In the opinion of Lawrence F. Eichenfield, MD, recent advances in the medical treatment of acne make it “an exciting time” for treating patients with the condition.

During the virtual annual Masters of Aesthetics Symposium, he highlighted the following new acne treatment options:

• Trifarotene cream 0.005% (Aklief). This marks the first new retinoid indicated for acne in several decades. It is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older and has been studied in acne of the face, chest, and back. “It’s nice to have in our armamentarium,” he said.
• Tazarotene lotion 0.045% (Arazlo). The 0.1% formulation of tazarotene is commonly used for acne, but it can cause skin irritation, dryness, and erythema. The new 0.045% formulation was developed in a three-dimensional mesh matrix, with ingredients from an oil-in-water emulsion. “This allows for graduated dosing on the skin without as much irritation,” said Dr. Eichenfield, who is chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego.
• Minocycline 4% topical foam (Amzeeq). This marks the first and only topical minocycline prescription treatment for acne. “Its hydrophobic composition allows for stable and efficient delivery of inherently unstable pharmaceutical ingredients,” he said. “There is no evidence of photosensitivity as you’d expect from a minocycline-based product, and there are low systemic levels compared with oral minocycline.”
• Clascoterone cream 1% (Winlevi). This first-in-class topical androgen receptor inhibitor has been approved for the treatment of acne in patients 12 years and older. It competes with dihydrotestosterone and selectively targets androgen receptors in sebocytes and hair papilla cells. “It has been studied on the face and trunk and has been shown to inhibit sebum production, reduce secretion of inflammatory cytokines, and inhibit inflammatory pathways,” said Dr. Eichenfield, who is also professor of dermatology and pediatrics at the University of California, San Diego.
• From a systemic standpoint, sarecycline, a new tetracycline class antibiotic, has been approved for the treatment of inflammatory lesions of nonnodular moderate to severe acne vulgaris in patients 9 years and older. The once-daily drug can be taken with or without food in a weight-based dose. “This medicine appears to have a narrow spectrum of antibacterial activity compared with other tetracyclines,” he said. “It may have less of a negative effect on gut microbiome than traditional oral antibiotics.”

As for integrating these new options into existing clinical practice, Dr. Eichenfield predicts that the general approach to acne treatment will remain the same. “We’ll have to wait to see where the topical androgens fit into the treatment algorithms,” he said. “Our goal is to minimize scarring, minimize disease, and to modulate the disease course.”

Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Foamix, Galderma, L’Oreal, and Ortho Dermatologics.

[email protected]

In the opinion of Lawrence F. Eichenfield, MD, recent advances in the medical treatment of acne make it “an exciting time” for treating patients with the condition.

During the virtual annual Masters of Aesthetics Symposium, he highlighted the following new acne treatment options:

• Trifarotene cream 0.005% (Aklief). This marks the first new retinoid indicated for acne in several decades. It is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older and has been studied in acne of the face, chest, and back. “It’s nice to have in our armamentarium,” he said.
• Tazarotene lotion 0.045% (Arazlo). The 0.1% formulation of tazarotene is commonly used for acne, but it can cause skin irritation, dryness, and erythema. The new 0.045% formulation was developed in a three-dimensional mesh matrix, with ingredients from an oil-in-water emulsion. “This allows for graduated dosing on the skin without as much irritation,” said Dr. Eichenfield, who is chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego.
• Minocycline 4% topical foam (Amzeeq). This marks the first and only topical minocycline prescription treatment for acne. “Its hydrophobic composition allows for stable and efficient delivery of inherently unstable pharmaceutical ingredients,” he said. “There is no evidence of photosensitivity as you’d expect from a minocycline-based product, and there are low systemic levels compared with oral minocycline.”
• Clascoterone cream 1% (Winlevi). This first-in-class topical androgen receptor inhibitor has been approved for the treatment of acne in patients 12 years and older. It competes with dihydrotestosterone and selectively targets androgen receptors in sebocytes and hair papilla cells. “It has been studied on the face and trunk and has been shown to inhibit sebum production, reduce secretion of inflammatory cytokines, and inhibit inflammatory pathways,” said Dr. Eichenfield, who is also professor of dermatology and pediatrics at the University of California, San Diego.
• From a systemic standpoint, sarecycline, a new tetracycline class antibiotic, has been approved for the treatment of inflammatory lesions of nonnodular moderate to severe acne vulgaris in patients 9 years and older. The once-daily drug can be taken with or without food in a weight-based dose. “This medicine appears to have a narrow spectrum of antibacterial activity compared with other tetracyclines,” he said. “It may have less of a negative effect on gut microbiome than traditional oral antibiotics.”

As for integrating these new options into existing clinical practice, Dr. Eichenfield predicts that the general approach to acne treatment will remain the same. “We’ll have to wait to see where the topical androgens fit into the treatment algorithms,” he said. “Our goal is to minimize scarring, minimize disease, and to modulate the disease course.”

Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Foamix, Galderma, L’Oreal, and Ortho Dermatologics.

[email protected]

In the opinion of Lawrence F. Eichenfield, MD, recent advances in the medical treatment of acne make it “an exciting time” for treating patients with the condition.

During the virtual annual Masters of Aesthetics Symposium, he highlighted the following new acne treatment options:

• Trifarotene cream 0.005% (Aklief). This marks the first new retinoid indicated for acne in several decades. It is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older and has been studied in acne of the face, chest, and back. “It’s nice to have in our armamentarium,” he said.
• Tazarotene lotion 0.045% (Arazlo). The 0.1% formulation of tazarotene is commonly used for acne, but it can cause skin irritation, dryness, and erythema. The new 0.045% formulation was developed in a three-dimensional mesh matrix, with ingredients from an oil-in-water emulsion. “This allows for graduated dosing on the skin without as much irritation,” said Dr. Eichenfield, who is chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego.
• Minocycline 4% topical foam (Amzeeq). This marks the first and only topical minocycline prescription treatment for acne. “Its hydrophobic composition allows for stable and efficient delivery of inherently unstable pharmaceutical ingredients,” he said. “There is no evidence of photosensitivity as you’d expect from a minocycline-based product, and there are low systemic levels compared with oral minocycline.”
• Clascoterone cream 1% (Winlevi). This first-in-class topical androgen receptor inhibitor has been approved for the treatment of acne in patients 12 years and older. It competes with dihydrotestosterone and selectively targets androgen receptors in sebocytes and hair papilla cells. “It has been studied on the face and trunk and has been shown to inhibit sebum production, reduce secretion of inflammatory cytokines, and inhibit inflammatory pathways,” said Dr. Eichenfield, who is also professor of dermatology and pediatrics at the University of California, San Diego.
• From a systemic standpoint, sarecycline, a new tetracycline class antibiotic, has been approved for the treatment of inflammatory lesions of nonnodular moderate to severe acne vulgaris in patients 9 years and older. The once-daily drug can be taken with or without food in a weight-based dose. “This medicine appears to have a narrow spectrum of antibacterial activity compared with other tetracyclines,” he said. “It may have less of a negative effect on gut microbiome than traditional oral antibiotics.”

As for integrating these new options into existing clinical practice, Dr. Eichenfield predicts that the general approach to acne treatment will remain the same. “We’ll have to wait to see where the topical androgens fit into the treatment algorithms,” he said. “Our goal is to minimize scarring, minimize disease, and to modulate the disease course.”

Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Foamix, Galderma, L’Oreal, and Ortho Dermatologics.

[email protected]

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are injectable incretin hormones approved for the treatment of type 2 diabetes mellitus (T2DM). They are highly efficacious agents with hemoglobin A_1c (Hb_A1c) reduction potential of approximately 0.8 to 1.6% and mechanisms of action that result in an average weight loss of 1 to 3 kg.^1,2 Published in 2016, The LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial established cardiovascular benefits associated with liraglutide, making it a preferred GLP-1 RA.³

In addition to HbA_1c reduction, weight loss, and cardiovascular benefits, liraglutide also has shown insulin-sparing effects when used in combination with insulin. A trial by Lane and colleagues revealed a 34% decrease in total daily insulin dose 6 months after the addition of liraglutide to insulin in patients with T2DM receiving > 100 units of insulin daily.⁴ When used in combination with basal insulin analogues (glargine or detemir) similar findings also were shown.⁵

The Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) in Houston, Texas, selected liraglutide as its preferred GLP-1 RA because of its favorable glycemic and cardiovascular outcomes. In addition, as part of a cost-savings initiative for fiscal year 2018, liraglutide 6 mg/mL injection 2-count pen packs was selected as the preferred liraglutide product. Before the availability of the 2-count pen packs, veterans previously received 3-count pen packs, which allowed for up to a 30-day supply of liraglutide 1.8 mg daily dosing. However, the cost-efficient 2-count pen packs allow for up to 1.2 mg daily dose of liraglutide for a 30-day supply. Due to these changes, veterans at MEDVAMC were converted from liraglutide 1.8 mg daily to 1.2 mg daily between May 2018 and August 2018.

The primary objective of this study was to assess sustained glycemic control and cost savings that resulted from this change. The secondary objectives were to assess sustained weight loss and adverse effects (AEs).

Methods

This study was approved by the MEDVAMC Quality Assurance and Regulatory Affairs committee. In this single-center study, a retrospective chart review was conducted on veterans with T2DM who underwent a liraglutide dose reduction from 1.8 mg daily to 1.2 mg daily between May 2018 and August 2018. Patients were included if they were aged ≥ 18 years with an active prescription for liraglutide 1.8 mg daily and insulin (with or without other antihyperglycemic agents) at the time of conversion. In addition, patients must have had ≥ 1 HbA_1c reading within 3 months of the dose conversion and a follow-up HbA1c within 6 months after the dose conversion. To assess the primary objective of glycemic control that resulted from the liraglutide dose reduction, mean change of HbA1c at time of dose conversion was compared with mean HbA_1c 6 months postconversion. To assess savings, cost information was obtained from the US Department of Veterans Affairs (VA) Drug Price Database and monthly and annual costs of liraglutide 6 mg/mL injection 2-count pen pack were compared with that of the 3-count pen pack. A chart review of patients’ electronic health records assessed secondary outcomes. The VA Computerized Patient Record System (CPRS) was used to collect patient data.

Patients and Characteristics

The following patient information was obtained from patients’ records: age, sex, race/ethnicity, diabetic medications (at time of conversion and 6 months after conversion), cardiovascular history and risk factors (hypertension, coronary artery disease, heart failure, arrhythmias, peripheral artery disease, obesity, etc), prescriber type (physician, nurse practitioner/physician assistant, pharmacist, etc), weight (at baseline, at time of conversion, and 6 months after conversion), HbA_1c (at baseline, at time of conversion, and 6 months after conversion), average blood glucose (at baseline, at time of conversion, and 6 months after conversion), insulin dose (at time of conversion and 6 months after conversion), and reported AEs.

Statistical Analysis

The 2-tailed, paired t test was used to assess changes in HbA_1c, average blood glucose, and body weight. Demographic data and other outcomes were assessed using descriptive statistics.

Results

Prior to the dose reduction, 312 veterans had active prescriptions for liraglutide 1.8 mg daily. Due to lack of glycemic control benefit (failing to achieve a HbA_1c reduction of at least 0.5% after at least 3 to 6 months following initiation of therapy) or nonadherence (assessed by medication refill history), 126 veterans did not meet the criteria for the dose conversion. As a result, liraglutide was discontinued, and veterans were sent patient letter notifications and health care providers were notified via medication review notes in the patient electronic health record “to make medication adjustments if warranted. A total of 186 veterans underwent a liraglutide dose reduction between May and August 2018. Thirty-two veterans were without active insulin prescriptions, 53 were without HbA1c results, and 4 veterans died; resulting in 97 veterans who were included in the study (Figure 1).

Most of the patients included in the study were male (90.7%) and White (63.9%) with an average (SD) age of 65.9 years (7.9) and a mean (SD) HbA1c at baseline of 8.4% (1.2). About 56.7% received concurrent T2DM treatment with metformin, and 8.3% received concurrent treatment with empagliflozin. The most common cardiovascular disease/risk factors included hypertension (93.8%), hyperlipidemia (85.6%), and obesity (85.6%) (Table 1).

Glycemic Control and Weight Loss

At the time of conversion, the average (SD) HbA_1c was 8.2% (1.4) and increased to an average (SD) of 8.7% (1.8) (P =.0005) 6 months after the dose reduction (Table 2). The average (SD) body weight was 116.2 kg (23.2) at time of conversion and increased to 116.5 (24.6) 6 months following the dose reduction; however, the difference was not statistically significant (P = .8).

As a result of the HbA_1c change, 41.2% of veterans underwent an insulin dose increase with dose increase of 5 to 200 units of total daily insulin during the 6-month period. Antihyperglycemic regimen remained unchanged for 40.2% of veterans, while additional glucose lowering agents were initiated in 6 veterans. Medications initiated included empagliflozin in 4 veterans and saxagliptin in 2 veterans.

HbA_1c reduction was noted in 33% of veterans (Figure 2) mostly due to improved diet and exercise habits. A majority of veterans, 62%, experienced an increase in HbA1c, whereas 5.2% of veterans maintained the same HbA_1c. Of 60 veterans with HbA_1c increases, 15 had an increase between 0.1% and 0.5%, another 15 with an increase between 0.5 to 0.9%, and half had HbA1c increases of at least 1% with a maximum increase of 5.1% (Figure 3).

Cost Savings

Cost information was obtained from the VA Drug Price Database. The estimated monthly cost savings per patient associated with the conversion from 3-count to 2-count injection pen packs of liraglutide 6 mg/mL was $103.46. With 186 veterans converted to the 2-count pen packs, MEDVAMC saved $115,461.36 in a 6-month period. The estimated annualized cost savings was estimated to be about $231,000 (Figure 4).

Adverse Effects During the 6-month period following the dose conversion, no major AEs associated with liraglutide were documented. Documented AEs included 3 cases of diarrhea, resulting in the discontinuation of metformin. Metformin also was discontinued in a veteran with worsened renal function and eGFR < 30 mL/min/1.73 m2.

Discussion

According to previous clinical trials, when used in combination with insulin, 1.2 mg and 1.8 mg daily liraglutide showed significant improvement in glycemic control and body weight and was associated with decreased insulin requirements.^4-6 However, subgroup analyses were not performed to show differences in benefit between the liraglutide 1.8 mg and 1.2 mg groups.^4-6 Similarly, cardiovascular benefit was observed in patients receiving liraglutide 1.2 mg daily and liraglutide 1.8 mg daily in the LEADER trial with no subgroup analysis or distinction between treatment doses.³ With this information and approval by the Veterans Integrated Services Network, the pharmacoeconomics team at MEDVAMC made the decision to select a more cost-efficient preparation and, hence, lower dose of liraglutide.

To ensure that patients only taking liraglutide for glycemic control were captured, patients without insulin therapies at baseline were excluded. Due to concerns of potential off-label use of liraglutide for weight loss, patients without active prescriptions for insulin at baseline were excluded.

A mean HbA_1c increase of 0.5% was observed over the 6-month period, supporting findings of a dose-dependent HbA_1c decrease observed in clinical trials. In the LEAD-3 MONO trial when used as monotherapy, liraglutide 1.8 mg was associated with significantly greater HbA_1c reduction than liraglutide 1.2 mg (–0·29%; –0·50 to –0.09, P = .005) after 52 weeks of treatment.⁷ Liraglutide 1.8 mg was also associated with higher rates of AEs; particularly gastrointestinal. ⁷ To minimize these AEs, it is recommended to initiate liraglutide at 0.6 mg daily for a week then increase to 1.2 mg daily. If tolerated, liraglutide can be further titrated to 1.8 mg daily to optimize glycemic control.⁸ Unsurprisingly, no major AEs were noted in this study, as AEs are typically noted with increased doses.

Despite the observed trend of increased HbA_1c, no changes were made to glucoselowering agents in 39 veterans. This group of veterans consisted primarily of those whose HbA_1c remained unchanged during the 6-month period, those whose HbA_1c improved (with no documented hypoglycemia), and older veterans with less stringent HbA_1c goals. As a result, doses of glucose lowering agents were maintained as appropriate.

No significant difference was noted in body weight during the 6-month period. The slight weight gain observed may have been due to several factors. Lack of exercise and dietary changes may have contributed to weight gain. In addition, insulin doses were increased in 40 veterans, which may have contributed to the observed weight gain.

As expected, significant cost savings were achieved as a result of the liraglutide dose reduction. Of note, liraglutide was discontinued in 126 veterans (prior to the dose reduction) due to nonadherence or inadequate response to therapy, which also resulted in additional savings. Although cost savings was achieved, the long-term benefit of this initiative still remains unknown. The worsened glycemic control that was detected may increase the risk of microvascular and macrovascular complications, thereby negating cost savings achieved. To assess this effect, longterm prospective studies are warranted.

Limitations

A number of issues limit these finding, including its retrospective data review, small sample size, additional factors contributing to HbA_1c increase, and missing documentation in some patient records. Only 97 patients were included in the study, reflecting less than half of the charts reviewed (52% exclusion rate). In addition, several confounding factors may have contributed to the increased HbA_1c observed. Medication changes and lifestyle factors may have contributed to the observed change in HbA_1c levels. Exclusion of patients without active prescriptions for insulin may have contributed to a selection bias, as most patients included in the study were veterans with uncontrolled T2DM requiring insulin. Finally, as a retrospective study involving patient records, investigators relied heavily on information provided in patients’ charts (HbA_1c, body weight, insulin doses, adverse effects, etc), which may not entirely be accurate and may have been missing other pertinent information.

Conclusions

The daily dose reduction of liraglutide from 1.8 mg to 1.2 mg due to a cost-savings initiative resulted in a HbA_1c increase of 0.5% in a 6-month period. Due to HbA1c increases, 41.2% of veterans underwent an insulin dose increase, negating the insulin-sparing role of liraglutide. Although this study further confirms the dose-dependent HbA_1c reduction with liraglutide that has been noted in previous trials, long-term prospective studies and cost-effectiveness analyses are warranted to assess the overall clinical significance and other benefits of the change, including its effects on cardiovascular outcomes.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are injectable incretin hormones approved for the treatment of type 2 diabetes mellitus (T2DM). They are highly efficacious agents with hemoglobin A_1c (Hb_A1c) reduction potential of approximately 0.8 to 1.6% and mechanisms of action that result in an average weight loss of 1 to 3 kg.^1,2 Published in 2016, The LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial established cardiovascular benefits associated with liraglutide, making it a preferred GLP-1 RA.³

In addition to HbA_1c reduction, weight loss, and cardiovascular benefits, liraglutide also has shown insulin-sparing effects when used in combination with insulin. A trial by Lane and colleagues revealed a 34% decrease in total daily insulin dose 6 months after the addition of liraglutide to insulin in patients with T2DM receiving > 100 units of insulin daily.⁴ When used in combination with basal insulin analogues (glargine or detemir) similar findings also were shown.⁵

The Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) in Houston, Texas, selected liraglutide as its preferred GLP-1 RA because of its favorable glycemic and cardiovascular outcomes. In addition, as part of a cost-savings initiative for fiscal year 2018, liraglutide 6 mg/mL injection 2-count pen packs was selected as the preferred liraglutide product. Before the availability of the 2-count pen packs, veterans previously received 3-count pen packs, which allowed for up to a 30-day supply of liraglutide 1.8 mg daily dosing. However, the cost-efficient 2-count pen packs allow for up to 1.2 mg daily dose of liraglutide for a 30-day supply. Due to these changes, veterans at MEDVAMC were converted from liraglutide 1.8 mg daily to 1.2 mg daily between May 2018 and August 2018.

The primary objective of this study was to assess sustained glycemic control and cost savings that resulted from this change. The secondary objectives were to assess sustained weight loss and adverse effects (AEs).

Methods

This study was approved by the MEDVAMC Quality Assurance and Regulatory Affairs committee. In this single-center study, a retrospective chart review was conducted on veterans with T2DM who underwent a liraglutide dose reduction from 1.8 mg daily to 1.2 mg daily between May 2018 and August 2018. Patients were included if they were aged ≥ 18 years with an active prescription for liraglutide 1.8 mg daily and insulin (with or without other antihyperglycemic agents) at the time of conversion. In addition, patients must have had ≥ 1 HbA_1c reading within 3 months of the dose conversion and a follow-up HbA1c within 6 months after the dose conversion. To assess the primary objective of glycemic control that resulted from the liraglutide dose reduction, mean change of HbA1c at time of dose conversion was compared with mean HbA_1c 6 months postconversion. To assess savings, cost information was obtained from the US Department of Veterans Affairs (VA) Drug Price Database and monthly and annual costs of liraglutide 6 mg/mL injection 2-count pen pack were compared with that of the 3-count pen pack. A chart review of patients’ electronic health records assessed secondary outcomes. The VA Computerized Patient Record System (CPRS) was used to collect patient data.

Patients and Characteristics

The following patient information was obtained from patients’ records: age, sex, race/ethnicity, diabetic medications (at time of conversion and 6 months after conversion), cardiovascular history and risk factors (hypertension, coronary artery disease, heart failure, arrhythmias, peripheral artery disease, obesity, etc), prescriber type (physician, nurse practitioner/physician assistant, pharmacist, etc), weight (at baseline, at time of conversion, and 6 months after conversion), HbA_1c (at baseline, at time of conversion, and 6 months after conversion), average blood glucose (at baseline, at time of conversion, and 6 months after conversion), insulin dose (at time of conversion and 6 months after conversion), and reported AEs.

Statistical Analysis

The 2-tailed, paired t test was used to assess changes in HbA_1c, average blood glucose, and body weight. Demographic data and other outcomes were assessed using descriptive statistics.

Results

Prior to the dose reduction, 312 veterans had active prescriptions for liraglutide 1.8 mg daily. Due to lack of glycemic control benefit (failing to achieve a HbA_1c reduction of at least 0.5% after at least 3 to 6 months following initiation of therapy) or nonadherence (assessed by medication refill history), 126 veterans did not meet the criteria for the dose conversion. As a result, liraglutide was discontinued, and veterans were sent patient letter notifications and health care providers were notified via medication review notes in the patient electronic health record “to make medication adjustments if warranted. A total of 186 veterans underwent a liraglutide dose reduction between May and August 2018. Thirty-two veterans were without active insulin prescriptions, 53 were without HbA1c results, and 4 veterans died; resulting in 97 veterans who were included in the study (Figure 1).

Most of the patients included in the study were male (90.7%) and White (63.9%) with an average (SD) age of 65.9 years (7.9) and a mean (SD) HbA1c at baseline of 8.4% (1.2). About 56.7% received concurrent T2DM treatment with metformin, and 8.3% received concurrent treatment with empagliflozin. The most common cardiovascular disease/risk factors included hypertension (93.8%), hyperlipidemia (85.6%), and obesity (85.6%) (Table 1).

