MDedge Rheumatology

Erosions and ankylosis in patients with sacroiliitis are detectable to a high degree of accuracy on CT images using an artificial intelligence (AI)–based algorithm, according to research presented at the 13th International Congress on Spondyloarthritides.

Lennart Jans, MD, head of clinics in musculoskeletal imaging in the department of radiology at Ghent (Belgium) University Hospital, shared data on the development and validation of the algorithm for automatic detection of erosion and ankylosis on CT images of the sacroiliac (SI) joints.

Becky McCall/MDedge News

“Essentially, in terms of statistics, this AI algorithm has 95% sensitivity for picking up erosions in patients with clinical symptoms of sacroiliitis, and if this is further developed as a tool, it could aid detection in people with erosions that would otherwise go undetected and undiagnosed,” Dr. Jans said in an interview, stressing that the results were still preliminary.

“We want to move from reporting one patient at a time to a system that detects and helps to diagnose larger numbers of patients and makes a larger impact on patient outcomes.”

He stressed that, with thousands of images per patient, it is an impossible workload for any radiology department to read every image necessary to inform diagnoses, and this is only exacerbated by the shortage of rheumatologists, especially in the United States.

Denis Poddubnyy, MD, head of rheumatology at Charité University Hospital, Berlin, acknowledged that AI has potential to improve the recognition of changes indicative of spondyloarthritis (SpA) on imaging. “A standardized, valid, and reliable detection of those changes is relevant for both diagnosis, including differential diagnosis, and classification of SpA.”

Dr. Poddubnyy added that the AI-based algorithm developed by Dr. Jans and associates is designed to detect very specific SpA structural changes in the SI joints on CT. “CT is usually applied in the clinical practice after MRI ... normally in cases where MRI does not provide conclusive results,” he said. Since MRI scans have also been recently used to develop an AI-based algorithm for the detection of active inflammation – not captured by CT – and structural changes in SI joints, he noted that the “generated data on CT should be, therefore, seen in a broader context toward standardization of imaging findings detection.”
 

Proof-of-concept findings are due for scale-up

Dr. Jans acknowledged that the current data only establish proof of concept. Among the study’s 145 patients, 60% were used for training the AI algorithm and 40% for testing it. All patients who had clinical symptoms of sacroiliitis and had undergone a SI joint CT scan were included from two hospitals: Ghent University Hospital and the University of Alberta Hospital, Edmonton. The majority of patients were female (81 of 145). They had a mean age of 40 years, 84 had diagnosed axial SpA, 15 had mechanical back pain, and 46 did not have a final diagnosis.

CT images were examined by three independent and blinded radiologists who annotated erosions more than 1 mm and ankylosis more than 2 mm, while a type of AI algorithm known as a neural network pipeline was developed to segment the SI joints and detect structural lesions.

In the first instance, Dr. Jans explained, examination of CT images using the AI algorithm from patients who enter the hospital for other reasons, such as trauma, rheumatic diseases, kidney stones, or appendicitis, might lead to the detection of otherwise unknown erosions. “Often patients have complained of backache for years, seeing various physiotherapists and similar, but had no idea what might be causing it,” he said. “We just don’t have the time for examining all the thousands of images separately. We need some kind of aid here. We need an extra pair of eyes. This is what AI software does.”

Dr. Jans said rheumatologists who ultimately want to detect and diagnose patients with SI erosions want to reduce the false-negative findings. “They want the system to pick up all the patients who have erosions. Here, the most important parameter is sensitivity, and we find that our algorithm shows a very high sensitivity. Optimization of the AI algorithm to reduce false negatives resulted in a sensitivity of 95% for detection of erosions on CT of the sacroiliac joints on a patient level.”

While overall accuracy was over 90%, Dr. Jans acknowledged that the algorithm was run in a relatively select population of dedicated CT scans of the joints. He is also aware that a good AI algorithm needs to work well across locations and populations. “If you make something within your institution alone, it will not work in a hospital on the other side of the street.”

However, he added, the researchers used images from four different CT scanners and images from two different institutions – one in Canada and their own in Belgium, providing a case mix that makes their algorithm more refined.
 

Next step: Test in an unselected population

When asked to comment on the study, Mikael Boesen, MD, PhD, of Bispebjerg and Frederiksberg Hospital, Copenhagen, congratulated Dr. Jans on the work and remarked that he found the research potentially clinically useful.

“The next steps would be to test the performance of the model in an unselected population of patients who have CT scans of the abdomen for other reasons to test the model’s ability to flag potential SI joint disease to the reader, which is often overlooked, as well as [to see] how the model performs in larger datasets from other hospitals, vendors, and CT-reconstruction algorithms.”

Finally, Dr. Boesen pointed out that it would be interesting to see if the AI algorithm can detect different reasons for erosions. “Especially [for] separation between mechanical and inflammatory courses. This could potentially be done by automatically mapping the location of the erosions in the SI joints.”

Dr. Jans has now opened up the project to other radiologists to collaborate and provide images to train and test the algorithm further. “We now have 2.4 million images that have been enriched, and we will use these in the near future as we move beyond the proof-of-concept stage.

He is looking for as for as many partners as possible to help collect enriched images and develop this into a real tool for use in hospitals worldwide on clinical patients. “We have joined forces with several hospitals but continue looking for further collaborations.

“We need, just like self-driving cars, not just thousands, but tens of thousands or millions of images to develop this.”

Dr. Jans declared receiving speaker fees from UCB, AbbVie, Lilly, and Novartis, and that he is cofounder of a future spin-off of Ghent University RheumaFinder. Dr. Poddubnyy and Dr. Boesen declared no relevant disclosures.
 

Erosions and ankylosis in patients with sacroiliitis are detectable to a high degree of accuracy on CT images using an artificial intelligence (AI)–based algorithm, according to research presented at the 13th International Congress on Spondyloarthritides.

Lennart Jans, MD, head of clinics in musculoskeletal imaging in the department of radiology at Ghent (Belgium) University Hospital, shared data on the development and validation of the algorithm for automatic detection of erosion and ankylosis on CT images of the sacroiliac (SI) joints.

Becky McCall/MDedge News

“Essentially, in terms of statistics, this AI algorithm has 95% sensitivity for picking up erosions in patients with clinical symptoms of sacroiliitis, and if this is further developed as a tool, it could aid detection in people with erosions that would otherwise go undetected and undiagnosed,” Dr. Jans said in an interview, stressing that the results were still preliminary.

“We want to move from reporting one patient at a time to a system that detects and helps to diagnose larger numbers of patients and makes a larger impact on patient outcomes.”

He stressed that, with thousands of images per patient, it is an impossible workload for any radiology department to read every image necessary to inform diagnoses, and this is only exacerbated by the shortage of rheumatologists, especially in the United States.

Denis Poddubnyy, MD, head of rheumatology at Charité University Hospital, Berlin, acknowledged that AI has potential to improve the recognition of changes indicative of spondyloarthritis (SpA) on imaging. “A standardized, valid, and reliable detection of those changes is relevant for both diagnosis, including differential diagnosis, and classification of SpA.”

Dr. Poddubnyy added that the AI-based algorithm developed by Dr. Jans and associates is designed to detect very specific SpA structural changes in the SI joints on CT. “CT is usually applied in the clinical practice after MRI ... normally in cases where MRI does not provide conclusive results,” he said. Since MRI scans have also been recently used to develop an AI-based algorithm for the detection of active inflammation – not captured by CT – and structural changes in SI joints, he noted that the “generated data on CT should be, therefore, seen in a broader context toward standardization of imaging findings detection.”
 

Proof-of-concept findings are due for scale-up

Dr. Jans acknowledged that the current data only establish proof of concept. Among the study’s 145 patients, 60% were used for training the AI algorithm and 40% for testing it. All patients who had clinical symptoms of sacroiliitis and had undergone a SI joint CT scan were included from two hospitals: Ghent University Hospital and the University of Alberta Hospital, Edmonton. The majority of patients were female (81 of 145). They had a mean age of 40 years, 84 had diagnosed axial SpA, 15 had mechanical back pain, and 46 did not have a final diagnosis.

CT images were examined by three independent and blinded radiologists who annotated erosions more than 1 mm and ankylosis more than 2 mm, while a type of AI algorithm known as a neural network pipeline was developed to segment the SI joints and detect structural lesions.

In the first instance, Dr. Jans explained, examination of CT images using the AI algorithm from patients who enter the hospital for other reasons, such as trauma, rheumatic diseases, kidney stones, or appendicitis, might lead to the detection of otherwise unknown erosions. “Often patients have complained of backache for years, seeing various physiotherapists and similar, but had no idea what might be causing it,” he said. “We just don’t have the time for examining all the thousands of images separately. We need some kind of aid here. We need an extra pair of eyes. This is what AI software does.”

Dr. Jans said rheumatologists who ultimately want to detect and diagnose patients with SI erosions want to reduce the false-negative findings. “They want the system to pick up all the patients who have erosions. Here, the most important parameter is sensitivity, and we find that our algorithm shows a very high sensitivity. Optimization of the AI algorithm to reduce false negatives resulted in a sensitivity of 95% for detection of erosions on CT of the sacroiliac joints on a patient level.”

While overall accuracy was over 90%, Dr. Jans acknowledged that the algorithm was run in a relatively select population of dedicated CT scans of the joints. He is also aware that a good AI algorithm needs to work well across locations and populations. “If you make something within your institution alone, it will not work in a hospital on the other side of the street.”

However, he added, the researchers used images from four different CT scanners and images from two different institutions – one in Canada and their own in Belgium, providing a case mix that makes their algorithm more refined.
 

Next step: Test in an unselected population

When asked to comment on the study, Mikael Boesen, MD, PhD, of Bispebjerg and Frederiksberg Hospital, Copenhagen, congratulated Dr. Jans on the work and remarked that he found the research potentially clinically useful.

“The next steps would be to test the performance of the model in an unselected population of patients who have CT scans of the abdomen for other reasons to test the model’s ability to flag potential SI joint disease to the reader, which is often overlooked, as well as [to see] how the model performs in larger datasets from other hospitals, vendors, and CT-reconstruction algorithms.”

Finally, Dr. Boesen pointed out that it would be interesting to see if the AI algorithm can detect different reasons for erosions. “Especially [for] separation between mechanical and inflammatory courses. This could potentially be done by automatically mapping the location of the erosions in the SI joints.”

Dr. Jans has now opened up the project to other radiologists to collaborate and provide images to train and test the algorithm further. “We now have 2.4 million images that have been enriched, and we will use these in the near future as we move beyond the proof-of-concept stage.

He is looking for as for as many partners as possible to help collect enriched images and develop this into a real tool for use in hospitals worldwide on clinical patients. “We have joined forces with several hospitals but continue looking for further collaborations.

“We need, just like self-driving cars, not just thousands, but tens of thousands or millions of images to develop this.”

Dr. Jans declared receiving speaker fees from UCB, AbbVie, Lilly, and Novartis, and that he is cofounder of a future spin-off of Ghent University RheumaFinder. Dr. Poddubnyy and Dr. Boesen declared no relevant disclosures.
 

Erosions and ankylosis in patients with sacroiliitis are detectable to a high degree of accuracy on CT images using an artificial intelligence (AI)–based algorithm, according to research presented at the 13th International Congress on Spondyloarthritides.

Lennart Jans, MD, head of clinics in musculoskeletal imaging in the department of radiology at Ghent (Belgium) University Hospital, shared data on the development and validation of the algorithm for automatic detection of erosion and ankylosis on CT images of the sacroiliac (SI) joints.

Becky McCall/MDedge News

“Essentially, in terms of statistics, this AI algorithm has 95% sensitivity for picking up erosions in patients with clinical symptoms of sacroiliitis, and if this is further developed as a tool, it could aid detection in people with erosions that would otherwise go undetected and undiagnosed,” Dr. Jans said in an interview, stressing that the results were still preliminary.

“We want to move from reporting one patient at a time to a system that detects and helps to diagnose larger numbers of patients and makes a larger impact on patient outcomes.”

He stressed that, with thousands of images per patient, it is an impossible workload for any radiology department to read every image necessary to inform diagnoses, and this is only exacerbated by the shortage of rheumatologists, especially in the United States.

Denis Poddubnyy, MD, head of rheumatology at Charité University Hospital, Berlin, acknowledged that AI has potential to improve the recognition of changes indicative of spondyloarthritis (SpA) on imaging. “A standardized, valid, and reliable detection of those changes is relevant for both diagnosis, including differential diagnosis, and classification of SpA.”

Dr. Poddubnyy added that the AI-based algorithm developed by Dr. Jans and associates is designed to detect very specific SpA structural changes in the SI joints on CT. “CT is usually applied in the clinical practice after MRI ... normally in cases where MRI does not provide conclusive results,” he said. Since MRI scans have also been recently used to develop an AI-based algorithm for the detection of active inflammation – not captured by CT – and structural changes in SI joints, he noted that the “generated data on CT should be, therefore, seen in a broader context toward standardization of imaging findings detection.”
 

Proof-of-concept findings are due for scale-up

Dr. Jans acknowledged that the current data only establish proof of concept. Among the study’s 145 patients, 60% were used for training the AI algorithm and 40% for testing it. All patients who had clinical symptoms of sacroiliitis and had undergone a SI joint CT scan were included from two hospitals: Ghent University Hospital and the University of Alberta Hospital, Edmonton. The majority of patients were female (81 of 145). They had a mean age of 40 years, 84 had diagnosed axial SpA, 15 had mechanical back pain, and 46 did not have a final diagnosis.

CT images were examined by three independent and blinded radiologists who annotated erosions more than 1 mm and ankylosis more than 2 mm, while a type of AI algorithm known as a neural network pipeline was developed to segment the SI joints and detect structural lesions.

In the first instance, Dr. Jans explained, examination of CT images using the AI algorithm from patients who enter the hospital for other reasons, such as trauma, rheumatic diseases, kidney stones, or appendicitis, might lead to the detection of otherwise unknown erosions. “Often patients have complained of backache for years, seeing various physiotherapists and similar, but had no idea what might be causing it,” he said. “We just don’t have the time for examining all the thousands of images separately. We need some kind of aid here. We need an extra pair of eyes. This is what AI software does.”

Dr. Jans said rheumatologists who ultimately want to detect and diagnose patients with SI erosions want to reduce the false-negative findings. “They want the system to pick up all the patients who have erosions. Here, the most important parameter is sensitivity, and we find that our algorithm shows a very high sensitivity. Optimization of the AI algorithm to reduce false negatives resulted in a sensitivity of 95% for detection of erosions on CT of the sacroiliac joints on a patient level.”

While overall accuracy was over 90%, Dr. Jans acknowledged that the algorithm was run in a relatively select population of dedicated CT scans of the joints. He is also aware that a good AI algorithm needs to work well across locations and populations. “If you make something within your institution alone, it will not work in a hospital on the other side of the street.”

However, he added, the researchers used images from four different CT scanners and images from two different institutions – one in Canada and their own in Belgium, providing a case mix that makes their algorithm more refined.
 

Next step: Test in an unselected population

When asked to comment on the study, Mikael Boesen, MD, PhD, of Bispebjerg and Frederiksberg Hospital, Copenhagen, congratulated Dr. Jans on the work and remarked that he found the research potentially clinically useful.

“The next steps would be to test the performance of the model in an unselected population of patients who have CT scans of the abdomen for other reasons to test the model’s ability to flag potential SI joint disease to the reader, which is often overlooked, as well as [to see] how the model performs in larger datasets from other hospitals, vendors, and CT-reconstruction algorithms.”

Finally, Dr. Boesen pointed out that it would be interesting to see if the AI algorithm can detect different reasons for erosions. “Especially [for] separation between mechanical and inflammatory courses. This could potentially be done by automatically mapping the location of the erosions in the SI joints.”

Dr. Jans has now opened up the project to other radiologists to collaborate and provide images to train and test the algorithm further. “We now have 2.4 million images that have been enriched, and we will use these in the near future as we move beyond the proof-of-concept stage.

He is looking for as for as many partners as possible to help collect enriched images and develop this into a real tool for use in hospitals worldwide on clinical patients. “We have joined forces with several hospitals but continue looking for further collaborations.

“We need, just like self-driving cars, not just thousands, but tens of thousands or millions of images to develop this.”

Dr. Jans declared receiving speaker fees from UCB, AbbVie, Lilly, and Novartis, and that he is cofounder of a future spin-off of Ghent University RheumaFinder. Dr. Poddubnyy and Dr. Boesen declared no relevant disclosures.
 

A new study provides evidence that two conditions that fall under the umbrella of spondyloarthritis – isolated axial disease in patients with psoriatic arthritis (PsA) and isolated axial disease in patients with ankylosing spondylitis (AS) accompanied by psoriasis – are different clinical entities and may need different treatments. These relatively rare rheumatologic conditions, defined by their back involvement, have considerable clinical overlap and are often lumped together under the label axial spondyloarthritis.

This is a hot topic and current matter of debate within the scientific community: Are axial PsA and axial AS two separate diseases or just two phenotypes under the spondyloarthritis umbrella? said Fabian Proft, MD, a rheumatologist and researcher at Charité Universitätsmedizin Berlin, commenting on the new study, which was published online in Annals of the Rheumatic Diseases.

