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CHICAGO – New results from a trial in patients with newly diagnosed multiple myeloma (MM) offer some answers to questions about which treatment route to choose.

The trial, known as DETERMINATION, found that newly diagnosed patients treated with a triplet of drugs had longer progression-free survival (PFS) if they received an autologous stem cell transplant (ASCT) soon after the drug therapy than if they simply had their stem cells collected for a possible future transplant.

Patients who received the triplet of lenalidomide, bortezomib, and dexamethasone (RVD) plus ASCT had a median PFS of 67.5 months, compared with 46.2 months for those who received RVD but did not have a transplant soon after.

However, patients were just as likely to be alive more than 6 years after treatment regardless of whether or not they underwent an immediate stem cell transplant.

In addition, treatment-related adverse events of grade 3 or above were higher in the group that received the transplant immediately after the triplet therapy.  

The results were presented during a plenary session at the American Society of Clinical Oncology annual meeting and simultaneously published in the New England Journal of Medicine.

“Our findings confirm the PFS benefit of transplantation as first-line treatment for patients with myeloma and confirms stem cell transplant as a standard of care with certain triplet therapy,” said lead author Paul G. Richardson, MD, professor of medicine, Harvard Medical School, and clinical program leader and director of clinical research at the Jerome Lipper Multiple Myeloma Center at Dana Farber Cancer Institute, Boston.

Another finding from the trial was that the use of maintenance lenalidomide in both groups continuously until progression conferred substantial clinical benefit.

“We can also say that the use of lenalidomide maintenance therapy is also a standard of care,” he added.
 

Study details

In this trial, Dr. Richardson and colleagues randomly assigned 873 patients newly diagnosed with multiple myeloma to the RVD-alone group (n = 357) or the transplantation group (n = 365). All patients had received one cycle of RVD prior to randomization and then received two additional RVD cycles plus stem-cell mobilization followed by either five additional RVD cycles (the RVD-alone group) or high-dose melphalan plus ASCT followed by two additional RVD cycles (the transplantation group). Lenalidomide was administered to all patients until disease progression, unacceptable side effects, or both.

At a median follow-up of 76.0 months, the risk of disease progression or death was 53% higher among patients who received RVD alone versus the transplantation group (hazard ratio [HR], 1.53; P < .001). The median duration of PFS among patients with a high-risk cytogenetic profile was 55.5 vs. 17.1 months, favoring the transplantation group.

The percentage of patients who were alive without progression at 5 years was 58.4% vs 41.6%, respectively (HR, 1.66) and median duration of response was 56.4 vs 38.9 months, also favoring transplantation (HR, 1.45).

The estimated 5-year overall survival was similar between groups: 80.7% for transplantation and 79.2% for RVD alone (HR for death, 1.10; P > .99). For patients with a high-risk cytogenetic profile, 5-year survival was 63.4% versus 54.3%, respectively.

“This tells us that for patients who had kept transplant in reserve, they had the same overall survival as those who had had a transplant right away, despite there being such impressive initial disease control for the patients in whom transplant was used early,” Dr. Richardson said in a press release from his institution.

Patients who did not undergo immediate transplant received treatment when their disease progressed with newer and active therapies, such as monoclonal antibodies and/or next-generation novel agents, he noted. Only 28% of patients used the reserve option of a transplant.

“It demonstrates the extent to which patients now have options and that we have new data to guide them in balancing the pluses and minuses of each approach,” he added.

When looking at safety, the authors noted that the most common treatment-related adverse events of grade 3 or higher occurred in 279 patients (78.2%) in the RVD-alone group and 344 patients (94.2%) in the transplantation group. Of those patients, 60.5% and 89.9%, respectively, reported hematologic events of grade 3 or higher (P < .001). The 5-year cumulative incidence of invasive second primary cancers was similar in both cohorts (RVD-alone group, 4.9%; transplantation group, 6.5%).

However, while the risk of secondary cancers was similar between groups, Dr. Richardson noted that there was a higher incidence of acute myeloid leukemia and myelodysplastic syndromes in the transplant cohort.

“There was also a significant drop in quality of life across transplant procedures, but the good news is that it was recoverable rapidly,” he said. “What is also really important is that we have prospective, multicenter, national comparative data on toxicity. That’s very important for providing patients with a choice as they move forward with their treatment plan.”

He noted that treatment continues to evolve. “This study was designed in 2009, begun in 2010, and now there is mature data in 2022,” Dr. Richardson said. “This is particularly relevant as we have now further improved the induction treatment for younger patients with newly diagnosed myeloma using quadruplet regimens incorporating monoclonal antibodies and novel next-generation therapies. The results from these studies are extremely exciting.

“Now more than ever, treatment for multiple myeloma can be adapted for each patient,” Dr. Richardson said. “Our study provides important information about the benefits of transplant in the era of highly effective novel therapies and continuous maintenance, as well as the potential risks, to help patients and their physicians decide what approach may be best for them. This is particularly relevant as we have now further improved the induction treatment for younger patients with newly diagnosed myeloma using quadruplet regimens incorporating monoclonal antibodies, such as RVD combined with daratumumab.”
 

Lack of difference in overall survival

These new results further support an already established role of autologous hematopoietic stem cell transplantation in the management of patients with multiple myeloma, said Samer Al-Homsi, MD, clinical professor of medicine and director of the blood and marrow transplant program at Perlmutter Cancer Center, NYU Langone, New York, who was approached for comment.

“The treatment regimen is applicable to patients who are determined by an expert in transplantation to be fit to receive autologous hematopoietic transplantation,” he added. “Although this study, like many others, establishes hematopoietic stem cell transplantation as part of the standard of care in multiple myeloma, only a fraction of patients are actually offered this important modality of treatment for a variety of reasons, including provider bias,” he noted. “In fact, although improvement in supportive care has enhanced the safety of the procedure, many patients are denied this therapy.” 

Dr. Al-Homsi noted that the lack of difference in overall survival might be due to the fact that some patients (28%) in the RVD-alone group did end up undergoing transplantation at the time of progression. “Also, longer follow-up might reveal a difference in overall survival,” he said.

The toxicities are manageable, and the incidence of secondary malignancies was not significantly different between cohorts. “However,” he emphasized, “lenalidomide has been associated in other studies with increased incidence of secondary malignancies and it must be noted that this study used extended administration of lenalidomide until progression.” 

Support for this study was provided by grants to the Blood and Marrow Transplant Clinical Trials Network from the National Heart, Lung, and Blood Institute, the National Cancer Institute, R. J. Corman Multiple Myeloma Foundation, Celgene/Bristol Myers Squibb, and Millennium/Takeda Pharmaceutical. Dr. Richardson has reported relationships with Celgene, Janssen, Jazz Pharmaceuticals, Karyopharm Therapeutics, Oncopeptides, Sanofi, Secura Bio, Takeda, and Bristol Myers Squibb. Dr. Al-Homsi has reported no relevant financial relationships.

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

CHICAGO – New results from a trial in patients with newly diagnosed multiple myeloma (MM) offer some answers to questions about which treatment route to choose.

The trial, known as DETERMINATION, found that newly diagnosed patients treated with a triplet of drugs had longer progression-free survival (PFS) if they received an autologous stem cell transplant (ASCT) soon after the drug therapy than if they simply had their stem cells collected for a possible future transplant.

Patients who received the triplet of lenalidomide, bortezomib, and dexamethasone (RVD) plus ASCT had a median PFS of 67.5 months, compared with 46.2 months for those who received RVD but did not have a transplant soon after.

However, patients were just as likely to be alive more than 6 years after treatment regardless of whether or not they underwent an immediate stem cell transplant.

In addition, treatment-related adverse events of grade 3 or above were higher in the group that received the transplant immediately after the triplet therapy.  

The results were presented during a plenary session at the American Society of Clinical Oncology annual meeting and simultaneously published in the New England Journal of Medicine.

“Our findings confirm the PFS benefit of transplantation as first-line treatment for patients with myeloma and confirms stem cell transplant as a standard of care with certain triplet therapy,” said lead author Paul G. Richardson, MD, professor of medicine, Harvard Medical School, and clinical program leader and director of clinical research at the Jerome Lipper Multiple Myeloma Center at Dana Farber Cancer Institute, Boston.

Another finding from the trial was that the use of maintenance lenalidomide in both groups continuously until progression conferred substantial clinical benefit.

“We can also say that the use of lenalidomide maintenance therapy is also a standard of care,” he added.
 

Study details

In this trial, Dr. Richardson and colleagues randomly assigned 873 patients newly diagnosed with multiple myeloma to the RVD-alone group (n = 357) or the transplantation group (n = 365). All patients had received one cycle of RVD prior to randomization and then received two additional RVD cycles plus stem-cell mobilization followed by either five additional RVD cycles (the RVD-alone group) or high-dose melphalan plus ASCT followed by two additional RVD cycles (the transplantation group). Lenalidomide was administered to all patients until disease progression, unacceptable side effects, or both.

At a median follow-up of 76.0 months, the risk of disease progression or death was 53% higher among patients who received RVD alone versus the transplantation group (hazard ratio [HR], 1.53; P < .001). The median duration of PFS among patients with a high-risk cytogenetic profile was 55.5 vs. 17.1 months, favoring the transplantation group.

The percentage of patients who were alive without progression at 5 years was 58.4% vs 41.6%, respectively (HR, 1.66) and median duration of response was 56.4 vs 38.9 months, also favoring transplantation (HR, 1.45).

The estimated 5-year overall survival was similar between groups: 80.7% for transplantation and 79.2% for RVD alone (HR for death, 1.10; P > .99). For patients with a high-risk cytogenetic profile, 5-year survival was 63.4% versus 54.3%, respectively.

“This tells us that for patients who had kept transplant in reserve, they had the same overall survival as those who had had a transplant right away, despite there being such impressive initial disease control for the patients in whom transplant was used early,” Dr. Richardson said in a press release from his institution.

Patients who did not undergo immediate transplant received treatment when their disease progressed with newer and active therapies, such as monoclonal antibodies and/or next-generation novel agents, he noted. Only 28% of patients used the reserve option of a transplant.

“It demonstrates the extent to which patients now have options and that we have new data to guide them in balancing the pluses and minuses of each approach,” he added.

When looking at safety, the authors noted that the most common treatment-related adverse events of grade 3 or higher occurred in 279 patients (78.2%) in the RVD-alone group and 344 patients (94.2%) in the transplantation group. Of those patients, 60.5% and 89.9%, respectively, reported hematologic events of grade 3 or higher (P < .001). The 5-year cumulative incidence of invasive second primary cancers was similar in both cohorts (RVD-alone group, 4.9%; transplantation group, 6.5%).

However, while the risk of secondary cancers was similar between groups, Dr. Richardson noted that there was a higher incidence of acute myeloid leukemia and myelodysplastic syndromes in the transplant cohort.

“There was also a significant drop in quality of life across transplant procedures, but the good news is that it was recoverable rapidly,” he said. “What is also really important is that we have prospective, multicenter, national comparative data on toxicity. That’s very important for providing patients with a choice as they move forward with their treatment plan.”

He noted that treatment continues to evolve. “This study was designed in 2009, begun in 2010, and now there is mature data in 2022,” Dr. Richardson said. “This is particularly relevant as we have now further improved the induction treatment for younger patients with newly diagnosed myeloma using quadruplet regimens incorporating monoclonal antibodies and novel next-generation therapies. The results from these studies are extremely exciting.

“Now more than ever, treatment for multiple myeloma can be adapted for each patient,” Dr. Richardson said. “Our study provides important information about the benefits of transplant in the era of highly effective novel therapies and continuous maintenance, as well as the potential risks, to help patients and their physicians decide what approach may be best for them. This is particularly relevant as we have now further improved the induction treatment for younger patients with newly diagnosed myeloma using quadruplet regimens incorporating monoclonal antibodies, such as RVD combined with daratumumab.”
 

Lack of difference in overall survival

These new results further support an already established role of autologous hematopoietic stem cell transplantation in the management of patients with multiple myeloma, said Samer Al-Homsi, MD, clinical professor of medicine and director of the blood and marrow transplant program at Perlmutter Cancer Center, NYU Langone, New York, who was approached for comment.

“The treatment regimen is applicable to patients who are determined by an expert in transplantation to be fit to receive autologous hematopoietic transplantation,” he added. “Although this study, like many others, establishes hematopoietic stem cell transplantation as part of the standard of care in multiple myeloma, only a fraction of patients are actually offered this important modality of treatment for a variety of reasons, including provider bias,” he noted. “In fact, although improvement in supportive care has enhanced the safety of the procedure, many patients are denied this therapy.” 

Dr. Al-Homsi noted that the lack of difference in overall survival might be due to the fact that some patients (28%) in the RVD-alone group did end up undergoing transplantation at the time of progression. “Also, longer follow-up might reveal a difference in overall survival,” he said.

The toxicities are manageable, and the incidence of secondary malignancies was not significantly different between cohorts. “However,” he emphasized, “lenalidomide has been associated in other studies with increased incidence of secondary malignancies and it must be noted that this study used extended administration of lenalidomide until progression.” 

Support for this study was provided by grants to the Blood and Marrow Transplant Clinical Trials Network from the National Heart, Lung, and Blood Institute, the National Cancer Institute, R. J. Corman Multiple Myeloma Foundation, Celgene/Bristol Myers Squibb, and Millennium/Takeda Pharmaceutical. Dr. Richardson has reported relationships with Celgene, Janssen, Jazz Pharmaceuticals, Karyopharm Therapeutics, Oncopeptides, Sanofi, Secura Bio, Takeda, and Bristol Myers Squibb. Dr. Al-Homsi has reported no relevant financial relationships.

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

CHICAGO – New results from a trial in patients with newly diagnosed multiple myeloma (MM) offer some answers to questions about which treatment route to choose.

The trial, known as DETERMINATION, found that newly diagnosed patients treated with a triplet of drugs had longer progression-free survival (PFS) if they received an autologous stem cell transplant (ASCT) soon after the drug therapy than if they simply had their stem cells collected for a possible future transplant.

Patients who received the triplet of lenalidomide, bortezomib, and dexamethasone (RVD) plus ASCT had a median PFS of 67.5 months, compared with 46.2 months for those who received RVD but did not have a transplant soon after.

However, patients were just as likely to be alive more than 6 years after treatment regardless of whether or not they underwent an immediate stem cell transplant.

In addition, treatment-related adverse events of grade 3 or above were higher in the group that received the transplant immediately after the triplet therapy.  

The results were presented during a plenary session at the American Society of Clinical Oncology annual meeting and simultaneously published in the New England Journal of Medicine.

“Our findings confirm the PFS benefit of transplantation as first-line treatment for patients with myeloma and confirms stem cell transplant as a standard of care with certain triplet therapy,” said lead author Paul G. Richardson, MD, professor of medicine, Harvard Medical School, and clinical program leader and director of clinical research at the Jerome Lipper Multiple Myeloma Center at Dana Farber Cancer Institute, Boston.

Another finding from the trial was that the use of maintenance lenalidomide in both groups continuously until progression conferred substantial clinical benefit.

“We can also say that the use of lenalidomide maintenance therapy is also a standard of care,” he added.
 

Study details

In this trial, Dr. Richardson and colleagues randomly assigned 873 patients newly diagnosed with multiple myeloma to the RVD-alone group (n = 357) or the transplantation group (n = 365). All patients had received one cycle of RVD prior to randomization and then received two additional RVD cycles plus stem-cell mobilization followed by either five additional RVD cycles (the RVD-alone group) or high-dose melphalan plus ASCT followed by two additional RVD cycles (the transplantation group). Lenalidomide was administered to all patients until disease progression, unacceptable side effects, or both.

At a median follow-up of 76.0 months, the risk of disease progression or death was 53% higher among patients who received RVD alone versus the transplantation group (hazard ratio [HR], 1.53; P < .001). The median duration of PFS among patients with a high-risk cytogenetic profile was 55.5 vs. 17.1 months, favoring the transplantation group.

The percentage of patients who were alive without progression at 5 years was 58.4% vs 41.6%, respectively (HR, 1.66) and median duration of response was 56.4 vs 38.9 months, also favoring transplantation (HR, 1.45).

The estimated 5-year overall survival was similar between groups: 80.7% for transplantation and 79.2% for RVD alone (HR for death, 1.10; P > .99). For patients with a high-risk cytogenetic profile, 5-year survival was 63.4% versus 54.3%, respectively.

“This tells us that for patients who had kept transplant in reserve, they had the same overall survival as those who had had a transplant right away, despite there being such impressive initial disease control for the patients in whom transplant was used early,” Dr. Richardson said in a press release from his institution.

Patients who did not undergo immediate transplant received treatment when their disease progressed with newer and active therapies, such as monoclonal antibodies and/or next-generation novel agents, he noted. Only 28% of patients used the reserve option of a transplant.

“It demonstrates the extent to which patients now have options and that we have new data to guide them in balancing the pluses and minuses of each approach,” he added.

When looking at safety, the authors noted that the most common treatment-related adverse events of grade 3 or higher occurred in 279 patients (78.2%) in the RVD-alone group and 344 patients (94.2%) in the transplantation group. Of those patients, 60.5% and 89.9%, respectively, reported hematologic events of grade 3 or higher (P < .001). The 5-year cumulative incidence of invasive second primary cancers was similar in both cohorts (RVD-alone group, 4.9%; transplantation group, 6.5%).

However, while the risk of secondary cancers was similar between groups, Dr. Richardson noted that there was a higher incidence of acute myeloid leukemia and myelodysplastic syndromes in the transplant cohort.

“There was also a significant drop in quality of life across transplant procedures, but the good news is that it was recoverable rapidly,” he said. “What is also really important is that we have prospective, multicenter, national comparative data on toxicity. That’s very important for providing patients with a choice as they move forward with their treatment plan.”

He noted that treatment continues to evolve. “This study was designed in 2009, begun in 2010, and now there is mature data in 2022,” Dr. Richardson said. “This is particularly relevant as we have now further improved the induction treatment for younger patients with newly diagnosed myeloma using quadruplet regimens incorporating monoclonal antibodies and novel next-generation therapies. The results from these studies are extremely exciting.

“Now more than ever, treatment for multiple myeloma can be adapted for each patient,” Dr. Richardson said. “Our study provides important information about the benefits of transplant in the era of highly effective novel therapies and continuous maintenance, as well as the potential risks, to help patients and their physicians decide what approach may be best for them. This is particularly relevant as we have now further improved the induction treatment for younger patients with newly diagnosed myeloma using quadruplet regimens incorporating monoclonal antibodies, such as RVD combined with daratumumab.”
 

Lack of difference in overall survival

These new results further support an already established role of autologous hematopoietic stem cell transplantation in the management of patients with multiple myeloma, said Samer Al-Homsi, MD, clinical professor of medicine and director of the blood and marrow transplant program at Perlmutter Cancer Center, NYU Langone, New York, who was approached for comment.

“The treatment regimen is applicable to patients who are determined by an expert in transplantation to be fit to receive autologous hematopoietic transplantation,” he added. “Although this study, like many others, establishes hematopoietic stem cell transplantation as part of the standard of care in multiple myeloma, only a fraction of patients are actually offered this important modality of treatment for a variety of reasons, including provider bias,” he noted. “In fact, although improvement in supportive care has enhanced the safety of the procedure, many patients are denied this therapy.” 

Dr. Al-Homsi noted that the lack of difference in overall survival might be due to the fact that some patients (28%) in the RVD-alone group did end up undergoing transplantation at the time of progression. “Also, longer follow-up might reveal a difference in overall survival,” he said.

The toxicities are manageable, and the incidence of secondary malignancies was not significantly different between cohorts. “However,” he emphasized, “lenalidomide has been associated in other studies with increased incidence of secondary malignancies and it must be noted that this study used extended administration of lenalidomide until progression.” 

Support for this study was provided by grants to the Blood and Marrow Transplant Clinical Trials Network from the National Heart, Lung, and Blood Institute, the National Cancer Institute, R. J. Corman Multiple Myeloma Foundation, Celgene/Bristol Myers Squibb, and Millennium/Takeda Pharmaceutical. Dr. Richardson has reported relationships with Celgene, Janssen, Jazz Pharmaceuticals, Karyopharm Therapeutics, Oncopeptides, Sanofi, Secura Bio, Takeda, and Bristol Myers Squibb. Dr. Al-Homsi has reported no relevant financial relationships.

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

A novel blood-based assay could one day be used to diagnose Parkinson’s disease and possibly other chronic inflammatory conditions, according to investigators. In addition to being highly accurate, the assay, which detects changes in expression of cytochrome P450s, is faster and easier to perform than other Parkinson’s disease assays under investigation, reported lead author Kohei Ihara, PhD, of Kobe University, Japan, and colleagues.

“Effective diagnostic systems and biomarkers for patients without subjective motor symptoms have not yet been established,” the investigators wrote in Nature Scientific Reports. “Consequently, the poor diagnostic options for Parkinson’s disease delay the development of therapeutic approaches and medication. Therefore, the development of efficient diagnostic systems and biomarkers is crucial for overcoming Parkinson’s disease.”

According to Dr. Ihara and colleagues, various cytochrome P450 expression patterns and associated serum metabolites correlate with chronic conditions, making them possible markers of disease. To detect these changes, they developed the present assay. It relies upon recombinant P450s expressed on the surface of Escherichia coli. By mixing the E. coli with serum and Vivid, a fluorescent substrate, the investigators can measure “the inhibition rate of the Vivid decomposition reaction” that was driven by “serum metabolites associated with P450s,” revealing underlying expression and, if present, disease.

