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Psychedelic drug therapy a potential ‘breakthrough’ for alcohol dependence
Results from the first randomized, placebo-controlled trial of psilocybin for alcohol dependence showed that during the 8 months after first treatment dose, participants who received psilocybin had less than half as many heavy drinking days as their counterparts who received placebo.
In addition, 7 months after the last dose of medication, twice as many psilocybin-treated patients as placebo-treated patients were abstinent.
The effects observed with psilocybin were “considerably larger” than those of currently approved treatments for AUD, senior investigator Michael Bogenschutz, MD, psychiatrist and director of the NYU Langone Center for Psychedelic Medicine, New York, said during an Aug. 24 press briefing.
If the findings hold up in future trials, psilocybin will be a “real breakthrough” in the treatment of the condition, Dr. Bogenschutz said.
The findings were published online in JAMA Psychiatry.
83% reduction in drinking days
The study included 93 adults (mean age, 46 years) with alcohol dependence who consumed an average of seven drinks on the days they drank and had had at least four heavy drinking days during the month prior to treatment.
Of the participants, 48 were randomly assigned to receive two doses of psilocybin, and 45 were assigned to receive an antihistamine (diphenhydramine) placebo. Study medication was administered during 2 day-long sessions at week 4 and week 8.
The participants also received 12 psychotherapy sessions over a 12-week period. All were assessed at intervals from the beginning of the study until 32 weeks after the first medication session.
The primary outcome was percentage of days in which the patient drank heavily during the 32-week period following first medication dose. Heavy drinking was defined as having five or more drinks in a day for a man and four or more drinks in a day for a woman.
The percentage of heavy drinking days during the 32-week period was 9.7% for the psilocybin group and 23.6% for the placebo group, for a mean difference of 13.9% (P = .01).
“Compared to their baseline before the study, after receiving medication, the psilocybin group decreased their heavy drinking days by 83%, while the placebo group reduced their heavy drinking by 51%,” Dr. Bogenschutz reported.
During the last month of follow-up, which was 7 months after the final dose of study medication, 48% of the psilocybin group were entirely abstinent vs. 24% of the placebo group.
“It is remarkable that the effects of psilocybin treatment persisted for 7 months after people received the last dose of medication. This suggests that psilocybin is treating the underlying disorder of alcohol addiction rather than merely treating symptoms,” Dr. Bogenschutz noted.
Total alcohol consumption and problems related to alcohol use were also significantly less in the psilocybin group.
‘Encouraged and hopeful’
Adverse events related to psilocybin were mostly mild, self-limiting, and consistent with other recent trials that evaluated the drug’s effects in various conditions.
However, the current investigators note that they implemented measures to ensure safety, including careful medical and psychiatric screening, therapy, and monitoring that was provided by well-trained therapists, including a licensed psychiatrist. In addition, medications were available to treat acute psychiatric reactions.
A cited limitation of the study was that blinding was not maintained because the average intensity of experience with psilocybin was high, whereas it was low with diphenhydramine.
This difference undermined the masking of treatment such that more than 90% of participants and therapists correctly guessed the treatment assignment.
Another limitation was that objective measures to validate self-reported drinking outcomes were available for only 54% of study participants.
Despite these limitations, the study builds on earlier work by the NYU team that showed that two doses of psilocybin taken over a period of 8 weeks significantly reduced alcohol use and cravings in patients with AUD.
“We’re very encouraged by these findings and hopeful about where they could lead. Personally, it’s been very meaningful and rewarding for me to do this work and inspiring to witness the remarkable recoveries that some of our participants have experienced,” Dr. Bogenschutz told briefing attendees.
Urgent need
The authors of an accompanying editorial note that novel medications for alcohol dependence are “sorely needed. Recent renewed interest in the potential of hallucinogens for treating psychiatric disorders, including AUD, represents a potential move in that direction.”
Henry Kranzler, MD, and Emily Hartwell, PhD, both with the Center for Studies of Addiction, University of Pennsylvania, Philadelphia, write that the new findings “underscore the potential of developing psilocybin as an addition to the alcohol treatment pharmacopeia.”
They question, however, the feasibility of using hallucinogens in routine clinical practice because intensive psychotherapy, such as that provided in this study, requires a significant investment of time and labor.
“Such concomitant therapy, if necessary to realize the therapeutic benefits of psilocybin for treating AUD, could limit its uptake by clinicians,” Dr. Kranzler and Dr. Hartwell write.
The study was funded by the Heffter Research Institute and by individual donations from Carey and Claudia Turnbull, Dr. Efrem Nulman, Rodrigo Niño, and Cody Swift. Dr. Bogenschutz reports having received research funds from and serving as a consultant to Mind Medicine, the Multidisciplinary Association for Psychedelic Studies, B. More, AJNA Labs, Beckley Psytech, Journey Colab, and Bright Minds Biosciences. Dr. Kranzler and Dr. Hartwell have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Results from the first randomized, placebo-controlled trial of psilocybin for alcohol dependence showed that during the 8 months after first treatment dose, participants who received psilocybin had less than half as many heavy drinking days as their counterparts who received placebo.
In addition, 7 months after the last dose of medication, twice as many psilocybin-treated patients as placebo-treated patients were abstinent.
The effects observed with psilocybin were “considerably larger” than those of currently approved treatments for AUD, senior investigator Michael Bogenschutz, MD, psychiatrist and director of the NYU Langone Center for Psychedelic Medicine, New York, said during an Aug. 24 press briefing.
If the findings hold up in future trials, psilocybin will be a “real breakthrough” in the treatment of the condition, Dr. Bogenschutz said.
The findings were published online in JAMA Psychiatry.
83% reduction in drinking days
The study included 93 adults (mean age, 46 years) with alcohol dependence who consumed an average of seven drinks on the days they drank and had had at least four heavy drinking days during the month prior to treatment.
Of the participants, 48 were randomly assigned to receive two doses of psilocybin, and 45 were assigned to receive an antihistamine (diphenhydramine) placebo. Study medication was administered during 2 day-long sessions at week 4 and week 8.
The participants also received 12 psychotherapy sessions over a 12-week period. All were assessed at intervals from the beginning of the study until 32 weeks after the first medication session.
The primary outcome was percentage of days in which the patient drank heavily during the 32-week period following first medication dose. Heavy drinking was defined as having five or more drinks in a day for a man and four or more drinks in a day for a woman.
The percentage of heavy drinking days during the 32-week period was 9.7% for the psilocybin group and 23.6% for the placebo group, for a mean difference of 13.9% (P = .01).
“Compared to their baseline before the study, after receiving medication, the psilocybin group decreased their heavy drinking days by 83%, while the placebo group reduced their heavy drinking by 51%,” Dr. Bogenschutz reported.
During the last month of follow-up, which was 7 months after the final dose of study medication, 48% of the psilocybin group were entirely abstinent vs. 24% of the placebo group.
“It is remarkable that the effects of psilocybin treatment persisted for 7 months after people received the last dose of medication. This suggests that psilocybin is treating the underlying disorder of alcohol addiction rather than merely treating symptoms,” Dr. Bogenschutz noted.
Total alcohol consumption and problems related to alcohol use were also significantly less in the psilocybin group.
‘Encouraged and hopeful’
Adverse events related to psilocybin were mostly mild, self-limiting, and consistent with other recent trials that evaluated the drug’s effects in various conditions.
However, the current investigators note that they implemented measures to ensure safety, including careful medical and psychiatric screening, therapy, and monitoring that was provided by well-trained therapists, including a licensed psychiatrist. In addition, medications were available to treat acute psychiatric reactions.
A cited limitation of the study was that blinding was not maintained because the average intensity of experience with psilocybin was high, whereas it was low with diphenhydramine.
This difference undermined the masking of treatment such that more than 90% of participants and therapists correctly guessed the treatment assignment.
Another limitation was that objective measures to validate self-reported drinking outcomes were available for only 54% of study participants.
Despite these limitations, the study builds on earlier work by the NYU team that showed that two doses of psilocybin taken over a period of 8 weeks significantly reduced alcohol use and cravings in patients with AUD.
“We’re very encouraged by these findings and hopeful about where they could lead. Personally, it’s been very meaningful and rewarding for me to do this work and inspiring to witness the remarkable recoveries that some of our participants have experienced,” Dr. Bogenschutz told briefing attendees.
Urgent need
The authors of an accompanying editorial note that novel medications for alcohol dependence are “sorely needed. Recent renewed interest in the potential of hallucinogens for treating psychiatric disorders, including AUD, represents a potential move in that direction.”
Henry Kranzler, MD, and Emily Hartwell, PhD, both with the Center for Studies of Addiction, University of Pennsylvania, Philadelphia, write that the new findings “underscore the potential of developing psilocybin as an addition to the alcohol treatment pharmacopeia.”
They question, however, the feasibility of using hallucinogens in routine clinical practice because intensive psychotherapy, such as that provided in this study, requires a significant investment of time and labor.
“Such concomitant therapy, if necessary to realize the therapeutic benefits of psilocybin for treating AUD, could limit its uptake by clinicians,” Dr. Kranzler and Dr. Hartwell write.
The study was funded by the Heffter Research Institute and by individual donations from Carey and Claudia Turnbull, Dr. Efrem Nulman, Rodrigo Niño, and Cody Swift. Dr. Bogenschutz reports having received research funds from and serving as a consultant to Mind Medicine, the Multidisciplinary Association for Psychedelic Studies, B. More, AJNA Labs, Beckley Psytech, Journey Colab, and Bright Minds Biosciences. Dr. Kranzler and Dr. Hartwell have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Results from the first randomized, placebo-controlled trial of psilocybin for alcohol dependence showed that during the 8 months after first treatment dose, participants who received psilocybin had less than half as many heavy drinking days as their counterparts who received placebo.
In addition, 7 months after the last dose of medication, twice as many psilocybin-treated patients as placebo-treated patients were abstinent.
The effects observed with psilocybin were “considerably larger” than those of currently approved treatments for AUD, senior investigator Michael Bogenschutz, MD, psychiatrist and director of the NYU Langone Center for Psychedelic Medicine, New York, said during an Aug. 24 press briefing.
If the findings hold up in future trials, psilocybin will be a “real breakthrough” in the treatment of the condition, Dr. Bogenschutz said.
The findings were published online in JAMA Psychiatry.
83% reduction in drinking days
The study included 93 adults (mean age, 46 years) with alcohol dependence who consumed an average of seven drinks on the days they drank and had had at least four heavy drinking days during the month prior to treatment.
Of the participants, 48 were randomly assigned to receive two doses of psilocybin, and 45 were assigned to receive an antihistamine (diphenhydramine) placebo. Study medication was administered during 2 day-long sessions at week 4 and week 8.
The participants also received 12 psychotherapy sessions over a 12-week period. All were assessed at intervals from the beginning of the study until 32 weeks after the first medication session.
The primary outcome was percentage of days in which the patient drank heavily during the 32-week period following first medication dose. Heavy drinking was defined as having five or more drinks in a day for a man and four or more drinks in a day for a woman.
The percentage of heavy drinking days during the 32-week period was 9.7% for the psilocybin group and 23.6% for the placebo group, for a mean difference of 13.9% (P = .01).
“Compared to their baseline before the study, after receiving medication, the psilocybin group decreased their heavy drinking days by 83%, while the placebo group reduced their heavy drinking by 51%,” Dr. Bogenschutz reported.
During the last month of follow-up, which was 7 months after the final dose of study medication, 48% of the psilocybin group were entirely abstinent vs. 24% of the placebo group.
“It is remarkable that the effects of psilocybin treatment persisted for 7 months after people received the last dose of medication. This suggests that psilocybin is treating the underlying disorder of alcohol addiction rather than merely treating symptoms,” Dr. Bogenschutz noted.
Total alcohol consumption and problems related to alcohol use were also significantly less in the psilocybin group.
‘Encouraged and hopeful’
Adverse events related to psilocybin were mostly mild, self-limiting, and consistent with other recent trials that evaluated the drug’s effects in various conditions.
However, the current investigators note that they implemented measures to ensure safety, including careful medical and psychiatric screening, therapy, and monitoring that was provided by well-trained therapists, including a licensed psychiatrist. In addition, medications were available to treat acute psychiatric reactions.
A cited limitation of the study was that blinding was not maintained because the average intensity of experience with psilocybin was high, whereas it was low with diphenhydramine.
This difference undermined the masking of treatment such that more than 90% of participants and therapists correctly guessed the treatment assignment.
Another limitation was that objective measures to validate self-reported drinking outcomes were available for only 54% of study participants.
Despite these limitations, the study builds on earlier work by the NYU team that showed that two doses of psilocybin taken over a period of 8 weeks significantly reduced alcohol use and cravings in patients with AUD.
“We’re very encouraged by these findings and hopeful about where they could lead. Personally, it’s been very meaningful and rewarding for me to do this work and inspiring to witness the remarkable recoveries that some of our participants have experienced,” Dr. Bogenschutz told briefing attendees.
Urgent need
The authors of an accompanying editorial note that novel medications for alcohol dependence are “sorely needed. Recent renewed interest in the potential of hallucinogens for treating psychiatric disorders, including AUD, represents a potential move in that direction.”