Both conditions belong to the spectrum of spondyloarthritis, but with varying viewpoints on nomenclature. They have intersections and overlaps, but not all treatments are equally effective for both. “We need to better understand their differences and similarities,” Dr. Proft said, adding that the new study is noteworthy for the size of the population included, its long-term follow-up data, and the researchers’ depth of experience treating these patients.

The researchers are based at the University of Toronto, which has separate clinics dedicated to PsA and to AS, said Dafna D. Gladman, MD, professor of medicine at the university, codirector of the PsA clinic, and corresponding author for the new study. The two clinics follow the same standardized protocols, including clinical, radiographic, genetic, and laboratory assessments. Even though the patients present quite similarly, she credits referring physicians for recognizing the distinctions by their referrals to the PsA or AS clinic.

According to previous research, pure axial PsA, without peripheral involvement, is rare, affecting about 2%-5% of patients with PsA. For this study, an observational cohort of 1,576 patients from the PsA clinic included 31% (n = 495) with axial disease, 2% (n = 32) with isolated axial PsA, and 29% (n = 463) with both axial and peripheral involvement. A total of 25 of the patients with isolated axial PsA ultimately developed peripheral disease by their most recent clinic follow-up visit. In a second cohort of 1,688 patients with AS, nearly 5% (n = 68) had isolated axial disease with psoriasis.

“In our logistic regression analysis, isolated axial PsA was found to be a different clinical entity than isolated AS with psoriasis. They are not the same patients,” Dr. Gladman said. The patients with isolated axial PsA were older at diagnosis, more likely to have psoriatic nail lesions, and less likely to have inflammatory back pain than were patients with isolated axial AS and accompanying psoriasis.

When interviewed in early September, Dr. Gladman was preparing to fly to Ghent, Belgium, to participate in a debate at the International Congress on Spondyloarthritides, taking the pro position on the thesis: Is axial inflammation in PsA distinct from axial spondyloarthritis? Taking the con position was to be Robert Landewé, MD, PhD, of Amsterdam University Medical Center in the Netherlands.

“This is an old debate, splitters versus lumpers,” Dr. Gladman told this news organization. “My message is that when you place patients in more homogeneous groups, you can learn more and perhaps find better opportunities for treating their disease.” For example, even with the similarities, do these patients need to be treated with different medications? Medications for psoriasis, including those targeting the interleukin-23 cytokine, may not be effective for AS, but patients with axial PsA may not get them because of the association with axial AS.

“Now is the opportunity to really understand what – if any – are the differences between various components of this disease group. If you lump people together, you may miss the forest for the trees,” Dr. Gladman said. “If, at the end of the day, we find out these patients essentially are the same, I will lump. But until we have proved that there are no important differences, I will split.” She added that it is important for practicing rheumatologists to make the correct diagnosis so that they know to access certain drugs.

Dr. Proft credited Dr. Gladman and colleagues’ study for adding another piece of the puzzle to better understand differences and similarities for these two axial diseases. He noted, however, that the study did not include MRI scans for every participating patient, which could have given a deeper picture.

“International efforts are being made to recruit patients for a multinational, multicenter study of axial involvement in PsA,” which will include MRI data, Dr. Gladman said. She and Dr. Proft are both part of AXIS, the Axial Involvement in Psoriatic Arthritis cohort, now recruiting patients for such a study. AXIS is a joint project of the Assessment of SpondyloArthritis international Society and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

“We don’t have final answers yet, although we have given evidence to support the differences.” The proof is in the pudding, she said, and that pudding will be the clinical trials.

The University of Toronto Psoriatic Arthritis Program is supported by a grant from the Krembil Foundation. The study authors declared no competing interests. Dr. Proft reported receiving research support from Novartis, Eli Lilly, and UCB, and fees for consulting and serving on speakers bureaus from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Hexal, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB.

A new study provides evidence that two conditions that fall under the umbrella of spondyloarthritis – isolated axial disease in patients with psoriatic arthritis (PsA) and isolated axial disease in patients with ankylosing spondylitis (AS) accompanied by psoriasis – are different clinical entities and may need different treatments. These relatively rare rheumatologic conditions, defined by their back involvement, have considerable clinical overlap and are often lumped together under the label axial spondyloarthritis.

This is a hot topic and current matter of debate within the scientific community: Are axial PsA and axial AS two separate diseases or just two phenotypes under the spondyloarthritis umbrella? said Fabian Proft, MD, a rheumatologist and researcher at Charité Universitätsmedizin Berlin, commenting on the new study, which was published online in Annals of the Rheumatic Diseases.

Both conditions belong to the spectrum of spondyloarthritis, but with varying viewpoints on nomenclature. They have intersections and overlaps, but not all treatments are equally effective for both. “We need to better understand their differences and similarities,” Dr. Proft said, adding that the new study is noteworthy for the size of the population included, its long-term follow-up data, and the researchers’ depth of experience treating these patients.

The researchers are based at the University of Toronto, which has separate clinics dedicated to PsA and to AS, said Dafna D. Gladman, MD, professor of medicine at the university, codirector of the PsA clinic, and corresponding author for the new study. The two clinics follow the same standardized protocols, including clinical, radiographic, genetic, and laboratory assessments. Even though the patients present quite similarly, she credits referring physicians for recognizing the distinctions by their referrals to the PsA or AS clinic.

According to previous research, pure axial PsA, without peripheral involvement, is rare, affecting about 2%-5% of patients with PsA. For this study, an observational cohort of 1,576 patients from the PsA clinic included 31% (n = 495) with axial disease, 2% (n = 32) with isolated axial PsA, and 29% (n = 463) with both axial and peripheral involvement. A total of 25 of the patients with isolated axial PsA ultimately developed peripheral disease by their most recent clinic follow-up visit. In a second cohort of 1,688 patients with AS, nearly 5% (n = 68) had isolated axial disease with psoriasis.

“In our logistic regression analysis, isolated axial PsA was found to be a different clinical entity than isolated AS with psoriasis. They are not the same patients,” Dr. Gladman said. The patients with isolated axial PsA were older at diagnosis, more likely to have psoriatic nail lesions, and less likely to have inflammatory back pain than were patients with isolated axial AS and accompanying psoriasis.

When interviewed in early September, Dr. Gladman was preparing to fly to Ghent, Belgium, to participate in a debate at the International Congress on Spondyloarthritides, taking the pro position on the thesis: Is axial inflammation in PsA distinct from axial spondyloarthritis? Taking the con position was to be Robert Landewé, MD, PhD, of Amsterdam University Medical Center in the Netherlands.

“This is an old debate, splitters versus lumpers,” Dr. Gladman told this news organization. “My message is that when you place patients in more homogeneous groups, you can learn more and perhaps find better opportunities for treating their disease.” For example, even with the similarities, do these patients need to be treated with different medications? Medications for psoriasis, including those targeting the interleukin-23 cytokine, may not be effective for AS, but patients with axial PsA may not get them because of the association with axial AS.

“Now is the opportunity to really understand what – if any – are the differences between various components of this disease group. If you lump people together, you may miss the forest for the trees,” Dr. Gladman said. “If, at the end of the day, we find out these patients essentially are the same, I will lump. But until we have proved that there are no important differences, I will split.” She added that it is important for practicing rheumatologists to make the correct diagnosis so that they know to access certain drugs.

Dr. Proft credited Dr. Gladman and colleagues’ study for adding another piece of the puzzle to better understand differences and similarities for these two axial diseases. He noted, however, that the study did not include MRI scans for every participating patient, which could have given a deeper picture.

“International efforts are being made to recruit patients for a multinational, multicenter study of axial involvement in PsA,” which will include MRI data, Dr. Gladman said. She and Dr. Proft are both part of AXIS, the Axial Involvement in Psoriatic Arthritis cohort, now recruiting patients for such a study. AXIS is a joint project of the Assessment of SpondyloArthritis international Society and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

“We don’t have final answers yet, although we have given evidence to support the differences.” The proof is in the pudding, she said, and that pudding will be the clinical trials.

The University of Toronto Psoriatic Arthritis Program is supported by a grant from the Krembil Foundation. The study authors declared no competing interests. Dr. Proft reported receiving research support from Novartis, Eli Lilly, and UCB, and fees for consulting and serving on speakers bureaus from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Hexal, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB.

A new study provides evidence that two conditions that fall under the umbrella of spondyloarthritis – isolated axial disease in patients with psoriatic arthritis (PsA) and isolated axial disease in patients with ankylosing spondylitis (AS) accompanied by psoriasis – are different clinical entities and may need different treatments. These relatively rare rheumatologic conditions, defined by their back involvement, have considerable clinical overlap and are often lumped together under the label axial spondyloarthritis.

This is a hot topic and current matter of debate within the scientific community: Are axial PsA and axial AS two separate diseases or just two phenotypes under the spondyloarthritis umbrella? said Fabian Proft, MD, a rheumatologist and researcher at Charité Universitätsmedizin Berlin, commenting on the new study, which was published online in Annals of the Rheumatic Diseases.

Both conditions belong to the spectrum of spondyloarthritis, but with varying viewpoints on nomenclature. They have intersections and overlaps, but not all treatments are equally effective for both. “We need to better understand their differences and similarities,” Dr. Proft said, adding that the new study is noteworthy for the size of the population included, its long-term follow-up data, and the researchers’ depth of experience treating these patients.

The researchers are based at the University of Toronto, which has separate clinics dedicated to PsA and to AS, said Dafna D. Gladman, MD, professor of medicine at the university, codirector of the PsA clinic, and corresponding author for the new study. The two clinics follow the same standardized protocols, including clinical, radiographic, genetic, and laboratory assessments. Even though the patients present quite similarly, she credits referring physicians for recognizing the distinctions by their referrals to the PsA or AS clinic.

According to previous research, pure axial PsA, without peripheral involvement, is rare, affecting about 2%-5% of patients with PsA. For this study, an observational cohort of 1,576 patients from the PsA clinic included 31% (n = 495) with axial disease, 2% (n = 32) with isolated axial PsA, and 29% (n = 463) with both axial and peripheral involvement. A total of 25 of the patients with isolated axial PsA ultimately developed peripheral disease by their most recent clinic follow-up visit. In a second cohort of 1,688 patients with AS, nearly 5% (n = 68) had isolated axial disease with psoriasis.

“In our logistic regression analysis, isolated axial PsA was found to be a different clinical entity than isolated AS with psoriasis. They are not the same patients,” Dr. Gladman said. The patients with isolated axial PsA were older at diagnosis, more likely to have psoriatic nail lesions, and less likely to have inflammatory back pain than were patients with isolated axial AS and accompanying psoriasis.

When interviewed in early September, Dr. Gladman was preparing to fly to Ghent, Belgium, to participate in a debate at the International Congress on Spondyloarthritides, taking the pro position on the thesis: Is axial inflammation in PsA distinct from axial spondyloarthritis? Taking the con position was to be Robert Landewé, MD, PhD, of Amsterdam University Medical Center in the Netherlands.

“This is an old debate, splitters versus lumpers,” Dr. Gladman told this news organization. “My message is that when you place patients in more homogeneous groups, you can learn more and perhaps find better opportunities for treating their disease.” For example, even with the similarities, do these patients need to be treated with different medications? Medications for psoriasis, including those targeting the interleukin-23 cytokine, may not be effective for AS, but patients with axial PsA may not get them because of the association with axial AS.

“Now is the opportunity to really understand what – if any – are the differences between various components of this disease group. If you lump people together, you may miss the forest for the trees,” Dr. Gladman said. “If, at the end of the day, we find out these patients essentially are the same, I will lump. But until we have proved that there are no important differences, I will split.” She added that it is important for practicing rheumatologists to make the correct diagnosis so that they know to access certain drugs.

Dr. Proft credited Dr. Gladman and colleagues’ study for adding another piece of the puzzle to better understand differences and similarities for these two axial diseases. He noted, however, that the study did not include MRI scans for every participating patient, which could have given a deeper picture.

“International efforts are being made to recruit patients for a multinational, multicenter study of axial involvement in PsA,” which will include MRI data, Dr. Gladman said. She and Dr. Proft are both part of AXIS, the Axial Involvement in Psoriatic Arthritis cohort, now recruiting patients for such a study. AXIS is a joint project of the Assessment of SpondyloArthritis international Society and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

“We don’t have final answers yet, although we have given evidence to support the differences.” The proof is in the pudding, she said, and that pudding will be the clinical trials.

The University of Toronto Psoriatic Arthritis Program is supported by a grant from the Krembil Foundation. The study authors declared no competing interests. Dr. Proft reported receiving research support from Novartis, Eli Lilly, and UCB, and fees for consulting and serving on speakers bureaus from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Hexal, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB.

Good news for pregnant women; bad news for fish

As soon as women find out they’re pregnant, doctors recommend they give up smoking, drinking, and eating certain types of fish. That last item may need to be reconsidered, since a recent study supports the idea that it doesn’t matter what type of fish pregnant women are eating, as long as they’re eating it.

franckreporter/Getty Images

Researchers collected data from two different studies that reviewed the mercury levels of mothers from Bristol, England, and the Seychelles, a island chain off East Africa where “fish consumption is high and prenatal mercury levels are 10 times higher than in the [United States],” they said in NeuroToxicology.

Those data showed that the mercury levels had no adverse effects on child development as long as the mother ate fish. The nutrients and vitamins in the fish – vitamin D, long-chain fatty acids, selenium, and iodine – provide protection against mercury. There’s also the already-known benefits to eyesight and intellectual abilities that have been associated with fish consumption.

This analysis goes starkly against the grain of what is commonly recommended to expectant mothers, which is to cut out fish altogether. The researchers suggested that governments should review and change those recommendations to focus on the benefits instead.

As long as women follow the researchers’ recommendation to eat “at least two portions of fish a week, one of which should be oily,” they may not have to lay off on the sushi after all.
 

We’ll show our gut worms the world

Never let it be said that mankind is not a generous species. Sure, we could maybe be kinder to our fellow human beings, maybe declare a little less war on each other, but for the past 50,000 years, we’ve been giving a free ride to millions upon millions to one of mankind’s closest companions: the whipworm.

oksmith/openclipart.org

This revelation into human kindness comes from Denmark, where researchers from Copenhagen conducted a genetic analysis of ancient preserved whipworm eggs found in old Viking and Norse settlements, some of which date back over 2,000 years. In normal conditions genetic material wouldn’t last very long, but these were Viking whipworms eggs with tiny little horned helmets, so the DNA within has remained unchanged. Or it may be the tough chitinous exterior of the eggs protecting the DNA from degrading, combined with their preservation in moist soil.

Once they had their Viking whipworm DNA, the researchers compared it with whipworm DNA from all over the world, tracing its history as it followed mankind from Africa. And it’s been a while: We brought whipworms with us during our initial migration into Asia and Europe over 50,000 years ago. When the Bering land bridge opened up and humanity moved into the Americas, the worms came as well.

This is all possible because the whipworm goes about its parasitic business quietly and cleverly. It mostly sits harmlessly in our digestive systems, producing thousands of eggs a day that get expelled through poop and picked up by another host (human or otherwise); whipworms only cause disease in those with compromised immune systems.

The researchers noted that their study, the first complete genetic analysis of the whipworm, could help combat the parasite, which to this day infects hundred of millions who don’t have access to modern medicine or sanitary conditions. Hopefully, though, the days of free rides will soon be over for the whipworm. After all, if we have to pay hundreds or thousands of dollars to visit other countries, it’s only fair that our parasites do as well.
 

From zero to vasectomy in 6.7 seconds

There’s an old saying that you’ve probably heard: When life gives you lemons, make lemonade. It’s meant to encourage optimism in the face of adversity. Then there’s the new saying we just made up: When life gives you a power outage, plug your surgical instruments into an electric pickup.

Rivian

That’s what Dr. Christopher Yang did, and now we’re making the urologist from Austin, Tex., famous by sharing his surgical/electrical adventure with all 17 of LOTME’s regular readers. That’s some serious lemonade.

Dr. Yang’s tale begins when the electricity went out at his clinic, seemingly forcing him to cancel or reschedule several surgical procedures. Not so fast. Dr. Yang happens to own a Rivian R1T, an electric pickup truck that has four power outlets. A staff member suggested plugging the surgical instruments into the truck and, surprisingly, one of the day’s patients agreed to go ahead with his vasectomy.

“We were fortunate that my normal parking spot is close enough to a patient room to run an extension cord,” Dr. Yang said on TheDrive.com. That extension cord was attached to an electrocautery device, with a handheld device available as backup, and “after we were done, I told his family. We all had a good laugh together too,” Dr. Yang told radio station WGLT in Normal, Ill.

To us, anyway, this opens up all sorts of alternative energy possibilities. Can a windmill power a liposuction? Is a gerbil running in a wheel enough to do a colonoscopy? How many potatoes do you need to keep an EHR going?
 

Learning through random acts of not-exactly noisiness

First things first. Transcranial random noise stimulation (tRNS) is not really noise in the auditory sense of the word. For some people with learning disabilities, though, it can actually be very helpful. The technology, which uses electrodes attached to the head so a weak current can pass through specific parts of the brain, may help those with learning disabilities, perhaps even those with brain injuries and visual deficits, learn, said Dr. Onno van der Groen of Edith Cowan University in Perth, Australia.

littlehenrabi/Getty Images

“When you add this type of stimulation during learning, you get better performance, faster learning and better attention afterwards as well,” he said in a statement from the university.

