Commentary

It’s 2 a.m. and my phone wakes me up with a start. My patient, Christine Z*, is vomiting uncontrollably, and Dr Google has diagnosed her with acute pancreatitis from semaglutide (Wegovy). Ten hours, several imaging studies, one blood draw, and many bags of fluids later, the verdict is in: Christine is alarmingly constipated. In fact, her entire large intestine is packed to the brim with stool. In residency, we called this diagnosis FOS, and I’ll leave it to your imagination to figure out what it stands for.

In retrospect, Christine mentions that upon raising her Wegovy dose, her bowel movements had become increasingly smaller and infrequent. This begs the question: How can practitioners help offset side effects through dietary changes, and while we are at it, what other dietary advice is prudent at treatment onset?

Proper nutrition always starts with drinking copious amounts of water. In general, I recommend a minimum of 64 ounces of water daily in patients taking incretins such as semaglutide (Wegovy for weight loss, Ozempic and Rybelsus for type 2 diabetes) or tirzepatide (Zepbound for weight loss, Mounjaro for type 2 diabetes). While these medications don’t directly dehydrate patients, they can increase the risk for dehydration due to severe nausea. Drinking copious amounts of water can prevent dehydration, preserve kidney function, and minimize fatigue and dizziness. In addition, fluids help soften bowel movements, making them easier to pass.

Occasionally incretins make it so easy for patients to drop pounds that their eating patterns become sloppier — more sweets and simple carbohydrates. I recommend a realistic and low glycemic index meal plan. While no foods are strictly contraindicated, processed, high-sugar, and fatty foods are likely to worsen side effects like nausea and gastrointestinal distress. Similarly, alcohol not only worsens nausea, but it’s also likely to exacerbate reflux by relaxing the sphincter that separates the stomach from the esophagus.

The next most important dietary advice is consuming sufficient fiber. In the majority of patients, increasing fiber intake relieves constipation. There are two types of fiber: soluble and insoluble. In practical terms, most fiber-rich foods contain a mixture of these two types. The general recommendation is 38 g/d for men and 25 g/d for women. The caveat to this advice is that a minority of patients, such as those with irritable bowel syndrome, may develop worsening constipation with increasing fiber.

To minimize side effects, some patients find it useful to eat five small meals throughout the day rather than three larger meals. In addition, I recommend eating slowly and stopping before the point of satiety. Finally, because weight loss of any kind is inevitably associated with muscle loss, I stress the importance of adequate protein. In general, I advise 25-30 g of protein per meal.

Christine eventually restarted her Wegovy after recovering from her grueling night in the emergency room. As this was her second go-around on Wegovy, she dug out my “guide to preventing side effects of incretins” and followed it to a T. So far, she’s feeling great.

*The patient’s name has been changed.
 

A version of this article appeared on Medscape.com.

It’s 2 a.m. and my phone wakes me up with a start. My patient, Christine Z*, is vomiting uncontrollably, and Dr Google has diagnosed her with acute pancreatitis from semaglutide (Wegovy). Ten hours, several imaging studies, one blood draw, and many bags of fluids later, the verdict is in: Christine is alarmingly constipated. In fact, her entire large intestine is packed to the brim with stool. In residency, we called this diagnosis FOS, and I’ll leave it to your imagination to figure out what it stands for.

In retrospect, Christine mentions that upon raising her Wegovy dose, her bowel movements had become increasingly smaller and infrequent. This begs the question: How can practitioners help offset side effects through dietary changes, and while we are at it, what other dietary advice is prudent at treatment onset?

Proper nutrition always starts with drinking copious amounts of water. In general, I recommend a minimum of 64 ounces of water daily in patients taking incretins such as semaglutide (Wegovy for weight loss, Ozempic and Rybelsus for type 2 diabetes) or tirzepatide (Zepbound for weight loss, Mounjaro for type 2 diabetes). While these medications don’t directly dehydrate patients, they can increase the risk for dehydration due to severe nausea. Drinking copious amounts of water can prevent dehydration, preserve kidney function, and minimize fatigue and dizziness. In addition, fluids help soften bowel movements, making them easier to pass.

Occasionally incretins make it so easy for patients to drop pounds that their eating patterns become sloppier — more sweets and simple carbohydrates. I recommend a realistic and low glycemic index meal plan. While no foods are strictly contraindicated, processed, high-sugar, and fatty foods are likely to worsen side effects like nausea and gastrointestinal distress. Similarly, alcohol not only worsens nausea, but it’s also likely to exacerbate reflux by relaxing the sphincter that separates the stomach from the esophagus.

The next most important dietary advice is consuming sufficient fiber. In the majority of patients, increasing fiber intake relieves constipation. There are two types of fiber: soluble and insoluble. In practical terms, most fiber-rich foods contain a mixture of these two types. The general recommendation is 38 g/d for men and 25 g/d for women. The caveat to this advice is that a minority of patients, such as those with irritable bowel syndrome, may develop worsening constipation with increasing fiber.

To minimize side effects, some patients find it useful to eat five small meals throughout the day rather than three larger meals. In addition, I recommend eating slowly and stopping before the point of satiety. Finally, because weight loss of any kind is inevitably associated with muscle loss, I stress the importance of adequate protein. In general, I advise 25-30 g of protein per meal.

Christine eventually restarted her Wegovy after recovering from her grueling night in the emergency room. As this was her second go-around on Wegovy, she dug out my “guide to preventing side effects of incretins” and followed it to a T. So far, she’s feeling great.

*The patient’s name has been changed.
 

A version of this article appeared on Medscape.com.

It’s 2 a.m. and my phone wakes me up with a start. My patient, Christine Z*, is vomiting uncontrollably, and Dr Google has diagnosed her with acute pancreatitis from semaglutide (Wegovy). Ten hours, several imaging studies, one blood draw, and many bags of fluids later, the verdict is in: Christine is alarmingly constipated. In fact, her entire large intestine is packed to the brim with stool. In residency, we called this diagnosis FOS, and I’ll leave it to your imagination to figure out what it stands for.

In retrospect, Christine mentions that upon raising her Wegovy dose, her bowel movements had become increasingly smaller and infrequent. This begs the question: How can practitioners help offset side effects through dietary changes, and while we are at it, what other dietary advice is prudent at treatment onset?

Proper nutrition always starts with drinking copious amounts of water. In general, I recommend a minimum of 64 ounces of water daily in patients taking incretins such as semaglutide (Wegovy for weight loss, Ozempic and Rybelsus for type 2 diabetes) or tirzepatide (Zepbound for weight loss, Mounjaro for type 2 diabetes). While these medications don’t directly dehydrate patients, they can increase the risk for dehydration due to severe nausea. Drinking copious amounts of water can prevent dehydration, preserve kidney function, and minimize fatigue and dizziness. In addition, fluids help soften bowel movements, making them easier to pass.

Occasionally incretins make it so easy for patients to drop pounds that their eating patterns become sloppier — more sweets and simple carbohydrates. I recommend a realistic and low glycemic index meal plan. While no foods are strictly contraindicated, processed, high-sugar, and fatty foods are likely to worsen side effects like nausea and gastrointestinal distress. Similarly, alcohol not only worsens nausea, but it’s also likely to exacerbate reflux by relaxing the sphincter that separates the stomach from the esophagus.

The next most important dietary advice is consuming sufficient fiber. In the majority of patients, increasing fiber intake relieves constipation. There are two types of fiber: soluble and insoluble. In practical terms, most fiber-rich foods contain a mixture of these two types. The general recommendation is 38 g/d for men and 25 g/d for women. The caveat to this advice is that a minority of patients, such as those with irritable bowel syndrome, may develop worsening constipation with increasing fiber.

To minimize side effects, some patients find it useful to eat five small meals throughout the day rather than three larger meals. In addition, I recommend eating slowly and stopping before the point of satiety. Finally, because weight loss of any kind is inevitably associated with muscle loss, I stress the importance of adequate protein. In general, I advise 25-30 g of protein per meal.

Christine eventually restarted her Wegovy after recovering from her grueling night in the emergency room. As this was her second go-around on Wegovy, she dug out my “guide to preventing side effects of incretins” and followed it to a T. So far, she’s feeling great.

*The patient’s name has been changed.
 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’ve been spending time recently reflecting on the biggest developments from last year. I have to say that the breakthrough of the year, based on the amount of data presented and the importance of the data, is chemotherapy. I never thought I would say that. Many folks have tried to relegate chemotherapy to the museum, but last year it came to the forefront.

Let’s start with neoadjuvant therapy. We now have multiple drug approvals for giving a checkpoint inhibitor and neoadjuvant therapy in what I would say is a new standard of care for patients with locally advanced lung cancers who are candidates for surgery. In all those trials, there was a clear improvement in progression-free survival by adding a checkpoint inhibitor to chemotherapy. The cornerstone of this regimen is chemotherapy.

What about adjuvant therapy? I think one of the most astounding pieces of data last year was in the adjuvant realm. In the trial comparing adjuvant osimertinib with placebo in patients with EGFR-mutant disease, patients who received chemotherapy in addition to osimertinib had a 7% improvement in 5-year survival. Patients who had placebo, who got chemotherapy vs didn’t, had a 9% improvement in 5-year survival. Those are huge numbers for that kind of metric, and it happened with chemotherapy.

What about targeted therapies? Again, I think people were astounded that, by adding chemotherapy to osimertinib compared with osimertinib alone, there was a 9-month improvement overall in progression-free survival. I think in the presentation of the data that has been made, the most remarkable piece of data is that, in patients with brain metastases, chemotherapy on top of osimertinib improved progression-free survival. Not only did it improve progression-free survival, but it did it with brain metastases, where people think it just doesn’t help at all.

What about other, newer agents with chemotherapy? Amivantamab, I would say, has hitched itself to chemotherapy. A trial in EGFR exon 20 compared chemo to amivantamab plus chemotherapy. There again, chemo is the common denominator. Amivantamab added approximately 5 months of improved progression-free survival. Again, chemo was used. In adjuvant, neoadjuvant, and targeted therapies, chemotherapy adds.

What about the second line? I think everybody was very disappointed when second-line sotorasib gave a very tiny amount of progression-free survival improvement over docetaxel. I think we all want more for our patients than we can deliver with docetaxel. The roughly 5-week improvement seen with sotorasib was one that raised a question about the place of sotorasib in this setting.

Clearly, we’ve all seen patients have an excellent result with sotorasib as an additional option for treating patients with long progression-free survival, high rates of response, and good tolerability even at the 960 mg dose. But in the randomized trial, it wasn’t better than docetaxel. Again, I think we were disappointed with tusamitamab ravtansine in that it could not beat docetaxel either. I think the idea here is that chemo still has a huge place and still remains the treatment that we have to beat.

We’re all very excited about the antibody-drug conjugates and I think everybody sees them as another advance. Many folks have said that they are just a more precise way of delivering chemotherapy, and when you look at the side effects, it supports that — they’re largely side effects of chemotherapy with these drugs across the board. Also, when you look at the patterns of resistance, the resistance really isn’t a resistance to the targeted therapy; it’s a resistance to chemotherapy more than anything else.

So we’re happy that the antibody-drug conjugates are available and we were disappointed with tusamitamab ravtansine because we thought that it could beat docetaxel. But in truth, it didn’t, and unfortunately, that pivotal trial led to the end of the entire development program for that agent, as stated in a press release.

The molecule or treatment of the year is chemotherapy — added to targeted therapies, used with immunotherapy, and now attached to antibodies as part of antibody-drug conjugates. I think it remains, more than any one treatment, a very effective treatment for patients and deserves to be used.

There are a lot of choices here. I think you have to be very careful to choose wisely, and you also have to be careful because chemotherapy has side effects. The nice thing is that many of those side effects can be ameliorated. We have to make sure that we use all the supportive medications we can.

Who would have thought that chemotherapy would be the treatment of the year in 2023 for lung cancers?
 

Dr. Kris is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer Inc, and PUMA.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’ve been spending time recently reflecting on the biggest developments from last year. I have to say that the breakthrough of the year, based on the amount of data presented and the importance of the data, is chemotherapy. I never thought I would say that. Many folks have tried to relegate chemotherapy to the museum, but last year it came to the forefront.

Let’s start with neoadjuvant therapy. We now have multiple drug approvals for giving a checkpoint inhibitor and neoadjuvant therapy in what I would say is a new standard of care for patients with locally advanced lung cancers who are candidates for surgery. In all those trials, there was a clear improvement in progression-free survival by adding a checkpoint inhibitor to chemotherapy. The cornerstone of this regimen is chemotherapy.

What about adjuvant therapy? I think one of the most astounding pieces of data last year was in the adjuvant realm. In the trial comparing adjuvant osimertinib with placebo in patients with EGFR-mutant disease, patients who received chemotherapy in addition to osimertinib had a 7% improvement in 5-year survival. Patients who had placebo, who got chemotherapy vs didn’t, had a 9% improvement in 5-year survival. Those are huge numbers for that kind of metric, and it happened with chemotherapy.

What about targeted therapies? Again, I think people were astounded that, by adding chemotherapy to osimertinib compared with osimertinib alone, there was a 9-month improvement overall in progression-free survival. I think in the presentation of the data that has been made, the most remarkable piece of data is that, in patients with brain metastases, chemotherapy on top of osimertinib improved progression-free survival. Not only did it improve progression-free survival, but it did it with brain metastases, where people think it just doesn’t help at all.

What about other, newer agents with chemotherapy? Amivantamab, I would say, has hitched itself to chemotherapy. A trial in EGFR exon 20 compared chemo to amivantamab plus chemotherapy. There again, chemo is the common denominator. Amivantamab added approximately 5 months of improved progression-free survival. Again, chemo was used. In adjuvant, neoadjuvant, and targeted therapies, chemotherapy adds.

What about the second line? I think everybody was very disappointed when second-line sotorasib gave a very tiny amount of progression-free survival improvement over docetaxel. I think we all want more for our patients than we can deliver with docetaxel. The roughly 5-week improvement seen with sotorasib was one that raised a question about the place of sotorasib in this setting.

Clearly, we’ve all seen patients have an excellent result with sotorasib as an additional option for treating patients with long progression-free survival, high rates of response, and good tolerability even at the 960 mg dose. But in the randomized trial, it wasn’t better than docetaxel. Again, I think we were disappointed with tusamitamab ravtansine in that it could not beat docetaxel either. I think the idea here is that chemo still has a huge place and still remains the treatment that we have to beat.

We’re all very excited about the antibody-drug conjugates and I think everybody sees them as another advance. Many folks have said that they are just a more precise way of delivering chemotherapy, and when you look at the side effects, it supports that — they’re largely side effects of chemotherapy with these drugs across the board. Also, when you look at the patterns of resistance, the resistance really isn’t a resistance to the targeted therapy; it’s a resistance to chemotherapy more than anything else.

So we’re happy that the antibody-drug conjugates are available and we were disappointed with tusamitamab ravtansine because we thought that it could beat docetaxel. But in truth, it didn’t, and unfortunately, that pivotal trial led to the end of the entire development program for that agent, as stated in a press release.

The molecule or treatment of the year is chemotherapy — added to targeted therapies, used with immunotherapy, and now attached to antibodies as part of antibody-drug conjugates. I think it remains, more than any one treatment, a very effective treatment for patients and deserves to be used.

There are a lot of choices here. I think you have to be very careful to choose wisely, and you also have to be careful because chemotherapy has side effects. The nice thing is that many of those side effects can be ameliorated. We have to make sure that we use all the supportive medications we can.

Who would have thought that chemotherapy would be the treatment of the year in 2023 for lung cancers?
 

Dr. Kris is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer Inc, and PUMA.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’ve been spending time recently reflecting on the biggest developments from last year. I have to say that the breakthrough of the year, based on the amount of data presented and the importance of the data, is chemotherapy. I never thought I would say that. Many folks have tried to relegate chemotherapy to the museum, but last year it came to the forefront.

Let’s start with neoadjuvant therapy. We now have multiple drug approvals for giving a checkpoint inhibitor and neoadjuvant therapy in what I would say is a new standard of care for patients with locally advanced lung cancers who are candidates for surgery. In all those trials, there was a clear improvement in progression-free survival by adding a checkpoint inhibitor to chemotherapy. The cornerstone of this regimen is chemotherapy.

What about adjuvant therapy? I think one of the most astounding pieces of data last year was in the adjuvant realm. In the trial comparing adjuvant osimertinib with placebo in patients with EGFR-mutant disease, patients who received chemotherapy in addition to osimertinib had a 7% improvement in 5-year survival. Patients who had placebo, who got chemotherapy vs didn’t, had a 9% improvement in 5-year survival. Those are huge numbers for that kind of metric, and it happened with chemotherapy.

What about targeted therapies? Again, I think people were astounded that, by adding chemotherapy to osimertinib compared with osimertinib alone, there was a 9-month improvement overall in progression-free survival. I think in the presentation of the data that has been made, the most remarkable piece of data is that, in patients with brain metastases, chemotherapy on top of osimertinib improved progression-free survival. Not only did it improve progression-free survival, but it did it with brain metastases, where people think it just doesn’t help at all.

What about other, newer agents with chemotherapy? Amivantamab, I would say, has hitched itself to chemotherapy. A trial in EGFR exon 20 compared chemo to amivantamab plus chemotherapy. There again, chemo is the common denominator. Amivantamab added approximately 5 months of improved progression-free survival. Again, chemo was used. In adjuvant, neoadjuvant, and targeted therapies, chemotherapy adds.

What about the second line? I think everybody was very disappointed when second-line sotorasib gave a very tiny amount of progression-free survival improvement over docetaxel. I think we all want more for our patients than we can deliver with docetaxel. The roughly 5-week improvement seen with sotorasib was one that raised a question about the place of sotorasib in this setting.

Clearly, we’ve all seen patients have an excellent result with sotorasib as an additional option for treating patients with long progression-free survival, high rates of response, and good tolerability even at the 960 mg dose. But in the randomized trial, it wasn’t better than docetaxel. Again, I think we were disappointed with tusamitamab ravtansine in that it could not beat docetaxel either. I think the idea here is that chemo still has a huge place and still remains the treatment that we have to beat.

We’re all very excited about the antibody-drug conjugates and I think everybody sees them as another advance. Many folks have said that they are just a more precise way of delivering chemotherapy, and when you look at the side effects, it supports that — they’re largely side effects of chemotherapy with these drugs across the board. Also, when you look at the patterns of resistance, the resistance really isn’t a resistance to the targeted therapy; it’s a resistance to chemotherapy more than anything else.

