increased the odds of developing postdisaster MDD by 16% (OR, 1.16; 95% CI, 1.06-1.27; P = .001).

Categorization of these stressors revealed that experiencing any number of stressors significantly increased the odds of developing postdisaster MDD in a dose-response fashion.

In other words, every predisaster stressor – even a single one – increased an individual’s risk of developing postdisaster MDD, and each additional stressor further increased the risk.

Predisaster stressors

Interestingly, the study also showed that the risk of developing both PTSD and MDD was particularly high among those who had experienced multiple predisaster stressors, such as serious illness or injury, death of a loved one, divorce, unemployment, financial struggles, legal troubles, or the loss of a valuable possession.

These findings, the researchers note, demonstrate that a history of stressors increases what they called “stress sensitization,” which may make individuals more vulnerable to the negative effects of subsequent stressors rather than more resilient.

As such, individuals who have experienced several stressors over the course of a lifetime are at higher risk of developing a psychiatric disorder.

This was the case with PTSD, in which exposure to at least four previous manageable stressors was associated with greater odds of developing postdisaster PTSD. For MDD, on the other hand, there was a distinct dose-response relationship between the number of manageable predisaster stressors and the risk for postdisaster MDD.

The investigators explain that these findings are particularly relevant in light of the COVID-19 pandemic and the current focus on racial and economic inequality in the United States. “The findings highlight the sectors of the population that are at greatest risk,” Dr. Buka said. “And those are the ones who’ve had more challenging and traumatic lives and more hardship.

“So it certainly calls for greater concentration of psychiatric services in traditionally underserved areas, because those are also areas that have greater histories of trauma.”
 

“Fascinating” research

Commenting on the findings fin an interview, Patricia A. Resick, PhD, who was not involved in the study, said she found the research fascinating.

“The fact that they had preexisting data and then had the wherewithal to go back after the earthquake is quite amazing,” she said.

The findings came as little surprise to Dr. Resick, professor of psychiatry and behavioral sciences at Duke University Medical Center in Durham, N.C.

“I think most people are in agreement that the more stress you have, the more likely you are to get PTSD when you experience a traumatic stressor,” she said.

Treating these individuals remains a challenge, Dr. Resick noted, though knowing their history of stressors and traumas is an important starting point.

“We have to get a good history and figure out where to start treating them, because we always want to start with the event that causes the most PTSD symptoms,” she explained.

She also characterized the issue as being as much a public health concern as one for psychiatrists. “These are people you will want to have surveillance on and encourage them to get help,” Dr. Resick added.

Dr. Fernandez agreed.

“In the face of a disaster,” she said, “there needs to be more attention paid to vulnerable populations, because they likely don’t have the support they need.

“At the clinical level, these findings help the clinician know which patients are more likely to need more intensive services,” Dr. Buka added. “And the more trauma and hardship they’ve experienced, the more attention they need and the less likely they’re going to be able to cope and manage on their own.”

The study was funded by the U.S. National Institute of Mental Health and FONDEF Chile. Dr. Fernandez, Dr. Buka, and Dr. Resick have disclosed no relevant financial relationships.
 

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

The famous quote from the German philosopher Friedrich Nietzsche, “That which does not kill us makes us stronger,” may not be true after all – at least when it comes to mental health.

Results of a new study show that individuals who have a history of a stressful life events are more likely to develop posttraumatic stress disorder (PTSD) and/or major depressive disorder (MDD) following a major natural disaster than their counterparts who do not have such a history.

The investigation of more than a thousand Chilean residents – all of whom experienced one of the most powerful earthquakes in the country’s history – showed that the odds of developing postdisaster PTSD or MDD increased according to the number of predisaster stressors participants had experienced.

“We’ve learned that Nietzsche was wrong in this case and that the people who have had prior stressful and traumatic histories were more likely to develop PTSD and depression than those with fewer, study investigator Stephen L. Buka, PhD, professor of epidemiology at Brown University, Providence, Rhode Island, said in an interview.

The study was published online June 11 in the British Journal of Psychiatry.

Stress inoculation hypothesis

The so-called stress inoculation hypothesis proposes that individuals who experience manageable stressors may be able to better cope with subsequent stressors, inasmuch as such experience affords them opportunities to practice effective coping skills and develop a sense of mastery over stressors.

It’s unclear whether the theory is true for individuals who are exposed to subsequent trauma, particularly with respect to such common mental health disorders as MDD and PTSD. Although less severe day-to-day stressors may be easier to cope with, major trauma can overwhelm an individual’s coping mechanisms.

Findings from previous research have been mixed. Some studiessuggest that prior stressors can increase the risk of developing later psychiatric disorders. On the other hand, previous research has also shown that exposure to prior trauma alone does not predict subsequent PTSD.

Given these contradictions, the investigators wanted to determine whether a history of prior stressors was associated with psychiatric resilience among individuals who had no psychiatric history of MDD or PTSD.

“Only a small minority of people who have experienced a traumatic event go on to develop PTSD or MDD,” said lead author Cristina Fernandez, PhD, a psychiatric epidemiologist at the PAHO/WHO Collaborating Center for Research on Psychiatric Epidemiology and Mental Health, Brown University, Providence, R.I.

“So most people are resilient and move on without developing these disorders. But what is unique about this minority of individuals that makes them more susceptible to developing these disorders?” she continued. “It’s one of the most significant questions in the PTSD literature,” she added.

The analysis included data from 10 sites in the Chilean cities of Concepción and Talcahuano that had participated in the PREDICT investigation, a prospective cohort study that sought to predict mental health outcomes among primary care patients.

While the PREDICT study was being conducted, in February 2010, a major earthquake struck the coast of central Chile, killing more than 500 people and displacing 800,000. Concepción and Talcahuano experienced the most damage from the earthquake and its subsequent effects, including a tsunami that ravaged Talcahuano.

Dose-dependent effect

At baseline and 1 year after the disaster, all participants completed the Composite International Diagnostic Interview, which assesses for the presence of PTSD and/or MDD. Participants also completed the List of Threatening Experiences, a 12-item questionnaire that measures major stressful life events.

Of 3,000 participants who initially agreed to take part in the trial, 1708 completed both the predisaster assessment in 2003 and the postdisaster assessment in 2011, 1 year after the earthquake and tsunami occurred. After excluding for a variety other criteria, 1,160 individuals were included in the final analysis.

“As it turns out, it was a very natural experiment,” said Dr. Buka. “We had a group of people whose past traumatic experiences we knew about, and then they were all subjected to this terrible earthquake, and then we were able to look forward into time and see who did and didn’t develop PTSD and MDD.”

When the study began in 2003, none of the 1,160 participants had a history of PTSD or MDD. After the 2010 earthquake, 9.1% of the survivors (n = 106) were diagnosed with PTSD, and 14.4% were diagnosed with MDD (n = 167).

