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‘Agony of choice’ for clinicians treating leukemia
“Targeted therapies have outnumbered chemoimmunotherapy-based treatment approaches, demonstrating superior efficacy and tolerability profiles across nearly all CLL patient subgroups in the frontline and relapsed disease treatment setting,” author Jan-Paul Bohn, MD, PhD, of the department of internal medicine V, hematology and oncology, at Medical University of Innsbruck (Austria), reported in the review published in Memo, the Magazine of European Medical Oncology.
The options leave clinicians “spoilt for choice when selecting optimal therapy,” he said.
The three major drug classes to emerge – inhibitors of Bruton tyrosine kinase (BTK), antiapoptotic protein B-cell lymphoma 2 (BCL2) and phosphoinositide 3’-kinase (PI3K) – all appear similar in efficacy and tolerability.
Particularly in high-risk patients, the drugs have been so effective that the less desirable previous standard of “chemoimmunotherapy has widely faded into the background in the Western hemisphere,” Dr. Bohn wrote.
However, with caveats of the newer drugs including acquired resistances and potential toxicities, challenges have shifted to determining how to best juggle and/or combine the agents.
Frontline therapy
In terms of frontline options for CLL therapy, the BTK inhibitors, along with the BCL2 inhibitor venetoclax have been key in negating the need for chemotherapy, with some of the latest data showing superiority of venetoclax in combination with obinutuzumab (GVe) over chemotherapy even in the higher-risk subset of patients with mutated IGHV status and without TP53 disruption.
Hence, “chemoimmunotherapy may now even be questioned in the remaining subset of CLL patients with mutated IGHV status and without TP53 disruption,” Dr. Bohn reported.
That being said, the criteria for treatment choices in the frontline setting among the newer drug classes can often come down to the key issues of patients’ comorbidities and treatment preferences.
For example, in terms of patients who have higher risk because of tumor lysis syndrome (TLS), or issues including declining renal function, continuous BTK inhibitor treatment may be the preferred choice over the combination of venetoclax plus obinutuzumab (GVe), Dr. Bohn noted.
Conversely, for patients with cardiac comorbidities or a higher risk of bleeding, the GVe combination may be preferred over ibrutinib, with recent findings showing ibrutinib to be associated with as much as an 18-times higher risk of sudden unexplained death or cardiac death in young and fit patients who had preexisting arterial hypertension and/or a history of cardiac disorders requiring therapy.
For those with cardiac comorbidities, the more selective second-generation BTK inhibitor acalabrutinib is a potentially favorable alternative, as the drug is “at least similarly effective and more favorable in terms of tolerability, compared with ibrutinib, particularly as far as cardiac and bleeding side effects are considered,” Dr. Bohn said.
And in higher-risk cases involving TP53 dysfunction, a BTK inhibitor may be superior to GVe for frontline treatment, Dr. Bohn noted, with data showing progression-free survival in patients with and without deletion 17p to be significantly reduced with GVe versus the BTK inhibitor ibrutinib.
Relapsed and refractory disease
With similarly high efficacy observed with the new drug classes among relapsed and/or refractory patients, chemoimmunotherapy has likewise “become obsolete in nearly all patients naive to novel agents at relapse who typically present with genetically high-risk disease,” Dr. Bohn noted.
He wrote that most of the recommendations for frontline therapy hold true in the relapsed and refractory patients, with comorbidities and personal preferences again key drivers of treatment choices.
While data is currently limited regarding benefits of venetoclax-based regimens over BTK inhibitors in relapsed/refractory patients, there is “growing evidence suggesting similar clinical outcomes achievable with these agents in either order,” Dr. Bohn wrote.
Further recommendations regarding relapsed or refractory patients include:
- Among patients who do experience disease progression while on continuous treatment with BTK inhibitors, venetoclax-based regimes seem most effective. However, with relapse after venetoclax-based regimes, some growing evidence supports retreatment with the drug “depending on depth and duration of response achieved after first venetoclax exposure,” Dr. Bohn noted.
- For patients with deletion 17p, venetoclax shows promising efficacy during relapse when given as monotherapy until disease progression or occurrence of unacceptable toxicity.
- And for patients with TP53 abnormalities, the considerations are the same as for frontline therapy, with venetoclax showing promising efficacy when given in monotherapy until disease progression or occurrence of unacceptable toxicity.
Of note, PI3K inhibitors are generally not used in CLL patients naive to BTK and BCL2 inhibitors because of the higher risk of immune-mediated toxicities and infectious complications associated with the currently approved PI3K inhibitors idelalisib and duvelisib, he reported.
Nevertheless, “PI3K inhibitors remain a valuable therapeutic addition in patients refractory or intolerant to BTK inhibitors and venetoclax-based regimens,” Dr. Bohn said.
Newer agents, fixed duration
Commenting on the review, hematologist Seema A. Bhat, MD, an assistant professor with the Ohio State University Comprehensive Cancer Center, Columbus, said that the advances with targeted therapies in CLL are paying off with improved survival.
“With these recent advances in the treatment of CLL, especially the availability of targeted therapies, there has been an improvement in survival of patients with CLL, as the CLL-related death rate steadily reduced by approximately 3% per year between 2006 and 2015,” she said in an interview.
She added that even-newer agents in development, including the reversibly binding BTK inhibitor–like pirtobrutinib and nemtabrutinib, when approved, will further add to the treatment choices for patients.
Meanwhile, a key area of focus is the combination of BTK inhibitors and BCL2 inhibitors, specifically for a fixed duration of time to obtain a deeper response and hence possibility a time-limited therapy, she noted. “We are also excited about the possibility of having more fixed-duration treatments available for our patients, which will make their treatment journey less troublesome, both physically as well as financially.”
Dr. Bohn reported receiving personal fees from AbbVie, AstraZeneca and Janssen for advisory board participation. Dr. Bhat has served on advisory board for AstraZeneca and received honorarium from them.
“Targeted therapies have outnumbered chemoimmunotherapy-based treatment approaches, demonstrating superior efficacy and tolerability profiles across nearly all CLL patient subgroups in the frontline and relapsed disease treatment setting,” author Jan-Paul Bohn, MD, PhD, of the department of internal medicine V, hematology and oncology, at Medical University of Innsbruck (Austria), reported in the review published in Memo, the Magazine of European Medical Oncology.
The options leave clinicians “spoilt for choice when selecting optimal therapy,” he said.
The three major drug classes to emerge – inhibitors of Bruton tyrosine kinase (BTK), antiapoptotic protein B-cell lymphoma 2 (BCL2) and phosphoinositide 3’-kinase (PI3K) – all appear similar in efficacy and tolerability.
Particularly in high-risk patients, the drugs have been so effective that the less desirable previous standard of “chemoimmunotherapy has widely faded into the background in the Western hemisphere,” Dr. Bohn wrote.
However, with caveats of the newer drugs including acquired resistances and potential toxicities, challenges have shifted to determining how to best juggle and/or combine the agents.
Frontline therapy
In terms of frontline options for CLL therapy, the BTK inhibitors, along with the BCL2 inhibitor venetoclax have been key in negating the need for chemotherapy, with some of the latest data showing superiority of venetoclax in combination with obinutuzumab (GVe) over chemotherapy even in the higher-risk subset of patients with mutated IGHV status and without TP53 disruption.
Hence, “chemoimmunotherapy may now even be questioned in the remaining subset of CLL patients with mutated IGHV status and without TP53 disruption,” Dr. Bohn reported.
That being said, the criteria for treatment choices in the frontline setting among the newer drug classes can often come down to the key issues of patients’ comorbidities and treatment preferences.
For example, in terms of patients who have higher risk because of tumor lysis syndrome (TLS), or issues including declining renal function, continuous BTK inhibitor treatment may be the preferred choice over the combination of venetoclax plus obinutuzumab (GVe), Dr. Bohn noted.
Conversely, for patients with cardiac comorbidities or a higher risk of bleeding, the GVe combination may be preferred over ibrutinib, with recent findings showing ibrutinib to be associated with as much as an 18-times higher risk of sudden unexplained death or cardiac death in young and fit patients who had preexisting arterial hypertension and/or a history of cardiac disorders requiring therapy.
For those with cardiac comorbidities, the more selective second-generation BTK inhibitor acalabrutinib is a potentially favorable alternative, as the drug is “at least similarly effective and more favorable in terms of tolerability, compared with ibrutinib, particularly as far as cardiac and bleeding side effects are considered,” Dr. Bohn said.
And in higher-risk cases involving TP53 dysfunction, a BTK inhibitor may be superior to GVe for frontline treatment, Dr. Bohn noted, with data showing progression-free survival in patients with and without deletion 17p to be significantly reduced with GVe versus the BTK inhibitor ibrutinib.
Relapsed and refractory disease
With similarly high efficacy observed with the new drug classes among relapsed and/or refractory patients, chemoimmunotherapy has likewise “become obsolete in nearly all patients naive to novel agents at relapse who typically present with genetically high-risk disease,” Dr. Bohn noted.
He wrote that most of the recommendations for frontline therapy hold true in the relapsed and refractory patients, with comorbidities and personal preferences again key drivers of treatment choices.
While data is currently limited regarding benefits of venetoclax-based regimens over BTK inhibitors in relapsed/refractory patients, there is “growing evidence suggesting similar clinical outcomes achievable with these agents in either order,” Dr. Bohn wrote.
Further recommendations regarding relapsed or refractory patients include:
- Among patients who do experience disease progression while on continuous treatment with BTK inhibitors, venetoclax-based regimes seem most effective. However, with relapse after venetoclax-based regimes, some growing evidence supports retreatment with the drug “depending on depth and duration of response achieved after first venetoclax exposure,” Dr. Bohn noted.
- For patients with deletion 17p, venetoclax shows promising efficacy during relapse when given as monotherapy until disease progression or occurrence of unacceptable toxicity.
- And for patients with TP53 abnormalities, the considerations are the same as for frontline therapy, with venetoclax showing promising efficacy when given in monotherapy until disease progression or occurrence of unacceptable toxicity.
Of note, PI3K inhibitors are generally not used in CLL patients naive to BTK and BCL2 inhibitors because of the higher risk of immune-mediated toxicities and infectious complications associated with the currently approved PI3K inhibitors idelalisib and duvelisib, he reported.
Nevertheless, “PI3K inhibitors remain a valuable therapeutic addition in patients refractory or intolerant to BTK inhibitors and venetoclax-based regimens,” Dr. Bohn said.
Newer agents, fixed duration
Commenting on the review, hematologist Seema A. Bhat, MD, an assistant professor with the Ohio State University Comprehensive Cancer Center, Columbus, said that the advances with targeted therapies in CLL are paying off with improved survival.
“With these recent advances in the treatment of CLL, especially the availability of targeted therapies, there has been an improvement in survival of patients with CLL, as the CLL-related death rate steadily reduced by approximately 3% per year between 2006 and 2015,” she said in an interview.
She added that even-newer agents in development, including the reversibly binding BTK inhibitor–like pirtobrutinib and nemtabrutinib, when approved, will further add to the treatment choices for patients.
Meanwhile, a key area of focus is the combination of BTK inhibitors and BCL2 inhibitors, specifically for a fixed duration of time to obtain a deeper response and hence possibility a time-limited therapy, she noted. “We are also excited about the possibility of having more fixed-duration treatments available for our patients, which will make their treatment journey less troublesome, both physically as well as financially.”
Dr. Bohn reported receiving personal fees from AbbVie, AstraZeneca and Janssen for advisory board participation. Dr. Bhat has served on advisory board for AstraZeneca and received honorarium from them.
“Targeted therapies have outnumbered chemoimmunotherapy-based treatment approaches, demonstrating superior efficacy and tolerability profiles across nearly all CLL patient subgroups in the frontline and relapsed disease treatment setting,” author Jan-Paul Bohn, MD, PhD, of the department of internal medicine V, hematology and oncology, at Medical University of Innsbruck (Austria), reported in the review published in Memo, the Magazine of European Medical Oncology.
The options leave clinicians “spoilt for choice when selecting optimal therapy,” he said.
The three major drug classes to emerge – inhibitors of Bruton tyrosine kinase (BTK), antiapoptotic protein B-cell lymphoma 2 (BCL2) and phosphoinositide 3’-kinase (PI3K) – all appear similar in efficacy and tolerability.
Particularly in high-risk patients, the drugs have been so effective that the less desirable previous standard of “chemoimmunotherapy has widely faded into the background in the Western hemisphere,” Dr. Bohn wrote.
However, with caveats of the newer drugs including acquired resistances and potential toxicities, challenges have shifted to determining how to best juggle and/or combine the agents.
Frontline therapy
In terms of frontline options for CLL therapy, the BTK inhibitors, along with the BCL2 inhibitor venetoclax have been key in negating the need for chemotherapy, with some of the latest data showing superiority of venetoclax in combination with obinutuzumab (GVe) over chemotherapy even in the higher-risk subset of patients with mutated IGHV status and without TP53 disruption.
Hence, “chemoimmunotherapy may now even be questioned in the remaining subset of CLL patients with mutated IGHV status and without TP53 disruption,” Dr. Bohn reported.
That being said, the criteria for treatment choices in the frontline setting among the newer drug classes can often come down to the key issues of patients’ comorbidities and treatment preferences.
For example, in terms of patients who have higher risk because of tumor lysis syndrome (TLS), or issues including declining renal function, continuous BTK inhibitor treatment may be the preferred choice over the combination of venetoclax plus obinutuzumab (GVe), Dr. Bohn noted.
Conversely, for patients with cardiac comorbidities or a higher risk of bleeding, the GVe combination may be preferred over ibrutinib, with recent findings showing ibrutinib to be associated with as much as an 18-times higher risk of sudden unexplained death or cardiac death in young and fit patients who had preexisting arterial hypertension and/or a history of cardiac disorders requiring therapy.
For those with cardiac comorbidities, the more selective second-generation BTK inhibitor acalabrutinib is a potentially favorable alternative, as the drug is “at least similarly effective and more favorable in terms of tolerability, compared with ibrutinib, particularly as far as cardiac and bleeding side effects are considered,” Dr. Bohn said.
And in higher-risk cases involving TP53 dysfunction, a BTK inhibitor may be superior to GVe for frontline treatment, Dr. Bohn noted, with data showing progression-free survival in patients with and without deletion 17p to be significantly reduced with GVe versus the BTK inhibitor ibrutinib.
Relapsed and refractory disease
With similarly high efficacy observed with the new drug classes among relapsed and/or refractory patients, chemoimmunotherapy has likewise “become obsolete in nearly all patients naive to novel agents at relapse who typically present with genetically high-risk disease,” Dr. Bohn noted.
He wrote that most of the recommendations for frontline therapy hold true in the relapsed and refractory patients, with comorbidities and personal preferences again key drivers of treatment choices.
While data is currently limited regarding benefits of venetoclax-based regimens over BTK inhibitors in relapsed/refractory patients, there is “growing evidence suggesting similar clinical outcomes achievable with these agents in either order,” Dr. Bohn wrote.
Further recommendations regarding relapsed or refractory patients include:
- Among patients who do experience disease progression while on continuous treatment with BTK inhibitors, venetoclax-based regimes seem most effective. However, with relapse after venetoclax-based regimes, some growing evidence supports retreatment with the drug “depending on depth and duration of response achieved after first venetoclax exposure,” Dr. Bohn noted.
- For patients with deletion 17p, venetoclax shows promising efficacy during relapse when given as monotherapy until disease progression or occurrence of unacceptable toxicity.
- And for patients with TP53 abnormalities, the considerations are the same as for frontline therapy, with venetoclax showing promising efficacy when given in monotherapy until disease progression or occurrence of unacceptable toxicity.
Of note, PI3K inhibitors are generally not used in CLL patients naive to BTK and BCL2 inhibitors because of the higher risk of immune-mediated toxicities and infectious complications associated with the currently approved PI3K inhibitors idelalisib and duvelisib, he reported.
Nevertheless, “PI3K inhibitors remain a valuable therapeutic addition in patients refractory or intolerant to BTK inhibitors and venetoclax-based regimens,” Dr. Bohn said.
Newer agents, fixed duration
Commenting on the review, hematologist Seema A. Bhat, MD, an assistant professor with the Ohio State University Comprehensive Cancer Center, Columbus, said that the advances with targeted therapies in CLL are paying off with improved survival.
“With these recent advances in the treatment of CLL, especially the availability of targeted therapies, there has been an improvement in survival of patients with CLL, as the CLL-related death rate steadily reduced by approximately 3% per year between 2006 and 2015,” she said in an interview.
She added that even-newer agents in development, including the reversibly binding BTK inhibitor–like pirtobrutinib and nemtabrutinib, when approved, will further add to the treatment choices for patients.
Meanwhile, a key area of focus is the combination of BTK inhibitors and BCL2 inhibitors, specifically for a fixed duration of time to obtain a deeper response and hence possibility a time-limited therapy, she noted. “We are also excited about the possibility of having more fixed-duration treatments available for our patients, which will make their treatment journey less troublesome, both physically as well as financially.”
Dr. Bohn reported receiving personal fees from AbbVie, AstraZeneca and Janssen for advisory board participation. Dr. Bhat has served on advisory board for AstraZeneca and received honorarium from them.
FROM MEMO – MAGAZINE OF EUROPEAN MEDICAL ONCOLOGY
Surgery shows no survival, morbidity benefit for mild hyperparathyroidism
Patients who receive parathyroidectomy for mild primary hyperparathyroidism show no benefits in survival or morbidity, including fractures, cancer, or cardiovascular outcomes over more than 10 years, compared with those not receiving the surgery, results from a randomized, prospective trial show.
“In contrast to existing data showing increased mortality and cardiovascular morbidity in mild primary hyperparathyroidism, we did not find any treatment effect of parathyroidectomy on these important clinical endpoints,” report the authors of the study, published in the Annals of Internal Medicine.
Reason to evaluate and revise current recommendations?
With mild primary hyperparathyroidism becoming the predominant form of hyperparathyroidism, the results suggest rethinking the current recommendations for the condition, the study authors note.
“Over the years, more active management of mild primary hyperparathyroidism has been recommended, with a widening of criteria for parathyroidectomy,” they write.
