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Aging HIV patients face comorbidities and hospitalizations
Thanks to effective treatment, people with HIV are living longer. But as they age, they face higher rates of age-related comorbidities and hospitalizations, according to a recent study of hospitalized patients.
Decision-makers will need to allocate resources, train providers, and plan ways to manage chronic diseases, such as diabetes and cancer, among geriatric HIV inpatients, according to the authors.
“There will be more [HIV] patients with age-related chronic conditions at an earlier age and who will utilize or will have a unique need for [health care for] these geriatric conditions,” first author Khairul A. Siddiqi, PhD, University of Florida, Gainesville, said in an interview. “Eventually, that may increase inpatient resource utilization and costs.”
The study was published online in HIV Medicine.
Aging with HIV
Analyzing the National Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project, the authors compared characteristics and comorbidities linked to hospital stays among people with HIV (HSWH) to those linked to hospital stays among people without HIV (HSWOH).
The NIS is a database of hospital records that captures 20% of discharges in the United States and covers all payers. Data in this analysis covered the years 2003-2015.
Among HSWH, patients aged 50 or older accounted for an increasing proportion over time, from fewer than 25% in 2003 to over 50% by 2015, the authors found. The subgroup aged 65-80 had risen from 2.39% to 8.63% by 2015.
The authors also studied rates of eight comorbidities, termed HIV-associated non-AIDS (HANA) conditions: cardiovascular, lung, liver, neurologic, and kidney diseases; diabetes; cancer; and bone loss.
The average number of these conditions among both HSWH and HSWOH rose over time. But this change was disproportionately high among HSWH aged 50-64 and those aged 65 and older.
Over the study period, among patients aged 65 or older, six of the eight age-related conditions the researchers studied rose disproportionately among HSWH in comparison with HSWOH; among those aged 50-64, five conditions did so.
The researchers are now building on the current study of HSWH by examining rates of resource utilization, such as MRIs and procedures, Dr. Siddiqi said.
Study limitations included a lack of data from long-term facilities, potential skewing by patients hospitalized multiple times, and the inherent limitations of administrative data.
A unique group of older people
Among people with HIV (PWH) in the United States, nearly half are aged 50 or older. By 2030, this group is expected to account for some 70% of PWH.
“We need to pay attention to what we know about aging generally. It is also important to study aging in this special population, because we don’t necessarily know a lot about that,” Amy Justice, MD, PhD, professor of medicine and of public health at Yale University, New Haven, Conn., said in an interview. Dr. Justice was not involved in the study.
The HIV epidemic has disproportionately affected people of color, men who have sex with men, and people with a history of injection drug use, Dr. Justice said.
“We don’t know about aging with [a] past history of injection drug use. We don’t even know much about aging with hepatitis C, necessarily,” she said. “So there are lots of reasons to pay some attention to this population to try to optimize their care.”
In addition, compared with their non–HIV-affected counterparts, these individuals are more susceptible to HANA comorbidities. They may experience these conditions at a younger age or more severely. Chronic inflammation and polypharmacy may be to blame, said Dr. Justice.
Given the burden of comorbidities and polypharmacy in this patient population, Dr. Siddiqi said, policy makers will need to focus on developing chronic disease management interventions for them.
However, Dr. Justice added, the risk for multimorbidity is higher among people with HIV throughout the age cycle: “It’s not like I turn 50 with HIV and all of a sudden all the wheels come off. There are ways to successfully age with HIV.”
Geriatric HIV expertise needed
Dr. Justice called the study’s analysis a useful addition to the literature and noted its implications for training.
“One of the biggest challenges with this large bolus of folks who are aging with HIV,” she said, “is to what extent should they be cared for by the people who have been caring for them – largely infectious disease docs – and to what extent should we really be transitioning their care to people with more experience with aging.”
Another key question, Dr. Justice said, relates to nursing homes and assisted-living facilities, whose staff may lack experience caring for HIV patients. Training them and hospital-based providers is crucial, in part to avoid key errors, such as missed antiretroviral doses, she said: “We need to really think about how to get non-HIV providers up to speed.”
That may begin by simply making it clear that this population is here.
“A decade ago, HIV patients used to have a lower life expectancy, so all HIV studies used to use 50 years as the cutoff point for [the] older population,” Dr. Siddiqi said. “Now we know they’re living longer.”
Added Dr. Justice: “Previously, people thought aging and HIV were not coincident findings.”
The study was funded by the Office of the Vice President for Research at the University of South Carolina. The authors and Dr. Justice disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Thanks to effective treatment, people with HIV are living longer. But as they age, they face higher rates of age-related comorbidities and hospitalizations, according to a recent study of hospitalized patients.
Decision-makers will need to allocate resources, train providers, and plan ways to manage chronic diseases, such as diabetes and cancer, among geriatric HIV inpatients, according to the authors.
“There will be more [HIV] patients with age-related chronic conditions at an earlier age and who will utilize or will have a unique need for [health care for] these geriatric conditions,” first author Khairul A. Siddiqi, PhD, University of Florida, Gainesville, said in an interview. “Eventually, that may increase inpatient resource utilization and costs.”
The study was published online in HIV Medicine.
Aging with HIV
Analyzing the National Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project, the authors compared characteristics and comorbidities linked to hospital stays among people with HIV (HSWH) to those linked to hospital stays among people without HIV (HSWOH).
The NIS is a database of hospital records that captures 20% of discharges in the United States and covers all payers. Data in this analysis covered the years 2003-2015.
Among HSWH, patients aged 50 or older accounted for an increasing proportion over time, from fewer than 25% in 2003 to over 50% by 2015, the authors found. The subgroup aged 65-80 had risen from 2.39% to 8.63% by 2015.
The authors also studied rates of eight comorbidities, termed HIV-associated non-AIDS (HANA) conditions: cardiovascular, lung, liver, neurologic, and kidney diseases; diabetes; cancer; and bone loss.
The average number of these conditions among both HSWH and HSWOH rose over time. But this change was disproportionately high among HSWH aged 50-64 and those aged 65 and older.
