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Progressive multifocal leukoencephalopathy
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Common parasite now tied to impaired cognitive function
Investigators reviewed and conducted a meta-analysis of 13 studies that encompassed more than 13,000 healthy adults and found a modest but significant association between T. gondii seropositivity and impaired performance on cognitive tests of processing speed, working memory, short-term verbal memory, and executive function. The average age of the persons in the studies was close to 50 years.
“Our findings show that T. gondii could have a negative but small effect on cognition,” study investigator Arjen Sutterland, MD, of the Amsterdam Neuroscience Research Institute and the Amsterdam Institute for Infection and Immunity, University of Amsterdam, said in an interview.
The study was published online July 14, 2021, in JAMA Psychiatry.
Mental illness link
T. gondii is “an intracellular parasite that produces quiescent infection in approximately 30% of humans worldwide,” the authors wrote. The parasite that causes the infection not only settles in muscle and liver tissue but also can cross the blood-brain barrier and settle quiescently in brain tissue. It can be spread through contact with cat feces or by consuming contaminated meat.
Previous research has shown that neurocognitive changes associated with toxoplasmosis can occur in humans, and meta-analyses suggest an association with neuropsychiatric disorders. Some research has also tied T. gondii infection to increased motor vehicle crashes and suicide attempts.
Dr. Sutterland said he had been inspired by the work of E. Fuller Torrey and Bob Yolken, who proposed the connection between T. gondii and schizophrenia.
Some years ago, Dr. Sutterland and his group analyzed the mental health consequences of T. gondii infection and found “several interesting associations,” but they were unable to “rule out reverse causation – i.e., people with mental health disorders more often get these infections – as well as determine the impact on the population of this common infection.”
For the current study, the investigators analyzed studies that examined specifically cognitive functioning in otherwise healthy individuals in relation to T. gondii infection, “because reverse causation would be less likely in this population and a grasp of global impact would become more clear.”
The researchers conducted a literature search of studies conducted through June 7, 2019, that analyzed cognitive function among healthy participants for whom data on T. gondii seropositivity were available.
A total of 13 studies (n = 13,289 participants; mean age, 46.7 years; 49.6% male) were used in the review and meta-analysis. Some of the studies enrolled a healthy population sample; other studies compared participants with and those without psychiatric disorders. From these, the researchers extracted only the data concerning healthy participants.
The studies analyzed four cognitive domains: processing speed, working memory, short-term verbal memory, and executive functioning.
All cognitive domains affected
Of all the participants, 22.6% had antibodies against T. gondii.
Participants who were seropositive for T. gondii had less favorable functioning in all cognitive domains, with “small but significant” differences. 
The researchers conducted a meta-regression analysis of mean age in the analysis of executive functioning and found greater effect sizes as age increased (Q = 6.17; R2 = 81%; P = .01).
The studies were of “high quality,” and there was “little suggestion of publication bias was detected,” the authors noted.
“Although the extent of the associations was modest, the ubiquitous prevalence of the quiescent infection worldwide ... suggests that the consequences for cognitive function of the population as a whole may be substantial, although it is difficult to quantify the global impact,” they wrote.
They note that because the studies were cross-sectional in nature, causality cannot be established.
Nevertheless, Dr. Sutterland suggested several possible mechanisms through which T. gondii might affect neurocognition.
“We know the parasite forms cysts in the brain and can influence dopaminergic neurotransmission, which, in turn, affects neurocognition. Alternatively, it is also possible that the immune response to the infection in the brain causes cognitive impairment. This remains an important question to explore further,” he said.
He noted that clinicians can reassure patients who test positive for T. gondii that although the infection can have a negative impact on cognition, the effect is “small.”
Prevention programs warranted
Commenting on the study in an interview, Shawn D. Gale, PhD, associate professor, department of psychology and neuroscience center, Brigham Young University, Provo, Utah, called it a “great meta-analysis.” He noted that his group is researching the subject and has obtained similar findings. A big plus is that the researchers assessed several cognitive domains, not just one.
Although the data showed “mild effects,” the findings could be important on a population level. Because 30% of the world’s population are seropositive for T. gondii, a potentially large number of people are at risk for cognitive impairment, noted Dr. Gale, who was not involved with the study.
“If you look at the United States, perhaps 10%-15% of people might test positive [for T. gondii], but in Germany and France, the number comes closer to 50%, and in other places in the world – especially countries that have a harder time economically – the rates are even higher. So if it can affect cognition, even a small effect is a big deal,” Dr. Gale said.
“I think prevention will be the most important thing, and perhaps down the road, I hope that a vaccine will be considered,” Dr. Gale added.
“These findings indicate that primary prevention of the infection could have substantial global impact on mental health” and that public health programs to prevent T. gondii “are warranted.”
These programs might consist of hygienic measures, especially after human contact with contaminated sources, as well as research into vaccine development.
No source of funding for the study was listed. The authors and Dr. Gale reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Investigators reviewed and conducted a meta-analysis of 13 studies that encompassed more than 13,000 healthy adults and found a modest but significant association between T. gondii seropositivity and impaired performance on cognitive tests of processing speed, working memory, short-term verbal memory, and executive function. The average age of the persons in the studies was close to 50 years.
“Our findings show that T. gondii could have a negative but small effect on cognition,” study investigator Arjen Sutterland, MD, of the Amsterdam Neuroscience Research Institute and the Amsterdam Institute for Infection and Immunity, University of Amsterdam, said in an interview.
The study was published online July 14, 2021, in JAMA Psychiatry.
Mental illness link
T. gondii is “an intracellular parasite that produces quiescent infection in approximately 30% of humans worldwide,” the authors wrote. The parasite that causes the infection not only settles in muscle and liver tissue but also can cross the blood-brain barrier and settle quiescently in brain tissue. It can be spread through contact with cat feces or by consuming contaminated meat.
Previous research has shown that neurocognitive changes associated with toxoplasmosis can occur in humans, and meta-analyses suggest an association with neuropsychiatric disorders. Some research has also tied T. gondii infection to increased motor vehicle crashes and suicide attempts.
Dr. Sutterland said he had been inspired by the work of E. Fuller Torrey and Bob Yolken, who proposed the connection between T. gondii and schizophrenia.
Some years ago, Dr. Sutterland and his group analyzed the mental health consequences of T. gondii infection and found “several interesting associations,” but they were unable to “rule out reverse causation – i.e., people with mental health disorders more often get these infections – as well as determine the impact on the population of this common infection.”
For the current study, the investigators analyzed studies that examined specifically cognitive functioning in otherwise healthy individuals in relation to T. gondii infection, “because reverse causation would be less likely in this population and a grasp of global impact would become more clear.”
The researchers conducted a literature search of studies conducted through June 7, 2019, that analyzed cognitive function among healthy participants for whom data on T. gondii seropositivity were available.
A total of 13 studies (n = 13,289 participants; mean age, 46.7 years; 49.6% male) were used in the review and meta-analysis. Some of the studies enrolled a healthy population sample; other studies compared participants with and those without psychiatric disorders. From these, the researchers extracted only the data concerning healthy participants.
The studies analyzed four cognitive domains: processing speed, working memory, short-term verbal memory, and executive functioning.
All cognitive domains affected
Of all the participants, 22.6% had antibodies against T. gondii.
Participants who were seropositive for T. gondii had less favorable functioning in all cognitive domains, with “small but significant” differences.
The researchers conducted a meta-regression analysis of mean age in the analysis of executive functioning and found greater effect sizes as age increased (Q = 6.17; R2 = 81%; P = .01).
The studies were of “high quality,” and there was “little suggestion of publication bias was detected,” the authors noted.
“Although the extent of the associations was modest, the ubiquitous prevalence of the quiescent infection worldwide ... suggests that the consequences for cognitive function of the population as a whole may be substantial, although it is difficult to quantify the global impact,” they wrote.
They note that because the studies were cross-sectional in nature, causality cannot be established.
Nevertheless, Dr. Sutterland suggested several possible mechanisms through which T. gondii might affect neurocognition.
“We know the parasite forms cysts in the brain and can influence dopaminergic neurotransmission, which, in turn, affects neurocognition. Alternatively, it is also possible that the immune response to the infection in the brain causes cognitive impairment. This remains an important question to explore further,” he said.
He noted that clinicians can reassure patients who test positive for T. gondii that although the infection can have a negative impact on cognition, the effect is “small.”
Prevention programs warranted
Commenting on the study in an interview, Shawn D. Gale, PhD, associate professor, department of psychology and neuroscience center, Brigham Young University, Provo, Utah, called it a “great meta-analysis.” He noted that his group is researching the subject and has obtained similar findings. A big plus is that the researchers assessed several cognitive domains, not just one.
Although the data showed “mild effects,” the findings could be important on a population level. Because 30% of the world’s population are seropositive for T. gondii, a potentially large number of people are at risk for cognitive impairment, noted Dr. Gale, who was not involved with the study.
“If you look at the United States, perhaps 10%-15% of people might test positive [for T. gondii], but in Germany and France, the number comes closer to 50%, and in other places in the world – especially countries that have a harder time economically – the rates are even higher. So if it can affect cognition, even a small effect is a big deal,” Dr. Gale said.
“I think prevention will be the most important thing, and perhaps down the road, I hope that a vaccine will be considered,” Dr. Gale added.
“These findings indicate that primary prevention of the infection could have substantial global impact on mental health” and that public health programs to prevent T. gondii “are warranted.”
These programs might consist of hygienic measures, especially after human contact with contaminated sources, as well as research into vaccine development.
No source of funding for the study was listed. The authors and Dr. Gale reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Investigators reviewed and conducted a meta-analysis of 13 studies that encompassed more than 13,000 healthy adults and found a modest but significant association between T. gondii seropositivity and impaired performance on cognitive tests of processing speed, working memory, short-term verbal memory, and executive function. The average age of the persons in the studies was close to 50 years.
“Our findings show that T. gondii could have a negative but small effect on cognition,” study investigator Arjen Sutterland, MD, of the Amsterdam Neuroscience Research Institute and the Amsterdam Institute for Infection and Immunity, University of Amsterdam, said in an interview.
The study was published online July 14, 2021, in JAMA Psychiatry.
Mental illness link
T. gondii is “an intracellular parasite that produces quiescent infection in approximately 30% of humans worldwide,” the authors wrote. The parasite that causes the infection not only settles in muscle and liver tissue but also can cross the blood-brain barrier and settle quiescently in brain tissue. It can be spread through contact with cat feces or by consuming contaminated meat.
Previous research has shown that neurocognitive changes associated with toxoplasmosis can occur in humans, and meta-analyses suggest an association with neuropsychiatric disorders. Some research has also tied T. gondii infection to increased motor vehicle crashes and suicide attempts.
Dr. Sutterland said he had been inspired by the work of E. Fuller Torrey and Bob Yolken, who proposed the connection between T. gondii and schizophrenia.
Some years ago, Dr. Sutterland and his group analyzed the mental health consequences of T. gondii infection and found “several interesting associations,” but they were unable to “rule out reverse causation – i.e., people with mental health disorders more often get these infections – as well as determine the impact on the population of this common infection.”
For the current study, the investigators analyzed studies that examined specifically cognitive functioning in otherwise healthy individuals in relation to T. gondii infection, “because reverse causation would be less likely in this population and a grasp of global impact would become more clear.”
The researchers conducted a literature search of studies conducted through June 7, 2019, that analyzed cognitive function among healthy participants for whom data on T. gondii seropositivity were available.
A total of 13 studies (n = 13,289 participants; mean age, 46.7 years; 49.6% male) were used in the review and meta-analysis. Some of the studies enrolled a healthy population sample; other studies compared participants with and those without psychiatric disorders. From these, the researchers extracted only the data concerning healthy participants.
The studies analyzed four cognitive domains: processing speed, working memory, short-term verbal memory, and executive functioning.
All cognitive domains affected
Of all the participants, 22.6% had antibodies against T. gondii.
Participants who were seropositive for T. gondii had less favorable functioning in all cognitive domains, with “small but significant” differences.
The researchers conducted a meta-regression analysis of mean age in the analysis of executive functioning and found greater effect sizes as age increased (Q = 6.17; R2 = 81%; P = .01).
The studies were of “high quality,” and there was “little suggestion of publication bias was detected,” the authors noted.
“Although the extent of the associations was modest, the ubiquitous prevalence of the quiescent infection worldwide ... suggests that the consequences for cognitive function of the population as a whole may be substantial, although it is difficult to quantify the global impact,” they wrote.
They note that because the studies were cross-sectional in nature, causality cannot be established.
Nevertheless, Dr. Sutterland suggested several possible mechanisms through which T. gondii might affect neurocognition.
“We know the parasite forms cysts in the brain and can influence dopaminergic neurotransmission, which, in turn, affects neurocognition. Alternatively, it is also possible that the immune response to the infection in the brain causes cognitive impairment. This remains an important question to explore further,” he said.
He noted that clinicians can reassure patients who test positive for T. gondii that although the infection can have a negative impact on cognition, the effect is “small.”
Prevention programs warranted
Commenting on the study in an interview, Shawn D. Gale, PhD, associate professor, department of psychology and neuroscience center, Brigham Young University, Provo, Utah, called it a “great meta-analysis.” He noted that his group is researching the subject and has obtained similar findings. A big plus is that the researchers assessed several cognitive domains, not just one.
Although the data showed “mild effects,” the findings could be important on a population level. Because 30% of the world’s population are seropositive for T. gondii, a potentially large number of people are at risk for cognitive impairment, noted Dr. Gale, who was not involved with the study.
“If you look at the United States, perhaps 10%-15% of people might test positive [for T. gondii], but in Germany and France, the number comes closer to 50%, and in other places in the world – especially countries that have a harder time economically – the rates are even higher. So if it can affect cognition, even a small effect is a big deal,” Dr. Gale said.
“I think prevention will be the most important thing, and perhaps down the road, I hope that a vaccine will be considered,” Dr. Gale added.
“These findings indicate that primary prevention of the infection could have substantial global impact on mental health” and that public health programs to prevent T. gondii “are warranted.”
These programs might consist of hygienic measures, especially after human contact with contaminated sources, as well as research into vaccine development.
No source of funding for the study was listed. The authors and Dr. Gale reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Trauma, psychiatric comorbidities tied to functional motor disorders
Most adults with functional motor disorders (FMDs) report a history of psychological or physical trauma 6 months before the onset of symptoms, a retrospective study of 482 individuals suggests. Those challenges prevent more than half of those patients – most of whom are women – from working, the researchers found.
“This finding points to the huge socioeconomical burden of FMD and emphasizes the need for better diagnostic procedure and active management,” wrote Béatrice Garcin, MD, of Sorbonne Université, Paris, and associates.
FMDs are a common presentation of functional neurologic disorders, but clinical characteristics of FMDs are not well understood because large series of consecutive patients are limited, Dr. Garcin and associates said.
In the study, published in the Journal of Psychosomatic Research, the investigators reviewed data from consecutive patients with FMD who were seen at a single hospital in France between 2008 and 2016. Half of the patients had functional motor weakness (241) and half had functional movement disorders (241). All of the patients had been referred for transcranial magnetic stimulation (TMS) as treatment for FMD.
The median age of the patients was 40 years, the median age at the onset of symptoms was 35.5 years, and 74% were women. The most common clinical presentations were tremor and dystonia (83.4%), and no demographic differences were observed between patients with functional motor weakness and functional movement disorders. Symptoms were bilateral in about half of the patients (51.7%), with left- and right-sided symptoms in 28.2% and 20.1%, respectively.
More than 80% of the patients reported a history of trauma within 6 months of the onset of their symptoms, mainly psychological trauma (50.6%). Another 20.1% reported a physical trauma, and 8.7% reported trauma from surgical procedures.