“With the low number of kidney stones (n = 5) and no effect of parathyroidectomy on fractures, there may be a need to evaluate and potentially revise the current recommendations.”
The authors of an accompanying editorial agree that “the [results] provide a strong rationale for nonoperative management of patients with mild primary hyperparathyroidism.”
“The findings suggest that most patients can be managed nonoperatively, with monitoring of serum calcium levels every 1 to 2 years or if symptoms occur,” write the editorial authors, Mark J. Bolland, PhD, and Andrew Grey, MD, of the department of medicine, University of Auckland, New Zealand.
Although parathyroidectomy is recommended for the treatment in patients with hyperparathyroidism with severe hypercalcemia or overt symptoms, there has been debate on the long-term benefits of surgery among those with milder cases.
Most previous studies that have shown benefits, such as reductions in the risk of fracture with parathyroidectomy, have importantly not distinguished between mild and more severe primary hyperparathyroidism, the authors note.
No significant differences in mortality between surgery, nonsurgery groups
For the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH) trial, first author Mikkel Pretorius, MD, Oslo University Hospital and Faculty of Medicine, University of Oslo, and colleagues enrolled 191 patients between 1998 and 2005 in Sweden, Norway, and Denmark, who were aged 50-80 years and had mild primary hyperparathyroidism, defined as serum calcium levels of 10.42-11.22 mg/dL.
Participants were randomized to receive surgery (n = 95) or nonoperative observation without intervention (n = 96).
After a 10-year follow-up, 129 patients had completed the final visit. The overall death rate was 7.6%, and, with eight deaths in the surgery group and seven in the nonsurgery group, there were no significant differences between groups in terms of mortality (HR, 1.17; P = .76).
During an extended observation period that lasted until 2018, mortality rates increased by 23%, but with a relatively even distribution of 24 deaths in the surgery group and 20 among those with no surgery.
Chronic hypercalcemia related to primary hyperparathyroidism has been debated as being associated with an increased risk of cardiovascular disease or cancer, however, “the absolute numbers for these and the other disease-specific causes of death were nearly identical between groups,” the authors write, with 17 deaths from cardiovascular disease, eight from cancer, and eight from cerebrovascular disease.
In terms of morbidity, including cardiovascular events, cerebrovascular events, cancer, peripheral fractures, and renal stones, there were 101 events overall, with 52 in the parathyroidectomy group and 49 in the nonsurgery group, which again, was not a significant difference.
Sixteen vertebral fractures occurred overall in 14 patients, which were evenly split at seven patients in each group.
The authors note that “the incidence of peripheral fractures for women in our study was around 2,900 per 100,000 person-years, in the same range as for 70-year-old women in a study in Gothenburg, Sweden (about 2,600 per 100,000 person-years).”
There were no between-group differences in terms of time to death or first morbidity event for any of the prespecified events.
Of the 96 patients originally assigned to the nonsurgery group, 17 (18%) had surgery during follow-up, including three for serious hypercalcemia, three by their own choice, two for decreasing bone density, one for kidney stones, and the others for unclear or unrelated reasons.
Study limitations include that only 26 men (13 in each group) were included, and only 16 completed the study. “The external validity for men based on this study is therefore limited,” the authors note.
And although most people with primary hyperparathyroidism are adults, the older age of participants suggests the results should not be generalized to younger patients with benign parathyroid tumors.
The editorialists note that age should be one of the few factors that may, indeed, suggest appropriate candidates for parathyroidectomy.
“Younger patients (aged < 50 years) may have more aggressive disease,” they explain.
In addition, “patients with serum calcium levels above 3 mmol/L (> 12 mg/dL) are at greater risk for symptomatic hypercalcemia, and patients with a recent history of kidney stones may have fewer future stones after surgical cure.”
“Yet, such patients are a small minority of those with primary hyperparathyroidism,” they note.
The study authors underscore that “our data add evidence to guide the decisionmaking process in deliberative dialogue between clinicians and patients.”
The study received funding from Swedish government grants, the Norwegian Research Council, and the South-Eastern Norway Regional Health Authority.
A version of this article first appeared on Medscape.com.
Patients who receive parathyroidectomy for mild primary hyperparathyroidism show no benefits in survival or morbidity, including fractures, cancer, or cardiovascular outcomes over more than 10 years, compared with those not receiving the surgery, results from a randomized, prospective trial show.
“In contrast to existing data showing increased mortality and cardiovascular morbidity in mild primary hyperparathyroidism, we did not find any treatment effect of parathyroidectomy on these important clinical endpoints,” report the authors of the study, published in the Annals of Internal Medicine.
Reason to evaluate and revise current recommendations?
With mild primary hyperparathyroidism becoming the predominant form of hyperparathyroidism, the results suggest rethinking the current recommendations for the condition, the study authors note.
“Over the years, more active management of mild primary hyperparathyroidism has been recommended, with a widening of criteria for parathyroidectomy,” they write.
“With the low number of kidney stones (n = 5) and no effect of parathyroidectomy on fractures, there may be a need to evaluate and potentially revise the current recommendations.”
The authors of an accompanying editorial agree that “the [results] provide a strong rationale for nonoperative management of patients with mild primary hyperparathyroidism.”
“The findings suggest that most patients can be managed nonoperatively, with monitoring of serum calcium levels every 1 to 2 years or if symptoms occur,” write the editorial authors, Mark J. Bolland, PhD, and Andrew Grey, MD, of the department of medicine, University of Auckland, New Zealand.
Although parathyroidectomy is recommended for the treatment in patients with hyperparathyroidism with severe hypercalcemia or overt symptoms, there has been debate on the long-term benefits of surgery among those with milder cases.
Most previous studies that have shown benefits, such as reductions in the risk of fracture with parathyroidectomy, have importantly not distinguished between mild and more severe primary hyperparathyroidism, the authors note.
No significant differences in mortality between surgery, nonsurgery groups
For the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH) trial, first author Mikkel Pretorius, MD, Oslo University Hospital and Faculty of Medicine, University of Oslo, and colleagues enrolled 191 patients between 1998 and 2005 in Sweden, Norway, and Denmark, who were aged 50-80 years and had mild primary hyperparathyroidism, defined as serum calcium levels of 10.42-11.22 mg/dL.
Participants were randomized to receive surgery (n = 95) or nonoperative observation without intervention (n = 96).
After a 10-year follow-up, 129 patients had completed the final visit. The overall death rate was 7.6%, and, with eight deaths in the surgery group and seven in the nonsurgery group, there were no significant differences between groups in terms of mortality (HR, 1.17; P = .76).
During an extended observation period that lasted until 2018, mortality rates increased by 23%, but with a relatively even distribution of 24 deaths in the surgery group and 20 among those with no surgery.
Chronic hypercalcemia related to primary hyperparathyroidism has been debated as being associated with an increased risk of cardiovascular disease or cancer, however, “the absolute numbers for these and the other disease-specific causes of death were nearly identical between groups,” the authors write, with 17 deaths from cardiovascular disease, eight from cancer, and eight from cerebrovascular disease.
In terms of morbidity, including cardiovascular events, cerebrovascular events, cancer, peripheral fractures, and renal stones, there were 101 events overall, with 52 in the parathyroidectomy group and 49 in the nonsurgery group, which again, was not a significant difference.
Sixteen vertebral fractures occurred overall in 14 patients, which were evenly split at seven patients in each group.
The authors note that “the incidence of peripheral fractures for women in our study was around 2,900 per 100,000 person-years, in the same range as for 70-year-old women in a study in Gothenburg, Sweden (about 2,600 per 100,000 person-years).”
There were no between-group differences in terms of time to death or first morbidity event for any of the prespecified events.
Of the 96 patients originally assigned to the nonsurgery group, 17 (18%) had surgery during follow-up, including three for serious hypercalcemia, three by their own choice, two for decreasing bone density, one for kidney stones, and the others for unclear or unrelated reasons.
Study limitations include that only 26 men (13 in each group) were included, and only 16 completed the study. “The external validity for men based on this study is therefore limited,” the authors note.
And although most people with primary hyperparathyroidism are adults, the older age of participants suggests the results should not be generalized to younger patients with benign parathyroid tumors.
The editorialists note that age should be one of the few factors that may, indeed, suggest appropriate candidates for parathyroidectomy.
“Younger patients (aged < 50 years) may have more aggressive disease,” they explain.
In addition, “patients with serum calcium levels above 3 mmol/L (> 12 mg/dL) are at greater risk for symptomatic hypercalcemia, and patients with a recent history of kidney stones may have fewer future stones after surgical cure.”
“Yet, such patients are a small minority of those with primary hyperparathyroidism,” they note.
The study authors underscore that “our data add evidence to guide the decisionmaking process in deliberative dialogue between clinicians and patients.”
The study received funding from Swedish government grants, the Norwegian Research Council, and the South-Eastern Norway Regional Health Authority.
A version of this article first appeared on Medscape.com.
Patients who receive parathyroidectomy for mild primary hyperparathyroidism show no benefits in survival or morbidity, including fractures, cancer, or cardiovascular outcomes over more than 10 years, compared with those not receiving the surgery, results from a randomized, prospective trial show.
“In contrast to existing data showing increased mortality and cardiovascular morbidity in mild primary hyperparathyroidism, we did not find any treatment effect of parathyroidectomy on these important clinical endpoints,” report the authors of the study, published in the Annals of Internal Medicine.
Reason to evaluate and revise current recommendations?
With mild primary hyperparathyroidism becoming the predominant form of hyperparathyroidism, the results suggest rethinking the current recommendations for the condition, the study authors note.
“Over the years, more active management of mild primary hyperparathyroidism has been recommended, with a widening of criteria for parathyroidectomy,” they write.
“With the low number of kidney stones (n = 5) and no effect of parathyroidectomy on fractures, there may be a need to evaluate and potentially revise the current recommendations.”
The authors of an accompanying editorial agree that “the [results] provide a strong rationale for nonoperative management of patients with mild primary hyperparathyroidism.”
“The findings suggest that most patients can be managed nonoperatively, with monitoring of serum calcium levels every 1 to 2 years or if symptoms occur,” write the editorial authors, Mark J. Bolland, PhD, and Andrew Grey, MD, of the department of medicine, University of Auckland, New Zealand.
Although parathyroidectomy is recommended for the treatment in patients with hyperparathyroidism with severe hypercalcemia or overt symptoms, there has been debate on the long-term benefits of surgery among those with milder cases.
Most previous studies that have shown benefits, such as reductions in the risk of fracture with parathyroidectomy, have importantly not distinguished between mild and more severe primary hyperparathyroidism, the authors note.
No significant differences in mortality between surgery, nonsurgery groups
For the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH) trial, first author Mikkel Pretorius, MD, Oslo University Hospital and Faculty of Medicine, University of Oslo, and colleagues enrolled 191 patients between 1998 and 2005 in Sweden, Norway, and Denmark, who were aged 50-80 years and had mild primary hyperparathyroidism, defined as serum calcium levels of 10.42-11.22 mg/dL.
Participants were randomized to receive surgery (n = 95) or nonoperative observation without intervention (n = 96).
After a 10-year follow-up, 129 patients had completed the final visit. The overall death rate was 7.6%, and, with eight deaths in the surgery group and seven in the nonsurgery group, there were no significant differences between groups in terms of mortality (HR, 1.17; P = .76).
During an extended observation period that lasted until 2018, mortality rates increased by 23%, but with a relatively even distribution of 24 deaths in the surgery group and 20 among those with no surgery.
Chronic hypercalcemia related to primary hyperparathyroidism has been debated as being associated with an increased risk of cardiovascular disease or cancer, however, “the absolute numbers for these and the other disease-specific causes of death were nearly identical between groups,” the authors write, with 17 deaths from cardiovascular disease, eight from cancer, and eight from cerebrovascular disease.
In terms of morbidity, including cardiovascular events, cerebrovascular events, cancer, peripheral fractures, and renal stones, there were 101 events overall, with 52 in the parathyroidectomy group and 49 in the nonsurgery group, which again, was not a significant difference.
Sixteen vertebral fractures occurred overall in 14 patients, which were evenly split at seven patients in each group.
The authors note that “the incidence of peripheral fractures for women in our study was around 2,900 per 100,000 person-years, in the same range as for 70-year-old women in a study in Gothenburg, Sweden (about 2,600 per 100,000 person-years).”
There were no between-group differences in terms of time to death or first morbidity event for any of the prespecified events.
Of the 96 patients originally assigned to the nonsurgery group, 17 (18%) had surgery during follow-up, including three for serious hypercalcemia, three by their own choice, two for decreasing bone density, one for kidney stones, and the others for unclear or unrelated reasons.
Study limitations include that only 26 men (13 in each group) were included, and only 16 completed the study. “The external validity for men based on this study is therefore limited,” the authors note.
And although most people with primary hyperparathyroidism are adults, the older age of participants suggests the results should not be generalized to younger patients with benign parathyroid tumors.
The editorialists note that age should be one of the few factors that may, indeed, suggest appropriate candidates for parathyroidectomy.
“Younger patients (aged < 50 years) may have more aggressive disease,” they explain.
In addition, “patients with serum calcium levels above 3 mmol/L (> 12 mg/dL) are at greater risk for symptomatic hypercalcemia, and patients with a recent history of kidney stones may have fewer future stones after surgical cure.”
“Yet, such patients are a small minority of those with primary hyperparathyroidism,” they note.
The study authors underscore that “our data add evidence to guide the decisionmaking process in deliberative dialogue between clinicians and patients.”
The study received funding from Swedish government grants, the Norwegian Research Council, and the South-Eastern Norway Regional Health Authority.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
Melanoma screening study stokes overdiagnosis debate
new research shows.
Without a corresponding decrease in melanoma mortality, an increase in the detection of those thin melanomas “raises the concern that early detection efforts, such as visual skin screening, may result in overdiagnosis,” the study authors wrote. “The value of a cancer screening program should most rigorously be measured not by the number of new, early cancers detected, but by its impact on the development of late-stage disease and its associated morbidity, cost, and mortality.”
The research, published in JAMA Dermatology, has reignited the controversy over the benefits and harms of primary care skin cancer screening, garnering two editorials that reflect different sides of the debate.
In one, Robert A. Swerlick, MD, pointed out that, “despite public messaging to the contrary, to my knowledge there is no evidence that routine skin examinations have any effect on melanoma mortality.
“The stage shift to smaller tumors should not be viewed as success and is very strong evidence of overdiagnosis,” wrote Dr. Swerlick, of the department of dermatology, Emory University, Atlanta.
The other editorial, however, argued that routine screening saves lives. “Most melanoma deaths are because of stage I disease, with an estimated 3%-15% of thin melanomas (≤ 1 mm) being lethal,” wrote a trio of editorialists from Oregon Health & Science University, Portland.
When considering the high mutation rate associated with melanoma and the current limits of treatment options, early diagnosis becomes “particularly important and counterbalances the risk of overdiagnosis,” the editorialists asserted.
Primary care screening study
The new findings come from an observational study of a quality improvement initiative conducted at the University of Pittsburgh Medical Center system between 2014 and 2018, in which primary care clinicians were offered training in melanoma identification through skin examination and were encouraged to offer annual skin cancer screening to patients aged 35 years and older.
Of 595,799 eligible patients, 144,851 (24.3%) were screened at least once during the study period. Those who received screening were more likely than unscreened patients to be older (median age, 59 vs. 55 years), women, and non-Hispanic White persons.
During a follow-up of 5 years, the researchers found that patients who received screening were significantly more likely than unscreened patients to be diagnosed with in situ melanoma (incidence, 30.4 vs. 14.4; hazard ratio, 2.6; P < .001) or thin invasive melanoma (incidence, 24.5 vs. 16.1; HR, 1.8; P < .001), after adjusting for factors that included age, sex, and race.
The screened patients were also more likely than unscreened patients to be diagnosed with in situ interval melanomas, defined as melanomas occurring at least 60 days after initial screening (incidence, 26.7 vs. 12.9; HR, 2.1; P < .001), as well as thin invasive interval melanomas (incidence, 18.5 vs. 14.4; HR, 1.3; P = .03).
The 60-day interval was included to account for the possible time to referral to a specialist for definitive diagnosis, the authors explained.
The incidence of the detection of melanomas thicker than 4 mm was lower in screened versus unscreened patients, but the difference was not statistically significant for all melanomas (2.7 vs. 3.3; HR, 0.8; P = .38) or interval melanomas (1.5 vs. 2.7; HR, 0.6; P = .15).
Experts weigh in
Although the follow-up period was of 5 years, not all patients were followed that long after undergoing screening. For instance, for some patients, follow-up occurred only 1 year after they had been screened.
The study’s senior author, Laura K. Ferris, MD, PhD, of the department of dermatology, University of Pittsburgh, noted that a longer follow-up could shift the results.
“When you look at the curves in our figures, you do start to see them separate more and more over time for the thicker melanomas,” Dr. Ferris said in an interview. “I do suspect that, if we followed patients longer, we might start to see a more significant difference.”
The findings nevertheless add to evidence that although routine screening substantially increases the detection of melanomas overall, these melanomas are often not the ones doctors are most worried about or that increase a person’s risk of mortality, Dr. Ferris noted.
When it comes to melanoma screening, balancing the risks and benefits is key. One major downside, Dr. Ferris said, is in regard to the burden such screening could place on the health care system, with potentially unproductive screenings causing delays in care for patients with more urgent needs.
“We are undersupplied in the dermatology workforce, and there is often a long wait to see dermatologists, so we really want to make sure, as trained professionals, that patients have access to us,” she said. “If we’re doing something that doesn’t have proven benefit and is increasing the wait time, that will come at the expense of other patients’ access.”
Costs involved in skin biopsies and excisions of borderline lesions as well as the potential to increase patients’ anxiety represent other important considerations, Dr. Ferris noted.
However, Sancy A. Leachman, MD, PhD, a coauthor of the editorial in favor of screening, said in an interview that “at the individual level, there are an almost infinite number of individual circumstances that could lead a person to decide that the potential benefits outweigh the harms.”