Over the study period, among patients aged 65 or older, six of the eight age-related conditions the researchers studied rose disproportionately among HSWH in comparison with HSWOH; among those aged 50-64, five conditions did so.
The researchers are now building on the current study of HSWH by examining rates of resource utilization, such as MRIs and procedures, Dr. Siddiqi said.
Study limitations included a lack of data from long-term facilities, potential skewing by patients hospitalized multiple times, and the inherent limitations of administrative data.
A unique group of older people
Among people with HIV (PWH) in the United States, nearly half are aged 50 or older. By 2030, this group is expected to account for some 70% of PWH.
“We need to pay attention to what we know about aging generally. It is also important to study aging in this special population, because we don’t necessarily know a lot about that,” Amy Justice, MD, PhD, professor of medicine and of public health at Yale University, New Haven, Conn., said in an interview. Dr. Justice was not involved in the study.
The HIV epidemic has disproportionately affected people of color, men who have sex with men, and people with a history of injection drug use, Dr. Justice said.
“We don’t know about aging with [a] past history of injection drug use. We don’t even know much about aging with hepatitis C, necessarily,” she said. “So there are lots of reasons to pay some attention to this population to try to optimize their care.”
In addition, compared with their non–HIV-affected counterparts, these individuals are more susceptible to HANA comorbidities. They may experience these conditions at a younger age or more severely. Chronic inflammation and polypharmacy may be to blame, said Dr. Justice.
Given the burden of comorbidities and polypharmacy in this patient population, Dr. Siddiqi said, policy makers will need to focus on developing chronic disease management interventions for them.
However, Dr. Justice added, the risk for multimorbidity is higher among people with HIV throughout the age cycle: “It’s not like I turn 50 with HIV and all of a sudden all the wheels come off. There are ways to successfully age with HIV.”
Geriatric HIV expertise needed
Dr. Justice called the study’s analysis a useful addition to the literature and noted its implications for training.
“One of the biggest challenges with this large bolus of folks who are aging with HIV,” she said, “is to what extent should they be cared for by the people who have been caring for them – largely infectious disease docs – and to what extent should we really be transitioning their care to people with more experience with aging.”
Another key question, Dr. Justice said, relates to nursing homes and assisted-living facilities, whose staff may lack experience caring for HIV patients. Training them and hospital-based providers is crucial, in part to avoid key errors, such as missed antiretroviral doses, she said: “We need to really think about how to get non-HIV providers up to speed.”
That may begin by simply making it clear that this population is here.
“A decade ago, HIV patients used to have a lower life expectancy, so all HIV studies used to use 50 years as the cutoff point for [the] older population,” Dr. Siddiqi said. “Now we know they’re living longer.”
Added Dr. Justice: “Previously, people thought aging and HIV were not coincident findings.”
The study was funded by the Office of the Vice President for Research at the University of South Carolina. The authors and Dr. Justice disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Thanks to effective treatment, people with HIV are living longer. But as they age, they face higher rates of age-related comorbidities and hospitalizations, according to a recent study of hospitalized patients.
Decision-makers will need to allocate resources, train providers, and plan ways to manage chronic diseases, such as diabetes and cancer, among geriatric HIV inpatients, according to the authors.
“There will be more [HIV] patients with age-related chronic conditions at an earlier age and who will utilize or will have a unique need for [health care for] these geriatric conditions,” first author Khairul A. Siddiqi, PhD, University of Florida, Gainesville, said in an interview. “Eventually, that may increase inpatient resource utilization and costs.”
The study was published online in HIV Medicine.
Aging with HIV
Analyzing the National Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project, the authors compared characteristics and comorbidities linked to hospital stays among people with HIV (HSWH) to those linked to hospital stays among people without HIV (HSWOH).
The NIS is a database of hospital records that captures 20% of discharges in the United States and covers all payers. Data in this analysis covered the years 2003-2015.
Among HSWH, patients aged 50 or older accounted for an increasing proportion over time, from fewer than 25% in 2003 to over 50% by 2015, the authors found. The subgroup aged 65-80 had risen from 2.39% to 8.63% by 2015.
The authors also studied rates of eight comorbidities, termed HIV-associated non-AIDS (HANA) conditions: cardiovascular, lung, liver, neurologic, and kidney diseases; diabetes; cancer; and bone loss.
The average number of these conditions among both HSWH and HSWOH rose over time. But this change was disproportionately high among HSWH aged 50-64 and those aged 65 and older.
Over the study period, among patients aged 65 or older, six of the eight age-related conditions the researchers studied rose disproportionately among HSWH in comparison with HSWOH; among those aged 50-64, five conditions did so.
The researchers are now building on the current study of HSWH by examining rates of resource utilization, such as MRIs and procedures, Dr. Siddiqi said.
Study limitations included a lack of data from long-term facilities, potential skewing by patients hospitalized multiple times, and the inherent limitations of administrative data.
A unique group of older people
Among people with HIV (PWH) in the United States, nearly half are aged 50 or older. By 2030, this group is expected to account for some 70% of PWH.
“We need to pay attention to what we know about aging generally. It is also important to study aging in this special population, because we don’t necessarily know a lot about that,” Amy Justice, MD, PhD, professor of medicine and of public health at Yale University, New Haven, Conn., said in an interview. Dr. Justice was not involved in the study.
The HIV epidemic has disproportionately affected people of color, men who have sex with men, and people with a history of injection drug use, Dr. Justice said.
“We don’t know about aging with [a] past history of injection drug use. We don’t even know much about aging with hepatitis C, necessarily,” she said. “So there are lots of reasons to pay some attention to this population to try to optimize their care.”
In addition, compared with their non–HIV-affected counterparts, these individuals are more susceptible to HANA comorbidities. They may experience these conditions at a younger age or more severely. Chronic inflammation and polypharmacy may be to blame, said Dr. Justice.
Given the burden of comorbidities and polypharmacy in this patient population, Dr. Siddiqi said, policy makers will need to focus on developing chronic disease management interventions for them.
However, Dr. Justice added, the risk for multimorbidity is higher among people with HIV throughout the age cycle: “It’s not like I turn 50 with HIV and all of a sudden all the wheels come off. There are ways to successfully age with HIV.”