After some promising initial experiments with mouse models of ulcerative colitis and diabetes, Dr. Ihara and colleagues focused on a rat model of Parkinson’s disease. Evaluating inhibition rates associated with four P450s revealed area-under-the-curve (AUC) values of 0.814-0.914. Two of those P450s were also associated with progression of disease symptoms.

“Therefore, we concluded that the P450 inhibition assay could discriminate between Parkinson’s disease model rats and control rats,” the investigators wrote.

Next, the investigators tested the approach with a case-control study involving 20 patients with Parkinson’s disease and 20 healthy volunteers. Twelve P450s were analyzed, three of which revealed significant differences between patients with Parkinson’s disease and controls, with AUCs ranging from 0.740-0.775. Each of the three P450 enzymes also correlated significantly with stage of disease on the Hoehn & Yahr scale, although severity and frequency of symptoms were not reported.

To increase accuracy of the technique, the investigators developed a logistic regression model using two of the three P450s, generating an AUC of 0.910. Further testing showed that the P450 inhibition assay could distinguish between patients with Parkinson’s disease and Alzheimer’s disease, as well as other chronic inflammatory diseases.

“The P450 inhibition assay is easier to perform and is faster than other assays because this assay does not require pretreatment, such as purification of exosomes, and it involves a single enzymatic reaction,” the investigators wrote, suggesting that the assay may be suitable for real-world diagnosis.
 

‘Promising’ findings need replication

According to Douglas Galasko, MD, a neurologist and professor of neurosciences at UC San Diego Health, the reported accuracy of the assay “seems spectacular,” and the findings are “promising,” but they need to be replicated, “particularly in early-stage patients where the diagnosis [of Parkinson’s disease] is more difficult and important to make.” In practice, the assay would likely see greatest usage for “early diagnosis or diagnosis of unusual or challenging cases,” so accuracy testing needs to be conducted in this setting, he said.

Dr. Galasko, who was not involved in the study, predicted that liquid biopsy for detecting Parkinson’s disease is unlikely to hit the clinic floor anytime soon. “We’re not really close with blood-based biomarkers for Parkinson’s disease,” he said, “unlike the situation for Alzheimer’s disease, where there are several promising blood-based biomarkers.”

For diagnosing Parkinson’s disease, Dr. Galasko suggested that assays using skin biopsies to measure alpha-synuclein accumulation may be closer to approval.

The study was supported by JSPS KAKENHI Grant Number 20K20223 and the Sumitomo Electric Industries Group Corporate Social Responsibility Foundation. The investigators disclosed no conflicts of interest.

A novel blood-based assay could one day be used to diagnose Parkinson’s disease and possibly other chronic inflammatory conditions, according to investigators. In addition to being highly accurate, the assay, which detects changes in expression of cytochrome P450s, is faster and easier to perform than other Parkinson’s disease assays under investigation, reported lead author Kohei Ihara, PhD, of Kobe University, Japan, and colleagues.

“Effective diagnostic systems and biomarkers for patients without subjective motor symptoms have not yet been established,” the investigators wrote in Nature Scientific Reports. “Consequently, the poor diagnostic options for Parkinson’s disease delay the development of therapeutic approaches and medication. Therefore, the development of efficient diagnostic systems and biomarkers is crucial for overcoming Parkinson’s disease.”

According to Dr. Ihara and colleagues, various cytochrome P450 expression patterns and associated serum metabolites correlate with chronic conditions, making them possible markers of disease. To detect these changes, they developed the present assay. It relies upon recombinant P450s expressed on the surface of Escherichia coli. By mixing the E. coli with serum and Vivid, a fluorescent substrate, the investigators can measure “the inhibition rate of the Vivid decomposition reaction” that was driven by “serum metabolites associated with P450s,” revealing underlying expression and, if present, disease.

After some promising initial experiments with mouse models of ulcerative colitis and diabetes, Dr. Ihara and colleagues focused on a rat model of Parkinson’s disease. Evaluating inhibition rates associated with four P450s revealed area-under-the-curve (AUC) values of 0.814-0.914. Two of those P450s were also associated with progression of disease symptoms.

“Therefore, we concluded that the P450 inhibition assay could discriminate between Parkinson’s disease model rats and control rats,” the investigators wrote.

Next, the investigators tested the approach with a case-control study involving 20 patients with Parkinson’s disease and 20 healthy volunteers. Twelve P450s were analyzed, three of which revealed significant differences between patients with Parkinson’s disease and controls, with AUCs ranging from 0.740-0.775. Each of the three P450 enzymes also correlated significantly with stage of disease on the Hoehn & Yahr scale, although severity and frequency of symptoms were not reported.

To increase accuracy of the technique, the investigators developed a logistic regression model using two of the three P450s, generating an AUC of 0.910. Further testing showed that the P450 inhibition assay could distinguish between patients with Parkinson’s disease and Alzheimer’s disease, as well as other chronic inflammatory diseases.

“The P450 inhibition assay is easier to perform and is faster than other assays because this assay does not require pretreatment, such as purification of exosomes, and it involves a single enzymatic reaction,” the investigators wrote, suggesting that the assay may be suitable for real-world diagnosis.
 

‘Promising’ findings need replication

According to Douglas Galasko, MD, a neurologist and professor of neurosciences at UC San Diego Health, the reported accuracy of the assay “seems spectacular,” and the findings are “promising,” but they need to be replicated, “particularly in early-stage patients where the diagnosis [of Parkinson’s disease] is more difficult and important to make.” In practice, the assay would likely see greatest usage for “early diagnosis or diagnosis of unusual or challenging cases,” so accuracy testing needs to be conducted in this setting, he said.

Dr. Galasko, who was not involved in the study, predicted that liquid biopsy for detecting Parkinson’s disease is unlikely to hit the clinic floor anytime soon. “We’re not really close with blood-based biomarkers for Parkinson’s disease,” he said, “unlike the situation for Alzheimer’s disease, where there are several promising blood-based biomarkers.”

For diagnosing Parkinson’s disease, Dr. Galasko suggested that assays using skin biopsies to measure alpha-synuclein accumulation may be closer to approval.

The study was supported by JSPS KAKENHI Grant Number 20K20223 and the Sumitomo Electric Industries Group Corporate Social Responsibility Foundation. The investigators disclosed no conflicts of interest.

A novel blood-based assay could one day be used to diagnose Parkinson’s disease and possibly other chronic inflammatory conditions, according to investigators. In addition to being highly accurate, the assay, which detects changes in expression of cytochrome P450s, is faster and easier to perform than other Parkinson’s disease assays under investigation, reported lead author Kohei Ihara, PhD, of Kobe University, Japan, and colleagues.

“Effective diagnostic systems and biomarkers for patients without subjective motor symptoms have not yet been established,” the investigators wrote in Nature Scientific Reports. “Consequently, the poor diagnostic options for Parkinson’s disease delay the development of therapeutic approaches and medication. Therefore, the development of efficient diagnostic systems and biomarkers is crucial for overcoming Parkinson’s disease.”

According to Dr. Ihara and colleagues, various cytochrome P450 expression patterns and associated serum metabolites correlate with chronic conditions, making them possible markers of disease. To detect these changes, they developed the present assay. It relies upon recombinant P450s expressed on the surface of Escherichia coli. By mixing the E. coli with serum and Vivid, a fluorescent substrate, the investigators can measure “the inhibition rate of the Vivid decomposition reaction” that was driven by “serum metabolites associated with P450s,” revealing underlying expression and, if present, disease.

After some promising initial experiments with mouse models of ulcerative colitis and diabetes, Dr. Ihara and colleagues focused on a rat model of Parkinson’s disease. Evaluating inhibition rates associated with four P450s revealed area-under-the-curve (AUC) values of 0.814-0.914. Two of those P450s were also associated with progression of disease symptoms.

“Therefore, we concluded that the P450 inhibition assay could discriminate between Parkinson’s disease model rats and control rats,” the investigators wrote.

Next, the investigators tested the approach with a case-control study involving 20 patients with Parkinson’s disease and 20 healthy volunteers. Twelve P450s were analyzed, three of which revealed significant differences between patients with Parkinson’s disease and controls, with AUCs ranging from 0.740-0.775. Each of the three P450 enzymes also correlated significantly with stage of disease on the Hoehn & Yahr scale, although severity and frequency of symptoms were not reported.

To increase accuracy of the technique, the investigators developed a logistic regression model using two of the three P450s, generating an AUC of 0.910. Further testing showed that the P450 inhibition assay could distinguish between patients with Parkinson’s disease and Alzheimer’s disease, as well as other chronic inflammatory diseases.

“The P450 inhibition assay is easier to perform and is faster than other assays because this assay does not require pretreatment, such as purification of exosomes, and it involves a single enzymatic reaction,” the investigators wrote, suggesting that the assay may be suitable for real-world diagnosis.
 

‘Promising’ findings need replication

According to Douglas Galasko, MD, a neurologist and professor of neurosciences at UC San Diego Health, the reported accuracy of the assay “seems spectacular,” and the findings are “promising,” but they need to be replicated, “particularly in early-stage patients where the diagnosis [of Parkinson’s disease] is more difficult and important to make.” In practice, the assay would likely see greatest usage for “early diagnosis or diagnosis of unusual or challenging cases,” so accuracy testing needs to be conducted in this setting, he said.

Dr. Galasko, who was not involved in the study, predicted that liquid biopsy for detecting Parkinson’s disease is unlikely to hit the clinic floor anytime soon. “We’re not really close with blood-based biomarkers for Parkinson’s disease,” he said, “unlike the situation for Alzheimer’s disease, where there are several promising blood-based biomarkers.”

For diagnosing Parkinson’s disease, Dr. Galasko suggested that assays using skin biopsies to measure alpha-synuclein accumulation may be closer to approval.

The study was supported by JSPS KAKENHI Grant Number 20K20223 and the Sumitomo Electric Industries Group Corporate Social Responsibility Foundation. The investigators disclosed no conflicts of interest.

Patients who are immunocompromised showed no increased risk of surgical site infection when undergoing Mohs micrographic surgery, regardless of whether or not they received antibiotics, suggesting that antibiotic prophylaxis, which is often used for these patients, may not be necessary, according to new research.

The retrospective cohort study found that “immunosuppressed patients had similar infection rates as immunocompetent patients following Mohs micrographic surgery,” first author Tuyet A. Nguyen, MD, of the department of dermatology, Cedars-Sinai Medical Center, Los Angeles, told this news organization.

“Therefore, antibiotic prescribing patterns should not change simply due to immunosuppression. Furthermore, immunosuppressed patients appear to respond well to antibiotics and recover similarly to immunocompetent patients,” she said.

Dr. Nguyen

Overall, postprocedural infections occurred in 1.6% (95) of patients, a rate that mirrors that of the general population, Dr. Nguyen noted. No significant differences in surgical site infection rates were observed between immunocompromised patients (2.1%, n = 15) and those who were immunocompetent (1.6%, n = 80; P = .30).

Importantly, among those who were immunocompromised, the rates of infection were not significantly different between those who did receive antibiotics (3.0%, n = 8) and those who did not receive antibiotics (1.5%, n = 7; P = .19).

The lack of a difference in surgical site infection rates among those who did and those who did not receive antibiotics extended to the entire study population (2.0% vs. 1.4%; P = .12).

The study cohort mainly comprised immunosuppressed transplant patients, notably, heart, lung, and kidney transplant patients. However, “even in this population, we did not see a higher rate of infection,” senior author Nima M. Gharavi, MD, PhD, director of dermatologic surgery and Mohs micrographic surgery and associate professor of medicine and pathology and laboratory medicine at Cedars-Sinai Medical Center, said in an interview.

Dr. Nima M. Gharavi

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

Patients who are immunocompromised showed no increased risk of surgical site infection when undergoing Mohs micrographic surgery, regardless of whether or not they received antibiotics, suggesting that antibiotic prophylaxis, which is often used for these patients, may not be necessary, according to new research.

The retrospective cohort study found that “immunosuppressed patients had similar infection rates as immunocompetent patients following Mohs micrographic surgery,” first author Tuyet A. Nguyen, MD, of the department of dermatology, Cedars-Sinai Medical Center, Los Angeles, told this news organization.

“Therefore, antibiotic prescribing patterns should not change simply due to immunosuppression. Furthermore, immunosuppressed patients appear to respond well to antibiotics and recover similarly to immunocompetent patients,” she said.

Dr. Nguyen

Overall, postprocedural infections occurred in 1.6% (95) of patients, a rate that mirrors that of the general population, Dr. Nguyen noted. No significant differences in surgical site infection rates were observed between immunocompromised patients (2.1%, n = 15) and those who were immunocompetent (1.6%, n = 80; P = .30).

Importantly, among those who were immunocompromised, the rates of infection were not significantly different between those who did receive antibiotics (3.0%, n = 8) and those who did not receive antibiotics (1.5%, n = 7; P = .19).

The lack of a difference in surgical site infection rates among those who did and those who did not receive antibiotics extended to the entire study population (2.0% vs. 1.4%; P = .12).

The study cohort mainly comprised immunosuppressed transplant patients, notably, heart, lung, and kidney transplant patients. However, “even in this population, we did not see a higher rate of infection,” senior author Nima M. Gharavi, MD, PhD, director of dermatologic surgery and Mohs micrographic surgery and associate professor of medicine and pathology and laboratory medicine at Cedars-Sinai Medical Center, said in an interview.

Dr. Nima M. Gharavi

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

Patients who are immunocompromised showed no increased risk of surgical site infection when undergoing Mohs micrographic surgery, regardless of whether or not they received antibiotics, suggesting that antibiotic prophylaxis, which is often used for these patients, may not be necessary, according to new research.

The retrospective cohort study found that “immunosuppressed patients had similar infection rates as immunocompetent patients following Mohs micrographic surgery,” first author Tuyet A. Nguyen, MD, of the department of dermatology, Cedars-Sinai Medical Center, Los Angeles, told this news organization.

“Therefore, antibiotic prescribing patterns should not change simply due to immunosuppression. Furthermore, immunosuppressed patients appear to respond well to antibiotics and recover similarly to immunocompetent patients,” she said.

Dr. Nguyen

Overall, postprocedural infections occurred in 1.6% (95) of patients, a rate that mirrors that of the general population, Dr. Nguyen noted. No significant differences in surgical site infection rates were observed between immunocompromised patients (2.1%, n = 15) and those who were immunocompetent (1.6%, n = 80; P = .30).

Importantly, among those who were immunocompromised, the rates of infection were not significantly different between those who did receive antibiotics (3.0%, n = 8) and those who did not receive antibiotics (1.5%, n = 7; P = .19).

The lack of a difference in surgical site infection rates among those who did and those who did not receive antibiotics extended to the entire study population (2.0% vs. 1.4%; P = .12).

The study cohort mainly comprised immunosuppressed transplant patients, notably, heart, lung, and kidney transplant patients. However, “even in this population, we did not see a higher rate of infection,” senior author Nima M. Gharavi, MD, PhD, director of dermatologic surgery and Mohs micrographic surgery and associate professor of medicine and pathology and laboratory medicine at Cedars-Sinai Medical Center, said in an interview.

Dr. Nima M. Gharavi

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

A new study provides more evidence that the substantial weight loss achieved with bariatric surgery offers long-term protection against cancer.

The study found that adults with obesity who had bariatric surgery had a 32% lower risk of developing cancer and a 48% lower risk of dying from cancer, compared with peers who did not have the surgery.

“The magnitude of the benefit was very large and dose-dependent, with more weight loss associated with greater reduction in cancer risk,” lead investigator Ali Aminian, MD, director of the Bariatric & Metabolic Institute, Cleveland Clinic, told this news organization.

The study was published online in the Journal of the American Medical Association.
 

Best evidence to date

“We know that obesity is strongly linked with different types of cancers, but we didn’t know if losing a significant amount of weight can significantly decrease the risk of cancer,” Dr. Aminian explained.

The SPLENDID study involved 30,318 adults with obesity (median age, 46 years; 77% women; median body mass index, 45 kg/m²). 

The 5,053 patients who underwent Roux-en-Y gastric bypass (66%) or sleeve gastrectomy (34%) were matched (1:5) to 25,265 patients who did not undergo bariatric surgery (nonsurgical control group).

At 10 years, patients who had bariatric surgery had lost 27.5 kg (60 pounds) compared with 2.7 kg (6 pounds) for peers who didn’t have the surgery, a difference of 19.2%. 

During a median follow-up of 6.1 years, 96 patients in the bariatric surgery group and 780 patients in the nonsurgical control group developed an obesity-associated cancer (incidence rate of 3.0 vs. 4.6 events per 1,000 person-years).

At 10 years, the cumulative incidence of obesity-associated cancer was significantly lower in the bariatric surgery group (2.9% vs. 4.9%; absolute risk difference, 2.0%; 95% confidence interval [CI], 1.2%-2.7%; adjusted hazard ratio [HR], 0.68; 95% CI, 0.53-0.87; P = .002).

Most cancer types were less common in the bariatric surgery group. However, a comprehensive analysis of the impact of bariatric surgery on individual cancer types was not possible.

In the fully-adjusted Cox models, the association between bariatric surgery and individual cancer types was significant only for endometrial cancer (adjusted HR, 0.47; 95% CI, 0.27-0.83). 

For the other individual cancers, there was a “trend or signal toward a reduction in their risk after the surgery,” Dr. Aminian said.

He noted that endometrial cancer has the strongest association with obesity, and patients who seek bariatric surgery are typically obese, middle-aged women.

“So, it was not surprising that we had more cases of endometrial cancer than other types of cancer,” he said.

The SPLENDID study also showed a significant reduction in cancer-related mortality at 10 years in patients with vs. without bariatric surgery (0.8% vs. 1.4%; adjusted HR, 0.52; 95% CI, 0.31-0.88; P = .01).

The benefits of bariatric surgery were evident in both women and men, younger and older patients, and Black and White patients, and were similarly observed after both gastric bypass and sleeve gastrectomy.

For the cancer protective effect, patients need to lose at least 20%-25% of their body weight, which is almost impossible with diet alone, Dr. Aminian said.

Obesity is “second only to tobacco” as a preventable cause of cancer in the United States, senior author Steven Nissen, MD, chief academic officer of the Heart, Vascular, and Thoracic Institute at Cleveland Clinic, said in a news release.

“This study provides the best possible evidence on the value of intentional weight loss to reduce cancer risk and mortality,” Dr. Nissen said.
 

Questions remain

In an accompanying editorial, Anita P. Courcoulas, MD, of the University of Pittsburgh Medical Center, said future studies should look at potential factors that influence the association between bariatric surgery and reduced cancer risk, with an eye toward individualizing treatment and figuring out who will benefit the most.

“It is likely that cancer risk reduction after bariatric surgery varies by sex, age, race and ethnicity, type of bariatric surgery, alcohol and smoking status, cancer site, diabetes status, body mass index, and other factors,” Dr. Courcoulas pointed out.

“In addition, there is a need to understand the specific biological mechanisms of effect responsible for the observed change in cancer risk because these mechanisms have not been clearly investigated and elucidated in humans,” she said.

“If this association is further validated, it would extend the benefits of bariatric surgery to another important area of long-term health and prevention. This additional information could then further guide for whom bariatric surgery is most beneficial,” Dr. Courcoulas concluded.

The study had no specific funding. Dr. Aminian reported receiving grants and speaking honoraria from Medtronic. Dr. Nissen reported receiving grants from Novartis, Eli Lilly, AbbVie, Silence Therapeutics, AstraZeneca, Esperion Therapeutics, Amgen, and Bristol Myers Squibb. A complete list of author disclosures is available with the original article.  Dr. Courcoulas had no relevant disclosures.

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

A new study provides more evidence that the substantial weight loss achieved with bariatric surgery offers long-term protection against cancer.

The study found that adults with obesity who had bariatric surgery had a 32% lower risk of developing cancer and a 48% lower risk of dying from cancer, compared with peers who did not have the surgery.

“The magnitude of the benefit was very large and dose-dependent, with more weight loss associated with greater reduction in cancer risk,” lead investigator Ali Aminian, MD, director of the Bariatric & Metabolic Institute, Cleveland Clinic, told this news organization.

The study was published online in the Journal of the American Medical Association.
 

Best evidence to date

“We know that obesity is strongly linked with different types of cancers, but we didn’t know if losing a significant amount of weight can significantly decrease the risk of cancer,” Dr. Aminian explained.

The SPLENDID study involved 30,318 adults with obesity (median age, 46 years; 77% women; median body mass index, 45 kg/m²). 

The 5,053 patients who underwent Roux-en-Y gastric bypass (66%) or sleeve gastrectomy (34%) were matched (1:5) to 25,265 patients who did not undergo bariatric surgery (nonsurgical control group).

At 10 years, patients who had bariatric surgery had lost 27.5 kg (60 pounds) compared with 2.7 kg (6 pounds) for peers who didn’t have the surgery, a difference of 19.2%. 

During a median follow-up of 6.1 years, 96 patients in the bariatric surgery group and 780 patients in the nonsurgical control group developed an obesity-associated cancer (incidence rate of 3.0 vs. 4.6 events per 1,000 person-years).

At 10 years, the cumulative incidence of obesity-associated cancer was significantly lower in the bariatric surgery group (2.9% vs. 4.9%; absolute risk difference, 2.0%; 95% confidence interval [CI], 1.2%-2.7%; adjusted hazard ratio [HR], 0.68; 95% CI, 0.53-0.87; P = .002).

Most cancer types were less common in the bariatric surgery group. However, a comprehensive analysis of the impact of bariatric surgery on individual cancer types was not possible.

In the fully-adjusted Cox models, the association between bariatric surgery and individual cancer types was significant only for endometrial cancer (adjusted HR, 0.47; 95% CI, 0.27-0.83). 