The researchers say that tRNS can allow the brain to form new connections and pathways, which in turn help a person learn more effectively. “If you do 10 sessions of a visual perception task with the tRNS and then come back and do it again without it, you’ll find you perform better than the control group who hasn’t used it,” Dr. van der Groen noted.

Can this also work for the average person? It’s possible, but tRNS didn’t seem to improve the math skills of a top-level mathematician who underwent the process, according to a case study that Dr. van der Groen mentioned.

This line of work is still pretty new, though, so researchers don’t have all the answers yet. As always, we’re rooting for you, science!

Good news for pregnant women; bad news for fish

As soon as women find out they’re pregnant, doctors recommend they give up smoking, drinking, and eating certain types of fish. That last item may need to be reconsidered, since a recent study supports the idea that it doesn’t matter what type of fish pregnant women are eating, as long as they’re eating it.

franckreporter/Getty Images

Researchers collected data from two different studies that reviewed the mercury levels of mothers from Bristol, England, and the Seychelles, a island chain off East Africa where “fish consumption is high and prenatal mercury levels are 10 times higher than in the [United States],” they said in NeuroToxicology.

Those data showed that the mercury levels had no adverse effects on child development as long as the mother ate fish. The nutrients and vitamins in the fish – vitamin D, long-chain fatty acids, selenium, and iodine – provide protection against mercury. There’s also the already-known benefits to eyesight and intellectual abilities that have been associated with fish consumption.

This analysis goes starkly against the grain of what is commonly recommended to expectant mothers, which is to cut out fish altogether. The researchers suggested that governments should review and change those recommendations to focus on the benefits instead.

As long as women follow the researchers’ recommendation to eat “at least two portions of fish a week, one of which should be oily,” they may not have to lay off on the sushi after all.
 

We’ll show our gut worms the world

Never let it be said that mankind is not a generous species. Sure, we could maybe be kinder to our fellow human beings, maybe declare a little less war on each other, but for the past 50,000 years, we’ve been giving a free ride to millions upon millions to one of mankind’s closest companions: the whipworm.

oksmith/openclipart.org

This revelation into human kindness comes from Denmark, where researchers from Copenhagen conducted a genetic analysis of ancient preserved whipworm eggs found in old Viking and Norse settlements, some of which date back over 2,000 years. In normal conditions genetic material wouldn’t last very long, but these were Viking whipworms eggs with tiny little horned helmets, so the DNA within has remained unchanged. Or it may be the tough chitinous exterior of the eggs protecting the DNA from degrading, combined with their preservation in moist soil.

Once they had their Viking whipworm DNA, the researchers compared it with whipworm DNA from all over the world, tracing its history as it followed mankind from Africa. And it’s been a while: We brought whipworms with us during our initial migration into Asia and Europe over 50,000 years ago. When the Bering land bridge opened up and humanity moved into the Americas, the worms came as well.

This is all possible because the whipworm goes about its parasitic business quietly and cleverly. It mostly sits harmlessly in our digestive systems, producing thousands of eggs a day that get expelled through poop and picked up by another host (human or otherwise); whipworms only cause disease in those with compromised immune systems.

The researchers noted that their study, the first complete genetic analysis of the whipworm, could help combat the parasite, which to this day infects hundred of millions who don’t have access to modern medicine or sanitary conditions. Hopefully, though, the days of free rides will soon be over for the whipworm. After all, if we have to pay hundreds or thousands of dollars to visit other countries, it’s only fair that our parasites do as well.
 

From zero to vasectomy in 6.7 seconds

There’s an old saying that you’ve probably heard: When life gives you lemons, make lemonade. It’s meant to encourage optimism in the face of adversity. Then there’s the new saying we just made up: When life gives you a power outage, plug your surgical instruments into an electric pickup.

Rivian

That’s what Dr. Christopher Yang did, and now we’re making the urologist from Austin, Tex., famous by sharing his surgical/electrical adventure with all 17 of LOTME’s regular readers. That’s some serious lemonade.

Dr. Yang’s tale begins when the electricity went out at his clinic, seemingly forcing him to cancel or reschedule several surgical procedures. Not so fast. Dr. Yang happens to own a Rivian R1T, an electric pickup truck that has four power outlets. A staff member suggested plugging the surgical instruments into the truck and, surprisingly, one of the day’s patients agreed to go ahead with his vasectomy.

“We were fortunate that my normal parking spot is close enough to a patient room to run an extension cord,” Dr. Yang said on TheDrive.com. That extension cord was attached to an electrocautery device, with a handheld device available as backup, and “after we were done, I told his family. We all had a good laugh together too,” Dr. Yang told radio station WGLT in Normal, Ill.

To us, anyway, this opens up all sorts of alternative energy possibilities. Can a windmill power a liposuction? Is a gerbil running in a wheel enough to do a colonoscopy? How many potatoes do you need to keep an EHR going?
 

Learning through random acts of not-exactly noisiness

First things first. Transcranial random noise stimulation (tRNS) is not really noise in the auditory sense of the word. For some people with learning disabilities, though, it can actually be very helpful. The technology, which uses electrodes attached to the head so a weak current can pass through specific parts of the brain, may help those with learning disabilities, perhaps even those with brain injuries and visual deficits, learn, said Dr. Onno van der Groen of Edith Cowan University in Perth, Australia.

littlehenrabi/Getty Images

“When you add this type of stimulation during learning, you get better performance, faster learning and better attention afterwards as well,” he said in a statement from the university.

The researchers say that tRNS can allow the brain to form new connections and pathways, which in turn help a person learn more effectively. “If you do 10 sessions of a visual perception task with the tRNS and then come back and do it again without it, you’ll find you perform better than the control group who hasn’t used it,” Dr. van der Groen noted.

Can this also work for the average person? It’s possible, but tRNS didn’t seem to improve the math skills of a top-level mathematician who underwent the process, according to a case study that Dr. van der Groen mentioned.

This line of work is still pretty new, though, so researchers don’t have all the answers yet. As always, we’re rooting for you, science!

Good news for pregnant women; bad news for fish

As soon as women find out they’re pregnant, doctors recommend they give up smoking, drinking, and eating certain types of fish. That last item may need to be reconsidered, since a recent study supports the idea that it doesn’t matter what type of fish pregnant women are eating, as long as they’re eating it.

franckreporter/Getty Images

Researchers collected data from two different studies that reviewed the mercury levels of mothers from Bristol, England, and the Seychelles, a island chain off East Africa where “fish consumption is high and prenatal mercury levels are 10 times higher than in the [United States],” they said in NeuroToxicology.

Those data showed that the mercury levels had no adverse effects on child development as long as the mother ate fish. The nutrients and vitamins in the fish – vitamin D, long-chain fatty acids, selenium, and iodine – provide protection against mercury. There’s also the already-known benefits to eyesight and intellectual abilities that have been associated with fish consumption.

This analysis goes starkly against the grain of what is commonly recommended to expectant mothers, which is to cut out fish altogether. The researchers suggested that governments should review and change those recommendations to focus on the benefits instead.

As long as women follow the researchers’ recommendation to eat “at least two portions of fish a week, one of which should be oily,” they may not have to lay off on the sushi after all.
 

We’ll show our gut worms the world

Never let it be said that mankind is not a generous species. Sure, we could maybe be kinder to our fellow human beings, maybe declare a little less war on each other, but for the past 50,000 years, we’ve been giving a free ride to millions upon millions to one of mankind’s closest companions: the whipworm.

oksmith/openclipart.org

This revelation into human kindness comes from Denmark, where researchers from Copenhagen conducted a genetic analysis of ancient preserved whipworm eggs found in old Viking and Norse settlements, some of which date back over 2,000 years. In normal conditions genetic material wouldn’t last very long, but these were Viking whipworms eggs with tiny little horned helmets, so the DNA within has remained unchanged. Or it may be the tough chitinous exterior of the eggs protecting the DNA from degrading, combined with their preservation in moist soil.

Once they had their Viking whipworm DNA, the researchers compared it with whipworm DNA from all over the world, tracing its history as it followed mankind from Africa. And it’s been a while: We brought whipworms with us during our initial migration into Asia and Europe over 50,000 years ago. When the Bering land bridge opened up and humanity moved into the Americas, the worms came as well.

This is all possible because the whipworm goes about its parasitic business quietly and cleverly. It mostly sits harmlessly in our digestive systems, producing thousands of eggs a day that get expelled through poop and picked up by another host (human or otherwise); whipworms only cause disease in those with compromised immune systems.

The researchers noted that their study, the first complete genetic analysis of the whipworm, could help combat the parasite, which to this day infects hundred of millions who don’t have access to modern medicine or sanitary conditions. Hopefully, though, the days of free rides will soon be over for the whipworm. After all, if we have to pay hundreds or thousands of dollars to visit other countries, it’s only fair that our parasites do as well.
 

From zero to vasectomy in 6.7 seconds

There’s an old saying that you’ve probably heard: When life gives you lemons, make lemonade. It’s meant to encourage optimism in the face of adversity. Then there’s the new saying we just made up: When life gives you a power outage, plug your surgical instruments into an electric pickup.

Rivian

That’s what Dr. Christopher Yang did, and now we’re making the urologist from Austin, Tex., famous by sharing his surgical/electrical adventure with all 17 of LOTME’s regular readers. That’s some serious lemonade.

Dr. Yang’s tale begins when the electricity went out at his clinic, seemingly forcing him to cancel or reschedule several surgical procedures. Not so fast. Dr. Yang happens to own a Rivian R1T, an electric pickup truck that has four power outlets. A staff member suggested plugging the surgical instruments into the truck and, surprisingly, one of the day’s patients agreed to go ahead with his vasectomy.

“We were fortunate that my normal parking spot is close enough to a patient room to run an extension cord,” Dr. Yang said on TheDrive.com. That extension cord was attached to an electrocautery device, with a handheld device available as backup, and “after we were done, I told his family. We all had a good laugh together too,” Dr. Yang told radio station WGLT in Normal, Ill.

To us, anyway, this opens up all sorts of alternative energy possibilities. Can a windmill power a liposuction? Is a gerbil running in a wheel enough to do a colonoscopy? How many potatoes do you need to keep an EHR going?
 

Learning through random acts of not-exactly noisiness

First things first. Transcranial random noise stimulation (tRNS) is not really noise in the auditory sense of the word. For some people with learning disabilities, though, it can actually be very helpful. The technology, which uses electrodes attached to the head so a weak current can pass through specific parts of the brain, may help those with learning disabilities, perhaps even those with brain injuries and visual deficits, learn, said Dr. Onno van der Groen of Edith Cowan University in Perth, Australia.

littlehenrabi/Getty Images

“When you add this type of stimulation during learning, you get better performance, faster learning and better attention afterwards as well,” he said in a statement from the university.

The researchers say that tRNS can allow the brain to form new connections and pathways, which in turn help a person learn more effectively. “If you do 10 sessions of a visual perception task with the tRNS and then come back and do it again without it, you’ll find you perform better than the control group who hasn’t used it,” Dr. van der Groen noted.

Can this also work for the average person? It’s possible, but tRNS didn’t seem to improve the math skills of a top-level mathematician who underwent the process, according to a case study that Dr. van der Groen mentioned.

This line of work is still pretty new, though, so researchers don’t have all the answers yet. As always, we’re rooting for you, science!

Recruiting health care workers is a challenge these days for both private practice and hospital employers, and competition can be fierce. In order to be competitive, employers need to review the package they are offering potential candidates and understand that it’s more than just compensation and benefits that matter.

When all else is equal, contract language can end up being the difference between capturing or losing a candidate.

As someone who reviews physician contracts extensively, there are some common examples of language that may cause a candidate to choose a different position.
 

Probationary period

Although every employer wants to find out if they like the physician or midlevel employee that they have just hired before fully committing, the inclusion of a probationary period (usually 90 days) is offensive to a candidate, especially one with a choice of contracts.

Essentially, the employer is asking the employee to (potentially) relocate, go through the credentialing process, and turn down other potential offers, all for the possibility that they could easily be terminated. Probationary periods typically allow an employee to be immediately terminated without notice or cause, which can then leave them stranded without a paycheck (and with a new home and/or other recent commitments).

Moreover, contracts with probationary periods tend to terminate the employee without covering any tail costs or clarifying that the employer will not enforce restrictive provisions (even if unlikely to be legally enforceable based on the short relationship).

It is important to understand that the process of a person finding a new position, which includes interviewing, contract negotiation, and credentialing, can take up to 6 months. For this reason, probationary provisions create real job insecurity for a candidate.

Entering into a new affiliation is a leap of faith both for the employer and the employee. If the circumstances do not work out, the employer should fairly compensate the employee for the notice period and ask them not to return to work or otherwise allow them to keep working the notice period while they search for a new position.
 

Acceleration of notice

Another objectionable provision that employers like to include in their contracts is one which allows the employer to accelerate and immediately terminate an employee who has given proper notice.

The contract will contain a standard notice provision, but when the health care professional submits notice, their last date is suddenly accelerated, and they are released without further compensation, notice, or benefits. This type of provision is particularly offensive to health care employees who take the step of giving proper contractual notice and, similar to the probationary language, can create real job insecurity for an employee who suddenly loses their paycheck and has no new job to start.

Medical workers should be paid for the entire notice period whether or not they are allowed to work. Unfortunately, this type of provision is sometimes hidden in contracts and not noticed by employees, who tend to focus on the notice provision itself. I consider this provision to be a red flag about the employer when I review clients’ contracts.
 

Malpractice tail

Although many employers will claim it is not unusual for an employee to pay for their own malpractice tail, in the current marketplace, the payment of tail can be a deciding factor in whether a candidate accepts a contract.

At a minimum, employers should consider paying for the tail under circumstances where they non-renew a contract, terminate without cause, or the contract is terminated for the employer’s breach. Similarly, I like to seek out payment of the tail by the employer where the contract is terminated owing to a change in the law, use of a force majeure provision, loss of the employer’s hospital contract, or similar provisions where termination is outside the control of the employee.

Employers should also consider a provision where they share the cost of a tail or cover the entire cost on the basis of years of service in order to stand out to a potential candidate.
 

Noncompete provisions

I do not find noncompete provisions to be generally unacceptable when properly written; however, employers should reevaluate the reasonableness of their noncompete language frequently, because such language can make the difference in whether a candidate accepts a contract.

A reasonable noncompete that only protects the employer as necessary and does not restrict the reasonable practice of medicine is always preferable and can be the deciding factor for a candidate. Tying enforcement of a noncompete to reasons for termination (similar to the tail) can also make a positive difference in a candidate’s review of a contract.

Egregious noncompetes, where the candidate is simply informed that the language is “not negotiable,” are unlikely to be compelling to a candidate with other options.
 

Specifics on location, call, schedule

One item potential employees find extremely frustrating about contracts is when it fails to include promises made regarding location, call, and schedule.

These particular items affect a physician’s expectations about a job, including commute time, family life, and lifestyle. An employer or recruiter that makes a lot of promises on these points but won’t commit to the details in writing (or at least offer mutual agreement on these issues) can cause an uncertain candidate to choose the job that offers greater certainty.

There are many provisions of a contract that can make a difference to a particular job applicant. A savvy employer seeking to capture a particular health care professional should find out what the specific goals and needs of the candidate might be and consider adjusting the contract to best satisfy the candidate.

At the end of the day, however, at least for those physicians and others reviewing contracts that are fairly equivalent, it may be the fairness of the contract provisions that end up being the deciding factor.

Ms. Adler is Health Law Group Practice Leader for the law firm Roetzel in Chicago. She reported no relevant conflicts of interest.

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

Recruiting health care workers is a challenge these days for both private practice and hospital employers, and competition can be fierce. In order to be competitive, employers need to review the package they are offering potential candidates and understand that it’s more than just compensation and benefits that matter.

When all else is equal, contract language can end up being the difference between capturing or losing a candidate.

As someone who reviews physician contracts extensively, there are some common examples of language that may cause a candidate to choose a different position.
 

Probationary period

Although every employer wants to find out if they like the physician or midlevel employee that they have just hired before fully committing, the inclusion of a probationary period (usually 90 days) is offensive to a candidate, especially one with a choice of contracts.

Essentially, the employer is asking the employee to (potentially) relocate, go through the credentialing process, and turn down other potential offers, all for the possibility that they could easily be terminated. Probationary periods typically allow an employee to be immediately terminated without notice or cause, which can then leave them stranded without a paycheck (and with a new home and/or other recent commitments).

Moreover, contracts with probationary periods tend to terminate the employee without covering any tail costs or clarifying that the employer will not enforce restrictive provisions (even if unlikely to be legally enforceable based on the short relationship).

It is important to understand that the process of a person finding a new position, which includes interviewing, contract negotiation, and credentialing, can take up to 6 months. For this reason, probationary provisions create real job insecurity for a candidate.

Entering into a new affiliation is a leap of faith both for the employer and the employee. If the circumstances do not work out, the employer should fairly compensate the employee for the notice period and ask them not to return to work or otherwise allow them to keep working the notice period while they search for a new position.
 

Acceleration of notice

Another objectionable provision that employers like to include in their contracts is one which allows the employer to accelerate and immediately terminate an employee who has given proper notice.