In addition, about two-thirds (66.4%) had psychiatric comorbidities; 52.7% of these were mood disorders: 49.3% depression and 3.3% bipolar disorder. “However, these results about psychiatric comorbidities should be taken with caution,” the researchers emphasized. “ and psychiatric diagnosis may lack precision because of the absence of systematic psychiatric interviews and psychiatric questionnaires in the present study.”
No significant differences appeared between the motor weakness and movement disorders groups in terms of occupation, level of education, medical somatic history, symptom onset, psychiatric comorbidities, or self-reported history of trauma. Patients in the motor weakness group were significantly younger at the time of TMS treatment and had a shorter disease duration prior to that treatment. No differences were noted between the groups with regard to clinical FMD phenotypes.
The study findings were limited by several factors, including the potential selection bias because of enrollment at a neurology referral center, lack of a control group, and underrepresentation of children and older adults, the researchers noted. Also, symptom severity was not assessed and could not be compared among phenotypes or demographic groups.
However, the results contribute to the characterization of FMD patients. “Future studies are needed to clarify the characteristics of FMD patients and the consequences of their symptoms on disability and work status,” they said.
The study received no outside funding. Lead author Dr. Garcin had no disclosures.
Most adults with functional motor disorders (FMDs) report a history of psychological or physical trauma 6 months before the onset of symptoms, a retrospective study of 482 individuals suggests. Those challenges prevent more than half of those patients – most of whom are women – from working, the researchers found.
“This finding points to the huge socioeconomical burden of FMD and emphasizes the need for better diagnostic procedure and active management,” wrote Béatrice Garcin, MD, of Sorbonne Université, Paris, and associates.
FMDs are a common presentation of functional neurologic disorders, but clinical characteristics of FMDs are not well understood because large series of consecutive patients are limited, Dr. Garcin and associates said.
In the study, published in the Journal of Psychosomatic Research, the investigators reviewed data from consecutive patients with FMD who were seen at a single hospital in France between 2008 and 2016. Half of the patients had functional motor weakness (241) and half had functional movement disorders (241). All of the patients had been referred for transcranial magnetic stimulation (TMS) as treatment for FMD.
The median age of the patients was 40 years, the median age at the onset of symptoms was 35.5 years, and 74% were women. The most common clinical presentations were tremor and dystonia (83.4%), and no demographic differences were observed between patients with functional motor weakness and functional movement disorders. Symptoms were bilateral in about half of the patients (51.7%), with left- and right-sided symptoms in 28.2% and 20.1%, respectively.
More than 80% of the patients reported a history of trauma within 6 months of the onset of their symptoms, mainly psychological trauma (50.6%). Another 20.1% reported a physical trauma, and 8.7% reported trauma from surgical procedures.
In addition, about two-thirds (66.4%) had psychiatric comorbidities; 52.7% of these were mood disorders: 49.3% depression and 3.3% bipolar disorder. “However, these results about psychiatric comorbidities should be taken with caution,” the researchers emphasized. “ and psychiatric diagnosis may lack precision because of the absence of systematic psychiatric interviews and psychiatric questionnaires in the present study.”
No significant differences appeared between the motor weakness and movement disorders groups in terms of occupation, level of education, medical somatic history, symptom onset, psychiatric comorbidities, or self-reported history of trauma. Patients in the motor weakness group were significantly younger at the time of TMS treatment and had a shorter disease duration prior to that treatment. No differences were noted between the groups with regard to clinical FMD phenotypes.
The study findings were limited by several factors, including the potential selection bias because of enrollment at a neurology referral center, lack of a control group, and underrepresentation of children and older adults, the researchers noted. Also, symptom severity was not assessed and could not be compared among phenotypes or demographic groups.
However, the results contribute to the characterization of FMD patients. “Future studies are needed to clarify the characteristics of FMD patients and the consequences of their symptoms on disability and work status,” they said.
The study received no outside funding. Lead author Dr. Garcin had no disclosures.
Most adults with functional motor disorders (FMDs) report a history of psychological or physical trauma 6 months before the onset of symptoms, a retrospective study of 482 individuals suggests. Those challenges prevent more than half of those patients – most of whom are women – from working, the researchers found.
“This finding points to the huge socioeconomical burden of FMD and emphasizes the need for better diagnostic procedure and active management,” wrote Béatrice Garcin, MD, of Sorbonne Université, Paris, and associates.
FMDs are a common presentation of functional neurologic disorders, but clinical characteristics of FMDs are not well understood because large series of consecutive patients are limited, Dr. Garcin and associates said.
In the study, published in the Journal of Psychosomatic Research, the investigators reviewed data from consecutive patients with FMD who were seen at a single hospital in France between 2008 and 2016. Half of the patients had functional motor weakness (241) and half had functional movement disorders (241). All of the patients had been referred for transcranial magnetic stimulation (TMS) as treatment for FMD.
The median age of the patients was 40 years, the median age at the onset of symptoms was 35.5 years, and 74% were women. The most common clinical presentations were tremor and dystonia (83.4%), and no demographic differences were observed between patients with functional motor weakness and functional movement disorders. Symptoms were bilateral in about half of the patients (51.7%), with left- and right-sided symptoms in 28.2% and 20.1%, respectively.
More than 80% of the patients reported a history of trauma within 6 months of the onset of their symptoms, mainly psychological trauma (50.6%). Another 20.1% reported a physical trauma, and 8.7% reported trauma from surgical procedures.
In addition, about two-thirds (66.4%) had psychiatric comorbidities; 52.7% of these were mood disorders: 49.3% depression and 3.3% bipolar disorder. “However, these results about psychiatric comorbidities should be taken with caution,” the researchers emphasized. “ and psychiatric diagnosis may lack precision because of the absence of systematic psychiatric interviews and psychiatric questionnaires in the present study.”
No significant differences appeared between the motor weakness and movement disorders groups in terms of occupation, level of education, medical somatic history, symptom onset, psychiatric comorbidities, or self-reported history of trauma. Patients in the motor weakness group were significantly younger at the time of TMS treatment and had a shorter disease duration prior to that treatment. No differences were noted between the groups with regard to clinical FMD phenotypes.
The study findings were limited by several factors, including the potential selection bias because of enrollment at a neurology referral center, lack of a control group, and underrepresentation of children and older adults, the researchers noted. Also, symptom severity was not assessed and could not be compared among phenotypes or demographic groups.
However, the results contribute to the characterization of FMD patients. “Future studies are needed to clarify the characteristics of FMD patients and the consequences of their symptoms on disability and work status,” they said.
The study received no outside funding. Lead author Dr. Garcin had no disclosures.
FROM THE JOURNAL OF PSYCHOSOMATIC RESEARCH
Novel gene therapy ‘reprograms’ cells to reverse neurologic deficits in children with rare disease
An experimental gene therapy produced marked clinical improvement in children with aromatic L-amino acid decarboxylase (AADC) deficiency, a rare genetic disorder that affects the synthesis of key neurotransmitters to cause severe developmental and motor disability.
In an article published July 12, 2021, in Nature Communications, a group of researchers based at the University of California, San Francisco, and Ohio State University, Columbus, described results from seven children ages 4-9 with AADC deficiency who underwent a novel form of surgery to deliver a viral vector expressing the human AADC gene to the midbrain.
Previous trials of this gene therapy in children with AADC deficiency targeted a different region of the brain, the putamen, with only slight clinical improvement. Here, investigators chose two midbrain regions – the substantia nigra pars compacta and the ventral tegmental area – in the hope of restoring healthy AADC enzyme activity in those neurons.
The study’s corresponding author, Krystof Bankiewicz, MD, PhD, professor and vice chair of research at Ohio State University, director of the Brain Health and Performance Center at Ohio State University, and professor emeritus and vice chair for research at UCSF, said in an interview that the brain regions chosen for this trial resulted from years of efforts to identify an ideal target in this disease.
“This particular vector undergoes axonal transport,” he said. “If you inject it into specific regions of the brain it will be transported into the terminals [of the nerve fibers]. And by looking at the imaging of these patients, we found that they still have the wiring in the brain that’s so critical. So we decided to aim at a much more difficult target, going directly to the source of the problem, which is the substantia nigra and the ventral tegmental area. This targets two critical pathways in the brain: one that drives motor responses and another that controls emotions.”
‘Surprising’ improvement seen
The children in the study – four girls and three boys – underwent surgery from 2016 to the end of 2018, and were divided into two dose cohorts, with one receiving three times the amount of vector as the other. Both groups, however, saw similar levels of improvement.
All but one child saw complete resolution of a hallmark symptom of the disease – oculogyric crises, or prolonged spasms of muscles controlling eye movement – within 3 months of surgery. Of the children followed at least 18 months, six attained head control within a year, two became able to eat and drink by mouth, and four gained the ability to sit up unaided in that time. At 18 months one child had learned to speak 50 words using an augmentative communication device.
One child died unexpectedly 7 months after the procedure, Dr. Bankiewicz said in an interview. This death appeared to be caused by cardiac complications of his disease, Dr. Bankiewicz said, which are common in AADC deficiency.
While the investigators are now looking at delivering the AADC gene therapy in younger children – who were excluded from this trial because of safety concerns surrounding the complex procedure – investigators were surprised by the level of improvement seen in older children.
“We initially didn’t believe – at least not all of us – that we could actually make an impact in the older patients, and that is not the case,” said Dr. Bankiewicz, who has since used the same gene therapy on a compassionate-use basis in Europe and seen durable clinical improvement in patients as old as 26. “The fact that we saw a response in that patient tells us something about how incredibly plastic the brain is.”
While the new study does not detail improvements in the children’s social and emotional well-being, Dr. Bankiewicz said these, too, were pronounced. “Kids fall into oculogyric crises in stress-inducing situation. They might be in a stroller being taken for a walk, and something in the environment would stress them. Sometimes they had to be kept in a dark room isolated from stress.” Following the gene therapy, “they’re laughing, they’re social, they can interact with their environment. It’s really touching to see them able to develop a bond now with their caregivers.”
Implication for other disorders
Dr. Bankiewicz and colleagues have previously used the same gene to boost AADC activity in patients with Parkinson’s disease. The group is also in trials to deliver a neuroprotective gene to the brains of people with early-stage Alzheimer’s disease, and a gene-silencing therapy in patients with Huntington’s disease. They will also continue recruiting pediatric patients for trials of the AADC gene therapy.
“We have been developing a method for safely treating younger children, so now we will go to 3 years old and maybe even below,” Dr. Bankiewicz said. “Earlier is probably better, but for technical and safety considerations we needed to be conservative first. It is hugely stressful to go into very sick patients with that type of therapy in that part of the brain. We had to get it right the first time, and it looks like we did.”
The study was funded by the National Institutes of Health, the AADC Research Trust, the Pediatric Neurotransmitter Disease Association, and Ohio State University, with materials and technical support donated by ClearPoint Neuro. Several coauthors disclosed financial relationships with producers of diagnostic tests or biotechnology firms. Dr. Bankiewicz is a founder and shareholder of Brain Neurotherapy Bio, a company that develops gene therapies for Parkinson’s and other diseases.
An experimental gene therapy produced marked clinical improvement in children with aromatic L-amino acid decarboxylase (AADC) deficiency, a rare genetic disorder that affects the synthesis of key neurotransmitters to cause severe developmental and motor disability.
In an article published July 12, 2021, in Nature Communications, a group of researchers based at the University of California, San Francisco, and Ohio State University, Columbus, described results from seven children ages 4-9 with AADC deficiency who underwent a novel form of surgery to deliver a viral vector expressing the human AADC gene to the midbrain.
Previous trials of this gene therapy in children with AADC deficiency targeted a different region of the brain, the putamen, with only slight clinical improvement. Here, investigators chose two midbrain regions – the substantia nigra pars compacta and the ventral tegmental area – in the hope of restoring healthy AADC enzyme activity in those neurons.
The study’s corresponding author, Krystof Bankiewicz, MD, PhD, professor and vice chair of research at Ohio State University, director of the Brain Health and Performance Center at Ohio State University, and professor emeritus and vice chair for research at UCSF, said in an interview that the brain regions chosen for this trial resulted from years of efforts to identify an ideal target in this disease.
“This particular vector undergoes axonal transport,” he said. “If you inject it into specific regions of the brain it will be transported into the terminals [of the nerve fibers]. And by looking at the imaging of these patients, we found that they still have the wiring in the brain that’s so critical. So we decided to aim at a much more difficult target, going directly to the source of the problem, which is the substantia nigra and the ventral tegmental area. This targets two critical pathways in the brain: one that drives motor responses and another that controls emotions.”
‘Surprising’ improvement seen
The children in the study – four girls and three boys – underwent surgery from 2016 to the end of 2018, and were divided into two dose cohorts, with one receiving three times the amount of vector as the other. Both groups, however, saw similar levels of improvement.
All but one child saw complete resolution of a hallmark symptom of the disease – oculogyric crises, or prolonged spasms of muscles controlling eye movement – within 3 months of surgery. Of the children followed at least 18 months, six attained head control within a year, two became able to eat and drink by mouth, and four gained the ability to sit up unaided in that time. At 18 months one child had learned to speak 50 words using an augmentative communication device.
One child died unexpectedly 7 months after the procedure, Dr. Bankiewicz said in an interview. This death appeared to be caused by cardiac complications of his disease, Dr. Bankiewicz said, which are common in AADC deficiency.
While the investigators are now looking at delivering the AADC gene therapy in younger children – who were excluded from this trial because of safety concerns surrounding the complex procedure – investigators were surprised by the level of improvement seen in older children.
“We initially didn’t believe – at least not all of us – that we could actually make an impact in the older patients, and that is not the case,” said Dr. Bankiewicz, who has since used the same gene therapy on a compassionate-use basis in Europe and seen durable clinical improvement in patients as old as 26. “The fact that we saw a response in that patient tells us something about how incredibly plastic the brain is.”
While the new study does not detail improvements in the children’s social and emotional well-being, Dr. Bankiewicz said these, too, were pronounced. “Kids fall into oculogyric crises in stress-inducing situation. They might be in a stroller being taken for a walk, and something in the environment would stress them. Sometimes they had to be kept in a dark room isolated from stress.” Following the gene therapy, “they’re laughing, they’re social, they can interact with their environment. It’s really touching to see them able to develop a bond now with their caregivers.”
Implication for other disorders
Dr. Bankiewicz and colleagues have previously used the same gene to boost AADC activity in patients with Parkinson’s disease. The group is also in trials to deliver a neuroprotective gene to the brains of people with early-stage Alzheimer’s disease, and a gene-silencing therapy in patients with Huntington’s disease. They will also continue recruiting pediatric patients for trials of the AADC gene therapy.
“We have been developing a method for safely treating younger children, so now we will go to 3 years old and maybe even below,” Dr. Bankiewicz said. “Earlier is probably better, but for technical and safety considerations we needed to be conservative first. It is hugely stressful to go into very sick patients with that type of therapy in that part of the brain. We had to get it right the first time, and it looks like we did.”
The study was funded by the National Institutes of Health, the AADC Research Trust, the Pediatric Neurotransmitter Disease Association, and Ohio State University, with materials and technical support donated by ClearPoint Neuro. Several coauthors disclosed financial relationships with producers of diagnostic tests or biotechnology firms. Dr. Bankiewicz is a founder and shareholder of Brain Neurotherapy Bio, a company that develops gene therapies for Parkinson’s and other diseases.
An experimental gene therapy produced marked clinical improvement in children with aromatic L-amino acid decarboxylase (AADC) deficiency, a rare genetic disorder that affects the synthesis of key neurotransmitters to cause severe developmental and motor disability.
In an article published July 12, 2021, in Nature Communications, a group of researchers based at the University of California, San Francisco, and Ohio State University, Columbus, described results from seven children ages 4-9 with AADC deficiency who underwent a novel form of surgery to deliver a viral vector expressing the human AADC gene to the midbrain.