Henry Kranzler, MD, and Emily Hartwell, PhD, both with the Center for Studies of Addiction, University of Pennsylvania, Philadelphia, write that the new findings “underscore the potential of developing psilocybin as an addition to the alcohol treatment pharmacopeia.”
They question, however, the feasibility of using hallucinogens in routine clinical practice because intensive psychotherapy, such as that provided in this study, requires a significant investment of time and labor.
“Such concomitant therapy, if necessary to realize the therapeutic benefits of psilocybin for treating AUD, could limit its uptake by clinicians,” Dr. Kranzler and Dr. Hartwell write.
The study was funded by the Heffter Research Institute and by individual donations from Carey and Claudia Turnbull, Dr. Efrem Nulman, Rodrigo Niño, and Cody Swift. Dr. Bogenschutz reports having received research funds from and serving as a consultant to Mind Medicine, the Multidisciplinary Association for Psychedelic Studies, B. More, AJNA Labs, Beckley Psytech, Journey Colab, and Bright Minds Biosciences. Dr. Kranzler and Dr. Hartwell have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA PSYCHIATRY
Former nurse charged with murder in death of 97-year-old war veteran
A former Kentucky nurse was charged with murder stemming from an incident in which she gave “something special” to a 97-year-old patient who died 5 days later, according to multiple sources, including police and nursing records.
Ms. Hunter allegedly gave lorazepam, typically used for anxiety, to Mr. Morris on April 30. He subsequently developed pneumonia and died on May 5.
Ms. Hunter “intentionally performed actions of medical maltreatment,” according to the Lexington Police Department’s report.
A Baptist Health Lexington spokeswoman told this news organization that the nurse who was charged hasn’t worked at the hospital since the April incident. “We have learned that a former nurse at our hospital has been arrested yesterday on criminal charges,” spokeswoman Ruth Ann Childers stated. “The hospital has fully cooperated with the police investigation. Patient care and safety are always our top priorities. Out of respect for the patient’s family and because this is criminal matter, we are not able to talk about the investigation.”
According to the Kentucky Board of Nursing, which suspended Ms. Hunter’s RN license on a temporary basis on Aug. 22, she allegedly asked the on-duty physician and a nurse practitioner separately for a medication order to calm Mr. Morris, who had become agitated and aggressive. They denied Ms. Hunter’s request, so she withdrew lorazepam intended for another patient and administered it to Mr. Morris, the nursing board suspension order states. “When asked what was administered, she replied ‘something special,’ “ the order states.
Another RN found the patient with labored breathing and “it was determined that respondent had disarmed/lowered the oxygen monitoring system several times as to not set off an alarm at the bedside,” the order continued. “The RN discussed with charge nurse that the patient had been given something intravenously that was causing his decline.”
When the charge nurse entered the room later, she found the patient in “respiratory distress with labored breathing and poor oxygen saturation. ... X-rays would show that the aspiration from the substances ingested by the patient while in his condition caused the patient to develop aspirational pneumonia,” the order continues.
“Despite the rapidly declining condition of the patient, respondent never called for rapid response nor acted with any sense of urgency. Respondent did however edit documentation of administration of Ativan on ‘patient B’ to state ‘not given.’ ”
Mr. Morris’ condition never improved. He was taken to hospice care on May 3 and died 2 days later, the order states.
Ms. Hunter was being held in the Lexington Jail on $100,000 bond, according to jail records.
A version of this article first appeared on Medscape.com.
A former Kentucky nurse was charged with murder stemming from an incident in which she gave “something special” to a 97-year-old patient who died 5 days later, according to multiple sources, including police and nursing records.
Ms. Hunter allegedly gave lorazepam, typically used for anxiety, to Mr. Morris on April 30. He subsequently developed pneumonia and died on May 5.
Ms. Hunter “intentionally performed actions of medical maltreatment,” according to the Lexington Police Department’s report.
A Baptist Health Lexington spokeswoman told this news organization that the nurse who was charged hasn’t worked at the hospital since the April incident. “We have learned that a former nurse at our hospital has been arrested yesterday on criminal charges,” spokeswoman Ruth Ann Childers stated. “The hospital has fully cooperated with the police investigation. Patient care and safety are always our top priorities. Out of respect for the patient’s family and because this is criminal matter, we are not able to talk about the investigation.”
According to the Kentucky Board of Nursing, which suspended Ms. Hunter’s RN license on a temporary basis on Aug. 22, she allegedly asked the on-duty physician and a nurse practitioner separately for a medication order to calm Mr. Morris, who had become agitated and aggressive. They denied Ms. Hunter’s request, so she withdrew lorazepam intended for another patient and administered it to Mr. Morris, the nursing board suspension order states. “When asked what was administered, she replied ‘something special,’ “ the order states.
Another RN found the patient with labored breathing and “it was determined that respondent had disarmed/lowered the oxygen monitoring system several times as to not set off an alarm at the bedside,” the order continued. “The RN discussed with charge nurse that the patient had been given something intravenously that was causing his decline.”
When the charge nurse entered the room later, she found the patient in “respiratory distress with labored breathing and poor oxygen saturation. ... X-rays would show that the aspiration from the substances ingested by the patient while in his condition caused the patient to develop aspirational pneumonia,” the order continues.
“Despite the rapidly declining condition of the patient, respondent never called for rapid response nor acted with any sense of urgency. Respondent did however edit documentation of administration of Ativan on ‘patient B’ to state ‘not given.’ ”
Mr. Morris’ condition never improved. He was taken to hospice care on May 3 and died 2 days later, the order states.
Ms. Hunter was being held in the Lexington Jail on $100,000 bond, according to jail records.
A version of this article first appeared on Medscape.com.
A former Kentucky nurse was charged with murder stemming from an incident in which she gave “something special” to a 97-year-old patient who died 5 days later, according to multiple sources, including police and nursing records.
Ms. Hunter allegedly gave lorazepam, typically used for anxiety, to Mr. Morris on April 30. He subsequently developed pneumonia and died on May 5.
Ms. Hunter “intentionally performed actions of medical maltreatment,” according to the Lexington Police Department’s report.
A Baptist Health Lexington spokeswoman told this news organization that the nurse who was charged hasn’t worked at the hospital since the April incident. “We have learned that a former nurse at our hospital has been arrested yesterday on criminal charges,” spokeswoman Ruth Ann Childers stated. “The hospital has fully cooperated with the police investigation. Patient care and safety are always our top priorities. Out of respect for the patient’s family and because this is criminal matter, we are not able to talk about the investigation.”
According to the Kentucky Board of Nursing, which suspended Ms. Hunter’s RN license on a temporary basis on Aug. 22, she allegedly asked the on-duty physician and a nurse practitioner separately for a medication order to calm Mr. Morris, who had become agitated and aggressive. They denied Ms. Hunter’s request, so she withdrew lorazepam intended for another patient and administered it to Mr. Morris, the nursing board suspension order states. “When asked what was administered, she replied ‘something special,’ “ the order states.
Another RN found the patient with labored breathing and “it was determined that respondent had disarmed/lowered the oxygen monitoring system several times as to not set off an alarm at the bedside,” the order continued. “The RN discussed with charge nurse that the patient had been given something intravenously that was causing his decline.”
When the charge nurse entered the room later, she found the patient in “respiratory distress with labored breathing and poor oxygen saturation. ... X-rays would show that the aspiration from the substances ingested by the patient while in his condition caused the patient to develop aspirational pneumonia,” the order continues.
“Despite the rapidly declining condition of the patient, respondent never called for rapid response nor acted with any sense of urgency. Respondent did however edit documentation of administration of Ativan on ‘patient B’ to state ‘not given.’ ”
Mr. Morris’ condition never improved. He was taken to hospice care on May 3 and died 2 days later, the order states.
Ms. Hunter was being held in the Lexington Jail on $100,000 bond, according to jail records.
A version of this article first appeared on Medscape.com.
COVID to blame as U.S. life expectancy falls
All 50 states and the District of Columbia saw drops in life expectancy, according to the report from the Centers for Disease Control and Prevention’s National Center for Health Statistics.
The declines were mostly because of COVID-19 and “unintentional injuries,” such as drug overdoses.
The overall drop took national life expectancy from 78.8 years in 2019 to 77 years in 2020, the first year of the pandemic, ABC News reported.
States in the West and Northwest generally had higher life expectancy, with states in the South having the lowest.
Hawaii had the highest life expectancy at 80.7 years. It was followed by Washington, Minnesota, California, and Massachusetts. Mississippi had the lowest at 71.9 years, the figures show. The others in the bottom five were West Virginia, Louisiana, Alabama, and Kentucky.
In 2020, COVID-19 was the third-highest cause of death, leading to more than 350,000, the CDC reported earlier this year. At the same time, more people are dying annually from drug overdoses. A record 83,500 fatal overdoses were reported in 2020.
A version of this article first appeared on WebMD.com.
All 50 states and the District of Columbia saw drops in life expectancy, according to the report from the Centers for Disease Control and Prevention’s National Center for Health Statistics.
The declines were mostly because of COVID-19 and “unintentional injuries,” such as drug overdoses.
The overall drop took national life expectancy from 78.8 years in 2019 to 77 years in 2020, the first year of the pandemic, ABC News reported.
States in the West and Northwest generally had higher life expectancy, with states in the South having the lowest.
Hawaii had the highest life expectancy at 80.7 years. It was followed by Washington, Minnesota, California, and Massachusetts. Mississippi had the lowest at 71.9 years, the figures show. The others in the bottom five were West Virginia, Louisiana, Alabama, and Kentucky.
In 2020, COVID-19 was the third-highest cause of death, leading to more than 350,000, the CDC reported earlier this year. At the same time, more people are dying annually from drug overdoses. A record 83,500 fatal overdoses were reported in 2020.
A version of this article first appeared on WebMD.com.
All 50 states and the District of Columbia saw drops in life expectancy, according to the report from the Centers for Disease Control and Prevention’s National Center for Health Statistics.
The declines were mostly because of COVID-19 and “unintentional injuries,” such as drug overdoses.
The overall drop took national life expectancy from 78.8 years in 2019 to 77 years in 2020, the first year of the pandemic, ABC News reported.
States in the West and Northwest generally had higher life expectancy, with states in the South having the lowest.
Hawaii had the highest life expectancy at 80.7 years. It was followed by Washington, Minnesota, California, and Massachusetts. Mississippi had the lowest at 71.9 years, the figures show. The others in the bottom five were West Virginia, Louisiana, Alabama, and Kentucky.
In 2020, COVID-19 was the third-highest cause of death, leading to more than 350,000, the CDC reported earlier this year. At the same time, more people are dying annually from drug overdoses. A record 83,500 fatal overdoses were reported in 2020.
A version of this article first appeared on WebMD.com.
Low-dose edoxaban curbs stroke risk in elderly with AF, despite frailty
Elderly patients with atrial fibrillation (AF) who are at high risk of bleeding may benefit from a low 15-mg dose of edoxaban, regardless of their frailty status, a subanalysis of the ELDERCARE-AF trial suggests.
Major bleeding and major or clinically relevant nonmajor bleeding events were both numerically higher in the edoxaban group than placebo, the authors reported, with no heterogeneity by frailty status.
The subanalysis extends findings of the overall study by teasing out stroke, systemic embolism (SSE) and bleeding events across frailty status among Japanese patients aged 80 and older who were ineligible for oral anticoagulants (OACs) at usual doses.
Findings from the original phase 3 ELDERCARE-AF study were previously reported during the virtual European Society of Cardiology Congress 2020 and simultaneously published in The New England Journal of Medicine. The current study was published online in JAMA Network Open.
All frailty levels benefited
Shintaro Akashi, MD, PhD, of National Hospital Organization Hamada Medical Center, Shimane, Japan, and colleagues analyzed data from 944 patients randomly assigned to edoxaban 15 mg or placebo for about 3 years. The mean age of participants was 86.6 years and 57% were women. Baseline characteristics, including history of bleeding, were similar between groups.
Patient physical condition was assessed via five parameters: weight loss, grip strength, walking speed, exhaustion, and activity level. This yielded a frailty score, with one point given for each parameter: 0 indicated robust; 1 or 2, prefrail; and 3 or higher, frail. For this analysis, robust (6.5% of patients) and prefrail (51%) were combined and categorized as nonfrail.
In the placebo group, estimated event rates for stroke or SSE were 7.1% per patient-year among frail patients and 6.1% per patient-year among those who were nonfrail.
In the edoxaban group, SSE occurred at an estimated event rate of 2.5% of frail patients and 1.5% of nonfrail patients (adjusted HR, 1.41).
The edoxaban group “consistently had fewer SSE events regardless of frailty status including each frailty assessment parameter, and there was no heterogeneity between the groups,” the authors wrote, with similar trends for the association of edoxaban 15 mg for each frailty assessment parameter.
However, major bleeding and major or clinically relevant nonmajor (CRNM) bleeding events were both higher with edoxaban, regardless of frailty status.
More specifically, in the placebo group, the incidence of major bleeding was 2.3% in the frail group and 1.5% in the nonfrail group (adjusted HR, 1.48) versus 3.7% and 2.9%, respectively, in the edoxaban group (adjusted HR, 1.04).