Geriatric HIV expertise needed
Dr. Justice called the study’s analysis a useful addition to the literature and noted its implications for training.
“One of the biggest challenges with this large bolus of folks who are aging with HIV,” she said, “is to what extent should they be cared for by the people who have been caring for them – largely infectious disease docs – and to what extent should we really be transitioning their care to people with more experience with aging.”
Another key question, Dr. Justice said, relates to nursing homes and assisted-living facilities, whose staff may lack experience caring for HIV patients. Training them and hospital-based providers is crucial, in part to avoid key errors, such as missed antiretroviral doses, she said: “We need to really think about how to get non-HIV providers up to speed.”
That may begin by simply making it clear that this population is here.
“A decade ago, HIV patients used to have a lower life expectancy, so all HIV studies used to use 50 years as the cutoff point for [the] older population,” Dr. Siddiqi said. “Now we know they’re living longer.”
Added Dr. Justice: “Previously, people thought aging and HIV were not coincident findings.”
The study was funded by the Office of the Vice President for Research at the University of South Carolina. The authors and Dr. Justice disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM HIV MEDICINE
Autoimmune disorder drugs top list of meds linked to headache
DENVER – in a federal side effect database that anyone can contribute to, according to a new study presented at the annual meeting of the American Headache Society.
“Surprising findings included the significant number of immunosuppressants and immunomodulators present in the data,” study lead author Brett Musialowicz, a medical student at Robert Wood Johnson Medical School, New Brunswich, N.J., said in an interview. “Additionally, our data provides evidence that suggests that several medications belonging to these drug classes were less likely to be associated with medication-induced headaches,” raising questions about the mechanism.
Drugs most frequently linked to headaches
The researchers launched their study to better understand headache as a side effect of medication use, Mr. Musialowicz said. They analyzed entries from the Food and Drug Administration’s Adverse Event Reporting System for the period from July 2018 to March 2020 and listed the top 30 most commonly reported medications linked to headaches and their reported odds ratio. According to a website devoted to pharmacovigilance training, ROR refers to “the odds of a certain event occurring with your medicinal product, compared with the odds of the same event occurring with all other medicinal products in the database.”
After generic and brand name data was consolidated, the drug most frequently linked to headaches was apremilast with 8,672 reports, followed by adalimumab (5,357), tofacitinib (4,276), fingolimod (4,123), and etanercept (4,111). These drugs treat autoimmune disorders such as psoriasis, multiple sclerosis, and Crohn’s disease.
The other drugs in the top 15 ranked by frequency are treatments for hepatitis C (4 drugs), pulmonary arterial hypertension (4 drugs), arthritis (1 drug), and asthma (1 drug).
Of the top 30 drugs most frequently linked to headaches, the pulmonary hypertension drug epoprostenol – ranked 23rd – had the highest ROR at 12.8. The next highest were the hepatitis C drugs glecaprevir and pibrentasvir, tied at 10th in the frequency analysis and both with an ROR of 9.4.
“Pulmonary arterial dilators and vasodilators are believed to cause headaches by sensitizing extracranial arteries. Clinical evidence suggests there a vascular component to some types of headache,” Mr. Musialowicz said. “Monoclonal antibodies are suggested to cause headache by means of an immune response. Several monoclonal antibodies are in trials targeting [the calcitonin gene-related peptide] receptor, which is believed to be involved in migraine headache. These trials will help further elucidate the mechanisms of headache and potential drugs to treat these conditions.”
Is the data useful?
Stewart Tepper, MD, a neurologist at Geisel School of Medicine at Dartmouth, Hanover, N.H., who’s familiar with the study findings, discounted the new research in an interview. He noted that any member of the public can contribute to the federal database of adverse effects (drug manufacturers are required to contribute to it), and the data says nothing about denominators.
“It’s not a reasonable way to evaluate adverse effects, to just have everyone and their uncle saying ‘This particular drug did this to me.’ It’s not in any way useful,” he said. However, he added that the database sometimes “gives you a bit of a signal so you can go back and try to get scientifically collected data.”
When asked to respond, study coauthor and neurologist Pengfei (Phil) Zhang, MD, of Robert Wood Johnson Medical School, noted that the FDA created the database “for a reason.” He also noted that the researchers used a statistical analysis technique – ROR – that was invented to adjust for weaknesses in databases.
No study funding is reported. Mr. Musialowicz reported no disclosures. Dr. Zhang has received honorarium from Alder Biopharmaceuticals, Board Vitals, and Fieve Clinical Research. He collaborates with Headache Science Incorporated without receiving financial support, and he has ownership interest in Cymbeline. Another author reports research grant support from the American Epilepsy Society and the New Jersey Health Foundation. Dr. Tepper reported multiple disclosures.
DENVER – in a federal side effect database that anyone can contribute to, according to a new study presented at the annual meeting of the American Headache Society.
“Surprising findings included the significant number of immunosuppressants and immunomodulators present in the data,” study lead author Brett Musialowicz, a medical student at Robert Wood Johnson Medical School, New Brunswich, N.J., said in an interview. “Additionally, our data provides evidence that suggests that several medications belonging to these drug classes were less likely to be associated with medication-induced headaches,” raising questions about the mechanism.
Drugs most frequently linked to headaches
The researchers launched their study to better understand headache as a side effect of medication use, Mr. Musialowicz said. They analyzed entries from the Food and Drug Administration’s Adverse Event Reporting System for the period from July 2018 to March 2020 and listed the top 30 most commonly reported medications linked to headaches and their reported odds ratio. According to a website devoted to pharmacovigilance training, ROR refers to “the odds of a certain event occurring with your medicinal product, compared with the odds of the same event occurring with all other medicinal products in the database.”
After generic and brand name data was consolidated, the drug most frequently linked to headaches was apremilast with 8,672 reports, followed by adalimumab (5,357), tofacitinib (4,276), fingolimod (4,123), and etanercept (4,111). These drugs treat autoimmune disorders such as psoriasis, multiple sclerosis, and Crohn’s disease.
The other drugs in the top 15 ranked by frequency are treatments for hepatitis C (4 drugs), pulmonary arterial hypertension (4 drugs), arthritis (1 drug), and asthma (1 drug).