The contract will contain a standard notice provision, but when the health care professional submits notice, their last date is suddenly accelerated, and they are released without further compensation, notice, or benefits. This type of provision is particularly offensive to health care employees who take the step of giving proper contractual notice and, similar to the probationary language, can create real job insecurity for an employee who suddenly loses their paycheck and has no new job to start.

Medical workers should be paid for the entire notice period whether or not they are allowed to work. Unfortunately, this type of provision is sometimes hidden in contracts and not noticed by employees, who tend to focus on the notice provision itself. I consider this provision to be a red flag about the employer when I review clients’ contracts.
 

Malpractice tail

Although many employers will claim it is not unusual for an employee to pay for their own malpractice tail, in the current marketplace, the payment of tail can be a deciding factor in whether a candidate accepts a contract.

At a minimum, employers should consider paying for the tail under circumstances where they non-renew a contract, terminate without cause, or the contract is terminated for the employer’s breach. Similarly, I like to seek out payment of the tail by the employer where the contract is terminated owing to a change in the law, use of a force majeure provision, loss of the employer’s hospital contract, or similar provisions where termination is outside the control of the employee.

Employers should also consider a provision where they share the cost of a tail or cover the entire cost on the basis of years of service in order to stand out to a potential candidate.
 

Noncompete provisions

I do not find noncompete provisions to be generally unacceptable when properly written; however, employers should reevaluate the reasonableness of their noncompete language frequently, because such language can make the difference in whether a candidate accepts a contract.

A reasonable noncompete that only protects the employer as necessary and does not restrict the reasonable practice of medicine is always preferable and can be the deciding factor for a candidate. Tying enforcement of a noncompete to reasons for termination (similar to the tail) can also make a positive difference in a candidate’s review of a contract.

Egregious noncompetes, where the candidate is simply informed that the language is “not negotiable,” are unlikely to be compelling to a candidate with other options.
 

Specifics on location, call, schedule

One item potential employees find extremely frustrating about contracts is when it fails to include promises made regarding location, call, and schedule.

These particular items affect a physician’s expectations about a job, including commute time, family life, and lifestyle. An employer or recruiter that makes a lot of promises on these points but won’t commit to the details in writing (or at least offer mutual agreement on these issues) can cause an uncertain candidate to choose the job that offers greater certainty.

There are many provisions of a contract that can make a difference to a particular job applicant. A savvy employer seeking to capture a particular health care professional should find out what the specific goals and needs of the candidate might be and consider adjusting the contract to best satisfy the candidate.

At the end of the day, however, at least for those physicians and others reviewing contracts that are fairly equivalent, it may be the fairness of the contract provisions that end up being the deciding factor.

Ms. Adler is Health Law Group Practice Leader for the law firm Roetzel in Chicago. She reported no relevant conflicts of interest.

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

Recruiting health care workers is a challenge these days for both private practice and hospital employers, and competition can be fierce. In order to be competitive, employers need to review the package they are offering potential candidates and understand that it’s more than just compensation and benefits that matter.

When all else is equal, contract language can end up being the difference between capturing or losing a candidate.

As someone who reviews physician contracts extensively, there are some common examples of language that may cause a candidate to choose a different position.
 

Probationary period

Although every employer wants to find out if they like the physician or midlevel employee that they have just hired before fully committing, the inclusion of a probationary period (usually 90 days) is offensive to a candidate, especially one with a choice of contracts.

Essentially, the employer is asking the employee to (potentially) relocate, go through the credentialing process, and turn down other potential offers, all for the possibility that they could easily be terminated. Probationary periods typically allow an employee to be immediately terminated without notice or cause, which can then leave them stranded without a paycheck (and with a new home and/or other recent commitments).

Moreover, contracts with probationary periods tend to terminate the employee without covering any tail costs or clarifying that the employer will not enforce restrictive provisions (even if unlikely to be legally enforceable based on the short relationship).

It is important to understand that the process of a person finding a new position, which includes interviewing, contract negotiation, and credentialing, can take up to 6 months. For this reason, probationary provisions create real job insecurity for a candidate.

Entering into a new affiliation is a leap of faith both for the employer and the employee. If the circumstances do not work out, the employer should fairly compensate the employee for the notice period and ask them not to return to work or otherwise allow them to keep working the notice period while they search for a new position.
 

Acceleration of notice

Another objectionable provision that employers like to include in their contracts is one which allows the employer to accelerate and immediately terminate an employee who has given proper notice.

The contract will contain a standard notice provision, but when the health care professional submits notice, their last date is suddenly accelerated, and they are released without further compensation, notice, or benefits. This type of provision is particularly offensive to health care employees who take the step of giving proper contractual notice and, similar to the probationary language, can create real job insecurity for an employee who suddenly loses their paycheck and has no new job to start.

Medical workers should be paid for the entire notice period whether or not they are allowed to work. Unfortunately, this type of provision is sometimes hidden in contracts and not noticed by employees, who tend to focus on the notice provision itself. I consider this provision to be a red flag about the employer when I review clients’ contracts.
 

Malpractice tail

Although many employers will claim it is not unusual for an employee to pay for their own malpractice tail, in the current marketplace, the payment of tail can be a deciding factor in whether a candidate accepts a contract.

At a minimum, employers should consider paying for the tail under circumstances where they non-renew a contract, terminate without cause, or the contract is terminated for the employer’s breach. Similarly, I like to seek out payment of the tail by the employer where the contract is terminated owing to a change in the law, use of a force majeure provision, loss of the employer’s hospital contract, or similar provisions where termination is outside the control of the employee.

Employers should also consider a provision where they share the cost of a tail or cover the entire cost on the basis of years of service in order to stand out to a potential candidate.
 

Noncompete provisions

I do not find noncompete provisions to be generally unacceptable when properly written; however, employers should reevaluate the reasonableness of their noncompete language frequently, because such language can make the difference in whether a candidate accepts a contract.

A reasonable noncompete that only protects the employer as necessary and does not restrict the reasonable practice of medicine is always preferable and can be the deciding factor for a candidate. Tying enforcement of a noncompete to reasons for termination (similar to the tail) can also make a positive difference in a candidate’s review of a contract.

Egregious noncompetes, where the candidate is simply informed that the language is “not negotiable,” are unlikely to be compelling to a candidate with other options.
 

Specifics on location, call, schedule

One item potential employees find extremely frustrating about contracts is when it fails to include promises made regarding location, call, and schedule.

These particular items affect a physician’s expectations about a job, including commute time, family life, and lifestyle. An employer or recruiter that makes a lot of promises on these points but won’t commit to the details in writing (or at least offer mutual agreement on these issues) can cause an uncertain candidate to choose the job that offers greater certainty.

There are many provisions of a contract that can make a difference to a particular job applicant. A savvy employer seeking to capture a particular health care professional should find out what the specific goals and needs of the candidate might be and consider adjusting the contract to best satisfy the candidate.

At the end of the day, however, at least for those physicians and others reviewing contracts that are fairly equivalent, it may be the fairness of the contract provisions that end up being the deciding factor.

Ms. Adler is Health Law Group Practice Leader for the law firm Roetzel in Chicago. She reported no relevant conflicts of interest.

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

The U.S. Food and Drug Administration has approved the biologic agent spesolimab (Spevigo) for the treatment of flares in adults with generalized pustular psoriasis (GPP), the company that manufactures the drug has announced.

Until this approval, “there were no FDA-approved options to treat patients experiencing a GPP flare,” Mark Lebwohl, MD, principal investigator in the pivotal spesolimab trial, told this news organization. The approval “is a turning point for dermatologists and clinicians who treat patients living with this devastating and debilitating disease,” he said. Treatment with spesolimab “rapidly improves the clinical symptoms of GPP flares and will greatly improve our ability to help our patients manage painful flares,” noted Dr. Lebwohl, dean of clinical therapeutics and professor of dermatology, Icahn School of Medicine at Mount Sinai, New York.

Spesolimab, manufactured by Boehringer Ingelheim, is a novel, selective monoclonal antibody that blocks interleukin-36 signaling known to be involved in GPP. It received priority review and had orphan drug and breakthrough therapy designation.

GPP affects an estimated 1 of every 10,000 people in the United States.

Though rare, GPP is a potentially life-threatening disease that is distinct from plaque psoriasis. GPP is caused by the accumulation of neutrophils in the skin. Throughout the course of the disease, patients may suffer recurring episodes of widespread eruptions of painful, sterile pustules across all parts of the body.

Spesolimab was evaluated in a global, 12-week, placebo-controlled clinical trial that involved 53 adults experiencing a GPP flare. After 1 week, significantly more patients treated with spesolimab than placebo showed no visible pustules (54% vs 6%), according to the company.

The most common adverse reactions, seen in at least 5% of patients treated with spesolimab, were asthenia and fatigue; nausea and vomiting; headache; pruritus and prurigo; hematoma and bruising at the infusion site; and urinary tract infection.

Dr. Lebwohl is a paid consultant to Boehringer Ingelheim.

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

This article was updated 9/6/22.

The U.S. Food and Drug Administration has approved the biologic agent spesolimab (Spevigo) for the treatment of flares in adults with generalized pustular psoriasis (GPP), the company that manufactures the drug has announced.

Until this approval, “there were no FDA-approved options to treat patients experiencing a GPP flare,” Mark Lebwohl, MD, principal investigator in the pivotal spesolimab trial, told this news organization. The approval “is a turning point for dermatologists and clinicians who treat patients living with this devastating and debilitating disease,” he said. Treatment with spesolimab “rapidly improves the clinical symptoms of GPP flares and will greatly improve our ability to help our patients manage painful flares,” noted Dr. Lebwohl, dean of clinical therapeutics and professor of dermatology, Icahn School of Medicine at Mount Sinai, New York.

Spesolimab, manufactured by Boehringer Ingelheim, is a novel, selective monoclonal antibody that blocks interleukin-36 signaling known to be involved in GPP. It received priority review and had orphan drug and breakthrough therapy designation.

GPP affects an estimated 1 of every 10,000 people in the United States.

Though rare, GPP is a potentially life-threatening disease that is distinct from plaque psoriasis. GPP is caused by the accumulation of neutrophils in the skin. Throughout the course of the disease, patients may suffer recurring episodes of widespread eruptions of painful, sterile pustules across all parts of the body.

Spesolimab was evaluated in a global, 12-week, placebo-controlled clinical trial that involved 53 adults experiencing a GPP flare. After 1 week, significantly more patients treated with spesolimab than placebo showed no visible pustules (54% vs 6%), according to the company.

The most common adverse reactions, seen in at least 5% of patients treated with spesolimab, were asthenia and fatigue; nausea and vomiting; headache; pruritus and prurigo; hematoma and bruising at the infusion site; and urinary tract infection.

Dr. Lebwohl is a paid consultant to Boehringer Ingelheim.

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

This article was updated 9/6/22.

The U.S. Food and Drug Administration has approved the biologic agent spesolimab (Spevigo) for the treatment of flares in adults with generalized pustular psoriasis (GPP), the company that manufactures the drug has announced.

Until this approval, “there were no FDA-approved options to treat patients experiencing a GPP flare,” Mark Lebwohl, MD, principal investigator in the pivotal spesolimab trial, told this news organization. The approval “is a turning point for dermatologists and clinicians who treat patients living with this devastating and debilitating disease,” he said. Treatment with spesolimab “rapidly improves the clinical symptoms of GPP flares and will greatly improve our ability to help our patients manage painful flares,” noted Dr. Lebwohl, dean of clinical therapeutics and professor of dermatology, Icahn School of Medicine at Mount Sinai, New York.

Spesolimab, manufactured by Boehringer Ingelheim, is a novel, selective monoclonal antibody that blocks interleukin-36 signaling known to be involved in GPP. It received priority review and had orphan drug and breakthrough therapy designation.

GPP affects an estimated 1 of every 10,000 people in the United States.

Though rare, GPP is a potentially life-threatening disease that is distinct from plaque psoriasis. GPP is caused by the accumulation of neutrophils in the skin. Throughout the course of the disease, patients may suffer recurring episodes of widespread eruptions of painful, sterile pustules across all parts of the body.

Spesolimab was evaluated in a global, 12-week, placebo-controlled clinical trial that involved 53 adults experiencing a GPP flare. After 1 week, significantly more patients treated with spesolimab than placebo showed no visible pustules (54% vs 6%), according to the company.

The most common adverse reactions, seen in at least 5% of patients treated with spesolimab, were asthenia and fatigue; nausea and vomiting; headache; pruritus and prurigo; hematoma and bruising at the infusion site; and urinary tract infection.

Dr. Lebwohl is a paid consultant to Boehringer Ingelheim.

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

This article was updated 9/6/22.

The kids aren’t alright (at identifying fake news online)

If there’s one thing today’s teenagers are good at, it’s the Internet. What with their TokTiks, Fortnights, and memes whose lifespans are measured in milliseconds, it’s only natural that a contingent of people who have never known a world where the Internet wasn’t omnipresent would be highly skilled at navigating the dense, labyrinthine virtual world and the many falsehoods contained within.

Ladies and gentlemen, we’ve been duped, bamboozled, and smeckledorfed. New research from Slovakia suggests the opposite, in fact: Teenagers are just as bad as the rest of us, if not worse, at distinguishing between fake and real online health messaging.

monkeybusinessimages/iStock/Getty Images Plus

For the study, 300 teenagers aged 16-19 years old were shown a group of messages about the health-promoting effects of fruits and vegetables; these messages were either false, true and neutral, or true with some sort of editing (a clickbait title or grammar mistakes) to mask their trustworthiness. Just under half of the subjects identified and trusted the true neutral messages over fake messages, while 41% couldn’t tell the difference and 11% trusted the fake messages more. In addition, they couldn’t tell the difference between fake and true messages when the content seemed plausible.

In a bit of good news, teenagers were just as likely to trust the edited true messages as the true neutral ones, except in instances when the edited message had a clickbait title. They were much less likely to trust those.

Based on their subjects’ rather poor performance, the study authors suggested teenagers go through health literacy and media literacy training, as well as develop their analytical and scientific reasoning. The LOTME staff rather suspects the study authors have never met a teenager. The only thing teenagers are going to get out of health literacy training is fodder for memes to put up on Myspace. Myspace is still a thing, right? We’re not old, we swear.
 

Can a computer help deliver babies?

Delivering babies can be a complicated business. Most doctors and midwives rely on their years of experience and training to make certain decisions for mothers in labor, but an artificial intelligence (AI) algorithm could make the entire process easier and safer.

©Paul Hakimata/thinkstockphotos.com

Researchers from the Mayo Clinic recently reported that using an AI to analyze women’s labor patterns was very successful in determining whether a vaginal or cesarean delivery was appropriate.

They examined over 700 factors and over 66,000 deliveries from the National Institute of Child Health and Human Development’s multicenter Consortium on Safe Labor database to produce a risk-prediction model that may “provide an alternative to conventional labor charts and promote individualization of clinical decisions using baseline and labor characteristics of each patient,” they said in a written statement from the clinic.

It is hoped that the AI will reduce the risk of possible complications and the costs associated with maternal mortality. The AI also could be a significant tool for doctors and midwives in rural areas to determine when a patient needs to be moved to a location with a higher level of care.

“We believe the algorithm will work in real time, meaning every input of new data during an expectant woman’s labor automatically recalculates the risk of adverse outcome,” said senior author Abimbola Famuyide, MD, of the Mayo Clinic.

If it all works out, many lives and dollars could be saved, thanks to science.
 

Democracy, meet COVID-19

Everywhere you look, it seems, someone is trying to keep someone else from doing something: Don’t carry a gun. Don’t get an abortion. Don’t drive so fast. Don’t inhale that whipped cream. Don’t get a vaccine. Don’t put that in your mouth.

One of the biggies these days is voting rights. Some people are trying to prevent other people from voting. But why? Well, turns out that turnout can be bad for your health … at least during a worldwide pandemic event.

mohamed mahmoud hassan

The evidence for that claim comes from researchers who examined the Italian national constitutional referendum conducted in September 2020 along with elections for assembly representatives in 7 of the country’s 20 regions and for mayors in about 12% of municipalities. The combination mattered: Voter turnout was higher in the municipalities that voted for both the referendum and local elections (69%), compared with municipalities voting only for the referendum (47%), the investigators reported in the Journal of Economic Behavior & Organization.

Also occurring in September of 2020 was, as we mentioned, a worldwide pandemic event. You may have heard about it.

The investigators considered the differences in election turnout between the various municipalities and compared them with new weekly COVID-19 infections at the municipality level. “Our model shows that something as fundamental as casting a vote can come at a cost,” investigator Giuseppe Moscelli, PhD, of the University of Surrey (England) said in a written statement.

What was the cost? Each 1% increase in turnout, they found, amounted to an average 1.1% increase in COVID infections after the elections.

See? More people voting means more COVID, which is bad. Which brings us to today’s lesson in people preventing other people from doing something. Don’t let COVID win. Stay in your house and never come out. And get that smeckledorf out of your mouth. You don’t know where it’s been.

The kids aren’t alright (at identifying fake news online)

If there’s one thing today’s teenagers are good at, it’s the Internet. What with their TokTiks, Fortnights, and memes whose lifespans are measured in milliseconds, it’s only natural that a contingent of people who have never known a world where the Internet wasn’t omnipresent would be highly skilled at navigating the dense, labyrinthine virtual world and the many falsehoods contained within.

