Click to view more from Federal Health Care Data Trends 2022

Click to view more from Federal Health Care Data Trends 2022

Click to view more from Federal Health Care Data Trends 2022

Managing type 1 diabetes is never easy. But if you ask 16-year-old climbing star Katie Bone, she’ll tell you that she will never let this disease get in the way of her goals.

“My motto is the same one as Bethany Hamilton’s – the surfer who lost her arm in a shark attack: ‘I don’t need easy, I just need possible,” said Ms. Bone, who lives in Albuquerque and has been a competitive rock climber since she was 8 years old. “That really stuck with me.”

Just watching her compete on NBC’s hit reality show American Ninja Warrior in June is proof of that. Not only did the nationally ranked climber fly through the obstacles with grace and grit, but she proudly showed off her two monitoring devices: a glucose monitor on one arm and a tubeless insulin pump on the other.

“I specifically decided to keep my devices visible when I went on the show,” she said. “It’s part of my life, and I wanted to show that I’m not ashamed to wear medical devices.”

Still, it has been a long journey since Bone was diagnosed in 2017. She was just 11 years old at the time and had recently done a climbing competition when she started feeling ill.

“I didn’t perform well,” she said. “I needed to go to the bathroom a lot and felt really nauseous. Three days later, we ended up in urgent care.”

When her doctor first told her she had diabetes, she started crying.

“My grandma had type 1 and was extremely sick and died from complications,” she said. “That was all I knew about diabetes, and it was scary to think my life could be like that.”

But her outlook brightened when her doctor assured her that she could keep climbing.

“When I was told that I could keep competing, a switch flipped for me and I made a decision that nothing would hold me back,” she says.

But every day isn’t easy.

“It’s sometimes really hard to manage my diabetes during competitions,” she said. “When we climb, for example, we’re not allowed to have our phones, and I manage my [glucose monitor] through my phone. This means accommodations have to be made for me.”

And managing her diabetes can be unpredictable at times.

“If my blood sugar is low or high, I might be put last in a competition,” she said. “That messes up my warm-up and my mental game. It’s a never-ending battle.”

Ultimately, Ms. Bone’s goal is to inspire others and advocate for diabetes awareness. She says she’s been overwhelmed by viewer responses to her appearance on the show.

“I heard from so many parents and kids,” she said. “I want the world to know that wearing a pump on your arm only makes you more amazing.”

She also draws inspiration from others with diabetes.

“Everyone with this disease is a role model for me, since everyone is fighting their own battles,” she said. “Diabetes is different for everyone, and seeing how people can do what they do despite the diagnosis has been incredibly inspiring.”

For now, the rising high school junior plans to continue training and competing.

“My goal is to make the 2024 Olympic climbing team in Paris,” she said. “I’ve always wanted to compete in the Olympics since I was a little kid. Nothing can stop me.”

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

Managing type 1 diabetes is never easy. But if you ask 16-year-old climbing star Katie Bone, she’ll tell you that she will never let this disease get in the way of her goals.

“My motto is the same one as Bethany Hamilton’s – the surfer who lost her arm in a shark attack: ‘I don’t need easy, I just need possible,” said Ms. Bone, who lives in Albuquerque and has been a competitive rock climber since she was 8 years old. “That really stuck with me.”

Just watching her compete on NBC’s hit reality show American Ninja Warrior in June is proof of that. Not only did the nationally ranked climber fly through the obstacles with grace and grit, but she proudly showed off her two monitoring devices: a glucose monitor on one arm and a tubeless insulin pump on the other.

“I specifically decided to keep my devices visible when I went on the show,” she said. “It’s part of my life, and I wanted to show that I’m not ashamed to wear medical devices.”

Still, it has been a long journey since Bone was diagnosed in 2017. She was just 11 years old at the time and had recently done a climbing competition when she started feeling ill.

“I didn’t perform well,” she said. “I needed to go to the bathroom a lot and felt really nauseous. Three days later, we ended up in urgent care.”

When her doctor first told her she had diabetes, she started crying.

“My grandma had type 1 and was extremely sick and died from complications,” she said. “That was all I knew about diabetes, and it was scary to think my life could be like that.”

But her outlook brightened when her doctor assured her that she could keep climbing.

“When I was told that I could keep competing, a switch flipped for me and I made a decision that nothing would hold me back,” she says.

But every day isn’t easy.

“It’s sometimes really hard to manage my diabetes during competitions,” she said. “When we climb, for example, we’re not allowed to have our phones, and I manage my [glucose monitor] through my phone. This means accommodations have to be made for me.”

And managing her diabetes can be unpredictable at times.

“If my blood sugar is low or high, I might be put last in a competition,” she said. “That messes up my warm-up and my mental game. It’s a never-ending battle.”

Ultimately, Ms. Bone’s goal is to inspire others and advocate for diabetes awareness. She says she’s been overwhelmed by viewer responses to her appearance on the show.

“I heard from so many parents and kids,” she said. “I want the world to know that wearing a pump on your arm only makes you more amazing.”

She also draws inspiration from others with diabetes.

“Everyone with this disease is a role model for me, since everyone is fighting their own battles,” she said. “Diabetes is different for everyone, and seeing how people can do what they do despite the diagnosis has been incredibly inspiring.”

For now, the rising high school junior plans to continue training and competing.

“My goal is to make the 2024 Olympic climbing team in Paris,” she said. “I’ve always wanted to compete in the Olympics since I was a little kid. Nothing can stop me.”

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

Managing type 1 diabetes is never easy. But if you ask 16-year-old climbing star Katie Bone, she’ll tell you that she will never let this disease get in the way of her goals.

“My motto is the same one as Bethany Hamilton’s – the surfer who lost her arm in a shark attack: ‘I don’t need easy, I just need possible,” said Ms. Bone, who lives in Albuquerque and has been a competitive rock climber since she was 8 years old. “That really stuck with me.”

Just watching her compete on NBC’s hit reality show American Ninja Warrior in June is proof of that. Not only did the nationally ranked climber fly through the obstacles with grace and grit, but she proudly showed off her two monitoring devices: a glucose monitor on one arm and a tubeless insulin pump on the other.

“I specifically decided to keep my devices visible when I went on the show,” she said. “It’s part of my life, and I wanted to show that I’m not ashamed to wear medical devices.”

Still, it has been a long journey since Bone was diagnosed in 2017. She was just 11 years old at the time and had recently done a climbing competition when she started feeling ill.

“I didn’t perform well,” she said. “I needed to go to the bathroom a lot and felt really nauseous. Three days later, we ended up in urgent care.”

When her doctor first told her she had diabetes, she started crying.

“My grandma had type 1 and was extremely sick and died from complications,” she said. “That was all I knew about diabetes, and it was scary to think my life could be like that.”

But her outlook brightened when her doctor assured her that she could keep climbing.

“When I was told that I could keep competing, a switch flipped for me and I made a decision that nothing would hold me back,” she says.

But every day isn’t easy.

“It’s sometimes really hard to manage my diabetes during competitions,” she said. “When we climb, for example, we’re not allowed to have our phones, and I manage my [glucose monitor] through my phone. This means accommodations have to be made for me.”

And managing her diabetes can be unpredictable at times.

“If my blood sugar is low or high, I might be put last in a competition,” she said. “That messes up my warm-up and my mental game. It’s a never-ending battle.”

Ultimately, Ms. Bone’s goal is to inspire others and advocate for diabetes awareness. She says she’s been overwhelmed by viewer responses to her appearance on the show.

“I heard from so many parents and kids,” she said. “I want the world to know that wearing a pump on your arm only makes you more amazing.”

She also draws inspiration from others with diabetes.

“Everyone with this disease is a role model for me, since everyone is fighting their own battles,” she said. “Diabetes is different for everyone, and seeing how people can do what they do despite the diagnosis has been incredibly inspiring.”

For now, the rising high school junior plans to continue training and competing.

“My goal is to make the 2024 Olympic climbing team in Paris,” she said. “I’ve always wanted to compete in the Olympics since I was a little kid. Nothing can stop me.”

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

Veterans’ access to medical care was expanded outside of US Department of Veterans Affairs (VA) facilities with the inception of the 2014 Veterans Access, Choice, and Accountability Act (Choice Act).¹ This legislation aimed to remove barriers some veterans were experiencing, specifically access to health care. In subsequent years, approximately 17% of veterans receiving care from the VA did so under the Choice Act.² The Choice Act positively impacted medical care access for veterans but presented new challenges for VA pharmacies processing community care (CC) prescriptions, including limited access to outside health records, lack of interface between CC prescribers and the VA order entry system, and limited awareness of the VA national formulary.^3,4 These factors made it difficult for VA pharmacies to assess prescriptions for clinical appropriateness, evaluate patient safety parameters, and manage expenditures.

In 2019, the Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act, which expanded CC support and better defined which veterans are able to receive care outside the VA, updated the Choice Act.^4,5 However, VA pharmacies faced challenges in managing pharmacy drug costs and ensuring clinical appropriateness of prescription drug therapy. As a result, VA pharmacy departments have adjusted how they allocate workload, time, and funds.⁵

Pharmacists improve clinical outcomes and reduce health care costs by decreasing medication errors, unnecessary prescribing, and adverse drug events.^6-12 Pharmacist-driven formulary management through evaluation of prior authorization drug requests (PADRs) has shown economic value.^13,14 VA pharmacy review of community care PADRs is important because outside health care professionals (HCPs) might not be familiar with the VA formulary. This could lead to high volume of PADRs that do not meet criteria and could result in increased potential for medication misuse, adverse drug events, medication errors, and cost to the health system. It is imperative that CC orders are evaluated as critically as traditional orders.

The value of a centralized CC pharmacy team has not been assessed in the literature. The primary objective of this study was to assess the direct cost savings achieved through a centralized CC PADR process. Secondary objectives were to characterize the CC PADRs submitted to the site, including approval rate, reason for nonapproval, which medications were requested and by whom, and to compare CC prescriptions with other high-complexity (1a) VA facilities.

Community Care Pharmacy

VA health systems are stratified according to complexity, which reflects size, patient population, and services offered. This study was conducted at the Durham Veterans Affairs Health Care System (DVAHCS), North Carolina, a high-complexity, 251-bed, tertiary care referral, teaching, and research system. DVAHCS provides general and specialty medical, surgical, inpatient psychiatric, and ambulatory services, and serves as a major referral center.

DVAHCS created a centralized pharmacy team for processing CC prescriptions and managing customer service. This team’s goal is to increase CC prescription processing efficiency and transparency, ensure accountability of the health care team, and promote veteran-centric customer service. The pharmacy team includes a pharmacist program manager and a dedicated CC pharmacist with administrative support from a health benefits assistant and 4 pharmacy technicians. The CC pharmacy team assesses every new prescription to ensure the veteran is authorized to receive care in the community. Once eligibility is verified, a pharmacy technician or pharmacist evaluates the prescription to ensure it contains all required information, then contacts the prescriber for any missing data. If clinically appropriate, the pharmacist processes the prescription.

In 2020, the CC pharmacy team implemented a new process for reviewing and documenting CC prescriptions that require a PADR. The closed national VA formulary is set up so that all nonformulary medications and some formulary medications, including those that are restricted because of safety and/or cost, require a PADR.¹⁵ After a CC pharmacy technician confirms a veteran’s eligibility, the technician assesses whether the requested medication requires submitting a PADR to the VA internal electronic health record. The PADR is then adjudicated by a formulary management pharmacist, CC program manager, or CC pharmacist who reviews health records to determine whether the CC prescription meets VA medication use policy requirements.