Further analyses showed that prior disaster exposure was not a significant predictor of postdisaster PTSD. Nevertheless, for every unit increase in prior nondisaster stressors, the odds of developing postdisaster PTSD increased (odds ratio, 1.21; 95% confidence interval, 1.08-1.37; P = .001).

When categorizing predisaster stressors, the investigators found that individuals who had four or more predisaster stressors had a significantly greater chance of developing postdisaster PTSD than those with no predisaster stressors (OR, 2.77; 95% CI, 1.52 – 5.04).

Similar logistic regression analyses were performed for MDD, with comparable results. Although prior disaster exposure was not a significant predictor of postdisaster MDD, each one-unit increase in prior nondisaster stressors increased the odds of developing postdisaster MDD by 16% (OR, 1.16; 95% CI, 1.06-1.27; P = .001).

Categorization of these stressors revealed that experiencing any number of stressors significantly increased the odds of developing postdisaster MDD in a dose-response fashion.

In other words, every predisaster stressor – even a single one – increased an individual’s risk of developing postdisaster MDD, and each additional stressor further increased the risk.

Predisaster stressors

Interestingly, the study also showed that the risk of developing both PTSD and MDD was particularly high among those who had experienced multiple predisaster stressors, such as serious illness or injury, death of a loved one, divorce, unemployment, financial struggles, legal troubles, or the loss of a valuable possession.

These findings, the researchers note, demonstrate that a history of stressors increases what they called “stress sensitization,” which may make individuals more vulnerable to the negative effects of subsequent stressors rather than more resilient.

As such, individuals who have experienced several stressors over the course of a lifetime are at higher risk of developing a psychiatric disorder.

This was the case with PTSD, in which exposure to at least four previous manageable stressors was associated with greater odds of developing postdisaster PTSD. For MDD, on the other hand, there was a distinct dose-response relationship between the number of manageable predisaster stressors and the risk for postdisaster MDD.

The investigators explain that these findings are particularly relevant in light of the COVID-19 pandemic and the current focus on racial and economic inequality in the United States. “The findings highlight the sectors of the population that are at greatest risk,” Dr. Buka said. “And those are the ones who’ve had more challenging and traumatic lives and more hardship.

“So it certainly calls for greater concentration of psychiatric services in traditionally underserved areas, because those are also areas that have greater histories of trauma.”
 

“Fascinating” research

Commenting on the findings fin an interview, Patricia A. Resick, PhD, who was not involved in the study, said she found the research fascinating.

“The fact that they had preexisting data and then had the wherewithal to go back after the earthquake is quite amazing,” she said.

The findings came as little surprise to Dr. Resick, professor of psychiatry and behavioral sciences at Duke University Medical Center in Durham, N.C.

“I think most people are in agreement that the more stress you have, the more likely you are to get PTSD when you experience a traumatic stressor,” she said.

Treating these individuals remains a challenge, Dr. Resick noted, though knowing their history of stressors and traumas is an important starting point.

“We have to get a good history and figure out where to start treating them, because we always want to start with the event that causes the most PTSD symptoms,” she explained.

She also characterized the issue as being as much a public health concern as one for psychiatrists. “These are people you will want to have surveillance on and encourage them to get help,” Dr. Resick added.

Dr. Fernandez agreed.

“In the face of a disaster,” she said, “there needs to be more attention paid to vulnerable populations, because they likely don’t have the support they need.

“At the clinical level, these findings help the clinician know which patients are more likely to need more intensive services,” Dr. Buka added. “And the more trauma and hardship they’ve experienced, the more attention they need and the less likely they’re going to be able to cope and manage on their own.”

The study was funded by the U.S. National Institute of Mental Health and FONDEF Chile. Dr. Fernandez, Dr. Buka, and Dr. Resick have disclosed no relevant financial relationships.
 

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

The famous quote from the German philosopher Friedrich Nietzsche, “That which does not kill us makes us stronger,” may not be true after all – at least when it comes to mental health.

Results of a new study show that individuals who have a history of a stressful life events are more likely to develop posttraumatic stress disorder (PTSD) and/or major depressive disorder (MDD) following a major natural disaster than their counterparts who do not have such a history.

The investigation of more than a thousand Chilean residents – all of whom experienced one of the most powerful earthquakes in the country’s history – showed that the odds of developing postdisaster PTSD or MDD increased according to the number of predisaster stressors participants had experienced.

“We’ve learned that Nietzsche was wrong in this case and that the people who have had prior stressful and traumatic histories were more likely to develop PTSD and depression than those with fewer, study investigator Stephen L. Buka, PhD, professor of epidemiology at Brown University, Providence, Rhode Island, said in an interview.

The study was published online June 11 in the British Journal of Psychiatry.

Stress inoculation hypothesis

The so-called stress inoculation hypothesis proposes that individuals who experience manageable stressors may be able to better cope with subsequent stressors, inasmuch as such experience affords them opportunities to practice effective coping skills and develop a sense of mastery over stressors.

It’s unclear whether the theory is true for individuals who are exposed to subsequent trauma, particularly with respect to such common mental health disorders as MDD and PTSD. Although less severe day-to-day stressors may be easier to cope with, major trauma can overwhelm an individual’s coping mechanisms.

Findings from previous research have been mixed. Some studiessuggest that prior stressors can increase the risk of developing later psychiatric disorders. On the other hand, previous research has also shown that exposure to prior trauma alone does not predict subsequent PTSD.

Given these contradictions, the investigators wanted to determine whether a history of prior stressors was associated with psychiatric resilience among individuals who had no psychiatric history of MDD or PTSD.

“Only a small minority of people who have experienced a traumatic event go on to develop PTSD or MDD,” said lead author Cristina Fernandez, PhD, a psychiatric epidemiologist at the PAHO/WHO Collaborating Center for Research on Psychiatric Epidemiology and Mental Health, Brown University, Providence, R.I.

“So most people are resilient and move on without developing these disorders. But what is unique about this minority of individuals that makes them more susceptible to developing these disorders?” she continued. “It’s one of the most significant questions in the PTSD literature,” she added.

The analysis included data from 10 sites in the Chilean cities of Concepción and Talcahuano that had participated in the PREDICT investigation, a prospective cohort study that sought to predict mental health outcomes among primary care patients.

While the PREDICT study was being conducted, in February 2010, a major earthquake struck the coast of central Chile, killing more than 500 people and displacing 800,000. Concepción and Talcahuano experienced the most damage from the earthquake and its subsequent effects, including a tsunami that ravaged Talcahuano.

Dose-dependent effect

At baseline and 1 year after the disaster, all participants completed the Composite International Diagnostic Interview, which assesses for the presence of PTSD and/or MDD. Participants also completed the List of Threatening Experiences, a 12-item questionnaire that measures major stressful life events.

Of 3,000 participants who initially agreed to take part in the trial, 1708 completed both the predisaster assessment in 2003 and the postdisaster assessment in 2011, 1 year after the earthquake and tsunami occurred. After excluding for a variety other criteria, 1,160 individuals were included in the final analysis.

