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FDA approves ‘rapid-acting’ oral drug for major depression
The U.S. Food and Drug Administration has approved the first oral N-methyl D-aspartate (NMDA) receptor antagonist for the treatment of major depressive disorder (MDD) in adults, its manufacturer has announced.
Auvelity (Axsome Therapeutics) is a proprietary extended-release oral tablet containing dextromethorphan (45 mg) and bupropion (105 mg).
,” the company said in a news release.
“The approval of Auvelity represents a milestone in depression treatment based on its novel oral NMDA antagonist mechanism, its rapid antidepressant efficacy demonstrated in controlled trials, and a relatively favorable safety profile,” Maurizio Fava, MD, psychiatrist-in-chief, Massachusetts General Hospital, Boston, added in the release.
‘Milestone’ in depression treatment?
Dr. Fava noted that nearly two-thirds of patients treated with currently available antidepressants fail to respond adequately, and those who do may not achieve clinically meaningful responses for up to 6-8 weeks.
“Given the debilitating nature of depression, the efficacy of Auvelity observed at 1 week and sustained thereafter may have a significant impact on the current treatment paradigm for this condition,” he said.
The company noted the drug was studied in a comprehensive clinical program that included more than 1,100 patients with MDD.
The efficacy of the drug was demonstrated in the GEMINI placebo-controlled study – with confirmatory evidence provided by the ASCEND study, which compared it with bupropion sustained-release tablets.
Axsome said it expects to launch the new oral medication in the fourth quarter of this year. It is not approved for use in children.
The full prescribing information and medication guide are available online.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved the first oral N-methyl D-aspartate (NMDA) receptor antagonist for the treatment of major depressive disorder (MDD) in adults, its manufacturer has announced.
Auvelity (Axsome Therapeutics) is a proprietary extended-release oral tablet containing dextromethorphan (45 mg) and bupropion (105 mg).
,” the company said in a news release.
“The approval of Auvelity represents a milestone in depression treatment based on its novel oral NMDA antagonist mechanism, its rapid antidepressant efficacy demonstrated in controlled trials, and a relatively favorable safety profile,” Maurizio Fava, MD, psychiatrist-in-chief, Massachusetts General Hospital, Boston, added in the release.
‘Milestone’ in depression treatment?
Dr. Fava noted that nearly two-thirds of patients treated with currently available antidepressants fail to respond adequately, and those who do may not achieve clinically meaningful responses for up to 6-8 weeks.
“Given the debilitating nature of depression, the efficacy of Auvelity observed at 1 week and sustained thereafter may have a significant impact on the current treatment paradigm for this condition,” he said.
The company noted the drug was studied in a comprehensive clinical program that included more than 1,100 patients with MDD.
The efficacy of the drug was demonstrated in the GEMINI placebo-controlled study – with confirmatory evidence provided by the ASCEND study, which compared it with bupropion sustained-release tablets.
Axsome said it expects to launch the new oral medication in the fourth quarter of this year. It is not approved for use in children.
The full prescribing information and medication guide are available online.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved the first oral N-methyl D-aspartate (NMDA) receptor antagonist for the treatment of major depressive disorder (MDD) in adults, its manufacturer has announced.
Auvelity (Axsome Therapeutics) is a proprietary extended-release oral tablet containing dextromethorphan (45 mg) and bupropion (105 mg).
,” the company said in a news release.
“The approval of Auvelity represents a milestone in depression treatment based on its novel oral NMDA antagonist mechanism, its rapid antidepressant efficacy demonstrated in controlled trials, and a relatively favorable safety profile,” Maurizio Fava, MD, psychiatrist-in-chief, Massachusetts General Hospital, Boston, added in the release.
‘Milestone’ in depression treatment?
Dr. Fava noted that nearly two-thirds of patients treated with currently available antidepressants fail to respond adequately, and those who do may not achieve clinically meaningful responses for up to 6-8 weeks.
“Given the debilitating nature of depression, the efficacy of Auvelity observed at 1 week and sustained thereafter may have a significant impact on the current treatment paradigm for this condition,” he said.
The company noted the drug was studied in a comprehensive clinical program that included more than 1,100 patients with MDD.
The efficacy of the drug was demonstrated in the GEMINI placebo-controlled study – with confirmatory evidence provided by the ASCEND study, which compared it with bupropion sustained-release tablets.
Axsome said it expects to launch the new oral medication in the fourth quarter of this year. It is not approved for use in children.
The full prescribing information and medication guide are available online.
A version of this article first appeared on Medscape.com.
Postpartum depression risk higher with family psych history
Mothers who have a family history of any psychiatric disorder have almost two times the risk of postpartum depression as do mothers without such history, according to a new study.
Mette-Marie Zacher Kjeldsen, MSc, with the National Centre for Register-based Research at Aarhus (Denmark) University, led the study, a meta-analysis that included 26 studies with information on 100,877 women.
Findings were published online in JAMA Psychiatry.
When mothers had a family history of psychiatric disorders, the odds ratio for PPD was 2.08 (95% confidence interval, 1.67-2.59). That corresponds to a risk ratio of 1.79 (95% CI, 1.52-2.09), assuming a 15% postpartum depression prevalence in the general population.
Not doomed to develop PPD
Polina Teslyar, MD, a perinatal psychiatrist at Brigham and Women’s Hospital in Boston told this news organization it’s important to point out that though the risk is higher, women with a family psychiatric history should not feel as though they are destined to develop PPD.
“You are still more likely to not have postpartum depression, but it is important to be aware of personal risk factors so that if a person is experiencing that, they ask for help quickly rather than suffering and not knowing something is amiss,” she emphasized. Dr. Teslyar says she does see the higher risk for PPD, which is preventable and treatable, in her own practice when women have had a family history of psychiatric disorders.
The association makes sense, but literature on why that is has been varied, she said, and likely involves both genetics and socioeconomic factors. It’s difficult to tease apart how big a part each plays.
In her perinatal practice she sees women even before they are pregnant to discuss risk factors for PPD so she does ask about family history of psychiatric disorders, specifically about history of PPD and anxiety.
The researchers suggest routine perinatal care should include an easy low-cost, two-part question about both personal and family history of psychiatric disorders.
“As the assessment is possible even prior to conception, this would leave time for planning preventive efforts, such as psychosocial and psychological interventions targeting these at-risk women,” the authors write.
Asking about family history a challenge
Dr. Teslyar noted though that one of the challenges in asking about family history is that families may not have openly shared psychiatric history details with offspring. Family members may also report conditions they suspect a family member had rather than having a documented diagnosis.
In places where there is universal health care, she noted, finding documented diagnoses is easier, but otherwise “you’re really taking a subjective interpretation.”
The researchers found that subgroup, sensitivity, and meta–regression analyses aligned with the primary findings. The overall certainty of evidence was graded as moderate.
This study was not able to make clear how the specific diagnoses of family members affect the risk of developing PPD because much of the data from the studies came from self-report and questions were not consistent across the studies.
For instance, only 7 studies asked specifically about first-degree family members and 10 asked about specific diagnoses. Diagnoses ranged from mild affective disorders to more intrusive disorders, such as schizophrenia.
And while this study doesn’t seek to determine why the family history and risk of PPD appear to be connected, the authors offer some possible explanations.
“Growing up in an environment with parents struggling with mental health problems potentially influences the social support received from these parents when going into motherhood,” the authors write. “This particular explanation is supported by umbrella reviews concluding that lack of social support is a significant PPD risk factor.”
Screening, extraction, and assessment of studies included was done independently by two reviewers, increasing validity, the authors note.
The authors state that approximately 10%-15% of new mothers experience PPD, but Dr. Teslyar points out the numbers in the United States are typically quoted at up to 20%-30%. PPD ranges from mild to severe episodes and includes symptoms like those for major depression outside the postpartum period.
Study authors received funding from The Lundbeck Foundation and the European Union’s Horizon 2020 Research and Innovation Programme. A coauthor, Vibe G. Frokjaer, MD, PhD, has served as consultant and lecturer for H. Lundbeck and Sage Therapeutics. No other disclosures were reported. Dr. Teslyar reports no relevant financial relationships.
Mothers who have a family history of any psychiatric disorder have almost two times the risk of postpartum depression as do mothers without such history, according to a new study.
Mette-Marie Zacher Kjeldsen, MSc, with the National Centre for Register-based Research at Aarhus (Denmark) University, led the study, a meta-analysis that included 26 studies with information on 100,877 women.
Findings were published online in JAMA Psychiatry.
When mothers had a family history of psychiatric disorders, the odds ratio for PPD was 2.08 (95% confidence interval, 1.67-2.59). That corresponds to a risk ratio of 1.79 (95% CI, 1.52-2.09), assuming a 15% postpartum depression prevalence in the general population.
Not doomed to develop PPD
Polina Teslyar, MD, a perinatal psychiatrist at Brigham and Women’s Hospital in Boston told this news organization it’s important to point out that though the risk is higher, women with a family psychiatric history should not feel as though they are destined to develop PPD.
“You are still more likely to not have postpartum depression, but it is important to be aware of personal risk factors so that if a person is experiencing that, they ask for help quickly rather than suffering and not knowing something is amiss,” she emphasized. Dr. Teslyar says she does see the higher risk for PPD, which is preventable and treatable, in her own practice when women have had a family history of psychiatric disorders.
The association makes sense, but literature on why that is has been varied, she said, and likely involves both genetics and socioeconomic factors. It’s difficult to tease apart how big a part each plays.
In her perinatal practice she sees women even before they are pregnant to discuss risk factors for PPD so she does ask about family history of psychiatric disorders, specifically about history of PPD and anxiety.
The researchers suggest routine perinatal care should include an easy low-cost, two-part question about both personal and family history of psychiatric disorders.
“As the assessment is possible even prior to conception, this would leave time for planning preventive efforts, such as psychosocial and psychological interventions targeting these at-risk women,” the authors write.
Asking about family history a challenge
Dr. Teslyar noted though that one of the challenges in asking about family history is that families may not have openly shared psychiatric history details with offspring. Family members may also report conditions they suspect a family member had rather than having a documented diagnosis.
In places where there is universal health care, she noted, finding documented diagnoses is easier, but otherwise “you’re really taking a subjective interpretation.”
The researchers found that subgroup, sensitivity, and meta–regression analyses aligned with the primary findings. The overall certainty of evidence was graded as moderate.
This study was not able to make clear how the specific diagnoses of family members affect the risk of developing PPD because much of the data from the studies came from self-report and questions were not consistent across the studies.
For instance, only 7 studies asked specifically about first-degree family members and 10 asked about specific diagnoses. Diagnoses ranged from mild affective disorders to more intrusive disorders, such as schizophrenia.
And while this study doesn’t seek to determine why the family history and risk of PPD appear to be connected, the authors offer some possible explanations.
“Growing up in an environment with parents struggling with mental health problems potentially influences the social support received from these parents when going into motherhood,” the authors write. “This particular explanation is supported by umbrella reviews concluding that lack of social support is a significant PPD risk factor.”
Screening, extraction, and assessment of studies included was done independently by two reviewers, increasing validity, the authors note.
The authors state that approximately 10%-15% of new mothers experience PPD, but Dr. Teslyar points out the numbers in the United States are typically quoted at up to 20%-30%. PPD ranges from mild to severe episodes and includes symptoms like those for major depression outside the postpartum period.
Study authors received funding from The Lundbeck Foundation and the European Union’s Horizon 2020 Research and Innovation Programme. A coauthor, Vibe G. Frokjaer, MD, PhD, has served as consultant and lecturer for H. Lundbeck and Sage Therapeutics. No other disclosures were reported. Dr. Teslyar reports no relevant financial relationships.
Mothers who have a family history of any psychiatric disorder have almost two times the risk of postpartum depression as do mothers without such history, according to a new study.
Mette-Marie Zacher Kjeldsen, MSc, with the National Centre for Register-based Research at Aarhus (Denmark) University, led the study, a meta-analysis that included 26 studies with information on 100,877 women.
Findings were published online in JAMA Psychiatry.
When mothers had a family history of psychiatric disorders, the odds ratio for PPD was 2.08 (95% confidence interval, 1.67-2.59). That corresponds to a risk ratio of 1.79 (95% CI, 1.52-2.09), assuming a 15% postpartum depression prevalence in the general population.
Not doomed to develop PPD
Polina Teslyar, MD, a perinatal psychiatrist at Brigham and Women’s Hospital in Boston told this news organization it’s important to point out that though the risk is higher, women with a family psychiatric history should not feel as though they are destined to develop PPD.
“You are still more likely to not have postpartum depression, but it is important to be aware of personal risk factors so that if a person is experiencing that, they ask for help quickly rather than suffering and not knowing something is amiss,” she emphasized. Dr. Teslyar says she does see the higher risk for PPD, which is preventable and treatable, in her own practice when women have had a family history of psychiatric disorders.
The association makes sense, but literature on why that is has been varied, she said, and likely involves both genetics and socioeconomic factors. It’s difficult to tease apart how big a part each plays.
In her perinatal practice she sees women even before they are pregnant to discuss risk factors for PPD so she does ask about family history of psychiatric disorders, specifically about history of PPD and anxiety.
The researchers suggest routine perinatal care should include an easy low-cost, two-part question about both personal and family history of psychiatric disorders.
“As the assessment is possible even prior to conception, this would leave time for planning preventive efforts, such as psychosocial and psychological interventions targeting these at-risk women,” the authors write.
Asking about family history a challenge
Dr. Teslyar noted though that one of the challenges in asking about family history is that families may not have openly shared psychiatric history details with offspring. Family members may also report conditions they suspect a family member had rather than having a documented diagnosis.
In places where there is universal health care, she noted, finding documented diagnoses is easier, but otherwise “you’re really taking a subjective interpretation.”
The researchers found that subgroup, sensitivity, and meta–regression analyses aligned with the primary findings. The overall certainty of evidence was graded as moderate.
This study was not able to make clear how the specific diagnoses of family members affect the risk of developing PPD because much of the data from the studies came from self-report and questions were not consistent across the studies.
For instance, only 7 studies asked specifically about first-degree family members and 10 asked about specific diagnoses. Diagnoses ranged from mild affective disorders to more intrusive disorders, such as schizophrenia.
And while this study doesn’t seek to determine why the family history and risk of PPD appear to be connected, the authors offer some possible explanations.
“Growing up in an environment with parents struggling with mental health problems potentially influences the social support received from these parents when going into motherhood,” the authors write. “This particular explanation is supported by umbrella reviews concluding that lack of social support is a significant PPD risk factor.”
Screening, extraction, and assessment of studies included was done independently by two reviewers, increasing validity, the authors note.
The authors state that approximately 10%-15% of new mothers experience PPD, but Dr. Teslyar points out the numbers in the United States are typically quoted at up to 20%-30%. PPD ranges from mild to severe episodes and includes symptoms like those for major depression outside the postpartum period.
Study authors received funding from The Lundbeck Foundation and the European Union’s Horizon 2020 Research and Innovation Programme. A coauthor, Vibe G. Frokjaer, MD, PhD, has served as consultant and lecturer for H. Lundbeck and Sage Therapeutics. No other disclosures were reported. Dr. Teslyar reports no relevant financial relationships.
FROM JAMA PSYCHIATRY
Vitamin D deficiency clearly linked to inflammation
Vitamin D deficiency has a causative role in the systemic inflammation that commonly accompanies it, with inflammation declining, reflected by reductions in elevated C-reactive protein (CRP), as vitamin D levels increase to normal levels, new research shows.
However, there is no reverse effect between the two: Changes in CRP levels did not appear to affect vitamin D levels.
first author Elina Hypponen, PhD, a professor in nutritional and genetic epidemiology and director of the Australian Centre for Precision Health, Adelaide, said in an interview.
“Given that the serum CRP level is a widely used biomarker for chronic inflammation, these results suggest that improving vitamin D status may reduce chronic inflammation, but only for people with vitamin D deficiency,” Dr. Hypponen and coauthors reported in their study, published in the International Journal of Epidemiology.
Vitamin D associated with CRP in ‘L-shaped’ manner
Nutritional factors are known to influence systemic inflammation in a variety of ways. However, there has been debate over the association between vitamin D – specifically, serum 25-hydroxyvitamin D (25[OH]D), an indicator of vitamin D status – and CRP, with some reports of observational associations between the two disputed in more robust randomized trials.
To further evaluate the relationship, the authors performed a bidirectional Mendelian randomization analysis, using a cohort of 294,970 unrelated participants of White/British ancestry in the UK Biobank, the largest cohort to date with measured serum 25(OH)D concentrations, they noted.
Overall, the average 25(OH)D concentration was 50.0 nmol/L (range, 10-340 nmol/L), with 11.7% (n = 34,403) of participants having concentrations of less than 25 nmol/L, considered deficient.
The analysis showed that genetically predicted serum 25(OH)D was associated with serum CRP in an L-shaped manner, with CRP levels, and hence inflammation, sharply decreasing in relation to increasing 25(OH)D concentration to normal levels.
However, the relationship was only significant among participants with 25(OH)D levels in the deficiency range (< 25 nmol/L), with the association leveling off at about 50 nmol/L of 25(OH)D, which is generally considered a normal level.
The association was supported in further stratified Mendelian randomization analyses, which confirmed an inverse association between serum 25(OH)D in the deficiency range and CRP, but not with higher concentrations of serum vitamin D.
Conversely, neither linear nor nonlinear Mendelian randomization analyses showed a causal effect of serum CRP level on 25(OH)D concentrations.
The findings suggest that “improving vitamin D status in the deficiency range could reduce systemic low-grade inflammation and potentially mitigate the risk or severity of chronic illnesses with an inflammatory component,” the authors noted.