Ladies and gentlemen, we’ve been duped, bamboozled, and smeckledorfed. New research from Slovakia suggests the opposite, in fact: Teenagers are just as bad as the rest of us, if not worse, at distinguishing between fake and real online health messaging.

monkeybusinessimages/iStock/Getty Images Plus

For the study, 300 teenagers aged 16-19 years old were shown a group of messages about the health-promoting effects of fruits and vegetables; these messages were either false, true and neutral, or true with some sort of editing (a clickbait title or grammar mistakes) to mask their trustworthiness. Just under half of the subjects identified and trusted the true neutral messages over fake messages, while 41% couldn’t tell the difference and 11% trusted the fake messages more. In addition, they couldn’t tell the difference between fake and true messages when the content seemed plausible.

In a bit of good news, teenagers were just as likely to trust the edited true messages as the true neutral ones, except in instances when the edited message had a clickbait title. They were much less likely to trust those.

Based on their subjects’ rather poor performance, the study authors suggested teenagers go through health literacy and media literacy training, as well as develop their analytical and scientific reasoning. The LOTME staff rather suspects the study authors have never met a teenager. The only thing teenagers are going to get out of health literacy training is fodder for memes to put up on Myspace. Myspace is still a thing, right? We’re not old, we swear.
 

Can a computer help deliver babies?

Delivering babies can be a complicated business. Most doctors and midwives rely on their years of experience and training to make certain decisions for mothers in labor, but an artificial intelligence (AI) algorithm could make the entire process easier and safer.

©Paul Hakimata/thinkstockphotos.com

Researchers from the Mayo Clinic recently reported that using an AI to analyze women’s labor patterns was very successful in determining whether a vaginal or cesarean delivery was appropriate.

They examined over 700 factors and over 66,000 deliveries from the National Institute of Child Health and Human Development’s multicenter Consortium on Safe Labor database to produce a risk-prediction model that may “provide an alternative to conventional labor charts and promote individualization of clinical decisions using baseline and labor characteristics of each patient,” they said in a written statement from the clinic.

It is hoped that the AI will reduce the risk of possible complications and the costs associated with maternal mortality. The AI also could be a significant tool for doctors and midwives in rural areas to determine when a patient needs to be moved to a location with a higher level of care.

“We believe the algorithm will work in real time, meaning every input of new data during an expectant woman’s labor automatically recalculates the risk of adverse outcome,” said senior author Abimbola Famuyide, MD, of the Mayo Clinic.

If it all works out, many lives and dollars could be saved, thanks to science.
 

Democracy, meet COVID-19

Everywhere you look, it seems, someone is trying to keep someone else from doing something: Don’t carry a gun. Don’t get an abortion. Don’t drive so fast. Don’t inhale that whipped cream. Don’t get a vaccine. Don’t put that in your mouth.

One of the biggies these days is voting rights. Some people are trying to prevent other people from voting. But why? Well, turns out that turnout can be bad for your health … at least during a worldwide pandemic event.

mohamed mahmoud hassan

The evidence for that claim comes from researchers who examined the Italian national constitutional referendum conducted in September 2020 along with elections for assembly representatives in 7 of the country’s 20 regions and for mayors in about 12% of municipalities. The combination mattered: Voter turnout was higher in the municipalities that voted for both the referendum and local elections (69%), compared with municipalities voting only for the referendum (47%), the investigators reported in the Journal of Economic Behavior & Organization.

Also occurring in September of 2020 was, as we mentioned, a worldwide pandemic event. You may have heard about it.

The investigators considered the differences in election turnout between the various municipalities and compared them with new weekly COVID-19 infections at the municipality level. “Our model shows that something as fundamental as casting a vote can come at a cost,” investigator Giuseppe Moscelli, PhD, of the University of Surrey (England) said in a written statement.

What was the cost? Each 1% increase in turnout, they found, amounted to an average 1.1% increase in COVID infections after the elections.

See? More people voting means more COVID, which is bad. Which brings us to today’s lesson in people preventing other people from doing something. Don’t let COVID win. Stay in your house and never come out. And get that smeckledorf out of your mouth. You don’t know where it’s been.

The kids aren’t alright (at identifying fake news online)

If there’s one thing today’s teenagers are good at, it’s the Internet. What with their TokTiks, Fortnights, and memes whose lifespans are measured in milliseconds, it’s only natural that a contingent of people who have never known a world where the Internet wasn’t omnipresent would be highly skilled at navigating the dense, labyrinthine virtual world and the many falsehoods contained within.

Ladies and gentlemen, we’ve been duped, bamboozled, and smeckledorfed. New research from Slovakia suggests the opposite, in fact: Teenagers are just as bad as the rest of us, if not worse, at distinguishing between fake and real online health messaging.

monkeybusinessimages/iStock/Getty Images Plus

For the study, 300 teenagers aged 16-19 years old were shown a group of messages about the health-promoting effects of fruits and vegetables; these messages were either false, true and neutral, or true with some sort of editing (a clickbait title or grammar mistakes) to mask their trustworthiness. Just under half of the subjects identified and trusted the true neutral messages over fake messages, while 41% couldn’t tell the difference and 11% trusted the fake messages more. In addition, they couldn’t tell the difference between fake and true messages when the content seemed plausible.

In a bit of good news, teenagers were just as likely to trust the edited true messages as the true neutral ones, except in instances when the edited message had a clickbait title. They were much less likely to trust those.

Based on their subjects’ rather poor performance, the study authors suggested teenagers go through health literacy and media literacy training, as well as develop their analytical and scientific reasoning. The LOTME staff rather suspects the study authors have never met a teenager. The only thing teenagers are going to get out of health literacy training is fodder for memes to put up on Myspace. Myspace is still a thing, right? We’re not old, we swear.
 

Can a computer help deliver babies?

Delivering babies can be a complicated business. Most doctors and midwives rely on their years of experience and training to make certain decisions for mothers in labor, but an artificial intelligence (AI) algorithm could make the entire process easier and safer.

©Paul Hakimata/thinkstockphotos.com

Researchers from the Mayo Clinic recently reported that using an AI to analyze women’s labor patterns was very successful in determining whether a vaginal or cesarean delivery was appropriate.

They examined over 700 factors and over 66,000 deliveries from the National Institute of Child Health and Human Development’s multicenter Consortium on Safe Labor database to produce a risk-prediction model that may “provide an alternative to conventional labor charts and promote individualization of clinical decisions using baseline and labor characteristics of each patient,” they said in a written statement from the clinic.

It is hoped that the AI will reduce the risk of possible complications and the costs associated with maternal mortality. The AI also could be a significant tool for doctors and midwives in rural areas to determine when a patient needs to be moved to a location with a higher level of care.

“We believe the algorithm will work in real time, meaning every input of new data during an expectant woman’s labor automatically recalculates the risk of adverse outcome,” said senior author Abimbola Famuyide, MD, of the Mayo Clinic.

If it all works out, many lives and dollars could be saved, thanks to science.
 

Democracy, meet COVID-19

Everywhere you look, it seems, someone is trying to keep someone else from doing something: Don’t carry a gun. Don’t get an abortion. Don’t drive so fast. Don’t inhale that whipped cream. Don’t get a vaccine. Don’t put that in your mouth.

One of the biggies these days is voting rights. Some people are trying to prevent other people from voting. But why? Well, turns out that turnout can be bad for your health … at least during a worldwide pandemic event.

mohamed mahmoud hassan

The evidence for that claim comes from researchers who examined the Italian national constitutional referendum conducted in September 2020 along with elections for assembly representatives in 7 of the country’s 20 regions and for mayors in about 12% of municipalities. The combination mattered: Voter turnout was higher in the municipalities that voted for both the referendum and local elections (69%), compared with municipalities voting only for the referendum (47%), the investigators reported in the Journal of Economic Behavior & Organization.

Also occurring in September of 2020 was, as we mentioned, a worldwide pandemic event. You may have heard about it.

The investigators considered the differences in election turnout between the various municipalities and compared them with new weekly COVID-19 infections at the municipality level. “Our model shows that something as fundamental as casting a vote can come at a cost,” investigator Giuseppe Moscelli, PhD, of the University of Surrey (England) said in a written statement.

What was the cost? Each 1% increase in turnout, they found, amounted to an average 1.1% increase in COVID infections after the elections.

See? More people voting means more COVID, which is bad. Which brings us to today’s lesson in people preventing other people from doing something. Don’t let COVID win. Stay in your house and never come out. And get that smeckledorf out of your mouth. You don’t know where it’s been.

Recent publications on psoriatic arthritis (PsA) have focused on targeted therapies, particularly those targeting interleukin (IL) 17 and 23. Bimekizumab is a novel biologic that dually inhibits IL-17A and IL-17F. Coates and colleagues reported 3-year results from the phase 2b BE ACTIVE trial that included 206 adults with active PsA randomly assigned to receive bimekizumab or placebo for 48 weeks, of which 184 patients were enrolled in the open-label extension phase for a further 104 weeks of treatment. They report that at least 20% improvement in American College of Rheumatology score was maintained by 64.1% of patients at week 152 compared with 72.3% of patients at week 48. By week 152, 89.3% of patients had reported one or more treatment-emergent adverse event (TEAE), with serious TEAE being reported by 10.7% of patients. Fungal infections are of special interest when inhibiting both IL-17A and IL-17F. It was observed that 9.7% had fungal infections (all mild-to-moderate and localized), of which 4.6% had candidiasis. Thus, bimekizumab shows promise as a new therapy for PsA.

In addition to improving signs and symptoms, clinically meaningful improvement in health-related quality of life is an important goal of treatment. Two studies reported improvement in patient reported outcomes on treatment with IL-23 inhibitors.

An analysis of data from the phase 3 DISCOVER 2 trial included 738 biologic-naive patients with active PsA and inadequate response to standard treatments. These patients were randomly assigned to receive 100 mg guselkumab every 4 weeks (Q4W) or every 8 weeks (Q8W) or placebo. Curtis and colleagues showed that a significantly higher proportion of patients receiving guselkumab Q4W/Q8W vs placebo reported achieving minimally important differences (MID) in the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index (56.0%/56.0% vs 43.4%; P < .006) and Visual Analog Scale (EQ-VAS) score (62.8%/63.5% vs 44.4%; P < .0001) at week 24, with more than 60% of patients reporting improvements at week 52.

Similarly, analyses of data by Kristensen and colleagues from two phase 3 trials, KEEPsAKE-1 and KEEPsAKE-2, included adults with PsA and inadequate response/intolerance to disease-modifying antirheumatic drugs or biologics. The patients were randomly assigned to receive risankizumab or placebo for 24 weeks and only risankizumab during weeks 24-52. At week 24, patients receiving risankizumab vs placebo were significantly more likely to report achieving MID in Patient's Global Assessment of Disease Activity (PtGA) in both KEEPsAKE-1 (odds ratio [OR] 2.0; P < .001) and KEEPsAKE-2 (OR 1.9; P < .01) studies, with further improvement at week 52. Improvement was also seen on the Patient's Assessment of Pain, Health Assessment Questionnaire – Disability Index, Short-Form 36 Physical and Mental Component Summary scores, EQ-5D-5L, Functional Assessment of Chronic Illness Therapy – Fatigue, and Work Productivity and Activity Impairment.

An interesting insight from two studies showed the importance of nail disease in predicting treatment response. A post hoc analysis by Helliwell and colleagues of the phase 3 SEAM-PsA trial of 851 biologic/methotrexate-naive patients with active PsA who were randomly assigned to receive methotrexate monotherapy, etanercept monotherapy, or methotrexate + etanercept combination therapy showed that the presence of both dactylitis and nail disease at baseline were significantly associated with the achievement of minimal disease activity (OR 1.4; P = .0457; and OR 1.8; P = .0233, respectively), as well as low PsA Disease Activity Score (OR 1.8; P = .0014; and OR 1.8; P = .0168, respectively).

Similarly, a post hoc analysis by Baraliakos and colleagues of the phase 3b MAXIMISE trial of 473 adult patients with PsA and axial manifestations who were randomly assigned to receive secukinumab (150 or 300 mg) or placebo showed that the presence vs the absence of nail dystrophy was associated with the achievement of significantly better Assessment of SpondyloArthritis International Society 20 response in the 300 mg secukinumab group (OR 5.0; 95% CI 1.47-17.19).

Recent publications on psoriatic arthritis (PsA) have focused on targeted therapies, particularly those targeting interleukin (IL) 17 and 23. Bimekizumab is a novel biologic that dually inhibits IL-17A and IL-17F. Coates and colleagues reported 3-year results from the phase 2b BE ACTIVE trial that included 206 adults with active PsA randomly assigned to receive bimekizumab or placebo for 48 weeks, of which 184 patients were enrolled in the open-label extension phase for a further 104 weeks of treatment. They report that at least 20% improvement in American College of Rheumatology score was maintained by 64.1% of patients at week 152 compared with 72.3% of patients at week 48. By week 152, 89.3% of patients had reported one or more treatment-emergent adverse event (TEAE), with serious TEAE being reported by 10.7% of patients. Fungal infections are of special interest when inhibiting both IL-17A and IL-17F. It was observed that 9.7% had fungal infections (all mild-to-moderate and localized), of which 4.6% had candidiasis. Thus, bimekizumab shows promise as a new therapy for PsA.

In addition to improving signs and symptoms, clinically meaningful improvement in health-related quality of life is an important goal of treatment. Two studies reported improvement in patient reported outcomes on treatment with IL-23 inhibitors.

An analysis of data from the phase 3 DISCOVER 2 trial included 738 biologic-naive patients with active PsA and inadequate response to standard treatments. These patients were randomly assigned to receive 100 mg guselkumab every 4 weeks (Q4W) or every 8 weeks (Q8W) or placebo. Curtis and colleagues showed that a significantly higher proportion of patients receiving guselkumab Q4W/Q8W vs placebo reported achieving minimally important differences (MID) in the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index (56.0%/56.0% vs 43.4%; P < .006) and Visual Analog Scale (EQ-VAS) score (62.8%/63.5% vs 44.4%; P < .0001) at week 24, with more than 60% of patients reporting improvements at week 52.

Similarly, analyses of data by Kristensen and colleagues from two phase 3 trials, KEEPsAKE-1 and KEEPsAKE-2, included adults with PsA and inadequate response/intolerance to disease-modifying antirheumatic drugs or biologics. The patients were randomly assigned to receive risankizumab or placebo for 24 weeks and only risankizumab during weeks 24-52. At week 24, patients receiving risankizumab vs placebo were significantly more likely to report achieving MID in Patient's Global Assessment of Disease Activity (PtGA) in both KEEPsAKE-1 (odds ratio [OR] 2.0; P < .001) and KEEPsAKE-2 (OR 1.9; P < .01) studies, with further improvement at week 52. Improvement was also seen on the Patient's Assessment of Pain, Health Assessment Questionnaire – Disability Index, Short-Form 36 Physical and Mental Component Summary scores, EQ-5D-5L, Functional Assessment of Chronic Illness Therapy – Fatigue, and Work Productivity and Activity Impairment.

An interesting insight from two studies showed the importance of nail disease in predicting treatment response. A post hoc analysis by Helliwell and colleagues of the phase 3 SEAM-PsA trial of 851 biologic/methotrexate-naive patients with active PsA who were randomly assigned to receive methotrexate monotherapy, etanercept monotherapy, or methotrexate + etanercept combination therapy showed that the presence of both dactylitis and nail disease at baseline were significantly associated with the achievement of minimal disease activity (OR 1.4; P = .0457; and OR 1.8; P = .0233, respectively), as well as low PsA Disease Activity Score (OR 1.8; P = .0014; and OR 1.8; P = .0168, respectively).

Similarly, a post hoc analysis by Baraliakos and colleagues of the phase 3b MAXIMISE trial of 473 adult patients with PsA and axial manifestations who were randomly assigned to receive secukinumab (150 or 300 mg) or placebo showed that the presence vs the absence of nail dystrophy was associated with the achievement of significantly better Assessment of SpondyloArthritis International Society 20 response in the 300 mg secukinumab group (OR 5.0; 95% CI 1.47-17.19).

Recent publications on psoriatic arthritis (PsA) have focused on targeted therapies, particularly those targeting interleukin (IL) 17 and 23. Bimekizumab is a novel biologic that dually inhibits IL-17A and IL-17F. Coates and colleagues reported 3-year results from the phase 2b BE ACTIVE trial that included 206 adults with active PsA randomly assigned to receive bimekizumab or placebo for 48 weeks, of which 184 patients were enrolled in the open-label extension phase for a further 104 weeks of treatment. They report that at least 20% improvement in American College of Rheumatology score was maintained by 64.1% of patients at week 152 compared with 72.3% of patients at week 48. By week 152, 89.3% of patients had reported one or more treatment-emergent adverse event (TEAE), with serious TEAE being reported by 10.7% of patients. Fungal infections are of special interest when inhibiting both IL-17A and IL-17F. It was observed that 9.7% had fungal infections (all mild-to-moderate and localized), of which 4.6% had candidiasis. Thus, bimekizumab shows promise as a new therapy for PsA.

In addition to improving signs and symptoms, clinically meaningful improvement in health-related quality of life is an important goal of treatment. Two studies reported improvement in patient reported outcomes on treatment with IL-23 inhibitors.