“As it turns out, it was a very natural experiment,” said Dr. Buka. “We had a group of people whose past traumatic experiences we knew about, and then they were all subjected to this terrible earthquake, and then we were able to look forward into time and see who did and didn’t develop PTSD and MDD.”

When the study began in 2003, none of the 1,160 participants had a history of PTSD or MDD. After the 2010 earthquake, 9.1% of the survivors (n = 106) were diagnosed with PTSD, and 14.4% were diagnosed with MDD (n = 167).

Further analyses showed that prior disaster exposure was not a significant predictor of postdisaster PTSD. Nevertheless, for every unit increase in prior nondisaster stressors, the odds of developing postdisaster PTSD increased (odds ratio, 1.21; 95% confidence interval, 1.08-1.37; P = .001).

When categorizing predisaster stressors, the investigators found that individuals who had four or more predisaster stressors had a significantly greater chance of developing postdisaster PTSD than those with no predisaster stressors (OR, 2.77; 95% CI, 1.52 – 5.04).

Similar logistic regression analyses were performed for MDD, with comparable results. Although prior disaster exposure was not a significant predictor of postdisaster MDD, each one-unit increase in prior nondisaster stressors increased the odds of developing postdisaster MDD by 16% (OR, 1.16; 95% CI, 1.06-1.27; P = .001).

Categorization of these stressors revealed that experiencing any number of stressors significantly increased the odds of developing postdisaster MDD in a dose-response fashion.

In other words, every predisaster stressor – even a single one – increased an individual’s risk of developing postdisaster MDD, and each additional stressor further increased the risk.

Predisaster stressors

Interestingly, the study also showed that the risk of developing both PTSD and MDD was particularly high among those who had experienced multiple predisaster stressors, such as serious illness or injury, death of a loved one, divorce, unemployment, financial struggles, legal troubles, or the loss of a valuable possession.

These findings, the researchers note, demonstrate that a history of stressors increases what they called “stress sensitization,” which may make individuals more vulnerable to the negative effects of subsequent stressors rather than more resilient.

As such, individuals who have experienced several stressors over the course of a lifetime are at higher risk of developing a psychiatric disorder.

This was the case with PTSD, in which exposure to at least four previous manageable stressors was associated with greater odds of developing postdisaster PTSD. For MDD, on the other hand, there was a distinct dose-response relationship between the number of manageable predisaster stressors and the risk for postdisaster MDD.

The investigators explain that these findings are particularly relevant in light of the COVID-19 pandemic and the current focus on racial and economic inequality in the United States. “The findings highlight the sectors of the population that are at greatest risk,” Dr. Buka said. “And those are the ones who’ve had more challenging and traumatic lives and more hardship.

“So it certainly calls for greater concentration of psychiatric services in traditionally underserved areas, because those are also areas that have greater histories of trauma.”
 

“Fascinating” research

Commenting on the findings fin an interview, Patricia A. Resick, PhD, who was not involved in the study, said she found the research fascinating.

“The fact that they had preexisting data and then had the wherewithal to go back after the earthquake is quite amazing,” she said.

The findings came as little surprise to Dr. Resick, professor of psychiatry and behavioral sciences at Duke University Medical Center in Durham, N.C.

“I think most people are in agreement that the more stress you have, the more likely you are to get PTSD when you experience a traumatic stressor,” she said.

Treating these individuals remains a challenge, Dr. Resick noted, though knowing their history of stressors and traumas is an important starting point.

“We have to get a good history and figure out where to start treating them, because we always want to start with the event that causes the most PTSD symptoms,” she explained.

She also characterized the issue as being as much a public health concern as one for psychiatrists. “These are people you will want to have surveillance on and encourage them to get help,” Dr. Resick added.

Dr. Fernandez agreed.

“In the face of a disaster,” she said, “there needs to be more attention paid to vulnerable populations, because they likely don’t have the support they need.

“At the clinical level, these findings help the clinician know which patients are more likely to need more intensive services,” Dr. Buka added. “And the more trauma and hardship they’ve experienced, the more attention they need and the less likely they’re going to be able to cope and manage on their own.”

The study was funded by the U.S. National Institute of Mental Health and FONDEF Chile. Dr. Fernandez, Dr. Buka, and Dr. Resick have disclosed no relevant financial relationships.
 

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

The ability to detect myocardial injury has never been more advanced. With the availability of high-­sensitivity troponin testing, microscopic evidence of myocyte death can now be detected, often within an hour or so of the inciting event. This, in turn, has facilitated quicker and more accurate identification and treatment of affected patients. However, these advances in detection have, in some cases, outstripped our understanding of the etiology and appropriate management of troponin elevation.

This dilemma is particularly apparent among patients undergoing noncardiac surgery. Annually, over 200 million of these surgeries occur worldwide, many in patients with elevated cardiac risk or overt cardiac disease. Naturally, physicians treating these patients are concerned that the stress of surgery will provoke myocardial injury. Since symptoms are often masked in the immediate postoperative period because of sedating or analgesic medications, many physicians rely on troponin testing to detect signs of myocardial injury. With the increased sensitivity of these assays, the prevalence of troponin elevation has increased, which currently affects nearly one in five postoperative patients. This knowledge, however, doesn’t lend itself to a clear management strategy, particularly in those patients with no other objective evidence of infarction. To paraphrase T.S. Eliot, have we lost the wisdom in our knowledge?

In this journal issue, Cohn and colleagues summarize the current information around this phenomenon of myocardial injury after noncardiac surgery, or MINS.¹ Consistent with the literature, they define MINS as an acute rise and/or fall in troponin (above the assay’s upper limit of normal) at any point in the 30 days following noncardiac surgery. Importantly, MINS is an umbrella term that can indicate either a myocardial infarction (MI) or nonischemic myocardial injury (NIMI). An MI exists if there are clinical signs of ischemia and/or objective evidence of infarction on imaging.

The authors found that MINS is highly prevalent (19.6%) and associated with both cardiac disease and perioperative hemodynamic stress. Between 2.9% and 13.5% of MINS patients experienced 30-day adverse cardiac events, with higher rates in patients with higher troponin elevations and/or accompanying ischemic symptoms. The authors suggested MINS management with standard cardio-protective medications, such as statins, beta-blockers, and angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers. For those patients at low bleeding risk, they also suggested dabigatran based on the recent MANAGE trial. Finally, they noted that US cardiac society guidelines suggested no screening for MINS, while the European and Canadian guidelines advocated for screening in patients at high risk for cardiac complications.

The authors are to be congratulated for highlighting an important and vexing area of postoperative management. To date, it has been difficult to chart the best path forward for these patients because we could “see” the issue, thanks to increasingly sensitive troponin assays, but we didn’t know what to do once we found it.