According to Dr. Leachman, who is chair of the department of dermatology, Oregon Health & Science University, these individual priorities may not align with those of the various decision-makers or with guidelines, such as those from the U.S. Preventive Services Task Force, which gives visual skin cancer screening of asymptomatic patients an “I” rating, indicating “insufficient evidence.”
“Many federal agencies and payer groups focus on minimizing costs and optimizing outcomes,” Dr. Leachman and coauthors wrote. As the only professional advocates for individual patients, physicians “have a responsibility to assure that the best interests of patients are served.”
The study was funded by the University of Pittsburgh Melanoma and Skin Cancer Program. Dr. Ferris and Dr. Swerlick disclosed no relevant financial relationships. Dr. Leachman is the principal investigator for War on Melanoma, an early-detection program in Oregon.
A version of this article first appeared on Medscape.com.
new research shows.
Without a corresponding decrease in melanoma mortality, an increase in the detection of those thin melanomas “raises the concern that early detection efforts, such as visual skin screening, may result in overdiagnosis,” the study authors wrote. “The value of a cancer screening program should most rigorously be measured not by the number of new, early cancers detected, but by its impact on the development of late-stage disease and its associated morbidity, cost, and mortality.”
The research, published in JAMA Dermatology, has reignited the controversy over the benefits and harms of primary care skin cancer screening, garnering two editorials that reflect different sides of the debate.
In one, Robert A. Swerlick, MD, pointed out that, “despite public messaging to the contrary, to my knowledge there is no evidence that routine skin examinations have any effect on melanoma mortality.
“The stage shift to smaller tumors should not be viewed as success and is very strong evidence of overdiagnosis,” wrote Dr. Swerlick, of the department of dermatology, Emory University, Atlanta.
The other editorial, however, argued that routine screening saves lives. “Most melanoma deaths are because of stage I disease, with an estimated 3%-15% of thin melanomas (≤ 1 mm) being lethal,” wrote a trio of editorialists from Oregon Health & Science University, Portland.
When considering the high mutation rate associated with melanoma and the current limits of treatment options, early diagnosis becomes “particularly important and counterbalances the risk of overdiagnosis,” the editorialists asserted.
Primary care screening study
The new findings come from an observational study of a quality improvement initiative conducted at the University of Pittsburgh Medical Center system between 2014 and 2018, in which primary care clinicians were offered training in melanoma identification through skin examination and were encouraged to offer annual skin cancer screening to patients aged 35 years and older.
Of 595,799 eligible patients, 144,851 (24.3%) were screened at least once during the study period. Those who received screening were more likely than unscreened patients to be older (median age, 59 vs. 55 years), women, and non-Hispanic White persons.
During a follow-up of 5 years, the researchers found that patients who received screening were significantly more likely than unscreened patients to be diagnosed with in situ melanoma (incidence, 30.4 vs. 14.4; hazard ratio, 2.6; P < .001) or thin invasive melanoma (incidence, 24.5 vs. 16.1; HR, 1.8; P < .001), after adjusting for factors that included age, sex, and race.
The screened patients were also more likely than unscreened patients to be diagnosed with in situ interval melanomas, defined as melanomas occurring at least 60 days after initial screening (incidence, 26.7 vs. 12.9; HR, 2.1; P < .001), as well as thin invasive interval melanomas (incidence, 18.5 vs. 14.4; HR, 1.3; P = .03).
The 60-day interval was included to account for the possible time to referral to a specialist for definitive diagnosis, the authors explained.
The incidence of the detection of melanomas thicker than 4 mm was lower in screened versus unscreened patients, but the difference was not statistically significant for all melanomas (2.7 vs. 3.3; HR, 0.8; P = .38) or interval melanomas (1.5 vs. 2.7; HR, 0.6; P = .15).
Experts weigh in
Although the follow-up period was of 5 years, not all patients were followed that long after undergoing screening. For instance, for some patients, follow-up occurred only 1 year after they had been screened.
The study’s senior author, Laura K. Ferris, MD, PhD, of the department of dermatology, University of Pittsburgh, noted that a longer follow-up could shift the results.
“When you look at the curves in our figures, you do start to see them separate more and more over time for the thicker melanomas,” Dr. Ferris said in an interview. “I do suspect that, if we followed patients longer, we might start to see a more significant difference.”
The findings nevertheless add to evidence that although routine screening substantially increases the detection of melanomas overall, these melanomas are often not the ones doctors are most worried about or that increase a person’s risk of mortality, Dr. Ferris noted.
When it comes to melanoma screening, balancing the risks and benefits is key. One major downside, Dr. Ferris said, is in regard to the burden such screening could place on the health care system, with potentially unproductive screenings causing delays in care for patients with more urgent needs.
“We are undersupplied in the dermatology workforce, and there is often a long wait to see dermatologists, so we really want to make sure, as trained professionals, that patients have access to us,” she said. “If we’re doing something that doesn’t have proven benefit and is increasing the wait time, that will come at the expense of other patients’ access.”
Costs involved in skin biopsies and excisions of borderline lesions as well as the potential to increase patients’ anxiety represent other important considerations, Dr. Ferris noted.
However, Sancy A. Leachman, MD, PhD, a coauthor of the editorial in favor of screening, said in an interview that “at the individual level, there are an almost infinite number of individual circumstances that could lead a person to decide that the potential benefits outweigh the harms.”
According to Dr. Leachman, who is chair of the department of dermatology, Oregon Health & Science University, these individual priorities may not align with those of the various decision-makers or with guidelines, such as those from the U.S. Preventive Services Task Force, which gives visual skin cancer screening of asymptomatic patients an “I” rating, indicating “insufficient evidence.”
“Many federal agencies and payer groups focus on minimizing costs and optimizing outcomes,” Dr. Leachman and coauthors wrote. As the only professional advocates for individual patients, physicians “have a responsibility to assure that the best interests of patients are served.”
The study was funded by the University of Pittsburgh Melanoma and Skin Cancer Program. Dr. Ferris and Dr. Swerlick disclosed no relevant financial relationships. Dr. Leachman is the principal investigator for War on Melanoma, an early-detection program in Oregon.
A version of this article first appeared on Medscape.com.
new research shows.
Without a corresponding decrease in melanoma mortality, an increase in the detection of those thin melanomas “raises the concern that early detection efforts, such as visual skin screening, may result in overdiagnosis,” the study authors wrote. “The value of a cancer screening program should most rigorously be measured not by the number of new, early cancers detected, but by its impact on the development of late-stage disease and its associated morbidity, cost, and mortality.”
The research, published in JAMA Dermatology, has reignited the controversy over the benefits and harms of primary care skin cancer screening, garnering two editorials that reflect different sides of the debate.
In one, Robert A. Swerlick, MD, pointed out that, “despite public messaging to the contrary, to my knowledge there is no evidence that routine skin examinations have any effect on melanoma mortality.
“The stage shift to smaller tumors should not be viewed as success and is very strong evidence of overdiagnosis,” wrote Dr. Swerlick, of the department of dermatology, Emory University, Atlanta.
The other editorial, however, argued that routine screening saves lives. “Most melanoma deaths are because of stage I disease, with an estimated 3%-15% of thin melanomas (≤ 1 mm) being lethal,” wrote a trio of editorialists from Oregon Health & Science University, Portland.
When considering the high mutation rate associated with melanoma and the current limits of treatment options, early diagnosis becomes “particularly important and counterbalances the risk of overdiagnosis,” the editorialists asserted.
Primary care screening study
The new findings come from an observational study of a quality improvement initiative conducted at the University of Pittsburgh Medical Center system between 2014 and 2018, in which primary care clinicians were offered training in melanoma identification through skin examination and were encouraged to offer annual skin cancer screening to patients aged 35 years and older.
Of 595,799 eligible patients, 144,851 (24.3%) were screened at least once during the study period. Those who received screening were more likely than unscreened patients to be older (median age, 59 vs. 55 years), women, and non-Hispanic White persons.
During a follow-up of 5 years, the researchers found that patients who received screening were significantly more likely than unscreened patients to be diagnosed with in situ melanoma (incidence, 30.4 vs. 14.4; hazard ratio, 2.6; P < .001) or thin invasive melanoma (incidence, 24.5 vs. 16.1; HR, 1.8; P < .001), after adjusting for factors that included age, sex, and race.
The screened patients were also more likely than unscreened patients to be diagnosed with in situ interval melanomas, defined as melanomas occurring at least 60 days after initial screening (incidence, 26.7 vs. 12.9; HR, 2.1; P < .001), as well as thin invasive interval melanomas (incidence, 18.5 vs. 14.4; HR, 1.3; P = .03).
The 60-day interval was included to account for the possible time to referral to a specialist for definitive diagnosis, the authors explained.
The incidence of the detection of melanomas thicker than 4 mm was lower in screened versus unscreened patients, but the difference was not statistically significant for all melanomas (2.7 vs. 3.3; HR, 0.8; P = .38) or interval melanomas (1.5 vs. 2.7; HR, 0.6; P = .15).
Experts weigh in
Although the follow-up period was of 5 years, not all patients were followed that long after undergoing screening. For instance, for some patients, follow-up occurred only 1 year after they had been screened.
The study’s senior author, Laura K. Ferris, MD, PhD, of the department of dermatology, University of Pittsburgh, noted that a longer follow-up could shift the results.
“When you look at the curves in our figures, you do start to see them separate more and more over time for the thicker melanomas,” Dr. Ferris said in an interview. “I do suspect that, if we followed patients longer, we might start to see a more significant difference.”
The findings nevertheless add to evidence that although routine screening substantially increases the detection of melanomas overall, these melanomas are often not the ones doctors are most worried about or that increase a person’s risk of mortality, Dr. Ferris noted.
When it comes to melanoma screening, balancing the risks and benefits is key. One major downside, Dr. Ferris said, is in regard to the burden such screening could place on the health care system, with potentially unproductive screenings causing delays in care for patients with more urgent needs.
“We are undersupplied in the dermatology workforce, and there is often a long wait to see dermatologists, so we really want to make sure, as trained professionals, that patients have access to us,” she said. “If we’re doing something that doesn’t have proven benefit and is increasing the wait time, that will come at the expense of other patients’ access.”
Costs involved in skin biopsies and excisions of borderline lesions as well as the potential to increase patients’ anxiety represent other important considerations, Dr. Ferris noted.
However, Sancy A. Leachman, MD, PhD, a coauthor of the editorial in favor of screening, said in an interview that “at the individual level, there are an almost infinite number of individual circumstances that could lead a person to decide that the potential benefits outweigh the harms.”
According to Dr. Leachman, who is chair of the department of dermatology, Oregon Health & Science University, these individual priorities may not align with those of the various decision-makers or with guidelines, such as those from the U.S. Preventive Services Task Force, which gives visual skin cancer screening of asymptomatic patients an “I” rating, indicating “insufficient evidence.”
“Many federal agencies and payer groups focus on minimizing costs and optimizing outcomes,” Dr. Leachman and coauthors wrote. As the only professional advocates for individual patients, physicians “have a responsibility to assure that the best interests of patients are served.”
The study was funded by the University of Pittsburgh Melanoma and Skin Cancer Program. Dr. Ferris and Dr. Swerlick disclosed no relevant financial relationships. Dr. Leachman is the principal investigator for War on Melanoma, an early-detection program in Oregon.
A version of this article first appeared on Medscape.com.
FROM JAMA DERMATOLOGY
‘Forever chemicals’ exposures may compound diabetes risk
Women in midlife exposed to combinations of perfluoroalkyl and polyfluoroalkyl substances (PFASs), dubbed “forever and everywhere chemicals”, are at increased risk of developing diabetes, similar to the magnitude of risk associated with overweight and even greater than the risk associated with smoking, new research shows.
“This is the first study to examine the joint effect of PFAS on incident diabetes,” first author Sung Kyun Park, ScD, MPH, told this news organization.
“We showed that multiple PFAS as mixtures have larger effects than individual PFAS,” said Dr. Park, of the department of epidemiology, School of Public Health, University of Michigan, Ann Arbor.
The results suggest that, “given that 1.5 million Americans are newly diagnosed with diabetes each year in the USA, approximately 370,000 new cases of diabetes annually in the U.S. are attributable to PFAS exposure,” Dr. Park and authors note in the study, published in Diabetologia.
However, Kevin McConway, PhD, emeritus professor of applied statistics, The Open University, U.K., told the UK Science Media Centre: “[Some] doubt about cause still remains. Yes, this study does show that PFAS may increase diabetes risk in middle-aged women, but it certainly can’t rule out other explanations for its findings.”
Is there any way to reduce exposure?
PFASs, known to be ubiquitous in the environment and also often dubbed “endocrine-disrupting” chemicals, have structures similar to fatty acids. They have been detected in the blood of most people and linked to health concerns including pre-eclampsia, altered levels of liver enzymes, inflammation, and altered lipid and glucose metabolism.
Sources of PFAS exposure can run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and even drinking water.
The authors note a recent Consumer Reports investigation of 118 food packaging products, for instance, which reported finding PFAS chemicals in the packaging of every fast-food chain and retailer examined, including Burger King, McDonald’s, and even more health-focused chains, such as Trader Joe’s.
While efforts to pressure industry to limit PFAS in products are ongoing, Dr. Park asserted that “PFAS exposure reduction at the individual-level is very limited, so a more important way is to change policies and to limit PFAS in the air, drinking water, and foods, etc.”
“It is impossible to completely avoid exposure to PFAS, but I think it is important to acknowledge such sources and change our mindset,” he said.
In terms of clinical practice, the authors add that “it is also important for clinicians to be aware of PFAS as unrecognized risk factors for diabetes and to be prepared to counsel patients in terms of sources of exposure and potential health effects.”
Prospective findings from the SWAN-MPS study
The findings come from a prospective study of 1,237 women, with a median age of 49.4 years, who were diabetes-free upon entering the Study of Women’s Health Across the Nation – Multi-Pollutant Study (SWAN-MPS) between 1999 and 2000 and followed until 2017.
Blood samples taken throughout the study were analyzed for serum concentrations of seven PFASs.
Over the study period, there were 102 cases of incident diabetes, representing a rate of 6 cases per 1,000 person-years. Type of diabetes was not determined, but given the age of study participants, most were assumed to have type 2 diabetes, Dr. Park and colleagues note.
After adjustment for key confounders including race/ethnicity, smoking status, alcohol consumption, total energy intake, physical activity, menopausal status, and body mass index (BMI), those in the highest tertile of exposure to a combination of all seven of the PFASs were significantly more likely to develop diabetes, compared with those in the lowest tertile for exposure (hazard ratio, 2.62).
This risk was greater than that seen with individual PFASs (HR, 1.36-1.85), suggesting a potential additive or synergistic effect of multiple PFASs on diabetes risk.
The association between the combined exposure to PFASs among the highest versus lowest tertile was similar to the risk of diabetes developing among those with overweight (BMI 25-< 30 kg/m2) versus normal weight (HR, 2.89) and higher than the risk among current versus never smokers (HR, 2.30).
“Our findings suggest that PFAS may be an important risk factor for diabetes that has a substantial public health impact,” the authors say.
“Given the widespread exposure to PFAS in the general population, the expected benefit of reducing exposure to these ubiquitous chemicals might be considerable,” they emphasize.
The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Women in midlife exposed to combinations of perfluoroalkyl and polyfluoroalkyl substances (PFASs), dubbed “forever and everywhere chemicals”, are at increased risk of developing diabetes, similar to the magnitude of risk associated with overweight and even greater than the risk associated with smoking, new research shows.
“This is the first study to examine the joint effect of PFAS on incident diabetes,” first author Sung Kyun Park, ScD, MPH, told this news organization.
“We showed that multiple PFAS as mixtures have larger effects than individual PFAS,” said Dr. Park, of the department of epidemiology, School of Public Health, University of Michigan, Ann Arbor.
The results suggest that, “given that 1.5 million Americans are newly diagnosed with diabetes each year in the USA, approximately 370,000 new cases of diabetes annually in the U.S. are attributable to PFAS exposure,” Dr. Park and authors note in the study, published in Diabetologia.
However, Kevin McConway, PhD, emeritus professor of applied statistics, The Open University, U.K., told the UK Science Media Centre: “[Some] doubt about cause still remains. Yes, this study does show that PFAS may increase diabetes risk in middle-aged women, but it certainly can’t rule out other explanations for its findings.”
Is there any way to reduce exposure?
PFASs, known to be ubiquitous in the environment and also often dubbed “endocrine-disrupting” chemicals, have structures similar to fatty acids. They have been detected in the blood of most people and linked to health concerns including pre-eclampsia, altered levels of liver enzymes, inflammation, and altered lipid and glucose metabolism.
Sources of PFAS exposure can run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and even drinking water.
The authors note a recent Consumer Reports investigation of 118 food packaging products, for instance, which reported finding PFAS chemicals in the packaging of every fast-food chain and retailer examined, including Burger King, McDonald’s, and even more health-focused chains, such as Trader Joe’s.
While efforts to pressure industry to limit PFAS in products are ongoing, Dr. Park asserted that “PFAS exposure reduction at the individual-level is very limited, so a more important way is to change policies and to limit PFAS in the air, drinking water, and foods, etc.”
“It is impossible to completely avoid exposure to PFAS, but I think it is important to acknowledge such sources and change our mindset,” he said.
In terms of clinical practice, the authors add that “it is also important for clinicians to be aware of PFAS as unrecognized risk factors for diabetes and to be prepared to counsel patients in terms of sources of exposure and potential health effects.”
Prospective findings from the SWAN-MPS study
The findings come from a prospective study of 1,237 women, with a median age of 49.4 years, who were diabetes-free upon entering the Study of Women’s Health Across the Nation – Multi-Pollutant Study (SWAN-MPS) between 1999 and 2000 and followed until 2017.
Blood samples taken throughout the study were analyzed for serum concentrations of seven PFASs.
Over the study period, there were 102 cases of incident diabetes, representing a rate of 6 cases per 1,000 person-years. Type of diabetes was not determined, but given the age of study participants, most were assumed to have type 2 diabetes, Dr. Park and colleagues note.