Dr. Hypponen added that the greatest reductions in CRP are observed with correction of the most severe vitamin D deficiency.
“The strongest benefits of improving concentrations will be seen for people with severe deficiency,” Dr. Hypponen said in an interview.
“In our study, much of the benefit was achieved when people reached the National Academy of Sciences endorsed cutoff of 50 nmol/L [for vitamin D sufficiency].”
Prohormone effects?
The anti-inflammatory effects observed with serum vitamin D could be related to its role as a prohormone that can impact vitamin D receptor–expressing immune cells, such as monocytes, B cells, T cells, and antigen-presenting cells, the authors noted.
“Indeed, cell experiments have shown that active vitamin D can inhibit the production of proinflammatory cytokines, including [tumor necrosis factor]–alpha, interleukin-1b, IL-6, IL-8, and IL-12, and promote the production of IL-10, an anti-inflammatory cytokine,” they explained.
In that regard, adequate vitamin D concentrations could be important in preventing inflammation-related complications from obesity and reduce the risk or severity of chronic illnesses with an inflammatory component, such as cardiovascular diseases, diabetes, autoimmune diseases, neurodegenerative conditions, and others, the authors noted.
Previous studies unable to assess effect of deficiency
While the current findings contradict other studies that have used Mendelian randomization and showed no causal effect of 25(OH)D on CRP, those previous studies only used a standard linear Mendelian randomization method that could not rule out the possibility of a ‘threshold effect’ restricted to vitamin D deficiency, the authors noted.
“Indeed, it is logical to expect that improving vitamin D status would be relevant only in the presence of vitamin D deficiency, whereas any further additions may be redundant and, in the ... extreme of supplementation, might become toxic,” they wrote.
However, the nonlinear Mendelian randomization approach used in the current study allows for better detection of the association, and the authors point out that the method has also been recently used in research showing an adverse effect of vitamin D deficiency on cardiovascular disease risk and mortality, which would not be visible using the standard linear Mendelian randomization approach.
Meanwhile, the current findings add to broader research showing benefits of increases in vitamin D to be mainly limited to those who are deficient, with limited benefit of supplementation for those who are not, Dr. Hypponen emphasized.
“We have repeatedly seen evidence for health benefits for increasing vitamin D concentrations in individuals with very low levels, while for others, there appears to be little to no benefit,” Dr. Hypponen said in a press statement.
“These findings highlight the importance of avoiding clinical vitamin D deficiency and provide further evidence for the wide-ranging effects of hormonal vitamin D,” she added.
The study was financially supported by the National Health and Medical Research Council, Australia. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Vitamin D deficiency has a causative role in the systemic inflammation that commonly accompanies it, with inflammation declining, reflected by reductions in elevated C-reactive protein (CRP), as vitamin D levels increase to normal levels, new research shows.
However, there is no reverse effect between the two: Changes in CRP levels did not appear to affect vitamin D levels.
first author Elina Hypponen, PhD, a professor in nutritional and genetic epidemiology and director of the Australian Centre for Precision Health, Adelaide, said in an interview.
“Given that the serum CRP level is a widely used biomarker for chronic inflammation, these results suggest that improving vitamin D status may reduce chronic inflammation, but only for people with vitamin D deficiency,” Dr. Hypponen and coauthors reported in their study, published in the International Journal of Epidemiology.
Vitamin D associated with CRP in ‘L-shaped’ manner
Nutritional factors are known to influence systemic inflammation in a variety of ways. However, there has been debate over the association between vitamin D – specifically, serum 25-hydroxyvitamin D (25[OH]D), an indicator of vitamin D status – and CRP, with some reports of observational associations between the two disputed in more robust randomized trials.
To further evaluate the relationship, the authors performed a bidirectional Mendelian randomization analysis, using a cohort of 294,970 unrelated participants of White/British ancestry in the UK Biobank, the largest cohort to date with measured serum 25(OH)D concentrations, they noted.
Overall, the average 25(OH)D concentration was 50.0 nmol/L (range, 10-340 nmol/L), with 11.7% (n = 34,403) of participants having concentrations of less than 25 nmol/L, considered deficient.
The analysis showed that genetically predicted serum 25(OH)D was associated with serum CRP in an L-shaped manner, with CRP levels, and hence inflammation, sharply decreasing in relation to increasing 25(OH)D concentration to normal levels.
However, the relationship was only significant among participants with 25(OH)D levels in the deficiency range (< 25 nmol/L), with the association leveling off at about 50 nmol/L of 25(OH)D, which is generally considered a normal level.
The association was supported in further stratified Mendelian randomization analyses, which confirmed an inverse association between serum 25(OH)D in the deficiency range and CRP, but not with higher concentrations of serum vitamin D.
Conversely, neither linear nor nonlinear Mendelian randomization analyses showed a causal effect of serum CRP level on 25(OH)D concentrations.
The findings suggest that “improving vitamin D status in the deficiency range could reduce systemic low-grade inflammation and potentially mitigate the risk or severity of chronic illnesses with an inflammatory component,” the authors noted.
Dr. Hypponen added that the greatest reductions in CRP are observed with correction of the most severe vitamin D deficiency.
“The strongest benefits of improving concentrations will be seen for people with severe deficiency,” Dr. Hypponen said in an interview.
“In our study, much of the benefit was achieved when people reached the National Academy of Sciences endorsed cutoff of 50 nmol/L [for vitamin D sufficiency].”
Prohormone effects?
The anti-inflammatory effects observed with serum vitamin D could be related to its role as a prohormone that can impact vitamin D receptor–expressing immune cells, such as monocytes, B cells, T cells, and antigen-presenting cells, the authors noted.
“Indeed, cell experiments have shown that active vitamin D can inhibit the production of proinflammatory cytokines, including [tumor necrosis factor]–alpha, interleukin-1b, IL-6, IL-8, and IL-12, and promote the production of IL-10, an anti-inflammatory cytokine,” they explained.
In that regard, adequate vitamin D concentrations could be important in preventing inflammation-related complications from obesity and reduce the risk or severity of chronic illnesses with an inflammatory component, such as cardiovascular diseases, diabetes, autoimmune diseases, neurodegenerative conditions, and others, the authors noted.
Previous studies unable to assess effect of deficiency
While the current findings contradict other studies that have used Mendelian randomization and showed no causal effect of 25(OH)D on CRP, those previous studies only used a standard linear Mendelian randomization method that could not rule out the possibility of a ‘threshold effect’ restricted to vitamin D deficiency, the authors noted.
“Indeed, it is logical to expect that improving vitamin D status would be relevant only in the presence of vitamin D deficiency, whereas any further additions may be redundant and, in the ... extreme of supplementation, might become toxic,” they wrote.
However, the nonlinear Mendelian randomization approach used in the current study allows for better detection of the association, and the authors point out that the method has also been recently used in research showing an adverse effect of vitamin D deficiency on cardiovascular disease risk and mortality, which would not be visible using the standard linear Mendelian randomization approach.
Meanwhile, the current findings add to broader research showing benefits of increases in vitamin D to be mainly limited to those who are deficient, with limited benefit of supplementation for those who are not, Dr. Hypponen emphasized.
“We have repeatedly seen evidence for health benefits for increasing vitamin D concentrations in individuals with very low levels, while for others, there appears to be little to no benefit,” Dr. Hypponen said in a press statement.
“These findings highlight the importance of avoiding clinical vitamin D deficiency and provide further evidence for the wide-ranging effects of hormonal vitamin D,” she added.
The study was financially supported by the National Health and Medical Research Council, Australia. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Vitamin D deficiency has a causative role in the systemic inflammation that commonly accompanies it, with inflammation declining, reflected by reductions in elevated C-reactive protein (CRP), as vitamin D levels increase to normal levels, new research shows.
However, there is no reverse effect between the two: Changes in CRP levels did not appear to affect vitamin D levels.
first author Elina Hypponen, PhD, a professor in nutritional and genetic epidemiology and director of the Australian Centre for Precision Health, Adelaide, said in an interview.
“Given that the serum CRP level is a widely used biomarker for chronic inflammation, these results suggest that improving vitamin D status may reduce chronic inflammation, but only for people with vitamin D deficiency,” Dr. Hypponen and coauthors reported in their study, published in the International Journal of Epidemiology.
Vitamin D associated with CRP in ‘L-shaped’ manner
Nutritional factors are known to influence systemic inflammation in a variety of ways. However, there has been debate over the association between vitamin D – specifically, serum 25-hydroxyvitamin D (25[OH]D), an indicator of vitamin D status – and CRP, with some reports of observational associations between the two disputed in more robust randomized trials.
To further evaluate the relationship, the authors performed a bidirectional Mendelian randomization analysis, using a cohort of 294,970 unrelated participants of White/British ancestry in the UK Biobank, the largest cohort to date with measured serum 25(OH)D concentrations, they noted.
Overall, the average 25(OH)D concentration was 50.0 nmol/L (range, 10-340 nmol/L), with 11.7% (n = 34,403) of participants having concentrations of less than 25 nmol/L, considered deficient.
The analysis showed that genetically predicted serum 25(OH)D was associated with serum CRP in an L-shaped manner, with CRP levels, and hence inflammation, sharply decreasing in relation to increasing 25(OH)D concentration to normal levels.
However, the relationship was only significant among participants with 25(OH)D levels in the deficiency range (< 25 nmol/L), with the association leveling off at about 50 nmol/L of 25(OH)D, which is generally considered a normal level.
The association was supported in further stratified Mendelian randomization analyses, which confirmed an inverse association between serum 25(OH)D in the deficiency range and CRP, but not with higher concentrations of serum vitamin D.
Conversely, neither linear nor nonlinear Mendelian randomization analyses showed a causal effect of serum CRP level on 25(OH)D concentrations.
The findings suggest that “improving vitamin D status in the deficiency range could reduce systemic low-grade inflammation and potentially mitigate the risk or severity of chronic illnesses with an inflammatory component,” the authors noted.
Dr. Hypponen added that the greatest reductions in CRP are observed with correction of the most severe vitamin D deficiency.
“The strongest benefits of improving concentrations will be seen for people with severe deficiency,” Dr. Hypponen said in an interview.
“In our study, much of the benefit was achieved when people reached the National Academy of Sciences endorsed cutoff of 50 nmol/L [for vitamin D sufficiency].”
Prohormone effects?
The anti-inflammatory effects observed with serum vitamin D could be related to its role as a prohormone that can impact vitamin D receptor–expressing immune cells, such as monocytes, B cells, T cells, and antigen-presenting cells, the authors noted.
“Indeed, cell experiments have shown that active vitamin D can inhibit the production of proinflammatory cytokines, including [tumor necrosis factor]–alpha, interleukin-1b, IL-6, IL-8, and IL-12, and promote the production of IL-10, an anti-inflammatory cytokine,” they explained.
In that regard, adequate vitamin D concentrations could be important in preventing inflammation-related complications from obesity and reduce the risk or severity of chronic illnesses with an inflammatory component, such as cardiovascular diseases, diabetes, autoimmune diseases, neurodegenerative conditions, and others, the authors noted.
Previous studies unable to assess effect of deficiency
While the current findings contradict other studies that have used Mendelian randomization and showed no causal effect of 25(OH)D on CRP, those previous studies only used a standard linear Mendelian randomization method that could not rule out the possibility of a ‘threshold effect’ restricted to vitamin D deficiency, the authors noted.
“Indeed, it is logical to expect that improving vitamin D status would be relevant only in the presence of vitamin D deficiency, whereas any further additions may be redundant and, in the ... extreme of supplementation, might become toxic,” they wrote.
However, the nonlinear Mendelian randomization approach used in the current study allows for better detection of the association, and the authors point out that the method has also been recently used in research showing an adverse effect of vitamin D deficiency on cardiovascular disease risk and mortality, which would not be visible using the standard linear Mendelian randomization approach.
Meanwhile, the current findings add to broader research showing benefits of increases in vitamin D to be mainly limited to those who are deficient, with limited benefit of supplementation for those who are not, Dr. Hypponen emphasized.
“We have repeatedly seen evidence for health benefits for increasing vitamin D concentrations in individuals with very low levels, while for others, there appears to be little to no benefit,” Dr. Hypponen said in a press statement.
“These findings highlight the importance of avoiding clinical vitamin D deficiency and provide further evidence for the wide-ranging effects of hormonal vitamin D,” she added.
The study was financially supported by the National Health and Medical Research Council, Australia. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
COVID-19 may trigger irritable bowel syndrome
Gastrointestinal symptoms are common with long COVID, also known as post-acute COVID-19 syndrome, according to Walter Chan, MD, MPH, and Madhusudan Grover, MBBS.
Dr. Chan, an assistant professor at Harvard Medical School, Boston, and Dr. Grover, an associate professor of medicine and physiology at Mayo Clinic, Rochester, Minn., conducted a review of the literature on COVID-19’s long-term gastrointestinal effects. Their review was published in Clinical Gastroenterology and Hepatology.
Estimates of the prevalence of gastrointestinal symptoms with COVID-19 have ranged as high as 60%, Dr. Chan and Dr. Grover report, and the symptoms may be present in patients with long COVID, a syndrome that continues 4 weeks or longer.
In one survey of 749 COVID-19 survivors, 29% reported at least one new chronic gastrointestinal symptom. The most common were heartburn, constipation, diarrhea, and abdominal pain. Of those with abdominal pain, 39% had symptoms that met Rome IV criteria for irritable bowel syndrome.
People who have gastrointestinal symptoms after their initial SARS-CoV-2 infection are more likely to have them with long COVID. Psychiatric diagnoses, hospitalization, and the loss of smell and taste are predictors of gastrointestinal symptoms.
Infectious gastroenteritis can increase the risk for disorders of gut-brain interaction, especially postinfection IBS, Dr. Chan and Dr. Grover write.
COVID-19 likely causes gastrointestinal symptoms through multiple mechanisms. It may suppress angiotensin-converting enzyme 2, which protects intestinal cells. It can alter the microbiome. It can cause or worsen weight gain and diabetes. It may disrupt the immune system and trigger an autoimmune reaction. It can cause depression and anxiety, and it can alter dietary habits.
No specific treatments for gastrointestinal symptoms associated with long COVID have emerged, so clinicians should make use of established therapies for disorders of gut-brain interaction, Dr. Chan and Dr. Grover recommend.
Beyond adequate sleep and exercise, these may include high-fiber, low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), gluten-free, low-carbohydrate, or elimination diets.
For diarrhea, they list loperamide, ondansetron, alosetron, eluxadoline, antispasmodics, rifaximin, and bile acid sequestrants.
For constipation, they mention fiber supplements, polyethylene glycol, linaclotide, plecanatide, lubiprostone, tenapanor, tegaserod, and prucalopride.
For modulating intestinal permeability, they recommend glutamine.
Neuromodulation may be achieved with tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, azaperones, and delta ligands, they write.
For psychological therapy, they recommend cognitive-behavioral therapy and gut-directed hypnotherapy.
A handful of studies have suggested benefits from Lactiplantibacillus plantarum and Pediococcus acidilactici as probiotic therapies. Additionally, one study showed positive results with a high-fiber formula, perhaps by nourishing short-chain fatty acid-producing bacteria, Dr. Chan and Dr. Grover write.
Dr. Chan reported financial relationships with Ironwood, Takeda, and Phathom Pharmaceuticals. Dr. Grover reported financial relationships with Takeda, Donga, Alexza Pharmaceuticals, and Alfasigma.
A version of this article first appeared on Medscape.com.
Gastrointestinal symptoms are common with long COVID, also known as post-acute COVID-19 syndrome, according to Walter Chan, MD, MPH, and Madhusudan Grover, MBBS.
Dr. Chan, an assistant professor at Harvard Medical School, Boston, and Dr. Grover, an associate professor of medicine and physiology at Mayo Clinic, Rochester, Minn., conducted a review of the literature on COVID-19’s long-term gastrointestinal effects. Their review was published in Clinical Gastroenterology and Hepatology.
Estimates of the prevalence of gastrointestinal symptoms with COVID-19 have ranged as high as 60%, Dr. Chan and Dr. Grover report, and the symptoms may be present in patients with long COVID, a syndrome that continues 4 weeks or longer.
In one survey of 749 COVID-19 survivors, 29% reported at least one new chronic gastrointestinal symptom. The most common were heartburn, constipation, diarrhea, and abdominal pain. Of those with abdominal pain, 39% had symptoms that met Rome IV criteria for irritable bowel syndrome.
People who have gastrointestinal symptoms after their initial SARS-CoV-2 infection are more likely to have them with long COVID. Psychiatric diagnoses, hospitalization, and the loss of smell and taste are predictors of gastrointestinal symptoms.
Infectious gastroenteritis can increase the risk for disorders of gut-brain interaction, especially postinfection IBS, Dr. Chan and Dr. Grover write.
COVID-19 likely causes gastrointestinal symptoms through multiple mechanisms. It may suppress angiotensin-converting enzyme 2, which protects intestinal cells. It can alter the microbiome. It can cause or worsen weight gain and diabetes. It may disrupt the immune system and trigger an autoimmune reaction. It can cause depression and anxiety, and it can alter dietary habits.
No specific treatments for gastrointestinal symptoms associated with long COVID have emerged, so clinicians should make use of established therapies for disorders of gut-brain interaction, Dr. Chan and Dr. Grover recommend.
Beyond adequate sleep and exercise, these may include high-fiber, low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), gluten-free, low-carbohydrate, or elimination diets.
For diarrhea, they list loperamide, ondansetron, alosetron, eluxadoline, antispasmodics, rifaximin, and bile acid sequestrants.
For constipation, they mention fiber supplements, polyethylene glycol, linaclotide, plecanatide, lubiprostone, tenapanor, tegaserod, and prucalopride.