If additional information is needed or an alternate medication is suggested, the pharmacist comments back on the PADR and a CC pharmacy technician contacts the prescriber. The PADR is canceled administratively then resubmitted once all information is obtained. While waiting for a response from the prescriber, the CC pharmacy technician contacts that veteran to give an update on the prescription status, as appropriate. Once there is sufficient information to adjudicate the PADR, the outcome is documented, and if approved, the order is processed.

Methods

The DVAHCS Institutional Review Board approved this retrospective review of CC PADRs submitted from June 1, 2020, through November 30, 2020. CC PADRs were excluded if they were duplicates or were reactivated administratively but had an initial submission date before the study period. Local data were collected for nonapproved CC PADRs including drug requested, dosage and directions, medication specialty, alternative drug recommended, drug acquisition cost, PADR submission date, PADR completion date, PADR nonapproval rationale, and documented time spent per PADR. Additional data was obtained for CC prescriptions at all 42 high-complexity VA facilities from the VA national CC prescription database for the study time interval and included total PADRs, PADR approval status, total CC prescription cost, and total CC fills.

Direct cost savings were calculated by assessing the cost of requested therapy that was not approved minus the cost of recommended therapy and cost to review all PADRs, as described by Britt and colleagues.¹³ The cost of the requested and recommended therapy was calculated based on VA drug acquisition cost at time of data collection and multiplied by the expected duration of therapy up to 1 year. For each CC prescription, duration of therapy was based on the duration limit in the prescription or annualized if no duration limit was documented. Cost of PADR review was calculated based on the total time pharmacists and pharmacy technicians documented for each step of the review process for a representative sample of 100 nonapproved PADRs and then multiplied by the salary plus benefits of an entry-level pharmacist and pharmacy technician.¹⁶ The eAppendix  describes specific equations used for determining direct cost savings. Descriptive statistics were used to evaluate study results.

Results

During the 6-month study period, 611 CC PADRs were submitted to the pharmacy and 526 met inclusion criteria (Figure 1). Of those, 243 (46.2%) were approved and 283 (53.8%) were not approved. The cost of requested therapies for nonapproved CC PADRs totaled $584,565.48 and the cost of all recommended therapies was $57,473.59. The mean time per CC PADR was 24 minutes; 16 minutes for pharmacists and 8 minutes for pharmacy technicians. Given an hourly wage (plus benefits) of $67.25 for a pharmacist and $25.53 for a pharmacy technician, the total cost of review per CC PADR was $21.33. After subtracting the costs of all recommended therapies and review of all included CC PADRs, the process generated $515,872.31 in direct cost savings. After factoring in administrative lag time, such as HCP communication, an average of 8 calendar days was needed to complete a nonapproved PADR.

The most common rationale for PADR nonapproval was that the formulary alternative was not exhausted. Ondansetron orally disintegrating tablets was the most commonly nonapproved medication and azelastine was the most commonly approved medication. Dulaglutide was the most expensive nonapproved and tafamidis was the most expensive approved PADR (Table 1). Gastroenterology, endocrinology, and neurology were the top specialties for nonapproved PADRs while neurology, pulmonology, and endocrinology were the top specialties for approved PADRs (Table 2).

Several high-complexity VA facilities had no reported data; we used the median for the analysis to account for these outliers (Figure 2). The median (IQR) adjudicated CC PADRs for all facilities was 97 (20-175), median (IQR) CC PADR approval rate was 80.9% (63.7%-96.8%), median (IQR) total CC prescriptions was 8440 (2464-14,466), and median (IQR) cost per fill was $136.05 ($76.27-$221.28).

Discussion

This study demonstrated direct cost savings of $515,872.31 over 6 months with theadjudication of CC PADRs by a centralized CC pharmacy team. This could result in > $1,000,000 of cost savings per fiscal year.

The CC PADRs observed at DVAHCS had a 46.2% approval rate; almost one-half the approval rate of 84.1% of all PADRs submitted to the study site by VA HCPs captured by Britt and colleagues.¹³ Results from this study showed that coordination of care for nonapproved CC PADRs between the VA pharmacy and non-VA prescriber took an average of 8 calendar days. The noted CC PADR approval rate and administrative burden might be because of lack of familiarity of non-VA providers regarding the VA national formulary. The National VA Pharmacy Benefits Management determines the formulary using cost-effectiveness criteria that considers the medical literature and VA-specific contract pricing and prepares extensive guidance for restricted medications via relevant criteria for use.¹⁵ HCPs outside the VA might not know this information is available online. Because gastroenterology, endocrinology, and neurology specialty medications were among the most frequently nonapproved PADRs, VA formulary education could begin with CC HCPs in these practice areas.

This study showed that the CC PADR process was not solely driven by cost, but also included patient safety. Nonapproval rationale for some requests included submission without an indication, submission by a prescriber that did not have the authority to prescribe a type of medication, or contraindication based on patient-specific factors.

Limitations

CC PADRs were assessed during the COVID-19 pandemic, which might have resulted in lower-than-normal CC prescription and PADR volumes, therefore underestimating the potential for direct cost savings. Entry-level salary was used to demonstrate cost savings potential from the perspective of a newly hired CC team; however, the cost savings might have been less if the actual salaries of site personnel were higher. National contract pricing data were gathered at the time of data collection and might have been different than at the time of PADR submission. Chronic medication prescriptions were annualized, which could overestimate cost savings if the medication was discontinued or changed to an alternative therapy within that time period.

The study’s exclusion criteria could only be applied locally and did not include data received from the VA CC prescription database. This can be seen by the discrepancy in CC PADR approval rates from the local and national data (46.2% vs 44.2%, respectively) and CC PADR volume. High-complexity VA facility data were captured without assessing the CC prescription process at each site. As a result, definitive conclusions cannot be made regarding the impact of a centralized CC pharmacy team compared with other facilities.

Conclusions

Adjudication of CC PADRs by a centralized CC pharmacy team over a 6-month period provided > $500,000 in direct cost savings to a VA health care system. Considering the CC PADR approval rate seen in this study, the VA could allocate resources to educate CC providers about the VA formulary to increase the PADR approval rate and reduce administrative burden for VA pharmacies and prescribers. Future research should evaluate CC prescription handling practices at other VA facilities to compare the effectiveness among varying approaches and develop recommendations for a nationally standardized process.

Acknowledgments

Concept and design (AJJ, JNB, RBB, LAM, MD, MGH); acquisition of data (AJJ, MGH); analysis and interpretation of data (AJJ, JNB, RBB, LAM, MD, MGH); drafting of the manuscript (AJJ); critical revision of the manuscript for important intellectual content (AJJ, JNB, RBB, LAM, MD, MGH); statistical analysis (AJJ); administrative, technical, or logistic support (LAM, MGH); and supervision (MGH).

Veterans’ access to medical care was expanded outside of US Department of Veterans Affairs (VA) facilities with the inception of the 2014 Veterans Access, Choice, and Accountability Act (Choice Act).¹ This legislation aimed to remove barriers some veterans were experiencing, specifically access to health care. In subsequent years, approximately 17% of veterans receiving care from the VA did so under the Choice Act.² The Choice Act positively impacted medical care access for veterans but presented new challenges for VA pharmacies processing community care (CC) prescriptions, including limited access to outside health records, lack of interface between CC prescribers and the VA order entry system, and limited awareness of the VA national formulary.^3,4 These factors made it difficult for VA pharmacies to assess prescriptions for clinical appropriateness, evaluate patient safety parameters, and manage expenditures.

In 2019, the Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act, which expanded CC support and better defined which veterans are able to receive care outside the VA, updated the Choice Act.^4,5 However, VA pharmacies faced challenges in managing pharmacy drug costs and ensuring clinical appropriateness of prescription drug therapy. As a result, VA pharmacy departments have adjusted how they allocate workload, time, and funds.⁵

Pharmacists improve clinical outcomes and reduce health care costs by decreasing medication errors, unnecessary prescribing, and adverse drug events.^6-12 Pharmacist-driven formulary management through evaluation of prior authorization drug requests (PADRs) has shown economic value.^13,14 VA pharmacy review of community care PADRs is important because outside health care professionals (HCPs) might not be familiar with the VA formulary. This could lead to high volume of PADRs that do not meet criteria and could result in increased potential for medication misuse, adverse drug events, medication errors, and cost to the health system. It is imperative that CC orders are evaluated as critically as traditional orders.

The value of a centralized CC pharmacy team has not been assessed in the literature. The primary objective of this study was to assess the direct cost savings achieved through a centralized CC PADR process. Secondary objectives were to characterize the CC PADRs submitted to the site, including approval rate, reason for nonapproval, which medications were requested and by whom, and to compare CC prescriptions with other high-complexity (1a) VA facilities.

Community Care Pharmacy

VA health systems are stratified according to complexity, which reflects size, patient population, and services offered. This study was conducted at the Durham Veterans Affairs Health Care System (DVAHCS), North Carolina, a high-complexity, 251-bed, tertiary care referral, teaching, and research system. DVAHCS provides general and specialty medical, surgical, inpatient psychiatric, and ambulatory services, and serves as a major referral center.

DVAHCS created a centralized pharmacy team for processing CC prescriptions and managing customer service. This team’s goal is to increase CC prescription processing efficiency and transparency, ensure accountability of the health care team, and promote veteran-centric customer service. The pharmacy team includes a pharmacist program manager and a dedicated CC pharmacist with administrative support from a health benefits assistant and 4 pharmacy technicians. The CC pharmacy team assesses every new prescription to ensure the veteran is authorized to receive care in the community. Once eligibility is verified, a pharmacy technician or pharmacist evaluates the prescription to ensure it contains all required information, then contacts the prescriber for any missing data. If clinically appropriate, the pharmacist processes the prescription.

In 2020, the CC pharmacy team implemented a new process for reviewing and documenting CC prescriptions that require a PADR. The closed national VA formulary is set up so that all nonformulary medications and some formulary medications, including those that are restricted because of safety and/or cost, require a PADR.¹⁵ After a CC pharmacy technician confirms a veteran’s eligibility, the technician assesses whether the requested medication requires submitting a PADR to the VA internal electronic health record. The PADR is then adjudicated by a formulary management pharmacist, CC program manager, or CC pharmacist who reviews health records to determine whether the CC prescription meets VA medication use policy requirements.

If additional information is needed or an alternate medication is suggested, the pharmacist comments back on the PADR and a CC pharmacy technician contacts the prescriber. The PADR is canceled administratively then resubmitted once all information is obtained. While waiting for a response from the prescriber, the CC pharmacy technician contacts that veteran to give an update on the prescription status, as appropriate. Once there is sufficient information to adjudicate the PADR, the outcome is documented, and if approved, the order is processed.

Methods

The DVAHCS Institutional Review Board approved this retrospective review of CC PADRs submitted from June 1, 2020, through November 30, 2020. CC PADRs were excluded if they were duplicates or were reactivated administratively but had an initial submission date before the study period. Local data were collected for nonapproved CC PADRs including drug requested, dosage and directions, medication specialty, alternative drug recommended, drug acquisition cost, PADR submission date, PADR completion date, PADR nonapproval rationale, and documented time spent per PADR. Additional data was obtained for CC prescriptions at all 42 high-complexity VA facilities from the VA national CC prescription database for the study time interval and included total PADRs, PADR approval status, total CC prescription cost, and total CC fills.