Previous trials of this gene therapy in children with AADC deficiency targeted a different region of the brain, the putamen, with only slight clinical improvement. Here, investigators chose two midbrain regions – the substantia nigra pars compacta and the ventral tegmental area – in the hope of restoring healthy AADC enzyme activity in those neurons.
The study’s corresponding author, Krystof Bankiewicz, MD, PhD, professor and vice chair of research at Ohio State University, director of the Brain Health and Performance Center at Ohio State University, and professor emeritus and vice chair for research at UCSF, said in an interview that the brain regions chosen for this trial resulted from years of efforts to identify an ideal target in this disease.
“This particular vector undergoes axonal transport,” he said. “If you inject it into specific regions of the brain it will be transported into the terminals [of the nerve fibers]. And by looking at the imaging of these patients, we found that they still have the wiring in the brain that’s so critical. So we decided to aim at a much more difficult target, going directly to the source of the problem, which is the substantia nigra and the ventral tegmental area. This targets two critical pathways in the brain: one that drives motor responses and another that controls emotions.”
‘Surprising’ improvement seen
The children in the study – four girls and three boys – underwent surgery from 2016 to the end of 2018, and were divided into two dose cohorts, with one receiving three times the amount of vector as the other. Both groups, however, saw similar levels of improvement.
All but one child saw complete resolution of a hallmark symptom of the disease – oculogyric crises, or prolonged spasms of muscles controlling eye movement – within 3 months of surgery. Of the children followed at least 18 months, six attained head control within a year, two became able to eat and drink by mouth, and four gained the ability to sit up unaided in that time. At 18 months one child had learned to speak 50 words using an augmentative communication device.
One child died unexpectedly 7 months after the procedure, Dr. Bankiewicz said in an interview. This death appeared to be caused by cardiac complications of his disease, Dr. Bankiewicz said, which are common in AADC deficiency.
While the investigators are now looking at delivering the AADC gene therapy in younger children – who were excluded from this trial because of safety concerns surrounding the complex procedure – investigators were surprised by the level of improvement seen in older children.
“We initially didn’t believe – at least not all of us – that we could actually make an impact in the older patients, and that is not the case,” said Dr. Bankiewicz, who has since used the same gene therapy on a compassionate-use basis in Europe and seen durable clinical improvement in patients as old as 26. “The fact that we saw a response in that patient tells us something about how incredibly plastic the brain is.”
While the new study does not detail improvements in the children’s social and emotional well-being, Dr. Bankiewicz said these, too, were pronounced. “Kids fall into oculogyric crises in stress-inducing situation. They might be in a stroller being taken for a walk, and something in the environment would stress them. Sometimes they had to be kept in a dark room isolated from stress.” Following the gene therapy, “they’re laughing, they’re social, they can interact with their environment. It’s really touching to see them able to develop a bond now with their caregivers.”
Implication for other disorders
Dr. Bankiewicz and colleagues have previously used the same gene to boost AADC activity in patients with Parkinson’s disease. The group is also in trials to deliver a neuroprotective gene to the brains of people with early-stage Alzheimer’s disease, and a gene-silencing therapy in patients with Huntington’s disease. They will also continue recruiting pediatric patients for trials of the AADC gene therapy.
“We have been developing a method for safely treating younger children, so now we will go to 3 years old and maybe even below,” Dr. Bankiewicz said. “Earlier is probably better, but for technical and safety considerations we needed to be conservative first. It is hugely stressful to go into very sick patients with that type of therapy in that part of the brain. We had to get it right the first time, and it looks like we did.”
The study was funded by the National Institutes of Health, the AADC Research Trust, the Pediatric Neurotransmitter Disease Association, and Ohio State University, with materials and technical support donated by ClearPoint Neuro. Several coauthors disclosed financial relationships with producers of diagnostic tests or biotechnology firms. Dr. Bankiewicz is a founder and shareholder of Brain Neurotherapy Bio, a company that develops gene therapies for Parkinson’s and other diseases.
FROM NATURE COMMUNICATIONS
On a scale of 1-5 ... How frustrating is this?
Like most American doctors, I take a variety of insurances and insurance plans.
Some of these, particularly HMOs, require a referring physician to send me a written, insurance-approved, referral (AKA authorization) before the visit, to submit with my bill.
Medical visits of all kinds are generally billed on a scale from 1 (brief/simple issue) to 5 (lots of time needed/very complicated).
After 23 years, I’m used to this.
But recently a new wrinkle has emerged.
In the last month I’ve gotten two referrals (both from the same internist), except these state, very clearly, that charges for any visit cannot exceed level 3.
And they’re telling me this before I’ve ever seen the patients, or have any idea how complicated they are, or how long a list of questions they and/or their families will have.
No.
I faxed them back asking for a referral allowing me to bill up to level 5 if needed. I might charge less than that, but none of us know how complicated or long a visit will be until someone comes in. There’s no crystal ball in medicine.
I’m sure someone will say I’m a money-grubbing doctor who couldn’t care less about the patient.
That’s far from the truth. I’m here for the patients. I like helping them. It’s why I do this.
But I can’t help anyone if I can’t afford to keep the office lights on, either.
I never heard back from them. Maybe they decided the patients didn’t need me that much. Maybe they sent them to another neurologist and took my name off their referral list. Maybe they never even noticed my return fax.
What will happen now, I have no idea. Maybe this was something that office tried, to see if I noticed. Maybe it’s the start of the next wave of medical cutbacks. Maybe it was a staff error at the other end.
But either way, This isn’t an amusement park or thrift store. People with problems need time, and time costs money. I need to pay my staff, my rent, and my mortgage. If I can’t do those things, I won’t be able to help anyone.
That’s just, for better or worse, the way it is.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Like most American doctors, I take a variety of insurances and insurance plans.
Some of these, particularly HMOs, require a referring physician to send me a written, insurance-approved, referral (AKA authorization) before the visit, to submit with my bill.
Medical visits of all kinds are generally billed on a scale from 1 (brief/simple issue) to 5 (lots of time needed/very complicated).
After 23 years, I’m used to this.
But recently a new wrinkle has emerged.
In the last month I’ve gotten two referrals (both from the same internist), except these state, very clearly, that charges for any visit cannot exceed level 3.
And they’re telling me this before I’ve ever seen the patients, or have any idea how complicated they are, or how long a list of questions they and/or their families will have.
No.
I faxed them back asking for a referral allowing me to bill up to level 5 if needed. I might charge less than that, but none of us know how complicated or long a visit will be until someone comes in. There’s no crystal ball in medicine.
I’m sure someone will say I’m a money-grubbing doctor who couldn’t care less about the patient.
That’s far from the truth. I’m here for the patients. I like helping them. It’s why I do this.
But I can’t help anyone if I can’t afford to keep the office lights on, either.
I never heard back from them. Maybe they decided the patients didn’t need me that much. Maybe they sent them to another neurologist and took my name off their referral list. Maybe they never even noticed my return fax.
What will happen now, I have no idea. Maybe this was something that office tried, to see if I noticed. Maybe it’s the start of the next wave of medical cutbacks. Maybe it was a staff error at the other end.
But either way, This isn’t an amusement park or thrift store. People with problems need time, and time costs money. I need to pay my staff, my rent, and my mortgage. If I can’t do those things, I won’t be able to help anyone.
That’s just, for better or worse, the way it is.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Like most American doctors, I take a variety of insurances and insurance plans.
Some of these, particularly HMOs, require a referring physician to send me a written, insurance-approved, referral (AKA authorization) before the visit, to submit with my bill.
Medical visits of all kinds are generally billed on a scale from 1 (brief/simple issue) to 5 (lots of time needed/very complicated).
After 23 years, I’m used to this.
But recently a new wrinkle has emerged.
In the last month I’ve gotten two referrals (both from the same internist), except these state, very clearly, that charges for any visit cannot exceed level 3.
And they’re telling me this before I’ve ever seen the patients, or have any idea how complicated they are, or how long a list of questions they and/or their families will have.
No.
I faxed them back asking for a referral allowing me to bill up to level 5 if needed. I might charge less than that, but none of us know how complicated or long a visit will be until someone comes in. There’s no crystal ball in medicine.
I’m sure someone will say I’m a money-grubbing doctor who couldn’t care less about the patient.
That’s far from the truth. I’m here for the patients. I like helping them. It’s why I do this.
But I can’t help anyone if I can’t afford to keep the office lights on, either.
I never heard back from them. Maybe they decided the patients didn’t need me that much. Maybe they sent them to another neurologist and took my name off their referral list. Maybe they never even noticed my return fax.
What will happen now, I have no idea. Maybe this was something that office tried, to see if I noticed. Maybe it’s the start of the next wave of medical cutbacks. Maybe it was a staff error at the other end.
But either way, This isn’t an amusement park or thrift store. People with problems need time, and time costs money. I need to pay my staff, my rent, and my mortgage. If I can’t do those things, I won’t be able to help anyone.
That’s just, for better or worse, the way it is.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Lucid abductions and Candy Crush addiction
I dream of alien abductions
There he goes! It’s lunchtime and your colleague Tom is going on and on again about that time he was abducted by aliens. It sounds ridiculous, but he does make some convincing arguments. Tom thinks it was real, but could it have all just been in his head?
Lucid dreaming may help explain alleged alien abductions. During a lucid dream, people know that they’re dreaming, and can also have some control over how the dreams play out. During some dream states, a person can feel intense sensations, such as terror and paralysis, so it’s no wonder these dreams feel so real.
In a recent study, scientists encouraged 152 participants who had self-identified as lucid dreamers to dream about aliens. Many (75%) of the participants were able to dream about alien encounters, and 15% “achieved relatively realistic experiences,” the investigators reported.
So cut Tom some slack. He’s not crazy, he might just have lucid dreaming privileges. Tell him he should dream about something more fun, like a vacation in the Bahamas.
Follow your heart: Drink more coffee
It seems like the world is divided into coffee drinkers and non–coffee drinkers. Then there’s decaf and regular drinkers. Whichever camp you fall into, know this: The widespread belief that caffeine consumption has an effect on your heart is all beans.
In what is the largest investigation of its kind, researchers from the University of California, San Francisco, looked into whether drinking caffeinated coffee was linked to a risk for heart arrhythmia. They also researched whether patients with genetic variants that affect their metabolism could change that association. Almost 400,000 people with a mean age of 56 years participated in the study. More than half of the participants were women.
The investigators analyzed the participants’ self-reported coffee consumption using a technique called Mendelian randomization to leverage genetic data with the participants’ relationship with caffeine, making it an even field and not relying on the participant consumption self-reporting for outcomes as in previous studies.
What they found, after the 4-year follow up, was nothing short of myth busting.
“We found no evidence that caffeine consumption leads to a greater risk of arrhythmias,” said senior and corresponding author Gregory Marcus, MD. “Our population-based study provides reassurance that common prohibitions against caffeine to reduce arrhythmia risk are likely unwarranted.”
There was no evidence of a heightened risk of arrhythmias in participants who were genetically predisposed to metabolize caffeine differently from those who were not. And, there was a 3% reduction of arrhythmias in patients who consumed higher amounts of coffee.
We are not lobbying for Big Caffeine, but this study adds to the reported health benefits linked to coffee, which already include reduced risk for cancer, diabetes, and Parkinson’s disease, with an added bonus of anti-inflammatory benefits. So, the next time you’re hesitant to pour that second cup of Joe, just go for it. Your heart can take it.
Bored? Feeling down? Don’t play Candy Crush
Now hang on, aren’t those the perfect times to play video games? If there’s nothing else to do, why not open Candy Crush and mindlessly power through the levels?
Because, according to a study by a group of Canadian researchers, it’s actually the worst thing you can do. Well, maybe not literally, but it’s not helpful. Researchers recruited 60 Candy Crush players who were at various levels in the game. They had the participants play early levels that were far too easy or levels balanced with their gameplay abilities.
Players in the easy-level group got bored and quit far earlier than did those in the advanced-level group. The group playing to their abilities were able to access a “flow” state and focus all their attention on the game. While this is all well and good for their gaming performance, according to the researchers, it confirms the theory that playing to escape boredom or negative emotions is more likely to lead to addiction. As with all addictions, the temporary high can give way to a self-repeating loop, causing patients to ignore real life and deepen depression.
The researchers hope their findings will encourage game developers to “consider implementing responsible video gaming tools directly within their games.” Comedy gold. Perhaps Canadians’ idea of capitalism is a little different from that of those south of the border.
Hiccups and vaccine refusal
Tonight, LOTME News dives into the fetid cesspool that is international politics and comes out with … hiccups?
But first, a word from our sponsor, Fearless Boxing Club of South Etobicoke, Ontario.
Are you looking to flout public health restrictions? Do you want to spend time in an enclosed space with other people who haven’t gotten the COVID-19 vaccine? Do you “feel safer waiting until more research is done on the side effects being discovered right now”? (We are not making this up.)
Then join the Fearless Boxing Club, because we “will not be accepting any vaccinated members.” Our founders, Mohammed Abedeen and Krystal Glazier-Roscoe, are working hard to exclude “those who received the experimental COVID vaccine.” (Still not making it up.)
And now, back to the news.
Brazilian president Jair Bolsonaro was hospitalized recently for a severe case of hiccups that may have been related to a stab wound he received in 2018. [Nope, didn’t make that up, either.]
Mr. Bolsonaro had been hiccuping for 10 days, and was experiencing abdominal pain and difficulty speaking, when he entered the hospital on July 14. Since being stabbed while on the campaign trail, he has undergone several operations, which may have led to the partial intestinal obstruction that caused his latest symptoms.
His medical team advised Mr. Bolsonaro to go on a diet to aid his recovery, but when he was released on July 18 he said, “I hope in 10 days I’ll be eating barbecued ribs.” (Maybe this is all just a lucid dream. Probably shouldn’t have had ribs right before bed.)
I dream of alien abductions
There he goes! It’s lunchtime and your colleague Tom is going on and on again about that time he was abducted by aliens. It sounds ridiculous, but he does make some convincing arguments. Tom thinks it was real, but could it have all just been in his head?
Lucid dreaming may help explain alleged alien abductions. During a lucid dream, people know that they’re dreaming, and can also have some control over how the dreams play out. During some dream states, a person can feel intense sensations, such as terror and paralysis, so it’s no wonder these dreams feel so real.
In a recent study, scientists encouraged 152 participants who had self-identified as lucid dreamers to dream about aliens. Many (75%) of the participants were able to dream about alien encounters, and 15% “achieved relatively realistic experiences,” the investigators reported.
So cut Tom some slack. He’s not crazy, he might just have lucid dreaming privileges. Tell him he should dream about something more fun, like a vacation in the Bahamas.
Follow your heart: Drink more coffee
It seems like the world is divided into coffee drinkers and non–coffee drinkers. Then there’s decaf and regular drinkers. Whichever camp you fall into, know this: The widespread belief that caffeine consumption has an effect on your heart is all beans.
In what is the largest investigation of its kind, researchers from the University of California, San Francisco, looked into whether drinking caffeinated coffee was linked to a risk for heart arrhythmia. They also researched whether patients with genetic variants that affect their metabolism could change that association. Almost 400,000 people with a mean age of 56 years participated in the study. More than half of the participants were women.
The investigators analyzed the participants’ self-reported coffee consumption using a technique called Mendelian randomization to leverage genetic data with the participants’ relationship with caffeine, making it an even field and not relying on the participant consumption self-reporting for outcomes as in previous studies.
What they found, after the 4-year follow up, was nothing short of myth busting.
“We found no evidence that caffeine consumption leads to a greater risk of arrhythmias,” said senior and corresponding author Gregory Marcus, MD. “Our population-based study provides reassurance that common prohibitions against caffeine to reduce arrhythmia risk are likely unwarranted.”
There was no evidence of a heightened risk of arrhythmias in participants who were genetically predisposed to metabolize caffeine differently from those who were not. And, there was a 3% reduction of arrhythmias in patients who consumed higher amounts of coffee.