So we’re happy that the antibody-drug conjugates are available and we were disappointed with tusamitamab ravtansine because we thought that it could beat docetaxel. But in truth, it didn’t, and unfortunately, that pivotal trial led to the end of the entire development program for that agent, as stated in a press release.

The molecule or treatment of the year is chemotherapy — added to targeted therapies, used with immunotherapy, and now attached to antibodies as part of antibody-drug conjugates. I think it remains, more than any one treatment, a very effective treatment for patients and deserves to be used.

There are a lot of choices here. I think you have to be very careful to choose wisely, and you also have to be careful because chemotherapy has side effects. The nice thing is that many of those side effects can be ameliorated. We have to make sure that we use all the supportive medications we can.

Who would have thought that chemotherapy would be the treatment of the year in 2023 for lung cancers?
 

Dr. Kris is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer Inc, and PUMA.

A version of this article appeared on Medscape.com.

Artificial intelligence (AI) has lagged in health care but has considerable potential to improve quality, safety, clinician experience, and access to care. It is being tested in areas like billing, hospital operations, and preventing adverse events (eg, sepsis mortality) with some early success. However, there are still many barriers preventing the widespread use of AI, such as data problems, mismatched rewards, and workplace obstacles. Innovative projects, partnerships, better rewards, and more investment could remove barriers. Implemented reliably and safely, AI can add to what clinicians know, help them work faster, cut costs, and, most importantly, improve patient care.¹

AI can potentially bring several clinical benefits, such as reducing the administrative strain on clinicians and granting them more time for direct patient care. It can also improve diagnostic accuracy by analyzing patient data and diagnostic images, providing differential diagnoses, and increasing access to care by providing medical information and essential online services to patients.²

High Reliability Organizations

High reliability health care organizations have considerable experience safely launching new programs. For example, the Patient Safety Adoption Framework gives practical tips for smoothly rolling out safety initiatives (Table 1). Developed with experts and diverse views, this framework has 5 key areas: leadership, culture and context, process, measurement, and person-centeredness. These address adoption problems, guide leaders step-by-step, and focus on leadership buy-in, safety culture, cooperation, and local customization. Checklists and tools make it systematic to go from ideas to action on patient safety.³

Leadership involves establishing organizational commitment behind new safety programs. This visible commitment signals importance and priorities to others. Leaders model desired behaviors and language around safety, allocate resources, remove obstacles, and keep initiatives energized over time through consistent messaging.⁴ Culture and context recognizes that safety culture differs across units and facilities. Local input tailors programs to fit and examines strengths to build on, like psychological safety. Surveys gauge the existing culture and its need for change. Process details how to plan, design, test, implement, and improve new safety practices and provides a phased roadmap from idea to results. Measurement collects data to drive improvement and show impact. Metrics track progress and allow benchmarking. Person-centeredness puts patients first in safety efforts through participation, education, and transparency.

The Veterans Health Administration piloted a comprehensive high reliability hospital (HRH) model. Over 3 years, the Veterans Health Administration focused on leadership, culture, and process improvement at a hospital. After initiating the model, the pilot hospital improved its safety culture, reported more minor safety issues, and reduced deaths and complications better than other hospitals. The high-reliability approach successfully instilled principles and improved culture and outcomes. The HRH model is set to be expanded to 18 more US Department of Veterans Affairs (VA) sites for further evaluation across diverse settings.⁵

Trustworthy AI Framework

AI systems are growing more powerful and widespread, including in health care. Unfortunately, irresponsible AI can introduce new harm. ChatGPT and other large language models, for example, sometimes are known to provide erroneous information in a compelling way. Clinicians and patients who use such programs can act on such information, which would lead to unforeseen negative consequences. Several frameworks on ethical AI have come from governmental groups.^6-9 In 2023, the VA National AI Institute suggested a Trustworthy AI Framework based on core principles tailored for federal health care. The framework has 6 key principles: purposeful, effective and safe, secure and private, fair and equitable, transparent and explainable, and accountable and monitored (Table 2).¹⁰

First, AI must clearly help veterans while minimizing risks. To ensure purpose, the VA will assess patient and clinician needs and design AI that targets meaningful problems to avoid scope creep or feature bloat. For example, adding new features to the AI software after release can clutter and complicate the interface, making it difficult to use. Rigorous testing will confirm that AI meets intent prior to deployment. Second, AI is designed and checked for effectiveness, safety, and reliability. The VA pledges to monitor AI’s impact to ensure it performs as expected without unintended consequences. Algorithms will be stress tested across representative datasets and approval processes will screen for safety issues. Third, AI models are secured from vulnerabilities and misuse. Technical controls will prevent unauthorized access or changes to AI systems. Audits will check for appropriate internal usage per policies. Continual patches and upgrades will maintain security. Fourth, the VA manages AI for fairness, avoiding bias. They will proactively assess datasets and algorithms for potential biases based on protected attributes like race, gender, or age. Biased outputs will be addressed through techniques such as data augmentation, reweighting, and algorithm tweaks. Fifth, transparency explains AI’s role in care. Documentation will detail an AI system’s data sources, methodology, testing, limitations, and integration with clinical workflows. Clinicians and patients will receive education on interpreting AI outputs. Finally, the VA pledges to closely monitor AI systems to sustain trust. The VA will establish oversight processes to quickly identify any declines in reliability or unfair impacts on subgroups. AI models will be retrained as needed based on incoming data patterns.

Each Trustworthy AI Framework principle connects to others in existing frameworks. The purpose principle aligns with human-centric AI focused on benefits. Effectiveness and safety link to technical robustness and risk management principles. Security maps to privacy protection principles. Fairness connects to principles of avoiding bias and discrimination. Transparency corresponds with accountable and explainable AI. Monitoring and accountability tie back to governance principles. Overall, the VA framework aims to guide ethical AI based on context. It offers a model for managing risks and building trust in health care AI.

Combining VA principles with high-reliability safety principles can ensure that AI benefits veterans. The leadership and culture aspects will drive commitment to trustworthy AI practices. Leaders will communicate the importance of responsible AI through words and actions. Culture surveys can assess baseline awareness of AI ethics issues to target education. AI security and fairness will be emphasized as safety critical. The process aspect will institute policies and procedures to uphold AI principles through the project lifecycle. For example, structured testing processes will validate safety. Measurement will collect data on principles like transparency and fairness. Dashboards can track metrics like explainability and biases. A patient-centered approach will incorporate veteran perspectives on AI through participatory design and advisory councils. They can give input on AI explainability and potential biases based on their diverse backgrounds.

Conclusions

Joint principles will lead to successful AI that improves care while proactively managing risks. Involve leaders to stress the necessity of eliminating biases. Build security into the AI development process. Co-design AI transparency features with end users. Closely monitor the impact of AI across safety, fairness, and other principles. Adhering to both Trustworthy AI and high reliability organizations principles will earn veterans’ confidence. Health care organizations like the VA can integrate ethical AI safely via established frameworks. With responsible design and implementation, AI’s potential to enhance care quality, safety, and access can be realized.

Acknowledgments

We would like to acknowledge Joshua Mueller, Theo Tiffney, John Zachary, and Gil Alterovitz for their excellent work creating the VA Trustworthy Principles. This material is the result of work supported by resources and the use of facilities at the James A. Haley Veterans’ Hospital.

Artificial intelligence (AI) has lagged in health care but has considerable potential to improve quality, safety, clinician experience, and access to care. It is being tested in areas like billing, hospital operations, and preventing adverse events (eg, sepsis mortality) with some early success. However, there are still many barriers preventing the widespread use of AI, such as data problems, mismatched rewards, and workplace obstacles. Innovative projects, partnerships, better rewards, and more investment could remove barriers. Implemented reliably and safely, AI can add to what clinicians know, help them work faster, cut costs, and, most importantly, improve patient care.¹

AI can potentially bring several clinical benefits, such as reducing the administrative strain on clinicians and granting them more time for direct patient care. It can also improve diagnostic accuracy by analyzing patient data and diagnostic images, providing differential diagnoses, and increasing access to care by providing medical information and essential online services to patients.²

High Reliability Organizations

High reliability health care organizations have considerable experience safely launching new programs. For example, the Patient Safety Adoption Framework gives practical tips for smoothly rolling out safety initiatives (Table 1). Developed with experts and diverse views, this framework has 5 key areas: leadership, culture and context, process, measurement, and person-centeredness. These address adoption problems, guide leaders step-by-step, and focus on leadership buy-in, safety culture, cooperation, and local customization. Checklists and tools make it systematic to go from ideas to action on patient safety.³

Leadership involves establishing organizational commitment behind new safety programs. This visible commitment signals importance and priorities to others. Leaders model desired behaviors and language around safety, allocate resources, remove obstacles, and keep initiatives energized over time through consistent messaging.⁴ Culture and context recognizes that safety culture differs across units and facilities. Local input tailors programs to fit and examines strengths to build on, like psychological safety. Surveys gauge the existing culture and its need for change. Process details how to plan, design, test, implement, and improve new safety practices and provides a phased roadmap from idea to results. Measurement collects data to drive improvement and show impact. Metrics track progress and allow benchmarking. Person-centeredness puts patients first in safety efforts through participation, education, and transparency.

The Veterans Health Administration piloted a comprehensive high reliability hospital (HRH) model. Over 3 years, the Veterans Health Administration focused on leadership, culture, and process improvement at a hospital. After initiating the model, the pilot hospital improved its safety culture, reported more minor safety issues, and reduced deaths and complications better than other hospitals. The high-reliability approach successfully instilled principles and improved culture and outcomes. The HRH model is set to be expanded to 18 more US Department of Veterans Affairs (VA) sites for further evaluation across diverse settings.⁵

Trustworthy AI Framework

AI systems are growing more powerful and widespread, including in health care. Unfortunately, irresponsible AI can introduce new harm. ChatGPT and other large language models, for example, sometimes are known to provide erroneous information in a compelling way. Clinicians and patients who use such programs can act on such information, which would lead to unforeseen negative consequences. Several frameworks on ethical AI have come from governmental groups.^6-9 In 2023, the VA National AI Institute suggested a Trustworthy AI Framework based on core principles tailored for federal health care. The framework has 6 key principles: purposeful, effective and safe, secure and private, fair and equitable, transparent and explainable, and accountable and monitored (Table 2).¹⁰

First, AI must clearly help veterans while minimizing risks. To ensure purpose, the VA will assess patient and clinician needs and design AI that targets meaningful problems to avoid scope creep or feature bloat. For example, adding new features to the AI software after release can clutter and complicate the interface, making it difficult to use. Rigorous testing will confirm that AI meets intent prior to deployment. Second, AI is designed and checked for effectiveness, safety, and reliability. The VA pledges to monitor AI’s impact to ensure it performs as expected without unintended consequences. Algorithms will be stress tested across representative datasets and approval processes will screen for safety issues. Third, AI models are secured from vulnerabilities and misuse. Technical controls will prevent unauthorized access or changes to AI systems. Audits will check for appropriate internal usage per policies. Continual patches and upgrades will maintain security. Fourth, the VA manages AI for fairness, avoiding bias. They will proactively assess datasets and algorithms for potential biases based on protected attributes like race, gender, or age. Biased outputs will be addressed through techniques such as data augmentation, reweighting, and algorithm tweaks. Fifth, transparency explains AI’s role in care. Documentation will detail an AI system’s data sources, methodology, testing, limitations, and integration with clinical workflows. Clinicians and patients will receive education on interpreting AI outputs. Finally, the VA pledges to closely monitor AI systems to sustain trust. The VA will establish oversight processes to quickly identify any declines in reliability or unfair impacts on subgroups. AI models will be retrained as needed based on incoming data patterns.

Each Trustworthy AI Framework principle connects to others in existing frameworks. The purpose principle aligns with human-centric AI focused on benefits. Effectiveness and safety link to technical robustness and risk management principles. Security maps to privacy protection principles. Fairness connects to principles of avoiding bias and discrimination. Transparency corresponds with accountable and explainable AI. Monitoring and accountability tie back to governance principles. Overall, the VA framework aims to guide ethical AI based on context. It offers a model for managing risks and building trust in health care AI.

Combining VA principles with high-reliability safety principles can ensure that AI benefits veterans. The leadership and culture aspects will drive commitment to trustworthy AI practices. Leaders will communicate the importance of responsible AI through words and actions. Culture surveys can assess baseline awareness of AI ethics issues to target education. AI security and fairness will be emphasized as safety critical. The process aspect will institute policies and procedures to uphold AI principles through the project lifecycle. For example, structured testing processes will validate safety. Measurement will collect data on principles like transparency and fairness. Dashboards can track metrics like explainability and biases. A patient-centered approach will incorporate veteran perspectives on AI through participatory design and advisory councils. They can give input on AI explainability and potential biases based on their diverse backgrounds.

Conclusions

Joint principles will lead to successful AI that improves care while proactively managing risks. Involve leaders to stress the necessity of eliminating biases. Build security into the AI development process. Co-design AI transparency features with end users. Closely monitor the impact of AI across safety, fairness, and other principles. Adhering to both Trustworthy AI and high reliability organizations principles will earn veterans’ confidence. Health care organizations like the VA can integrate ethical AI safely via established frameworks. With responsible design and implementation, AI’s potential to enhance care quality, safety, and access can be realized.

Acknowledgments

We would like to acknowledge Joshua Mueller, Theo Tiffney, John Zachary, and Gil Alterovitz for their excellent work creating the VA Trustworthy Principles. This material is the result of work supported by resources and the use of facilities at the James A. Haley Veterans’ Hospital.

Artificial intelligence (AI) has lagged in health care but has considerable potential to improve quality, safety, clinician experience, and access to care. It is being tested in areas like billing, hospital operations, and preventing adverse events (eg, sepsis mortality) with some early success. However, there are still many barriers preventing the widespread use of AI, such as data problems, mismatched rewards, and workplace obstacles. Innovative projects, partnerships, better rewards, and more investment could remove barriers. Implemented reliably and safely, AI can add to what clinicians know, help them work faster, cut costs, and, most importantly, improve patient care.¹

AI can potentially bring several clinical benefits, such as reducing the administrative strain on clinicians and granting them more time for direct patient care. It can also improve diagnostic accuracy by analyzing patient data and diagnostic images, providing differential diagnoses, and increasing access to care by providing medical information and essential online services to patients.²

High Reliability Organizations

High reliability health care organizations have considerable experience safely launching new programs. For example, the Patient Safety Adoption Framework gives practical tips for smoothly rolling out safety initiatives (Table 1). Developed with experts and diverse views, this framework has 5 key areas: leadership, culture and context, process, measurement, and person-centeredness. These address adoption problems, guide leaders step-by-step, and focus on leadership buy-in, safety culture, cooperation, and local customization. Checklists and tools make it systematic to go from ideas to action on patient safety.³

Leadership involves establishing organizational commitment behind new safety programs. This visible commitment signals importance and priorities to others. Leaders model desired behaviors and language around safety, allocate resources, remove obstacles, and keep initiatives energized over time through consistent messaging.⁴ Culture and context recognizes that safety culture differs across units and facilities. Local input tailors programs to fit and examines strengths to build on, like psychological safety. Surveys gauge the existing culture and its need for change. Process details how to plan, design, test, implement, and improve new safety practices and provides a phased roadmap from idea to results. Measurement collects data to drive improvement and show impact. Metrics track progress and allow benchmarking. Person-centeredness puts patients first in safety efforts through participation, education, and transparency.

The Veterans Health Administration piloted a comprehensive high reliability hospital (HRH) model. Over 3 years, the Veterans Health Administration focused on leadership, culture, and process improvement at a hospital. After initiating the model, the pilot hospital improved its safety culture, reported more minor safety issues, and reduced deaths and complications better than other hospitals. The high-reliability approach successfully instilled principles and improved culture and outcomes. The HRH model is set to be expanded to 18 more US Department of Veterans Affairs (VA) sites for further evaluation across diverse settings.⁵

Trustworthy AI Framework

AI systems are growing more powerful and widespread, including in health care. Unfortunately, irresponsible AI can introduce new harm. ChatGPT and other large language models, for example, sometimes are known to provide erroneous information in a compelling way. Clinicians and patients who use such programs can act on such information, which would lead to unforeseen negative consequences. Several frameworks on ethical AI have come from governmental groups.^6-9 In 2023, the VA National AI Institute suggested a Trustworthy AI Framework based on core principles tailored for federal health care. The framework has 6 key principles: purposeful, effective and safe, secure and private, fair and equitable, transparent and explainable, and accountable and monitored (Table 2).¹⁰

First, AI must clearly help veterans while minimizing risks. To ensure purpose, the VA will assess patient and clinician needs and design AI that targets meaningful problems to avoid scope creep or feature bloat. For example, adding new features to the AI software after release can clutter and complicate the interface, making it difficult to use. Rigorous testing will confirm that AI meets intent prior to deployment. Second, AI is designed and checked for effectiveness, safety, and reliability. The VA pledges to monitor AI’s impact to ensure it performs as expected without unintended consequences. Algorithms will be stress tested across representative datasets and approval processes will screen for safety issues. Third, AI models are secured from vulnerabilities and misuse. Technical controls will prevent unauthorized access or changes to AI systems. Audits will check for appropriate internal usage per policies. Continual patches and upgrades will maintain security. Fourth, the VA manages AI for fairness, avoiding bias. They will proactively assess datasets and algorithms for potential biases based on protected attributes like race, gender, or age. Biased outputs will be addressed through techniques such as data augmentation, reweighting, and algorithm tweaks. Fifth, transparency explains AI’s role in care. Documentation will detail an AI system’s data sources, methodology, testing, limitations, and integration with clinical workflows. Clinicians and patients will receive education on interpreting AI outputs. Finally, the VA pledges to closely monitor AI systems to sustain trust. The VA will establish oversight processes to quickly identify any declines in reliability or unfair impacts on subgroups. AI models will be retrained as needed based on incoming data patterns.

Each Trustworthy AI Framework principle connects to others in existing frameworks. The purpose principle aligns with human-centric AI focused on benefits. Effectiveness and safety link to technical robustness and risk management principles. Security maps to privacy protection principles. Fairness connects to principles of avoiding bias and discrimination. Transparency corresponds with accountable and explainable AI. Monitoring and accountability tie back to governance principles. Overall, the VA framework aims to guide ethical AI based on context. It offers a model for managing risks and building trust in health care AI.