Direct cost savings were calculated by assessing the cost of requested therapy that was not approved minus the cost of recommended therapy and cost to review all PADRs, as described by Britt and colleagues.¹³ The cost of the requested and recommended therapy was calculated based on VA drug acquisition cost at time of data collection and multiplied by the expected duration of therapy up to 1 year. For each CC prescription, duration of therapy was based on the duration limit in the prescription or annualized if no duration limit was documented. Cost of PADR review was calculated based on the total time pharmacists and pharmacy technicians documented for each step of the review process for a representative sample of 100 nonapproved PADRs and then multiplied by the salary plus benefits of an entry-level pharmacist and pharmacy technician.¹⁶ The eAppendix  describes specific equations used for determining direct cost savings. Descriptive statistics were used to evaluate study results.

Results

During the 6-month study period, 611 CC PADRs were submitted to the pharmacy and 526 met inclusion criteria (Figure 1). Of those, 243 (46.2%) were approved and 283 (53.8%) were not approved. The cost of requested therapies for nonapproved CC PADRs totaled $584,565.48 and the cost of all recommended therapies was $57,473.59. The mean time per CC PADR was 24 minutes; 16 minutes for pharmacists and 8 minutes for pharmacy technicians. Given an hourly wage (plus benefits) of $67.25 for a pharmacist and $25.53 for a pharmacy technician, the total cost of review per CC PADR was $21.33. After subtracting the costs of all recommended therapies and review of all included CC PADRs, the process generated $515,872.31 in direct cost savings. After factoring in administrative lag time, such as HCP communication, an average of 8 calendar days was needed to complete a nonapproved PADR.

The most common rationale for PADR nonapproval was that the formulary alternative was not exhausted. Ondansetron orally disintegrating tablets was the most commonly nonapproved medication and azelastine was the most commonly approved medication. Dulaglutide was the most expensive nonapproved and tafamidis was the most expensive approved PADR (Table 1). Gastroenterology, endocrinology, and neurology were the top specialties for nonapproved PADRs while neurology, pulmonology, and endocrinology were the top specialties for approved PADRs (Table 2).

Several high-complexity VA facilities had no reported data; we used the median for the analysis to account for these outliers (Figure 2). The median (IQR) adjudicated CC PADRs for all facilities was 97 (20-175), median (IQR) CC PADR approval rate was 80.9% (63.7%-96.8%), median (IQR) total CC prescriptions was 8440 (2464-14,466), and median (IQR) cost per fill was $136.05 ($76.27-$221.28).

Discussion

This study demonstrated direct cost savings of $515,872.31 over 6 months with theadjudication of CC PADRs by a centralized CC pharmacy team. This could result in > $1,000,000 of cost savings per fiscal year.

The CC PADRs observed at DVAHCS had a 46.2% approval rate; almost one-half the approval rate of 84.1% of all PADRs submitted to the study site by VA HCPs captured by Britt and colleagues.¹³ Results from this study showed that coordination of care for nonapproved CC PADRs between the VA pharmacy and non-VA prescriber took an average of 8 calendar days. The noted CC PADR approval rate and administrative burden might be because of lack of familiarity of non-VA providers regarding the VA national formulary. The National VA Pharmacy Benefits Management determines the formulary using cost-effectiveness criteria that considers the medical literature and VA-specific contract pricing and prepares extensive guidance for restricted medications via relevant criteria for use.¹⁵ HCPs outside the VA might not know this information is available online. Because gastroenterology, endocrinology, and neurology specialty medications were among the most frequently nonapproved PADRs, VA formulary education could begin with CC HCPs in these practice areas.

This study showed that the CC PADR process was not solely driven by cost, but also included patient safety. Nonapproval rationale for some requests included submission without an indication, submission by a prescriber that did not have the authority to prescribe a type of medication, or contraindication based on patient-specific factors.

Limitations

CC PADRs were assessed during the COVID-19 pandemic, which might have resulted in lower-than-normal CC prescription and PADR volumes, therefore underestimating the potential for direct cost savings. Entry-level salary was used to demonstrate cost savings potential from the perspective of a newly hired CC team; however, the cost savings might have been less if the actual salaries of site personnel were higher. National contract pricing data were gathered at the time of data collection and might have been different than at the time of PADR submission. Chronic medication prescriptions were annualized, which could overestimate cost savings if the medication was discontinued or changed to an alternative therapy within that time period.

The study’s exclusion criteria could only be applied locally and did not include data received from the VA CC prescription database. This can be seen by the discrepancy in CC PADR approval rates from the local and national data (46.2% vs 44.2%, respectively) and CC PADR volume. High-complexity VA facility data were captured without assessing the CC prescription process at each site. As a result, definitive conclusions cannot be made regarding the impact of a centralized CC pharmacy team compared with other facilities.

Conclusions

Adjudication of CC PADRs by a centralized CC pharmacy team over a 6-month period provided > $500,000 in direct cost savings to a VA health care system. Considering the CC PADR approval rate seen in this study, the VA could allocate resources to educate CC providers about the VA formulary to increase the PADR approval rate and reduce administrative burden for VA pharmacies and prescribers. Future research should evaluate CC prescription handling practices at other VA facilities to compare the effectiveness among varying approaches and develop recommendations for a nationally standardized process.

Acknowledgments

Concept and design (AJJ, JNB, RBB, LAM, MD, MGH); acquisition of data (AJJ, MGH); analysis and interpretation of data (AJJ, JNB, RBB, LAM, MD, MGH); drafting of the manuscript (AJJ); critical revision of the manuscript for important intellectual content (AJJ, JNB, RBB, LAM, MD, MGH); statistical analysis (AJJ); administrative, technical, or logistic support (LAM, MGH); and supervision (MGH).

Veterans’ access to medical care was expanded outside of US Department of Veterans Affairs (VA) facilities with the inception of the 2014 Veterans Access, Choice, and Accountability Act (Choice Act).¹ This legislation aimed to remove barriers some veterans were experiencing, specifically access to health care. In subsequent years, approximately 17% of veterans receiving care from the VA did so under the Choice Act.² The Choice Act positively impacted medical care access for veterans but presented new challenges for VA pharmacies processing community care (CC) prescriptions, including limited access to outside health records, lack of interface between CC prescribers and the VA order entry system, and limited awareness of the VA national formulary.^3,4 These factors made it difficult for VA pharmacies to assess prescriptions for clinical appropriateness, evaluate patient safety parameters, and manage expenditures.

In 2019, the Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act, which expanded CC support and better defined which veterans are able to receive care outside the VA, updated the Choice Act.^4,5 However, VA pharmacies faced challenges in managing pharmacy drug costs and ensuring clinical appropriateness of prescription drug therapy. As a result, VA pharmacy departments have adjusted how they allocate workload, time, and funds.⁵

Pharmacists improve clinical outcomes and reduce health care costs by decreasing medication errors, unnecessary prescribing, and adverse drug events.^6-12 Pharmacist-driven formulary management through evaluation of prior authorization drug requests (PADRs) has shown economic value.^13,14 VA pharmacy review of community care PADRs is important because outside health care professionals (HCPs) might not be familiar with the VA formulary. This could lead to high volume of PADRs that do not meet criteria and could result in increased potential for medication misuse, adverse drug events, medication errors, and cost to the health system. It is imperative that CC orders are evaluated as critically as traditional orders.

The value of a centralized CC pharmacy team has not been assessed in the literature. The primary objective of this study was to assess the direct cost savings achieved through a centralized CC PADR process. Secondary objectives were to characterize the CC PADRs submitted to the site, including approval rate, reason for nonapproval, which medications were requested and by whom, and to compare CC prescriptions with other high-complexity (1a) VA facilities.

Community Care Pharmacy

VA health systems are stratified according to complexity, which reflects size, patient population, and services offered. This study was conducted at the Durham Veterans Affairs Health Care System (DVAHCS), North Carolina, a high-complexity, 251-bed, tertiary care referral, teaching, and research system. DVAHCS provides general and specialty medical, surgical, inpatient psychiatric, and ambulatory services, and serves as a major referral center.

DVAHCS created a centralized pharmacy team for processing CC prescriptions and managing customer service. This team’s goal is to increase CC prescription processing efficiency and transparency, ensure accountability of the health care team, and promote veteran-centric customer service. The pharmacy team includes a pharmacist program manager and a dedicated CC pharmacist with administrative support from a health benefits assistant and 4 pharmacy technicians. The CC pharmacy team assesses every new prescription to ensure the veteran is authorized to receive care in the community. Once eligibility is verified, a pharmacy technician or pharmacist evaluates the prescription to ensure it contains all required information, then contacts the prescriber for any missing data. If clinically appropriate, the pharmacist processes the prescription.

In 2020, the CC pharmacy team implemented a new process for reviewing and documenting CC prescriptions that require a PADR. The closed national VA formulary is set up so that all nonformulary medications and some formulary medications, including those that are restricted because of safety and/or cost, require a PADR.¹⁵ After a CC pharmacy technician confirms a veteran’s eligibility, the technician assesses whether the requested medication requires submitting a PADR to the VA internal electronic health record. The PADR is then adjudicated by a formulary management pharmacist, CC program manager, or CC pharmacist who reviews health records to determine whether the CC prescription meets VA medication use policy requirements.

If additional information is needed or an alternate medication is suggested, the pharmacist comments back on the PADR and a CC pharmacy technician contacts the prescriber. The PADR is canceled administratively then resubmitted once all information is obtained. While waiting for a response from the prescriber, the CC pharmacy technician contacts that veteran to give an update on the prescription status, as appropriate. Once there is sufficient information to adjudicate the PADR, the outcome is documented, and if approved, the order is processed.

Methods

The DVAHCS Institutional Review Board approved this retrospective review of CC PADRs submitted from June 1, 2020, through November 30, 2020. CC PADRs were excluded if they were duplicates or were reactivated administratively but had an initial submission date before the study period. Local data were collected for nonapproved CC PADRs including drug requested, dosage and directions, medication specialty, alternative drug recommended, drug acquisition cost, PADR submission date, PADR completion date, PADR nonapproval rationale, and documented time spent per PADR. Additional data was obtained for CC prescriptions at all 42 high-complexity VA facilities from the VA national CC prescription database for the study time interval and included total PADRs, PADR approval status, total CC prescription cost, and total CC fills.

Direct cost savings were calculated by assessing the cost of requested therapy that was not approved minus the cost of recommended therapy and cost to review all PADRs, as described by Britt and colleagues.¹³ The cost of the requested and recommended therapy was calculated based on VA drug acquisition cost at time of data collection and multiplied by the expected duration of therapy up to 1 year. For each CC prescription, duration of therapy was based on the duration limit in the prescription or annualized if no duration limit was documented. Cost of PADR review was calculated based on the total time pharmacists and pharmacy technicians documented for each step of the review process for a representative sample of 100 nonapproved PADRs and then multiplied by the salary plus benefits of an entry-level pharmacist and pharmacy technician.¹⁶ The eAppendix  describes specific equations used for determining direct cost savings. Descriptive statistics were used to evaluate study results.

Results

During the 6-month study period, 611 CC PADRs were submitted to the pharmacy and 526 met inclusion criteria (Figure 1). Of those, 243 (46.2%) were approved and 283 (53.8%) were not approved. The cost of requested therapies for nonapproved CC PADRs totaled $584,565.48 and the cost of all recommended therapies was $57,473.59. The mean time per CC PADR was 24 minutes; 16 minutes for pharmacists and 8 minutes for pharmacy technicians. Given an hourly wage (plus benefits) of $67.25 for a pharmacist and $25.53 for a pharmacy technician, the total cost of review per CC PADR was $21.33. After subtracting the costs of all recommended therapies and review of all included CC PADRs, the process generated $515,872.31 in direct cost savings. After factoring in administrative lag time, such as HCP communication, an average of 8 calendar days was needed to complete a nonapproved PADR.