We are not lobbying for Big Caffeine, but this study adds to the reported health benefits linked to coffee, which already include reduced risk for cancer, diabetes, and Parkinson’s disease, with an added bonus of anti-inflammatory benefits. So, the next time you’re hesitant to pour that second cup of Joe, just go for it. Your heart can take it.
Bored? Feeling down? Don’t play Candy Crush
Now hang on, aren’t those the perfect times to play video games? If there’s nothing else to do, why not open Candy Crush and mindlessly power through the levels?
Because, according to a study by a group of Canadian researchers, it’s actually the worst thing you can do. Well, maybe not literally, but it’s not helpful. Researchers recruited 60 Candy Crush players who were at various levels in the game. They had the participants play early levels that were far too easy or levels balanced with their gameplay abilities.
Players in the easy-level group got bored and quit far earlier than did those in the advanced-level group. The group playing to their abilities were able to access a “flow” state and focus all their attention on the game. While this is all well and good for their gaming performance, according to the researchers, it confirms the theory that playing to escape boredom or negative emotions is more likely to lead to addiction. As with all addictions, the temporary high can give way to a self-repeating loop, causing patients to ignore real life and deepen depression.
The researchers hope their findings will encourage game developers to “consider implementing responsible video gaming tools directly within their games.” Comedy gold. Perhaps Canadians’ idea of capitalism is a little different from that of those south of the border.
Hiccups and vaccine refusal
Tonight, LOTME News dives into the fetid cesspool that is international politics and comes out with … hiccups?
But first, a word from our sponsor, Fearless Boxing Club of South Etobicoke, Ontario.
Are you looking to flout public health restrictions? Do you want to spend time in an enclosed space with other people who haven’t gotten the COVID-19 vaccine? Do you “feel safer waiting until more research is done on the side effects being discovered right now”? (We are not making this up.)
Then join the Fearless Boxing Club, because we “will not be accepting any vaccinated members.” Our founders, Mohammed Abedeen and Krystal Glazier-Roscoe, are working hard to exclude “those who received the experimental COVID vaccine.” (Still not making it up.)
And now, back to the news.
Brazilian president Jair Bolsonaro was hospitalized recently for a severe case of hiccups that may have been related to a stab wound he received in 2018. [Nope, didn’t make that up, either.]
Mr. Bolsonaro had been hiccuping for 10 days, and was experiencing abdominal pain and difficulty speaking, when he entered the hospital on July 14. Since being stabbed while on the campaign trail, he has undergone several operations, which may have led to the partial intestinal obstruction that caused his latest symptoms.
His medical team advised Mr. Bolsonaro to go on a diet to aid his recovery, but when he was released on July 18 he said, “I hope in 10 days I’ll be eating barbecued ribs.” (Maybe this is all just a lucid dream. Probably shouldn’t have had ribs right before bed.)
I dream of alien abductions
There he goes! It’s lunchtime and your colleague Tom is going on and on again about that time he was abducted by aliens. It sounds ridiculous, but he does make some convincing arguments. Tom thinks it was real, but could it have all just been in his head?
Lucid dreaming may help explain alleged alien abductions. During a lucid dream, people know that they’re dreaming, and can also have some control over how the dreams play out. During some dream states, a person can feel intense sensations, such as terror and paralysis, so it’s no wonder these dreams feel so real.
In a recent study, scientists encouraged 152 participants who had self-identified as lucid dreamers to dream about aliens. Many (75%) of the participants were able to dream about alien encounters, and 15% “achieved relatively realistic experiences,” the investigators reported.
So cut Tom some slack. He’s not crazy, he might just have lucid dreaming privileges. Tell him he should dream about something more fun, like a vacation in the Bahamas.
Follow your heart: Drink more coffee
It seems like the world is divided into coffee drinkers and non–coffee drinkers. Then there’s decaf and regular drinkers. Whichever camp you fall into, know this: The widespread belief that caffeine consumption has an effect on your heart is all beans.
In what is the largest investigation of its kind, researchers from the University of California, San Francisco, looked into whether drinking caffeinated coffee was linked to a risk for heart arrhythmia. They also researched whether patients with genetic variants that affect their metabolism could change that association. Almost 400,000 people with a mean age of 56 years participated in the study. More than half of the participants were women.
The investigators analyzed the participants’ self-reported coffee consumption using a technique called Mendelian randomization to leverage genetic data with the participants’ relationship with caffeine, making it an even field and not relying on the participant consumption self-reporting for outcomes as in previous studies.
What they found, after the 4-year follow up, was nothing short of myth busting.
“We found no evidence that caffeine consumption leads to a greater risk of arrhythmias,” said senior and corresponding author Gregory Marcus, MD. “Our population-based study provides reassurance that common prohibitions against caffeine to reduce arrhythmia risk are likely unwarranted.”
There was no evidence of a heightened risk of arrhythmias in participants who were genetically predisposed to metabolize caffeine differently from those who were not. And, there was a 3% reduction of arrhythmias in patients who consumed higher amounts of coffee.
We are not lobbying for Big Caffeine, but this study adds to the reported health benefits linked to coffee, which already include reduced risk for cancer, diabetes, and Parkinson’s disease, with an added bonus of anti-inflammatory benefits. So, the next time you’re hesitant to pour that second cup of Joe, just go for it. Your heart can take it.
Bored? Feeling down? Don’t play Candy Crush
Now hang on, aren’t those the perfect times to play video games? If there’s nothing else to do, why not open Candy Crush and mindlessly power through the levels?
Because, according to a study by a group of Canadian researchers, it’s actually the worst thing you can do. Well, maybe not literally, but it’s not helpful. Researchers recruited 60 Candy Crush players who were at various levels in the game. They had the participants play early levels that were far too easy or levels balanced with their gameplay abilities.
Players in the easy-level group got bored and quit far earlier than did those in the advanced-level group. The group playing to their abilities were able to access a “flow” state and focus all their attention on the game. While this is all well and good for their gaming performance, according to the researchers, it confirms the theory that playing to escape boredom or negative emotions is more likely to lead to addiction. As with all addictions, the temporary high can give way to a self-repeating loop, causing patients to ignore real life and deepen depression.
The researchers hope their findings will encourage game developers to “consider implementing responsible video gaming tools directly within their games.” Comedy gold. Perhaps Canadians’ idea of capitalism is a little different from that of those south of the border.
Hiccups and vaccine refusal
Tonight, LOTME News dives into the fetid cesspool that is international politics and comes out with … hiccups?
But first, a word from our sponsor, Fearless Boxing Club of South Etobicoke, Ontario.
Are you looking to flout public health restrictions? Do you want to spend time in an enclosed space with other people who haven’t gotten the COVID-19 vaccine? Do you “feel safer waiting until more research is done on the side effects being discovered right now”? (We are not making this up.)
Then join the Fearless Boxing Club, because we “will not be accepting any vaccinated members.” Our founders, Mohammed Abedeen and Krystal Glazier-Roscoe, are working hard to exclude “those who received the experimental COVID vaccine.” (Still not making it up.)
And now, back to the news.
Brazilian president Jair Bolsonaro was hospitalized recently for a severe case of hiccups that may have been related to a stab wound he received in 2018. [Nope, didn’t make that up, either.]
Mr. Bolsonaro had been hiccuping for 10 days, and was experiencing abdominal pain and difficulty speaking, when he entered the hospital on July 14. Since being stabbed while on the campaign trail, he has undergone several operations, which may have led to the partial intestinal obstruction that caused his latest symptoms.
His medical team advised Mr. Bolsonaro to go on a diet to aid his recovery, but when he was released on July 18 he said, “I hope in 10 days I’ll be eating barbecued ribs.” (Maybe this is all just a lucid dream. Probably shouldn’t have had ribs right before bed.)
Five risk factors may predict thrombus on LAA occlusion implants
, itself an important risk factor for cerebrovascular events, in patients with implants for left atrial appendage occlusion (LAAO), new research suggests.
The identified independent predictors of DRT in the largest dedicated multicenter LAAO-DRT registry to date were presence of a hypercoagulability disorder, pericardial effusion, renal insufficiency, an implantation depth greater than 10 mm from the pulmonary ridge, and presence of nonparoxysmal atrial fibrillation (AFib).
“Unfortunately, most of them are not modifiable, like hypercoaguable disorders or nonparoxysmal atrial fibrillation. But we can avoid deep implants because that’s been associated with creating a little bit of a crater or valley where the clot can form,” senior author Mohamad Alkhouli, MD, said in an interview.
But most important, and “really why we wanted to do this,” he said, is that “we want to give the patient a realistic prediction of adverse events for this procedure.”
LAAO has taken off in recent years for preventing thrombus formation and stroke in patients with AFib. Predicting DRT is a priority for the LAAO field, the authors note, especially given its expansion to younger, lower-risk patients and the increasing procedural volumes.
“This is a problem, DRT, that’s been discussed a lot because this is a preventative procedure,” observed Dr. Alkhouli, professor of medicine at Mayo Medical School, Rochester, Minn.
“The actual stroke risk every year – even if you don’t take any blood thinner and you have a CHADsVASc score of 9, the highest – is 11%. So if the chance of having thrombus is close, then that’s not a good tradeoff.”
Previous studies have also identified implantation depth and nonparoxysmal AFib as risk factors for DRT. But most of them have been small, he noted, with one of the largest reporting 65 DRTs in four prospective trials.
To cast a wider net, the investigators, led by Trevor Simard, MD, also from the Mayo Clinic, invited more than 50 international sites to contribute data to the registry. Of these, 37 centers reported on 237 DRTs and 474 device-matched control subjects from the same site.
Three-fourths of patients received a first-generation Watchman or a FLEX device (Boston Scientific).
Medical regimens were similar between the DRT and control cohorts at discharge after LAA closure. Most patients were managed with single (36.3%) or dual antiplatelet therapy (26.2%) at the time of DRT diagnosis.
As reported July 19 in the Journal of the American College of Cardiology, the timing of DRT development varied widely, with 24.9% appearing in the first 45 days, 38.8% between days 45 and 180, 16.0% between days 180 to 365, and 20.3% beyond 1 year. At last known follow-up, one-quarter of patients had DRT.
The odds ratios for DRT associated with the five identified risk factors were:
- 17.50 (95% confidence interval, 3.39-90.45) for hypercoagulability disorder
- 13.45 (95% CI, 1.46-123.52) for pericardial effusion
- 4.02 (95% CI, 1.22-13.25) for renal insufficiency
- 2.41 (95% CI, 1.57-3.69) for implantation depth >10 mm
- 1.90 (95% CI, 1.22-2.97) for nonparoxysmal AFib
The risk for a composite of death, ischemic stroke, and systemic embolization was twofold higher in the DRT cohort than in the control cohort (29.5% vs. 14.4%; hazard ratio, 2.37; 95% CI, 1.58-3.56) and driven by a higher rate of ischemic stroke (16.9% vs. 3.6%; HR, 3.49; 95% CI, 1.35-9.00).
The incidence of bleeding and intracerebral hemorrhage, however, was similar in the DRT and control cohorts.
One of the surprises of the study was that medications prescribed in the short term after LAA closure were not associated with DRT, Dr. Alkhouli said. A previous meta-analysis of 66 studies by the investigators also found that antithrombotic regimen did not explain the heterogeneity of DRT formation.
“I think we’ll have to take that with a grain of salt, because there’s so many variations in the practice, and this is observational data. But that, in my mind, brings up a mechanistic issue,” he said.
It’s often recommended “that we should put patients on blood thinners for 3 months or 6 weeks, or whatever it is, to decrease the chance of thrombus, assuming the patients will have a normal endothelialization of the device,” Dr. Alkhouli said.
“Well, we know that’s not the reality,” he continued. “We know many patients don’t endothelialize, and, even if some patients do, there may be some endothelial damage. So I think the whole mechanism of prescribing a little bit of a blood thinner to avoid that risk may be missing the point. It’s a bit more complex than that, evidenced also by the fact that three-fourths of all the DRTs happened after 45 days, when patients are typically not taking a blood thinner.”
Based on the five independent risk factors, the investigators created a clinical DRT risk score that assigned 1 point for renal insufficiency, implantation depth greater than 10 mm from the pulmonary ridge, and nonparoxysmal AFib; and 4 points for iatrogenic pericardial effusion and for hypercoagulability disorder. Low risk was categorized as 1 point and high risk as 2 or more points.
The presence of one major risk factor or two minor risk factors, for example, led to a 2.1-fold increased risk for DRT, compared with those with no DRT risk factors.
The risk score will require validation in a prospective cohort but is “a step forward in addressing DRT” and triaging patients, Dr. Alkhouli said. The findings highlight the need to avoid deep device implantation and the importance of shared decision-making with patients, especially with those at high risk.
“And third, which is most important, I think, in my mind, is that it tells us not to put a blind eye to this topic and just say with improved devices it will go away,” he said. “That’s a bit unrealistic.”
In an accompanying editorial, Oussama Wazni, MD, Walid Saliba, MD, and Ayman A. Hussein, MD, all from the Cleveland Clinic, write that “the study sheds light on this yet unresolved issue, and the observations may help with risk stratification and optimization of procedural techniques.”
Whereas many of the nonmodifiable risk factors are helpful in shared decision-making decisions, they continue, “knowledge of these risk factors may not preclude implantation in patients who are otherwise at risk of both stroke off anticoagulation and bleeding on anticoagulation.”
Dr. Wazni and colleagues acknowledge that the small number of events in the study limits statistical power for definitive conclusions and say that further studies are needed to clarify the natural history of DRTs and their management, resolution, and impact on cardiovascular events.
Practitioners should also continue to cautiously assess for LAAO clinical indications for implant, according to the editorialists, who point out that the regulatory approval language in the United States was “flexible and nonspecific.”
“As the field grows wider, enhancing LAAO safety with optimal design, implantation, and periprocedural management is critically important, yet the main focus should remain on optimal patient selection for the purpose of achieving safe and successful outcomes,” the editorialists conclude.
Dr. Alkhouli has served as a consultant for Boston Scientific. Coauthor disclosures are listed in the paper. Dr. Wazni and Dr. Hussein have received research grant support from Boston Scientific. Dr. Wazni and Dr. Saliba have been consultants for Boston Scientific.
A version of this article first appeared on Medscape.com.
, itself an important risk factor for cerebrovascular events, in patients with implants for left atrial appendage occlusion (LAAO), new research suggests.
The identified independent predictors of DRT in the largest dedicated multicenter LAAO-DRT registry to date were presence of a hypercoagulability disorder, pericardial effusion, renal insufficiency, an implantation depth greater than 10 mm from the pulmonary ridge, and presence of nonparoxysmal atrial fibrillation (AFib).
“Unfortunately, most of them are not modifiable, like hypercoaguable disorders or nonparoxysmal atrial fibrillation. But we can avoid deep implants because that’s been associated with creating a little bit of a crater or valley where the clot can form,” senior author Mohamad Alkhouli, MD, said in an interview.
But most important, and “really why we wanted to do this,” he said, is that “we want to give the patient a realistic prediction of adverse events for this procedure.”
LAAO has taken off in recent years for preventing thrombus formation and stroke in patients with AFib. Predicting DRT is a priority for the LAAO field, the authors note, especially given its expansion to younger, lower-risk patients and the increasing procedural volumes.
“This is a problem, DRT, that’s been discussed a lot because this is a preventative procedure,” observed Dr. Alkhouli, professor of medicine at Mayo Medical School, Rochester, Minn.
“The actual stroke risk every year – even if you don’t take any blood thinner and you have a CHADsVASc score of 9, the highest – is 11%. So if the chance of having thrombus is close, then that’s not a good tradeoff.”
Previous studies have also identified implantation depth and nonparoxysmal AFib as risk factors for DRT. But most of them have been small, he noted, with one of the largest reporting 65 DRTs in four prospective trials.