Glycemic Control and Weight Loss

At the time of conversion, the average (SD) HbA_1c was 8.2% (1.4) and increased to an average (SD) of 8.7% (1.8) (P =.0005) 6 months after the dose reduction (Table 2). The average (SD) body weight was 116.2 kg (23.2) at time of conversion and increased to 116.5 (24.6) 6 months following the dose reduction; however, the difference was not statistically significant (P = .8).

As a result of the HbA_1c change, 41.2% of veterans underwent an insulin dose increase with dose increase of 5 to 200 units of total daily insulin during the 6-month period. Antihyperglycemic regimen remained unchanged for 40.2% of veterans, while additional glucose lowering agents were initiated in 6 veterans. Medications initiated included empagliflozin in 4 veterans and saxagliptin in 2 veterans.

HbA_1c reduction was noted in 33% of veterans (Figure 2) mostly due to improved diet and exercise habits. A majority of veterans, 62%, experienced an increase in HbA1c, whereas 5.2% of veterans maintained the same HbA_1c. Of 60 veterans with HbA_1c increases, 15 had an increase between 0.1% and 0.5%, another 15 with an increase between 0.5 to 0.9%, and half had HbA1c increases of at least 1% with a maximum increase of 5.1% (Figure 3).

Cost Savings

Cost information was obtained from the VA Drug Price Database. The estimated monthly cost savings per patient associated with the conversion from 3-count to 2-count injection pen packs of liraglutide 6 mg/mL was $103.46. With 186 veterans converted to the 2-count pen packs, MEDVAMC saved $115,461.36 in a 6-month period. The estimated annualized cost savings was estimated to be about $231,000 (Figure 4).

Adverse Effects During the 6-month period following the dose conversion, no major AEs associated with liraglutide were documented. Documented AEs included 3 cases of diarrhea, resulting in the discontinuation of metformin. Metformin also was discontinued in a veteran with worsened renal function and eGFR < 30 mL/min/1.73 m2.

Discussion

According to previous clinical trials, when used in combination with insulin, 1.2 mg and 1.8 mg daily liraglutide showed significant improvement in glycemic control and body weight and was associated with decreased insulin requirements.^4-6 However, subgroup analyses were not performed to show differences in benefit between the liraglutide 1.8 mg and 1.2 mg groups.^4-6 Similarly, cardiovascular benefit was observed in patients receiving liraglutide 1.2 mg daily and liraglutide 1.8 mg daily in the LEADER trial with no subgroup analysis or distinction between treatment doses.³ With this information and approval by the Veterans Integrated Services Network, the pharmacoeconomics team at MEDVAMC made the decision to select a more cost-efficient preparation and, hence, lower dose of liraglutide.

To ensure that patients only taking liraglutide for glycemic control were captured, patients without insulin therapies at baseline were excluded. Due to concerns of potential off-label use of liraglutide for weight loss, patients without active prescriptions for insulin at baseline were excluded.

A mean HbA_1c increase of 0.5% was observed over the 6-month period, supporting findings of a dose-dependent HbA_1c decrease observed in clinical trials. In the LEAD-3 MONO trial when used as monotherapy, liraglutide 1.8 mg was associated with significantly greater HbA_1c reduction than liraglutide 1.2 mg (–0·29%; –0·50 to –0.09, P = .005) after 52 weeks of treatment.⁷ Liraglutide 1.8 mg was also associated with higher rates of AEs; particularly gastrointestinal. ⁷ To minimize these AEs, it is recommended to initiate liraglutide at 0.6 mg daily for a week then increase to 1.2 mg daily. If tolerated, liraglutide can be further titrated to 1.8 mg daily to optimize glycemic control.⁸ Unsurprisingly, no major AEs were noted in this study, as AEs are typically noted with increased doses.

Despite the observed trend of increased HbA_1c, no changes were made to glucoselowering agents in 39 veterans. This group of veterans consisted primarily of those whose HbA_1c remained unchanged during the 6-month period, those whose HbA_1c improved (with no documented hypoglycemia), and older veterans with less stringent HbA_1c goals. As a result, doses of glucose lowering agents were maintained as appropriate.

No significant difference was noted in body weight during the 6-month period. The slight weight gain observed may have been due to several factors. Lack of exercise and dietary changes may have contributed to weight gain. In addition, insulin doses were increased in 40 veterans, which may have contributed to the observed weight gain.

As expected, significant cost savings were achieved as a result of the liraglutide dose reduction. Of note, liraglutide was discontinued in 126 veterans (prior to the dose reduction) due to nonadherence or inadequate response to therapy, which also resulted in additional savings. Although cost savings was achieved, the long-term benefit of this initiative still remains unknown. The worsened glycemic control that was detected may increase the risk of microvascular and macrovascular complications, thereby negating cost savings achieved. To assess this effect, longterm prospective studies are warranted.

Limitations

A number of issues limit these finding, including its retrospective data review, small sample size, additional factors contributing to HbA_1c increase, and missing documentation in some patient records. Only 97 patients were included in the study, reflecting less than half of the charts reviewed (52% exclusion rate). In addition, several confounding factors may have contributed to the increased HbA_1c observed. Medication changes and lifestyle factors may have contributed to the observed change in HbA_1c levels. Exclusion of patients without active prescriptions for insulin may have contributed to a selection bias, as most patients included in the study were veterans with uncontrolled T2DM requiring insulin. Finally, as a retrospective study involving patient records, investigators relied heavily on information provided in patients’ charts (HbA_1c, body weight, insulin doses, adverse effects, etc), which may not entirely be accurate and may have been missing other pertinent information.

Conclusions

The daily dose reduction of liraglutide from 1.8 mg to 1.2 mg due to a cost-savings initiative resulted in a HbA_1c increase of 0.5% in a 6-month period. Due to HbA1c increases, 41.2% of veterans underwent an insulin dose increase, negating the insulin-sparing role of liraglutide. Although this study further confirms the dose-dependent HbA_1c reduction with liraglutide that has been noted in previous trials, long-term prospective studies and cost-effectiveness analyses are warranted to assess the overall clinical significance and other benefits of the change, including its effects on cardiovascular outcomes.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are injectable incretin hormones approved for the treatment of type 2 diabetes mellitus (T2DM). They are highly efficacious agents with hemoglobin A_1c (Hb_A1c) reduction potential of approximately 0.8 to 1.6% and mechanisms of action that result in an average weight loss of 1 to 3 kg.^1,2 Published in 2016, The LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial established cardiovascular benefits associated with liraglutide, making it a preferred GLP-1 RA.³

In addition to HbA_1c reduction, weight loss, and cardiovascular benefits, liraglutide also has shown insulin-sparing effects when used in combination with insulin. A trial by Lane and colleagues revealed a 34% decrease in total daily insulin dose 6 months after the addition of liraglutide to insulin in patients with T2DM receiving > 100 units of insulin daily.⁴ When used in combination with basal insulin analogues (glargine or detemir) similar findings also were shown.⁵

The Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) in Houston, Texas, selected liraglutide as its preferred GLP-1 RA because of its favorable glycemic and cardiovascular outcomes. In addition, as part of a cost-savings initiative for fiscal year 2018, liraglutide 6 mg/mL injection 2-count pen packs was selected as the preferred liraglutide product. Before the availability of the 2-count pen packs, veterans previously received 3-count pen packs, which allowed for up to a 30-day supply of liraglutide 1.8 mg daily dosing. However, the cost-efficient 2-count pen packs allow for up to 1.2 mg daily dose of liraglutide for a 30-day supply. Due to these changes, veterans at MEDVAMC were converted from liraglutide 1.8 mg daily to 1.2 mg daily between May 2018 and August 2018.

The primary objective of this study was to assess sustained glycemic control and cost savings that resulted from this change. The secondary objectives were to assess sustained weight loss and adverse effects (AEs).

Methods

This study was approved by the MEDVAMC Quality Assurance and Regulatory Affairs committee. In this single-center study, a retrospective chart review was conducted on veterans with T2DM who underwent a liraglutide dose reduction from 1.8 mg daily to 1.2 mg daily between May 2018 and August 2018. Patients were included if they were aged ≥ 18 years with an active prescription for liraglutide 1.8 mg daily and insulin (with or without other antihyperglycemic agents) at the time of conversion. In addition, patients must have had ≥ 1 HbA_1c reading within 3 months of the dose conversion and a follow-up HbA1c within 6 months after the dose conversion. To assess the primary objective of glycemic control that resulted from the liraglutide dose reduction, mean change of HbA1c at time of dose conversion was compared with mean HbA_1c 6 months postconversion. To assess savings, cost information was obtained from the US Department of Veterans Affairs (VA) Drug Price Database and monthly and annual costs of liraglutide 6 mg/mL injection 2-count pen pack were compared with that of the 3-count pen pack. A chart review of patients’ electronic health records assessed secondary outcomes. The VA Computerized Patient Record System (CPRS) was used to collect patient data.

Patients and Characteristics

The following patient information was obtained from patients’ records: age, sex, race/ethnicity, diabetic medications (at time of conversion and 6 months after conversion), cardiovascular history and risk factors (hypertension, coronary artery disease, heart failure, arrhythmias, peripheral artery disease, obesity, etc), prescriber type (physician, nurse practitioner/physician assistant, pharmacist, etc), weight (at baseline, at time of conversion, and 6 months after conversion), HbA_1c (at baseline, at time of conversion, and 6 months after conversion), average blood glucose (at baseline, at time of conversion, and 6 months after conversion), insulin dose (at time of conversion and 6 months after conversion), and reported AEs.

Statistical Analysis

The 2-tailed, paired t test was used to assess changes in HbA_1c, average blood glucose, and body weight. Demographic data and other outcomes were assessed using descriptive statistics.

Results

Prior to the dose reduction, 312 veterans had active prescriptions for liraglutide 1.8 mg daily. Due to lack of glycemic control benefit (failing to achieve a HbA_1c reduction of at least 0.5% after at least 3 to 6 months following initiation of therapy) or nonadherence (assessed by medication refill history), 126 veterans did not meet the criteria for the dose conversion. As a result, liraglutide was discontinued, and veterans were sent patient letter notifications and health care providers were notified via medication review notes in the patient electronic health record “to make medication adjustments if warranted. A total of 186 veterans underwent a liraglutide dose reduction between May and August 2018. Thirty-two veterans were without active insulin prescriptions, 53 were without HbA1c results, and 4 veterans died; resulting in 97 veterans who were included in the study (Figure 1).

Most of the patients included in the study were male (90.7%) and White (63.9%) with an average (SD) age of 65.9 years (7.9) and a mean (SD) HbA1c at baseline of 8.4% (1.2). About 56.7% received concurrent T2DM treatment with metformin, and 8.3% received concurrent treatment with empagliflozin. The most common cardiovascular disease/risk factors included hypertension (93.8%), hyperlipidemia (85.6%), and obesity (85.6%) (Table 1).

Glycemic Control and Weight Loss

At the time of conversion, the average (SD) HbA_1c was 8.2% (1.4) and increased to an average (SD) of 8.7% (1.8) (P =.0005) 6 months after the dose reduction (Table 2). The average (SD) body weight was 116.2 kg (23.2) at time of conversion and increased to 116.5 (24.6) 6 months following the dose reduction; however, the difference was not statistically significant (P = .8).

As a result of the HbA_1c change, 41.2% of veterans underwent an insulin dose increase with dose increase of 5 to 200 units of total daily insulin during the 6-month period. Antihyperglycemic regimen remained unchanged for 40.2% of veterans, while additional glucose lowering agents were initiated in 6 veterans. Medications initiated included empagliflozin in 4 veterans and saxagliptin in 2 veterans.

HbA_1c reduction was noted in 33% of veterans (Figure 2) mostly due to improved diet and exercise habits. A majority of veterans, 62%, experienced an increase in HbA1c, whereas 5.2% of veterans maintained the same HbA_1c. Of 60 veterans with HbA_1c increases, 15 had an increase between 0.1% and 0.5%, another 15 with an increase between 0.5 to 0.9%, and half had HbA1c increases of at least 1% with a maximum increase of 5.1% (Figure 3).

Cost Savings

Cost information was obtained from the VA Drug Price Database. The estimated monthly cost savings per patient associated with the conversion from 3-count to 2-count injection pen packs of liraglutide 6 mg/mL was $103.46. With 186 veterans converted to the 2-count pen packs, MEDVAMC saved $115,461.36 in a 6-month period. The estimated annualized cost savings was estimated to be about $231,000 (Figure 4).

Adverse Effects During the 6-month period following the dose conversion, no major AEs associated with liraglutide were documented. Documented AEs included 3 cases of diarrhea, resulting in the discontinuation of metformin. Metformin also was discontinued in a veteran with worsened renal function and eGFR < 30 mL/min/1.73 m2.

Discussion

According to previous clinical trials, when used in combination with insulin, 1.2 mg and 1.8 mg daily liraglutide showed significant improvement in glycemic control and body weight and was associated with decreased insulin requirements.^4-6 However, subgroup analyses were not performed to show differences in benefit between the liraglutide 1.8 mg and 1.2 mg groups.^4-6 Similarly, cardiovascular benefit was observed in patients receiving liraglutide 1.2 mg daily and liraglutide 1.8 mg daily in the LEADER trial with no subgroup analysis or distinction between treatment doses.³ With this information and approval by the Veterans Integrated Services Network, the pharmacoeconomics team at MEDVAMC made the decision to select a more cost-efficient preparation and, hence, lower dose of liraglutide.

To ensure that patients only taking liraglutide for glycemic control were captured, patients without insulin therapies at baseline were excluded. Due to concerns of potential off-label use of liraglutide for weight loss, patients without active prescriptions for insulin at baseline were excluded.

A mean HbA_1c increase of 0.5% was observed over the 6-month period, supporting findings of a dose-dependent HbA_1c decrease observed in clinical trials. In the LEAD-3 MONO trial when used as monotherapy, liraglutide 1.8 mg was associated with significantly greater HbA_1c reduction than liraglutide 1.2 mg (–0·29%; –0·50 to –0.09, P = .005) after 52 weeks of treatment.⁷ Liraglutide 1.8 mg was also associated with higher rates of AEs; particularly gastrointestinal. ⁷ To minimize these AEs, it is recommended to initiate liraglutide at 0.6 mg daily for a week then increase to 1.2 mg daily. If tolerated, liraglutide can be further titrated to 1.8 mg daily to optimize glycemic control.⁸ Unsurprisingly, no major AEs were noted in this study, as AEs are typically noted with increased doses.

Despite the observed trend of increased HbA_1c, no changes were made to glucoselowering agents in 39 veterans. This group of veterans consisted primarily of those whose HbA_1c remained unchanged during the 6-month period, those whose HbA_1c improved (with no documented hypoglycemia), and older veterans with less stringent HbA_1c goals. As a result, doses of glucose lowering agents were maintained as appropriate.

No significant difference was noted in body weight during the 6-month period. The slight weight gain observed may have been due to several factors. Lack of exercise and dietary changes may have contributed to weight gain. In addition, insulin doses were increased in 40 veterans, which may have contributed to the observed weight gain.

As expected, significant cost savings were achieved as a result of the liraglutide dose reduction. Of note, liraglutide was discontinued in 126 veterans (prior to the dose reduction) due to nonadherence or inadequate response to therapy, which also resulted in additional savings. Although cost savings was achieved, the long-term benefit of this initiative still remains unknown. The worsened glycemic control that was detected may increase the risk of microvascular and macrovascular complications, thereby negating cost savings achieved. To assess this effect, longterm prospective studies are warranted.

Limitations

A number of issues limit these finding, including its retrospective data review, small sample size, additional factors contributing to HbA_1c increase, and missing documentation in some patient records. Only 97 patients were included in the study, reflecting less than half of the charts reviewed (52% exclusion rate). In addition, several confounding factors may have contributed to the increased HbA_1c observed. Medication changes and lifestyle factors may have contributed to the observed change in HbA_1c levels. Exclusion of patients without active prescriptions for insulin may have contributed to a selection bias, as most patients included in the study were veterans with uncontrolled T2DM requiring insulin. Finally, as a retrospective study involving patient records, investigators relied heavily on information provided in patients’ charts (HbA_1c, body weight, insulin doses, adverse effects, etc), which may not entirely be accurate and may have been missing other pertinent information.

Conclusions

The daily dose reduction of liraglutide from 1.8 mg to 1.2 mg due to a cost-savings initiative resulted in a HbA_1c increase of 0.5% in a 6-month period. Due to HbA1c increases, 41.2% of veterans underwent an insulin dose increase, negating the insulin-sparing role of liraglutide. Although this study further confirms the dose-dependent HbA_1c reduction with liraglutide that has been noted in previous trials, long-term prospective studies and cost-effectiveness analyses are warranted to assess the overall clinical significance and other benefits of the change, including its effects on cardiovascular outcomes.

Editor’s Note: This transcript from the October 7 episode of Psychcast and the October 8 episode of Blood & Cancer has been edited for clarity.

David Henry, MD: Welcome to this episode of Blood And Cancer. I’m your host, Dr. David Henry, and I’m joined today by another host in the MDedge family, Dr. Lorenzo Norris, who is the host of MDedge Psychcast on MDedge.com or wherever you get your podcasts. He is associate dean of student affairs and administration at the George Washington School of Medicine in Washington, DC. Dr. Norris, thank you so much for taking the time to do this today.

Dr. Norris: CBT in a nutshell -- how you think influences greatly your emotions, which influences your behavior. Very simple and very powerful. With breast cancer, as an example, patients are dealing with a great deal of stress. They are literally fighting for their lives.

And that’s going to allow you to actually think about or to screen for patients that you’re going to need to refer for treatment. So if you have a patient with advanced cancer, as an example, and you use the PHQ-2 or PHQ-9, then that’s going to give you a very evidence-based avenue in which to refer for treatment. Now you may be asking yourself, maybe I don’t want to use a PHQ-2 or 9, or I’m in a community practice or a private practice, I just don’t have the bandwidth to process this.

So I want to go off of just my own patient interaction. What are things that I can cue on?

With a patient with cancer, there’s going to be roughly four things that we’re considering in terms of depressive spectrum disorders: Adjustment disorder with depressed mood, major depression, a mood disorder due to cancer itself, or substance-induced mood disorder.

For our audience I want you to concentrate on right now on adjustment disorder with depressed mood and major depression. Now when you look at the evidence, there are roughly nine things that some people like to think about in regard to depressive symptoms to key on. For all of us as health practitioners, these are the things I would like for you to focus on in particular:

1. Non-adherence with treatment for cancer.

2. Impairment of their social or occupational function.

3. Your patient becomes demoralized when they start to lose a little bit of confidence or hope.

When you have those three things, or any one of them, in an advanced stage of cancer, with or without a PHQ screening, you need to really think about how you’re going to refer this patient for treatment. So we can break this down into three different types of interventions. One, the biggest thing, is just to ask, “How are you feeling? What is your mood? Are you suffering from a clinical depression?” You know, take a little bit of inspiration from Dr. Henry. Just give it to people straight and just ask. That’s the biggest thing people don’t do. They don’t ask.

The next thing, if you want to use an evidence-based scale, use a PHQ-2...You would have to follow up, but you-- rather you’re practicing solo or in a group practice or whether you have, your nurse or PA -- they generally assist with that.

And then the third thing is, when you’re interacting with the patient, look for those three things that I talked about: Non-adherence with treatment, impairment of social or occupational function, and then demoralization.

And then the final thing I want to focus on, because you can’t talk about depression without talking about suicide or really significant distress. Obviously, you can ask and you should ask about suicide if that is in your wheelhouse, but to be perfectly frank, most oncologists are not going to-- or most people outside of psychiatrists aren’t going to necessarily just routinely ask that question.

But here’s what I would say. It’s an old one but it’s a good one: Listen to that little voice. Listen to that little voice, all right? Depending on the evidence that you look at, a lot of detecting suicide can be aided by a clinician listening to their own gut instincts. What I mean by that is, you feel a sense of distress. You feel a sense of lack of connection. You find yourself [saying], “Wait a minute, why do I want to call that patient and checkup? Why do I want to reach out?”

When you start to feel like this, you need to listen. More importantly, you need to stop and then you need to make sure that that patient has a referral in place.

Dr. Henry: So they’re just tuning out so badly, you’re really losing the connection, and that’s when your little voice talks to you.

Dr. Norris: Exactly. Well said, Dr. Henry. Well said.

Dr. Henry: In my long career, drug abuse, narcotics, and suicide have been extremely rare. I can think of one patient who was a drug abuser with cancer, or it turned out she was a drug abuser before she had cancer. And then suicide, really quite rare. I’m sure they occur, and we have to watch for them, as you say, but fortunately I’ve not seen that so much. Thanks to your comments, I want to be sure I’m watching and looking.

And the PHQ-2 and -9, I’m sure, with so many of us having electronic medical records, you can simply Google while you’re talking to the patient for those two questionnaires and say, oh, you know, how about you answer these two questions, these nine questions, and see how many points the patient gets and worry about referral or even medication yourself if it looks like an antidepressant is in order.

Dr. Norris: Absolutely. Absolutely.

Dr. Henry: Well, I think we’ve covered an awful lot of ground. I really want to thank you. Any get-away thoughts? We worry about the cognitive behavioral therapy. We worry about it, and we should listen to it and do it.

Practicing in the COVID era is stressful for all of us. I told Dr. Norris at the outset, if I broke down and started baring my soul, he wouldn’t be surprised. Fortunately, I’ve kept it together while talking to a psychiatrist.

And finally watch for clinically significant depression, either by your own questions, which you’ve outlined, or the PHQ-2 and -9.

Really appreciate your thoughts today. Lorenzo, thanks so much for taking the time to do this today.


To hear the entire conversation, go to mdedge.com/podcasts or listen wherever you find your podcasts. David Henry, MD, is a clinical professor of medicine at the University of Pennsylvania and vice chairman of the department of medicine at Pennsylvania Hospital in Philadelphia. He is editor in chief of MDedge Hematology-Oncology and the host of the Blood & Cancer podcast. Dr. Henry reported being on the advisory board for Amgen, AMAG Pharmaceuticals, and Pharmacosmos. He reported institutional funding from the National Institutes of Health and FibroGen.

Lorenzo Norris, MD, is host of the MDedge Psychcast, editor in chief of MDedge Psychiatry, and assistant professor of psychiatry and behavioral sciences at George Washington University, Washington. He also serves as assistant dean of student affairs at the university, and medical director of psychiatric and behavioral sciences at GWU Hospital. Dr. Lorenzo Norris has no conflicts.

Editor’s Note: This transcript from the October 7 episode of Psychcast and the October 8 episode of Blood & Cancer has been edited for clarity.

David Henry, MD: Welcome to this episode of Blood And Cancer. I’m your host, Dr. David Henry, and I’m joined today by another host in the MDedge family, Dr. Lorenzo Norris, who is the host of MDedge Psychcast on MDedge.com or wherever you get your podcasts. He is associate dean of student affairs and administration at the George Washington School of Medicine in Washington, DC. Dr. Norris, thank you so much for taking the time to do this today.