For the other individual cancers, there was a “trend or signal toward a reduction in their risk after the surgery,” Dr. Aminian said.

He noted that endometrial cancer has the strongest association with obesity, and patients who seek bariatric surgery are typically obese, middle-aged women.

“So, it was not surprising that we had more cases of endometrial cancer than other types of cancer,” he said.

The SPLENDID study also showed a significant reduction in cancer-related mortality at 10 years in patients with vs. without bariatric surgery (0.8% vs. 1.4%; adjusted HR, 0.52; 95% CI, 0.31-0.88; P = .01).

The benefits of bariatric surgery were evident in both women and men, younger and older patients, and Black and White patients, and were similarly observed after both gastric bypass and sleeve gastrectomy.

For the cancer protective effect, patients need to lose at least 20%-25% of their body weight, which is almost impossible with diet alone, Dr. Aminian said.

Obesity is “second only to tobacco” as a preventable cause of cancer in the United States, senior author Steven Nissen, MD, chief academic officer of the Heart, Vascular, and Thoracic Institute at Cleveland Clinic, said in a news release.

“This study provides the best possible evidence on the value of intentional weight loss to reduce cancer risk and mortality,” Dr. Nissen said.
 

Questions remain

In an accompanying editorial, Anita P. Courcoulas, MD, of the University of Pittsburgh Medical Center, said future studies should look at potential factors that influence the association between bariatric surgery and reduced cancer risk, with an eye toward individualizing treatment and figuring out who will benefit the most.

“It is likely that cancer risk reduction after bariatric surgery varies by sex, age, race and ethnicity, type of bariatric surgery, alcohol and smoking status, cancer site, diabetes status, body mass index, and other factors,” Dr. Courcoulas pointed out.

“In addition, there is a need to understand the specific biological mechanisms of effect responsible for the observed change in cancer risk because these mechanisms have not been clearly investigated and elucidated in humans,” she said.

“If this association is further validated, it would extend the benefits of bariatric surgery to another important area of long-term health and prevention. This additional information could then further guide for whom bariatric surgery is most beneficial,” Dr. Courcoulas concluded.

The study had no specific funding. Dr. Aminian reported receiving grants and speaking honoraria from Medtronic. Dr. Nissen reported receiving grants from Novartis, Eli Lilly, AbbVie, Silence Therapeutics, AstraZeneca, Esperion Therapeutics, Amgen, and Bristol Myers Squibb. A complete list of author disclosures is available with the original article.  Dr. Courcoulas had no relevant disclosures.

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

A new study provides more evidence that the substantial weight loss achieved with bariatric surgery offers long-term protection against cancer.

The study found that adults with obesity who had bariatric surgery had a 32% lower risk of developing cancer and a 48% lower risk of dying from cancer, compared with peers who did not have the surgery.

“The magnitude of the benefit was very large and dose-dependent, with more weight loss associated with greater reduction in cancer risk,” lead investigator Ali Aminian, MD, director of the Bariatric & Metabolic Institute, Cleveland Clinic, told this news organization.

The study was published online in the Journal of the American Medical Association.
 

Best evidence to date

“We know that obesity is strongly linked with different types of cancers, but we didn’t know if losing a significant amount of weight can significantly decrease the risk of cancer,” Dr. Aminian explained.

The SPLENDID study involved 30,318 adults with obesity (median age, 46 years; 77% women; median body mass index, 45 kg/m²). 

The 5,053 patients who underwent Roux-en-Y gastric bypass (66%) or sleeve gastrectomy (34%) were matched (1:5) to 25,265 patients who did not undergo bariatric surgery (nonsurgical control group).

At 10 years, patients who had bariatric surgery had lost 27.5 kg (60 pounds) compared with 2.7 kg (6 pounds) for peers who didn’t have the surgery, a difference of 19.2%. 

During a median follow-up of 6.1 years, 96 patients in the bariatric surgery group and 780 patients in the nonsurgical control group developed an obesity-associated cancer (incidence rate of 3.0 vs. 4.6 events per 1,000 person-years).

At 10 years, the cumulative incidence of obesity-associated cancer was significantly lower in the bariatric surgery group (2.9% vs. 4.9%; absolute risk difference, 2.0%; 95% confidence interval [CI], 1.2%-2.7%; adjusted hazard ratio [HR], 0.68; 95% CI, 0.53-0.87; P = .002).

Most cancer types were less common in the bariatric surgery group. However, a comprehensive analysis of the impact of bariatric surgery on individual cancer types was not possible.

In the fully-adjusted Cox models, the association between bariatric surgery and individual cancer types was significant only for endometrial cancer (adjusted HR, 0.47; 95% CI, 0.27-0.83). 

For the other individual cancers, there was a “trend or signal toward a reduction in their risk after the surgery,” Dr. Aminian said.

He noted that endometrial cancer has the strongest association with obesity, and patients who seek bariatric surgery are typically obese, middle-aged women.

“So, it was not surprising that we had more cases of endometrial cancer than other types of cancer,” he said.

The SPLENDID study also showed a significant reduction in cancer-related mortality at 10 years in patients with vs. without bariatric surgery (0.8% vs. 1.4%; adjusted HR, 0.52; 95% CI, 0.31-0.88; P = .01).

The benefits of bariatric surgery were evident in both women and men, younger and older patients, and Black and White patients, and were similarly observed after both gastric bypass and sleeve gastrectomy.

For the cancer protective effect, patients need to lose at least 20%-25% of their body weight, which is almost impossible with diet alone, Dr. Aminian said.

Obesity is “second only to tobacco” as a preventable cause of cancer in the United States, senior author Steven Nissen, MD, chief academic officer of the Heart, Vascular, and Thoracic Institute at Cleveland Clinic, said in a news release.

“This study provides the best possible evidence on the value of intentional weight loss to reduce cancer risk and mortality,” Dr. Nissen said.
 

Questions remain

In an accompanying editorial, Anita P. Courcoulas, MD, of the University of Pittsburgh Medical Center, said future studies should look at potential factors that influence the association between bariatric surgery and reduced cancer risk, with an eye toward individualizing treatment and figuring out who will benefit the most.

“It is likely that cancer risk reduction after bariatric surgery varies by sex, age, race and ethnicity, type of bariatric surgery, alcohol and smoking status, cancer site, diabetes status, body mass index, and other factors,” Dr. Courcoulas pointed out.

“In addition, there is a need to understand the specific biological mechanisms of effect responsible for the observed change in cancer risk because these mechanisms have not been clearly investigated and elucidated in humans,” she said.

“If this association is further validated, it would extend the benefits of bariatric surgery to another important area of long-term health and prevention. This additional information could then further guide for whom bariatric surgery is most beneficial,” Dr. Courcoulas concluded.

The study had no specific funding. Dr. Aminian reported receiving grants and speaking honoraria from Medtronic. Dr. Nissen reported receiving grants from Novartis, Eli Lilly, AbbVie, Silence Therapeutics, AstraZeneca, Esperion Therapeutics, Amgen, and Bristol Myers Squibb. A complete list of author disclosures is available with the original article.  Dr. Courcoulas had no relevant disclosures.

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

The U.S. Food and Drug Administration has declined to take further action against a group of investigators at Hennepin County Medical Center/Hennepin Healthcare (HCMC) who conducted controversial studies involving ketamine and other sedatives on agitated persons without their consent.

A citizen petition filed by Public Citizen, a consumer advocacy group, had asked the FDA to initiate clinical-investigator disqualification proceedings against Jon Cole, MD, and Lauren Klein, MD, along with other researchers who participated in the studies, for “repeatedly and deliberately initiating and conducting clinical investigations of investigational drug products” without having submitted or having in effect the investigational new drug applications (INDs) required by the FDA.

In certain situations, wherein the FDA alleges that a clinical investigator has violated applicable regulations, the agency may initiate clinical investigator disqualification proceedings. The names of the disqualified researchers are then added to a federal database.

The petition, which was filed in November 2021, also requested that the FDA initiate disqualification proceedings against the institutional review board (IRB) at HCMC for repeatedly failing to comply with federal regulations that adversely affected the rights and welfare of the individuals who were enrolled in the study without their consent.

Of note, Public Citizen stated that the FDA should have required the hospital to contact the more than 1,700 patients who “were unwittingly enrolled in unethical experiments” and inform them that their rights had been violated and their health potentially endangered by the research team.

Michael A. Carome, MD, director of Public Citizen’s Health Research Group, told this news organization that it is uncommon for the FDA to disqualify researchers. “It should be more common than it is,” he said. “I think that FDA is just reluctant to take more action.”

The actions of the Hennepin investigators were “repetitive and appeared to be in deliberate violation of regulations,” he added. “The case for the FDA disqualifying the HCMC researchers is overwhelming. The FDA’s slap-on-the-wrist approach to such appalling regulatory and ethical violations risks emboldening other researchers to disregard the rights and welfare of human subjects.”

Carl Elliott, MD, PhD, a bioethicist at the University of Minnesota, Minneapolis, agrees that the researcher from HCMC should be disqualified. “They didn’t just conduct risky, exploitative studies – they conducted them after the FDA had warned them not to proceed,” he said. “The message sent by this slap on the wrist is that investigators can do whatever they want to nonconsenting subjects, and the FDA will look the other way.”
 

Initial complaint

Public Citizen initially filed a complaint with the FDA in 2018, after learning that researchers affiliated with HCMC were conducting high-risk clinical trials involving ketamine to control agitation outside of the hospital setting. The complaint was cosigned by 64 doctors, bioethicists, and academic researchers and was also submitted to the Office for Human Research Protections.

The FDA typically allows investigational drugs to be used in emergency situation without obtaining informed consent if the therapies are known to carry a minimal risk. The IRB at HCMC had determined that this was the case with ketamine and approved the trials.

But according to Public Citizen’s complaint, prior research had suggested that ketamine could cause more complications and severe adverse events, compared with other sedatives.

The trials were conducted between 2014 and 2018, and in its letter, Public Citizen alleged that the investigators and the IRB had allowed these trials to proceed without obtaining informed consent from patients. The goal was to evaluate how well ketamine worked, compared with other drugs in calming agitated individuals: “The patients were given either ketamine or haloperidol for agitation by paramedics who responded to medical emergencies, and the goal was to see which drug worked faster,” said Dr. Carome. “Patients were only notified afterwards that they had received a sedative. Informed consent had been waived by IRB.”

In the first clinical trial conducted by HCMC, published in 2016, the researchers had hypothesized that 5 mg/kg of intramuscular ketamine would be superior to 10 mg of intramuscular haloperidol for severe prehospital agitation. Time to adequate sedation was the primary outcome measure. The study included 146 people; 64 received ketamine and 82 received haloperidol. They found that ketamine worked far more quickly than haloperidol (5 minutes vs. 17 minutes) but that the risk for complications was much higher. Complications occurred in 49% of patients receiving ketamine, compared with 5%.

“There was a 10-fold risk of adverse events,” said Dr. Carome. “And 39% of patients given ketamine had respiratory problems requiring intubation, compared to 4% who received haloperidol.”

A second study was launched in 2017, wherein ketamine was compared with midazolam in agitated patients. During the first 6-month period of the study, individuals would receive a ketamine-based protocol for prehospital agitation, and during the second 6 months, that would switch to midazolam. However, the study was halted in June 2018 after the local newspaper, the Star Tribune, reported that the city police had encouraged medical personnel to sedate agitated patients. This included individuals who had already been physically restrained.

The report stated that “in many cases, the individual being detained or arrested was not only handcuffed but strapped down on a stretcher in an ambulance before receiving ketamine,” and that it raised a “concerning question” over why these people were given the drug before they were transported to the hospital, “given the immediate effects on breathing and heart function that the drug induces.”

Along with halting the trial, HCMC asked for a review of cases involving its paramedics; an independent investigation led by former U.S. Deputy Attorney General Sally Yates was initiated to assess whether the Minneapolis police had crossed a line and urged paramedics to use ketamine.

“The decision to use ketamine was based on the study’s timeline and not on clinical judgment,” said Dr. Carome.

The FDA acknowledged receipt of the complaint and inspected the IRB records and the clinical trial data. Preliminary reports received by Public Citizen confirmed their allegations. “There were not appropriate protections for vulnerable subjects,” he said. “In 2019, the FDA did further investigations, and those reports had similar findings.”
 

FDA letters

The FDA had sent warning letters to Dr. Cole and Dr. Klein, citing them for ignoring federal safety laws in experimental research on the public. In their investigations, the FDA cited “objectionable conditions” for the studies led by Dr. Cole and Dr. Klein, according to the letters. Both researchers seemingly ignored FDA regulations and used practices that subjected patients to “significantly increased risk,” and the hospital defended its research with “factually incorrect” statements.

In a letter to Dr. Cole, the FDA noted that he never filed INDs for the trials with the FDA, as required by law, and that he also failed to write appropriate protocols to ensure that children and pregnant women were not enrolled in the research. Individuals under the influence of intoxicants also were not excluded, though the use of ketamine is cautioned in this population.

“Administration of the investigational drugs to these subjects placed them at significantly increased risk of the adverse events associated with the investigational products and decreased the acceptability of those risks,” the FDA said in its letter. “Your failure to exclude, and the lack of any precautions for, subjects under the influence of various intoxicants significantly increased the risks and/or decreased the acceptability of the risks associated with the investigational drugs.”

However, Dr. Cole conducted both studies in the prehospital setting and failed to initiate any specific measures to protect study participants, according to the FDA.
 

Petition denied

Dr. Carome noted that the researchers had committed repetitive egregious regulatory violations over a 4-year period, which were documented by the FDA in their warning letters to Dr. Cole and Dr. Klein. “We felt that they were so egregious that we need to send a signal to the community that this sort of behavior will not be tolerated,” he said. “The FDA denied our petition, and we think that sends the wrong signal to the research community.”

In their response, the FDA noted that as with judicial enforcement, “the Agency makes decisions regarding whether to pursue administrative enforcement action, including disqualification proceedings, on a case-by-case basis, considering all relevant facts and circumstances.” They added that at this time, they would not be taking further action against Dr. Cole and Dr. Klein.

“However, we intend to continue to consider all the options available to the Agency as we determine whether to pursue additional compliance actions related to this matter,” the FDA concluded.

The FDA declined to comment further on their decision.

Dr. Cole also declined to comment, but Hennepin Healthcare told this news organization that the “decision by the FDA to deny the petition validates the changes we made to strengthen and improve the clinical research program across the institution since the closing of the studies in 2018. We look forward to continuing to work with the FDA to ensure full compliance with the standards in place to protect research subjects.”

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

The U.S. Food and Drug Administration has declined to take further action against a group of investigators at Hennepin County Medical Center/Hennepin Healthcare (HCMC) who conducted controversial studies involving ketamine and other sedatives on agitated persons without their consent.

A citizen petition filed by Public Citizen, a consumer advocacy group, had asked the FDA to initiate clinical-investigator disqualification proceedings against Jon Cole, MD, and Lauren Klein, MD, along with other researchers who participated in the studies, for “repeatedly and deliberately initiating and conducting clinical investigations of investigational drug products” without having submitted or having in effect the investigational new drug applications (INDs) required by the FDA.

In certain situations, wherein the FDA alleges that a clinical investigator has violated applicable regulations, the agency may initiate clinical investigator disqualification proceedings. The names of the disqualified researchers are then added to a federal database.

The petition, which was filed in November 2021, also requested that the FDA initiate disqualification proceedings against the institutional review board (IRB) at HCMC for repeatedly failing to comply with federal regulations that adversely affected the rights and welfare of the individuals who were enrolled in the study without their consent.

Of note, Public Citizen stated that the FDA should have required the hospital to contact the more than 1,700 patients who “were unwittingly enrolled in unethical experiments” and inform them that their rights had been violated and their health potentially endangered by the research team.

Michael A. Carome, MD, director of Public Citizen’s Health Research Group, told this news organization that it is uncommon for the FDA to disqualify researchers. “It should be more common than it is,” he said. “I think that FDA is just reluctant to take more action.”

The actions of the Hennepin investigators were “repetitive and appeared to be in deliberate violation of regulations,” he added. “The case for the FDA disqualifying the HCMC researchers is overwhelming. The FDA’s slap-on-the-wrist approach to such appalling regulatory and ethical violations risks emboldening other researchers to disregard the rights and welfare of human subjects.”

Carl Elliott, MD, PhD, a bioethicist at the University of Minnesota, Minneapolis, agrees that the researcher from HCMC should be disqualified. “They didn’t just conduct risky, exploitative studies – they conducted them after the FDA had warned them not to proceed,” he said. “The message sent by this slap on the wrist is that investigators can do whatever they want to nonconsenting subjects, and the FDA will look the other way.”
 

Initial complaint

Public Citizen initially filed a complaint with the FDA in 2018, after learning that researchers affiliated with HCMC were conducting high-risk clinical trials involving ketamine to control agitation outside of the hospital setting. The complaint was cosigned by 64 doctors, bioethicists, and academic researchers and was also submitted to the Office for Human Research Protections.

The FDA typically allows investigational drugs to be used in emergency situation without obtaining informed consent if the therapies are known to carry a minimal risk. The IRB at HCMC had determined that this was the case with ketamine and approved the trials.

But according to Public Citizen’s complaint, prior research had suggested that ketamine could cause more complications and severe adverse events, compared with other sedatives.

The trials were conducted between 2014 and 2018, and in its letter, Public Citizen alleged that the investigators and the IRB had allowed these trials to proceed without obtaining informed consent from patients. The goal was to evaluate how well ketamine worked, compared with other drugs in calming agitated individuals: “The patients were given either ketamine or haloperidol for agitation by paramedics who responded to medical emergencies, and the goal was to see which drug worked faster,” said Dr. Carome. “Patients were only notified afterwards that they had received a sedative. Informed consent had been waived by IRB.”

In the first clinical trial conducted by HCMC, published in 2016, the researchers had hypothesized that 5 mg/kg of intramuscular ketamine would be superior to 10 mg of intramuscular haloperidol for severe prehospital agitation. Time to adequate sedation was the primary outcome measure. The study included 146 people; 64 received ketamine and 82 received haloperidol. They found that ketamine worked far more quickly than haloperidol (5 minutes vs. 17 minutes) but that the risk for complications was much higher. Complications occurred in 49% of patients receiving ketamine, compared with 5%.

“There was a 10-fold risk of adverse events,” said Dr. Carome. “And 39% of patients given ketamine had respiratory problems requiring intubation, compared to 4% who received haloperidol.”

A second study was launched in 2017, wherein ketamine was compared with midazolam in agitated patients. During the first 6-month period of the study, individuals would receive a ketamine-based protocol for prehospital agitation, and during the second 6 months, that would switch to midazolam. However, the study was halted in June 2018 after the local newspaper, the Star Tribune, reported that the city police had encouraged medical personnel to sedate agitated patients. This included individuals who had already been physically restrained.

The report stated that “in many cases, the individual being detained or arrested was not only handcuffed but strapped down on a stretcher in an ambulance before receiving ketamine,” and that it raised a “concerning question” over why these people were given the drug before they were transported to the hospital, “given the immediate effects on breathing and heart function that the drug induces.”

Along with halting the trial, HCMC asked for a review of cases involving its paramedics; an independent investigation led by former U.S. Deputy Attorney General Sally Yates was initiated to assess whether the Minneapolis police had crossed a line and urged paramedics to use ketamine.

“The decision to use ketamine was based on the study’s timeline and not on clinical judgment,” said Dr. Carome.

The FDA acknowledged receipt of the complaint and inspected the IRB records and the clinical trial data. Preliminary reports received by Public Citizen confirmed their allegations. “There were not appropriate protections for vulnerable subjects,” he said. “In 2019, the FDA did further investigations, and those reports had similar findings.”
 

FDA letters

The FDA had sent warning letters to Dr. Cole and Dr. Klein, citing them for ignoring federal safety laws in experimental research on the public. In their investigations, the FDA cited “objectionable conditions” for the studies led by Dr. Cole and Dr. Klein, according to the letters. Both researchers seemingly ignored FDA regulations and used practices that subjected patients to “significantly increased risk,” and the hospital defended its research with “factually incorrect” statements.

In a letter to Dr. Cole, the FDA noted that he never filed INDs for the trials with the FDA, as required by law, and that he also failed to write appropriate protocols to ensure that children and pregnant women were not enrolled in the research. Individuals under the influence of intoxicants also were not excluded, though the use of ketamine is cautioned in this population.

“Administration of the investigational drugs to these subjects placed them at significantly increased risk of the adverse events associated with the investigational products and decreased the acceptability of those risks,” the FDA said in its letter. “Your failure to exclude, and the lack of any precautions for, subjects under the influence of various intoxicants significantly increased the risks and/or decreased the acceptability of the risks associated with the investigational drugs.”

However, Dr. Cole conducted both studies in the prehospital setting and failed to initiate any specific measures to protect study participants, according to the FDA.
 

Petition denied

Dr. Carome noted that the researchers had committed repetitive egregious regulatory violations over a 4-year period, which were documented by the FDA in their warning letters to Dr. Cole and Dr. Klein. “We felt that they were so egregious that we need to send a signal to the community that this sort of behavior will not be tolerated,” he said. “The FDA denied our petition, and we think that sends the wrong signal to the research community.”

In their response, the FDA noted that as with judicial enforcement, “the Agency makes decisions regarding whether to pursue administrative enforcement action, including disqualification proceedings, on a case-by-case basis, considering all relevant facts and circumstances.” They added that at this time, they would not be taking further action against Dr. Cole and Dr. Klein.

“However, we intend to continue to consider all the options available to the Agency as we determine whether to pursue additional compliance actions related to this matter,” the FDA concluded.