In addition, exhaustion was related to a significantly increased risk of major or CRNM bleeding in frail versus nonfrail patients (16.3% vs. 8.4%; adjusted HR, 1.97). The incidences were all higher in the edoxaban group, irrespective of frailty status.
Furthermore, although both all-cause death and the net clinical composite outcome of stroke or SSE occurred more frequently in frail than in nonfrail patients, there was no association with frailty status between the edoxaban and placebo groups.
Findings unrelated to edoxaban were also noteworthy. “Surprisingly, grip strength showed an association with adverse events,” the authors wrote. Among those with lower grip strength, “there was nearly a 3-fold increase in risk of SSE and major bleeding and a more than 16-fold significant increase in risk of death. In addition, in those with exhaustion, there was nearly a 2-fold significant increase in major or CRNM bleeding.”
Thus, they suggested, in this patient population, “an objective physical assessment of grip strength or exhaustion in addition to the well-known walking speed may more accurately estimate the risks of clinical outcomes than the overall frailty assessment.”
Head-to-head comparisons needed
Commenting on the findings, Richard Kovach, MD, chair of the interventional cardiology division at Deborah Heart and Lung Center, Browns Mills, N.J., said, “It is interesting that the lower dose of edoxaban still appears to have a statistically significant reduction in the incidence of stroke in this subgroup of extremely frail elderly patients, and it may be useful in this highly selected subset.
“That being said,” he added, “the major complication of oral anticoagulants – major bleeding – appears to be similar to other NOACs prescribed more frequently in the U.S., specifically rivaroxaban and apixaban.”
“Furthermore, in the U.S., frail or complex patients who are not candidates for oral anticoagulant therapy are much more likely to receive a left atrial appendage closure device such as a Watchman or Amulet in order to avoid the risk of bleeding complications completely,” he said. “Procedural success with these devices is extremely high and procedural complications are extremely low. With both devices, the long-term reduction in stroke risk is equivalent to the use of anticoagulant therapy.
“Clearly, more research is needed to compare the outcomes with edoxaban against other NOACs,” Dr. Kovach concluded. “A head-to-head comparison of low-dose edoxaban versus left atrial appendage closure in this high-risk group would also be of great clinical value.”
The study was funded by Daiichi Sankyo. Two coauthors are employees of and five have received fees from the company. Dr. Kovach has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Elderly patients with atrial fibrillation (AF) who are at high risk of bleeding may benefit from a low 15-mg dose of edoxaban, regardless of their frailty status, a subanalysis of the ELDERCARE-AF trial suggests.
Major bleeding and major or clinically relevant nonmajor bleeding events were both numerically higher in the edoxaban group than placebo, the authors reported, with no heterogeneity by frailty status.
The subanalysis extends findings of the overall study by teasing out stroke, systemic embolism (SSE) and bleeding events across frailty status among Japanese patients aged 80 and older who were ineligible for oral anticoagulants (OACs) at usual doses.
Findings from the original phase 3 ELDERCARE-AF study were previously reported during the virtual European Society of Cardiology Congress 2020 and simultaneously published in The New England Journal of Medicine. The current study was published online in JAMA Network Open.
All frailty levels benefited
Shintaro Akashi, MD, PhD, of National Hospital Organization Hamada Medical Center, Shimane, Japan, and colleagues analyzed data from 944 patients randomly assigned to edoxaban 15 mg or placebo for about 3 years. The mean age of participants was 86.6 years and 57% were women. Baseline characteristics, including history of bleeding, were similar between groups.
Patient physical condition was assessed via five parameters: weight loss, grip strength, walking speed, exhaustion, and activity level. This yielded a frailty score, with one point given for each parameter: 0 indicated robust; 1 or 2, prefrail; and 3 or higher, frail. For this analysis, robust (6.5% of patients) and prefrail (51%) were combined and categorized as nonfrail.
In the placebo group, estimated event rates for stroke or SSE were 7.1% per patient-year among frail patients and 6.1% per patient-year among those who were nonfrail.
In the edoxaban group, SSE occurred at an estimated event rate of 2.5% of frail patients and 1.5% of nonfrail patients (adjusted HR, 1.41).
The edoxaban group “consistently had fewer SSE events regardless of frailty status including each frailty assessment parameter, and there was no heterogeneity between the groups,” the authors wrote, with similar trends for the association of edoxaban 15 mg for each frailty assessment parameter.
However, major bleeding and major or clinically relevant nonmajor (CRNM) bleeding events were both higher with edoxaban, regardless of frailty status.
More specifically, in the placebo group, the incidence of major bleeding was 2.3% in the frail group and 1.5% in the nonfrail group (adjusted HR, 1.48) versus 3.7% and 2.9%, respectively, in the edoxaban group (adjusted HR, 1.04).
In addition, exhaustion was related to a significantly increased risk of major or CRNM bleeding in frail versus nonfrail patients (16.3% vs. 8.4%; adjusted HR, 1.97). The incidences were all higher in the edoxaban group, irrespective of frailty status.
Furthermore, although both all-cause death and the net clinical composite outcome of stroke or SSE occurred more frequently in frail than in nonfrail patients, there was no association with frailty status between the edoxaban and placebo groups.
Findings unrelated to edoxaban were also noteworthy. “Surprisingly, grip strength showed an association with adverse events,” the authors wrote. Among those with lower grip strength, “there was nearly a 3-fold increase in risk of SSE and major bleeding and a more than 16-fold significant increase in risk of death. In addition, in those with exhaustion, there was nearly a 2-fold significant increase in major or CRNM bleeding.”
Thus, they suggested, in this patient population, “an objective physical assessment of grip strength or exhaustion in addition to the well-known walking speed may more accurately estimate the risks of clinical outcomes than the overall frailty assessment.”
Head-to-head comparisons needed
Commenting on the findings, Richard Kovach, MD, chair of the interventional cardiology division at Deborah Heart and Lung Center, Browns Mills, N.J., said, “It is interesting that the lower dose of edoxaban still appears to have a statistically significant reduction in the incidence of stroke in this subgroup of extremely frail elderly patients, and it may be useful in this highly selected subset.
“That being said,” he added, “the major complication of oral anticoagulants – major bleeding – appears to be similar to other NOACs prescribed more frequently in the U.S., specifically rivaroxaban and apixaban.”
“Furthermore, in the U.S., frail or complex patients who are not candidates for oral anticoagulant therapy are much more likely to receive a left atrial appendage closure device such as a Watchman or Amulet in order to avoid the risk of bleeding complications completely,” he said. “Procedural success with these devices is extremely high and procedural complications are extremely low. With both devices, the long-term reduction in stroke risk is equivalent to the use of anticoagulant therapy.
“Clearly, more research is needed to compare the outcomes with edoxaban against other NOACs,” Dr. Kovach concluded. “A head-to-head comparison of low-dose edoxaban versus left atrial appendage closure in this high-risk group would also be of great clinical value.”
The study was funded by Daiichi Sankyo. Two coauthors are employees of and five have received fees from the company. Dr. Kovach has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Elderly patients with atrial fibrillation (AF) who are at high risk of bleeding may benefit from a low 15-mg dose of edoxaban, regardless of their frailty status, a subanalysis of the ELDERCARE-AF trial suggests.
Major bleeding and major or clinically relevant nonmajor bleeding events were both numerically higher in the edoxaban group than placebo, the authors reported, with no heterogeneity by frailty status.
The subanalysis extends findings of the overall study by teasing out stroke, systemic embolism (SSE) and bleeding events across frailty status among Japanese patients aged 80 and older who were ineligible for oral anticoagulants (OACs) at usual doses.
Findings from the original phase 3 ELDERCARE-AF study were previously reported during the virtual European Society of Cardiology Congress 2020 and simultaneously published in The New England Journal of Medicine. The current study was published online in JAMA Network Open.
All frailty levels benefited
Shintaro Akashi, MD, PhD, of National Hospital Organization Hamada Medical Center, Shimane, Japan, and colleagues analyzed data from 944 patients randomly assigned to edoxaban 15 mg or placebo for about 3 years. The mean age of participants was 86.6 years and 57% were women. Baseline characteristics, including history of bleeding, were similar between groups.
Patient physical condition was assessed via five parameters: weight loss, grip strength, walking speed, exhaustion, and activity level. This yielded a frailty score, with one point given for each parameter: 0 indicated robust; 1 or 2, prefrail; and 3 or higher, frail. For this analysis, robust (6.5% of patients) and prefrail (51%) were combined and categorized as nonfrail.
In the placebo group, estimated event rates for stroke or SSE were 7.1% per patient-year among frail patients and 6.1% per patient-year among those who were nonfrail.
In the edoxaban group, SSE occurred at an estimated event rate of 2.5% of frail patients and 1.5% of nonfrail patients (adjusted HR, 1.41).
The edoxaban group “consistently had fewer SSE events regardless of frailty status including each frailty assessment parameter, and there was no heterogeneity between the groups,” the authors wrote, with similar trends for the association of edoxaban 15 mg for each frailty assessment parameter.
However, major bleeding and major or clinically relevant nonmajor (CRNM) bleeding events were both higher with edoxaban, regardless of frailty status.
More specifically, in the placebo group, the incidence of major bleeding was 2.3% in the frail group and 1.5% in the nonfrail group (adjusted HR, 1.48) versus 3.7% and 2.9%, respectively, in the edoxaban group (adjusted HR, 1.04).
In addition, exhaustion was related to a significantly increased risk of major or CRNM bleeding in frail versus nonfrail patients (16.3% vs. 8.4%; adjusted HR, 1.97). The incidences were all higher in the edoxaban group, irrespective of frailty status.
Furthermore, although both all-cause death and the net clinical composite outcome of stroke or SSE occurred more frequently in frail than in nonfrail patients, there was no association with frailty status between the edoxaban and placebo groups.
Findings unrelated to edoxaban were also noteworthy. “Surprisingly, grip strength showed an association with adverse events,” the authors wrote. Among those with lower grip strength, “there was nearly a 3-fold increase in risk of SSE and major bleeding and a more than 16-fold significant increase in risk of death. In addition, in those with exhaustion, there was nearly a 2-fold significant increase in major or CRNM bleeding.”
Thus, they suggested, in this patient population, “an objective physical assessment of grip strength or exhaustion in addition to the well-known walking speed may more accurately estimate the risks of clinical outcomes than the overall frailty assessment.”
Head-to-head comparisons needed
Commenting on the findings, Richard Kovach, MD, chair of the interventional cardiology division at Deborah Heart and Lung Center, Browns Mills, N.J., said, “It is interesting that the lower dose of edoxaban still appears to have a statistically significant reduction in the incidence of stroke in this subgroup of extremely frail elderly patients, and it may be useful in this highly selected subset.
“That being said,” he added, “the major complication of oral anticoagulants – major bleeding – appears to be similar to other NOACs prescribed more frequently in the U.S., specifically rivaroxaban and apixaban.”
“Furthermore, in the U.S., frail or complex patients who are not candidates for oral anticoagulant therapy are much more likely to receive a left atrial appendage closure device such as a Watchman or Amulet in order to avoid the risk of bleeding complications completely,” he said. “Procedural success with these devices is extremely high and procedural complications are extremely low. With both devices, the long-term reduction in stroke risk is equivalent to the use of anticoagulant therapy.
“Clearly, more research is needed to compare the outcomes with edoxaban against other NOACs,” Dr. Kovach concluded. “A head-to-head comparison of low-dose edoxaban versus left atrial appendage closure in this high-risk group would also be of great clinical value.”
The study was funded by Daiichi Sankyo. Two coauthors are employees of and five have received fees from the company. Dr. Kovach has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FDA clears tubeless, automated insulin system for children age 2 and older
The Food and Drug Administration has approved use of the Omnipod 5 automated insulin delivery system (Insulet Corp) for children aged 2 years and older with type 1 diabetes, the company announced on Aug. 22.
Omnipod 5 was originally cleared for use in individuals age 6 and older in Jan. 2022, as previously reported by this news organization. It is the third semi-automated closed-loop system approved in the United States but the first that is tubing-free. It integrates with the Dexcom G6 continuous glucose monitor system and a compatible smartphone to automatically adjust insulin and protect against high and low glucose levels.
“We received tremendous first-hand reports of how Omnipod 5 made diabetes management easier for our pivotal trial participants, and the clinical data demonstrated impressive glycemic improvements as well,” Trang Ly, MBBS, PhD, senior vice president and medical director at Insulet, said in a news release. “This expanded indication for younger children gives us great pride, knowing we can further ease the burden of glucose management for these children and their caregivers with our simple to use, elegant, automated insulin delivery system.”
In a recent clinical trial in very young children (age 2-5.9 years) with type 1 diabetes, Jennifer L. Sherr, MD, PhD, and colleagues found that the Omnipod 5 lowered A1c by 0.55 percentage points and reduced time in hypoglycemia (< 70 mg/dL) by 0.27%. According to their findings, published in Diabetes Care, time spent in target glucose range (70-180 mg/dL) increased by 11%, or by 2.6 hours more per day, in children in the study.
According to the release, the Omnipod 5 can now be prescribed to patients with insurance coverage. Patients can access their prescription through the pharmacy.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved use of the Omnipod 5 automated insulin delivery system (Insulet Corp) for children aged 2 years and older with type 1 diabetes, the company announced on Aug. 22.