After adjustment for key confounders including race/ethnicity, smoking status, alcohol consumption, total energy intake, physical activity, menopausal status, and body mass index (BMI), those in the highest tertile of exposure to a combination of all seven of the PFASs were significantly more likely to develop diabetes, compared with those in the lowest tertile for exposure (hazard ratio, 2.62).
This risk was greater than that seen with individual PFASs (HR, 1.36-1.85), suggesting a potential additive or synergistic effect of multiple PFASs on diabetes risk.
The association between the combined exposure to PFASs among the highest versus lowest tertile was similar to the risk of diabetes developing among those with overweight (BMI 25-< 30 kg/m2) versus normal weight (HR, 2.89) and higher than the risk among current versus never smokers (HR, 2.30).
“Our findings suggest that PFAS may be an important risk factor for diabetes that has a substantial public health impact,” the authors say.
“Given the widespread exposure to PFAS in the general population, the expected benefit of reducing exposure to these ubiquitous chemicals might be considerable,” they emphasize.
The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Women in midlife exposed to combinations of perfluoroalkyl and polyfluoroalkyl substances (PFASs), dubbed “forever and everywhere chemicals”, are at increased risk of developing diabetes, similar to the magnitude of risk associated with overweight and even greater than the risk associated with smoking, new research shows.
“This is the first study to examine the joint effect of PFAS on incident diabetes,” first author Sung Kyun Park, ScD, MPH, told this news organization.
“We showed that multiple PFAS as mixtures have larger effects than individual PFAS,” said Dr. Park, of the department of epidemiology, School of Public Health, University of Michigan, Ann Arbor.
The results suggest that, “given that 1.5 million Americans are newly diagnosed with diabetes each year in the USA, approximately 370,000 new cases of diabetes annually in the U.S. are attributable to PFAS exposure,” Dr. Park and authors note in the study, published in Diabetologia.
However, Kevin McConway, PhD, emeritus professor of applied statistics, The Open University, U.K., told the UK Science Media Centre: “[Some] doubt about cause still remains. Yes, this study does show that PFAS may increase diabetes risk in middle-aged women, but it certainly can’t rule out other explanations for its findings.”
Is there any way to reduce exposure?
PFASs, known to be ubiquitous in the environment and also often dubbed “endocrine-disrupting” chemicals, have structures similar to fatty acids. They have been detected in the blood of most people and linked to health concerns including pre-eclampsia, altered levels of liver enzymes, inflammation, and altered lipid and glucose metabolism.
Sources of PFAS exposure can run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and even drinking water.
The authors note a recent Consumer Reports investigation of 118 food packaging products, for instance, which reported finding PFAS chemicals in the packaging of every fast-food chain and retailer examined, including Burger King, McDonald’s, and even more health-focused chains, such as Trader Joe’s.
While efforts to pressure industry to limit PFAS in products are ongoing, Dr. Park asserted that “PFAS exposure reduction at the individual-level is very limited, so a more important way is to change policies and to limit PFAS in the air, drinking water, and foods, etc.”
“It is impossible to completely avoid exposure to PFAS, but I think it is important to acknowledge such sources and change our mindset,” he said.
In terms of clinical practice, the authors add that “it is also important for clinicians to be aware of PFAS as unrecognized risk factors for diabetes and to be prepared to counsel patients in terms of sources of exposure and potential health effects.”
Prospective findings from the SWAN-MPS study
The findings come from a prospective study of 1,237 women, with a median age of 49.4 years, who were diabetes-free upon entering the Study of Women’s Health Across the Nation – Multi-Pollutant Study (SWAN-MPS) between 1999 and 2000 and followed until 2017.
Blood samples taken throughout the study were analyzed for serum concentrations of seven PFASs.
Over the study period, there were 102 cases of incident diabetes, representing a rate of 6 cases per 1,000 person-years. Type of diabetes was not determined, but given the age of study participants, most were assumed to have type 2 diabetes, Dr. Park and colleagues note.
After adjustment for key confounders including race/ethnicity, smoking status, alcohol consumption, total energy intake, physical activity, menopausal status, and body mass index (BMI), those in the highest tertile of exposure to a combination of all seven of the PFASs were significantly more likely to develop diabetes, compared with those in the lowest tertile for exposure (hazard ratio, 2.62).
This risk was greater than that seen with individual PFASs (HR, 1.36-1.85), suggesting a potential additive or synergistic effect of multiple PFASs on diabetes risk.
The association between the combined exposure to PFASs among the highest versus lowest tertile was similar to the risk of diabetes developing among those with overweight (BMI 25-< 30 kg/m2) versus normal weight (HR, 2.89) and higher than the risk among current versus never smokers (HR, 2.30).
“Our findings suggest that PFAS may be an important risk factor for diabetes that has a substantial public health impact,” the authors say.
“Given the widespread exposure to PFAS in the general population, the expected benefit of reducing exposure to these ubiquitous chemicals might be considerable,” they emphasize.
The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM DIABETOLOGIA
CO2 laser excision therapy for hidradenitis suppurativa shows no keloid risk
BOSTON – The use of , new research shows.
“With keloids disproportionately affecting Black and other skin of color patients, denying treatment on a notion that lacks evidentiary support further potentiates the health disparities experienced by these marginalized groups,” the researchers reported at the Annual Meeting of the Skin of Color Society Scientific Symposium (SOCS) 2022. In their retrospective study of 129 patients with HS treated with CO2 laser, “there were no cases of keloid formation,” they say.
HS, a potentially debilitating chronic inflammatory condition that involves painful nodules, boils, and abscesses, is often refractory to standard treatment. CO2 laser excision therapy has yielded favorable outcomes in some studies.
Although CO2 laser therapy is also used to treat keloids, some clinicians hesitate to use this treatment in these patients because of concerns that its use for treating HS could trigger the development of keloids.
“Many patients come in telling us they were denied [CO2 laser] surgery due to keloids,” senior author Iltefat Hamzavi, MD, a senior staff physician in the Department of Dermatology at the Henry Ford Health System, Detroit, told this news organization.
Although patients with HS are commonly treated with CO2 laser excision in his department, this treatment approach “is underused nationally,” he said.
“Of note, the sinus tunnels of hidradenitis suppurativa can look like keloids, so this might drive surgeons away from treating [those] lesions,” Dr. Hamzavi said.
To further evaluate the risk of developing keloids with the treatment, Dr. Hamzavi and his colleagues conducted a retrospective review of 129 patients with HS treated at Henry Ford who had undergone follicular destruction with CO2 laser between 2014 and 2021; 102 (79%) patients were female. The mean age was about 38 years (range, 15-78 years).
Of the patients, almost half were Black, almost 40% were White, 5% were Asian, and 3% were of unknown ethnicity.
Medical records of nine patients included diagnoses of keloids or hypertrophic scars. Further review indicated that none of the diagnoses were for keloids but were for hypertrophic scars, hypertrophic granulation tissue, an HS nodule, or contracture scar, the authors report.
“While the emergence of hypertrophic scars, hypertrophic granulation tissue, and scar contracture following CO2 laser excision therapy for hidradenitis suppurativa has been documented in the literature, existing evidence does not support postoperative keloid formation,” the authors conclude.
Because healing time with CO2 laser treatment is prolonged and there is an increase in risk of adverse events, Dr. Hamzavi underscored that “safety protocols for CO2 lasers should be followed, and wound prep instructions should be provided along with counseling on healing times.”
Regarding patient selection, he noted that “the disease should be medically stable with reduction in drainage to help control postop bleeding risk.”
The findings of the study are supported by a recent systematic review that compared outcomes and adverse effects of treatment with ablative laser therapies with nonablative lasers for skin resurfacing. The review included 34 studies and involved 1,093 patients. The conditions that were treated ranged from photodamage and acne scars to HS and post-traumatic scarring from basal cell carcinoma excision.
That review found that overall, rates of adverse events were higher with nonablative therapies (12.2%, 31 events), compared with ablative laser therapy, such as with CO2 laser (8.28%, 81 events). In addition, when transient events were excluded, ablative lasers were associated with fewer complications overall, compared with nonablative lasers (2.56% vs. 7.48%).
The authors conclude: “It is our hope that this study will facilitate continued research in this domain in an effort to combat these inequities and improve access to CO2 excision or standardized excisional therapy for hidradenitis suppurativa treatment.”
Dr. Hamzavi and the other authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON – The use of , new research shows.
“With keloids disproportionately affecting Black and other skin of color patients, denying treatment on a notion that lacks evidentiary support further potentiates the health disparities experienced by these marginalized groups,” the researchers reported at the Annual Meeting of the Skin of Color Society Scientific Symposium (SOCS) 2022. In their retrospective study of 129 patients with HS treated with CO2 laser, “there were no cases of keloid formation,” they say.
HS, a potentially debilitating chronic inflammatory condition that involves painful nodules, boils, and abscesses, is often refractory to standard treatment. CO2 laser excision therapy has yielded favorable outcomes in some studies.
Although CO2 laser therapy is also used to treat keloids, some clinicians hesitate to use this treatment in these patients because of concerns that its use for treating HS could trigger the development of keloids.
“Many patients come in telling us they were denied [CO2 laser] surgery due to keloids,” senior author Iltefat Hamzavi, MD, a senior staff physician in the Department of Dermatology at the Henry Ford Health System, Detroit, told this news organization.
Although patients with HS are commonly treated with CO2 laser excision in his department, this treatment approach “is underused nationally,” he said.
“Of note, the sinus tunnels of hidradenitis suppurativa can look like keloids, so this might drive surgeons away from treating [those] lesions,” Dr. Hamzavi said.
To further evaluate the risk of developing keloids with the treatment, Dr. Hamzavi and his colleagues conducted a retrospective review of 129 patients with HS treated at Henry Ford who had undergone follicular destruction with CO2 laser between 2014 and 2021; 102 (79%) patients were female. The mean age was about 38 years (range, 15-78 years).
Of the patients, almost half were Black, almost 40% were White, 5% were Asian, and 3% were of unknown ethnicity.
Medical records of nine patients included diagnoses of keloids or hypertrophic scars. Further review indicated that none of the diagnoses were for keloids but were for hypertrophic scars, hypertrophic granulation tissue, an HS nodule, or contracture scar, the authors report.
“While the emergence of hypertrophic scars, hypertrophic granulation tissue, and scar contracture following CO2 laser excision therapy for hidradenitis suppurativa has been documented in the literature, existing evidence does not support postoperative keloid formation,” the authors conclude.
Because healing time with CO2 laser treatment is prolonged and there is an increase in risk of adverse events, Dr. Hamzavi underscored that “safety protocols for CO2 lasers should be followed, and wound prep instructions should be provided along with counseling on healing times.”
Regarding patient selection, he noted that “the disease should be medically stable with reduction in drainage to help control postop bleeding risk.”
The findings of the study are supported by a recent systematic review that compared outcomes and adverse effects of treatment with ablative laser therapies with nonablative lasers for skin resurfacing. The review included 34 studies and involved 1,093 patients. The conditions that were treated ranged from photodamage and acne scars to HS and post-traumatic scarring from basal cell carcinoma excision.
That review found that overall, rates of adverse events were higher with nonablative therapies (12.2%, 31 events), compared with ablative laser therapy, such as with CO2 laser (8.28%, 81 events). In addition, when transient events were excluded, ablative lasers were associated with fewer complications overall, compared with nonablative lasers (2.56% vs. 7.48%).
The authors conclude: “It is our hope that this study will facilitate continued research in this domain in an effort to combat these inequities and improve access to CO2 excision or standardized excisional therapy for hidradenitis suppurativa treatment.”
Dr. Hamzavi and the other authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON – The use of , new research shows.
“With keloids disproportionately affecting Black and other skin of color patients, denying treatment on a notion that lacks evidentiary support further potentiates the health disparities experienced by these marginalized groups,” the researchers reported at the Annual Meeting of the Skin of Color Society Scientific Symposium (SOCS) 2022. In their retrospective study of 129 patients with HS treated with CO2 laser, “there were no cases of keloid formation,” they say.
HS, a potentially debilitating chronic inflammatory condition that involves painful nodules, boils, and abscesses, is often refractory to standard treatment. CO2 laser excision therapy has yielded favorable outcomes in some studies.
Although CO2 laser therapy is also used to treat keloids, some clinicians hesitate to use this treatment in these patients because of concerns that its use for treating HS could trigger the development of keloids.
“Many patients come in telling us they were denied [CO2 laser] surgery due to keloids,” senior author Iltefat Hamzavi, MD, a senior staff physician in the Department of Dermatology at the Henry Ford Health System, Detroit, told this news organization.
Although patients with HS are commonly treated with CO2 laser excision in his department, this treatment approach “is underused nationally,” he said.
“Of note, the sinus tunnels of hidradenitis suppurativa can look like keloids, so this might drive surgeons away from treating [those] lesions,” Dr. Hamzavi said.
To further evaluate the risk of developing keloids with the treatment, Dr. Hamzavi and his colleagues conducted a retrospective review of 129 patients with HS treated at Henry Ford who had undergone follicular destruction with CO2 laser between 2014 and 2021; 102 (79%) patients were female. The mean age was about 38 years (range, 15-78 years).
Of the patients, almost half were Black, almost 40% were White, 5% were Asian, and 3% were of unknown ethnicity.
Medical records of nine patients included diagnoses of keloids or hypertrophic scars. Further review indicated that none of the diagnoses were for keloids but were for hypertrophic scars, hypertrophic granulation tissue, an HS nodule, or contracture scar, the authors report.
“While the emergence of hypertrophic scars, hypertrophic granulation tissue, and scar contracture following CO2 laser excision therapy for hidradenitis suppurativa has been documented in the literature, existing evidence does not support postoperative keloid formation,” the authors conclude.
Because healing time with CO2 laser treatment is prolonged and there is an increase in risk of adverse events, Dr. Hamzavi underscored that “safety protocols for CO2 lasers should be followed, and wound prep instructions should be provided along with counseling on healing times.”
Regarding patient selection, he noted that “the disease should be medically stable with reduction in drainage to help control postop bleeding risk.”
The findings of the study are supported by a recent systematic review that compared outcomes and adverse effects of treatment with ablative laser therapies with nonablative lasers for skin resurfacing. The review included 34 studies and involved 1,093 patients. The conditions that were treated ranged from photodamage and acne scars to HS and post-traumatic scarring from basal cell carcinoma excision.
That review found that overall, rates of adverse events were higher with nonablative therapies (12.2%, 31 events), compared with ablative laser therapy, such as with CO2 laser (8.28%, 81 events). In addition, when transient events were excluded, ablative lasers were associated with fewer complications overall, compared with nonablative lasers (2.56% vs. 7.48%).
The authors conclude: “It is our hope that this study will facilitate continued research in this domain in an effort to combat these inequities and improve access to CO2 excision or standardized excisional therapy for hidradenitis suppurativa treatment.”
Dr. Hamzavi and the other authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT SOCS 2022
Study finds discrepancies in biopsy decisions, diagnoses based on skin type
BOSTON – compared with White patients, new research shows.
“Our findings suggest diagnostic biases based on skin color exist in dermatology practice,” lead author Loren Krueger, MD, assistant professor in the department of dermatology, Emory University School of Medicine, Atlanta, said at the Annual Skin of Color Society Scientific Symposium. “A lower likelihood of biopsy of malignancy in darker skin types could contribute to disparities in cutaneous malignancies,” she added.
Disparities in dermatologic care among Black patients, compared with White patients, have been well documented. Recent evidence includes a 2020 study that showed significant shortcomings among medical students in correctly diagnosing squamous cell carcinoma, urticaria, and atopic dermatitis for patients with skin of color.
“It’s no secret that our images do not accurately or in the right quantity include skin of color,” Dr. Krueger said. “Yet few papers talk about how these biases actually impact our care. Importantly, this study demonstrates that diagnostic bias develops as early as the medical student level.”
To further investigate the role of skin color in the assessment of neoplastic and inflammatory skin conditions and decisions to perform biopsy, Dr. Krueger and her colleagues surveyed 144 dermatology residents and attending dermatologists to evaluate their clinical decisionmaking skills in assessing skin conditions for patients with lighter skin and those with darker skin. Almost 80% (113) provided complete responses and were included in the study.
For the survey, participants were shown photos of 10 neoplastic and 10 inflammatory skin conditions. Each image was matched in lighter (skin types I-II) and darker (skin types IV-VI) skinned patients in random order. Participants were asked to identify the suspected underlying etiology (neoplastic–benign, neoplastic–malignant, papulosquamous, lichenoid, infectious, bullous, or no suspected etiology) and whether they would choose to perform biopsy for the pictured condition.
Overall, their responses showed a slightly higher probability of recommending a biopsy for patients with skin types IV-V (odds ratio, 1.18; P = .054).
However, respondents were more than twice as likely to recommend a biopsy for benign neoplasms for patients with skin of color, compared with those with lighter skin types (OR, 2.57; P < .0001). They were significantly less likely to recommend a biopsy for a malignant neoplasm for patients with skin of color (OR, 0.42; P < .0001).
In addition, the correct etiology was much more commonly missed in diagnosing patients with skin of color, even after adjusting for years in dermatology practice (OR, 0.569; P < .0001).
Conversely, respondents were significantly less likely to recommend a biopsy for benign neoplasms and were more likely to recommend a biopsy for malignant neoplasms among White patients. Etiology was more commonly correct.
The findings underscore that “for skin of color patients, you’re more likely to have a benign neoplasm biopsied, you’re less likely to have a malignant neoplasm biopsied, and more often, your etiology may be missed,” Dr. Krueger said at the meeting.
Of note, while 45% of respondents were dermatology residents or fellows, 20.4% had 1-5 years of experience, and about 28% had 10 to more than 25 years of experience.
And while 75% of the dermatology residents, fellows, and attendings were White, there was no difference in the probability of correctly identifying the underlying etiology in dark or light skin types based on the provider’s self-identified race.
Importantly, the patterns in the study of diagnostic discrepancies are reflected in broader dermatologic outcomes. The 5-year melanoma survival rate is 74.1% among Black patients and 92.9% among White patients. Dr. Krueger referred to data showing that only 52.6% of Black patients have stage I melanoma at diagnosis, whereas among White patients, the rate is much higher, at 75.9%.