Dr. Norris: CBT in a nutshell -- how you think influences greatly your emotions, which influences your behavior. Very simple and very powerful. With breast cancer, as an example, patients are dealing with a great deal of stress. They are literally fighting for their lives.

And that’s going to allow you to actually think about or to screen for patients that you’re going to need to refer for treatment. So if you have a patient with advanced cancer, as an example, and you use the PHQ-2 or PHQ-9, then that’s going to give you a very evidence-based avenue in which to refer for treatment. Now you may be asking yourself, maybe I don’t want to use a PHQ-2 or 9, or I’m in a community practice or a private practice, I just don’t have the bandwidth to process this.

So I want to go off of just my own patient interaction. What are things that I can cue on?

With a patient with cancer, there’s going to be roughly four things that we’re considering in terms of depressive spectrum disorders: Adjustment disorder with depressed mood, major depression, a mood disorder due to cancer itself, or substance-induced mood disorder.

For our audience I want you to concentrate on right now on adjustment disorder with depressed mood and major depression. Now when you look at the evidence, there are roughly nine things that some people like to think about in regard to depressive symptoms to key on. For all of us as health practitioners, these are the things I would like for you to focus on in particular:

1. Non-adherence with treatment for cancer.

2. Impairment of their social or occupational function.

3. Your patient becomes demoralized when they start to lose a little bit of confidence or hope.

When you have those three things, or any one of them, in an advanced stage of cancer, with or without a PHQ screening, you need to really think about how you’re going to refer this patient for treatment. So we can break this down into three different types of interventions. One, the biggest thing, is just to ask, “How are you feeling? What is your mood? Are you suffering from a clinical depression?” You know, take a little bit of inspiration from Dr. Henry. Just give it to people straight and just ask. That’s the biggest thing people don’t do. They don’t ask.

The next thing, if you want to use an evidence-based scale, use a PHQ-2...You would have to follow up, but you-- rather you’re practicing solo or in a group practice or whether you have, your nurse or PA -- they generally assist with that.

And then the third thing is, when you’re interacting with the patient, look for those three things that I talked about: Non-adherence with treatment, impairment of social or occupational function, and then demoralization.

And then the final thing I want to focus on, because you can’t talk about depression without talking about suicide or really significant distress. Obviously, you can ask and you should ask about suicide if that is in your wheelhouse, but to be perfectly frank, most oncologists are not going to-- or most people outside of psychiatrists aren’t going to necessarily just routinely ask that question.

But here’s what I would say. It’s an old one but it’s a good one: Listen to that little voice. Listen to that little voice, all right? Depending on the evidence that you look at, a lot of detecting suicide can be aided by a clinician listening to their own gut instincts. What I mean by that is, you feel a sense of distress. You feel a sense of lack of connection. You find yourself [saying], “Wait a minute, why do I want to call that patient and checkup? Why do I want to reach out?”

When you start to feel like this, you need to listen. More importantly, you need to stop and then you need to make sure that that patient has a referral in place.

Dr. Henry: So they’re just tuning out so badly, you’re really losing the connection, and that’s when your little voice talks to you.

Dr. Norris: Exactly. Well said, Dr. Henry. Well said.

Dr. Henry: In my long career, drug abuse, narcotics, and suicide have been extremely rare. I can think of one patient who was a drug abuser with cancer, or it turned out she was a drug abuser before she had cancer. And then suicide, really quite rare. I’m sure they occur, and we have to watch for them, as you say, but fortunately I’ve not seen that so much. Thanks to your comments, I want to be sure I’m watching and looking.

And the PHQ-2 and -9, I’m sure, with so many of us having electronic medical records, you can simply Google while you’re talking to the patient for those two questionnaires and say, oh, you know, how about you answer these two questions, these nine questions, and see how many points the patient gets and worry about referral or even medication yourself if it looks like an antidepressant is in order.

Dr. Norris: Absolutely. Absolutely.

Dr. Henry: Well, I think we’ve covered an awful lot of ground. I really want to thank you. Any get-away thoughts? We worry about the cognitive behavioral therapy. We worry about it, and we should listen to it and do it.

Practicing in the COVID era is stressful for all of us. I told Dr. Norris at the outset, if I broke down and started baring my soul, he wouldn’t be surprised. Fortunately, I’ve kept it together while talking to a psychiatrist.

And finally watch for clinically significant depression, either by your own questions, which you’ve outlined, or the PHQ-2 and -9.

Really appreciate your thoughts today. Lorenzo, thanks so much for taking the time to do this today.


To hear the entire conversation, go to mdedge.com/podcasts or listen wherever you find your podcasts. David Henry, MD, is a clinical professor of medicine at the University of Pennsylvania and vice chairman of the department of medicine at Pennsylvania Hospital in Philadelphia. He is editor in chief of MDedge Hematology-Oncology and the host of the Blood & Cancer podcast. Dr. Henry reported being on the advisory board for Amgen, AMAG Pharmaceuticals, and Pharmacosmos. He reported institutional funding from the National Institutes of Health and FibroGen.

Lorenzo Norris, MD, is host of the MDedge Psychcast, editor in chief of MDedge Psychiatry, and assistant professor of psychiatry and behavioral sciences at George Washington University, Washington. He also serves as assistant dean of student affairs at the university, and medical director of psychiatric and behavioral sciences at GWU Hospital. Dr. Lorenzo Norris has no conflicts.

Editor’s Note: This transcript from the October 7 episode of Psychcast and the October 8 episode of Blood & Cancer has been edited for clarity.

David Henry, MD: Welcome to this episode of Blood And Cancer. I’m your host, Dr. David Henry, and I’m joined today by another host in the MDedge family, Dr. Lorenzo Norris, who is the host of MDedge Psychcast on MDedge.com or wherever you get your podcasts. He is associate dean of student affairs and administration at the George Washington School of Medicine in Washington, DC. Dr. Norris, thank you so much for taking the time to do this today.

Dr. Norris: CBT in a nutshell -- how you think influences greatly your emotions, which influences your behavior. Very simple and very powerful. With breast cancer, as an example, patients are dealing with a great deal of stress. They are literally fighting for their lives.

And that’s going to allow you to actually think about or to screen for patients that you’re going to need to refer for treatment. So if you have a patient with advanced cancer, as an example, and you use the PHQ-2 or PHQ-9, then that’s going to give you a very evidence-based avenue in which to refer for treatment. Now you may be asking yourself, maybe I don’t want to use a PHQ-2 or 9, or I’m in a community practice or a private practice, I just don’t have the bandwidth to process this.

So I want to go off of just my own patient interaction. What are things that I can cue on?

With a patient with cancer, there’s going to be roughly four things that we’re considering in terms of depressive spectrum disorders: Adjustment disorder with depressed mood, major depression, a mood disorder due to cancer itself, or substance-induced mood disorder.

For our audience I want you to concentrate on right now on adjustment disorder with depressed mood and major depression. Now when you look at the evidence, there are roughly nine things that some people like to think about in regard to depressive symptoms to key on. For all of us as health practitioners, these are the things I would like for you to focus on in particular:

1. Non-adherence with treatment for cancer.

2. Impairment of their social or occupational function.

3. Your patient becomes demoralized when they start to lose a little bit of confidence or hope.

When you have those three things, or any one of them, in an advanced stage of cancer, with or without a PHQ screening, you need to really think about how you’re going to refer this patient for treatment. So we can break this down into three different types of interventions. One, the biggest thing, is just to ask, “How are you feeling? What is your mood? Are you suffering from a clinical depression?” You know, take a little bit of inspiration from Dr. Henry. Just give it to people straight and just ask. That’s the biggest thing people don’t do. They don’t ask.

The next thing, if you want to use an evidence-based scale, use a PHQ-2...You would have to follow up, but you-- rather you’re practicing solo or in a group practice or whether you have, your nurse or PA -- they generally assist with that.

And then the third thing is, when you’re interacting with the patient, look for those three things that I talked about: Non-adherence with treatment, impairment of social or occupational function, and then demoralization.

And then the final thing I want to focus on, because you can’t talk about depression without talking about suicide or really significant distress. Obviously, you can ask and you should ask about suicide if that is in your wheelhouse, but to be perfectly frank, most oncologists are not going to-- or most people outside of psychiatrists aren’t going to necessarily just routinely ask that question.

But here’s what I would say. It’s an old one but it’s a good one: Listen to that little voice. Listen to that little voice, all right? Depending on the evidence that you look at, a lot of detecting suicide can be aided by a clinician listening to their own gut instincts. What I mean by that is, you feel a sense of distress. You feel a sense of lack of connection. You find yourself [saying], “Wait a minute, why do I want to call that patient and checkup? Why do I want to reach out?”

When you start to feel like this, you need to listen. More importantly, you need to stop and then you need to make sure that that patient has a referral in place.

Dr. Henry: So they’re just tuning out so badly, you’re really losing the connection, and that’s when your little voice talks to you.

Dr. Norris: Exactly. Well said, Dr. Henry. Well said.

Dr. Henry: In my long career, drug abuse, narcotics, and suicide have been extremely rare. I can think of one patient who was a drug abuser with cancer, or it turned out she was a drug abuser before she had cancer. And then suicide, really quite rare. I’m sure they occur, and we have to watch for them, as you say, but fortunately I’ve not seen that so much. Thanks to your comments, I want to be sure I’m watching and looking.

And the PHQ-2 and -9, I’m sure, with so many of us having electronic medical records, you can simply Google while you’re talking to the patient for those two questionnaires and say, oh, you know, how about you answer these two questions, these nine questions, and see how many points the patient gets and worry about referral or even medication yourself if it looks like an antidepressant is in order.

Dr. Norris: Absolutely. Absolutely.

Dr. Henry: Well, I think we’ve covered an awful lot of ground. I really want to thank you. Any get-away thoughts? We worry about the cognitive behavioral therapy. We worry about it, and we should listen to it and do it.

Practicing in the COVID era is stressful for all of us. I told Dr. Norris at the outset, if I broke down and started baring my soul, he wouldn’t be surprised. Fortunately, I’ve kept it together while talking to a psychiatrist.

And finally watch for clinically significant depression, either by your own questions, which you’ve outlined, or the PHQ-2 and -9.

Really appreciate your thoughts today. Lorenzo, thanks so much for taking the time to do this today.


To hear the entire conversation, go to mdedge.com/podcasts or listen wherever you find your podcasts. David Henry, MD, is a clinical professor of medicine at the University of Pennsylvania and vice chairman of the department of medicine at Pennsylvania Hospital in Philadelphia. He is editor in chief of MDedge Hematology-Oncology and the host of the Blood & Cancer podcast. Dr. Henry reported being on the advisory board for Amgen, AMAG Pharmaceuticals, and Pharmacosmos. He reported institutional funding from the National Institutes of Health and FibroGen.

Lorenzo Norris, MD, is host of the MDedge Psychcast, editor in chief of MDedge Psychiatry, and assistant professor of psychiatry and behavioral sciences at George Washington University, Washington. He also serves as assistant dean of student affairs at the university, and medical director of psychiatric and behavioral sciences at GWU Hospital. Dr. Lorenzo Norris has no conflicts.

The popular new weight-loss approach of eating within a restricted window of time during the day, allowing for an extended period of fasting – also known as intermittent fasting – does not result in greater weight loss, compared with nonrestricted meal timing, results from a randomized clinical trial show.

“I was very surprised by all of [the results],” senior author Ethan J. Weiss, MD, said in an interview.

“Part of the reason we did the study was because I had been doing time-restricted eating myself for years and even recommending it to friends and patients as an effective weight-loss tool,” said Dr. Weiss, of the Cardiovascular Research Institute, University of California, San Francisco.

“But no matter how you slice it, prescription of time-restricted eating – at least this version –is not a very effective weight-loss strategy,” Dr. Weiss said.

The study, published online in JAMA Internal Medicine by Dylan A. Lowe, PhD, also of the University of California, San Francisco, involved 116 participants who were randomized to a 12-week regimen of either three structured meals per day or time-restricted eating, with instructions to eat only between 12:00 p.m. and 8:00 p.m. and to completely abstain from eating at other times.

The participants were not given any specific instructions regarding caloric or macronutrient intake “so as to offer a simple, real-world recommendation to free-living individuals,” the authors wrote.

Although some prior research has shown improvements in measures such as glucose tolerance with time-restricted eating, studies showing weight loss with the approach, including one recently reported by Medscape Medical News, have been small and lacked control groups.

“To my knowledge this is the first randomized, controlled trial and definitely the biggest,” Dr. Weiss. “I think it is the most comprehensive dataset available in people, at least for this intervention.”
 

Participants used app to log details

At baseline, participants had a mean weight of 99.2 kg (approximately 219 lb). Their mean age was 46.5 years and 60.3% were men. They were drawn from anywhere in the United States and received study surveys through a custom mobile study application on the Eureka Research Platform. They were given a Bluetooth weight scale to use daily, which was connected with the app, and randomized to one of the two interventions. A subset of 50 participants living near San Francisco underwent in-person testing.

At the end of the 12 weeks, those in the time-restricted eating group (n = 59) did have a significant decrease in weight, compared with baseline (−0.94 kg; P = .01), while weight loss in the consistent-meal group (n = 57) was not significant (−0.68 kg; P = .07).

But importantly, the difference in weight loss between the groups was not significant (−0.26 kg; P = .63).

There were no significant differences in secondary outcomes of fasting insulin, glucose, hemoglobin A1c, or blood lipids within or between the time-restricted eating and consistent-meal group either. Nor were there any significant differences in resting metabolic rate.

Although participants did not self-report their caloric intake, the authors estimated that the differences were not significant using mathematical modeling developed at the National Institutes of Health.

Rates of adherence to the diets were 92.1% in the consistent-meal group versus 83.5% in the time-restricted group.
 

Not all diets are equal: Time-restricted eating group lost more lean mass

In a subset analysis, loss of lean mass was significantly greater in the time-restricted eating group, compared with the consistent-meals group, in terms of both appendicular lean mass (P = .009) and the appendicular lean mass index (P = .005).

In fact, as much as 65% of the weight lost (1.10 kg of the average 1.70 kg) in the time-restricted eating group consisted of lean mass, while much less was fat mass (0.51 kg).

“The proportion of lean mass loss in this study (approximately 65%) far exceeds the normal range of 20%-30%,” the authors wrote. “In addition, there was a highly significant between-group difference in appendicular lean mass.”

Appendicular lean mass correlates with nutritional and physical status, and its reduction can lead to weakness, disability, and impaired quality of life.

“This serves as a caution for patient populations at risk for sarcopenia because time-restricted eating could exacerbate muscle loss,” the authors asserted.

Furthermore, previous studies suggest that the loss of lean mass in such studies is positively linked with weight regain.

While a limitation of the work is that self-reported measures of energy or macronutrient or protein intake were not obtained, the authors speculated that the role of protein intake could be linked to the greater loss of lean mass.

“Given the loss of appendicular lean mass in participants in the time-restricted eating arm and previous reports of decreased protein consumption from time-restricted eating, it is possible that protein intake was altered by time-restricted eating in this cohort, and this clearly warrants future study,” they wrote.

Dr. Weiss said the findings underscore that not all weight loss in dieting is beneficial.

“Losing 1 kg of lean mass (is not equal) to a kilogram of fat,” he said. “Indeed, if one loses 0.65 kg of lean mass and only 0.35 kg of fat mass, that is an intervention I’d probably pass on.”
 

Time-restricted eating is popular, perhaps because it’s easy?

Time-restricted eating has gained popularity in recent years.

The approach “is attractive as a weight-loss option in that it does not require tedious and time-consuming methods such as calorie counting or adherence to complicated diets,” the authors noted. “Indeed, we found that self-reported adherence to the time-restricted eating schedule was high; however, in contrast to our hypothesis, there was no greater weight loss with time-restricted eating compared with the consistent meal timing.”

They explain that the 12 p.m. to 8 p.m. window for eating was chosen because they thought people might find it easier culturally to skip breakfast than dinner, the more social meal.

However, an 8 p.m. cutoff is somewhat late given there is some suggestion that fasting several hours before bedtime is most beneficial, Dr. Weiss noted. So it may be worth examining different time windows.

“I am very intrigued about looking at early time-restricted eating – 6 a.m. to 2 p.m.,” for example, he said. “It is on our list.”

Meanwhile, the study results support previous research showing no effect on weight outcomes in relation to skipping breakfast.

The study received funding from the UCSF cardiology division’s Cardiology Innovations Award Program and the National Institute of Diabetes and Digestive and Kidney Diseases, with additional support from the James Peter Read Foundation. Dr. Weiss has reported nonfinancial support from Mocacare and nonfinancial support from iHealth Labs during the conduct of the study. He also is a cofounder and equity stakeholder of Keyto, and owns stock and was formerly on the board of Virta.

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

The popular new weight-loss approach of eating within a restricted window of time during the day, allowing for an extended period of fasting – also known as intermittent fasting – does not result in greater weight loss, compared with nonrestricted meal timing, results from a randomized clinical trial show.

“I was very surprised by all of [the results],” senior author Ethan J. Weiss, MD, said in an interview.

“Part of the reason we did the study was because I had been doing time-restricted eating myself for years and even recommending it to friends and patients as an effective weight-loss tool,” said Dr. Weiss, of the Cardiovascular Research Institute, University of California, San Francisco.

“But no matter how you slice it, prescription of time-restricted eating – at least this version –is not a very effective weight-loss strategy,” Dr. Weiss said.

The study, published online in JAMA Internal Medicine by Dylan A. Lowe, PhD, also of the University of California, San Francisco, involved 116 participants who were randomized to a 12-week regimen of either three structured meals per day or time-restricted eating, with instructions to eat only between 12:00 p.m. and 8:00 p.m. and to completely abstain from eating at other times.

The participants were not given any specific instructions regarding caloric or macronutrient intake “so as to offer a simple, real-world recommendation to free-living individuals,” the authors wrote.

Although some prior research has shown improvements in measures such as glucose tolerance with time-restricted eating, studies showing weight loss with the approach, including one recently reported by Medscape Medical News, have been small and lacked control groups.

“To my knowledge this is the first randomized, controlled trial and definitely the biggest,” Dr. Weiss. “I think it is the most comprehensive dataset available in people, at least for this intervention.”
 

Participants used app to log details

At baseline, participants had a mean weight of 99.2 kg (approximately 219 lb). Their mean age was 46.5 years and 60.3% were men. They were drawn from anywhere in the United States and received study surveys through a custom mobile study application on the Eureka Research Platform. They were given a Bluetooth weight scale to use daily, which was connected with the app, and randomized to one of the two interventions. A subset of 50 participants living near San Francisco underwent in-person testing.

At the end of the 12 weeks, those in the time-restricted eating group (n = 59) did have a significant decrease in weight, compared with baseline (−0.94 kg; P = .01), while weight loss in the consistent-meal group (n = 57) was not significant (−0.68 kg; P = .07).

But importantly, the difference in weight loss between the groups was not significant (−0.26 kg; P = .63).

There were no significant differences in secondary outcomes of fasting insulin, glucose, hemoglobin A1c, or blood lipids within or between the time-restricted eating and consistent-meal group either. Nor were there any significant differences in resting metabolic rate.

Although participants did not self-report their caloric intake, the authors estimated that the differences were not significant using mathematical modeling developed at the National Institutes of Health.

Rates of adherence to the diets were 92.1% in the consistent-meal group versus 83.5% in the time-restricted group.
 

Not all diets are equal: Time-restricted eating group lost more lean mass

In a subset analysis, loss of lean mass was significantly greater in the time-restricted eating group, compared with the consistent-meals group, in terms of both appendicular lean mass (P = .009) and the appendicular lean mass index (P = .005).

In fact, as much as 65% of the weight lost (1.10 kg of the average 1.70 kg) in the time-restricted eating group consisted of lean mass, while much less was fat mass (0.51 kg).

“The proportion of lean mass loss in this study (approximately 65%) far exceeds the normal range of 20%-30%,” the authors wrote. “In addition, there was a highly significant between-group difference in appendicular lean mass.”

Appendicular lean mass correlates with nutritional and physical status, and its reduction can lead to weakness, disability, and impaired quality of life.

“This serves as a caution for patient populations at risk for sarcopenia because time-restricted eating could exacerbate muscle loss,” the authors asserted.

Furthermore, previous studies suggest that the loss of lean mass in such studies is positively linked with weight regain.

While a limitation of the work is that self-reported measures of energy or macronutrient or protein intake were not obtained, the authors speculated that the role of protein intake could be linked to the greater loss of lean mass.

“Given the loss of appendicular lean mass in participants in the time-restricted eating arm and previous reports of decreased protein consumption from time-restricted eating, it is possible that protein intake was altered by time-restricted eating in this cohort, and this clearly warrants future study,” they wrote.

Dr. Weiss said the findings underscore that not all weight loss in dieting is beneficial.

“Losing 1 kg of lean mass (is not equal) to a kilogram of fat,” he said. “Indeed, if one loses 0.65 kg of lean mass and only 0.35 kg of fat mass, that is an intervention I’d probably pass on.”
 

Time-restricted eating is popular, perhaps because it’s easy?

Time-restricted eating has gained popularity in recent years.

The approach “is attractive as a weight-loss option in that it does not require tedious and time-consuming methods such as calorie counting or adherence to complicated diets,” the authors noted. “Indeed, we found that self-reported adherence to the time-restricted eating schedule was high; however, in contrast to our hypothesis, there was no greater weight loss with time-restricted eating compared with the consistent meal timing.”

They explain that the 12 p.m. to 8 p.m. window for eating was chosen because they thought people might find it easier culturally to skip breakfast than dinner, the more social meal.

However, an 8 p.m. cutoff is somewhat late given there is some suggestion that fasting several hours before bedtime is most beneficial, Dr. Weiss noted. So it may be worth examining different time windows.

“I am very intrigued about looking at early time-restricted eating – 6 a.m. to 2 p.m.,” for example, he said. “It is on our list.”

Meanwhile, the study results support previous research showing no effect on weight outcomes in relation to skipping breakfast.

The study received funding from the UCSF cardiology division’s Cardiology Innovations Award Program and the National Institute of Diabetes and Digestive and Kidney Diseases, with additional support from the James Peter Read Foundation. Dr. Weiss has reported nonfinancial support from Mocacare and nonfinancial support from iHealth Labs during the conduct of the study. He also is a cofounder and equity stakeholder of Keyto, and owns stock and was formerly on the board of Virta.

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

The popular new weight-loss approach of eating within a restricted window of time during the day, allowing for an extended period of fasting – also known as intermittent fasting – does not result in greater weight loss, compared with nonrestricted meal timing, results from a randomized clinical trial show.

“I was very surprised by all of [the results],” senior author Ethan J. Weiss, MD, said in an interview.