To cast a wider net, the investigators, led by Trevor Simard, MD, also from the Mayo Clinic, invited more than 50 international sites to contribute data to the registry. Of these, 37 centers reported on 237 DRTs and 474 device-matched control subjects from the same site.
Three-fourths of patients received a first-generation Watchman or a FLEX device (Boston Scientific).
Medical regimens were similar between the DRT and control cohorts at discharge after LAA closure. Most patients were managed with single (36.3%) or dual antiplatelet therapy (26.2%) at the time of DRT diagnosis.
As reported July 19 in the Journal of the American College of Cardiology, the timing of DRT development varied widely, with 24.9% appearing in the first 45 days, 38.8% between days 45 and 180, 16.0% between days 180 to 365, and 20.3% beyond 1 year. At last known follow-up, one-quarter of patients had DRT.
The odds ratios for DRT associated with the five identified risk factors were:
- 17.50 (95% confidence interval, 3.39-90.45) for hypercoagulability disorder
- 13.45 (95% CI, 1.46-123.52) for pericardial effusion
- 4.02 (95% CI, 1.22-13.25) for renal insufficiency
- 2.41 (95% CI, 1.57-3.69) for implantation depth >10 mm
- 1.90 (95% CI, 1.22-2.97) for nonparoxysmal AFib
The risk for a composite of death, ischemic stroke, and systemic embolization was twofold higher in the DRT cohort than in the control cohort (29.5% vs. 14.4%; hazard ratio, 2.37; 95% CI, 1.58-3.56) and driven by a higher rate of ischemic stroke (16.9% vs. 3.6%; HR, 3.49; 95% CI, 1.35-9.00).
The incidence of bleeding and intracerebral hemorrhage, however, was similar in the DRT and control cohorts.
One of the surprises of the study was that medications prescribed in the short term after LAA closure were not associated with DRT, Dr. Alkhouli said. A previous meta-analysis of 66 studies by the investigators also found that antithrombotic regimen did not explain the heterogeneity of DRT formation.
“I think we’ll have to take that with a grain of salt, because there’s so many variations in the practice, and this is observational data. But that, in my mind, brings up a mechanistic issue,” he said.
It’s often recommended “that we should put patients on blood thinners for 3 months or 6 weeks, or whatever it is, to decrease the chance of thrombus, assuming the patients will have a normal endothelialization of the device,” Dr. Alkhouli said.
“Well, we know that’s not the reality,” he continued. “We know many patients don’t endothelialize, and, even if some patients do, there may be some endothelial damage. So I think the whole mechanism of prescribing a little bit of a blood thinner to avoid that risk may be missing the point. It’s a bit more complex than that, evidenced also by the fact that three-fourths of all the DRTs happened after 45 days, when patients are typically not taking a blood thinner.”
Based on the five independent risk factors, the investigators created a clinical DRT risk score that assigned 1 point for renal insufficiency, implantation depth greater than 10 mm from the pulmonary ridge, and nonparoxysmal AFib; and 4 points for iatrogenic pericardial effusion and for hypercoagulability disorder. Low risk was categorized as 1 point and high risk as 2 or more points.
The presence of one major risk factor or two minor risk factors, for example, led to a 2.1-fold increased risk for DRT, compared with those with no DRT risk factors.
The risk score will require validation in a prospective cohort but is “a step forward in addressing DRT” and triaging patients, Dr. Alkhouli said. The findings highlight the need to avoid deep device implantation and the importance of shared decision-making with patients, especially with those at high risk.
“And third, which is most important, I think, in my mind, is that it tells us not to put a blind eye to this topic and just say with improved devices it will go away,” he said. “That’s a bit unrealistic.”
In an accompanying editorial, Oussama Wazni, MD, Walid Saliba, MD, and Ayman A. Hussein, MD, all from the Cleveland Clinic, write that “the study sheds light on this yet unresolved issue, and the observations may help with risk stratification and optimization of procedural techniques.”
Whereas many of the nonmodifiable risk factors are helpful in shared decision-making decisions, they continue, “knowledge of these risk factors may not preclude implantation in patients who are otherwise at risk of both stroke off anticoagulation and bleeding on anticoagulation.”
Dr. Wazni and colleagues acknowledge that the small number of events in the study limits statistical power for definitive conclusions and say that further studies are needed to clarify the natural history of DRTs and their management, resolution, and impact on cardiovascular events.
Practitioners should also continue to cautiously assess for LAAO clinical indications for implant, according to the editorialists, who point out that the regulatory approval language in the United States was “flexible and nonspecific.”
“As the field grows wider, enhancing LAAO safety with optimal design, implantation, and periprocedural management is critically important, yet the main focus should remain on optimal patient selection for the purpose of achieving safe and successful outcomes,” the editorialists conclude.
Dr. Alkhouli has served as a consultant for Boston Scientific. Coauthor disclosures are listed in the paper. Dr. Wazni and Dr. Hussein have received research grant support from Boston Scientific. Dr. Wazni and Dr. Saliba have been consultants for Boston Scientific.
A version of this article first appeared on Medscape.com.
, itself an important risk factor for cerebrovascular events, in patients with implants for left atrial appendage occlusion (LAAO), new research suggests.
The identified independent predictors of DRT in the largest dedicated multicenter LAAO-DRT registry to date were presence of a hypercoagulability disorder, pericardial effusion, renal insufficiency, an implantation depth greater than 10 mm from the pulmonary ridge, and presence of nonparoxysmal atrial fibrillation (AFib).
“Unfortunately, most of them are not modifiable, like hypercoaguable disorders or nonparoxysmal atrial fibrillation. But we can avoid deep implants because that’s been associated with creating a little bit of a crater or valley where the clot can form,” senior author Mohamad Alkhouli, MD, said in an interview.
But most important, and “really why we wanted to do this,” he said, is that “we want to give the patient a realistic prediction of adverse events for this procedure.”
LAAO has taken off in recent years for preventing thrombus formation and stroke in patients with AFib. Predicting DRT is a priority for the LAAO field, the authors note, especially given its expansion to younger, lower-risk patients and the increasing procedural volumes.
“This is a problem, DRT, that’s been discussed a lot because this is a preventative procedure,” observed Dr. Alkhouli, professor of medicine at Mayo Medical School, Rochester, Minn.
“The actual stroke risk every year – even if you don’t take any blood thinner and you have a CHADsVASc score of 9, the highest – is 11%. So if the chance of having thrombus is close, then that’s not a good tradeoff.”
Previous studies have also identified implantation depth and nonparoxysmal AFib as risk factors for DRT. But most of them have been small, he noted, with one of the largest reporting 65 DRTs in four prospective trials.
To cast a wider net, the investigators, led by Trevor Simard, MD, also from the Mayo Clinic, invited more than 50 international sites to contribute data to the registry. Of these, 37 centers reported on 237 DRTs and 474 device-matched control subjects from the same site.
Three-fourths of patients received a first-generation Watchman or a FLEX device (Boston Scientific).
Medical regimens were similar between the DRT and control cohorts at discharge after LAA closure. Most patients were managed with single (36.3%) or dual antiplatelet therapy (26.2%) at the time of DRT diagnosis.
As reported July 19 in the Journal of the American College of Cardiology, the timing of DRT development varied widely, with 24.9% appearing in the first 45 days, 38.8% between days 45 and 180, 16.0% between days 180 to 365, and 20.3% beyond 1 year. At last known follow-up, one-quarter of patients had DRT.
The odds ratios for DRT associated with the five identified risk factors were:
- 17.50 (95% confidence interval, 3.39-90.45) for hypercoagulability disorder
- 13.45 (95% CI, 1.46-123.52) for pericardial effusion
- 4.02 (95% CI, 1.22-13.25) for renal insufficiency
- 2.41 (95% CI, 1.57-3.69) for implantation depth >10 mm
- 1.90 (95% CI, 1.22-2.97) for nonparoxysmal AFib
The risk for a composite of death, ischemic stroke, and systemic embolization was twofold higher in the DRT cohort than in the control cohort (29.5% vs. 14.4%; hazard ratio, 2.37; 95% CI, 1.58-3.56) and driven by a higher rate of ischemic stroke (16.9% vs. 3.6%; HR, 3.49; 95% CI, 1.35-9.00).
The incidence of bleeding and intracerebral hemorrhage, however, was similar in the DRT and control cohorts.
One of the surprises of the study was that medications prescribed in the short term after LAA closure were not associated with DRT, Dr. Alkhouli said. A previous meta-analysis of 66 studies by the investigators also found that antithrombotic regimen did not explain the heterogeneity of DRT formation.
“I think we’ll have to take that with a grain of salt, because there’s so many variations in the practice, and this is observational data. But that, in my mind, brings up a mechanistic issue,” he said.
It’s often recommended “that we should put patients on blood thinners for 3 months or 6 weeks, or whatever it is, to decrease the chance of thrombus, assuming the patients will have a normal endothelialization of the device,” Dr. Alkhouli said.
“Well, we know that’s not the reality,” he continued. “We know many patients don’t endothelialize, and, even if some patients do, there may be some endothelial damage. So I think the whole mechanism of prescribing a little bit of a blood thinner to avoid that risk may be missing the point. It’s a bit more complex than that, evidenced also by the fact that three-fourths of all the DRTs happened after 45 days, when patients are typically not taking a blood thinner.”
Based on the five independent risk factors, the investigators created a clinical DRT risk score that assigned 1 point for renal insufficiency, implantation depth greater than 10 mm from the pulmonary ridge, and nonparoxysmal AFib; and 4 points for iatrogenic pericardial effusion and for hypercoagulability disorder. Low risk was categorized as 1 point and high risk as 2 or more points.
The presence of one major risk factor or two minor risk factors, for example, led to a 2.1-fold increased risk for DRT, compared with those with no DRT risk factors.
The risk score will require validation in a prospective cohort but is “a step forward in addressing DRT” and triaging patients, Dr. Alkhouli said. The findings highlight the need to avoid deep device implantation and the importance of shared decision-making with patients, especially with those at high risk.
“And third, which is most important, I think, in my mind, is that it tells us not to put a blind eye to this topic and just say with improved devices it will go away,” he said. “That’s a bit unrealistic.”
In an accompanying editorial, Oussama Wazni, MD, Walid Saliba, MD, and Ayman A. Hussein, MD, all from the Cleveland Clinic, write that “the study sheds light on this yet unresolved issue, and the observations may help with risk stratification and optimization of procedural techniques.”
Whereas many of the nonmodifiable risk factors are helpful in shared decision-making decisions, they continue, “knowledge of these risk factors may not preclude implantation in patients who are otherwise at risk of both stroke off anticoagulation and bleeding on anticoagulation.”
Dr. Wazni and colleagues acknowledge that the small number of events in the study limits statistical power for definitive conclusions and say that further studies are needed to clarify the natural history of DRTs and their management, resolution, and impact on cardiovascular events.
Practitioners should also continue to cautiously assess for LAAO clinical indications for implant, according to the editorialists, who point out that the regulatory approval language in the United States was “flexible and nonspecific.”
“As the field grows wider, enhancing LAAO safety with optimal design, implantation, and periprocedural management is critically important, yet the main focus should remain on optimal patient selection for the purpose of achieving safe and successful outcomes,” the editorialists conclude.
Dr. Alkhouli has served as a consultant for Boston Scientific. Coauthor disclosures are listed in the paper. Dr. Wazni and Dr. Hussein have received research grant support from Boston Scientific. Dr. Wazni and Dr. Saliba have been consultants for Boston Scientific.
A version of this article first appeared on Medscape.com.
HIV-associated cryptococcal meningitis: Single-dose regimen found non-inferior
A single high dose of the antifungal agent liposomal amphotericin B (L-AmB; AmBisome, Gilead Sciences), with a background regimen of flucytosine and fluconazole, is non-inferior and significantly safer in preventing mortality in HIV-associated cryptococcal meningitis than a conventional seven-day regimen that is the current standard of care, according to a new study.
“The results of this phase 3 [AMBITION-cm] trial make it clear that this approach is just as good as the current World Health Organization-recommended first-line treatment in preventing death,” first author David S. Lawrence, MD, AMBITION study lead clinician, of the London School of Hygiene and Tropical Medicine, United Kingdom, said in an interview.
“The fact that this was the largest ever trial [on HIV-associated cryptococcal meningitis] conducted to date… gives us a high level of confidence in these results,” he said of the study, which was presented at the virtual annual meeting of the International AIDS Society.
“We believe that this should become the WHO-recommended first-line regimen,” he emphasized.
In commenting on the study, Meg Doherty, MD, PhD, director of global HIV, hepatitis, and STI programs at WHO, agreed that a shorter regimen could be vital, particularly in settings with limited resources.
“The results from the AMBITION trial are important for low- and middle-income countries, where the cost and complexity of implementing the current standard seven-day course of L-ambisome or cryptococcal meningitis treatment can put this out of reach for many,” she told this news organization.
“Simplification that maintains the highest quality of care is an important component of the public health approach for HIV treatment and care,” she added.
Dr. Doherty could not comment on any possible changes to WHO recommendations, which are formulated by an independent guideline development group, but a spokesperson said that “WHO is preparing an updated review of the evidence for treating cryptococcal disease as a first step towards updating guidance.”
Conventional treatment toxicities
Cryptococcal meningitis is a leading cause of death in HIV, and the conventional treatment of amphotericin B deoxycholate, though less expensive than L-AmB, is more toxic, causing anemia, renal impairment, and electrolyte abnormalities, Dr. Lawrence explained
Having previously shown a single 10 mg/kg dose of L-AmB to be as effective as the longer regimen of 14 daily doses in terms of clearing cryptococcus from the cerebrospinal fluid, Dr. Lawrence and his colleagues conducted the phase 3 AMBITION-Cm trial to evaluate the effect on mortality, enrolling 844 patients in Botswana, Malawi, South Africa, Uganda, and Zimbabwe who were HIV-positive and had a first episode of cryptococcal meningitis.
Participants in the study were randomized to treatment either with single, high-dose L-AmB (10 mg/kg), combined with 14 days of flucytosine 100 mg/kg/day and fluconazole 1,200 mg/day or to a control group receiving 7 daily doses of AmB deoxycholate (1 mg/kg) plus 7 days of flucytosine 100 mg/kg/day, followed by 7 days of fluconazole 1,200 mg/day.
All patients were also provided with consolidation therapy of fluconazole 800 mg/day for eight weeks. Of the patients, 60.2% were male, their median age was 37, and their median CD4 count was 27 cells/mm3.
For the primary endpoint in the intention-to-treat analysis of 814 patients, the 10-week mortality rate in the single-dose L-AmB group was 24.82% (101 of 407) and 28.75% (117 of 407) in the control arm, for a difference (-3.93%) that was well within the pre-specified non-inferiority margin of 10%.
As expected, the safety measures were significantly improved with the single-dose of L-AmB: Rates of grade 3 or 4 adverse events within the initial 21 days of treatment in the single-dose L-AmB group were 50% versus 62.3% in the control group, and severe anemia occurred in just 13% of single-dose L-AmB participants, compared with 41% in the AmB deoxycholate control arm (both P < .001), Dr. Lawrence reported.
Furthermore, the average decline in hemoglobin over the first week was 0.3 g/dL in the single-dose L-AmB arm and 1.9 g/dL in the control arm, resulting in the need for more blood transfusions in the control arm (P < .001).
The impact on kidney function was also worse in the higher dose arm, with an average increase in creatinine over the first week of 20.2% in the L-AmB group versus 49.7% in the control group, while hypokalemia and thrombophlebitis were also more common with the higher dose group, Dr. Lawrence noted.
In the adjusted analysis, the single-dose L-AmB measures were in fact superior after adjusting for factors including research site, age, sex, baseline Glasgow Coma Scale, CD4 count, CSF cryptococcal colony-forming units/mL, antiretroviral therapy status, hemoglobin, and CSF opening pressure.