Combining VA principles with high-reliability safety principles can ensure that AI benefits veterans. The leadership and culture aspects will drive commitment to trustworthy AI practices. Leaders will communicate the importance of responsible AI through words and actions. Culture surveys can assess baseline awareness of AI ethics issues to target education. AI security and fairness will be emphasized as safety critical. The process aspect will institute policies and procedures to uphold AI principles through the project lifecycle. For example, structured testing processes will validate safety. Measurement will collect data on principles like transparency and fairness. Dashboards can track metrics like explainability and biases. A patient-centered approach will incorporate veteran perspectives on AI through participatory design and advisory councils. They can give input on AI explainability and potential biases based on their diverse backgrounds.

Conclusions

Joint principles will lead to successful AI that improves care while proactively managing risks. Involve leaders to stress the necessity of eliminating biases. Build security into the AI development process. Co-design AI transparency features with end users. Closely monitor the impact of AI across safety, fairness, and other principles. Adhering to both Trustworthy AI and high reliability organizations principles will earn veterans’ confidence. Health care organizations like the VA can integrate ethical AI safely via established frameworks. With responsible design and implementation, AI’s potential to enhance care quality, safety, and access can be realized.

Acknowledgments

We would like to acknowledge Joshua Mueller, Theo Tiffney, John Zachary, and Gil Alterovitz for their excellent work creating the VA Trustworthy Principles. This material is the result of work supported by resources and the use of facilities at the James A. Haley Veterans’ Hospital.

As an organization, AGA has invested heavily in programs and initiatives to support the professional development of its members across career stages. This includes programs such as the AGA-AASLD Academic Skills Workshop (in which I was fortunate to participate in 2016), Women’s Leadership and Executive Leadership Conferences (with the Midwest Women in GI Regional Workshop taking place later this month), and the AGA Research Foundation Awards Program, which distributes over $2 million in funding annually to support promising early career and senior investigators.

AGA’s Fostering Opportunities Resulting in Workforce and Research Diversity (FORWARD) Program, which was first funded by the National Institutes of Health in 2018 and is focused on improving the diversity of the GI research workforce, is another shining example. Led by Dr. Byron Cryer and Dr. Sandra Quezada, the program recently welcomed its 3rd cohort of participants, including 14 mentees and 28 senior and near-peer mentors.

As a longstanding AGA member, I am proud to be a part of an organization that values diversity and invests in cutting-edge programs to support development of future leaders in our field across multiple domains. We are pleased to frequently highlight these programs in the pages of GI & Hepatology News, and hope you enjoy learning more about each of these initiatives in future issues.

University of Michigan

Megan A. Adams, MD, JD, MSc

Editor-in-Chief

As an organization, AGA has invested heavily in programs and initiatives to support the professional development of its members across career stages. This includes programs such as the AGA-AASLD Academic Skills Workshop (in which I was fortunate to participate in 2016), Women’s Leadership and Executive Leadership Conferences (with the Midwest Women in GI Regional Workshop taking place later this month), and the AGA Research Foundation Awards Program, which distributes over $2 million in funding annually to support promising early career and senior investigators.

AGA’s Fostering Opportunities Resulting in Workforce and Research Diversity (FORWARD) Program, which was first funded by the National Institutes of Health in 2018 and is focused on improving the diversity of the GI research workforce, is another shining example. Led by Dr. Byron Cryer and Dr. Sandra Quezada, the program recently welcomed its 3rd cohort of participants, including 14 mentees and 28 senior and near-peer mentors.

As a longstanding AGA member, I am proud to be a part of an organization that values diversity and invests in cutting-edge programs to support development of future leaders in our field across multiple domains. We are pleased to frequently highlight these programs in the pages of GI & Hepatology News, and hope you enjoy learning more about each of these initiatives in future issues.

University of Michigan

Megan A. Adams, MD, JD, MSc

Editor-in-Chief

As an organization, AGA has invested heavily in programs and initiatives to support the professional development of its members across career stages. This includes programs such as the AGA-AASLD Academic Skills Workshop (in which I was fortunate to participate in 2016), Women’s Leadership and Executive Leadership Conferences (with the Midwest Women in GI Regional Workshop taking place later this month), and the AGA Research Foundation Awards Program, which distributes over $2 million in funding annually to support promising early career and senior investigators.

AGA’s Fostering Opportunities Resulting in Workforce and Research Diversity (FORWARD) Program, which was first funded by the National Institutes of Health in 2018 and is focused on improving the diversity of the GI research workforce, is another shining example. Led by Dr. Byron Cryer and Dr. Sandra Quezada, the program recently welcomed its 3rd cohort of participants, including 14 mentees and 28 senior and near-peer mentors.

As a longstanding AGA member, I am proud to be a part of an organization that values diversity and invests in cutting-edge programs to support development of future leaders in our field across multiple domains. We are pleased to frequently highlight these programs in the pages of GI & Hepatology News, and hope you enjoy learning more about each of these initiatives in future issues.

University of Michigan

Megan A. Adams, MD, JD, MSc

Editor-in-Chief

It’s that time of the year, when social media is rife with many top 5 and top 10 lists. Perhaps the beginning of a new year is a good time to review how different medications can have side effects beyond the disease state they’re used to address. Among the most common complications of many medications is the potential to disrupt glycemic control. Let’s revisit some of the most commonly used medications known to increase glucose levels and look at some practical tips on overcoming these.

1. Glucocorticoids

Without a doubt, corticosteroids are at the top of the list when it comes to the potential for increasing blood glucose levels. High-dose glucocorticoid therapy is known to lead to new-onset diabetes (steroid-induced diabetes). Similarly, people with preexisting diabetes may notice significant worsening of glycemic control when they start on glucocorticoid therapy. The extent of glucose elevation depends on their glycemic status prior to initiation on steroids, the dose and duration of glucocorticoid therapy, and comorbid conditions, among other factors.

Management tip: For those with previously well-controlled diabetes or borderline diabetes, glucocorticoid-induced hyperglycemia may be managed by metformin with or without sulfonylurea therapy, especially if corticosteroid treatment is low-dose and for a shorter duration. However, for many individuals with preexisting poorly controlled diabetes or those initiated on high-dose corticosteroids, insulin therapy would perhaps be the treatment of choice. Glucocorticoid therapy generally leads to more pronounced postprandial hyperglycemia compared with fasting hyperglycemia; hence, the use of short-acting insulin therapy or perhaps NPH insulin in the morning might be a better option for many individuals. Dietary modification plays an important role in limiting the extent of postprandial hyperglycemia. Use of continuous glucose monitoring (CGM) devices may also be very helpful for understanding glycemic excursions and how to adjust insulin. In individuals for whom glucocorticoid therapy is tapered down, it is important to adjust the dose of medications with potential to cause hypoglycemia, such as insulin/sulfonylurea therapy, as the degree of hyperglycemia may decrease with decreased dose of the glucocorticoid therapy.

2. Antipsychotic Therapy

Antipsychotic medications can be obesogenic; between 15% and 72% of people who take second-generation antipsychotics experience weight gain of 7% or more. Increases in weight are not the only factor contributing to an elevated risk of developing type 2 diabetes. Antipsychotics are thought to cause downregulation of intracellular insulin signaling, leading to insulin resistance. At the same time, there seems to be a direct effect on the pancreatic beta cells. Antagonism of the dopamine D2, serotonin 5-HT2C, and muscarinic M3 receptors impairs beta-cell response to changes in blood glucose. In addition to the pharmacologic effects, cell culture experiments have shown that antipsychotics increase apoptosis of beta cells. Increased weight and concomitant development of type 2 diabetes is seen particularly in agents that exhibit high muscarinic M3 and histamine H1 receptor blockade. The effect on glucose metabolism is seen the most with agents such as clozapine, olanzapine, and haloperidol and the least with agents such as ziprasidone.

Management tip: Given the ongoing change in the understanding of increases in weight and their association with the risk of developing type 2 diabetes, a metabolically safer approach involves starting with medications that have a lower propensity for weight gain, and the partial agonists/third-generation antipsychotics as a family presently have the best overall data.

3. Thiazide Diuretics

Thiazide diuretics are commonly used for the management of hypertension and are associated with metabolic complications including hypokalemia; higher cholesterol, triglycerides, and other circulating lipids; and elevated glucose. It’s thought that the reduced potassium level occurring as a result of these medications might contribute to new-onset diabetes. The hypokalemia occurring from these medications is thought to lead to a decrease in insulin secretion and sensitivity, which is dose dependent. Studies show that the number needed to harm for chlorthalidone-induced diabetes is 29 over 1 year. There is believed to be no additional risk beyond 1 year.

Management tip: It’s important to monitor potassium levels for those initiated on thiazide diuretics. If hypokalemia occurs, it would be pertinent to correct the hypokalemia with potassium supplements to mitigate the risk for new-onset diabetes.

4. Statin Therapy

Statin therapy is thought to be associated with decreased insulin sensitivity and impairment in insulin secretion. The overall incidence of diabetes is pegged to be between 9% and 12% on statin therapy on the basis of meta-analysis studies, and higher on the basis of population-based studies. Overall, the estimated number needed to harm is: 1 out of every 255 patients on statin therapy for 4 years may develop new-onset diabetes. Compare this with the extremely strong evidence for number needed to treat being 39 for 5 years with statin therapy in patients with preexisting heart disease to prevent one occurrence of a nonfatal myocardial infarction.

Management tip: Although statins are associated with a small incident increase in the risk of developing diabetes, the potential benefits of using statin therapy for both primary and secondary prevention of cardiovascular disease significantly outweigh any of the potential risks associated with hyperglycemia. This is an important discussion to have with patients who are reluctant to use statin therapy because of the potential risk for new-onset diabetes as a side effect.

5. Beta-Blockers

Beta-blockers are another commonly used group of medications for managing hypertension, heart failure, coronary artery disease, and arrhythmia. Nonvasodilating beta-blockers such as metoprolol and atenolol are more likely to be associated with increases in A1c, mean plasma glucose, body weight, and triglycerides compared with vasodilating beta-blockers such as carvedilol, nebivolol, and labetalol (Bakris GL et al; Giugliano D et al). Similarly, studies have also shown that atenolol and metoprolol are associated with increased odds of hypoglycemia compared with carvedilol. People on beta-blockers may have masking of some of the symptoms of hypoglycemia, such as tremor, irritability, and palpitations, while other symptoms such as diaphoresis may remain unaffected on beta-blockers.

Management tip: Education on recognizing and managing hypoglycemia would be important when starting patients on beta-blockers if they are on preexisting insulin/sulfonylurea therapy. Use of CGM devices may be helpful if there is a high risk for hypoglycemia, especially as symptoms of hypoglycemia are often masked.

Honorable Mention

Several other medications — including antiretroviral therapy, tyrosine kinase inhibitors, mechanistic target of rapamycin (mTOR) inhibitors, immunosuppressants, and interferon alpha — are associated with worsening glycemic control and new-onset diabetes. Consider these agents’ effects on blood glucose, especially in people with an elevated risk of developing diabetes or those with preexisting diabetes, when prescribing.

A special mention should also be made of androgen deprivation therapy. These include treatment options like goserelin and leuprolide, which are gonadotropin-releasing hormone (GnRH) agonist therapies and are commonly used for prostate cancer management. Depending on the patient, these agents may be used for prolonged duration. Androgen deprivation therapy, by definition, decreases testosterone levels in men, thereby leading to worsening insulin resistance. Increase in fat mass and concomitant muscle wasting have been associated with the use of these medications; these, in turn, lead to peripheral insulin resistance. Nearly 1 out of every 5 men treated with long-term androgen deprivation therapy may be prone to developing worsening of A1c by 1% or more.

Management tip: Men on androgen deprivation therapy should be encouraged to participate in regular physical activity to reduce the burden of insulin resistance and to promote cardiovascular health.

Drug-induced diabetes is potentially reversible in many cases. Similarly, worsening of glycemic control due to medications in people with preexisting diabetes may also attenuate once the effect of the drug wears off. Blood glucose should be monitored on an ongoing basis so that diabetes medications can be adjusted. For some individuals, however, the worsening of glycemic status may be more chronic and may require long-term use of antihyperglycemic agents, especially if the benefits of continuation of the medication leading to hyperglycemia far exceed any potential risks.
 

Dr. Jain is Clinical Instructor, Department of Endocrinology, University of British Columbia; Endocrinologist, Fraser River Endocrinology, Vancouver, British Columbia, Canada. He disclosed ties with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk.

A version of this article appeared on Medscape.com.

It’s that time of the year, when social media is rife with many top 5 and top 10 lists. Perhaps the beginning of a new year is a good time to review how different medications can have side effects beyond the disease state they’re used to address. Among the most common complications of many medications is the potential to disrupt glycemic control. Let’s revisit some of the most commonly used medications known to increase glucose levels and look at some practical tips on overcoming these.

1. Glucocorticoids

Without a doubt, corticosteroids are at the top of the list when it comes to the potential for increasing blood glucose levels. High-dose glucocorticoid therapy is known to lead to new-onset diabetes (steroid-induced diabetes). Similarly, people with preexisting diabetes may notice significant worsening of glycemic control when they start on glucocorticoid therapy. The extent of glucose elevation depends on their glycemic status prior to initiation on steroids, the dose and duration of glucocorticoid therapy, and comorbid conditions, among other factors.

Management tip: For those with previously well-controlled diabetes or borderline diabetes, glucocorticoid-induced hyperglycemia may be managed by metformin with or without sulfonylurea therapy, especially if corticosteroid treatment is low-dose and for a shorter duration. However, for many individuals with preexisting poorly controlled diabetes or those initiated on high-dose corticosteroids, insulin therapy would perhaps be the treatment of choice. Glucocorticoid therapy generally leads to more pronounced postprandial hyperglycemia compared with fasting hyperglycemia; hence, the use of short-acting insulin therapy or perhaps NPH insulin in the morning might be a better option for many individuals. Dietary modification plays an important role in limiting the extent of postprandial hyperglycemia. Use of continuous glucose monitoring (CGM) devices may also be very helpful for understanding glycemic excursions and how to adjust insulin. In individuals for whom glucocorticoid therapy is tapered down, it is important to adjust the dose of medications with potential to cause hypoglycemia, such as insulin/sulfonylurea therapy, as the degree of hyperglycemia may decrease with decreased dose of the glucocorticoid therapy.

2. Antipsychotic Therapy

Antipsychotic medications can be obesogenic; between 15% and 72% of people who take second-generation antipsychotics experience weight gain of 7% or more. Increases in weight are not the only factor contributing to an elevated risk of developing type 2 diabetes. Antipsychotics are thought to cause downregulation of intracellular insulin signaling, leading to insulin resistance. At the same time, there seems to be a direct effect on the pancreatic beta cells. Antagonism of the dopamine D2, serotonin 5-HT2C, and muscarinic M3 receptors impairs beta-cell response to changes in blood glucose. In addition to the pharmacologic effects, cell culture experiments have shown that antipsychotics increase apoptosis of beta cells. Increased weight and concomitant development of type 2 diabetes is seen particularly in agents that exhibit high muscarinic M3 and histamine H1 receptor blockade. The effect on glucose metabolism is seen the most with agents such as clozapine, olanzapine, and haloperidol and the least with agents such as ziprasidone.

Management tip: Given the ongoing change in the understanding of increases in weight and their association with the risk of developing type 2 diabetes, a metabolically safer approach involves starting with medications that have a lower propensity for weight gain, and the partial agonists/third-generation antipsychotics as a family presently have the best overall data.

3. Thiazide Diuretics

Thiazide diuretics are commonly used for the management of hypertension and are associated with metabolic complications including hypokalemia; higher cholesterol, triglycerides, and other circulating lipids; and elevated glucose. It’s thought that the reduced potassium level occurring as a result of these medications might contribute to new-onset diabetes. The hypokalemia occurring from these medications is thought to lead to a decrease in insulin secretion and sensitivity, which is dose dependent. Studies show that the number needed to harm for chlorthalidone-induced diabetes is 29 over 1 year. There is believed to be no additional risk beyond 1 year.

Management tip: It’s important to monitor potassium levels for those initiated on thiazide diuretics. If hypokalemia occurs, it would be pertinent to correct the hypokalemia with potassium supplements to mitigate the risk for new-onset diabetes.

4. Statin Therapy

Statin therapy is thought to be associated with decreased insulin sensitivity and impairment in insulin secretion. The overall incidence of diabetes is pegged to be between 9% and 12% on statin therapy on the basis of meta-analysis studies, and higher on the basis of population-based studies. Overall, the estimated number needed to harm is: 1 out of every 255 patients on statin therapy for 4 years may develop new-onset diabetes. Compare this with the extremely strong evidence for number needed to treat being 39 for 5 years with statin therapy in patients with preexisting heart disease to prevent one occurrence of a nonfatal myocardial infarction.

Management tip: Although statins are associated with a small incident increase in the risk of developing diabetes, the potential benefits of using statin therapy for both primary and secondary prevention of cardiovascular disease significantly outweigh any of the potential risks associated with hyperglycemia. This is an important discussion to have with patients who are reluctant to use statin therapy because of the potential risk for new-onset diabetes as a side effect.

5. Beta-Blockers

Beta-blockers are another commonly used group of medications for managing hypertension, heart failure, coronary artery disease, and arrhythmia. Nonvasodilating beta-blockers such as metoprolol and atenolol are more likely to be associated with increases in A1c, mean plasma glucose, body weight, and triglycerides compared with vasodilating beta-blockers such as carvedilol, nebivolol, and labetalol (Bakris GL et al; Giugliano D et al). Similarly, studies have also shown that atenolol and metoprolol are associated with increased odds of hypoglycemia compared with carvedilol. People on beta-blockers may have masking of some of the symptoms of hypoglycemia, such as tremor, irritability, and palpitations, while other symptoms such as diaphoresis may remain unaffected on beta-blockers.

Management tip: Education on recognizing and managing hypoglycemia would be important when starting patients on beta-blockers if they are on preexisting insulin/sulfonylurea therapy. Use of CGM devices may be helpful if there is a high risk for hypoglycemia, especially as symptoms of hypoglycemia are often masked.

Honorable Mention

Several other medications — including antiretroviral therapy, tyrosine kinase inhibitors, mechanistic target of rapamycin (mTOR) inhibitors, immunosuppressants, and interferon alpha — are associated with worsening glycemic control and new-onset diabetes. Consider these agents’ effects on blood glucose, especially in people with an elevated risk of developing diabetes or those with preexisting diabetes, when prescribing.