“Part of the reason we did the study was because I had been doing time-restricted eating myself for years and even recommending it to friends and patients as an effective weight-loss tool,” said Dr. Weiss, of the Cardiovascular Research Institute, University of California, San Francisco.

“But no matter how you slice it, prescription of time-restricted eating – at least this version –is not a very effective weight-loss strategy,” Dr. Weiss said.

The study, published online in JAMA Internal Medicine by Dylan A. Lowe, PhD, also of the University of California, San Francisco, involved 116 participants who were randomized to a 12-week regimen of either three structured meals per day or time-restricted eating, with instructions to eat only between 12:00 p.m. and 8:00 p.m. and to completely abstain from eating at other times.

The participants were not given any specific instructions regarding caloric or macronutrient intake “so as to offer a simple, real-world recommendation to free-living individuals,” the authors wrote.

Although some prior research has shown improvements in measures such as glucose tolerance with time-restricted eating, studies showing weight loss with the approach, including one recently reported by Medscape Medical News, have been small and lacked control groups.

“To my knowledge this is the first randomized, controlled trial and definitely the biggest,” Dr. Weiss. “I think it is the most comprehensive dataset available in people, at least for this intervention.”
 

Participants used app to log details

At baseline, participants had a mean weight of 99.2 kg (approximately 219 lb). Their mean age was 46.5 years and 60.3% were men. They were drawn from anywhere in the United States and received study surveys through a custom mobile study application on the Eureka Research Platform. They were given a Bluetooth weight scale to use daily, which was connected with the app, and randomized to one of the two interventions. A subset of 50 participants living near San Francisco underwent in-person testing.

At the end of the 12 weeks, those in the time-restricted eating group (n = 59) did have a significant decrease in weight, compared with baseline (−0.94 kg; P = .01), while weight loss in the consistent-meal group (n = 57) was not significant (−0.68 kg; P = .07).

But importantly, the difference in weight loss between the groups was not significant (−0.26 kg; P = .63).

There were no significant differences in secondary outcomes of fasting insulin, glucose, hemoglobin A1c, or blood lipids within or between the time-restricted eating and consistent-meal group either. Nor were there any significant differences in resting metabolic rate.

Although participants did not self-report their caloric intake, the authors estimated that the differences were not significant using mathematical modeling developed at the National Institutes of Health.

Rates of adherence to the diets were 92.1% in the consistent-meal group versus 83.5% in the time-restricted group.
 

Not all diets are equal: Time-restricted eating group lost more lean mass

In a subset analysis, loss of lean mass was significantly greater in the time-restricted eating group, compared with the consistent-meals group, in terms of both appendicular lean mass (P = .009) and the appendicular lean mass index (P = .005).

In fact, as much as 65% of the weight lost (1.10 kg of the average 1.70 kg) in the time-restricted eating group consisted of lean mass, while much less was fat mass (0.51 kg).

“The proportion of lean mass loss in this study (approximately 65%) far exceeds the normal range of 20%-30%,” the authors wrote. “In addition, there was a highly significant between-group difference in appendicular lean mass.”

Appendicular lean mass correlates with nutritional and physical status, and its reduction can lead to weakness, disability, and impaired quality of life.

“This serves as a caution for patient populations at risk for sarcopenia because time-restricted eating could exacerbate muscle loss,” the authors asserted.

Furthermore, previous studies suggest that the loss of lean mass in such studies is positively linked with weight regain.

While a limitation of the work is that self-reported measures of energy or macronutrient or protein intake were not obtained, the authors speculated that the role of protein intake could be linked to the greater loss of lean mass.

“Given the loss of appendicular lean mass in participants in the time-restricted eating arm and previous reports of decreased protein consumption from time-restricted eating, it is possible that protein intake was altered by time-restricted eating in this cohort, and this clearly warrants future study,” they wrote.

Dr. Weiss said the findings underscore that not all weight loss in dieting is beneficial.

“Losing 1 kg of lean mass (is not equal) to a kilogram of fat,” he said. “Indeed, if one loses 0.65 kg of lean mass and only 0.35 kg of fat mass, that is an intervention I’d probably pass on.”
 

Time-restricted eating is popular, perhaps because it’s easy?

Time-restricted eating has gained popularity in recent years.

The approach “is attractive as a weight-loss option in that it does not require tedious and time-consuming methods such as calorie counting or adherence to complicated diets,” the authors noted. “Indeed, we found that self-reported adherence to the time-restricted eating schedule was high; however, in contrast to our hypothesis, there was no greater weight loss with time-restricted eating compared with the consistent meal timing.”

They explain that the 12 p.m. to 8 p.m. window for eating was chosen because they thought people might find it easier culturally to skip breakfast than dinner, the more social meal.

However, an 8 p.m. cutoff is somewhat late given there is some suggestion that fasting several hours before bedtime is most beneficial, Dr. Weiss noted. So it may be worth examining different time windows.

“I am very intrigued about looking at early time-restricted eating – 6 a.m. to 2 p.m.,” for example, he said. “It is on our list.”

Meanwhile, the study results support previous research showing no effect on weight outcomes in relation to skipping breakfast.

The study received funding from the UCSF cardiology division’s Cardiology Innovations Award Program and the National Institute of Diabetes and Digestive and Kidney Diseases, with additional support from the James Peter Read Foundation. Dr. Weiss has reported nonfinancial support from Mocacare and nonfinancial support from iHealth Labs during the conduct of the study. He also is a cofounder and equity stakeholder of Keyto, and owns stock and was formerly on the board of Virta.

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

Patients given antibiotics for appendicitis fared no worse in quality of life, at least in the short term, than did patients whose appendix was removed, according to a large, randomized, nonblinded, noninferiority study published online Oct. 5 in The New England Journal of Medicine.

One expert says the body of data, including this trial, indicates that the best appendicitis treatment now comes down to individual patients and choice.

David Flum, MD, director of the Surgical Outcomes Research Center at the University of Washington in Seattle, and colleagues conducted the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial, which compared a 10-day course of antibiotics with appendectomy for patients with appendicitis at 25 US centers.

Although some may interpret the study as praising the potential role of antibiotics, the author of an accompanying editorial warns against rushing to antibiotics, even during a pandemic when hospital resources may be strained.

In the study of 1552 adults (414 with an appendicolith), 776 were randomly assigned to the antibiotics group and 776 to appendectomy (96% of whom underwent a laparoscopic procedure).

After 30 days, antibiotics were found to be noninferior to appendectomy, the standard of treatment for 120 years, as determined on the basis of 30-day scores for the European Quality of Life–5 Dimensions (EQ-5D) questionnaire (mean difference, 0.01 points; 95% CI, −0.001 to 0.03).

EQ-5D at 30 days was chosen as the primary endpoint because it has been validated as an overall measure of health after appendicitis treatment and the 30-day time frame mimics the typical recovery period for appendectomy, Flum and colleagues explain.
 

Some results favored appendectomy

However, editorialist Danny Jacobs, MD, MPH, president of Oregon Health and Science University in Portland, points out that about a third (29%) of the patients in the antibiotics group had undergone appendectomy by 90 days.

Appendicolith, a well-established potential complication, he acknowledges, was the main driver of the need for surgery (41% with that complication needed appendectomy), but it was not the sole reason.

Complications were more common in the antibiotics group than in the appendectomy group (8.1 vs 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 – 3.98). The rate of serious adverse events was 4.0 per 100 participants in the antibiotics group and 3.0 per 100 participants in the appendectomy group (rate ratio, 1.29; 95% CI, 0.67 – 2.50). Additionally, the number of emergency department visits was nearly three times higher in the antibiotics group, and more time was spent in the hospital by that group, Jacobs points out.

He notes that the article mentions circumstances such as the COVID-19 pandemic may figure into consideration when weighing antibiotics against appendectomy. But he warns that there also may be a danger of treatment bias in vulnerable populations and that COVID-19 has highlighted disparities in care overall.

“It will be important to ensure that some people, in particular vulnerable populations, are not offered antibiotic therapy preferentially or without adequate education regarding the longer-term implications,” Jacobs writes.

Flum told Medscape Medical News he agrees with Jacobs that the potential for bias is important.

“We should all be worried that new healthcare options won’t be equally applied,” he said.

But he and his coauthors offer an alternative view of the results of the study.

“In the antibiotics group,” they write, “more than 7 in 10 participants avoided surgery, many were treated on an outpatient basis, and participants and caregivers missed less time at work than with appendectomy.”

Flum said, “[T]hat’s going to be attractive to some patients. Not all, but some.”

Douglas Smink, MD, MPH, chief of surgery at Brigham and Women’s Faulkner Hospital in Boston, told Medscape Medical News that he sees this study as an argument for surgery remaining the go-to option for appendicitis, unless there is a safety reason for not performing the surgery.

Patients come in and want their appendix out immediately, he said, and surgery offers a quick option with short length of stay and few complications.

Additionally, he said, if patients are told that, with antibiotics, “there’s a 1 in 3 chance you’re going to need [an appendectomy] in the next 3 months, I think most people would say, ‘Just take it out then,’ ” he said.
 

Can research decide which is best?

The controversy has been well studied. But with no clear answer in any of the studies about whether appendectomy or use of antibiotics is better, should the current study put the research to rest?

Flum told Medscape Medical News that this study, which is three times the size of the next-largest study, makes clear “there are choices.”

Previous trials in Europe “did not move the needle” on the issue, he said, “in part because they didn’t include the patients who typically get appendectomies.”

He said their team tried to build on those studies and include “typical patients in typical hospitals with typical appendicitis” and found that both surgery and antibiotics are safe and have advantages and disadvantages, depending on the patient.

Smink says one thing that has been definitively answered with this trial is that patients with appendicolith are “more likely to fail with antibiotics.”

Previous trials have excluded patients with appendicolith, and this one did not.

“That’s something we’ve not really known for sure but we’ve assumed,” he said.

But now, Smink says, he thinks the research on the topic has gone about as far as it can go.

He notes that none of the trials has shown antibiotics to be better than appendectomy. “I have a hard time believing we are going to find anything different if we did another study like this. This is a really well-done one,” he said.

“If the best you can do is show noninferiority, which is where we are with these studies on appendicitis, you’re always going to have both options, which is great for patients and doctors,” he said.

The study was funded by the Patient-Centered Outcomes Research Institute. The original article lists the authors’ relevant financial relationships. Jacobs and Smink reported no such relationships.
 

This article first appeared on Medscape.com.

Patients given antibiotics for appendicitis fared no worse in quality of life, at least in the short term, than did patients whose appendix was removed, according to a large, randomized, nonblinded, noninferiority study published online Oct. 5 in The New England Journal of Medicine.

One expert says the body of data, including this trial, indicates that the best appendicitis treatment now comes down to individual patients and choice.

David Flum, MD, director of the Surgical Outcomes Research Center at the University of Washington in Seattle, and colleagues conducted the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial, which compared a 10-day course of antibiotics with appendectomy for patients with appendicitis at 25 US centers.

Although some may interpret the study as praising the potential role of antibiotics, the author of an accompanying editorial warns against rushing to antibiotics, even during a pandemic when hospital resources may be strained.

In the study of 1552 adults (414 with an appendicolith), 776 were randomly assigned to the antibiotics group and 776 to appendectomy (96% of whom underwent a laparoscopic procedure).

After 30 days, antibiotics were found to be noninferior to appendectomy, the standard of treatment for 120 years, as determined on the basis of 30-day scores for the European Quality of Life–5 Dimensions (EQ-5D) questionnaire (mean difference, 0.01 points; 95% CI, −0.001 to 0.03).

EQ-5D at 30 days was chosen as the primary endpoint because it has been validated as an overall measure of health after appendicitis treatment and the 30-day time frame mimics the typical recovery period for appendectomy, Flum and colleagues explain.
 

Some results favored appendectomy

However, editorialist Danny Jacobs, MD, MPH, president of Oregon Health and Science University in Portland, points out that about a third (29%) of the patients in the antibiotics group had undergone appendectomy by 90 days.

Appendicolith, a well-established potential complication, he acknowledges, was the main driver of the need for surgery (41% with that complication needed appendectomy), but it was not the sole reason.

Complications were more common in the antibiotics group than in the appendectomy group (8.1 vs 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 – 3.98). The rate of serious adverse events was 4.0 per 100 participants in the antibiotics group and 3.0 per 100 participants in the appendectomy group (rate ratio, 1.29; 95% CI, 0.67 – 2.50). Additionally, the number of emergency department visits was nearly three times higher in the antibiotics group, and more time was spent in the hospital by that group, Jacobs points out.

He notes that the article mentions circumstances such as the COVID-19 pandemic may figure into consideration when weighing antibiotics against appendectomy. But he warns that there also may be a danger of treatment bias in vulnerable populations and that COVID-19 has highlighted disparities in care overall.

“It will be important to ensure that some people, in particular vulnerable populations, are not offered antibiotic therapy preferentially or without adequate education regarding the longer-term implications,” Jacobs writes.

Flum told Medscape Medical News he agrees with Jacobs that the potential for bias is important.

“We should all be worried that new healthcare options won’t be equally applied,” he said.

But he and his coauthors offer an alternative view of the results of the study.

“In the antibiotics group,” they write, “more than 7 in 10 participants avoided surgery, many were treated on an outpatient basis, and participants and caregivers missed less time at work than with appendectomy.”

Flum said, “[T]hat’s going to be attractive to some patients. Not all, but some.”

Douglas Smink, MD, MPH, chief of surgery at Brigham and Women’s Faulkner Hospital in Boston, told Medscape Medical News that he sees this study as an argument for surgery remaining the go-to option for appendicitis, unless there is a safety reason for not performing the surgery.

Patients come in and want their appendix out immediately, he said, and surgery offers a quick option with short length of stay and few complications.

Additionally, he said, if patients are told that, with antibiotics, “there’s a 1 in 3 chance you’re going to need [an appendectomy] in the next 3 months, I think most people would say, ‘Just take it out then,’ ” he said.
 

Can research decide which is best?

The controversy has been well studied. But with no clear answer in any of the studies about whether appendectomy or use of antibiotics is better, should the current study put the research to rest?

Flum told Medscape Medical News that this study, which is three times the size of the next-largest study, makes clear “there are choices.”

Previous trials in Europe “did not move the needle” on the issue, he said, “in part because they didn’t include the patients who typically get appendectomies.”

He said their team tried to build on those studies and include “typical patients in typical hospitals with typical appendicitis” and found that both surgery and antibiotics are safe and have advantages and disadvantages, depending on the patient.

Smink says one thing that has been definitively answered with this trial is that patients with appendicolith are “more likely to fail with antibiotics.”

Previous trials have excluded patients with appendicolith, and this one did not.

“That’s something we’ve not really known for sure but we’ve assumed,” he said.

But now, Smink says, he thinks the research on the topic has gone about as far as it can go.

He notes that none of the trials has shown antibiotics to be better than appendectomy. “I have a hard time believing we are going to find anything different if we did another study like this. This is a really well-done one,” he said.

“If the best you can do is show noninferiority, which is where we are with these studies on appendicitis, you’re always going to have both options, which is great for patients and doctors,” he said.

The study was funded by the Patient-Centered Outcomes Research Institute. The original article lists the authors’ relevant financial relationships. Jacobs and Smink reported no such relationships.
 

This article first appeared on Medscape.com.

Patients given antibiotics for appendicitis fared no worse in quality of life, at least in the short term, than did patients whose appendix was removed, according to a large, randomized, nonblinded, noninferiority study published online Oct. 5 in The New England Journal of Medicine.

One expert says the body of data, including this trial, indicates that the best appendicitis treatment now comes down to individual patients and choice.

David Flum, MD, director of the Surgical Outcomes Research Center at the University of Washington in Seattle, and colleagues conducted the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial, which compared a 10-day course of antibiotics with appendectomy for patients with appendicitis at 25 US centers.

Although some may interpret the study as praising the potential role of antibiotics, the author of an accompanying editorial warns against rushing to antibiotics, even during a pandemic when hospital resources may be strained.

In the study of 1552 adults (414 with an appendicolith), 776 were randomly assigned to the antibiotics group and 776 to appendectomy (96% of whom underwent a laparoscopic procedure).

After 30 days, antibiotics were found to be noninferior to appendectomy, the standard of treatment for 120 years, as determined on the basis of 30-day scores for the European Quality of Life–5 Dimensions (EQ-5D) questionnaire (mean difference, 0.01 points; 95% CI, −0.001 to 0.03).

EQ-5D at 30 days was chosen as the primary endpoint because it has been validated as an overall measure of health after appendicitis treatment and the 30-day time frame mimics the typical recovery period for appendectomy, Flum and colleagues explain.
 

Some results favored appendectomy

However, editorialist Danny Jacobs, MD, MPH, president of Oregon Health and Science University in Portland, points out that about a third (29%) of the patients in the antibiotics group had undergone appendectomy by 90 days.

Appendicolith, a well-established potential complication, he acknowledges, was the main driver of the need for surgery (41% with that complication needed appendectomy), but it was not the sole reason.

Complications were more common in the antibiotics group than in the appendectomy group (8.1 vs 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 – 3.98). The rate of serious adverse events was 4.0 per 100 participants in the antibiotics group and 3.0 per 100 participants in the appendectomy group (rate ratio, 1.29; 95% CI, 0.67 – 2.50). Additionally, the number of emergency department visits was nearly three times higher in the antibiotics group, and more time was spent in the hospital by that group, Jacobs points out.

He notes that the article mentions circumstances such as the COVID-19 pandemic may figure into consideration when weighing antibiotics against appendectomy. But he warns that there also may be a danger of treatment bias in vulnerable populations and that COVID-19 has highlighted disparities in care overall.

“It will be important to ensure that some people, in particular vulnerable populations, are not offered antibiotic therapy preferentially or without adequate education regarding the longer-term implications,” Jacobs writes.

Flum told Medscape Medical News he agrees with Jacobs that the potential for bias is important.

“We should all be worried that new healthcare options won’t be equally applied,” he said.

But he and his coauthors offer an alternative view of the results of the study.

“In the antibiotics group,” they write, “more than 7 in 10 participants avoided surgery, many were treated on an outpatient basis, and participants and caregivers missed less time at work than with appendectomy.”

Flum said, “[T]hat’s going to be attractive to some patients. Not all, but some.”

Douglas Smink, MD, MPH, chief of surgery at Brigham and Women’s Faulkner Hospital in Boston, told Medscape Medical News that he sees this study as an argument for surgery remaining the go-to option for appendicitis, unless there is a safety reason for not performing the surgery.

Patients come in and want their appendix out immediately, he said, and surgery offers a quick option with short length of stay and few complications.

Additionally, he said, if patients are told that, with antibiotics, “there’s a 1 in 3 chance you’re going to need [an appendectomy] in the next 3 months, I think most people would say, ‘Just take it out then,’ ” he said.
 

Can research decide which is best?

The controversy has been well studied. But with no clear answer in any of the studies about whether appendectomy or use of antibiotics is better, should the current study put the research to rest?

Flum told Medscape Medical News that this study, which is three times the size of the next-largest study, makes clear “there are choices.”

Previous trials in Europe “did not move the needle” on the issue, he said, “in part because they didn’t include the patients who typically get appendectomies.”

He said their team tried to build on those studies and include “typical patients in typical hospitals with typical appendicitis” and found that both surgery and antibiotics are safe and have advantages and disadvantages, depending on the patient.

Smink says one thing that has been definitively answered with this trial is that patients with appendicolith are “more likely to fail with antibiotics.”

Previous trials have excluded patients with appendicolith, and this one did not.

“That’s something we’ve not really known for sure but we’ve assumed,” he said.

But now, Smink says, he thinks the research on the topic has gone about as far as it can go.

He notes that none of the trials has shown antibiotics to be better than appendectomy. “I have a hard time believing we are going to find anything different if we did another study like this. This is a really well-done one,” he said.

“If the best you can do is show noninferiority, which is where we are with these studies on appendicitis, you’re always going to have both options, which is great for patients and doctors,” he said.

The study was funded by the Patient-Centered Outcomes Research Institute. The original article lists the authors’ relevant financial relationships. Jacobs and Smink reported no such relationships.
 

This article first appeared on Medscape.com.

“Diabetes drugs may cure dementia.”

How many of you saw that headline (or similar) earlier this year, before the pandemic took over the news?

My patients sure did. And their families. And people who aren’t my patients but found my name in the phone book after reading the headline. Of course, all of them wanted to be put on diabetes drugs to cure or prevent dementia, like the headline said.

The key word in the headline, though, is “may,” which promises nothing. Not only that, but if you actually read the story you quickly learn that the study was done in people who have diabetes, and lowers the risk of dementia.

While there could, possibly, maybe, be something interesting underlying the finding, it could also be as simple as controlling your vascular risk factors, which is good for you.

Of course, the lay public rarely reads past the first few paragraphs. To the nonmedical reader, the cure has been found, and they want it. Where’s the phone?

I’m sure this is good for business in the lay press. People see the headline and don’t bother to read the story but they immediately forward it to friends, family, Facebook and Twitter groups ... That’s a lot of clicks and advertising.

The study might genuinely mean something, but that’s a big “might.” A lot of common drugs have been hyped as being treatments for dementia – statins, ibuprofen, estrogen patches, to name a few – only to quietly die in larger controlled trials. But that part of the research never seems to make the news, only the first small, preliminary, results.

People want us to find answers. Isn’t that what doctors and scientists are supposed to do? I understand that. But by the same token, it’s generally not that easy. And if we try to explain the difficulty, then we’re often accused of being part of “them,” some secretive group trying to hide inexpensive miracle cures from the public to keep Big Pharma in business.

The real truth is that a lot of things initially seem to be good (or bad) and these things change like the seasons. Everyone should be on daily aspirin, oops, maybe not. Saccharine causes bladder cancer, wait, I take that back. And so on.

While diabetes treatments may indeed lower the risk of dementia in patients who have diabetes, people too often extrapolate that to everyone, and wishfully think the headline says “does cure” instead of “may cure.”

I have nothing against research. Everything we have now came from it. But preliminary results are just that – preliminary. Like many other things in this world, they have to be taken with a grain of salt.

Dr. Block has a solo neurology practice in Scottsdale, Arizona. He has no relevant disclosures.

“Diabetes drugs may cure dementia.”

How many of you saw that headline (or similar) earlier this year, before the pandemic took over the news?

My patients sure did. And their families. And people who aren’t my patients but found my name in the phone book after reading the headline. Of course, all of them wanted to be put on diabetes drugs to cure or prevent dementia, like the headline said.

The key word in the headline, though, is “may,” which promises nothing. Not only that, but if you actually read the story you quickly learn that the study was done in people who have diabetes, and lowers the risk of dementia.

While there could, possibly, maybe, be something interesting underlying the finding, it could also be as simple as controlling your vascular risk factors, which is good for you.

Of course, the lay public rarely reads past the first few paragraphs. To the nonmedical reader, the cure has been found, and they want it. Where’s the phone?