Mortality rate still high – but significantly reduced
The mortality rate of about 25% in the study after the treatment is still significantly higher than typically seen in high-income countries such as the United States, where HIV-associated cryptococcal meningitis is less common and associated with a mortality of roughly 10-15%, Dr. Lawrence noted.
The rate is nevertheless among the lowest mortality rates ever reported within a clinical trial conducted in resource-limited settings, he explained.
“These results are a step in the right direction and a significant improvement on the rates of 40% to 45% reported with two-week L-AmB-based regimens in African settings,” Dr. Lawrence underscored.
Higher cost — but potentially more cost-effective
With a higher cost than AmB deoxycholate, L-AmB’s utilization in resource-limited settings has been a challenge: A single vial of L-AmB ranges from $80 to $200, according to some reports, and while 14-day dosing requires as many as 42 vials of L-AmB, even a 7-day regimen still requires 21 vials.
In comparison, the single-dose L-AmB regimen only requires an average of 10 to 11 vials per patient, but the regimen’s higher safety could translate to far greater cost savings, Dr. Lawrence explained.
“While the AmBisome regimen is technically more expensive in terms of drugs, we expect it to be cost-effective or possibly cost-saving when taking into account that there is less toxicity, fewer blood tests, less transfusions, etc., and possibly shorter duration of hospital admission,” he said.
Cost, supply controversy: ‘Black fungus’-related demand
The drug’s cost — as well as supply issues — have meanwhile become even more of a problem as L-AmB has unexpectedly also become urgently needed in the treatment of mucormycosis in India and Nepal, where the otherwise rare fungal disease, commonly known as “black fungus,” has been increasingly affecting COVID-19 patients and survivors.
Gilead had previously announced in 2018 its intention to make L-AmB more widely available at a price of $16.25 per vial, but “implementation of this has been slow,” Dr. Lawrence said.
As a result, Gilead is facing heightened pressure to implement the lower prices – and also improve substantial supply issues, with Médecins Sans Frontières (Doctors Without Borders) and dozens of other global organizations issuing an open letter to Gilead and partner Viatris in June calling for immediate action to implement the lower price and improve supply of L-AmB.
In a company statement, Gilead responded, detailing its “commit[ment] to the non-profit pricing for the treatment of cryptococcal meningitis” and to efforts to improve the public health crisis in India.
For their part, Dr. Lawrence and his colleagues are working on producing more research on the issue.
“We hope that the conclusive results of the AMBITION trial will give a much needed push to implement this program,” he said.
“We are also currently completing the cost-effectiveness analysis of the study, which we hope will provide additional evidence to support widespread implementation of this regimen and highlight further the urgent need to broaden access to AmBisome and flucytosine,” he said.
The trial was supported by a grant through the European Developing Countries Clinical Trials Partnership (EDCTP), the Swedish International Development Cooperation Agency (SIDA) (TRIA2015-1092), and the Wellcome Trust / Medical Research Council (UK)/UKAID Joint Global Health Trials (MR/P006922/1. The AmBisome was donated by Gilead Sciences. Dr. Lawrence had no disclosures to report.
A single high dose of the antifungal agent liposomal amphotericin B (L-AmB; AmBisome, Gilead Sciences), with a background regimen of flucytosine and fluconazole, is non-inferior and significantly safer in preventing mortality in HIV-associated cryptococcal meningitis than a conventional seven-day regimen that is the current standard of care, according to a new study.
“The results of this phase 3 [AMBITION-cm] trial make it clear that this approach is just as good as the current World Health Organization-recommended first-line treatment in preventing death,” first author David S. Lawrence, MD, AMBITION study lead clinician, of the London School of Hygiene and Tropical Medicine, United Kingdom, said in an interview.
“The fact that this was the largest ever trial [on HIV-associated cryptococcal meningitis] conducted to date… gives us a high level of confidence in these results,” he said of the study, which was presented at the virtual annual meeting of the International AIDS Society.
“We believe that this should become the WHO-recommended first-line regimen,” he emphasized.
In commenting on the study, Meg Doherty, MD, PhD, director of global HIV, hepatitis, and STI programs at WHO, agreed that a shorter regimen could be vital, particularly in settings with limited resources.
“The results from the AMBITION trial are important for low- and middle-income countries, where the cost and complexity of implementing the current standard seven-day course of L-ambisome or cryptococcal meningitis treatment can put this out of reach for many,” she told this news organization.
“Simplification that maintains the highest quality of care is an important component of the public health approach for HIV treatment and care,” she added.
Dr. Doherty could not comment on any possible changes to WHO recommendations, which are formulated by an independent guideline development group, but a spokesperson said that “WHO is preparing an updated review of the evidence for treating cryptococcal disease as a first step towards updating guidance.”
Conventional treatment toxicities
Cryptococcal meningitis is a leading cause of death in HIV, and the conventional treatment of amphotericin B deoxycholate, though less expensive than L-AmB, is more toxic, causing anemia, renal impairment, and electrolyte abnormalities, Dr. Lawrence explained
Having previously shown a single 10 mg/kg dose of L-AmB to be as effective as the longer regimen of 14 daily doses in terms of clearing cryptococcus from the cerebrospinal fluid, Dr. Lawrence and his colleagues conducted the phase 3 AMBITION-Cm trial to evaluate the effect on mortality, enrolling 844 patients in Botswana, Malawi, South Africa, Uganda, and Zimbabwe who were HIV-positive and had a first episode of cryptococcal meningitis.
Participants in the study were randomized to treatment either with single, high-dose L-AmB (10 mg/kg), combined with 14 days of flucytosine 100 mg/kg/day and fluconazole 1,200 mg/day or to a control group receiving 7 daily doses of AmB deoxycholate (1 mg/kg) plus 7 days of flucytosine 100 mg/kg/day, followed by 7 days of fluconazole 1,200 mg/day.
All patients were also provided with consolidation therapy of fluconazole 800 mg/day for eight weeks. Of the patients, 60.2% were male, their median age was 37, and their median CD4 count was 27 cells/mm3.
For the primary endpoint in the intention-to-treat analysis of 814 patients, the 10-week mortality rate in the single-dose L-AmB group was 24.82% (101 of 407) and 28.75% (117 of 407) in the control arm, for a difference (-3.93%) that was well within the pre-specified non-inferiority margin of 10%.
As expected, the safety measures were significantly improved with the single-dose of L-AmB: Rates of grade 3 or 4 adverse events within the initial 21 days of treatment in the single-dose L-AmB group were 50% versus 62.3% in the control group, and severe anemia occurred in just 13% of single-dose L-AmB participants, compared with 41% in the AmB deoxycholate control arm (both P < .001), Dr. Lawrence reported.
Furthermore, the average decline in hemoglobin over the first week was 0.3 g/dL in the single-dose L-AmB arm and 1.9 g/dL in the control arm, resulting in the need for more blood transfusions in the control arm (P < .001).
The impact on kidney function was also worse in the higher dose arm, with an average increase in creatinine over the first week of 20.2% in the L-AmB group versus 49.7% in the control group, while hypokalemia and thrombophlebitis were also more common with the higher dose group, Dr. Lawrence noted.
In the adjusted analysis, the single-dose L-AmB measures were in fact superior after adjusting for factors including research site, age, sex, baseline Glasgow Coma Scale, CD4 count, CSF cryptococcal colony-forming units/mL, antiretroviral therapy status, hemoglobin, and CSF opening pressure.
Mortality rate still high – but significantly reduced
The mortality rate of about 25% in the study after the treatment is still significantly higher than typically seen in high-income countries such as the United States, where HIV-associated cryptococcal meningitis is less common and associated with a mortality of roughly 10-15%, Dr. Lawrence noted.
The rate is nevertheless among the lowest mortality rates ever reported within a clinical trial conducted in resource-limited settings, he explained.
“These results are a step in the right direction and a significant improvement on the rates of 40% to 45% reported with two-week L-AmB-based regimens in African settings,” Dr. Lawrence underscored.
Higher cost — but potentially more cost-effective
With a higher cost than AmB deoxycholate, L-AmB’s utilization in resource-limited settings has been a challenge: A single vial of L-AmB ranges from $80 to $200, according to some reports, and while 14-day dosing requires as many as 42 vials of L-AmB, even a 7-day regimen still requires 21 vials.
In comparison, the single-dose L-AmB regimen only requires an average of 10 to 11 vials per patient, but the regimen’s higher safety could translate to far greater cost savings, Dr. Lawrence explained.
“While the AmBisome regimen is technically more expensive in terms of drugs, we expect it to be cost-effective or possibly cost-saving when taking into account that there is less toxicity, fewer blood tests, less transfusions, etc., and possibly shorter duration of hospital admission,” he said.
Cost, supply controversy: ‘Black fungus’-related demand
The drug’s cost — as well as supply issues — have meanwhile become even more of a problem as L-AmB has unexpectedly also become urgently needed in the treatment of mucormycosis in India and Nepal, where the otherwise rare fungal disease, commonly known as “black fungus,” has been increasingly affecting COVID-19 patients and survivors.
Gilead had previously announced in 2018 its intention to make L-AmB more widely available at a price of $16.25 per vial, but “implementation of this has been slow,” Dr. Lawrence said.
As a result, Gilead is facing heightened pressure to implement the lower prices – and also improve substantial supply issues, with Médecins Sans Frontières (Doctors Without Borders) and dozens of other global organizations issuing an open letter to Gilead and partner Viatris in June calling for immediate action to implement the lower price and improve supply of L-AmB.
In a company statement, Gilead responded, detailing its “commit[ment] to the non-profit pricing for the treatment of cryptococcal meningitis” and to efforts to improve the public health crisis in India.
For their part, Dr. Lawrence and his colleagues are working on producing more research on the issue.
“We hope that the conclusive results of the AMBITION trial will give a much needed push to implement this program,” he said.
“We are also currently completing the cost-effectiveness analysis of the study, which we hope will provide additional evidence to support widespread implementation of this regimen and highlight further the urgent need to broaden access to AmBisome and flucytosine,” he said.
The trial was supported by a grant through the European Developing Countries Clinical Trials Partnership (EDCTP), the Swedish International Development Cooperation Agency (SIDA) (TRIA2015-1092), and the Wellcome Trust / Medical Research Council (UK)/UKAID Joint Global Health Trials (MR/P006922/1. The AmBisome was donated by Gilead Sciences. Dr. Lawrence had no disclosures to report.
A single high dose of the antifungal agent liposomal amphotericin B (L-AmB; AmBisome, Gilead Sciences), with a background regimen of flucytosine and fluconazole, is non-inferior and significantly safer in preventing mortality in HIV-associated cryptococcal meningitis than a conventional seven-day regimen that is the current standard of care, according to a new study.
“The results of this phase 3 [AMBITION-cm] trial make it clear that this approach is just as good as the current World Health Organization-recommended first-line treatment in preventing death,” first author David S. Lawrence, MD, AMBITION study lead clinician, of the London School of Hygiene and Tropical Medicine, United Kingdom, said in an interview.
“The fact that this was the largest ever trial [on HIV-associated cryptococcal meningitis] conducted to date… gives us a high level of confidence in these results,” he said of the study, which was presented at the virtual annual meeting of the International AIDS Society.
“We believe that this should become the WHO-recommended first-line regimen,” he emphasized.
In commenting on the study, Meg Doherty, MD, PhD, director of global HIV, hepatitis, and STI programs at WHO, agreed that a shorter regimen could be vital, particularly in settings with limited resources.
“The results from the AMBITION trial are important for low- and middle-income countries, where the cost and complexity of implementing the current standard seven-day course of L-ambisome or cryptococcal meningitis treatment can put this out of reach for many,” she told this news organization.
“Simplification that maintains the highest quality of care is an important component of the public health approach for HIV treatment and care,” she added.
Dr. Doherty could not comment on any possible changes to WHO recommendations, which are formulated by an independent guideline development group, but a spokesperson said that “WHO is preparing an updated review of the evidence for treating cryptococcal disease as a first step towards updating guidance.”
Conventional treatment toxicities
Cryptococcal meningitis is a leading cause of death in HIV, and the conventional treatment of amphotericin B deoxycholate, though less expensive than L-AmB, is more toxic, causing anemia, renal impairment, and electrolyte abnormalities, Dr. Lawrence explained
Having previously shown a single 10 mg/kg dose of L-AmB to be as effective as the longer regimen of 14 daily doses in terms of clearing cryptococcus from the cerebrospinal fluid, Dr. Lawrence and his colleagues conducted the phase 3 AMBITION-Cm trial to evaluate the effect on mortality, enrolling 844 patients in Botswana, Malawi, South Africa, Uganda, and Zimbabwe who were HIV-positive and had a first episode of cryptococcal meningitis.
Participants in the study were randomized to treatment either with single, high-dose L-AmB (10 mg/kg), combined with 14 days of flucytosine 100 mg/kg/day and fluconazole 1,200 mg/day or to a control group receiving 7 daily doses of AmB deoxycholate (1 mg/kg) plus 7 days of flucytosine 100 mg/kg/day, followed by 7 days of fluconazole 1,200 mg/day.
All patients were also provided with consolidation therapy of fluconazole 800 mg/day for eight weeks. Of the patients, 60.2% were male, their median age was 37, and their median CD4 count was 27 cells/mm3.
For the primary endpoint in the intention-to-treat analysis of 814 patients, the 10-week mortality rate in the single-dose L-AmB group was 24.82% (101 of 407) and 28.75% (117 of 407) in the control arm, for a difference (-3.93%) that was well within the pre-specified non-inferiority margin of 10%.
As expected, the safety measures were significantly improved with the single-dose of L-AmB: Rates of grade 3 or 4 adverse events within the initial 21 days of treatment in the single-dose L-AmB group were 50% versus 62.3% in the control group, and severe anemia occurred in just 13% of single-dose L-AmB participants, compared with 41% in the AmB deoxycholate control arm (both P < .001), Dr. Lawrence reported.
Furthermore, the average decline in hemoglobin over the first week was 0.3 g/dL in the single-dose L-AmB arm and 1.9 g/dL in the control arm, resulting in the need for more blood transfusions in the control arm (P < .001).
The impact on kidney function was also worse in the higher dose arm, with an average increase in creatinine over the first week of 20.2% in the L-AmB group versus 49.7% in the control group, while hypokalemia and thrombophlebitis were also more common with the higher dose group, Dr. Lawrence noted.
In the adjusted analysis, the single-dose L-AmB measures were in fact superior after adjusting for factors including research site, age, sex, baseline Glasgow Coma Scale, CD4 count, CSF cryptococcal colony-forming units/mL, antiretroviral therapy status, hemoglobin, and CSF opening pressure.
Mortality rate still high – but significantly reduced
The mortality rate of about 25% in the study after the treatment is still significantly higher than typically seen in high-income countries such as the United States, where HIV-associated cryptococcal meningitis is less common and associated with a mortality of roughly 10-15%, Dr. Lawrence noted.
The rate is nevertheless among the lowest mortality rates ever reported within a clinical trial conducted in resource-limited settings, he explained.
“These results are a step in the right direction and a significant improvement on the rates of 40% to 45% reported with two-week L-AmB-based regimens in African settings,” Dr. Lawrence underscored.
Higher cost — but potentially more cost-effective
With a higher cost than AmB deoxycholate, L-AmB’s utilization in resource-limited settings has been a challenge: A single vial of L-AmB ranges from $80 to $200, according to some reports, and while 14-day dosing requires as many as 42 vials of L-AmB, even a 7-day regimen still requires 21 vials.
In comparison, the single-dose L-AmB regimen only requires an average of 10 to 11 vials per patient, but the regimen’s higher safety could translate to far greater cost savings, Dr. Lawrence explained.
“While the AmBisome regimen is technically more expensive in terms of drugs, we expect it to be cost-effective or possibly cost-saving when taking into account that there is less toxicity, fewer blood tests, less transfusions, etc., and possibly shorter duration of hospital admission,” he said.