The most common rationale for PADR nonapproval was that the formulary alternative was not exhausted. Ondansetron orally disintegrating tablets was the most commonly nonapproved medication and azelastine was the most commonly approved medication. Dulaglutide was the most expensive nonapproved and tafamidis was the most expensive approved PADR (Table 1). Gastroenterology, endocrinology, and neurology were the top specialties for nonapproved PADRs while neurology, pulmonology, and endocrinology were the top specialties for approved PADRs (Table 2).

Several high-complexity VA facilities had no reported data; we used the median for the analysis to account for these outliers (Figure 2). The median (IQR) adjudicated CC PADRs for all facilities was 97 (20-175), median (IQR) CC PADR approval rate was 80.9% (63.7%-96.8%), median (IQR) total CC prescriptions was 8440 (2464-14,466), and median (IQR) cost per fill was $136.05 ($76.27-$221.28).

Discussion

This study demonstrated direct cost savings of $515,872.31 over 6 months with theadjudication of CC PADRs by a centralized CC pharmacy team. This could result in > $1,000,000 of cost savings per fiscal year.

The CC PADRs observed at DVAHCS had a 46.2% approval rate; almost one-half the approval rate of 84.1% of all PADRs submitted to the study site by VA HCPs captured by Britt and colleagues.¹³ Results from this study showed that coordination of care for nonapproved CC PADRs between the VA pharmacy and non-VA prescriber took an average of 8 calendar days. The noted CC PADR approval rate and administrative burden might be because of lack of familiarity of non-VA providers regarding the VA national formulary. The National VA Pharmacy Benefits Management determines the formulary using cost-effectiveness criteria that considers the medical literature and VA-specific contract pricing and prepares extensive guidance for restricted medications via relevant criteria for use.¹⁵ HCPs outside the VA might not know this information is available online. Because gastroenterology, endocrinology, and neurology specialty medications were among the most frequently nonapproved PADRs, VA formulary education could begin with CC HCPs in these practice areas.

This study showed that the CC PADR process was not solely driven by cost, but also included patient safety. Nonapproval rationale for some requests included submission without an indication, submission by a prescriber that did not have the authority to prescribe a type of medication, or contraindication based on patient-specific factors.

Limitations

CC PADRs were assessed during the COVID-19 pandemic, which might have resulted in lower-than-normal CC prescription and PADR volumes, therefore underestimating the potential for direct cost savings. Entry-level salary was used to demonstrate cost savings potential from the perspective of a newly hired CC team; however, the cost savings might have been less if the actual salaries of site personnel were higher. National contract pricing data were gathered at the time of data collection and might have been different than at the time of PADR submission. Chronic medication prescriptions were annualized, which could overestimate cost savings if the medication was discontinued or changed to an alternative therapy within that time period.

The study’s exclusion criteria could only be applied locally and did not include data received from the VA CC prescription database. This can be seen by the discrepancy in CC PADR approval rates from the local and national data (46.2% vs 44.2%, respectively) and CC PADR volume. High-complexity VA facility data were captured without assessing the CC prescription process at each site. As a result, definitive conclusions cannot be made regarding the impact of a centralized CC pharmacy team compared with other facilities.

Conclusions

Adjudication of CC PADRs by a centralized CC pharmacy team over a 6-month period provided > $500,000 in direct cost savings to a VA health care system. Considering the CC PADR approval rate seen in this study, the VA could allocate resources to educate CC providers about the VA formulary to increase the PADR approval rate and reduce administrative burden for VA pharmacies and prescribers. Future research should evaluate CC prescription handling practices at other VA facilities to compare the effectiveness among varying approaches and develop recommendations for a nationally standardized process.

Acknowledgments

Concept and design (AJJ, JNB, RBB, LAM, MD, MGH); acquisition of data (AJJ, MGH); analysis and interpretation of data (AJJ, JNB, RBB, LAM, MD, MGH); drafting of the manuscript (AJJ); critical revision of the manuscript for important intellectual content (AJJ, JNB, RBB, LAM, MD, MGH); statistical analysis (AJJ); administrative, technical, or logistic support (LAM, MGH); and supervision (MGH).

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Taking a brief walk after eating can help lower the risk of type 2 diabetes, according to a recent study published in Sports Medicine (2022 Aug;52:1765-87).

Light walking after a meal – even for 2-5 minutes – can reduce blood sugar and insulin levels, the researchers found.

Blood sugar levels spike after eating, and the insulin produced to control them can lead to diabetes and cardiovascular issues, the researchers explained.

“With standing and walking, there are contractions of your muscles” that use glucose and lower blood sugar levels, Aidan Buffey, the lead study author and a PhD student in physical education and sport sciences at the University of Limerick (Ireland), told The Times.

“If you can do physical activity before the glucose peak, typically 60-90 minutes [after eating], that is when you’re going to have the benefit of not having the glucose spike,” he said.

Mr. Buffey and colleagues looked at seven studies to understand what would happen if you used standing or easy walking to interrupt prolonged sitting.

In five of the studies, none of the participants had prediabetes or type 2 diabetes. The other two studies included people with and without diabetes. The people in the studies were asked to either stand or walk for 2-5 minutes every 20-30 minutes over the course of a full day.

All seven studies showed that standing after a meal is better than sitting, and taking a short walk offered even better health benefits. Those who stood up for a short period of time after a meal had improved blood sugar levels but not insulin, while those who took a brief walk after a meal had lower blood sugar and insulin levels. Those who walked also had blood sugar levels that rose and fell more gradually, which is critical for managing diabetes.

Going for a walk, doing housework, or finding other ways to move your body within 60-90 minutes after eating could offer the best results, the study authors concluded.

These “mini-walks” could also be useful during the workday to break up prolonged periods of sitting at a desk.

“People are not going to get up and run on a treadmill or run around the office,” Mr. Buffey told The New York Times.

But making mini-walks a normal thing during the workday could be easy and acceptable at the office, he said. Even if people can’t take walks, standing up will help somewhat.

“Each small thing you do will have benefits, even if it is a small step,” Kershaw Patel, MD, a preventive cardiologist at Houston Methodist Hospital, told the newspaper. Dr. Patel wasn’t involved with the study.

“It’s a gradual effect of more activity, better health,” he said. “Each incremental step, each incremental stand or brisk walk appears to have a benefit.”

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

Taking a brief walk after eating can help lower the risk of type 2 diabetes, according to a recent study published in Sports Medicine (2022 Aug;52:1765-87).

Light walking after a meal – even for 2-5 minutes – can reduce blood sugar and insulin levels, the researchers found.

Blood sugar levels spike after eating, and the insulin produced to control them can lead to diabetes and cardiovascular issues, the researchers explained.

“With standing and walking, there are contractions of your muscles” that use glucose and lower blood sugar levels, Aidan Buffey, the lead study author and a PhD student in physical education and sport sciences at the University of Limerick (Ireland), told The Times.

“If you can do physical activity before the glucose peak, typically 60-90 minutes [after eating], that is when you’re going to have the benefit of not having the glucose spike,” he said.

Mr. Buffey and colleagues looked at seven studies to understand what would happen if you used standing or easy walking to interrupt prolonged sitting.

In five of the studies, none of the participants had prediabetes or type 2 diabetes. The other two studies included people with and without diabetes. The people in the studies were asked to either stand or walk for 2-5 minutes every 20-30 minutes over the course of a full day.

All seven studies showed that standing after a meal is better than sitting, and taking a short walk offered even better health benefits. Those who stood up for a short period of time after a meal had improved blood sugar levels but not insulin, while those who took a brief walk after a meal had lower blood sugar and insulin levels. Those who walked also had blood sugar levels that rose and fell more gradually, which is critical for managing diabetes.

Going for a walk, doing housework, or finding other ways to move your body within 60-90 minutes after eating could offer the best results, the study authors concluded.

These “mini-walks” could also be useful during the workday to break up prolonged periods of sitting at a desk.

“People are not going to get up and run on a treadmill or run around the office,” Mr. Buffey told The New York Times.

But making mini-walks a normal thing during the workday could be easy and acceptable at the office, he said. Even if people can’t take walks, standing up will help somewhat.

“Each small thing you do will have benefits, even if it is a small step,” Kershaw Patel, MD, a preventive cardiologist at Houston Methodist Hospital, told the newspaper. Dr. Patel wasn’t involved with the study.

“It’s a gradual effect of more activity, better health,” he said. “Each incremental step, each incremental stand or brisk walk appears to have a benefit.”

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

Taking a brief walk after eating can help lower the risk of type 2 diabetes, according to a recent study published in Sports Medicine (2022 Aug;52:1765-87).

Light walking after a meal – even for 2-5 minutes – can reduce blood sugar and insulin levels, the researchers found.

Blood sugar levels spike after eating, and the insulin produced to control them can lead to diabetes and cardiovascular issues, the researchers explained.

“With standing and walking, there are contractions of your muscles” that use glucose and lower blood sugar levels, Aidan Buffey, the lead study author and a PhD student in physical education and sport sciences at the University of Limerick (Ireland), told The Times.

“If you can do physical activity before the glucose peak, typically 60-90 minutes [after eating], that is when you’re going to have the benefit of not having the glucose spike,” he said.

Mr. Buffey and colleagues looked at seven studies to understand what would happen if you used standing or easy walking to interrupt prolonged sitting.

In five of the studies, none of the participants had prediabetes or type 2 diabetes. The other two studies included people with and without diabetes. The people in the studies were asked to either stand or walk for 2-5 minutes every 20-30 minutes over the course of a full day.

All seven studies showed that standing after a meal is better than sitting, and taking a short walk offered even better health benefits. Those who stood up for a short period of time after a meal had improved blood sugar levels but not insulin, while those who took a brief walk after a meal had lower blood sugar and insulin levels. Those who walked also had blood sugar levels that rose and fell more gradually, which is critical for managing diabetes.

Going for a walk, doing housework, or finding other ways to move your body within 60-90 minutes after eating could offer the best results, the study authors concluded.

These “mini-walks” could also be useful during the workday to break up prolonged periods of sitting at a desk.

“People are not going to get up and run on a treadmill or run around the office,” Mr. Buffey told The New York Times.

But making mini-walks a normal thing during the workday could be easy and acceptable at the office, he said. Even if people can’t take walks, standing up will help somewhat.

“Each small thing you do will have benefits, even if it is a small step,” Kershaw Patel, MD, a preventive cardiologist at Houston Methodist Hospital, told the newspaper. Dr. Patel wasn’t involved with the study.

“It’s a gradual effect of more activity, better health,” he said. “Each incremental step, each incremental stand or brisk walk appears to have a benefit.”

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

Click to view more from Federal Health Care Data Trends 2022

Click to view more from Federal Health Care Data Trends 2022

Click to view more from Federal Health Care Data Trends 2022

Nearly one-third of smokers who were offered smoking cessation support on the spot when they showed up for lung cancer screening remained off cigarettes 1 year later, a quit-smoking rate considerably higher than that reported in clinical studies, investigators from the United Kingdom found.

When they added a stop-smoking component to the Yorkshire Lung Screening Trial, Rachael Murray, PhD, and colleagues at the University of Nottingham (England), found that immediately offering a combination of behavioral support and pharmacotherapy to help smokers kick the habit resulted in a 7-day validated point prevalent abstinence rate at 3 months of 30% among smokers randomized to a standard smoking cessation program, and 33.6% among patients randomized to also receive a personalized intervention that included images of their heart and lungs to demonstrate the harmful effects of tobacco.

In contrast, smoking cessation rates reported in trials of lung cancer screening have ranged from approximately 10% to 20%.

Although there was no overall statistical difference in quit-smoking rates between the standard and enhanced intervention arms of the study, the investigators found that women, but not men, were significantly more likely to quit when shown the heart and lung images, compared with those who received the standard smoking cessation support, Dr. Murray said at the World Conference on Lung Cancer held this week in Vienna.