I’m sure this is good for business in the lay press. People see the headline and don’t bother to read the story but they immediately forward it to friends, family, Facebook and Twitter groups ... That’s a lot of clicks and advertising.

The study might genuinely mean something, but that’s a big “might.” A lot of common drugs have been hyped as being treatments for dementia – statins, ibuprofen, estrogen patches, to name a few – only to quietly die in larger controlled trials. But that part of the research never seems to make the news, only the first small, preliminary, results.

People want us to find answers. Isn’t that what doctors and scientists are supposed to do? I understand that. But by the same token, it’s generally not that easy. And if we try to explain the difficulty, then we’re often accused of being part of “them,” some secretive group trying to hide inexpensive miracle cures from the public to keep Big Pharma in business.

The real truth is that a lot of things initially seem to be good (or bad) and these things change like the seasons. Everyone should be on daily aspirin, oops, maybe not. Saccharine causes bladder cancer, wait, I take that back. And so on.

While diabetes treatments may indeed lower the risk of dementia in patients who have diabetes, people too often extrapolate that to everyone, and wishfully think the headline says “does cure” instead of “may cure.”

I have nothing against research. Everything we have now came from it. But preliminary results are just that – preliminary. Like many other things in this world, they have to be taken with a grain of salt.

Dr. Block has a solo neurology practice in Scottsdale, Arizona. He has no relevant disclosures.

“Diabetes drugs may cure dementia.”

How many of you saw that headline (or similar) earlier this year, before the pandemic took over the news?

My patients sure did. And their families. And people who aren’t my patients but found my name in the phone book after reading the headline. Of course, all of them wanted to be put on diabetes drugs to cure or prevent dementia, like the headline said.

The key word in the headline, though, is “may,” which promises nothing. Not only that, but if you actually read the story you quickly learn that the study was done in people who have diabetes, and lowers the risk of dementia.

While there could, possibly, maybe, be something interesting underlying the finding, it could also be as simple as controlling your vascular risk factors, which is good for you.

Of course, the lay public rarely reads past the first few paragraphs. To the nonmedical reader, the cure has been found, and they want it. Where’s the phone?

I’m sure this is good for business in the lay press. People see the headline and don’t bother to read the story but they immediately forward it to friends, family, Facebook and Twitter groups ... That’s a lot of clicks and advertising.

The study might genuinely mean something, but that’s a big “might.” A lot of common drugs have been hyped as being treatments for dementia – statins, ibuprofen, estrogen patches, to name a few – only to quietly die in larger controlled trials. But that part of the research never seems to make the news, only the first small, preliminary, results.

People want us to find answers. Isn’t that what doctors and scientists are supposed to do? I understand that. But by the same token, it’s generally not that easy. And if we try to explain the difficulty, then we’re often accused of being part of “them,” some secretive group trying to hide inexpensive miracle cures from the public to keep Big Pharma in business.

The real truth is that a lot of things initially seem to be good (or bad) and these things change like the seasons. Everyone should be on daily aspirin, oops, maybe not. Saccharine causes bladder cancer, wait, I take that back. And so on.

While diabetes treatments may indeed lower the risk of dementia in patients who have diabetes, people too often extrapolate that to everyone, and wishfully think the headline says “does cure” instead of “may cure.”

I have nothing against research. Everything we have now came from it. But preliminary results are just that – preliminary. Like many other things in this world, they have to be taken with a grain of salt.

Dr. Block has a solo neurology practice in Scottsdale, Arizona. He has no relevant disclosures.

An ADHD brain thrives with daily routines, and requires spontaneity and challenge to remain engaged in work, academics, relationships, and even leisure activities. ADHD is a performance issue and not one of intellectual understanding. It is not a problem of knowing what to do, but rather, difficulty doing it.

The COVID-19 pandemic has led to the loss of structure, with many parents working out of their homes alongside their children engaged in virtual learning. There has been a significant loss of impromptu events, since all activities outside of the house require proper planning and safety precautions.

To help normalize the struggles of the adult patient with ADHD during the pandemic, I have compiled a list of everything I want my adult ADHD patients and their family members to know so they don’t feel shame, guilt, or hopelessness when others’ coping strategies do not work for their ADHD brains.
 

Adult ADHD is a misnomer – and not just a disorder of inattention and hyperactivity

A better name for this often misconstrued disorder is inconsistent attention and motivation disorder with internal or external hyperactivity/impulsivity.

An ADHD brain vacillates between inattention and hyperfocus. It is not uncommon for individuals with ADHD to lose interest in a new television series when they become hyperfocused on finding the best pandemic-friendly toy for their 5-year-olds, which inevitably turns into a 3-hour Google rabbit-hole search.

These same individuals with ADHD may have low motivation for mundane household chores but become highly motivated when their nonessential Amazon purchases arrive. They may even go as far as pulling an all-nighter to have an electric toy jeep built and ready for the youngster by morning.

Adults with ADHD can also exhibit hyperactive symptoms, such as physical restlessness with fidgeting, and an internal restlessness with anxious and repetitive thoughts that affect their ability to unwind, relax, and even sleep. Impulsivity in adults with ADHD can present as rushing through tasks that one finds uninteresting or unimportant, interrupting others on a Zoom work call, or impulse buying an expensive hot tub instead of a more affordable on their spouse agreed to.
 

ADHD is a risk factor for contracting COVID-19

Untreated ADHD can increase one’s risk of contracting COVID-19. Israeli researchers published a study in the Journal of Attention Disorders showing that individuals with ADHD are 52% more likely to test positive for COVID-19, compared with those without ADHD, because of risk-taking behaviors, impulsivity, and carelessness. However, individuals whose ADHD symptoms are treated with stimulant medication do not increase their risk of contracting COVID-19, the researchers wrote.

ADHD might be noticed in family members

ADHD is a neurodevelopmental disorder that affects the development of the brain. We know that structural, functional, and chemical differences affect our patients’ ability to regulate attention, motivation, impulses, and emotions. ADHD tends to run in families and is highly genetic. Since spending more time with family members during the pandemic, patients might even recognize ADHD symptoms in siblings, children, and one or both of parents. A child who has ADHD has a 25% chance of having a parent with ADHD.

Strengths and attributes are related to ADHD

Your ability to thrive in new, stressful, and challenging situations is an ADHD attribute that will be beneficial during the pandemic. Creativity, great problem-solving skills, and ability to be flexible will be admired and helpful to our patients with ADHD and others during these uncertain times.

Those with ADHD might be highly sensitive to their environments

As previously mentioned, ADHD is a misnomer and not just a disorder of inattention but also too much attention. Unfortunately, this hyperfocused attention is usually on the wrong things. Those with ADHD might find it difficult to filter and process sensory information correctly and, therefore, can be easily distracted by auditory, visual, tactile, and olfactory stimuli. The change to working at home during the pandemic might make it hard to ignore children’s voices, the uncomfortable new mask bought after losing yet another mask over the weekend, and the smell of cookies emanating from the kitchen. This increased sensitivity may affect one’s emotions.

Heightened emotions are expected during the pandemic and even more so among adults with ADHD. The inability of adults with ADHD to properly filter information can also affect emotional stimuli. These intense emotions, coupled with impulsive behaviors, can cause disagreements with partners, lack of patience with children, and conflict with colleagues. When individuals with ADHD feel attacked or invalidated, they can become emotionally dysregulated and “vomit” their pent up feelings.
 

ADHD may affect interpersonal relationships

ADHD symptoms of inattention and impulsivity can affect the ability to connect with friends and family. When one is easily distracted by the pandemic’s chaos, it is harder to be mindful and emotionally and physically connected to one’s partner, which also disrupts their sex life and intimacy.

ADHD sensory integration issues can make people sensitive to particular touches, smells, and sensory information. A gentle touch from one’s partner might be annoying during the pandemic, since other senses may already be overstimulated by the loud sounds of children screaming, the visual and auditory distractions of a neighbor mowing the lawn, and the sun beating down because one forgot to get blinds in the home office before the pandemic.

These minor distractions that are usually insignificant to a non-ADHD brain can profoundly affect an ADHD brain since one must use valuable energy to tune out these unwanted disturbances.
 

Your brain uses a different motivational system than a non-ADHD brain

You have a deficiency in the neurotransmitter dopamine, which affects your motivational system. Your motivational system is based on what you find interesting, challenging, new, exciting, and urgent. Your non-ADHD partner, family members, friends, and colleagues motivate and accomplish their daily tasks differently from you and most likely use a system based on rewards and consequences.

Do not be surprised if you notice that your motivation is diminished during the pandemic because of less novelty and excitement in your life. The coronavirus’s chronic importance level may make everything else in your life not as essential and, therefore, less urgent, which indirectly also lowers your motivation.

Your non-ADHD partner may see that you can focus, prioritize, initiate, and complete tasks when you “choose” to, and confuse your inconsistent behaviors as being within your control. However, this lack of motivation for things that do not pique your interest, challenge you, and are not urgent is not voluntary. It is caused by a lack of neural connections in the area of the brain that controls motivation.
 

You can still have ADHD even though you were not diagnosed as a child or adolescent

Your symptoms of ADHD may not affect your level of functioning until you go away to college, obtain your first job, marry your partner, start a family, or even until a global pandemic alters every aspect of your daily life.

It is, therefore, never too late to get assessed and treated for ADHD. Stimulants are the first line of treatment for adult ADHD. Nonstimulants may also be prescribed if you do not tolerate the side effects of stimulants or have a history of certain medical conditions. These options include some antidepressants and high blood pressure medicines. Sometimes, just identifying the deficits of those with ADHD and how they may affect their performance at work, school, and interpersonal relationships can help the person living with ADHD. Many other any nonmedication types of effective treatment are available for adults with ADHD, including therapy, executive skills, and mindfulness training.

• ADHD focused cognitive-behavioral therapy can help one change your distorted, negative, and irrational thoughts about themselves, others, and situations and replace them with more realistic and rational thoughts that allow for helpful and adaptive behaviors.
• Executive skills training is a type of ADHD treatment that focuses on developing effective systems, routines, improving time management, organization, planning, productivity, and emotional self-regulation.
• Mindfulness meditation training is an additional treatment for adult ADHD. Mindfulness training teaches skills to focus on the present moment and become aware of one’s thoughts, emotions, and actions without judgment. The goal is to learn to accept your ADHD deficits and all that is out of your control while remaining mindful of your ADHD strengths and focusing on the daily choices within your control.

Silver linings of the pandemic

Numerous underserved and rural geographic areas lack adequate psychiatric care. Many primary care physicians and even some psychiatrists are uncomfortable diagnosing and treating attentional disorders because of a lack of proper training in medical school and fear related to the fact that the first-line treatment for adult ADHD is a controlled substance.

In response to the pandemic, the expansion of telepsychiatry services, state waivers that allow clinicians to practice across state lines, exemptions that enable the prescribing of controlled substances without an in-person medical evaluation, and the acceptance of employees working from home during the COVID-19 pandemic have increased the accessibility of adult ADHD psychiatric assessments and treatment.

It is hoped that when the COVID-19 pandemic is behind us, many of the benefits that have emerged, such as the growth of telepsychiatry, changes in state licensure and prescriber regulations, and reduced work commutes will continue into our postpandemic lives.
 

Dr. Abraham is a psychiatrist in private practice in Philadelphia. She has no disclosures.

An ADHD brain thrives with daily routines, and requires spontaneity and challenge to remain engaged in work, academics, relationships, and even leisure activities. ADHD is a performance issue and not one of intellectual understanding. It is not a problem of knowing what to do, but rather, difficulty doing it.

The COVID-19 pandemic has led to the loss of structure, with many parents working out of their homes alongside their children engaged in virtual learning. There has been a significant loss of impromptu events, since all activities outside of the house require proper planning and safety precautions.

To help normalize the struggles of the adult patient with ADHD during the pandemic, I have compiled a list of everything I want my adult ADHD patients and their family members to know so they don’t feel shame, guilt, or hopelessness when others’ coping strategies do not work for their ADHD brains.
 

Adult ADHD is a misnomer – and not just a disorder of inattention and hyperactivity

A better name for this often misconstrued disorder is inconsistent attention and motivation disorder with internal or external hyperactivity/impulsivity.

An ADHD brain vacillates between inattention and hyperfocus. It is not uncommon for individuals with ADHD to lose interest in a new television series when they become hyperfocused on finding the best pandemic-friendly toy for their 5-year-olds, which inevitably turns into a 3-hour Google rabbit-hole search.

These same individuals with ADHD may have low motivation for mundane household chores but become highly motivated when their nonessential Amazon purchases arrive. They may even go as far as pulling an all-nighter to have an electric toy jeep built and ready for the youngster by morning.

Adults with ADHD can also exhibit hyperactive symptoms, such as physical restlessness with fidgeting, and an internal restlessness with anxious and repetitive thoughts that affect their ability to unwind, relax, and even sleep. Impulsivity in adults with ADHD can present as rushing through tasks that one finds uninteresting or unimportant, interrupting others on a Zoom work call, or impulse buying an expensive hot tub instead of a more affordable on their spouse agreed to.
 

ADHD is a risk factor for contracting COVID-19

Untreated ADHD can increase one’s risk of contracting COVID-19. Israeli researchers published a study in the Journal of Attention Disorders showing that individuals with ADHD are 52% more likely to test positive for COVID-19, compared with those without ADHD, because of risk-taking behaviors, impulsivity, and carelessness. However, individuals whose ADHD symptoms are treated with stimulant medication do not increase their risk of contracting COVID-19, the researchers wrote.

ADHD might be noticed in family members

ADHD is a neurodevelopmental disorder that affects the development of the brain. We know that structural, functional, and chemical differences affect our patients’ ability to regulate attention, motivation, impulses, and emotions. ADHD tends to run in families and is highly genetic. Since spending more time with family members during the pandemic, patients might even recognize ADHD symptoms in siblings, children, and one or both of parents. A child who has ADHD has a 25% chance of having a parent with ADHD.

Strengths and attributes are related to ADHD

Your ability to thrive in new, stressful, and challenging situations is an ADHD attribute that will be beneficial during the pandemic. Creativity, great problem-solving skills, and ability to be flexible will be admired and helpful to our patients with ADHD and others during these uncertain times.

Those with ADHD might be highly sensitive to their environments

As previously mentioned, ADHD is a misnomer and not just a disorder of inattention but also too much attention. Unfortunately, this hyperfocused attention is usually on the wrong things. Those with ADHD might find it difficult to filter and process sensory information correctly and, therefore, can be easily distracted by auditory, visual, tactile, and olfactory stimuli. The change to working at home during the pandemic might make it hard to ignore children’s voices, the uncomfortable new mask bought after losing yet another mask over the weekend, and the smell of cookies emanating from the kitchen. This increased sensitivity may affect one’s emotions.

Heightened emotions are expected during the pandemic and even more so among adults with ADHD. The inability of adults with ADHD to properly filter information can also affect emotional stimuli. These intense emotions, coupled with impulsive behaviors, can cause disagreements with partners, lack of patience with children, and conflict with colleagues. When individuals with ADHD feel attacked or invalidated, they can become emotionally dysregulated and “vomit” their pent up feelings.
 

ADHD may affect interpersonal relationships

ADHD symptoms of inattention and impulsivity can affect the ability to connect with friends and family. When one is easily distracted by the pandemic’s chaos, it is harder to be mindful and emotionally and physically connected to one’s partner, which also disrupts their sex life and intimacy.

ADHD sensory integration issues can make people sensitive to particular touches, smells, and sensory information. A gentle touch from one’s partner might be annoying during the pandemic, since other senses may already be overstimulated by the loud sounds of children screaming, the visual and auditory distractions of a neighbor mowing the lawn, and the sun beating down because one forgot to get blinds in the home office before the pandemic.

These minor distractions that are usually insignificant to a non-ADHD brain can profoundly affect an ADHD brain since one must use valuable energy to tune out these unwanted disturbances.
 

Your brain uses a different motivational system than a non-ADHD brain

You have a deficiency in the neurotransmitter dopamine, which affects your motivational system. Your motivational system is based on what you find interesting, challenging, new, exciting, and urgent. Your non-ADHD partner, family members, friends, and colleagues motivate and accomplish their daily tasks differently from you and most likely use a system based on rewards and consequences.

Do not be surprised if you notice that your motivation is diminished during the pandemic because of less novelty and excitement in your life. The coronavirus’s chronic importance level may make everything else in your life not as essential and, therefore, less urgent, which indirectly also lowers your motivation.

Your non-ADHD partner may see that you can focus, prioritize, initiate, and complete tasks when you “choose” to, and confuse your inconsistent behaviors as being within your control. However, this lack of motivation for things that do not pique your interest, challenge you, and are not urgent is not voluntary. It is caused by a lack of neural connections in the area of the brain that controls motivation.
 

You can still have ADHD even though you were not diagnosed as a child or adolescent

Your symptoms of ADHD may not affect your level of functioning until you go away to college, obtain your first job, marry your partner, start a family, or even until a global pandemic alters every aspect of your daily life.

It is, therefore, never too late to get assessed and treated for ADHD. Stimulants are the first line of treatment for adult ADHD. Nonstimulants may also be prescribed if you do not tolerate the side effects of stimulants or have a history of certain medical conditions. These options include some antidepressants and high blood pressure medicines. Sometimes, just identifying the deficits of those with ADHD and how they may affect their performance at work, school, and interpersonal relationships can help the person living with ADHD. Many other any nonmedication types of effective treatment are available for adults with ADHD, including therapy, executive skills, and mindfulness training.

• ADHD focused cognitive-behavioral therapy can help one change your distorted, negative, and irrational thoughts about themselves, others, and situations and replace them with more realistic and rational thoughts that allow for helpful and adaptive behaviors.
• Executive skills training is a type of ADHD treatment that focuses on developing effective systems, routines, improving time management, organization, planning, productivity, and emotional self-regulation.
• Mindfulness meditation training is an additional treatment for adult ADHD. Mindfulness training teaches skills to focus on the present moment and become aware of one’s thoughts, emotions, and actions without judgment. The goal is to learn to accept your ADHD deficits and all that is out of your control while remaining mindful of your ADHD strengths and focusing on the daily choices within your control.

Silver linings of the pandemic

Numerous underserved and rural geographic areas lack adequate psychiatric care. Many primary care physicians and even some psychiatrists are uncomfortable diagnosing and treating attentional disorders because of a lack of proper training in medical school and fear related to the fact that the first-line treatment for adult ADHD is a controlled substance.

In response to the pandemic, the expansion of telepsychiatry services, state waivers that allow clinicians to practice across state lines, exemptions that enable the prescribing of controlled substances without an in-person medical evaluation, and the acceptance of employees working from home during the COVID-19 pandemic have increased the accessibility of adult ADHD psychiatric assessments and treatment.

It is hoped that when the COVID-19 pandemic is behind us, many of the benefits that have emerged, such as the growth of telepsychiatry, changes in state licensure and prescriber regulations, and reduced work commutes will continue into our postpandemic lives.
 

Dr. Abraham is a psychiatrist in private practice in Philadelphia. She has no disclosures.

An ADHD brain thrives with daily routines, and requires spontaneity and challenge to remain engaged in work, academics, relationships, and even leisure activities. ADHD is a performance issue and not one of intellectual understanding. It is not a problem of knowing what to do, but rather, difficulty doing it.

The COVID-19 pandemic has led to the loss of structure, with many parents working out of their homes alongside their children engaged in virtual learning. There has been a significant loss of impromptu events, since all activities outside of the house require proper planning and safety precautions.

To help normalize the struggles of the adult patient with ADHD during the pandemic, I have compiled a list of everything I want my adult ADHD patients and their family members to know so they don’t feel shame, guilt, or hopelessness when others’ coping strategies do not work for their ADHD brains.
 

Adult ADHD is a misnomer – and not just a disorder of inattention and hyperactivity

A better name for this often misconstrued disorder is inconsistent attention and motivation disorder with internal or external hyperactivity/impulsivity.

An ADHD brain vacillates between inattention and hyperfocus. It is not uncommon for individuals with ADHD to lose interest in a new television series when they become hyperfocused on finding the best pandemic-friendly toy for their 5-year-olds, which inevitably turns into a 3-hour Google rabbit-hole search.

These same individuals with ADHD may have low motivation for mundane household chores but become highly motivated when their nonessential Amazon purchases arrive. They may even go as far as pulling an all-nighter to have an electric toy jeep built and ready for the youngster by morning.

Adults with ADHD can also exhibit hyperactive symptoms, such as physical restlessness with fidgeting, and an internal restlessness with anxious and repetitive thoughts that affect their ability to unwind, relax, and even sleep. Impulsivity in adults with ADHD can present as rushing through tasks that one finds uninteresting or unimportant, interrupting others on a Zoom work call, or impulse buying an expensive hot tub instead of a more affordable on their spouse agreed to.
 

ADHD is a risk factor for contracting COVID-19

Untreated ADHD can increase one’s risk of contracting COVID-19. Israeli researchers published a study in the Journal of Attention Disorders showing that individuals with ADHD are 52% more likely to test positive for COVID-19, compared with those without ADHD, because of risk-taking behaviors, impulsivity, and carelessness. However, individuals whose ADHD symptoms are treated with stimulant medication do not increase their risk of contracting COVID-19, the researchers wrote.

ADHD might be noticed in family members

ADHD is a neurodevelopmental disorder that affects the development of the brain. We know that structural, functional, and chemical differences affect our patients’ ability to regulate attention, motivation, impulses, and emotions. ADHD tends to run in families and is highly genetic. Since spending more time with family members during the pandemic, patients might even recognize ADHD symptoms in siblings, children, and one or both of parents. A child who has ADHD has a 25% chance of having a parent with ADHD.

Strengths and attributes are related to ADHD

Your ability to thrive in new, stressful, and challenging situations is an ADHD attribute that will be beneficial during the pandemic. Creativity, great problem-solving skills, and ability to be flexible will be admired and helpful to our patients with ADHD and others during these uncertain times.

Those with ADHD might be highly sensitive to their environments

As previously mentioned, ADHD is a misnomer and not just a disorder of inattention but also too much attention. Unfortunately, this hyperfocused attention is usually on the wrong things. Those with ADHD might find it difficult to filter and process sensory information correctly and, therefore, can be easily distracted by auditory, visual, tactile, and olfactory stimuli. The change to working at home during the pandemic might make it hard to ignore children’s voices, the uncomfortable new mask bought after losing yet another mask over the weekend, and the smell of cookies emanating from the kitchen. This increased sensitivity may affect one’s emotions.

Heightened emotions are expected during the pandemic and even more so among adults with ADHD. The inability of adults with ADHD to properly filter information can also affect emotional stimuli. These intense emotions, coupled with impulsive behaviors, can cause disagreements with partners, lack of patience with children, and conflict with colleagues. When individuals with ADHD feel attacked or invalidated, they can become emotionally dysregulated and “vomit” their pent up feelings.
 