Of the top 30 drugs most frequently linked to headaches, the pulmonary hypertension drug epoprostenol – ranked 23rd – had the highest ROR at 12.8. The next highest were the hepatitis C drugs glecaprevir and pibrentasvir, tied at 10th in the frequency analysis and both with an ROR of 9.4.
“Pulmonary arterial dilators and vasodilators are believed to cause headaches by sensitizing extracranial arteries. Clinical evidence suggests there a vascular component to some types of headache,” Mr. Musialowicz said. “Monoclonal antibodies are suggested to cause headache by means of an immune response. Several monoclonal antibodies are in trials targeting [the calcitonin gene-related peptide] receptor, which is believed to be involved in migraine headache. These trials will help further elucidate the mechanisms of headache and potential drugs to treat these conditions.”
Is the data useful?
Stewart Tepper, MD, a neurologist at Geisel School of Medicine at Dartmouth, Hanover, N.H., who’s familiar with the study findings, discounted the new research in an interview. He noted that any member of the public can contribute to the federal database of adverse effects (drug manufacturers are required to contribute to it), and the data says nothing about denominators.
“It’s not a reasonable way to evaluate adverse effects, to just have everyone and their uncle saying ‘This particular drug did this to me.’ It’s not in any way useful,” he said. However, he added that the database sometimes “gives you a bit of a signal so you can go back and try to get scientifically collected data.”
When asked to respond, study coauthor and neurologist Pengfei (Phil) Zhang, MD, of Robert Wood Johnson Medical School, noted that the FDA created the database “for a reason.” He also noted that the researchers used a statistical analysis technique – ROR – that was invented to adjust for weaknesses in databases.
No study funding is reported. Mr. Musialowicz reported no disclosures. Dr. Zhang has received honorarium from Alder Biopharmaceuticals, Board Vitals, and Fieve Clinical Research. He collaborates with Headache Science Incorporated without receiving financial support, and he has ownership interest in Cymbeline. Another author reports research grant support from the American Epilepsy Society and the New Jersey Health Foundation. Dr. Tepper reported multiple disclosures.
DENVER – in a federal side effect database that anyone can contribute to, according to a new study presented at the annual meeting of the American Headache Society.
“Surprising findings included the significant number of immunosuppressants and immunomodulators present in the data,” study lead author Brett Musialowicz, a medical student at Robert Wood Johnson Medical School, New Brunswich, N.J., said in an interview. “Additionally, our data provides evidence that suggests that several medications belonging to these drug classes were less likely to be associated with medication-induced headaches,” raising questions about the mechanism.
Drugs most frequently linked to headaches
The researchers launched their study to better understand headache as a side effect of medication use, Mr. Musialowicz said. They analyzed entries from the Food and Drug Administration’s Adverse Event Reporting System for the period from July 2018 to March 2020 and listed the top 30 most commonly reported medications linked to headaches and their reported odds ratio. According to a website devoted to pharmacovigilance training, ROR refers to “the odds of a certain event occurring with your medicinal product, compared with the odds of the same event occurring with all other medicinal products in the database.”
After generic and brand name data was consolidated, the drug most frequently linked to headaches was apremilast with 8,672 reports, followed by adalimumab (5,357), tofacitinib (4,276), fingolimod (4,123), and etanercept (4,111). These drugs treat autoimmune disorders such as psoriasis, multiple sclerosis, and Crohn’s disease.
The other drugs in the top 15 ranked by frequency are treatments for hepatitis C (4 drugs), pulmonary arterial hypertension (4 drugs), arthritis (1 drug), and asthma (1 drug).
Of the top 30 drugs most frequently linked to headaches, the pulmonary hypertension drug epoprostenol – ranked 23rd – had the highest ROR at 12.8. The next highest were the hepatitis C drugs glecaprevir and pibrentasvir, tied at 10th in the frequency analysis and both with an ROR of 9.4.
“Pulmonary arterial dilators and vasodilators are believed to cause headaches by sensitizing extracranial arteries. Clinical evidence suggests there a vascular component to some types of headache,” Mr. Musialowicz said. “Monoclonal antibodies are suggested to cause headache by means of an immune response. Several monoclonal antibodies are in trials targeting [the calcitonin gene-related peptide] receptor, which is believed to be involved in migraine headache. These trials will help further elucidate the mechanisms of headache and potential drugs to treat these conditions.”
Is the data useful?
Stewart Tepper, MD, a neurologist at Geisel School of Medicine at Dartmouth, Hanover, N.H., who’s familiar with the study findings, discounted the new research in an interview. He noted that any member of the public can contribute to the federal database of adverse effects (drug manufacturers are required to contribute to it), and the data says nothing about denominators.
“It’s not a reasonable way to evaluate adverse effects, to just have everyone and their uncle saying ‘This particular drug did this to me.’ It’s not in any way useful,” he said. However, he added that the database sometimes “gives you a bit of a signal so you can go back and try to get scientifically collected data.”
When asked to respond, study coauthor and neurologist Pengfei (Phil) Zhang, MD, of Robert Wood Johnson Medical School, noted that the FDA created the database “for a reason.” He also noted that the researchers used a statistical analysis technique – ROR – that was invented to adjust for weaknesses in databases.
No study funding is reported. Mr. Musialowicz reported no disclosures. Dr. Zhang has received honorarium from Alder Biopharmaceuticals, Board Vitals, and Fieve Clinical Research. He collaborates with Headache Science Incorporated without receiving financial support, and he has ownership interest in Cymbeline. Another author reports research grant support from the American Epilepsy Society and the New Jersey Health Foundation. Dr. Tepper reported multiple disclosures.
AT AHS 2022
Artificial intelligence: The Netflix of cancer treatment
Chemotherapy, now streaming at just $15.99 a month!
It’s a lazy Sunday and you flip on Netflix, looking for something new to watch. There’s an almost-overwhelming number of shows out there, but right at the top of the recommended list is something that strikes your fancy right away. The algorithm behind the scenes is doing its job well, winnowing the universe of content right down to the few things you’ll find relevant, based on what you’ve watched and liked in the past.