The FDA declined to comment further on their decision.

Dr. Cole also declined to comment, but Hennepin Healthcare told this news organization that the “decision by the FDA to deny the petition validates the changes we made to strengthen and improve the clinical research program across the institution since the closing of the studies in 2018. We look forward to continuing to work with the FDA to ensure full compliance with the standards in place to protect research subjects.”

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

The U.S. Food and Drug Administration has declined to take further action against a group of investigators at Hennepin County Medical Center/Hennepin Healthcare (HCMC) who conducted controversial studies involving ketamine and other sedatives on agitated persons without their consent.

A citizen petition filed by Public Citizen, a consumer advocacy group, had asked the FDA to initiate clinical-investigator disqualification proceedings against Jon Cole, MD, and Lauren Klein, MD, along with other researchers who participated in the studies, for “repeatedly and deliberately initiating and conducting clinical investigations of investigational drug products” without having submitted or having in effect the investigational new drug applications (INDs) required by the FDA.

In certain situations, wherein the FDA alleges that a clinical investigator has violated applicable regulations, the agency may initiate clinical investigator disqualification proceedings. The names of the disqualified researchers are then added to a federal database.

The petition, which was filed in November 2021, also requested that the FDA initiate disqualification proceedings against the institutional review board (IRB) at HCMC for repeatedly failing to comply with federal regulations that adversely affected the rights and welfare of the individuals who were enrolled in the study without their consent.

Of note, Public Citizen stated that the FDA should have required the hospital to contact the more than 1,700 patients who “were unwittingly enrolled in unethical experiments” and inform them that their rights had been violated and their health potentially endangered by the research team.

Michael A. Carome, MD, director of Public Citizen’s Health Research Group, told this news organization that it is uncommon for the FDA to disqualify researchers. “It should be more common than it is,” he said. “I think that FDA is just reluctant to take more action.”

The actions of the Hennepin investigators were “repetitive and appeared to be in deliberate violation of regulations,” he added. “The case for the FDA disqualifying the HCMC researchers is overwhelming. The FDA’s slap-on-the-wrist approach to such appalling regulatory and ethical violations risks emboldening other researchers to disregard the rights and welfare of human subjects.”

Carl Elliott, MD, PhD, a bioethicist at the University of Minnesota, Minneapolis, agrees that the researcher from HCMC should be disqualified. “They didn’t just conduct risky, exploitative studies – they conducted them after the FDA had warned them not to proceed,” he said. “The message sent by this slap on the wrist is that investigators can do whatever they want to nonconsenting subjects, and the FDA will look the other way.”
 

Initial complaint

Public Citizen initially filed a complaint with the FDA in 2018, after learning that researchers affiliated with HCMC were conducting high-risk clinical trials involving ketamine to control agitation outside of the hospital setting. The complaint was cosigned by 64 doctors, bioethicists, and academic researchers and was also submitted to the Office for Human Research Protections.

The FDA typically allows investigational drugs to be used in emergency situation without obtaining informed consent if the therapies are known to carry a minimal risk. The IRB at HCMC had determined that this was the case with ketamine and approved the trials.

But according to Public Citizen’s complaint, prior research had suggested that ketamine could cause more complications and severe adverse events, compared with other sedatives.

The trials were conducted between 2014 and 2018, and in its letter, Public Citizen alleged that the investigators and the IRB had allowed these trials to proceed without obtaining informed consent from patients. The goal was to evaluate how well ketamine worked, compared with other drugs in calming agitated individuals: “The patients were given either ketamine or haloperidol for agitation by paramedics who responded to medical emergencies, and the goal was to see which drug worked faster,” said Dr. Carome. “Patients were only notified afterwards that they had received a sedative. Informed consent had been waived by IRB.”

In the first clinical trial conducted by HCMC, published in 2016, the researchers had hypothesized that 5 mg/kg of intramuscular ketamine would be superior to 10 mg of intramuscular haloperidol for severe prehospital agitation. Time to adequate sedation was the primary outcome measure. The study included 146 people; 64 received ketamine and 82 received haloperidol. They found that ketamine worked far more quickly than haloperidol (5 minutes vs. 17 minutes) but that the risk for complications was much higher. Complications occurred in 49% of patients receiving ketamine, compared with 5%.

“There was a 10-fold risk of adverse events,” said Dr. Carome. “And 39% of patients given ketamine had respiratory problems requiring intubation, compared to 4% who received haloperidol.”

A second study was launched in 2017, wherein ketamine was compared with midazolam in agitated patients. During the first 6-month period of the study, individuals would receive a ketamine-based protocol for prehospital agitation, and during the second 6 months, that would switch to midazolam. However, the study was halted in June 2018 after the local newspaper, the Star Tribune, reported that the city police had encouraged medical personnel to sedate agitated patients. This included individuals who had already been physically restrained.

The report stated that “in many cases, the individual being detained or arrested was not only handcuffed but strapped down on a stretcher in an ambulance before receiving ketamine,” and that it raised a “concerning question” over why these people were given the drug before they were transported to the hospital, “given the immediate effects on breathing and heart function that the drug induces.”

Along with halting the trial, HCMC asked for a review of cases involving its paramedics; an independent investigation led by former U.S. Deputy Attorney General Sally Yates was initiated to assess whether the Minneapolis police had crossed a line and urged paramedics to use ketamine.

“The decision to use ketamine was based on the study’s timeline and not on clinical judgment,” said Dr. Carome.

The FDA acknowledged receipt of the complaint and inspected the IRB records and the clinical trial data. Preliminary reports received by Public Citizen confirmed their allegations. “There were not appropriate protections for vulnerable subjects,” he said. “In 2019, the FDA did further investigations, and those reports had similar findings.”
 

FDA letters

The FDA had sent warning letters to Dr. Cole and Dr. Klein, citing them for ignoring federal safety laws in experimental research on the public. In their investigations, the FDA cited “objectionable conditions” for the studies led by Dr. Cole and Dr. Klein, according to the letters. Both researchers seemingly ignored FDA regulations and used practices that subjected patients to “significantly increased risk,” and the hospital defended its research with “factually incorrect” statements.

In a letter to Dr. Cole, the FDA noted that he never filed INDs for the trials with the FDA, as required by law, and that he also failed to write appropriate protocols to ensure that children and pregnant women were not enrolled in the research. Individuals under the influence of intoxicants also were not excluded, though the use of ketamine is cautioned in this population.

“Administration of the investigational drugs to these subjects placed them at significantly increased risk of the adverse events associated with the investigational products and decreased the acceptability of those risks,” the FDA said in its letter. “Your failure to exclude, and the lack of any precautions for, subjects under the influence of various intoxicants significantly increased the risks and/or decreased the acceptability of the risks associated with the investigational drugs.”

However, Dr. Cole conducted both studies in the prehospital setting and failed to initiate any specific measures to protect study participants, according to the FDA.
 

Petition denied

Dr. Carome noted that the researchers had committed repetitive egregious regulatory violations over a 4-year period, which were documented by the FDA in their warning letters to Dr. Cole and Dr. Klein. “We felt that they were so egregious that we need to send a signal to the community that this sort of behavior will not be tolerated,” he said. “The FDA denied our petition, and we think that sends the wrong signal to the research community.”

In their response, the FDA noted that as with judicial enforcement, “the Agency makes decisions regarding whether to pursue administrative enforcement action, including disqualification proceedings, on a case-by-case basis, considering all relevant facts and circumstances.” They added that at this time, they would not be taking further action against Dr. Cole and Dr. Klein.

“However, we intend to continue to consider all the options available to the Agency as we determine whether to pursue additional compliance actions related to this matter,” the FDA concluded.

The FDA declined to comment further on their decision.

Dr. Cole also declined to comment, but Hennepin Healthcare told this news organization that the “decision by the FDA to deny the petition validates the changes we made to strengthen and improve the clinical research program across the institution since the closing of the studies in 2018. We look forward to continuing to work with the FDA to ensure full compliance with the standards in place to protect research subjects.”

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

As increasing numbers of patients in their 80s, 90s, and even 100s present for possible Mohs micrographic surgery, surgeons are confronted with deciding when the risks of treatment may outweigh the benefits.

In one of two presentations at the annual meeting of the American College of Mohs Surgery that addressed this topic, Howard W. Rogers, MD, of Advanced Dermatology in Norwich, Conn., said that the crux of the issue is the concern not to undertreat. He noted that reduced access to dermatologic care during the pandemic has provided a stark lesson in the risks of delaying treatment in all age groups. “Mohs surgeons have all seen the consequences of delayed treatment due to the pandemic with enormous, destructive, and sometimes fatal cancers coming to the office in the last year,” he told this news organization.

“Pandemic-related treatment delay has caused increased suffering and morbidity for countless skin cancer patients across the U.S.,” he said. “In general, not treating skin cancer and hoping it’s not going to grow or having significant delays in treatment are a recipe for disastrous outcomes.”

That said, active monitoring may be appropriate “for select small cancers that tend to grow slowly in the very elderly,” added Dr. Rogers, the incoming ACMS president. Among the key situations where the benefits of active monitoring may outweigh the risks of surgery are small, slowly growing cancers, when frailty is an issue.

Frailty has been equated to compromised functionality, which can increase the risk of an array of complications, including prolonged wound healing and secondary complications stemming from immobility. The toll those issues can take on patients’ quality of life can be considerable, Dr. Rogers said.

When weighing treatment options with elderly patients, he emphasized that careful consideration should be given to whether the “time needed to benefit from a Mohs procedure is longer than the patient’s life expectancy.” Furthermore, a decision not to treat does not have to be the last word. “We need to have an honest dialogue on the consequences of nontreatment, but part of that should be that just because we don’t treat today, doesn’t mean we can’t treat it tomorrow, if necessary.”

Of note, he added, “more than 100,00 patients have surgery for basal cell carcinoma [BCC] in their last year of life.” And that figure will likely rise exponentially if population projections come to fruition, considering that the population of people over the age of 85 is predicted to increase to nearly 18 million in 2050, from 5.8 million in 2012, Dr. Rogers said.

Until more research emerges on how to best treat this age group, Dr. Rogers noted that experts recommend that for elderly patients, “treatment should be individualized with consideration of active monitoring of primary BCC that is not in the H-zone, asymptomatic, smaller than 1 cm, with treatment initiated if there is substantial growth or symptoms.” Ultimately, he urged surgeons to “be sensitive and treat our patients like ourselves or our family members.”
 

When appropriate – Mohs is safe in the very elderly

Taking on the issue in a separate presentation, Deborah MacFarlane, MD, professor of dermatology and head and neck surgery at MD Anderson Cancer Center, Houston, said that for skin cancer cases that warrant treatment, clinicians should not let age alone stand in the way of Mohs surgery.

The evidence of its safety in the elderly dates back to a paper published in 1997 that Dr. MacFarlane coauthored, describing Mohs surgery of BCCs, squamous cell cancers (SCCs), and melanomas among 115 patients aged 90 and older (average, 92.4 years) who had an average of 1.9 comorbid medical conditions, and were taking an average of 2.3 medications. “Overall, we had just one complication among the patients,” she said.

In a subsequent paper, Dr. MacFarlane and her colleagues found that age at the time of Mohs surgery, even in older patients, was unrelated to survival, stage of cancer, or the type of repair. “We have concluded that this rapidly growing segment of the population can undergo Mohs surgery and should not be relegated to less effective treatment out of fear of its affecting their survival,” Dr. MacFarlane said.

She agreed with the concern about frailty and hence functionality, which may need to be factored in when making a decision to perform Mohs surgery. “I think this is something we do intuitively anyway,” she added. “We’re going to offer Mohs to someone who we think will survive and who is in relatively good health,” Dr. MacFarlane noted.

The point is illustrated in a new multicenter study of 1,181 patients at 22 U.S. sites, aged 85 years and older with nonmelanoma skin cancer referred for Mohs surgery. In the study, published in JAMA Dermatology after the ACMS meeting, patients who had Mohs surgery were almost four times more likely to have high functional status (P < .001) and were more likely to have facial tumors (P < .001), compared with those who had an alternate surgery.

The main reasons provided by the surgeons for opting to treat with Mohs included a patient’s desire for treatment with a high cure rate (66%), good/excellent patient functional status for age (57%), and a high risk associated with the tumor based on histology (40%), noted Dr. MacFarlane, one of the authors.

She reiterated the point raised by Dr. Rogers that “this is something we’re going to increasingly face,” noting that people over 85 represent the fastest growing segment of the population. “I have more patients over the age of 100 than I’ve ever had before,” she said.

Nevertheless, her own experience with elderly patients speaks to the safety of Mohs surgery in this population: Dr. MacFarlane reported a review of her practice’s records of 171 patients aged 85 years and older between May 2016 and May 2022, who received 414 separate procedures, without a single complication.

Sharing many of Dr. Rogers’ concerns about using caution in at-risk patients, Dr. MacFarlane offered recommendations for the optimal treatment of elderly patients receiving Mohs, including handling tissue delicately, and “keep undermining to a minimum.” She noted that intermediate closures and full thickness skin grafts are ideal closures for the elderly, while flaps may be performed in selected robust skin. It is also important to involve caretakers from the onset, talk and listen to patients – and play their choice of music during treatment, she said.

Commenting on the debate, comoderator Nahid Y. Vidal, MD, of the department of dermatology, Mayo Clinic, Rochester, Minn., noted that the expanding older population is accompanied by increases in skin cancer, in addition to more immunosenescence that is related to development of infections, autoimmune disease, and malignant tumors.

“In our academic practice, as with both the reference speakers, we do frequently see elderly, and not uncommonly the super-elderly,” she told this news organization. “The take-home point for me is to treat your whole patient, not just the tumor,” considering social factors, frailty/spry factor, and preferences, “and to do the humanistic thing, while also remaining evidence based,” she said.

“Don’t assume that increased age translates to morbidity, worse outcomes, or futility of treatment,” she added. “Chances are, if [a patient] made it to 90 years old with only a few medications and few medical problems, they may make it to 100, so why put the patient at risk for metastasis and death from a treatable/curable skin cancer,” in the case of SCC, she said.

“By the same token, why not perform more conservative treatments such as ED&C [electrodesiccation and curettage] for very low-risk skin cancers in low-risk locations, such as a superficial basal cell carcinoma on the trunk?” Overall, instead of trying to determine how long a super-elderly individual will live, Dr. Vidal said that “it’s better to educate the patient, engage in a discussion about goals of care, and to make few assumptions.”

Dr. Rogers, Dr. MacFarlane, and Dr. Vidal report no disclosures.

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

As increasing numbers of patients in their 80s, 90s, and even 100s present for possible Mohs micrographic surgery, surgeons are confronted with deciding when the risks of treatment may outweigh the benefits.

In one of two presentations at the annual meeting of the American College of Mohs Surgery that addressed this topic, Howard W. Rogers, MD, of Advanced Dermatology in Norwich, Conn., said that the crux of the issue is the concern not to undertreat. He noted that reduced access to dermatologic care during the pandemic has provided a stark lesson in the risks of delaying treatment in all age groups. “Mohs surgeons have all seen the consequences of delayed treatment due to the pandemic with enormous, destructive, and sometimes fatal cancers coming to the office in the last year,” he told this news organization.

“Pandemic-related treatment delay has caused increased suffering and morbidity for countless skin cancer patients across the U.S.,” he said. “In general, not treating skin cancer and hoping it’s not going to grow or having significant delays in treatment are a recipe for disastrous outcomes.”

That said, active monitoring may be appropriate “for select small cancers that tend to grow slowly in the very elderly,” added Dr. Rogers, the incoming ACMS president. Among the key situations where the benefits of active monitoring may outweigh the risks of surgery are small, slowly growing cancers, when frailty is an issue.

Frailty has been equated to compromised functionality, which can increase the risk of an array of complications, including prolonged wound healing and secondary complications stemming from immobility. The toll those issues can take on patients’ quality of life can be considerable, Dr. Rogers said.

When weighing treatment options with elderly patients, he emphasized that careful consideration should be given to whether the “time needed to benefit from a Mohs procedure is longer than the patient’s life expectancy.” Furthermore, a decision not to treat does not have to be the last word. “We need to have an honest dialogue on the consequences of nontreatment, but part of that should be that just because we don’t treat today, doesn’t mean we can’t treat it tomorrow, if necessary.”

Of note, he added, “more than 100,00 patients have surgery for basal cell carcinoma [BCC] in their last year of life.” And that figure will likely rise exponentially if population projections come to fruition, considering that the population of people over the age of 85 is predicted to increase to nearly 18 million in 2050, from 5.8 million in 2012, Dr. Rogers said.

Until more research emerges on how to best treat this age group, Dr. Rogers noted that experts recommend that for elderly patients, “treatment should be individualized with consideration of active monitoring of primary BCC that is not in the H-zone, asymptomatic, smaller than 1 cm, with treatment initiated if there is substantial growth or symptoms.” Ultimately, he urged surgeons to “be sensitive and treat our patients like ourselves or our family members.”
 

When appropriate – Mohs is safe in the very elderly

Taking on the issue in a separate presentation, Deborah MacFarlane, MD, professor of dermatology and head and neck surgery at MD Anderson Cancer Center, Houston, said that for skin cancer cases that warrant treatment, clinicians should not let age alone stand in the way of Mohs surgery.

The evidence of its safety in the elderly dates back to a paper published in 1997 that Dr. MacFarlane coauthored, describing Mohs surgery of BCCs, squamous cell cancers (SCCs), and melanomas among 115 patients aged 90 and older (average, 92.4 years) who had an average of 1.9 comorbid medical conditions, and were taking an average of 2.3 medications. “Overall, we had just one complication among the patients,” she said.

In a subsequent paper, Dr. MacFarlane and her colleagues found that age at the time of Mohs surgery, even in older patients, was unrelated to survival, stage of cancer, or the type of repair. “We have concluded that this rapidly growing segment of the population can undergo Mohs surgery and should not be relegated to less effective treatment out of fear of its affecting their survival,” Dr. MacFarlane said.

She agreed with the concern about frailty and hence functionality, which may need to be factored in when making a decision to perform Mohs surgery. “I think this is something we do intuitively anyway,” she added. “We’re going to offer Mohs to someone who we think will survive and who is in relatively good health,” Dr. MacFarlane noted.

The point is illustrated in a new multicenter study of 1,181 patients at 22 U.S. sites, aged 85 years and older with nonmelanoma skin cancer referred for Mohs surgery. In the study, published in JAMA Dermatology after the ACMS meeting, patients who had Mohs surgery were almost four times more likely to have high functional status (P < .001) and were more likely to have facial tumors (P < .001), compared with those who had an alternate surgery.

The main reasons provided by the surgeons for opting to treat with Mohs included a patient’s desire for treatment with a high cure rate (66%), good/excellent patient functional status for age (57%), and a high risk associated with the tumor based on histology (40%), noted Dr. MacFarlane, one of the authors.

She reiterated the point raised by Dr. Rogers that “this is something we’re going to increasingly face,” noting that people over 85 represent the fastest growing segment of the population. “I have more patients over the age of 100 than I’ve ever had before,” she said.

Nevertheless, her own experience with elderly patients speaks to the safety of Mohs surgery in this population: Dr. MacFarlane reported a review of her practice’s records of 171 patients aged 85 years and older between May 2016 and May 2022, who received 414 separate procedures, without a single complication.

Sharing many of Dr. Rogers’ concerns about using caution in at-risk patients, Dr. MacFarlane offered recommendations for the optimal treatment of elderly patients receiving Mohs, including handling tissue delicately, and “keep undermining to a minimum.” She noted that intermediate closures and full thickness skin grafts are ideal closures for the elderly, while flaps may be performed in selected robust skin. It is also important to involve caretakers from the onset, talk and listen to patients – and play their choice of music during treatment, she said.

Commenting on the debate, comoderator Nahid Y. Vidal, MD, of the department of dermatology, Mayo Clinic, Rochester, Minn., noted that the expanding older population is accompanied by increases in skin cancer, in addition to more immunosenescence that is related to development of infections, autoimmune disease, and malignant tumors.

“In our academic practice, as with both the reference speakers, we do frequently see elderly, and not uncommonly the super-elderly,” she told this news organization. “The take-home point for me is to treat your whole patient, not just the tumor,” considering social factors, frailty/spry factor, and preferences, “and to do the humanistic thing, while also remaining evidence based,” she said.

“Don’t assume that increased age translates to morbidity, worse outcomes, or futility of treatment,” she added. “Chances are, if [a patient] made it to 90 years old with only a few medications and few medical problems, they may make it to 100, so why put the patient at risk for metastasis and death from a treatable/curable skin cancer,” in the case of SCC, she said.

“By the same token, why not perform more conservative treatments such as ED&C [electrodesiccation and curettage] for very low-risk skin cancers in low-risk locations, such as a superficial basal cell carcinoma on the trunk?” Overall, instead of trying to determine how long a super-elderly individual will live, Dr. Vidal said that “it’s better to educate the patient, engage in a discussion about goals of care, and to make few assumptions.”

Dr. Rogers, Dr. MacFarlane, and Dr. Vidal report no disclosures.

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

As increasing numbers of patients in their 80s, 90s, and even 100s present for possible Mohs micrographic surgery, surgeons are confronted with deciding when the risks of treatment may outweigh the benefits.

In one of two presentations at the annual meeting of the American College of Mohs Surgery that addressed this topic, Howard W. Rogers, MD, of Advanced Dermatology in Norwich, Conn., said that the crux of the issue is the concern not to undertreat. He noted that reduced access to dermatologic care during the pandemic has provided a stark lesson in the risks of delaying treatment in all age groups. “Mohs surgeons have all seen the consequences of delayed treatment due to the pandemic with enormous, destructive, and sometimes fatal cancers coming to the office in the last year,” he told this news organization.

