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Health care workers face unimaginable decisions in Ukraine
The effects of the Russian invasion of Ukraine have been devastating, with the loss of tens of thousands of civilian lives and about one-third of the population having been displaced. The war has put a great strain on health care in the country.
“The Russian army is targeting civilian infrastructure, trying to plunge Ukrainians into cold and darkness. (It) is also deliberately targeting hospitals and clinics in Ukraine,” said Nataliya Kovalchuk, PhD, during a session on Ukraine health care at the annual meeting of the American Society for Radiation Oncology held this week in San Antonio. She is a clinical associate professor of radiation oncology at Stanford (Calif.) University.
Analysis of previous wars have shown an increase in cancer incidence and mortality, and the same should be expected in the future in Ukraine, according to Ruslan Zelinskyi, MS, who is president of the Ukrainian Association of Medical Physicists and practices at Spizhenko Clinic in Ukraine. “We must prepare for it now, and we do it. During the full-scale war in Ukraine, three new linear accelerators were installed and put into clinical use,” he said during his talk.
He also gave a personal perspective of the terrible conditions and choices facing Ukrainian health care workers. “I have often heard that science is outside of politics. Perhaps in peacetime, but when fragments of missiles pass through the wall” – here, Mr. Zelinskyi paused to swing the camera around to show bomb damage on the walls of the room where he was conducting his virtual talk – “it is impossible to be outside of politics when 900 medical facilities were destroyed or damaged.” Health care workers have been killed, and patients have lost months or years because they could not receive medical care.
That reality is forcing Ukrainians to make choices most health care workers would struggle to imagine. “For many years, I put on medical clothes and fight against cancer. But (for) me comes the moment when I will change my medical clothes to military (clothes), like many, many other Ukrainians of various professions, because we must preserve the freedom of Ukraine and the security of Europe to do science in a peaceful world,” Mr. Zelinskyi said.
Following Mr. Zelinskyi’s talk, Asya Agulnik, MD, MPH, director of the St. Jude’s Global Critical Care Program and a pediatric intensivist at St. Jude’s Children’s Research Hospital, Memphis, described St. Jude’s efforts with pediatric cancer patients. St. Jude’s Global Critical Care Program created a Eurasian Regional Program in 2018 to serve Central Asia and Eastern Europe, which now includes 48 institutions and more than 250 clinicians and members that help care for children with cancer.
In the aftermath of the invasion, the Eurasian Regional Program launched the Safer Ukraine network to ensure continued care for children with cancer and blood disorders. Initially, the patient’s family or physician identifies a child has having a medical need that cannot be met locally and requiring evacuation. The nongovernmental organization Tabletochki, which has worked with children with cancer in Ukraine since 2011, then arranges transport of the child and his or her medical records to the Ukrainian Specialized Children’s Center in Lviv, Ukraine, for evaluation and stabilization. From there, patients along with their mother and sometimes siblings are transferred to Poland. Transportation methods include ambulance, helicopter, bus, and medical trains that have a full intensive care unit aboard.
In Poland, hospitals estimated they could take on another 200 patients without compromising care for their existing patients, but evacuations reached that number within the first few weeks of the war. It was clear patients would have to be transferred to other countries. To do that, Safer Ukraine set up the Unicorn Marian Wilemski Clinic, which is a converted hotel operated as a partnership between many foundations and governments. It sends unstable patients to nearby emergency rooms, and stable patients stay at the clinic until they can be evaluated and matched with an international care provider from a registry of more than 200 hospitals in 29 countries that have agreed to take patients. A 24/7 Zoom call began on the first day of the war, initially staffed by St. Jude volunteers and now by a contractor. It serves as a command center.
Over the first 12 weeks of the war, the program evacuated over 1,000 children, and over 200 medical records per week were being translated at peak activity. Nearly 300 patients went to Poland, and the rest to 18 countries in Europe and North America.
The success of the initiative stems in part from the fact that it leveraged preexisting collaborations that focused on childhood cancer, according to Dr. Agulnik. “Many stakeholders that came together had previously worked together, but then quickly came together around this unified initiative with the goal of helping these patients,” she said during her talk.
Roman Kowalchuk, MD, who is a radiation oncology resident at Mayo Clinic, spoke about telemedicine efforts to assist physicians and patients in Ukraine.
“I’ve been especially interested in trying to help through telemedicine. We have so much expertise, so many things that we can offer, even if we can’t be there physically, through some of these avenues that really, especially through COVID, have been further developed in terms of virtual support, virtual expertise, and consultations. That presents the opportunity to be able to share some of that knowledge, some of that expertise, to help clinical care in Ukraine given the current circumstance,” said Dr. Kowalchuk during his presentation.
Efforts have used technology like the telemedicine platform Viveo, based in Estonia. One app, called HealUA, takes descriptions from physicians needing advice, and volunteers can scroll through inquiries and provide input. This is especially useful since most physicians in Ukraine are generalists, according to Dr. Kowalchuk, and so may need assistance with diagnosis and management of rare conditions.
Other telehealth approaches include TeleHelp Ukraine. There are WhatsApp groups with hundreds of volunteers who translate Ukrainian medical records to other languages to help non-Ukrainian physicians understand a patient’s history. Expertise is also needed in engineering, emergency medicine, surgery, various fields of oncology, and other specialties. Dr. Kowalchuk noted that Good Samaritan laws generally shield volunteers in these types of programs from legal liability.
International hospital networks taking part in these efforts include St. Jude, European Cancer Organization, American Cancer Society, American Society for Clinical Oncology, and ASTRO.
None of the presenters have relevant financial disclosures.
The effects of the Russian invasion of Ukraine have been devastating, with the loss of tens of thousands of civilian lives and about one-third of the population having been displaced. The war has put a great strain on health care in the country.
“The Russian army is targeting civilian infrastructure, trying to plunge Ukrainians into cold and darkness. (It) is also deliberately targeting hospitals and clinics in Ukraine,” said Nataliya Kovalchuk, PhD, during a session on Ukraine health care at the annual meeting of the American Society for Radiation Oncology held this week in San Antonio. She is a clinical associate professor of radiation oncology at Stanford (Calif.) University.
Analysis of previous wars have shown an increase in cancer incidence and mortality, and the same should be expected in the future in Ukraine, according to Ruslan Zelinskyi, MS, who is president of the Ukrainian Association of Medical Physicists and practices at Spizhenko Clinic in Ukraine. “We must prepare for it now, and we do it. During the full-scale war in Ukraine, three new linear accelerators were installed and put into clinical use,” he said during his talk.
He also gave a personal perspective of the terrible conditions and choices facing Ukrainian health care workers. “I have often heard that science is outside of politics. Perhaps in peacetime, but when fragments of missiles pass through the wall” – here, Mr. Zelinskyi paused to swing the camera around to show bomb damage on the walls of the room where he was conducting his virtual talk – “it is impossible to be outside of politics when 900 medical facilities were destroyed or damaged.” Health care workers have been killed, and patients have lost months or years because they could not receive medical care.
That reality is forcing Ukrainians to make choices most health care workers would struggle to imagine. “For many years, I put on medical clothes and fight against cancer. But (for) me comes the moment when I will change my medical clothes to military (clothes), like many, many other Ukrainians of various professions, because we must preserve the freedom of Ukraine and the security of Europe to do science in a peaceful world,” Mr. Zelinskyi said.
Following Mr. Zelinskyi’s talk, Asya Agulnik, MD, MPH, director of the St. Jude’s Global Critical Care Program and a pediatric intensivist at St. Jude’s Children’s Research Hospital, Memphis, described St. Jude’s efforts with pediatric cancer patients. St. Jude’s Global Critical Care Program created a Eurasian Regional Program in 2018 to serve Central Asia and Eastern Europe, which now includes 48 institutions and more than 250 clinicians and members that help care for children with cancer.
In the aftermath of the invasion, the Eurasian Regional Program launched the Safer Ukraine network to ensure continued care for children with cancer and blood disorders. Initially, the patient’s family or physician identifies a child has having a medical need that cannot be met locally and requiring evacuation. The nongovernmental organization Tabletochki, which has worked with children with cancer in Ukraine since 2011, then arranges transport of the child and his or her medical records to the Ukrainian Specialized Children’s Center in Lviv, Ukraine, for evaluation and stabilization. From there, patients along with their mother and sometimes siblings are transferred to Poland. Transportation methods include ambulance, helicopter, bus, and medical trains that have a full intensive care unit aboard.
In Poland, hospitals estimated they could take on another 200 patients without compromising care for their existing patients, but evacuations reached that number within the first few weeks of the war. It was clear patients would have to be transferred to other countries. To do that, Safer Ukraine set up the Unicorn Marian Wilemski Clinic, which is a converted hotel operated as a partnership between many foundations and governments. It sends unstable patients to nearby emergency rooms, and stable patients stay at the clinic until they can be evaluated and matched with an international care provider from a registry of more than 200 hospitals in 29 countries that have agreed to take patients. A 24/7 Zoom call began on the first day of the war, initially staffed by St. Jude volunteers and now by a contractor. It serves as a command center.
Over the first 12 weeks of the war, the program evacuated over 1,000 children, and over 200 medical records per week were being translated at peak activity. Nearly 300 patients went to Poland, and the rest to 18 countries in Europe and North America.
The success of the initiative stems in part from the fact that it leveraged preexisting collaborations that focused on childhood cancer, according to Dr. Agulnik. “Many stakeholders that came together had previously worked together, but then quickly came together around this unified initiative with the goal of helping these patients,” she said during her talk.
Roman Kowalchuk, MD, who is a radiation oncology resident at Mayo Clinic, spoke about telemedicine efforts to assist physicians and patients in Ukraine.
“I’ve been especially interested in trying to help through telemedicine. We have so much expertise, so many things that we can offer, even if we can’t be there physically, through some of these avenues that really, especially through COVID, have been further developed in terms of virtual support, virtual expertise, and consultations. That presents the opportunity to be able to share some of that knowledge, some of that expertise, to help clinical care in Ukraine given the current circumstance,” said Dr. Kowalchuk during his presentation.
Efforts have used technology like the telemedicine platform Viveo, based in Estonia. One app, called HealUA, takes descriptions from physicians needing advice, and volunteers can scroll through inquiries and provide input. This is especially useful since most physicians in Ukraine are generalists, according to Dr. Kowalchuk, and so may need assistance with diagnosis and management of rare conditions.
Other telehealth approaches include TeleHelp Ukraine. There are WhatsApp groups with hundreds of volunteers who translate Ukrainian medical records to other languages to help non-Ukrainian physicians understand a patient’s history. Expertise is also needed in engineering, emergency medicine, surgery, various fields of oncology, and other specialties. Dr. Kowalchuk noted that Good Samaritan laws generally shield volunteers in these types of programs from legal liability.
International hospital networks taking part in these efforts include St. Jude, European Cancer Organization, American Cancer Society, American Society for Clinical Oncology, and ASTRO.
None of the presenters have relevant financial disclosures.
The effects of the Russian invasion of Ukraine have been devastating, with the loss of tens of thousands of civilian lives and about one-third of the population having been displaced. The war has put a great strain on health care in the country.
“The Russian army is targeting civilian infrastructure, trying to plunge Ukrainians into cold and darkness. (It) is also deliberately targeting hospitals and clinics in Ukraine,” said Nataliya Kovalchuk, PhD, during a session on Ukraine health care at the annual meeting of the American Society for Radiation Oncology held this week in San Antonio. She is a clinical associate professor of radiation oncology at Stanford (Calif.) University.
Analysis of previous wars have shown an increase in cancer incidence and mortality, and the same should be expected in the future in Ukraine, according to Ruslan Zelinskyi, MS, who is president of the Ukrainian Association of Medical Physicists and practices at Spizhenko Clinic in Ukraine. “We must prepare for it now, and we do it. During the full-scale war in Ukraine, three new linear accelerators were installed and put into clinical use,” he said during his talk.
He also gave a personal perspective of the terrible conditions and choices facing Ukrainian health care workers. “I have often heard that science is outside of politics. Perhaps in peacetime, but when fragments of missiles pass through the wall” – here, Mr. Zelinskyi paused to swing the camera around to show bomb damage on the walls of the room where he was conducting his virtual talk – “it is impossible to be outside of politics when 900 medical facilities were destroyed or damaged.” Health care workers have been killed, and patients have lost months or years because they could not receive medical care.
That reality is forcing Ukrainians to make choices most health care workers would struggle to imagine. “For many years, I put on medical clothes and fight against cancer. But (for) me comes the moment when I will change my medical clothes to military (clothes), like many, many other Ukrainians of various professions, because we must preserve the freedom of Ukraine and the security of Europe to do science in a peaceful world,” Mr. Zelinskyi said.
Following Mr. Zelinskyi’s talk, Asya Agulnik, MD, MPH, director of the St. Jude’s Global Critical Care Program and a pediatric intensivist at St. Jude’s Children’s Research Hospital, Memphis, described St. Jude’s efforts with pediatric cancer patients. St. Jude’s Global Critical Care Program created a Eurasian Regional Program in 2018 to serve Central Asia and Eastern Europe, which now includes 48 institutions and more than 250 clinicians and members that help care for children with cancer.
In the aftermath of the invasion, the Eurasian Regional Program launched the Safer Ukraine network to ensure continued care for children with cancer and blood disorders. Initially, the patient’s family or physician identifies a child has having a medical need that cannot be met locally and requiring evacuation. The nongovernmental organization Tabletochki, which has worked with children with cancer in Ukraine since 2011, then arranges transport of the child and his or her medical records to the Ukrainian Specialized Children’s Center in Lviv, Ukraine, for evaluation and stabilization. From there, patients along with their mother and sometimes siblings are transferred to Poland. Transportation methods include ambulance, helicopter, bus, and medical trains that have a full intensive care unit aboard.
In Poland, hospitals estimated they could take on another 200 patients without compromising care for their existing patients, but evacuations reached that number within the first few weeks of the war. It was clear patients would have to be transferred to other countries. To do that, Safer Ukraine set up the Unicorn Marian Wilemski Clinic, which is a converted hotel operated as a partnership between many foundations and governments. It sends unstable patients to nearby emergency rooms, and stable patients stay at the clinic until they can be evaluated and matched with an international care provider from a registry of more than 200 hospitals in 29 countries that have agreed to take patients. A 24/7 Zoom call began on the first day of the war, initially staffed by St. Jude volunteers and now by a contractor. It serves as a command center.
Over the first 12 weeks of the war, the program evacuated over 1,000 children, and over 200 medical records per week were being translated at peak activity. Nearly 300 patients went to Poland, and the rest to 18 countries in Europe and North America.
The success of the initiative stems in part from the fact that it leveraged preexisting collaborations that focused on childhood cancer, according to Dr. Agulnik. “Many stakeholders that came together had previously worked together, but then quickly came together around this unified initiative with the goal of helping these patients,” she said during her talk.
Roman Kowalchuk, MD, who is a radiation oncology resident at Mayo Clinic, spoke about telemedicine efforts to assist physicians and patients in Ukraine.
“I’ve been especially interested in trying to help through telemedicine. We have so much expertise, so many things that we can offer, even if we can’t be there physically, through some of these avenues that really, especially through COVID, have been further developed in terms of virtual support, virtual expertise, and consultations. That presents the opportunity to be able to share some of that knowledge, some of that expertise, to help clinical care in Ukraine given the current circumstance,” said Dr. Kowalchuk during his presentation.
Efforts have used technology like the telemedicine platform Viveo, based in Estonia. One app, called HealUA, takes descriptions from physicians needing advice, and volunteers can scroll through inquiries and provide input. This is especially useful since most physicians in Ukraine are generalists, according to Dr. Kowalchuk, and so may need assistance with diagnosis and management of rare conditions.
Other telehealth approaches include TeleHelp Ukraine. There are WhatsApp groups with hundreds of volunteers who translate Ukrainian medical records to other languages to help non-Ukrainian physicians understand a patient’s history. Expertise is also needed in engineering, emergency medicine, surgery, various fields of oncology, and other specialties. Dr. Kowalchuk noted that Good Samaritan laws generally shield volunteers in these types of programs from legal liability.
International hospital networks taking part in these efforts include St. Jude, European Cancer Organization, American Cancer Society, American Society for Clinical Oncology, and ASTRO.
None of the presenters have relevant financial disclosures.
FROM ASTRO 2022
Brussels terror attack victim euthanized in Belgium at age 23
This article was originally published on MediQuality.com, an online service for health care professionals in the Benelux and a member of the Medscape Professional Network.