So what rationale exists to justify screening? Some advocate that the presence of MINS suggests a need for further imaging and closer monitoring of these patients to identify those with an MI. Indeed, several recent MINS registry studies have found that 20% to 40% of MINS patients had definitive evidence of MI.^2-4 But what about those patients with troponin elevation and no evidence of MI? A small, propensity-matched, observational study of MINS patients, including those without MI, noted positive associations between cardioprotective medications, such as aspirin and statins, and cardiac outcomes.⁵ In addition, the MANAGE trial suggested that MINS patients, with or without evidence of an MI, receiving dabigatran had reduced vascular events without increased bleeding complications.⁶ With this growing base of evidence, the rationale for systematic screening for MINS appears to be standing on stronger footing.

As noted by the authors, the recommendations for MINS screening differ across three major cardiovascular societies. How does the practicing clinician make sense of this discordant advice? Differences often occur when the evidence is of moderate or low quality, which means guideline committees must make their own interpretations of equivocal findings. Another driver of discordant recommendations is the timing of the guidelines. Both the US and European guidelines were published in 2014, while the Canadian guidelines were published in 2017. Over time, experience with postoperative troponin testing increased, which may have influenced the Canadian guidelines. Finally, many members of the Canadian guideline writing committee were the ones conducting the various studies identifying management options for MINS patients, which may have guided their ultimate recommendation. Regardless, practicing physicians should collectively view the guidelines as acceptable “guardrails” to guide their practice. Selection of the appropriate strategy can then be tailored to the individual patient’s risks and benefits, as well as available management options.

In this era of high-sensitivity troponin testing, we now possess an exquisite opportunity to “see” minute levels of myocardial injury among postoperative patients. Our growing ability to effectively act on this knowledge will enable us to make wise decisions with our patients to optimize their cardiac outcomes during the vulnerable postoperative period.

The ability to detect myocardial injury has never been more advanced. With the availability of high-­sensitivity troponin testing, microscopic evidence of myocyte death can now be detected, often within an hour or so of the inciting event. This, in turn, has facilitated quicker and more accurate identification and treatment of affected patients. However, these advances in detection have, in some cases, outstripped our understanding of the etiology and appropriate management of troponin elevation.

This dilemma is particularly apparent among patients undergoing noncardiac surgery. Annually, over 200 million of these surgeries occur worldwide, many in patients with elevated cardiac risk or overt cardiac disease. Naturally, physicians treating these patients are concerned that the stress of surgery will provoke myocardial injury. Since symptoms are often masked in the immediate postoperative period because of sedating or analgesic medications, many physicians rely on troponin testing to detect signs of myocardial injury. With the increased sensitivity of these assays, the prevalence of troponin elevation has increased, which currently affects nearly one in five postoperative patients. This knowledge, however, doesn’t lend itself to a clear management strategy, particularly in those patients with no other objective evidence of infarction. To paraphrase T.S. Eliot, have we lost the wisdom in our knowledge?

In this journal issue, Cohn and colleagues summarize the current information around this phenomenon of myocardial injury after noncardiac surgery, or MINS.¹ Consistent with the literature, they define MINS as an acute rise and/or fall in troponin (above the assay’s upper limit of normal) at any point in the 30 days following noncardiac surgery. Importantly, MINS is an umbrella term that can indicate either a myocardial infarction (MI) or nonischemic myocardial injury (NIMI). An MI exists if there are clinical signs of ischemia and/or objective evidence of infarction on imaging.

The authors found that MINS is highly prevalent (19.6%) and associated with both cardiac disease and perioperative hemodynamic stress. Between 2.9% and 13.5% of MINS patients experienced 30-day adverse cardiac events, with higher rates in patients with higher troponin elevations and/or accompanying ischemic symptoms. The authors suggested MINS management with standard cardio-protective medications, such as statins, beta-blockers, and angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers. For those patients at low bleeding risk, they also suggested dabigatran based on the recent MANAGE trial. Finally, they noted that US cardiac society guidelines suggested no screening for MINS, while the European and Canadian guidelines advocated for screening in patients at high risk for cardiac complications.

The authors are to be congratulated for highlighting an important and vexing area of postoperative management. To date, it has been difficult to chart the best path forward for these patients because we could “see” the issue, thanks to increasingly sensitive troponin assays, but we didn’t know what to do once we found it.

So what rationale exists to justify screening? Some advocate that the presence of MINS suggests a need for further imaging and closer monitoring of these patients to identify those with an MI. Indeed, several recent MINS registry studies have found that 20% to 40% of MINS patients had definitive evidence of MI.^2-4 But what about those patients with troponin elevation and no evidence of MI? A small, propensity-matched, observational study of MINS patients, including those without MI, noted positive associations between cardioprotective medications, such as aspirin and statins, and cardiac outcomes.⁵ In addition, the MANAGE trial suggested that MINS patients, with or without evidence of an MI, receiving dabigatran had reduced vascular events without increased bleeding complications.⁶ With this growing base of evidence, the rationale for systematic screening for MINS appears to be standing on stronger footing.

As noted by the authors, the recommendations for MINS screening differ across three major cardiovascular societies. How does the practicing clinician make sense of this discordant advice? Differences often occur when the evidence is of moderate or low quality, which means guideline committees must make their own interpretations of equivocal findings. Another driver of discordant recommendations is the timing of the guidelines. Both the US and European guidelines were published in 2014, while the Canadian guidelines were published in 2017. Over time, experience with postoperative troponin testing increased, which may have influenced the Canadian guidelines. Finally, many members of the Canadian guideline writing committee were the ones conducting the various studies identifying management options for MINS patients, which may have guided their ultimate recommendation. Regardless, practicing physicians should collectively view the guidelines as acceptable “guardrails” to guide their practice. Selection of the appropriate strategy can then be tailored to the individual patient’s risks and benefits, as well as available management options.

In this era of high-sensitivity troponin testing, we now possess an exquisite opportunity to “see” minute levels of myocardial injury among postoperative patients. Our growing ability to effectively act on this knowledge will enable us to make wise decisions with our patients to optimize their cardiac outcomes during the vulnerable postoperative period.

The ability to detect myocardial injury has never been more advanced. With the availability of high-­sensitivity troponin testing, microscopic evidence of myocyte death can now be detected, often within an hour or so of the inciting event. This, in turn, has facilitated quicker and more accurate identification and treatment of affected patients. However, these advances in detection have, in some cases, outstripped our understanding of the etiology and appropriate management of troponin elevation.

This dilemma is particularly apparent among patients undergoing noncardiac surgery. Annually, over 200 million of these surgeries occur worldwide, many in patients with elevated cardiac risk or overt cardiac disease. Naturally, physicians treating these patients are concerned that the stress of surgery will provoke myocardial injury. Since symptoms are often masked in the immediate postoperative period because of sedating or analgesic medications, many physicians rely on troponin testing to detect signs of myocardial injury. With the increased sensitivity of these assays, the prevalence of troponin elevation has increased, which currently affects nearly one in five postoperative patients. This knowledge, however, doesn’t lend itself to a clear management strategy, particularly in those patients with no other objective evidence of infarction. To paraphrase T.S. Eliot, have we lost the wisdom in our knowledge?