Omnipod 5 was originally cleared for use in individuals age 6 and older in Jan. 2022, as previously reported by this news organization. It is the third semi-automated closed-loop system approved in the United States but the first that is tubing-free. It integrates with the Dexcom G6 continuous glucose monitor system and a compatible smartphone to automatically adjust insulin and protect against high and low glucose levels.
“We received tremendous first-hand reports of how Omnipod 5 made diabetes management easier for our pivotal trial participants, and the clinical data demonstrated impressive glycemic improvements as well,” Trang Ly, MBBS, PhD, senior vice president and medical director at Insulet, said in a news release. “This expanded indication for younger children gives us great pride, knowing we can further ease the burden of glucose management for these children and their caregivers with our simple to use, elegant, automated insulin delivery system.”
In a recent clinical trial in very young children (age 2-5.9 years) with type 1 diabetes, Jennifer L. Sherr, MD, PhD, and colleagues found that the Omnipod 5 lowered A1c by 0.55 percentage points and reduced time in hypoglycemia (< 70 mg/dL) by 0.27%. According to their findings, published in Diabetes Care, time spent in target glucose range (70-180 mg/dL) increased by 11%, or by 2.6 hours more per day, in children in the study.
According to the release, the Omnipod 5 can now be prescribed to patients with insurance coverage. Patients can access their prescription through the pharmacy.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved use of the Omnipod 5 automated insulin delivery system (Insulet Corp) for children aged 2 years and older with type 1 diabetes, the company announced on Aug. 22.
Omnipod 5 was originally cleared for use in individuals age 6 and older in Jan. 2022, as previously reported by this news organization. It is the third semi-automated closed-loop system approved in the United States but the first that is tubing-free. It integrates with the Dexcom G6 continuous glucose monitor system and a compatible smartphone to automatically adjust insulin and protect against high and low glucose levels.
“We received tremendous first-hand reports of how Omnipod 5 made diabetes management easier for our pivotal trial participants, and the clinical data demonstrated impressive glycemic improvements as well,” Trang Ly, MBBS, PhD, senior vice president and medical director at Insulet, said in a news release. “This expanded indication for younger children gives us great pride, knowing we can further ease the burden of glucose management for these children and their caregivers with our simple to use, elegant, automated insulin delivery system.”
In a recent clinical trial in very young children (age 2-5.9 years) with type 1 diabetes, Jennifer L. Sherr, MD, PhD, and colleagues found that the Omnipod 5 lowered A1c by 0.55 percentage points and reduced time in hypoglycemia (< 70 mg/dL) by 0.27%. According to their findings, published in Diabetes Care, time spent in target glucose range (70-180 mg/dL) increased by 11%, or by 2.6 hours more per day, in children in the study.
According to the release, the Omnipod 5 can now be prescribed to patients with insurance coverage. Patients can access their prescription through the pharmacy.
A version of this article first appeared on Medscape.com.
Metformin fails as early COVID-19 treatment but shows potential
Neither metformin, ivermectin, or fluvoxamine had any impact on reducing disease severity, hospitalization, or death from COVID-19, according to results from more than 1,000 overweight or obese adult patients in the COVID-OUT randomized trial.
However, metformin showed some potential in a secondary analysis.
Early treatment to prevent severe disease remains a goal in managing the ongoing COVID-19 pandemic, and biophysical modeling suggested that metformin, ivermectin, and fluvoxamine may serve as antivirals to help reduce severe disease in COVID-19 patients, Carolyn T. Bramante, MD, of the University of Minnesota, Minneapolis, and colleagues wrote.
“We started enrolling patients at the end of December 2020,” Dr. Bramante said in an interview. “At that time, even though vaccine data were coming out, we thought it was important to test early outpatient treatment with widely available safe medications with no interactions, because the virus would evolve and vaccine availability may be limited.”
In a study published in the New England Journal of Medicine, the researchers used a two-by-three factorial design to test the ability of metformin, ivermectin, and fluvoxamine to prevent severe COVID-19 infection in nonhospitalized adults aged 30-85 years. A total of 1,431 patients at six U.S. sites were enrolled within 3 days of a confirmed infection and less than 7 days after the start of symptoms, then randomized to one of six groups: metformin plus fluvoxamine; metformin plus ivermectin; metformin plus placebo; placebo plus fluvoxamine; placebo plus ivermectin; and placebo plus placebo.
A total of 1,323 patients were included in the primary analysis. The median age of the patients was 46 years, 56% were female (of whom 6% were pregnant), and all individuals met criteria for overweight or obesity. About half (52%) of the patients had been vaccinated against COVID-19.
The primary endpoint was a composite of hypoxemia, ED visit, hospitalization, or death. The analyses were adjusted for COVID-19 vaccination and other trial medications. Overall, the adjusted odds ratios of any primary event, compared with placebo, was 0.84 for metformin (P = .19), 1.05 for ivermectin (P = .78), and 0.94 for fluvoxamine (P = .75).
The researchers also conducted a prespecified secondary analysis of components of the primary endpoint. In this analysis, the aORs for an ED visit, hospitalization, or death was 0.58 for metformin, 1.39 for ivermectin, and 1.17 for fluvoxamine. The aORs for hospitalization or death were 0.47, 0.73, and 1.11 for metformin, ivermectin, and fluvoxamine, respectively. No medication-related serious adverse events were reported with any of the drugs during the study period.
The possible benefit for prevention of severe COVID-19 with metformin was a prespecified secondary endpoint, and therefore not definitive until more research has been completed, the researchers said. Metformin has demonstrated anti-inflammatory actions in previous studies, and has shown protective effects against COVID-19 lung injury in animal studies.
Previous observational studies also have shown an association between metformin use and less severe COVID-19 in patients already taking metformin. “The proposed mechanisms of action against COVID-19 for metformin include anti-inflammatory and antiviral activity and the prevention of hyperglycemia during acute illness,” they added.
The study findings were limited by several factors including the population age range and focus on overweight and obese patients, which may limit generalizability, the researchers noted. Other limitations include the disproportionately small percentage of Black and Latino patients and the potential lack of accuracy in identifying hypoxemia via home oxygen monitors.
However, the results demonstrate that none of the three repurposed drugs – metformin, ivermectin, and fluvoxamine – prevented primary events or reduced symptom severity in COVID-19, compared with placebos, the researchers concluded.
“Metformin had several streams of evidence supporting its use: in vitro, in silico [computer modeled], observational, and in tissue. We were not surprised to see that it reduced emergency department visits, hospitalization, and death,” Dr. Bramante said in an interview.
The take-home message for clinicians is to continue to look to guideline committees for direction on COVID-19 treatments, but to continue to consider metformin along with other treatments, she said.
“All research should be replicated, whether the primary outcome is positive or negative,” Dr. Bramante emphasized. “In this case, when our positive outcome was negative and secondary outcome was positive, a confirmatory trial for metformin is particularly important.”
Ineffective drugs are inefficient use of resources
“The results of the COVID-OUT trial provide persuasive additional data that increase the confidence and degree of certainty that fluvoxamine and ivermectin are not effective in preventing progression to severe disease,” wrote Salim S. Abdool Karim, MB, and Nikita Devnarain, PhD, of the Centre for the AIDS Programme of Research in South Africa, Durban, in an accompanying editorial.
At the start of the study, in 2020, data on the use of the three drugs to prevent severe COVID-19 were “either unavailable or equivocal,” they said. Since then, accumulating data support the current study findings of the nonefficacy of ivermectin and fluvoxamine, and the World Health Organization has advised against their use for COVID-19, although the WHO has not provided guidance for the use of metformin.
The authors called on clinicians to stop using ivermectin and fluvoxamine to treat COVID-19 patients.
“With respect to clinical decisions about COVID-19 treatment, some drug choices, especially those that have negative [World Health Organization] recommendations, are clearly wrong,” they wrote. “In keeping with evidence-based medical practice, patients with COVID-19 must be treated with efficacious medications; they deserve nothing less.”
The study was supported by the Parsemus Foundation, Rainwater Charitable Foundation, Fast Grants, and UnitedHealth Group Foundation. The fluvoxamine placebo tablets were donated by Apotex Pharmaceuticals. The ivermectin placebo and active tablets were donated by Edenbridge Pharmaceuticals. Lead author Dr. Bramante was supported the National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases. The researchers had no financial conflicts to disclose. Dr. Abdool Karim serves as a member of the World Health Organization Science Council. Dr. Devnarain had no financial conflicts to disclose.
Neither metformin, ivermectin, or fluvoxamine had any impact on reducing disease severity, hospitalization, or death from COVID-19, according to results from more than 1,000 overweight or obese adult patients in the COVID-OUT randomized trial.
However, metformin showed some potential in a secondary analysis.
Early treatment to prevent severe disease remains a goal in managing the ongoing COVID-19 pandemic, and biophysical modeling suggested that metformin, ivermectin, and fluvoxamine may serve as antivirals to help reduce severe disease in COVID-19 patients, Carolyn T. Bramante, MD, of the University of Minnesota, Minneapolis, and colleagues wrote.
“We started enrolling patients at the end of December 2020,” Dr. Bramante said in an interview. “At that time, even though vaccine data were coming out, we thought it was important to test early outpatient treatment with widely available safe medications with no interactions, because the virus would evolve and vaccine availability may be limited.”
In a study published in the New England Journal of Medicine, the researchers used a two-by-three factorial design to test the ability of metformin, ivermectin, and fluvoxamine to prevent severe COVID-19 infection in nonhospitalized adults aged 30-85 years. A total of 1,431 patients at six U.S. sites were enrolled within 3 days of a confirmed infection and less than 7 days after the start of symptoms, then randomized to one of six groups: metformin plus fluvoxamine; metformin plus ivermectin; metformin plus placebo; placebo plus fluvoxamine; placebo plus ivermectin; and placebo plus placebo.
A total of 1,323 patients were included in the primary analysis. The median age of the patients was 46 years, 56% were female (of whom 6% were pregnant), and all individuals met criteria for overweight or obesity. About half (52%) of the patients had been vaccinated against COVID-19.
The primary endpoint was a composite of hypoxemia, ED visit, hospitalization, or death. The analyses were adjusted for COVID-19 vaccination and other trial medications. Overall, the adjusted odds ratios of any primary event, compared with placebo, was 0.84 for metformin (P = .19), 1.05 for ivermectin (P = .78), and 0.94 for fluvoxamine (P = .75).
The researchers also conducted a prespecified secondary analysis of components of the primary endpoint. In this analysis, the aORs for an ED visit, hospitalization, or death was 0.58 for metformin, 1.39 for ivermectin, and 1.17 for fluvoxamine. The aORs for hospitalization or death were 0.47, 0.73, and 1.11 for metformin, ivermectin, and fluvoxamine, respectively. No medication-related serious adverse events were reported with any of the drugs during the study period.
The possible benefit for prevention of severe COVID-19 with metformin was a prespecified secondary endpoint, and therefore not definitive until more research has been completed, the researchers said. Metformin has demonstrated anti-inflammatory actions in previous studies, and has shown protective effects against COVID-19 lung injury in animal studies.
Previous observational studies also have shown an association between metformin use and less severe COVID-19 in patients already taking metformin. “The proposed mechanisms of action against COVID-19 for metformin include anti-inflammatory and antiviral activity and the prevention of hyperglycemia during acute illness,” they added.
The study findings were limited by several factors including the population age range and focus on overweight and obese patients, which may limit generalizability, the researchers noted. Other limitations include the disproportionately small percentage of Black and Latino patients and the potential lack of accuracy in identifying hypoxemia via home oxygen monitors.
However, the results demonstrate that none of the three repurposed drugs – metformin, ivermectin, and fluvoxamine – prevented primary events or reduced symptom severity in COVID-19, compared with placebos, the researchers concluded.
“Metformin had several streams of evidence supporting its use: in vitro, in silico [computer modeled], observational, and in tissue. We were not surprised to see that it reduced emergency department visits, hospitalization, and death,” Dr. Bramante said in an interview.
The take-home message for clinicians is to continue to look to guideline committees for direction on COVID-19 treatments, but to continue to consider metformin along with other treatments, she said.
“All research should be replicated, whether the primary outcome is positive or negative,” Dr. Bramante emphasized. “In this case, when our positive outcome was negative and secondary outcome was positive, a confirmatory trial for metformin is particularly important.”
Ineffective drugs are inefficient use of resources
“The results of the COVID-OUT trial provide persuasive additional data that increase the confidence and degree of certainty that fluvoxamine and ivermectin are not effective in preventing progression to severe disease,” wrote Salim S. Abdool Karim, MB, and Nikita Devnarain, PhD, of the Centre for the AIDS Programme of Research in South Africa, Durban, in an accompanying editorial.
At the start of the study, in 2020, data on the use of the three drugs to prevent severe COVID-19 were “either unavailable or equivocal,” they said. Since then, accumulating data support the current study findings of the nonefficacy of ivermectin and fluvoxamine, and the World Health Organization has advised against their use for COVID-19, although the WHO has not provided guidance for the use of metformin.