Now, the almighty content algorithm is coming for something a little more useful than binge watching obscure 80s sitcoms: cancer treatment.
By plugging the fully sequenced genomes of nearly 10,000 patients with 33 different types of cancer into an algorithm powered by the same sort of artificial intelligence used by Netflix, researchers from London and San Diego found 21 common faults in the chromosomes of tumors, which they called copy number signatures. While cancer is a complex disease, when faults occur in those copy number signatures, the results were similar across the board. If X genetic defect occurs within a tumor, Y result will happen, even across cancer types. For example, tumors whose chromosomes had shattered and reformed had by far the worst disease outcomes.
The eventual hope is that, just as Netflix can predict what you’ll want to watch based on what you’ve already seen, oncologists will be able to predict the course of a cancer, based on the tumor’s early genetic traits, and get ahead of future genetic degradation to prevent the worst outcomes. A sort of “Oh, your tumor has enjoyed The Office. Might we suggest a treatment of 30 Rock” situation. Further research will be required to determine whether or not the cancer algorithm can get us part 2 of “Stranger Things 4” a week early.
Pay criminals, cut crime?
What is the best method for punishing those who commit wrongdoing? Fines? Jail time? Actually, no. A recent study says that financial compensation works best.
In other words, pay them for their actions. Really.
Psychologist Tage S. Rai, PhD, of the University of California, San Diego, Rady School of Management, found that people who hurt others or commit crimes are actually doing it because they think it’s the right thing to do. The results of this study say play at the angle of their morality. When that’s compromised, the offender is less likely to do it again.
Four different experiments were conducted using an online economics game with nearly 1,500 participants. Dr. Rai found that providing a monetary bonus for inflicting a punishment on a third party within the game cut the participants’ willingness to do it again by 50%.
“People punish others to signal their own goodness and receiving compensation might make it seem as though they’re driven by greed rather than justice,” he said.
The big deterrent, though, was negative judgment from peers. People in the study were even more hesitant to inflict harm and gain a profit if they thought they were going to be judged for it.
So maybe the answer to cutting crime isn’t as simple as slapping on a fine. It’s slapping on shame and paying them for it.
A conspiracy of chronobiologic proportions
The Golden State Warriors just won the NBA championship – that much is true – but we’ve got some news that you didn’t get from ESPN. The kind of news that their “partners” from the NBA didn’t want them to report. Unlike most conspiracy theories, however, this one has some science behind it.
In this case, science in the form of a study published in Frontiers in Physiology says that jet lag had a greater effect on the Boston Celtics than it did on the Warriors.
“Eastward travel – where the destination time is later than the origin time – requires the athlete to shorten their day (known as a phase advance). During phase advance, athletes often struggle to fall asleep at an earlier bedtime, leading to sleep loss and, consequently, potential impaired physiological performance and motivation the next day,” senior author Elise Facer-Childs, PhD, of Monash University, Melbourne, said in written statement.
Dr. Facer-Childs and associates took a very close look at 10 seasons’ worth of NBA games – 11,481 games, to be exact – and found “that eastward (but not westward) jet lag was associated with impaired performance for home (but not away) teams.” The existence of a pro-Western bias against teams that traveled eastward for their home games was clear:
- The chance of winning for eastern teams was reduced by 6.0%.
- They grabbed 1.3 fewer rebounds per game.
- Their field goal percentage was 1.2% lower.
And here’s the final nail in the conspiracy coffin: The NBA knew about the jet lag effect and changed the schedule of the finals in 2014 in a way that makes it worse. Before that, the higher-seeded team got two home games, then the lower-seeded team had three at home, followed by two more at the home of the higher seed. Now it’s a 2-2-1-1-1 arrangement that leads to more travel and, of course, more jet lag.
The study was published during the championship series, so the investigators suggested that the Celtics “might benefit from chronobiology-informed strategies designed to mitigate eastward jet lag symptomatology.”
So there you have it, sports fans/conspiracy theorists: You can’t chase Steph Curry around the court for 48 minutes without the right chronobiology-informed strategy. Everyone knows that.
Being hungry can alter your ‘type’
Fasting and being hungry can be a dangerous mix for becoming “hangry” and irritable, but did you know being hungry can also affect your attraction to other people?
Evidence has shown that being hungry can affect important things such as decision-making, memory, cognition, and function. It might affect decision-making in the sense that those six tacos at Taco Bell might win out over grilled chicken breast and veggies at home, but can hunger make you think that the person you just swiped right on isn’t really your type after all?
We’ll leave that up to Valentina Cazzato of Liverpool (England) John Moores University and associates, whose study involved 44 people, of whom 21 were women in their early 20s. The participants were shown computer-generated images of men and women of different sizes. The same background was used for each picture and all the expressions of the models were neutral. Participants were asked to rate each image on how much they liked it. One study was done on participants who had been fasting for 12 hours, and the second was done on those who had just eaten something.
The subjects generally preferred slim models over more rounded ones, but not after fasting. When they were hungry, they found the round human bodies and faces more attractive. So, yes, it’s definitely possible that hunger can alter your attraction to others.
“Future work might seek to elucidate the relationship between physiological states of hunger and shifts in appreciation of the human bodies and whether this relationship might be mediated by individual traits associated with to beholder’s body adiposity,” said researchers.
Chemotherapy, now streaming at just $15.99 a month!
It’s a lazy Sunday and you flip on Netflix, looking for something new to watch. There’s an almost-overwhelming number of shows out there, but right at the top of the recommended list is something that strikes your fancy right away. The algorithm behind the scenes is doing its job well, winnowing the universe of content right down to the few things you’ll find relevant, based on what you’ve watched and liked in the past.
Now, the almighty content algorithm is coming for something a little more useful than binge watching obscure 80s sitcoms: cancer treatment.
By plugging the fully sequenced genomes of nearly 10,000 patients with 33 different types of cancer into an algorithm powered by the same sort of artificial intelligence used by Netflix, researchers from London and San Diego found 21 common faults in the chromosomes of tumors, which they called copy number signatures. While cancer is a complex disease, when faults occur in those copy number signatures, the results were similar across the board. If X genetic defect occurs within a tumor, Y result will happen, even across cancer types. For example, tumors whose chromosomes had shattered and reformed had by far the worst disease outcomes.