Performing euthanasia for “mental suffering that cannot be alleviated” is still considered an extraordinary measure in Belgium. Indeed, fewer than 2% of the requests for euthanasia fall within that category, and few such requests are made by young patients.
to be applicable. It’s something that Belgian broadcaster RTBF brought up during a recent episode of #Investigation, which reported on the aftermath of the 2016 Brussels attacks.
On May 7, surrounded by her family, Ms. De Corte was euthanized. She was 23 years old. Six years earlier, on March 22, 2016, Ms. De Corte had been at Brussels Airport when terrorists set off bombs. She was in the departures area with 90 other students from Sint-Rita Campus College, located in the northern town of Kontich. Ms. De Corte was only a few meters away from the blast. Although she was not physically injured, the Flemish teen was traumatized by the attack. This was confirmed by the school psychologist who treated the students. “There were some students who reacted worse than others to these traumatic events. And having had two discussions with Shanti, I can tell you that she was one of these students who were more sensitive to the effects. To me, it’s quite clear. Even before the attacks, she’d experienced serious psychological issues. Therefore, I referred her for psychiatric care.”
Eleven antidepressants daily
A few weeks after that March day, Ms. De Corte was admitted to a psychiatric hospital in Antwerp. It was a place she knew well, having been an inpatient there several times before the attacks. Ms. De Corte was treated with antidepressants. She shared her thoughts about them on numerous occasions. “I get several drugs at breakfast and up to 11 antidepressants a day. I couldn’t do without them. With all the drugs I take, I feel like a ghost who doesn’t feel anything anymore. Perhaps there were solutions other than the drugs.”
It was a brief respite. In 2020, Ms. De Corte attempted suicide. Her spirits were at their lowest. She was heavily medicated, and her medication had been increased over time. She turned down therapeutic help that was offered by a therapist who specializes in treating the victims of the Brussels attacks. The student got in touch with the Life End Information Forum, an association that supports the right to die with dignity. In April 2022, Ms. De Corte submitted a new euthanasia request, stating that she was in a medically futile condition of mental suffering. Two psychiatrists granted their approval.
A small proportion
Last March, Belgium’s Federal Commission for the Control and Evaluation of Euthanasia reported on data from 2021. “There continues to be a very small number of euthanasia requests that cite mental and behavioral disorders (psychiatric conditions, such as personality disorders, and cognitive issues, like Alzheimer’s disease, are included in this group): 1.9% of all cases of euthanasia. Like all euthanasia files, these requests meet the legal conditions (the patient is legally competent, the request is in writing, the condition is medically futile, and the suffering – which is constant, unbearable, and cannot be alleviated – results from a serious and incurable disorder; the request is well-considered and repeated),” the report states.
This article was translated from MediQuality and appeared on Medscape.com.
This article was originally published on MediQuality.com, an online service for health care professionals in the Benelux and a member of the Medscape Professional Network.
Performing euthanasia for “mental suffering that cannot be alleviated” is still considered an extraordinary measure in Belgium. Indeed, fewer than 2% of the requests for euthanasia fall within that category, and few such requests are made by young patients.
to be applicable. It’s something that Belgian broadcaster RTBF brought up during a recent episode of #Investigation, which reported on the aftermath of the 2016 Brussels attacks.
On May 7, surrounded by her family, Ms. De Corte was euthanized. She was 23 years old. Six years earlier, on March 22, 2016, Ms. De Corte had been at Brussels Airport when terrorists set off bombs. She was in the departures area with 90 other students from Sint-Rita Campus College, located in the northern town of Kontich. Ms. De Corte was only a few meters away from the blast. Although she was not physically injured, the Flemish teen was traumatized by the attack. This was confirmed by the school psychologist who treated the students. “There were some students who reacted worse than others to these traumatic events. And having had two discussions with Shanti, I can tell you that she was one of these students who were more sensitive to the effects. To me, it’s quite clear. Even before the attacks, she’d experienced serious psychological issues. Therefore, I referred her for psychiatric care.”
Eleven antidepressants daily
A few weeks after that March day, Ms. De Corte was admitted to a psychiatric hospital in Antwerp. It was a place she knew well, having been an inpatient there several times before the attacks. Ms. De Corte was treated with antidepressants. She shared her thoughts about them on numerous occasions. “I get several drugs at breakfast and up to 11 antidepressants a day. I couldn’t do without them. With all the drugs I take, I feel like a ghost who doesn’t feel anything anymore. Perhaps there were solutions other than the drugs.”
It was a brief respite. In 2020, Ms. De Corte attempted suicide. Her spirits were at their lowest. She was heavily medicated, and her medication had been increased over time. She turned down therapeutic help that was offered by a therapist who specializes in treating the victims of the Brussels attacks. The student got in touch with the Life End Information Forum, an association that supports the right to die with dignity. In April 2022, Ms. De Corte submitted a new euthanasia request, stating that she was in a medically futile condition of mental suffering. Two psychiatrists granted their approval.
A small proportion
Last March, Belgium’s Federal Commission for the Control and Evaluation of Euthanasia reported on data from 2021. “There continues to be a very small number of euthanasia requests that cite mental and behavioral disorders (psychiatric conditions, such as personality disorders, and cognitive issues, like Alzheimer’s disease, are included in this group): 1.9% of all cases of euthanasia. Like all euthanasia files, these requests meet the legal conditions (the patient is legally competent, the request is in writing, the condition is medically futile, and the suffering – which is constant, unbearable, and cannot be alleviated – results from a serious and incurable disorder; the request is well-considered and repeated),” the report states.
This article was translated from MediQuality and appeared on Medscape.com.
This article was originally published on MediQuality.com, an online service for health care professionals in the Benelux and a member of the Medscape Professional Network.
Performing euthanasia for “mental suffering that cannot be alleviated” is still considered an extraordinary measure in Belgium. Indeed, fewer than 2% of the requests for euthanasia fall within that category, and few such requests are made by young patients.
to be applicable. It’s something that Belgian broadcaster RTBF brought up during a recent episode of #Investigation, which reported on the aftermath of the 2016 Brussels attacks.
On May 7, surrounded by her family, Ms. De Corte was euthanized. She was 23 years old. Six years earlier, on March 22, 2016, Ms. De Corte had been at Brussels Airport when terrorists set off bombs. She was in the departures area with 90 other students from Sint-Rita Campus College, located in the northern town of Kontich. Ms. De Corte was only a few meters away from the blast. Although she was not physically injured, the Flemish teen was traumatized by the attack. This was confirmed by the school psychologist who treated the students. “There were some students who reacted worse than others to these traumatic events. And having had two discussions with Shanti, I can tell you that she was one of these students who were more sensitive to the effects. To me, it’s quite clear. Even before the attacks, she’d experienced serious psychological issues. Therefore, I referred her for psychiatric care.”
Eleven antidepressants daily
A few weeks after that March day, Ms. De Corte was admitted to a psychiatric hospital in Antwerp. It was a place she knew well, having been an inpatient there several times before the attacks. Ms. De Corte was treated with antidepressants. She shared her thoughts about them on numerous occasions. “I get several drugs at breakfast and up to 11 antidepressants a day. I couldn’t do without them. With all the drugs I take, I feel like a ghost who doesn’t feel anything anymore. Perhaps there were solutions other than the drugs.”
It was a brief respite. In 2020, Ms. De Corte attempted suicide. Her spirits were at their lowest. She was heavily medicated, and her medication had been increased over time. She turned down therapeutic help that was offered by a therapist who specializes in treating the victims of the Brussels attacks. The student got in touch with the Life End Information Forum, an association that supports the right to die with dignity. In April 2022, Ms. De Corte submitted a new euthanasia request, stating that she was in a medically futile condition of mental suffering. Two psychiatrists granted their approval.
A small proportion
Last March, Belgium’s Federal Commission for the Control and Evaluation of Euthanasia reported on data from 2021. “There continues to be a very small number of euthanasia requests that cite mental and behavioral disorders (psychiatric conditions, such as personality disorders, and cognitive issues, like Alzheimer’s disease, are included in this group): 1.9% of all cases of euthanasia. Like all euthanasia files, these requests meet the legal conditions (the patient is legally competent, the request is in writing, the condition is medically futile, and the suffering – which is constant, unbearable, and cannot be alleviated – results from a serious and incurable disorder; the request is well-considered and repeated),” the report states.
This article was translated from MediQuality and appeared on Medscape.com.
Vitamin D deficiency linked to death, new study finds
Vitamin D deficiency increases mortality risk and raising levels even slightly could decrease the risk, researchers examining data from the UK Biobank have found.
They used a Mendelian randomization approach, which uses genetic variants as “proxy indicators” for external factors that affect vitamin D levels, such as sun exposure or dietary intake. It allows for analysis of the relationship between deficiency and outcomes including mortality, which can’t be done in randomized clinical trials for ethical reasons.
Using this method, nutritionist Joshua P. Sutherland, PhD, of the Australian Centre for Precision Health, Adelaide, and colleagues found an association between genetically predicted vitamin D levels [25-(OH)D] and mortality from several major causes, with evidence of causality among people with measured concentrations below, but not above, 50 nmol/L. The findings were published online in Annals of Internal Medicine.
“Unlike other types of observational studies, we have overcome some of the methodological obstacles. What is special about this new study is we were able to look at people with very low vitamin D concentrations and what would happen if their concentrations were a little bit higher. Most randomized controlled trials don’t show much of an effect. That’s because most people have sufficient concentrations. Ethically you can’t do a trial of people with very low levels without treating them,” senior author Elina Hypp
The data support the 50 nmol/L cut-off endorsed by the United States National Academy of Medicine and align with previous data suggesting the benefit of vitamin D supplementation is largely seen in people with deficiency.
“Everybody with vitamin D levels less than 50 nmol/L is recommended to increase their levels. Our results suggest there’s no need to go very high. The positive message is that if we are able to raise levels to just the current U.S. recommendations, that’s fine. There’s no need to use large supplement doses,” Dr. Hyppönen explained.
Thus, she advised, “Supplementation will clearly help, especially during wintertime or if a person isn’t getting enough vitamin D from the sun or in places where food isn’t fortified with vitamin D.”
But the data don’t support the approach of using large intermittent doses, she added.
“Sometimes doctors want to fix the deficiency quickly with a large ‘bolus’ dose, then continue with a maintenance dose. Increasing evidence suggests that’s not beneficial and might disturb the body’s metabolism so that it can’t get the amount it needs. It’s safe overall but might not work the way we want it to work.”
Rather, Dr. Hyppönen said, “My sense is that daily modest vitamin D dose supplementation when it’s needed is the best way forward.”
Genetic approach reveals causal relationship
The investigators analyzed data from 307,601 individuals in the UK Biobank, a prospective cohort of people recruited from England, Scotland, and Wales during March 2006 and July 2010. Most were of White European ancestry and were aged 37-73 years at baseline.
Genetically predicted vitamin D levels were estimated using 35 confirmed 25-(OH)D variants. Participants were followed for outcomes up to June 2020.
The average baseline measured 25-(OH)D concentration was 45.2 nmol/L, and 11.7% (n = 36,009) of participants had levels between 10.0 and 24.9 nmol/L. Higher levels were seen in people living in southern areas and nonsmokers as well as those with a higher level of physical activity, less socioeconomic deprivation, and lower body mass index.
During follow-up, 6.1% of participants died (n = 18,700). After adjustment for variables, odds ratios for all causes of mortality were highest among people with 25-(OH)D levels below 25 nmol/L and appeared to plateau between 50 and 75 nmol/L, with no further reduction in mortality at values of 75-125 nmol/L.
Mortality 36% higher in those deficient in vitamin D
The risk for mortality was a significant 36% higher for participants with 25-(OH)D 25 nmol/L compared with 50 nmol/L.
With the Mendelian randomization, there was an L-shaped association between genetically predicted 25-(OH)D level and all-cause mortality (P for nonlinearity < .001) and for mortality because of cancer and cardiovascular disease (P for nonlinearity ≤ .033).
Again, the strongest association with those outcomes and genetically predicted 25-(OH)D was found at levels below 25 nmol/L and a plateau was seen by 50 nmol/L.
Compared with a measured 25-(OH)D concentration of 50 nmol/L, investigators estimated that the genetically predicted odds of all-cause mortality would increase sixfold (odds ratio, 6.00) for participants at 10 nmol/L and by 25% (OR, 1.25) for those at 25 nmol/L.
And, compared with a measured 25-(OH)D concentration of 50 nmol/L, those with 10 nmol/L had genetically predicted odds ratios of 5.98 for cardiovascular mortality, 3.37 for cancer mortality, and 12.44 for respiratory mortality.
Comparing measured 25-(OH)D concentrations of 25 nmol/L versus 50 nmol/L, odds ratios for those outcomes were 1.25, 1.16, and 1.96 (95% confidence interval, 1.88-4.67), respectively. All were statistically significant.
Consistent results supportive of a causal effect of genetically predicted 25-(OH)D on all-cause mortality in those with low measured vitamin D concentrations were also found in a sensitivity analysis of 20,837 people of non-White ethnic origin.
The study was funded by the Australian National Health and Medical Research Council. Dr. Sutherland’s studentship is funded by an Australian Research Training Program Scholarship.
A version of this article first appeared on Medscape.com.
Vitamin D deficiency increases mortality risk and raising levels even slightly could decrease the risk, researchers examining data from the UK Biobank have found.
They used a Mendelian randomization approach, which uses genetic variants as “proxy indicators” for external factors that affect vitamin D levels, such as sun exposure or dietary intake. It allows for analysis of the relationship between deficiency and outcomes including mortality, which can’t be done in randomized clinical trials for ethical reasons.
Using this method, nutritionist Joshua P. Sutherland, PhD, of the Australian Centre for Precision Health, Adelaide, and colleagues found an association between genetically predicted vitamin D levels [25-(OH)D] and mortality from several major causes, with evidence of causality among people with measured concentrations below, but not above, 50 nmol/L. The findings were published online in Annals of Internal Medicine.
“Unlike other types of observational studies, we have overcome some of the methodological obstacles. What is special about this new study is we were able to look at people with very low vitamin D concentrations and what would happen if their concentrations were a little bit higher. Most randomized controlled trials don’t show much of an effect. That’s because most people have sufficient concentrations. Ethically you can’t do a trial of people with very low levels without treating them,” senior author Elina Hypp
The data support the 50 nmol/L cut-off endorsed by the United States National Academy of Medicine and align with previous data suggesting the benefit of vitamin D supplementation is largely seen in people with deficiency.
“Everybody with vitamin D levels less than 50 nmol/L is recommended to increase their levels. Our results suggest there’s no need to go very high. The positive message is that if we are able to raise levels to just the current U.S. recommendations, that’s fine. There’s no need to use large supplement doses,” Dr. Hyppönen explained.
Thus, she advised, “Supplementation will clearly help, especially during wintertime or if a person isn’t getting enough vitamin D from the sun or in places where food isn’t fortified with vitamin D.”
But the data don’t support the approach of using large intermittent doses, she added.
“Sometimes doctors want to fix the deficiency quickly with a large ‘bolus’ dose, then continue with a maintenance dose. Increasing evidence suggests that’s not beneficial and might disturb the body’s metabolism so that it can’t get the amount it needs. It’s safe overall but might not work the way we want it to work.”
Rather, Dr. Hyppönen said, “My sense is that daily modest vitamin D dose supplementation when it’s needed is the best way forward.”
Genetic approach reveals causal relationship
The investigators analyzed data from 307,601 individuals in the UK Biobank, a prospective cohort of people recruited from England, Scotland, and Wales during March 2006 and July 2010. Most were of White European ancestry and were aged 37-73 years at baseline.
Genetically predicted vitamin D levels were estimated using 35 confirmed 25-(OH)D variants. Participants were followed for outcomes up to June 2020.
The average baseline measured 25-(OH)D concentration was 45.2 nmol/L, and 11.7% (n = 36,009) of participants had levels between 10.0 and 24.9 nmol/L. Higher levels were seen in people living in southern areas and nonsmokers as well as those with a higher level of physical activity, less socioeconomic deprivation, and lower body mass index.
During follow-up, 6.1% of participants died (n = 18,700). After adjustment for variables, odds ratios for all causes of mortality were highest among people with 25-(OH)D levels below 25 nmol/L and appeared to plateau between 50 and 75 nmol/L, with no further reduction in mortality at values of 75-125 nmol/L.
Mortality 36% higher in those deficient in vitamin D
The risk for mortality was a significant 36% higher for participants with 25-(OH)D 25 nmol/L compared with 50 nmol/L.