The authors called on clinicians to stop using ivermectin and fluvoxamine to treat COVID-19 patients.
“With respect to clinical decisions about COVID-19 treatment, some drug choices, especially those that have negative [World Health Organization] recommendations, are clearly wrong,” they wrote. “In keeping with evidence-based medical practice, patients with COVID-19 must be treated with efficacious medications; they deserve nothing less.”
The study was supported by the Parsemus Foundation, Rainwater Charitable Foundation, Fast Grants, and UnitedHealth Group Foundation. The fluvoxamine placebo tablets were donated by Apotex Pharmaceuticals. The ivermectin placebo and active tablets were donated by Edenbridge Pharmaceuticals. Lead author Dr. Bramante was supported the National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases. The researchers had no financial conflicts to disclose. Dr. Abdool Karim serves as a member of the World Health Organization Science Council. Dr. Devnarain had no financial conflicts to disclose.
Neither metformin, ivermectin, or fluvoxamine had any impact on reducing disease severity, hospitalization, or death from COVID-19, according to results from more than 1,000 overweight or obese adult patients in the COVID-OUT randomized trial.
However, metformin showed some potential in a secondary analysis.
Early treatment to prevent severe disease remains a goal in managing the ongoing COVID-19 pandemic, and biophysical modeling suggested that metformin, ivermectin, and fluvoxamine may serve as antivirals to help reduce severe disease in COVID-19 patients, Carolyn T. Bramante, MD, of the University of Minnesota, Minneapolis, and colleagues wrote.
“We started enrolling patients at the end of December 2020,” Dr. Bramante said in an interview. “At that time, even though vaccine data were coming out, we thought it was important to test early outpatient treatment with widely available safe medications with no interactions, because the virus would evolve and vaccine availability may be limited.”
In a study published in the New England Journal of Medicine, the researchers used a two-by-three factorial design to test the ability of metformin, ivermectin, and fluvoxamine to prevent severe COVID-19 infection in nonhospitalized adults aged 30-85 years. A total of 1,431 patients at six U.S. sites were enrolled within 3 days of a confirmed infection and less than 7 days after the start of symptoms, then randomized to one of six groups: metformin plus fluvoxamine; metformin plus ivermectin; metformin plus placebo; placebo plus fluvoxamine; placebo plus ivermectin; and placebo plus placebo.
A total of 1,323 patients were included in the primary analysis. The median age of the patients was 46 years, 56% were female (of whom 6% were pregnant), and all individuals met criteria for overweight or obesity. About half (52%) of the patients had been vaccinated against COVID-19.
The primary endpoint was a composite of hypoxemia, ED visit, hospitalization, or death. The analyses were adjusted for COVID-19 vaccination and other trial medications. Overall, the adjusted odds ratios of any primary event, compared with placebo, was 0.84 for metformin (P = .19), 1.05 for ivermectin (P = .78), and 0.94 for fluvoxamine (P = .75).
The researchers also conducted a prespecified secondary analysis of components of the primary endpoint. In this analysis, the aORs for an ED visit, hospitalization, or death was 0.58 for metformin, 1.39 for ivermectin, and 1.17 for fluvoxamine. The aORs for hospitalization or death were 0.47, 0.73, and 1.11 for metformin, ivermectin, and fluvoxamine, respectively. No medication-related serious adverse events were reported with any of the drugs during the study period.
The possible benefit for prevention of severe COVID-19 with metformin was a prespecified secondary endpoint, and therefore not definitive until more research has been completed, the researchers said. Metformin has demonstrated anti-inflammatory actions in previous studies, and has shown protective effects against COVID-19 lung injury in animal studies.
Previous observational studies also have shown an association between metformin use and less severe COVID-19 in patients already taking metformin. “The proposed mechanisms of action against COVID-19 for metformin include anti-inflammatory and antiviral activity and the prevention of hyperglycemia during acute illness,” they added.
The study findings were limited by several factors including the population age range and focus on overweight and obese patients, which may limit generalizability, the researchers noted. Other limitations include the disproportionately small percentage of Black and Latino patients and the potential lack of accuracy in identifying hypoxemia via home oxygen monitors.
However, the results demonstrate that none of the three repurposed drugs – metformin, ivermectin, and fluvoxamine – prevented primary events or reduced symptom severity in COVID-19, compared with placebos, the researchers concluded.
“Metformin had several streams of evidence supporting its use: in vitro, in silico [computer modeled], observational, and in tissue. We were not surprised to see that it reduced emergency department visits, hospitalization, and death,” Dr. Bramante said in an interview.
The take-home message for clinicians is to continue to look to guideline committees for direction on COVID-19 treatments, but to continue to consider metformin along with other treatments, she said.
“All research should be replicated, whether the primary outcome is positive or negative,” Dr. Bramante emphasized. “In this case, when our positive outcome was negative and secondary outcome was positive, a confirmatory trial for metformin is particularly important.”
Ineffective drugs are inefficient use of resources
“The results of the COVID-OUT trial provide persuasive additional data that increase the confidence and degree of certainty that fluvoxamine and ivermectin are not effective in preventing progression to severe disease,” wrote Salim S. Abdool Karim, MB, and Nikita Devnarain, PhD, of the Centre for the AIDS Programme of Research in South Africa, Durban, in an accompanying editorial.
At the start of the study, in 2020, data on the use of the three drugs to prevent severe COVID-19 were “either unavailable or equivocal,” they said. Since then, accumulating data support the current study findings of the nonefficacy of ivermectin and fluvoxamine, and the World Health Organization has advised against their use for COVID-19, although the WHO has not provided guidance for the use of metformin.
The authors called on clinicians to stop using ivermectin and fluvoxamine to treat COVID-19 patients.
“With respect to clinical decisions about COVID-19 treatment, some drug choices, especially those that have negative [World Health Organization] recommendations, are clearly wrong,” they wrote. “In keeping with evidence-based medical practice, patients with COVID-19 must be treated with efficacious medications; they deserve nothing less.”
The study was supported by the Parsemus Foundation, Rainwater Charitable Foundation, Fast Grants, and UnitedHealth Group Foundation. The fluvoxamine placebo tablets were donated by Apotex Pharmaceuticals. The ivermectin placebo and active tablets were donated by Edenbridge Pharmaceuticals. Lead author Dr. Bramante was supported the National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases. The researchers had no financial conflicts to disclose. Dr. Abdool Karim serves as a member of the World Health Organization Science Council. Dr. Devnarain had no financial conflicts to disclose.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Call for Neurology Papers
Federal Practitioner invites VA, DoD, and PHS health care professionals and researchers to contribute to a future special issue on neurology. Topics of interest include epilepsy, headache and migraine, COVID-19 and neurology, Alzheimer and dementia, MS, and other neurological disorders.
Interested authors should submit an abstract to fedprac@mdedge.com with the subject line “Neurology Special Issue” for consideration. Once the editorial team confirms the article is eligible for consideration, authors will be asked to submit their manuscript in full through Editorial Manager.
Federal Practitioner never charges authors or readers. All submissions undergo a double-blinded peer review before publication. Accepted manuscripts are always available for free online at www.mdedge.com/fedprac and on PubMed Central.
Federal Practitioner welcomes original research, commentaries, clinical reviews, program profiles, case reports, and other evidence-based articles. The updated and complete submission guidelines, including details about the style and format, can be found here:
Federal Practitioner invites VA, DoD, and PHS health care professionals and researchers to contribute to a future special issue on neurology. Topics of interest include epilepsy, headache and migraine, COVID-19 and neurology, Alzheimer and dementia, MS, and other neurological disorders.
Interested authors should submit an abstract to fedprac@mdedge.com with the subject line “Neurology Special Issue” for consideration. Once the editorial team confirms the article is eligible for consideration, authors will be asked to submit their manuscript in full through Editorial Manager.
Federal Practitioner never charges authors or readers. All submissions undergo a double-blinded peer review before publication. Accepted manuscripts are always available for free online at www.mdedge.com/fedprac and on PubMed Central.
Federal Practitioner welcomes original research, commentaries, clinical reviews, program profiles, case reports, and other evidence-based articles. The updated and complete submission guidelines, including details about the style and format, can be found here:
Federal Practitioner invites VA, DoD, and PHS health care professionals and researchers to contribute to a future special issue on neurology. Topics of interest include epilepsy, headache and migraine, COVID-19 and neurology, Alzheimer and dementia, MS, and other neurological disorders.
Interested authors should submit an abstract to fedprac@mdedge.com with the subject line “Neurology Special Issue” for consideration. Once the editorial team confirms the article is eligible for consideration, authors will be asked to submit their manuscript in full through Editorial Manager.
Federal Practitioner never charges authors or readers. All submissions undergo a double-blinded peer review before publication. Accepted manuscripts are always available for free online at www.mdedge.com/fedprac and on PubMed Central.
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Large genetic study links 72 genes to autism spectrum disorders
according to a study published in Nature Genetics. The findings, based on analysis of more than 150,000 people’s genetics, arose from a collaboration of five research groups whose work included comparisons of ASD cohorts with separate cohorts of individuals with developmental delay or schizophrenia.
“We know that many genes, when mutated, contribute to autism,” and this study brought together “multiple types of mutations in a wide array of samples to get a much richer sense of the genes and genetic architecture involved in autism and other neurodevelopmental conditions,” co–senior author Joseph D. Buxbaum, PhD, director of the Seaver Autism Center for Research and Treatment at Mount Sinai and a professor at the Icahn School of Medicine at Mount Sinai, both in New York, said in a prepared statement. “This is significant in that we now have more insights as to the biology of the brain changes that underlie autism and more potential targets for treatment.”
Glen Elliott, PhD, MD, a clinical professor of psychiatry at Stanford (Calif.) University who was not involved in the study, said the paper is important paper for informing clinicians of where the basic research is headed. “We’re still in for a long road” before it bears fruit in terms of therapeutics. The value of studies like these, that investigate which genes are most associated with ASD, is that they may lead toward understanding the pathways in the brain that give rise to certain symptoms of ASD, which can then become therapeutic targets, Dr. Elliott said.
Investigating large cohorts
The researchers analyzed genetic exome sequencing data from 33 ASD cohorts with a total of 63,237 people and then compared these data with another cohort of people with developmental delay and a cohort of people with schizophrenia. The combined ASD cohorts included 15,036 individuals with ASD, 28,522 parents, and 5,492 unaffected siblings. The remaining participants were 5,591 people with ASD and 8,597 matched controls from case control studies.
In the ASD cohorts, the researchers identified 72 genes that were associated with ASD. De novo variants were eight times more likely in cases (4%) than in controls (0.5%). Ten genes occurred at least twice in ASD cases but never occurred in unaffected siblings.
Then the researchers integrated these ASD genetic data with a cohort of 91,605 people that included 31,058 people with developmental delay and their parents. Substantial overlap with gene mutations existed between these two cohorts: 70.1% of the genes related to developmental delay appeared linked to risk for ASD, and 86.6% of genes associated with ASD risk also had associations with developmental delay. Overall, the researchers identified 373 genes strongly associated with ASD and/or developmental delay and 664 genes with a likely association.
“Isolating genes that exert a greater effect on ASD than they do on other developmental delays has remained challenging due to the frequent comorbidity of these phenotypes,” wrote lead author Jack M. Fu, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues. “Still, an estimated 13.4% of the transmission and de novo association–ASD genes show little evidence for association in the developmental delay cohort.”
ASD, developmental delay, and schizophrenia
When the researchers compared the cells where the genetic mutations occurred in fetal brains, they found that genes associated with developmental delay more often occurred in less differentiated cell types – less mature cells in the developmental process. Gene mutations associated with ASD, on the other hand, occurred in more mature cell types, particularly in maturing excitatory neurons and related cells.
”Our results are consistent with developmental delay-predominant genes being expressed earlier in development and in less differentiated cells than ASD-predominant genes,” they wrote.
The researchers also compared the specific gene mutations found in these two cohorts with a previously published set of 244 genes associated with schizophrenia. Of these, 234 genes are among those with a transmission and de novo association to ASD and/or developmental delay. Of the 72 genes linked to ASD, eight appear in the set of genes linked to schizophrenia, and 61 were associated with developmental delay, though these two subsets do not overlap each other much.
“The ASD-schizophrenia overlap was significantly enriched, while the developmental delay-schizophrenia overlap was not,” they reported. ”Together, these data suggest that one subset of ASD risk genes may overlap developmental delay while a different subset overlaps schizophrenia.”
Chasing therapy targets by backtracking through genes
The findings are a substantial step forward in understanding the potential genetic contribution to ASD, but they also highlight the challenges of eventually trying to use this information in a clinically meaningful way.
“Given the substantial overlap between the genes implicated in neurodevelopmental disorders writ large and those implicated directly in ASD, disentangling the relative impact of individual genes on neurodevelopment and phenotypic spectra is a daunting yet important challenge,” the researchers wrote. “To identify the key neurobiological features of ASD will likely require convergence of evidence from many ASD genes and studies.”
Dr. Elliott said the biggest takeaway from this study is a better understanding of how the paradigm has shifted away from finding “one gene” for autism or a cure based on genetics and more toward understanding the pathophysiology of symptoms that can point to therapies for better management of the condition.