“Pandemic-related treatment delay has caused increased suffering and morbidity for countless skin cancer patients across the U.S.,” he said. “In general, not treating skin cancer and hoping it’s not going to grow or having significant delays in treatment are a recipe for disastrous outcomes.”

That said, active monitoring may be appropriate “for select small cancers that tend to grow slowly in the very elderly,” added Dr. Rogers, the incoming ACMS president. Among the key situations where the benefits of active monitoring may outweigh the risks of surgery are small, slowly growing cancers, when frailty is an issue.

Frailty has been equated to compromised functionality, which can increase the risk of an array of complications, including prolonged wound healing and secondary complications stemming from immobility. The toll those issues can take on patients’ quality of life can be considerable, Dr. Rogers said.

When weighing treatment options with elderly patients, he emphasized that careful consideration should be given to whether the “time needed to benefit from a Mohs procedure is longer than the patient’s life expectancy.” Furthermore, a decision not to treat does not have to be the last word. “We need to have an honest dialogue on the consequences of nontreatment, but part of that should be that just because we don’t treat today, doesn’t mean we can’t treat it tomorrow, if necessary.”

Of note, he added, “more than 100,00 patients have surgery for basal cell carcinoma [BCC] in their last year of life.” And that figure will likely rise exponentially if population projections come to fruition, considering that the population of people over the age of 85 is predicted to increase to nearly 18 million in 2050, from 5.8 million in 2012, Dr. Rogers said.

Until more research emerges on how to best treat this age group, Dr. Rogers noted that experts recommend that for elderly patients, “treatment should be individualized with consideration of active monitoring of primary BCC that is not in the H-zone, asymptomatic, smaller than 1 cm, with treatment initiated if there is substantial growth or symptoms.” Ultimately, he urged surgeons to “be sensitive and treat our patients like ourselves or our family members.”
 

When appropriate – Mohs is safe in the very elderly

Taking on the issue in a separate presentation, Deborah MacFarlane, MD, professor of dermatology and head and neck surgery at MD Anderson Cancer Center, Houston, said that for skin cancer cases that warrant treatment, clinicians should not let age alone stand in the way of Mohs surgery.

The evidence of its safety in the elderly dates back to a paper published in 1997 that Dr. MacFarlane coauthored, describing Mohs surgery of BCCs, squamous cell cancers (SCCs), and melanomas among 115 patients aged 90 and older (average, 92.4 years) who had an average of 1.9 comorbid medical conditions, and were taking an average of 2.3 medications. “Overall, we had just one complication among the patients,” she said.

In a subsequent paper, Dr. MacFarlane and her colleagues found that age at the time of Mohs surgery, even in older patients, was unrelated to survival, stage of cancer, or the type of repair. “We have concluded that this rapidly growing segment of the population can undergo Mohs surgery and should not be relegated to less effective treatment out of fear of its affecting their survival,” Dr. MacFarlane said.

She agreed with the concern about frailty and hence functionality, which may need to be factored in when making a decision to perform Mohs surgery. “I think this is something we do intuitively anyway,” she added. “We’re going to offer Mohs to someone who we think will survive and who is in relatively good health,” Dr. MacFarlane noted.

The point is illustrated in a new multicenter study of 1,181 patients at 22 U.S. sites, aged 85 years and older with nonmelanoma skin cancer referred for Mohs surgery. In the study, published in JAMA Dermatology after the ACMS meeting, patients who had Mohs surgery were almost four times more likely to have high functional status (P < .001) and were more likely to have facial tumors (P < .001), compared with those who had an alternate surgery.

The main reasons provided by the surgeons for opting to treat with Mohs included a patient’s desire for treatment with a high cure rate (66%), good/excellent patient functional status for age (57%), and a high risk associated with the tumor based on histology (40%), noted Dr. MacFarlane, one of the authors.

She reiterated the point raised by Dr. Rogers that “this is something we’re going to increasingly face,” noting that people over 85 represent the fastest growing segment of the population. “I have more patients over the age of 100 than I’ve ever had before,” she said.

Nevertheless, her own experience with elderly patients speaks to the safety of Mohs surgery in this population: Dr. MacFarlane reported a review of her practice’s records of 171 patients aged 85 years and older between May 2016 and May 2022, who received 414 separate procedures, without a single complication.

Sharing many of Dr. Rogers’ concerns about using caution in at-risk patients, Dr. MacFarlane offered recommendations for the optimal treatment of elderly patients receiving Mohs, including handling tissue delicately, and “keep undermining to a minimum.” She noted that intermediate closures and full thickness skin grafts are ideal closures for the elderly, while flaps may be performed in selected robust skin. It is also important to involve caretakers from the onset, talk and listen to patients – and play their choice of music during treatment, she said.

Commenting on the debate, comoderator Nahid Y. Vidal, MD, of the department of dermatology, Mayo Clinic, Rochester, Minn., noted that the expanding older population is accompanied by increases in skin cancer, in addition to more immunosenescence that is related to development of infections, autoimmune disease, and malignant tumors.

“In our academic practice, as with both the reference speakers, we do frequently see elderly, and not uncommonly the super-elderly,” she told this news organization. “The take-home point for me is to treat your whole patient, not just the tumor,” considering social factors, frailty/spry factor, and preferences, “and to do the humanistic thing, while also remaining evidence based,” she said.

“Don’t assume that increased age translates to morbidity, worse outcomes, or futility of treatment,” she added. “Chances are, if [a patient] made it to 90 years old with only a few medications and few medical problems, they may make it to 100, so why put the patient at risk for metastasis and death from a treatable/curable skin cancer,” in the case of SCC, she said.

“By the same token, why not perform more conservative treatments such as ED&C [electrodesiccation and curettage] for very low-risk skin cancers in low-risk locations, such as a superficial basal cell carcinoma on the trunk?” Overall, instead of trying to determine how long a super-elderly individual will live, Dr. Vidal said that “it’s better to educate the patient, engage in a discussion about goals of care, and to make few assumptions.”

Dr. Rogers, Dr. MacFarlane, and Dr. Vidal report no disclosures.

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

Headache medicine expert Joel Saper, MD once saw the formation of the United Council for Neurologic Subspecialties as a sign of progress in the field. In 2005, he even helped write their first certification exam for headache medicine.

Now he’s calling fraud.

After Dr. Saper’s initial 10-year certification expired, he paid $1,800 to take a recertification test. Passing this, he earned another decade of diplomate status; or so he thought, until a couple years later, when he received word from the UCNS.

“They were changing the rules,” Dr. Saper said in an interview. “The 10-year certificate was no longer valid. You had to go through another process.”

That process, known as continuous certification, has become the new standard among medical boards. In contrast with a more conventional recertification process that depends upon high-fee, high-stakes exams taken years apart, continuous certification typically involves a relatively small annual fee coupled with online reading and assessments designed to ensure familiarity with advances in the field.

It’s not just the physicians that need to study up. Medical boards are under pressure to ensure that they are maintaining retention, a potentially challenging task with approximately 200 medical certifying boards in the United States competing for attention, and in some cases, credibility.

Pivots to new systems of recertification have been a particular flash point among physicians. In 2015, a Newsweek article described how a group of “nationally known physicians revolted against the American Board of Internal Medicine” after the board “attempted to expand its program for recertifying doctors, adding boatloads of requirements and fees to be paid by physicians.”

In response, ABIM attacked both the journalist and Newsweek, citing a conflict of interest (the journalist was married to a doctor). The journalist went on to uncover some uncomfortable statistics, including the fact that, over a 5-year period, the ABIM Foundation lost $39.8 million while paying senior administrators $125.7 million. Such revelations have likely added to a collective skepticism about medical boards and their motives.
 

The changing landscape of recertification

According to Brenda Riggott, executive director of the UCNS, the switch to continuous certification was driven by a need to keep up with new standards.

“We really found the landscape of maintaining medical certifications in general was changing,” Ms. Riggott said, highlighting how the UCNS “evaluated 13 different continuous certification models being administered by medical boards” before settling upon the present model.

Continuous certification with the UCNS now requires a $175 annual fee. Each year, diplomates read 10 journal articles, then take a 25-question online quiz to demonstrate their understanding.

“It’s really about patient care,” Ms. Riggott said in an interview. “Medicine changes rapidly. And there are a lot of advances. Evaluating that once a decade is really not enough to verify that somebody is maintaining their skills, their knowledge.”

Dr. Saper, a clinical professor of neurology at Michigan State University, East Lansing, and founder-director of the Michigan Head Pain and Neurological Institute, Ann Arbor, had no inherent qualm with transitioning to this newer process, but he did take umbrage at its execution, since his UCNS certificate still had about 7 years until expiry.

He said the UCNS should have honored existing certificates through their stated duration, citing precedent set by the American Academy of Neurology. When the AAN transitioned from lifetime board certification to a periodic recertification process, they honored the lifetime status of those who already held it, according to Dr. Saper.

“[The AAN] looked at those of us who had been boarded under the premise that we were going to be lifetime boarded ... and they said: ‘We’re going to grandfather you ... because that was the rule under which you took your initial exams.’ ... That’s what UCNS should have done,” Dr. Saper said.
 

A compromise

Under pressure from Dr. Saper and others, UCNS compromised by endorsing 10-year diplomates until the 5-year mark.

Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and the editor-in-chief of Neurology Reviews, was among those who spoke up, only to see the duration of his certification cut in half.

“UCNS obviously realized that they had been wrong,” Dr. Rapoport said, referring to the compromise they made.

At the 5-year mark, physicians who didn’t adopt the new system were deleted from the UCNS online database, eliminating “the only way the public would know whether or not we were certified. This was after UCNS told us we would stay on the list with a note next to our name suggesting our certification was incomplete. They did not care that this might have hurt our reputations,” Dr. Rapoport said.

“To this day, no refunds, partial or full, have been given for the $1,800 we paid for the privilege of sitting for the exam, or for our time studying, or for the expenses accrued from canceling a day in the office and traveling to a testing center,” Dr. Rapoport said. “I did not want the money back; I wanted the certification promised to me. Since they have removed my name from this list, they do owe me the $1,800. They say they do not return their fees if you fail. How about if you pass and they remove you from their list?”

Yet he went on to make clear that the real issue is the principle of the matter. “This is not about money,” Dr. Rapoport said. “This is about what is fair and right.”

“The UCNS issued me a certificate for 10 years of certification in headache medicine; it is unethical and unlawful to break that contract and grant me only 5 years. Worse, they removed my name as though I do not exist. Along with Dr. Saper, I was one of the doctors that spent time and effort to advance headache medicine from October 1979, when I became a headache specialist, to today. I supported the principles of UCNS and took the first exam. I became the President of the International Headache Society and traveled the world promoting headache medicine; and this is how I am treated. Who can respect this type of certification, or this organization?”

Dr. Saper agreed: “It’s not about the money. It’s about the commitment. It’s very fraudulent.”

After the UCNS decision, Dr. Rapoport and Dr. Saper sought legal counsel, but ultimately decided not to sue the UCNS because of the lengthy process it would entail and the cost, estimated to be over $100,000.

“Our lawyers said: ‘It’s going to be years to get through it. You’ll probably win in the end, because it was fraudulent behavior,’ ” Dr. Saper said.
 

A different viewpoint

Ms. Riggott offered a different viewpoint: Nobody was guaranteed 10 years of certification.

“People do not pay for certification [from the UCNS],” Ms. Riggott said. “They pay to sit for an exam. It’s an exam administration fee. That can be construed as: ‘They paid for 10 years.’ They did not. They paid to sit for an exam. There are people who pay for an exam, and they don’t pass it, and they’re not certified. They don’t get a refund. That’s just the way high-stakes certification exams go.”

Dr. Saper and Dr. Rapoport see it differently. “The inherent reason any of us sit for an exam is to get certified.” Dr. Rapoport added. “Ms. Riggott is not being honest. There was an implied contract that if we passed, we would be granted a 10-year certification because that was what we did previously and that is what they told us would happen. Why would they have sent me this nice certificate for 10 more years of certification if she were telling the truth?”

Courtesy Dr. Alan M. Rapoport

Profits over promises

Dr. Rapoport estimates that many other neurologists had their certificates cut short and were dropped from this official list, some of them eminent members of the field, including David Watson, MD, professor and chair of neurology at West Virginia University Rockefeller Neuroscience Institute, Morgantown, and Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University.

“It is troubling when the organizations charged with maintaining the integrity of our specialization do not act with integrity,” Dr. Watson said. “The UCNS chose profits over promises and has refused to meaningfully engage with those of us whom they have wronged. What was once a point of pride for me (being in the second class of certified headache medicine diplomates) has become a meaningless piece of paper. This makes me sad.”

Dr. Cowan said the UCNS actions angered him while affirming his lifelong skepticism of clubs. “I was very sorry, but not surprised, to see the UCNS change the rules when the opportunity to make more money presented itself, and not surprised they did not honor their contracts. UCNS is just another scam like Best Doctors in the US and similar hypes. Neither are worth another dime of my money nor the time spent discussing them. One thing more: I have no quarrel with efforts to encourage keeping up with the field, although no one I know needs codification or direction as to which articles should be read. My outrage comes when responsible behavior is used as an excuse to line the pockets of dishonest, immoral individuals. I’m done.”

According to Ms. Riggott, the UCNS continuous certification process continues to evolve based on feedback from diplomates. She noted that “change is hard,” although the challenges of the transition appear to be paying off. “Initial retention for continuing certification is much higher than we would have expected from a high-stakes recertification exam,” she said. “So we are very, very happy about that.”
 

Proprietary tests drive revenue

According to Katie Collins, executive director of the National Board of Physicians and Surgeons, proprietary tests are a key revenue driver for medical boards, casting doubt on their educational motives.

“This isn’t really about maintaining their education, it’s really about having control over what they learn,” Ms. Collins said. “And unfortunately, physicians no longer have control over what they learn.”

NBPAS was formed largely in response to physicians dissatisfied with this situation. For $189 every 2 years, plus $25 for a paper certificate, NBPAS recertifies doctors originally credentialed by the American Board of Medical Specialties or the American Osteopathic Association.

Instead of making physicians take proprietary tests, NBPAS requires them to earn 50 hours of Accreditation Council for Continuing Medical Education–accredited CME every 2 years. Physicians can select where they seek this credit, giving them the agency to “pick and choose where they want to learn more,” Ms. Collins said, noting that this allows physicians to address personal knowledge gaps, instead of mastering the prescriptive lessons issued by other boards.

While this benefits physicians, Ms. Collins added, it also reduces the bottom line.

NBPAS is a “true 501(c)(3),” she said. “We have money for rainy days, but certainly not millions. We don’t have anything close to a million in savings.” Most medical boards are making millions on top of their services, she said. “That’s not for me to rein in, but it’s for me to point out.”

Noah Rosen, MD, associate professor of neurology and psychiatry at Northwell Health, Great Neck, N.Y., and former UCNS board member, said the UCNS was not motivated by money when they decided to switch to continuous recertification.

“The UCNS budget is publicly available,” Dr. Rosen said in an interview. “This is not a money-making organization,” he added, noting that the UCNS has “been basically operating on a breakeven budget,” and that certification “is not really a money-making proposition.”

Public IRS filings from 2019 and 2020 suggest a slightly different picture. In 2019, the UCNS reported net income of $72,256. In 2020, the inaugural year of the continuous certification program, net income jumped almost fivefold to $349,108. Over the same period, total assets held by the UCNS rose from $1.97 million to $2.37 million.

For comparison, NBPAS controls approximately $500,000 in total assets. The ABIM? Just shy of $72 million.
 

Recertification highlights a generational gap

Dr. Rosen, who was not a voting board member when the UCNS decided to switch to continuous certification, suggested that the transition could have been handled more effectively.

“I think Dr. Rapoport speaks to the frustration of how they made the transition, and that it could have been done in a way that recognizes people that held the certificate in a better way,” Dr. Rosen said.

He said that the departure of Dr. Rapoport and other neurologists from the UCNS points to another trend in the certification space. “I do think it brings up a deeper issue: What’s the value of certification? Dr. Rapoport and other people have brought up the question: What actually does this certificate bring you, if it’s not recognized by the federal government, and actually is not recognized by a lot of state governments, as well, as an official certification?”

He said the answer could depend on age.

“There seems to be a difference between younger people entering into the field and people that are more established in the field already,” Dr. Rosen said. “Younger people entering the field, they see certification as a distinction, something that separates them from the experiences and maybe every other neurologist.”

Ms. Collins independently pointed out the same generational gap. She noted that when the ABMS changed their maintenance model from lifelong to periodic in 2000, approximately 60% of their physicians had to change with the times, while the remainder did not.

“They grandfathered the other 40% – the older, probably more Caucasian male physicians,” she said. “It’s just the field. It’s evolved, it’s become more diverse. They created a divide in the physician community about what is the best means to maintain your board.”

In response to these comments, and despite his negative experiences with the UCNS, Dr. Rapoport emphasized that he still places high value on subspecialty certification.

“I care a lot about certification and that is why I decided to study for and take the only exam offered at the time,” he said, “I do not need it to continue my practice in headache medicine. No one asks me if I am certified in headache medicine. My patients are referred to me because of my reputation. But I have always sought the highest level of certification I could get. What UCNS has done is to cheapen the value of their certification.”

Dr. Rosen and Ms. Collins highlighted the other side of the same conclusion: For younger physicians, board certifications are more of a career consideration than they are for older physicians, as they could mean the difference between landing or losing a job.

“The American Board of Medical Specialties and [their] 24 member boards have really woven board certification into a requirement for employment for hospital privileges and for reimbursement,” Ms. Collins said.

And so, the practical value of board certification may depend most on the tenure of the person holding paper.

“I have not gone back to get any further certification [from the UCNS],” Dr. Saper said.

Even if his name has been removed from the UCNS register, he pointed out that his printed certificate still shows it’s valid until October 31st, 2026: “If anybody asks: ‘Are you certified?’ I say: ‘Here’s my certificate.’ ”

Courtesy Joel R. Saper, MD

Headache medicine expert Joel Saper, MD once saw the formation of the United Council for Neurologic Subspecialties as a sign of progress in the field. In 2005, he even helped write their first certification exam for headache medicine.

Now he’s calling fraud.

After Dr. Saper’s initial 10-year certification expired, he paid $1,800 to take a recertification test. Passing this, he earned another decade of diplomate status; or so he thought, until a couple years later, when he received word from the UCNS.

“They were changing the rules,” Dr. Saper said in an interview. “The 10-year certificate was no longer valid. You had to go through another process.”

That process, known as continuous certification, has become the new standard among medical boards. In contrast with a more conventional recertification process that depends upon high-fee, high-stakes exams taken years apart, continuous certification typically involves a relatively small annual fee coupled with online reading and assessments designed to ensure familiarity with advances in the field.

It’s not just the physicians that need to study up. Medical boards are under pressure to ensure that they are maintaining retention, a potentially challenging task with approximately 200 medical certifying boards in the United States competing for attention, and in some cases, credibility.

Pivots to new systems of recertification have been a particular flash point among physicians. In 2015, a Newsweek article described how a group of “nationally known physicians revolted against the American Board of Internal Medicine” after the board “attempted to expand its program for recertifying doctors, adding boatloads of requirements and fees to be paid by physicians.”

In response, ABIM attacked both the journalist and Newsweek, citing a conflict of interest (the journalist was married to a doctor). The journalist went on to uncover some uncomfortable statistics, including the fact that, over a 5-year period, the ABIM Foundation lost $39.8 million while paying senior administrators $125.7 million. Such revelations have likely added to a collective skepticism about medical boards and their motives.
 

The changing landscape of recertification

According to Brenda Riggott, executive director of the UCNS, the switch to continuous certification was driven by a need to keep up with new standards.

“We really found the landscape of maintaining medical certifications in general was changing,” Ms. Riggott said, highlighting how the UCNS “evaluated 13 different continuous certification models being administered by medical boards” before settling upon the present model.

Continuous certification with the UCNS now requires a $175 annual fee. Each year, diplomates read 10 journal articles, then take a 25-question online quiz to demonstrate their understanding.

“It’s really about patient care,” Ms. Riggott said in an interview. “Medicine changes rapidly. And there are a lot of advances. Evaluating that once a decade is really not enough to verify that somebody is maintaining their skills, their knowledge.”

Dr. Saper, a clinical professor of neurology at Michigan State University, East Lansing, and founder-director of the Michigan Head Pain and Neurological Institute, Ann Arbor, had no inherent qualm with transitioning to this newer process, but he did take umbrage at its execution, since his UCNS certificate still had about 7 years until expiry.

He said the UCNS should have honored existing certificates through their stated duration, citing precedent set by the American Academy of Neurology. When the AAN transitioned from lifetime board certification to a periodic recertification process, they honored the lifetime status of those who already held it, according to Dr. Saper.

“[The AAN] looked at those of us who had been boarded under the premise that we were going to be lifetime boarded ... and they said: ‘We’re going to grandfather you ... because that was the rule under which you took your initial exams.’ ... That’s what UCNS should have done,” Dr. Saper said.
 

A compromise

Under pressure from Dr. Saper and others, UCNS compromised by endorsing 10-year diplomates until the 5-year mark.

Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and the editor-in-chief of Neurology Reviews, was among those who spoke up, only to see the duration of his certification cut in half.

“UCNS obviously realized that they had been wrong,” Dr. Rapoport said, referring to the compromise they made.

At the 5-year mark, physicians who didn’t adopt the new system were deleted from the UCNS online database, eliminating “the only way the public would know whether or not we were certified. This was after UCNS told us we would stay on the list with a note next to our name suggesting our certification was incomplete. They did not care that this might have hurt our reputations,” Dr. Rapoport said.