“We know skin malignancy can be more aggressive and late-stage in skin of color populations, leading to increased morbidity and later stage at initial diagnosis,” Dr. Krueger told this news organization. “We routinely attribute this to limited access to care and lack of awareness on skin malignancy. However, we have no evidence on how we, as dermatologists, may be playing a role.”
Furthermore, the decision to perform biopsy or not can affect the size and stage at diagnosis of a cutaneous malignancy, she noted.
Key changes needed to prevent the disparities – and their implications – should start at the training level, she emphasized. “I would love to see increased photo representation in training materials – this is a great place to start,” Dr. Krueger said.
In addition, “encouraging medical students, residents, and dermatologists to learn from skin of color experts is vital,” she said. “We should also provide hands-on experience and training with diverse patient populations.”
The first step to addressing biases “is to acknowledge they exist,” Dr. Krueger added. “I am hopeful this inspires others to continue to investigate these biases, as well as how we can eliminate them.”
The study was funded by the Rudin Resident Research Award. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON – compared with White patients, new research shows.
“Our findings suggest diagnostic biases based on skin color exist in dermatology practice,” lead author Loren Krueger, MD, assistant professor in the department of dermatology, Emory University School of Medicine, Atlanta, said at the Annual Skin of Color Society Scientific Symposium. “A lower likelihood of biopsy of malignancy in darker skin types could contribute to disparities in cutaneous malignancies,” she added.
Disparities in dermatologic care among Black patients, compared with White patients, have been well documented. Recent evidence includes a 2020 study that showed significant shortcomings among medical students in correctly diagnosing squamous cell carcinoma, urticaria, and atopic dermatitis for patients with skin of color.
“It’s no secret that our images do not accurately or in the right quantity include skin of color,” Dr. Krueger said. “Yet few papers talk about how these biases actually impact our care. Importantly, this study demonstrates that diagnostic bias develops as early as the medical student level.”
To further investigate the role of skin color in the assessment of neoplastic and inflammatory skin conditions and decisions to perform biopsy, Dr. Krueger and her colleagues surveyed 144 dermatology residents and attending dermatologists to evaluate their clinical decisionmaking skills in assessing skin conditions for patients with lighter skin and those with darker skin. Almost 80% (113) provided complete responses and were included in the study.
For the survey, participants were shown photos of 10 neoplastic and 10 inflammatory skin conditions. Each image was matched in lighter (skin types I-II) and darker (skin types IV-VI) skinned patients in random order. Participants were asked to identify the suspected underlying etiology (neoplastic–benign, neoplastic–malignant, papulosquamous, lichenoid, infectious, bullous, or no suspected etiology) and whether they would choose to perform biopsy for the pictured condition.
Overall, their responses showed a slightly higher probability of recommending a biopsy for patients with skin types IV-V (odds ratio, 1.18; P = .054).
However, respondents were more than twice as likely to recommend a biopsy for benign neoplasms for patients with skin of color, compared with those with lighter skin types (OR, 2.57; P < .0001). They were significantly less likely to recommend a biopsy for a malignant neoplasm for patients with skin of color (OR, 0.42; P < .0001).
In addition, the correct etiology was much more commonly missed in diagnosing patients with skin of color, even after adjusting for years in dermatology practice (OR, 0.569; P < .0001).
Conversely, respondents were significantly less likely to recommend a biopsy for benign neoplasms and were more likely to recommend a biopsy for malignant neoplasms among White patients. Etiology was more commonly correct.
The findings underscore that “for skin of color patients, you’re more likely to have a benign neoplasm biopsied, you’re less likely to have a malignant neoplasm biopsied, and more often, your etiology may be missed,” Dr. Krueger said at the meeting.
Of note, while 45% of respondents were dermatology residents or fellows, 20.4% had 1-5 years of experience, and about 28% had 10 to more than 25 years of experience.
And while 75% of the dermatology residents, fellows, and attendings were White, there was no difference in the probability of correctly identifying the underlying etiology in dark or light skin types based on the provider’s self-identified race.
Importantly, the patterns in the study of diagnostic discrepancies are reflected in broader dermatologic outcomes. The 5-year melanoma survival rate is 74.1% among Black patients and 92.9% among White patients. Dr. Krueger referred to data showing that only 52.6% of Black patients have stage I melanoma at diagnosis, whereas among White patients, the rate is much higher, at 75.9%.
“We know skin malignancy can be more aggressive and late-stage in skin of color populations, leading to increased morbidity and later stage at initial diagnosis,” Dr. Krueger told this news organization. “We routinely attribute this to limited access to care and lack of awareness on skin malignancy. However, we have no evidence on how we, as dermatologists, may be playing a role.”
Furthermore, the decision to perform biopsy or not can affect the size and stage at diagnosis of a cutaneous malignancy, she noted.
Key changes needed to prevent the disparities – and their implications – should start at the training level, she emphasized. “I would love to see increased photo representation in training materials – this is a great place to start,” Dr. Krueger said.
In addition, “encouraging medical students, residents, and dermatologists to learn from skin of color experts is vital,” she said. “We should also provide hands-on experience and training with diverse patient populations.”
The first step to addressing biases “is to acknowledge they exist,” Dr. Krueger added. “I am hopeful this inspires others to continue to investigate these biases, as well as how we can eliminate them.”
The study was funded by the Rudin Resident Research Award. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON – compared with White patients, new research shows.
“Our findings suggest diagnostic biases based on skin color exist in dermatology practice,” lead author Loren Krueger, MD, assistant professor in the department of dermatology, Emory University School of Medicine, Atlanta, said at the Annual Skin of Color Society Scientific Symposium. “A lower likelihood of biopsy of malignancy in darker skin types could contribute to disparities in cutaneous malignancies,” she added.
Disparities in dermatologic care among Black patients, compared with White patients, have been well documented. Recent evidence includes a 2020 study that showed significant shortcomings among medical students in correctly diagnosing squamous cell carcinoma, urticaria, and atopic dermatitis for patients with skin of color.
“It’s no secret that our images do not accurately or in the right quantity include skin of color,” Dr. Krueger said. “Yet few papers talk about how these biases actually impact our care. Importantly, this study demonstrates that diagnostic bias develops as early as the medical student level.”
To further investigate the role of skin color in the assessment of neoplastic and inflammatory skin conditions and decisions to perform biopsy, Dr. Krueger and her colleagues surveyed 144 dermatology residents and attending dermatologists to evaluate their clinical decisionmaking skills in assessing skin conditions for patients with lighter skin and those with darker skin. Almost 80% (113) provided complete responses and were included in the study.
For the survey, participants were shown photos of 10 neoplastic and 10 inflammatory skin conditions. Each image was matched in lighter (skin types I-II) and darker (skin types IV-VI) skinned patients in random order. Participants were asked to identify the suspected underlying etiology (neoplastic–benign, neoplastic–malignant, papulosquamous, lichenoid, infectious, bullous, or no suspected etiology) and whether they would choose to perform biopsy for the pictured condition.
Overall, their responses showed a slightly higher probability of recommending a biopsy for patients with skin types IV-V (odds ratio, 1.18; P = .054).
However, respondents were more than twice as likely to recommend a biopsy for benign neoplasms for patients with skin of color, compared with those with lighter skin types (OR, 2.57; P < .0001). They were significantly less likely to recommend a biopsy for a malignant neoplasm for patients with skin of color (OR, 0.42; P < .0001).
In addition, the correct etiology was much more commonly missed in diagnosing patients with skin of color, even after adjusting for years in dermatology practice (OR, 0.569; P < .0001).
Conversely, respondents were significantly less likely to recommend a biopsy for benign neoplasms and were more likely to recommend a biopsy for malignant neoplasms among White patients. Etiology was more commonly correct.
The findings underscore that “for skin of color patients, you’re more likely to have a benign neoplasm biopsied, you’re less likely to have a malignant neoplasm biopsied, and more often, your etiology may be missed,” Dr. Krueger said at the meeting.
Of note, while 45% of respondents were dermatology residents or fellows, 20.4% had 1-5 years of experience, and about 28% had 10 to more than 25 years of experience.
And while 75% of the dermatology residents, fellows, and attendings were White, there was no difference in the probability of correctly identifying the underlying etiology in dark or light skin types based on the provider’s self-identified race.
Importantly, the patterns in the study of diagnostic discrepancies are reflected in broader dermatologic outcomes. The 5-year melanoma survival rate is 74.1% among Black patients and 92.9% among White patients. Dr. Krueger referred to data showing that only 52.6% of Black patients have stage I melanoma at diagnosis, whereas among White patients, the rate is much higher, at 75.9%.
“We know skin malignancy can be more aggressive and late-stage in skin of color populations, leading to increased morbidity and later stage at initial diagnosis,” Dr. Krueger told this news organization. “We routinely attribute this to limited access to care and lack of awareness on skin malignancy. However, we have no evidence on how we, as dermatologists, may be playing a role.”
Furthermore, the decision to perform biopsy or not can affect the size and stage at diagnosis of a cutaneous malignancy, she noted.
Key changes needed to prevent the disparities – and their implications – should start at the training level, she emphasized. “I would love to see increased photo representation in training materials – this is a great place to start,” Dr. Krueger said.
In addition, “encouraging medical students, residents, and dermatologists to learn from skin of color experts is vital,” she said. “We should also provide hands-on experience and training with diverse patient populations.”
The first step to addressing biases “is to acknowledge they exist,” Dr. Krueger added. “I am hopeful this inspires others to continue to investigate these biases, as well as how we can eliminate them.”
The study was funded by the Rudin Resident Research Award. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Live-donor liver transplants for patients with CRC liver mets
These patients usually have a poor prognosis, and for many, palliative chemotherapy is the standard of care.
“For the first time, we have been able to demonstrate [outside of Norway] that liver transplantation for patients with unresectable liver metastases is feasible with good outcomes,” lead author Gonzalo Sapisochin, MD, PhD, an assistant professor of surgery at the University of Toronto, said in an interview.
“Furthermore, this is the first time we are able to prove that living donation may be a good strategy in this setting,” Dr. Sapisochin said of the series of 10 cases that they published in JAMA Surgery.
The series showed “excellent perioperative outcomes for both donors and recipients,” noted the authors of an accompanying commentary. They said the team “should be commended for adding liver-donor live transplantation to the armamentarium of surgical options for patients with CRC liver metastases.”
However, they express concern about the relatively short follow-up of 1.5 years and the “very high” recurrence rate of 30%.
Commenting in an interview, lead editorialist Shimul Shah, MD, an associate professor of surgery and the chief of solid organ transplantation at the University of Cincinnati, said: “I agree that overall survival is an important measure to look at, but it’s hard to look at overall survival with [1.5] years of follow-up.”
Other key areas of concern are the need for more standardized practices and for more data on how liver transplantation compares with patients who just continue to receive chemotherapy.
“I certainly think that there’s a role for liver transplantation in these patients, and I am a big fan of this,” Dr. Shah emphasized, noting that four patients at his own center have recently received liver transplants, including three from deceased donors.
“However, I just think that as a community, we need to be cautious and not get too excited too early,” he said. “We need to keep studying it and take it one step at a time.”
Moving from deceased to living donors
Nearly 70% of patients with CRC develop liver metastases, and when these are unresectable, the prognosis is poor, with 5-year survival rates of less than 10%.
The option of liver transplantation was first reported in 2015 by a group in Norway. Their study included 21 patients with CRC and unresectable liver tumors. They reported a striking improvement in overall survival at 5 years (56% vs. 9% among patients who started first-line chemotherapy).
But with shortages of donor livers, this approach has not caught on. Deceased-donor liver allografts are in short supply in most countries, and recent allocation changes have further shifted available organs away from patients with liver tumors.
An alternative is to use living donors. In a recent study, Dr. Sapisochin and colleagues showed viability and a survival advantage, compared with deceased-donor liver transplantation.
Building on that work, they established treatment protocols at three centers – the University of Rochester (N.Y.) Medical Center, the Cleveland Clinic, , and the University Health Network in Toronto.
Of 91 evaluated patients who were prospectively enrolled with liver-confined, unresectable CRC liver metastases, 10 met all inclusion criteria and received living-donor liver transplants between December 2017 and May 2021. The median age of the patients was 45 years; six were men, and four were women.
These patients all had primary tumors greater than stage T2 (six T3 and four T4b). Lymphovascular invasion was present in two patients, and perineural invasion was present in one patient.
The median time from diagnosis of the liver metastases to liver transplant was 1.7 years (range, 1.1-7.8 years).
At a median follow-up of 1.5 years (range, 0.4-2.9 years), recurrences occurred in three patients, with a rate of recurrence-free survival, using Kaplan-Meier estimates, of 62% and a rate of overall survival of 100%.
Rates of morbidity associated with transplantation were no higher than those observed in established standards for the donors or recipients, the authors noted.
Among transplant recipients, three patients had no Clavien-Dindo complications; three had grade II, and four had grade III complications. Among donors, five had no complications, four had grade I, and one had grade III complications.
All 10 donors were discharged from the hospital 4-7 days after surgery and recovered fully.
All three patients who experienced recurrences were treated with palliative chemotherapy. One died of disease after 3 months of treatment. As of the time of publication of the study, the other two had survived for 2 or more years following their live donor liver transplant.
Patient selection key
The authors are now investigating tumor subtypes, responses in CRC liver metastases, and other factors, with the aim of developing a novel screening method to identify appropriate candidates more quickly.
In the meantime, they emphasized that indicators of disease biology, such as the Oslo Score, the Clinical Risk Score, and sustained clinical response to systemic therapy, “remain the key filters through which to select patients who have sufficient opportunity for long-term cancer control, which is necessary to justify the risk to a living donor.”
Dr. Sapisochin reported receiving grants from Roche and Bayer and personal fees from Integra, Roche, AstraZeneca, and Novartis outside the submitted work. Dr. Shah disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
These patients usually have a poor prognosis, and for many, palliative chemotherapy is the standard of care.
“For the first time, we have been able to demonstrate [outside of Norway] that liver transplantation for patients with unresectable liver metastases is feasible with good outcomes,” lead author Gonzalo Sapisochin, MD, PhD, an assistant professor of surgery at the University of Toronto, said in an interview.
“Furthermore, this is the first time we are able to prove that living donation may be a good strategy in this setting,” Dr. Sapisochin said of the series of 10 cases that they published in JAMA Surgery.
The series showed “excellent perioperative outcomes for both donors and recipients,” noted the authors of an accompanying commentary. They said the team “should be commended for adding liver-donor live transplantation to the armamentarium of surgical options for patients with CRC liver metastases.”
However, they express concern about the relatively short follow-up of 1.5 years and the “very high” recurrence rate of 30%.
Commenting in an interview, lead editorialist Shimul Shah, MD, an associate professor of surgery and the chief of solid organ transplantation at the University of Cincinnati, said: “I agree that overall survival is an important measure to look at, but it’s hard to look at overall survival with [1.5] years of follow-up.”
Other key areas of concern are the need for more standardized practices and for more data on how liver transplantation compares with patients who just continue to receive chemotherapy.
“I certainly think that there’s a role for liver transplantation in these patients, and I am a big fan of this,” Dr. Shah emphasized, noting that four patients at his own center have recently received liver transplants, including three from deceased donors.
“However, I just think that as a community, we need to be cautious and not get too excited too early,” he said. “We need to keep studying it and take it one step at a time.”
Moving from deceased to living donors
Nearly 70% of patients with CRC develop liver metastases, and when these are unresectable, the prognosis is poor, with 5-year survival rates of less than 10%.
The option of liver transplantation was first reported in 2015 by a group in Norway. Their study included 21 patients with CRC and unresectable liver tumors. They reported a striking improvement in overall survival at 5 years (56% vs. 9% among patients who started first-line chemotherapy).
But with shortages of donor livers, this approach has not caught on. Deceased-donor liver allografts are in short supply in most countries, and recent allocation changes have further shifted available organs away from patients with liver tumors.
An alternative is to use living donors. In a recent study, Dr. Sapisochin and colleagues showed viability and a survival advantage, compared with deceased-donor liver transplantation.
Building on that work, they established treatment protocols at three centers – the University of Rochester (N.Y.) Medical Center, the Cleveland Clinic, , and the University Health Network in Toronto.
Of 91 evaluated patients who were prospectively enrolled with liver-confined, unresectable CRC liver metastases, 10 met all inclusion criteria and received living-donor liver transplants between December 2017 and May 2021. The median age of the patients was 45 years; six were men, and four were women.
These patients all had primary tumors greater than stage T2 (six T3 and four T4b). Lymphovascular invasion was present in two patients, and perineural invasion was present in one patient.
The median time from diagnosis of the liver metastases to liver transplant was 1.7 years (range, 1.1-7.8 years).
At a median follow-up of 1.5 years (range, 0.4-2.9 years), recurrences occurred in three patients, with a rate of recurrence-free survival, using Kaplan-Meier estimates, of 62% and a rate of overall survival of 100%.
Rates of morbidity associated with transplantation were no higher than those observed in established standards for the donors or recipients, the authors noted.
Among transplant recipients, three patients had no Clavien-Dindo complications; three had grade II, and four had grade III complications. Among donors, five had no complications, four had grade I, and one had grade III complications.
All 10 donors were discharged from the hospital 4-7 days after surgery and recovered fully.
All three patients who experienced recurrences were treated with palliative chemotherapy. One died of disease after 3 months of treatment. As of the time of publication of the study, the other two had survived for 2 or more years following their live donor liver transplant.
Patient selection key
The authors are now investigating tumor subtypes, responses in CRC liver metastases, and other factors, with the aim of developing a novel screening method to identify appropriate candidates more quickly.
In the meantime, they emphasized that indicators of disease biology, such as the Oslo Score, the Clinical Risk Score, and sustained clinical response to systemic therapy, “remain the key filters through which to select patients who have sufficient opportunity for long-term cancer control, which is necessary to justify the risk to a living donor.”