“I think having smoking cessation as an integrated part of the lung cancer track was really positively received by our participants, particularly through having a physical presence and being conveniently located within the setting,” she said in a presidential symposium highlighting the best abstracts presented at the meeting.

“We’ve offered a high-intensity intervention, which is not going to be cheap to offer but I think is really important for these individuals with complex smoking histories and multiple comorbidities,” she added.
 

No judgment

In an interview, Dr. Murray noted that colocating stop-smoking services with lung screening is important for capturing smokers who may have the will but not the means to quit, and that participants especially appreciated the offer of help without the usual condescending attitude.

“We’re not an add-on: We’re there and physically present at the time of the lung health check,” she said. “It’s a standard of care that our smoking cessation advisers are able to provide. It’s very nonjudgmental and very holistic, providing social support that these people need. They’ve got long smoking histories, and they’re often made to feel guilty for that, and just being able to approach them in a nonjudgmental way makes a big difference.”

Smoking cessation is known to be the most effective way to reduce lung cancer deaths, Dr. Murray said in her presentation, pointing to a 2020 study by University of Michigan researchers showing that adding tobacco treatment to lung cancer screening can reduce deaths by 14% and increase the overall number of life-years gained by 81%.
 

Reduce smoking?

To see whether adding a personalized on-site smoking cessation program to lung cancer screening could improve quit-smoking rates, Dr. Murray and colleagues enrolled 1,003 smokers who attended the lung cancer screening program and randomly assigned them to either the intervention arm with personalized feedback, supportive communications, ongoing behavioral support and pharmacotherapy, or to a control arm consisting of ongoing behavioral support and pharmacotherapy.

Participants in the intervention arm were shown CT scans of the heart and lungs plus drawings highlighting coronary artery calcification and areas of their lungs damaged by smoking, and information on how quitting smoking can help to improve their health. The smoking cessation advisers followed a tightly controlled script to ensure that the messages were delivered in a uniform fashion to all participants.

As noted before, rates of 7-day validated point prevalent abstinence, measured by exhaled carbon dioxide, were 33.8% in the intervention arm, and 30% in the control arm. The respective costs per quitter were £521.30 ($630.77) and £412.80 ($499.48).

The validated 12-month smoking-free rates were 29.% in the intervention arm, and 28.6% in the control arm. None of the differences were statistically significant.

However, when they looked at between-arm differences by sex, the investigators found that significantly more women assigned to the intervention arm remained abstinent at 3 months, with rates of 33.9% compared with 23.1% of controls, a difference that translated into an unadjusted odds ratio of 1.70 favoring the intervention among women (P = .008).
 

Effective and durable

“My interpretation of this study is that the abstinence rates were very high, and this in fact was durable because this effect was maintained after 12 months,” commented invited discussant and smoking cessation expert Jacek Jassem, MD, from the University of Gdansk (Poland).

He said that the lack of a difference between the intervention and control arms might be attributable to lower levels of concern about heart disease or emphysema among participants, or possibly to the efficacy of the on-site support program itself.

The differences in efficacy of the intervention between men and women suggest that there may be a need for a sex- or gender-adapted approach, he said at the conference sponsored by the International Association for the Study of Lung Cancer.

“Lung cancer screening is a unique opportunity to motivate smoking cessation. All cancer screening programs should included best available and ongoing cessation support, and please, don’t blame smoking persons: Be compassionate, and helpful, and smile like our British colleagues did,” he concluded.

The study was supported by Yorkshire Cancer Research. Dr. Murray and Dr. Jassem reported no financial conflicts of interest.

Nearly one-third of smokers who were offered smoking cessation support on the spot when they showed up for lung cancer screening remained off cigarettes 1 year later, a quit-smoking rate considerably higher than that reported in clinical studies, investigators from the United Kingdom found.

When they added a stop-smoking component to the Yorkshire Lung Screening Trial, Rachael Murray, PhD, and colleagues at the University of Nottingham (England), found that immediately offering a combination of behavioral support and pharmacotherapy to help smokers kick the habit resulted in a 7-day validated point prevalent abstinence rate at 3 months of 30% among smokers randomized to a standard smoking cessation program, and 33.6% among patients randomized to also receive a personalized intervention that included images of their heart and lungs to demonstrate the harmful effects of tobacco.

In contrast, smoking cessation rates reported in trials of lung cancer screening have ranged from approximately 10% to 20%.

Although there was no overall statistical difference in quit-smoking rates between the standard and enhanced intervention arms of the study, the investigators found that women, but not men, were significantly more likely to quit when shown the heart and lung images, compared with those who received the standard smoking cessation support, Dr. Murray said at the World Conference on Lung Cancer held this week in Vienna.

“I think having smoking cessation as an integrated part of the lung cancer track was really positively received by our participants, particularly through having a physical presence and being conveniently located within the setting,” she said in a presidential symposium highlighting the best abstracts presented at the meeting.

“We’ve offered a high-intensity intervention, which is not going to be cheap to offer but I think is really important for these individuals with complex smoking histories and multiple comorbidities,” she added.
 

No judgment

In an interview, Dr. Murray noted that colocating stop-smoking services with lung screening is important for capturing smokers who may have the will but not the means to quit, and that participants especially appreciated the offer of help without the usual condescending attitude.

“We’re not an add-on: We’re there and physically present at the time of the lung health check,” she said. “It’s a standard of care that our smoking cessation advisers are able to provide. It’s very nonjudgmental and very holistic, providing social support that these people need. They’ve got long smoking histories, and they’re often made to feel guilty for that, and just being able to approach them in a nonjudgmental way makes a big difference.”

Smoking cessation is known to be the most effective way to reduce lung cancer deaths, Dr. Murray said in her presentation, pointing to a 2020 study by University of Michigan researchers showing that adding tobacco treatment to lung cancer screening can reduce deaths by 14% and increase the overall number of life-years gained by 81%.
 

Reduce smoking?

To see whether adding a personalized on-site smoking cessation program to lung cancer screening could improve quit-smoking rates, Dr. Murray and colleagues enrolled 1,003 smokers who attended the lung cancer screening program and randomly assigned them to either the intervention arm with personalized feedback, supportive communications, ongoing behavioral support and pharmacotherapy, or to a control arm consisting of ongoing behavioral support and pharmacotherapy.

Participants in the intervention arm were shown CT scans of the heart and lungs plus drawings highlighting coronary artery calcification and areas of their lungs damaged by smoking, and information on how quitting smoking can help to improve their health. The smoking cessation advisers followed a tightly controlled script to ensure that the messages were delivered in a uniform fashion to all participants.

As noted before, rates of 7-day validated point prevalent abstinence, measured by exhaled carbon dioxide, were 33.8% in the intervention arm, and 30% in the control arm. The respective costs per quitter were £521.30 ($630.77) and £412.80 ($499.48).

The validated 12-month smoking-free rates were 29.% in the intervention arm, and 28.6% in the control arm. None of the differences were statistically significant.

However, when they looked at between-arm differences by sex, the investigators found that significantly more women assigned to the intervention arm remained abstinent at 3 months, with rates of 33.9% compared with 23.1% of controls, a difference that translated into an unadjusted odds ratio of 1.70 favoring the intervention among women (P = .008).
 

Effective and durable

“My interpretation of this study is that the abstinence rates were very high, and this in fact was durable because this effect was maintained after 12 months,” commented invited discussant and smoking cessation expert Jacek Jassem, MD, from the University of Gdansk (Poland).

He said that the lack of a difference between the intervention and control arms might be attributable to lower levels of concern about heart disease or emphysema among participants, or possibly to the efficacy of the on-site support program itself.

The differences in efficacy of the intervention between men and women suggest that there may be a need for a sex- or gender-adapted approach, he said at the conference sponsored by the International Association for the Study of Lung Cancer.

“Lung cancer screening is a unique opportunity to motivate smoking cessation. All cancer screening programs should included best available and ongoing cessation support, and please, don’t blame smoking persons: Be compassionate, and helpful, and smile like our British colleagues did,” he concluded.

The study was supported by Yorkshire Cancer Research. Dr. Murray and Dr. Jassem reported no financial conflicts of interest.

Nearly one-third of smokers who were offered smoking cessation support on the spot when they showed up for lung cancer screening remained off cigarettes 1 year later, a quit-smoking rate considerably higher than that reported in clinical studies, investigators from the United Kingdom found.

When they added a stop-smoking component to the Yorkshire Lung Screening Trial, Rachael Murray, PhD, and colleagues at the University of Nottingham (England), found that immediately offering a combination of behavioral support and pharmacotherapy to help smokers kick the habit resulted in a 7-day validated point prevalent abstinence rate at 3 months of 30% among smokers randomized to a standard smoking cessation program, and 33.6% among patients randomized to also receive a personalized intervention that included images of their heart and lungs to demonstrate the harmful effects of tobacco.

In contrast, smoking cessation rates reported in trials of lung cancer screening have ranged from approximately 10% to 20%.

Although there was no overall statistical difference in quit-smoking rates between the standard and enhanced intervention arms of the study, the investigators found that women, but not men, were significantly more likely to quit when shown the heart and lung images, compared with those who received the standard smoking cessation support, Dr. Murray said at the World Conference on Lung Cancer held this week in Vienna.

“I think having smoking cessation as an integrated part of the lung cancer track was really positively received by our participants, particularly through having a physical presence and being conveniently located within the setting,” she said in a presidential symposium highlighting the best abstracts presented at the meeting.

“We’ve offered a high-intensity intervention, which is not going to be cheap to offer but I think is really important for these individuals with complex smoking histories and multiple comorbidities,” she added.
 

No judgment

In an interview, Dr. Murray noted that colocating stop-smoking services with lung screening is important for capturing smokers who may have the will but not the means to quit, and that participants especially appreciated the offer of help without the usual condescending attitude.

“We’re not an add-on: We’re there and physically present at the time of the lung health check,” she said. “It’s a standard of care that our smoking cessation advisers are able to provide. It’s very nonjudgmental and very holistic, providing social support that these people need. They’ve got long smoking histories, and they’re often made to feel guilty for that, and just being able to approach them in a nonjudgmental way makes a big difference.”

Smoking cessation is known to be the most effective way to reduce lung cancer deaths, Dr. Murray said in her presentation, pointing to a 2020 study by University of Michigan researchers showing that adding tobacco treatment to lung cancer screening can reduce deaths by 14% and increase the overall number of life-years gained by 81%.
 

Reduce smoking?

To see whether adding a personalized on-site smoking cessation program to lung cancer screening could improve quit-smoking rates, Dr. Murray and colleagues enrolled 1,003 smokers who attended the lung cancer screening program and randomly assigned them to either the intervention arm with personalized feedback, supportive communications, ongoing behavioral support and pharmacotherapy, or to a control arm consisting of ongoing behavioral support and pharmacotherapy.

Participants in the intervention arm were shown CT scans of the heart and lungs plus drawings highlighting coronary artery calcification and areas of their lungs damaged by smoking, and information on how quitting smoking can help to improve their health. The smoking cessation advisers followed a tightly controlled script to ensure that the messages were delivered in a uniform fashion to all participants.

As noted before, rates of 7-day validated point prevalent abstinence, measured by exhaled carbon dioxide, were 33.8% in the intervention arm, and 30% in the control arm. The respective costs per quitter were £521.30 ($630.77) and £412.80 ($499.48).

The validated 12-month smoking-free rates were 29.% in the intervention arm, and 28.6% in the control arm. None of the differences were statistically significant.