“To this day, no refunds, partial or full, have been given for the $1,800 we paid for the privilege of sitting for the exam, or for our time studying, or for the expenses accrued from canceling a day in the office and traveling to a testing center,” Dr. Rapoport said. “I did not want the money back; I wanted the certification promised to me. Since they have removed my name from this list, they do owe me the $1,800. They say they do not return their fees if you fail. How about if you pass and they remove you from their list?”

Yet he went on to make clear that the real issue is the principle of the matter. “This is not about money,” Dr. Rapoport said. “This is about what is fair and right.”

“The UCNS issued me a certificate for 10 years of certification in headache medicine; it is unethical and unlawful to break that contract and grant me only 5 years. Worse, they removed my name as though I do not exist. Along with Dr. Saper, I was one of the doctors that spent time and effort to advance headache medicine from October 1979, when I became a headache specialist, to today. I supported the principles of UCNS and took the first exam. I became the President of the International Headache Society and traveled the world promoting headache medicine; and this is how I am treated. Who can respect this type of certification, or this organization?”

Dr. Saper agreed: “It’s not about the money. It’s about the commitment. It’s very fraudulent.”

After the UCNS decision, Dr. Rapoport and Dr. Saper sought legal counsel, but ultimately decided not to sue the UCNS because of the lengthy process it would entail and the cost, estimated to be over $100,000.

“Our lawyers said: ‘It’s going to be years to get through it. You’ll probably win in the end, because it was fraudulent behavior,’ ” Dr. Saper said.
 

A different viewpoint

Ms. Riggott offered a different viewpoint: Nobody was guaranteed 10 years of certification.

“People do not pay for certification [from the UCNS],” Ms. Riggott said. “They pay to sit for an exam. It’s an exam administration fee. That can be construed as: ‘They paid for 10 years.’ They did not. They paid to sit for an exam. There are people who pay for an exam, and they don’t pass it, and they’re not certified. They don’t get a refund. That’s just the way high-stakes certification exams go.”

Dr. Saper and Dr. Rapoport see it differently. “The inherent reason any of us sit for an exam is to get certified.” Dr. Rapoport added. “Ms. Riggott is not being honest. There was an implied contract that if we passed, we would be granted a 10-year certification because that was what we did previously and that is what they told us would happen. Why would they have sent me this nice certificate for 10 more years of certification if she were telling the truth?”

Courtesy Dr. Alan M. Rapoport

Profits over promises

Dr. Rapoport estimates that many other neurologists had their certificates cut short and were dropped from this official list, some of them eminent members of the field, including David Watson, MD, professor and chair of neurology at West Virginia University Rockefeller Neuroscience Institute, Morgantown, and Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University.

“It is troubling when the organizations charged with maintaining the integrity of our specialization do not act with integrity,” Dr. Watson said. “The UCNS chose profits over promises and has refused to meaningfully engage with those of us whom they have wronged. What was once a point of pride for me (being in the second class of certified headache medicine diplomates) has become a meaningless piece of paper. This makes me sad.”

Dr. Cowan said the UCNS actions angered him while affirming his lifelong skepticism of clubs. “I was very sorry, but not surprised, to see the UCNS change the rules when the opportunity to make more money presented itself, and not surprised they did not honor their contracts. UCNS is just another scam like Best Doctors in the US and similar hypes. Neither are worth another dime of my money nor the time spent discussing them. One thing more: I have no quarrel with efforts to encourage keeping up with the field, although no one I know needs codification or direction as to which articles should be read. My outrage comes when responsible behavior is used as an excuse to line the pockets of dishonest, immoral individuals. I’m done.”

According to Ms. Riggott, the UCNS continuous certification process continues to evolve based on feedback from diplomates. She noted that “change is hard,” although the challenges of the transition appear to be paying off. “Initial retention for continuing certification is much higher than we would have expected from a high-stakes recertification exam,” she said. “So we are very, very happy about that.”
 

Proprietary tests drive revenue

According to Katie Collins, executive director of the National Board of Physicians and Surgeons, proprietary tests are a key revenue driver for medical boards, casting doubt on their educational motives.

“This isn’t really about maintaining their education, it’s really about having control over what they learn,” Ms. Collins said. “And unfortunately, physicians no longer have control over what they learn.”

NBPAS was formed largely in response to physicians dissatisfied with this situation. For $189 every 2 years, plus $25 for a paper certificate, NBPAS recertifies doctors originally credentialed by the American Board of Medical Specialties or the American Osteopathic Association.

Instead of making physicians take proprietary tests, NBPAS requires them to earn 50 hours of Accreditation Council for Continuing Medical Education–accredited CME every 2 years. Physicians can select where they seek this credit, giving them the agency to “pick and choose where they want to learn more,” Ms. Collins said, noting that this allows physicians to address personal knowledge gaps, instead of mastering the prescriptive lessons issued by other boards.

While this benefits physicians, Ms. Collins added, it also reduces the bottom line.

NBPAS is a “true 501(c)(3),” she said. “We have money for rainy days, but certainly not millions. We don’t have anything close to a million in savings.” Most medical boards are making millions on top of their services, she said. “That’s not for me to rein in, but it’s for me to point out.”

Noah Rosen, MD, associate professor of neurology and psychiatry at Northwell Health, Great Neck, N.Y., and former UCNS board member, said the UCNS was not motivated by money when they decided to switch to continuous recertification.

“The UCNS budget is publicly available,” Dr. Rosen said in an interview. “This is not a money-making organization,” he added, noting that the UCNS has “been basically operating on a breakeven budget,” and that certification “is not really a money-making proposition.”

Public IRS filings from 2019 and 2020 suggest a slightly different picture. In 2019, the UCNS reported net income of $72,256. In 2020, the inaugural year of the continuous certification program, net income jumped almost fivefold to $349,108. Over the same period, total assets held by the UCNS rose from $1.97 million to $2.37 million.

For comparison, NBPAS controls approximately $500,000 in total assets. The ABIM? Just shy of $72 million.
 

Recertification highlights a generational gap

Dr. Rosen, who was not a voting board member when the UCNS decided to switch to continuous certification, suggested that the transition could have been handled more effectively.

“I think Dr. Rapoport speaks to the frustration of how they made the transition, and that it could have been done in a way that recognizes people that held the certificate in a better way,” Dr. Rosen said.

He said that the departure of Dr. Rapoport and other neurologists from the UCNS points to another trend in the certification space. “I do think it brings up a deeper issue: What’s the value of certification? Dr. Rapoport and other people have brought up the question: What actually does this certificate bring you, if it’s not recognized by the federal government, and actually is not recognized by a lot of state governments, as well, as an official certification?”

He said the answer could depend on age.

“There seems to be a difference between younger people entering into the field and people that are more established in the field already,” Dr. Rosen said. “Younger people entering the field, they see certification as a distinction, something that separates them from the experiences and maybe every other neurologist.”

Ms. Collins independently pointed out the same generational gap. She noted that when the ABMS changed their maintenance model from lifelong to periodic in 2000, approximately 60% of their physicians had to change with the times, while the remainder did not.

“They grandfathered the other 40% – the older, probably more Caucasian male physicians,” she said. “It’s just the field. It’s evolved, it’s become more diverse. They created a divide in the physician community about what is the best means to maintain your board.”

In response to these comments, and despite his negative experiences with the UCNS, Dr. Rapoport emphasized that he still places high value on subspecialty certification.

“I care a lot about certification and that is why I decided to study for and take the only exam offered at the time,” he said, “I do not need it to continue my practice in headache medicine. No one asks me if I am certified in headache medicine. My patients are referred to me because of my reputation. But I have always sought the highest level of certification I could get. What UCNS has done is to cheapen the value of their certification.”

Dr. Rosen and Ms. Collins highlighted the other side of the same conclusion: For younger physicians, board certifications are more of a career consideration than they are for older physicians, as they could mean the difference between landing or losing a job.

“The American Board of Medical Specialties and [their] 24 member boards have really woven board certification into a requirement for employment for hospital privileges and for reimbursement,” Ms. Collins said.

And so, the practical value of board certification may depend most on the tenure of the person holding paper.

“I have not gone back to get any further certification [from the UCNS],” Dr. Saper said.

Even if his name has been removed from the UCNS register, he pointed out that his printed certificate still shows it’s valid until October 31st, 2026: “If anybody asks: ‘Are you certified?’ I say: ‘Here’s my certificate.’ ”

Courtesy Joel R. Saper, MD

Headache medicine expert Joel Saper, MD once saw the formation of the United Council for Neurologic Subspecialties as a sign of progress in the field. In 2005, he even helped write their first certification exam for headache medicine.

Now he’s calling fraud.

After Dr. Saper’s initial 10-year certification expired, he paid $1,800 to take a recertification test. Passing this, he earned another decade of diplomate status; or so he thought, until a couple years later, when he received word from the UCNS.

“They were changing the rules,” Dr. Saper said in an interview. “The 10-year certificate was no longer valid. You had to go through another process.”

That process, known as continuous certification, has become the new standard among medical boards. In contrast with a more conventional recertification process that depends upon high-fee, high-stakes exams taken years apart, continuous certification typically involves a relatively small annual fee coupled with online reading and assessments designed to ensure familiarity with advances in the field.

It’s not just the physicians that need to study up. Medical boards are under pressure to ensure that they are maintaining retention, a potentially challenging task with approximately 200 medical certifying boards in the United States competing for attention, and in some cases, credibility.

Pivots to new systems of recertification have been a particular flash point among physicians. In 2015, a Newsweek article described how a group of “nationally known physicians revolted against the American Board of Internal Medicine” after the board “attempted to expand its program for recertifying doctors, adding boatloads of requirements and fees to be paid by physicians.”

In response, ABIM attacked both the journalist and Newsweek, citing a conflict of interest (the journalist was married to a doctor). The journalist went on to uncover some uncomfortable statistics, including the fact that, over a 5-year period, the ABIM Foundation lost $39.8 million while paying senior administrators $125.7 million. Such revelations have likely added to a collective skepticism about medical boards and their motives.
 

The changing landscape of recertification

According to Brenda Riggott, executive director of the UCNS, the switch to continuous certification was driven by a need to keep up with new standards.

“We really found the landscape of maintaining medical certifications in general was changing,” Ms. Riggott said, highlighting how the UCNS “evaluated 13 different continuous certification models being administered by medical boards” before settling upon the present model.

Continuous certification with the UCNS now requires a $175 annual fee. Each year, diplomates read 10 journal articles, then take a 25-question online quiz to demonstrate their understanding.

“It’s really about patient care,” Ms. Riggott said in an interview. “Medicine changes rapidly. And there are a lot of advances. Evaluating that once a decade is really not enough to verify that somebody is maintaining their skills, their knowledge.”

Dr. Saper, a clinical professor of neurology at Michigan State University, East Lansing, and founder-director of the Michigan Head Pain and Neurological Institute, Ann Arbor, had no inherent qualm with transitioning to this newer process, but he did take umbrage at its execution, since his UCNS certificate still had about 7 years until expiry.

He said the UCNS should have honored existing certificates through their stated duration, citing precedent set by the American Academy of Neurology. When the AAN transitioned from lifetime board certification to a periodic recertification process, they honored the lifetime status of those who already held it, according to Dr. Saper.

“[The AAN] looked at those of us who had been boarded under the premise that we were going to be lifetime boarded ... and they said: ‘We’re going to grandfather you ... because that was the rule under which you took your initial exams.’ ... That’s what UCNS should have done,” Dr. Saper said.
 

A compromise

Under pressure from Dr. Saper and others, UCNS compromised by endorsing 10-year diplomates until the 5-year mark.

Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and the editor-in-chief of Neurology Reviews, was among those who spoke up, only to see the duration of his certification cut in half.

“UCNS obviously realized that they had been wrong,” Dr. Rapoport said, referring to the compromise they made.

At the 5-year mark, physicians who didn’t adopt the new system were deleted from the UCNS online database, eliminating “the only way the public would know whether or not we were certified. This was after UCNS told us we would stay on the list with a note next to our name suggesting our certification was incomplete. They did not care that this might have hurt our reputations,” Dr. Rapoport said.

“To this day, no refunds, partial or full, have been given for the $1,800 we paid for the privilege of sitting for the exam, or for our time studying, or for the expenses accrued from canceling a day in the office and traveling to a testing center,” Dr. Rapoport said. “I did not want the money back; I wanted the certification promised to me. Since they have removed my name from this list, they do owe me the $1,800. They say they do not return their fees if you fail. How about if you pass and they remove you from their list?”

Yet he went on to make clear that the real issue is the principle of the matter. “This is not about money,” Dr. Rapoport said. “This is about what is fair and right.”

“The UCNS issued me a certificate for 10 years of certification in headache medicine; it is unethical and unlawful to break that contract and grant me only 5 years. Worse, they removed my name as though I do not exist. Along with Dr. Saper, I was one of the doctors that spent time and effort to advance headache medicine from October 1979, when I became a headache specialist, to today. I supported the principles of UCNS and took the first exam. I became the President of the International Headache Society and traveled the world promoting headache medicine; and this is how I am treated. Who can respect this type of certification, or this organization?”

Dr. Saper agreed: “It’s not about the money. It’s about the commitment. It’s very fraudulent.”

After the UCNS decision, Dr. Rapoport and Dr. Saper sought legal counsel, but ultimately decided not to sue the UCNS because of the lengthy process it would entail and the cost, estimated to be over $100,000.

“Our lawyers said: ‘It’s going to be years to get through it. You’ll probably win in the end, because it was fraudulent behavior,’ ” Dr. Saper said.
 

A different viewpoint

Ms. Riggott offered a different viewpoint: Nobody was guaranteed 10 years of certification.

“People do not pay for certification [from the UCNS],” Ms. Riggott said. “They pay to sit for an exam. It’s an exam administration fee. That can be construed as: ‘They paid for 10 years.’ They did not. They paid to sit for an exam. There are people who pay for an exam, and they don’t pass it, and they’re not certified. They don’t get a refund. That’s just the way high-stakes certification exams go.”

Dr. Saper and Dr. Rapoport see it differently. “The inherent reason any of us sit for an exam is to get certified.” Dr. Rapoport added. “Ms. Riggott is not being honest. There was an implied contract that if we passed, we would be granted a 10-year certification because that was what we did previously and that is what they told us would happen. Why would they have sent me this nice certificate for 10 more years of certification if she were telling the truth?”

Courtesy Dr. Alan M. Rapoport

Profits over promises

Dr. Rapoport estimates that many other neurologists had their certificates cut short and were dropped from this official list, some of them eminent members of the field, including David Watson, MD, professor and chair of neurology at West Virginia University Rockefeller Neuroscience Institute, Morgantown, and Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University.

“It is troubling when the organizations charged with maintaining the integrity of our specialization do not act with integrity,” Dr. Watson said. “The UCNS chose profits over promises and has refused to meaningfully engage with those of us whom they have wronged. What was once a point of pride for me (being in the second class of certified headache medicine diplomates) has become a meaningless piece of paper. This makes me sad.”

Dr. Cowan said the UCNS actions angered him while affirming his lifelong skepticism of clubs. “I was very sorry, but not surprised, to see the UCNS change the rules when the opportunity to make more money presented itself, and not surprised they did not honor their contracts. UCNS is just another scam like Best Doctors in the US and similar hypes. Neither are worth another dime of my money nor the time spent discussing them. One thing more: I have no quarrel with efforts to encourage keeping up with the field, although no one I know needs codification or direction as to which articles should be read. My outrage comes when responsible behavior is used as an excuse to line the pockets of dishonest, immoral individuals. I’m done.”

According to Ms. Riggott, the UCNS continuous certification process continues to evolve based on feedback from diplomates. She noted that “change is hard,” although the challenges of the transition appear to be paying off. “Initial retention for continuing certification is much higher than we would have expected from a high-stakes recertification exam,” she said. “So we are very, very happy about that.”
 

Proprietary tests drive revenue

According to Katie Collins, executive director of the National Board of Physicians and Surgeons, proprietary tests are a key revenue driver for medical boards, casting doubt on their educational motives.

“This isn’t really about maintaining their education, it’s really about having control over what they learn,” Ms. Collins said. “And unfortunately, physicians no longer have control over what they learn.”

NBPAS was formed largely in response to physicians dissatisfied with this situation. For $189 every 2 years, plus $25 for a paper certificate, NBPAS recertifies doctors originally credentialed by the American Board of Medical Specialties or the American Osteopathic Association.

Instead of making physicians take proprietary tests, NBPAS requires them to earn 50 hours of Accreditation Council for Continuing Medical Education–accredited CME every 2 years. Physicians can select where they seek this credit, giving them the agency to “pick and choose where they want to learn more,” Ms. Collins said, noting that this allows physicians to address personal knowledge gaps, instead of mastering the prescriptive lessons issued by other boards.

While this benefits physicians, Ms. Collins added, it also reduces the bottom line.

NBPAS is a “true 501(c)(3),” she said. “We have money for rainy days, but certainly not millions. We don’t have anything close to a million in savings.” Most medical boards are making millions on top of their services, she said. “That’s not for me to rein in, but it’s for me to point out.”

Noah Rosen, MD, associate professor of neurology and psychiatry at Northwell Health, Great Neck, N.Y., and former UCNS board member, said the UCNS was not motivated by money when they decided to switch to continuous recertification.

“The UCNS budget is publicly available,” Dr. Rosen said in an interview. “This is not a money-making organization,” he added, noting that the UCNS has “been basically operating on a breakeven budget,” and that certification “is not really a money-making proposition.”

Public IRS filings from 2019 and 2020 suggest a slightly different picture. In 2019, the UCNS reported net income of $72,256. In 2020, the inaugural year of the continuous certification program, net income jumped almost fivefold to $349,108. Over the same period, total assets held by the UCNS rose from $1.97 million to $2.37 million.

For comparison, NBPAS controls approximately $500,000 in total assets. The ABIM? Just shy of $72 million.
 

Recertification highlights a generational gap

Dr. Rosen, who was not a voting board member when the UCNS decided to switch to continuous certification, suggested that the transition could have been handled more effectively.

“I think Dr. Rapoport speaks to the frustration of how they made the transition, and that it could have been done in a way that recognizes people that held the certificate in a better way,” Dr. Rosen said.

He said that the departure of Dr. Rapoport and other neurologists from the UCNS points to another trend in the certification space. “I do think it brings up a deeper issue: What’s the value of certification? Dr. Rapoport and other people have brought up the question: What actually does this certificate bring you, if it’s not recognized by the federal government, and actually is not recognized by a lot of state governments, as well, as an official certification?”

He said the answer could depend on age.

“There seems to be a difference between younger people entering into the field and people that are more established in the field already,” Dr. Rosen said. “Younger people entering the field, they see certification as a distinction, something that separates them from the experiences and maybe every other neurologist.”

Ms. Collins independently pointed out the same generational gap. She noted that when the ABMS changed their maintenance model from lifelong to periodic in 2000, approximately 60% of their physicians had to change with the times, while the remainder did not.

“They grandfathered the other 40% – the older, probably more Caucasian male physicians,” she said. “It’s just the field. It’s evolved, it’s become more diverse. They created a divide in the physician community about what is the best means to maintain your board.”

In response to these comments, and despite his negative experiences with the UCNS, Dr. Rapoport emphasized that he still places high value on subspecialty certification.

“I care a lot about certification and that is why I decided to study for and take the only exam offered at the time,” he said, “I do not need it to continue my practice in headache medicine. No one asks me if I am certified in headache medicine. My patients are referred to me because of my reputation. But I have always sought the highest level of certification I could get. What UCNS has done is to cheapen the value of their certification.”

Dr. Rosen and Ms. Collins highlighted the other side of the same conclusion: For younger physicians, board certifications are more of a career consideration than they are for older physicians, as they could mean the difference between landing or losing a job.

“The American Board of Medical Specialties and [their] 24 member boards have really woven board certification into a requirement for employment for hospital privileges and for reimbursement,” Ms. Collins said.

And so, the practical value of board certification may depend most on the tenure of the person holding paper.

“I have not gone back to get any further certification [from the UCNS],” Dr. Saper said.

Even if his name has been removed from the UCNS register, he pointed out that his printed certificate still shows it’s valid until October 31st, 2026: “If anybody asks: ‘Are you certified?’ I say: ‘Here’s my certificate.’ ”

Courtesy Joel R. Saper, MD

Teamwork by a wide range of professional staff, coupled with support from leadership, enabled one academic community hospital to cut its rate of hospital-onset Clostridioides difficile infections (HO-CDIs) by almost two-thirds in 1 year and by over three-quarters in 3 years, a study published in the American Journal of Infection Control reports.

C. diff. is a major health threat. According to the U.S. Centers for Disease Control and Prevention, CDIs, mainly linked with hospitals, caused an estimated 223,900 cases in hospitalized patients and 12,800 deaths in the United States in 2017.

“The interventions and outcomes of the project improved patient care by ensuring early testing, diagnosis, treatment if warranted, and proper isolation, which helped reduce C. diff. transmission to staff and other patients,” lead study author Cherith Walter, MSN, RN, a clinical nurse specialist at Emory Saint Joseph’s Hospital, Atlanta, told this news organization. “Had we not worked together as a team, we would not have had the ability to carry out such a robust project,” she added in an email.

Each HO-CDI case costs a health care system an estimated $12,313, and high rates of HO-CDIs incur fines from the Hospital-Acquired Condition Reduction Program of the Centers for Medicare & Medicaid Services (CMS), the authors write.
 