ADHD may affect interpersonal relationships

ADHD symptoms of inattention and impulsivity can affect the ability to connect with friends and family. When one is easily distracted by the pandemic’s chaos, it is harder to be mindful and emotionally and physically connected to one’s partner, which also disrupts their sex life and intimacy.

ADHD sensory integration issues can make people sensitive to particular touches, smells, and sensory information. A gentle touch from one’s partner might be annoying during the pandemic, since other senses may already be overstimulated by the loud sounds of children screaming, the visual and auditory distractions of a neighbor mowing the lawn, and the sun beating down because one forgot to get blinds in the home office before the pandemic.

These minor distractions that are usually insignificant to a non-ADHD brain can profoundly affect an ADHD brain since one must use valuable energy to tune out these unwanted disturbances.
 

Your brain uses a different motivational system than a non-ADHD brain

You have a deficiency in the neurotransmitter dopamine, which affects your motivational system. Your motivational system is based on what you find interesting, challenging, new, exciting, and urgent. Your non-ADHD partner, family members, friends, and colleagues motivate and accomplish their daily tasks differently from you and most likely use a system based on rewards and consequences.

Do not be surprised if you notice that your motivation is diminished during the pandemic because of less novelty and excitement in your life. The coronavirus’s chronic importance level may make everything else in your life not as essential and, therefore, less urgent, which indirectly also lowers your motivation.

Your non-ADHD partner may see that you can focus, prioritize, initiate, and complete tasks when you “choose” to, and confuse your inconsistent behaviors as being within your control. However, this lack of motivation for things that do not pique your interest, challenge you, and are not urgent is not voluntary. It is caused by a lack of neural connections in the area of the brain that controls motivation.
 

You can still have ADHD even though you were not diagnosed as a child or adolescent

Your symptoms of ADHD may not affect your level of functioning until you go away to college, obtain your first job, marry your partner, start a family, or even until a global pandemic alters every aspect of your daily life.

It is, therefore, never too late to get assessed and treated for ADHD. Stimulants are the first line of treatment for adult ADHD. Nonstimulants may also be prescribed if you do not tolerate the side effects of stimulants or have a history of certain medical conditions. These options include some antidepressants and high blood pressure medicines. Sometimes, just identifying the deficits of those with ADHD and how they may affect their performance at work, school, and interpersonal relationships can help the person living with ADHD. Many other any nonmedication types of effective treatment are available for adults with ADHD, including therapy, executive skills, and mindfulness training.

• ADHD focused cognitive-behavioral therapy can help one change your distorted, negative, and irrational thoughts about themselves, others, and situations and replace them with more realistic and rational thoughts that allow for helpful and adaptive behaviors.
• Executive skills training is a type of ADHD treatment that focuses on developing effective systems, routines, improving time management, organization, planning, productivity, and emotional self-regulation.
• Mindfulness meditation training is an additional treatment for adult ADHD. Mindfulness training teaches skills to focus on the present moment and become aware of one’s thoughts, emotions, and actions without judgment. The goal is to learn to accept your ADHD deficits and all that is out of your control while remaining mindful of your ADHD strengths and focusing on the daily choices within your control.

Silver linings of the pandemic

Numerous underserved and rural geographic areas lack adequate psychiatric care. Many primary care physicians and even some psychiatrists are uncomfortable diagnosing and treating attentional disorders because of a lack of proper training in medical school and fear related to the fact that the first-line treatment for adult ADHD is a controlled substance.

In response to the pandemic, the expansion of telepsychiatry services, state waivers that allow clinicians to practice across state lines, exemptions that enable the prescribing of controlled substances without an in-person medical evaluation, and the acceptance of employees working from home during the COVID-19 pandemic have increased the accessibility of adult ADHD psychiatric assessments and treatment.

It is hoped that when the COVID-19 pandemic is behind us, many of the benefits that have emerged, such as the growth of telepsychiatry, changes in state licensure and prescriber regulations, and reduced work commutes will continue into our postpandemic lives.
 

Dr. Abraham is a psychiatrist in private practice in Philadelphia. She has no disclosures.

The Food and Drug Administration on Tuesday signaled its resistance to President Donald J. Trump’s drive for an accelerated clearance of a COVID-19 vaccine, while medical and trade associations called for a thorough review of any such product before approval.

The FDA took the unusual step of posting background materials much earlier than usual for its planned Oct. 22 advisory committee meeting on potential vaccines for COVID-19. The FDA also on Tuesday afternoon released a new guidance document, expanding on a previous set of recommendations the agency released in June.

In the new guidance document, FDA officials outline what will be required for even a limited clearance, known as an emergency use authorization (EUA), for a COVID-19 vaccine.

“Data from phase 3 studies should include a median follow-up duration of at least 2 months after completion of the full vaccination regimen to help provide adequate information to assess a vaccine’s benefit-risk profile,” the FDA said in the document.

FDA staff have emphasized the higher bar that drugmakers and regulators face in considering approval of a COVID-19 vaccine.

“Vaccines are complex biological products, and an EUA for a COVID-19 vaccine may allow for rapid and widespread deployment for administration of the vaccine to millions of individuals, including healthy people,” the agency staff said in the briefing documents.

The FDA’s briefing document for the Oct. 22 meeting appears to be markedly at odds with the claim Trump made in a video Monday night, in which he told the American public that “vaccines are coming momentarily.”

Trump, who is in a tightly contested presidential race against Democratic candidate Joe Biden, has repeatedly made claims of the potential arrival of COVID vaccines that are at odds with timelines offered with guarded optimism by experts in infectious diseases.

But based on these new guidelines from the FDA, it appears that the White House may now endorse the FDA’s stance, according to a Wall Street Journal report based on “people familiar with the matter.”

The publication reports that the White House, which has yet to officially comment, “endorsed the U.S. Food and Drug Administration’s plans for assessing whether a Covid-19 vaccine should be given widely, casting aside objections to requirements that would likely mean a shot won’t be cleared until after Election Day, people familiar with the matter said.”

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, on Monday night said during a virtual appearance at the twenty-first annual New Yorker Festival that there could be evidence as early as November or December about whether one of the vaccines now in testing will work out. He declared himself to have “cautious optimism” about potential rollout of vaccines as early as late 2020 or early 2021.

Peter Lurie, MD, MPH, who earlier served as the FDA’s associate commissioner for public health strategy and analysis, described the agency’s release of the briefing document as being a positive development.

News organizations, including the New York Times, have reported that the White House had sought to block the FDA from releasing further instructions for companies developing COVID-19 vaccines. The Associated Press on Tuesday said that a senior Trump administration official confirmed that the White House had blocked earlier FDA plans to formally publish the safety guidelines based on the 2-month data requirement, arguing that there was “no clinical or medical reason” for it.

“It is an encouraging sign that, despite opposition from the White House, the Food and Drug Administration has effectively published guidelines for emergency release of a vaccine for COVID-19 by disclosing the advice it has been providing to individual sponsors,” said Dr. Lurie, who is now executive director and president of the Center for Science in the Public Interest.

In a news release, he said the White House had sought to keep the FDA guidance under wraps “so it could maintain the public fiction that a safe and effective vaccine could be available before Election Day or even so that it could force emergency authorization of a vaccine with more limited follow-up.”

“Even the pharmaceutical industry has been clamoring for the release of these guidelines. We all want a safe and effective vaccine to end the pandemic, and we want it sooner rather than later,” Dr. Lurie said. “But we can’t afford for the Trump administration to bungle vaccine review the way they’ve bungled nearly every other aspect of its pandemic response.”

Tuesday also saw a flood of statements in support of FDA officials, including tweets from the chief executive of Pfizer, which is among the leaders in the race to develop a COVID-19 vaccine. Pfizer’s Albert Bourla, DVM, PhD, said that the FDA’s “public servants are known for their high integrity and scientific expertise and we have full faith in their ability to set appropriate standards for the approval of a COVID vaccine or treatment.”

The American Medical Association on Tuesday announced a public webinar on Wednesday where its president, Susan R. Bailey, MD, will discuss the COVID-19 vaccine review process with Peter Marks, MD, PhD, director of the Center for Biologics Evaluation and Research at the FDA. The AMA described this webinar as part of work “to restore trust in science and science-based decision-making among policymakers and the public.”

“To ensure media and the physician community are continuously informed about the federal review process for COVID-19 vaccine candidates, the AMA will host a webinar series to gain fact-based insights from the nation’s highest-ranking subject matter experts working to protect the health of the public,” the organization said in announcing the webinar.

In a statement, leaders of the Association of American Medical Colleges said that the FDA’s Vaccines and Related Biological Products Advisory Committee should evaluate any COVID-19 candidate vaccines prior to the FDA issuing an EUA.

“Full approval of a new vaccine or biologic requires demonstration of safety and effectiveness through a process that includes evaluation by the VRBPAC. Their recommendations are considered by FDA staff who ultimately have the authority to approve the new product,” said AAMC chief scientific officer Ross McKinney Jr, MD, and AAMC CEO David J. Skorton, MD, in the statement.

Thomas M. File Jr., MD, president of the Infectious Diseases Society of America, said in a statement that his association again asked the White House to “follow medical and scientific expertise in efforts to combat COVID-19.”

“It is imperative that a vaccine be approved on the basis of FDA’s quality standards and that its safety and efficacy are established before it is authorized,” Dr. File said. “A vaccine that has been approved with speed, rather than safety and efficacy, at the forefront will compound the challenges posed by this pandemic. FDA guidelines for approval that set standards the American people can trust are essential to the success of a vaccine.”

Stephen J. Ubl, chief executive of the Pharmaceutical Research and Manufacturers of America, said in a statement that his association “supports any efforts by FDA to provide clarifying guidance and we have engaged with the agency to support bringing greater transparency to the review process for COVID-19 vaccines.”

“To help address this public health crisis, our companies have also taken unprecedented steps to share vaccine clinical trial protocols and data in real time,” Mr. Ubl said. “We welcome the agency’s efforts to instill confidence in the rigorous safety of these potential vaccines.”

On Oct. 1, Michelle McMurry-Heath, MD, PhD, president and chief executive of the Biotechnology Innovation Organization, released publicly her letter urging Department of Health & Human Services Secretary Alex Azar to “publicly release all new guidance” related to a COVID-19 vaccine. Such a move would bolster public confidence in the vaccine, she said.

“We cannot allow a lack of transparency to undermine confidence in the vaccine development process. The public must have full faith in the scientific process and the rigor of FDA’s regulatory oversight if we are to end the pandemic,” she wrote in the Oct. 1 letter to Azar. “Releasing any additional guidance on granting emergency use authorization for a vaccine will go a long way in accomplishing this critical goal.”

This article first appeared on Medscape.com.

The Food and Drug Administration on Tuesday signaled its resistance to President Donald J. Trump’s drive for an accelerated clearance of a COVID-19 vaccine, while medical and trade associations called for a thorough review of any such product before approval.

The FDA took the unusual step of posting background materials much earlier than usual for its planned Oct. 22 advisory committee meeting on potential vaccines for COVID-19. The FDA also on Tuesday afternoon released a new guidance document, expanding on a previous set of recommendations the agency released in June.

In the new guidance document, FDA officials outline what will be required for even a limited clearance, known as an emergency use authorization (EUA), for a COVID-19 vaccine.

“Data from phase 3 studies should include a median follow-up duration of at least 2 months after completion of the full vaccination regimen to help provide adequate information to assess a vaccine’s benefit-risk profile,” the FDA said in the document.

FDA staff have emphasized the higher bar that drugmakers and regulators face in considering approval of a COVID-19 vaccine.

“Vaccines are complex biological products, and an EUA for a COVID-19 vaccine may allow for rapid and widespread deployment for administration of the vaccine to millions of individuals, including healthy people,” the agency staff said in the briefing documents.

The FDA’s briefing document for the Oct. 22 meeting appears to be markedly at odds with the claim Trump made in a video Monday night, in which he told the American public that “vaccines are coming momentarily.”

Trump, who is in a tightly contested presidential race against Democratic candidate Joe Biden, has repeatedly made claims of the potential arrival of COVID vaccines that are at odds with timelines offered with guarded optimism by experts in infectious diseases.

But based on these new guidelines from the FDA, it appears that the White House may now endorse the FDA’s stance, according to a Wall Street Journal report based on “people familiar with the matter.”

The publication reports that the White House, which has yet to officially comment, “endorsed the U.S. Food and Drug Administration’s plans for assessing whether a Covid-19 vaccine should be given widely, casting aside objections to requirements that would likely mean a shot won’t be cleared until after Election Day, people familiar with the matter said.”

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, on Monday night said during a virtual appearance at the twenty-first annual New Yorker Festival that there could be evidence as early as November or December about whether one of the vaccines now in testing will work out. He declared himself to have “cautious optimism” about potential rollout of vaccines as early as late 2020 or early 2021.

Peter Lurie, MD, MPH, who earlier served as the FDA’s associate commissioner for public health strategy and analysis, described the agency’s release of the briefing document as being a positive development.

News organizations, including the New York Times, have reported that the White House had sought to block the FDA from releasing further instructions for companies developing COVID-19 vaccines. The Associated Press on Tuesday said that a senior Trump administration official confirmed that the White House had blocked earlier FDA plans to formally publish the safety guidelines based on the 2-month data requirement, arguing that there was “no clinical or medical reason” for it.

“It is an encouraging sign that, despite opposition from the White House, the Food and Drug Administration has effectively published guidelines for emergency release of a vaccine for COVID-19 by disclosing the advice it has been providing to individual sponsors,” said Dr. Lurie, who is now executive director and president of the Center for Science in the Public Interest.

In a news release, he said the White House had sought to keep the FDA guidance under wraps “so it could maintain the public fiction that a safe and effective vaccine could be available before Election Day or even so that it could force emergency authorization of a vaccine with more limited follow-up.”

“Even the pharmaceutical industry has been clamoring for the release of these guidelines. We all want a safe and effective vaccine to end the pandemic, and we want it sooner rather than later,” Dr. Lurie said. “But we can’t afford for the Trump administration to bungle vaccine review the way they’ve bungled nearly every other aspect of its pandemic response.”

Tuesday also saw a flood of statements in support of FDA officials, including tweets from the chief executive of Pfizer, which is among the leaders in the race to develop a COVID-19 vaccine. Pfizer’s Albert Bourla, DVM, PhD, said that the FDA’s “public servants are known for their high integrity and scientific expertise and we have full faith in their ability to set appropriate standards for the approval of a COVID vaccine or treatment.”

The American Medical Association on Tuesday announced a public webinar on Wednesday where its president, Susan R. Bailey, MD, will discuss the COVID-19 vaccine review process with Peter Marks, MD, PhD, director of the Center for Biologics Evaluation and Research at the FDA. The AMA described this webinar as part of work “to restore trust in science and science-based decision-making among policymakers and the public.”

“To ensure media and the physician community are continuously informed about the federal review process for COVID-19 vaccine candidates, the AMA will host a webinar series to gain fact-based insights from the nation’s highest-ranking subject matter experts working to protect the health of the public,” the organization said in announcing the webinar.

In a statement, leaders of the Association of American Medical Colleges said that the FDA’s Vaccines and Related Biological Products Advisory Committee should evaluate any COVID-19 candidate vaccines prior to the FDA issuing an EUA.

“Full approval of a new vaccine or biologic requires demonstration of safety and effectiveness through a process that includes evaluation by the VRBPAC. Their recommendations are considered by FDA staff who ultimately have the authority to approve the new product,” said AAMC chief scientific officer Ross McKinney Jr, MD, and AAMC CEO David J. Skorton, MD, in the statement.

Thomas M. File Jr., MD, president of the Infectious Diseases Society of America, said in a statement that his association again asked the White House to “follow medical and scientific expertise in efforts to combat COVID-19.”

“It is imperative that a vaccine be approved on the basis of FDA’s quality standards and that its safety and efficacy are established before it is authorized,” Dr. File said. “A vaccine that has been approved with speed, rather than safety and efficacy, at the forefront will compound the challenges posed by this pandemic. FDA guidelines for approval that set standards the American people can trust are essential to the success of a vaccine.”

Stephen J. Ubl, chief executive of the Pharmaceutical Research and Manufacturers of America, said in a statement that his association “supports any efforts by FDA to provide clarifying guidance and we have engaged with the agency to support bringing greater transparency to the review process for COVID-19 vaccines.”

“To help address this public health crisis, our companies have also taken unprecedented steps to share vaccine clinical trial protocols and data in real time,” Mr. Ubl said. “We welcome the agency’s efforts to instill confidence in the rigorous safety of these potential vaccines.”

On Oct. 1, Michelle McMurry-Heath, MD, PhD, president and chief executive of the Biotechnology Innovation Organization, released publicly her letter urging Department of Health & Human Services Secretary Alex Azar to “publicly release all new guidance” related to a COVID-19 vaccine. Such a move would bolster public confidence in the vaccine, she said.

“We cannot allow a lack of transparency to undermine confidence in the vaccine development process. The public must have full faith in the scientific process and the rigor of FDA’s regulatory oversight if we are to end the pandemic,” she wrote in the Oct. 1 letter to Azar. “Releasing any additional guidance on granting emergency use authorization for a vaccine will go a long way in accomplishing this critical goal.”

This article first appeared on Medscape.com.

The Food and Drug Administration on Tuesday signaled its resistance to President Donald J. Trump’s drive for an accelerated clearance of a COVID-19 vaccine, while medical and trade associations called for a thorough review of any such product before approval.

The FDA took the unusual step of posting background materials much earlier than usual for its planned Oct. 22 advisory committee meeting on potential vaccines for COVID-19. The FDA also on Tuesday afternoon released a new guidance document, expanding on a previous set of recommendations the agency released in June.

In the new guidance document, FDA officials outline what will be required for even a limited clearance, known as an emergency use authorization (EUA), for a COVID-19 vaccine.

“Data from phase 3 studies should include a median follow-up duration of at least 2 months after completion of the full vaccination regimen to help provide adequate information to assess a vaccine’s benefit-risk profile,” the FDA said in the document.

FDA staff have emphasized the higher bar that drugmakers and regulators face in considering approval of a COVID-19 vaccine.

“Vaccines are complex biological products, and an EUA for a COVID-19 vaccine may allow for rapid and widespread deployment for administration of the vaccine to millions of individuals, including healthy people,” the agency staff said in the briefing documents.

The FDA’s briefing document for the Oct. 22 meeting appears to be markedly at odds with the claim Trump made in a video Monday night, in which he told the American public that “vaccines are coming momentarily.”

Trump, who is in a tightly contested presidential race against Democratic candidate Joe Biden, has repeatedly made claims of the potential arrival of COVID vaccines that are at odds with timelines offered with guarded optimism by experts in infectious diseases.

But based on these new guidelines from the FDA, it appears that the White House may now endorse the FDA’s stance, according to a Wall Street Journal report based on “people familiar with the matter.”

The publication reports that the White House, which has yet to officially comment, “endorsed the U.S. Food and Drug Administration’s plans for assessing whether a Covid-19 vaccine should be given widely, casting aside objections to requirements that would likely mean a shot won’t be cleared until after Election Day, people familiar with the matter said.”

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, on Monday night said during a virtual appearance at the twenty-first annual New Yorker Festival that there could be evidence as early as November or December about whether one of the vaccines now in testing will work out. He declared himself to have “cautious optimism” about potential rollout of vaccines as early as late 2020 or early 2021.

Peter Lurie, MD, MPH, who earlier served as the FDA’s associate commissioner for public health strategy and analysis, described the agency’s release of the briefing document as being a positive development.

News organizations, including the New York Times, have reported that the White House had sought to block the FDA from releasing further instructions for companies developing COVID-19 vaccines. The Associated Press on Tuesday said that a senior Trump administration official confirmed that the White House had blocked earlier FDA plans to formally publish the safety guidelines based on the 2-month data requirement, arguing that there was “no clinical or medical reason” for it.

“It is an encouraging sign that, despite opposition from the White House, the Food and Drug Administration has effectively published guidelines for emergency release of a vaccine for COVID-19 by disclosing the advice it has been providing to individual sponsors,” said Dr. Lurie, who is now executive director and president of the Center for Science in the Public Interest.

In a news release, he said the White House had sought to keep the FDA guidance under wraps “so it could maintain the public fiction that a safe and effective vaccine could be available before Election Day or even so that it could force emergency authorization of a vaccine with more limited follow-up.”

“Even the pharmaceutical industry has been clamoring for the release of these guidelines. We all want a safe and effective vaccine to end the pandemic, and we want it sooner rather than later,” Dr. Lurie said. “But we can’t afford for the Trump administration to bungle vaccine review the way they’ve bungled nearly every other aspect of its pandemic response.”

Tuesday also saw a flood of statements in support of FDA officials, including tweets from the chief executive of Pfizer, which is among the leaders in the race to develop a COVID-19 vaccine. Pfizer’s Albert Bourla, DVM, PhD, said that the FDA’s “public servants are known for their high integrity and scientific expertise and we have full faith in their ability to set appropriate standards for the approval of a COVID vaccine or treatment.”

The American Medical Association on Tuesday announced a public webinar on Wednesday where its president, Susan R. Bailey, MD, will discuss the COVID-19 vaccine review process with Peter Marks, MD, PhD, director of the Center for Biologics Evaluation and Research at the FDA. The AMA described this webinar as part of work “to restore trust in science and science-based decision-making among policymakers and the public.”

“To ensure media and the physician community are continuously informed about the federal review process for COVID-19 vaccine candidates, the AMA will host a webinar series to gain fact-based insights from the nation’s highest-ranking subject matter experts working to protect the health of the public,” the organization said in announcing the webinar.

In a statement, leaders of the Association of American Medical Colleges said that the FDA’s Vaccines and Related Biological Products Advisory Committee should evaluate any COVID-19 candidate vaccines prior to the FDA issuing an EUA.

“Full approval of a new vaccine or biologic requires demonstration of safety and effectiveness through a process that includes evaluation by the VRBPAC. Their recommendations are considered by FDA staff who ultimately have the authority to approve the new product,” said AAMC chief scientific officer Ross McKinney Jr, MD, and AAMC CEO David J. Skorton, MD, in the statement.

Thomas M. File Jr., MD, president of the Infectious Diseases Society of America, said in a statement that his association again asked the White House to “follow medical and scientific expertise in efforts to combat COVID-19.”

“It is imperative that a vaccine be approved on the basis of FDA’s quality standards and that its safety and efficacy are established before it is authorized,” Dr. File said. “A vaccine that has been approved with speed, rather than safety and efficacy, at the forefront will compound the challenges posed by this pandemic. FDA guidelines for approval that set standards the American people can trust are essential to the success of a vaccine.”

Stephen J. Ubl, chief executive of the Pharmaceutical Research and Manufacturers of America, said in a statement that his association “supports any efforts by FDA to provide clarifying guidance and we have engaged with the agency to support bringing greater transparency to the review process for COVID-19 vaccines.”