For modulating intestinal permeability, they recommend glutamine.
Neuromodulation may be achieved with tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, azaperones, and delta ligands, they write.
For psychological therapy, they recommend cognitive-behavioral therapy and gut-directed hypnotherapy.
A handful of studies have suggested benefits from Lactiplantibacillus plantarum and Pediococcus acidilactici as probiotic therapies. Additionally, one study showed positive results with a high-fiber formula, perhaps by nourishing short-chain fatty acid-producing bacteria, Dr. Chan and Dr. Grover write.
Dr. Chan reported financial relationships with Ironwood, Takeda, and Phathom Pharmaceuticals. Dr. Grover reported financial relationships with Takeda, Donga, Alexza Pharmaceuticals, and Alfasigma.
A version of this article first appeared on Medscape.com.
Gastrointestinal symptoms are common with long COVID, also known as post-acute COVID-19 syndrome, according to Walter Chan, MD, MPH, and Madhusudan Grover, MBBS.
Dr. Chan, an assistant professor at Harvard Medical School, Boston, and Dr. Grover, an associate professor of medicine and physiology at Mayo Clinic, Rochester, Minn., conducted a review of the literature on COVID-19’s long-term gastrointestinal effects. Their review was published in Clinical Gastroenterology and Hepatology.
Estimates of the prevalence of gastrointestinal symptoms with COVID-19 have ranged as high as 60%, Dr. Chan and Dr. Grover report, and the symptoms may be present in patients with long COVID, a syndrome that continues 4 weeks or longer.
In one survey of 749 COVID-19 survivors, 29% reported at least one new chronic gastrointestinal symptom. The most common were heartburn, constipation, diarrhea, and abdominal pain. Of those with abdominal pain, 39% had symptoms that met Rome IV criteria for irritable bowel syndrome.
People who have gastrointestinal symptoms after their initial SARS-CoV-2 infection are more likely to have them with long COVID. Psychiatric diagnoses, hospitalization, and the loss of smell and taste are predictors of gastrointestinal symptoms.
Infectious gastroenteritis can increase the risk for disorders of gut-brain interaction, especially postinfection IBS, Dr. Chan and Dr. Grover write.
COVID-19 likely causes gastrointestinal symptoms through multiple mechanisms. It may suppress angiotensin-converting enzyme 2, which protects intestinal cells. It can alter the microbiome. It can cause or worsen weight gain and diabetes. It may disrupt the immune system and trigger an autoimmune reaction. It can cause depression and anxiety, and it can alter dietary habits.
No specific treatments for gastrointestinal symptoms associated with long COVID have emerged, so clinicians should make use of established therapies for disorders of gut-brain interaction, Dr. Chan and Dr. Grover recommend.
Beyond adequate sleep and exercise, these may include high-fiber, low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), gluten-free, low-carbohydrate, or elimination diets.
For diarrhea, they list loperamide, ondansetron, alosetron, eluxadoline, antispasmodics, rifaximin, and bile acid sequestrants.
For constipation, they mention fiber supplements, polyethylene glycol, linaclotide, plecanatide, lubiprostone, tenapanor, tegaserod, and prucalopride.
For modulating intestinal permeability, they recommend glutamine.
Neuromodulation may be achieved with tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, azaperones, and delta ligands, they write.
For psychological therapy, they recommend cognitive-behavioral therapy and gut-directed hypnotherapy.
A handful of studies have suggested benefits from Lactiplantibacillus plantarum and Pediococcus acidilactici as probiotic therapies. Additionally, one study showed positive results with a high-fiber formula, perhaps by nourishing short-chain fatty acid-producing bacteria, Dr. Chan and Dr. Grover write.
Dr. Chan reported financial relationships with Ironwood, Takeda, and Phathom Pharmaceuticals. Dr. Grover reported financial relationships with Takeda, Donga, Alexza Pharmaceuticals, and Alfasigma.
A version of this article first appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Large study amplifies evidence of COVID vaccine safety in pregnancy
The research team wrote in the BMJ that their reassuring findings – drawn from a registry of all births in Ontario over an 8-month period – “can inform evidence-based decision-making” about COVID vaccination during pregnancy.
Previous research has found that pregnant patients are at higher risk of severe complications and death if they become infected with COVID and that vaccination before or during pregnancy prevents such outcomes and reduces the risk of newborn infection, noted Jeffrey Ecker, chief of obstetrics and gynecology at Massachusetts General Hospital, Boston.
This new study “adds to a growing body of information arguing clearly and reassuringly that vaccination during pregnancy is not associated with complications during pregnancy,” said Dr. Ecker, who was not involved in the new study.
He added that it “should help obstetric providers further reassure those who are hesitant that vaccination is safe and best both for the pregnant patient and their pregnancy.”
Methods and results
For the new study, researchers tapped a provincial registry of all live and stillborn infants with a gestational age of at least 20 weeks or birth weight of at least 500 g. Unique health card numbers were used to link birth records to a database of COVID vaccinations.
Of 85,162 infants born from May through December of 2021, 43,099 (50.6%) were born to individuals who received at least one vaccine dose during pregnancy. Among those, 99.7% received an mRNA vaccine such as Pfizer-BioNTech or Moderna.
Vaccination during pregnancy was not associated with greater risk of overall preterm birth (6.5% among vaccinated individuals versus 6.9% among unvaccinated; hazard ratio, 1.02; 95% confidence interval, 0.96-1.08), spontaneous preterm birth (3.7% versus 4.4%; hazard ratio, 0.96; 95% CI, 0.90-1.03) or very preterm birth (0.59% versus 0.89%; hazard ratio, 0.80; 95% CI, 0.67-0.95).
Likewise, no increase was observed in the risk of an infant being small for gestational age at birth (9.1% versus 9.2%; hazard ratio, 0.98; 95% CI, 0.93-1.03).
The researchers observed a reduction in the risk of stillbirth, even after adjusting for potential confounders. Stillbirths occurred in 0.25% of vaccinated individuals, compared with 0.44% of unvaccinated individuals (hazard ratio, 0.65; 95% CI, 0.51-0.84).
A reduced risk of stillbirth – albeit to a smaller degree – was also found in a Scandinavian registry study that included 28,506 babies born to individuals who were vaccinated during pregnancy.
“Collectively, the findings from these two studies are reassuring and are consistent with no increased risk of stillbirth after COVID-19 vaccination during pregnancy. In contrast, COVID-19 disease during pregnancy has been associated with an increased risk of stillbirth,” the researchers wrote.
Findings did not vary by which mRNA vaccine a mother received, the number of doses she received, or the trimester in which a vaccine was given, the researchers reported.
Stillbirth findings will be ‘very reassuring’ for patients
The lead investigator, Deshayne Fell, PhD, said in an interview, the fact that the study comprised the entire population of pregnant people in Ontario during the study period “increases our confidence” about the validity and relevance of the findings for other geographic settings.
Dr. Fell, an associate professor in epidemiology and public health at the University of Ottawa and a scientist at the Children’s Hospital of Eastern Ontario Research Institute, Ottawa, said the evaluation of stillbirth in particular, “a rare but devastating outcome,” will be “very reassuring and useful for clinical counseling.”
A limitation cited by the research team included a lack of data on vaccination prior to pregnancy.
In the new study, Dr, Ecker said, “Though the investigators were able to adjust for many variables they cannot be certain that some unmeasured variable that, accordingly, was not adjusted for does not hide a small risk. This seems very unlikely, however.”
The Canadian research team said similar studies of non-mRNA COVID vaccines “should be a research priority.” However, such studies are not underway in Canada, where only mRNA vaccines are used in pregnancy, Dr. Fell said.
This study was supported by the Public Health Agency of Canada.
Dr. Fell and Dr. Ecker reported no competing financial interests.
The research team wrote in the BMJ that their reassuring findings – drawn from a registry of all births in Ontario over an 8-month period – “can inform evidence-based decision-making” about COVID vaccination during pregnancy.
Previous research has found that pregnant patients are at higher risk of severe complications and death if they become infected with COVID and that vaccination before or during pregnancy prevents such outcomes and reduces the risk of newborn infection, noted Jeffrey Ecker, chief of obstetrics and gynecology at Massachusetts General Hospital, Boston.
This new study “adds to a growing body of information arguing clearly and reassuringly that vaccination during pregnancy is not associated with complications during pregnancy,” said Dr. Ecker, who was not involved in the new study.
He added that it “should help obstetric providers further reassure those who are hesitant that vaccination is safe and best both for the pregnant patient and their pregnancy.”
Methods and results
For the new study, researchers tapped a provincial registry of all live and stillborn infants with a gestational age of at least 20 weeks or birth weight of at least 500 g. Unique health card numbers were used to link birth records to a database of COVID vaccinations.
Of 85,162 infants born from May through December of 2021, 43,099 (50.6%) were born to individuals who received at least one vaccine dose during pregnancy. Among those, 99.7% received an mRNA vaccine such as Pfizer-BioNTech or Moderna.
Vaccination during pregnancy was not associated with greater risk of overall preterm birth (6.5% among vaccinated individuals versus 6.9% among unvaccinated; hazard ratio, 1.02; 95% confidence interval, 0.96-1.08), spontaneous preterm birth (3.7% versus 4.4%; hazard ratio, 0.96; 95% CI, 0.90-1.03) or very preterm birth (0.59% versus 0.89%; hazard ratio, 0.80; 95% CI, 0.67-0.95).
Likewise, no increase was observed in the risk of an infant being small for gestational age at birth (9.1% versus 9.2%; hazard ratio, 0.98; 95% CI, 0.93-1.03).
The researchers observed a reduction in the risk of stillbirth, even after adjusting for potential confounders. Stillbirths occurred in 0.25% of vaccinated individuals, compared with 0.44% of unvaccinated individuals (hazard ratio, 0.65; 95% CI, 0.51-0.84).
A reduced risk of stillbirth – albeit to a smaller degree – was also found in a Scandinavian registry study that included 28,506 babies born to individuals who were vaccinated during pregnancy.
“Collectively, the findings from these two studies are reassuring and are consistent with no increased risk of stillbirth after COVID-19 vaccination during pregnancy. In contrast, COVID-19 disease during pregnancy has been associated with an increased risk of stillbirth,” the researchers wrote.
Findings did not vary by which mRNA vaccine a mother received, the number of doses she received, or the trimester in which a vaccine was given, the researchers reported.
Stillbirth findings will be ‘very reassuring’ for patients
The lead investigator, Deshayne Fell, PhD, said in an interview, the fact that the study comprised the entire population of pregnant people in Ontario during the study period “increases our confidence” about the validity and relevance of the findings for other geographic settings.
Dr. Fell, an associate professor in epidemiology and public health at the University of Ottawa and a scientist at the Children’s Hospital of Eastern Ontario Research Institute, Ottawa, said the evaluation of stillbirth in particular, “a rare but devastating outcome,” will be “very reassuring and useful for clinical counseling.”
A limitation cited by the research team included a lack of data on vaccination prior to pregnancy.
In the new study, Dr, Ecker said, “Though the investigators were able to adjust for many variables they cannot be certain that some unmeasured variable that, accordingly, was not adjusted for does not hide a small risk. This seems very unlikely, however.”
The Canadian research team said similar studies of non-mRNA COVID vaccines “should be a research priority.” However, such studies are not underway in Canada, where only mRNA vaccines are used in pregnancy, Dr. Fell said.
This study was supported by the Public Health Agency of Canada.
Dr. Fell and Dr. Ecker reported no competing financial interests.
The research team wrote in the BMJ that their reassuring findings – drawn from a registry of all births in Ontario over an 8-month period – “can inform evidence-based decision-making” about COVID vaccination during pregnancy.
Previous research has found that pregnant patients are at higher risk of severe complications and death if they become infected with COVID and that vaccination before or during pregnancy prevents such outcomes and reduces the risk of newborn infection, noted Jeffrey Ecker, chief of obstetrics and gynecology at Massachusetts General Hospital, Boston.
This new study “adds to a growing body of information arguing clearly and reassuringly that vaccination during pregnancy is not associated with complications during pregnancy,” said Dr. Ecker, who was not involved in the new study.
He added that it “should help obstetric providers further reassure those who are hesitant that vaccination is safe and best both for the pregnant patient and their pregnancy.”
Methods and results
For the new study, researchers tapped a provincial registry of all live and stillborn infants with a gestational age of at least 20 weeks or birth weight of at least 500 g. Unique health card numbers were used to link birth records to a database of COVID vaccinations.
Of 85,162 infants born from May through December of 2021, 43,099 (50.6%) were born to individuals who received at least one vaccine dose during pregnancy. Among those, 99.7% received an mRNA vaccine such as Pfizer-BioNTech or Moderna.
Vaccination during pregnancy was not associated with greater risk of overall preterm birth (6.5% among vaccinated individuals versus 6.9% among unvaccinated; hazard ratio, 1.02; 95% confidence interval, 0.96-1.08), spontaneous preterm birth (3.7% versus 4.4%; hazard ratio, 0.96; 95% CI, 0.90-1.03) or very preterm birth (0.59% versus 0.89%; hazard ratio, 0.80; 95% CI, 0.67-0.95).
Likewise, no increase was observed in the risk of an infant being small for gestational age at birth (9.1% versus 9.2%; hazard ratio, 0.98; 95% CI, 0.93-1.03).
The researchers observed a reduction in the risk of stillbirth, even after adjusting for potential confounders. Stillbirths occurred in 0.25% of vaccinated individuals, compared with 0.44% of unvaccinated individuals (hazard ratio, 0.65; 95% CI, 0.51-0.84).
A reduced risk of stillbirth – albeit to a smaller degree – was also found in a Scandinavian registry study that included 28,506 babies born to individuals who were vaccinated during pregnancy.
“Collectively, the findings from these two studies are reassuring and are consistent with no increased risk of stillbirth after COVID-19 vaccination during pregnancy. In contrast, COVID-19 disease during pregnancy has been associated with an increased risk of stillbirth,” the researchers wrote.
Findings did not vary by which mRNA vaccine a mother received, the number of doses she received, or the trimester in which a vaccine was given, the researchers reported.
Stillbirth findings will be ‘very reassuring’ for patients
The lead investigator, Deshayne Fell, PhD, said in an interview, the fact that the study comprised the entire population of pregnant people in Ontario during the study period “increases our confidence” about the validity and relevance of the findings for other geographic settings.
Dr. Fell, an associate professor in epidemiology and public health at the University of Ottawa and a scientist at the Children’s Hospital of Eastern Ontario Research Institute, Ottawa, said the evaluation of stillbirth in particular, “a rare but devastating outcome,” will be “very reassuring and useful for clinical counseling.”
A limitation cited by the research team included a lack of data on vaccination prior to pregnancy.
In the new study, Dr, Ecker said, “Though the investigators were able to adjust for many variables they cannot be certain that some unmeasured variable that, accordingly, was not adjusted for does not hide a small risk. This seems very unlikely, however.”
The Canadian research team said similar studies of non-mRNA COVID vaccines “should be a research priority.” However, such studies are not underway in Canada, where only mRNA vaccines are used in pregnancy, Dr. Fell said.
This study was supported by the Public Health Agency of Canada.
Dr. Fell and Dr. Ecker reported no competing financial interests.
FROM BMJ
Where women’s voices still get heard less
“Our study provides the first analysis of gender and early-career faculty disparities in speakers at hematology and medical oncology board review meetings,” the authors reported in research published in Blood Advances.
“We covered six major board reviews over the last 5 years that are either conducted yearly or every other year, [and] the general trend across all meetings showed skewness toward men speakers,” the authors reported.
Recent data from 2021 suggests a closing of the gender gap in oncology, with women making up 44.6% of oncologists in training. However, they still only represented 35.2% of practicing oncologists and are underrepresented in leadership positions in academic oncology, the authors reported.
With speaking roles at academic meetings potentially marking a key step in career advancement and improved opportunities, the authors sought to investigate the balance of gender, as well as early-career faculty among speakers at prominent hematology and/or oncology board review lecture series taking place in the United States between 2017 and 2021.
The five institutions and one society presenting the board review lecture series included Baylor College of Medicine/MD Anderson Cancer Center, both in Houston; Dana-Farber Brigham Cancer Center, Boston; George Washington University, Washington; Memorial Sloan Kettering Cancer Center, New York; Seattle Cancer Care Alliance; and the hematology board review series from the American Society of Hematology.
During the period in question, among 1,224 board review lectures presented, women constituted only 37.7% of the speakers. In lectures presented by American Board of Internal Medicine–certified speakers (n = 1,016, 83%), women were found to have made up fewer than 50% of speakers in five of six courses.
Men were also more likely to be recurrent speakers; across all courses, 13 men but only 2 women conducted 10 or more lectures. And while 35 men gave six or more lectures across all courses, only 12 women did so.
The lecture topics with the lowest rates of women presenters included malignant hematology (24.8%), solid tumors (38.9%), and benign hematology lectures (44.1%).
“We suspected [the imbalance in malignant hematology] since multiple recurrent roles were concentrated in the malignant hematology,” senior author Samer Al Hadidi, MD, of the Myeloma Center, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AK, said in an interview.
He noted that “there are no regulations that such courses need to follow to ensure certain proportions of women and junior faculty are involved.”
Early-career faculty
In terms of early-career representation, more than 50% of lectures were given by faculty who had received their initial certifications more than 15 years earlier. The median time from initial certification was 12.5 years for hematology and 14 years for medical oncology.
The findings that more than half of the board review lectures were presented by faculty with more than 15 years’ experience since initial certification “reflects a lack of appropriate involvement of early-career faculty, who arguably may have more recent experience with board certification,” the authors wrote.