“Basic researchers have completely changed the strategy for trying to understand the biology of major disorders,” including, in this case, autism, Dr. Elliott said. “The intent is to try to find the underlying systems [in the brain] by backtracking through genes. Meanwhile, given that scientists have made substantial progress in identifying genes that have specific effects on brain development, “the hope is that will mesh with this kind of research, to begin to identify systems that might ultimately be targets for treating.”
The end goal is to be able to offer targeted approaches, based on the pathways causing a symptom, which can be linked backward to a gene.
”So this is not going to offer an immediate cure – it’s probably not going to offer a cure at all – but it may actually lead to much more targeted medications than we currently have for specific types of symptoms within the autism spectrum,” Dr. Elliott said. “What they’re trying to do, ultimately, is to say, when this system is really badly affected because of a genetic abnormality, even though that genetic abnormality is very rare, it leads to these specific kinds of symptoms. If we can find out the neuroregulators underlying that change, then that would be the target, even if that gene were not present.”
The research was funded by the Simons Foundation for Autism Research Initiative, the SPARK project, the National Human Genome Research Institute Home, the National Institute of Mental Health, the National Institute of Child Health and Development, AMED, and the Beatrice and Samuel Seaver Foundation. Five authors reported financial disclosures linked to Desitin, Roche, BioMarin, BrigeBio Pharma, Illumina, Levo Therapeutics, and Microsoft.
according to a study published in Nature Genetics. The findings, based on analysis of more than 150,000 people’s genetics, arose from a collaboration of five research groups whose work included comparisons of ASD cohorts with separate cohorts of individuals with developmental delay or schizophrenia.
“We know that many genes, when mutated, contribute to autism,” and this study brought together “multiple types of mutations in a wide array of samples to get a much richer sense of the genes and genetic architecture involved in autism and other neurodevelopmental conditions,” co–senior author Joseph D. Buxbaum, PhD, director of the Seaver Autism Center for Research and Treatment at Mount Sinai and a professor at the Icahn School of Medicine at Mount Sinai, both in New York, said in a prepared statement. “This is significant in that we now have more insights as to the biology of the brain changes that underlie autism and more potential targets for treatment.”
Glen Elliott, PhD, MD, a clinical professor of psychiatry at Stanford (Calif.) University who was not involved in the study, said the paper is important paper for informing clinicians of where the basic research is headed. “We’re still in for a long road” before it bears fruit in terms of therapeutics. The value of studies like these, that investigate which genes are most associated with ASD, is that they may lead toward understanding the pathways in the brain that give rise to certain symptoms of ASD, which can then become therapeutic targets, Dr. Elliott said.
Investigating large cohorts
The researchers analyzed genetic exome sequencing data from 33 ASD cohorts with a total of 63,237 people and then compared these data with another cohort of people with developmental delay and a cohort of people with schizophrenia. The combined ASD cohorts included 15,036 individuals with ASD, 28,522 parents, and 5,492 unaffected siblings. The remaining participants were 5,591 people with ASD and 8,597 matched controls from case control studies.
In the ASD cohorts, the researchers identified 72 genes that were associated with ASD. De novo variants were eight times more likely in cases (4%) than in controls (0.5%). Ten genes occurred at least twice in ASD cases but never occurred in unaffected siblings.
Then the researchers integrated these ASD genetic data with a cohort of 91,605 people that included 31,058 people with developmental delay and their parents. Substantial overlap with gene mutations existed between these two cohorts: 70.1% of the genes related to developmental delay appeared linked to risk for ASD, and 86.6% of genes associated with ASD risk also had associations with developmental delay. Overall, the researchers identified 373 genes strongly associated with ASD and/or developmental delay and 664 genes with a likely association.
“Isolating genes that exert a greater effect on ASD than they do on other developmental delays has remained challenging due to the frequent comorbidity of these phenotypes,” wrote lead author Jack M. Fu, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues. “Still, an estimated 13.4% of the transmission and de novo association–ASD genes show little evidence for association in the developmental delay cohort.”
ASD, developmental delay, and schizophrenia
When the researchers compared the cells where the genetic mutations occurred in fetal brains, they found that genes associated with developmental delay more often occurred in less differentiated cell types – less mature cells in the developmental process. Gene mutations associated with ASD, on the other hand, occurred in more mature cell types, particularly in maturing excitatory neurons and related cells.
”Our results are consistent with developmental delay-predominant genes being expressed earlier in development and in less differentiated cells than ASD-predominant genes,” they wrote.
The researchers also compared the specific gene mutations found in these two cohorts with a previously published set of 244 genes associated with schizophrenia. Of these, 234 genes are among those with a transmission and de novo association to ASD and/or developmental delay. Of the 72 genes linked to ASD, eight appear in the set of genes linked to schizophrenia, and 61 were associated with developmental delay, though these two subsets do not overlap each other much.
“The ASD-schizophrenia overlap was significantly enriched, while the developmental delay-schizophrenia overlap was not,” they reported. ”Together, these data suggest that one subset of ASD risk genes may overlap developmental delay while a different subset overlaps schizophrenia.”
Chasing therapy targets by backtracking through genes
The findings are a substantial step forward in understanding the potential genetic contribution to ASD, but they also highlight the challenges of eventually trying to use this information in a clinically meaningful way.
“Given the substantial overlap between the genes implicated in neurodevelopmental disorders writ large and those implicated directly in ASD, disentangling the relative impact of individual genes on neurodevelopment and phenotypic spectra is a daunting yet important challenge,” the researchers wrote. “To identify the key neurobiological features of ASD will likely require convergence of evidence from many ASD genes and studies.”
Dr. Elliott said the biggest takeaway from this study is a better understanding of how the paradigm has shifted away from finding “one gene” for autism or a cure based on genetics and more toward understanding the pathophysiology of symptoms that can point to therapies for better management of the condition.
“Basic researchers have completely changed the strategy for trying to understand the biology of major disorders,” including, in this case, autism, Dr. Elliott said. “The intent is to try to find the underlying systems [in the brain] by backtracking through genes. Meanwhile, given that scientists have made substantial progress in identifying genes that have specific effects on brain development, “the hope is that will mesh with this kind of research, to begin to identify systems that might ultimately be targets for treating.”
The end goal is to be able to offer targeted approaches, based on the pathways causing a symptom, which can be linked backward to a gene.
”So this is not going to offer an immediate cure – it’s probably not going to offer a cure at all – but it may actually lead to much more targeted medications than we currently have for specific types of symptoms within the autism spectrum,” Dr. Elliott said. “What they’re trying to do, ultimately, is to say, when this system is really badly affected because of a genetic abnormality, even though that genetic abnormality is very rare, it leads to these specific kinds of symptoms. If we can find out the neuroregulators underlying that change, then that would be the target, even if that gene were not present.”
The research was funded by the Simons Foundation for Autism Research Initiative, the SPARK project, the National Human Genome Research Institute Home, the National Institute of Mental Health, the National Institute of Child Health and Development, AMED, and the Beatrice and Samuel Seaver Foundation. Five authors reported financial disclosures linked to Desitin, Roche, BioMarin, BrigeBio Pharma, Illumina, Levo Therapeutics, and Microsoft.
according to a study published in Nature Genetics. The findings, based on analysis of more than 150,000 people’s genetics, arose from a collaboration of five research groups whose work included comparisons of ASD cohorts with separate cohorts of individuals with developmental delay or schizophrenia.
“We know that many genes, when mutated, contribute to autism,” and this study brought together “multiple types of mutations in a wide array of samples to get a much richer sense of the genes and genetic architecture involved in autism and other neurodevelopmental conditions,” co–senior author Joseph D. Buxbaum, PhD, director of the Seaver Autism Center for Research and Treatment at Mount Sinai and a professor at the Icahn School of Medicine at Mount Sinai, both in New York, said in a prepared statement. “This is significant in that we now have more insights as to the biology of the brain changes that underlie autism and more potential targets for treatment.”
Glen Elliott, PhD, MD, a clinical professor of psychiatry at Stanford (Calif.) University who was not involved in the study, said the paper is important paper for informing clinicians of where the basic research is headed. “We’re still in for a long road” before it bears fruit in terms of therapeutics. The value of studies like these, that investigate which genes are most associated with ASD, is that they may lead toward understanding the pathways in the brain that give rise to certain symptoms of ASD, which can then become therapeutic targets, Dr. Elliott said.
Investigating large cohorts
The researchers analyzed genetic exome sequencing data from 33 ASD cohorts with a total of 63,237 people and then compared these data with another cohort of people with developmental delay and a cohort of people with schizophrenia. The combined ASD cohorts included 15,036 individuals with ASD, 28,522 parents, and 5,492 unaffected siblings. The remaining participants were 5,591 people with ASD and 8,597 matched controls from case control studies.
In the ASD cohorts, the researchers identified 72 genes that were associated with ASD. De novo variants were eight times more likely in cases (4%) than in controls (0.5%). Ten genes occurred at least twice in ASD cases but never occurred in unaffected siblings.
Then the researchers integrated these ASD genetic data with a cohort of 91,605 people that included 31,058 people with developmental delay and their parents. Substantial overlap with gene mutations existed between these two cohorts: 70.1% of the genes related to developmental delay appeared linked to risk for ASD, and 86.6% of genes associated with ASD risk also had associations with developmental delay. Overall, the researchers identified 373 genes strongly associated with ASD and/or developmental delay and 664 genes with a likely association.
“Isolating genes that exert a greater effect on ASD than they do on other developmental delays has remained challenging due to the frequent comorbidity of these phenotypes,” wrote lead author Jack M. Fu, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues. “Still, an estimated 13.4% of the transmission and de novo association–ASD genes show little evidence for association in the developmental delay cohort.”
ASD, developmental delay, and schizophrenia
When the researchers compared the cells where the genetic mutations occurred in fetal brains, they found that genes associated with developmental delay more often occurred in less differentiated cell types – less mature cells in the developmental process. Gene mutations associated with ASD, on the other hand, occurred in more mature cell types, particularly in maturing excitatory neurons and related cells.
”Our results are consistent with developmental delay-predominant genes being expressed earlier in development and in less differentiated cells than ASD-predominant genes,” they wrote.
The researchers also compared the specific gene mutations found in these two cohorts with a previously published set of 244 genes associated with schizophrenia. Of these, 234 genes are among those with a transmission and de novo association to ASD and/or developmental delay. Of the 72 genes linked to ASD, eight appear in the set of genes linked to schizophrenia, and 61 were associated with developmental delay, though these two subsets do not overlap each other much.
“The ASD-schizophrenia overlap was significantly enriched, while the developmental delay-schizophrenia overlap was not,” they reported. ”Together, these data suggest that one subset of ASD risk genes may overlap developmental delay while a different subset overlaps schizophrenia.”
Chasing therapy targets by backtracking through genes
The findings are a substantial step forward in understanding the potential genetic contribution to ASD, but they also highlight the challenges of eventually trying to use this information in a clinically meaningful way.
“Given the substantial overlap between the genes implicated in neurodevelopmental disorders writ large and those implicated directly in ASD, disentangling the relative impact of individual genes on neurodevelopment and phenotypic spectra is a daunting yet important challenge,” the researchers wrote. “To identify the key neurobiological features of ASD will likely require convergence of evidence from many ASD genes and studies.”
Dr. Elliott said the biggest takeaway from this study is a better understanding of how the paradigm has shifted away from finding “one gene” for autism or a cure based on genetics and more toward understanding the pathophysiology of symptoms that can point to therapies for better management of the condition.
“Basic researchers have completely changed the strategy for trying to understand the biology of major disorders,” including, in this case, autism, Dr. Elliott said. “The intent is to try to find the underlying systems [in the brain] by backtracking through genes. Meanwhile, given that scientists have made substantial progress in identifying genes that have specific effects on brain development, “the hope is that will mesh with this kind of research, to begin to identify systems that might ultimately be targets for treating.”
The end goal is to be able to offer targeted approaches, based on the pathways causing a symptom, which can be linked backward to a gene.
”So this is not going to offer an immediate cure – it’s probably not going to offer a cure at all – but it may actually lead to much more targeted medications than we currently have for specific types of symptoms within the autism spectrum,” Dr. Elliott said. “What they’re trying to do, ultimately, is to say, when this system is really badly affected because of a genetic abnormality, even though that genetic abnormality is very rare, it leads to these specific kinds of symptoms. If we can find out the neuroregulators underlying that change, then that would be the target, even if that gene were not present.”
The research was funded by the Simons Foundation for Autism Research Initiative, the SPARK project, the National Human Genome Research Institute Home, the National Institute of Mental Health, the National Institute of Child Health and Development, AMED, and the Beatrice and Samuel Seaver Foundation. Five authors reported financial disclosures linked to Desitin, Roche, BioMarin, BrigeBio Pharma, Illumina, Levo Therapeutics, and Microsoft.
FROM NATURE GENETICS
Use of antidotes in pregnancy and lactation
The human pregnancy data reported for these 16 agents are very limited as only 8 of the drugs have this data. However, the 8 reports indicated that the use of these drugs was highly important for the mother and did not cause embryo/fetal harm.