With the Mendelian randomization, there was an L-shaped association between genetically predicted 25-(OH)D level and all-cause mortality (P for nonlinearity < .001) and for mortality because of cancer and cardiovascular disease (P for nonlinearity ≤ .033).
Again, the strongest association with those outcomes and genetically predicted 25-(OH)D was found at levels below 25 nmol/L and a plateau was seen by 50 nmol/L.
Compared with a measured 25-(OH)D concentration of 50 nmol/L, investigators estimated that the genetically predicted odds of all-cause mortality would increase sixfold (odds ratio, 6.00) for participants at 10 nmol/L and by 25% (OR, 1.25) for those at 25 nmol/L.
And, compared with a measured 25-(OH)D concentration of 50 nmol/L, those with 10 nmol/L had genetically predicted odds ratios of 5.98 for cardiovascular mortality, 3.37 for cancer mortality, and 12.44 for respiratory mortality.
Comparing measured 25-(OH)D concentrations of 25 nmol/L versus 50 nmol/L, odds ratios for those outcomes were 1.25, 1.16, and 1.96 (95% confidence interval, 1.88-4.67), respectively. All were statistically significant.
Consistent results supportive of a causal effect of genetically predicted 25-(OH)D on all-cause mortality in those with low measured vitamin D concentrations were also found in a sensitivity analysis of 20,837 people of non-White ethnic origin.
The study was funded by the Australian National Health and Medical Research Council. Dr. Sutherland’s studentship is funded by an Australian Research Training Program Scholarship.
A version of this article first appeared on Medscape.com.
Vitamin D deficiency increases mortality risk and raising levels even slightly could decrease the risk, researchers examining data from the UK Biobank have found.
They used a Mendelian randomization approach, which uses genetic variants as “proxy indicators” for external factors that affect vitamin D levels, such as sun exposure or dietary intake. It allows for analysis of the relationship between deficiency and outcomes including mortality, which can’t be done in randomized clinical trials for ethical reasons.
Using this method, nutritionist Joshua P. Sutherland, PhD, of the Australian Centre for Precision Health, Adelaide, and colleagues found an association between genetically predicted vitamin D levels [25-(OH)D] and mortality from several major causes, with evidence of causality among people with measured concentrations below, but not above, 50 nmol/L. The findings were published online in Annals of Internal Medicine.
“Unlike other types of observational studies, we have overcome some of the methodological obstacles. What is special about this new study is we were able to look at people with very low vitamin D concentrations and what would happen if their concentrations were a little bit higher. Most randomized controlled trials don’t show much of an effect. That’s because most people have sufficient concentrations. Ethically you can’t do a trial of people with very low levels without treating them,” senior author Elina Hypp
The data support the 50 nmol/L cut-off endorsed by the United States National Academy of Medicine and align with previous data suggesting the benefit of vitamin D supplementation is largely seen in people with deficiency.
“Everybody with vitamin D levels less than 50 nmol/L is recommended to increase their levels. Our results suggest there’s no need to go very high. The positive message is that if we are able to raise levels to just the current U.S. recommendations, that’s fine. There’s no need to use large supplement doses,” Dr. Hyppönen explained.
Thus, she advised, “Supplementation will clearly help, especially during wintertime or if a person isn’t getting enough vitamin D from the sun or in places where food isn’t fortified with vitamin D.”
But the data don’t support the approach of using large intermittent doses, she added.
“Sometimes doctors want to fix the deficiency quickly with a large ‘bolus’ dose, then continue with a maintenance dose. Increasing evidence suggests that’s not beneficial and might disturb the body’s metabolism so that it can’t get the amount it needs. It’s safe overall but might not work the way we want it to work.”
Rather, Dr. Hyppönen said, “My sense is that daily modest vitamin D dose supplementation when it’s needed is the best way forward.”
Genetic approach reveals causal relationship
The investigators analyzed data from 307,601 individuals in the UK Biobank, a prospective cohort of people recruited from England, Scotland, and Wales during March 2006 and July 2010. Most were of White European ancestry and were aged 37-73 years at baseline.
Genetically predicted vitamin D levels were estimated using 35 confirmed 25-(OH)D variants. Participants were followed for outcomes up to June 2020.
The average baseline measured 25-(OH)D concentration was 45.2 nmol/L, and 11.7% (n = 36,009) of participants had levels between 10.0 and 24.9 nmol/L. Higher levels were seen in people living in southern areas and nonsmokers as well as those with a higher level of physical activity, less socioeconomic deprivation, and lower body mass index.
During follow-up, 6.1% of participants died (n = 18,700). After adjustment for variables, odds ratios for all causes of mortality were highest among people with 25-(OH)D levels below 25 nmol/L and appeared to plateau between 50 and 75 nmol/L, with no further reduction in mortality at values of 75-125 nmol/L.
Mortality 36% higher in those deficient in vitamin D
The risk for mortality was a significant 36% higher for participants with 25-(OH)D 25 nmol/L compared with 50 nmol/L.
With the Mendelian randomization, there was an L-shaped association between genetically predicted 25-(OH)D level and all-cause mortality (P for nonlinearity < .001) and for mortality because of cancer and cardiovascular disease (P for nonlinearity ≤ .033).
Again, the strongest association with those outcomes and genetically predicted 25-(OH)D was found at levels below 25 nmol/L and a plateau was seen by 50 nmol/L.
Compared with a measured 25-(OH)D concentration of 50 nmol/L, investigators estimated that the genetically predicted odds of all-cause mortality would increase sixfold (odds ratio, 6.00) for participants at 10 nmol/L and by 25% (OR, 1.25) for those at 25 nmol/L.
And, compared with a measured 25-(OH)D concentration of 50 nmol/L, those with 10 nmol/L had genetically predicted odds ratios of 5.98 for cardiovascular mortality, 3.37 for cancer mortality, and 12.44 for respiratory mortality.
Comparing measured 25-(OH)D concentrations of 25 nmol/L versus 50 nmol/L, odds ratios for those outcomes were 1.25, 1.16, and 1.96 (95% confidence interval, 1.88-4.67), respectively. All were statistically significant.
Consistent results supportive of a causal effect of genetically predicted 25-(OH)D on all-cause mortality in those with low measured vitamin D concentrations were also found in a sensitivity analysis of 20,837 people of non-White ethnic origin.
The study was funded by the Australian National Health and Medical Research Council. Dr. Sutherland’s studentship is funded by an Australian Research Training Program Scholarship.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
Four commonly abused drugs linked with atrial fibrillation
Cocaine, methamphetamine, opioids, and cannabis may independently increase risk of atrial fibrillation (AFib), based on data from almost 24 million people.
While more work is needed to uncover causal links, physicians should be aware that these commonly abused substances could be driving new cases of AFib, reported investigators from the University of California, San Francisco.
“Though alcohol and tobacco smoking have each been associated with a heightened risk of [AFib], relationships between other drug use and [AFib] are poorly understood,” they wrote in European Heart Journal.
Some previous studies have ventured into this terrain, but most focused on fatal arrhythmias, or offered anecdotal evidence. This knowledge gap is particularly concerning for cannabis, the researchers noted, as medical and recreational use are on the rise.
The present analysis included data from 23.5 million adults in California who received care through a hospital, emergency department, or outpatient surgery center during 2005-2015. Based on ICD-9 diagnostic codes, 132,834 of these patients used cannabis, 98,271 used methamphetamines, 48,701 used cocaine, and 10,032 used opiates. Inclusion required lack of AFib at baseline.
Reliance on ICD-9 codes makes the data “quite specific,” but lacking sensitivity, according to principal author Gregory M. Marcus, MD, cardiologist and professor of medicine at UCSF.
“If they were designated as using these drugs, that is very likely true,” Dr. Marcus said in an interview. “But certainly, the absence of any mention of use of these drugs does not exclude the possibility that some people were still using them. That would not create spurious false-positive relationships; if anything, it attenuates existing relationships.”
In other words, using ICD-9 codes reduced the power to detect an association between each drug and AFib, meaning any relationship needed to be sufficiently strong enough to generate a significant result.
At the end of the decade-long study period, 998,747 patients (4.2%) had developed incident AFib. After adjusting for potential confounders and mediators, all four drugs showed significant, independent associations with AFib. Methamphetamines presented the greatest risk (hazard ratio, 1.86%), followed by opiates (HR, 1.74), cocaine (HR, 1.61), and cannabis (HR, 1.35).
“Our findings provide the first evidence utilizing a longitudinal cohort to demonstrate that cannabis use predicts the future onset of AFib,” Dr. Marcus and colleagues wrote.
Dose-response relationships were not detected for any of the substances; however, usage levels were also derived from ICD-9 codes, which may have been insufficient for this purpose, according to the investigators.
Causal mechanisms deserve a closer look
Causal links between AFib and each of the drugs remain unclear. Citing prior research, Dr. Marcus and colleagues explained how methamphetamines are capable of “significant cardiac electrical remodeling,” while cocaine may cause sodium channel dysregulation, and opioids can render atrial myocytes more susceptible to oxidative damage. Although cannabis has previously been linked with hospitalization for arrhythmia, a pharmacologic driver of this phenomenon remains largely unexamined.
“We don’t know for sure precisely what the constituents are that are responsible for our findings,” Dr. Marcus said. “It’s possible that there are some effects that are much more generic, such as inhaling a burned substance. There is good evidence that if you inhale pretty much any sort of particulate matter, that increases inflammation in the body. Inflammation is known to be a trigger for atrial fibrillation.”
Alternatively, all four drugs – whether stimulants or depressants – cause “quite dramatic and often rapid effects on the autonomic nervous system,” Dr. Marcus said, noting that these rapid swings are a known trigger for AFib.
Brian Olshansky, MD, emeritus professor of internal medicine-cardiovascular medicine at the University of Iowa, Iowa City, suggested that nonpharmacologic factors are likely also playing a role.
“All these drugs have slightly different mechanisms of action, so there’s not one mechanism that would explain why all of them would cause atrial fibrillation,” Dr. Olshansky said in an interview. “That does suggest that there’s something else going on, besides just the drug itself. It would be potentially concerning if we were to lay the blame totally on these drugs.”
Dr. Olshansky, who recently coauthored a review of stimulant drugs and arrhythmias, suggested that lifestyle, comorbidities, and drug impurities may have added to the risk of AF.
“[The investigators] did try to correct for that kind of stuff, but it’s very hard to correct for a lot of the issues that may be ongoing with individuals who partake in these drugs,” Dr. Olshansky said in an interview. “They may not be a healthy lot, in general.”
Still, considering previous data linking drugs of abuse with arrhythmias, he said the detected risks were “intriguing,” and deserved a closer look.
“It’s a nice groundbreaking study, with regard to the fact that they showed unique relationships that we don’t completely understand,” Dr. Olshansky said. “It opens up a new opportunity for further investigation.”
The investigators disclosed relationships with InCarda, Baylis Medical, Johnson & Johnson, and others. Dr. Olshansky disclosed no relevant competing interests.
Cocaine, methamphetamine, opioids, and cannabis may independently increase risk of atrial fibrillation (AFib), based on data from almost 24 million people.
While more work is needed to uncover causal links, physicians should be aware that these commonly abused substances could be driving new cases of AFib, reported investigators from the University of California, San Francisco.
“Though alcohol and tobacco smoking have each been associated with a heightened risk of [AFib], relationships between other drug use and [AFib] are poorly understood,” they wrote in European Heart Journal.
Some previous studies have ventured into this terrain, but most focused on fatal arrhythmias, or offered anecdotal evidence. This knowledge gap is particularly concerning for cannabis, the researchers noted, as medical and recreational use are on the rise.
The present analysis included data from 23.5 million adults in California who received care through a hospital, emergency department, or outpatient surgery center during 2005-2015. Based on ICD-9 diagnostic codes, 132,834 of these patients used cannabis, 98,271 used methamphetamines, 48,701 used cocaine, and 10,032 used opiates. Inclusion required lack of AFib at baseline.
Reliance on ICD-9 codes makes the data “quite specific,” but lacking sensitivity, according to principal author Gregory M. Marcus, MD, cardiologist and professor of medicine at UCSF.
“If they were designated as using these drugs, that is very likely true,” Dr. Marcus said in an interview. “But certainly, the absence of any mention of use of these drugs does not exclude the possibility that some people were still using them. That would not create spurious false-positive relationships; if anything, it attenuates existing relationships.”
In other words, using ICD-9 codes reduced the power to detect an association between each drug and AFib, meaning any relationship needed to be sufficiently strong enough to generate a significant result.
At the end of the decade-long study period, 998,747 patients (4.2%) had developed incident AFib. After adjusting for potential confounders and mediators, all four drugs showed significant, independent associations with AFib. Methamphetamines presented the greatest risk (hazard ratio, 1.86%), followed by opiates (HR, 1.74), cocaine (HR, 1.61), and cannabis (HR, 1.35).
“Our findings provide the first evidence utilizing a longitudinal cohort to demonstrate that cannabis use predicts the future onset of AFib,” Dr. Marcus and colleagues wrote.
Dose-response relationships were not detected for any of the substances; however, usage levels were also derived from ICD-9 codes, which may have been insufficient for this purpose, according to the investigators.
Causal mechanisms deserve a closer look
Causal links between AFib and each of the drugs remain unclear. Citing prior research, Dr. Marcus and colleagues explained how methamphetamines are capable of “significant cardiac electrical remodeling,” while cocaine may cause sodium channel dysregulation, and opioids can render atrial myocytes more susceptible to oxidative damage. Although cannabis has previously been linked with hospitalization for arrhythmia, a pharmacologic driver of this phenomenon remains largely unexamined.
“We don’t know for sure precisely what the constituents are that are responsible for our findings,” Dr. Marcus said. “It’s possible that there are some effects that are much more generic, such as inhaling a burned substance. There is good evidence that if you inhale pretty much any sort of particulate matter, that increases inflammation in the body. Inflammation is known to be a trigger for atrial fibrillation.”
Alternatively, all four drugs – whether stimulants or depressants – cause “quite dramatic and often rapid effects on the autonomic nervous system,” Dr. Marcus said, noting that these rapid swings are a known trigger for AFib.
Brian Olshansky, MD, emeritus professor of internal medicine-cardiovascular medicine at the University of Iowa, Iowa City, suggested that nonpharmacologic factors are likely also playing a role.
“All these drugs have slightly different mechanisms of action, so there’s not one mechanism that would explain why all of them would cause atrial fibrillation,” Dr. Olshansky said in an interview. “That does suggest that there’s something else going on, besides just the drug itself. It would be potentially concerning if we were to lay the blame totally on these drugs.”
Dr. Olshansky, who recently coauthored a review of stimulant drugs and arrhythmias, suggested that lifestyle, comorbidities, and drug impurities may have added to the risk of AF.
“[The investigators] did try to correct for that kind of stuff, but it’s very hard to correct for a lot of the issues that may be ongoing with individuals who partake in these drugs,” Dr. Olshansky said in an interview. “They may not be a healthy lot, in general.”
Still, considering previous data linking drugs of abuse with arrhythmias, he said the detected risks were “intriguing,” and deserved a closer look.
“It’s a nice groundbreaking study, with regard to the fact that they showed unique relationships that we don’t completely understand,” Dr. Olshansky said. “It opens up a new opportunity for further investigation.”
The investigators disclosed relationships with InCarda, Baylis Medical, Johnson & Johnson, and others. Dr. Olshansky disclosed no relevant competing interests.
Cocaine, methamphetamine, opioids, and cannabis may independently increase risk of atrial fibrillation (AFib), based on data from almost 24 million people.
While more work is needed to uncover causal links, physicians should be aware that these commonly abused substances could be driving new cases of AFib, reported investigators from the University of California, San Francisco.
“Though alcohol and tobacco smoking have each been associated with a heightened risk of [AFib], relationships between other drug use and [AFib] are poorly understood,” they wrote in European Heart Journal.
Some previous studies have ventured into this terrain, but most focused on fatal arrhythmias, or offered anecdotal evidence. This knowledge gap is particularly concerning for cannabis, the researchers noted, as medical and recreational use are on the rise.
The present analysis included data from 23.5 million adults in California who received care through a hospital, emergency department, or outpatient surgery center during 2005-2015. Based on ICD-9 diagnostic codes, 132,834 of these patients used cannabis, 98,271 used methamphetamines, 48,701 used cocaine, and 10,032 used opiates. Inclusion required lack of AFib at baseline.