While being underrepresented in such roles is detrimental, there are no regulations that such courses follow to ensure certain proportions of women and junior faculty are involved, Dr. Al Hadidi noted.
Equal representation remains elusive
The study does suggest some notable gains. In a previous study of 181 academic conferences in the United States and Canada between 2007 and 2017, the rate of women speakers was only 15%, compared with 37.7% in the new study.
And an overall trend analysis in the study shows an approximately 10% increase in representation of women in all of the board reviews. However, only the ASH hematology board review achieved more than 50% women in their two courses.
“Overall, the proportion of women speakers is improving over the years, though it remains suboptimal,” Dr. Al Hadidi said.
The authors noted that oncology is clearly not the only specialty with gender disparities. They documented a lack of women speakers at conferences involving otolaryngology head and neck meetings, radiation oncology, emergency medicine, and research conferences.
They pointed to the work of ASH’s Women in Hematology Working Group as an important example of the needed effort to improve the balance of women hematologists.
Ariela Marshall, MD, director of women’s thrombosis and hemostasis at Penn Medicine in Philadelphia and a leader of ASH’s Women in Hematology Working Group, agreed that more efforts are needed to address both gender disparities as well as those of early career speakers. She asserted that the two disparities appear to be connected.
“If you broke down gender representation over time and the faculty/time since initial certification, the findings may mirror the percent of women in hematology-oncology at that given point in time,” Dr. Marshall said in an interview.
“If an institution is truly committed to taking action on gender equity, it needs to look at gender and experience equity of speakers,” she said. “Perhaps it’s the time to say ‘Dr. X has been doing this review course for 15 years. Let’s give someone else a chance.’
“This is not even just from a gender equity perspective but from a career development perspective overall,” she added. “Junior faculty need these speaking engagements a lot more than senior faculty.”
Meanwhile, the higher number of female trainees is a trend that ideally will be sustained as those trainees move into positions of leadership, Dr. Marshall noted.
“We do see that over time, we have achieved gender equity in the percent of women matriculating to medical school. And my hope is that, 20 years down the line, we will see the effects of this reflected in increased equity in leadership positions such as division/department chair, dean, and hospital CEO,” she said. “However, we have a lot of work to do because there are still huge inequities in the culture of medicine (institutional and more broadly), including gender-based discrimination, maternal discrimination, and high attrition rates for women physicians, compared to male physicians.
“It’s not enough to simply say ‘well, we have fixed the problem because our incoming medical student classes are now equitable in gender distribution,’ ”
The authors and Dr. Marshall had no disclosures to report.
“Our study provides the first analysis of gender and early-career faculty disparities in speakers at hematology and medical oncology board review meetings,” the authors reported in research published in Blood Advances.
“We covered six major board reviews over the last 5 years that are either conducted yearly or every other year, [and] the general trend across all meetings showed skewness toward men speakers,” the authors reported.
Recent data from 2021 suggests a closing of the gender gap in oncology, with women making up 44.6% of oncologists in training. However, they still only represented 35.2% of practicing oncologists and are underrepresented in leadership positions in academic oncology, the authors reported.
With speaking roles at academic meetings potentially marking a key step in career advancement and improved opportunities, the authors sought to investigate the balance of gender, as well as early-career faculty among speakers at prominent hematology and/or oncology board review lecture series taking place in the United States between 2017 and 2021.
The five institutions and one society presenting the board review lecture series included Baylor College of Medicine/MD Anderson Cancer Center, both in Houston; Dana-Farber Brigham Cancer Center, Boston; George Washington University, Washington; Memorial Sloan Kettering Cancer Center, New York; Seattle Cancer Care Alliance; and the hematology board review series from the American Society of Hematology.
During the period in question, among 1,224 board review lectures presented, women constituted only 37.7% of the speakers. In lectures presented by American Board of Internal Medicine–certified speakers (n = 1,016, 83%), women were found to have made up fewer than 50% of speakers in five of six courses.
Men were also more likely to be recurrent speakers; across all courses, 13 men but only 2 women conducted 10 or more lectures. And while 35 men gave six or more lectures across all courses, only 12 women did so.
The lecture topics with the lowest rates of women presenters included malignant hematology (24.8%), solid tumors (38.9%), and benign hematology lectures (44.1%).
“We suspected [the imbalance in malignant hematology] since multiple recurrent roles were concentrated in the malignant hematology,” senior author Samer Al Hadidi, MD, of the Myeloma Center, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AK, said in an interview.
He noted that “there are no regulations that such courses need to follow to ensure certain proportions of women and junior faculty are involved.”
Early-career faculty
In terms of early-career representation, more than 50% of lectures were given by faculty who had received their initial certifications more than 15 years earlier. The median time from initial certification was 12.5 years for hematology and 14 years for medical oncology.
The findings that more than half of the board review lectures were presented by faculty with more than 15 years’ experience since initial certification “reflects a lack of appropriate involvement of early-career faculty, who arguably may have more recent experience with board certification,” the authors wrote.
While being underrepresented in such roles is detrimental, there are no regulations that such courses follow to ensure certain proportions of women and junior faculty are involved, Dr. Al Hadidi noted.
Equal representation remains elusive
The study does suggest some notable gains. In a previous study of 181 academic conferences in the United States and Canada between 2007 and 2017, the rate of women speakers was only 15%, compared with 37.7% in the new study.
And an overall trend analysis in the study shows an approximately 10% increase in representation of women in all of the board reviews. However, only the ASH hematology board review achieved more than 50% women in their two courses.
“Overall, the proportion of women speakers is improving over the years, though it remains suboptimal,” Dr. Al Hadidi said.
The authors noted that oncology is clearly not the only specialty with gender disparities. They documented a lack of women speakers at conferences involving otolaryngology head and neck meetings, radiation oncology, emergency medicine, and research conferences.
They pointed to the work of ASH’s Women in Hematology Working Group as an important example of the needed effort to improve the balance of women hematologists.
Ariela Marshall, MD, director of women’s thrombosis and hemostasis at Penn Medicine in Philadelphia and a leader of ASH’s Women in Hematology Working Group, agreed that more efforts are needed to address both gender disparities as well as those of early career speakers. She asserted that the two disparities appear to be connected.
“If you broke down gender representation over time and the faculty/time since initial certification, the findings may mirror the percent of women in hematology-oncology at that given point in time,” Dr. Marshall said in an interview.
“If an institution is truly committed to taking action on gender equity, it needs to look at gender and experience equity of speakers,” she said. “Perhaps it’s the time to say ‘Dr. X has been doing this review course for 15 years. Let’s give someone else a chance.’
“This is not even just from a gender equity perspective but from a career development perspective overall,” she added. “Junior faculty need these speaking engagements a lot more than senior faculty.”
Meanwhile, the higher number of female trainees is a trend that ideally will be sustained as those trainees move into positions of leadership, Dr. Marshall noted.
“We do see that over time, we have achieved gender equity in the percent of women matriculating to medical school. And my hope is that, 20 years down the line, we will see the effects of this reflected in increased equity in leadership positions such as division/department chair, dean, and hospital CEO,” she said. “However, we have a lot of work to do because there are still huge inequities in the culture of medicine (institutional and more broadly), including gender-based discrimination, maternal discrimination, and high attrition rates for women physicians, compared to male physicians.
“It’s not enough to simply say ‘well, we have fixed the problem because our incoming medical student classes are now equitable in gender distribution,’ ”
The authors and Dr. Marshall had no disclosures to report.
“Our study provides the first analysis of gender and early-career faculty disparities in speakers at hematology and medical oncology board review meetings,” the authors reported in research published in Blood Advances.
“We covered six major board reviews over the last 5 years that are either conducted yearly or every other year, [and] the general trend across all meetings showed skewness toward men speakers,” the authors reported.
Recent data from 2021 suggests a closing of the gender gap in oncology, with women making up 44.6% of oncologists in training. However, they still only represented 35.2% of practicing oncologists and are underrepresented in leadership positions in academic oncology, the authors reported.
With speaking roles at academic meetings potentially marking a key step in career advancement and improved opportunities, the authors sought to investigate the balance of gender, as well as early-career faculty among speakers at prominent hematology and/or oncology board review lecture series taking place in the United States between 2017 and 2021.
The five institutions and one society presenting the board review lecture series included Baylor College of Medicine/MD Anderson Cancer Center, both in Houston; Dana-Farber Brigham Cancer Center, Boston; George Washington University, Washington; Memorial Sloan Kettering Cancer Center, New York; Seattle Cancer Care Alliance; and the hematology board review series from the American Society of Hematology.
During the period in question, among 1,224 board review lectures presented, women constituted only 37.7% of the speakers. In lectures presented by American Board of Internal Medicine–certified speakers (n = 1,016, 83%), women were found to have made up fewer than 50% of speakers in five of six courses.
Men were also more likely to be recurrent speakers; across all courses, 13 men but only 2 women conducted 10 or more lectures. And while 35 men gave six or more lectures across all courses, only 12 women did so.
The lecture topics with the lowest rates of women presenters included malignant hematology (24.8%), solid tumors (38.9%), and benign hematology lectures (44.1%).
“We suspected [the imbalance in malignant hematology] since multiple recurrent roles were concentrated in the malignant hematology,” senior author Samer Al Hadidi, MD, of the Myeloma Center, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AK, said in an interview.
He noted that “there are no regulations that such courses need to follow to ensure certain proportions of women and junior faculty are involved.”
Early-career faculty
In terms of early-career representation, more than 50% of lectures were given by faculty who had received their initial certifications more than 15 years earlier. The median time from initial certification was 12.5 years for hematology and 14 years for medical oncology.
The findings that more than half of the board review lectures were presented by faculty with more than 15 years’ experience since initial certification “reflects a lack of appropriate involvement of early-career faculty, who arguably may have more recent experience with board certification,” the authors wrote.
While being underrepresented in such roles is detrimental, there are no regulations that such courses follow to ensure certain proportions of women and junior faculty are involved, Dr. Al Hadidi noted.
Equal representation remains elusive
The study does suggest some notable gains. In a previous study of 181 academic conferences in the United States and Canada between 2007 and 2017, the rate of women speakers was only 15%, compared with 37.7% in the new study.
And an overall trend analysis in the study shows an approximately 10% increase in representation of women in all of the board reviews. However, only the ASH hematology board review achieved more than 50% women in their two courses.
“Overall, the proportion of women speakers is improving over the years, though it remains suboptimal,” Dr. Al Hadidi said.
The authors noted that oncology is clearly not the only specialty with gender disparities. They documented a lack of women speakers at conferences involving otolaryngology head and neck meetings, radiation oncology, emergency medicine, and research conferences.
They pointed to the work of ASH’s Women in Hematology Working Group as an important example of the needed effort to improve the balance of women hematologists.
Ariela Marshall, MD, director of women’s thrombosis and hemostasis at Penn Medicine in Philadelphia and a leader of ASH’s Women in Hematology Working Group, agreed that more efforts are needed to address both gender disparities as well as those of early career speakers. She asserted that the two disparities appear to be connected.
“If you broke down gender representation over time and the faculty/time since initial certification, the findings may mirror the percent of women in hematology-oncology at that given point in time,” Dr. Marshall said in an interview.
“If an institution is truly committed to taking action on gender equity, it needs to look at gender and experience equity of speakers,” she said. “Perhaps it’s the time to say ‘Dr. X has been doing this review course for 15 years. Let’s give someone else a chance.’
“This is not even just from a gender equity perspective but from a career development perspective overall,” she added. “Junior faculty need these speaking engagements a lot more than senior faculty.”
Meanwhile, the higher number of female trainees is a trend that ideally will be sustained as those trainees move into positions of leadership, Dr. Marshall noted.
“We do see that over time, we have achieved gender equity in the percent of women matriculating to medical school. And my hope is that, 20 years down the line, we will see the effects of this reflected in increased equity in leadership positions such as division/department chair, dean, and hospital CEO,” she said. “However, we have a lot of work to do because there are still huge inequities in the culture of medicine (institutional and more broadly), including gender-based discrimination, maternal discrimination, and high attrition rates for women physicians, compared to male physicians.
“It’s not enough to simply say ‘well, we have fixed the problem because our incoming medical student classes are now equitable in gender distribution,’ ”
The authors and Dr. Marshall had no disclosures to report.
FROM BLOOD ADVANCES
Ultrasound helps predict gout flares over the next year
Adding ultrasound (US) to the clinical exam helps predict the likelihood of future gout flares, results of a prospective, observational study conducted in Italy suggest.
“Baseline US findings indicative of MSU [monosodium urate] burden and US-detected inflammation are independent predictors of gout flares over 12 months,” lead author Edoardo Cipolletta, MD, of the rheumatology unit, department of clinical and molecular sciences at Marche Polytechnic University in Ancona, Italy, and colleagues wrote in Rheumatology.
“We demonstrated that US findings provided an additional value over clinical data in estimating the risk of flares. Moreover, we reported an association between US findings at a joint and the occurrence of gout flares at the same joint,” they added.
Predicting risk of flares and reducing their occurrence are two main challenges in managing gout, the authors wrote. US can be used to scan multiple joints and is widely used in Europe as a low-cost, radiation-free imaging tool that’s easily integrated into clinical practice.
To investigate whether US can predict gout flares, the researchers enrolled 81 consecutive adult patients with gout in the study between April 2019 and March 2021 at one academic rheumatology treatment site in Italy and followed them for 12 months. The authors compared cases (who developed at least one flare within 12 months of the baseline visit) with controls (who self-reported no gout flares over that period).
Patients diagnosed with other inflammatory arthritis and those with coexisting calcium pyrophosphate deposition disease were excluded from the study.
The 71 participants who completed the study were, on average, in their early 60s, and in both groups, all but one were male. At the baseline visit, all had been on stable urate-lowering therapy for at least 6 months and had not had any gout flares in 4 weeks. The mean gout duration was 7 years in the case group and 8 years in controls.
At baseline, all participants underwent physical examination and US of elbows, wrists, second metacarpophalangeal joints, knees, ankles, and first metatarsophalangeal joints by a member of the research team who was blinded to the clinical and laboratory data.
Clinical assessments were scheduled at baseline and at 6-month intervals, and all participants were evaluated by a second researcher who was blinded to US findings.
During follow-up visits, participants were asked to report any gout flare, considered to meet at least three of four criteria: patient-defined flare, pain at rest score higher than 3 on a 0-10 scale, at least one swollen joint, and at least one warm joint. Patients not reaching their target serum urate goal received escalated urate-lowering therapy dosage and anti-inflammatory prophylaxis.
The US indicators of MSU deposits – aggregates, double contour sign, and tophi – were recorded as present or absent. The power Doppler signal was scored from 0 through 4, and summated scores for each US finding were calculated.
Over 12 months, the researchers found:
- Thirty (42.3%) patients had at least one flare, with a median of 2.0 flares. Patients with flares had higher a US median total MSU score (5.0 vs. 2.0; P = .01) and power Doppler signal (3.0 vs. 0; P < .01) than controls.
- In multivariate analysis, baseline US scores indicating MSU deposits and US-detected inflammation were significantly linked with the occurrence of flares. The adjusted odds ratio for total MSU score was 1.75 (95% confidence interval, 1.26-2.43) and for power Doppler score was 1.63 (95% CI, 1.12-2.40).
- Also in a multivariate analysis, baseline US scores indicating MSU deposits and US-detected inflammation were significantly linked with the number of flares. The incidence risk ratio for total MSU score adjusted was 1.17 (95% CI, 1.08-1.26) and for power Doppler score was 1.29 (95% CI, 1.19-1.40).
Four rheumatologists welcome findings
Gout remains the most common cause of inflammatory arthritis and a significant reason for hospital visits, noted Narender Annapureddy, MD, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn..
“The study adds to the growing utility of musculoskeletal ultrasound in rheumatology practices to treat various diseases,” he said. “Data that could provide risk prediction for gout flares would be associated with significant benefits in terms of reducing ED visits, hospital admission, and lost work productivity.”
One study limitation, Dr. Annapureddy mentioned, was the single experienced US reader, “which may limit generalizability of results at this time, at least in the United States.”
Yeohan Song, MD, an instructor at Ohio State University Wexner Medical Center, Columbus, integrates US into his practice.
“In gout management, musculoskeletal ultrasound is a useful adjunct to the clinical exam and laboratory markers, particularly [in patients] with recurrent flares despite guideline-directed target serum urate levels,” he said.
Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston, pointed out that the US protocol in the study involved imaging knees, ankles, first metatarsophalangeal joints, elbows, wrists, and second metacarpophalangeal joints, and took around 30 minutes to complete.
“That would not be practical in the United States due to time constraints in most rheumatology clinics,” she said.
“The authors report that a ‘reduced scanning protocol’ of the bilateral knees, ankles, and first metatarsophalangeal joints demonstrated similar predictive ability as the full protocol,” she added, “although scanning six joints still might not be feasible during a typical return patient clinic visit in the United States.”
Philip Chu, MD, clinical associate at Duke University, Durham, N.C., uses diagnostic US to help differentiate borderline gout cases from other arthropathies.
“A baseline scan, a follow-up scan before deciding to stop prophylaxis, or a follow-up scan in the setting of recurrent gout flares despite reaching goal serum uric acid, may be cost-effective time points to perform diagnostic US,” he advised.
“Unfortunately,” he added, “reimbursement for diagnostic US has been decreasing over the years, which makes it challenging to increase diagnostic US to the [frequency of its use] in Europe.”
Asked how most gout care being provided by primary care doctors in the United States affects gout management, Dr. Chu said: “Depending on which guidelines one follows for treating gout – from the American College of Rheumatology or the American College of Physicians – one may be more or less likely to start urate-lowering therapy after the first gout flare.”