The eventual hope is that, just as Netflix can predict what you’ll want to watch based on what you’ve already seen, oncologists will be able to predict the course of a cancer, based on the tumor’s early genetic traits, and get ahead of future genetic degradation to prevent the worst outcomes. A sort of “Oh, your tumor has enjoyed The Office. Might we suggest a treatment of 30 Rock” situation. Further research will be required to determine whether or not the cancer algorithm can get us part 2 of “Stranger Things 4” a week early.
Pay criminals, cut crime?
What is the best method for punishing those who commit wrongdoing? Fines? Jail time? Actually, no. A recent study says that financial compensation works best.
In other words, pay them for their actions. Really.
Psychologist Tage S. Rai, PhD, of the University of California, San Diego, Rady School of Management, found that people who hurt others or commit crimes are actually doing it because they think it’s the right thing to do. The results of this study say play at the angle of their morality. When that’s compromised, the offender is less likely to do it again.
Four different experiments were conducted using an online economics game with nearly 1,500 participants. Dr. Rai found that providing a monetary bonus for inflicting a punishment on a third party within the game cut the participants’ willingness to do it again by 50%.
“People punish others to signal their own goodness and receiving compensation might make it seem as though they’re driven by greed rather than justice,” he said.
The big deterrent, though, was negative judgment from peers. People in the study were even more hesitant to inflict harm and gain a profit if they thought they were going to be judged for it.
So maybe the answer to cutting crime isn’t as simple as slapping on a fine. It’s slapping on shame and paying them for it.
A conspiracy of chronobiologic proportions
The Golden State Warriors just won the NBA championship – that much is true – but we’ve got some news that you didn’t get from ESPN. The kind of news that their “partners” from the NBA didn’t want them to report. Unlike most conspiracy theories, however, this one has some science behind it.
In this case, science in the form of a study published in Frontiers in Physiology says that jet lag had a greater effect on the Boston Celtics than it did on the Warriors.
“Eastward travel – where the destination time is later than the origin time – requires the athlete to shorten their day (known as a phase advance). During phase advance, athletes often struggle to fall asleep at an earlier bedtime, leading to sleep loss and, consequently, potential impaired physiological performance and motivation the next day,” senior author Elise Facer-Childs, PhD, of Monash University, Melbourne, said in written statement.
Dr. Facer-Childs and associates took a very close look at 10 seasons’ worth of NBA games – 11,481 games, to be exact – and found “that eastward (but not westward) jet lag was associated with impaired performance for home (but not away) teams.” The existence of a pro-Western bias against teams that traveled eastward for their home games was clear:
- The chance of winning for eastern teams was reduced by 6.0%.
- They grabbed 1.3 fewer rebounds per game.
- Their field goal percentage was 1.2% lower.
And here’s the final nail in the conspiracy coffin: The NBA knew about the jet lag effect and changed the schedule of the finals in 2014 in a way that makes it worse. Before that, the higher-seeded team got two home games, then the lower-seeded team had three at home, followed by two more at the home of the higher seed. Now it’s a 2-2-1-1-1 arrangement that leads to more travel and, of course, more jet lag.
The study was published during the championship series, so the investigators suggested that the Celtics “might benefit from chronobiology-informed strategies designed to mitigate eastward jet lag symptomatology.”
So there you have it, sports fans/conspiracy theorists: You can’t chase Steph Curry around the court for 48 minutes without the right chronobiology-informed strategy. Everyone knows that.
Being hungry can alter your ‘type’
Fasting and being hungry can be a dangerous mix for becoming “hangry” and irritable, but did you know being hungry can also affect your attraction to other people?
Evidence has shown that being hungry can affect important things such as decision-making, memory, cognition, and function. It might affect decision-making in the sense that those six tacos at Taco Bell might win out over grilled chicken breast and veggies at home, but can hunger make you think that the person you just swiped right on isn’t really your type after all?
We’ll leave that up to Valentina Cazzato of Liverpool (England) John Moores University and associates, whose study involved 44 people, of whom 21 were women in their early 20s. The participants were shown computer-generated images of men and women of different sizes. The same background was used for each picture and all the expressions of the models were neutral. Participants were asked to rate each image on how much they liked it. One study was done on participants who had been fasting for 12 hours, and the second was done on those who had just eaten something.
The subjects generally preferred slim models over more rounded ones, but not after fasting. When they were hungry, they found the round human bodies and faces more attractive. So, yes, it’s definitely possible that hunger can alter your attraction to others.
“Future work might seek to elucidate the relationship between physiological states of hunger and shifts in appreciation of the human bodies and whether this relationship might be mediated by individual traits associated with to beholder’s body adiposity,” said researchers.
Chemotherapy, now streaming at just $15.99 a month!
It’s a lazy Sunday and you flip on Netflix, looking for something new to watch. There’s an almost-overwhelming number of shows out there, but right at the top of the recommended list is something that strikes your fancy right away. The algorithm behind the scenes is doing its job well, winnowing the universe of content right down to the few things you’ll find relevant, based on what you’ve watched and liked in the past.
Now, the almighty content algorithm is coming for something a little more useful than binge watching obscure 80s sitcoms: cancer treatment.
By plugging the fully sequenced genomes of nearly 10,000 patients with 33 different types of cancer into an algorithm powered by the same sort of artificial intelligence used by Netflix, researchers from London and San Diego found 21 common faults in the chromosomes of tumors, which they called copy number signatures. While cancer is a complex disease, when faults occur in those copy number signatures, the results were similar across the board. If X genetic defect occurs within a tumor, Y result will happen, even across cancer types. For example, tumors whose chromosomes had shattered and reformed had by far the worst disease outcomes.
The eventual hope is that, just as Netflix can predict what you’ll want to watch based on what you’ve already seen, oncologists will be able to predict the course of a cancer, based on the tumor’s early genetic traits, and get ahead of future genetic degradation to prevent the worst outcomes. A sort of “Oh, your tumor has enjoyed The Office. Might we suggest a treatment of 30 Rock” situation. Further research will be required to determine whether or not the cancer algorithm can get us part 2 of “Stranger Things 4” a week early.