Reliance on ICD-9 codes makes the data “quite specific,” but lacking sensitivity, according to principal author Gregory M. Marcus, MD, cardiologist and professor of medicine at UCSF.
“If they were designated as using these drugs, that is very likely true,” Dr. Marcus said in an interview. “But certainly, the absence of any mention of use of these drugs does not exclude the possibility that some people were still using them. That would not create spurious false-positive relationships; if anything, it attenuates existing relationships.”
In other words, using ICD-9 codes reduced the power to detect an association between each drug and AFib, meaning any relationship needed to be sufficiently strong enough to generate a significant result.
At the end of the decade-long study period, 998,747 patients (4.2%) had developed incident AFib. After adjusting for potential confounders and mediators, all four drugs showed significant, independent associations with AFib. Methamphetamines presented the greatest risk (hazard ratio, 1.86%), followed by opiates (HR, 1.74), cocaine (HR, 1.61), and cannabis (HR, 1.35).
“Our findings provide the first evidence utilizing a longitudinal cohort to demonstrate that cannabis use predicts the future onset of AFib,” Dr. Marcus and colleagues wrote.
Dose-response relationships were not detected for any of the substances; however, usage levels were also derived from ICD-9 codes, which may have been insufficient for this purpose, according to the investigators.
Causal mechanisms deserve a closer look
Causal links between AFib and each of the drugs remain unclear. Citing prior research, Dr. Marcus and colleagues explained how methamphetamines are capable of “significant cardiac electrical remodeling,” while cocaine may cause sodium channel dysregulation, and opioids can render atrial myocytes more susceptible to oxidative damage. Although cannabis has previously been linked with hospitalization for arrhythmia, a pharmacologic driver of this phenomenon remains largely unexamined.
“We don’t know for sure precisely what the constituents are that are responsible for our findings,” Dr. Marcus said. “It’s possible that there are some effects that are much more generic, such as inhaling a burned substance. There is good evidence that if you inhale pretty much any sort of particulate matter, that increases inflammation in the body. Inflammation is known to be a trigger for atrial fibrillation.”
Alternatively, all four drugs – whether stimulants or depressants – cause “quite dramatic and often rapid effects on the autonomic nervous system,” Dr. Marcus said, noting that these rapid swings are a known trigger for AFib.
Brian Olshansky, MD, emeritus professor of internal medicine-cardiovascular medicine at the University of Iowa, Iowa City, suggested that nonpharmacologic factors are likely also playing a role.
“All these drugs have slightly different mechanisms of action, so there’s not one mechanism that would explain why all of them would cause atrial fibrillation,” Dr. Olshansky said in an interview. “That does suggest that there’s something else going on, besides just the drug itself. It would be potentially concerning if we were to lay the blame totally on these drugs.”
Dr. Olshansky, who recently coauthored a review of stimulant drugs and arrhythmias, suggested that lifestyle, comorbidities, and drug impurities may have added to the risk of AF.
“[The investigators] did try to correct for that kind of stuff, but it’s very hard to correct for a lot of the issues that may be ongoing with individuals who partake in these drugs,” Dr. Olshansky said in an interview. “They may not be a healthy lot, in general.”
Still, considering previous data linking drugs of abuse with arrhythmias, he said the detected risks were “intriguing,” and deserved a closer look.
“It’s a nice groundbreaking study, with regard to the fact that they showed unique relationships that we don’t completely understand,” Dr. Olshansky said. “It opens up a new opportunity for further investigation.”
The investigators disclosed relationships with InCarda, Baylis Medical, Johnson & Johnson, and others. Dr. Olshansky disclosed no relevant competing interests.
FROM EUROPEAN HEART JOURNAL
Time to ditch clarithromycin for H. pylori?
Rates of resistance to clarithromycin among Helicobacter pylori isolates in the United States and Europe are high enough to warrant discontinuation of empiric use of proton pump inhibitor (PPI)–based triple therapy that includes the antibiotic in these regions, a new study has found.
Overall, 22.2% of participants were resistant to clarithromycin – a rate that is above the currently recommended threshold of 15% or higher for avoidance of PPI-based triple therapy that includes clarithromycin.
, study investigator William Chey, MD, professor and chief, Division of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, said in an interview.
Judith Kim, MD, a gastroenterologist at NYU Langone Health and clinical instructor of medicine at NYU Grossman School of Medicine, who wasn’t involved in the study, agrees.
“The use of PPI-based triple therapy is still common practice despite recent recommendations to avoid clarithromycin in areas with high resistance rates,” Dr. Kim told this news organization.
“This study shows that multiple parts of the United States and Europe have high resistance rates,” rendering clarithromycin-based regimens “more likely to ineffectively eradicate H pylori,” Dr. Kim said.
The study was published online in The American Journal of Gastroenterology.
Better options now available
Guidelines advise against the use of PPI-based triple regimens with clarithromycin for H. pylori infection in areas where resistance is 15% or higher or for patients who have previously received macrolides. However, up-to-date information on H. pylori antimicrobial resistance patterns is limited, especially in the United States.
Dr. Chey and colleagues assessed resistance rates to antibiotics commonly used to treat H. pylori in isolates from 907 adults with the infection in the United States and Europe. They included four U.S. subregions and five participating European countries.
In all U.S. subregions and European countries, clarithromycin resistance rates were above 15% except possibly in the United Kingdom, where the sample size was too small to provide a reliable estimate.
Three-quarters of the clarithromycin-resistant isolates were also resistant to metronidazole.
The study also found that, overall, 1.2% of patients had isolates that were resistant to amoxicillin, and 69.2% had isolates resistant to metronidazole. Resistance patterns were similar in the United States and Europe; metronidazole resistance was the most common (50%-79% of isolates), and amoxicillin was the least common (≤ 5%).
“Overall, these data provide robust evidence to support a shift away from the default empiric prescription of triple combinations containing a PPI and clarithromycin for H. pylori infection in the United States and Europe,” the study team writes.
The high prevalence of resistance, including dual resistance, highlights the need for antibiotic stewardship and resistance surveillance, as well as novel treatment strategies for H. pylori infection, they add.
Last spring, as previously reported, the United States Food and Drug Administration approved two vonoprazan-based treatments for H. pylori: Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), both from Phathom Pharmaceuticals.
“Vonoprazan-based treatment may be superior to standard PPI triple therapy for clarithromycin-resistant infections based on prior studies and is a potential good option,” Dr. Kim said.
Still, she added, she “would most likely first recommend regimens that do not have clarithromycin, such as bismuth quadruple therapy.”
Study’s importance
Because the study drew upon the largest dataset to date on U.S. resistance rates, it should be used to more precisely guide first-line therapy decisions, said Richard Peek, Jr., MD, professor of medicine and director of gastroenterology at Vanderbilt University Medical Center, Nashville, Tenn.
“To date, there has been a dearth of information in the United States regarding H. pylori resistance rates, which has often led to the use of ineffective empiric therapies and inappropriate exposure to antibiotics,” Dr. Peek, who wasn’t involved in the study, told this news organization.
“These data are particularly exciting when viewed within the context of new genomic sequencing tests that can determine H. pylori resistance patterns using DNA isolated from the stomach or the stool,” he said.
Dr. Peek agreed that the recent approval of vonoprazan-based therapies “adds another regimen to the therapeutic armamentarium available for eradicating H. pylori, and its value seems to be particularly beneficial for eradication failures.”
The research was funded by Phathom Pharmaceuticals. Dr. Chey is a board member of the American College of Gastroenterology, GI on Demand, the International Foundation of Functional GI Disorders, and the Rome Foundation. He has received compensation as a consultant from AbbVie, Alfasigma, Allakos, Alnylam, Bayer, BioAmerica, Cosmo, Intrinsic Medicine, Ironwood Pharmaceuticals, QOL Medical, Nestle, Phathom Pharmaceuticals, RedHill Biopharma, Salix/Valeant, Takeda, Urovant, and Vibrant; grant/research support from BioAmerica, Commonwealth Diagnostics International, QOL Medical, Salix, and Vibrant; owns stock/stock options in GI on Demand and Modify Health; and owns patents relating to methods and kits for identifying food sensitivities and intolerances, digital manometry, and a rectal expulsion device. Dr. Peek and Dr. Kim report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Rates of resistance to clarithromycin among Helicobacter pylori isolates in the United States and Europe are high enough to warrant discontinuation of empiric use of proton pump inhibitor (PPI)–based triple therapy that includes the antibiotic in these regions, a new study has found.
Overall, 22.2% of participants were resistant to clarithromycin – a rate that is above the currently recommended threshold of 15% or higher for avoidance of PPI-based triple therapy that includes clarithromycin.
, study investigator William Chey, MD, professor and chief, Division of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, said in an interview.
Judith Kim, MD, a gastroenterologist at NYU Langone Health and clinical instructor of medicine at NYU Grossman School of Medicine, who wasn’t involved in the study, agrees.
“The use of PPI-based triple therapy is still common practice despite recent recommendations to avoid clarithromycin in areas with high resistance rates,” Dr. Kim told this news organization.
“This study shows that multiple parts of the United States and Europe have high resistance rates,” rendering clarithromycin-based regimens “more likely to ineffectively eradicate H pylori,” Dr. Kim said.
The study was published online in The American Journal of Gastroenterology.
Better options now available
Guidelines advise against the use of PPI-based triple regimens with clarithromycin for H. pylori infection in areas where resistance is 15% or higher or for patients who have previously received macrolides. However, up-to-date information on H. pylori antimicrobial resistance patterns is limited, especially in the United States.
Dr. Chey and colleagues assessed resistance rates to antibiotics commonly used to treat H. pylori in isolates from 907 adults with the infection in the United States and Europe. They included four U.S. subregions and five participating European countries.
In all U.S. subregions and European countries, clarithromycin resistance rates were above 15% except possibly in the United Kingdom, where the sample size was too small to provide a reliable estimate.
Three-quarters of the clarithromycin-resistant isolates were also resistant to metronidazole.
The study also found that, overall, 1.2% of patients had isolates that were resistant to amoxicillin, and 69.2% had isolates resistant to metronidazole. Resistance patterns were similar in the United States and Europe; metronidazole resistance was the most common (50%-79% of isolates), and amoxicillin was the least common (≤ 5%).
“Overall, these data provide robust evidence to support a shift away from the default empiric prescription of triple combinations containing a PPI and clarithromycin for H. pylori infection in the United States and Europe,” the study team writes.
The high prevalence of resistance, including dual resistance, highlights the need for antibiotic stewardship and resistance surveillance, as well as novel treatment strategies for H. pylori infection, they add.
Last spring, as previously reported, the United States Food and Drug Administration approved two vonoprazan-based treatments for H. pylori: Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), both from Phathom Pharmaceuticals.
“Vonoprazan-based treatment may be superior to standard PPI triple therapy for clarithromycin-resistant infections based on prior studies and is a potential good option,” Dr. Kim said.
Still, she added, she “would most likely first recommend regimens that do not have clarithromycin, such as bismuth quadruple therapy.”
Study’s importance
Because the study drew upon the largest dataset to date on U.S. resistance rates, it should be used to more precisely guide first-line therapy decisions, said Richard Peek, Jr., MD, professor of medicine and director of gastroenterology at Vanderbilt University Medical Center, Nashville, Tenn.
“To date, there has been a dearth of information in the United States regarding H. pylori resistance rates, which has often led to the use of ineffective empiric therapies and inappropriate exposure to antibiotics,” Dr. Peek, who wasn’t involved in the study, told this news organization.
“These data are particularly exciting when viewed within the context of new genomic sequencing tests that can determine H. pylori resistance patterns using DNA isolated from the stomach or the stool,” he said.
Dr. Peek agreed that the recent approval of vonoprazan-based therapies “adds another regimen to the therapeutic armamentarium available for eradicating H. pylori, and its value seems to be particularly beneficial for eradication failures.”
The research was funded by Phathom Pharmaceuticals. Dr. Chey is a board member of the American College of Gastroenterology, GI on Demand, the International Foundation of Functional GI Disorders, and the Rome Foundation. He has received compensation as a consultant from AbbVie, Alfasigma, Allakos, Alnylam, Bayer, BioAmerica, Cosmo, Intrinsic Medicine, Ironwood Pharmaceuticals, QOL Medical, Nestle, Phathom Pharmaceuticals, RedHill Biopharma, Salix/Valeant, Takeda, Urovant, and Vibrant; grant/research support from BioAmerica, Commonwealth Diagnostics International, QOL Medical, Salix, and Vibrant; owns stock/stock options in GI on Demand and Modify Health; and owns patents relating to methods and kits for identifying food sensitivities and intolerances, digital manometry, and a rectal expulsion device. Dr. Peek and Dr. Kim report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Rates of resistance to clarithromycin among Helicobacter pylori isolates in the United States and Europe are high enough to warrant discontinuation of empiric use of proton pump inhibitor (PPI)–based triple therapy that includes the antibiotic in these regions, a new study has found.
Overall, 22.2% of participants were resistant to clarithromycin – a rate that is above the currently recommended threshold of 15% or higher for avoidance of PPI-based triple therapy that includes clarithromycin.
, study investigator William Chey, MD, professor and chief, Division of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, said in an interview.
Judith Kim, MD, a gastroenterologist at NYU Langone Health and clinical instructor of medicine at NYU Grossman School of Medicine, who wasn’t involved in the study, agrees.
“The use of PPI-based triple therapy is still common practice despite recent recommendations to avoid clarithromycin in areas with high resistance rates,” Dr. Kim told this news organization.
“This study shows that multiple parts of the United States and Europe have high resistance rates,” rendering clarithromycin-based regimens “more likely to ineffectively eradicate H pylori,” Dr. Kim said.
The study was published online in The American Journal of Gastroenterology.
Better options now available
Guidelines advise against the use of PPI-based triple regimens with clarithromycin for H. pylori infection in areas where resistance is 15% or higher or for patients who have previously received macrolides. However, up-to-date information on H. pylori antimicrobial resistance patterns is limited, especially in the United States.
Dr. Chey and colleagues assessed resistance rates to antibiotics commonly used to treat H. pylori in isolates from 907 adults with the infection in the United States and Europe. They included four U.S. subregions and five participating European countries.
In all U.S. subregions and European countries, clarithromycin resistance rates were above 15% except possibly in the United Kingdom, where the sample size was too small to provide a reliable estimate.
Three-quarters of the clarithromycin-resistant isolates were also resistant to metronidazole.
The study also found that, overall, 1.2% of patients had isolates that were resistant to amoxicillin, and 69.2% had isolates resistant to metronidazole. Resistance patterns were similar in the United States and Europe; metronidazole resistance was the most common (50%-79% of isolates), and amoxicillin was the least common (≤ 5%).
“Overall, these data provide robust evidence to support a shift away from the default empiric prescription of triple combinations containing a PPI and clarithromycin for H. pylori infection in the United States and Europe,” the study team writes.
The high prevalence of resistance, including dual resistance, highlights the need for antibiotic stewardship and resistance surveillance, as well as novel treatment strategies for H. pylori infection, they add.
Last spring, as previously reported, the United States Food and Drug Administration approved two vonoprazan-based treatments for H. pylori: Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin), both from Phathom Pharmaceuticals.
“Vonoprazan-based treatment may be superior to standard PPI triple therapy for clarithromycin-resistant infections based on prior studies and is a potential good option,” Dr. Kim said.
Still, she added, she “would most likely first recommend regimens that do not have clarithromycin, such as bismuth quadruple therapy.”
Study’s importance
Because the study drew upon the largest dataset to date on U.S. resistance rates, it should be used to more precisely guide first-line therapy decisions, said Richard Peek, Jr., MD, professor of medicine and director of gastroenterology at Vanderbilt University Medical Center, Nashville, Tenn.
“To date, there has been a dearth of information in the United States regarding H. pylori resistance rates, which has often led to the use of ineffective empiric therapies and inappropriate exposure to antibiotics,” Dr. Peek, who wasn’t involved in the study, told this news organization.
“These data are particularly exciting when viewed within the context of new genomic sequencing tests that can determine H. pylori resistance patterns using DNA isolated from the stomach or the stool,” he said.
Dr. Peek agreed that the recent approval of vonoprazan-based therapies “adds another regimen to the therapeutic armamentarium available for eradicating H. pylori, and its value seems to be particularly beneficial for eradication failures.”