A special mention should also be made of androgen deprivation therapy. These include treatment options like goserelin and leuprolide, which are gonadotropin-releasing hormone (GnRH) agonist therapies and are commonly used for prostate cancer management. Depending on the patient, these agents may be used for prolonged duration. Androgen deprivation therapy, by definition, decreases testosterone levels in men, thereby leading to worsening insulin resistance. Increase in fat mass and concomitant muscle wasting have been associated with the use of these medications; these, in turn, lead to peripheral insulin resistance. Nearly 1 out of every 5 men treated with long-term androgen deprivation therapy may be prone to developing worsening of A1c by 1% or more.

Management tip: Men on androgen deprivation therapy should be encouraged to participate in regular physical activity to reduce the burden of insulin resistance and to promote cardiovascular health.

Drug-induced diabetes is potentially reversible in many cases. Similarly, worsening of glycemic control due to medications in people with preexisting diabetes may also attenuate once the effect of the drug wears off. Blood glucose should be monitored on an ongoing basis so that diabetes medications can be adjusted. For some individuals, however, the worsening of glycemic status may be more chronic and may require long-term use of antihyperglycemic agents, especially if the benefits of continuation of the medication leading to hyperglycemia far exceed any potential risks.
 

Dr. Jain is Clinical Instructor, Department of Endocrinology, University of British Columbia; Endocrinologist, Fraser River Endocrinology, Vancouver, British Columbia, Canada. He disclosed ties with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk.

A version of this article appeared on Medscape.com.

It’s that time of the year, when social media is rife with many top 5 and top 10 lists. Perhaps the beginning of a new year is a good time to review how different medications can have side effects beyond the disease state they’re used to address. Among the most common complications of many medications is the potential to disrupt glycemic control. Let’s revisit some of the most commonly used medications known to increase glucose levels and look at some practical tips on overcoming these.

1. Glucocorticoids

Without a doubt, corticosteroids are at the top of the list when it comes to the potential for increasing blood glucose levels. High-dose glucocorticoid therapy is known to lead to new-onset diabetes (steroid-induced diabetes). Similarly, people with preexisting diabetes may notice significant worsening of glycemic control when they start on glucocorticoid therapy. The extent of glucose elevation depends on their glycemic status prior to initiation on steroids, the dose and duration of glucocorticoid therapy, and comorbid conditions, among other factors.

Management tip: For those with previously well-controlled diabetes or borderline diabetes, glucocorticoid-induced hyperglycemia may be managed by metformin with or without sulfonylurea therapy, especially if corticosteroid treatment is low-dose and for a shorter duration. However, for many individuals with preexisting poorly controlled diabetes or those initiated on high-dose corticosteroids, insulin therapy would perhaps be the treatment of choice. Glucocorticoid therapy generally leads to more pronounced postprandial hyperglycemia compared with fasting hyperglycemia; hence, the use of short-acting insulin therapy or perhaps NPH insulin in the morning might be a better option for many individuals. Dietary modification plays an important role in limiting the extent of postprandial hyperglycemia. Use of continuous glucose monitoring (CGM) devices may also be very helpful for understanding glycemic excursions and how to adjust insulin. In individuals for whom glucocorticoid therapy is tapered down, it is important to adjust the dose of medications with potential to cause hypoglycemia, such as insulin/sulfonylurea therapy, as the degree of hyperglycemia may decrease with decreased dose of the glucocorticoid therapy.

2. Antipsychotic Therapy

Antipsychotic medications can be obesogenic; between 15% and 72% of people who take second-generation antipsychotics experience weight gain of 7% or more. Increases in weight are not the only factor contributing to an elevated risk of developing type 2 diabetes. Antipsychotics are thought to cause downregulation of intracellular insulin signaling, leading to insulin resistance. At the same time, there seems to be a direct effect on the pancreatic beta cells. Antagonism of the dopamine D2, serotonin 5-HT2C, and muscarinic M3 receptors impairs beta-cell response to changes in blood glucose. In addition to the pharmacologic effects, cell culture experiments have shown that antipsychotics increase apoptosis of beta cells. Increased weight and concomitant development of type 2 diabetes is seen particularly in agents that exhibit high muscarinic M3 and histamine H1 receptor blockade. The effect on glucose metabolism is seen the most with agents such as clozapine, olanzapine, and haloperidol and the least with agents such as ziprasidone.

Management tip: Given the ongoing change in the understanding of increases in weight and their association with the risk of developing type 2 diabetes, a metabolically safer approach involves starting with medications that have a lower propensity for weight gain, and the partial agonists/third-generation antipsychotics as a family presently have the best overall data.

3. Thiazide Diuretics

Thiazide diuretics are commonly used for the management of hypertension and are associated with metabolic complications including hypokalemia; higher cholesterol, triglycerides, and other circulating lipids; and elevated glucose. It’s thought that the reduced potassium level occurring as a result of these medications might contribute to new-onset diabetes. The hypokalemia occurring from these medications is thought to lead to a decrease in insulin secretion and sensitivity, which is dose dependent. Studies show that the number needed to harm for chlorthalidone-induced diabetes is 29 over 1 year. There is believed to be no additional risk beyond 1 year.

Management tip: It’s important to monitor potassium levels for those initiated on thiazide diuretics. If hypokalemia occurs, it would be pertinent to correct the hypokalemia with potassium supplements to mitigate the risk for new-onset diabetes.

4. Statin Therapy

Statin therapy is thought to be associated with decreased insulin sensitivity and impairment in insulin secretion. The overall incidence of diabetes is pegged to be between 9% and 12% on statin therapy on the basis of meta-analysis studies, and higher on the basis of population-based studies. Overall, the estimated number needed to harm is: 1 out of every 255 patients on statin therapy for 4 years may develop new-onset diabetes. Compare this with the extremely strong evidence for number needed to treat being 39 for 5 years with statin therapy in patients with preexisting heart disease to prevent one occurrence of a nonfatal myocardial infarction.

Management tip: Although statins are associated with a small incident increase in the risk of developing diabetes, the potential benefits of using statin therapy for both primary and secondary prevention of cardiovascular disease significantly outweigh any of the potential risks associated with hyperglycemia. This is an important discussion to have with patients who are reluctant to use statin therapy because of the potential risk for new-onset diabetes as a side effect.

5. Beta-Blockers

Beta-blockers are another commonly used group of medications for managing hypertension, heart failure, coronary artery disease, and arrhythmia. Nonvasodilating beta-blockers such as metoprolol and atenolol are more likely to be associated with increases in A1c, mean plasma glucose, body weight, and triglycerides compared with vasodilating beta-blockers such as carvedilol, nebivolol, and labetalol (Bakris GL et al; Giugliano D et al). Similarly, studies have also shown that atenolol and metoprolol are associated with increased odds of hypoglycemia compared with carvedilol. People on beta-blockers may have masking of some of the symptoms of hypoglycemia, such as tremor, irritability, and palpitations, while other symptoms such as diaphoresis may remain unaffected on beta-blockers.

Management tip: Education on recognizing and managing hypoglycemia would be important when starting patients on beta-blockers if they are on preexisting insulin/sulfonylurea therapy. Use of CGM devices may be helpful if there is a high risk for hypoglycemia, especially as symptoms of hypoglycemia are often masked.

Honorable Mention

Several other medications — including antiretroviral therapy, tyrosine kinase inhibitors, mechanistic target of rapamycin (mTOR) inhibitors, immunosuppressants, and interferon alpha — are associated with worsening glycemic control and new-onset diabetes. Consider these agents’ effects on blood glucose, especially in people with an elevated risk of developing diabetes or those with preexisting diabetes, when prescribing.

A special mention should also be made of androgen deprivation therapy. These include treatment options like goserelin and leuprolide, which are gonadotropin-releasing hormone (GnRH) agonist therapies and are commonly used for prostate cancer management. Depending on the patient, these agents may be used for prolonged duration. Androgen deprivation therapy, by definition, decreases testosterone levels in men, thereby leading to worsening insulin resistance. Increase in fat mass and concomitant muscle wasting have been associated with the use of these medications; these, in turn, lead to peripheral insulin resistance. Nearly 1 out of every 5 men treated with long-term androgen deprivation therapy may be prone to developing worsening of A1c by 1% or more.

Management tip: Men on androgen deprivation therapy should be encouraged to participate in regular physical activity to reduce the burden of insulin resistance and to promote cardiovascular health.

Drug-induced diabetes is potentially reversible in many cases. Similarly, worsening of glycemic control due to medications in people with preexisting diabetes may also attenuate once the effect of the drug wears off. Blood glucose should be monitored on an ongoing basis so that diabetes medications can be adjusted. For some individuals, however, the worsening of glycemic status may be more chronic and may require long-term use of antihyperglycemic agents, especially if the benefits of continuation of the medication leading to hyperglycemia far exceed any potential risks.
 

Dr. Jain is Clinical Instructor, Department of Endocrinology, University of British Columbia; Endocrinologist, Fraser River Endocrinology, Vancouver, British Columbia, Canada. He disclosed ties with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk.

A version of this article appeared on Medscape.com.

Psoriasis is a chronic inflammatory skin disease for which several lifestyle factors—smoking, alcohol use, and psychological stress—are associated with higher incidence and more severe disease.^1-3 Diet also has been implicated as a factor that can affect psoriasis,⁴ and many patients have shown interest in possible dietary interventions to help their disease.⁵

In 2018, the National Psoriasis Foundation (NPF) presented dietary recommendations for patients based on results from a systematic review. From the available literature, only dietary weight reduction with hypocaloric diets in overweight or obese patients could be strongly recommended, and it has been proven that obesity is associated with worse psoriasis severity.⁶ Other more recent studies have shown that dietary modifications such as intermittent fasting and the ketogenic diet also led to weight loss and improved psoriasis severity in overweight patients; however, it is difficult to discern if the improvement was due to weight loss alone or if the dietary patterns themselves played a role.^7,8 The paucity of well-designed studies evaluating the effects of other dietary changes has prevented further guidelines from being written. We propose that dietary patterns such as the Mediterranean diet (MeD) and vegan/vegetarian diets—even without strong data showing benefits in skin disease—may help to decrease systemic inflammation, improve gut dysbiosis, and help decrease the risk for cardiometabolic comorbidities that are associated with psoriasis.

Mediterranean Diet

The MeD is based on the dietary tendencies of inhabitants from the regions surrounding the Mediterranean Sea and is centered around nutrient-rich foods such as vegetables, olive oil, and legumes while limiting meat and dairy.⁹ The NPF recommended considering a trial of the MeD based on low-quality evidence.⁶ Observational studies have indicated that psoriasis patients are less likely to adhere to the MeD, but those who do have less severe disease.⁸ However, a search of PubMed articles indexed for MEDLINE using the terms Mediterranean diet and psoriasis yielded no prospective interventional studies. Given the association of the MeD with less severe disease, it is important to understand which specific foods in the MeD could be beneficial. Intake of omega-3 fatty acids, such as those found in fatty fish, are important for modulation of systemic inflammation.⁷ High intake of polyphenols—found in fruits and vegetables, extra-virgin olive oil, and wine—also have been implicated in improving inflammatory diseases due to potent antioxidant and anti-inflammatory properties. Individually, fruits, vegetables, whole grains, and sea fish have been associated with lowering C-reactive protein levels, which also is indicative of the benefits of these foods on systemic inflammation.⁷

Vegan/Vegetarian Diets

Although fruits, vegetables, legumes, and whole grains are a substantial component of the MeD, there are limited data on vegetarian or purely vegan plant-based diets. An observational study from the NPF found that only 48.4% (15/31) of patients on the MeD vs 69.0% (20/29) on a vegan diet reported a favorable skin response.⁵ Two case reports also have shown beneficial results of a strict vegan diet for psoriasis and psoriatic arthritis, where whole-food plant-based diets also improved joint symptoms.^10-12 As with any diet, those who pursue a plant-based diet should strive to consume a variety of foods to avoid nutrient deficiencies. A recent systematic meta-analysis of 141 studies evaluated nutrient status of vegan and vegetarian diets compared to pescovegetarians and those who consume meat. All dietary patterns showed varying degrees of low levels of different nutrients.¹³ Of note, the researchers found that vitamin B₁₂, vitamin D, iron, zinc, iodine, calcium, and docosahexaenoic acid were lower in plant-based diets. In contrast, folate; vitamins B₁, B₆, C, and E; polyunsaturated fatty acids; α-linolenic acid; and magnesium intake were higher. Those who consumed meat were at risk for inadequate intake of fiber, polyunsaturated fatty acids, α-linolenic acid, folate, vitamin E, calcium, magnesium, and vitamin D, though vitamin D intake was higher than in vegans/vegetarians.¹³ The results of this meta-analysis indicated the importance of educating patients on what constitutes a well-rounded, micronutrient-rich diet or appropriate supplementation for any diet.

Effects on Gut Microbiome

Any changes in diet can lead to alterations in the gut microbiome, which may impact skin disease, as evidence indicates a bidirectional relationship between gut and skin health.¹⁰ A metagenomic analysis of the gut microbiota in patients with untreated plaque psoriasis revealed a signature dysbiosis for which the researchers developed a psoriasis microbiota index, suggesting the gut microbiota may play a role in psoriasis pathophysiology.¹⁴ Research shows that both the MeD and vegan/vegetarian diets, which are relatively rich in fiber and omega-3 fatty acids and low in saturated fat and animal protein compared to many diets, cause increases in dietary fiber–metabolizing bacteria that produce short-chain fatty acids. These short-chain fatty acids improve gut epithelial integrity and alleviate both gut and systemic inflammation.¹⁰

The changes to the gut microbiome induced by a high-fat diet also are concerning. In contrast to the MeD or vegan/vegetarian diets, consumption of a high-fat diet induces alterations in the composition of the gut microbiota that in turn increase the release of proinflammatory cytokines and promote higher intestinal permeability.¹⁰ Similarly, high sugar consumption promotes increased intestinal permeability and shifts the gut microbiota to organisms that can rapidly utilize simple carbohydrates at the expense of other beneficial organisms, reducing bacterial diversity.¹⁵ The Western diet, which is notable for both high fat and high sugar content, is sometimes referred to as a proinflammatory diet and has been shown to worsen psoriasiformlike lesions in mice.¹⁶ Importantly, most research indicates that high fat and high sugar consumption appear to be more prevalent in psoriasis patients,⁸ but the type of fat consumed in the diet matters. The Western diet includes abundant saturated fat found in meat, dairy products, palm and coconut oils, and processed foods, as well as omega-6 fatty acids that are found in meat, poultry, and eggs. Saturated fat has been shown to promote helper T cell (T_H17) accumulation in the skin, and omega-6 fatty acids serve as precursors to various inflammatory lipid mediators.⁴ This distinction of sources of fat between the Western diet and MeD is important in understanding the diets’ different effects on psoriasis and overall health. As previously discussed, the high intake of omega-3 acids in the MeD is one of the ways it may exert its anti-inflammatory benefits.⁷

Next Steps in Advising Psoriasis Patients

A major limitation of the data for MeD and vegan/vegetarian diets is limited randomized controlled trials evaluating the impact of these diets on psoriasis. Thus, dietary recommendations for psoriasis are not as strong as for other diseases for which more conclusive data exist.⁸ Although the data on diet and psoriasis are not definitive, perhaps dermatologists should shift the question from “Does this diet definitely improve psoriasis?” to “Does this diet definitely improve my patient’s health as a whole and maybe also their psoriasis?” For instance, the MeD has been shown to reduce the risk for type 2 diabetes mellitus and cardiovascular disease as well as to slow cognitive decline.¹⁷ Vegan/vegetarian diets focusing on whole vs processed foods have been shown to be highly effective in combatting obesity, type 2 diabetes mellitus, coronary artery disease including severe atherosclerosis, and hypertension.¹⁸ Psoriasis patients are at increased risk for many of the ailments that the MeD and plant-based diets protect against, making these diets potentially even more impactful than for someone without psoriasis.¹⁹ Dietary recommendations should still be made in conjunction with continuing traditional therapies for psoriasis and in consultation with the patient’s primary care physician and/or dietitian; however, rather than waiting for more randomized controlled trials before making health-promoting recommendations, what would be the downside of starting now? At worst, the dietary change decreases their risk for several metabolic conditions, and at best they may even see an improvement in their psoriasis.

Psoriasis is a chronic inflammatory skin disease for which several lifestyle factors—smoking, alcohol use, and psychological stress—are associated with higher incidence and more severe disease.^1-3 Diet also has been implicated as a factor that can affect psoriasis,⁴ and many patients have shown interest in possible dietary interventions to help their disease.⁵

In 2018, the National Psoriasis Foundation (NPF) presented dietary recommendations for patients based on results from a systematic review. From the available literature, only dietary weight reduction with hypocaloric diets in overweight or obese patients could be strongly recommended, and it has been proven that obesity is associated with worse psoriasis severity.⁶ Other more recent studies have shown that dietary modifications such as intermittent fasting and the ketogenic diet also led to weight loss and improved psoriasis severity in overweight patients; however, it is difficult to discern if the improvement was due to weight loss alone or if the dietary patterns themselves played a role.^7,8 The paucity of well-designed studies evaluating the effects of other dietary changes has prevented further guidelines from being written. We propose that dietary patterns such as the Mediterranean diet (MeD) and vegan/vegetarian diets—even without strong data showing benefits in skin disease—may help to decrease systemic inflammation, improve gut dysbiosis, and help decrease the risk for cardiometabolic comorbidities that are associated with psoriasis.