Cost, supply controversy: ‘Black fungus’-related demand
The drug’s cost — as well as supply issues — have meanwhile become even more of a problem as L-AmB has unexpectedly also become urgently needed in the treatment of mucormycosis in India and Nepal, where the otherwise rare fungal disease, commonly known as “black fungus,” has been increasingly affecting COVID-19 patients and survivors.
Gilead had previously announced in 2018 its intention to make L-AmB more widely available at a price of $16.25 per vial, but “implementation of this has been slow,” Dr. Lawrence said.
As a result, Gilead is facing heightened pressure to implement the lower prices – and also improve substantial supply issues, with Médecins Sans Frontières (Doctors Without Borders) and dozens of other global organizations issuing an open letter to Gilead and partner Viatris in June calling for immediate action to implement the lower price and improve supply of L-AmB.
In a company statement, Gilead responded, detailing its “commit[ment] to the non-profit pricing for the treatment of cryptococcal meningitis” and to efforts to improve the public health crisis in India.
For their part, Dr. Lawrence and his colleagues are working on producing more research on the issue.
“We hope that the conclusive results of the AMBITION trial will give a much needed push to implement this program,” he said.
“We are also currently completing the cost-effectiveness analysis of the study, which we hope will provide additional evidence to support widespread implementation of this regimen and highlight further the urgent need to broaden access to AmBisome and flucytosine,” he said.
The trial was supported by a grant through the European Developing Countries Clinical Trials Partnership (EDCTP), the Swedish International Development Cooperation Agency (SIDA) (TRIA2015-1092), and the Wellcome Trust / Medical Research Council (UK)/UKAID Joint Global Health Trials (MR/P006922/1. The AmBisome was donated by Gilead Sciences. Dr. Lawrence had no disclosures to report.
REPORTING FROM IAS 2021
FDA OKs spinal cord stimulation for diabetic neuropathy pain
The Food and Drug Administration has approved the first high-frequency spinal cord stimulation (SCS) therapy for treating painful diabetic neuropathy (PDN).
The approval is specific for the treatment of chronic pain associated with PDN using the Nevro’s Senza System with 10 kHz stimulation. It is intended for patients whose pain is refractory to, or who can’t tolerate, conventional medical treatment. According to the company, there are currently about 2.3 million individuals with refractory PDN in the United States.
The 10 kHz device, called HFX, involves minimally invasive epidural implantation of the stimulator device, which delivers mild electrical impulses to the nerves to interrupt pain signal to the brain. Such spinal cord stimulation “is a straightforward, well-established treatment for chronic pain that’s been used for over 30 years,” according to the company, although this is the first approval of the modality specifically for PDN.
Asked to comment, Rodica Pop-Busui MD, PhD, the Larry D. Soderquist Professor in Diabetes at the University of Michigan, Ann Arbor, said that “the approval of the Nevro 10kHz high-frequency spinal cord stimulation to treat pain associated with diabetic neuropathy has the potential for benefit for many patients with diabetes and painful diabetic peripheral neuropathy.”
She noted that, “although there are several other pharmacological agents that currently carry the FDA approval for PDN, this is a condition that is notoriously difficult to treat, particularly when taking into account the actual number needed to treat with a specific agent to achieve a clinically meaningful pain reduction, as well as the spectrum of side effects and drug-drug interactions in a patient population that require many other additional agents to manage diabetes and comorbidities on a daily basis. Thus, this new therapeutic approach besides effective pain reduction has the additional benefit of bypassing drug interactions.” Dr. Pop-Busui was the lead author on the American Diabetes Association’s 2017 position statement on diabetic neuropathy.
She also cautioned, on the other hand, that “it is not very clear yet how easy it will be for all eligible patients to have access to this technology, what will be the actual costs, the insurance coverage, or the acceptance by patients across various sociodemographic backgrounds from the at-large clinical care. However, given the challenges we encounter to treat diabetic neuropathy and particularly the pain associated with it, it is quite encouraging to see that the tools available to help our patients are now broader.”
Both 6-and 12-month results show benefit
The FDA approval was based on 6-month data from a prospective, multicenter, open-label randomized clinical trial published in JAMA Neurology.
Use of the 10-kHz SCS device was compared with conventional treatment alone in 216 patients with PDN refractory to gabapentinoids and at least one other analgesic class and lower limb pain intensity of 5 cm or more on a 10-cm visual analog scale.
The primary endpoint, percentage of participants reporting 50% pain relief or more without worsening of baseline neurologic deficits at 3 months, was met by 5 of 94 (5%) patients in the conventional group, compared with 75 of 95 (79%) with the 10-kHz SCS plus conventional treatment (P < .001).
Infections requiring device explant occurred in two patients in the 10-kHz SCS group (2%).
At 12 months, those in the original SCS group plus 86% of subjects given the option to cross over from the conventional treatment group showed “clear and sustained” benefits of the 10-kHz SCS with regard to lower-limb pain, pain interference with daily living, sleep quality, and activity, Erika Petersen, MD, director of the section of functional and restorative neurosurgery at the University of Arkansas for Medical Sciences, Little Rock , reported at the 2021 annual scientific sessions of the ADA.
Infection was the most common study-related adverse event, affecting 8 of 154 patients with the SCS implants (5.2%). Three resolved with conservative treatment and five (3.2%) required removal of the device.
The patients will be followed for a total of 24 months.
Commercial launch of HFX in the United States will begin immediately, the company said.
Dr. Pop-Busui has received consultant fees in the last 12 months from Averitas Pharma, Boehringer Ingelheim, Nevro, and Novo Nordisk. Dr. Petersen has financial relationships with Nevro, Medtronic, and several other neuromodulator makers.
The Food and Drug Administration has approved the first high-frequency spinal cord stimulation (SCS) therapy for treating painful diabetic neuropathy (PDN).
The approval is specific for the treatment of chronic pain associated with PDN using the Nevro’s Senza System with 10 kHz stimulation. It is intended for patients whose pain is refractory to, or who can’t tolerate, conventional medical treatment. According to the company, there are currently about 2.3 million individuals with refractory PDN in the United States.
The 10 kHz device, called HFX, involves minimally invasive epidural implantation of the stimulator device, which delivers mild electrical impulses to the nerves to interrupt pain signal to the brain. Such spinal cord stimulation “is a straightforward, well-established treatment for chronic pain that’s been used for over 30 years,” according to the company, although this is the first approval of the modality specifically for PDN.
Asked to comment, Rodica Pop-Busui MD, PhD, the Larry D. Soderquist Professor in Diabetes at the University of Michigan, Ann Arbor, said that “the approval of the Nevro 10kHz high-frequency spinal cord stimulation to treat pain associated with diabetic neuropathy has the potential for benefit for many patients with diabetes and painful diabetic peripheral neuropathy.”
She noted that, “although there are several other pharmacological agents that currently carry the FDA approval for PDN, this is a condition that is notoriously difficult to treat, particularly when taking into account the actual number needed to treat with a specific agent to achieve a clinically meaningful pain reduction, as well as the spectrum of side effects and drug-drug interactions in a patient population that require many other additional agents to manage diabetes and comorbidities on a daily basis. Thus, this new therapeutic approach besides effective pain reduction has the additional benefit of bypassing drug interactions.” Dr. Pop-Busui was the lead author on the American Diabetes Association’s 2017 position statement on diabetic neuropathy.
She also cautioned, on the other hand, that “it is not very clear yet how easy it will be for all eligible patients to have access to this technology, what will be the actual costs, the insurance coverage, or the acceptance by patients across various sociodemographic backgrounds from the at-large clinical care. However, given the challenges we encounter to treat diabetic neuropathy and particularly the pain associated with it, it is quite encouraging to see that the tools available to help our patients are now broader.”
Both 6-and 12-month results show benefit
The FDA approval was based on 6-month data from a prospective, multicenter, open-label randomized clinical trial published in JAMA Neurology.
Use of the 10-kHz SCS device was compared with conventional treatment alone in 216 patients with PDN refractory to gabapentinoids and at least one other analgesic class and lower limb pain intensity of 5 cm or more on a 10-cm visual analog scale.
The primary endpoint, percentage of participants reporting 50% pain relief or more without worsening of baseline neurologic deficits at 3 months, was met by 5 of 94 (5%) patients in the conventional group, compared with 75 of 95 (79%) with the 10-kHz SCS plus conventional treatment (P < .001).
Infections requiring device explant occurred in two patients in the 10-kHz SCS group (2%).
At 12 months, those in the original SCS group plus 86% of subjects given the option to cross over from the conventional treatment group showed “clear and sustained” benefits of the 10-kHz SCS with regard to lower-limb pain, pain interference with daily living, sleep quality, and activity, Erika Petersen, MD, director of the section of functional and restorative neurosurgery at the University of Arkansas for Medical Sciences, Little Rock , reported at the 2021 annual scientific sessions of the ADA.
Infection was the most common study-related adverse event, affecting 8 of 154 patients with the SCS implants (5.2%). Three resolved with conservative treatment and five (3.2%) required removal of the device.
The patients will be followed for a total of 24 months.
Commercial launch of HFX in the United States will begin immediately, the company said.
Dr. Pop-Busui has received consultant fees in the last 12 months from Averitas Pharma, Boehringer Ingelheim, Nevro, and Novo Nordisk. Dr. Petersen has financial relationships with Nevro, Medtronic, and several other neuromodulator makers.
The Food and Drug Administration has approved the first high-frequency spinal cord stimulation (SCS) therapy for treating painful diabetic neuropathy (PDN).
The approval is specific for the treatment of chronic pain associated with PDN using the Nevro’s Senza System with 10 kHz stimulation. It is intended for patients whose pain is refractory to, or who can’t tolerate, conventional medical treatment. According to the company, there are currently about 2.3 million individuals with refractory PDN in the United States.
The 10 kHz device, called HFX, involves minimally invasive epidural implantation of the stimulator device, which delivers mild electrical impulses to the nerves to interrupt pain signal to the brain. Such spinal cord stimulation “is a straightforward, well-established treatment for chronic pain that’s been used for over 30 years,” according to the company, although this is the first approval of the modality specifically for PDN.
Asked to comment, Rodica Pop-Busui MD, PhD, the Larry D. Soderquist Professor in Diabetes at the University of Michigan, Ann Arbor, said that “the approval of the Nevro 10kHz high-frequency spinal cord stimulation to treat pain associated with diabetic neuropathy has the potential for benefit for many patients with diabetes and painful diabetic peripheral neuropathy.”
She noted that, “although there are several other pharmacological agents that currently carry the FDA approval for PDN, this is a condition that is notoriously difficult to treat, particularly when taking into account the actual number needed to treat with a specific agent to achieve a clinically meaningful pain reduction, as well as the spectrum of side effects and drug-drug interactions in a patient population that require many other additional agents to manage diabetes and comorbidities on a daily basis. Thus, this new therapeutic approach besides effective pain reduction has the additional benefit of bypassing drug interactions.” Dr. Pop-Busui was the lead author on the American Diabetes Association’s 2017 position statement on diabetic neuropathy.
She also cautioned, on the other hand, that “it is not very clear yet how easy it will be for all eligible patients to have access to this technology, what will be the actual costs, the insurance coverage, or the acceptance by patients across various sociodemographic backgrounds from the at-large clinical care. However, given the challenges we encounter to treat diabetic neuropathy and particularly the pain associated with it, it is quite encouraging to see that the tools available to help our patients are now broader.”
Both 6-and 12-month results show benefit
The FDA approval was based on 6-month data from a prospective, multicenter, open-label randomized clinical trial published in JAMA Neurology.
Use of the 10-kHz SCS device was compared with conventional treatment alone in 216 patients with PDN refractory to gabapentinoids and at least one other analgesic class and lower limb pain intensity of 5 cm or more on a 10-cm visual analog scale.
The primary endpoint, percentage of participants reporting 50% pain relief or more without worsening of baseline neurologic deficits at 3 months, was met by 5 of 94 (5%) patients in the conventional group, compared with 75 of 95 (79%) with the 10-kHz SCS plus conventional treatment (P < .001).
Infections requiring device explant occurred in two patients in the 10-kHz SCS group (2%).
At 12 months, those in the original SCS group plus 86% of subjects given the option to cross over from the conventional treatment group showed “clear and sustained” benefits of the 10-kHz SCS with regard to lower-limb pain, pain interference with daily living, sleep quality, and activity, Erika Petersen, MD, director of the section of functional and restorative neurosurgery at the University of Arkansas for Medical Sciences, Little Rock , reported at the 2021 annual scientific sessions of the ADA.
Infection was the most common study-related adverse event, affecting 8 of 154 patients with the SCS implants (5.2%). Three resolved with conservative treatment and five (3.2%) required removal of the device.
The patients will be followed for a total of 24 months.
Commercial launch of HFX in the United States will begin immediately, the company said.
Dr. Pop-Busui has received consultant fees in the last 12 months from Averitas Pharma, Boehringer Ingelheim, Nevro, and Novo Nordisk. Dr. Petersen has financial relationships with Nevro, Medtronic, and several other neuromodulator makers.
Zero benefit of aducanumab for Alzheimer’s disease, expert panel rules
adding to growing opposition from medical experts to the Food and Drug Administration’s approval of this controversial drug.
The Institute for Clinical and Economic Review asked one of its expert panels, the California Technology Assessment Forum, to consider the available data about aducanumab and requested that members vote on whether there was sufficient evidence of a net benefit of aducanumab plus supportive care versus supportive care alone. All 15 panelists voted no.
Several panelists, including ICER President Steven D. Pearson, MD, talked about their personal experience with family members who have the disease.
There was universal agreement among the panelists that there is an urgent need for effective medications to treat the disease. However, the panel of clinicians and researchers also agreed that the evidence to date does not show that the drug helps patients with this debilitating disease.
Panelist Sei Lee, MD, a geriatrician at the University of California, San Francisco, said he lost his mother to AD 6 years ago. In addition to his clinical work, Dr. Lee has conducted research focused on improving the targeting of preventive AD interventions for older adults to maximize benefits and minimize harms.
Dr. Lee said he frequently felt completely overwhelmed by the challenges of his mother’s disease.
“I absolutely hear everyone who is saying we need an effective therapy for this,” Dr. Lee said.
Dr. Lee added that, as an experienced researcher who has weighed the aducanumab data, he saw no clear proof of a benefit that would outweigh the drug’s documented side effects in the two phase 3 trials of the drug. Those side effects include temporary brain swelling. Dr. Lee suggested that Biogen do more to address concerns about this side effect, saying it should not be ignored.
“There’s clearly substantial uncertainty” about aducanumab, Dr. Lee said. “If I had to guess, I think the data is stronger for net harm than it is for that benefit.”
Questions persist about the data Biogen used in support of aducanumab after announcing that the drug had failed in a dual-track phase 3 program.
In March 2019, it was announced that two phase 3 clinical trials, EMERGE and ENGAGE, were scrapped because of disappointing results. The trials were intended to show that aducanumab could slow progression of cognitive and functional impairment, as measured by changes in scores on the Clinical Dementia Rating–Sum of Boxes (CDR-SB).
However, in October 2019, there was an about-face – Biogen announced that, in one of the studies, there were positive findings for a subset of patients who received a higher dose of aducanumab.
No treatment benefit was observed in either the high- or low-dose arms at week 78 in the ENGAGE trial. In the EMERGE trial, however, there was a statistically significant difference in change from baseline in CDR-SB score in the high-dose arm (difference vs. placebo, –0.39; 95% confidence interval, –0.69 to –0.09) but not in the low-dose arm, ICER noted in a draft report.
Still, there are questions about whether this difference would translate into clinical benefit. “Although statistically significant, the change in CDR-SB score in the high-dose group was less than the 1- to 2-point change that has been suggested as a minimal clinically important difference,” ICER staff wrote.
More push back
Other influential organizations also remain skeptical.