The research was funded by Phathom Pharmaceuticals. Dr. Chey is a board member of the American College of Gastroenterology, GI on Demand, the International Foundation of Functional GI Disorders, and the Rome Foundation. He has received compensation as a consultant from AbbVie, Alfasigma, Allakos, Alnylam, Bayer, BioAmerica, Cosmo, Intrinsic Medicine, Ironwood Pharmaceuticals, QOL Medical, Nestle, Phathom Pharmaceuticals, RedHill Biopharma, Salix/Valeant, Takeda, Urovant, and Vibrant; grant/research support from BioAmerica, Commonwealth Diagnostics International, QOL Medical, Salix, and Vibrant; owns stock/stock options in GI on Demand and Modify Health; and owns patents relating to methods and kits for identifying food sensitivities and intolerances, digital manometry, and a rectal expulsion device. Dr. Peek and Dr. Kim report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Does exposure to cell phone Wi-Fi spell trouble for sperm?
A small new study suggests – but doesn’t prove – that exposure to Wi-Fi signals from cell phones in pants pockets could disrupt male fertility. Researchers found that sperm placed next to an in-use iPhone on the Wi-Fi setting over 6 hours had less motility (50% vs. 38%, P = .024) and viability (60% vs. 47%, P = .003) than those set to 4G and 5G.
The findings, presented at the American Society for Reproductive Medicine’s 2022 meeting, don’t confirm that cell phones are harmful, lead author Kevin Y. Chu, MD, a Los Angeles urologist, said in an interview. “We cannot draw conclusions from this study, as the study population was too small. What we did observe was that Wi-Fi, which was previously less studied, may have had an impact on sperm. We did not see an effect on sperm quality by the 4G or 5G wireless spectrum.”
According to Dr. Chu, dozens of studies have examined the possible effect of cell phone exposure on sperm quality. “In human survey studies, there was no association of use and decline of sperm quality,” he said. “In human sperm in vitro studies, there was a decline of sperm motility and viability. And in animal studies, there was decline of sperm motility and viability.”
The new study is a pilot “to see if it is feasible to do a large-scale project” to analyze any possible effects from radiofrequency-electromagnetic radiation (RF-EMR) transmitted by cell phones, he said.
According to the study, cell phones emit radiation when they “transmit data for social media, web browsing, and music/podcast streaming,” and the rise of Bluetooth earbuds “presumably prolonged the amount of time the cell phone resides in the trouser pockets of men. This places the cell phone and its respective RF-EMR near the testicles for prolonged [periods].”
Researchers obtained semen samples from 27 men aged 25-35 who were fertile with normal sperm. Then they placed the samples on top of a current-generation iPhone that was set to talk mode via WhatsApp and transmitted/received signals via Wi-Fi, 4G, or 5G.
The researchers found no difference in sperm quality between control samples and those exposed to 4G or 5G (n = 9), but Wi-Fi (n = 18) seemed to have an effect. “We also tested conditions with the phone in a cover, as well as separating it by about 6 inches [from the sperm samples]. We found that both did dampen the effect of what we were seeing in comparison to direct exposure,” Dr. Chu said. “It appears that heat that is emanated from the device contributes to this effect.”
Dr. Chu cautioned that the study examined only ejaculated sperm, and “does not replicate real life where there is scrotal wall protection [and] pants material.”
For now, he said, there’s not enough evidence to allow clinicians to provide guidance to patients about possible links between cell phone exposure and male fertility. None of the study authors have changed their own use of cell phones as a result of the findings, he added.
Moving forward, he said, “continued research on exposure effects is needed and the current association should be considered cautiously as hypothesis generating.”
In an interview, University of Utah urologist James Hotaling, MD, who’s familiar with the study findings but didn’t take part in the research, said the authors “have done a good job looking at this issue,” but with acknowledged limitations.
The study size is very small, he said, “making generalizability difficult.” And “while the results, particularly on the Wi-Fi part, are interesting, they must be validated.”
In the big picture, he said, “the decline in sperm counts over the last 40 years is multifactorial so it cannot all be attributed to this. Finally, to really make the claim that Wi-Fi impacted fertility, you would need to have a much larger study and, ideally, look at pregnancy rates in couples trying to conceive.”
Overall, he said, the scientific community is “still skeptical” about a link between cell phone use and a decline in male fertility.
The study authors and Dr. Hotaling have no relevant disclosures.
A small new study suggests – but doesn’t prove – that exposure to Wi-Fi signals from cell phones in pants pockets could disrupt male fertility. Researchers found that sperm placed next to an in-use iPhone on the Wi-Fi setting over 6 hours had less motility (50% vs. 38%, P = .024) and viability (60% vs. 47%, P = .003) than those set to 4G and 5G.
The findings, presented at the American Society for Reproductive Medicine’s 2022 meeting, don’t confirm that cell phones are harmful, lead author Kevin Y. Chu, MD, a Los Angeles urologist, said in an interview. “We cannot draw conclusions from this study, as the study population was too small. What we did observe was that Wi-Fi, which was previously less studied, may have had an impact on sperm. We did not see an effect on sperm quality by the 4G or 5G wireless spectrum.”
According to Dr. Chu, dozens of studies have examined the possible effect of cell phone exposure on sperm quality. “In human survey studies, there was no association of use and decline of sperm quality,” he said. “In human sperm in vitro studies, there was a decline of sperm motility and viability. And in animal studies, there was decline of sperm motility and viability.”
The new study is a pilot “to see if it is feasible to do a large-scale project” to analyze any possible effects from radiofrequency-electromagnetic radiation (RF-EMR) transmitted by cell phones, he said.
According to the study, cell phones emit radiation when they “transmit data for social media, web browsing, and music/podcast streaming,” and the rise of Bluetooth earbuds “presumably prolonged the amount of time the cell phone resides in the trouser pockets of men. This places the cell phone and its respective RF-EMR near the testicles for prolonged [periods].”
Researchers obtained semen samples from 27 men aged 25-35 who were fertile with normal sperm. Then they placed the samples on top of a current-generation iPhone that was set to talk mode via WhatsApp and transmitted/received signals via Wi-Fi, 4G, or 5G.
The researchers found no difference in sperm quality between control samples and those exposed to 4G or 5G (n = 9), but Wi-Fi (n = 18) seemed to have an effect. “We also tested conditions with the phone in a cover, as well as separating it by about 6 inches [from the sperm samples]. We found that both did dampen the effect of what we were seeing in comparison to direct exposure,” Dr. Chu said. “It appears that heat that is emanated from the device contributes to this effect.”
Dr. Chu cautioned that the study examined only ejaculated sperm, and “does not replicate real life where there is scrotal wall protection [and] pants material.”
For now, he said, there’s not enough evidence to allow clinicians to provide guidance to patients about possible links between cell phone exposure and male fertility. None of the study authors have changed their own use of cell phones as a result of the findings, he added.
Moving forward, he said, “continued research on exposure effects is needed and the current association should be considered cautiously as hypothesis generating.”
In an interview, University of Utah urologist James Hotaling, MD, who’s familiar with the study findings but didn’t take part in the research, said the authors “have done a good job looking at this issue,” but with acknowledged limitations.
The study size is very small, he said, “making generalizability difficult.” And “while the results, particularly on the Wi-Fi part, are interesting, they must be validated.”
In the big picture, he said, “the decline in sperm counts over the last 40 years is multifactorial so it cannot all be attributed to this. Finally, to really make the claim that Wi-Fi impacted fertility, you would need to have a much larger study and, ideally, look at pregnancy rates in couples trying to conceive.”
Overall, he said, the scientific community is “still skeptical” about a link between cell phone use and a decline in male fertility.
The study authors and Dr. Hotaling have no relevant disclosures.
A small new study suggests – but doesn’t prove – that exposure to Wi-Fi signals from cell phones in pants pockets could disrupt male fertility. Researchers found that sperm placed next to an in-use iPhone on the Wi-Fi setting over 6 hours had less motility (50% vs. 38%, P = .024) and viability (60% vs. 47%, P = .003) than those set to 4G and 5G.
The findings, presented at the American Society for Reproductive Medicine’s 2022 meeting, don’t confirm that cell phones are harmful, lead author Kevin Y. Chu, MD, a Los Angeles urologist, said in an interview. “We cannot draw conclusions from this study, as the study population was too small. What we did observe was that Wi-Fi, which was previously less studied, may have had an impact on sperm. We did not see an effect on sperm quality by the 4G or 5G wireless spectrum.”
According to Dr. Chu, dozens of studies have examined the possible effect of cell phone exposure on sperm quality. “In human survey studies, there was no association of use and decline of sperm quality,” he said. “In human sperm in vitro studies, there was a decline of sperm motility and viability. And in animal studies, there was decline of sperm motility and viability.”
The new study is a pilot “to see if it is feasible to do a large-scale project” to analyze any possible effects from radiofrequency-electromagnetic radiation (RF-EMR) transmitted by cell phones, he said.
According to the study, cell phones emit radiation when they “transmit data for social media, web browsing, and music/podcast streaming,” and the rise of Bluetooth earbuds “presumably prolonged the amount of time the cell phone resides in the trouser pockets of men. This places the cell phone and its respective RF-EMR near the testicles for prolonged [periods].”
Researchers obtained semen samples from 27 men aged 25-35 who were fertile with normal sperm. Then they placed the samples on top of a current-generation iPhone that was set to talk mode via WhatsApp and transmitted/received signals via Wi-Fi, 4G, or 5G.
The researchers found no difference in sperm quality between control samples and those exposed to 4G or 5G (n = 9), but Wi-Fi (n = 18) seemed to have an effect. “We also tested conditions with the phone in a cover, as well as separating it by about 6 inches [from the sperm samples]. We found that both did dampen the effect of what we were seeing in comparison to direct exposure,” Dr. Chu said. “It appears that heat that is emanated from the device contributes to this effect.”
Dr. Chu cautioned that the study examined only ejaculated sperm, and “does not replicate real life where there is scrotal wall protection [and] pants material.”
For now, he said, there’s not enough evidence to allow clinicians to provide guidance to patients about possible links between cell phone exposure and male fertility. None of the study authors have changed their own use of cell phones as a result of the findings, he added.
Moving forward, he said, “continued research on exposure effects is needed and the current association should be considered cautiously as hypothesis generating.”
In an interview, University of Utah urologist James Hotaling, MD, who’s familiar with the study findings but didn’t take part in the research, said the authors “have done a good job looking at this issue,” but with acknowledged limitations.
The study size is very small, he said, “making generalizability difficult.” And “while the results, particularly on the Wi-Fi part, are interesting, they must be validated.”
In the big picture, he said, “the decline in sperm counts over the last 40 years is multifactorial so it cannot all be attributed to this. Finally, to really make the claim that Wi-Fi impacted fertility, you would need to have a much larger study and, ideally, look at pregnancy rates in couples trying to conceive.”
Overall, he said, the scientific community is “still skeptical” about a link between cell phone use and a decline in male fertility.
The study authors and Dr. Hotaling have no relevant disclosures.
BY RANDY DOTINGA FROM ASRM 2022
Criminal profiles of medical murderers
Today’s health care professionals run the very real risk of being sued. This is especially true when a patient dies unexpectedly. But many times, doctors find that they’re defending themselves against very serious charges, such as murder and attempted murder.
In Mexico, a physician can be wrongfully accused of such crimes, as was Azucena Calvillo, MD, last year in Durango. The case drew much media attention, and the accusations were so implausible and ridiculous that the charges were dropped and the case was dismissed.
There are instances in which the authorities create a circuslike atmosphere by making farcical and false accusations against healthcare professionals. Still, there are medical murderers – and these killers are among the most difficult to identify. As John E. Douglas put it, “Medical murderers (physicians, nurses, elder care workers) can have a long list of victims, longer than other kinds of serial killers.” Ted Bundy, one of the most written-about serial killers, confessed to 30 murders. The cases discussed below involve from 60 to 200.
Mr. Douglas was a special agent with the United States Federal Bureau of Investigation. He is the author of Mindhunter, a nonfiction crime book in which he recounts the early days of the FBI’s Behavioral Science Unit and how he and his colleagues began to study the criminal profiles of serial killers. The book has been adapted into a Netflix TV series of the same name.
He is also one of the authors of Crime Classification Manual: A Standard System for Investigating and Classifying Violent Crime. In this book, there are descriptions of criminal profiles of medical murderers.
According to the authors, Each type is associated with a different motive. In the former, the murderers believe that they’re alleviating the patient’s suffering; in the latter, the murderers create a medical emergency so that they can play the hero in what they know will be an unsuccessful attempt to save the patient’s life.
Pseudo-mercy homicide
An example of pseudo-mercy homicide is the infamous case of Harold Shipman, MD, who was convicted of killing 15 people, although an investigation found that more than 200 persons, and possibly as many as 250, died at his hands. In Prescription for Murder: The True Story of Dr. Harold Frederick Shipman, biographer Brian Whittle writes that the general practitioner is England’s (if not the world’s) most prolific serial killer. Dr. Shipman is the only physician in that country’s history to have been convicted of killing his patients.
His modus operandi? Injecting morphine. Most of his victims were elderly women. And though unconfirmed, his youngest victim may have been only 4 years old. It was the death of 81-year-old Kathleen Grundy that led to the physician’s arrest. Her family became extremely suspicious when they learned that her will named Dr. Shipman as the beneficiary of her entire estate.
He always denied being involved in the murders, for which authorities have yet to determine a motive. The speculation is that he enjoyed watching people die. Almost none of the cases attributed to Dr. Shipman involved a critically ill individual with a life-threatening condition. Therefore, his acts were not real acts of mercy. He would make a house call to carry out a routine visit. Once in the patient’s home, he would inject a lethal dose of morphine. Sometimes, relatives and physicians alike would be struck by the strange turn of events.
In 2004, Dr. Shipman committed suicide in prison. His case led to numerous changes to British law with respect to the use of controlled substances, the issuance of death certificates, and the procedure for reporting healthcare staff suspected of engaging in illegal activities. Biographer Whittle concluded, “It is very unlikely that the world will ever see another physician as unrelentingly wicked as Dr. Shipman.”
Pseudo-hero homicide
The pseudo-hero creates serious situations, generally by administering drugs, and then tries to save the patient. Mr. Douglas presents a terrifying case study: Genene Jones, a nurse known as the “Angel of Death.”
Many of Ms. Jones’ colleagues considered her an excellent nurse, an expert at handling unexpected emergencies. If a child died while she was on duty, she would sometimes accompany their body to the morgue. She would even sing children’s songs to their lifeless body. When people started to question the number of deaths that were occurring during her shifts, the staff stood up for Ms. Jones, saying that it was because she took on the most serious cases.
Ms. Jones was found out when a vial of succinylcholine went missing. After it was located, a physician, who had been suspicious of the nurse, noticed that there were two puncture holes in the stopper. None of the staff could offer any explanation. A few days before this event, that same physician had left a healthy 15-month-old girl in Jones’ care. Within a few minutes, the child was showing signs of paralysis and started to have seizures. It appears that Ms. Jones had used succinylcholine to make it appear that the children were sick or were experiencing some sort of emergency so that she could then attempt to save them, and they could die in her arms.
This case highlights the need for mortality review committees and for proper statistical analysis to discern trends in deaths and complications among patients. Genene Jones was convicted of killing the 15-month-old girl and was sentenced to 99 years in prison. Authorities suspect that the nurse was responsible for the deaths of up to 60 children.
A new criminal profile?
Through the podcast and subsequent TV series Dr. Death, many people have come to know of a more recent medical murderer: Christopher Duntsch, MD, PhD. The Texas neurosurgeon killed at least two patients, and his actions left several others with adverse outcomes and serious injuries.
These acts occurred during surgical procedures. Witnesses said that the deaths and injuries were the result of unprecedented, egregious negligence, as though the operations had been performed by someone who had never been trained in the specialty. This is something that resonates very strongly for those who are aware of what’s going on in Mexico, where it’s well known that many physicians who lack specialty training perform operations (mainly cosmetic surgery). No doubt cases such as Dr. Duntsch’s are more frequent in Mexico.
What makes the situation in the United States involving Christopher Duntsch so astonishing is that it resulted from a perfect storm of a physician whom some colleagues described as a “sociopath” and legal loopholes in the country’s healthcare system. Apparently, during his residency, Dr. Duntsch never developed the skills necessary to perform operations. He spent more time carrying out research and engaging in other activities than in participating in the operating room. This is a case that calls into question the way specialists are trained, as it seems that what matters is not how much time they’re spending inside the hospital but what they’re doing and learning there.
Dr. Duntsch’s license was suspended and then permanently revoked. He is currently serving a life sentence. Through the podcast or the TV series, one comes to realize that it’s not easy to catch medical murderers. They are among the most difficult to identify – serial killers who commit numerous homicides before they are captured. Reading about the case of Christopher Duntsch, one might ask, What’s his criminal profile: pseudo-hero? Pseudo-mercy? It is hard to say. Maybe his is a different kind of profile – one that will open a new chapter in the books on medical murderers.