- Acetylcysteine
The need for this antidote in a pregnant or lactating woman is most likely a rare requirement. However, the need for this agent does occur in women who have taken a potentially hepatic toxic dose of acetaminophen (e.g., Tylenol).
- Black widow spider antivenin
Only three reports of the use of this agent in a pregnant woman have been located. In each case, the symptoms from the spider bite did not respond to other therapies but did within 1 hour to the antivenin. There was no fetal harm in these cases.
- Deferasirox
This agent is an oral iron-chelating agent used for the treatment of chronic iron overload. Five case reports have described its use without causing any fetal harm.
- Deferoxamine
This agent has been used in more than 65 pregnancies for acute iron overdose or for transfusion-dependent thalassemia. No reports have observed adverse human developmental effects.
- Digoxin immune FAB (ovine)
Several reports have described the use of this agent in pregnancy. No fetal harm has been observed, but none of the reports involved exposure during organogenesis. However, in cases of digoxin overdose, the maternal benefits of therapy should take priority over the embryo/fetus.
- Dimercaprol
Although the limited animal data suggest low risk, there are no reports of the use of this drug in human organogenesis. The absence of data prevents an assessment of the embryo-fetal risk, but the maternal benefit and indirect embryo-fetal benefit appears to outweigh that risk.
- Edetate calcium disodium
This agent is used to treat acute or chronic lead poisoning. It is compatible in pregnancy because the maternal and possibly the embryo-fetal benefit appears to outweigh any unknown direct or indirect risks.
- Flumazenil
The use of this drug in the third trimester has been reported in two cases. Because the drug is indicated to reverse the effects of benzodiazepines on the central nervous system, the maternal benefit should far outweigh the unknown embryo-fetal risk.
- Glucagon
The embryo-fetal risks appear to be very low. Apparently, the drug does not cross the placenta.
- Glucarpidase
This drug is indicated for the treatment of methotrexate toxicity. There are no reports describing the use of this drug in pregnancy or during breastfeeding.
- Idarucizumab
This agent is a humanized monoclonal antibody fragment that is indicated for the reversal of the anticoagulant effects of dabigatran. No reports describing its use in human or animal pregnancy have been located. However, the maternal benefit appears to be high and probably outweighs the unknown risk to the embryo/fetus.
- Lanthanum carbonate
There are no human pregnancy or lactation data. It is used to reduce blood levels of phosphate in people with kidney disease.
- Pralidoxime
This agent relieves the paralysis of the muscles of respiration caused by an organophosphate pesticide or related compound. The human pregnancy experience is limited to two cases, one at 36 weeks and the other at 16 weeks, both of which delivered normal infants.
- Sapropterin
Four reports have described the use of sapropterin to lower blood phenylalanine levels in 31 pregnancies. There were no embryo-fetal adverse effects attributable to the drug.
- Sevelamer
Sevelamer is used to control high blood levels of phosphorus in people with chronic kidney disease who are on dialysis. There are no human pregnancy or breastfeeding data.
- Succimer
This drug is a heavy metal–chelating agent that is indicated for the treatment of lead poisoning in pediatric patients. The drug was teratogenic in rats and mice. Two reports described the use of the drug in two pregnant women for lead poisoning. It has also been used as an antidote for the treatment of arsenic, mercury, and cadmium poisoning in adults, but there have been no reports of this use in pregnant patients.
Mr. Briggs, now retired, was a clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.
The human pregnancy data reported for these 16 agents are very limited as only 8 of the drugs have this data. However, the 8 reports indicated that the use of these drugs was highly important for the mother and did not cause embryo/fetal harm.
- Acetylcysteine
The need for this antidote in a pregnant or lactating woman is most likely a rare requirement. However, the need for this agent does occur in women who have taken a potentially hepatic toxic dose of acetaminophen (e.g., Tylenol).
- Black widow spider antivenin
Only three reports of the use of this agent in a pregnant woman have been located. In each case, the symptoms from the spider bite did not respond to other therapies but did within 1 hour to the antivenin. There was no fetal harm in these cases.
- Deferasirox
This agent is an oral iron-chelating agent used for the treatment of chronic iron overload. Five case reports have described its use without causing any fetal harm.
- Deferoxamine
This agent has been used in more than 65 pregnancies for acute iron overdose or for transfusion-dependent thalassemia. No reports have observed adverse human developmental effects.
- Digoxin immune FAB (ovine)
Several reports have described the use of this agent in pregnancy. No fetal harm has been observed, but none of the reports involved exposure during organogenesis. However, in cases of digoxin overdose, the maternal benefits of therapy should take priority over the embryo/fetus.
- Dimercaprol
Although the limited animal data suggest low risk, there are no reports of the use of this drug in human organogenesis. The absence of data prevents an assessment of the embryo-fetal risk, but the maternal benefit and indirect embryo-fetal benefit appears to outweigh that risk.
- Edetate calcium disodium
This agent is used to treat acute or chronic lead poisoning. It is compatible in pregnancy because the maternal and possibly the embryo-fetal benefit appears to outweigh any unknown direct or indirect risks.
- Flumazenil
The use of this drug in the third trimester has been reported in two cases. Because the drug is indicated to reverse the effects of benzodiazepines on the central nervous system, the maternal benefit should far outweigh the unknown embryo-fetal risk.
- Glucagon
The embryo-fetal risks appear to be very low. Apparently, the drug does not cross the placenta.
- Glucarpidase
This drug is indicated for the treatment of methotrexate toxicity. There are no reports describing the use of this drug in pregnancy or during breastfeeding.
- Idarucizumab
This agent is a humanized monoclonal antibody fragment that is indicated for the reversal of the anticoagulant effects of dabigatran. No reports describing its use in human or animal pregnancy have been located. However, the maternal benefit appears to be high and probably outweighs the unknown risk to the embryo/fetus.
- Lanthanum carbonate
There are no human pregnancy or lactation data. It is used to reduce blood levels of phosphate in people with kidney disease.
- Pralidoxime
This agent relieves the paralysis of the muscles of respiration caused by an organophosphate pesticide or related compound. The human pregnancy experience is limited to two cases, one at 36 weeks and the other at 16 weeks, both of which delivered normal infants.
- Sapropterin
Four reports have described the use of sapropterin to lower blood phenylalanine levels in 31 pregnancies. There were no embryo-fetal adverse effects attributable to the drug.
- Sevelamer
Sevelamer is used to control high blood levels of phosphorus in people with chronic kidney disease who are on dialysis. There are no human pregnancy or breastfeeding data.
- Succimer
This drug is a heavy metal–chelating agent that is indicated for the treatment of lead poisoning in pediatric patients. The drug was teratogenic in rats and mice. Two reports described the use of the drug in two pregnant women for lead poisoning. It has also been used as an antidote for the treatment of arsenic, mercury, and cadmium poisoning in adults, but there have been no reports of this use in pregnant patients.
Mr. Briggs, now retired, was a clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.
The human pregnancy data reported for these 16 agents are very limited as only 8 of the drugs have this data. However, the 8 reports indicated that the use of these drugs was highly important for the mother and did not cause embryo/fetal harm.
- Acetylcysteine
The need for this antidote in a pregnant or lactating woman is most likely a rare requirement. However, the need for this agent does occur in women who have taken a potentially hepatic toxic dose of acetaminophen (e.g., Tylenol).
- Black widow spider antivenin
Only three reports of the use of this agent in a pregnant woman have been located. In each case, the symptoms from the spider bite did not respond to other therapies but did within 1 hour to the antivenin. There was no fetal harm in these cases.
- Deferasirox
This agent is an oral iron-chelating agent used for the treatment of chronic iron overload. Five case reports have described its use without causing any fetal harm.
- Deferoxamine
This agent has been used in more than 65 pregnancies for acute iron overdose or for transfusion-dependent thalassemia. No reports have observed adverse human developmental effects.
- Digoxin immune FAB (ovine)
Several reports have described the use of this agent in pregnancy. No fetal harm has been observed, but none of the reports involved exposure during organogenesis. However, in cases of digoxin overdose, the maternal benefits of therapy should take priority over the embryo/fetus.
- Dimercaprol
Although the limited animal data suggest low risk, there are no reports of the use of this drug in human organogenesis. The absence of data prevents an assessment of the embryo-fetal risk, but the maternal benefit and indirect embryo-fetal benefit appears to outweigh that risk.
- Edetate calcium disodium
This agent is used to treat acute or chronic lead poisoning. It is compatible in pregnancy because the maternal and possibly the embryo-fetal benefit appears to outweigh any unknown direct or indirect risks.
- Flumazenil
The use of this drug in the third trimester has been reported in two cases. Because the drug is indicated to reverse the effects of benzodiazepines on the central nervous system, the maternal benefit should far outweigh the unknown embryo-fetal risk.
- Glucagon
The embryo-fetal risks appear to be very low. Apparently, the drug does not cross the placenta.
- Glucarpidase
This drug is indicated for the treatment of methotrexate toxicity. There are no reports describing the use of this drug in pregnancy or during breastfeeding.
- Idarucizumab
This agent is a humanized monoclonal antibody fragment that is indicated for the reversal of the anticoagulant effects of dabigatran. No reports describing its use in human or animal pregnancy have been located. However, the maternal benefit appears to be high and probably outweighs the unknown risk to the embryo/fetus.
- Lanthanum carbonate
There are no human pregnancy or lactation data. It is used to reduce blood levels of phosphate in people with kidney disease.
- Pralidoxime
This agent relieves the paralysis of the muscles of respiration caused by an organophosphate pesticide or related compound. The human pregnancy experience is limited to two cases, one at 36 weeks and the other at 16 weeks, both of which delivered normal infants.
- Sapropterin
Four reports have described the use of sapropterin to lower blood phenylalanine levels in 31 pregnancies. There were no embryo-fetal adverse effects attributable to the drug.
- Sevelamer
Sevelamer is used to control high blood levels of phosphorus in people with chronic kidney disease who are on dialysis. There are no human pregnancy or breastfeeding data.
- Succimer
This drug is a heavy metal–chelating agent that is indicated for the treatment of lead poisoning in pediatric patients. The drug was teratogenic in rats and mice. Two reports described the use of the drug in two pregnant women for lead poisoning. It has also been used as an antidote for the treatment of arsenic, mercury, and cadmium poisoning in adults, but there have been no reports of this use in pregnant patients.
Mr. Briggs, now retired, was a clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.
No fish can escape this net ... of COVID testing
Something about this COVID testing smells fishy
The Chinese have been challenging America’s political and economic hegemony (yes, we did have to look that one up – you’re rude to ask) for some time, but now they’ve gone too far. Are we going to just sit here and let China do something more ridiculous than us in response to COVID? No way!
Here’s the deal: The government of the Chinese coastal city of Xiamen has decided that it’s not just the workers on returning fishing boats who have the potential to introduce COVID to the rest of the population. The fish also present a problem. So when the authorities say that everyone needs to be tested before they can enter the city, they mean everyone.
An employee of the municipal ocean development bureau told local media that “all people in Xiamen City need nucleic acid testing, and the fish catches must be tested as well,” according to the Guardian, which also said that “TV news reports showed officials swabbing the mouths of fish and the underside of crabs.”
In the words of George Takei: “Oh my.”
Hold on there a second, George Takei, because we here in the good old US of A have still got Los Angeles, where COVID testing also has taken a nonhuman turn. The LA County public health department recently announced that pets are now eligible for a free SARS-CoV-2 test through veterinarians and other animal care facilities.
“Our goal is to test many different species of animals including wildlife (deer, bats, raccoons), pets (dogs, cats, hamsters, pocket pets), marine mammals (seals), and more,” Veterinary Public Health announced.
Hegemony restored.
Not even God could save them from worms
The Dark Ages may not have been as dark and violent as many people think, but there’s no denying that life in medieval Europe kind of sucked. The only real alternative to serfdom was a job with the Catholic Church. Medieval friars, for example, lived in stone buildings, had access to fresh fruits and vegetables, and even had latrines and running water. Luxuries compared with the life of the average peasant.
So why then, despite having access to more modern sanitation and amenities, did the friars have so many gut parasites? That’s the question raised by a group of researchers from the University of Cambridge, who conducted a study of 19 medieval friars buried at a local friary (Oh, doesn’t your town have one of those?) and 25 local people buried at a nonreligious cemetery during a similar time period. Of those 19 friars, 11 were infected with worms and parasites, compared with just 8 of 25 townspeople.
This doesn’t make a lot of sense. The friars had a good life by old-time standards: They had basic sanitation down and a solid diet. These things should lead to a healthier population. The problem, the researchers found, is two pronged and a vicious cycle. First off, the friars had plenty of fresh food, but they used human feces to fertilize their produce. There’s a reason modern practice for human waste fertilization is to let the waste compost for 6 months: The waiting period allows the parasites a chance to kindly die off, which prevents reinfection.
Secondly, the friars’ diet of fresh fruits and vegetables mixed together into a salad, while appealing to our modern-day sensibilities, was not a great choice. By comparison, laypeople tended to eat a boiled mishmash of whatever they could find, and while that’s kind of gross, the key here is that their food was cooked. And heat kills parasites. The uncooked salads did no such thing, so the monks ate infected food, expelled infected poop, and grew more infected food with their infected poop.