A diverse staff team collaborated

Emory Saint Joseph’s, a 410-bed hospital in Atlanta, had a history of being above the national CMS benchmark for HO-CDIs. To reduce these infections, comply with CMS requirements, and avoid fines, Ms. Walter and colleagues launched a quality improvement project between 2015 and 2020.

With the approval of the chief nursing officer, chief quality officer, and hospital board, researchers mobilized a diverse team of professionals: a clinical nurse specialist, a physician champion, unit nurse champions, a hospital epidemiologist, an infection preventionist, a clinical microbiologist, an antimicrobial stewardship pharmacist, and an environmental services representative.

The team investigated what caused their hospital’s HO-CDIs from 2014 through 2016 and developed appropriate, evidence-based infection prevention interventions. The integrated approach involved:

• Diagnostic stewardship, including a diarrhea decision-tree algorithm that enabled nurses to order tests of any loose or unformed stool for C. diff. during the first 3 days of admission.
• Enhanced environmental cleaning, which involved switching from sporicidal disinfectant only in isolation rooms to using a more effective Environmental Protection Agency–approved sporicidal disinfectant containing hydrogen peroxide and peracetic acid in all patient rooms for daily cleaning and after discharge. Every day, high-touch surfaces in C. diff. isolation rooms were cleaned and shared equipment was disinfected with bleach wipes. After patient discharge, staff cleaned mattresses on all sides, wiped walls with disinfectant, and used ultraviolet light.
• Antimicrobial stewardship. Formulary fluoroquinolones were removed as standalone orders and made available only through order sets with built-in clinical decision support.
• Education of staff on best practices, through emails, flyers, meetings, and training sessions. Two nurses needed to approve the appropriateness of testing specific specimens for CDI. All HO-CDIs were reviewed and findings presented at CDI team meetings.
• Accountability. Staff on the team and units received emailed notices about compliance issues and held meetings to discuss how to improve compliance.

After 1 year, HO-CDI incidence dropped 63% from baseline, from above 12 cases per 10,000 patient-days to 4.72 per 10,000 patient-days. And after 3 years, infections dropped 77% to 2.80 per 10,000 patient-days.

The hospital’s HO-CDI standardized infection ratio – the total number of infections divided by the National Healthcare Safety Network’s risk-adjusted predicted number of infections – dropped below the national benchmark, from 1.11 in 2015 to 0.43 in 2020.

The hospital also increased testing of appropriate patients for CDI within the first 3 days of admission, from 54% in 2014 to 81% in late 2019.

“By testing patients within 3 days of admission, we discovered that many had acquired C. diff. before admission,” Ms. Walter said. “I don’t think we realized how prevalent C. diff. was in the community.”

Benjamin D. Galvan, MLS(ASCP), CIC, an infection preventionist at Tampa General Hospital and a member of the Association for Professionals in Infection Control and Epidemiology, welcomed the study’s results.  

“Effective collaboration within the health care setting is a highly effective way to implement and sustain evidence-based practices related to infection reduction. When buy-in is obtained from the top, and pertinent stakeholders are engaged for their expertise, we can see sustainable change and improved patient outcomes,” Mr. Galvan, who was not involved in the study, said in an email.

“The researchers did a fantastic job,” he added. “I am grateful to see this important work addressed in the literature, as it will only improve buy-in for improvement efforts aimed at reducing infections moving forward across the health care continuum.”

Douglas S. Paauw, MD, a professor of medicine and chair for patient-centered clinical education at the University of Washington School of Medicine, Seattle, said that the team’s most important interventions were changing the environmental cleaning protocol and using agents that kill C. diff. spores.

“We know that as many as 10%-20% of hospitalized patients carry C. diff. Cleaning only the rooms where you know you have C. diff. (isolation rooms) will miss most of it,” said Dr. Paauw, who was also not involved in the study. “Cleaning every room with cleaners that actually work is very important but costs money.”
 

Handwashing with soap and water works, alcohol hand gels do not

“We know that handwashing with soap and water is the most important way to prevent hospital C. diff. transmission,” Dr. Paauw noted. “Handwashing protocols implemented prior to the study were probably a big part of the team’s success.”

Handwashing with soap and water works but alcohol hand gels do not, he cautioned.

“C. diff. rates in hospitals went up years ago when we started putting alcohol gels outside patients’ rooms,” Dr. Paauw explained. “Now, instead of washing their hands, staff quickly pump gel before they see patients. Applying gel is easy, but gel does not eliminate C. diff. spores. Handwashing is such a simple way to fix the C. diff. problem, but doctors don’t take the time.”

“We need to take the C. diff. problem seriously. We have enough information, and we know the right things to do. We need to wash our hands. We need to clean the rooms. We need to stop cutting corners if we want to give good care,” he said.

The authors plan to conduct further related research.

The study was not funded. All study authors, as well as Mr. Galvan and Dr. Paauw, have reported no relevant financial interests.

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

Teamwork by a wide range of professional staff, coupled with support from leadership, enabled one academic community hospital to cut its rate of hospital-onset Clostridioides difficile infections (HO-CDIs) by almost two-thirds in 1 year and by over three-quarters in 3 years, a study published in the American Journal of Infection Control reports.

C. diff. is a major health threat. According to the U.S. Centers for Disease Control and Prevention, CDIs, mainly linked with hospitals, caused an estimated 223,900 cases in hospitalized patients and 12,800 deaths in the United States in 2017.

“The interventions and outcomes of the project improved patient care by ensuring early testing, diagnosis, treatment if warranted, and proper isolation, which helped reduce C. diff. transmission to staff and other patients,” lead study author Cherith Walter, MSN, RN, a clinical nurse specialist at Emory Saint Joseph’s Hospital, Atlanta, told this news organization. “Had we not worked together as a team, we would not have had the ability to carry out such a robust project,” she added in an email.

Each HO-CDI case costs a health care system an estimated $12,313, and high rates of HO-CDIs incur fines from the Hospital-Acquired Condition Reduction Program of the Centers for Medicare & Medicaid Services (CMS), the authors write.
 

A diverse staff team collaborated

Emory Saint Joseph’s, a 410-bed hospital in Atlanta, had a history of being above the national CMS benchmark for HO-CDIs. To reduce these infections, comply with CMS requirements, and avoid fines, Ms. Walter and colleagues launched a quality improvement project between 2015 and 2020.

With the approval of the chief nursing officer, chief quality officer, and hospital board, researchers mobilized a diverse team of professionals: a clinical nurse specialist, a physician champion, unit nurse champions, a hospital epidemiologist, an infection preventionist, a clinical microbiologist, an antimicrobial stewardship pharmacist, and an environmental services representative.

The team investigated what caused their hospital’s HO-CDIs from 2014 through 2016 and developed appropriate, evidence-based infection prevention interventions. The integrated approach involved:

• Diagnostic stewardship, including a diarrhea decision-tree algorithm that enabled nurses to order tests of any loose or unformed stool for C. diff. during the first 3 days of admission.
• Enhanced environmental cleaning, which involved switching from sporicidal disinfectant only in isolation rooms to using a more effective Environmental Protection Agency–approved sporicidal disinfectant containing hydrogen peroxide and peracetic acid in all patient rooms for daily cleaning and after discharge. Every day, high-touch surfaces in C. diff. isolation rooms were cleaned and shared equipment was disinfected with bleach wipes. After patient discharge, staff cleaned mattresses on all sides, wiped walls with disinfectant, and used ultraviolet light.
• Antimicrobial stewardship. Formulary fluoroquinolones were removed as standalone orders and made available only through order sets with built-in clinical decision support.
• Education of staff on best practices, through emails, flyers, meetings, and training sessions. Two nurses needed to approve the appropriateness of testing specific specimens for CDI. All HO-CDIs were reviewed and findings presented at CDI team meetings.
• Accountability. Staff on the team and units received emailed notices about compliance issues and held meetings to discuss how to improve compliance.

After 1 year, HO-CDI incidence dropped 63% from baseline, from above 12 cases per 10,000 patient-days to 4.72 per 10,000 patient-days. And after 3 years, infections dropped 77% to 2.80 per 10,000 patient-days.

The hospital’s HO-CDI standardized infection ratio – the total number of infections divided by the National Healthcare Safety Network’s risk-adjusted predicted number of infections – dropped below the national benchmark, from 1.11 in 2015 to 0.43 in 2020.

The hospital also increased testing of appropriate patients for CDI within the first 3 days of admission, from 54% in 2014 to 81% in late 2019.

“By testing patients within 3 days of admission, we discovered that many had acquired C. diff. before admission,” Ms. Walter said. “I don’t think we realized how prevalent C. diff. was in the community.”

Benjamin D. Galvan, MLS(ASCP), CIC, an infection preventionist at Tampa General Hospital and a member of the Association for Professionals in Infection Control and Epidemiology, welcomed the study’s results.  

“Effective collaboration within the health care setting is a highly effective way to implement and sustain evidence-based practices related to infection reduction. When buy-in is obtained from the top, and pertinent stakeholders are engaged for their expertise, we can see sustainable change and improved patient outcomes,” Mr. Galvan, who was not involved in the study, said in an email.

“The researchers did a fantastic job,” he added. “I am grateful to see this important work addressed in the literature, as it will only improve buy-in for improvement efforts aimed at reducing infections moving forward across the health care continuum.”

Douglas S. Paauw, MD, a professor of medicine and chair for patient-centered clinical education at the University of Washington School of Medicine, Seattle, said that the team’s most important interventions were changing the environmental cleaning protocol and using agents that kill C. diff. spores.

“We know that as many as 10%-20% of hospitalized patients carry C. diff. Cleaning only the rooms where you know you have C. diff. (isolation rooms) will miss most of it,” said Dr. Paauw, who was also not involved in the study. “Cleaning every room with cleaners that actually work is very important but costs money.”
 

Handwashing with soap and water works, alcohol hand gels do not

“We know that handwashing with soap and water is the most important way to prevent hospital C. diff. transmission,” Dr. Paauw noted. “Handwashing protocols implemented prior to the study were probably a big part of the team’s success.”

Handwashing with soap and water works but alcohol hand gels do not, he cautioned.

“C. diff. rates in hospitals went up years ago when we started putting alcohol gels outside patients’ rooms,” Dr. Paauw explained. “Now, instead of washing their hands, staff quickly pump gel before they see patients. Applying gel is easy, but gel does not eliminate C. diff. spores. Handwashing is such a simple way to fix the C. diff. problem, but doctors don’t take the time.”

“We need to take the C. diff. problem seriously. We have enough information, and we know the right things to do. We need to wash our hands. We need to clean the rooms. We need to stop cutting corners if we want to give good care,” he said.

The authors plan to conduct further related research.

The study was not funded. All study authors, as well as Mr. Galvan and Dr. Paauw, have reported no relevant financial interests.

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

Teamwork by a wide range of professional staff, coupled with support from leadership, enabled one academic community hospital to cut its rate of hospital-onset Clostridioides difficile infections (HO-CDIs) by almost two-thirds in 1 year and by over three-quarters in 3 years, a study published in the American Journal of Infection Control reports.

C. diff. is a major health threat. According to the U.S. Centers for Disease Control and Prevention, CDIs, mainly linked with hospitals, caused an estimated 223,900 cases in hospitalized patients and 12,800 deaths in the United States in 2017.

“The interventions and outcomes of the project improved patient care by ensuring early testing, diagnosis, treatment if warranted, and proper isolation, which helped reduce C. diff. transmission to staff and other patients,” lead study author Cherith Walter, MSN, RN, a clinical nurse specialist at Emory Saint Joseph’s Hospital, Atlanta, told this news organization. “Had we not worked together as a team, we would not have had the ability to carry out such a robust project,” she added in an email.

Each HO-CDI case costs a health care system an estimated $12,313, and high rates of HO-CDIs incur fines from the Hospital-Acquired Condition Reduction Program of the Centers for Medicare & Medicaid Services (CMS), the authors write.
 

A diverse staff team collaborated

Emory Saint Joseph’s, a 410-bed hospital in Atlanta, had a history of being above the national CMS benchmark for HO-CDIs. To reduce these infections, comply with CMS requirements, and avoid fines, Ms. Walter and colleagues launched a quality improvement project between 2015 and 2020.

With the approval of the chief nursing officer, chief quality officer, and hospital board, researchers mobilized a diverse team of professionals: a clinical nurse specialist, a physician champion, unit nurse champions, a hospital epidemiologist, an infection preventionist, a clinical microbiologist, an antimicrobial stewardship pharmacist, and an environmental services representative.

The team investigated what caused their hospital’s HO-CDIs from 2014 through 2016 and developed appropriate, evidence-based infection prevention interventions. The integrated approach involved:

• Diagnostic stewardship, including a diarrhea decision-tree algorithm that enabled nurses to order tests of any loose or unformed stool for C. diff. during the first 3 days of admission.
• Enhanced environmental cleaning, which involved switching from sporicidal disinfectant only in isolation rooms to using a more effective Environmental Protection Agency–approved sporicidal disinfectant containing hydrogen peroxide and peracetic acid in all patient rooms for daily cleaning and after discharge. Every day, high-touch surfaces in C. diff. isolation rooms were cleaned and shared equipment was disinfected with bleach wipes. After patient discharge, staff cleaned mattresses on all sides, wiped walls with disinfectant, and used ultraviolet light.
• Antimicrobial stewardship. Formulary fluoroquinolones were removed as standalone orders and made available only through order sets with built-in clinical decision support.
• Education of staff on best practices, through emails, flyers, meetings, and training sessions. Two nurses needed to approve the appropriateness of testing specific specimens for CDI. All HO-CDIs were reviewed and findings presented at CDI team meetings.
• Accountability. Staff on the team and units received emailed notices about compliance issues and held meetings to discuss how to improve compliance.

After 1 year, HO-CDI incidence dropped 63% from baseline, from above 12 cases per 10,000 patient-days to 4.72 per 10,000 patient-days. And after 3 years, infections dropped 77% to 2.80 per 10,000 patient-days.

The hospital’s HO-CDI standardized infection ratio – the total number of infections divided by the National Healthcare Safety Network’s risk-adjusted predicted number of infections – dropped below the national benchmark, from 1.11 in 2015 to 0.43 in 2020.

The hospital also increased testing of appropriate patients for CDI within the first 3 days of admission, from 54% in 2014 to 81% in late 2019.

“By testing patients within 3 days of admission, we discovered that many had acquired C. diff. before admission,” Ms. Walter said. “I don’t think we realized how prevalent C. diff. was in the community.”

Benjamin D. Galvan, MLS(ASCP), CIC, an infection preventionist at Tampa General Hospital and a member of the Association for Professionals in Infection Control and Epidemiology, welcomed the study’s results.  

“Effective collaboration within the health care setting is a highly effective way to implement and sustain evidence-based practices related to infection reduction. When buy-in is obtained from the top, and pertinent stakeholders are engaged for their expertise, we can see sustainable change and improved patient outcomes,” Mr. Galvan, who was not involved in the study, said in an email.

“The researchers did a fantastic job,” he added. “I am grateful to see this important work addressed in the literature, as it will only improve buy-in for improvement efforts aimed at reducing infections moving forward across the health care continuum.”

Douglas S. Paauw, MD, a professor of medicine and chair for patient-centered clinical education at the University of Washington School of Medicine, Seattle, said that the team’s most important interventions were changing the environmental cleaning protocol and using agents that kill C. diff. spores.

“We know that as many as 10%-20% of hospitalized patients carry C. diff. Cleaning only the rooms where you know you have C. diff. (isolation rooms) will miss most of it,” said Dr. Paauw, who was also not involved in the study. “Cleaning every room with cleaners that actually work is very important but costs money.”
 

Handwashing with soap and water works, alcohol hand gels do not

“We know that handwashing with soap and water is the most important way to prevent hospital C. diff. transmission,” Dr. Paauw noted. “Handwashing protocols implemented prior to the study were probably a big part of the team’s success.”

Handwashing with soap and water works but alcohol hand gels do not, he cautioned.

“C. diff. rates in hospitals went up years ago when we started putting alcohol gels outside patients’ rooms,” Dr. Paauw explained. “Now, instead of washing their hands, staff quickly pump gel before they see patients. Applying gel is easy, but gel does not eliminate C. diff. spores. Handwashing is such a simple way to fix the C. diff. problem, but doctors don’t take the time.”

“We need to take the C. diff. problem seriously. We have enough information, and we know the right things to do. We need to wash our hands. We need to clean the rooms. We need to stop cutting corners if we want to give good care,” he said.

The authors plan to conduct further related research.

The study was not funded. All study authors, as well as Mr. Galvan and Dr. Paauw, have reported no relevant financial interests.

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

Most COVID-19 long-haulers continue to have brain fog, fatigue, and compromised quality of life more than a year after the initial infection, results from the most extensive follow-up to date of a group of long COVID patients show.

Most patients continue to experience debilitating neurologic symptoms an average of 15 months from symptom onset, Igor Koralnik, MD, who oversees the Neuro COVID-19 Clinic at Northwestern Medicine in Chicago, said during a press briefing.

Surprisingly, in some cases, new symptoms appear that didn’t exist before, including variation of heart rate and blood pressure, and gastrointestinal symptoms, indicating there may be a late appearance in dysfunction of the autonomic nervous system in those patients, Dr. Koralnik said.

The study was published online in Annals of Clinical and Translational Neurology.
 

Evolving symptoms

The investigators evaluated the evolution of neurologic symptoms in 52 adults who had mild COVID-19 symptoms and were not admitted to the hospital.

Their mean age was 43 years, 73% were women and 77% had received a COVID-19 vaccine. These patients have now been followed for between 11 and 18 months since their initial infection.

Overall, between first and follow-up evaluations, there was no significant change in the frequency of most neurologic symptoms, including brain fog (81% vs. 71%), numbness/tingling (69% vs. 65%), headache (67% vs. 54%), dizziness (50% vs. 54%), blurred vision (34% vs. 44%), tinnitus (33% vs. 42%), and fatigue (87% vs. 81%).

The only neurologic symptoms that decreased over time were loss of taste (63% vs. 27%) and smell (58% vs. 21%).

Conversely, heart rate and blood pressure variation (35% vs. 56%) and gastrointestinal symptoms (27% vs. 48%; P = .04) increased at follow-up evaluations.

Patients reported subjective improvements in their recovery, cognitive function and fatigue, but quality of life measures remained lower than the average population of the United States.

There was a neutral effect of COVID vaccination on long COVID symptoms – it didn’t cure long COVID or make long COVID worse, which is a reason given by some long-haulers for not getting vaccinated, Dr. Koralnik told the briefing.

Therefore, “we continue to encourage our patients to get vaccinated and boosted according to the Centers for Disease Control and Prevention recommendation,” he said.
 

Escape from the ‘pit of despair’

To date, the Northwestern Medicine Neuro COVID-19 Clinic has treated nearly 1,400 COVID long-haulers from across the United States.

Emily Caffee, a physical therapist from Wheaton, Ill., is one of them.

Speaking at the briefing, the 36-year-old described her saga and roller coaster of recovering from long COVID in three acts: her initial infection, followed by a descent into a pit of physical and emotional despair, followed by her eventual escape from that pit more than two years later.

Following a fairly mild case of COVID, Ms. Caffee said worsening neurologic symptoms forced her to take medical leave from her very physical and cognitively demanding job. 

Ms. Caffee said she experienced crushing fatigue and brain fog, as well as rapid heart rate and blood pressure changes going from sitting to standing position.

She went from being a competitive athlete to someone who could barely get off the couch or empty the dishwasher.

With the ongoing help of her medical team, she slowly returned to daily activities and eventually to work on a limited basis.

Today, Ms. Caffee says she’s 90%-95% better but still she has some lingering symptoms and does not yet feel like her pre-COVID self.

It’s been a very slow climb out of the pit, Ms. Caffee said.

This study has no specific funding. The authors disclosed no relevant conflicts of interest.

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

Most COVID-19 long-haulers continue to have brain fog, fatigue, and compromised quality of life more than a year after the initial infection, results from the most extensive follow-up to date of a group of long COVID patients show.

Most patients continue to experience debilitating neurologic symptoms an average of 15 months from symptom onset, Igor Koralnik, MD, who oversees the Neuro COVID-19 Clinic at Northwestern Medicine in Chicago, said during a press briefing.

Surprisingly, in some cases, new symptoms appear that didn’t exist before, including variation of heart rate and blood pressure, and gastrointestinal symptoms, indicating there may be a late appearance in dysfunction of the autonomic nervous system in those patients, Dr. Koralnik said.

The study was published online in Annals of Clinical and Translational Neurology.
 

Evolving symptoms

The investigators evaluated the evolution of neurologic symptoms in 52 adults who had mild COVID-19 symptoms and were not admitted to the hospital.

Their mean age was 43 years, 73% were women and 77% had received a COVID-19 vaccine. These patients have now been followed for between 11 and 18 months since their initial infection.

Overall, between first and follow-up evaluations, there was no significant change in the frequency of most neurologic symptoms, including brain fog (81% vs. 71%), numbness/tingling (69% vs. 65%), headache (67% vs. 54%), dizziness (50% vs. 54%), blurred vision (34% vs. 44%), tinnitus (33% vs. 42%), and fatigue (87% vs. 81%).

The only neurologic symptoms that decreased over time were loss of taste (63% vs. 27%) and smell (58% vs. 21%).

Conversely, heart rate and blood pressure variation (35% vs. 56%) and gastrointestinal symptoms (27% vs. 48%; P = .04) increased at follow-up evaluations.

Patients reported subjective improvements in their recovery, cognitive function and fatigue, but quality of life measures remained lower than the average population of the United States.

There was a neutral effect of COVID vaccination on long COVID symptoms – it didn’t cure long COVID or make long COVID worse, which is a reason given by some long-haulers for not getting vaccinated, Dr. Koralnik told the briefing.