An analysis of data from the phase 3 DISCOVER 2 trial included 738 biologic-naive patients with active PsA and inadequate response to standard treatments. These patients were randomly assigned to receive 100 mg guselkumab every 4 weeks (Q4W) or every 8 weeks (Q8W) or placebo. Curtis and colleagues showed that a significantly higher proportion of patients receiving guselkumab Q4W/Q8W vs placebo reported achieving minimally important differences (MID) in the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index (56.0%/56.0% vs 43.4%; P < .006) and Visual Analog Scale (EQ-VAS) score (62.8%/63.5% vs 44.4%; P < .0001) at week 24, with more than 60% of patients reporting improvements at week 52.

Similarly, analyses of data by Kristensen and colleagues from two phase 3 trials, KEEPsAKE-1 and KEEPsAKE-2, included adults with PsA and inadequate response/intolerance to disease-modifying antirheumatic drugs or biologics. The patients were randomly assigned to receive risankizumab or placebo for 24 weeks and only risankizumab during weeks 24-52. At week 24, patients receiving risankizumab vs placebo were significantly more likely to report achieving MID in Patient's Global Assessment of Disease Activity (PtGA) in both KEEPsAKE-1 (odds ratio [OR] 2.0; P < .001) and KEEPsAKE-2 (OR 1.9; P < .01) studies, with further improvement at week 52. Improvement was also seen on the Patient's Assessment of Pain, Health Assessment Questionnaire – Disability Index, Short-Form 36 Physical and Mental Component Summary scores, EQ-5D-5L, Functional Assessment of Chronic Illness Therapy – Fatigue, and Work Productivity and Activity Impairment.

An interesting insight from two studies showed the importance of nail disease in predicting treatment response. A post hoc analysis by Helliwell and colleagues of the phase 3 SEAM-PsA trial of 851 biologic/methotrexate-naive patients with active PsA who were randomly assigned to receive methotrexate monotherapy, etanercept monotherapy, or methotrexate + etanercept combination therapy showed that the presence of both dactylitis and nail disease at baseline were significantly associated with the achievement of minimal disease activity (OR 1.4; P = .0457; and OR 1.8; P = .0233, respectively), as well as low PsA Disease Activity Score (OR 1.8; P = .0014; and OR 1.8; P = .0168, respectively).

Similarly, a post hoc analysis by Baraliakos and colleagues of the phase 3b MAXIMISE trial of 473 adult patients with PsA and axial manifestations who were randomly assigned to receive secukinumab (150 or 300 mg) or placebo showed that the presence vs the absence of nail dystrophy was associated with the achievement of significantly better Assessment of SpondyloArthritis International Society 20 response in the 300 mg secukinumab group (OR 5.0; 95% CI 1.47-17.19).

The potential to prevent clinical rheumatoid arthritis (RA) in patients at risk of developing arthritis is of long-standing interest in the rheumatology community. Other studies have addressed the potential for early treatment with glucocorticoids, hydroxychloroquine, or biologics to prevent arthritis, with mixed results. Few published studies have assessed the efficacy of methotrexate in the prevention of arthritis. A randomized controlled trial by Krijbolder and colleagues of adults with arthralgias deemed to be at risk for progression to RA evaluated the use of a single intramuscular steroid injection combined with 1 year of oral methotrexate, compared with placebo, for preventing the development of RA according to the 2010 American College of Rheumatology classification criteria. Although no difference was seen between the groups in development of RA, those treated with methotrexate did have lower levels of joint inflammation seen on MRI and better functional status as per Health Assessment Questionnaire score.

Su and colleagues also looked at the impact of different medications on the development of RA. Using a national health insurance database in Taiwan (between 1997 and 2013), they studied the use of biguanides and sulfonylureas in patients with diabetes and the risk for incident RA. In over 90,000 patients with diabetes, a longer duration of sulfonylurea or biguanide prescription within the first 3 years of diabetes diagnosis was associated with a lower risk for RA compared with non-use. However, use of any antihyperglycemic agents was also associated with lower risk for RA incidence. Limited information is available on both the severity of diabetes and activity of RA, so even a potential mechanism in terms of reduction of blood glucose or inflammation is hard to determine, and more detailed studies are needed.

The safety of different treatments during pregnancy, as well as the effect of both RA and its treatment on pregnancy outcomes, have been areas of research interest in terms of counseling patients with RA about pregnancy planning and management of medications. Gerardi and colleagues followed 63 patients with RA prospectively during pregnancy. They found that although the general understanding is that inflammatory arthritis improves during pregnancy, the percentage of patients with moderate and high disease activity increased slightly, and 37% of patients experienced a flare. Flares were associated with elevated C-reactive protein (CRP) levels and use of multiple prior biologic disease-modifying antirheumatic drugs (bDMARD) (suggesting overall more active arthritis), as well as bDMARD discontinuation in early pregnancy. Similarly, preterm delivery was associated with elevated CRP, higher Disease Activity Score-28 scores, and flares. The study findings provide further support for the importance of controlling maternal disease activity in favoring a better RA course as well as better pregnancy outcomes.

Smeele and colleagues recently published an analysis of the PreCARA cohort study looking at birthweight in pregnant patients with RA. RA is associated with children being born small for gestational age. In this cohort study of 188 pregnant patients with RA, the treatment protocol before pregnancy included hydroxychloroquine, sulfasalazine, prednisone, and anti–tumor necrosis factor (TNF) agents (adalimumab, infliximab, etanercept, and certolizumab). Anti-TNF medications were stopped at 20, 20, 28, or 38 weeks, respectively, according to the European Alliance of Associations for Rheumatology (EULAR) recommendations. In terms of gestational age at delivery and congenital malformations, no difference was seen between patients who used anti-TNF agents during pregnancy and those who did not. Anti-TNF use during pregnancy was associated, however, with increased birthweight and a lower percentage of infants who were small for gestational age. These findings are in keeping with those of prior studies, although larger studies would be helpful in determining whether there are critical periods during pregnancy that have a significant effect on birthweight or whether overall control of inflammation is the predominant factor.

The potential to prevent clinical rheumatoid arthritis (RA) in patients at risk of developing arthritis is of long-standing interest in the rheumatology community. Other studies have addressed the potential for early treatment with glucocorticoids, hydroxychloroquine, or biologics to prevent arthritis, with mixed results. Few published studies have assessed the efficacy of methotrexate in the prevention of arthritis. A randomized controlled trial by Krijbolder and colleagues of adults with arthralgias deemed to be at risk for progression to RA evaluated the use of a single intramuscular steroid injection combined with 1 year of oral methotrexate, compared with placebo, for preventing the development of RA according to the 2010 American College of Rheumatology classification criteria. Although no difference was seen between the groups in development of RA, those treated with methotrexate did have lower levels of joint inflammation seen on MRI and better functional status as per Health Assessment Questionnaire score.

Su and colleagues also looked at the impact of different medications on the development of RA. Using a national health insurance database in Taiwan (between 1997 and 2013), they studied the use of biguanides and sulfonylureas in patients with diabetes and the risk for incident RA. In over 90,000 patients with diabetes, a longer duration of sulfonylurea or biguanide prescription within the first 3 years of diabetes diagnosis was associated with a lower risk for RA compared with non-use. However, use of any antihyperglycemic agents was also associated with lower risk for RA incidence. Limited information is available on both the severity of diabetes and activity of RA, so even a potential mechanism in terms of reduction of blood glucose or inflammation is hard to determine, and more detailed studies are needed.

The safety of different treatments during pregnancy, as well as the effect of both RA and its treatment on pregnancy outcomes, have been areas of research interest in terms of counseling patients with RA about pregnancy planning and management of medications. Gerardi and colleagues followed 63 patients with RA prospectively during pregnancy. They found that although the general understanding is that inflammatory arthritis improves during pregnancy, the percentage of patients with moderate and high disease activity increased slightly, and 37% of patients experienced a flare. Flares were associated with elevated C-reactive protein (CRP) levels and use of multiple prior biologic disease-modifying antirheumatic drugs (bDMARD) (suggesting overall more active arthritis), as well as bDMARD discontinuation in early pregnancy. Similarly, preterm delivery was associated with elevated CRP, higher Disease Activity Score-28 scores, and flares. The study findings provide further support for the importance of controlling maternal disease activity in favoring a better RA course as well as better pregnancy outcomes.

Smeele and colleagues recently published an analysis of the PreCARA cohort study looking at birthweight in pregnant patients with RA. RA is associated with children being born small for gestational age. In this cohort study of 188 pregnant patients with RA, the treatment protocol before pregnancy included hydroxychloroquine, sulfasalazine, prednisone, and anti–tumor necrosis factor (TNF) agents (adalimumab, infliximab, etanercept, and certolizumab). Anti-TNF medications were stopped at 20, 20, 28, or 38 weeks, respectively, according to the European Alliance of Associations for Rheumatology (EULAR) recommendations. In terms of gestational age at delivery and congenital malformations, no difference was seen between patients who used anti-TNF agents during pregnancy and those who did not. Anti-TNF use during pregnancy was associated, however, with increased birthweight and a lower percentage of infants who were small for gestational age. These findings are in keeping with those of prior studies, although larger studies would be helpful in determining whether there are critical periods during pregnancy that have a significant effect on birthweight or whether overall control of inflammation is the predominant factor.

The potential to prevent clinical rheumatoid arthritis (RA) in patients at risk of developing arthritis is of long-standing interest in the rheumatology community. Other studies have addressed the potential for early treatment with glucocorticoids, hydroxychloroquine, or biologics to prevent arthritis, with mixed results. Few published studies have assessed the efficacy of methotrexate in the prevention of arthritis. A randomized controlled trial by Krijbolder and colleagues of adults with arthralgias deemed to be at risk for progression to RA evaluated the use of a single intramuscular steroid injection combined with 1 year of oral methotrexate, compared with placebo, for preventing the development of RA according to the 2010 American College of Rheumatology classification criteria. Although no difference was seen between the groups in development of RA, those treated with methotrexate did have lower levels of joint inflammation seen on MRI and better functional status as per Health Assessment Questionnaire score.

Su and colleagues also looked at the impact of different medications on the development of RA. Using a national health insurance database in Taiwan (between 1997 and 2013), they studied the use of biguanides and sulfonylureas in patients with diabetes and the risk for incident RA. In over 90,000 patients with diabetes, a longer duration of sulfonylurea or biguanide prescription within the first 3 years of diabetes diagnosis was associated with a lower risk for RA compared with non-use. However, use of any antihyperglycemic agents was also associated with lower risk for RA incidence. Limited information is available on both the severity of diabetes and activity of RA, so even a potential mechanism in terms of reduction of blood glucose or inflammation is hard to determine, and more detailed studies are needed.

The safety of different treatments during pregnancy, as well as the effect of both RA and its treatment on pregnancy outcomes, have been areas of research interest in terms of counseling patients with RA about pregnancy planning and management of medications. Gerardi and colleagues followed 63 patients with RA prospectively during pregnancy. They found that although the general understanding is that inflammatory arthritis improves during pregnancy, the percentage of patients with moderate and high disease activity increased slightly, and 37% of patients experienced a flare. Flares were associated with elevated C-reactive protein (CRP) levels and use of multiple prior biologic disease-modifying antirheumatic drugs (bDMARD) (suggesting overall more active arthritis), as well as bDMARD discontinuation in early pregnancy. Similarly, preterm delivery was associated with elevated CRP, higher Disease Activity Score-28 scores, and flares. The study findings provide further support for the importance of controlling maternal disease activity in favoring a better RA course as well as better pregnancy outcomes.

Smeele and colleagues recently published an analysis of the PreCARA cohort study looking at birthweight in pregnant patients with RA. RA is associated with children being born small for gestational age. In this cohort study of 188 pregnant patients with RA, the treatment protocol before pregnancy included hydroxychloroquine, sulfasalazine, prednisone, and anti–tumor necrosis factor (TNF) agents (adalimumab, infliximab, etanercept, and certolizumab). Anti-TNF medications were stopped at 20, 20, 28, or 38 weeks, respectively, according to the European Alliance of Associations for Rheumatology (EULAR) recommendations. In terms of gestational age at delivery and congenital malformations, no difference was seen between patients who used anti-TNF agents during pregnancy and those who did not. Anti-TNF use during pregnancy was associated, however, with increased birthweight and a lower percentage of infants who were small for gestational age. These findings are in keeping with those of prior studies, although larger studies would be helpful in determining whether there are critical periods during pregnancy that have a significant effect on birthweight or whether overall control of inflammation is the predominant factor.

New research links the use of glucocorticoids with changes in white matter microstructure – which may explain the development of anxiety, depression, and other neuropsychiatric side effects related to these drugs, investigators say.

Results from a cross-sectional study showed that use of both systemic and inhaled glucocorticoids was associated with widespread reductions in fractional anisotropy (FA) and increases in mean diffusivity.

Glucocorticoids have “a whole catalogue” of adverse events, and effects on brain structure “adds to the list,” co-investigator Onno C. Meijer, PhD, professor of molecular neuroendocrinology of corticosteroids, department of medicine, Leiden University Medical Center, the Netherlands, told this news organization.

Serious side effects

Glucocorticoids, a class of synthetic steroids with immunosuppressive properties, are prescribed for a wide range of conditions, including rheumatoid arthritis and asthma.

However, they are also associated with potentially serious metabolic, cardiovascular, and musculoskeletal side effects as well as neuropsychiatric side effects such as depression, mania, and cognitive impairment.

About 1 in 3 patients exposed to “quite a lot of these drugs” will experience neuropsychiatric symptoms, Dr. Meijer said.

Most previous studies that investigated effects from high levels of glucocorticoids on brain structure have been small and involved selected populations, such as those with Cushing disease.

The new study included participants from the UK Biobank, a large population-based cohort. Participants had undergone imaging and did not have a history of psychiatric disease – although they could have conditions associated with glucocorticoid use, including anxiety, depression, mania, or delirium.

The analysis included 222 patients using oral or parenteral glucocorticoids at the time of imaging (systemic group), 557 using inhaled glucocorticoids, and 24,106 not using glucocorticoids (the control group).

Inhaled steroids target the lungs, whereas a steroid in pill form “travels in the blood and reaches each and every organ and cell in the body and typically requires higher doses,” Dr. Meijer noted.

The groups were similar with respect to sex, education, and smoking status. However, the systemic glucocorticoid group was slightly older (mean age, 66.1 years vs. 63.3 years for inhaled glucocorticoid users and 63.5 years for the control group).

In addition to age, researchers adjusted for sex, education level, head position in the scanner, head size, assessment center, and year of imaging.
 

Imaging analyses

Imaging analyses showed systemic glucocorticoid use was associated with reduced global FA (adjusted mean difference, -3.7e-3; 95% confidence interval, -6.4e-3 to 1.0e-3), and reductions in regional FA in the body and genu of the corpus callosum versus the control group.

Inhaled glucocorticoid use was associated with reduced global FA (AMD, -2.3e-3; 95% CI, -4.0e-3 to -5.7e-4), and lower FA in the splenium of the corpus callosum and the cingulum of the hippocampus.

Global mean diffusivity was higher in systemic glucocorticoid users (AMD, 7.2e-6; 95% CI, 3.2e-6 to 1.1e-5) and inhaled glucocorticoid users (AMD, 2.7e-6; 95% CI, 1.7e-7 to 5.2e-6), compared with the control group.

The effects of glucocorticoids on white matter were “pervasive,” and the “most important finding” of the study, Dr. Meijer said. “We were impressed by the fact white matter is so sensitive to these drugs.”

He noted that it is likely that functional connectivity between brain regions is affected by use of glucocorticoids. “You could say communication between brain regions is probably somewhat impaired or challenged,” he said.

Subgroup analyses among participants using glucocorticoids chronically, defined as reported at two consecutive visits, suggested a potential dose-dependent or duration-dependent effect of glucocorticoids on white matter microstructure.

Systemic glucocorticoid use was also associated with an increase in total and grey matter volume of the caudate nucleus.

In addition, there was a significant association between inhaled glucocorticoid use and decreased grey matter volume of the amygdala, which Dr. Meijer said was surprising because studies have shown that glucocorticoids “can drive amygdala big time.”
 

Move away from ‘one dose for all’?

Another surprise was that the results showed no hippocampal volume differences with steroid use, Dr. Meijer noted.

The modest association between glucocorticoid use and brain volumes could indicate that white matter integrity is more sensitive to glucocorticoids than is grey matter volume, “at least at the structural level,” he said.

He added that longer use or higher doses may be necessary to also induce volumetric changes.

Participants also completed a questionnaire to assess mood over the previous 2 weeks. Systemic glucocorticoid users had more depressive symptoms, disinterest, tenseness/restlessness, and tiredness/lethargy, compared with the control group. Inhaled glucocorticoid users only reported more tiredness/lethargy.

The investigators note that mood-related effects could be linked to the condition for which glucocorticoids were prescribed: for example, rheumatoid arthritis or chronic obstructive pulmonary disease.

In terms of cognition, systemic glucocorticoid users performed significantly worse on the symbol digit substitution task, compared with participants in the control group.

In light of these findings, pharmaceutical companies that make inhaled corticosteroids “should perhaps find out if glucocorticoids can be dosed by kilogram body weight rather than simply one dose fits all,” which is currently the case, Dr. Meijer said.
 