Dr. Sarmiento studied medicine and did his residency in anatomic pathology, internal medicine, and clinical hematology. He went on to study at Central University City Campus Law School, National Autonomous University of Mexico. He now runs a law firm that, among other things, advises physicians on matters of civil liability, administrative processes, and the legal implications of practicing medicine.
This article was translated from the Medscape Spanish edition.
Today’s health care professionals run the very real risk of being sued. This is especially true when a patient dies unexpectedly. But many times, doctors find that they’re defending themselves against very serious charges, such as murder and attempted murder.
In Mexico, a physician can be wrongfully accused of such crimes, as was Azucena Calvillo, MD, last year in Durango. The case drew much media attention, and the accusations were so implausible and ridiculous that the charges were dropped and the case was dismissed.
There are instances in which the authorities create a circuslike atmosphere by making farcical and false accusations against healthcare professionals. Still, there are medical murderers – and these killers are among the most difficult to identify. As John E. Douglas put it, “Medical murderers (physicians, nurses, elder care workers) can have a long list of victims, longer than other kinds of serial killers.” Ted Bundy, one of the most written-about serial killers, confessed to 30 murders. The cases discussed below involve from 60 to 200.
Mr. Douglas was a special agent with the United States Federal Bureau of Investigation. He is the author of Mindhunter, a nonfiction crime book in which he recounts the early days of the FBI’s Behavioral Science Unit and how he and his colleagues began to study the criminal profiles of serial killers. The book has been adapted into a Netflix TV series of the same name.
He is also one of the authors of Crime Classification Manual: A Standard System for Investigating and Classifying Violent Crime. In this book, there are descriptions of criminal profiles of medical murderers.
According to the authors, Each type is associated with a different motive. In the former, the murderers believe that they’re alleviating the patient’s suffering; in the latter, the murderers create a medical emergency so that they can play the hero in what they know will be an unsuccessful attempt to save the patient’s life.
Pseudo-mercy homicide
An example of pseudo-mercy homicide is the infamous case of Harold Shipman, MD, who was convicted of killing 15 people, although an investigation found that more than 200 persons, and possibly as many as 250, died at his hands. In Prescription for Murder: The True Story of Dr. Harold Frederick Shipman, biographer Brian Whittle writes that the general practitioner is England’s (if not the world’s) most prolific serial killer. Dr. Shipman is the only physician in that country’s history to have been convicted of killing his patients.
His modus operandi? Injecting morphine. Most of his victims were elderly women. And though unconfirmed, his youngest victim may have been only 4 years old. It was the death of 81-year-old Kathleen Grundy that led to the physician’s arrest. Her family became extremely suspicious when they learned that her will named Dr. Shipman as the beneficiary of her entire estate.
He always denied being involved in the murders, for which authorities have yet to determine a motive. The speculation is that he enjoyed watching people die. Almost none of the cases attributed to Dr. Shipman involved a critically ill individual with a life-threatening condition. Therefore, his acts were not real acts of mercy. He would make a house call to carry out a routine visit. Once in the patient’s home, he would inject a lethal dose of morphine. Sometimes, relatives and physicians alike would be struck by the strange turn of events.
In 2004, Dr. Shipman committed suicide in prison. His case led to numerous changes to British law with respect to the use of controlled substances, the issuance of death certificates, and the procedure for reporting healthcare staff suspected of engaging in illegal activities. Biographer Whittle concluded, “It is very unlikely that the world will ever see another physician as unrelentingly wicked as Dr. Shipman.”
Pseudo-hero homicide
The pseudo-hero creates serious situations, generally by administering drugs, and then tries to save the patient. Mr. Douglas presents a terrifying case study: Genene Jones, a nurse known as the “Angel of Death.”
Many of Ms. Jones’ colleagues considered her an excellent nurse, an expert at handling unexpected emergencies. If a child died while she was on duty, she would sometimes accompany their body to the morgue. She would even sing children’s songs to their lifeless body. When people started to question the number of deaths that were occurring during her shifts, the staff stood up for Ms. Jones, saying that it was because she took on the most serious cases.
Ms. Jones was found out when a vial of succinylcholine went missing. After it was located, a physician, who had been suspicious of the nurse, noticed that there were two puncture holes in the stopper. None of the staff could offer any explanation. A few days before this event, that same physician had left a healthy 15-month-old girl in Jones’ care. Within a few minutes, the child was showing signs of paralysis and started to have seizures. It appears that Ms. Jones had used succinylcholine to make it appear that the children were sick or were experiencing some sort of emergency so that she could then attempt to save them, and they could die in her arms.
This case highlights the need for mortality review committees and for proper statistical analysis to discern trends in deaths and complications among patients. Genene Jones was convicted of killing the 15-month-old girl and was sentenced to 99 years in prison. Authorities suspect that the nurse was responsible for the deaths of up to 60 children.
A new criminal profile?
Through the podcast and subsequent TV series Dr. Death, many people have come to know of a more recent medical murderer: Christopher Duntsch, MD, PhD. The Texas neurosurgeon killed at least two patients, and his actions left several others with adverse outcomes and serious injuries.
These acts occurred during surgical procedures. Witnesses said that the deaths and injuries were the result of unprecedented, egregious negligence, as though the operations had been performed by someone who had never been trained in the specialty. This is something that resonates very strongly for those who are aware of what’s going on in Mexico, where it’s well known that many physicians who lack specialty training perform operations (mainly cosmetic surgery). No doubt cases such as Dr. Duntsch’s are more frequent in Mexico.
What makes the situation in the United States involving Christopher Duntsch so astonishing is that it resulted from a perfect storm of a physician whom some colleagues described as a “sociopath” and legal loopholes in the country’s healthcare system. Apparently, during his residency, Dr. Duntsch never developed the skills necessary to perform operations. He spent more time carrying out research and engaging in other activities than in participating in the operating room. This is a case that calls into question the way specialists are trained, as it seems that what matters is not how much time they’re spending inside the hospital but what they’re doing and learning there.
Dr. Duntsch’s license was suspended and then permanently revoked. He is currently serving a life sentence. Through the podcast or the TV series, one comes to realize that it’s not easy to catch medical murderers. They are among the most difficult to identify – serial killers who commit numerous homicides before they are captured. Reading about the case of Christopher Duntsch, one might ask, What’s his criminal profile: pseudo-hero? Pseudo-mercy? It is hard to say. Maybe his is a different kind of profile – one that will open a new chapter in the books on medical murderers.
Dr. Sarmiento studied medicine and did his residency in anatomic pathology, internal medicine, and clinical hematology. He went on to study at Central University City Campus Law School, National Autonomous University of Mexico. He now runs a law firm that, among other things, advises physicians on matters of civil liability, administrative processes, and the legal implications of practicing medicine.
This article was translated from the Medscape Spanish edition.
Today’s health care professionals run the very real risk of being sued. This is especially true when a patient dies unexpectedly. But many times, doctors find that they’re defending themselves against very serious charges, such as murder and attempted murder.
In Mexico, a physician can be wrongfully accused of such crimes, as was Azucena Calvillo, MD, last year in Durango. The case drew much media attention, and the accusations were so implausible and ridiculous that the charges were dropped and the case was dismissed.
There are instances in which the authorities create a circuslike atmosphere by making farcical and false accusations against healthcare professionals. Still, there are medical murderers – and these killers are among the most difficult to identify. As John E. Douglas put it, “Medical murderers (physicians, nurses, elder care workers) can have a long list of victims, longer than other kinds of serial killers.” Ted Bundy, one of the most written-about serial killers, confessed to 30 murders. The cases discussed below involve from 60 to 200.
Mr. Douglas was a special agent with the United States Federal Bureau of Investigation. He is the author of Mindhunter, a nonfiction crime book in which he recounts the early days of the FBI’s Behavioral Science Unit and how he and his colleagues began to study the criminal profiles of serial killers. The book has been adapted into a Netflix TV series of the same name.
He is also one of the authors of Crime Classification Manual: A Standard System for Investigating and Classifying Violent Crime. In this book, there are descriptions of criminal profiles of medical murderers.
According to the authors, Each type is associated with a different motive. In the former, the murderers believe that they’re alleviating the patient’s suffering; in the latter, the murderers create a medical emergency so that they can play the hero in what they know will be an unsuccessful attempt to save the patient’s life.
Pseudo-mercy homicide
An example of pseudo-mercy homicide is the infamous case of Harold Shipman, MD, who was convicted of killing 15 people, although an investigation found that more than 200 persons, and possibly as many as 250, died at his hands. In Prescription for Murder: The True Story of Dr. Harold Frederick Shipman, biographer Brian Whittle writes that the general practitioner is England’s (if not the world’s) most prolific serial killer. Dr. Shipman is the only physician in that country’s history to have been convicted of killing his patients.
His modus operandi? Injecting morphine. Most of his victims were elderly women. And though unconfirmed, his youngest victim may have been only 4 years old. It was the death of 81-year-old Kathleen Grundy that led to the physician’s arrest. Her family became extremely suspicious when they learned that her will named Dr. Shipman as the beneficiary of her entire estate.
He always denied being involved in the murders, for which authorities have yet to determine a motive. The speculation is that he enjoyed watching people die. Almost none of the cases attributed to Dr. Shipman involved a critically ill individual with a life-threatening condition. Therefore, his acts were not real acts of mercy. He would make a house call to carry out a routine visit. Once in the patient’s home, he would inject a lethal dose of morphine. Sometimes, relatives and physicians alike would be struck by the strange turn of events.
In 2004, Dr. Shipman committed suicide in prison. His case led to numerous changes to British law with respect to the use of controlled substances, the issuance of death certificates, and the procedure for reporting healthcare staff suspected of engaging in illegal activities. Biographer Whittle concluded, “It is very unlikely that the world will ever see another physician as unrelentingly wicked as Dr. Shipman.”
Pseudo-hero homicide
The pseudo-hero creates serious situations, generally by administering drugs, and then tries to save the patient. Mr. Douglas presents a terrifying case study: Genene Jones, a nurse known as the “Angel of Death.”
Many of Ms. Jones’ colleagues considered her an excellent nurse, an expert at handling unexpected emergencies. If a child died while she was on duty, she would sometimes accompany their body to the morgue. She would even sing children’s songs to their lifeless body. When people started to question the number of deaths that were occurring during her shifts, the staff stood up for Ms. Jones, saying that it was because she took on the most serious cases.
Ms. Jones was found out when a vial of succinylcholine went missing. After it was located, a physician, who had been suspicious of the nurse, noticed that there were two puncture holes in the stopper. None of the staff could offer any explanation. A few days before this event, that same physician had left a healthy 15-month-old girl in Jones’ care. Within a few minutes, the child was showing signs of paralysis and started to have seizures. It appears that Ms. Jones had used succinylcholine to make it appear that the children were sick or were experiencing some sort of emergency so that she could then attempt to save them, and they could die in her arms.
This case highlights the need for mortality review committees and for proper statistical analysis to discern trends in deaths and complications among patients. Genene Jones was convicted of killing the 15-month-old girl and was sentenced to 99 years in prison. Authorities suspect that the nurse was responsible for the deaths of up to 60 children.
A new criminal profile?
Through the podcast and subsequent TV series Dr. Death, many people have come to know of a more recent medical murderer: Christopher Duntsch, MD, PhD. The Texas neurosurgeon killed at least two patients, and his actions left several others with adverse outcomes and serious injuries.
These acts occurred during surgical procedures. Witnesses said that the deaths and injuries were the result of unprecedented, egregious negligence, as though the operations had been performed by someone who had never been trained in the specialty. This is something that resonates very strongly for those who are aware of what’s going on in Mexico, where it’s well known that many physicians who lack specialty training perform operations (mainly cosmetic surgery). No doubt cases such as Dr. Duntsch’s are more frequent in Mexico.
What makes the situation in the United States involving Christopher Duntsch so astonishing is that it resulted from a perfect storm of a physician whom some colleagues described as a “sociopath” and legal loopholes in the country’s healthcare system. Apparently, during his residency, Dr. Duntsch never developed the skills necessary to perform operations. He spent more time carrying out research and engaging in other activities than in participating in the operating room. This is a case that calls into question the way specialists are trained, as it seems that what matters is not how much time they’re spending inside the hospital but what they’re doing and learning there.
Dr. Duntsch’s license was suspended and then permanently revoked. He is currently serving a life sentence. Through the podcast or the TV series, one comes to realize that it’s not easy to catch medical murderers. They are among the most difficult to identify – serial killers who commit numerous homicides before they are captured. Reading about the case of Christopher Duntsch, one might ask, What’s his criminal profile: pseudo-hero? Pseudo-mercy? It is hard to say. Maybe his is a different kind of profile – one that will open a new chapter in the books on medical murderers.
Dr. Sarmiento studied medicine and did his residency in anatomic pathology, internal medicine, and clinical hematology. He went on to study at Central University City Campus Law School, National Autonomous University of Mexico. He now runs a law firm that, among other things, advises physicians on matters of civil liability, administrative processes, and the legal implications of practicing medicine.
This article was translated from the Medscape Spanish edition.
Less than 6 hours of sleep a night linked to serious, chronic illness
, results of a large study show.
Researchers at University College London and Université Paris Cité found that beginning at age 50, those who slept 5 hours or fewer a night had a 30% higher risk of developing multiple chronic diseases over time than those who slept at least 7 hours a night. By the time the participants were aged 70 years, that risk had increased to 40%.
Diseases for which there was a higher risk included diabetes, cancer, coronary heart disease, stroke, heart failure, chronic obstructive pulmonary disease, chronic kidney disease, liver disease, depression, dementia, Parkinson’s disease, and arthritis.
“It is important to take care of our sleep,” lead investigator Séverine Sabia, PhD, said in an interview. Dr. Sabia is a researcher and epidemiologist at Université Paris Cité and INSERM in Paris, and the University College London.
She noted that the source of the sleep problem must be addressed, but in cases in which there is no medical reason for sleep paucity, “healthy sleep habits are a must. These include keeping a regular sleep schedule, a healthy lifestyle – physical activity and light exposure during the day, and a light dinner – and avoidance of screens for a half hour before sleep.”
The study was published online in PLOS Medicine.
Risk of multiple chronic diseases
Prior research suggests that sleeping for 5 hours or less or 9 hours or more is associated with cancer and cardiovascular disease (CVD).
For the current study, Dr. Sabia and her team asked nearly 8,000 civil servants in the United Kingdom as part of the Whitehall II cohort study to report the amount of sleep they received beginning at age 50 every 4 to 5 years for the next 25 years. Study participants were free of chronic disease at age 50 and were mostly male (67.5%) and White (90%).
The investigators found that at age 50, those who slept 5 hours or less were 30% more likely to be diagnosed with multiple chronic diseases over time, (hazard ratio, 1.30; 95% confidence interval, 1.12-1.50; P < .001) compared with their peers who slept 7 hours.
At age 60, those who slept 5 hours or less had a 32% greater risk of developing more than one chronic disease (HR, 1.32; 95% CI, 1.13-1.55; P < .001), and by age 70, this risk increased to 40% compared with their peers who slept 7 hours a night (HR, 1.40; 95% CI, 1.16-1.68; P < .001).
For participants who slept 9 or more hours per night, only those aged 60 (HR, 1.54; 95% CI, 1.15-2.06; P = .003) and 70 (HR, 1.51; 95% CI, 1.10-2.08; P = .010) were at increased risk of developing more than one chronic disease.
Dr. Sabia noted that previous studies have shown that those who slept less than 5 hours a night were more likely to develop diabetes, hypertension, CVD, or dementia. “However, chronic diseases often coexist, particularly at older ages, and it remains unclear how sleep duration may be associated with risk of multimorbidity,” she said. She noted that several biological hypotheses have been proposed as underlying the association.
“Sleep is important for the regulation of several body functions, such as metabolic, endocrine, and inflammatory regulation over the day, that in turn, when dysregulated, may contribute to increased risk of several chronic conditions.”
The authors acknowledge several study limitations, including the fact that the data were obtained via participant self-reports, which may be affected by reporting bias. There was also a lack of diversity within the study sample, as the civil servants were mostly male and White. In addition to this, the investigators note that the study population of British civil servants tended to be healthier than the general population.
Chicken or egg?