Dr. Sapisochin reported receiving grants from Roche and Bayer and personal fees from Integra, Roche, AstraZeneca, and Novartis outside the submitted work. Dr. Shah disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
These patients usually have a poor prognosis, and for many, palliative chemotherapy is the standard of care.
“For the first time, we have been able to demonstrate [outside of Norway] that liver transplantation for patients with unresectable liver metastases is feasible with good outcomes,” lead author Gonzalo Sapisochin, MD, PhD, an assistant professor of surgery at the University of Toronto, said in an interview.
“Furthermore, this is the first time we are able to prove that living donation may be a good strategy in this setting,” Dr. Sapisochin said of the series of 10 cases that they published in JAMA Surgery.
The series showed “excellent perioperative outcomes for both donors and recipients,” noted the authors of an accompanying commentary. They said the team “should be commended for adding liver-donor live transplantation to the armamentarium of surgical options for patients with CRC liver metastases.”
However, they express concern about the relatively short follow-up of 1.5 years and the “very high” recurrence rate of 30%.
Commenting in an interview, lead editorialist Shimul Shah, MD, an associate professor of surgery and the chief of solid organ transplantation at the University of Cincinnati, said: “I agree that overall survival is an important measure to look at, but it’s hard to look at overall survival with [1.5] years of follow-up.”
Other key areas of concern are the need for more standardized practices and for more data on how liver transplantation compares with patients who just continue to receive chemotherapy.
“I certainly think that there’s a role for liver transplantation in these patients, and I am a big fan of this,” Dr. Shah emphasized, noting that four patients at his own center have recently received liver transplants, including three from deceased donors.
“However, I just think that as a community, we need to be cautious and not get too excited too early,” he said. “We need to keep studying it and take it one step at a time.”
Moving from deceased to living donors
Nearly 70% of patients with CRC develop liver metastases, and when these are unresectable, the prognosis is poor, with 5-year survival rates of less than 10%.
The option of liver transplantation was first reported in 2015 by a group in Norway. Their study included 21 patients with CRC and unresectable liver tumors. They reported a striking improvement in overall survival at 5 years (56% vs. 9% among patients who started first-line chemotherapy).
But with shortages of donor livers, this approach has not caught on. Deceased-donor liver allografts are in short supply in most countries, and recent allocation changes have further shifted available organs away from patients with liver tumors.
An alternative is to use living donors. In a recent study, Dr. Sapisochin and colleagues showed viability and a survival advantage, compared with deceased-donor liver transplantation.
Building on that work, they established treatment protocols at three centers – the University of Rochester (N.Y.) Medical Center, the Cleveland Clinic, , and the University Health Network in Toronto.
Of 91 evaluated patients who were prospectively enrolled with liver-confined, unresectable CRC liver metastases, 10 met all inclusion criteria and received living-donor liver transplants between December 2017 and May 2021. The median age of the patients was 45 years; six were men, and four were women.
These patients all had primary tumors greater than stage T2 (six T3 and four T4b). Lymphovascular invasion was present in two patients, and perineural invasion was present in one patient.
The median time from diagnosis of the liver metastases to liver transplant was 1.7 years (range, 1.1-7.8 years).
At a median follow-up of 1.5 years (range, 0.4-2.9 years), recurrences occurred in three patients, with a rate of recurrence-free survival, using Kaplan-Meier estimates, of 62% and a rate of overall survival of 100%.
Rates of morbidity associated with transplantation were no higher than those observed in established standards for the donors or recipients, the authors noted.
Among transplant recipients, three patients had no Clavien-Dindo complications; three had grade II, and four had grade III complications. Among donors, five had no complications, four had grade I, and one had grade III complications.
All 10 donors were discharged from the hospital 4-7 days after surgery and recovered fully.
All three patients who experienced recurrences were treated with palliative chemotherapy. One died of disease after 3 months of treatment. As of the time of publication of the study, the other two had survived for 2 or more years following their live donor liver transplant.
Patient selection key
The authors are now investigating tumor subtypes, responses in CRC liver metastases, and other factors, with the aim of developing a novel screening method to identify appropriate candidates more quickly.
In the meantime, they emphasized that indicators of disease biology, such as the Oslo Score, the Clinical Risk Score, and sustained clinical response to systemic therapy, “remain the key filters through which to select patients who have sufficient opportunity for long-term cancer control, which is necessary to justify the risk to a living donor.”
Dr. Sapisochin reported receiving grants from Roche and Bayer and personal fees from Integra, Roche, AstraZeneca, and Novartis outside the submitted work. Dr. Shah disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA SURGERY
Novel medication tied to better quality of life in major depression
DENVER –
In a phase 3 trial that included more than 500 adult patients with MDD, those who received zuranolone for 14 days showed greater improvement at day 15 across numerous QoL outcomes, compared with their counterparts in the placebo group.
In addition, combined analysis of four zuranolone clinical trials showed “mental well-being and functioning improved to near general population norm levels” for the active-treatment group, reported the researchers, led by Anita H. Clayton, MD, chair and professor of psychiatry, University of Virginia, Charlottesville.
“Based on these integrated analyses, the benefit of treatment with zuranolone may extend beyond reduction in depressive symptoms to include potential improvement in quality of life and overall health, as perceived by patients,” they add.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
First oral formulation
Zuranolone represents the second entry in the new class of neuroactive steroid drugs, which modulate GABA-A receptor activity – but it would be the first to have an oral formulation. Brexanolone, which was approved by the Food and Drug Administration in 2019 for postpartum depression, is administered through continuous IV infusion over 60 hours.
As previously reported by this news organization, zuranolone improved depressive symptoms as early as day 3, achieving the primary endpoint of significantly greater reduction in scores on the 17-item Hamilton Rating Scale for Depression from baseline to day 15 versus placebo (P = .014).
In the new analysis, patient-reported measures of functional health and well-being were assessed in the WATERFALL trial. It included 266 patients with MDD who were treated with zuranolone 50 mg daily for 2 weeks and 268 patients with MDD who were treated with placebo.
The study used the Short Form–36 (SF-36v2), which covers a wide range of patient-reported measures, including physical function, bodily pain, general health, vitality, social function, and “role-emotional” symptoms.
Results showed that although the treatment and placebo groups had similar baseline SF-36v2 scores, those receiving zuranolone reported significantly greater improvements at day 15 in almost all of the assessment’s domains, including physical function (treatment difference, 0.8), general health (1.0), vitality (3.1), social functioning (1.1), and role-emotional symptoms (1.5; for all comparisons, P < .05). The only exceptions were in role-physical symptoms and bodily pain.
In measures that included physical function, bodily pain, and general health, the patients achieved improvements at day 15 that were consistent with normal levels, with the improvement in vitality considered clinically meaningful versus placebo.
Integrated data
In further analysis of integrated data from four zuranolone clinical trials in the NEST and LANDSCAPE programs for patients with MDD and postpartum depression, results showed similar improvements at day 15 for zuranolone in QoL and overall health across all of the SF-36v2 functioning and well-being domains (P <.05), with the exceptions of physical measure and bodily pain.
By day 42, all of the domains showed significantly greater improvement with zuranolone versus placebo (all, P <.05).
Among the strongest score improvements in the integrated trials were measures in social functioning, which improved from baseline scores of 29.66 to 42.82 on day 15 and to 43.59 on day 42.
Emotional domain scores improved from 24.43 at baseline to 39.13 on day 15 and to 39.82 on day 42. For mental health, the integrated scores for the zuranolone group improved from 27.13 at baseline to 42.40 on day 15 and 42.62 on day 42.
Of note, the baseline scores for mental health represented just 54.3% of those in the normal population; with the increase at day 15, the level was 84.8% of the normal population.
“Across four completed placebo-controlled NEST and LANDSCAPE clinical trials, patient reports of functional health and well-being as assessed by the SF-36v2 indicated substantial impairment at baseline compared to the population norm,” the researchers reported.
The improvements are especially important in light of the fact that in some patients with MDD, functional improvement is a top priority.
“Patients have often prioritized returning to their usual level of functioning over reduction in depressive symptoms, and functional recovery has been associated with better prognosis of depression,” the investigators wrote.
Zuranolone trials have shown that treatment-emergent adverse events (AEs) occur among about 60% of patients, versus about 44% with placebo. The most common AEs are somnolence, dizziness, headache, sedation, and diarrhea, with no increases in suicidal ideation or withdrawal.
The rates of severe AEs are low, and they are observed in about 3% of patients, versus 1.1% with placebo, the researchers noted.
Further, as opposed to serotonergic antidepressants such as SNRIs and SSRIs, zuranolone does not appear to have the undesirable side effects of decreased libido and sexual dysfunction, they added.
Clinically meaningful?
Andrew J. Cutler, MD, clinical associate professor of psychiatry at State University of New York, Syracuse, said the data are “very significant” for a number of reasons.
“We need more options to treat depression, especially ones with novel mechanisms of action and faster onset of efficacy, such as zuranolone,” said Dr. Cutler, who was not involved in the current study. He has coauthored other studies on zuranolone.
Regarding the study’s QoL outcomes, “while improvement in depressive symptoms is very important, what really matters to patients is improvement in function and quality of life,” Dr. Cutler noted.
Also commenting on the study, Jonathan E. Alpert, MD, PhD, chair of the department of psychiatry and behavioral sciences and professor of psychiatry, neuroscience, and pediatrics at Albert Einstein College of Medicine, New York, said the investigational drug could represent an important addition to the armamentarium for treating depression.
“Zuranolone has good oral bioavailability and would represent the first neuroactive steroid antidepressant available in oral form and, indeed, the first non–monoamine-based antidepressant available in oral form,” he said in an interview.
Dr. Alpert was not involved in the research and has no relationship with the drug’s development.
He noted that although there are modest differences between the patients who received zuranolone and those who received placebo in the trials, “this may have been related to high placebo response rates, which often complicate antidepressant trials.
“Further research is needed to determine whether differences between zuranolone and placebo are clinically meaningful, though the separation between drug and placebo on the primary endpoint, as well as some other measures, such as quality of life measures, is promising,” Dr. Alpert said.
However, he added that comparisons with other active antidepressants in terms of efficacy and tolerability remain to be seen.
“Given the large number of individuals with major depressive disorder who have incomplete response to or do not tolerate monoaminergic antidepressants, the development of agents that leverage novel nonmonoaminergic mechanisms is important,” Dr. Alpert concluded.
The study was funded by Sage Therapeutics and Biogen. Dr. Cutler has been involved in research of zuranolone for Sage Therapeutics. Dr. Alpert has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
DENVER –
In a phase 3 trial that included more than 500 adult patients with MDD, those who received zuranolone for 14 days showed greater improvement at day 15 across numerous QoL outcomes, compared with their counterparts in the placebo group.
In addition, combined analysis of four zuranolone clinical trials showed “mental well-being and functioning improved to near general population norm levels” for the active-treatment group, reported the researchers, led by Anita H. Clayton, MD, chair and professor of psychiatry, University of Virginia, Charlottesville.
“Based on these integrated analyses, the benefit of treatment with zuranolone may extend beyond reduction in depressive symptoms to include potential improvement in quality of life and overall health, as perceived by patients,” they add.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
First oral formulation
Zuranolone represents the second entry in the new class of neuroactive steroid drugs, which modulate GABA-A receptor activity – but it would be the first to have an oral formulation. Brexanolone, which was approved by the Food and Drug Administration in 2019 for postpartum depression, is administered through continuous IV infusion over 60 hours.
As previously reported by this news organization, zuranolone improved depressive symptoms as early as day 3, achieving the primary endpoint of significantly greater reduction in scores on the 17-item Hamilton Rating Scale for Depression from baseline to day 15 versus placebo (P = .014).
In the new analysis, patient-reported measures of functional health and well-being were assessed in the WATERFALL trial. It included 266 patients with MDD who were treated with zuranolone 50 mg daily for 2 weeks and 268 patients with MDD who were treated with placebo.
The study used the Short Form–36 (SF-36v2), which covers a wide range of patient-reported measures, including physical function, bodily pain, general health, vitality, social function, and “role-emotional” symptoms.
Results showed that although the treatment and placebo groups had similar baseline SF-36v2 scores, those receiving zuranolone reported significantly greater improvements at day 15 in almost all of the assessment’s domains, including physical function (treatment difference, 0.8), general health (1.0), vitality (3.1), social functioning (1.1), and role-emotional symptoms (1.5; for all comparisons, P < .05). The only exceptions were in role-physical symptoms and bodily pain.
In measures that included physical function, bodily pain, and general health, the patients achieved improvements at day 15 that were consistent with normal levels, with the improvement in vitality considered clinically meaningful versus placebo.
Integrated data
In further analysis of integrated data from four zuranolone clinical trials in the NEST and LANDSCAPE programs for patients with MDD and postpartum depression, results showed similar improvements at day 15 for zuranolone in QoL and overall health across all of the SF-36v2 functioning and well-being domains (P <.05), with the exceptions of physical measure and bodily pain.
By day 42, all of the domains showed significantly greater improvement with zuranolone versus placebo (all, P <.05).
Among the strongest score improvements in the integrated trials were measures in social functioning, which improved from baseline scores of 29.66 to 42.82 on day 15 and to 43.59 on day 42.
Emotional domain scores improved from 24.43 at baseline to 39.13 on day 15 and to 39.82 on day 42. For mental health, the integrated scores for the zuranolone group improved from 27.13 at baseline to 42.40 on day 15 and 42.62 on day 42.
Of note, the baseline scores for mental health represented just 54.3% of those in the normal population; with the increase at day 15, the level was 84.8% of the normal population.
“Across four completed placebo-controlled NEST and LANDSCAPE clinical trials, patient reports of functional health and well-being as assessed by the SF-36v2 indicated substantial impairment at baseline compared to the population norm,” the researchers reported.
The improvements are especially important in light of the fact that in some patients with MDD, functional improvement is a top priority.
“Patients have often prioritized returning to their usual level of functioning over reduction in depressive symptoms, and functional recovery has been associated with better prognosis of depression,” the investigators wrote.
Zuranolone trials have shown that treatment-emergent adverse events (AEs) occur among about 60% of patients, versus about 44% with placebo. The most common AEs are somnolence, dizziness, headache, sedation, and diarrhea, with no increases in suicidal ideation or withdrawal.
The rates of severe AEs are low, and they are observed in about 3% of patients, versus 1.1% with placebo, the researchers noted.
Further, as opposed to serotonergic antidepressants such as SNRIs and SSRIs, zuranolone does not appear to have the undesirable side effects of decreased libido and sexual dysfunction, they added.
Clinically meaningful?
Andrew J. Cutler, MD, clinical associate professor of psychiatry at State University of New York, Syracuse, said the data are “very significant” for a number of reasons.
“We need more options to treat depression, especially ones with novel mechanisms of action and faster onset of efficacy, such as zuranolone,” said Dr. Cutler, who was not involved in the current study. He has coauthored other studies on zuranolone.
Regarding the study’s QoL outcomes, “while improvement in depressive symptoms is very important, what really matters to patients is improvement in function and quality of life,” Dr. Cutler noted.
Also commenting on the study, Jonathan E. Alpert, MD, PhD, chair of the department of psychiatry and behavioral sciences and professor of psychiatry, neuroscience, and pediatrics at Albert Einstein College of Medicine, New York, said the investigational drug could represent an important addition to the armamentarium for treating depression.
“Zuranolone has good oral bioavailability and would represent the first neuroactive steroid antidepressant available in oral form and, indeed, the first non–monoamine-based antidepressant available in oral form,” he said in an interview.
Dr. Alpert was not involved in the research and has no relationship with the drug’s development.
He noted that although there are modest differences between the patients who received zuranolone and those who received placebo in the trials, “this may have been related to high placebo response rates, which often complicate antidepressant trials.
“Further research is needed to determine whether differences between zuranolone and placebo are clinically meaningful, though the separation between drug and placebo on the primary endpoint, as well as some other measures, such as quality of life measures, is promising,” Dr. Alpert said.
However, he added that comparisons with other active antidepressants in terms of efficacy and tolerability remain to be seen.
“Given the large number of individuals with major depressive disorder who have incomplete response to or do not tolerate monoaminergic antidepressants, the development of agents that leverage novel nonmonoaminergic mechanisms is important,” Dr. Alpert concluded.
The study was funded by Sage Therapeutics and Biogen. Dr. Cutler has been involved in research of zuranolone for Sage Therapeutics. Dr. Alpert has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
DENVER –
In a phase 3 trial that included more than 500 adult patients with MDD, those who received zuranolone for 14 days showed greater improvement at day 15 across numerous QoL outcomes, compared with their counterparts in the placebo group.
In addition, combined analysis of four zuranolone clinical trials showed “mental well-being and functioning improved to near general population norm levels” for the active-treatment group, reported the researchers, led by Anita H. Clayton, MD, chair and professor of psychiatry, University of Virginia, Charlottesville.
“Based on these integrated analyses, the benefit of treatment with zuranolone may extend beyond reduction in depressive symptoms to include potential improvement in quality of life and overall health, as perceived by patients,” they add.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
First oral formulation
Zuranolone represents the second entry in the new class of neuroactive steroid drugs, which modulate GABA-A receptor activity – but it would be the first to have an oral formulation. Brexanolone, which was approved by the Food and Drug Administration in 2019 for postpartum depression, is administered through continuous IV infusion over 60 hours.
As previously reported by this news organization, zuranolone improved depressive symptoms as early as day 3, achieving the primary endpoint of significantly greater reduction in scores on the 17-item Hamilton Rating Scale for Depression from baseline to day 15 versus placebo (P = .014).
In the new analysis, patient-reported measures of functional health and well-being were assessed in the WATERFALL trial. It included 266 patients with MDD who were treated with zuranolone 50 mg daily for 2 weeks and 268 patients with MDD who were treated with placebo.
The study used the Short Form–36 (SF-36v2), which covers a wide range of patient-reported measures, including physical function, bodily pain, general health, vitality, social function, and “role-emotional” symptoms.
Results showed that although the treatment and placebo groups had similar baseline SF-36v2 scores, those receiving zuranolone reported significantly greater improvements at day 15 in almost all of the assessment’s domains, including physical function (treatment difference, 0.8), general health (1.0), vitality (3.1), social functioning (1.1), and role-emotional symptoms (1.5; for all comparisons, P < .05). The only exceptions were in role-physical symptoms and bodily pain.