Pay criminals, cut crime?
What is the best method for punishing those who commit wrongdoing? Fines? Jail time? Actually, no. A recent study says that financial compensation works best.
In other words, pay them for their actions. Really.
Psychologist Tage S. Rai, PhD, of the University of California, San Diego, Rady School of Management, found that people who hurt others or commit crimes are actually doing it because they think it’s the right thing to do. The results of this study say play at the angle of their morality. When that’s compromised, the offender is less likely to do it again.
Four different experiments were conducted using an online economics game with nearly 1,500 participants. Dr. Rai found that providing a monetary bonus for inflicting a punishment on a third party within the game cut the participants’ willingness to do it again by 50%.
“People punish others to signal their own goodness and receiving compensation might make it seem as though they’re driven by greed rather than justice,” he said.
The big deterrent, though, was negative judgment from peers. People in the study were even more hesitant to inflict harm and gain a profit if they thought they were going to be judged for it.
So maybe the answer to cutting crime isn’t as simple as slapping on a fine. It’s slapping on shame and paying them for it.
A conspiracy of chronobiologic proportions
The Golden State Warriors just won the NBA championship – that much is true – but we’ve got some news that you didn’t get from ESPN. The kind of news that their “partners” from the NBA didn’t want them to report. Unlike most conspiracy theories, however, this one has some science behind it.
In this case, science in the form of a study published in Frontiers in Physiology says that jet lag had a greater effect on the Boston Celtics than it did on the Warriors.
“Eastward travel – where the destination time is later than the origin time – requires the athlete to shorten their day (known as a phase advance). During phase advance, athletes often struggle to fall asleep at an earlier bedtime, leading to sleep loss and, consequently, potential impaired physiological performance and motivation the next day,” senior author Elise Facer-Childs, PhD, of Monash University, Melbourne, said in written statement.
Dr. Facer-Childs and associates took a very close look at 10 seasons’ worth of NBA games – 11,481 games, to be exact – and found “that eastward (but not westward) jet lag was associated with impaired performance for home (but not away) teams.” The existence of a pro-Western bias against teams that traveled eastward for their home games was clear:
- The chance of winning for eastern teams was reduced by 6.0%.
- They grabbed 1.3 fewer rebounds per game.
- Their field goal percentage was 1.2% lower.
And here’s the final nail in the conspiracy coffin: The NBA knew about the jet lag effect and changed the schedule of the finals in 2014 in a way that makes it worse. Before that, the higher-seeded team got two home games, then the lower-seeded team had three at home, followed by two more at the home of the higher seed. Now it’s a 2-2-1-1-1 arrangement that leads to more travel and, of course, more jet lag.
The study was published during the championship series, so the investigators suggested that the Celtics “might benefit from chronobiology-informed strategies designed to mitigate eastward jet lag symptomatology.”
So there you have it, sports fans/conspiracy theorists: You can’t chase Steph Curry around the court for 48 minutes without the right chronobiology-informed strategy. Everyone knows that.
Being hungry can alter your ‘type’
Fasting and being hungry can be a dangerous mix for becoming “hangry” and irritable, but did you know being hungry can also affect your attraction to other people?
Evidence has shown that being hungry can affect important things such as decision-making, memory, cognition, and function. It might affect decision-making in the sense that those six tacos at Taco Bell might win out over grilled chicken breast and veggies at home, but can hunger make you think that the person you just swiped right on isn’t really your type after all?
We’ll leave that up to Valentina Cazzato of Liverpool (England) John Moores University and associates, whose study involved 44 people, of whom 21 were women in their early 20s. The participants were shown computer-generated images of men and women of different sizes. The same background was used for each picture and all the expressions of the models were neutral. Participants were asked to rate each image on how much they liked it. One study was done on participants who had been fasting for 12 hours, and the second was done on those who had just eaten something.
The subjects generally preferred slim models over more rounded ones, but not after fasting. When they were hungry, they found the round human bodies and faces more attractive. So, yes, it’s definitely possible that hunger can alter your attraction to others.
“Future work might seek to elucidate the relationship between physiological states of hunger and shifts in appreciation of the human bodies and whether this relationship might be mediated by individual traits associated with to beholder’s body adiposity,” said researchers.
Biden moves to limit nicotine levels in cigarettes
The Department of Health and Human Services posted a notice that details plans for a new rule to create a maximum allowed amount of nicotine in certain tobacco products. The Food and Drug Administration would take the action, the notice said, “to reduce addictiveness to certain tobacco products, thus giving addicted users a greater ability to quit.” The product standard would also help keep nonsmokers interested in trying tobacco, mainly youth, from starting to smoke and become regulars.
“Lowering nicotine levels to minimally addictive or non-addictive levels would decrease the likelihood that future generations of young people become addicted to cigarettes and help more currently addicted smokers to quit,” FDA Commissioner Robert Califf, MD, said in a statement.
The FDA, in charge of regulating cigarettes, issues a proposed rule when changes are discussed. That would be followed by a period for public comments before a final rule could be issued.
The proposed rule was first reported by The Washington Post.
The FDA in 2018 published a study in the New England Journal of Medicine that estimated that a potential limit on nicotine in cigarettes could, by the year 2100, prevent more than 33 million people from becoming regular smokers, and prevent the deaths of more than 8 million people from tobacco-related illnesses.
The action to reduce nicotine levels would fit in with President Joe Biden’s goal of reducing cancer death rates by half over 25 years. Each year, according to the American Cancer Society, about 480,000 deaths (about 1 in 5) are related to smoking. Currently, about 34 million American adults still smoke cigarettes.
Matthew Myers, president of the Campaign for Tobacco-Free Kids, called the proposed rule a “truly game-changing proposal.”
“There is no other single action our country can take that would prevent more young people from becoming addicted to tobacco or have a greater impact on reducing deaths from cancer, cardiovascular disease and respiratory disease,” Mr. Myers said in a statement.