Commenting on the findings for this article, Charlene Gamaldo, MD, urged caution in interpreting the findings. She noted that self-reporting of sleep has been established as “potentially problematic” because it doesn’t always correlate with actual sleep.
Dr. Gamaldo, who is professor of neurology and psychiatry at Johns Hopkins University in Baltimore and the medical director of the JHU Center for Sleep and Wellness, said previous studies have shown that underestimation of sleep can occur among those suffering with insomnia and that overestimation can be seen among individuals with behaviorally based chronic, insufficient sleep.
Dr. Gamaldo also raised the issue of sleep quality.
“Getting 5 hours of high-quality sleep is less worrisome than one getting 8 hours of terrible-quality, based on untreated sleep apnea, for instance,” she noted.
In addition, she pointed out that chronic health problems can interrupt sleep. “Which is the chicken, and which is the egg?” she asked.
“For me, the take-home of current literature and supported by this paper is that individuals with sleep quality complaints, short duration, or related impact in daytime function should address them with their treating provider to assess for the underlying cause.
“Those sleeping under 5 hours without complaints should consider whether 5 hours really represents the amount of sleep they need to wake rested and function at their best. If answer is no, they should prioritize getting more sleep,” she concluded.
The study was funded by the National Institute on Aging, the National Institute of Health, the UK Research Medical Council, the British Heart Foundation, the Wellcome Trust, and the French National Research Agency. The investigators and Dr. Gamaldo report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, results of a large study show.
Researchers at University College London and Université Paris Cité found that beginning at age 50, those who slept 5 hours or fewer a night had a 30% higher risk of developing multiple chronic diseases over time than those who slept at least 7 hours a night. By the time the participants were aged 70 years, that risk had increased to 40%.
Diseases for which there was a higher risk included diabetes, cancer, coronary heart disease, stroke, heart failure, chronic obstructive pulmonary disease, chronic kidney disease, liver disease, depression, dementia, Parkinson’s disease, and arthritis.
“It is important to take care of our sleep,” lead investigator Séverine Sabia, PhD, said in an interview. Dr. Sabia is a researcher and epidemiologist at Université Paris Cité and INSERM in Paris, and the University College London.
She noted that the source of the sleep problem must be addressed, but in cases in which there is no medical reason for sleep paucity, “healthy sleep habits are a must. These include keeping a regular sleep schedule, a healthy lifestyle – physical activity and light exposure during the day, and a light dinner – and avoidance of screens for a half hour before sleep.”
The study was published online in PLOS Medicine.
Risk of multiple chronic diseases
Prior research suggests that sleeping for 5 hours or less or 9 hours or more is associated with cancer and cardiovascular disease (CVD).
For the current study, Dr. Sabia and her team asked nearly 8,000 civil servants in the United Kingdom as part of the Whitehall II cohort study to report the amount of sleep they received beginning at age 50 every 4 to 5 years for the next 25 years. Study participants were free of chronic disease at age 50 and were mostly male (67.5%) and White (90%).
The investigators found that at age 50, those who slept 5 hours or less were 30% more likely to be diagnosed with multiple chronic diseases over time, (hazard ratio, 1.30; 95% confidence interval, 1.12-1.50; P < .001) compared with their peers who slept 7 hours.
At age 60, those who slept 5 hours or less had a 32% greater risk of developing more than one chronic disease (HR, 1.32; 95% CI, 1.13-1.55; P < .001), and by age 70, this risk increased to 40% compared with their peers who slept 7 hours a night (HR, 1.40; 95% CI, 1.16-1.68; P < .001).
For participants who slept 9 or more hours per night, only those aged 60 (HR, 1.54; 95% CI, 1.15-2.06; P = .003) and 70 (HR, 1.51; 95% CI, 1.10-2.08; P = .010) were at increased risk of developing more than one chronic disease.
Dr. Sabia noted that previous studies have shown that those who slept less than 5 hours a night were more likely to develop diabetes, hypertension, CVD, or dementia. “However, chronic diseases often coexist, particularly at older ages, and it remains unclear how sleep duration may be associated with risk of multimorbidity,” she said. She noted that several biological hypotheses have been proposed as underlying the association.
“Sleep is important for the regulation of several body functions, such as metabolic, endocrine, and inflammatory regulation over the day, that in turn, when dysregulated, may contribute to increased risk of several chronic conditions.”
The authors acknowledge several study limitations, including the fact that the data were obtained via participant self-reports, which may be affected by reporting bias. There was also a lack of diversity within the study sample, as the civil servants were mostly male and White. In addition to this, the investigators note that the study population of British civil servants tended to be healthier than the general population.
Chicken or egg?
Commenting on the findings for this article, Charlene Gamaldo, MD, urged caution in interpreting the findings. She noted that self-reporting of sleep has been established as “potentially problematic” because it doesn’t always correlate with actual sleep.
Dr. Gamaldo, who is professor of neurology and psychiatry at Johns Hopkins University in Baltimore and the medical director of the JHU Center for Sleep and Wellness, said previous studies have shown that underestimation of sleep can occur among those suffering with insomnia and that overestimation can be seen among individuals with behaviorally based chronic, insufficient sleep.
Dr. Gamaldo also raised the issue of sleep quality.
“Getting 5 hours of high-quality sleep is less worrisome than one getting 8 hours of terrible-quality, based on untreated sleep apnea, for instance,” she noted.
In addition, she pointed out that chronic health problems can interrupt sleep. “Which is the chicken, and which is the egg?” she asked.
“For me, the take-home of current literature and supported by this paper is that individuals with sleep quality complaints, short duration, or related impact in daytime function should address them with their treating provider to assess for the underlying cause.
“Those sleeping under 5 hours without complaints should consider whether 5 hours really represents the amount of sleep they need to wake rested and function at their best. If answer is no, they should prioritize getting more sleep,” she concluded.
The study was funded by the National Institute on Aging, the National Institute of Health, the UK Research Medical Council, the British Heart Foundation, the Wellcome Trust, and the French National Research Agency. The investigators and Dr. Gamaldo report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, results of a large study show.
Researchers at University College London and Université Paris Cité found that beginning at age 50, those who slept 5 hours or fewer a night had a 30% higher risk of developing multiple chronic diseases over time than those who slept at least 7 hours a night. By the time the participants were aged 70 years, that risk had increased to 40%.
Diseases for which there was a higher risk included diabetes, cancer, coronary heart disease, stroke, heart failure, chronic obstructive pulmonary disease, chronic kidney disease, liver disease, depression, dementia, Parkinson’s disease, and arthritis.
“It is important to take care of our sleep,” lead investigator Séverine Sabia, PhD, said in an interview. Dr. Sabia is a researcher and epidemiologist at Université Paris Cité and INSERM in Paris, and the University College London.
She noted that the source of the sleep problem must be addressed, but in cases in which there is no medical reason for sleep paucity, “healthy sleep habits are a must. These include keeping a regular sleep schedule, a healthy lifestyle – physical activity and light exposure during the day, and a light dinner – and avoidance of screens for a half hour before sleep.”
The study was published online in PLOS Medicine.
Risk of multiple chronic diseases
Prior research suggests that sleeping for 5 hours or less or 9 hours or more is associated with cancer and cardiovascular disease (CVD).
For the current study, Dr. Sabia and her team asked nearly 8,000 civil servants in the United Kingdom as part of the Whitehall II cohort study to report the amount of sleep they received beginning at age 50 every 4 to 5 years for the next 25 years. Study participants were free of chronic disease at age 50 and were mostly male (67.5%) and White (90%).
The investigators found that at age 50, those who slept 5 hours or less were 30% more likely to be diagnosed with multiple chronic diseases over time, (hazard ratio, 1.30; 95% confidence interval, 1.12-1.50; P < .001) compared with their peers who slept 7 hours.
At age 60, those who slept 5 hours or less had a 32% greater risk of developing more than one chronic disease (HR, 1.32; 95% CI, 1.13-1.55; P < .001), and by age 70, this risk increased to 40% compared with their peers who slept 7 hours a night (HR, 1.40; 95% CI, 1.16-1.68; P < .001).
For participants who slept 9 or more hours per night, only those aged 60 (HR, 1.54; 95% CI, 1.15-2.06; P = .003) and 70 (HR, 1.51; 95% CI, 1.10-2.08; P = .010) were at increased risk of developing more than one chronic disease.
Dr. Sabia noted that previous studies have shown that those who slept less than 5 hours a night were more likely to develop diabetes, hypertension, CVD, or dementia. “However, chronic diseases often coexist, particularly at older ages, and it remains unclear how sleep duration may be associated with risk of multimorbidity,” she said. She noted that several biological hypotheses have been proposed as underlying the association.
“Sleep is important for the regulation of several body functions, such as metabolic, endocrine, and inflammatory regulation over the day, that in turn, when dysregulated, may contribute to increased risk of several chronic conditions.”
The authors acknowledge several study limitations, including the fact that the data were obtained via participant self-reports, which may be affected by reporting bias. There was also a lack of diversity within the study sample, as the civil servants were mostly male and White. In addition to this, the investigators note that the study population of British civil servants tended to be healthier than the general population.
Chicken or egg?
Commenting on the findings for this article, Charlene Gamaldo, MD, urged caution in interpreting the findings. She noted that self-reporting of sleep has been established as “potentially problematic” because it doesn’t always correlate with actual sleep.
Dr. Gamaldo, who is professor of neurology and psychiatry at Johns Hopkins University in Baltimore and the medical director of the JHU Center for Sleep and Wellness, said previous studies have shown that underestimation of sleep can occur among those suffering with insomnia and that overestimation can be seen among individuals with behaviorally based chronic, insufficient sleep.
Dr. Gamaldo also raised the issue of sleep quality.
“Getting 5 hours of high-quality sleep is less worrisome than one getting 8 hours of terrible-quality, based on untreated sleep apnea, for instance,” she noted.
In addition, she pointed out that chronic health problems can interrupt sleep. “Which is the chicken, and which is the egg?” she asked.
“For me, the take-home of current literature and supported by this paper is that individuals with sleep quality complaints, short duration, or related impact in daytime function should address them with their treating provider to assess for the underlying cause.
“Those sleeping under 5 hours without complaints should consider whether 5 hours really represents the amount of sleep they need to wake rested and function at their best. If answer is no, they should prioritize getting more sleep,” she concluded.
The study was funded by the National Institute on Aging, the National Institute of Health, the UK Research Medical Council, the British Heart Foundation, the Wellcome Trust, and the French National Research Agency. The investigators and Dr. Gamaldo report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM PLOS MEDICINE
Study finds systemic AD treatment relieves depressive symptoms along with skin symptoms
MONTREAL – presented at the annual meeting of the International Society of Atopic Dermatitis.
“Randomized, controlled, phase 3 studies have shown that systemic treatment of AD reduces depressive symptoms, but whether this holds true in real-world cohorts remains to be shown,” said study investigator Lina Ivert, MD, PhD, of the dermatology and venereology unit in the department of medicine at the Karolinska Institutet, Stockholm.
The study used data from SwedAD, a newly launched web-based Swedish national registry of patients with AD on systemic treatment between June 2017 and August 2021. Participants were followed at 6 and 12 months for the primary outcome of depressive symptoms using the Montgomery–Åsberg Depression Rating Scale–self-report (MADRS-S). Secondary outcomes included the Eczema Area and Severity Index (EASI) score, Patient-Oriented Eczema Measure (POEM), the Dermatology Life Quality Index (DLQI), and pruritus visual analog scale/numeric rating scale (VAS/NRS).
At baseline, 120 patients (median age, 39 years; 57.5% men) were started on dupilumab (n = 91), methotrexate (26), or cyclosporin (3). Although almost half had no depression at baseline, mild depression was present in 29.2%, with moderate and severe depression in 20% and 4.2%, respectively.
Among 59 patients with 6-month follow-up data (48 on dupilumab, 10 on methotrexate, 1 on cyclosporin), all nine depressive symptoms in MADRS-S improved significantly, with reduced sleep improving the most (from a median of 3 points to a median of 1 point). Similarly, overall MADRS-S scores improved (from a median of 14 points to a median of 5; P < .001), as did EASI scores (from a median of 20.5 to 2), POEM scores (from a median of 22 to 6), DLQI (from a median of 15 to 3), and pruritus scores (from a median of 7.1 to 1.8; all P < .001).
The analysis also found a strong correlation between the MADRS-S score and all of the secondary outcomes (P < .001 for all). All these improvements remained significant among the 36 patients with 12-month follow-up data.
“The median MADRS-S reduction also remained when we excluded eight patients who were on antidepressants during the study period, so these results cannot be explained by psychiatric medication,” noted Dr. Ivert, adding that three patients with severe suicide ideation at baseline improved their MADRS-S suicide item to less than 2 points. “So, this study taught us to look at the suicide item score and not only the total MADRS-S score,” she commented.
Comparing patients treated with dupilumab with those treated with methotrexate, the analysis showed that though baseline median MADRS-S scores did not differ significantly between them, there was a significant 6-month reduction in the dupilumab group but not in the methotrexate group.
Asked to comment on the findings, moderator Marissa Joseph, MD, a pediatric dermatologist at the University of Toronto, said that “the mental health effects of inflammatory skin conditions like atopic dermatitis are well known, but whether or not they are well explored in the patient-physician interaction is a whole other scenario.” There are time constraints, she said, adding, “it sometimes takes some deep-diving ... but exploring those types of symptoms is something we need to do more of, and the severity of the disease and reasons for treatment are not just what you can see.”
Dr. Joseph pointed out that taking the deep dive also involves being prepared for what comes up. “Once you’ve established there’s a mental health issue, what do you do then?” she said. “If you are a dermatologist, is that in your wheelhouse to address? There’s the education and connection piece for the physician, creating networks where – if you identify a patient who has an issue – who is a person I can send them to? We have these types of connections with infectious disease or with ophthalmologists if there are ocular symptoms, but mental health is one area where there may not be as much support for dermatologists.”
She noted that though all doctors learn how to screen for depression, “there’s the formulaic, yes/no answers, and then there’s the nuanced history-taking, creating a safe space, where the patient is going to answer you fulsomely ... and feel heard. Many of us know how to do that. The question is time.”
Dr. Ivert had no disclosures connected to this study. Dr. Joseph had no disclosures.
A version of this article first appeared on Medscape.com.
MONTREAL – presented at the annual meeting of the International Society of Atopic Dermatitis.
“Randomized, controlled, phase 3 studies have shown that systemic treatment of AD reduces depressive symptoms, but whether this holds true in real-world cohorts remains to be shown,” said study investigator Lina Ivert, MD, PhD, of the dermatology and venereology unit in the department of medicine at the Karolinska Institutet, Stockholm.
The study used data from SwedAD, a newly launched web-based Swedish national registry of patients with AD on systemic treatment between June 2017 and August 2021. Participants were followed at 6 and 12 months for the primary outcome of depressive symptoms using the Montgomery–Åsberg Depression Rating Scale–self-report (MADRS-S). Secondary outcomes included the Eczema Area and Severity Index (EASI) score, Patient-Oriented Eczema Measure (POEM), the Dermatology Life Quality Index (DLQI), and pruritus visual analog scale/numeric rating scale (VAS/NRS).
At baseline, 120 patients (median age, 39 years; 57.5% men) were started on dupilumab (n = 91), methotrexate (26), or cyclosporin (3). Although almost half had no depression at baseline, mild depression was present in 29.2%, with moderate and severe depression in 20% and 4.2%, respectively.
Among 59 patients with 6-month follow-up data (48 on dupilumab, 10 on methotrexate, 1 on cyclosporin), all nine depressive symptoms in MADRS-S improved significantly, with reduced sleep improving the most (from a median of 3 points to a median of 1 point). Similarly, overall MADRS-S scores improved (from a median of 14 points to a median of 5; P < .001), as did EASI scores (from a median of 20.5 to 2), POEM scores (from a median of 22 to 6), DLQI (from a median of 15 to 3), and pruritus scores (from a median of 7.1 to 1.8; all P < .001).
The analysis also found a strong correlation between the MADRS-S score and all of the secondary outcomes (P < .001 for all). All these improvements remained significant among the 36 patients with 12-month follow-up data.
“The median MADRS-S reduction also remained when we excluded eight patients who were on antidepressants during the study period, so these results cannot be explained by psychiatric medication,” noted Dr. Ivert, adding that three patients with severe suicide ideation at baseline improved their MADRS-S suicide item to less than 2 points. “So, this study taught us to look at the suicide item score and not only the total MADRS-S score,” she commented.