Mediterranean Diet

The MeD is based on the dietary tendencies of inhabitants from the regions surrounding the Mediterranean Sea and is centered around nutrient-rich foods such as vegetables, olive oil, and legumes while limiting meat and dairy.⁹ The NPF recommended considering a trial of the MeD based on low-quality evidence.⁶ Observational studies have indicated that psoriasis patients are less likely to adhere to the MeD, but those who do have less severe disease.⁸ However, a search of PubMed articles indexed for MEDLINE using the terms Mediterranean diet and psoriasis yielded no prospective interventional studies. Given the association of the MeD with less severe disease, it is important to understand which specific foods in the MeD could be beneficial. Intake of omega-3 fatty acids, such as those found in fatty fish, are important for modulation of systemic inflammation.⁷ High intake of polyphenols—found in fruits and vegetables, extra-virgin olive oil, and wine—also have been implicated in improving inflammatory diseases due to potent antioxidant and anti-inflammatory properties. Individually, fruits, vegetables, whole grains, and sea fish have been associated with lowering C-reactive protein levels, which also is indicative of the benefits of these foods on systemic inflammation.⁷

Vegan/Vegetarian Diets

Although fruits, vegetables, legumes, and whole grains are a substantial component of the MeD, there are limited data on vegetarian or purely vegan plant-based diets. An observational study from the NPF found that only 48.4% (15/31) of patients on the MeD vs 69.0% (20/29) on a vegan diet reported a favorable skin response.⁵ Two case reports also have shown beneficial results of a strict vegan diet for psoriasis and psoriatic arthritis, where whole-food plant-based diets also improved joint symptoms.^10-12 As with any diet, those who pursue a plant-based diet should strive to consume a variety of foods to avoid nutrient deficiencies. A recent systematic meta-analysis of 141 studies evaluated nutrient status of vegan and vegetarian diets compared to pescovegetarians and those who consume meat. All dietary patterns showed varying degrees of low levels of different nutrients.¹³ Of note, the researchers found that vitamin B₁₂, vitamin D, iron, zinc, iodine, calcium, and docosahexaenoic acid were lower in plant-based diets. In contrast, folate; vitamins B₁, B₆, C, and E; polyunsaturated fatty acids; α-linolenic acid; and magnesium intake were higher. Those who consumed meat were at risk for inadequate intake of fiber, polyunsaturated fatty acids, α-linolenic acid, folate, vitamin E, calcium, magnesium, and vitamin D, though vitamin D intake was higher than in vegans/vegetarians.¹³ The results of this meta-analysis indicated the importance of educating patients on what constitutes a well-rounded, micronutrient-rich diet or appropriate supplementation for any diet.

Effects on Gut Microbiome

Any changes in diet can lead to alterations in the gut microbiome, which may impact skin disease, as evidence indicates a bidirectional relationship between gut and skin health.¹⁰ A metagenomic analysis of the gut microbiota in patients with untreated plaque psoriasis revealed a signature dysbiosis for which the researchers developed a psoriasis microbiota index, suggesting the gut microbiota may play a role in psoriasis pathophysiology.¹⁴ Research shows that both the MeD and vegan/vegetarian diets, which are relatively rich in fiber and omega-3 fatty acids and low in saturated fat and animal protein compared to many diets, cause increases in dietary fiber–metabolizing bacteria that produce short-chain fatty acids. These short-chain fatty acids improve gut epithelial integrity and alleviate both gut and systemic inflammation.¹⁰

The changes to the gut microbiome induced by a high-fat diet also are concerning. In contrast to the MeD or vegan/vegetarian diets, consumption of a high-fat diet induces alterations in the composition of the gut microbiota that in turn increase the release of proinflammatory cytokines and promote higher intestinal permeability.¹⁰ Similarly, high sugar consumption promotes increased intestinal permeability and shifts the gut microbiota to organisms that can rapidly utilize simple carbohydrates at the expense of other beneficial organisms, reducing bacterial diversity.¹⁵ The Western diet, which is notable for both high fat and high sugar content, is sometimes referred to as a proinflammatory diet and has been shown to worsen psoriasiformlike lesions in mice.¹⁶ Importantly, most research indicates that high fat and high sugar consumption appear to be more prevalent in psoriasis patients,⁸ but the type of fat consumed in the diet matters. The Western diet includes abundant saturated fat found in meat, dairy products, palm and coconut oils, and processed foods, as well as omega-6 fatty acids that are found in meat, poultry, and eggs. Saturated fat has been shown to promote helper T cell (T_H17) accumulation in the skin, and omega-6 fatty acids serve as precursors to various inflammatory lipid mediators.⁴ This distinction of sources of fat between the Western diet and MeD is important in understanding the diets’ different effects on psoriasis and overall health. As previously discussed, the high intake of omega-3 acids in the MeD is one of the ways it may exert its anti-inflammatory benefits.⁷

Next Steps in Advising Psoriasis Patients

A major limitation of the data for MeD and vegan/vegetarian diets is limited randomized controlled trials evaluating the impact of these diets on psoriasis. Thus, dietary recommendations for psoriasis are not as strong as for other diseases for which more conclusive data exist.⁸ Although the data on diet and psoriasis are not definitive, perhaps dermatologists should shift the question from “Does this diet definitely improve psoriasis?” to “Does this diet definitely improve my patient’s health as a whole and maybe also their psoriasis?” For instance, the MeD has been shown to reduce the risk for type 2 diabetes mellitus and cardiovascular disease as well as to slow cognitive decline.¹⁷ Vegan/vegetarian diets focusing on whole vs processed foods have been shown to be highly effective in combatting obesity, type 2 diabetes mellitus, coronary artery disease including severe atherosclerosis, and hypertension.¹⁸ Psoriasis patients are at increased risk for many of the ailments that the MeD and plant-based diets protect against, making these diets potentially even more impactful than for someone without psoriasis.¹⁹ Dietary recommendations should still be made in conjunction with continuing traditional therapies for psoriasis and in consultation with the patient’s primary care physician and/or dietitian; however, rather than waiting for more randomized controlled trials before making health-promoting recommendations, what would be the downside of starting now? At worst, the dietary change decreases their risk for several metabolic conditions, and at best they may even see an improvement in their psoriasis.

Psoriasis is a chronic inflammatory skin disease for which several lifestyle factors—smoking, alcohol use, and psychological stress—are associated with higher incidence and more severe disease.^1-3 Diet also has been implicated as a factor that can affect psoriasis,⁴ and many patients have shown interest in possible dietary interventions to help their disease.⁵

In 2018, the National Psoriasis Foundation (NPF) presented dietary recommendations for patients based on results from a systematic review. From the available literature, only dietary weight reduction with hypocaloric diets in overweight or obese patients could be strongly recommended, and it has been proven that obesity is associated with worse psoriasis severity.⁶ Other more recent studies have shown that dietary modifications such as intermittent fasting and the ketogenic diet also led to weight loss and improved psoriasis severity in overweight patients; however, it is difficult to discern if the improvement was due to weight loss alone or if the dietary patterns themselves played a role.^7,8 The paucity of well-designed studies evaluating the effects of other dietary changes has prevented further guidelines from being written. We propose that dietary patterns such as the Mediterranean diet (MeD) and vegan/vegetarian diets—even without strong data showing benefits in skin disease—may help to decrease systemic inflammation, improve gut dysbiosis, and help decrease the risk for cardiometabolic comorbidities that are associated with psoriasis.

Mediterranean Diet

The MeD is based on the dietary tendencies of inhabitants from the regions surrounding the Mediterranean Sea and is centered around nutrient-rich foods such as vegetables, olive oil, and legumes while limiting meat and dairy.⁹ The NPF recommended considering a trial of the MeD based on low-quality evidence.⁶ Observational studies have indicated that psoriasis patients are less likely to adhere to the MeD, but those who do have less severe disease.⁸ However, a search of PubMed articles indexed for MEDLINE using the terms Mediterranean diet and psoriasis yielded no prospective interventional studies. Given the association of the MeD with less severe disease, it is important to understand which specific foods in the MeD could be beneficial. Intake of omega-3 fatty acids, such as those found in fatty fish, are important for modulation of systemic inflammation.⁷ High intake of polyphenols—found in fruits and vegetables, extra-virgin olive oil, and wine—also have been implicated in improving inflammatory diseases due to potent antioxidant and anti-inflammatory properties. Individually, fruits, vegetables, whole grains, and sea fish have been associated with lowering C-reactive protein levels, which also is indicative of the benefits of these foods on systemic inflammation.⁷

Vegan/Vegetarian Diets

Although fruits, vegetables, legumes, and whole grains are a substantial component of the MeD, there are limited data on vegetarian or purely vegan plant-based diets. An observational study from the NPF found that only 48.4% (15/31) of patients on the MeD vs 69.0% (20/29) on a vegan diet reported a favorable skin response.⁵ Two case reports also have shown beneficial results of a strict vegan diet for psoriasis and psoriatic arthritis, where whole-food plant-based diets also improved joint symptoms.^10-12 As with any diet, those who pursue a plant-based diet should strive to consume a variety of foods to avoid nutrient deficiencies. A recent systematic meta-analysis of 141 studies evaluated nutrient status of vegan and vegetarian diets compared to pescovegetarians and those who consume meat. All dietary patterns showed varying degrees of low levels of different nutrients.¹³ Of note, the researchers found that vitamin B₁₂, vitamin D, iron, zinc, iodine, calcium, and docosahexaenoic acid were lower in plant-based diets. In contrast, folate; vitamins B₁, B₆, C, and E; polyunsaturated fatty acids; α-linolenic acid; and magnesium intake were higher. Those who consumed meat were at risk for inadequate intake of fiber, polyunsaturated fatty acids, α-linolenic acid, folate, vitamin E, calcium, magnesium, and vitamin D, though vitamin D intake was higher than in vegans/vegetarians.¹³ The results of this meta-analysis indicated the importance of educating patients on what constitutes a well-rounded, micronutrient-rich diet or appropriate supplementation for any diet.

Effects on Gut Microbiome

Any changes in diet can lead to alterations in the gut microbiome, which may impact skin disease, as evidence indicates a bidirectional relationship between gut and skin health.¹⁰ A metagenomic analysis of the gut microbiota in patients with untreated plaque psoriasis revealed a signature dysbiosis for which the researchers developed a psoriasis microbiota index, suggesting the gut microbiota may play a role in psoriasis pathophysiology.¹⁴ Research shows that both the MeD and vegan/vegetarian diets, which are relatively rich in fiber and omega-3 fatty acids and low in saturated fat and animal protein compared to many diets, cause increases in dietary fiber–metabolizing bacteria that produce short-chain fatty acids. These short-chain fatty acids improve gut epithelial integrity and alleviate both gut and systemic inflammation.¹⁰

The changes to the gut microbiome induced by a high-fat diet also are concerning. In contrast to the MeD or vegan/vegetarian diets, consumption of a high-fat diet induces alterations in the composition of the gut microbiota that in turn increase the release of proinflammatory cytokines and promote higher intestinal permeability.¹⁰ Similarly, high sugar consumption promotes increased intestinal permeability and shifts the gut microbiota to organisms that can rapidly utilize simple carbohydrates at the expense of other beneficial organisms, reducing bacterial diversity.¹⁵ The Western diet, which is notable for both high fat and high sugar content, is sometimes referred to as a proinflammatory diet and has been shown to worsen psoriasiformlike lesions in mice.¹⁶ Importantly, most research indicates that high fat and high sugar consumption appear to be more prevalent in psoriasis patients,⁸ but the type of fat consumed in the diet matters. The Western diet includes abundant saturated fat found in meat, dairy products, palm and coconut oils, and processed foods, as well as omega-6 fatty acids that are found in meat, poultry, and eggs. Saturated fat has been shown to promote helper T cell (T_H17) accumulation in the skin, and omega-6 fatty acids serve as precursors to various inflammatory lipid mediators.⁴ This distinction of sources of fat between the Western diet and MeD is important in understanding the diets’ different effects on psoriasis and overall health. As previously discussed, the high intake of omega-3 acids in the MeD is one of the ways it may exert its anti-inflammatory benefits.⁷

Next Steps in Advising Psoriasis Patients

A major limitation of the data for MeD and vegan/vegetarian diets is limited randomized controlled trials evaluating the impact of these diets on psoriasis. Thus, dietary recommendations for psoriasis are not as strong as for other diseases for which more conclusive data exist.⁸ Although the data on diet and psoriasis are not definitive, perhaps dermatologists should shift the question from “Does this diet definitely improve psoriasis?” to “Does this diet definitely improve my patient’s health as a whole and maybe also their psoriasis?” For instance, the MeD has been shown to reduce the risk for type 2 diabetes mellitus and cardiovascular disease as well as to slow cognitive decline.¹⁷ Vegan/vegetarian diets focusing on whole vs processed foods have been shown to be highly effective in combatting obesity, type 2 diabetes mellitus, coronary artery disease including severe atherosclerosis, and hypertension.¹⁸ Psoriasis patients are at increased risk for many of the ailments that the MeD and plant-based diets protect against, making these diets potentially even more impactful than for someone without psoriasis.¹⁹ Dietary recommendations should still be made in conjunction with continuing traditional therapies for psoriasis and in consultation with the patient’s primary care physician and/or dietitian; however, rather than waiting for more randomized controlled trials before making health-promoting recommendations, what would be the downside of starting now? At worst, the dietary change decreases their risk for several metabolic conditions, and at best they may even see an improvement in their psoriasis.

Psoriasis is a chronic autoimmune skin condition that affects approximately 2% to 4% of the US population and notably impacts overall quality of life.^1,2 There is no cure for this long-lasting condition. Fortunately, recent developments in research have led to more targeted therapies, paving the way for a more promising transformative landscape of psoriasis management. Herein, we explore the most up-to-date advancements and developments in the realm of psoriasis care.

Emerging Systemic Therapies

Biologics are cutting-edge treatments available for moderate to severe plaque psoriasis, as IL-17A, IL-23, and tumor necrosis factor α (TNF-α) have been recognized as key targets.³

IL-17—Bimekizumab is a unique monoclonal antibody that inhibits the activity of both IL-17A and IL-17F cytokines.³ This treatment was approved by the US Food and Drug Administration (FDA) in October 2023 for patients with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.⁴

Bimekizumab outperformed ustekinumab in the BE VIVID phase 3 trial, with 273 of 321 patients (85%) receiving bimekizumab vs 81 of 163 patients (50%) receiving ustekinumab experiencing at least 90% improvement in psoriasis area and severity index (PASI) score at week 16.⁴ In a 2020 observational study (PSO-BIO-REAL), the efficacy rate of skin clearance after 6 months of treatment with biologics was only 25% (1/4).⁵ Aside from moderate to severe plaque psoriasis, bimekizumab demonstrated notable improvement in patients with psoriatic arthritis who had inadequate response or intolerance to TNF-α inhibitors compared to a placebo group in the BE COMPLETE phase 3 trial.⁶

IL-23—Guselkumab, risankizumab, and tildrakizumab are injectable therapies approved by the FDA in 2017 for moderate to severe plaque psoriasis.³ They inhibit IL-23 signaling by targeting the p19 subunit in addition to sparing IL-12.^3,7

A novel oral therapeutic peptide, JNJ-2113—the first oral IL-23 receptor antagonist peptide that blocks IL-23 signaling—has been developed, offering a new way to treat moderate to severe plaque psoriasis. Trial results from a phase 2 study (FRONTIER1) have supported JNJ-2113’s advancement into phase 3.^7,8 Patients who received JNJ-2113 successfully achieved PASI75 in addition to surpassing PASI90 and PASI100 at greater proportions compared to placebo at week 16.⁷

The promising early results of JNJ-2113 provide patients with greater flexibility and convenience for treatment options to address the manifestations of psoriasis. Although a considerable number of patients with moderate to severe plaque psoriasis qualify for advanced therapies, a substantial proportion remain untreated. Introducing an oral route of medication administration may help overcome barriers to therapy access due to a greater preference for pills over injections.⁹

TNF-α Inhibitors—Adalimumab is a TNF-α inhibitor that is used to treat moderate to severe chronic plaque psoriasis in adults who are candidates for systemic phototherapy.^1,10 However, one of the main barriers to initiating treatment has been cost. Biosimilars contribute to market competition, thus allowing the possibility of lower drug prices.¹⁰

There are 9 FDA-approved biosimilar products for adalimumab, with 2 having interchangeable designation. The first interchangeable biosimilar to enter the US market, adalimumab-adbm, became available in July 2023. In October 2023, adalimumab-afzb was granted interchangeable designation,¹¹ which enables pharmacists to swiftly substitute brand products for lower-cost biosimilars, providing patients with equally safe and effective alternatives without the delay of involving the prescribing clinician.¹² Pricing information indicates an initial 5% discount, which may later increase to 60%, from brand name adalimumab. Hopefully, reduced drug costs due to market competition will allow more patients to overcome barriers to therapy access.

IL-12/IL-23—Ustekinumab is a monoclonal antibody that targets IL-12 and IL-23. The FDA recently approved ustekinumab-auub as the first interchangeable ustekinumab biosimilar for the treatment of various inflammatory diseases, including moderate to severe plaque psoriasis and psoriatic arthritis.^12,13 The approval of ustekinumab-auub expands therapeutic options for the treatment of diverse inflammatory diseases. As the first interchangeable biosimilar in its category, this development underscores the importance of biosimilars in providing effective and accessible treatment.^12,14

Topical Innovations

In October 2023, the FDA approved an expanded indication for roflumilast cream 0.3% to treat children as young as 6 years for plaque psoriasis, even for use in intertriginous areas,¹⁵ which is a milestone given the lack of treatment options for the pediatric population because topical steroids, the most common treatment option for plaque psoriasis, can have safety concerns related to long-term use. With the advent of this steroid-free topical agent, pediatric patients have a safe and well-tolerated option for managing plaque psoriasis.¹⁶ This promising effort will now expand to trials in children as young as 2 years to test efficacy.¹⁶

Engel et al¹⁷ proposed a new algorithmic approach to the topical management of psoriasis with roflumilast cream and tapinarof cream as first-line treatments for mild disease due to their novelty in treating intertriginous areas, whereas traditional topical steroids in these areas would be inapt.¹⁷ The latest indication for roflumilast cream suggests that this proposed recommendation could be a promising and convenient enhancement to psoriasis management, potentially outperforming traditional topical corticosteroids.^15,17

Final Thoughts

Innovative targeted therapies ranging from new biologic agents to broader applications of topical treatments hold the potential to transform conventional psoriasis management with greater efficacy and safety, which can help create a more effective and personalized approach with greater patient satisfaction, ultimately enhancing overall quality of life. The choice of treatment is dependent not only on the severity of the disease but also on accessibility considerations such as cost. Overall, these innovative therapies add substantial value to the treatment armamentarium for psoriasis.

Psoriasis is a chronic autoimmune skin condition that affects approximately 2% to 4% of the US population and notably impacts overall quality of life.^1,2 There is no cure for this long-lasting condition. Fortunately, recent developments in research have led to more targeted therapies, paving the way for a more promising transformative landscape of psoriasis management. Herein, we explore the most up-to-date advancements and developments in the realm of psoriasis care.