“To help address this public health crisis, our companies have also taken unprecedented steps to share vaccine clinical trial protocols and data in real time,” Mr. Ubl said. “We welcome the agency’s efforts to instill confidence in the rigorous safety of these potential vaccines.”

On Oct. 1, Michelle McMurry-Heath, MD, PhD, president and chief executive of the Biotechnology Innovation Organization, released publicly her letter urging Department of Health & Human Services Secretary Alex Azar to “publicly release all new guidance” related to a COVID-19 vaccine. Such a move would bolster public confidence in the vaccine, she said.

“We cannot allow a lack of transparency to undermine confidence in the vaccine development process. The public must have full faith in the scientific process and the rigor of FDA’s regulatory oversight if we are to end the pandemic,” she wrote in the Oct. 1 letter to Azar. “Releasing any additional guidance on granting emergency use authorization for a vaccine will go a long way in accomplishing this critical goal.”

This article first appeared on Medscape.com.

Chronic obstructive pulmonary disease (COPD) has been the third leading cause of death in the US since 2008.¹ Current management of COPD includes smoking cessation, adequate nutrition, medication therapy, pulmonary rehabilitation, and vaccines.² Outside of pharmacologic management, oxygen therapy has become a staple treatment of chronic hypoxemic respiratory failure due to COPD. Landmark trials, including the Nocturnal Oxygen Therapy Trial (NOTT) and Medical Research Council (MRC) study, demonstrated improved survival in patients with COPD and hypoxemia, particularly if these patients received oxygen for 18 hours per day.^3,4 NOTT prospectively evaluated 203 patients at 6 centers who were randomly allocated to either continuous oxygen therapy or 12-hour nocturnal oxygen therapy. The overall mortality in the nocturnal oxygen therapy group was 1.94 times that in the continuous oxygen therapy group (P = .01).³ The MRC study included 87 patients who were randomized to oxygen therapy or no oxygen; risk of death was 12% per year in the treated group vs 29% per year in the control group (P = .04).⁴ The effectiveness of long-term oxygen therapy (LTOT) in active smokers continues to be a source of debate; although 50% of patients in the NOTT trial were smokers, there was no subgroup analysis of whether smoking status had an impact on survival in those on continuous oxygen therapy.

Although many therapies are available for the treatment of COPD, the most effective treatment to prevent the progression of COPD is smoking cessation. Resources like smoking cessation programs, nicotine patches, and medications, such as bupropion and varenicline, are available to aid smoking cessation.⁵ However, many patients are unable to quit tobacco use despite their best efforts using available resources, and they continue to smoke even with progressive COPD. Long-time smokers also are likely to continue smoking while on LTOT, which increases their risk for fire-related injury.^6-8

Traditional indications are being scrutinized after the LTOT trial found no benefit with respect to time to death or first hospitalization among patients with stable COPD and resting or exercise-induced moderate desaturation.⁹

Although oxygen accelerates combustion and is a potential fire hazard, LTOT has been prescribed even to active smokers as the 2 landmark trials did not exclude patients who were active smokers from receiving oxygen therapy.^3,4 Therefore, LTOT has traditionally been prescribed to veterans who are actively smoking, despite the fire hazard. Attempts at mitigating hazards related to oxygen therapy in active smokers include counseling extensively about safety measures (which includes avoiding open flames such as candles, large fires, or sparks when on LTOT and providing Home Safety Agreements—a written contract between prescriber and patient wherein the patient agrees to abide by the terms of the US Department of Veterans Affairs (VA) to mitigate hazards related to LTOT in order to receive LTOT (eAppendix 

Methods

With this practice in mind, we conducted an institutional review board approved retrospective chart review of all veterans with diagnosis of COPD within the Central Texas Veterans Health Care System (CTVHCS) who were prescribed new LTOT between October 1, 2010 and September 30, 2015. Given the retrospective nature of the chart review, patient consent was not obtained. Inclusion criteria were veterans aged > 18 years who had a confirmed diagnosis of COPD by spirometry and who met criteria for either continuous or ambulation- only oxygen therapy.

Criteria for exclusion included patients with hypoxemia not solely attributable to COPD or due to diseases other than COPD. We reviewed encounters in these patients’ charts, including follow-up in the clinic of the providers prescribing oxygen, to assess for fire-related incidents, defined as events wherein fire was visualized by the patient or by individuals living with the patient and with report provided to medical equipment company providing oxygen; the patient did not have to seek medical care to qualify for fire-related incident. Of the 158 patients who met the criteria for inclusion in the study, 152 were male.

Statistics

Bayesian logistic regression was used to model the outcome variable fire-related incident with the predictors smoking status, age, race, depression, PTSD, and type of oxygen used. Mental health disorders have significant effect on substance use disorders, such as alcohol use. Depression and PTSD were more common mental health diagnoses found in our patient population. Additionally, due to the small sample size, these psychiatric diagnoses were chosen to evaluate the impact of mental health disorders on firerelated events.

Although the sample size of events was small, weakly informative normal priors (0, 2.5) were used to shrink parameter estimates toward 0 and minimize overfitting. Weakly informative normal priors have also been suggested to deal with the problem of quasi-complete separation, where in our case, both smoking and no-PTSD perfectly predicted the 9 fire-related incidents.¹⁰ All input variables were centered and scaled as recommended. ⁹ The model fit well as assessed by posterior predictive checks, and Rhat was 1.00 for all parameters, indicating that all chains converged. Analysis was completed in R version 3.5.1 using the ‘brms’ package for Bayesian modeling.¹¹

Results

The mean age for the 158 included patients was 71.3 years in nonsmokers and 65.9 years in smokers. Fifty-three of the included patients were active smokers when LTOT was initiated. Nine veterans had fire-related incidents during the study period. All 9 patients were actively smoking (about 17%) at the time of the fire incidents. There were no deaths, and 5 patients required hospitalization due to facial burns resulting from the fire-related incidents. Our study focused on 5 baseline characteristics in our population (Table 1). After gathering data, our group inferred that these characteristics had a potential relationship to fire-related incidents compared with other variables that were studied. Future studies could look at other patient characteristics that may be linked to fire-related incidents in patients on LTOT. For example, not having PTSD also perfectly predicts fire-related incidents in our data (ie, none of the participants who had fire-related incidents had PTSD). Although this finding was not within the 95% confidence interval (CI) in the model, it does show that care must be taken when interpreting effects from small samples (Table 2). The modelestimated odds of a fire-related incident occurring in a smoker were 31.6 (5.1-372.7) times more likely than were the odds of a firerelated incident occurring in a nonsmoker, holding all other predictors at their reference level; 95% CI for the odds ratios for all other predictors in the model included a value of 1.

Discussion

This study showed evidence of increased odds of fire-related events in actively smoking patients receiving LTOT compared with patients who do not actively smoke while attempting to adjust for potential confounders. Of the 9 patients who had fire events, 5 required hospitalization for burns.

A similar retrospective cohort study by Sharma and colleagues in 2015 demonstrated an increased risk of burn-related injury when on LTOT but reiterated that the benefit of oxygen outweighs the risk of burn-related injury in patients requiring oxygen therapy.¹² Interestingly, Sharma and colleagues were unable to identify smoking status for the patients studied but further identified factors associated with burn injury to include male sex, low socioeconomic status, oxygen therapy use, and ≥ 3 comorbidities. The study’s conclusion recommended continued education by health care professionals (HCPs) to their patients on LTOT regarding potential for burn injury. In the same vein, the VA National Center for Ethics in Health Care noted that “clinicians should familiarize themselves with the risks and benefits of LTOT; should inform their patients of the risks and benefits without exaggerating the risk associated with smoking; avoid undue coercion inherent in the clinician’s ability to withdraw LTOT; reduce the risk to the greatest degree possible; and consider termination of LTOT in very extreme cases and in consultation with a multidisciplinary committee.”¹³

This statement is in contrast to the guidelines and policies of other countries, such as Sweden, where smoking is a direct contraindication for prescription of oxygen therapy, or in Australia and New Zealand, where the Thoracic Society of Australia and New Zealand oxygen therapy guidelines recommend against prescription of LTOT, citing “increased fire risk and the probability that the poorer prognosis conferred by smoking will offset treatment benefit.”^6,14

The prevalence of oxygen therapy introduces the potential for fire-related incidents with subsequent injury requiring medical care. There are few studies regarding home oxygen fire in the US due to the lack of a uniform reporting system. One study by Wendling and Pelletier analyzed deaths in Maine, Massachusetts, New Hampshire, and Oklahoma between 2000 and 2007 and found 38 deaths directly attributable to home oxygen fires as a result of smoking^.15 Further, the Consumer Product Safety Commission’s National Electronic Injury Surveillance System between 2003 and 2006 attributed 1,190 thermal burns related to home oxygen fires; the majority of which were ignited by tobacco smoking.¹⁵ The Swedish National Register of Respiratory Failure (Swedevox) published prospective population-based, consecutive cohort study that collected data over 17 years and evaluated the risk of fire-related incident in those on LTOT. Of the 12,497 patients sampled, 17 had a burn injury and 2 patients died. The low incidence of burn injury on LTOT was attributed to the strict guidelines instituted in Sweden for doctors to avoid prescribing LTOT to actively smoking patients.⁶ A follow-up study by Tanash and colleagues compared the risk of burn injury in each country, respectively. The results found an increased number of burn injuries in those on oxygen therapy in Denmark, a country with fewer restrictions on smoking compared with those of Sweden.⁷ Similarly, our results showed that the rate of fire and burn injuries was exclusively among veterans who were active smokers. All patients who were prescribed oxygen therapy at CTVHCS received counseling and signed Home Safety Agreements. Despite following the recommendations set forth by the VA on counseling, extensive harm reduction techniques, and close follow-up, we found there was still a high incidence of fires in veterans with COPD on LTOT who continue to smoke.

The findings from our study concur with those previously published regarding the risk of home oxygen fire and concomitant smoking, supporting the idea for more regulated and concrete guidelines for prescribing LTOT to those requiring it.⁸

Limitations

The major limitation was the small sample size of our study. Another limitation was that our study population is predominantly male as is common in veteran cohorts. In fiscal year 2016, the veteran population of Texas was 1,434,361 males and 168,967 females.¹⁶ According to Franklin and colleagues, HCPs noticed an increase use of long-term oxygen among women compared with that of men.¹⁷

Conclusions

Our study showed an increased odds of firerelated incidents of patients while on LTOT, strengthening the argument that even with extensive education, those who smoke and are on LTOT continue to put themselves at risk of a fire-related incident. This finding stresses the importance of continuing patient education on the importance of smoking cessation prior to administration of LTOT or avoiding fire hazards while on LTOT. Further research into LTOT and fire hazards could help in implementing a more structured approval process for patients who want to obtain LTOT. We propose further studies evaluating risk factors for the incidence of fire events among patients prescribed LTOT. A growing and aging population with a need for LTOT necessitates examination of oxygen safe prescribing.

Chronic obstructive pulmonary disease (COPD) has been the third leading cause of death in the US since 2008.¹ Current management of COPD includes smoking cessation, adequate nutrition, medication therapy, pulmonary rehabilitation, and vaccines.² Outside of pharmacologic management, oxygen therapy has become a staple treatment of chronic hypoxemic respiratory failure due to COPD. Landmark trials, including the Nocturnal Oxygen Therapy Trial (NOTT) and Medical Research Council (MRC) study, demonstrated improved survival in patients with COPD and hypoxemia, particularly if these patients received oxygen for 18 hours per day.^3,4 NOTT prospectively evaluated 203 patients at 6 centers who were randomly allocated to either continuous oxygen therapy or 12-hour nocturnal oxygen therapy. The overall mortality in the nocturnal oxygen therapy group was 1.94 times that in the continuous oxygen therapy group (P = .01).³ The MRC study included 87 patients who were randomized to oxygen therapy or no oxygen; risk of death was 12% per year in the treated group vs 29% per year in the control group (P = .04).⁴ The effectiveness of long-term oxygen therapy (LTOT) in active smokers continues to be a source of debate; although 50% of patients in the NOTT trial were smokers, there was no subgroup analysis of whether smoking status had an impact on survival in those on continuous oxygen therapy.

Although many therapies are available for the treatment of COPD, the most effective treatment to prevent the progression of COPD is smoking cessation. Resources like smoking cessation programs, nicotine patches, and medications, such as bupropion and varenicline, are available to aid smoking cessation.⁵ However, many patients are unable to quit tobacco use despite their best efforts using available resources, and they continue to smoke even with progressive COPD. Long-time smokers also are likely to continue smoking while on LTOT, which increases their risk for fire-related injury.^6-8

Traditional indications are being scrutinized after the LTOT trial found no benefit with respect to time to death or first hospitalization among patients with stable COPD and resting or exercise-induced moderate desaturation.⁹

Although oxygen accelerates combustion and is a potential fire hazard, LTOT has been prescribed even to active smokers as the 2 landmark trials did not exclude patients who were active smokers from receiving oxygen therapy.^3,4 Therefore, LTOT has traditionally been prescribed to veterans who are actively smoking, despite the fire hazard. Attempts at mitigating hazards related to oxygen therapy in active smokers include counseling extensively about safety measures (which includes avoiding open flames such as candles, large fires, or sparks when on LTOT and providing Home Safety Agreements—a written contract between prescriber and patient wherein the patient agrees to abide by the terms of the US Department of Veterans Affairs (VA) to mitigate hazards related to LTOT in order to receive LTOT (eAppendix 

Methods

With this practice in mind, we conducted an institutional review board approved retrospective chart review of all veterans with diagnosis of COPD within the Central Texas Veterans Health Care System (CTVHCS) who were prescribed new LTOT between October 1, 2010 and September 30, 2015. Given the retrospective nature of the chart review, patient consent was not obtained. Inclusion criteria were veterans aged > 18 years who had a confirmed diagnosis of COPD by spirometry and who met criteria for either continuous or ambulation- only oxygen therapy.

Criteria for exclusion included patients with hypoxemia not solely attributable to COPD or due to diseases other than COPD. We reviewed encounters in these patients’ charts, including follow-up in the clinic of the providers prescribing oxygen, to assess for fire-related incidents, defined as events wherein fire was visualized by the patient or by individuals living with the patient and with report provided to medical equipment company providing oxygen; the patient did not have to seek medical care to qualify for fire-related incident. Of the 158 patients who met the criteria for inclusion in the study, 152 were male.

Statistics

Bayesian logistic regression was used to model the outcome variable fire-related incident with the predictors smoking status, age, race, depression, PTSD, and type of oxygen used. Mental health disorders have significant effect on substance use disorders, such as alcohol use. Depression and PTSD were more common mental health diagnoses found in our patient population. Additionally, due to the small sample size, these psychiatric diagnoses were chosen to evaluate the impact of mental health disorders on firerelated events.

Although the sample size of events was small, weakly informative normal priors (0, 2.5) were used to shrink parameter estimates toward 0 and minimize overfitting. Weakly informative normal priors have also been suggested to deal with the problem of quasi-complete separation, where in our case, both smoking and no-PTSD perfectly predicted the 9 fire-related incidents.¹⁰ All input variables were centered and scaled as recommended. ⁹ The model fit well as assessed by posterior predictive checks, and Rhat was 1.00 for all parameters, indicating that all chains converged. Analysis was completed in R version 3.5.1 using the ‘brms’ package for Bayesian modeling.¹¹

Results

The mean age for the 158 included patients was 71.3 years in nonsmokers and 65.9 years in smokers. Fifty-three of the included patients were active smokers when LTOT was initiated. Nine veterans had fire-related incidents during the study period. All 9 patients were actively smoking (about 17%) at the time of the fire incidents. There were no deaths, and 5 patients required hospitalization due to facial burns resulting from the fire-related incidents. Our study focused on 5 baseline characteristics in our population (Table 1). After gathering data, our group inferred that these characteristics had a potential relationship to fire-related incidents compared with other variables that were studied. Future studies could look at other patient characteristics that may be linked to fire-related incidents in patients on LTOT. For example, not having PTSD also perfectly predicts fire-related incidents in our data (ie, none of the participants who had fire-related incidents had PTSD). Although this finding was not within the 95% confidence interval (CI) in the model, it does show that care must be taken when interpreting effects from small samples (Table 2). The modelestimated odds of a fire-related incident occurring in a smoker were 31.6 (5.1-372.7) times more likely than were the odds of a firerelated incident occurring in a nonsmoker, holding all other predictors at their reference level; 95% CI for the odds ratios for all other predictors in the model included a value of 1.

Discussion

This study showed evidence of increased odds of fire-related events in actively smoking patients receiving LTOT compared with patients who do not actively smoke while attempting to adjust for potential confounders. Of the 9 patients who had fire events, 5 required hospitalization for burns.

A similar retrospective cohort study by Sharma and colleagues in 2015 demonstrated an increased risk of burn-related injury when on LTOT but reiterated that the benefit of oxygen outweighs the risk of burn-related injury in patients requiring oxygen therapy.¹² Interestingly, Sharma and colleagues were unable to identify smoking status for the patients studied but further identified factors associated with burn injury to include male sex, low socioeconomic status, oxygen therapy use, and ≥ 3 comorbidities. The study’s conclusion recommended continued education by health care professionals (HCPs) to their patients on LTOT regarding potential for burn injury. In the same vein, the VA National Center for Ethics in Health Care noted that “clinicians should familiarize themselves with the risks and benefits of LTOT; should inform their patients of the risks and benefits without exaggerating the risk associated with smoking; avoid undue coercion inherent in the clinician’s ability to withdraw LTOT; reduce the risk to the greatest degree possible; and consider termination of LTOT in very extreme cases and in consultation with a multidisciplinary committee.”¹³

This statement is in contrast to the guidelines and policies of other countries, such as Sweden, where smoking is a direct contraindication for prescription of oxygen therapy, or in Australia and New Zealand, where the Thoracic Society of Australia and New Zealand oxygen therapy guidelines recommend against prescription of LTOT, citing “increased fire risk and the probability that the poorer prognosis conferred by smoking will offset treatment benefit.”^6,14

The prevalence of oxygen therapy introduces the potential for fire-related incidents with subsequent injury requiring medical care. There are few studies regarding home oxygen fire in the US due to the lack of a uniform reporting system. One study by Wendling and Pelletier analyzed deaths in Maine, Massachusetts, New Hampshire, and Oklahoma between 2000 and 2007 and found 38 deaths directly attributable to home oxygen fires as a result of smoking^.15 Further, the Consumer Product Safety Commission’s National Electronic Injury Surveillance System between 2003 and 2006 attributed 1,190 thermal burns related to home oxygen fires; the majority of which were ignited by tobacco smoking.¹⁵ The Swedish National Register of Respiratory Failure (Swedevox) published prospective population-based, consecutive cohort study that collected data over 17 years and evaluated the risk of fire-related incident in those on LTOT. Of the 12,497 patients sampled, 17 had a burn injury and 2 patients died. The low incidence of burn injury on LTOT was attributed to the strict guidelines instituted in Sweden for doctors to avoid prescribing LTOT to actively smoking patients.⁶ A follow-up study by Tanash and colleagues compared the risk of burn injury in each country, respectively. The results found an increased number of burn injuries in those on oxygen therapy in Denmark, a country with fewer restrictions on smoking compared with those of Sweden.⁷ Similarly, our results showed that the rate of fire and burn injuries was exclusively among veterans who were active smokers. All patients who were prescribed oxygen therapy at CTVHCS received counseling and signed Home Safety Agreements. Despite following the recommendations set forth by the VA on counseling, extensive harm reduction techniques, and close follow-up, we found there was still a high incidence of fires in veterans with COPD on LTOT who continue to smoke.

The findings from our study concur with those previously published regarding the risk of home oxygen fire and concomitant smoking, supporting the idea for more regulated and concrete guidelines for prescribing LTOT to those requiring it.⁸

Limitations

The major limitation was the small sample size of our study. Another limitation was that our study population is predominantly male as is common in veteran cohorts. In fiscal year 2016, the veteran population of Texas was 1,434,361 males and 168,967 females.¹⁶ According to Franklin and colleagues, HCPs noticed an increase use of long-term oxygen among women compared with that of men.¹⁷

Conclusions

Our study showed an increased odds of firerelated incidents of patients while on LTOT, strengthening the argument that even with extensive education, those who smoke and are on LTOT continue to put themselves at risk of a fire-related incident. This finding stresses the importance of continuing patient education on the importance of smoking cessation prior to administration of LTOT or avoiding fire hazards while on LTOT. Further research into LTOT and fire hazards could help in implementing a more structured approval process for patients who want to obtain LTOT. We propose further studies evaluating risk factors for the incidence of fire events among patients prescribed LTOT. A growing and aging population with a need for LTOT necessitates examination of oxygen safe prescribing.

Chronic obstructive pulmonary disease (COPD) has been the third leading cause of death in the US since 2008.¹ Current management of COPD includes smoking cessation, adequate nutrition, medication therapy, pulmonary rehabilitation, and vaccines.² Outside of pharmacologic management, oxygen therapy has become a staple treatment of chronic hypoxemic respiratory failure due to COPD. Landmark trials, including the Nocturnal Oxygen Therapy Trial (NOTT) and Medical Research Council (MRC) study, demonstrated improved survival in patients with COPD and hypoxemia, particularly if these patients received oxygen for 18 hours per day.^3,4 NOTT prospectively evaluated 203 patients at 6 centers who were randomly allocated to either continuous oxygen therapy or 12-hour nocturnal oxygen therapy. The overall mortality in the nocturnal oxygen therapy group was 1.94 times that in the continuous oxygen therapy group (P = .01).³ The MRC study included 87 patients who were randomized to oxygen therapy or no oxygen; risk of death was 12% per year in the treated group vs 29% per year in the control group (P = .04).⁴ The effectiveness of long-term oxygen therapy (LTOT) in active smokers continues to be a source of debate; although 50% of patients in the NOTT trial were smokers, there was no subgroup analysis of whether smoking status had an impact on survival in those on continuous oxygen therapy.