Impressive, but several limitations

Commenting on the findings, E. Sherwood Brown, MD, PhD, Distinguished Chair in Psychiatric Research and professor and vice chair for clinical research, department of psychiatry, The University of Texas Southwestern Medical Center, Dallas, called the study sample size “impressive.”

In addition, the study is the first to look at systemic as well as inhaled corticosteroids, said Dr. Brown, who was not involved with the research. He noted that previously, there had been only case reports of psychiatric symptoms with inhaled corticosteroids.

That results are in the same direction but greater with systemic, compared with inhaled corticosteroids, is “particularly interesting” because this might suggest dose-dependent effects, Dr. Brown said.

He noted that cognitive differences were also only observed with systemic corticosteroids.

Some study observations, such as smaller amygdala volume with inhaled but not systemic corticosteroids, “are harder to understand,” said Dr. Brown.

However, he pointed out some study limitations. For example, data were apparently unavailable for verbal and declarative memory test data, despite corticosteroids probably affecting the hippocampus and causing memory changes.

Other drawbacks were that the dose and duration of corticosteroid use, as well as the medical histories of study participants, were not available, Dr. Brown said.

No study funding was reported. Dr. Meijer has received research grants and honorariums from Corcept Therapeutics and a speakers’ fee from Ipsen. Dr. Brown is on an advisory board for Sage Pharmaceuticals, which is developing neurosteroids (not corticosteroids) for mood disorders. He is also on a Medscape advisory board related to bipolar disorder.

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

New research links the use of glucocorticoids with changes in white matter microstructure – which may explain the development of anxiety, depression, and other neuropsychiatric side effects related to these drugs, investigators say.

Results from a cross-sectional study showed that use of both systemic and inhaled glucocorticoids was associated with widespread reductions in fractional anisotropy (FA) and increases in mean diffusivity.

Glucocorticoids have “a whole catalogue” of adverse events, and effects on brain structure “adds to the list,” co-investigator Onno C. Meijer, PhD, professor of molecular neuroendocrinology of corticosteroids, department of medicine, Leiden University Medical Center, the Netherlands, told this news organization.

Serious side effects

Glucocorticoids, a class of synthetic steroids with immunosuppressive properties, are prescribed for a wide range of conditions, including rheumatoid arthritis and asthma.

However, they are also associated with potentially serious metabolic, cardiovascular, and musculoskeletal side effects as well as neuropsychiatric side effects such as depression, mania, and cognitive impairment.

About 1 in 3 patients exposed to “quite a lot of these drugs” will experience neuropsychiatric symptoms, Dr. Meijer said.

Most previous studies that investigated effects from high levels of glucocorticoids on brain structure have been small and involved selected populations, such as those with Cushing disease.

The new study included participants from the UK Biobank, a large population-based cohort. Participants had undergone imaging and did not have a history of psychiatric disease – although they could have conditions associated with glucocorticoid use, including anxiety, depression, mania, or delirium.

The analysis included 222 patients using oral or parenteral glucocorticoids at the time of imaging (systemic group), 557 using inhaled glucocorticoids, and 24,106 not using glucocorticoids (the control group).

Inhaled steroids target the lungs, whereas a steroid in pill form “travels in the blood and reaches each and every organ and cell in the body and typically requires higher doses,” Dr. Meijer noted.

The groups were similar with respect to sex, education, and smoking status. However, the systemic glucocorticoid group was slightly older (mean age, 66.1 years vs. 63.3 years for inhaled glucocorticoid users and 63.5 years for the control group).

In addition to age, researchers adjusted for sex, education level, head position in the scanner, head size, assessment center, and year of imaging.
 

Imaging analyses

Imaging analyses showed systemic glucocorticoid use was associated with reduced global FA (adjusted mean difference, -3.7e-3; 95% confidence interval, -6.4e-3 to 1.0e-3), and reductions in regional FA in the body and genu of the corpus callosum versus the control group.

Inhaled glucocorticoid use was associated with reduced global FA (AMD, -2.3e-3; 95% CI, -4.0e-3 to -5.7e-4), and lower FA in the splenium of the corpus callosum and the cingulum of the hippocampus.

Global mean diffusivity was higher in systemic glucocorticoid users (AMD, 7.2e-6; 95% CI, 3.2e-6 to 1.1e-5) and inhaled glucocorticoid users (AMD, 2.7e-6; 95% CI, 1.7e-7 to 5.2e-6), compared with the control group.

The effects of glucocorticoids on white matter were “pervasive,” and the “most important finding” of the study, Dr. Meijer said. “We were impressed by the fact white matter is so sensitive to these drugs.”

He noted that it is likely that functional connectivity between brain regions is affected by use of glucocorticoids. “You could say communication between brain regions is probably somewhat impaired or challenged,” he said.

Subgroup analyses among participants using glucocorticoids chronically, defined as reported at two consecutive visits, suggested a potential dose-dependent or duration-dependent effect of glucocorticoids on white matter microstructure.

Systemic glucocorticoid use was also associated with an increase in total and grey matter volume of the caudate nucleus.

In addition, there was a significant association between inhaled glucocorticoid use and decreased grey matter volume of the amygdala, which Dr. Meijer said was surprising because studies have shown that glucocorticoids “can drive amygdala big time.”
 

Move away from ‘one dose for all’?

Another surprise was that the results showed no hippocampal volume differences with steroid use, Dr. Meijer noted.

The modest association between glucocorticoid use and brain volumes could indicate that white matter integrity is more sensitive to glucocorticoids than is grey matter volume, “at least at the structural level,” he said.

He added that longer use or higher doses may be necessary to also induce volumetric changes.

Participants also completed a questionnaire to assess mood over the previous 2 weeks. Systemic glucocorticoid users had more depressive symptoms, disinterest, tenseness/restlessness, and tiredness/lethargy, compared with the control group. Inhaled glucocorticoid users only reported more tiredness/lethargy.

The investigators note that mood-related effects could be linked to the condition for which glucocorticoids were prescribed: for example, rheumatoid arthritis or chronic obstructive pulmonary disease.

In terms of cognition, systemic glucocorticoid users performed significantly worse on the symbol digit substitution task, compared with participants in the control group.

In light of these findings, pharmaceutical companies that make inhaled corticosteroids “should perhaps find out if glucocorticoids can be dosed by kilogram body weight rather than simply one dose fits all,” which is currently the case, Dr. Meijer said.
 

Impressive, but several limitations

Commenting on the findings, E. Sherwood Brown, MD, PhD, Distinguished Chair in Psychiatric Research and professor and vice chair for clinical research, department of psychiatry, The University of Texas Southwestern Medical Center, Dallas, called the study sample size “impressive.”

In addition, the study is the first to look at systemic as well as inhaled corticosteroids, said Dr. Brown, who was not involved with the research. He noted that previously, there had been only case reports of psychiatric symptoms with inhaled corticosteroids.

That results are in the same direction but greater with systemic, compared with inhaled corticosteroids, is “particularly interesting” because this might suggest dose-dependent effects, Dr. Brown said.

He noted that cognitive differences were also only observed with systemic corticosteroids.

Some study observations, such as smaller amygdala volume with inhaled but not systemic corticosteroids, “are harder to understand,” said Dr. Brown.

However, he pointed out some study limitations. For example, data were apparently unavailable for verbal and declarative memory test data, despite corticosteroids probably affecting the hippocampus and causing memory changes.

Other drawbacks were that the dose and duration of corticosteroid use, as well as the medical histories of study participants, were not available, Dr. Brown said.

No study funding was reported. Dr. Meijer has received research grants and honorariums from Corcept Therapeutics and a speakers’ fee from Ipsen. Dr. Brown is on an advisory board for Sage Pharmaceuticals, which is developing neurosteroids (not corticosteroids) for mood disorders. He is also on a Medscape advisory board related to bipolar disorder.

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

New research links the use of glucocorticoids with changes in white matter microstructure – which may explain the development of anxiety, depression, and other neuropsychiatric side effects related to these drugs, investigators say.

Results from a cross-sectional study showed that use of both systemic and inhaled glucocorticoids was associated with widespread reductions in fractional anisotropy (FA) and increases in mean diffusivity.

Glucocorticoids have “a whole catalogue” of adverse events, and effects on brain structure “adds to the list,” co-investigator Onno C. Meijer, PhD, professor of molecular neuroendocrinology of corticosteroids, department of medicine, Leiden University Medical Center, the Netherlands, told this news organization.

Serious side effects

Glucocorticoids, a class of synthetic steroids with immunosuppressive properties, are prescribed for a wide range of conditions, including rheumatoid arthritis and asthma.

However, they are also associated with potentially serious metabolic, cardiovascular, and musculoskeletal side effects as well as neuropsychiatric side effects such as depression, mania, and cognitive impairment.

About 1 in 3 patients exposed to “quite a lot of these drugs” will experience neuropsychiatric symptoms, Dr. Meijer said.

Most previous studies that investigated effects from high levels of glucocorticoids on brain structure have been small and involved selected populations, such as those with Cushing disease.

The new study included participants from the UK Biobank, a large population-based cohort. Participants had undergone imaging and did not have a history of psychiatric disease – although they could have conditions associated with glucocorticoid use, including anxiety, depression, mania, or delirium.

The analysis included 222 patients using oral or parenteral glucocorticoids at the time of imaging (systemic group), 557 using inhaled glucocorticoids, and 24,106 not using glucocorticoids (the control group).

Inhaled steroids target the lungs, whereas a steroid in pill form “travels in the blood and reaches each and every organ and cell in the body and typically requires higher doses,” Dr. Meijer noted.

The groups were similar with respect to sex, education, and smoking status. However, the systemic glucocorticoid group was slightly older (mean age, 66.1 years vs. 63.3 years for inhaled glucocorticoid users and 63.5 years for the control group).

In addition to age, researchers adjusted for sex, education level, head position in the scanner, head size, assessment center, and year of imaging.
 

Imaging analyses

Imaging analyses showed systemic glucocorticoid use was associated with reduced global FA (adjusted mean difference, -3.7e-3; 95% confidence interval, -6.4e-3 to 1.0e-3), and reductions in regional FA in the body and genu of the corpus callosum versus the control group.

Inhaled glucocorticoid use was associated with reduced global FA (AMD, -2.3e-3; 95% CI, -4.0e-3 to -5.7e-4), and lower FA in the splenium of the corpus callosum and the cingulum of the hippocampus.

Global mean diffusivity was higher in systemic glucocorticoid users (AMD, 7.2e-6; 95% CI, 3.2e-6 to 1.1e-5) and inhaled glucocorticoid users (AMD, 2.7e-6; 95% CI, 1.7e-7 to 5.2e-6), compared with the control group.

The effects of glucocorticoids on white matter were “pervasive,” and the “most important finding” of the study, Dr. Meijer said. “We were impressed by the fact white matter is so sensitive to these drugs.”

He noted that it is likely that functional connectivity between brain regions is affected by use of glucocorticoids. “You could say communication between brain regions is probably somewhat impaired or challenged,” he said.

Subgroup analyses among participants using glucocorticoids chronically, defined as reported at two consecutive visits, suggested a potential dose-dependent or duration-dependent effect of glucocorticoids on white matter microstructure.

Systemic glucocorticoid use was also associated with an increase in total and grey matter volume of the caudate nucleus.

In addition, there was a significant association between inhaled glucocorticoid use and decreased grey matter volume of the amygdala, which Dr. Meijer said was surprising because studies have shown that glucocorticoids “can drive amygdala big time.”
 

Move away from ‘one dose for all’?

Another surprise was that the results showed no hippocampal volume differences with steroid use, Dr. Meijer noted.

The modest association between glucocorticoid use and brain volumes could indicate that white matter integrity is more sensitive to glucocorticoids than is grey matter volume, “at least at the structural level,” he said.

He added that longer use or higher doses may be necessary to also induce volumetric changes.

Participants also completed a questionnaire to assess mood over the previous 2 weeks. Systemic glucocorticoid users had more depressive symptoms, disinterest, tenseness/restlessness, and tiredness/lethargy, compared with the control group. Inhaled glucocorticoid users only reported more tiredness/lethargy.

The investigators note that mood-related effects could be linked to the condition for which glucocorticoids were prescribed: for example, rheumatoid arthritis or chronic obstructive pulmonary disease.

In terms of cognition, systemic glucocorticoid users performed significantly worse on the symbol digit substitution task, compared with participants in the control group.

In light of these findings, pharmaceutical companies that make inhaled corticosteroids “should perhaps find out if glucocorticoids can be dosed by kilogram body weight rather than simply one dose fits all,” which is currently the case, Dr. Meijer said.
 

Impressive, but several limitations

Commenting on the findings, E. Sherwood Brown, MD, PhD, Distinguished Chair in Psychiatric Research and professor and vice chair for clinical research, department of psychiatry, The University of Texas Southwestern Medical Center, Dallas, called the study sample size “impressive.”

In addition, the study is the first to look at systemic as well as inhaled corticosteroids, said Dr. Brown, who was not involved with the research. He noted that previously, there had been only case reports of psychiatric symptoms with inhaled corticosteroids.

That results are in the same direction but greater with systemic, compared with inhaled corticosteroids, is “particularly interesting” because this might suggest dose-dependent effects, Dr. Brown said.

He noted that cognitive differences were also only observed with systemic corticosteroids.

Some study observations, such as smaller amygdala volume with inhaled but not systemic corticosteroids, “are harder to understand,” said Dr. Brown.

However, he pointed out some study limitations. For example, data were apparently unavailable for verbal and declarative memory test data, despite corticosteroids probably affecting the hippocampus and causing memory changes.

Other drawbacks were that the dose and duration of corticosteroid use, as well as the medical histories of study participants, were not available, Dr. Brown said.

No study funding was reported. Dr. Meijer has received research grants and honorariums from Corcept Therapeutics and a speakers’ fee from Ipsen. Dr. Brown is on an advisory board for Sage Pharmaceuticals, which is developing neurosteroids (not corticosteroids) for mood disorders. He is also on a Medscape advisory board related to bipolar disorder.

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

In the vast majority of people who experience muscle pain or weakness while taking a statin, those symptoms are not related to the statin, a new individual patient data meta-analysis of randomized controlled trials shows.

The Cholesterol Trialists Collaboration meta-analysis examined 19 large randomized double-blind trials that compared statin therapy with placebo and involved almost 124,000 patients.

RogerAshford/Thinkstock

“Our results show that, in people who experience muscle symptoms in the first year of taking a statin, those symptoms are actually due to the statin in only 1 of 15 of those people. For the other 14 of the 15 people who experience muscle symptoms in the first year of taking a statin, that muscle pain is not due to the statin,” lead investigator Colin Baigent, MD, said.

After the first year, there was no difference in muscle symptoms between patients taking a statin or those taking placebo.

Dr. Baigent, who is director of the Population Health Research Unit at the University of Oxford (England), presented the data on Aug. 29 at the European Society of Cardiology 2022 Congress.

It was also simultaneously published online in The Lancet. 

Dr. Baigent explained that statins very rarely cause serious muscle adverse effects with biochemical evidence of cellular damage, such as myopathy (which occurs in less than 1 in 10,000 patients per year) and rhabdomyolysis (which occurs in about 0.2 per 10,000 patients per year).

The effect of statins on other less serious muscle symptoms without biochemical evidence of cellular damage is less clear, but misinformation about the risks have arisen from nonrandomized studies, with social media and press reports suggesting that the risk for muscle symptoms with statins is extremely common, Dr. Baigent said.  

In response to this, the Cholesterol Trialists Collaboration put together a new program of data collection, validation, and analysis to provide reliable information from large double-blind randomized trials that are free from bias and confounding.

“Overall, when we look at all these data, we find there is about a 3% relative increase in the risks of experiencing muscle pain or weakness with a statin versus with placebo,” Dr. Baigent reported.

Muscle pain or weakness was reported by 16,835 of 62,028 patients taking a statin, (27.1%), compared with 16,446 of 61,912 patients taking placebo (26.6%), for a rate ratio of 1.03 (95% confidence interval, 1.01-1.06).

In absolute terms, the results show a rate of 166 reports of muscle symptoms per 1,000 patient-years in those taking a statin, compared with 155 per 1,000-patient-years in those taking placebo in the first year. This gives a rate ratio of 1.07 and an excess of 11 cases of muscle pain or weakness per 1,000 patients in the first year of statin therapy. 

“The very small excess of muscle symptoms in the statin patients were generally mild, with most patients able to continue treatment,” Dr. Baigent added. 

After the first year, the rate of muscle pain or weakness was exactly the same in the statin and placebo groups, at 50 per 1,000 patient-years.

“Therefore, for the vast majority of people who experience muscle pain or weakness on a statin, those symptoms are not due to the statin itself. It is due to something else, which could be ageing, thyroid disease, or exercise,” Dr. Baigent said. “After the first year of taking a statin, there is no excess risk of muscle pain or weakness at all.”

“To summarize, the excess risk of muscle pain or weakness with statin use is tiny, and almost nonexistent after the first year,” he added.

“Muscle pain is very common in the general population, and it was very common in both patients taking a statin and those given placebo in these randomized trials. We can only detect a difference by looking at all the data combined in this enormous study. And we now know for sure that over 90% of cases of muscle symptoms experienced by people taking a statin are not due to the statin.”