“Understanding MSU burden in each patient, or even seeing active inflammation at these sites by increased Doppler signal, may change the threshold for physicians to initiate therapy,” he added.
The study received no funding. Three study authors reported financial involvements with pharmaceutical companies. Dr. Cipolletta, Dr. Annapureddy, Dr. Song, Dr. Tedeschi, and Dr. Chu reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
Adding ultrasound (US) to the clinical exam helps predict the likelihood of future gout flares, results of a prospective, observational study conducted in Italy suggest.
“Baseline US findings indicative of MSU [monosodium urate] burden and US-detected inflammation are independent predictors of gout flares over 12 months,” lead author Edoardo Cipolletta, MD, of the rheumatology unit, department of clinical and molecular sciences at Marche Polytechnic University in Ancona, Italy, and colleagues wrote in Rheumatology.
“We demonstrated that US findings provided an additional value over clinical data in estimating the risk of flares. Moreover, we reported an association between US findings at a joint and the occurrence of gout flares at the same joint,” they added.
Predicting risk of flares and reducing their occurrence are two main challenges in managing gout, the authors wrote. US can be used to scan multiple joints and is widely used in Europe as a low-cost, radiation-free imaging tool that’s easily integrated into clinical practice.
To investigate whether US can predict gout flares, the researchers enrolled 81 consecutive adult patients with gout in the study between April 2019 and March 2021 at one academic rheumatology treatment site in Italy and followed them for 12 months. The authors compared cases (who developed at least one flare within 12 months of the baseline visit) with controls (who self-reported no gout flares over that period).
Patients diagnosed with other inflammatory arthritis and those with coexisting calcium pyrophosphate deposition disease were excluded from the study.
The 71 participants who completed the study were, on average, in their early 60s, and in both groups, all but one were male. At the baseline visit, all had been on stable urate-lowering therapy for at least 6 months and had not had any gout flares in 4 weeks. The mean gout duration was 7 years in the case group and 8 years in controls.
At baseline, all participants underwent physical examination and US of elbows, wrists, second metacarpophalangeal joints, knees, ankles, and first metatarsophalangeal joints by a member of the research team who was blinded to the clinical and laboratory data.
Clinical assessments were scheduled at baseline and at 6-month intervals, and all participants were evaluated by a second researcher who was blinded to US findings.
During follow-up visits, participants were asked to report any gout flare, considered to meet at least three of four criteria: patient-defined flare, pain at rest score higher than 3 on a 0-10 scale, at least one swollen joint, and at least one warm joint. Patients not reaching their target serum urate goal received escalated urate-lowering therapy dosage and anti-inflammatory prophylaxis.
The US indicators of MSU deposits – aggregates, double contour sign, and tophi – were recorded as present or absent. The power Doppler signal was scored from 0 through 4, and summated scores for each US finding were calculated.
Over 12 months, the researchers found:
- Thirty (42.3%) patients had at least one flare, with a median of 2.0 flares. Patients with flares had higher a US median total MSU score (5.0 vs. 2.0; P = .01) and power Doppler signal (3.0 vs. 0; P < .01) than controls.
- In multivariate analysis, baseline US scores indicating MSU deposits and US-detected inflammation were significantly linked with the occurrence of flares. The adjusted odds ratio for total MSU score was 1.75 (95% confidence interval, 1.26-2.43) and for power Doppler score was 1.63 (95% CI, 1.12-2.40).
- Also in a multivariate analysis, baseline US scores indicating MSU deposits and US-detected inflammation were significantly linked with the number of flares. The incidence risk ratio for total MSU score adjusted was 1.17 (95% CI, 1.08-1.26) and for power Doppler score was 1.29 (95% CI, 1.19-1.40).
Four rheumatologists welcome findings
Gout remains the most common cause of inflammatory arthritis and a significant reason for hospital visits, noted Narender Annapureddy, MD, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn..
“The study adds to the growing utility of musculoskeletal ultrasound in rheumatology practices to treat various diseases,” he said. “Data that could provide risk prediction for gout flares would be associated with significant benefits in terms of reducing ED visits, hospital admission, and lost work productivity.”
One study limitation, Dr. Annapureddy mentioned, was the single experienced US reader, “which may limit generalizability of results at this time, at least in the United States.”
Yeohan Song, MD, an instructor at Ohio State University Wexner Medical Center, Columbus, integrates US into his practice.
“In gout management, musculoskeletal ultrasound is a useful adjunct to the clinical exam and laboratory markers, particularly [in patients] with recurrent flares despite guideline-directed target serum urate levels,” he said.
Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston, pointed out that the US protocol in the study involved imaging knees, ankles, first metatarsophalangeal joints, elbows, wrists, and second metacarpophalangeal joints, and took around 30 minutes to complete.
“That would not be practical in the United States due to time constraints in most rheumatology clinics,” she said.
“The authors report that a ‘reduced scanning protocol’ of the bilateral knees, ankles, and first metatarsophalangeal joints demonstrated similar predictive ability as the full protocol,” she added, “although scanning six joints still might not be feasible during a typical return patient clinic visit in the United States.”
Philip Chu, MD, clinical associate at Duke University, Durham, N.C., uses diagnostic US to help differentiate borderline gout cases from other arthropathies.
“A baseline scan, a follow-up scan before deciding to stop prophylaxis, or a follow-up scan in the setting of recurrent gout flares despite reaching goal serum uric acid, may be cost-effective time points to perform diagnostic US,” he advised.
“Unfortunately,” he added, “reimbursement for diagnostic US has been decreasing over the years, which makes it challenging to increase diagnostic US to the [frequency of its use] in Europe.”
Asked how most gout care being provided by primary care doctors in the United States affects gout management, Dr. Chu said: “Depending on which guidelines one follows for treating gout – from the American College of Rheumatology or the American College of Physicians – one may be more or less likely to start urate-lowering therapy after the first gout flare.”
“Understanding MSU burden in each patient, or even seeing active inflammation at these sites by increased Doppler signal, may change the threshold for physicians to initiate therapy,” he added.
The study received no funding. Three study authors reported financial involvements with pharmaceutical companies. Dr. Cipolletta, Dr. Annapureddy, Dr. Song, Dr. Tedeschi, and Dr. Chu reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
Adding ultrasound (US) to the clinical exam helps predict the likelihood of future gout flares, results of a prospective, observational study conducted in Italy suggest.
“Baseline US findings indicative of MSU [monosodium urate] burden and US-detected inflammation are independent predictors of gout flares over 12 months,” lead author Edoardo Cipolletta, MD, of the rheumatology unit, department of clinical and molecular sciences at Marche Polytechnic University in Ancona, Italy, and colleagues wrote in Rheumatology.
“We demonstrated that US findings provided an additional value over clinical data in estimating the risk of flares. Moreover, we reported an association between US findings at a joint and the occurrence of gout flares at the same joint,” they added.
Predicting risk of flares and reducing their occurrence are two main challenges in managing gout, the authors wrote. US can be used to scan multiple joints and is widely used in Europe as a low-cost, radiation-free imaging tool that’s easily integrated into clinical practice.
To investigate whether US can predict gout flares, the researchers enrolled 81 consecutive adult patients with gout in the study between April 2019 and March 2021 at one academic rheumatology treatment site in Italy and followed them for 12 months. The authors compared cases (who developed at least one flare within 12 months of the baseline visit) with controls (who self-reported no gout flares over that period).
Patients diagnosed with other inflammatory arthritis and those with coexisting calcium pyrophosphate deposition disease were excluded from the study.
The 71 participants who completed the study were, on average, in their early 60s, and in both groups, all but one were male. At the baseline visit, all had been on stable urate-lowering therapy for at least 6 months and had not had any gout flares in 4 weeks. The mean gout duration was 7 years in the case group and 8 years in controls.
At baseline, all participants underwent physical examination and US of elbows, wrists, second metacarpophalangeal joints, knees, ankles, and first metatarsophalangeal joints by a member of the research team who was blinded to the clinical and laboratory data.
Clinical assessments were scheduled at baseline and at 6-month intervals, and all participants were evaluated by a second researcher who was blinded to US findings.
During follow-up visits, participants were asked to report any gout flare, considered to meet at least three of four criteria: patient-defined flare, pain at rest score higher than 3 on a 0-10 scale, at least one swollen joint, and at least one warm joint. Patients not reaching their target serum urate goal received escalated urate-lowering therapy dosage and anti-inflammatory prophylaxis.
The US indicators of MSU deposits – aggregates, double contour sign, and tophi – were recorded as present or absent. The power Doppler signal was scored from 0 through 4, and summated scores for each US finding were calculated.
Over 12 months, the researchers found:
- Thirty (42.3%) patients had at least one flare, with a median of 2.0 flares. Patients with flares had higher a US median total MSU score (5.0 vs. 2.0; P = .01) and power Doppler signal (3.0 vs. 0; P < .01) than controls.
- In multivariate analysis, baseline US scores indicating MSU deposits and US-detected inflammation were significantly linked with the occurrence of flares. The adjusted odds ratio for total MSU score was 1.75 (95% confidence interval, 1.26-2.43) and for power Doppler score was 1.63 (95% CI, 1.12-2.40).
- Also in a multivariate analysis, baseline US scores indicating MSU deposits and US-detected inflammation were significantly linked with the number of flares. The incidence risk ratio for total MSU score adjusted was 1.17 (95% CI, 1.08-1.26) and for power Doppler score was 1.29 (95% CI, 1.19-1.40).
Four rheumatologists welcome findings
Gout remains the most common cause of inflammatory arthritis and a significant reason for hospital visits, noted Narender Annapureddy, MD, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn..
“The study adds to the growing utility of musculoskeletal ultrasound in rheumatology practices to treat various diseases,” he said. “Data that could provide risk prediction for gout flares would be associated with significant benefits in terms of reducing ED visits, hospital admission, and lost work productivity.”
One study limitation, Dr. Annapureddy mentioned, was the single experienced US reader, “which may limit generalizability of results at this time, at least in the United States.”
Yeohan Song, MD, an instructor at Ohio State University Wexner Medical Center, Columbus, integrates US into his practice.
“In gout management, musculoskeletal ultrasound is a useful adjunct to the clinical exam and laboratory markers, particularly [in patients] with recurrent flares despite guideline-directed target serum urate levels,” he said.
Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston, pointed out that the US protocol in the study involved imaging knees, ankles, first metatarsophalangeal joints, elbows, wrists, and second metacarpophalangeal joints, and took around 30 minutes to complete.
“That would not be practical in the United States due to time constraints in most rheumatology clinics,” she said.
“The authors report that a ‘reduced scanning protocol’ of the bilateral knees, ankles, and first metatarsophalangeal joints demonstrated similar predictive ability as the full protocol,” she added, “although scanning six joints still might not be feasible during a typical return patient clinic visit in the United States.”
Philip Chu, MD, clinical associate at Duke University, Durham, N.C., uses diagnostic US to help differentiate borderline gout cases from other arthropathies.
“A baseline scan, a follow-up scan before deciding to stop prophylaxis, or a follow-up scan in the setting of recurrent gout flares despite reaching goal serum uric acid, may be cost-effective time points to perform diagnostic US,” he advised.
“Unfortunately,” he added, “reimbursement for diagnostic US has been decreasing over the years, which makes it challenging to increase diagnostic US to the [frequency of its use] in Europe.”
Asked how most gout care being provided by primary care doctors in the United States affects gout management, Dr. Chu said: “Depending on which guidelines one follows for treating gout – from the American College of Rheumatology or the American College of Physicians – one may be more or less likely to start urate-lowering therapy after the first gout flare.”
“Understanding MSU burden in each patient, or even seeing active inflammation at these sites by increased Doppler signal, may change the threshold for physicians to initiate therapy,” he added.
The study received no funding. Three study authors reported financial involvements with pharmaceutical companies. Dr. Cipolletta, Dr. Annapureddy, Dr. Song, Dr. Tedeschi, and Dr. Chu reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM RHEUMATOLOGY
Primary care now offering physicians the 26.7-hour day
Taking ‘not enough hours in the day’ to new heights
It’s no secret that there’s a big doctor shortage in the United States. Going through medical school is long, expensive, and stressful, and it’s not like those long, stressful hours stop once you finally do get that degree. There is, however, an excellent reason to take that dive into doctorhood: You’ll gain mastery over time itself.
A study from the University of Chicago, Johns Hopkins University, and Imperial College London has revealed the truth. By using data pulled from the National Health and Nutrition Examination Survey, the researchers found that primary care physicians who see an average number of patients and follow all the current national guidelines for preventive care, chronic disease care, and acute care – plus administrative tasks – must work 26.7 hours a day. That works out to 14.1 hours of preventive care, 7.2 hours of chronic disease care, 2.2 hours of acute care, and 3.2 hours of documentation and inbox management.
Astute readers may note that this is a bit more than the traditional 8-hour workday. It is, in fact, more hours than there actually are in a day. As it turns out, Doctor Strange is more of a documentary than …
Hang on, we’re receiving word that doctors are not in fact wizards who can bend time and space to their will, nor are they sitting on a stash of Time-Turners they saved from the Ministry of Magic before Voldemort destroyed them all. They are, according to the study, overworked and overburdened with too many things and too little time. This is why outcomes haven’t improved despite technological advances and why burnout is so common. We’d be burned out too, having to work temporally impossible hours.
The study authors suggested a team-based approach to medicine that would spread the workload out to nurses, physician assistants, dietitians, etc., estimating that about two-thirds of what a primary care physician does can be handled by someone else. A team-based approach would reduce the physician’s required hours down to 9.3 hours a day, which is at least physically possible. It’s either that or we make the day longer, which sounds like the plot of an episode of Futurama. Swap overwork for global warming and a longer day for a longer year and it is actually the plot of an episode of Futurama.
After a hard day of thinking, brains need their rest
Do you ever feel like you have no more capacity to think or make any more decisions after a long day at work? Do you need a few extra cups of coffee to even make it through the day, even though you’re mostly just sitting around talking and typing? Have we got the research for you: Mental exhaustion is an actual thing. Imagine that double whammy of having a job that’s physically and mentally demanding.
A recent study in Current Biology explained why we feel so exhausted after doing something mentally demanding for several hours. Over that time, glutamate builds up in synapses of the prefrontal cortex, which affects our decision making and leads to cognitive lethargy. Your brain eventually becomes more interested in tasks that are less mentally fatiguing, and that’s probably why you’re reading this LOTME right now instead of getting back to work.
“Our findings show that cognitive work results in a true functional alteration – accumulation of noxious substances – so fatigue would indeed be a signal that makes us stop working but for a different purpose: to preserve the integrity of brain functioning,” senior author Mathias Pessiglione of Pitié-Salpêtrière University, Paris, said in a written statement.
The group of researchers conducted studies by using magnetic resonance spectroscopy to look at two groups of people over the course of a workday: One group had mentally tasking jobs and one didn’t. Those who had to think harder for their jobs had more signs of fatigue, such as reduced pupil dilation and glutamate in synapses of the prefrontal cortex. They also looked for more rewards that required less thinking.
For those whose mentally exhausting jobs probably won’t get better or change, the researchers suggest getting as much rest as possible. Those who don’t have that option will have to continue drinking those 7 cups of coffee a day. ... and reading LOTME.
Hmm, might be a new tagline for us in there somewhere. LOTME: Tired brains love us? When you’re too tired to think, think of LOTME? You can’t spell mental exhaustion without L-O-T-M-E?
Testosterone shows its warm and fuzzy side
Stereotypically, men are loud, knuckle-dragging Neanderthals. The hair coming out of our faces is kind of a dead giveaway, right? We grunt, we scratch, we start wars, we watch sports on TV. But why? It’s the testosterone. Everyone knows that. Testosterone makes men aggressive … or does it?
Since this sort of research generally isn’t done with actual men, investigators at Emory University used Mongolian gerbils. The advantage being that males exhibit cuddling behavior after females become pregnant and they don’t watch a lot of sports on TV. They introduced a male and female gerbil, who then formed a pair bond and the female became pregnant. When the male started displaying cuddling behaviors, the researchers injected him with testosterone, expecting to see his antisocial side.
“Instead, we were surprised that a male gerbil became even more cuddly and prosocial with his partner. He became like ‘super partner,’ ” lead author Aubrey Kelly, PhD, said in a written statement from the university.
For the next experiment, the female was removed and another male was introduced to a male who had already received a testosterone injection. That male was surprisingly unaggressive toward the intruder, at least initially. Then he received a second injection of testosterone. “It was like they suddenly woke up and realized they weren’t supposed to be friendly in that context,” Dr. Kelly said.
The testosterone seemed to influence the activity of oxytocin, the so-called “love hormone,” the investigators suggested. “It’s surprising because normally we think of testosterone as increasing sexual behaviors and aggression. But we’ve shown that it can have more nuanced effects, depending on the social context.”
The researchers were not as surprised when their use of the phrase “super partner” led to a bidding war between DC and Marvel. Then came the contact from the Department of Defense, wondering about weaponized testosterone: Would it be possible for some sort of bomb to turn Vlad “the Impaler” Putin into Vlad “the Cuddler” Putin?
Are instruments spreading the sounds of COVID?
COVID restrictions are practically a thing of the past now. With more people laxed on being in close proximity to each other and the CDC not even recommending social distancing anymore, live concerts and events are back in full swing. But with new variants on the rise and people being a little more cautious, should we be worried about musical instruments spreading COVID?
Yes and no.
A study published in Physics of Fluids looked at wind instruments specifically and how much aerosol is produced and dispersed when playing them. For the study, the investigators measured fog particles with a laser and aerosol concentration with a particle counter to see how fast these particles decay in the air from the distance of the instrument.