Although many therapies are available for the treatment of COPD, the most effective treatment to prevent the progression of COPD is smoking cessation. Resources like smoking cessation programs, nicotine patches, and medications, such as bupropion and varenicline, are available to aid smoking cessation.⁵ However, many patients are unable to quit tobacco use despite their best efforts using available resources, and they continue to smoke even with progressive COPD. Long-time smokers also are likely to continue smoking while on LTOT, which increases their risk for fire-related injury.^6-8

Traditional indications are being scrutinized after the LTOT trial found no benefit with respect to time to death or first hospitalization among patients with stable COPD and resting or exercise-induced moderate desaturation.⁹

Although oxygen accelerates combustion and is a potential fire hazard, LTOT has been prescribed even to active smokers as the 2 landmark trials did not exclude patients who were active smokers from receiving oxygen therapy.^3,4 Therefore, LTOT has traditionally been prescribed to veterans who are actively smoking, despite the fire hazard. Attempts at mitigating hazards related to oxygen therapy in active smokers include counseling extensively about safety measures (which includes avoiding open flames such as candles, large fires, or sparks when on LTOT and providing Home Safety Agreements—a written contract between prescriber and patient wherein the patient agrees to abide by the terms of the US Department of Veterans Affairs (VA) to mitigate hazards related to LTOT in order to receive LTOT (eAppendix 

Methods

With this practice in mind, we conducted an institutional review board approved retrospective chart review of all veterans with diagnosis of COPD within the Central Texas Veterans Health Care System (CTVHCS) who were prescribed new LTOT between October 1, 2010 and September 30, 2015. Given the retrospective nature of the chart review, patient consent was not obtained. Inclusion criteria were veterans aged > 18 years who had a confirmed diagnosis of COPD by spirometry and who met criteria for either continuous or ambulation- only oxygen therapy.

Criteria for exclusion included patients with hypoxemia not solely attributable to COPD or due to diseases other than COPD. We reviewed encounters in these patients’ charts, including follow-up in the clinic of the providers prescribing oxygen, to assess for fire-related incidents, defined as events wherein fire was visualized by the patient or by individuals living with the patient and with report provided to medical equipment company providing oxygen; the patient did not have to seek medical care to qualify for fire-related incident. Of the 158 patients who met the criteria for inclusion in the study, 152 were male.

Statistics

Bayesian logistic regression was used to model the outcome variable fire-related incident with the predictors smoking status, age, race, depression, PTSD, and type of oxygen used. Mental health disorders have significant effect on substance use disorders, such as alcohol use. Depression and PTSD were more common mental health diagnoses found in our patient population. Additionally, due to the small sample size, these psychiatric diagnoses were chosen to evaluate the impact of mental health disorders on firerelated events.

Although the sample size of events was small, weakly informative normal priors (0, 2.5) were used to shrink parameter estimates toward 0 and minimize overfitting. Weakly informative normal priors have also been suggested to deal with the problem of quasi-complete separation, where in our case, both smoking and no-PTSD perfectly predicted the 9 fire-related incidents.¹⁰ All input variables were centered and scaled as recommended. ⁹ The model fit well as assessed by posterior predictive checks, and Rhat was 1.00 for all parameters, indicating that all chains converged. Analysis was completed in R version 3.5.1 using the ‘brms’ package for Bayesian modeling.¹¹

Results

The mean age for the 158 included patients was 71.3 years in nonsmokers and 65.9 years in smokers. Fifty-three of the included patients were active smokers when LTOT was initiated. Nine veterans had fire-related incidents during the study period. All 9 patients were actively smoking (about 17%) at the time of the fire incidents. There were no deaths, and 5 patients required hospitalization due to facial burns resulting from the fire-related incidents. Our study focused on 5 baseline characteristics in our population (Table 1). After gathering data, our group inferred that these characteristics had a potential relationship to fire-related incidents compared with other variables that were studied. Future studies could look at other patient characteristics that may be linked to fire-related incidents in patients on LTOT. For example, not having PTSD also perfectly predicts fire-related incidents in our data (ie, none of the participants who had fire-related incidents had PTSD). Although this finding was not within the 95% confidence interval (CI) in the model, it does show that care must be taken when interpreting effects from small samples (Table 2). The modelestimated odds of a fire-related incident occurring in a smoker were 31.6 (5.1-372.7) times more likely than were the odds of a firerelated incident occurring in a nonsmoker, holding all other predictors at their reference level; 95% CI for the odds ratios for all other predictors in the model included a value of 1.

Discussion

This study showed evidence of increased odds of fire-related events in actively smoking patients receiving LTOT compared with patients who do not actively smoke while attempting to adjust for potential confounders. Of the 9 patients who had fire events, 5 required hospitalization for burns.

A similar retrospective cohort study by Sharma and colleagues in 2015 demonstrated an increased risk of burn-related injury when on LTOT but reiterated that the benefit of oxygen outweighs the risk of burn-related injury in patients requiring oxygen therapy.¹² Interestingly, Sharma and colleagues were unable to identify smoking status for the patients studied but further identified factors associated with burn injury to include male sex, low socioeconomic status, oxygen therapy use, and ≥ 3 comorbidities. The study’s conclusion recommended continued education by health care professionals (HCPs) to their patients on LTOT regarding potential for burn injury. In the same vein, the VA National Center for Ethics in Health Care noted that “clinicians should familiarize themselves with the risks and benefits of LTOT; should inform their patients of the risks and benefits without exaggerating the risk associated with smoking; avoid undue coercion inherent in the clinician’s ability to withdraw LTOT; reduce the risk to the greatest degree possible; and consider termination of LTOT in very extreme cases and in consultation with a multidisciplinary committee.”¹³

This statement is in contrast to the guidelines and policies of other countries, such as Sweden, where smoking is a direct contraindication for prescription of oxygen therapy, or in Australia and New Zealand, where the Thoracic Society of Australia and New Zealand oxygen therapy guidelines recommend against prescription of LTOT, citing “increased fire risk and the probability that the poorer prognosis conferred by smoking will offset treatment benefit.”^6,14

The prevalence of oxygen therapy introduces the potential for fire-related incidents with subsequent injury requiring medical care. There are few studies regarding home oxygen fire in the US due to the lack of a uniform reporting system. One study by Wendling and Pelletier analyzed deaths in Maine, Massachusetts, New Hampshire, and Oklahoma between 2000 and 2007 and found 38 deaths directly attributable to home oxygen fires as a result of smoking^.15 Further, the Consumer Product Safety Commission’s National Electronic Injury Surveillance System between 2003 and 2006 attributed 1,190 thermal burns related to home oxygen fires; the majority of which were ignited by tobacco smoking.¹⁵ The Swedish National Register of Respiratory Failure (Swedevox) published prospective population-based, consecutive cohort study that collected data over 17 years and evaluated the risk of fire-related incident in those on LTOT. Of the 12,497 patients sampled, 17 had a burn injury and 2 patients died. The low incidence of burn injury on LTOT was attributed to the strict guidelines instituted in Sweden for doctors to avoid prescribing LTOT to actively smoking patients.⁶ A follow-up study by Tanash and colleagues compared the risk of burn injury in each country, respectively. The results found an increased number of burn injuries in those on oxygen therapy in Denmark, a country with fewer restrictions on smoking compared with those of Sweden.⁷ Similarly, our results showed that the rate of fire and burn injuries was exclusively among veterans who were active smokers. All patients who were prescribed oxygen therapy at CTVHCS received counseling and signed Home Safety Agreements. Despite following the recommendations set forth by the VA on counseling, extensive harm reduction techniques, and close follow-up, we found there was still a high incidence of fires in veterans with COPD on LTOT who continue to smoke.

The findings from our study concur with those previously published regarding the risk of home oxygen fire and concomitant smoking, supporting the idea for more regulated and concrete guidelines for prescribing LTOT to those requiring it.⁸

Limitations

The major limitation was the small sample size of our study. Another limitation was that our study population is predominantly male as is common in veteran cohorts. In fiscal year 2016, the veteran population of Texas was 1,434,361 males and 168,967 females.¹⁶ According to Franklin and colleagues, HCPs noticed an increase use of long-term oxygen among women compared with that of men.¹⁷

Conclusions

Our study showed an increased odds of firerelated incidents of patients while on LTOT, strengthening the argument that even with extensive education, those who smoke and are on LTOT continue to put themselves at risk of a fire-related incident. This finding stresses the importance of continuing patient education on the importance of smoking cessation prior to administration of LTOT or avoiding fire hazards while on LTOT. Further research into LTOT and fire hazards could help in implementing a more structured approval process for patients who want to obtain LTOT. We propose further studies evaluating risk factors for the incidence of fire events among patients prescribed LTOT. A growing and aging population with a need for LTOT necessitates examination of oxygen safe prescribing.

Restarting breast cancer screening programs after the COVID-19 disruption will be challenging given a trade-off between minimizing excess mortality from the disease and strain on programs, according to a modeling study reported at the 12th European Breast Cancer Conference.

Fallout of the pandemic has included reductions in cancer screening and diagnosis, said study investigator Lindy M. Kregting, a PhD student in the department of public health at Erasmus Medical Center, University Medical Center Rotterdam (the Netherlands).

In the Netherlands, new breast cancer diagnoses fell dramatically from historical levels starting in February. The number in April was less than half of that expected.

Ms. Kregting and colleagues used modeling to assess the impact of four strategies for restarting breast cancer screening in the Netherlands. The strategies differed regarding the population affected, the duration of the effects, and changes in stopping age. The usual situation, without any disruption, served as the comparator.

Results showed wide variation across strategies with respect to the increase in screening capacity needed during the latter half of this year – from 0% to 100% – and the excess breast cancer mortality occurring during 2020-2030 – from as many as 181 excess breast cancer deaths to as few as 14.

“The effects of the disruption are dependent on the chosen restart strategy,” Ms. Kregting summarized. “It would be preferred to immediately catch up because this minimizes the impact, but it also requires a very high capacity, so it may not always be possible. A proper alternative would be to increase the stopping age, so no screens are omitted, because this requires a rather normal capacity, and it will result in only small effects on incidence and mortality.”

As screening programs restart in some countries, there are still a lot of unknowns that could affect outcomes, including how many women will attend given that some may stay away out of fear, Ms. Kregting cautioned.

“We plan to do further model calculations when we know exactly what has happened. ... For now, we just assumed some reasonable disruption periods, and we assumed that capacity would be back to the original, before COVID-19, but I think we can say this is probably not the case,” she added.
 

Study details

Ms. Kregting and colleagues used Dutch breast cancer screening program parameters (biennial digital mammography for women aged 50-75 years) and a microsimulation screening analysis model to simulate four strategies for restarting breast cancer screening after a 6-month disruption:

• “Everyone delay,” a strategy in which all screening continues in the order planned with no change in the stopping age of 75 years (so that one in four women ultimately miss a screening during their lifetime)
• “First rounds no delay,” in which there is a delay in screening except for women having their first screening
• “Continue after stopping age,” in which there is a delay in screening but temporary increasing of the stopping age (to 76.5 years) to ensure all women get their final screen
• “Catch-up after stop,” in which capacity is increased to ensure full catch-up, with all delayed screens caught up in a 6-month period (the second half of 2020).

Results showed that 5,872 women would be screened in the latter half of 2020 if screening proceeded as usual without disruption. The necessary capacity was essentially the same with all of the restarting strategies, except for the catch-up-after-stop strategy, which would require a doubling of that number.

The temporal pattern of breast cancer incidence varied according to restart strategy early on, but incidence essentially returned to that expected with undisrupted screening by 2025 for all four strategies, with some small fluctuations thereafter.

The impact on breast cancer mortality differed considerably long term. It increased slightly and transiently above the expected level with the catch-up-after-stop strategy, but there were sizable, long-lasting increases with the other strategies, with excess deaths still seen in 2060 for the everyone-delay strategy.

In absolute terms, the excess number of breast cancer deaths during 2020-2030, compared with undisrupted screening, was 181 with the everyone-delay strategy, 155 with the first-rounds-no-delay strategy, 145 with the continue-after-stopping-age strategy, and just 14 with the catch-up-after-stop strategy. Ms. Kregting declined to provide numbers for other countries, given that the model is based on the Dutch population and screening program.
 

Results in context

“The unprecedented burden of COVID-19 on health systems worldwide has important implications for cancer care,” said invited discussant Alessandra Gennari, MD, PhD, of the University of Eastern Piedmont and Maggiore della Carità Hospital, both in Novara, Italy.

“There is a delay in diagnosis due to the fact that screening programs and diagnostic programs have been decreased or suspended in many Western countries where this is standard of care. Patients also are more reluctant to present to health care services, delaying their diagnosis,” Dr. Gennari said.

Findings of this new study add to those of similar studies undertaken in Italy (published in In Vivo) and the United Kingdom (published in The Lancet Oncology) showing the likely marked toll of the pandemic on cancer diagnosis and mortality, Dr. Gennari noted. Taken together, the findings underscore the urgent need for policy interventions to mitigate this impact.

“These interventions should focus on increasing routine diagnostic capacity, through which up to 40% of patients with cancer are diagnosed,” Dr. Gennari recommended. “Public health messaging is needed that accurately conveys the risk of severe illness from COVID-19 versus the risks of not seeking health care advice if patients are symptomatic. Finally, there is a need for provision of evidence-based data on which clinicians can adequately base their decision on how to manage the risks of cancer patients and the risks and benefits of procedures during the pandemic.”

The current study did not have any specific funding, and Ms. Kregting disclosed no conflicts of interest. Dr. Gennari disclosed relationships with Roche, Eisai, Lilly, AstraZeneca, Daiichi Sankyo, Merck, Novartis, and Pfizer.

SOURCE: Kregting L et al. EBCC-12 Virtual Conference, Abstract 24.

Restarting breast cancer screening programs after the COVID-19 disruption will be challenging given a trade-off between minimizing excess mortality from the disease and strain on programs, according to a modeling study reported at the 12th European Breast Cancer Conference.

Fallout of the pandemic has included reductions in cancer screening and diagnosis, said study investigator Lindy M. Kregting, a PhD student in the department of public health at Erasmus Medical Center, University Medical Center Rotterdam (the Netherlands).

In the Netherlands, new breast cancer diagnoses fell dramatically from historical levels starting in February. The number in April was less than half of that expected.

Ms. Kregting and colleagues used modeling to assess the impact of four strategies for restarting breast cancer screening in the Netherlands. The strategies differed regarding the population affected, the duration of the effects, and changes in stopping age. The usual situation, without any disruption, served as the comparator.

Results showed wide variation across strategies with respect to the increase in screening capacity needed during the latter half of this year – from 0% to 100% – and the excess breast cancer mortality occurring during 2020-2030 – from as many as 181 excess breast cancer deaths to as few as 14.

“The effects of the disruption are dependent on the chosen restart strategy,” Ms. Kregting summarized. “It would be preferred to immediately catch up because this minimizes the impact, but it also requires a very high capacity, so it may not always be possible. A proper alternative would be to increase the stopping age, so no screens are omitted, because this requires a rather normal capacity, and it will result in only small effects on incidence and mortality.”

As screening programs restart in some countries, there are still a lot of unknowns that could affect outcomes, including how many women will attend given that some may stay away out of fear, Ms. Kregting cautioned.

“We plan to do further model calculations when we know exactly what has happened. ... For now, we just assumed some reasonable disruption periods, and we assumed that capacity would be back to the original, before COVID-19, but I think we can say this is probably not the case,” she added.
 

Study details

Ms. Kregting and colleagues used Dutch breast cancer screening program parameters (biennial digital mammography for women aged 50-75 years) and a microsimulation screening analysis model to simulate four strategies for restarting breast cancer screening after a 6-month disruption:

• “Everyone delay,” a strategy in which all screening continues in the order planned with no change in the stopping age of 75 years (so that one in four women ultimately miss a screening during their lifetime)
• “First rounds no delay,” in which there is a delay in screening except for women having their first screening
• “Continue after stopping age,” in which there is a delay in screening but temporary increasing of the stopping age (to 76.5 years) to ensure all women get their final screen
• “Catch-up after stop,” in which capacity is increased to ensure full catch-up, with all delayed screens caught up in a 6-month period (the second half of 2020).

Results showed that 5,872 women would be screened in the latter half of 2020 if screening proceeded as usual without disruption. The necessary capacity was essentially the same with all of the restarting strategies, except for the catch-up-after-stop strategy, which would require a doubling of that number.

The temporal pattern of breast cancer incidence varied according to restart strategy early on, but incidence essentially returned to that expected with undisrupted screening by 2025 for all four strategies, with some small fluctuations thereafter.

The impact on breast cancer mortality differed considerably long term. It increased slightly and transiently above the expected level with the catch-up-after-stop strategy, but there were sizable, long-lasting increases with the other strategies, with excess deaths still seen in 2060 for the everyone-delay strategy.

In absolute terms, the excess number of breast cancer deaths during 2020-2030, compared with undisrupted screening, was 181 with the everyone-delay strategy, 155 with the first-rounds-no-delay strategy, 145 with the continue-after-stopping-age strategy, and just 14 with the catch-up-after-stop strategy. Ms. Kregting declined to provide numbers for other countries, given that the model is based on the Dutch population and screening program.
 

Results in context

“The unprecedented burden of COVID-19 on health systems worldwide has important implications for cancer care,” said invited discussant Alessandra Gennari, MD, PhD, of the University of Eastern Piedmont and Maggiore della Carità Hospital, both in Novara, Italy.

“There is a delay in diagnosis due to the fact that screening programs and diagnostic programs have been decreased or suspended in many Western countries where this is standard of care. Patients also are more reluctant to present to health care services, delaying their diagnosis,” Dr. Gennari said.

Findings of this new study add to those of similar studies undertaken in Italy (published in In Vivo) and the United Kingdom (published in The Lancet Oncology) showing the likely marked toll of the pandemic on cancer diagnosis and mortality, Dr. Gennari noted. Taken together, the findings underscore the urgent need for policy interventions to mitigate this impact.

“These interventions should focus on increasing routine diagnostic capacity, through which up to 40% of patients with cancer are diagnosed,” Dr. Gennari recommended. “Public health messaging is needed that accurately conveys the risk of severe illness from COVID-19 versus the risks of not seeking health care advice if patients are symptomatic. Finally, there is a need for provision of evidence-based data on which clinicians can adequately base their decision on how to manage the risks of cancer patients and the risks and benefits of procedures during the pandemic.”

The current study did not have any specific funding, and Ms. Kregting disclosed no conflicts of interest. Dr. Gennari disclosed relationships with Roche, Eisai, Lilly, AstraZeneca, Daiichi Sankyo, Merck, Novartis, and Pfizer.

SOURCE: Kregting L et al. EBCC-12 Virtual Conference, Abstract 24.

Restarting breast cancer screening programs after the COVID-19 disruption will be challenging given a trade-off between minimizing excess mortality from the disease and strain on programs, according to a modeling study reported at the 12th European Breast Cancer Conference.

Fallout of the pandemic has included reductions in cancer screening and diagnosis, said study investigator Lindy M. Kregting, a PhD student in the department of public health at Erasmus Medical Center, University Medical Center Rotterdam (the Netherlands).

In the Netherlands, new breast cancer diagnoses fell dramatically from historical levels starting in February. The number in April was less than half of that expected.

Ms. Kregting and colleagues used modeling to assess the impact of four strategies for restarting breast cancer screening in the Netherlands. The strategies differed regarding the population affected, the duration of the effects, and changes in stopping age. The usual situation, without any disruption, served as the comparator.

Results showed wide variation across strategies with respect to the increase in screening capacity needed during the latter half of this year – from 0% to 100% – and the excess breast cancer mortality occurring during 2020-2030 – from as many as 181 excess breast cancer deaths to as few as 14.

“The effects of the disruption are dependent on the chosen restart strategy,” Ms. Kregting summarized. “It would be preferred to immediately catch up because this minimizes the impact, but it also requires a very high capacity, so it may not always be possible. A proper alternative would be to increase the stopping age, so no screens are omitted, because this requires a rather normal capacity, and it will result in only small effects on incidence and mortality.”

As screening programs restart in some countries, there are still a lot of unknowns that could affect outcomes, including how many women will attend given that some may stay away out of fear, Ms. Kregting cautioned.

“We plan to do further model calculations when we know exactly what has happened. ... For now, we just assumed some reasonable disruption periods, and we assumed that capacity would be back to the original, before COVID-19, but I think we can say this is probably not the case,” she added.
 

Study details

Ms. Kregting and colleagues used Dutch breast cancer screening program parameters (biennial digital mammography for women aged 50-75 years) and a microsimulation screening analysis model to simulate four strategies for restarting breast cancer screening after a 6-month disruption:

• “Everyone delay,” a strategy in which all screening continues in the order planned with no change in the stopping age of 75 years (so that one in four women ultimately miss a screening during their lifetime)
• “First rounds no delay,” in which there is a delay in screening except for women having their first screening
• “Continue after stopping age,” in which there is a delay in screening but temporary increasing of the stopping age (to 76.5 years) to ensure all women get their final screen
• “Catch-up after stop,” in which capacity is increased to ensure full catch-up, with all delayed screens caught up in a 6-month period (the second half of 2020).

Results showed that 5,872 women would be screened in the latter half of 2020 if screening proceeded as usual without disruption. The necessary capacity was essentially the same with all of the restarting strategies, except for the catch-up-after-stop strategy, which would require a doubling of that number.

The temporal pattern of breast cancer incidence varied according to restart strategy early on, but incidence essentially returned to that expected with undisrupted screening by 2025 for all four strategies, with some small fluctuations thereafter.

The impact on breast cancer mortality differed considerably long term. It increased slightly and transiently above the expected level with the catch-up-after-stop strategy, but there were sizable, long-lasting increases with the other strategies, with excess deaths still seen in 2060 for the everyone-delay strategy.

In absolute terms, the excess number of breast cancer deaths during 2020-2030, compared with undisrupted screening, was 181 with the everyone-delay strategy, 155 with the first-rounds-no-delay strategy, 145 with the continue-after-stopping-age strategy, and just 14 with the catch-up-after-stop strategy. Ms. Kregting declined to provide numbers for other countries, given that the model is based on the Dutch population and screening program.
 

Results in context

“The unprecedented burden of COVID-19 on health systems worldwide has important implications for cancer care,” said invited discussant Alessandra Gennari, MD, PhD, of the University of Eastern Piedmont and Maggiore della Carità Hospital, both in Novara, Italy.

“There is a delay in diagnosis due to the fact that screening programs and diagnostic programs have been decreased or suspended in many Western countries where this is standard of care. Patients also are more reluctant to present to health care services, delaying their diagnosis,” Dr. Gennari said.

Findings of this new study add to those of similar studies undertaken in Italy (published in In Vivo) and the United Kingdom (published in The Lancet Oncology) showing the likely marked toll of the pandemic on cancer diagnosis and mortality, Dr. Gennari noted. Taken together, the findings underscore the urgent need for policy interventions to mitigate this impact.

“These interventions should focus on increasing routine diagnostic capacity, through which up to 40% of patients with cancer are diagnosed,” Dr. Gennari recommended. “Public health messaging is needed that accurately conveys the risk of severe illness from COVID-19 versus the risks of not seeking health care advice if patients are symptomatic. Finally, there is a need for provision of evidence-based data on which clinicians can adequately base their decision on how to manage the risks of cancer patients and the risks and benefits of procedures during the pandemic.”

The current study did not have any specific funding, and Ms. Kregting disclosed no conflicts of interest. Dr. Gennari disclosed relationships with Roche, Eisai, Lilly, AstraZeneca, Daiichi Sankyo, Merck, Novartis, and Pfizer.

SOURCE: Kregting L et al. EBCC-12 Virtual Conference, Abstract 24.