However, when they looked at between-arm differences by sex, the investigators found that significantly more women assigned to the intervention arm remained abstinent at 3 months, with rates of 33.9% compared with 23.1% of controls, a difference that translated into an unadjusted odds ratio of 1.70 favoring the intervention among women (P = .008).
 

Effective and durable

“My interpretation of this study is that the abstinence rates were very high, and this in fact was durable because this effect was maintained after 12 months,” commented invited discussant and smoking cessation expert Jacek Jassem, MD, from the University of Gdansk (Poland).

He said that the lack of a difference between the intervention and control arms might be attributable to lower levels of concern about heart disease or emphysema among participants, or possibly to the efficacy of the on-site support program itself.

The differences in efficacy of the intervention between men and women suggest that there may be a need for a sex- or gender-adapted approach, he said at the conference sponsored by the International Association for the Study of Lung Cancer.

“Lung cancer screening is a unique opportunity to motivate smoking cessation. All cancer screening programs should included best available and ongoing cessation support, and please, don’t blame smoking persons: Be compassionate, and helpful, and smile like our British colleagues did,” he concluded.

The study was supported by Yorkshire Cancer Research. Dr. Murray and Dr. Jassem reported no financial conflicts of interest.

Drug-induced hypersensitivity syndrome (DIHS), also called drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, is a potentially fatal drug-induced hypersensitivity reaction that is characterized by a cutaneous eruption, multiorgan involvement, viral reactivation, and hematologic abnormalities. As the nomenclature of this disease advances, consensus groups have adopted DIHS/DRESS to underscore that both names refer to the same clinical phenomenon.¹ Autoimmune sequelae have been reported after DIHS/DRESS that include vitiligo, thyroid disease, and type 1 diabetes mellitus (T1DM). We present a case of lamotrigine-associated DIHS/DRESS complicated by an unusually prolonged course requiring oral corticosteroids and narrow-band ultraviolet B (UVB) treatment and with development of extensive alopecia areata and autoimmune thyroiditis.

Case Presentation

A 35-year-old female Filipino patient was prescribed lamotrigine 25 mg daily for bipolar II disorder and titrated to 100 mg twice daily after 1 month. One week after the increase, the patient developed a diffuse morbilliform rash covering their entire body along with facial swelling and generalized pruritus. Lamotrigine was discontinued after lamotrigine allergy was diagnosed. The patient improved following a 9-day oral prednisone taper and was placed on oxcarbazepine 300 mg twice daily to manage their bipolar disorder. One day after completing the taper, the patient presented again with worsening rash, swelling, and cervical lymphadenopathy. Oxcarbazepine was discontinued, and oral prednisone 60 mg was reinstituted for an additional 11 days.

Dermatology evaluated the patient 10 days after completion of the second oral steroid taper (1 month after cessation of lamotrigine). The patient had erythroderma along with malaise, fevers, chills, and fatigue and a diffuse burning sensation (Figure 1). The patient was hypotensive and tachycardic with significant eosinophilia (42%; reference range, 0%-8%), transaminitis, and renal insufficiency. The patient was diagnosed with DIHS/DRESS based on their clinical presentation and calculated RegiSCAR score of 7 (score > 5 corresponds with definite DIHS/DRESS and points were given for fever, enlarged lymph nodes, eosinophilia ≥ 20%, skin rash extending > 50% of their body, edema and scaling, and 2 organs involved).² A punch biopsy was confirmatory (Figure 2A).³ The patient was started on prednisone 80 mg once daily along with topical fluocinonide 0.05% ointment. However, the patient’s clinical status deteriorated, requiring hospital admission for heart failure evaluation. The echocardiogram revealed hyperdynamic circulation but was otherwise unremarkable.

Four months after DIHS/DRESS resolution and cessation of steroids, the patient noted significant patches of smooth alopecia on their posterior scalp and was diagnosed with alopecia areata. Treatment with intralesional triamcinolone over 2 months resulted in regrowth of hair (Figure 3). A month later, the patient reported increasing fatigue and anorexia. The patient was evaluated once more for AI, this time with low morning cortisol and low adrenocorticotrophic hormone (ACTH) levels—consistent with AI secondary to prolonged glucocorticoid therapy. The patient also was concomitantly evaluated for hypothyroidism with significantly elevated thyroperoxidase antibodies—confirming the diagnosis of Hashimoto thyroiditis.

Discussion

DIHS/DRESS syndrome is a rare, but potentially life-threatening hypersensitivity to a medication, often beginning 2 to 6 weeks after exposure to the causative agent. The incidence of DIHS/DRESS in the general population is about 2 per 100,000.³ Our patient presented with DIHS/DRESS 33 days after starting lamotrigine, which corresponds with the published mean onset of anticonvulsant-induced DIHS/DRESS (29.7-33.3 days).⁴ Recent evidence shows that time from drug exposure to DIHS/DRESS symptoms may vary by drug class, with antibiotics implicated as precipitating DIHS/DRESS in < 15 days.³ The diagnosis of DIHS/DRESS may be complicated for many reasons. The accompanying rash may be morbilliform, erythroderma, or exfoliative dermatitis with multiple anatomic regions affected.⁵ Systemic involvement with various internal organs occurs in > 90% of cases, with the liver and kidney involved most frequently.⁵ Overall mortality rate may be as high as 10% most commonly due to acute liver failure.⁵ Biopsy may be helpful in the diagnosis but is not always specific.⁵ Diagnostic criteria include RegiSCAR and J-SCAR scores; our patient met criteria for both (Table).⁵ 

The pathogenesis of DIHS/DRESS remains unclear. Proposed mechanisms include genetic predisposition with human leukocyte antigen (HLA) haplotypes, autoimmune with a delayed cell-mediated immune response associated with herpesviruses, and abnormal enzymatic pathways that metabolize medications.² Although no HLA has been identified between lamotrigine and DIHS, HLA-A*02:07 and HLA-B*15:02 have been associated with lamotrigine-induced cutaneous drug reactions in patients of Thai ancestry.⁶ Immunosuppression also is a risk factor, especially when accompanied by a primary or reactivated HHV-6 infection, as seen in our patient.² Additionally, HHV-6 infection may be a common link between DIHS/DRESS and autoimmune thyroiditis but is believed to involve elevated levels of interferon-γ-induced protein-10 (IP-10) that may lead to excessive recruitment of cytotoxic T cells into target tissues.⁷ Elevated levels of IP-10 are seen in many autoimmune conditions, such as autoimmune thyroiditis, Sjögren syndrome, and Graves disease.⁸

Treatment

For management, early recognition and discontinuation of the offending agent is paramount. Systemic corticosteroids are the accepted treatment standard. Symptoms of DIHS/DRESS usually resolve between 3 and 18 weeks, with the mean resolution time at 7 weeks.¹⁰ Our patient developed a prolonged course with persistent eosinophilia for 20 weeks and cutaneous symptoms for 32 weeks—requiring 40 weeks of oral prednisone. The most significant clinical improvement occurred during the 8-week period low-dose nbUVB was used (Figure 4). There also are reports outlining the successful use of intravenous immunoglobulin, cyclosporine, cyclophosphamide, rituximab, or plasma exchange in cases refractory to oral corticosteroids.¹¹

A recent retrospective case control study showed that treatment of DIHS/DRESS with cyclosporine in patients who had a contraindication to steroids resulted in faster resolution of symptoms, shorter treatment durations, and shorter hospitalizations than did those treated with corticosteroids.¹² However, the data are limited by a significantly smaller number of patients treated with cyclosporine than steroids and the cyclosporine treatment group having milder cases of DIHS/DRESS.¹²

The risk of AI is increased for patients who have taken > 20 mg of prednisone daily ≥ 3 weeks, an evening dose ≥ 5 mg for a few weeks, or have a Cushingoid appearance.¹³ Patients may not regain full adrenal function for 12 to 18 months.¹⁴ Our patient had a normal basal serum cortisol level 2 weeks after prednisone cessation and then presented 5 months later with AI. While the reason for this period of normality is unclear, it may partly be due to the variable length of hypothalamic-pituitary-adrenal axis recovery time. Thus, ACTH stimulation tests in addition to serum cortisol may be done in patients with suspected AI for higher diagnostic certainty.¹⁰

Conclusions

DIHS/DRESS is a severe cutaneous adverse reaction that may require a prolonged treatment course until symptom resolution (40 weeks of oral prednisone in our patient). Oral corticosteroids are the mainstay of treatment, but long-term use is associated with significant adverse effects, such as AI in our patient. Alternative therapies, such as cyclosporine, look promising, but further studies are needed to determine safety profile and efficacy.¹² Additionally, patients with DIHS/DRESS should be educated and followed for potential autoimmune sequelae; in our patient alopecia areata and autoimmune thyroiditis were late sequelae, occurring 14 and 15 months, respectively, after onset of DIHS/DRESS.

Drug-induced hypersensitivity syndrome (DIHS), also called drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, is a potentially fatal drug-induced hypersensitivity reaction that is characterized by a cutaneous eruption, multiorgan involvement, viral reactivation, and hematologic abnormalities. As the nomenclature of this disease advances, consensus groups have adopted DIHS/DRESS to underscore that both names refer to the same clinical phenomenon.¹ Autoimmune sequelae have been reported after DIHS/DRESS that include vitiligo, thyroid disease, and type 1 diabetes mellitus (T1DM). We present a case of lamotrigine-associated DIHS/DRESS complicated by an unusually prolonged course requiring oral corticosteroids and narrow-band ultraviolet B (UVB) treatment and with development of extensive alopecia areata and autoimmune thyroiditis.

Case Presentation

A 35-year-old female Filipino patient was prescribed lamotrigine 25 mg daily for bipolar II disorder and titrated to 100 mg twice daily after 1 month. One week after the increase, the patient developed a diffuse morbilliform rash covering their entire body along with facial swelling and generalized pruritus. Lamotrigine was discontinued after lamotrigine allergy was diagnosed. The patient improved following a 9-day oral prednisone taper and was placed on oxcarbazepine 300 mg twice daily to manage their bipolar disorder. One day after completing the taper, the patient presented again with worsening rash, swelling, and cervical lymphadenopathy. Oxcarbazepine was discontinued, and oral prednisone 60 mg was reinstituted for an additional 11 days.

Dermatology evaluated the patient 10 days after completion of the second oral steroid taper (1 month after cessation of lamotrigine). The patient had erythroderma along with malaise, fevers, chills, and fatigue and a diffuse burning sensation (Figure 1). The patient was hypotensive and tachycardic with significant eosinophilia (42%; reference range, 0%-8%), transaminitis, and renal insufficiency. The patient was diagnosed with DIHS/DRESS based on their clinical presentation and calculated RegiSCAR score of 7 (score > 5 corresponds with definite DIHS/DRESS and points were given for fever, enlarged lymph nodes, eosinophilia ≥ 20%, skin rash extending > 50% of their body, edema and scaling, and 2 organs involved).² A punch biopsy was confirmatory (Figure 2A).³ The patient was started on prednisone 80 mg once daily along with topical fluocinonide 0.05% ointment. However, the patient’s clinical status deteriorated, requiring hospital admission for heart failure evaluation. The echocardiogram revealed hyperdynamic circulation but was otherwise unremarkable.

Four months after DIHS/DRESS resolution and cessation of steroids, the patient noted significant patches of smooth alopecia on their posterior scalp and was diagnosed with alopecia areata. Treatment with intralesional triamcinolone over 2 months resulted in regrowth of hair (Figure 3). A month later, the patient reported increasing fatigue and anorexia. The patient was evaluated once more for AI, this time with low morning cortisol and low adrenocorticotrophic hormone (ACTH) levels—consistent with AI secondary to prolonged glucocorticoid therapy. The patient also was concomitantly evaluated for hypothyroidism with significantly elevated thyroperoxidase antibodies—confirming the diagnosis of Hashimoto thyroiditis.