In this journal issue, Cohn and colleagues summarize the current information around this phenomenon of myocardial injury after noncardiac surgery, or MINS.¹ Consistent with the literature, they define MINS as an acute rise and/or fall in troponin (above the assay’s upper limit of normal) at any point in the 30 days following noncardiac surgery. Importantly, MINS is an umbrella term that can indicate either a myocardial infarction (MI) or nonischemic myocardial injury (NIMI). An MI exists if there are clinical signs of ischemia and/or objective evidence of infarction on imaging.

The authors found that MINS is highly prevalent (19.6%) and associated with both cardiac disease and perioperative hemodynamic stress. Between 2.9% and 13.5% of MINS patients experienced 30-day adverse cardiac events, with higher rates in patients with higher troponin elevations and/or accompanying ischemic symptoms. The authors suggested MINS management with standard cardio-protective medications, such as statins, beta-blockers, and angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers. For those patients at low bleeding risk, they also suggested dabigatran based on the recent MANAGE trial. Finally, they noted that US cardiac society guidelines suggested no screening for MINS, while the European and Canadian guidelines advocated for screening in patients at high risk for cardiac complications.

The authors are to be congratulated for highlighting an important and vexing area of postoperative management. To date, it has been difficult to chart the best path forward for these patients because we could “see” the issue, thanks to increasingly sensitive troponin assays, but we didn’t know what to do once we found it.

So what rationale exists to justify screening? Some advocate that the presence of MINS suggests a need for further imaging and closer monitoring of these patients to identify those with an MI. Indeed, several recent MINS registry studies have found that 20% to 40% of MINS patients had definitive evidence of MI.^2-4 But what about those patients with troponin elevation and no evidence of MI? A small, propensity-matched, observational study of MINS patients, including those without MI, noted positive associations between cardioprotective medications, such as aspirin and statins, and cardiac outcomes.⁵ In addition, the MANAGE trial suggested that MINS patients, with or without evidence of an MI, receiving dabigatran had reduced vascular events without increased bleeding complications.⁶ With this growing base of evidence, the rationale for systematic screening for MINS appears to be standing on stronger footing.

As noted by the authors, the recommendations for MINS screening differ across three major cardiovascular societies. How does the practicing clinician make sense of this discordant advice? Differences often occur when the evidence is of moderate or low quality, which means guideline committees must make their own interpretations of equivocal findings. Another driver of discordant recommendations is the timing of the guidelines. Both the US and European guidelines were published in 2014, while the Canadian guidelines were published in 2017. Over time, experience with postoperative troponin testing increased, which may have influenced the Canadian guidelines. Finally, many members of the Canadian guideline writing committee were the ones conducting the various studies identifying management options for MINS patients, which may have guided their ultimate recommendation. Regardless, practicing physicians should collectively view the guidelines as acceptable “guardrails” to guide their practice. Selection of the appropriate strategy can then be tailored to the individual patient’s risks and benefits, as well as available management options.

In this era of high-sensitivity troponin testing, we now possess an exquisite opportunity to “see” minute levels of myocardial injury among postoperative patients. Our growing ability to effectively act on this knowledge will enable us to make wise decisions with our patients to optimize their cardiac outcomes during the vulnerable postoperative period.

In this issue of the Journal of Hospital Medicine, Dr. Thomson and colleagues present an analysis of 4,700 hospitalizations in the Pediatric Health Information System (PHIS) database to compare the effectiveness of different antibiotic regimens for children with neurological impairment and aspiration pneumonia.¹ After adjusting for potential confounders, including illness severity markers and demographic factors, they observed that receiving anaerobic coverage was associated with improvements in rates of acute respiratory failure, intensive care unit (ICU) transfer frequency, and length of stay. Given that the authors used an administrative database, several considerations limit the generalizability of the current study. These limitations include that only patients hospitalized at freestanding children’s hospitals were included, the incomplete ability to assess illness severity, and the absence of validated clinical criteria for the diagnosis of aspiration pneumonia. Despite the limitations of a retrospective study using administrative data, the authors should be commended for their rigorous analyses and for their important contribution to the care of this understudied population.

Optimizing appropriate antibiotic therapy for children with suspected aspiration pneumonia is challenging for several reasons. First, previous epidemiological studies demonstrated that viruses cause most pediatric community-acquired pneumonia²; however, we lack tools to identify patients who do not require antibiotic therapy. Second, current clinical guidelines on community-acquired pneumonia do not address aspiration pneumonia diagnosis and management.³ Similar to community-acquired pneumonia, aspiration pneumonia is a clinical diagnosis supported by patient history and laboratory and radiographic data. Given the lack of a gold standard, diagnosis of aspiration pneumonia is difficult to confirm. Previous studies using the PHIS database have demonstrated that, compared with children with nonaspiration pneumonia, those with aspiration pneumonia International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes feature higher rates of mortality, ICU-level care, and 30-day readmission rates.^4,5 However, in these studies, patients with an ICD-9-CM code for aspiration pneumonia were also more medically complex, with a higher number of complex chronic conditions and rates of technology use. Lastly, aspiration pneumonia is occasionally synonymous with pneumonia in medically complex patients, which leads to the increased exposure to broad-­spectrum antibiotics. The exposure to broad-spectrum antibiotics causes complications, such as Clostridioides difficile infection and potential antibiotic resistance in a patient population that already experiences significant antibiotic exposure.

Growing concerns about antibiotic overuse and the declining prevalence of anaerobic isolates among adult pneumonia patients recently prompted the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) to discourage routine anaerobic coverage among adults with suspected aspiration pneumonia and no abscess or empyema.⁶ These guidelines overturn years of habit for most adult hospitalists, although the IDSA and ATS acknowledge the extremely low quality of evidence informing the recommendation. Thus, the dilemma is whether the IDSA/ATS guidelines should be reconciled with the conclusions of Thomson et al. The answer is “not necessarily.” Fundamentally, different causes of neurological impairment, such as dementia and stroke, afflict elderly adults with aspiration pneumonia along with important differences in physiological and microbiological exposures. Instead, adult and pediatric hospitalists can find common ground around the shared uncertainty and variability in diagnosing aspiration pneumonia and the need for more credible evidence. Unfortunately, wide variation in diagnosis and coding practices might complicate the efforts to reproduce Thomson’s rigorous retrospective cohort study in large adult databases⁷ given that Medicare-quality comparison programs may have inadvertently encouraged changes in coding behaviors during the last decade. Attributing pneumonia cases to aspiration removed high-risk patients from reporting cohorts, thus improving a hospital’s apparent mortality rate for community-acquired pneumonia. Although the United States Centers for Medicare & Medicaid Services amended rules in 2017 to address this concern, years of overdiagnosis of aspiration pneumonia possibly biased adult administrative data sets.