Musicians in an orchestra typically would sit close together to produce the best sound, but with COVID that became an issue, senior author Paulo Arratia of the University of Pennsylvania, Philadelphia, noted in a separate written statement. By looking at the distance traveled by the particles coming from a single instrument and how quickly they decayed, they could determine if sitting in close proximity is an actual threat.
Well, the threat was no greater than talking to someone face to face. Particle exit speeds were lower than for a cough or a sneeze, and the maximum decay length was 2 meters from the instrument’s opening.
But that’s just one instrument: What kind of impact does a whole orchestra have on a space? The researchers are looking into that too, but for now they suggest that musicians continue to stay 6 feet away from each other.
So, yeah, there is a threat, but it’s probably safer for you to see that orchestra than have someone sneeze on you.
Music to our ears.
Taking ‘not enough hours in the day’ to new heights
It’s no secret that there’s a big doctor shortage in the United States. Going through medical school is long, expensive, and stressful, and it’s not like those long, stressful hours stop once you finally do get that degree. There is, however, an excellent reason to take that dive into doctorhood: You’ll gain mastery over time itself.
A study from the University of Chicago, Johns Hopkins University, and Imperial College London has revealed the truth. By using data pulled from the National Health and Nutrition Examination Survey, the researchers found that primary care physicians who see an average number of patients and follow all the current national guidelines for preventive care, chronic disease care, and acute care – plus administrative tasks – must work 26.7 hours a day. That works out to 14.1 hours of preventive care, 7.2 hours of chronic disease care, 2.2 hours of acute care, and 3.2 hours of documentation and inbox management.
Astute readers may note that this is a bit more than the traditional 8-hour workday. It is, in fact, more hours than there actually are in a day. As it turns out, Doctor Strange is more of a documentary than …
Hang on, we’re receiving word that doctors are not in fact wizards who can bend time and space to their will, nor are they sitting on a stash of Time-Turners they saved from the Ministry of Magic before Voldemort destroyed them all. They are, according to the study, overworked and overburdened with too many things and too little time. This is why outcomes haven’t improved despite technological advances and why burnout is so common. We’d be burned out too, having to work temporally impossible hours.
The study authors suggested a team-based approach to medicine that would spread the workload out to nurses, physician assistants, dietitians, etc., estimating that about two-thirds of what a primary care physician does can be handled by someone else. A team-based approach would reduce the physician’s required hours down to 9.3 hours a day, which is at least physically possible. It’s either that or we make the day longer, which sounds like the plot of an episode of Futurama. Swap overwork for global warming and a longer day for a longer year and it is actually the plot of an episode of Futurama.
After a hard day of thinking, brains need their rest
Do you ever feel like you have no more capacity to think or make any more decisions after a long day at work? Do you need a few extra cups of coffee to even make it through the day, even though you’re mostly just sitting around talking and typing? Have we got the research for you: Mental exhaustion is an actual thing. Imagine that double whammy of having a job that’s physically and mentally demanding.
A recent study in Current Biology explained why we feel so exhausted after doing something mentally demanding for several hours. Over that time, glutamate builds up in synapses of the prefrontal cortex, which affects our decision making and leads to cognitive lethargy. Your brain eventually becomes more interested in tasks that are less mentally fatiguing, and that’s probably why you’re reading this LOTME right now instead of getting back to work.
“Our findings show that cognitive work results in a true functional alteration – accumulation of noxious substances – so fatigue would indeed be a signal that makes us stop working but for a different purpose: to preserve the integrity of brain functioning,” senior author Mathias Pessiglione of Pitié-Salpêtrière University, Paris, said in a written statement.
The group of researchers conducted studies by using magnetic resonance spectroscopy to look at two groups of people over the course of a workday: One group had mentally tasking jobs and one didn’t. Those who had to think harder for their jobs had more signs of fatigue, such as reduced pupil dilation and glutamate in synapses of the prefrontal cortex. They also looked for more rewards that required less thinking.
For those whose mentally exhausting jobs probably won’t get better or change, the researchers suggest getting as much rest as possible. Those who don’t have that option will have to continue drinking those 7 cups of coffee a day. ... and reading LOTME.
Hmm, might be a new tagline for us in there somewhere. LOTME: Tired brains love us? When you’re too tired to think, think of LOTME? You can’t spell mental exhaustion without L-O-T-M-E?
Testosterone shows its warm and fuzzy side
Stereotypically, men are loud, knuckle-dragging Neanderthals. The hair coming out of our faces is kind of a dead giveaway, right? We grunt, we scratch, we start wars, we watch sports on TV. But why? It’s the testosterone. Everyone knows that. Testosterone makes men aggressive … or does it?
Since this sort of research generally isn’t done with actual men, investigators at Emory University used Mongolian gerbils. The advantage being that males exhibit cuddling behavior after females become pregnant and they don’t watch a lot of sports on TV. They introduced a male and female gerbil, who then formed a pair bond and the female became pregnant. When the male started displaying cuddling behaviors, the researchers injected him with testosterone, expecting to see his antisocial side.
“Instead, we were surprised that a male gerbil became even more cuddly and prosocial with his partner. He became like ‘super partner,’ ” lead author Aubrey Kelly, PhD, said in a written statement from the university.
For the next experiment, the female was removed and another male was introduced to a male who had already received a testosterone injection. That male was surprisingly unaggressive toward the intruder, at least initially. Then he received a second injection of testosterone. “It was like they suddenly woke up and realized they weren’t supposed to be friendly in that context,” Dr. Kelly said.
The testosterone seemed to influence the activity of oxytocin, the so-called “love hormone,” the investigators suggested. “It’s surprising because normally we think of testosterone as increasing sexual behaviors and aggression. But we’ve shown that it can have more nuanced effects, depending on the social context.”
The researchers were not as surprised when their use of the phrase “super partner” led to a bidding war between DC and Marvel. Then came the contact from the Department of Defense, wondering about weaponized testosterone: Would it be possible for some sort of bomb to turn Vlad “the Impaler” Putin into Vlad “the Cuddler” Putin?
Are instruments spreading the sounds of COVID?
COVID restrictions are practically a thing of the past now. With more people laxed on being in close proximity to each other and the CDC not even recommending social distancing anymore, live concerts and events are back in full swing. But with new variants on the rise and people being a little more cautious, should we be worried about musical instruments spreading COVID?
Yes and no.
A study published in Physics of Fluids looked at wind instruments specifically and how much aerosol is produced and dispersed when playing them. For the study, the investigators measured fog particles with a laser and aerosol concentration with a particle counter to see how fast these particles decay in the air from the distance of the instrument.
Musicians in an orchestra typically would sit close together to produce the best sound, but with COVID that became an issue, senior author Paulo Arratia of the University of Pennsylvania, Philadelphia, noted in a separate written statement. By looking at the distance traveled by the particles coming from a single instrument and how quickly they decayed, they could determine if sitting in close proximity is an actual threat.
Well, the threat was no greater than talking to someone face to face. Particle exit speeds were lower than for a cough or a sneeze, and the maximum decay length was 2 meters from the instrument’s opening.
But that’s just one instrument: What kind of impact does a whole orchestra have on a space? The researchers are looking into that too, but for now they suggest that musicians continue to stay 6 feet away from each other.
So, yeah, there is a threat, but it’s probably safer for you to see that orchestra than have someone sneeze on you.
Music to our ears.
Taking ‘not enough hours in the day’ to new heights
It’s no secret that there’s a big doctor shortage in the United States. Going through medical school is long, expensive, and stressful, and it’s not like those long, stressful hours stop once you finally do get that degree. There is, however, an excellent reason to take that dive into doctorhood: You’ll gain mastery over time itself.
A study from the University of Chicago, Johns Hopkins University, and Imperial College London has revealed the truth. By using data pulled from the National Health and Nutrition Examination Survey, the researchers found that primary care physicians who see an average number of patients and follow all the current national guidelines for preventive care, chronic disease care, and acute care – plus administrative tasks – must work 26.7 hours a day. That works out to 14.1 hours of preventive care, 7.2 hours of chronic disease care, 2.2 hours of acute care, and 3.2 hours of documentation and inbox management.
Astute readers may note that this is a bit more than the traditional 8-hour workday. It is, in fact, more hours than there actually are in a day. As it turns out, Doctor Strange is more of a documentary than …
Hang on, we’re receiving word that doctors are not in fact wizards who can bend time and space to their will, nor are they sitting on a stash of Time-Turners they saved from the Ministry of Magic before Voldemort destroyed them all. They are, according to the study, overworked and overburdened with too many things and too little time. This is why outcomes haven’t improved despite technological advances and why burnout is so common. We’d be burned out too, having to work temporally impossible hours.
The study authors suggested a team-based approach to medicine that would spread the workload out to nurses, physician assistants, dietitians, etc., estimating that about two-thirds of what a primary care physician does can be handled by someone else. A team-based approach would reduce the physician’s required hours down to 9.3 hours a day, which is at least physically possible. It’s either that or we make the day longer, which sounds like the plot of an episode of Futurama. Swap overwork for global warming and a longer day for a longer year and it is actually the plot of an episode of Futurama.
After a hard day of thinking, brains need their rest
Do you ever feel like you have no more capacity to think or make any more decisions after a long day at work? Do you need a few extra cups of coffee to even make it through the day, even though you’re mostly just sitting around talking and typing? Have we got the research for you: Mental exhaustion is an actual thing. Imagine that double whammy of having a job that’s physically and mentally demanding.
A recent study in Current Biology explained why we feel so exhausted after doing something mentally demanding for several hours. Over that time, glutamate builds up in synapses of the prefrontal cortex, which affects our decision making and leads to cognitive lethargy. Your brain eventually becomes more interested in tasks that are less mentally fatiguing, and that’s probably why you’re reading this LOTME right now instead of getting back to work.
“Our findings show that cognitive work results in a true functional alteration – accumulation of noxious substances – so fatigue would indeed be a signal that makes us stop working but for a different purpose: to preserve the integrity of brain functioning,” senior author Mathias Pessiglione of Pitié-Salpêtrière University, Paris, said in a written statement.
The group of researchers conducted studies by using magnetic resonance spectroscopy to look at two groups of people over the course of a workday: One group had mentally tasking jobs and one didn’t. Those who had to think harder for their jobs had more signs of fatigue, such as reduced pupil dilation and glutamate in synapses of the prefrontal cortex. They also looked for more rewards that required less thinking.
For those whose mentally exhausting jobs probably won’t get better or change, the researchers suggest getting as much rest as possible. Those who don’t have that option will have to continue drinking those 7 cups of coffee a day. ... and reading LOTME.
Hmm, might be a new tagline for us in there somewhere. LOTME: Tired brains love us? When you’re too tired to think, think of LOTME? You can’t spell mental exhaustion without L-O-T-M-E?
Testosterone shows its warm and fuzzy side
Stereotypically, men are loud, knuckle-dragging Neanderthals. The hair coming out of our faces is kind of a dead giveaway, right? We grunt, we scratch, we start wars, we watch sports on TV. But why? It’s the testosterone. Everyone knows that. Testosterone makes men aggressive … or does it?
Since this sort of research generally isn’t done with actual men, investigators at Emory University used Mongolian gerbils. The advantage being that males exhibit cuddling behavior after females become pregnant and they don’t watch a lot of sports on TV. They introduced a male and female gerbil, who then formed a pair bond and the female became pregnant. When the male started displaying cuddling behaviors, the researchers injected him with testosterone, expecting to see his antisocial side.
“Instead, we were surprised that a male gerbil became even more cuddly and prosocial with his partner. He became like ‘super partner,’ ” lead author Aubrey Kelly, PhD, said in a written statement from the university.
For the next experiment, the female was removed and another male was introduced to a male who had already received a testosterone injection. That male was surprisingly unaggressive toward the intruder, at least initially. Then he received a second injection of testosterone. “It was like they suddenly woke up and realized they weren’t supposed to be friendly in that context,” Dr. Kelly said.
The testosterone seemed to influence the activity of oxytocin, the so-called “love hormone,” the investigators suggested. “It’s surprising because normally we think of testosterone as increasing sexual behaviors and aggression. But we’ve shown that it can have more nuanced effects, depending on the social context.”
The researchers were not as surprised when their use of the phrase “super partner” led to a bidding war between DC and Marvel. Then came the contact from the Department of Defense, wondering about weaponized testosterone: Would it be possible for some sort of bomb to turn Vlad “the Impaler” Putin into Vlad “the Cuddler” Putin?
Are instruments spreading the sounds of COVID?
COVID restrictions are practically a thing of the past now. With more people laxed on being in close proximity to each other and the CDC not even recommending social distancing anymore, live concerts and events are back in full swing. But with new variants on the rise and people being a little more cautious, should we be worried about musical instruments spreading COVID?
Yes and no.
A study published in Physics of Fluids looked at wind instruments specifically and how much aerosol is produced and dispersed when playing them. For the study, the investigators measured fog particles with a laser and aerosol concentration with a particle counter to see how fast these particles decay in the air from the distance of the instrument.
Musicians in an orchestra typically would sit close together to produce the best sound, but with COVID that became an issue, senior author Paulo Arratia of the University of Pennsylvania, Philadelphia, noted in a separate written statement. By looking at the distance traveled by the particles coming from a single instrument and how quickly they decayed, they could determine if sitting in close proximity is an actual threat.
Well, the threat was no greater than talking to someone face to face. Particle exit speeds were lower than for a cough or a sneeze, and the maximum decay length was 2 meters from the instrument’s opening.
But that’s just one instrument: What kind of impact does a whole orchestra have on a space? The researchers are looking into that too, but for now they suggest that musicians continue to stay 6 feet away from each other.
So, yeah, there is a threat, but it’s probably safer for you to see that orchestra than have someone sneeze on you.
Music to our ears.
What ketamine and psilocybin can and cannot do in depression
Recent studies with hallucinogens have raised hopes for an effective drug-based therapy to treat chronic depression. At the German Congress of Psychosomatic Medicine and Psychotherapy, Torsten Passie, MD, PhD, professor of psychiatry and psychotherapy at the Hannover (Germay) Medical School, gave a presentation on the current state of psilocybin and ketamine/esketamine research.
Dr. Passie, who also is head physician of the specialist unit for addiction and addiction prevention at the Diakonisches Werk in Hannover, has been investigating hallucinogenic substances and their application in psychotherapy for decades.
New therapies sought
In depression, gloom extends beyond the patient’s mood. For some time there has been little cause for joy with regard to chronic depression therapy. Established drug therapies hardly perform any better than placebo in meta-analyses, as a study recently confirmed. The pharmaceutical industry pulled out of psycho-pharmaceutical development more than 10 years ago. What’s more, the number of cases is rising, especially among young people, and there are long waiting times for psychotherapy appointments.
It is no wonder that some are welcoming new drug-based approaches with lysergic acid diethylamide (LSD)–like hallucinogens. In 2016, a study on psilocybin was published in The Lancet Psychiatry, although the study was unblinded and included only 24 patients.
Evoking emotions
A range of substances can be classed as hallucinogens, including psilocybin, mescaline, LSD, 3,4-methylenedioxy-methamphetamine (MDMA, also known as ecstasy), and ketamine.
Taking hallucinogens can cause a release of serotonin and dopamine, an increase in activity levels in the brain, a shift in stimulus filtering, an increase in the production of internal stimuli (inner experiences), and a change in sensory integration (for example, synesthesia).
Besides falling into a dreamlike state, patients can achieve an expansion or narrowing of consciousness if they focus on an inner experience. Internal perception increases. Perceptual routines are broken apart. Thought processes become more image-based and are more associative than normal.
Patients therefore are more capable of making new and unusual connections between different biographical or current situations. Previously unconscious ideas can become conscious. At higher doses, ego loss can occur, which can be associated with a mystical feeling of connectedness.
Hallucinogens mainly evoke and heighten emotions. Those effects may be experienced strongly as internal visions or in physical manifestations (for example, crying or laughing). In contrast, conventional antidepressants work by suppressing emotions (that is, emotional blunting).
These different mechanisms result in two contrasting management strategies. For example, SSRI antidepressants cause a patient to perceive workplace bullying as less severe and to do nothing to change the situation; the patient remains passive.
In contrast, a therapeutically guided, emotionally activating experience on hallucinogens can help the patient to try more actively to change the stressful situation.
Ketamine has a special place among hallucinogens. Unlike other hallucinogens, ketamine causes a strong clouding of consciousness, a reduction in physical sensory perception, and significant disruption in thinking and memory. It is therefore only suitable as a short-term intervention and is therapeutically impractical over the long term.
Ketamine’s effects
Ketamine, a racemic mixture of the enantiomers S-ketamine and R-ketamine, was originally used only as an analgesic and anesthetic. Owing to its rapid antidepressant effect, it has since also been used as an emergency medication for severe depression, sometimes in combination with SSRIs or serotonin noradrenaline reuptake inhibitors.
Approximately 60% of patients respond to the treatment. Whereas with conventional antidepressants, onset of action requires 10-14 days, ketamine is effective within a few hours. However, relapse always occurs, usually very quickly. After 2-3 days, the effect is usually approximately that of a placebo. An administration interval of about 2 days is optimal. However, “resistance” to the effect often develops after some time: the drug’s antidepressant effect diminishes.
Ketamine also has some unpleasant side effects, such as depersonalization, dissociation, impaired thinking, nystagmus, and psychotomimetic effects. Nausea and vomiting also occur. Interestingly, the latter does not bother the patient much, owing to the drug’s psychological effects, and it does not lead to treatment discontinuation, said Dr. Passie, who described his clinical experiences with ketamine.
Since ketamine causes a considerable clouding of consciousness, sensory disorders, and significant memory problems, it is not suitable for psychedelic-assisted psychotherapy, unlike LSD or psilocybin, he emphasized.