The researchers also looked at statin intensity and found that the more intense statins tend to cause slightly more muscle pain. “There was also some evidence, although this was not very clear, that the muscle pain with the more intensive statins may persist for longer than 1 year,” Dr. Baigent said.

But in terms of different moderate-intensity and high-intensity statins, there was no evidence of differences in muscle pain between the individual statin brands, he added.
 

Better patient information needed

Dr. Baigent called for better information in statin package inserts about the real risk for muscle symptoms with these drugs.

“We need to do a better job of communicating the real risk of muscle symptom to patients who are taking statins and to their doctors. At the moment, doctors often stop statins if patients complain of muscle pain, but our data show that in 14 out of 15 times, they would be wrong for doing that. Stopping the statin is nearly always a mistake,” he commented.

“At present, the package inserts include a whole load of rubbish from observational studies, which are completely unreliable,” he added. “This is of no value to patients. They go through this information and find several symptoms they are experiencing, which they attribute to the drugs. We really need to divide up the information into the evidence that we really know for sure and then the more speculative stuff.”

Dr. Baigent also highlighted the large benefits of statins, compared with the small risk for muscle symptoms.

“While statins may cause 11 patients per 1,000 to experience some mild muscle pain in the first year of taking these drugs, and this was reduced to none in subsequent years, statins, when used for the primary prevention of cardiovascular disease, prevent 25 cardiovascular events per 1,000 patients every year they are taken. And for secondary prevention this rises to 50 events prevented per 1,000 patients each year,” he noted.  

The individual participant data meta-analysis involved 23 trials with information on almost 155,000 patients. All trials included at least 1,000 patients and at least 2 years of scheduled treatment. Adverse-event data were collected for all individual participants in 19 large randomized double-blind trials comparing statin therapy with placebo (123,940 patients) and in four randomized double-blind trials comparing more-intensive with less-intensive statin therapy (30,724 patients).

In the four trials of more-intensive versus less-intensive statin therapy, high-intensity regimens (atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily) resulted in a larger relative increase in the rate of muscle pain or weakness than moderate-intensity regimens, with rate ratios of 1.08 (95% CI, 1.04-1.13) and 1.02 (95% CI, 1.00-1.05), respectively.
 

‘Reassuring information’

Discussant of the study at the ESC Hotline session, Erin Bohula, MD, Brigham and Women’s Hospital, Boston, said this new analysis had many strengths and used a rigorous approach to look at the issue of muscle symptoms with statins.

She pointed out some challenges, including the fact that the definition of adverse muscle events has changed over time and differed in the various trials, with heterogeneous data capture across trials. “So, this was a Herculean task to harmonize this very complicated dataset.”

Dr. Bohula concluded: “I think this is a very significant undertaking, resulting in a rich dataset that enhances our understanding of muscle symptoms related to statin use. The take-home for me is that muscle symptoms are a common complaint in the general population but are very rarely attributable to statins. This is very reassuring to me, and I hope it is reassuring to patients and can help us encourage them with adherence, given the clear cardiovascular benefits of statins.”

Chair of the ESC Hotline session at which the study was presented, Gabriel Steg, MD, Hôpital Bichat, Paris, asked whether some statin patients who experienced muscle symptoms with the drugs in active run-in periods in the trials may have been excluded from the main trials, so that this information might not have been captured, but Dr. Baigent replied that they also examined those data, which had been accounted for in the analysis.

“That’s really good news,” Dr. Steg commented. “This study is going to be one more tool in our response to statin skeptics and I think, as such, this work is a really a service to public health.”

The meta-analysis was funded by the British Heart Foundation, the U.K. Medical Research Council, and the Australian National Health and Medical Research Council.

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

In the vast majority of people who experience muscle pain or weakness while taking a statin, those symptoms are not related to the statin, a new individual patient data meta-analysis of randomized controlled trials shows.

The Cholesterol Trialists Collaboration meta-analysis examined 19 large randomized double-blind trials that compared statin therapy with placebo and involved almost 124,000 patients.

RogerAshford/Thinkstock

“Our results show that, in people who experience muscle symptoms in the first year of taking a statin, those symptoms are actually due to the statin in only 1 of 15 of those people. For the other 14 of the 15 people who experience muscle symptoms in the first year of taking a statin, that muscle pain is not due to the statin,” lead investigator Colin Baigent, MD, said.

After the first year, there was no difference in muscle symptoms between patients taking a statin or those taking placebo.

Dr. Baigent, who is director of the Population Health Research Unit at the University of Oxford (England), presented the data on Aug. 29 at the European Society of Cardiology 2022 Congress.

It was also simultaneously published online in The Lancet. 

Dr. Baigent explained that statins very rarely cause serious muscle adverse effects with biochemical evidence of cellular damage, such as myopathy (which occurs in less than 1 in 10,000 patients per year) and rhabdomyolysis (which occurs in about 0.2 per 10,000 patients per year).

The effect of statins on other less serious muscle symptoms without biochemical evidence of cellular damage is less clear, but misinformation about the risks have arisen from nonrandomized studies, with social media and press reports suggesting that the risk for muscle symptoms with statins is extremely common, Dr. Baigent said.  

In response to this, the Cholesterol Trialists Collaboration put together a new program of data collection, validation, and analysis to provide reliable information from large double-blind randomized trials that are free from bias and confounding.

“Overall, when we look at all these data, we find there is about a 3% relative increase in the risks of experiencing muscle pain or weakness with a statin versus with placebo,” Dr. Baigent reported.

Muscle pain or weakness was reported by 16,835 of 62,028 patients taking a statin, (27.1%), compared with 16,446 of 61,912 patients taking placebo (26.6%), for a rate ratio of 1.03 (95% confidence interval, 1.01-1.06).

In absolute terms, the results show a rate of 166 reports of muscle symptoms per 1,000 patient-years in those taking a statin, compared with 155 per 1,000-patient-years in those taking placebo in the first year. This gives a rate ratio of 1.07 and an excess of 11 cases of muscle pain or weakness per 1,000 patients in the first year of statin therapy. 

“The very small excess of muscle symptoms in the statin patients were generally mild, with most patients able to continue treatment,” Dr. Baigent added. 

After the first year, the rate of muscle pain or weakness was exactly the same in the statin and placebo groups, at 50 per 1,000 patient-years.

“Therefore, for the vast majority of people who experience muscle pain or weakness on a statin, those symptoms are not due to the statin itself. It is due to something else, which could be ageing, thyroid disease, or exercise,” Dr. Baigent said. “After the first year of taking a statin, there is no excess risk of muscle pain or weakness at all.”

“To summarize, the excess risk of muscle pain or weakness with statin use is tiny, and almost nonexistent after the first year,” he added.

“Muscle pain is very common in the general population, and it was very common in both patients taking a statin and those given placebo in these randomized trials. We can only detect a difference by looking at all the data combined in this enormous study. And we now know for sure that over 90% of cases of muscle symptoms experienced by people taking a statin are not due to the statin.”

The researchers also looked at statin intensity and found that the more intense statins tend to cause slightly more muscle pain. “There was also some evidence, although this was not very clear, that the muscle pain with the more intensive statins may persist for longer than 1 year,” Dr. Baigent said.

But in terms of different moderate-intensity and high-intensity statins, there was no evidence of differences in muscle pain between the individual statin brands, he added.
 

Better patient information needed

Dr. Baigent called for better information in statin package inserts about the real risk for muscle symptoms with these drugs.

“We need to do a better job of communicating the real risk of muscle symptom to patients who are taking statins and to their doctors. At the moment, doctors often stop statins if patients complain of muscle pain, but our data show that in 14 out of 15 times, they would be wrong for doing that. Stopping the statin is nearly always a mistake,” he commented.

“At present, the package inserts include a whole load of rubbish from observational studies, which are completely unreliable,” he added. “This is of no value to patients. They go through this information and find several symptoms they are experiencing, which they attribute to the drugs. We really need to divide up the information into the evidence that we really know for sure and then the more speculative stuff.”

Dr. Baigent also highlighted the large benefits of statins, compared with the small risk for muscle symptoms.

“While statins may cause 11 patients per 1,000 to experience some mild muscle pain in the first year of taking these drugs, and this was reduced to none in subsequent years, statins, when used for the primary prevention of cardiovascular disease, prevent 25 cardiovascular events per 1,000 patients every year they are taken. And for secondary prevention this rises to 50 events prevented per 1,000 patients each year,” he noted.  

The individual participant data meta-analysis involved 23 trials with information on almost 155,000 patients. All trials included at least 1,000 patients and at least 2 years of scheduled treatment. Adverse-event data were collected for all individual participants in 19 large randomized double-blind trials comparing statin therapy with placebo (123,940 patients) and in four randomized double-blind trials comparing more-intensive with less-intensive statin therapy (30,724 patients).

In the four trials of more-intensive versus less-intensive statin therapy, high-intensity regimens (atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily) resulted in a larger relative increase in the rate of muscle pain or weakness than moderate-intensity regimens, with rate ratios of 1.08 (95% CI, 1.04-1.13) and 1.02 (95% CI, 1.00-1.05), respectively.
 

‘Reassuring information’

Discussant of the study at the ESC Hotline session, Erin Bohula, MD, Brigham and Women’s Hospital, Boston, said this new analysis had many strengths and used a rigorous approach to look at the issue of muscle symptoms with statins.

She pointed out some challenges, including the fact that the definition of adverse muscle events has changed over time and differed in the various trials, with heterogeneous data capture across trials. “So, this was a Herculean task to harmonize this very complicated dataset.”

Dr. Bohula concluded: “I think this is a very significant undertaking, resulting in a rich dataset that enhances our understanding of muscle symptoms related to statin use. The take-home for me is that muscle symptoms are a common complaint in the general population but are very rarely attributable to statins. This is very reassuring to me, and I hope it is reassuring to patients and can help us encourage them with adherence, given the clear cardiovascular benefits of statins.”

Chair of the ESC Hotline session at which the study was presented, Gabriel Steg, MD, Hôpital Bichat, Paris, asked whether some statin patients who experienced muscle symptoms with the drugs in active run-in periods in the trials may have been excluded from the main trials, so that this information might not have been captured, but Dr. Baigent replied that they also examined those data, which had been accounted for in the analysis.

“That’s really good news,” Dr. Steg commented. “This study is going to be one more tool in our response to statin skeptics and I think, as such, this work is a really a service to public health.”

The meta-analysis was funded by the British Heart Foundation, the U.K. Medical Research Council, and the Australian National Health and Medical Research Council.

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

In the vast majority of people who experience muscle pain or weakness while taking a statin, those symptoms are not related to the statin, a new individual patient data meta-analysis of randomized controlled trials shows.

The Cholesterol Trialists Collaboration meta-analysis examined 19 large randomized double-blind trials that compared statin therapy with placebo and involved almost 124,000 patients.

RogerAshford/Thinkstock

“Our results show that, in people who experience muscle symptoms in the first year of taking a statin, those symptoms are actually due to the statin in only 1 of 15 of those people. For the other 14 of the 15 people who experience muscle symptoms in the first year of taking a statin, that muscle pain is not due to the statin,” lead investigator Colin Baigent, MD, said.

After the first year, there was no difference in muscle symptoms between patients taking a statin or those taking placebo.

Dr. Baigent, who is director of the Population Health Research Unit at the University of Oxford (England), presented the data on Aug. 29 at the European Society of Cardiology 2022 Congress.

It was also simultaneously published online in The Lancet. 

Dr. Baigent explained that statins very rarely cause serious muscle adverse effects with biochemical evidence of cellular damage, such as myopathy (which occurs in less than 1 in 10,000 patients per year) and rhabdomyolysis (which occurs in about 0.2 per 10,000 patients per year).

The effect of statins on other less serious muscle symptoms without biochemical evidence of cellular damage is less clear, but misinformation about the risks have arisen from nonrandomized studies, with social media and press reports suggesting that the risk for muscle symptoms with statins is extremely common, Dr. Baigent said.  

In response to this, the Cholesterol Trialists Collaboration put together a new program of data collection, validation, and analysis to provide reliable information from large double-blind randomized trials that are free from bias and confounding.

“Overall, when we look at all these data, we find there is about a 3% relative increase in the risks of experiencing muscle pain or weakness with a statin versus with placebo,” Dr. Baigent reported.

Muscle pain or weakness was reported by 16,835 of 62,028 patients taking a statin, (27.1%), compared with 16,446 of 61,912 patients taking placebo (26.6%), for a rate ratio of 1.03 (95% confidence interval, 1.01-1.06).

In absolute terms, the results show a rate of 166 reports of muscle symptoms per 1,000 patient-years in those taking a statin, compared with 155 per 1,000-patient-years in those taking placebo in the first year. This gives a rate ratio of 1.07 and an excess of 11 cases of muscle pain or weakness per 1,000 patients in the first year of statin therapy. 

“The very small excess of muscle symptoms in the statin patients were generally mild, with most patients able to continue treatment,” Dr. Baigent added. 

After the first year, the rate of muscle pain or weakness was exactly the same in the statin and placebo groups, at 50 per 1,000 patient-years.

“Therefore, for the vast majority of people who experience muscle pain or weakness on a statin, those symptoms are not due to the statin itself. It is due to something else, which could be ageing, thyroid disease, or exercise,” Dr. Baigent said. “After the first year of taking a statin, there is no excess risk of muscle pain or weakness at all.”

“To summarize, the excess risk of muscle pain or weakness with statin use is tiny, and almost nonexistent after the first year,” he added.

“Muscle pain is very common in the general population, and it was very common in both patients taking a statin and those given placebo in these randomized trials. We can only detect a difference by looking at all the data combined in this enormous study. And we now know for sure that over 90% of cases of muscle symptoms experienced by people taking a statin are not due to the statin.”

The researchers also looked at statin intensity and found that the more intense statins tend to cause slightly more muscle pain. “There was also some evidence, although this was not very clear, that the muscle pain with the more intensive statins may persist for longer than 1 year,” Dr. Baigent said.

But in terms of different moderate-intensity and high-intensity statins, there was no evidence of differences in muscle pain between the individual statin brands, he added.
 

Better patient information needed

Dr. Baigent called for better information in statin package inserts about the real risk for muscle symptoms with these drugs.

“We need to do a better job of communicating the real risk of muscle symptom to patients who are taking statins and to their doctors. At the moment, doctors often stop statins if patients complain of muscle pain, but our data show that in 14 out of 15 times, they would be wrong for doing that. Stopping the statin is nearly always a mistake,” he commented.

“At present, the package inserts include a whole load of rubbish from observational studies, which are completely unreliable,” he added. “This is of no value to patients. They go through this information and find several symptoms they are experiencing, which they attribute to the drugs. We really need to divide up the information into the evidence that we really know for sure and then the more speculative stuff.”

Dr. Baigent also highlighted the large benefits of statins, compared with the small risk for muscle symptoms.

“While statins may cause 11 patients per 1,000 to experience some mild muscle pain in the first year of taking these drugs, and this was reduced to none in subsequent years, statins, when used for the primary prevention of cardiovascular disease, prevent 25 cardiovascular events per 1,000 patients every year they are taken. And for secondary prevention this rises to 50 events prevented per 1,000 patients each year,” he noted.  

The individual participant data meta-analysis involved 23 trials with information on almost 155,000 patients. All trials included at least 1,000 patients and at least 2 years of scheduled treatment. Adverse-event data were collected for all individual participants in 19 large randomized double-blind trials comparing statin therapy with placebo (123,940 patients) and in four randomized double-blind trials comparing more-intensive with less-intensive statin therapy (30,724 patients).

In the four trials of more-intensive versus less-intensive statin therapy, high-intensity regimens (atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily) resulted in a larger relative increase in the rate of muscle pain or weakness than moderate-intensity regimens, with rate ratios of 1.08 (95% CI, 1.04-1.13) and 1.02 (95% CI, 1.00-1.05), respectively.
 

‘Reassuring information’

Discussant of the study at the ESC Hotline session, Erin Bohula, MD, Brigham and Women’s Hospital, Boston, said this new analysis had many strengths and used a rigorous approach to look at the issue of muscle symptoms with statins.

She pointed out some challenges, including the fact that the definition of adverse muscle events has changed over time and differed in the various trials, with heterogeneous data capture across trials. “So, this was a Herculean task to harmonize this very complicated dataset.”

Dr. Bohula concluded: “I think this is a very significant undertaking, resulting in a rich dataset that enhances our understanding of muscle symptoms related to statin use. The take-home for me is that muscle symptoms are a common complaint in the general population but are very rarely attributable to statins. This is very reassuring to me, and I hope it is reassuring to patients and can help us encourage them with adherence, given the clear cardiovascular benefits of statins.”

Chair of the ESC Hotline session at which the study was presented, Gabriel Steg, MD, Hôpital Bichat, Paris, asked whether some statin patients who experienced muscle symptoms with the drugs in active run-in periods in the trials may have been excluded from the main trials, so that this information might not have been captured, but Dr. Baigent replied that they also examined those data, which had been accounted for in the analysis.

“That’s really good news,” Dr. Steg commented. “This study is going to be one more tool in our response to statin skeptics and I think, as such, this work is a really a service to public health.”

The meta-analysis was funded by the British Heart Foundation, the U.K. Medical Research Council, and the Australian National Health and Medical Research Council.

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