Therefore, “we continue to encourage our patients to get vaccinated and boosted according to the Centers for Disease Control and Prevention recommendation,” he said.
 

Escape from the ‘pit of despair’

To date, the Northwestern Medicine Neuro COVID-19 Clinic has treated nearly 1,400 COVID long-haulers from across the United States.

Emily Caffee, a physical therapist from Wheaton, Ill., is one of them.

Speaking at the briefing, the 36-year-old described her saga and roller coaster of recovering from long COVID in three acts: her initial infection, followed by a descent into a pit of physical and emotional despair, followed by her eventual escape from that pit more than two years later.

Following a fairly mild case of COVID, Ms. Caffee said worsening neurologic symptoms forced her to take medical leave from her very physical and cognitively demanding job. 

Ms. Caffee said she experienced crushing fatigue and brain fog, as well as rapid heart rate and blood pressure changes going from sitting to standing position.

She went from being a competitive athlete to someone who could barely get off the couch or empty the dishwasher.

With the ongoing help of her medical team, she slowly returned to daily activities and eventually to work on a limited basis.

Today, Ms. Caffee says she’s 90%-95% better but still she has some lingering symptoms and does not yet feel like her pre-COVID self.

It’s been a very slow climb out of the pit, Ms. Caffee said.

This study has no specific funding. The authors disclosed no relevant conflicts of interest.

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

Most COVID-19 long-haulers continue to have brain fog, fatigue, and compromised quality of life more than a year after the initial infection, results from the most extensive follow-up to date of a group of long COVID patients show.

Most patients continue to experience debilitating neurologic symptoms an average of 15 months from symptom onset, Igor Koralnik, MD, who oversees the Neuro COVID-19 Clinic at Northwestern Medicine in Chicago, said during a press briefing.

Surprisingly, in some cases, new symptoms appear that didn’t exist before, including variation of heart rate and blood pressure, and gastrointestinal symptoms, indicating there may be a late appearance in dysfunction of the autonomic nervous system in those patients, Dr. Koralnik said.

The study was published online in Annals of Clinical and Translational Neurology.
 

Evolving symptoms

The investigators evaluated the evolution of neurologic symptoms in 52 adults who had mild COVID-19 symptoms and were not admitted to the hospital.

Their mean age was 43 years, 73% were women and 77% had received a COVID-19 vaccine. These patients have now been followed for between 11 and 18 months since their initial infection.

Overall, between first and follow-up evaluations, there was no significant change in the frequency of most neurologic symptoms, including brain fog (81% vs. 71%), numbness/tingling (69% vs. 65%), headache (67% vs. 54%), dizziness (50% vs. 54%), blurred vision (34% vs. 44%), tinnitus (33% vs. 42%), and fatigue (87% vs. 81%).

The only neurologic symptoms that decreased over time were loss of taste (63% vs. 27%) and smell (58% vs. 21%).

Conversely, heart rate and blood pressure variation (35% vs. 56%) and gastrointestinal symptoms (27% vs. 48%; P = .04) increased at follow-up evaluations.

Patients reported subjective improvements in their recovery, cognitive function and fatigue, but quality of life measures remained lower than the average population of the United States.

There was a neutral effect of COVID vaccination on long COVID symptoms – it didn’t cure long COVID or make long COVID worse, which is a reason given by some long-haulers for not getting vaccinated, Dr. Koralnik told the briefing.

Therefore, “we continue to encourage our patients to get vaccinated and boosted according to the Centers for Disease Control and Prevention recommendation,” he said.
 

Escape from the ‘pit of despair’

To date, the Northwestern Medicine Neuro COVID-19 Clinic has treated nearly 1,400 COVID long-haulers from across the United States.

Emily Caffee, a physical therapist from Wheaton, Ill., is one of them.

Speaking at the briefing, the 36-year-old described her saga and roller coaster of recovering from long COVID in three acts: her initial infection, followed by a descent into a pit of physical and emotional despair, followed by her eventual escape from that pit more than two years later.

Following a fairly mild case of COVID, Ms. Caffee said worsening neurologic symptoms forced her to take medical leave from her very physical and cognitively demanding job. 

Ms. Caffee said she experienced crushing fatigue and brain fog, as well as rapid heart rate and blood pressure changes going from sitting to standing position.

She went from being a competitive athlete to someone who could barely get off the couch or empty the dishwasher.

With the ongoing help of her medical team, she slowly returned to daily activities and eventually to work on a limited basis.

Today, Ms. Caffee says she’s 90%-95% better but still she has some lingering symptoms and does not yet feel like her pre-COVID self.

It’s been a very slow climb out of the pit, Ms. Caffee said.

This study has no specific funding. The authors disclosed no relevant conflicts of interest.

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

Sildenafil (Viagra, Pfizer), a phosphodieterase-5 (PDE-5) inhibitor and a pulmonary-selective vasodilator, may reduce mortality in patients with idiopathic pulmonary fibrosis (IPF), compared with placebo or standard of care but it does not reduce hospitalizations or acute exacerbations from the disorder, a small meta-analysis suggests.

“There have only been four trials investigating sildenafil [in IPF] and the results were very close to being statistically significant so the addition of a few events would cause that to be true,” Tyler Pitre, MD, McMaster University, Hamilton, Ont., and Dena Zeraatkar, PhD, Harvard Medical School, Boston, told this news organization in a joint email.

“So lack of statistical significance does not preclude benefit,” they added, “and we think these results warrant additional trials and, if results remain consistent, [we] suspect the next update of the analysis may demonstrate statistical significance.”

The study was published online in Pulmonary Pharmacology & Therapeutics.
 

Reanalysis necessary

As the investigators pointed out, the most recent international guidelines have a conditional recommendation against the use of sildenafil in IPF patients so reanalysis of the data was felt to be necessary in order to inform upcoming guidelines. The purpose of the review was to provide an update of the evidence as to whether sildenafil not only provides mortality benefit in this patient population but also whether it improves overall lung function, reduces exacerbations and hospitalizations along with adverse events (AEs) leading to drug discontinuation.

The four studies included in the meta-analysis were all randomized, controlled trials in which either standalone PDE-5 inhibitors were compared with placebo or with standard IPF care with either pirfenidone (Esbroef ) or nintedanib (Ofev). The age of participants across the trials ranged from 68.6 years to 70.4 years and participants were predominantly male.

Follow-up ranged from just 12 weeks to 52 weeks. “Four trials including 659 patients and 88 deaths, reported on mortality,” the investigators noted. At a relative risk reduction of 0.73 (95% confidence interval, 0.51-1.04), the investigators concluded with moderate certainty that sildenafil probably reduces mortality in IPF patients.

Four trials including 659 patients reported on acute exacerbations and hospitalizations. At a RR of 1.10 (95% CI, 0.61-1.67), pooled results showed sildenafil may not reduce hospitalizations or acute exacerbations, compared with controls, although this conclusion was reached with low certainty. Four trials containing slightly more patients at 661 participants reported on AEs leading to drug discontinuation.

Again with moderate certainty, the authors concluded there is probably no difference in drug discontinuation rates because of AEs when comparing sildenafil to controls, at a RR of 0.79 (95% CI, 0.56-1.10). Four trials including 602 patients reported on lung function changes while diffusion capacity of carbon monoxide (DLCO) results were available for 487 patients. Based on these four trials, sildenafil may not change the decline of forced vital capacity (FVC) at a mean difference of 0.61% (95% CI, –0.29 to 1.59), compared with standard of care or placebo.

Nor may it change the rate of DLCO decline at a MD of 0.97 (95% CI, 0.04-1.90), both outcomes again being rated with moderate certainty. Asked if the combination of either nintedanib plus sildenafil or pirfenidone plus sildenafil led to a mortality benefit in IPF patients, Dr. Pitre and Dr. Zeraatkar noted that there was no mortality benefit in either the INSTAGE trial or in another recent study published in Lancet Respiratory Medicine.

“However, both of these trials were quite small and therefore unlikely to detect a mortality benefit,” Dr. Pitre and Dr. Zeraatkar noted. Indeed, the benefit of doing a systematic review is the ability to pool event rates across trials to see if a benefit emerges as well as to evaluate the consistency of the direction of these effects.

“Our review presented the most up-to-date and comprehensive summary of the evidence on sildenafil therapy for IPF patients,” the authors stated.

While they did acknowledge that the mortality benefit seen with sildenafil over placebo or standard of care did not reach statistical significance, this was likely because of too few patients and events. For example, in a systematic review published in the New England Journal of Medicine in 1988, the authors were able to show a statistically significant benefit on 5-year mortality risk with the combination of tamoxifen and cytotoxic therapy whereas none of the individual trials analyzed were able to detect a mortality benefit because they were underpowered.

“Similarly, we suggest that something like this is possible with sildenafil, as the three major trials addressing sildenafil show the same direction toward benefit with little inconsistency,” Dr. Pitre and Dr. Zeraatkar noted.

“We should not exclude benefits based on P values alone,” they said, adding: “Clearly out systematic review is not going to change clinical practice given the uncertainty of the results but I do think that in a disease such as IPF, further research is warranted in targeted patient populations [and] for clinicians, we suggest they keep an open mind to sildenafil.”

Commentary

Asked to comment on the findings, Krishna Thavarajah, MD, director of the interstitial lung disease program at Henry Ford Hospital and clinical assistant professor at Wayne State University, both in Detroit, agreed with the authors that the lack of a statistically significant mortality benefit seen in the meta-analysis does not necessarily translate into a lack of benefit from the use of sildenafil in IPF patients. “As the authors point out, there are simply not enough data available to know if there is a mortality benefit, limited by the variable follow-up times and IPF patients targeted with or without pulmonary hypertension.”

Indeed, Dr. Thavarajah felt that a mortality benefit might be difficult to show in IPF patients, especially those on antifibrotics, given the duration of the studies analyzed and the number of patients needed to be able to show a statistically significant difference. “I myself have not prescribed sildenafil for IPF patients given the lack of clear data,” Dr. Thavarajah acknowledged.

“[But] the meta-analysis shows that sildenafil could have a mortality benefit in IPF patients without evidence of a benefit in FVC, DLCO, or acute exacerbations,” she confirmed, agreeing that further study would be helpful in assessing the potential for sildenafil to provide a mortality benefit in IPF patients.

No funding for the study was reported. Neither the authors nor Dr. Thavarajah had any conflicts of interest to declare.

Sildenafil (Viagra, Pfizer), a phosphodieterase-5 (PDE-5) inhibitor and a pulmonary-selective vasodilator, may reduce mortality in patients with idiopathic pulmonary fibrosis (IPF), compared with placebo or standard of care but it does not reduce hospitalizations or acute exacerbations from the disorder, a small meta-analysis suggests.

“There have only been four trials investigating sildenafil [in IPF] and the results were very close to being statistically significant so the addition of a few events would cause that to be true,” Tyler Pitre, MD, McMaster University, Hamilton, Ont., and Dena Zeraatkar, PhD, Harvard Medical School, Boston, told this news organization in a joint email.

“So lack of statistical significance does not preclude benefit,” they added, “and we think these results warrant additional trials and, if results remain consistent, [we] suspect the next update of the analysis may demonstrate statistical significance.”

The study was published online in Pulmonary Pharmacology & Therapeutics.
 

Reanalysis necessary

As the investigators pointed out, the most recent international guidelines have a conditional recommendation against the use of sildenafil in IPF patients so reanalysis of the data was felt to be necessary in order to inform upcoming guidelines. The purpose of the review was to provide an update of the evidence as to whether sildenafil not only provides mortality benefit in this patient population but also whether it improves overall lung function, reduces exacerbations and hospitalizations along with adverse events (AEs) leading to drug discontinuation.

The four studies included in the meta-analysis were all randomized, controlled trials in which either standalone PDE-5 inhibitors were compared with placebo or with standard IPF care with either pirfenidone (Esbroef ) or nintedanib (Ofev). The age of participants across the trials ranged from 68.6 years to 70.4 years and participants were predominantly male.

Follow-up ranged from just 12 weeks to 52 weeks. “Four trials including 659 patients and 88 deaths, reported on mortality,” the investigators noted. At a relative risk reduction of 0.73 (95% confidence interval, 0.51-1.04), the investigators concluded with moderate certainty that sildenafil probably reduces mortality in IPF patients.

Four trials including 659 patients reported on acute exacerbations and hospitalizations. At a RR of 1.10 (95% CI, 0.61-1.67), pooled results showed sildenafil may not reduce hospitalizations or acute exacerbations, compared with controls, although this conclusion was reached with low certainty. Four trials containing slightly more patients at 661 participants reported on AEs leading to drug discontinuation.

Again with moderate certainty, the authors concluded there is probably no difference in drug discontinuation rates because of AEs when comparing sildenafil to controls, at a RR of 0.79 (95% CI, 0.56-1.10). Four trials including 602 patients reported on lung function changes while diffusion capacity of carbon monoxide (DLCO) results were available for 487 patients. Based on these four trials, sildenafil may not change the decline of forced vital capacity (FVC) at a mean difference of 0.61% (95% CI, –0.29 to 1.59), compared with standard of care or placebo.

Nor may it change the rate of DLCO decline at a MD of 0.97 (95% CI, 0.04-1.90), both outcomes again being rated with moderate certainty. Asked if the combination of either nintedanib plus sildenafil or pirfenidone plus sildenafil led to a mortality benefit in IPF patients, Dr. Pitre and Dr. Zeraatkar noted that there was no mortality benefit in either the INSTAGE trial or in another recent study published in Lancet Respiratory Medicine.

“However, both of these trials were quite small and therefore unlikely to detect a mortality benefit,” Dr. Pitre and Dr. Zeraatkar noted. Indeed, the benefit of doing a systematic review is the ability to pool event rates across trials to see if a benefit emerges as well as to evaluate the consistency of the direction of these effects.

“Our review presented the most up-to-date and comprehensive summary of the evidence on sildenafil therapy for IPF patients,” the authors stated.

While they did acknowledge that the mortality benefit seen with sildenafil over placebo or standard of care did not reach statistical significance, this was likely because of too few patients and events. For example, in a systematic review published in the New England Journal of Medicine in 1988, the authors were able to show a statistically significant benefit on 5-year mortality risk with the combination of tamoxifen and cytotoxic therapy whereas none of the individual trials analyzed were able to detect a mortality benefit because they were underpowered.

“Similarly, we suggest that something like this is possible with sildenafil, as the three major trials addressing sildenafil show the same direction toward benefit with little inconsistency,” Dr. Pitre and Dr. Zeraatkar noted.

“We should not exclude benefits based on P values alone,” they said, adding: “Clearly out systematic review is not going to change clinical practice given the uncertainty of the results but I do think that in a disease such as IPF, further research is warranted in targeted patient populations [and] for clinicians, we suggest they keep an open mind to sildenafil.”

Commentary

Asked to comment on the findings, Krishna Thavarajah, MD, director of the interstitial lung disease program at Henry Ford Hospital and clinical assistant professor at Wayne State University, both in Detroit, agreed with the authors that the lack of a statistically significant mortality benefit seen in the meta-analysis does not necessarily translate into a lack of benefit from the use of sildenafil in IPF patients. “As the authors point out, there are simply not enough data available to know if there is a mortality benefit, limited by the variable follow-up times and IPF patients targeted with or without pulmonary hypertension.”

Indeed, Dr. Thavarajah felt that a mortality benefit might be difficult to show in IPF patients, especially those on antifibrotics, given the duration of the studies analyzed and the number of patients needed to be able to show a statistically significant difference. “I myself have not prescribed sildenafil for IPF patients given the lack of clear data,” Dr. Thavarajah acknowledged.

“[But] the meta-analysis shows that sildenafil could have a mortality benefit in IPF patients without evidence of a benefit in FVC, DLCO, or acute exacerbations,” she confirmed, agreeing that further study would be helpful in assessing the potential for sildenafil to provide a mortality benefit in IPF patients.

No funding for the study was reported. Neither the authors nor Dr. Thavarajah had any conflicts of interest to declare.

Sildenafil (Viagra, Pfizer), a phosphodieterase-5 (PDE-5) inhibitor and a pulmonary-selective vasodilator, may reduce mortality in patients with idiopathic pulmonary fibrosis (IPF), compared with placebo or standard of care but it does not reduce hospitalizations or acute exacerbations from the disorder, a small meta-analysis suggests.

“There have only been four trials investigating sildenafil [in IPF] and the results were very close to being statistically significant so the addition of a few events would cause that to be true,” Tyler Pitre, MD, McMaster University, Hamilton, Ont., and Dena Zeraatkar, PhD, Harvard Medical School, Boston, told this news organization in a joint email.

“So lack of statistical significance does not preclude benefit,” they added, “and we think these results warrant additional trials and, if results remain consistent, [we] suspect the next update of the analysis may demonstrate statistical significance.”

The study was published online in Pulmonary Pharmacology & Therapeutics.
 

Reanalysis necessary

As the investigators pointed out, the most recent international guidelines have a conditional recommendation against the use of sildenafil in IPF patients so reanalysis of the data was felt to be necessary in order to inform upcoming guidelines. The purpose of the review was to provide an update of the evidence as to whether sildenafil not only provides mortality benefit in this patient population but also whether it improves overall lung function, reduces exacerbations and hospitalizations along with adverse events (AEs) leading to drug discontinuation.

The four studies included in the meta-analysis were all randomized, controlled trials in which either standalone PDE-5 inhibitors were compared with placebo or with standard IPF care with either pirfenidone (Esbroef ) or nintedanib (Ofev). The age of participants across the trials ranged from 68.6 years to 70.4 years and participants were predominantly male.

Follow-up ranged from just 12 weeks to 52 weeks. “Four trials including 659 patients and 88 deaths, reported on mortality,” the investigators noted. At a relative risk reduction of 0.73 (95% confidence interval, 0.51-1.04), the investigators concluded with moderate certainty that sildenafil probably reduces mortality in IPF patients.

Four trials including 659 patients reported on acute exacerbations and hospitalizations. At a RR of 1.10 (95% CI, 0.61-1.67), pooled results showed sildenafil may not reduce hospitalizations or acute exacerbations, compared with controls, although this conclusion was reached with low certainty. Four trials containing slightly more patients at 661 participants reported on AEs leading to drug discontinuation.

Again with moderate certainty, the authors concluded there is probably no difference in drug discontinuation rates because of AEs when comparing sildenafil to controls, at a RR of 0.79 (95% CI, 0.56-1.10). Four trials including 602 patients reported on lung function changes while diffusion capacity of carbon monoxide (DLCO) results were available for 487 patients. Based on these four trials, sildenafil may not change the decline of forced vital capacity (FVC) at a mean difference of 0.61% (95% CI, –0.29 to 1.59), compared with standard of care or placebo.

Nor may it change the rate of DLCO decline at a MD of 0.97 (95% CI, 0.04-1.90), both outcomes again being rated with moderate certainty. Asked if the combination of either nintedanib plus sildenafil or pirfenidone plus sildenafil led to a mortality benefit in IPF patients, Dr. Pitre and Dr. Zeraatkar noted that there was no mortality benefit in either the INSTAGE trial or in another recent study published in Lancet Respiratory Medicine.

“However, both of these trials were quite small and therefore unlikely to detect a mortality benefit,” Dr. Pitre and Dr. Zeraatkar noted. Indeed, the benefit of doing a systematic review is the ability to pool event rates across trials to see if a benefit emerges as well as to evaluate the consistency of the direction of these effects.

“Our review presented the most up-to-date and comprehensive summary of the evidence on sildenafil therapy for IPF patients,” the authors stated.

While they did acknowledge that the mortality benefit seen with sildenafil over placebo or standard of care did not reach statistical significance, this was likely because of too few patients and events. For example, in a systematic review published in the New England Journal of Medicine in 1988, the authors were able to show a statistically significant benefit on 5-year mortality risk with the combination of tamoxifen and cytotoxic therapy whereas none of the individual trials analyzed were able to detect a mortality benefit because they were underpowered.

“Similarly, we suggest that something like this is possible with sildenafil, as the three major trials addressing sildenafil show the same direction toward benefit with little inconsistency,” Dr. Pitre and Dr. Zeraatkar noted.

“We should not exclude benefits based on P values alone,” they said, adding: “Clearly out systematic review is not going to change clinical practice given the uncertainty of the results but I do think that in a disease such as IPF, further research is warranted in targeted patient populations [and] for clinicians, we suggest they keep an open mind to sildenafil.”

Commentary

Asked to comment on the findings, Krishna Thavarajah, MD, director of the interstitial lung disease program at Henry Ford Hospital and clinical assistant professor at Wayne State University, both in Detroit, agreed with the authors that the lack of a statistically significant mortality benefit seen in the meta-analysis does not necessarily translate into a lack of benefit from the use of sildenafil in IPF patients. “As the authors point out, there are simply not enough data available to know if there is a mortality benefit, limited by the variable follow-up times and IPF patients targeted with or without pulmonary hypertension.”

Indeed, Dr. Thavarajah felt that a mortality benefit might be difficult to show in IPF patients, especially those on antifibrotics, given the duration of the studies analyzed and the number of patients needed to be able to show a statistically significant difference. “I myself have not prescribed sildenafil for IPF patients given the lack of clear data,” Dr. Thavarajah acknowledged.

“[But] the meta-analysis shows that sildenafil could have a mortality benefit in IPF patients without evidence of a benefit in FVC, DLCO, or acute exacerbations,” she confirmed, agreeing that further study would be helpful in assessing the potential for sildenafil to provide a mortality benefit in IPF patients.

No funding for the study was reported. Neither the authors nor Dr. Thavarajah had any conflicts of interest to declare.