Comparing patients treated with dupilumab with those treated with methotrexate, the analysis showed that though baseline median MADRS-S scores did not differ significantly between them, there was a significant 6-month reduction in the dupilumab group but not in the methotrexate group.
Asked to comment on the findings, moderator Marissa Joseph, MD, a pediatric dermatologist at the University of Toronto, said that “the mental health effects of inflammatory skin conditions like atopic dermatitis are well known, but whether or not they are well explored in the patient-physician interaction is a whole other scenario.” There are time constraints, she said, adding, “it sometimes takes some deep-diving ... but exploring those types of symptoms is something we need to do more of, and the severity of the disease and reasons for treatment are not just what you can see.”
Dr. Joseph pointed out that taking the deep dive also involves being prepared for what comes up. “Once you’ve established there’s a mental health issue, what do you do then?” she said. “If you are a dermatologist, is that in your wheelhouse to address? There’s the education and connection piece for the physician, creating networks where – if you identify a patient who has an issue – who is a person I can send them to? We have these types of connections with infectious disease or with ophthalmologists if there are ocular symptoms, but mental health is one area where there may not be as much support for dermatologists.”
She noted that though all doctors learn how to screen for depression, “there’s the formulaic, yes/no answers, and then there’s the nuanced history-taking, creating a safe space, where the patient is going to answer you fulsomely ... and feel heard. Many of us know how to do that. The question is time.”
Dr. Ivert had no disclosures connected to this study. Dr. Joseph had no disclosures.
A version of this article first appeared on Medscape.com.
MONTREAL – presented at the annual meeting of the International Society of Atopic Dermatitis.
“Randomized, controlled, phase 3 studies have shown that systemic treatment of AD reduces depressive symptoms, but whether this holds true in real-world cohorts remains to be shown,” said study investigator Lina Ivert, MD, PhD, of the dermatology and venereology unit in the department of medicine at the Karolinska Institutet, Stockholm.
The study used data from SwedAD, a newly launched web-based Swedish national registry of patients with AD on systemic treatment between June 2017 and August 2021. Participants were followed at 6 and 12 months for the primary outcome of depressive symptoms using the Montgomery–Åsberg Depression Rating Scale–self-report (MADRS-S). Secondary outcomes included the Eczema Area and Severity Index (EASI) score, Patient-Oriented Eczema Measure (POEM), the Dermatology Life Quality Index (DLQI), and pruritus visual analog scale/numeric rating scale (VAS/NRS).
At baseline, 120 patients (median age, 39 years; 57.5% men) were started on dupilumab (n = 91), methotrexate (26), or cyclosporin (3). Although almost half had no depression at baseline, mild depression was present in 29.2%, with moderate and severe depression in 20% and 4.2%, respectively.
Among 59 patients with 6-month follow-up data (48 on dupilumab, 10 on methotrexate, 1 on cyclosporin), all nine depressive symptoms in MADRS-S improved significantly, with reduced sleep improving the most (from a median of 3 points to a median of 1 point). Similarly, overall MADRS-S scores improved (from a median of 14 points to a median of 5; P < .001), as did EASI scores (from a median of 20.5 to 2), POEM scores (from a median of 22 to 6), DLQI (from a median of 15 to 3), and pruritus scores (from a median of 7.1 to 1.8; all P < .001).
The analysis also found a strong correlation between the MADRS-S score and all of the secondary outcomes (P < .001 for all). All these improvements remained significant among the 36 patients with 12-month follow-up data.
“The median MADRS-S reduction also remained when we excluded eight patients who were on antidepressants during the study period, so these results cannot be explained by psychiatric medication,” noted Dr. Ivert, adding that three patients with severe suicide ideation at baseline improved their MADRS-S suicide item to less than 2 points. “So, this study taught us to look at the suicide item score and not only the total MADRS-S score,” she commented.
Comparing patients treated with dupilumab with those treated with methotrexate, the analysis showed that though baseline median MADRS-S scores did not differ significantly between them, there was a significant 6-month reduction in the dupilumab group but not in the methotrexate group.
Asked to comment on the findings, moderator Marissa Joseph, MD, a pediatric dermatologist at the University of Toronto, said that “the mental health effects of inflammatory skin conditions like atopic dermatitis are well known, but whether or not they are well explored in the patient-physician interaction is a whole other scenario.” There are time constraints, she said, adding, “it sometimes takes some deep-diving ... but exploring those types of symptoms is something we need to do more of, and the severity of the disease and reasons for treatment are not just what you can see.”
Dr. Joseph pointed out that taking the deep dive also involves being prepared for what comes up. “Once you’ve established there’s a mental health issue, what do you do then?” she said. “If you are a dermatologist, is that in your wheelhouse to address? There’s the education and connection piece for the physician, creating networks where – if you identify a patient who has an issue – who is a person I can send them to? We have these types of connections with infectious disease or with ophthalmologists if there are ocular symptoms, but mental health is one area where there may not be as much support for dermatologists.”
She noted that though all doctors learn how to screen for depression, “there’s the formulaic, yes/no answers, and then there’s the nuanced history-taking, creating a safe space, where the patient is going to answer you fulsomely ... and feel heard. Many of us know how to do that. The question is time.”
Dr. Ivert had no disclosures connected to this study. Dr. Joseph had no disclosures.
A version of this article first appeared on Medscape.com.
FROM ISAD 2022
C. diff recurrence drops with highly targeted ridinilazole
WASHINGTON – (CDI), according to phase 3 trial results presented at an annual scientific meeting on infectious diseases.
According to the Centers for Disease Control and Prevention, CDI is the top cause of antibiotic-associated diarrhea and one of the most common health care–associated infections in the United States. About 200,000 people in the United States are infected with C. difficile every year in the hospital or clinical care setting.
Most infections are currently treated with vancomycin. Although vancomycin has been shown to be more than 80% effective, it has been linked with recurrence rates ranging from 20% to 30% and interferes with the protective role of the gut microbiome against infection. The current study compared ridinilazole with vancomycin.
Results of the global, double-blinded, randomized trial were presented by Pablo C. Okhuysen, MD, professor of infectious disease at the University of Texas MD Anderson Cancer Center, Houston.
Participants with CDI received a 10-day course of ridinilazole 200 mg twice a day plus placebo or vancomycin 125 mg four times a day. The primary endpoint was sustained clinical response, defined as a clinical response with no recurrent CDI through 30 days after the end of treatment. Recurrent CDI was defined as a new episode of diarrhea with confirmed positive free toxin test requiring additional therapy.
Of the 759 patients enrolled, 745 were included in the modified intention-to-treat population (ridinilazole, n = 370; vancomycin, n = 375). Ridinilazole achieved a numerically higher rate of sustained clinical response than vancomycin (73.0% vs. 70.7%; P = .467), although the difference was not significant. Ridinilazole also resulted in a significant reduction in recurrence rate (8.1% vs. 17.3%; P < .001).
Ridinilazole’s effect was most notable in a subgroup of patients who were not receiving other antibiotics at time of enrollment – about 70% of participants. In that subgroup, the recurrence rate was 6.7% with ridinilazole versus 16.5% with vancomycin (P < .001), Dr. Okhuysen reported.
“That resulted in a relative risk reduction of 60%,” Dr. Okhuysen told this news organization.
Dr. Okhuysen pointed out that there are currently very few treatment options for CDI other than vancomycin.
“We need new agents to treat C. difficile,” he said, “particularly for those at risk of recurrence. In our study, we found that those exposed to vancomycin had very dramatic shifts in their microbiome.”
Vancomycin depletes the gut microbiome, which decreases the conversion of primary acids to secondary bile acids, the researchers noted.
“A dysbiotic microbiome is fertile ground for C. difficile to grow,” Dr. Okhuysen said. Ridinilazole does not disrupt the microbiome, he added.
Ridinilazole was well-tolerated in the study. The proportion of patients with at least one treatment-emergent adverse effect was 36.4% versus 35.5%, respectively, in the ridinilazole and vancomycin groups. And the proportion who stopped treatment because of treatment-related side effects was 0.8% versus 2.9%.
Mary Hayden, MD, pathology director in the division of infectious diseases at Rush University Medical Center, Chicago, who was not involved with the study, said the results are encouraging as “alternative agents or strategies to prevent recurrence are important to reduce CDI morbidity.”
Its double-blind, randomized, multicenter design strengthens the findings, she explained, adding that “the secondary outcomes of higher concentrations of secondary bile acids and microbiota diversity and composition lend biological plausibility.”
Ridinilazole’s narrow spectrum of activity “should result in less disruption of the colonic microbiota, which has theoretical benefit for both reducing CDI recurrence and for reducing risk of acquisition of multidrug-resistant organisms,” Dr. Hayden said.
Dr. Okhuysen shared that the team is in talks with the Food and Drug Administration and is preparing a manuscript for publication.
The study was supported by Summit Pharmaceuticals and funded by the Biomedical and Advanced Research and Development Authority. Dr. Okhuysen has reported receiving research support from and/or consulting for Summit, Merck, Deinove, Melinta, and Ferring Pharmaceuticals. Some of the coauthors have financial relationships with or received research support from Summit. Dr. Hayden has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WASHINGTON – (CDI), according to phase 3 trial results presented at an annual scientific meeting on infectious diseases.
According to the Centers for Disease Control and Prevention, CDI is the top cause of antibiotic-associated diarrhea and one of the most common health care–associated infections in the United States. About 200,000 people in the United States are infected with C. difficile every year in the hospital or clinical care setting.
Most infections are currently treated with vancomycin. Although vancomycin has been shown to be more than 80% effective, it has been linked with recurrence rates ranging from 20% to 30% and interferes with the protective role of the gut microbiome against infection. The current study compared ridinilazole with vancomycin.
Results of the global, double-blinded, randomized trial were presented by Pablo C. Okhuysen, MD, professor of infectious disease at the University of Texas MD Anderson Cancer Center, Houston.
Participants with CDI received a 10-day course of ridinilazole 200 mg twice a day plus placebo or vancomycin 125 mg four times a day. The primary endpoint was sustained clinical response, defined as a clinical response with no recurrent CDI through 30 days after the end of treatment. Recurrent CDI was defined as a new episode of diarrhea with confirmed positive free toxin test requiring additional therapy.
Of the 759 patients enrolled, 745 were included in the modified intention-to-treat population (ridinilazole, n = 370; vancomycin, n = 375). Ridinilazole achieved a numerically higher rate of sustained clinical response than vancomycin (73.0% vs. 70.7%; P = .467), although the difference was not significant. Ridinilazole also resulted in a significant reduction in recurrence rate (8.1% vs. 17.3%; P < .001).
Ridinilazole’s effect was most notable in a subgroup of patients who were not receiving other antibiotics at time of enrollment – about 70% of participants. In that subgroup, the recurrence rate was 6.7% with ridinilazole versus 16.5% with vancomycin (P < .001), Dr. Okhuysen reported.
“That resulted in a relative risk reduction of 60%,” Dr. Okhuysen told this news organization.
Dr. Okhuysen pointed out that there are currently very few treatment options for CDI other than vancomycin.
“We need new agents to treat C. difficile,” he said, “particularly for those at risk of recurrence. In our study, we found that those exposed to vancomycin had very dramatic shifts in their microbiome.”
Vancomycin depletes the gut microbiome, which decreases the conversion of primary acids to secondary bile acids, the researchers noted.
“A dysbiotic microbiome is fertile ground for C. difficile to grow,” Dr. Okhuysen said. Ridinilazole does not disrupt the microbiome, he added.
Ridinilazole was well-tolerated in the study. The proportion of patients with at least one treatment-emergent adverse effect was 36.4% versus 35.5%, respectively, in the ridinilazole and vancomycin groups. And the proportion who stopped treatment because of treatment-related side effects was 0.8% versus 2.9%.
Mary Hayden, MD, pathology director in the division of infectious diseases at Rush University Medical Center, Chicago, who was not involved with the study, said the results are encouraging as “alternative agents or strategies to prevent recurrence are important to reduce CDI morbidity.”
Its double-blind, randomized, multicenter design strengthens the findings, she explained, adding that “the secondary outcomes of higher concentrations of secondary bile acids and microbiota diversity and composition lend biological plausibility.”
Ridinilazole’s narrow spectrum of activity “should result in less disruption of the colonic microbiota, which has theoretical benefit for both reducing CDI recurrence and for reducing risk of acquisition of multidrug-resistant organisms,” Dr. Hayden said.
Dr. Okhuysen shared that the team is in talks with the Food and Drug Administration and is preparing a manuscript for publication.
The study was supported by Summit Pharmaceuticals and funded by the Biomedical and Advanced Research and Development Authority. Dr. Okhuysen has reported receiving research support from and/or consulting for Summit, Merck, Deinove, Melinta, and Ferring Pharmaceuticals. Some of the coauthors have financial relationships with or received research support from Summit. Dr. Hayden has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WASHINGTON – (CDI), according to phase 3 trial results presented at an annual scientific meeting on infectious diseases.
According to the Centers for Disease Control and Prevention, CDI is the top cause of antibiotic-associated diarrhea and one of the most common health care–associated infections in the United States. About 200,000 people in the United States are infected with C. difficile every year in the hospital or clinical care setting.
Most infections are currently treated with vancomycin. Although vancomycin has been shown to be more than 80% effective, it has been linked with recurrence rates ranging from 20% to 30% and interferes with the protective role of the gut microbiome against infection. The current study compared ridinilazole with vancomycin.
Results of the global, double-blinded, randomized trial were presented by Pablo C. Okhuysen, MD, professor of infectious disease at the University of Texas MD Anderson Cancer Center, Houston.
Participants with CDI received a 10-day course of ridinilazole 200 mg twice a day plus placebo or vancomycin 125 mg four times a day. The primary endpoint was sustained clinical response, defined as a clinical response with no recurrent CDI through 30 days after the end of treatment. Recurrent CDI was defined as a new episode of diarrhea with confirmed positive free toxin test requiring additional therapy.
Of the 759 patients enrolled, 745 were included in the modified intention-to-treat population (ridinilazole, n = 370; vancomycin, n = 375). Ridinilazole achieved a numerically higher rate of sustained clinical response than vancomycin (73.0% vs. 70.7%; P = .467), although the difference was not significant. Ridinilazole also resulted in a significant reduction in recurrence rate (8.1% vs. 17.3%; P < .001).
Ridinilazole’s effect was most notable in a subgroup of patients who were not receiving other antibiotics at time of enrollment – about 70% of participants. In that subgroup, the recurrence rate was 6.7% with ridinilazole versus 16.5% with vancomycin (P < .001), Dr. Okhuysen reported.
“That resulted in a relative risk reduction of 60%,” Dr. Okhuysen told this news organization.
Dr. Okhuysen pointed out that there are currently very few treatment options for CDI other than vancomycin.
“We need new agents to treat C. difficile,” he said, “particularly for those at risk of recurrence. In our study, we found that those exposed to vancomycin had very dramatic shifts in their microbiome.”
Vancomycin depletes the gut microbiome, which decreases the conversion of primary acids to secondary bile acids, the researchers noted.
“A dysbiotic microbiome is fertile ground for C. difficile to grow,” Dr. Okhuysen said. Ridinilazole does not disrupt the microbiome, he added.
Ridinilazole was well-tolerated in the study. The proportion of patients with at least one treatment-emergent adverse effect was 36.4% versus 35.5%, respectively, in the ridinilazole and vancomycin groups. And the proportion who stopped treatment because of treatment-related side effects was 0.8% versus 2.9%.
Mary Hayden, MD, pathology director in the division of infectious diseases at Rush University Medical Center, Chicago, who was not involved with the study, said the results are encouraging as “alternative agents or strategies to prevent recurrence are important to reduce CDI morbidity.”
Its double-blind, randomized, multicenter design strengthens the findings, she explained, adding that “the secondary outcomes of higher concentrations of secondary bile acids and microbiota diversity and composition lend biological plausibility.”
Ridinilazole’s narrow spectrum of activity “should result in less disruption of the colonic microbiota, which has theoretical benefit for both reducing CDI recurrence and for reducing risk of acquisition of multidrug-resistant organisms,” Dr. Hayden said.
Dr. Okhuysen shared that the team is in talks with the Food and Drug Administration and is preparing a manuscript for publication.
The study was supported by Summit Pharmaceuticals and funded by the Biomedical and Advanced Research and Development Authority. Dr. Okhuysen has reported receiving research support from and/or consulting for Summit, Merck, Deinove, Melinta, and Ferring Pharmaceuticals. Some of the coauthors have financial relationships with or received research support from Summit. Dr. Hayden has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT IDWEEK 2022