Emerging Systemic Therapies

Biologics are cutting-edge treatments available for moderate to severe plaque psoriasis, as IL-17A, IL-23, and tumor necrosis factor α (TNF-α) have been recognized as key targets.³

IL-17—Bimekizumab is a unique monoclonal antibody that inhibits the activity of both IL-17A and IL-17F cytokines.³ This treatment was approved by the US Food and Drug Administration (FDA) in October 2023 for patients with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.⁴

Bimekizumab outperformed ustekinumab in the BE VIVID phase 3 trial, with 273 of 321 patients (85%) receiving bimekizumab vs 81 of 163 patients (50%) receiving ustekinumab experiencing at least 90% improvement in psoriasis area and severity index (PASI) score at week 16.⁴ In a 2020 observational study (PSO-BIO-REAL), the efficacy rate of skin clearance after 6 months of treatment with biologics was only 25% (1/4).⁵ Aside from moderate to severe plaque psoriasis, bimekizumab demonstrated notable improvement in patients with psoriatic arthritis who had inadequate response or intolerance to TNF-α inhibitors compared to a placebo group in the BE COMPLETE phase 3 trial.⁶

IL-23—Guselkumab, risankizumab, and tildrakizumab are injectable therapies approved by the FDA in 2017 for moderate to severe plaque psoriasis.³ They inhibit IL-23 signaling by targeting the p19 subunit in addition to sparing IL-12.^3,7

A novel oral therapeutic peptide, JNJ-2113—the first oral IL-23 receptor antagonist peptide that blocks IL-23 signaling—has been developed, offering a new way to treat moderate to severe plaque psoriasis. Trial results from a phase 2 study (FRONTIER1) have supported JNJ-2113’s advancement into phase 3.^7,8 Patients who received JNJ-2113 successfully achieved PASI75 in addition to surpassing PASI90 and PASI100 at greater proportions compared to placebo at week 16.⁷

The promising early results of JNJ-2113 provide patients with greater flexibility and convenience for treatment options to address the manifestations of psoriasis. Although a considerable number of patients with moderate to severe plaque psoriasis qualify for advanced therapies, a substantial proportion remain untreated. Introducing an oral route of medication administration may help overcome barriers to therapy access due to a greater preference for pills over injections.⁹

TNF-α Inhibitors—Adalimumab is a TNF-α inhibitor that is used to treat moderate to severe chronic plaque psoriasis in adults who are candidates for systemic phototherapy.^1,10 However, one of the main barriers to initiating treatment has been cost. Biosimilars contribute to market competition, thus allowing the possibility of lower drug prices.¹⁰

There are 9 FDA-approved biosimilar products for adalimumab, with 2 having interchangeable designation. The first interchangeable biosimilar to enter the US market, adalimumab-adbm, became available in July 2023. In October 2023, adalimumab-afzb was granted interchangeable designation,¹¹ which enables pharmacists to swiftly substitute brand products for lower-cost biosimilars, providing patients with equally safe and effective alternatives without the delay of involving the prescribing clinician.¹² Pricing information indicates an initial 5% discount, which may later increase to 60%, from brand name adalimumab. Hopefully, reduced drug costs due to market competition will allow more patients to overcome barriers to therapy access.

IL-12/IL-23—Ustekinumab is a monoclonal antibody that targets IL-12 and IL-23. The FDA recently approved ustekinumab-auub as the first interchangeable ustekinumab biosimilar for the treatment of various inflammatory diseases, including moderate to severe plaque psoriasis and psoriatic arthritis.^12,13 The approval of ustekinumab-auub expands therapeutic options for the treatment of diverse inflammatory diseases. As the first interchangeable biosimilar in its category, this development underscores the importance of biosimilars in providing effective and accessible treatment.^12,14

Topical Innovations

In October 2023, the FDA approved an expanded indication for roflumilast cream 0.3% to treat children as young as 6 years for plaque psoriasis, even for use in intertriginous areas,¹⁵ which is a milestone given the lack of treatment options for the pediatric population because topical steroids, the most common treatment option for plaque psoriasis, can have safety concerns related to long-term use. With the advent of this steroid-free topical agent, pediatric patients have a safe and well-tolerated option for managing plaque psoriasis.¹⁶ This promising effort will now expand to trials in children as young as 2 years to test efficacy.¹⁶

Engel et al¹⁷ proposed a new algorithmic approach to the topical management of psoriasis with roflumilast cream and tapinarof cream as first-line treatments for mild disease due to their novelty in treating intertriginous areas, whereas traditional topical steroids in these areas would be inapt.¹⁷ The latest indication for roflumilast cream suggests that this proposed recommendation could be a promising and convenient enhancement to psoriasis management, potentially outperforming traditional topical corticosteroids.^15,17

Final Thoughts

Innovative targeted therapies ranging from new biologic agents to broader applications of topical treatments hold the potential to transform conventional psoriasis management with greater efficacy and safety, which can help create a more effective and personalized approach with greater patient satisfaction, ultimately enhancing overall quality of life. The choice of treatment is dependent not only on the severity of the disease but also on accessibility considerations such as cost. Overall, these innovative therapies add substantial value to the treatment armamentarium for psoriasis.

Psoriasis is a chronic autoimmune skin condition that affects approximately 2% to 4% of the US population and notably impacts overall quality of life.^1,2 There is no cure for this long-lasting condition. Fortunately, recent developments in research have led to more targeted therapies, paving the way for a more promising transformative landscape of psoriasis management. Herein, we explore the most up-to-date advancements and developments in the realm of psoriasis care.

Emerging Systemic Therapies

Biologics are cutting-edge treatments available for moderate to severe plaque psoriasis, as IL-17A, IL-23, and tumor necrosis factor α (TNF-α) have been recognized as key targets.³

IL-17—Bimekizumab is a unique monoclonal antibody that inhibits the activity of both IL-17A and IL-17F cytokines.³ This treatment was approved by the US Food and Drug Administration (FDA) in October 2023 for patients with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.⁴

Bimekizumab outperformed ustekinumab in the BE VIVID phase 3 trial, with 273 of 321 patients (85%) receiving bimekizumab vs 81 of 163 patients (50%) receiving ustekinumab experiencing at least 90% improvement in psoriasis area and severity index (PASI) score at week 16.⁴ In a 2020 observational study (PSO-BIO-REAL), the efficacy rate of skin clearance after 6 months of treatment with biologics was only 25% (1/4).⁵ Aside from moderate to severe plaque psoriasis, bimekizumab demonstrated notable improvement in patients with psoriatic arthritis who had inadequate response or intolerance to TNF-α inhibitors compared to a placebo group in the BE COMPLETE phase 3 trial.⁶

IL-23—Guselkumab, risankizumab, and tildrakizumab are injectable therapies approved by the FDA in 2017 for moderate to severe plaque psoriasis.³ They inhibit IL-23 signaling by targeting the p19 subunit in addition to sparing IL-12.^3,7

A novel oral therapeutic peptide, JNJ-2113—the first oral IL-23 receptor antagonist peptide that blocks IL-23 signaling—has been developed, offering a new way to treat moderate to severe plaque psoriasis. Trial results from a phase 2 study (FRONTIER1) have supported JNJ-2113’s advancement into phase 3.^7,8 Patients who received JNJ-2113 successfully achieved PASI75 in addition to surpassing PASI90 and PASI100 at greater proportions compared to placebo at week 16.⁷

The promising early results of JNJ-2113 provide patients with greater flexibility and convenience for treatment options to address the manifestations of psoriasis. Although a considerable number of patients with moderate to severe plaque psoriasis qualify for advanced therapies, a substantial proportion remain untreated. Introducing an oral route of medication administration may help overcome barriers to therapy access due to a greater preference for pills over injections.⁹

TNF-α Inhibitors—Adalimumab is a TNF-α inhibitor that is used to treat moderate to severe chronic plaque psoriasis in adults who are candidates for systemic phototherapy.^1,10 However, one of the main barriers to initiating treatment has been cost. Biosimilars contribute to market competition, thus allowing the possibility of lower drug prices.¹⁰

There are 9 FDA-approved biosimilar products for adalimumab, with 2 having interchangeable designation. The first interchangeable biosimilar to enter the US market, adalimumab-adbm, became available in July 2023. In October 2023, adalimumab-afzb was granted interchangeable designation,¹¹ which enables pharmacists to swiftly substitute brand products for lower-cost biosimilars, providing patients with equally safe and effective alternatives without the delay of involving the prescribing clinician.¹² Pricing information indicates an initial 5% discount, which may later increase to 60%, from brand name adalimumab. Hopefully, reduced drug costs due to market competition will allow more patients to overcome barriers to therapy access.

IL-12/IL-23—Ustekinumab is a monoclonal antibody that targets IL-12 and IL-23. The FDA recently approved ustekinumab-auub as the first interchangeable ustekinumab biosimilar for the treatment of various inflammatory diseases, including moderate to severe plaque psoriasis and psoriatic arthritis.^12,13 The approval of ustekinumab-auub expands therapeutic options for the treatment of diverse inflammatory diseases. As the first interchangeable biosimilar in its category, this development underscores the importance of biosimilars in providing effective and accessible treatment.^12,14

Topical Innovations

In October 2023, the FDA approved an expanded indication for roflumilast cream 0.3% to treat children as young as 6 years for plaque psoriasis, even for use in intertriginous areas,¹⁵ which is a milestone given the lack of treatment options for the pediatric population because topical steroids, the most common treatment option for plaque psoriasis, can have safety concerns related to long-term use. With the advent of this steroid-free topical agent, pediatric patients have a safe and well-tolerated option for managing plaque psoriasis.¹⁶ This promising effort will now expand to trials in children as young as 2 years to test efficacy.¹⁶

Engel et al¹⁷ proposed a new algorithmic approach to the topical management of psoriasis with roflumilast cream and tapinarof cream as first-line treatments for mild disease due to their novelty in treating intertriginous areas, whereas traditional topical steroids in these areas would be inapt.¹⁷ The latest indication for roflumilast cream suggests that this proposed recommendation could be a promising and convenient enhancement to psoriasis management, potentially outperforming traditional topical corticosteroids.^15,17

Final Thoughts

Innovative targeted therapies ranging from new biologic agents to broader applications of topical treatments hold the potential to transform conventional psoriasis management with greater efficacy and safety, which can help create a more effective and personalized approach with greater patient satisfaction, ultimately enhancing overall quality of life. The choice of treatment is dependent not only on the severity of the disease but also on accessibility considerations such as cost. Overall, these innovative therapies add substantial value to the treatment armamentarium for psoriasis.

In April 2023, the US Preventive Services Task Force (USPSTF) issued a controversial recommendation that the current evidence is insufficient to assess the benefits vs harms of visual skin examination by clinicians for skin cancer screening in adolescents and adults who do not have signs or symptoms of skin cancer.^1,2 This recommendation by the USPSTF has not changed in a quarter century,³ but a recent study described an interesting paradox that should trigger wide evaluation and debate.

Patel et al⁴ analyzed data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program from January 2000 to December 2018 to identify adults with a diagnosis of first primary melanoma in situ (MIS). Overall mortality was then determined through the National Vital Statistics System, which provides cause-of-death information for all deaths in the United States. The authors found 137,872 patients who had 1—and only 1—MIS discovered over the observation period. These patients predominantly were White (96.7%), and the mean (SD) age at diagnosis was 61.9 (16.5) years. During 910,308 total person-years of follow-up (mean [SD], 6.6 [5.1] years), 893 (0.6%) patients died of melanoma and 17,327 (12.6%) died of any cause. The 15-year melanoma-specific standardized mortality rate (SMR) was 1.89 (95% CI, 1.77-2.02), yet the 15-year overall survival relative to matched population controls was 112.4% (95% CI, 112.0%-112.8%), thus all-cause SMR was significantly lower at 0.68 (95% CI, 0.67-0.7). Although MIS was associated with a small increase in cohort melanoma mortality, overall mortality was actually lower than in the general population.⁴

Patel et al⁴ did a further broader search that included an additional 18,379 patients who also experienced a second primary melanoma, of which 6751 (36.7%) were invasive and 11,628 (63.3%) were in situ, with a melanoma-specific survival of 98.2% (95% CI, 97.6%-98.5%). Yet relative all-cause survival was significantly higher at 126.7% (95% CI, 125.5%-128.0%). Even among patients in whom a second primary melanoma was invasive, melanoma-specific survival was reduced to 91.1% (95% CI, 90.0%-92.1%), but relative all-cause survival was 116.7% (95% CI, 115%-118.4%). These data in the overall cohort of 155,251 patients showed a discordance between melanoma mortality, which was 4.27-times higher than in the general population (SMR, 4.27; 95% CI, 4.07-4.48), and a lower risk for death from all causes that was approximately 27% lower than in the general population (SMR, 0.73; 95% CI, 0.72-0.74). The authors showed that their findings were not associated with socioeconomic status.⁴

The analysis by Patel et al⁴ is now the second study in the literature to show this discordant melanoma survival pattern. In an earlier Australian study of 2452 melanoma patients, Watts et al⁵ reported that melanoma detection during routine skin checks was associated with a 25% lower all-cause mortality (hazard ratio, 0.75; 95% CI, 0.63-0.90) but not melanoma-specific mortality after multivariable adjustment for a variety of factors including socioeconomic status.These analyses by 2 different groups of investigators have broad implications. Both groups suggested that the improved life span in melanoma patients may be due to health-seeking behavior, which has been defined as “any action undertaken by individuals who perceive themselves to have a health problem or to be ill for the purpose of finding an appropriate remedy.”⁶

Once treated for melanoma, it is clear that patients are likely to return at regular intervals for thorough full-body skin examinations, but this activity alone could not be responsible for improved all-cause mortality in the face of increased melanoma-specific mortality. It seems the authors are implying a broader concept of good health behavior, originally defined by MacKian⁷ as encompassing “activities undertaken to maintain good health, to prevent ill health, as well as dealing with any departure from a good state of health,” such as overt behavioral patterns, actions, and habits with the goal of maintenance, restoration, and improvement of one’s health. A variety of behaviors fall within such a definition including smoking cessation, decreased alcohol use, good diet, more physical activity, safe sexual behavior, scheduling physician visits, medication adherence, vaccination, and yes—screening examinations for health problems.⁸

The concept that individuals who are diagnosed with melanoma fall into a pattern of good health behavior is an interesting hypothesis that must remain speculative until the multiple aspects of good health behavior are rigorously studied. This concept coexists with the hypothesis of melanoma “overdiagnosis”—the idea that many melanomas are detected that will never lead to death.⁹ Both concepts deserve further analysis. Unquestionably, a randomized controlled trial could never recruit patients willing to undergo long-term untreated observation of their melanomas to test the hypothesis that their melanoma diagnosis would eventually lead to death. Furthermore, Patel et al⁴ do suggest that even MIS carries a small but measurable increased risk for death from the disease, which is not particularly supportive of the overdiagnosis hypothesis; however, analysis of the concept that improved individual health behavior is at least in part responsible for the first discovery of melanomas is certainly approachable. Here is the key question: Did the melanoma diagnosis trigger a sudden change in multiple aspects of health behavior that led to significant all-cause mortality benefits? The average age of the population studied by Patel et al⁴ was approximately 62 years. One wonders whether the consequences of a lifetime of established health behavior patterns can be rapidly ­modified—certainly possible but again remains to be proven by further studies.

Conversely, the alternative hypothesis is that discovery of MIS was the result of active pursuit of self-examination and screening procedures as part of individually ingrained good health behavior over a lifetime. Goodwin et al¹⁰ carried out a study in a sample of the Medicare population aged 69 to 90 years looking at men who had prostate cancer screening via prostate-specific antigen measurement and women who had undergone mammography in older age, compared to the contrast population who had not had these screening procedures. They tracked date of death in Medicare enrollment files. They identified 543,970 women and 362,753 men who were aged 69 to 90 years as of January 1, 2003. Patients were stratified by life expectancy based on age and comorbidity. Within each stratum, the patients with cancer screening had higher actual median survival than those who were not screened, with differences ranging from 1.7 to 2.1 years for women and 0.9 to 1.1 years for men.¹⁰ These results were not the result of lower prostate or breast cancer mortality. Rather, one surmises that other health factors yielded lower mortality in the screened cohorts.

A full-body skin examination is a time-consuming process. Patients who come to their physician for a routine annual physical don’t expect a skin examination and very few physicians have the time for a long detailed full-body skin examination. When the patient presents to a dermatologist for an examination, it often is because they have real concerns; for example, they may have had a family member who died of skin cancer, or the patient themself may have noticed a worrisome lesion. Patients, not physicians, are the drivers of skin cancer screening, a fact that often is dismissed by those who are not necessarily supportive of the practice.

In light of the findings of Patel et al,⁴ it is essential that the USPSTF reviews be reanalyzed to compare skin cancer–specific mortality, all-cause mortality, and lifespan in individuals who pursue skin cancer screening; the reanalysis also should not be exclusively limited to survival. With the advent of the immune checkpoint inhibitors, patients with metastatic melanoma are living much longer.¹¹ The burden of living with metastatic cancer must be characterized and measured to have a complete picture and a valid analysis.

After the release of the USPSTF recommendation, there have been calls for large-scale studies to prove the benefits of skin cancer screening.¹² Such studies may be valuable; however, if the hypothesis that overall healthy behavior as the major outcome determinant is substantiated, it may prove quite challenging to perform tests of association with specific interventions. It has been shown that skin cancer screening does lead to discovery of more melanomas,¹³ yet in light of the paradox described by Patel et al,⁴ it also is likely that causes of death other than melanoma impact overall mortality. Patients who pursue skin examinations may engage in multiple different health activities that are beneficial in the long term, making it difficult to analyze the specific benefit of skin cancer screening in isolation. It may prove difficult to ask patients to omit selected aspects of healthy behavior to try to prove the point. At this time, there is much more work to be done prior to offering opinions on the importance of skin cancer examination in isolation to improve overall health care. In the meantime, dermatologists owe it to our patients to continue to diligently pursue thorough and detailed skin examinations.

In April 2023, the US Preventive Services Task Force (USPSTF) issued a controversial recommendation that the current evidence is insufficient to assess the benefits vs harms of visual skin examination by clinicians for skin cancer screening in adolescents and adults who do not have signs or symptoms of skin cancer.^1,2 This recommendation by the USPSTF has not changed in a quarter century,³ but a recent study described an interesting paradox that should trigger wide evaluation and debate.