On July 14, the Cleveland Clinic announced it would not use aducanumab at this time, following a staff review of the evidence. Physicians from the clinic could prescribe it to appropriate patients, who would receive their infusions at external facilities, a spokeswoman for the clinic told this news organization. The Cleveland Clinic said it will reevaluate this position as additional data become available.
In addition, as reported by the New York Times, the Mount Sinai Health System in New York also decided not to administer the drug.
The drug received accelerated approval from the FDA. That approval was conditional upon Biogen’s conducting further research by 2030 that demonstrates that the drug has clinical benefit.
On July 14, the executive committee of the American Neurological Association issued a statement asking for a speedier timeline.
The FDA should ensure that Biogen completes the required confirmatory study “as soon as possible, preferably within 3 years, to confirm or not whether clinical efficacy is observed,” the ANA executive committee wrote in the letter.
The ANA executive committee also criticized the FDA’s decision to allow Biogen to begin sales of the drug. In light of the clinical evidence available at this time, aducanumab “should not have been approved” in the first place, the ANA executive committee stated.
drawing from the discussion at the meeting and the panel’s votes. The work of the Boston-based group is used by private insurers to inform medication coverage decisions.
Lawmakers have taken an interest in aducanumab. On July 12, two top Democrats in the U.S. House of Representatives released a letter that they had sent to Biogen as part of their investigation into how the FDA handled the aducanumab approval and Biogen’s pricing for the drug.
In the letter, House Energy and Commerce Chairman Frank Pallone Jr. (D-N.J.) and Oversight and Reform Chairwoman Carolyn B. Maloney (D-N.Y.) wrote that they had “significant questions about the drug’s clinical benefit, and the steep $56,000 annual price tag.”
At the ICER meeting on July 15, Dr. Lee said patients with AD and their caregivers would benefit more from increased spending on supportive services, such as home health care.
“There’s so many things we could do” with money that Biogen may get for aducanumab, Dr. Lee said. “To spend it on a medication that is more likely to do more harm than help seems really ill advised.”
A version of this article first appeared on Medscape.com.
adding to growing opposition from medical experts to the Food and Drug Administration’s approval of this controversial drug.
The Institute for Clinical and Economic Review asked one of its expert panels, the California Technology Assessment Forum, to consider the available data about aducanumab and requested that members vote on whether there was sufficient evidence of a net benefit of aducanumab plus supportive care versus supportive care alone. All 15 panelists voted no.
Several panelists, including ICER President Steven D. Pearson, MD, talked about their personal experience with family members who have the disease.
There was universal agreement among the panelists that there is an urgent need for effective medications to treat the disease. However, the panel of clinicians and researchers also agreed that the evidence to date does not show that the drug helps patients with this debilitating disease.
Panelist Sei Lee, MD, a geriatrician at the University of California, San Francisco, said he lost his mother to AD 6 years ago. In addition to his clinical work, Dr. Lee has conducted research focused on improving the targeting of preventive AD interventions for older adults to maximize benefits and minimize harms.
Dr. Lee said he frequently felt completely overwhelmed by the challenges of his mother’s disease.
“I absolutely hear everyone who is saying we need an effective therapy for this,” Dr. Lee said.
Dr. Lee added that, as an experienced researcher who has weighed the aducanumab data, he saw no clear proof of a benefit that would outweigh the drug’s documented side effects in the two phase 3 trials of the drug. Those side effects include temporary brain swelling. Dr. Lee suggested that Biogen do more to address concerns about this side effect, saying it should not be ignored.
“There’s clearly substantial uncertainty” about aducanumab, Dr. Lee said. “If I had to guess, I think the data is stronger for net harm than it is for that benefit.”
Questions persist about the data Biogen used in support of aducanumab after announcing that the drug had failed in a dual-track phase 3 program.
In March 2019, it was announced that two phase 3 clinical trials, EMERGE and ENGAGE, were scrapped because of disappointing results. The trials were intended to show that aducanumab could slow progression of cognitive and functional impairment, as measured by changes in scores on the Clinical Dementia Rating–Sum of Boxes (CDR-SB).
However, in October 2019, there was an about-face – Biogen announced that, in one of the studies, there were positive findings for a subset of patients who received a higher dose of aducanumab.
No treatment benefit was observed in either the high- or low-dose arms at week 78 in the ENGAGE trial. In the EMERGE trial, however, there was a statistically significant difference in change from baseline in CDR-SB score in the high-dose arm (difference vs. placebo, –0.39; 95% confidence interval, –0.69 to –0.09) but not in the low-dose arm, ICER noted in a draft report.
Still, there are questions about whether this difference would translate into clinical benefit. “Although statistically significant, the change in CDR-SB score in the high-dose group was less than the 1- to 2-point change that has been suggested as a minimal clinically important difference,” ICER staff wrote.
More push back
Other influential organizations also remain skeptical.
On July 14, the Cleveland Clinic announced it would not use aducanumab at this time, following a staff review of the evidence. Physicians from the clinic could prescribe it to appropriate patients, who would receive their infusions at external facilities, a spokeswoman for the clinic told this news organization. The Cleveland Clinic said it will reevaluate this position as additional data become available.
In addition, as reported by the New York Times, the Mount Sinai Health System in New York also decided not to administer the drug.
The drug received accelerated approval from the FDA. That approval was conditional upon Biogen’s conducting further research by 2030 that demonstrates that the drug has clinical benefit.
On July 14, the executive committee of the American Neurological Association issued a statement asking for a speedier timeline.
The FDA should ensure that Biogen completes the required confirmatory study “as soon as possible, preferably within 3 years, to confirm or not whether clinical efficacy is observed,” the ANA executive committee wrote in the letter.
The ANA executive committee also criticized the FDA’s decision to allow Biogen to begin sales of the drug. In light of the clinical evidence available at this time, aducanumab “should not have been approved” in the first place, the ANA executive committee stated.
drawing from the discussion at the meeting and the panel’s votes. The work of the Boston-based group is used by private insurers to inform medication coverage decisions.
Lawmakers have taken an interest in aducanumab. On July 12, two top Democrats in the U.S. House of Representatives released a letter that they had sent to Biogen as part of their investigation into how the FDA handled the aducanumab approval and Biogen’s pricing for the drug.
In the letter, House Energy and Commerce Chairman Frank Pallone Jr. (D-N.J.) and Oversight and Reform Chairwoman Carolyn B. Maloney (D-N.Y.) wrote that they had “significant questions about the drug’s clinical benefit, and the steep $56,000 annual price tag.”
At the ICER meeting on July 15, Dr. Lee said patients with AD and their caregivers would benefit more from increased spending on supportive services, such as home health care.
“There’s so many things we could do” with money that Biogen may get for aducanumab, Dr. Lee said. “To spend it on a medication that is more likely to do more harm than help seems really ill advised.”
A version of this article first appeared on Medscape.com.
adding to growing opposition from medical experts to the Food and Drug Administration’s approval of this controversial drug.
The Institute for Clinical and Economic Review asked one of its expert panels, the California Technology Assessment Forum, to consider the available data about aducanumab and requested that members vote on whether there was sufficient evidence of a net benefit of aducanumab plus supportive care versus supportive care alone. All 15 panelists voted no.
Several panelists, including ICER President Steven D. Pearson, MD, talked about their personal experience with family members who have the disease.
There was universal agreement among the panelists that there is an urgent need for effective medications to treat the disease. However, the panel of clinicians and researchers also agreed that the evidence to date does not show that the drug helps patients with this debilitating disease.
Panelist Sei Lee, MD, a geriatrician at the University of California, San Francisco, said he lost his mother to AD 6 years ago. In addition to his clinical work, Dr. Lee has conducted research focused on improving the targeting of preventive AD interventions for older adults to maximize benefits and minimize harms.
Dr. Lee said he frequently felt completely overwhelmed by the challenges of his mother’s disease.
“I absolutely hear everyone who is saying we need an effective therapy for this,” Dr. Lee said.
Dr. Lee added that, as an experienced researcher who has weighed the aducanumab data, he saw no clear proof of a benefit that would outweigh the drug’s documented side effects in the two phase 3 trials of the drug. Those side effects include temporary brain swelling. Dr. Lee suggested that Biogen do more to address concerns about this side effect, saying it should not be ignored.
“There’s clearly substantial uncertainty” about aducanumab, Dr. Lee said. “If I had to guess, I think the data is stronger for net harm than it is for that benefit.”
Questions persist about the data Biogen used in support of aducanumab after announcing that the drug had failed in a dual-track phase 3 program.
In March 2019, it was announced that two phase 3 clinical trials, EMERGE and ENGAGE, were scrapped because of disappointing results. The trials were intended to show that aducanumab could slow progression of cognitive and functional impairment, as measured by changes in scores on the Clinical Dementia Rating–Sum of Boxes (CDR-SB).
However, in October 2019, there was an about-face – Biogen announced that, in one of the studies, there were positive findings for a subset of patients who received a higher dose of aducanumab.
No treatment benefit was observed in either the high- or low-dose arms at week 78 in the ENGAGE trial. In the EMERGE trial, however, there was a statistically significant difference in change from baseline in CDR-SB score in the high-dose arm (difference vs. placebo, –0.39; 95% confidence interval, –0.69 to –0.09) but not in the low-dose arm, ICER noted in a draft report.
Still, there are questions about whether this difference would translate into clinical benefit. “Although statistically significant, the change in CDR-SB score in the high-dose group was less than the 1- to 2-point change that has been suggested as a minimal clinically important difference,” ICER staff wrote.
More push back
Other influential organizations also remain skeptical.
On July 14, the Cleveland Clinic announced it would not use aducanumab at this time, following a staff review of the evidence. Physicians from the clinic could prescribe it to appropriate patients, who would receive their infusions at external facilities, a spokeswoman for the clinic told this news organization. The Cleveland Clinic said it will reevaluate this position as additional data become available.
In addition, as reported by the New York Times, the Mount Sinai Health System in New York also decided not to administer the drug.
The drug received accelerated approval from the FDA. That approval was conditional upon Biogen’s conducting further research by 2030 that demonstrates that the drug has clinical benefit.
On July 14, the executive committee of the American Neurological Association issued a statement asking for a speedier timeline.
The FDA should ensure that Biogen completes the required confirmatory study “as soon as possible, preferably within 3 years, to confirm or not whether clinical efficacy is observed,” the ANA executive committee wrote in the letter.
The ANA executive committee also criticized the FDA’s decision to allow Biogen to begin sales of the drug. In light of the clinical evidence available at this time, aducanumab “should not have been approved” in the first place, the ANA executive committee stated.
drawing from the discussion at the meeting and the panel’s votes. The work of the Boston-based group is used by private insurers to inform medication coverage decisions.
Lawmakers have taken an interest in aducanumab. On July 12, two top Democrats in the U.S. House of Representatives released a letter that they had sent to Biogen as part of their investigation into how the FDA handled the aducanumab approval and Biogen’s pricing for the drug.
In the letter, House Energy and Commerce Chairman Frank Pallone Jr. (D-N.J.) and Oversight and Reform Chairwoman Carolyn B. Maloney (D-N.Y.) wrote that they had “significant questions about the drug’s clinical benefit, and the steep $56,000 annual price tag.”
At the ICER meeting on July 15, Dr. Lee said patients with AD and their caregivers would benefit more from increased spending on supportive services, such as home health care.
“There’s so many things we could do” with money that Biogen may get for aducanumab, Dr. Lee said. “To spend it on a medication that is more likely to do more harm than help seems really ill advised.”
A version of this article first appeared on Medscape.com.
Sen. Schumer backs federal decriminalization of marijuana
U.S. Sen. Chuck Schumer, the Senate majority leader, is cosponsoring legislation that would decriminalize marijuana at the federal level.
The Cannabis Administration & Opportunity Act would allow the federal government to regulate and tax marijuana sales for the first time and would stop the federal prosecution of people for possessing and selling the drug, The New York Times reported. States could still make their own marijuana laws, however.
The bill calls for using money raised by taxing marijuana to help poor people and communities of color that have been unduly affected by marijuana laws.
Arrests and convictions for nonviolent marijuana offenses would be automatically expunged, The New York Times reported.
“The War on Drugs has been a war on people – particularly people of color,” a draft of the bill said, adding that the bill “aims to end the decades of harm inflicted on communities of color by removing cannabis from the federal list of controlled substances and empowering states to implement their own cannabis laws.”
But passage of the bill is highly uncertain because of strong Republican opposition in the Senate, where Democrats hold a narrow majority, according to The New York Times.
Sen. Schumer signaled his intentions when he spoke on April 20, the unofficial holiday for marijuana smokers.
“Hopefully, the next time this unofficial holiday of 4/20 rolls around, our country will have made progress in addressing the massive overcriminalization of marijuana in a meaningful and comprehensive way,” he said at the time, the newspaper reported.
Cosponsors were U.S. Sen. Cory Booker of New Jersey and U.S. Sen. Ron Wyden of Oregon, chairman of the Senate Finance Committee.
A version of this article first appeared on WebMD.com.
U.S. Sen. Chuck Schumer, the Senate majority leader, is cosponsoring legislation that would decriminalize marijuana at the federal level.
The Cannabis Administration & Opportunity Act would allow the federal government to regulate and tax marijuana sales for the first time and would stop the federal prosecution of people for possessing and selling the drug, The New York Times reported. States could still make their own marijuana laws, however.
The bill calls for using money raised by taxing marijuana to help poor people and communities of color that have been unduly affected by marijuana laws.
Arrests and convictions for nonviolent marijuana offenses would be automatically expunged, The New York Times reported.
“The War on Drugs has been a war on people – particularly people of color,” a draft of the bill said, adding that the bill “aims to end the decades of harm inflicted on communities of color by removing cannabis from the federal list of controlled substances and empowering states to implement their own cannabis laws.”
But passage of the bill is highly uncertain because of strong Republican opposition in the Senate, where Democrats hold a narrow majority, according to The New York Times.
Sen. Schumer signaled his intentions when he spoke on April 20, the unofficial holiday for marijuana smokers.
“Hopefully, the next time this unofficial holiday of 4/20 rolls around, our country will have made progress in addressing the massive overcriminalization of marijuana in a meaningful and comprehensive way,” he said at the time, the newspaper reported.
Cosponsors were U.S. Sen. Cory Booker of New Jersey and U.S. Sen. Ron Wyden of Oregon, chairman of the Senate Finance Committee.
A version of this article first appeared on WebMD.com.
U.S. Sen. Chuck Schumer, the Senate majority leader, is cosponsoring legislation that would decriminalize marijuana at the federal level.
The Cannabis Administration & Opportunity Act would allow the federal government to regulate and tax marijuana sales for the first time and would stop the federal prosecution of people for possessing and selling the drug, The New York Times reported. States could still make their own marijuana laws, however.
The bill calls for using money raised by taxing marijuana to help poor people and communities of color that have been unduly affected by marijuana laws.
Arrests and convictions for nonviolent marijuana offenses would be automatically expunged, The New York Times reported.
“The War on Drugs has been a war on people – particularly people of color,” a draft of the bill said, adding that the bill “aims to end the decades of harm inflicted on communities of color by removing cannabis from the federal list of controlled substances and empowering states to implement their own cannabis laws.”
But passage of the bill is highly uncertain because of strong Republican opposition in the Senate, where Democrats hold a narrow majority, according to The New York Times.
Sen. Schumer signaled his intentions when he spoke on April 20, the unofficial holiday for marijuana smokers.
“Hopefully, the next time this unofficial holiday of 4/20 rolls around, our country will have made progress in addressing the massive overcriminalization of marijuana in a meaningful and comprehensive way,” he said at the time, the newspaper reported.
Cosponsors were U.S. Sen. Cory Booker of New Jersey and U.S. Sen. Ron Wyden of Oregon, chairman of the Senate Finance Committee.
A version of this article first appeared on WebMD.com.