Although the association between the use of anaerobic antibiotic coverage and improved pediatric outcomes is promising, these results also point out the need for rigorous prospective studies to improve the evidence base for the diagnosis and treatment of suspected aspiration pneumonia in hospitalized patients of all ages. Given the heterogeneity in the use of aspiration pneumonia diagnoses, foundational work might include assessing the factors that influence clinicians in deciding on the diagnosis of aspiration pneumonia (versus community-­acquired pneumonia). On the patient side, parallel trials may start with multicenter, prospective cohort studies to gain insights into the demographic, clinical, and laboratory factors that are associated with the diagnosis of aspiration pneumonia. This research direction may lead to the development and standardization of diagnostic criteria for aspiration pneumonia. Ultimately, prospective randomized controlled trials are needed to assess the comparative effectiveness of different antibiotic choices on clinical outcomes.

In this issue of the Journal of Hospital Medicine, Dr. Thomson and colleagues present an analysis of 4,700 hospitalizations in the Pediatric Health Information System (PHIS) database to compare the effectiveness of different antibiotic regimens for children with neurological impairment and aspiration pneumonia.¹ After adjusting for potential confounders, including illness severity markers and demographic factors, they observed that receiving anaerobic coverage was associated with improvements in rates of acute respiratory failure, intensive care unit (ICU) transfer frequency, and length of stay. Given that the authors used an administrative database, several considerations limit the generalizability of the current study. These limitations include that only patients hospitalized at freestanding children’s hospitals were included, the incomplete ability to assess illness severity, and the absence of validated clinical criteria for the diagnosis of aspiration pneumonia. Despite the limitations of a retrospective study using administrative data, the authors should be commended for their rigorous analyses and for their important contribution to the care of this understudied population.

Optimizing appropriate antibiotic therapy for children with suspected aspiration pneumonia is challenging for several reasons. First, previous epidemiological studies demonstrated that viruses cause most pediatric community-acquired pneumonia²; however, we lack tools to identify patients who do not require antibiotic therapy. Second, current clinical guidelines on community-acquired pneumonia do not address aspiration pneumonia diagnosis and management.³ Similar to community-acquired pneumonia, aspiration pneumonia is a clinical diagnosis supported by patient history and laboratory and radiographic data. Given the lack of a gold standard, diagnosis of aspiration pneumonia is difficult to confirm. Previous studies using the PHIS database have demonstrated that, compared with children with nonaspiration pneumonia, those with aspiration pneumonia International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes feature higher rates of mortality, ICU-level care, and 30-day readmission rates.^4,5 However, in these studies, patients with an ICD-9-CM code for aspiration pneumonia were also more medically complex, with a higher number of complex chronic conditions and rates of technology use. Lastly, aspiration pneumonia is occasionally synonymous with pneumonia in medically complex patients, which leads to the increased exposure to broad-­spectrum antibiotics. The exposure to broad-spectrum antibiotics causes complications, such as Clostridioides difficile infection and potential antibiotic resistance in a patient population that already experiences significant antibiotic exposure.

Growing concerns about antibiotic overuse and the declining prevalence of anaerobic isolates among adult pneumonia patients recently prompted the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) to discourage routine anaerobic coverage among adults with suspected aspiration pneumonia and no abscess or empyema.⁶ These guidelines overturn years of habit for most adult hospitalists, although the IDSA and ATS acknowledge the extremely low quality of evidence informing the recommendation. Thus, the dilemma is whether the IDSA/ATS guidelines should be reconciled with the conclusions of Thomson et al. The answer is “not necessarily.” Fundamentally, different causes of neurological impairment, such as dementia and stroke, afflict elderly adults with aspiration pneumonia along with important differences in physiological and microbiological exposures. Instead, adult and pediatric hospitalists can find common ground around the shared uncertainty and variability in diagnosing aspiration pneumonia and the need for more credible evidence. Unfortunately, wide variation in diagnosis and coding practices might complicate the efforts to reproduce Thomson’s rigorous retrospective cohort study in large adult databases⁷ given that Medicare-quality comparison programs may have inadvertently encouraged changes in coding behaviors during the last decade. Attributing pneumonia cases to aspiration removed high-risk patients from reporting cohorts, thus improving a hospital’s apparent mortality rate for community-acquired pneumonia. Although the United States Centers for Medicare & Medicaid Services amended rules in 2017 to address this concern, years of overdiagnosis of aspiration pneumonia possibly biased adult administrative data sets.

Although the association between the use of anaerobic antibiotic coverage and improved pediatric outcomes is promising, these results also point out the need for rigorous prospective studies to improve the evidence base for the diagnosis and treatment of suspected aspiration pneumonia in hospitalized patients of all ages. Given the heterogeneity in the use of aspiration pneumonia diagnoses, foundational work might include assessing the factors that influence clinicians in deciding on the diagnosis of aspiration pneumonia (versus community-­acquired pneumonia). On the patient side, parallel trials may start with multicenter, prospective cohort studies to gain insights into the demographic, clinical, and laboratory factors that are associated with the diagnosis of aspiration pneumonia. This research direction may lead to the development and standardization of diagnostic criteria for aspiration pneumonia. Ultimately, prospective randomized controlled trials are needed to assess the comparative effectiveness of different antibiotic choices on clinical outcomes.

In this issue of the Journal of Hospital Medicine, Dr. Thomson and colleagues present an analysis of 4,700 hospitalizations in the Pediatric Health Information System (PHIS) database to compare the effectiveness of different antibiotic regimens for children with neurological impairment and aspiration pneumonia.¹ After adjusting for potential confounders, including illness severity markers and demographic factors, they observed that receiving anaerobic coverage was associated with improvements in rates of acute respiratory failure, intensive care unit (ICU) transfer frequency, and length of stay. Given that the authors used an administrative database, several considerations limit the generalizability of the current study. These limitations include that only patients hospitalized at freestanding children’s hospitals were included, the incomplete ability to assess illness severity, and the absence of validated clinical criteria for the diagnosis of aspiration pneumonia. Despite the limitations of a retrospective study using administrative data, the authors should be commended for their rigorous analyses and for their important contribution to the care of this understudied population.

Optimizing appropriate antibiotic therapy for children with suspected aspiration pneumonia is challenging for several reasons. First, previous epidemiological studies demonstrated that viruses cause most pediatric community-acquired pneumonia²; however, we lack tools to identify patients who do not require antibiotic therapy. Second, current clinical guidelines on community-acquired pneumonia do not address aspiration pneumonia diagnosis and management.³ Similar to community-acquired pneumonia, aspiration pneumonia is a clinical diagnosis supported by patient history and laboratory and radiographic data. Given the lack of a gold standard, diagnosis of aspiration pneumonia is difficult to confirm. Previous studies using the PHIS database have demonstrated that, compared with children with nonaspiration pneumonia, those with aspiration pneumonia International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes feature higher rates of mortality, ICU-level care, and 30-day readmission rates.^4,5 However, in these studies, patients with an ICD-9-CM code for aspiration pneumonia were also more medically complex, with a higher number of complex chronic conditions and rates of technology use. Lastly, aspiration pneumonia is occasionally synonymous with pneumonia in medically complex patients, which leads to the increased exposure to broad-­spectrum antibiotics. The exposure to broad-spectrum antibiotics causes complications, such as Clostridioides difficile infection and potential antibiotic resistance in a patient population that already experiences significant antibiotic exposure.