Patel et al⁴ analyzed data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program from January 2000 to December 2018 to identify adults with a diagnosis of first primary melanoma in situ (MIS). Overall mortality was then determined through the National Vital Statistics System, which provides cause-of-death information for all deaths in the United States. The authors found 137,872 patients who had 1—and only 1—MIS discovered over the observation period. These patients predominantly were White (96.7%), and the mean (SD) age at diagnosis was 61.9 (16.5) years. During 910,308 total person-years of follow-up (mean [SD], 6.6 [5.1] years), 893 (0.6%) patients died of melanoma and 17,327 (12.6%) died of any cause. The 15-year melanoma-specific standardized mortality rate (SMR) was 1.89 (95% CI, 1.77-2.02), yet the 15-year overall survival relative to matched population controls was 112.4% (95% CI, 112.0%-112.8%), thus all-cause SMR was significantly lower at 0.68 (95% CI, 0.67-0.7). Although MIS was associated with a small increase in cohort melanoma mortality, overall mortality was actually lower than in the general population.⁴

Patel et al⁴ did a further broader search that included an additional 18,379 patients who also experienced a second primary melanoma, of which 6751 (36.7%) were invasive and 11,628 (63.3%) were in situ, with a melanoma-specific survival of 98.2% (95% CI, 97.6%-98.5%). Yet relative all-cause survival was significantly higher at 126.7% (95% CI, 125.5%-128.0%). Even among patients in whom a second primary melanoma was invasive, melanoma-specific survival was reduced to 91.1% (95% CI, 90.0%-92.1%), but relative all-cause survival was 116.7% (95% CI, 115%-118.4%). These data in the overall cohort of 155,251 patients showed a discordance between melanoma mortality, which was 4.27-times higher than in the general population (SMR, 4.27; 95% CI, 4.07-4.48), and a lower risk for death from all causes that was approximately 27% lower than in the general population (SMR, 0.73; 95% CI, 0.72-0.74). The authors showed that their findings were not associated with socioeconomic status.⁴

The analysis by Patel et al⁴ is now the second study in the literature to show this discordant melanoma survival pattern. In an earlier Australian study of 2452 melanoma patients, Watts et al⁵ reported that melanoma detection during routine skin checks was associated with a 25% lower all-cause mortality (hazard ratio, 0.75; 95% CI, 0.63-0.90) but not melanoma-specific mortality after multivariable adjustment for a variety of factors including socioeconomic status.These analyses by 2 different groups of investigators have broad implications. Both groups suggested that the improved life span in melanoma patients may be due to health-seeking behavior, which has been defined as “any action undertaken by individuals who perceive themselves to have a health problem or to be ill for the purpose of finding an appropriate remedy.”⁶

Once treated for melanoma, it is clear that patients are likely to return at regular intervals for thorough full-body skin examinations, but this activity alone could not be responsible for improved all-cause mortality in the face of increased melanoma-specific mortality. It seems the authors are implying a broader concept of good health behavior, originally defined by MacKian⁷ as encompassing “activities undertaken to maintain good health, to prevent ill health, as well as dealing with any departure from a good state of health,” such as overt behavioral patterns, actions, and habits with the goal of maintenance, restoration, and improvement of one’s health. A variety of behaviors fall within such a definition including smoking cessation, decreased alcohol use, good diet, more physical activity, safe sexual behavior, scheduling physician visits, medication adherence, vaccination, and yes—screening examinations for health problems.⁸

The concept that individuals who are diagnosed with melanoma fall into a pattern of good health behavior is an interesting hypothesis that must remain speculative until the multiple aspects of good health behavior are rigorously studied. This concept coexists with the hypothesis of melanoma “overdiagnosis”—the idea that many melanomas are detected that will never lead to death.⁹ Both concepts deserve further analysis. Unquestionably, a randomized controlled trial could never recruit patients willing to undergo long-term untreated observation of their melanomas to test the hypothesis that their melanoma diagnosis would eventually lead to death. Furthermore, Patel et al⁴ do suggest that even MIS carries a small but measurable increased risk for death from the disease, which is not particularly supportive of the overdiagnosis hypothesis; however, analysis of the concept that improved individual health behavior is at least in part responsible for the first discovery of melanomas is certainly approachable. Here is the key question: Did the melanoma diagnosis trigger a sudden change in multiple aspects of health behavior that led to significant all-cause mortality benefits? The average age of the population studied by Patel et al⁴ was approximately 62 years. One wonders whether the consequences of a lifetime of established health behavior patterns can be rapidly ­modified—certainly possible but again remains to be proven by further studies.

Conversely, the alternative hypothesis is that discovery of MIS was the result of active pursuit of self-examination and screening procedures as part of individually ingrained good health behavior over a lifetime. Goodwin et al¹⁰ carried out a study in a sample of the Medicare population aged 69 to 90 years looking at men who had prostate cancer screening via prostate-specific antigen measurement and women who had undergone mammography in older age, compared to the contrast population who had not had these screening procedures. They tracked date of death in Medicare enrollment files. They identified 543,970 women and 362,753 men who were aged 69 to 90 years as of January 1, 2003. Patients were stratified by life expectancy based on age and comorbidity. Within each stratum, the patients with cancer screening had higher actual median survival than those who were not screened, with differences ranging from 1.7 to 2.1 years for women and 0.9 to 1.1 years for men.¹⁰ These results were not the result of lower prostate or breast cancer mortality. Rather, one surmises that other health factors yielded lower mortality in the screened cohorts.

A full-body skin examination is a time-consuming process. Patients who come to their physician for a routine annual physical don’t expect a skin examination and very few physicians have the time for a long detailed full-body skin examination. When the patient presents to a dermatologist for an examination, it often is because they have real concerns; for example, they may have had a family member who died of skin cancer, or the patient themself may have noticed a worrisome lesion. Patients, not physicians, are the drivers of skin cancer screening, a fact that often is dismissed by those who are not necessarily supportive of the practice.

In light of the findings of Patel et al,⁴ it is essential that the USPSTF reviews be reanalyzed to compare skin cancer–specific mortality, all-cause mortality, and lifespan in individuals who pursue skin cancer screening; the reanalysis also should not be exclusively limited to survival. With the advent of the immune checkpoint inhibitors, patients with metastatic melanoma are living much longer.¹¹ The burden of living with metastatic cancer must be characterized and measured to have a complete picture and a valid analysis.

After the release of the USPSTF recommendation, there have been calls for large-scale studies to prove the benefits of skin cancer screening.¹² Such studies may be valuable; however, if the hypothesis that overall healthy behavior as the major outcome determinant is substantiated, it may prove quite challenging to perform tests of association with specific interventions. It has been shown that skin cancer screening does lead to discovery of more melanomas,¹³ yet in light of the paradox described by Patel et al,⁴ it also is likely that causes of death other than melanoma impact overall mortality. Patients who pursue skin examinations may engage in multiple different health activities that are beneficial in the long term, making it difficult to analyze the specific benefit of skin cancer screening in isolation. It may prove difficult to ask patients to omit selected aspects of healthy behavior to try to prove the point. At this time, there is much more work to be done prior to offering opinions on the importance of skin cancer examination in isolation to improve overall health care. In the meantime, dermatologists owe it to our patients to continue to diligently pursue thorough and detailed skin examinations.

In April 2023, the US Preventive Services Task Force (USPSTF) issued a controversial recommendation that the current evidence is insufficient to assess the benefits vs harms of visual skin examination by clinicians for skin cancer screening in adolescents and adults who do not have signs or symptoms of skin cancer.^1,2 This recommendation by the USPSTF has not changed in a quarter century,³ but a recent study described an interesting paradox that should trigger wide evaluation and debate.

Patel et al⁴ analyzed data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program from January 2000 to December 2018 to identify adults with a diagnosis of first primary melanoma in situ (MIS). Overall mortality was then determined through the National Vital Statistics System, which provides cause-of-death information for all deaths in the United States. The authors found 137,872 patients who had 1—and only 1—MIS discovered over the observation period. These patients predominantly were White (96.7%), and the mean (SD) age at diagnosis was 61.9 (16.5) years. During 910,308 total person-years of follow-up (mean [SD], 6.6 [5.1] years), 893 (0.6%) patients died of melanoma and 17,327 (12.6%) died of any cause. The 15-year melanoma-specific standardized mortality rate (SMR) was 1.89 (95% CI, 1.77-2.02), yet the 15-year overall survival relative to matched population controls was 112.4% (95% CI, 112.0%-112.8%), thus all-cause SMR was significantly lower at 0.68 (95% CI, 0.67-0.7). Although MIS was associated with a small increase in cohort melanoma mortality, overall mortality was actually lower than in the general population.⁴

Patel et al⁴ did a further broader search that included an additional 18,379 patients who also experienced a second primary melanoma, of which 6751 (36.7%) were invasive and 11,628 (63.3%) were in situ, with a melanoma-specific survival of 98.2% (95% CI, 97.6%-98.5%). Yet relative all-cause survival was significantly higher at 126.7% (95% CI, 125.5%-128.0%). Even among patients in whom a second primary melanoma was invasive, melanoma-specific survival was reduced to 91.1% (95% CI, 90.0%-92.1%), but relative all-cause survival was 116.7% (95% CI, 115%-118.4%). These data in the overall cohort of 155,251 patients showed a discordance between melanoma mortality, which was 4.27-times higher than in the general population (SMR, 4.27; 95% CI, 4.07-4.48), and a lower risk for death from all causes that was approximately 27% lower than in the general population (SMR, 0.73; 95% CI, 0.72-0.74). The authors showed that their findings were not associated with socioeconomic status.⁴

The analysis by Patel et al⁴ is now the second study in the literature to show this discordant melanoma survival pattern. In an earlier Australian study of 2452 melanoma patients, Watts et al⁵ reported that melanoma detection during routine skin checks was associated with a 25% lower all-cause mortality (hazard ratio, 0.75; 95% CI, 0.63-0.90) but not melanoma-specific mortality after multivariable adjustment for a variety of factors including socioeconomic status.These analyses by 2 different groups of investigators have broad implications. Both groups suggested that the improved life span in melanoma patients may be due to health-seeking behavior, which has been defined as “any action undertaken by individuals who perceive themselves to have a health problem or to be ill for the purpose of finding an appropriate remedy.”⁶

Once treated for melanoma, it is clear that patients are likely to return at regular intervals for thorough full-body skin examinations, but this activity alone could not be responsible for improved all-cause mortality in the face of increased melanoma-specific mortality. It seems the authors are implying a broader concept of good health behavior, originally defined by MacKian⁷ as encompassing “activities undertaken to maintain good health, to prevent ill health, as well as dealing with any departure from a good state of health,” such as overt behavioral patterns, actions, and habits with the goal of maintenance, restoration, and improvement of one’s health. A variety of behaviors fall within such a definition including smoking cessation, decreased alcohol use, good diet, more physical activity, safe sexual behavior, scheduling physician visits, medication adherence, vaccination, and yes—screening examinations for health problems.⁸

The concept that individuals who are diagnosed with melanoma fall into a pattern of good health behavior is an interesting hypothesis that must remain speculative until the multiple aspects of good health behavior are rigorously studied. This concept coexists with the hypothesis of melanoma “overdiagnosis”—the idea that many melanomas are detected that will never lead to death.⁹ Both concepts deserve further analysis. Unquestionably, a randomized controlled trial could never recruit patients willing to undergo long-term untreated observation of their melanomas to test the hypothesis that their melanoma diagnosis would eventually lead to death. Furthermore, Patel et al⁴ do suggest that even MIS carries a small but measurable increased risk for death from the disease, which is not particularly supportive of the overdiagnosis hypothesis; however, analysis of the concept that improved individual health behavior is at least in part responsible for the first discovery of melanomas is certainly approachable. Here is the key question: Did the melanoma diagnosis trigger a sudden change in multiple aspects of health behavior that led to significant all-cause mortality benefits? The average age of the population studied by Patel et al⁴ was approximately 62 years. One wonders whether the consequences of a lifetime of established health behavior patterns can be rapidly ­modified—certainly possible but again remains to be proven by further studies.

Conversely, the alternative hypothesis is that discovery of MIS was the result of active pursuit of self-examination and screening procedures as part of individually ingrained good health behavior over a lifetime. Goodwin et al¹⁰ carried out a study in a sample of the Medicare population aged 69 to 90 years looking at men who had prostate cancer screening via prostate-specific antigen measurement and women who had undergone mammography in older age, compared to the contrast population who had not had these screening procedures. They tracked date of death in Medicare enrollment files. They identified 543,970 women and 362,753 men who were aged 69 to 90 years as of January 1, 2003. Patients were stratified by life expectancy based on age and comorbidity. Within each stratum, the patients with cancer screening had higher actual median survival than those who were not screened, with differences ranging from 1.7 to 2.1 years for women and 0.9 to 1.1 years for men.¹⁰ These results were not the result of lower prostate or breast cancer mortality. Rather, one surmises that other health factors yielded lower mortality in the screened cohorts.

A full-body skin examination is a time-consuming process. Patients who come to their physician for a routine annual physical don’t expect a skin examination and very few physicians have the time for a long detailed full-body skin examination. When the patient presents to a dermatologist for an examination, it often is because they have real concerns; for example, they may have had a family member who died of skin cancer, or the patient themself may have noticed a worrisome lesion. Patients, not physicians, are the drivers of skin cancer screening, a fact that often is dismissed by those who are not necessarily supportive of the practice.

In light of the findings of Patel et al,⁴ it is essential that the USPSTF reviews be reanalyzed to compare skin cancer–specific mortality, all-cause mortality, and lifespan in individuals who pursue skin cancer screening; the reanalysis also should not be exclusively limited to survival. With the advent of the immune checkpoint inhibitors, patients with metastatic melanoma are living much longer.¹¹ The burden of living with metastatic cancer must be characterized and measured to have a complete picture and a valid analysis.

After the release of the USPSTF recommendation, there have been calls for large-scale studies to prove the benefits of skin cancer screening.¹² Such studies may be valuable; however, if the hypothesis that overall healthy behavior as the major outcome determinant is substantiated, it may prove quite challenging to perform tests of association with specific interventions. It has been shown that skin cancer screening does lead to discovery of more melanomas,¹³ yet in light of the paradox described by Patel et al,⁴ it also is likely that causes of death other than melanoma impact overall mortality. Patients who pursue skin examinations may engage in multiple different health activities that are beneficial in the long term, making it difficult to analyze the specific benefit of skin cancer screening in isolation. It may prove difficult to ask patients to omit selected aspects of healthy behavior to try to prove the point. At this time, there is much more work to be done prior to offering opinions on the importance of skin cancer examination in isolation to improve overall health care. In the meantime, dermatologists owe it to our patients to continue to diligently pursue thorough and detailed skin examinations.

A pair of dueling editorials in the journal Hypertension debate whether our focus should be on sodium or its often neglected partner, potassium.

Should we cut sodium from our diet or eat more potassium to lower blood pressure? The answer requires an intricate understanding of renal physiology that is fascinating. To nephrologists. A meta-analysis of 85 trials showed a consistent and linear. It may also depend on where you live and whether your concern is treating individuals or implementing effective food policy.

The Case for Sodium Restriction

Stephen Juraschek, MD, PhD, of the Beth Israel Deaconess Medical Center, Boston, Massachusetts, co-author of one editorial, told me in a zoom interview that he believes his side of the debate clearly has the stronger argument. Of the two cations in question, there has been infinitely more ink spilled about sodium.

Studies such as INTERSALT, the DASH diet, and TOHP may be the most well-known, but there are many, many intervention studies of sodium restriction’s effect on blood pressure. A meta-analysis of 85 trials of showed a consistent and linear relationship between sodium reduction and blood pressure. In contrast, the evidence base for potassium is more limited and less consistent. There are half as many trials with potassium, and its ability to lower blood pressure may depend on how much sodium is present in the diet.

An outlier in the sodium restriction evidence base is the PURE study, which suggested that extreme sodium restriction could increase cardiovascular mortality, but the trial suffered from two potential issues. First, it used a single spot urine specimen to measure sodium rather than the generally accepted more accurate 24-hour urine collection. A reanalysis of the TOHP study using a spot urine rather than a 24-hour urine collection changed the relationship between sodium intake and mortality and possibly explained the U-shaped association observed in PURE. Second, PURE was an observational cohort and was prone to confounding, or in this case, reverse causation. Why did people who consumed very little salt have an increased risk for cardiovascular disease? It is very possible that people with a high risk for cardiovascular disease were told to consume less salt to begin with. Hence B led to A rather than A leading to B.

The debate on sodium restriction has been bitter at times. Opposing camps formed, and people took sides in the “salt wars.” A group of researchers, termed the Jackson 6, met and decided to end the controversy by running a randomized trial in US prisons (having discounted the options of long-term care homes and military bases). They detailed their plan in an editorial in Hypertension. The study never came to fruition for two reasons: the obvious ethical problems of experimenting on prisoners and the revelation of undisclosed salt industry funding.

More recent studies have mercifully been more conventional. The SSaSS study, a randomized controlled trial of a salt substitute, provided the cardiovascular outcomes data that many were waiting for. And CARDIA-SSBP, a cross-over randomized trial recently presented at the American Heart Association meeting, showed that reducing dietary sodium was on par with medication when it came to lowering blood pressure.

For Dr. Juraschek, the evidence is clear: “If you were going to choose one, I would say the weight of the evidence is still really heavily on the sodium side.”

The Case for Potassium Supplementation

The evidence for salt restriction notwithstanding, Swapnil Hiremath, MD, MPH, from the University of Ottawa, Ontario, Canada, argued in his editorial that potassium supplementation has gotten short shrift. Though he admits the studies for potassium supplementation have been smaller and sometimes rely on observational evidence, the evidence is there. In the distal convoluted tubule, the sodium chloride cotransporter (NCC), aka the potassium switch, is turned on by low potassium levels and leads to sodium reabsorption by the kidney even in settings of high sodium intake (Figure). To nonnephrologists, renal physiology may be a black box. But if you quickly brush up on the mechanism of action of thiazide diuretics, the preceding descriptor will make more sense.

Medscape

Realistic Diets and Taste Issues

“We know that increasing potassium, decreasing sodium is useful. The question is how do we do that?” says Dr. Hiremath. Should we encourage fruit and vegetable consumption in a healthy diet, give potassium supplements, or encourage the use of low-sodium salt substitutes?

Recommending a healthier diet with more fruits and vegetables is a no-brainer. But getting people to do it is hard. In a world where fruit is more expensive than junk food is, economic realities may drive food choice regardless of our best efforts. The 4700 mg of potassium in the DASH eating plan is the equivalent of eleven bananas daily; although not impossible, it would require a substantive shift in eating patterns for most people.