Once the worms arrived, they never left, making them the worst kind of house guest. Read the room, worms, take your dinner and move on. You don’t have to go home, but you can’t stay here.
What’s a shared genotype between friends?
Do you find it hard to tell the difference between Katy Perry and Zooey Deschanel? They look alike, but they’re not related. Or are they? According to new research, people who look and act very similar but are not related may share DNA.
“Our study provides a rare insight into human likeness by showing that people with extreme look-alike faces share common genotypes, whereas they are discordant at the epigenome and microbiome levels,” senior author Manel Esteller of the Josep Carreras Leukemia Research Institute in Barcelona said in a written statement. “Genomics clusters them together, and the rest sets them apart.”
The Internet has been a great source in being able to find look-alikes. The research team found photos of doppelgangers photographed by François Brunelle, a Canadian artist. Using facial recognition algorithms, the investigators were able to measure likeness between the each pair of look-alikes. The participants also completed a questionnaire about lifestyle and provided a saliva sample.
The results showed that the look-alikes had similar genotypes but different DNA methylation and microbiome landscapes. The look-alikes also seemed to have similarities in weight, height, and behaviors such as smoking, proving that doppelgangers not only look alike but also share common interests.
Next time someone tells you that you look like their best friend Steve, you won’t have to wonder much what Steve is like.
The secret to a good relationship? It’s a secret
Strong relationships are built on honesty and trust, right? Being open with your partner and/or friends is usually a good practice for keeping the relationship healthy, but the latest evidence suggests that maybe you shouldn’t share everything.
According to the first known study on the emotional, behavioral, and relational aspect of consumer behavior, not disclosing certain purchases to your partner can actually be a good thing for the relationship. How? Well, it all has to do with guilt.
In a series of studies, the researchers asked couples about their secret consumptions. The most commonly hidden thing by far was a product (65%).
“We found that 90% of people have recently kept everyday consumer behaviors a secret from a close other – like a friend or spouse – even though they also report that they don’t think their partner would care if they knew about it,” Kelley Gullo Wight, one of the study’s two lead authors, said in a written statement.
Keeping a hidden stash of chocolate produces guilt, which the researchers found to be the key factor, making the perpetrator want to do more in the relationship to ease that sense of betrayal or dishonesty. They called it a “greater relationship investment,” meaning the person is more likely to do a little extra for their partner, like shell out more money for the next anniversary gift or yield to watching their partner’s favorite program.
So don’t feel too bad about that secret Amazon purchase. As long as the other person doesn’t see the box, nobody has to know. Your relationship can only improve.
Something about this COVID testing smells fishy
The Chinese have been challenging America’s political and economic hegemony (yes, we did have to look that one up – you’re rude to ask) for some time, but now they’ve gone too far. Are we going to just sit here and let China do something more ridiculous than us in response to COVID? No way!
Here’s the deal: The government of the Chinese coastal city of Xiamen has decided that it’s not just the workers on returning fishing boats who have the potential to introduce COVID to the rest of the population. The fish also present a problem. So when the authorities say that everyone needs to be tested before they can enter the city, they mean everyone.
An employee of the municipal ocean development bureau told local media that “all people in Xiamen City need nucleic acid testing, and the fish catches must be tested as well,” according to the Guardian, which also said that “TV news reports showed officials swabbing the mouths of fish and the underside of crabs.”
In the words of George Takei: “Oh my.”
Hold on there a second, George Takei, because we here in the good old US of A have still got Los Angeles, where COVID testing also has taken a nonhuman turn. The LA County public health department recently announced that pets are now eligible for a free SARS-CoV-2 test through veterinarians and other animal care facilities.
“Our goal is to test many different species of animals including wildlife (deer, bats, raccoons), pets (dogs, cats, hamsters, pocket pets), marine mammals (seals), and more,” Veterinary Public Health announced.
Hegemony restored.
Not even God could save them from worms
The Dark Ages may not have been as dark and violent as many people think, but there’s no denying that life in medieval Europe kind of sucked. The only real alternative to serfdom was a job with the Catholic Church. Medieval friars, for example, lived in stone buildings, had access to fresh fruits and vegetables, and even had latrines and running water. Luxuries compared with the life of the average peasant.
So why then, despite having access to more modern sanitation and amenities, did the friars have so many gut parasites? That’s the question raised by a group of researchers from the University of Cambridge, who conducted a study of 19 medieval friars buried at a local friary (Oh, doesn’t your town have one of those?) and 25 local people buried at a nonreligious cemetery during a similar time period. Of those 19 friars, 11 were infected with worms and parasites, compared with just 8 of 25 townspeople.
This doesn’t make a lot of sense. The friars had a good life by old-time standards: They had basic sanitation down and a solid diet. These things should lead to a healthier population. The problem, the researchers found, is two pronged and a vicious cycle. First off, the friars had plenty of fresh food, but they used human feces to fertilize their produce. There’s a reason modern practice for human waste fertilization is to let the waste compost for 6 months: The waiting period allows the parasites a chance to kindly die off, which prevents reinfection.
Secondly, the friars’ diet of fresh fruits and vegetables mixed together into a salad, while appealing to our modern-day sensibilities, was not a great choice. By comparison, laypeople tended to eat a boiled mishmash of whatever they could find, and while that’s kind of gross, the key here is that their food was cooked. And heat kills parasites. The uncooked salads did no such thing, so the monks ate infected food, expelled infected poop, and grew more infected food with their infected poop.
Once the worms arrived, they never left, making them the worst kind of house guest. Read the room, worms, take your dinner and move on. You don’t have to go home, but you can’t stay here.
What’s a shared genotype between friends?
Do you find it hard to tell the difference between Katy Perry and Zooey Deschanel? They look alike, but they’re not related. Or are they? According to new research, people who look and act very similar but are not related may share DNA.
“Our study provides a rare insight into human likeness by showing that people with extreme look-alike faces share common genotypes, whereas they are discordant at the epigenome and microbiome levels,” senior author Manel Esteller of the Josep Carreras Leukemia Research Institute in Barcelona said in a written statement. “Genomics clusters them together, and the rest sets them apart.”
The Internet has been a great source in being able to find look-alikes. The research team found photos of doppelgangers photographed by François Brunelle, a Canadian artist. Using facial recognition algorithms, the investigators were able to measure likeness between the each pair of look-alikes. The participants also completed a questionnaire about lifestyle and provided a saliva sample.
The results showed that the look-alikes had similar genotypes but different DNA methylation and microbiome landscapes. The look-alikes also seemed to have similarities in weight, height, and behaviors such as smoking, proving that doppelgangers not only look alike but also share common interests.
Next time someone tells you that you look like their best friend Steve, you won’t have to wonder much what Steve is like.
The secret to a good relationship? It’s a secret
Strong relationships are built on honesty and trust, right? Being open with your partner and/or friends is usually a good practice for keeping the relationship healthy, but the latest evidence suggests that maybe you shouldn’t share everything.
According to the first known study on the emotional, behavioral, and relational aspect of consumer behavior, not disclosing certain purchases to your partner can actually be a good thing for the relationship. How? Well, it all has to do with guilt.
In a series of studies, the researchers asked couples about their secret consumptions. The most commonly hidden thing by far was a product (65%).
“We found that 90% of people have recently kept everyday consumer behaviors a secret from a close other – like a friend or spouse – even though they also report that they don’t think their partner would care if they knew about it,” Kelley Gullo Wight, one of the study’s two lead authors, said in a written statement.
Keeping a hidden stash of chocolate produces guilt, which the researchers found to be the key factor, making the perpetrator want to do more in the relationship to ease that sense of betrayal or dishonesty. They called it a “greater relationship investment,” meaning the person is more likely to do a little extra for their partner, like shell out more money for the next anniversary gift or yield to watching their partner’s favorite program.
So don’t feel too bad about that secret Amazon purchase. As long as the other person doesn’t see the box, nobody has to know. Your relationship can only improve.
Something about this COVID testing smells fishy
The Chinese have been challenging America’s political and economic hegemony (yes, we did have to look that one up – you’re rude to ask) for some time, but now they’ve gone too far. Are we going to just sit here and let China do something more ridiculous than us in response to COVID? No way!
Here’s the deal: The government of the Chinese coastal city of Xiamen has decided that it’s not just the workers on returning fishing boats who have the potential to introduce COVID to the rest of the population. The fish also present a problem. So when the authorities say that everyone needs to be tested before they can enter the city, they mean everyone.
An employee of the municipal ocean development bureau told local media that “all people in Xiamen City need nucleic acid testing, and the fish catches must be tested as well,” according to the Guardian, which also said that “TV news reports showed officials swabbing the mouths of fish and the underside of crabs.”
In the words of George Takei: “Oh my.”
Hold on there a second, George Takei, because we here in the good old US of A have still got Los Angeles, where COVID testing also has taken a nonhuman turn. The LA County public health department recently announced that pets are now eligible for a free SARS-CoV-2 test through veterinarians and other animal care facilities.
“Our goal is to test many different species of animals including wildlife (deer, bats, raccoons), pets (dogs, cats, hamsters, pocket pets), marine mammals (seals), and more,” Veterinary Public Health announced.
Hegemony restored.
Not even God could save them from worms
The Dark Ages may not have been as dark and violent as many people think, but there’s no denying that life in medieval Europe kind of sucked. The only real alternative to serfdom was a job with the Catholic Church. Medieval friars, for example, lived in stone buildings, had access to fresh fruits and vegetables, and even had latrines and running water. Luxuries compared with the life of the average peasant.
So why then, despite having access to more modern sanitation and amenities, did the friars have so many gut parasites? That’s the question raised by a group of researchers from the University of Cambridge, who conducted a study of 19 medieval friars buried at a local friary (Oh, doesn’t your town have one of those?) and 25 local people buried at a nonreligious cemetery during a similar time period. Of those 19 friars, 11 were infected with worms and parasites, compared with just 8 of 25 townspeople.
This doesn’t make a lot of sense. The friars had a good life by old-time standards: They had basic sanitation down and a solid diet. These things should lead to a healthier population. The problem, the researchers found, is two pronged and a vicious cycle. First off, the friars had plenty of fresh food, but they used human feces to fertilize their produce. There’s a reason modern practice for human waste fertilization is to let the waste compost for 6 months: The waiting period allows the parasites a chance to kindly die off, which prevents reinfection.
Secondly, the friars’ diet of fresh fruits and vegetables mixed together into a salad, while appealing to our modern-day sensibilities, was not a great choice. By comparison, laypeople tended to eat a boiled mishmash of whatever they could find, and while that’s kind of gross, the key here is that their food was cooked. And heat kills parasites. The uncooked salads did no such thing, so the monks ate infected food, expelled infected poop, and grew more infected food with their infected poop.
Once the worms arrived, they never left, making them the worst kind of house guest. Read the room, worms, take your dinner and move on. You don’t have to go home, but you can’t stay here.
What’s a shared genotype between friends?
Do you find it hard to tell the difference between Katy Perry and Zooey Deschanel? They look alike, but they’re not related. Or are they? According to new research, people who look and act very similar but are not related may share DNA.
“Our study provides a rare insight into human likeness by showing that people with extreme look-alike faces share common genotypes, whereas they are discordant at the epigenome and microbiome levels,” senior author Manel Esteller of the Josep Carreras Leukemia Research Institute in Barcelona said in a written statement. “Genomics clusters them together, and the rest sets them apart.”
The Internet has been a great source in being able to find look-alikes. The research team found photos of doppelgangers photographed by François Brunelle, a Canadian artist. Using facial recognition algorithms, the investigators were able to measure likeness between the each pair of look-alikes. The participants also completed a questionnaire about lifestyle and provided a saliva sample.
The results showed that the look-alikes had similar genotypes but different DNA methylation and microbiome landscapes. The look-alikes also seemed to have similarities in weight, height, and behaviors such as smoking, proving that doppelgangers not only look alike but also share common interests.
Next time someone tells you that you look like their best friend Steve, you won’t have to wonder much what Steve is like.
The secret to a good relationship? It’s a secret
Strong relationships are built on honesty and trust, right? Being open with your partner and/or friends is usually a good practice for keeping the relationship healthy, but the latest evidence suggests that maybe you shouldn’t share everything.
According to the first known study on the emotional, behavioral, and relational aspect of consumer behavior, not disclosing certain purchases to your partner can actually be a good thing for the relationship. How? Well, it all has to do with guilt.
In a series of studies, the researchers asked couples about their secret consumptions. The most commonly hidden thing by far was a product (65%).
“We found that 90% of people have recently kept everyday consumer behaviors a secret from a close other – like a friend or spouse – even though they also report that they don’t think their partner would care if they knew about it,” Kelley Gullo Wight, one of the study’s two lead authors, said in a written statement.
Keeping a hidden stash of chocolate produces guilt, which the researchers found to be the key factor, making the perpetrator want to do more in the relationship to ease that sense of betrayal or dishonesty. They called it a “greater relationship investment,” meaning the person is more likely to do a little extra for their partner, like shell out more money for the next anniversary gift or yield to watching their partner’s favorite program.
So don’t feel too bad about that secret Amazon purchase. As long as the other person doesn’t see the box, nobody has to know. Your relationship can only improve.