Growing concerns about antibiotic overuse and the declining prevalence of anaerobic isolates among adult pneumonia patients recently prompted the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) to discourage routine anaerobic coverage among adults with suspected aspiration pneumonia and no abscess or empyema.⁶ These guidelines overturn years of habit for most adult hospitalists, although the IDSA and ATS acknowledge the extremely low quality of evidence informing the recommendation. Thus, the dilemma is whether the IDSA/ATS guidelines should be reconciled with the conclusions of Thomson et al. The answer is “not necessarily.” Fundamentally, different causes of neurological impairment, such as dementia and stroke, afflict elderly adults with aspiration pneumonia along with important differences in physiological and microbiological exposures. Instead, adult and pediatric hospitalists can find common ground around the shared uncertainty and variability in diagnosing aspiration pneumonia and the need for more credible evidence. Unfortunately, wide variation in diagnosis and coding practices might complicate the efforts to reproduce Thomson’s rigorous retrospective cohort study in large adult databases⁷ given that Medicare-quality comparison programs may have inadvertently encouraged changes in coding behaviors during the last decade. Attributing pneumonia cases to aspiration removed high-risk patients from reporting cohorts, thus improving a hospital’s apparent mortality rate for community-acquired pneumonia. Although the United States Centers for Medicare & Medicaid Services amended rules in 2017 to address this concern, years of overdiagnosis of aspiration pneumonia possibly biased adult administrative data sets.

Although the association between the use of anaerobic antibiotic coverage and improved pediatric outcomes is promising, these results also point out the need for rigorous prospective studies to improve the evidence base for the diagnosis and treatment of suspected aspiration pneumonia in hospitalized patients of all ages. Given the heterogeneity in the use of aspiration pneumonia diagnoses, foundational work might include assessing the factors that influence clinicians in deciding on the diagnosis of aspiration pneumonia (versus community-­acquired pneumonia). On the patient side, parallel trials may start with multicenter, prospective cohort studies to gain insights into the demographic, clinical, and laboratory factors that are associated with the diagnosis of aspiration pneumonia. This research direction may lead to the development and standardization of diagnostic criteria for aspiration pneumonia. Ultimately, prospective randomized controlled trials are needed to assess the comparative effectiveness of different antibiotic choices on clinical outcomes.

Core competencies are intended to provide defined expectations in a field of medicine. The newly published Pediatric Hospital Medicine (PHM) Core Competencies: 2020 Revision are an update of the original 2010 competencies¹ with added and restructured content based on relevance to current practice.^2,3 This is timely given the 2017 update to the Society of Hospital Medicine (SHM) core competencies⁴ and recent designation of PHM as a boarded subspecialty by the American Board of Pediatrics (ABP). The competencies help define the knowledge, skills, and attitudes of a pediatric hospital medicine specialist and inform curriculum development to achieve the determined expectations.

In this update to the PHM core competencies, key adjustments were made to the editorial process. Importantly, a community hospitalist was added to the editorial team; this change better reflects the proportion of care provided to hospitalized children at community sites nationwide.⁵ Content updates were considered using a two-pronged needs assessment: (1) review of recent PHM conference, textbook, and handbook content and (2) survey of the SHM, Academic Pediatric Association, and American Academy of Pediatrics stakeholder groups. These processes led to the addition of 12 chapters, the major revision of 7 chapters, and the addition of content to 29 of the original chapters.

The increased focus on mental health in the sections “Common Clinical Diagnoses and Conditions” and “Specialized Services” is a necessary update. Chapters on neonatal abstinence syndrome (NAS), substance abuse, and altered mental status were added to the “Common Clinical Diagnoses and Conditions” section. The increasing incidence of NAS has been well described, and the field of PHM has been instrumental in improving care for these patients.⁶ Children hospitalized with mental health diagnoses constitute a substantial portion of pediatric inpatient admissions,⁷ and we anticipate that it will be a continued area of need in PHM. Therefore, the addition of chapters on acute and chronic behavioral and psychiatric conditions in the “Specialized Services” section is noteworthy. In contrast, with the added chapters on constipation and gastrointestinal and digestive disorders, the gastrointestinal disorders may be disproportionately represented in the updated competencies and may be an area to streamline in future iterations.

Recognition of changing procedural needs in the inpatient pediatric setting, particularly with the growing population of children with medical complexity, resulted in removal of suprapubic bladder taps and addition of vesicostomy care to the “Core Skills” section. In future updates, it will be important to continue to remove practices that are no longer relevant or widespread and include advances in procedural skills applicable to PHM such as point-of-care ultrasound.⁸

The “Healthcare Systems” section highlights additional skills ranging from quality improvement and research to family-­centered care that PHM physicians bring to healthcare institutions. According to a recent survey of early-career hospitalists, skills in these areas are often not adequately developed during residency training.⁹ Therefore, the competencies outlined in this section are a key part of proposed PHM fellowship curricula¹⁰ and should be recognized as potential development opportunities for junior faculty in the field. This section also highlights the increasing medical complexity of patients and evolving role of PHM expertise in comanagement and consultation to improve quality and safety of care. Appreciating the unique needs of underserved communities is another important addition in the new chapter on family-centered care.

Looking ahead to future updates, we appreciate that the editors commented on diversity in both editorship and authorship. In line with the recent call for improved representation of women and racial and ethnic minorities in academic medicine by the Journal of Hospital Medicine,¹¹ future core competency publications should broadly consider diversity in editors, authors, and reviewers and more explicitly address methods for increasing diversity. We also anticipate that technological advances, such as telemedicine and remote patient monitoring, will be at the forefront in subsequent updates, which will allow higher levels of care to be provided outside of the traditional hospital structure. With the recent inauguration of the ABP PHM certification exam and the first cycle of Accreditation Council for Graduate Medical Education accreditation for PHM fellowships, these updated competencies are timely and relevant. The authors’ ongoing efforts are crucial for our young and evolving field as we strive to improve the health of all hospitalized children.

The authors have nothing to disclose.

Core competencies are intended to provide defined expectations in a field of medicine. The newly published Pediatric Hospital Medicine (PHM) Core Competencies: 2020 Revision are an update of the original 2010 competencies¹ with added and restructured content based on relevance to current practice.^2,3 This is timely given the 2017 update to the Society of Hospital Medicine (SHM) core competencies⁴ and recent designation of PHM as a boarded subspecialty by the American Board of Pediatrics (ABP). The competencies help define the knowledge, skills, and attitudes of a pediatric hospital medicine specialist and inform curriculum development to achieve the determined expectations.