In measures that included physical function, bodily pain, and general health, the patients achieved improvements at day 15 that were consistent with normal levels, with the improvement in vitality considered clinically meaningful versus placebo.
Integrated data
In further analysis of integrated data from four zuranolone clinical trials in the NEST and LANDSCAPE programs for patients with MDD and postpartum depression, results showed similar improvements at day 15 for zuranolone in QoL and overall health across all of the SF-36v2 functioning and well-being domains (P <.05), with the exceptions of physical measure and bodily pain.
By day 42, all of the domains showed significantly greater improvement with zuranolone versus placebo (all, P <.05).
Among the strongest score improvements in the integrated trials were measures in social functioning, which improved from baseline scores of 29.66 to 42.82 on day 15 and to 43.59 on day 42.
Emotional domain scores improved from 24.43 at baseline to 39.13 on day 15 and to 39.82 on day 42. For mental health, the integrated scores for the zuranolone group improved from 27.13 at baseline to 42.40 on day 15 and 42.62 on day 42.
Of note, the baseline scores for mental health represented just 54.3% of those in the normal population; with the increase at day 15, the level was 84.8% of the normal population.
“Across four completed placebo-controlled NEST and LANDSCAPE clinical trials, patient reports of functional health and well-being as assessed by the SF-36v2 indicated substantial impairment at baseline compared to the population norm,” the researchers reported.
The improvements are especially important in light of the fact that in some patients with MDD, functional improvement is a top priority.
“Patients have often prioritized returning to their usual level of functioning over reduction in depressive symptoms, and functional recovery has been associated with better prognosis of depression,” the investigators wrote.
Zuranolone trials have shown that treatment-emergent adverse events (AEs) occur among about 60% of patients, versus about 44% with placebo. The most common AEs are somnolence, dizziness, headache, sedation, and diarrhea, with no increases in suicidal ideation or withdrawal.
The rates of severe AEs are low, and they are observed in about 3% of patients, versus 1.1% with placebo, the researchers noted.
Further, as opposed to serotonergic antidepressants such as SNRIs and SSRIs, zuranolone does not appear to have the undesirable side effects of decreased libido and sexual dysfunction, they added.
Clinically meaningful?
Andrew J. Cutler, MD, clinical associate professor of psychiatry at State University of New York, Syracuse, said the data are “very significant” for a number of reasons.
“We need more options to treat depression, especially ones with novel mechanisms of action and faster onset of efficacy, such as zuranolone,” said Dr. Cutler, who was not involved in the current study. He has coauthored other studies on zuranolone.
Regarding the study’s QoL outcomes, “while improvement in depressive symptoms is very important, what really matters to patients is improvement in function and quality of life,” Dr. Cutler noted.
Also commenting on the study, Jonathan E. Alpert, MD, PhD, chair of the department of psychiatry and behavioral sciences and professor of psychiatry, neuroscience, and pediatrics at Albert Einstein College of Medicine, New York, said the investigational drug could represent an important addition to the armamentarium for treating depression.
“Zuranolone has good oral bioavailability and would represent the first neuroactive steroid antidepressant available in oral form and, indeed, the first non–monoamine-based antidepressant available in oral form,” he said in an interview.
Dr. Alpert was not involved in the research and has no relationship with the drug’s development.
He noted that although there are modest differences between the patients who received zuranolone and those who received placebo in the trials, “this may have been related to high placebo response rates, which often complicate antidepressant trials.
“Further research is needed to determine whether differences between zuranolone and placebo are clinically meaningful, though the separation between drug and placebo on the primary endpoint, as well as some other measures, such as quality of life measures, is promising,” Dr. Alpert said.
However, he added that comparisons with other active antidepressants in terms of efficacy and tolerability remain to be seen.
“Given the large number of individuals with major depressive disorder who have incomplete response to or do not tolerate monoaminergic antidepressants, the development of agents that leverage novel nonmonoaminergic mechanisms is important,” Dr. Alpert concluded.
The study was funded by Sage Therapeutics and Biogen. Dr. Cutler has been involved in research of zuranolone for Sage Therapeutics. Dr. Alpert has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ADAA 2022
Performance anxiety highly common among surgeons
a new study of surgeons in the United Kingdom shows.
“Performance anxiety or stage fright is a widely recognized problem in music and sports, and there are many similarities between these arenas and the operating theater,” first author Robert Miller, MRCS, of the Surgical Psychology and Performance Group and the department of plastic and reconstructive surgery at St. George’s Hospital NHS Trust, London, said in an interview. “We were aware of it anecdotally in a surgical context, but for one reason or another, perhaps professional pride and fear of negative perception, this is rarely openly discussed amongst surgeons.”
In the cross-sectional study, published in Annals of Surgery, Dr. Miller and colleagues surveyed surgeons in all specialties working in the United Kingdom who had at least 1 year of postgraduate surgical training.
Of a total of 631 responses received, 523 (83%) were included in the analysis. The median age of those who responded was 41.2 years, and the mean duration of surgical experience was 15.3 years (range, 1-52 years). Among them, 62% were men, and 52% were of consultant/attending grade.
All of the respondents – 100% – said they believed that performance anxiety affected surgeons, 87% reported having experienced it themselves, and 65% said they felt that performance anxiety had an effect on their surgical performance.
Both male and female surgeons who reported experiencing performance anxiety had significantly worse mental well-being, as assessed using the Short Warwick Edinburgh Mental Wellbeing Scale, compared with those who did not have performance anxiety (P < .0001 for men and P < .001 for women).
Overall, however, male surgeons had significantly better mental well-being, compared with female surgeons (P = .003), yet both genders had significantly lower mental well-being scores compared with U.K. population norms (P = .0019 for men and P = .0001 for women).
The gender differences are “clearly an important topic, which is likely multifactorial,” Dr. Miller told this news organization. “The gender well-being gap requires more in-depth research, and qualitative work involving female surgeons is critical.”
Surgical perfectionism was significantly more common among respondents who did have performance anxiety in comparison with those who did not (P < .0001).
“Although perfectionism may be a beneficial trait in surgery, our findings from hierarchical multiple regression analysis also indicate that perfectionism, [as well as] sex and experience, may drive surgical performance anxiety and help predict those experiencing [the anxiety],” the authors noted.
Performing in presence of colleagues a key trigger
By far, the leading trigger that was identified as prompting surgeon performance anxiety was the presence – and scrutiny – of colleagues within the parent specialty. This was reported by 151 respondents. Other triggers were having to perform on highly complex or high-risk cases (66 responses) and a lack of experience (30 responses).
Next to planning and preparation, opening up and talking about the anxiety and shedding light on the issue was seen as a leading strategy to help with the problem, but very few respondents reported openly sharing their struggles. Only 9% reported that they had shared it openly; 27% said they had confided in someone, and 47% did not respond to the question.
“I wish we talked about it more and shared our insecurities,” one respondent lamented. “Most of my colleagues pretend they are living gods.”
Only about 45% of respondents reported a specific technique for overcoming their anxiety. In addition to being open about the problem, other techniques included self-care, such as exercise; and distraction outside of work to get perspective; relaxation techniques such as deep or controlled breathing; music; mindfulness; and positive self-statements.
About 9% said they had received psychological counseling for performance anxiety, and only 3% reported using medication for the problem.
Anxiety a positive factor?
Surprisingly, 70% of respondents reported feeling that surgical performance anxiety could have a positive impact on surgical performance, which the authors noted is consistent with some theories.
“This may be explained by the traditional bell-curve relationship between arousal and performance, which describes a dose-dependent relationship between performance and arousal until a ‘tipping point,’ after which performance declines,” the authors explained. “A heightened awareness secondary to anxiety may be beneficial, but at high doses, anxiety can negatively affect attentional control and cause somatic symptoms.”
They noted that “the challenge would be to reap the benefits of low-level stimulation without incurring possible adverse effects.”
Dr. Miller said that, in determining whether selection bias had a role in the results, a detailed analysis showed that “our respondents were not skewed to those with only high levels of trait anxiety.
“We also had a good spread of consultants versus trainees [about half and half], and different specialties, so we feel this is likely to be a representative sample,” he told this news organization.
That being said, the results underscore the need for increased awareness – and open discussion – of the issue of surgical performance anxiety.
“Within other professions, particularly the performing arts and sports, performance psychology is becoming an integral part of training and development,” Dr. Miller said. “We feel surgeons should be supported in a similar manner.
“Surgical performance anxiety is normal for surgeons at all levels and not something to be ashamed about,” Dr. Miller added. “Talk about it, acknowledge it, and be supportive to your colleagues.”
Many keep it to themselves in ‘prevailing culture of stoicism’
Commenting on the study, Carter C. Lebares, MD, an associate professor of surgery and director of the Center for Mindfulness in Surgery, department of surgery, University of California, San Francisco, said she was not surprised to see the high rates of performance anxiety among surgeons.
“As surgeons, no matter how hard we train or how thoroughly we prepare our intellectual understanding or the patient, the disease process, and the operation, there may be surprises, unforeseen challenges, or off days,” Dr. Lebares said.
“And whatever we encounter, we are managing these things directly under the scrutiny of others – people who can affect our reputation, operating privileges, and mental health. So, I am not surprised this is a prevalent and widely recognized issue.”
Dr. Lebares noted that the reluctance to share the anxiety is part of a “challenging and recognized conundrum in both medicine and surgery and is a matter of the prevailing culture of stoicism.
“We often are called to shoulder tremendous weight intraoperatively (having perseverance, self-confidence, or sustained focus), and in owning the weight of complications (which eventually we all will have),” she said.
“So, we do need to be strong and not complain, [but] we also need to be able to set that aside [when appropriate] and ask for help or allow others to shoulder the weight for a while, and this is not [yet] a common part of surgical culture.”
Dr. Lebares added that randomized, controlled trials have shown benefits of mindfulness interventions on burnout and anxiety.
“We have observed positive effects on mental noise, self-perception, conflict resolution, and resilience in surgical residents trained in mindfulness-based cognitive skills,” she said. “[Residents] report applying these skills in the OR, in their home lives, and in how they approach their training/education.”
The authors disclosed no relevant financial relationships. Dr. Lebares has developed mindfulness-based cognitive skills training for surgeons but receives no financial compensation for the activities.
A version of this article first appeared on Medscape.com.
a new study of surgeons in the United Kingdom shows.
“Performance anxiety or stage fright is a widely recognized problem in music and sports, and there are many similarities between these arenas and the operating theater,” first author Robert Miller, MRCS, of the Surgical Psychology and Performance Group and the department of plastic and reconstructive surgery at St. George’s Hospital NHS Trust, London, said in an interview. “We were aware of it anecdotally in a surgical context, but for one reason or another, perhaps professional pride and fear of negative perception, this is rarely openly discussed amongst surgeons.”
In the cross-sectional study, published in Annals of Surgery, Dr. Miller and colleagues surveyed surgeons in all specialties working in the United Kingdom who had at least 1 year of postgraduate surgical training.
Of a total of 631 responses received, 523 (83%) were included in the analysis. The median age of those who responded was 41.2 years, and the mean duration of surgical experience was 15.3 years (range, 1-52 years). Among them, 62% were men, and 52% were of consultant/attending grade.
All of the respondents – 100% – said they believed that performance anxiety affected surgeons, 87% reported having experienced it themselves, and 65% said they felt that performance anxiety had an effect on their surgical performance.
Both male and female surgeons who reported experiencing performance anxiety had significantly worse mental well-being, as assessed using the Short Warwick Edinburgh Mental Wellbeing Scale, compared with those who did not have performance anxiety (P < .0001 for men and P < .001 for women).
Overall, however, male surgeons had significantly better mental well-being, compared with female surgeons (P = .003), yet both genders had significantly lower mental well-being scores compared with U.K. population norms (P = .0019 for men and P = .0001 for women).
The gender differences are “clearly an important topic, which is likely multifactorial,” Dr. Miller told this news organization. “The gender well-being gap requires more in-depth research, and qualitative work involving female surgeons is critical.”
Surgical perfectionism was significantly more common among respondents who did have performance anxiety in comparison with those who did not (P < .0001).
“Although perfectionism may be a beneficial trait in surgery, our findings from hierarchical multiple regression analysis also indicate that perfectionism, [as well as] sex and experience, may drive surgical performance anxiety and help predict those experiencing [the anxiety],” the authors noted.
Performing in presence of colleagues a key trigger
By far, the leading trigger that was identified as prompting surgeon performance anxiety was the presence – and scrutiny – of colleagues within the parent specialty. This was reported by 151 respondents. Other triggers were having to perform on highly complex or high-risk cases (66 responses) and a lack of experience (30 responses).
Next to planning and preparation, opening up and talking about the anxiety and shedding light on the issue was seen as a leading strategy to help with the problem, but very few respondents reported openly sharing their struggles. Only 9% reported that they had shared it openly; 27% said they had confided in someone, and 47% did not respond to the question.
“I wish we talked about it more and shared our insecurities,” one respondent lamented. “Most of my colleagues pretend they are living gods.”
Only about 45% of respondents reported a specific technique for overcoming their anxiety. In addition to being open about the problem, other techniques included self-care, such as exercise; and distraction outside of work to get perspective; relaxation techniques such as deep or controlled breathing; music; mindfulness; and positive self-statements.
About 9% said they had received psychological counseling for performance anxiety, and only 3% reported using medication for the problem.
Anxiety a positive factor?
Surprisingly, 70% of respondents reported feeling that surgical performance anxiety could have a positive impact on surgical performance, which the authors noted is consistent with some theories.
“This may be explained by the traditional bell-curve relationship between arousal and performance, which describes a dose-dependent relationship between performance and arousal until a ‘tipping point,’ after which performance declines,” the authors explained. “A heightened awareness secondary to anxiety may be beneficial, but at high doses, anxiety can negatively affect attentional control and cause somatic symptoms.”
They noted that “the challenge would be to reap the benefits of low-level stimulation without incurring possible adverse effects.”
Dr. Miller said that, in determining whether selection bias had a role in the results, a detailed analysis showed that “our respondents were not skewed to those with only high levels of trait anxiety.
“We also had a good spread of consultants versus trainees [about half and half], and different specialties, so we feel this is likely to be a representative sample,” he told this news organization.
That being said, the results underscore the need for increased awareness – and open discussion – of the issue of surgical performance anxiety.
“Within other professions, particularly the performing arts and sports, performance psychology is becoming an integral part of training and development,” Dr. Miller said. “We feel surgeons should be supported in a similar manner.
“Surgical performance anxiety is normal for surgeons at all levels and not something to be ashamed about,” Dr. Miller added. “Talk about it, acknowledge it, and be supportive to your colleagues.”
Many keep it to themselves in ‘prevailing culture of stoicism’
Commenting on the study, Carter C. Lebares, MD, an associate professor of surgery and director of the Center for Mindfulness in Surgery, department of surgery, University of California, San Francisco, said she was not surprised to see the high rates of performance anxiety among surgeons.
“As surgeons, no matter how hard we train or how thoroughly we prepare our intellectual understanding or the patient, the disease process, and the operation, there may be surprises, unforeseen challenges, or off days,” Dr. Lebares said.
“And whatever we encounter, we are managing these things directly under the scrutiny of others – people who can affect our reputation, operating privileges, and mental health. So, I am not surprised this is a prevalent and widely recognized issue.”
Dr. Lebares noted that the reluctance to share the anxiety is part of a “challenging and recognized conundrum in both medicine and surgery and is a matter of the prevailing culture of stoicism.
“We often are called to shoulder tremendous weight intraoperatively (having perseverance, self-confidence, or sustained focus), and in owning the weight of complications (which eventually we all will have),” she said.
“So, we do need to be strong and not complain, [but] we also need to be able to set that aside [when appropriate] and ask for help or allow others to shoulder the weight for a while, and this is not [yet] a common part of surgical culture.”
Dr. Lebares added that randomized, controlled trials have shown benefits of mindfulness interventions on burnout and anxiety.
“We have observed positive effects on mental noise, self-perception, conflict resolution, and resilience in surgical residents trained in mindfulness-based cognitive skills,” she said. “[Residents] report applying these skills in the OR, in their home lives, and in how they approach their training/education.”
The authors disclosed no relevant financial relationships. Dr. Lebares has developed mindfulness-based cognitive skills training for surgeons but receives no financial compensation for the activities.
A version of this article first appeared on Medscape.com.
a new study of surgeons in the United Kingdom shows.
“Performance anxiety or stage fright is a widely recognized problem in music and sports, and there are many similarities between these arenas and the operating theater,” first author Robert Miller, MRCS, of the Surgical Psychology and Performance Group and the department of plastic and reconstructive surgery at St. George’s Hospital NHS Trust, London, said in an interview. “We were aware of it anecdotally in a surgical context, but for one reason or another, perhaps professional pride and fear of negative perception, this is rarely openly discussed amongst surgeons.”
In the cross-sectional study, published in Annals of Surgery, Dr. Miller and colleagues surveyed surgeons in all specialties working in the United Kingdom who had at least 1 year of postgraduate surgical training.
Of a total of 631 responses received, 523 (83%) were included in the analysis. The median age of those who responded was 41.2 years, and the mean duration of surgical experience was 15.3 years (range, 1-52 years). Among them, 62% were men, and 52% were of consultant/attending grade.
All of the respondents – 100% – said they believed that performance anxiety affected surgeons, 87% reported having experienced it themselves, and 65% said they felt that performance anxiety had an effect on their surgical performance.
Both male and female surgeons who reported experiencing performance anxiety had significantly worse mental well-being, as assessed using the Short Warwick Edinburgh Mental Wellbeing Scale, compared with those who did not have performance anxiety (P < .0001 for men and P < .001 for women).
Overall, however, male surgeons had significantly better mental well-being, compared with female surgeons (P = .003), yet both genders had significantly lower mental well-being scores compared with U.K. population norms (P = .0019 for men and P = .0001 for women).
The gender differences are “clearly an important topic, which is likely multifactorial,” Dr. Miller told this news organization. “The gender well-being gap requires more in-depth research, and qualitative work involving female surgeons is critical.”