Ketamine 2.0?
Esketamine, the pure S-enantiomer of ketamine, has been on the market since 2019 in the form of a nasal spray (Spravato). Esketamine has been approved in combination with oral antidepressant therapy for adults with a moderate to severe episode of major depression for acute treatment of a psychiatric emergency.
A meta-analysis from 2022 concluded that the original racemic ketamine is better than the new esketamine in reducing symptoms of depression.
In his own comprehensive study, Dr. Passie concluded that the mental impairments that occur during therapy did not differ significantly between substances. The patients even felt that the side effects from esketamine therapy were much more mentally unpleasant, said Dr. Passie. He concluded that the R-enantiomer may have a kind of protective effect against some of the psychopathological effects of the S-enantiomer (esketamine).
In addition, preclinical studies have indicated that the antidepressant effects of R-enantiomer, which is not contained in esketamine, are longer lasting and stronger.
Another problem is absorption, which can be inconsistent with a nasal spray. It may differ, for example, depending on the ambient humidity or whether the patient has recently had a cold. In addition, the spray is far more expensive than the ketamine injection, said Dr. Passie. Patients must also use the nasal spray under supervision at a medical practice (as with the intravenous application) and must receive follow-up care there. It therefore offers no advantage over the ketamine injection.
According to the Institute for Quality and Efficiency in Healthcare, no additional benefit has been proven for esketamine over standard therapies for adults who have experienced a moderate to severe depressive episode when used as short-term treatment for the rapid reduction of depressive symptoms in a psychiatric emergency. The German Medical Association agreed with this evaluation in October 2021.
In the United Kingdom, the medication was never approved, owing to the fact that it was too expensive and that no studies comparing it with psychotherapy were available.
Add-on psilocybin?
What was experienced under the influence of psilocybin can also be subsequently processed and used in psychotherapy.
The acute effect of psilocybin begins after approximately 40 minutes and lasts for 4-6 hours. The antidepressant effect, if it occurs at all, is of immediate onset. Unlike ketamine/esketamine, psilocybin hardly has any physical side effects.
The neurologic mechanism of action has been investigated recently using fMRI and PET techniques. According to the investigations, the substance causes individual networks of activity in the patient’s brain to interconnect more strongly, said Dr. Passie. The thalamus, the filter station for sensory information, as well as the limbic and paralimbic structures, which generate emotions, and the cortex are all activated more strongly.
Two therapeutic settings
Psilocybin, at least in the context of studies, is used in two settings: psycholytic therapy and psychedelic therapy. Both settings originated in the 1950s and were also used with LSD as the active substance.
Psycholytic therapy with psilocybin entails multiple administrations at low doses (for example, 10-18 mg), incorporated into a longer, mostly psychodynamic therapy of around 50-100 hours (often on an inpatient basis at the beginning). It results in what is described as an extended encounter with oneself. The focus is on psychodynamic experiences, such as memories and internal conflicts. In addition, novel experiences with oneself and self-recognition are important.
Psychedelic therapy generally entails one or two sessions with a high dose (for example, 25-35 mg psilocybin). The preparation and follow-up are limited to a few sessions. These methods refer to so-called transpersonal psychology, which addresses extraordinary states of consciousness in line with religious experiences. It often leads to an intense self-confrontation as well as to new evaluations of self and world. The central element to this therapy is the experience of a mystical ego loss and the concomitant feeling of connectedness, which should help to expand one’s perspective.
Euphoria and disillusionment
The first promising studies with a few patients suffering from depression were followed by others in which the euphoria was allowed to fade away somewhat. In the first direct comparison in a methodically high-grade double-blind study, psilocybin was inferior to the SSRI antidepressant escitalopram.
“There is a great variation in response from person to person,” said Dr. Passie. “The better the study is methodically controlled, the worse the results,” he hypothesized.
“Since the method is up to 50 times more expensive in practice, compared to SSRI therapy over 6-12 weeks, the question clearly must be asked as to whether it really has any great future.”
Outlook for psilocybin
Nevertheless, Dr. Passie still sees potential in psilocybin. He considers an approach in which psilocybin therapy is more firmly incorporated into psychotherapy, with between four and 10 therapy sessions before and after administration of a lower therapeutic dose of the substance, to be more promising.
“With this kind of intensive preparation and follow-up, as well as the repeated psilocybin sessions, the patient can benefit much more than is possible with one or two high-dose sessions,” said Dr. Passie, who also is chair of the International Society for Substance-Assisted Psychotherapy. “The constant ‘in-depth work on the ego’ required for drastic therapeutic changes can be more effective and lead to permanent improvements. I have no doubt about this.”
In Dr. Passie’s opinion, the best approach would involve a dignified inpatient setting with a longer period of follow-up care and consistent posttreatment care, including group therapy. The shape of future psilocybin therapy depends on whether the rather abrupt change seen with high-dose psychedelic therapy is permanent. The answer to this question will be decisive for the method and manner of its future clinical use.
Because of the somewhat negative study results, however, the initial investors are pulling out. Dr. Passie is therefore skeptical about whether the necessary larger studies will take place and whether psilocybin will make it onto the market.
In Switzerland, which is not subject to EU restrictions, more than 30 physicians have been authorized to use psilocybin, LSD, and MDMA in psychotherapy sessions. Still, in some respects this is a special case that cannot be transferred easily to other countries, said Dr. Passie.
Possible psilocybin improvement?
Various chemical derivatives of psychoactive substances have been researched, including a psilocybin variant with the label CYB003. With CYB003, the length of the acute psychedelic experience is reduced from around 6 hours (such as with psilocybin) to 1 hour. The plasma concentration of the substance is less variable between different patients. It is assumed that its effects will also differ less from person to person.
In July, researchers began a study of the use of CYB003 in the treatment of major depression. In the randomized, double-blind, placebo-controlled study with 40 patients, multiple doses of the substance will be administered.
When asked, Dr. Passie was rather skeptical about the study. He considers the approaches with psilocybin derivatives to be the consequences of a “gold-rush atmosphere” and expects there will be no real additional benefit, especially not a reduction in the period of action.
A version of this article first appeared on Medscape.com.
Recent studies with hallucinogens have raised hopes for an effective drug-based therapy to treat chronic depression. At the German Congress of Psychosomatic Medicine and Psychotherapy, Torsten Passie, MD, PhD, professor of psychiatry and psychotherapy at the Hannover (Germay) Medical School, gave a presentation on the current state of psilocybin and ketamine/esketamine research.
Dr. Passie, who also is head physician of the specialist unit for addiction and addiction prevention at the Diakonisches Werk in Hannover, has been investigating hallucinogenic substances and their application in psychotherapy for decades.
New therapies sought
In depression, gloom extends beyond the patient’s mood. For some time there has been little cause for joy with regard to chronic depression therapy. Established drug therapies hardly perform any better than placebo in meta-analyses, as a study recently confirmed. The pharmaceutical industry pulled out of psycho-pharmaceutical development more than 10 years ago. What’s more, the number of cases is rising, especially among young people, and there are long waiting times for psychotherapy appointments.
It is no wonder that some are welcoming new drug-based approaches with lysergic acid diethylamide (LSD)–like hallucinogens. In 2016, a study on psilocybin was published in The Lancet Psychiatry, although the study was unblinded and included only 24 patients.
Evoking emotions
A range of substances can be classed as hallucinogens, including psilocybin, mescaline, LSD, 3,4-methylenedioxy-methamphetamine (MDMA, also known as ecstasy), and ketamine.
Taking hallucinogens can cause a release of serotonin and dopamine, an increase in activity levels in the brain, a shift in stimulus filtering, an increase in the production of internal stimuli (inner experiences), and a change in sensory integration (for example, synesthesia).
Besides falling into a dreamlike state, patients can achieve an expansion or narrowing of consciousness if they focus on an inner experience. Internal perception increases. Perceptual routines are broken apart. Thought processes become more image-based and are more associative than normal.
Patients therefore are more capable of making new and unusual connections between different biographical or current situations. Previously unconscious ideas can become conscious. At higher doses, ego loss can occur, which can be associated with a mystical feeling of connectedness.
Hallucinogens mainly evoke and heighten emotions. Those effects may be experienced strongly as internal visions or in physical manifestations (for example, crying or laughing). In contrast, conventional antidepressants work by suppressing emotions (that is, emotional blunting).
These different mechanisms result in two contrasting management strategies. For example, SSRI antidepressants cause a patient to perceive workplace bullying as less severe and to do nothing to change the situation; the patient remains passive.
In contrast, a therapeutically guided, emotionally activating experience on hallucinogens can help the patient to try more actively to change the stressful situation.
Ketamine has a special place among hallucinogens. Unlike other hallucinogens, ketamine causes a strong clouding of consciousness, a reduction in physical sensory perception, and significant disruption in thinking and memory. It is therefore only suitable as a short-term intervention and is therapeutically impractical over the long term.
Ketamine’s effects
Ketamine, a racemic mixture of the enantiomers S-ketamine and R-ketamine, was originally used only as an analgesic and anesthetic. Owing to its rapid antidepressant effect, it has since also been used as an emergency medication for severe depression, sometimes in combination with SSRIs or serotonin noradrenaline reuptake inhibitors.
Approximately 60% of patients respond to the treatment. Whereas with conventional antidepressants, onset of action requires 10-14 days, ketamine is effective within a few hours. However, relapse always occurs, usually very quickly. After 2-3 days, the effect is usually approximately that of a placebo. An administration interval of about 2 days is optimal. However, “resistance” to the effect often develops after some time: the drug’s antidepressant effect diminishes.
Ketamine also has some unpleasant side effects, such as depersonalization, dissociation, impaired thinking, nystagmus, and psychotomimetic effects. Nausea and vomiting also occur. Interestingly, the latter does not bother the patient much, owing to the drug’s psychological effects, and it does not lead to treatment discontinuation, said Dr. Passie, who described his clinical experiences with ketamine.
Since ketamine causes a considerable clouding of consciousness, sensory disorders, and significant memory problems, it is not suitable for psychedelic-assisted psychotherapy, unlike LSD or psilocybin, he emphasized.
Ketamine 2.0?
Esketamine, the pure S-enantiomer of ketamine, has been on the market since 2019 in the form of a nasal spray (Spravato). Esketamine has been approved in combination with oral antidepressant therapy for adults with a moderate to severe episode of major depression for acute treatment of a psychiatric emergency.
A meta-analysis from 2022 concluded that the original racemic ketamine is better than the new esketamine in reducing symptoms of depression.
In his own comprehensive study, Dr. Passie concluded that the mental impairments that occur during therapy did not differ significantly between substances. The patients even felt that the side effects from esketamine therapy were much more mentally unpleasant, said Dr. Passie. He concluded that the R-enantiomer may have a kind of protective effect against some of the psychopathological effects of the S-enantiomer (esketamine).
In addition, preclinical studies have indicated that the antidepressant effects of R-enantiomer, which is not contained in esketamine, are longer lasting and stronger.
Another problem is absorption, which can be inconsistent with a nasal spray. It may differ, for example, depending on the ambient humidity or whether the patient has recently had a cold. In addition, the spray is far more expensive than the ketamine injection, said Dr. Passie. Patients must also use the nasal spray under supervision at a medical practice (as with the intravenous application) and must receive follow-up care there. It therefore offers no advantage over the ketamine injection.
According to the Institute for Quality and Efficiency in Healthcare, no additional benefit has been proven for esketamine over standard therapies for adults who have experienced a moderate to severe depressive episode when used as short-term treatment for the rapid reduction of depressive symptoms in a psychiatric emergency. The German Medical Association agreed with this evaluation in October 2021.
In the United Kingdom, the medication was never approved, owing to the fact that it was too expensive and that no studies comparing it with psychotherapy were available.
Add-on psilocybin?
What was experienced under the influence of psilocybin can also be subsequently processed and used in psychotherapy.
The acute effect of psilocybin begins after approximately 40 minutes and lasts for 4-6 hours. The antidepressant effect, if it occurs at all, is of immediate onset. Unlike ketamine/esketamine, psilocybin hardly has any physical side effects.
The neurologic mechanism of action has been investigated recently using fMRI and PET techniques. According to the investigations, the substance causes individual networks of activity in the patient’s brain to interconnect more strongly, said Dr. Passie. The thalamus, the filter station for sensory information, as well as the limbic and paralimbic structures, which generate emotions, and the cortex are all activated more strongly.
Two therapeutic settings
Psilocybin, at least in the context of studies, is used in two settings: psycholytic therapy and psychedelic therapy. Both settings originated in the 1950s and were also used with LSD as the active substance.
Psycholytic therapy with psilocybin entails multiple administrations at low doses (for example, 10-18 mg), incorporated into a longer, mostly psychodynamic therapy of around 50-100 hours (often on an inpatient basis at the beginning). It results in what is described as an extended encounter with oneself. The focus is on psychodynamic experiences, such as memories and internal conflicts. In addition, novel experiences with oneself and self-recognition are important.
Psychedelic therapy generally entails one or two sessions with a high dose (for example, 25-35 mg psilocybin). The preparation and follow-up are limited to a few sessions. These methods refer to so-called transpersonal psychology, which addresses extraordinary states of consciousness in line with religious experiences. It often leads to an intense self-confrontation as well as to new evaluations of self and world. The central element to this therapy is the experience of a mystical ego loss and the concomitant feeling of connectedness, which should help to expand one’s perspective.
Euphoria and disillusionment
The first promising studies with a few patients suffering from depression were followed by others in which the euphoria was allowed to fade away somewhat. In the first direct comparison in a methodically high-grade double-blind study, psilocybin was inferior to the SSRI antidepressant escitalopram.
“There is a great variation in response from person to person,” said Dr. Passie. “The better the study is methodically controlled, the worse the results,” he hypothesized.
“Since the method is up to 50 times more expensive in practice, compared to SSRI therapy over 6-12 weeks, the question clearly must be asked as to whether it really has any great future.”
Outlook for psilocybin
Nevertheless, Dr. Passie still sees potential in psilocybin. He considers an approach in which psilocybin therapy is more firmly incorporated into psychotherapy, with between four and 10 therapy sessions before and after administration of a lower therapeutic dose of the substance, to be more promising.
“With this kind of intensive preparation and follow-up, as well as the repeated psilocybin sessions, the patient can benefit much more than is possible with one or two high-dose sessions,” said Dr. Passie, who also is chair of the International Society for Substance-Assisted Psychotherapy. “The constant ‘in-depth work on the ego’ required for drastic therapeutic changes can be more effective and lead to permanent improvements. I have no doubt about this.”
In Dr. Passie’s opinion, the best approach would involve a dignified inpatient setting with a longer period of follow-up care and consistent posttreatment care, including group therapy. The shape of future psilocybin therapy depends on whether the rather abrupt change seen with high-dose psychedelic therapy is permanent. The answer to this question will be decisive for the method and manner of its future clinical use.
Because of the somewhat negative study results, however, the initial investors are pulling out. Dr. Passie is therefore skeptical about whether the necessary larger studies will take place and whether psilocybin will make it onto the market.
In Switzerland, which is not subject to EU restrictions, more than 30 physicians have been authorized to use psilocybin, LSD, and MDMA in psychotherapy sessions. Still, in some respects this is a special case that cannot be transferred easily to other countries, said Dr. Passie.
Possible psilocybin improvement?
Various chemical derivatives of psychoactive substances have been researched, including a psilocybin variant with the label CYB003. With CYB003, the length of the acute psychedelic experience is reduced from around 6 hours (such as with psilocybin) to 1 hour. The plasma concentration of the substance is less variable between different patients. It is assumed that its effects will also differ less from person to person.
In July, researchers began a study of the use of CYB003 in the treatment of major depression. In the randomized, double-blind, placebo-controlled study with 40 patients, multiple doses of the substance will be administered.
When asked, Dr. Passie was rather skeptical about the study. He considers the approaches with psilocybin derivatives to be the consequences of a “gold-rush atmosphere” and expects there will be no real additional benefit, especially not a reduction in the period of action.
A version of this article first appeared on Medscape.com.
Recent studies with hallucinogens have raised hopes for an effective drug-based therapy to treat chronic depression. At the German Congress of Psychosomatic Medicine and Psychotherapy, Torsten Passie, MD, PhD, professor of psychiatry and psychotherapy at the Hannover (Germay) Medical School, gave a presentation on the current state of psilocybin and ketamine/esketamine research.
Dr. Passie, who also is head physician of the specialist unit for addiction and addiction prevention at the Diakonisches Werk in Hannover, has been investigating hallucinogenic substances and their application in psychotherapy for decades.
New therapies sought
In depression, gloom extends beyond the patient’s mood. For some time there has been little cause for joy with regard to chronic depression therapy. Established drug therapies hardly perform any better than placebo in meta-analyses, as a study recently confirmed. The pharmaceutical industry pulled out of psycho-pharmaceutical development more than 10 years ago. What’s more, the number of cases is rising, especially among young people, and there are long waiting times for psychotherapy appointments.
It is no wonder that some are welcoming new drug-based approaches with lysergic acid diethylamide (LSD)–like hallucinogens. In 2016, a study on psilocybin was published in The Lancet Psychiatry, although the study was unblinded and included only 24 patients.
Evoking emotions
A range of substances can be classed as hallucinogens, including psilocybin, mescaline, LSD, 3,4-methylenedioxy-methamphetamine (MDMA, also known as ecstasy), and ketamine.
Taking hallucinogens can cause a release of serotonin and dopamine, an increase in activity levels in the brain, a shift in stimulus filtering, an increase in the production of internal stimuli (inner experiences), and a change in sensory integration (for example, synesthesia).