Given that we prescribe iron, vitamin B12, calcium, and vitamin D to patients who need them, why not potassium tablets to help with blood pressure? Granted, there are concerns about inducing hyperkalemia. Also, why not just prescribe a proven anti-hypertensive, such as ramipril, which has the added benefit of helping with renal protection or cardiac remodeling? Dr. Hiremath points out that patients are far less reluctant to take dietary supplements. Medication is something you take when sick. A supplement is seen as “natural” and “healthy” and might be more attractive to people resistant to prescription meds.

Another drawback of oral potassium supplementation is taste. In a Consumer Reports taste test, potassium chloride fared poorly. It was bitter and had a metallic aftertaste. At least one tester wouldn’t ever consume it again. Potassium citrate is slightly more palpable.

Salt substitutes, like the 75:25 ratio of sodium to potassium used in SSaSS, may be as high as you can go for potassium in any low-sodium salt alternative. If you go any higher than that, the taste will just turn people off, suggests Dr. Hiremath.

But SsaSS, which was done in China, may not be relevant to North America. In China, most sodium is added during cooking at home, and the consumption of processed foods is low. For the typical North American, roughly three quarters of the sodium eaten is added to their food by someone else; only about 15% is added during cooking at home or at the dinner table. If you aren’t someone who cooks, buying a salt substitute is probably not going to have much impact.

Given that reality, Dr. Juraschek thinks we need to target the sodium in processed foods. “There’s just so much sodium in so many products,” he says. “When you think about public policy, it’s most expeditious for there to be more regulation about how much is added to our food supply vs trying to get people to consume eight to 12 servings of fruit.”

No Salt War Here

Despite their different editorial takes, Dr. Hiremath and Dr. Juraschek largely agree on the broad strokes of the problem. This isn’t X (or Twitter) after all. Potassium supplementation may be useful in some parts of the world but may not address the underlying problem in countries where processed foods are the source of most dietary sodium.

The CARDIA-SSBP trial showed that a very low–sodium diet had the same blood pressure–lowering effect as a first-line antihypertensive, but most people will not be able to limit themselves to 500 mg of dietary sodium per day. In CARDIA-SSBP, just as in DASH, participants were provided with meals from study kitchens. They were not just told to eat less salt, which would almost certainly have failed.

“We should aim for stuff that is practical and doable rather than aim for stuff that cannot be done,” according to Dr. Hiremath. Whether that should be salt substitutes or policy change may depend on which part of the planet you live on.

One recent positive change may herald the beginning of a policy change, at least in the United States. In March 2023, the US Food and Drug Administration proposed a rule change to allow salt substitutes to be labeled as salt. This would make it easier for food manufacturers to swap out sodium chloride for a low-sodium alternative and reduce the amount of sodium in the US diet without having a large impact on taste and consumer uptake. Both Dr. Hiremath and Dr. Juraschek agree that it may not be enough on its own but that it’s a start.

Christopher Labos is a cardiologist with a degree in epidemiology. He spends most of his time doing things that he doesn’t get paid for, like research, teaching, and podcasting. Occasionally, he finds time to practice cardiology to pay the rent. He realizes that half of his research findings will be disproved in 5 years; he just doesn’t know which half. He is a regular contributor to the Montreal Gazette, CJAD radio, and CTV television in Montreal, and is host of the award-winning podcast The Body of Evidence.

A version of this article appeared on Medscape.com.

A pair of dueling editorials in the journal Hypertension debate whether our focus should be on sodium or its often neglected partner, potassium.

Should we cut sodium from our diet or eat more potassium to lower blood pressure? The answer requires an intricate understanding of renal physiology that is fascinating. To nephrologists. A meta-analysis of 85 trials showed a consistent and linear. It may also depend on where you live and whether your concern is treating individuals or implementing effective food policy.

The Case for Sodium Restriction

Stephen Juraschek, MD, PhD, of the Beth Israel Deaconess Medical Center, Boston, Massachusetts, co-author of one editorial, told me in a zoom interview that he believes his side of the debate clearly has the stronger argument. Of the two cations in question, there has been infinitely more ink spilled about sodium.

Studies such as INTERSALT, the DASH diet, and TOHP may be the most well-known, but there are many, many intervention studies of sodium restriction’s effect on blood pressure. A meta-analysis of 85 trials of showed a consistent and linear relationship between sodium reduction and blood pressure. In contrast, the evidence base for potassium is more limited and less consistent. There are half as many trials with potassium, and its ability to lower blood pressure may depend on how much sodium is present in the diet.

An outlier in the sodium restriction evidence base is the PURE study, which suggested that extreme sodium restriction could increase cardiovascular mortality, but the trial suffered from two potential issues. First, it used a single spot urine specimen to measure sodium rather than the generally accepted more accurate 24-hour urine collection. A reanalysis of the TOHP study using a spot urine rather than a 24-hour urine collection changed the relationship between sodium intake and mortality and possibly explained the U-shaped association observed in PURE. Second, PURE was an observational cohort and was prone to confounding, or in this case, reverse causation. Why did people who consumed very little salt have an increased risk for cardiovascular disease? It is very possible that people with a high risk for cardiovascular disease were told to consume less salt to begin with. Hence B led to A rather than A leading to B.

The debate on sodium restriction has been bitter at times. Opposing camps formed, and people took sides in the “salt wars.” A group of researchers, termed the Jackson 6, met and decided to end the controversy by running a randomized trial in US prisons (having discounted the options of long-term care homes and military bases). They detailed their plan in an editorial in Hypertension. The study never came to fruition for two reasons: the obvious ethical problems of experimenting on prisoners and the revelation of undisclosed salt industry funding.

More recent studies have mercifully been more conventional. The SSaSS study, a randomized controlled trial of a salt substitute, provided the cardiovascular outcomes data that many were waiting for. And CARDIA-SSBP, a cross-over randomized trial recently presented at the American Heart Association meeting, showed that reducing dietary sodium was on par with medication when it came to lowering blood pressure.

For Dr. Juraschek, the evidence is clear: “If you were going to choose one, I would say the weight of the evidence is still really heavily on the sodium side.”

The Case for Potassium Supplementation

The evidence for salt restriction notwithstanding, Swapnil Hiremath, MD, MPH, from the University of Ottawa, Ontario, Canada, argued in his editorial that potassium supplementation has gotten short shrift. Though he admits the studies for potassium supplementation have been smaller and sometimes rely on observational evidence, the evidence is there. In the distal convoluted tubule, the sodium chloride cotransporter (NCC), aka the potassium switch, is turned on by low potassium levels and leads to sodium reabsorption by the kidney even in settings of high sodium intake (Figure). To nonnephrologists, renal physiology may be a black box. But if you quickly brush up on the mechanism of action of thiazide diuretics, the preceding descriptor will make more sense.

Medscape

Realistic Diets and Taste Issues

“We know that increasing potassium, decreasing sodium is useful. The question is how do we do that?” says Dr. Hiremath. Should we encourage fruit and vegetable consumption in a healthy diet, give potassium supplements, or encourage the use of low-sodium salt substitutes?

Recommending a healthier diet with more fruits and vegetables is a no-brainer. But getting people to do it is hard. In a world where fruit is more expensive than junk food is, economic realities may drive food choice regardless of our best efforts. The 4700 mg of potassium in the DASH eating plan is the equivalent of eleven bananas daily; although not impossible, it would require a substantive shift in eating patterns for most people.

Given that we prescribe iron, vitamin B12, calcium, and vitamin D to patients who need them, why not potassium tablets to help with blood pressure? Granted, there are concerns about inducing hyperkalemia. Also, why not just prescribe a proven anti-hypertensive, such as ramipril, which has the added benefit of helping with renal protection or cardiac remodeling? Dr. Hiremath points out that patients are far less reluctant to take dietary supplements. Medication is something you take when sick. A supplement is seen as “natural” and “healthy” and might be more attractive to people resistant to prescription meds.

Another drawback of oral potassium supplementation is taste. In a Consumer Reports taste test, potassium chloride fared poorly. It was bitter and had a metallic aftertaste. At least one tester wouldn’t ever consume it again. Potassium citrate is slightly more palpable.

Salt substitutes, like the 75:25 ratio of sodium to potassium used in SSaSS, may be as high as you can go for potassium in any low-sodium salt alternative. If you go any higher than that, the taste will just turn people off, suggests Dr. Hiremath.

But SsaSS, which was done in China, may not be relevant to North America. In China, most sodium is added during cooking at home, and the consumption of processed foods is low. For the typical North American, roughly three quarters of the sodium eaten is added to their food by someone else; only about 15% is added during cooking at home or at the dinner table. If you aren’t someone who cooks, buying a salt substitute is probably not going to have much impact.

Given that reality, Dr. Juraschek thinks we need to target the sodium in processed foods. “There’s just so much sodium in so many products,” he says. “When you think about public policy, it’s most expeditious for there to be more regulation about how much is added to our food supply vs trying to get people to consume eight to 12 servings of fruit.”

No Salt War Here

Despite their different editorial takes, Dr. Hiremath and Dr. Juraschek largely agree on the broad strokes of the problem. This isn’t X (or Twitter) after all. Potassium supplementation may be useful in some parts of the world but may not address the underlying problem in countries where processed foods are the source of most dietary sodium.

The CARDIA-SSBP trial showed that a very low–sodium diet had the same blood pressure–lowering effect as a first-line antihypertensive, but most people will not be able to limit themselves to 500 mg of dietary sodium per day. In CARDIA-SSBP, just as in DASH, participants were provided with meals from study kitchens. They were not just told to eat less salt, which would almost certainly have failed.

“We should aim for stuff that is practical and doable rather than aim for stuff that cannot be done,” according to Dr. Hiremath. Whether that should be salt substitutes or policy change may depend on which part of the planet you live on.

One recent positive change may herald the beginning of a policy change, at least in the United States. In March 2023, the US Food and Drug Administration proposed a rule change to allow salt substitutes to be labeled as salt. This would make it easier for food manufacturers to swap out sodium chloride for a low-sodium alternative and reduce the amount of sodium in the US diet without having a large impact on taste and consumer uptake. Both Dr. Hiremath and Dr. Juraschek agree that it may not be enough on its own but that it’s a start.

Christopher Labos is a cardiologist with a degree in epidemiology. He spends most of his time doing things that he doesn’t get paid for, like research, teaching, and podcasting. Occasionally, he finds time to practice cardiology to pay the rent. He realizes that half of his research findings will be disproved in 5 years; he just doesn’t know which half. He is a regular contributor to the Montreal Gazette, CJAD radio, and CTV television in Montreal, and is host of the award-winning podcast The Body of Evidence.

A version of this article appeared on Medscape.com.

A pair of dueling editorials in the journal Hypertension debate whether our focus should be on sodium or its often neglected partner, potassium.

Should we cut sodium from our diet or eat more potassium to lower blood pressure? The answer requires an intricate understanding of renal physiology that is fascinating. To nephrologists. A meta-analysis of 85 trials showed a consistent and linear. It may also depend on where you live and whether your concern is treating individuals or implementing effective food policy.

The Case for Sodium Restriction

Stephen Juraschek, MD, PhD, of the Beth Israel Deaconess Medical Center, Boston, Massachusetts, co-author of one editorial, told me in a zoom interview that he believes his side of the debate clearly has the stronger argument. Of the two cations in question, there has been infinitely more ink spilled about sodium.

Studies such as INTERSALT, the DASH diet, and TOHP may be the most well-known, but there are many, many intervention studies of sodium restriction’s effect on blood pressure. A meta-analysis of 85 trials of showed a consistent and linear relationship between sodium reduction and blood pressure. In contrast, the evidence base for potassium is more limited and less consistent. There are half as many trials with potassium, and its ability to lower blood pressure may depend on how much sodium is present in the diet.

An outlier in the sodium restriction evidence base is the PURE study, which suggested that extreme sodium restriction could increase cardiovascular mortality, but the trial suffered from two potential issues. First, it used a single spot urine specimen to measure sodium rather than the generally accepted more accurate 24-hour urine collection. A reanalysis of the TOHP study using a spot urine rather than a 24-hour urine collection changed the relationship between sodium intake and mortality and possibly explained the U-shaped association observed in PURE. Second, PURE was an observational cohort and was prone to confounding, or in this case, reverse causation. Why did people who consumed very little salt have an increased risk for cardiovascular disease? It is very possible that people with a high risk for cardiovascular disease were told to consume less salt to begin with. Hence B led to A rather than A leading to B.

The debate on sodium restriction has been bitter at times. Opposing camps formed, and people took sides in the “salt wars.” A group of researchers, termed the Jackson 6, met and decided to end the controversy by running a randomized trial in US prisons (having discounted the options of long-term care homes and military bases). They detailed their plan in an editorial in Hypertension. The study never came to fruition for two reasons: the obvious ethical problems of experimenting on prisoners and the revelation of undisclosed salt industry funding.

More recent studies have mercifully been more conventional. The SSaSS study, a randomized controlled trial of a salt substitute, provided the cardiovascular outcomes data that many were waiting for. And CARDIA-SSBP, a cross-over randomized trial recently presented at the American Heart Association meeting, showed that reducing dietary sodium was on par with medication when it came to lowering blood pressure.

For Dr. Juraschek, the evidence is clear: “If you were going to choose one, I would say the weight of the evidence is still really heavily on the sodium side.”

The Case for Potassium Supplementation

The evidence for salt restriction notwithstanding, Swapnil Hiremath, MD, MPH, from the University of Ottawa, Ontario, Canada, argued in his editorial that potassium supplementation has gotten short shrift. Though he admits the studies for potassium supplementation have been smaller and sometimes rely on observational evidence, the evidence is there. In the distal convoluted tubule, the sodium chloride cotransporter (NCC), aka the potassium switch, is turned on by low potassium levels and leads to sodium reabsorption by the kidney even in settings of high sodium intake (Figure). To nonnephrologists, renal physiology may be a black box. But if you quickly brush up on the mechanism of action of thiazide diuretics, the preceding descriptor will make more sense.

Medscape

Realistic Diets and Taste Issues

“We know that increasing potassium, decreasing sodium is useful. The question is how do we do that?” says Dr. Hiremath. Should we encourage fruit and vegetable consumption in a healthy diet, give potassium supplements, or encourage the use of low-sodium salt substitutes?

Recommending a healthier diet with more fruits and vegetables is a no-brainer. But getting people to do it is hard. In a world where fruit is more expensive than junk food is, economic realities may drive food choice regardless of our best efforts. The 4700 mg of potassium in the DASH eating plan is the equivalent of eleven bananas daily; although not impossible, it would require a substantive shift in eating patterns for most people.

Given that we prescribe iron, vitamin B12, calcium, and vitamin D to patients who need them, why not potassium tablets to help with blood pressure? Granted, there are concerns about inducing hyperkalemia. Also, why not just prescribe a proven anti-hypertensive, such as ramipril, which has the added benefit of helping with renal protection or cardiac remodeling? Dr. Hiremath points out that patients are far less reluctant to take dietary supplements. Medication is something you take when sick. A supplement is seen as “natural” and “healthy” and might be more attractive to people resistant to prescription meds.

Another drawback of oral potassium supplementation is taste. In a Consumer Reports taste test, potassium chloride fared poorly. It was bitter and had a metallic aftertaste. At least one tester wouldn’t ever consume it again. Potassium citrate is slightly more palpable.

Salt substitutes, like the 75:25 ratio of sodium to potassium used in SSaSS, may be as high as you can go for potassium in any low-sodium salt alternative. If you go any higher than that, the taste will just turn people off, suggests Dr. Hiremath.

But SsaSS, which was done in China, may not be relevant to North America. In China, most sodium is added during cooking at home, and the consumption of processed foods is low. For the typical North American, roughly three quarters of the sodium eaten is added to their food by someone else; only about 15% is added during cooking at home or at the dinner table. If you aren’t someone who cooks, buying a salt substitute is probably not going to have much impact.

Given that reality, Dr. Juraschek thinks we need to target the sodium in processed foods. “There’s just so much sodium in so many products,” he says. “When you think about public policy, it’s most expeditious for there to be more regulation about how much is added to our food supply vs trying to get people to consume eight to 12 servings of fruit.”

No Salt War Here

Despite their different editorial takes, Dr. Hiremath and Dr. Juraschek largely agree on the broad strokes of the problem. This isn’t X (or Twitter) after all. Potassium supplementation may be useful in some parts of the world but may not address the underlying problem in countries where processed foods are the source of most dietary sodium.

The CARDIA-SSBP trial showed that a very low–sodium diet had the same blood pressure–lowering effect as a first-line antihypertensive, but most people will not be able to limit themselves to 500 mg of dietary sodium per day. In CARDIA-SSBP, just as in DASH, participants were provided with meals from study kitchens. They were not just told to eat less salt, which would almost certainly have failed.

“We should aim for stuff that is practical and doable rather than aim for stuff that cannot be done,” according to Dr. Hiremath. Whether that should be salt substitutes or policy change may depend on which part of the planet you live on.

One recent positive change may herald the beginning of a policy change, at least in the United States. In March 2023, the US Food and Drug Administration proposed a rule change to allow salt substitutes to be labeled as salt. This would make it easier for food manufacturers to swap out sodium chloride for a low-sodium alternative and reduce the amount of sodium in the US diet without having a large impact on taste and consumer uptake. Both Dr. Hiremath and Dr. Juraschek agree that it may not be enough on its own but that it’s a start.

Christopher Labos is a cardiologist with a degree in epidemiology. He spends most of his time doing things that he doesn’t get paid for, like research, teaching, and podcasting. Occasionally, he finds time to practice cardiology to pay the rent. He realizes that half of his research findings will be disproved in 5 years; he just doesn’t know which half. He is a regular contributor to the Montreal Gazette, CJAD radio, and CTV television in Montreal, and is host of the award-winning podcast The Body of Evidence.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

From the year 2000 until around 2016, the incidence of breast cancer among young women — those under age 50 — rose steadily, if slowly.

JAMA Network Open

JAMA Network Open

JAMA Network Open

Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

From the year 2000 until around 2016, the incidence of breast cancer among young women — those under age 50 — rose steadily, if slowly.

JAMA Network Open

JAMA Network Open

JAMA Network Open

Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

From the year 2000 until around 2016, the incidence of breast cancer among young women — those under age 50 — rose steadily, if slowly.

JAMA Network Open

JAMA Network Open

JAMA Network Open

Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.