Discussion

DIHS/DRESS syndrome is a rare, but potentially life-threatening hypersensitivity to a medication, often beginning 2 to 6 weeks after exposure to the causative agent. The incidence of DIHS/DRESS in the general population is about 2 per 100,000.³ Our patient presented with DIHS/DRESS 33 days after starting lamotrigine, which corresponds with the published mean onset of anticonvulsant-induced DIHS/DRESS (29.7-33.3 days).⁴ Recent evidence shows that time from drug exposure to DIHS/DRESS symptoms may vary by drug class, with antibiotics implicated as precipitating DIHS/DRESS in < 15 days.³ The diagnosis of DIHS/DRESS may be complicated for many reasons. The accompanying rash may be morbilliform, erythroderma, or exfoliative dermatitis with multiple anatomic regions affected.⁵ Systemic involvement with various internal organs occurs in > 90% of cases, with the liver and kidney involved most frequently.⁵ Overall mortality rate may be as high as 10% most commonly due to acute liver failure.⁵ Biopsy may be helpful in the diagnosis but is not always specific.⁵ Diagnostic criteria include RegiSCAR and J-SCAR scores; our patient met criteria for both (Table).⁵ 

The pathogenesis of DIHS/DRESS remains unclear. Proposed mechanisms include genetic predisposition with human leukocyte antigen (HLA) haplotypes, autoimmune with a delayed cell-mediated immune response associated with herpesviruses, and abnormal enzymatic pathways that metabolize medications.² Although no HLA has been identified between lamotrigine and DIHS, HLA-A*02:07 and HLA-B*15:02 have been associated with lamotrigine-induced cutaneous drug reactions in patients of Thai ancestry.⁶ Immunosuppression also is a risk factor, especially when accompanied by a primary or reactivated HHV-6 infection, as seen in our patient.² Additionally, HHV-6 infection may be a common link between DIHS/DRESS and autoimmune thyroiditis but is believed to involve elevated levels of interferon-γ-induced protein-10 (IP-10) that may lead to excessive recruitment of cytotoxic T cells into target tissues.⁷ Elevated levels of IP-10 are seen in many autoimmune conditions, such as autoimmune thyroiditis, Sjögren syndrome, and Graves disease.⁸

Treatment

For management, early recognition and discontinuation of the offending agent is paramount. Systemic corticosteroids are the accepted treatment standard. Symptoms of DIHS/DRESS usually resolve between 3 and 18 weeks, with the mean resolution time at 7 weeks.¹⁰ Our patient developed a prolonged course with persistent eosinophilia for 20 weeks and cutaneous symptoms for 32 weeks—requiring 40 weeks of oral prednisone. The most significant clinical improvement occurred during the 8-week period low-dose nbUVB was used (Figure 4). There also are reports outlining the successful use of intravenous immunoglobulin, cyclosporine, cyclophosphamide, rituximab, or plasma exchange in cases refractory to oral corticosteroids.¹¹

A recent retrospective case control study showed that treatment of DIHS/DRESS with cyclosporine in patients who had a contraindication to steroids resulted in faster resolution of symptoms, shorter treatment durations, and shorter hospitalizations than did those treated with corticosteroids.¹² However, the data are limited by a significantly smaller number of patients treated with cyclosporine than steroids and the cyclosporine treatment group having milder cases of DIHS/DRESS.¹²

The risk of AI is increased for patients who have taken > 20 mg of prednisone daily ≥ 3 weeks, an evening dose ≥ 5 mg for a few weeks, or have a Cushingoid appearance.¹³ Patients may not regain full adrenal function for 12 to 18 months.¹⁴ Our patient had a normal basal serum cortisol level 2 weeks after prednisone cessation and then presented 5 months later with AI. While the reason for this period of normality is unclear, it may partly be due to the variable length of hypothalamic-pituitary-adrenal axis recovery time. Thus, ACTH stimulation tests in addition to serum cortisol may be done in patients with suspected AI for higher diagnostic certainty.¹⁰

Conclusions

DIHS/DRESS is a severe cutaneous adverse reaction that may require a prolonged treatment course until symptom resolution (40 weeks of oral prednisone in our patient). Oral corticosteroids are the mainstay of treatment, but long-term use is associated with significant adverse effects, such as AI in our patient. Alternative therapies, such as cyclosporine, look promising, but further studies are needed to determine safety profile and efficacy.¹² Additionally, patients with DIHS/DRESS should be educated and followed for potential autoimmune sequelae; in our patient alopecia areata and autoimmune thyroiditis were late sequelae, occurring 14 and 15 months, respectively, after onset of DIHS/DRESS.

Drug-induced hypersensitivity syndrome (DIHS), also called drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, is a potentially fatal drug-induced hypersensitivity reaction that is characterized by a cutaneous eruption, multiorgan involvement, viral reactivation, and hematologic abnormalities. As the nomenclature of this disease advances, consensus groups have adopted DIHS/DRESS to underscore that both names refer to the same clinical phenomenon.¹ Autoimmune sequelae have been reported after DIHS/DRESS that include vitiligo, thyroid disease, and type 1 diabetes mellitus (T1DM). We present a case of lamotrigine-associated DIHS/DRESS complicated by an unusually prolonged course requiring oral corticosteroids and narrow-band ultraviolet B (UVB) treatment and with development of extensive alopecia areata and autoimmune thyroiditis.

Case Presentation

A 35-year-old female Filipino patient was prescribed lamotrigine 25 mg daily for bipolar II disorder and titrated to 100 mg twice daily after 1 month. One week after the increase, the patient developed a diffuse morbilliform rash covering their entire body along with facial swelling and generalized pruritus. Lamotrigine was discontinued after lamotrigine allergy was diagnosed. The patient improved following a 9-day oral prednisone taper and was placed on oxcarbazepine 300 mg twice daily to manage their bipolar disorder. One day after completing the taper, the patient presented again with worsening rash, swelling, and cervical lymphadenopathy. Oxcarbazepine was discontinued, and oral prednisone 60 mg was reinstituted for an additional 11 days.

Dermatology evaluated the patient 10 days after completion of the second oral steroid taper (1 month after cessation of lamotrigine). The patient had erythroderma along with malaise, fevers, chills, and fatigue and a diffuse burning sensation (Figure 1). The patient was hypotensive and tachycardic with significant eosinophilia (42%; reference range, 0%-8%), transaminitis, and renal insufficiency. The patient was diagnosed with DIHS/DRESS based on their clinical presentation and calculated RegiSCAR score of 7 (score > 5 corresponds with definite DIHS/DRESS and points were given for fever, enlarged lymph nodes, eosinophilia ≥ 20%, skin rash extending > 50% of their body, edema and scaling, and 2 organs involved).² A punch biopsy was confirmatory (Figure 2A).³ The patient was started on prednisone 80 mg once daily along with topical fluocinonide 0.05% ointment. However, the patient’s clinical status deteriorated, requiring hospital admission for heart failure evaluation. The echocardiogram revealed hyperdynamic circulation but was otherwise unremarkable.

Four months after DIHS/DRESS resolution and cessation of steroids, the patient noted significant patches of smooth alopecia on their posterior scalp and was diagnosed with alopecia areata. Treatment with intralesional triamcinolone over 2 months resulted in regrowth of hair (Figure 3). A month later, the patient reported increasing fatigue and anorexia. The patient was evaluated once more for AI, this time with low morning cortisol and low adrenocorticotrophic hormone (ACTH) levels—consistent with AI secondary to prolonged glucocorticoid therapy. The patient also was concomitantly evaluated for hypothyroidism with significantly elevated thyroperoxidase antibodies—confirming the diagnosis of Hashimoto thyroiditis.

Discussion

DIHS/DRESS syndrome is a rare, but potentially life-threatening hypersensitivity to a medication, often beginning 2 to 6 weeks after exposure to the causative agent. The incidence of DIHS/DRESS in the general population is about 2 per 100,000.³ Our patient presented with DIHS/DRESS 33 days after starting lamotrigine, which corresponds with the published mean onset of anticonvulsant-induced DIHS/DRESS (29.7-33.3 days).⁴ Recent evidence shows that time from drug exposure to DIHS/DRESS symptoms may vary by drug class, with antibiotics implicated as precipitating DIHS/DRESS in < 15 days.³ The diagnosis of DIHS/DRESS may be complicated for many reasons. The accompanying rash may be morbilliform, erythroderma, or exfoliative dermatitis with multiple anatomic regions affected.⁵ Systemic involvement with various internal organs occurs in > 90% of cases, with the liver and kidney involved most frequently.⁵ Overall mortality rate may be as high as 10% most commonly due to acute liver failure.⁵ Biopsy may be helpful in the diagnosis but is not always specific.⁵ Diagnostic criteria include RegiSCAR and J-SCAR scores; our patient met criteria for both (Table).⁵ 

The pathogenesis of DIHS/DRESS remains unclear. Proposed mechanisms include genetic predisposition with human leukocyte antigen (HLA) haplotypes, autoimmune with a delayed cell-mediated immune response associated with herpesviruses, and abnormal enzymatic pathways that metabolize medications.² Although no HLA has been identified between lamotrigine and DIHS, HLA-A*02:07 and HLA-B*15:02 have been associated with lamotrigine-induced cutaneous drug reactions in patients of Thai ancestry.⁶ Immunosuppression also is a risk factor, especially when accompanied by a primary or reactivated HHV-6 infection, as seen in our patient.² Additionally, HHV-6 infection may be a common link between DIHS/DRESS and autoimmune thyroiditis but is believed to involve elevated levels of interferon-γ-induced protein-10 (IP-10) that may lead to excessive recruitment of cytotoxic T cells into target tissues.⁷ Elevated levels of IP-10 are seen in many autoimmune conditions, such as autoimmune thyroiditis, Sjögren syndrome, and Graves disease.⁸

Treatment

For management, early recognition and discontinuation of the offending agent is paramount. Systemic corticosteroids are the accepted treatment standard. Symptoms of DIHS/DRESS usually resolve between 3 and 18 weeks, with the mean resolution time at 7 weeks.¹⁰ Our patient developed a prolonged course with persistent eosinophilia for 20 weeks and cutaneous symptoms for 32 weeks—requiring 40 weeks of oral prednisone. The most significant clinical improvement occurred during the 8-week period low-dose nbUVB was used (Figure 4). There also are reports outlining the successful use of intravenous immunoglobulin, cyclosporine, cyclophosphamide, rituximab, or plasma exchange in cases refractory to oral corticosteroids.¹¹

A recent retrospective case control study showed that treatment of DIHS/DRESS with cyclosporine in patients who had a contraindication to steroids resulted in faster resolution of symptoms, shorter treatment durations, and shorter hospitalizations than did those treated with corticosteroids.¹² However, the data are limited by a significantly smaller number of patients treated with cyclosporine than steroids and the cyclosporine treatment group having milder cases of DIHS/DRESS.¹²

The risk of AI is increased for patients who have taken > 20 mg of prednisone daily ≥ 3 weeks, an evening dose ≥ 5 mg for a few weeks, or have a Cushingoid appearance.¹³ Patients may not regain full adrenal function for 12 to 18 months.¹⁴ Our patient had a normal basal serum cortisol level 2 weeks after prednisone cessation and then presented 5 months later with AI. While the reason for this period of normality is unclear, it may partly be due to the variable length of hypothalamic-pituitary-adrenal axis recovery time. Thus, ACTH stimulation tests in addition to serum cortisol may be done in patients with suspected AI for higher diagnostic certainty.¹⁰

Conclusions

DIHS/DRESS is a severe cutaneous adverse reaction that may require a prolonged treatment course until symptom resolution (40 weeks of oral prednisone in our patient). Oral corticosteroids are the mainstay of treatment, but long-term use is associated with significant adverse effects, such as AI in our patient. Alternative therapies, such as cyclosporine, look promising, but further studies are needed to determine safety profile and efficacy.¹² Additionally, patients with DIHS/DRESS should be educated and followed for potential autoimmune sequelae; in our patient alopecia areata and autoimmune thyroiditis were late sequelae, occurring 14 and 15 months, respectively, after onset of DIHS/DRESS.