Besides falling into a dreamlike state, patients can achieve an expansion or narrowing of consciousness if they focus on an inner experience. Internal perception increases. Perceptual routines are broken apart. Thought processes become more image-based and are more associative than normal.
Patients therefore are more capable of making new and unusual connections between different biographical or current situations. Previously unconscious ideas can become conscious. At higher doses, ego loss can occur, which can be associated with a mystical feeling of connectedness.
Hallucinogens mainly evoke and heighten emotions. Those effects may be experienced strongly as internal visions or in physical manifestations (for example, crying or laughing). In contrast, conventional antidepressants work by suppressing emotions (that is, emotional blunting).
These different mechanisms result in two contrasting management strategies. For example, SSRI antidepressants cause a patient to perceive workplace bullying as less severe and to do nothing to change the situation; the patient remains passive.
In contrast, a therapeutically guided, emotionally activating experience on hallucinogens can help the patient to try more actively to change the stressful situation.
Ketamine has a special place among hallucinogens. Unlike other hallucinogens, ketamine causes a strong clouding of consciousness, a reduction in physical sensory perception, and significant disruption in thinking and memory. It is therefore only suitable as a short-term intervention and is therapeutically impractical over the long term.
Ketamine’s effects
Ketamine, a racemic mixture of the enantiomers S-ketamine and R-ketamine, was originally used only as an analgesic and anesthetic. Owing to its rapid antidepressant effect, it has since also been used as an emergency medication for severe depression, sometimes in combination with SSRIs or serotonin noradrenaline reuptake inhibitors.
Approximately 60% of patients respond to the treatment. Whereas with conventional antidepressants, onset of action requires 10-14 days, ketamine is effective within a few hours. However, relapse always occurs, usually very quickly. After 2-3 days, the effect is usually approximately that of a placebo. An administration interval of about 2 days is optimal. However, “resistance” to the effect often develops after some time: the drug’s antidepressant effect diminishes.
Ketamine also has some unpleasant side effects, such as depersonalization, dissociation, impaired thinking, nystagmus, and psychotomimetic effects. Nausea and vomiting also occur. Interestingly, the latter does not bother the patient much, owing to the drug’s psychological effects, and it does not lead to treatment discontinuation, said Dr. Passie, who described his clinical experiences with ketamine.
Since ketamine causes a considerable clouding of consciousness, sensory disorders, and significant memory problems, it is not suitable for psychedelic-assisted psychotherapy, unlike LSD or psilocybin, he emphasized.
Ketamine 2.0?
Esketamine, the pure S-enantiomer of ketamine, has been on the market since 2019 in the form of a nasal spray (Spravato). Esketamine has been approved in combination with oral antidepressant therapy for adults with a moderate to severe episode of major depression for acute treatment of a psychiatric emergency.
A meta-analysis from 2022 concluded that the original racemic ketamine is better than the new esketamine in reducing symptoms of depression.
In his own comprehensive study, Dr. Passie concluded that the mental impairments that occur during therapy did not differ significantly between substances. The patients even felt that the side effects from esketamine therapy were much more mentally unpleasant, said Dr. Passie. He concluded that the R-enantiomer may have a kind of protective effect against some of the psychopathological effects of the S-enantiomer (esketamine).
In addition, preclinical studies have indicated that the antidepressant effects of R-enantiomer, which is not contained in esketamine, are longer lasting and stronger.
Another problem is absorption, which can be inconsistent with a nasal spray. It may differ, for example, depending on the ambient humidity or whether the patient has recently had a cold. In addition, the spray is far more expensive than the ketamine injection, said Dr. Passie. Patients must also use the nasal spray under supervision at a medical practice (as with the intravenous application) and must receive follow-up care there. It therefore offers no advantage over the ketamine injection.
According to the Institute for Quality and Efficiency in Healthcare, no additional benefit has been proven for esketamine over standard therapies for adults who have experienced a moderate to severe depressive episode when used as short-term treatment for the rapid reduction of depressive symptoms in a psychiatric emergency. The German Medical Association agreed with this evaluation in October 2021.
In the United Kingdom, the medication was never approved, owing to the fact that it was too expensive and that no studies comparing it with psychotherapy were available.
Add-on psilocybin?
What was experienced under the influence of psilocybin can also be subsequently processed and used in psychotherapy.
The acute effect of psilocybin begins after approximately 40 minutes and lasts for 4-6 hours. The antidepressant effect, if it occurs at all, is of immediate onset. Unlike ketamine/esketamine, psilocybin hardly has any physical side effects.
The neurologic mechanism of action has been investigated recently using fMRI and PET techniques. According to the investigations, the substance causes individual networks of activity in the patient’s brain to interconnect more strongly, said Dr. Passie. The thalamus, the filter station for sensory information, as well as the limbic and paralimbic structures, which generate emotions, and the cortex are all activated more strongly.
Two therapeutic settings
Psilocybin, at least in the context of studies, is used in two settings: psycholytic therapy and psychedelic therapy. Both settings originated in the 1950s and were also used with LSD as the active substance.
Psycholytic therapy with psilocybin entails multiple administrations at low doses (for example, 10-18 mg), incorporated into a longer, mostly psychodynamic therapy of around 50-100 hours (often on an inpatient basis at the beginning). It results in what is described as an extended encounter with oneself. The focus is on psychodynamic experiences, such as memories and internal conflicts. In addition, novel experiences with oneself and self-recognition are important.
Psychedelic therapy generally entails one or two sessions with a high dose (for example, 25-35 mg psilocybin). The preparation and follow-up are limited to a few sessions. These methods refer to so-called transpersonal psychology, which addresses extraordinary states of consciousness in line with religious experiences. It often leads to an intense self-confrontation as well as to new evaluations of self and world. The central element to this therapy is the experience of a mystical ego loss and the concomitant feeling of connectedness, which should help to expand one’s perspective.
Euphoria and disillusionment
The first promising studies with a few patients suffering from depression were followed by others in which the euphoria was allowed to fade away somewhat. In the first direct comparison in a methodically high-grade double-blind study, psilocybin was inferior to the SSRI antidepressant escitalopram.
“There is a great variation in response from person to person,” said Dr. Passie. “The better the study is methodically controlled, the worse the results,” he hypothesized.
“Since the method is up to 50 times more expensive in practice, compared to SSRI therapy over 6-12 weeks, the question clearly must be asked as to whether it really has any great future.”
Outlook for psilocybin
Nevertheless, Dr. Passie still sees potential in psilocybin. He considers an approach in which psilocybin therapy is more firmly incorporated into psychotherapy, with between four and 10 therapy sessions before and after administration of a lower therapeutic dose of the substance, to be more promising.
“With this kind of intensive preparation and follow-up, as well as the repeated psilocybin sessions, the patient can benefit much more than is possible with one or two high-dose sessions,” said Dr. Passie, who also is chair of the International Society for Substance-Assisted Psychotherapy. “The constant ‘in-depth work on the ego’ required for drastic therapeutic changes can be more effective and lead to permanent improvements. I have no doubt about this.”
In Dr. Passie’s opinion, the best approach would involve a dignified inpatient setting with a longer period of follow-up care and consistent posttreatment care, including group therapy. The shape of future psilocybin therapy depends on whether the rather abrupt change seen with high-dose psychedelic therapy is permanent. The answer to this question will be decisive for the method and manner of its future clinical use.
Because of the somewhat negative study results, however, the initial investors are pulling out. Dr. Passie is therefore skeptical about whether the necessary larger studies will take place and whether psilocybin will make it onto the market.
In Switzerland, which is not subject to EU restrictions, more than 30 physicians have been authorized to use psilocybin, LSD, and MDMA in psychotherapy sessions. Still, in some respects this is a special case that cannot be transferred easily to other countries, said Dr. Passie.
Possible psilocybin improvement?
Various chemical derivatives of psychoactive substances have been researched, including a psilocybin variant with the label CYB003. With CYB003, the length of the acute psychedelic experience is reduced from around 6 hours (such as with psilocybin) to 1 hour. The plasma concentration of the substance is less variable between different patients. It is assumed that its effects will also differ less from person to person.
In July, researchers began a study of the use of CYB003 in the treatment of major depression. In the randomized, double-blind, placebo-controlled study with 40 patients, multiple doses of the substance will be administered.
When asked, Dr. Passie was rather skeptical about the study. He considers the approaches with psilocybin derivatives to be the consequences of a “gold-rush atmosphere” and expects there will be no real additional benefit, especially not a reduction in the period of action.
A version of this article first appeared on Medscape.com.
Oncologists’ wealth and debt: COVID had little impact
concludes the latest Medscape Oncologist Wealth & Debt Report 2022.
Comparing the findings with those in the larger Medscape Physician Wealth & Debt Report 2022, which surveyed more than 13,000 physicians in 29 specialties, the findings for oncologists show how they compare with those who chose other paths in medicine.
Oncologists’ income rose, on average, by 2% in the past year and now stands at an average of $411,000 annually, up from $403,000 in the 2021 report.
This puts oncologists in the top third of specialties, with plastic surgeons again in the top slot (with average income of $576,000 in 2022).
One-fifth (20%) of oncologists surveyed reported a family worth of more than $5 million, which represents substantial family wealth, the report comments.
However, 22% of oncologists reported that their family net worth was less than $500,000, and another 10% estimated that it to fall between $500,000 and $1 million.
For comparison, the average U.S. family net worth is about $749,000, according to data from the Federal Reserve.
Most live ‘within their means’
Most oncologists (94%) and also most (94%) of all of the physicians surveyed said that they live within or below their means.
How does one do this? Just paying off credit cards each month and contributing enough to a 401(k) account to receive an employer match does not meet this standard, said Joel Greenwald MD, CFP, a wealth management advisor for physicians. To live within or below your means, you also need to be saving at least 20% toward retirement, pay down student loans, contribute to your kids’ college savings, and set aside rainy day cash, he explained.
When physicians were asked about their favorite cost-cutting tactics, replies included bringing lunch to work, keeping a car for 15 years, and carrying out their own household maintenance and repairs. One doctor described a “24-hour rule” when it comes to shopping: “Revisit the desired purchase after 24 hours to see if it’s still desired.”
But how well do these tactics go down with ‘the other half’ and the rest of the household? Two-thirds (66%) of oncologists, and a similar proportion of all physicians, said that they argue with their significant other about spending. This appears to be high in comparison with the finding from a recent survey that across the United States, about one in four couples (25%) argue about money at least once a month.
Regarding spending, the top expense among oncologists was for childcare (16%), private tuition for offspring (14%), mortgage on a second home (14%), college tuition for offspring (14%), and a car lease (12%).
Around 17% of oncologists reported that they are still paying off their own college or medical school loans. For this statistic, they are about in the middle of all specialties.
The report notes that freeing oneself from medical school debt is very costly. Physicians in the United States pay an average of $356,000-$440,000, about half of which is interest.
Little change over 2021
The COVID pandemic had much less of an impact on physicians than it had on the general population when it comes to keeping up with payments, and most physicians were not affected. Only 3% of oncologists said they fell behind with payments for mortgage; 6% fell behind with payments for other bills.
In comparison, nearly half (46%) of Americans missed one or more payments of rent or mortgage because of COVID, according to a 2021 industry survey.
Over the past year, most oncologists (70%) did not change their spending habits, and only 11% cut expenses by deferring or refinancing loans. Also, most oncologists (75%) avoided major financial loses. Only 8% reported financial losses because of problems at their medical practice.
However, a slightly higher percentage of oncologists reported a stock or company investment that had turned sour in 2022 (37%) in comparison with 2021 (28%).
A version of this article first appeared on Medscape.com.
concludes the latest Medscape Oncologist Wealth & Debt Report 2022.
Comparing the findings with those in the larger Medscape Physician Wealth & Debt Report 2022, which surveyed more than 13,000 physicians in 29 specialties, the findings for oncologists show how they compare with those who chose other paths in medicine.
Oncologists’ income rose, on average, by 2% in the past year and now stands at an average of $411,000 annually, up from $403,000 in the 2021 report.
This puts oncologists in the top third of specialties, with plastic surgeons again in the top slot (with average income of $576,000 in 2022).
One-fifth (20%) of oncologists surveyed reported a family worth of more than $5 million, which represents substantial family wealth, the report comments.
However, 22% of oncologists reported that their family net worth was less than $500,000, and another 10% estimated that it to fall between $500,000 and $1 million.
For comparison, the average U.S. family net worth is about $749,000, according to data from the Federal Reserve.
Most live ‘within their means’
Most oncologists (94%) and also most (94%) of all of the physicians surveyed said that they live within or below their means.
How does one do this? Just paying off credit cards each month and contributing enough to a 401(k) account to receive an employer match does not meet this standard, said Joel Greenwald MD, CFP, a wealth management advisor for physicians. To live within or below your means, you also need to be saving at least 20% toward retirement, pay down student loans, contribute to your kids’ college savings, and set aside rainy day cash, he explained.
When physicians were asked about their favorite cost-cutting tactics, replies included bringing lunch to work, keeping a car for 15 years, and carrying out their own household maintenance and repairs. One doctor described a “24-hour rule” when it comes to shopping: “Revisit the desired purchase after 24 hours to see if it’s still desired.”
But how well do these tactics go down with ‘the other half’ and the rest of the household? Two-thirds (66%) of oncologists, and a similar proportion of all physicians, said that they argue with their significant other about spending. This appears to be high in comparison with the finding from a recent survey that across the United States, about one in four couples (25%) argue about money at least once a month.
Regarding spending, the top expense among oncologists was for childcare (16%), private tuition for offspring (14%), mortgage on a second home (14%), college tuition for offspring (14%), and a car lease (12%).
Around 17% of oncologists reported that they are still paying off their own college or medical school loans. For this statistic, they are about in the middle of all specialties.
The report notes that freeing oneself from medical school debt is very costly. Physicians in the United States pay an average of $356,000-$440,000, about half of which is interest.
Little change over 2021
The COVID pandemic had much less of an impact on physicians than it had on the general population when it comes to keeping up with payments, and most physicians were not affected. Only 3% of oncologists said they fell behind with payments for mortgage; 6% fell behind with payments for other bills.
In comparison, nearly half (46%) of Americans missed one or more payments of rent or mortgage because of COVID, according to a 2021 industry survey.
Over the past year, most oncologists (70%) did not change their spending habits, and only 11% cut expenses by deferring or refinancing loans. Also, most oncologists (75%) avoided major financial loses. Only 8% reported financial losses because of problems at their medical practice.
However, a slightly higher percentage of oncologists reported a stock or company investment that had turned sour in 2022 (37%) in comparison with 2021 (28%).
A version of this article first appeared on Medscape.com.
concludes the latest Medscape Oncologist Wealth & Debt Report 2022.
Comparing the findings with those in the larger Medscape Physician Wealth & Debt Report 2022, which surveyed more than 13,000 physicians in 29 specialties, the findings for oncologists show how they compare with those who chose other paths in medicine.
Oncologists’ income rose, on average, by 2% in the past year and now stands at an average of $411,000 annually, up from $403,000 in the 2021 report.
This puts oncologists in the top third of specialties, with plastic surgeons again in the top slot (with average income of $576,000 in 2022).
One-fifth (20%) of oncologists surveyed reported a family worth of more than $5 million, which represents substantial family wealth, the report comments.
However, 22% of oncologists reported that their family net worth was less than $500,000, and another 10% estimated that it to fall between $500,000 and $1 million.
For comparison, the average U.S. family net worth is about $749,000, according to data from the Federal Reserve.
Most live ‘within their means’
Most oncologists (94%) and also most (94%) of all of the physicians surveyed said that they live within or below their means.
How does one do this? Just paying off credit cards each month and contributing enough to a 401(k) account to receive an employer match does not meet this standard, said Joel Greenwald MD, CFP, a wealth management advisor for physicians. To live within or below your means, you also need to be saving at least 20% toward retirement, pay down student loans, contribute to your kids’ college savings, and set aside rainy day cash, he explained.
When physicians were asked about their favorite cost-cutting tactics, replies included bringing lunch to work, keeping a car for 15 years, and carrying out their own household maintenance and repairs. One doctor described a “24-hour rule” when it comes to shopping: “Revisit the desired purchase after 24 hours to see if it’s still desired.”
But how well do these tactics go down with ‘the other half’ and the rest of the household? Two-thirds (66%) of oncologists, and a similar proportion of all physicians, said that they argue with their significant other about spending. This appears to be high in comparison with the finding from a recent survey that across the United States, about one in four couples (25%) argue about money at least once a month.
Regarding spending, the top expense among oncologists was for childcare (16%), private tuition for offspring (14%), mortgage on a second home (14%), college tuition for offspring (14%), and a car lease (12%).
Around 17% of oncologists reported that they are still paying off their own college or medical school loans. For this statistic, they are about in the middle of all specialties.
The report notes that freeing oneself from medical school debt is very costly. Physicians in the United States pay an average of $356,000-$440,000, about half of which is interest.
Little change over 2021
The COVID pandemic had much less of an impact on physicians than it had on the general population when it comes to keeping up with payments, and most physicians were not affected. Only 3% of oncologists said they fell behind with payments for mortgage; 6% fell behind with payments for other bills.
In comparison, nearly half (46%) of Americans missed one or more payments of rent or mortgage because of COVID, according to a 2021 industry survey.
Over the past year, most oncologists (70%) did not change their spending habits, and only 11% cut expenses by deferring or refinancing loans. Also, most oncologists (75%) avoided major financial loses. Only 8% reported financial losses because of problems at their medical practice.
However, a slightly higher percentage of oncologists reported a stock or company investment that had turned sour in 2022 (37%) in comparison with 2021 (28%).
A version of this article first appeared on Medscape.com.