In this update to the PHM core competencies, key adjustments were made to the editorial process. Importantly, a community hospitalist was added to the editorial team; this change better reflects the proportion of care provided to hospitalized children at community sites nationwide.⁵ Content updates were considered using a two-pronged needs assessment: (1) review of recent PHM conference, textbook, and handbook content and (2) survey of the SHM, Academic Pediatric Association, and American Academy of Pediatrics stakeholder groups. These processes led to the addition of 12 chapters, the major revision of 7 chapters, and the addition of content to 29 of the original chapters.

The increased focus on mental health in the sections “Common Clinical Diagnoses and Conditions” and “Specialized Services” is a necessary update. Chapters on neonatal abstinence syndrome (NAS), substance abuse, and altered mental status were added to the “Common Clinical Diagnoses and Conditions” section. The increasing incidence of NAS has been well described, and the field of PHM has been instrumental in improving care for these patients.⁶ Children hospitalized with mental health diagnoses constitute a substantial portion of pediatric inpatient admissions,⁷ and we anticipate that it will be a continued area of need in PHM. Therefore, the addition of chapters on acute and chronic behavioral and psychiatric conditions in the “Specialized Services” section is noteworthy. In contrast, with the added chapters on constipation and gastrointestinal and digestive disorders, the gastrointestinal disorders may be disproportionately represented in the updated competencies and may be an area to streamline in future iterations.

Recognition of changing procedural needs in the inpatient pediatric setting, particularly with the growing population of children with medical complexity, resulted in removal of suprapubic bladder taps and addition of vesicostomy care to the “Core Skills” section. In future updates, it will be important to continue to remove practices that are no longer relevant or widespread and include advances in procedural skills applicable to PHM such as point-of-care ultrasound.⁸

The “Healthcare Systems” section highlights additional skills ranging from quality improvement and research to family-­centered care that PHM physicians bring to healthcare institutions. According to a recent survey of early-career hospitalists, skills in these areas are often not adequately developed during residency training.⁹ Therefore, the competencies outlined in this section are a key part of proposed PHM fellowship curricula¹⁰ and should be recognized as potential development opportunities for junior faculty in the field. This section also highlights the increasing medical complexity of patients and evolving role of PHM expertise in comanagement and consultation to improve quality and safety of care. Appreciating the unique needs of underserved communities is another important addition in the new chapter on family-centered care.

Looking ahead to future updates, we appreciate that the editors commented on diversity in both editorship and authorship. In line with the recent call for improved representation of women and racial and ethnic minorities in academic medicine by the Journal of Hospital Medicine,¹¹ future core competency publications should broadly consider diversity in editors, authors, and reviewers and more explicitly address methods for increasing diversity. We also anticipate that technological advances, such as telemedicine and remote patient monitoring, will be at the forefront in subsequent updates, which will allow higher levels of care to be provided outside of the traditional hospital structure. With the recent inauguration of the ABP PHM certification exam and the first cycle of Accreditation Council for Graduate Medical Education accreditation for PHM fellowships, these updated competencies are timely and relevant. The authors’ ongoing efforts are crucial for our young and evolving field as we strive to improve the health of all hospitalized children.

The authors have nothing to disclose.

Core competencies are intended to provide defined expectations in a field of medicine. The newly published Pediatric Hospital Medicine (PHM) Core Competencies: 2020 Revision are an update of the original 2010 competencies¹ with added and restructured content based on relevance to current practice.^2,3 This is timely given the 2017 update to the Society of Hospital Medicine (SHM) core competencies⁴ and recent designation of PHM as a boarded subspecialty by the American Board of Pediatrics (ABP). The competencies help define the knowledge, skills, and attitudes of a pediatric hospital medicine specialist and inform curriculum development to achieve the determined expectations.

In this update to the PHM core competencies, key adjustments were made to the editorial process. Importantly, a community hospitalist was added to the editorial team; this change better reflects the proportion of care provided to hospitalized children at community sites nationwide.⁵ Content updates were considered using a two-pronged needs assessment: (1) review of recent PHM conference, textbook, and handbook content and (2) survey of the SHM, Academic Pediatric Association, and American Academy of Pediatrics stakeholder groups. These processes led to the addition of 12 chapters, the major revision of 7 chapters, and the addition of content to 29 of the original chapters.

The increased focus on mental health in the sections “Common Clinical Diagnoses and Conditions” and “Specialized Services” is a necessary update. Chapters on neonatal abstinence syndrome (NAS), substance abuse, and altered mental status were added to the “Common Clinical Diagnoses and Conditions” section. The increasing incidence of NAS has been well described, and the field of PHM has been instrumental in improving care for these patients.⁶ Children hospitalized with mental health diagnoses constitute a substantial portion of pediatric inpatient admissions,⁷ and we anticipate that it will be a continued area of need in PHM. Therefore, the addition of chapters on acute and chronic behavioral and psychiatric conditions in the “Specialized Services” section is noteworthy. In contrast, with the added chapters on constipation and gastrointestinal and digestive disorders, the gastrointestinal disorders may be disproportionately represented in the updated competencies and may be an area to streamline in future iterations.

Recognition of changing procedural needs in the inpatient pediatric setting, particularly with the growing population of children with medical complexity, resulted in removal of suprapubic bladder taps and addition of vesicostomy care to the “Core Skills” section. In future updates, it will be important to continue to remove practices that are no longer relevant or widespread and include advances in procedural skills applicable to PHM such as point-of-care ultrasound.⁸

The “Healthcare Systems” section highlights additional skills ranging from quality improvement and research to family-­centered care that PHM physicians bring to healthcare institutions. According to a recent survey of early-career hospitalists, skills in these areas are often not adequately developed during residency training.⁹ Therefore, the competencies outlined in this section are a key part of proposed PHM fellowship curricula¹⁰ and should be recognized as potential development opportunities for junior faculty in the field. This section also highlights the increasing medical complexity of patients and evolving role of PHM expertise in comanagement and consultation to improve quality and safety of care. Appreciating the unique needs of underserved communities is another important addition in the new chapter on family-centered care.

Looking ahead to future updates, we appreciate that the editors commented on diversity in both editorship and authorship. In line with the recent call for improved representation of women and racial and ethnic minorities in academic medicine by the Journal of Hospital Medicine,¹¹ future core competency publications should broadly consider diversity in editors, authors, and reviewers and more explicitly address methods for increasing diversity. We also anticipate that technological advances, such as telemedicine and remote patient monitoring, will be at the forefront in subsequent updates, which will allow higher levels of care to be provided outside of the traditional hospital structure. With the recent inauguration of the ABP PHM certification exam and the first cycle of Accreditation Council for Graduate Medical Education accreditation for PHM fellowships, these updated competencies are timely and relevant. The authors’ ongoing efforts are crucial for our young and evolving field as we strive to improve the health of all hospitalized children.

The authors have nothing to disclose.