Click to view more from Federal Health Care Data Trends 2022

Click to view more from Federal Health Care Data Trends 2022

Click to view more from Federal Health Care Data Trends 2022

In a recently obtained plan by Politico, the Biden administration is zeroing in on a broad student loan forgiveness plan to be released imminently. The plan would broadly forgive $10,000 in federal student loans, including graduate and PLUS loans. However, there’s a rub: The plan restricts the forgiveness to those with incomes below $150,000.

This would unfairly exclude many in health care from receiving this forgiveness, an egregious oversight given how much health care providers have sacrificed during the pandemic.
 

What was proposed?

Previously, it was reported that the Biden administration was considering this same amount of forgiveness, but with plans to exclude borrowers by either career or income. Student loan payments have been on an extended CARES Act forbearance since March 2020, with payment resumption planned for Aug. 31. The administration has said that they would deliver a plan for further extensions before this date and have repeatedly teased including forgiveness.

Forgiveness for some ...

Forgiving $10,000 of federal student loans would relieve some 15 million borrowers of student debt, roughly one-third of the 45 million borrowers with debt.

This would provide a massive boost to these borrowers (who disproportionately are female, low-income, and non-White), many of whom were targeted by predatory institutions whose education didn’t offer any actual tangible benefit to their earnings. While this is a group that absolutely ought to have their loans forgiven, drawing an income line inappropriately restricts those in health care from receiving any forgiveness.
 

... But not for others

Someone making an annual gross income of $150,000 is in the 80th percentile of earners in the United States (for comparison, the top 1% took home more than $505,000 in 2021). What student loan borrowers make up the remaining 20%? Overwhelmingly, health care providers occupy that tier: physicians, dentists, veterinarians, and advanced-practice nurses.

These schools leave their graduates with some of the highest student loan burdens, with veterinarians, dentists, and physicians having the highest debt-to-income ratios of any professional careers.
 

Flat forgiveness is regressive

Forgiving any student debt is the right direction. Too may have fallen victim to an industry without quality control, appropriate regulation, or price control. Quite the opposite, the blank-check model of student loan financing has led to an arms race as it comes to capital improvements in university spending.

The price of medical schools has risen more than four times as fast as inflation over the past 30 years, with dental and veterinary schools and nursing education showing similarly exaggerated price increases. Trainees in these fields are more likely to have taken on six-figure debt, with average debt loads at graduation in the table below. While $10,000 will move the proverbial needle less for these borrowers, does that mean they should be excluded?
 

Health care workers’ income declines during the pandemic

Now, over 2½ years since the start of the COVID pandemic, multiple reports have demonstrated that health care workers have suffered a loss in income. This loss in income was never compensated for, as the Paycheck Protection Program and the individual economic stimuli typically excluded doctors and high earners.

COVID and the hazard tax

As a provider during the COVID-19 pandemic, I didn’t ask for hazard pay. I supported those who did but recognized their requests were more ceremonial than they were likely to be successful.

However, I flatly reject the idea that my fellow health care practitioners are not deserving of student loan forgiveness simply based on an arbitrary income threshold. Health care providers are saddled with high debt burden, have suffered lost income, and have given of themselves during a devastating pandemic, where more than 1 million perished in the United States.
 

Bottom line

Health care workers should not be excluded from student loan forgiveness. Sadly, the Biden administration has signaled that they are dropping career-based exclusions in favor of more broadly harmful income-based forgiveness restrictions. This will disproportionately harm physicians and other health care workers.

These practitioners have suffered financially as a result of working through the COVID pandemic; should they also be forced to shoulder another financial injury by being excluded from student loan forgiveness?

Dr. Palmer is the chief operating officer and cofounder of Panacea Financial. He is also a practicing pediatric hospitalist at Boston Children’s Hospital and is on faculty at Harvard Medical School, also in Boston.



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

In a recently obtained plan by Politico, the Biden administration is zeroing in on a broad student loan forgiveness plan to be released imminently. The plan would broadly forgive $10,000 in federal student loans, including graduate and PLUS loans. However, there’s a rub: The plan restricts the forgiveness to those with incomes below $150,000.

This would unfairly exclude many in health care from receiving this forgiveness, an egregious oversight given how much health care providers have sacrificed during the pandemic.
 

What was proposed?

Previously, it was reported that the Biden administration was considering this same amount of forgiveness, but with plans to exclude borrowers by either career or income. Student loan payments have been on an extended CARES Act forbearance since March 2020, with payment resumption planned for Aug. 31. The administration has said that they would deliver a plan for further extensions before this date and have repeatedly teased including forgiveness.

Forgiveness for some ...

Forgiving $10,000 of federal student loans would relieve some 15 million borrowers of student debt, roughly one-third of the 45 million borrowers with debt.

This would provide a massive boost to these borrowers (who disproportionately are female, low-income, and non-White), many of whom were targeted by predatory institutions whose education didn’t offer any actual tangible benefit to their earnings. While this is a group that absolutely ought to have their loans forgiven, drawing an income line inappropriately restricts those in health care from receiving any forgiveness.
 

... But not for others

Someone making an annual gross income of $150,000 is in the 80th percentile of earners in the United States (for comparison, the top 1% took home more than $505,000 in 2021). What student loan borrowers make up the remaining 20%? Overwhelmingly, health care providers occupy that tier: physicians, dentists, veterinarians, and advanced-practice nurses.

These schools leave their graduates with some of the highest student loan burdens, with veterinarians, dentists, and physicians having the highest debt-to-income ratios of any professional careers.
 

Flat forgiveness is regressive

Forgiving any student debt is the right direction. Too may have fallen victim to an industry without quality control, appropriate regulation, or price control. Quite the opposite, the blank-check model of student loan financing has led to an arms race as it comes to capital improvements in university spending.

The price of medical schools has risen more than four times as fast as inflation over the past 30 years, with dental and veterinary schools and nursing education showing similarly exaggerated price increases. Trainees in these fields are more likely to have taken on six-figure debt, with average debt loads at graduation in the table below. While $10,000 will move the proverbial needle less for these borrowers, does that mean they should be excluded?
 

Health care workers’ income declines during the pandemic

Now, over 2½ years since the start of the COVID pandemic, multiple reports have demonstrated that health care workers have suffered a loss in income. This loss in income was never compensated for, as the Paycheck Protection Program and the individual economic stimuli typically excluded doctors and high earners.

COVID and the hazard tax

As a provider during the COVID-19 pandemic, I didn’t ask for hazard pay. I supported those who did but recognized their requests were more ceremonial than they were likely to be successful.

However, I flatly reject the idea that my fellow health care practitioners are not deserving of student loan forgiveness simply based on an arbitrary income threshold. Health care providers are saddled with high debt burden, have suffered lost income, and have given of themselves during a devastating pandemic, where more than 1 million perished in the United States.
 

Bottom line

Health care workers should not be excluded from student loan forgiveness. Sadly, the Biden administration has signaled that they are dropping career-based exclusions in favor of more broadly harmful income-based forgiveness restrictions. This will disproportionately harm physicians and other health care workers.

These practitioners have suffered financially as a result of working through the COVID pandemic; should they also be forced to shoulder another financial injury by being excluded from student loan forgiveness?

Dr. Palmer is the chief operating officer and cofounder of Panacea Financial. He is also a practicing pediatric hospitalist at Boston Children’s Hospital and is on faculty at Harvard Medical School, also in Boston.



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

In a recently obtained plan by Politico, the Biden administration is zeroing in on a broad student loan forgiveness plan to be released imminently. The plan would broadly forgive $10,000 in federal student loans, including graduate and PLUS loans. However, there’s a rub: The plan restricts the forgiveness to those with incomes below $150,000.

This would unfairly exclude many in health care from receiving this forgiveness, an egregious oversight given how much health care providers have sacrificed during the pandemic.
 

What was proposed?

Previously, it was reported that the Biden administration was considering this same amount of forgiveness, but with plans to exclude borrowers by either career or income. Student loan payments have been on an extended CARES Act forbearance since March 2020, with payment resumption planned for Aug. 31. The administration has said that they would deliver a plan for further extensions before this date and have repeatedly teased including forgiveness.

Forgiveness for some ...

Forgiving $10,000 of federal student loans would relieve some 15 million borrowers of student debt, roughly one-third of the 45 million borrowers with debt.

This would provide a massive boost to these borrowers (who disproportionately are female, low-income, and non-White), many of whom were targeted by predatory institutions whose education didn’t offer any actual tangible benefit to their earnings. While this is a group that absolutely ought to have their loans forgiven, drawing an income line inappropriately restricts those in health care from receiving any forgiveness.
 

... But not for others

Someone making an annual gross income of $150,000 is in the 80th percentile of earners in the United States (for comparison, the top 1% took home more than $505,000 in 2021). What student loan borrowers make up the remaining 20%? Overwhelmingly, health care providers occupy that tier: physicians, dentists, veterinarians, and advanced-practice nurses.

These schools leave their graduates with some of the highest student loan burdens, with veterinarians, dentists, and physicians having the highest debt-to-income ratios of any professional careers.
 

Flat forgiveness is regressive

Forgiving any student debt is the right direction. Too may have fallen victim to an industry without quality control, appropriate regulation, or price control. Quite the opposite, the blank-check model of student loan financing has led to an arms race as it comes to capital improvements in university spending.

The price of medical schools has risen more than four times as fast as inflation over the past 30 years, with dental and veterinary schools and nursing education showing similarly exaggerated price increases. Trainees in these fields are more likely to have taken on six-figure debt, with average debt loads at graduation in the table below. While $10,000 will move the proverbial needle less for these borrowers, does that mean they should be excluded?
 

Health care workers’ income declines during the pandemic

Now, over 2½ years since the start of the COVID pandemic, multiple reports have demonstrated that health care workers have suffered a loss in income. This loss in income was never compensated for, as the Paycheck Protection Program and the individual economic stimuli typically excluded doctors and high earners.

COVID and the hazard tax

As a provider during the COVID-19 pandemic, I didn’t ask for hazard pay. I supported those who did but recognized their requests were more ceremonial than they were likely to be successful.

However, I flatly reject the idea that my fellow health care practitioners are not deserving of student loan forgiveness simply based on an arbitrary income threshold. Health care providers are saddled with high debt burden, have suffered lost income, and have given of themselves during a devastating pandemic, where more than 1 million perished in the United States.
 

Bottom line

Health care workers should not be excluded from student loan forgiveness. Sadly, the Biden administration has signaled that they are dropping career-based exclusions in favor of more broadly harmful income-based forgiveness restrictions. This will disproportionately harm physicians and other health care workers.

These practitioners have suffered financially as a result of working through the COVID pandemic; should they also be forced to shoulder another financial injury by being excluded from student loan forgiveness?

Dr. Palmer is the chief operating officer and cofounder of Panacea Financial. He is also a practicing pediatric hospitalist at Boston Children’s Hospital and is on faculty at Harvard Medical School, also in Boston.



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