Surgical perfectionism was significantly more common among respondents who did have performance anxiety in comparison with those who did not (P < .0001).
“Although perfectionism may be a beneficial trait in surgery, our findings from hierarchical multiple regression analysis also indicate that perfectionism, [as well as] sex and experience, may drive surgical performance anxiety and help predict those experiencing [the anxiety],” the authors noted.
Performing in presence of colleagues a key trigger
By far, the leading trigger that was identified as prompting surgeon performance anxiety was the presence – and scrutiny – of colleagues within the parent specialty. This was reported by 151 respondents. Other triggers were having to perform on highly complex or high-risk cases (66 responses) and a lack of experience (30 responses).
Next to planning and preparation, opening up and talking about the anxiety and shedding light on the issue was seen as a leading strategy to help with the problem, but very few respondents reported openly sharing their struggles. Only 9% reported that they had shared it openly; 27% said they had confided in someone, and 47% did not respond to the question.
“I wish we talked about it more and shared our insecurities,” one respondent lamented. “Most of my colleagues pretend they are living gods.”
Only about 45% of respondents reported a specific technique for overcoming their anxiety. In addition to being open about the problem, other techniques included self-care, such as exercise; and distraction outside of work to get perspective; relaxation techniques such as deep or controlled breathing; music; mindfulness; and positive self-statements.
About 9% said they had received psychological counseling for performance anxiety, and only 3% reported using medication for the problem.
Anxiety a positive factor?
Surprisingly, 70% of respondents reported feeling that surgical performance anxiety could have a positive impact on surgical performance, which the authors noted is consistent with some theories.
“This may be explained by the traditional bell-curve relationship between arousal and performance, which describes a dose-dependent relationship between performance and arousal until a ‘tipping point,’ after which performance declines,” the authors explained. “A heightened awareness secondary to anxiety may be beneficial, but at high doses, anxiety can negatively affect attentional control and cause somatic symptoms.”
They noted that “the challenge would be to reap the benefits of low-level stimulation without incurring possible adverse effects.”
Dr. Miller said that, in determining whether selection bias had a role in the results, a detailed analysis showed that “our respondents were not skewed to those with only high levels of trait anxiety.
“We also had a good spread of consultants versus trainees [about half and half], and different specialties, so we feel this is likely to be a representative sample,” he told this news organization.
That being said, the results underscore the need for increased awareness – and open discussion – of the issue of surgical performance anxiety.
“Within other professions, particularly the performing arts and sports, performance psychology is becoming an integral part of training and development,” Dr. Miller said. “We feel surgeons should be supported in a similar manner.
“Surgical performance anxiety is normal for surgeons at all levels and not something to be ashamed about,” Dr. Miller added. “Talk about it, acknowledge it, and be supportive to your colleagues.”
Many keep it to themselves in ‘prevailing culture of stoicism’
Commenting on the study, Carter C. Lebares, MD, an associate professor of surgery and director of the Center for Mindfulness in Surgery, department of surgery, University of California, San Francisco, said she was not surprised to see the high rates of performance anxiety among surgeons.
“As surgeons, no matter how hard we train or how thoroughly we prepare our intellectual understanding or the patient, the disease process, and the operation, there may be surprises, unforeseen challenges, or off days,” Dr. Lebares said.
“And whatever we encounter, we are managing these things directly under the scrutiny of others – people who can affect our reputation, operating privileges, and mental health. So, I am not surprised this is a prevalent and widely recognized issue.”
Dr. Lebares noted that the reluctance to share the anxiety is part of a “challenging and recognized conundrum in both medicine and surgery and is a matter of the prevailing culture of stoicism.
“We often are called to shoulder tremendous weight intraoperatively (having perseverance, self-confidence, or sustained focus), and in owning the weight of complications (which eventually we all will have),” she said.
“So, we do need to be strong and not complain, [but] we also need to be able to set that aside [when appropriate] and ask for help or allow others to shoulder the weight for a while, and this is not [yet] a common part of surgical culture.”
Dr. Lebares added that randomized, controlled trials have shown benefits of mindfulness interventions on burnout and anxiety.
“We have observed positive effects on mental noise, self-perception, conflict resolution, and resilience in surgical residents trained in mindfulness-based cognitive skills,” she said. “[Residents] report applying these skills in the OR, in their home lives, and in how they approach their training/education.”
The authors disclosed no relevant financial relationships. Dr. Lebares has developed mindfulness-based cognitive skills training for surgeons but receives no financial compensation for the activities.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF SURGERY
Progressive muscle relaxation outperforms mindfulness in reducing grief severity
DENVER –
“Both progressive muscle relaxation and mindfulness training were shown to improve grief severity, yearning, depression symptoms, and stress, [but] the results from this study suggest that progressive muscle relaxation is most effective, compared to a wait-list control condition for improving grief,” study investigator Lindsey Knowles, PhD, senior fellow, MS Center of Excellence, Veterans Affairs Puget Sound Health Care System, and University of Washington, Seattle, told this news organization.
“With replication, progressive muscle relaxation could be a standalone intervention for nondisordered grief or a component of treatment for disordered grief,” Dr. Knowles said.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Disordered grief
Approximately 10% of individuals grappling with loss “get stuck” in their grief and develop disordered grief, which is distinguished by repetitive thought processes of yearning and grief rumination, the investigators noted.
The researchers hypothesized that mindfulness training, which has been shown to reduce maladaptive repetitive thought, could be an effective intervention to prevent disordered grief.
To investigate, they enrolled 94 widows and widowers (mean age, 67.5 years) who were experiencing bereavement-related grief and were between 6 months and 4 years post loss.
The researchers compared a 6-week mindfulness intervention (n = 37) with a 6-week progressive muscle relaxation intervention (n = 35), Dr. Knowles said, because there has been speculation that benefits from mindfulness training may be related more to the relaxation response than to the actual mindfulness component.
Both study groups received the intervention in similar settings with matched instructors.
The mindfulness intervention sessions included 10-25 minutes of meditation and mindfulness practices. It also included instructions for home practice.
Participants in the progressive muscle relaxation group were trained to tense and relax the body’s various muscle groups with an end goal of learning to relax four key muscle groups without initial tensing.
A third group of patients were placed on a wait list with no intervention (n = 22).
Measures taken throughout the study interventions and at 1 month postintervention showed reductions in the study’s two primary outcomes of grief severity and yearning for both interventions versus baseline (P = < .003).
However, only the progressive muscle relaxation group had a significantly greater reduction in grief severity vs the wait-list control group (P = .020).
The muscle relaxation group also showed lower grief severity at 1month follow-up versus the wait-list group (P = .049) – with a value at that time falling below an established cutoff for complicated grief, based on the Revised Inventory of Complicated Grief.
All three treatment groups showed a drop in the third primary outcome of grief rumination (P < .001).
Secondary outcomes of depression and stress were reduced in both active study groups versus the wait-list group (P = .028). Sleep quality also improved in both active intervention groups.
Simple technique
Dr. Knowles said the study’s findings were unexpected.
“We had hypothesized that mindfulness training would outperform progressive muscle relaxation and wait-list for improving grief outcomes,” she said.
Mindfulness experts underscore that a state of global relaxation is considered integral to the benefits of mindfulness, which could explain the benefits of progressive muscle relaxation, Dr. Knowles noted.
Importantly, progressive muscle relaxation has a key advantage: It is quickly and easily learned, which may partially explain the study’s findings, she added.
“Progressive muscle relaxation is a relatively simple technique, so it is also likely that participants were able to master [the technique] over the 6-week intervention,” Dr. Knowles said. “On the other hand, the mindfulness intervention was an introduction to mindfulness, and mastery was not expected or likely over the 6-week intervention.”
Either way, the results shed important light on a potentially beneficial grief intervention.
“Although mindfulness training and progressive muscle relaxation practices may both be perceived as relaxing, mastering progressive muscle relaxation may in fact enable people to maintain better focus in the present moment and generalize nonreactive awareness to both positively and negatively balanced phenomena,” Dr. Knowles said.
However, “more research is necessary to clarify how progressive muscle relaxation improves grief outcomes in widows and widowers.”
CNS benefits?
Zoe Donaldson, PhD, assistant professor in behavioral neuroscience, department of psychology and neuroscience, University of Colorado, Boulder, said the study is important for ongoing efforts in finding effective therapies for grief.
“We often struggle to try to help those experiencing the pain of loss and this study suggests a discrete set of exercises that may help,” said Dr. Donaldson, who was not involved with the research.
She also described the study results as surprising, and speculated that a combination of factors could explain the findings.
“First, mindfulness is hard to achieve, so the moderate beneficial effects might increase with more substantial mindfulness training. Secondly, it is not clear why progressive muscle relaxation had an effect, but the focus and attention to detail may engage the central nervous system in a beneficial way that we don’t fully understand,” Dr. Donaldson said.
Importantly, it’s key to remember that grief is an individual condition when investigating therapies, Dr. Donaldson noted.
“We likely need to develop multiple interventions to help those who are grieving. Incorporating loss can take many forms,” she said.
The investigators and Dr. Donaldson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
DENVER –
“Both progressive muscle relaxation and mindfulness training were shown to improve grief severity, yearning, depression symptoms, and stress, [but] the results from this study suggest that progressive muscle relaxation is most effective, compared to a wait-list control condition for improving grief,” study investigator Lindsey Knowles, PhD, senior fellow, MS Center of Excellence, Veterans Affairs Puget Sound Health Care System, and University of Washington, Seattle, told this news organization.
“With replication, progressive muscle relaxation could be a standalone intervention for nondisordered grief or a component of treatment for disordered grief,” Dr. Knowles said.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Disordered grief
Approximately 10% of individuals grappling with loss “get stuck” in their grief and develop disordered grief, which is distinguished by repetitive thought processes of yearning and grief rumination, the investigators noted.
The researchers hypothesized that mindfulness training, which has been shown to reduce maladaptive repetitive thought, could be an effective intervention to prevent disordered grief.
To investigate, they enrolled 94 widows and widowers (mean age, 67.5 years) who were experiencing bereavement-related grief and were between 6 months and 4 years post loss.
The researchers compared a 6-week mindfulness intervention (n = 37) with a 6-week progressive muscle relaxation intervention (n = 35), Dr. Knowles said, because there has been speculation that benefits from mindfulness training may be related more to the relaxation response than to the actual mindfulness component.
Both study groups received the intervention in similar settings with matched instructors.
The mindfulness intervention sessions included 10-25 minutes of meditation and mindfulness practices. It also included instructions for home practice.
Participants in the progressive muscle relaxation group were trained to tense and relax the body’s various muscle groups with an end goal of learning to relax four key muscle groups without initial tensing.
A third group of patients were placed on a wait list with no intervention (n = 22).
Measures taken throughout the study interventions and at 1 month postintervention showed reductions in the study’s two primary outcomes of grief severity and yearning for both interventions versus baseline (P = < .003).
However, only the progressive muscle relaxation group had a significantly greater reduction in grief severity vs the wait-list control group (P = .020).
The muscle relaxation group also showed lower grief severity at 1month follow-up versus the wait-list group (P = .049) – with a value at that time falling below an established cutoff for complicated grief, based on the Revised Inventory of Complicated Grief.
All three treatment groups showed a drop in the third primary outcome of grief rumination (P < .001).
Secondary outcomes of depression and stress were reduced in both active study groups versus the wait-list group (P = .028). Sleep quality also improved in both active intervention groups.
Simple technique
Dr. Knowles said the study’s findings were unexpected.
“We had hypothesized that mindfulness training would outperform progressive muscle relaxation and wait-list for improving grief outcomes,” she said.
Mindfulness experts underscore that a state of global relaxation is considered integral to the benefits of mindfulness, which could explain the benefits of progressive muscle relaxation, Dr. Knowles noted.
Importantly, progressive muscle relaxation has a key advantage: It is quickly and easily learned, which may partially explain the study’s findings, she added.
“Progressive muscle relaxation is a relatively simple technique, so it is also likely that participants were able to master [the technique] over the 6-week intervention,” Dr. Knowles said. “On the other hand, the mindfulness intervention was an introduction to mindfulness, and mastery was not expected or likely over the 6-week intervention.”
Either way, the results shed important light on a potentially beneficial grief intervention.
“Although mindfulness training and progressive muscle relaxation practices may both be perceived as relaxing, mastering progressive muscle relaxation may in fact enable people to maintain better focus in the present moment and generalize nonreactive awareness to both positively and negatively balanced phenomena,” Dr. Knowles said.
However, “more research is necessary to clarify how progressive muscle relaxation improves grief outcomes in widows and widowers.”
CNS benefits?
Zoe Donaldson, PhD, assistant professor in behavioral neuroscience, department of psychology and neuroscience, University of Colorado, Boulder, said the study is important for ongoing efforts in finding effective therapies for grief.
“We often struggle to try to help those experiencing the pain of loss and this study suggests a discrete set of exercises that may help,” said Dr. Donaldson, who was not involved with the research.
She also described the study results as surprising, and speculated that a combination of factors could explain the findings.
“First, mindfulness is hard to achieve, so the moderate beneficial effects might increase with more substantial mindfulness training. Secondly, it is not clear why progressive muscle relaxation had an effect, but the focus and attention to detail may engage the central nervous system in a beneficial way that we don’t fully understand,” Dr. Donaldson said.
Importantly, it’s key to remember that grief is an individual condition when investigating therapies, Dr. Donaldson noted.
“We likely need to develop multiple interventions to help those who are grieving. Incorporating loss can take many forms,” she said.
The investigators and Dr. Donaldson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
DENVER –
“Both progressive muscle relaxation and mindfulness training were shown to improve grief severity, yearning, depression symptoms, and stress, [but] the results from this study suggest that progressive muscle relaxation is most effective, compared to a wait-list control condition for improving grief,” study investigator Lindsey Knowles, PhD, senior fellow, MS Center of Excellence, Veterans Affairs Puget Sound Health Care System, and University of Washington, Seattle, told this news organization.
“With replication, progressive muscle relaxation could be a standalone intervention for nondisordered grief or a component of treatment for disordered grief,” Dr. Knowles said.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Disordered grief
Approximately 10% of individuals grappling with loss “get stuck” in their grief and develop disordered grief, which is distinguished by repetitive thought processes of yearning and grief rumination, the investigators noted.
The researchers hypothesized that mindfulness training, which has been shown to reduce maladaptive repetitive thought, could be an effective intervention to prevent disordered grief.
To investigate, they enrolled 94 widows and widowers (mean age, 67.5 years) who were experiencing bereavement-related grief and were between 6 months and 4 years post loss.
The researchers compared a 6-week mindfulness intervention (n = 37) with a 6-week progressive muscle relaxation intervention (n = 35), Dr. Knowles said, because there has been speculation that benefits from mindfulness training may be related more to the relaxation response than to the actual mindfulness component.
Both study groups received the intervention in similar settings with matched instructors.
The mindfulness intervention sessions included 10-25 minutes of meditation and mindfulness practices. It also included instructions for home practice.
Participants in the progressive muscle relaxation group were trained to tense and relax the body’s various muscle groups with an end goal of learning to relax four key muscle groups without initial tensing.
A third group of patients were placed on a wait list with no intervention (n = 22).
Measures taken throughout the study interventions and at 1 month postintervention showed reductions in the study’s two primary outcomes of grief severity and yearning for both interventions versus baseline (P = < .003).
However, only the progressive muscle relaxation group had a significantly greater reduction in grief severity vs the wait-list control group (P = .020).
The muscle relaxation group also showed lower grief severity at 1month follow-up versus the wait-list group (P = .049) – with a value at that time falling below an established cutoff for complicated grief, based on the Revised Inventory of Complicated Grief.
All three treatment groups showed a drop in the third primary outcome of grief rumination (P < .001).
Secondary outcomes of depression and stress were reduced in both active study groups versus the wait-list group (P = .028). Sleep quality also improved in both active intervention groups.
Simple technique
Dr. Knowles said the study’s findings were unexpected.
“We had hypothesized that mindfulness training would outperform progressive muscle relaxation and wait-list for improving grief outcomes,” she said.
Mindfulness experts underscore that a state of global relaxation is considered integral to the benefits of mindfulness, which could explain the benefits of progressive muscle relaxation, Dr. Knowles noted.
Importantly, progressive muscle relaxation has a key advantage: It is quickly and easily learned, which may partially explain the study’s findings, she added.
“Progressive muscle relaxation is a relatively simple technique, so it is also likely that participants were able to master [the technique] over the 6-week intervention,” Dr. Knowles said. “On the other hand, the mindfulness intervention was an introduction to mindfulness, and mastery was not expected or likely over the 6-week intervention.”
Either way, the results shed important light on a potentially beneficial grief intervention.
“Although mindfulness training and progressive muscle relaxation practices may both be perceived as relaxing, mastering progressive muscle relaxation may in fact enable people to maintain better focus in the present moment and generalize nonreactive awareness to both positively and negatively balanced phenomena,” Dr. Knowles said.
However, “more research is necessary to clarify how progressive muscle relaxation improves grief outcomes in widows and widowers.”
CNS benefits?
Zoe Donaldson, PhD, assistant professor in behavioral neuroscience, department of psychology and neuroscience, University of Colorado, Boulder, said the study is important for ongoing efforts in finding effective therapies for grief.
“We often struggle to try to help those experiencing the pain of loss and this study suggests a discrete set of exercises that may help,” said Dr. Donaldson, who was not involved with the research.
She also described the study results as surprising, and speculated that a combination of factors could explain the findings.
“First, mindfulness is hard to achieve, so the moderate beneficial effects might increase with more substantial mindfulness training. Secondly, it is not clear why progressive muscle relaxation had an effect, but the focus and attention to detail may engage the central nervous system in a beneficial way that we don’t fully understand,” Dr. Donaldson said.
Importantly, it’s key to remember that grief is an individual condition when investigating therapies, Dr. Donaldson noted.
“We likely need to develop multiple interventions to help those who are grieving. Incorporating loss can take many forms,” she said.
The investigators and Dr. Donaldson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ADAA 2022