However, he said, “these gains will only be realized if the administration and the FDA demonstrate a full-throated commitment to finalizing and implementing this proposal.”
The FDA proposed the nicotine reduction strategy in talks with the White House and the Department of Health and Human Services early in 2021, according to the Post.
Earlier this year, the FDA issued a proposed rule to ban menthol flavoring in cigarettes. The agency is accepting public comments though July 5.
The action of reducing nicotine levels would likely take years to complete, Mitch Zeller, JD, recently retired director of the FDA Center for Tobacco Products, told the Post.
In 2018, the FDA issued a proposed ruling to set a standard for maximum nicotine levels in cigarettes.
Advocates say the action of slashing nicotine, the active – and addictive – ingredient in cigarettes, would save millions of lives for generations to come. Opponents liken it to the prohibition of alcohol in the 1920s and predict the action will fail.
Others say that if limits are put on nicotine levels, adults should have greater access to noncombustible alternatives.
A version of this article first appeared on WebMD.com.
The Department of Health and Human Services posted a notice that details plans for a new rule to create a maximum allowed amount of nicotine in certain tobacco products. The Food and Drug Administration would take the action, the notice said, “to reduce addictiveness to certain tobacco products, thus giving addicted users a greater ability to quit.” The product standard would also help keep nonsmokers interested in trying tobacco, mainly youth, from starting to smoke and become regulars.
“Lowering nicotine levels to minimally addictive or non-addictive levels would decrease the likelihood that future generations of young people become addicted to cigarettes and help more currently addicted smokers to quit,” FDA Commissioner Robert Califf, MD, said in a statement.
The FDA, in charge of regulating cigarettes, issues a proposed rule when changes are discussed. That would be followed by a period for public comments before a final rule could be issued.
The proposed rule was first reported by The Washington Post.
The FDA in 2018 published a study in the New England Journal of Medicine that estimated that a potential limit on nicotine in cigarettes could, by the year 2100, prevent more than 33 million people from becoming regular smokers, and prevent the deaths of more than 8 million people from tobacco-related illnesses.
The action to reduce nicotine levels would fit in with President Joe Biden’s goal of reducing cancer death rates by half over 25 years. Each year, according to the American Cancer Society, about 480,000 deaths (about 1 in 5) are related to smoking. Currently, about 34 million American adults still smoke cigarettes.
Matthew Myers, president of the Campaign for Tobacco-Free Kids, called the proposed rule a “truly game-changing proposal.”
“There is no other single action our country can take that would prevent more young people from becoming addicted to tobacco or have a greater impact on reducing deaths from cancer, cardiovascular disease and respiratory disease,” Mr. Myers said in a statement.
However, he said, “these gains will only be realized if the administration and the FDA demonstrate a full-throated commitment to finalizing and implementing this proposal.”
The FDA proposed the nicotine reduction strategy in talks with the White House and the Department of Health and Human Services early in 2021, according to the Post.
Earlier this year, the FDA issued a proposed rule to ban menthol flavoring in cigarettes. The agency is accepting public comments though July 5.
The action of reducing nicotine levels would likely take years to complete, Mitch Zeller, JD, recently retired director of the FDA Center for Tobacco Products, told the Post.
In 2018, the FDA issued a proposed ruling to set a standard for maximum nicotine levels in cigarettes.
Advocates say the action of slashing nicotine, the active – and addictive – ingredient in cigarettes, would save millions of lives for generations to come. Opponents liken it to the prohibition of alcohol in the 1920s and predict the action will fail.
Others say that if limits are put on nicotine levels, adults should have greater access to noncombustible alternatives.
A version of this article first appeared on WebMD.com.
The Department of Health and Human Services posted a notice that details plans for a new rule to create a maximum allowed amount of nicotine in certain tobacco products. The Food and Drug Administration would take the action, the notice said, “to reduce addictiveness to certain tobacco products, thus giving addicted users a greater ability to quit.” The product standard would also help keep nonsmokers interested in trying tobacco, mainly youth, from starting to smoke and become regulars.
“Lowering nicotine levels to minimally addictive or non-addictive levels would decrease the likelihood that future generations of young people become addicted to cigarettes and help more currently addicted smokers to quit,” FDA Commissioner Robert Califf, MD, said in a statement.
The FDA, in charge of regulating cigarettes, issues a proposed rule when changes are discussed. That would be followed by a period for public comments before a final rule could be issued.
The proposed rule was first reported by The Washington Post.
The FDA in 2018 published a study in the New England Journal of Medicine that estimated that a potential limit on nicotine in cigarettes could, by the year 2100, prevent more than 33 million people from becoming regular smokers, and prevent the deaths of more than 8 million people from tobacco-related illnesses.
The action to reduce nicotine levels would fit in with President Joe Biden’s goal of reducing cancer death rates by half over 25 years. Each year, according to the American Cancer Society, about 480,000 deaths (about 1 in 5) are related to smoking. Currently, about 34 million American adults still smoke cigarettes.
Matthew Myers, president of the Campaign for Tobacco-Free Kids, called the proposed rule a “truly game-changing proposal.”
“There is no other single action our country can take that would prevent more young people from becoming addicted to tobacco or have a greater impact on reducing deaths from cancer, cardiovascular disease and respiratory disease,” Mr. Myers said in a statement.
However, he said, “these gains will only be realized if the administration and the FDA demonstrate a full-throated commitment to finalizing and implementing this proposal.”
The FDA proposed the nicotine reduction strategy in talks with the White House and the Department of Health and Human Services early in 2021, according to the Post.
Earlier this year, the FDA issued a proposed rule to ban menthol flavoring in cigarettes. The agency is accepting public comments though July 5.
The action of reducing nicotine levels would likely take years to complete, Mitch Zeller, JD, recently retired director of the FDA Center for Tobacco Products, told the Post.
In 2018, the FDA issued a proposed ruling to set a standard for maximum nicotine levels in cigarettes.
Advocates say the action of slashing nicotine, the active – and addictive – ingredient in cigarettes, would save millions of lives for generations to come. Opponents liken it to the prohibition of alcohol in the 1920s and predict the action will fail.
Others say that if limits are put on nicotine levels, adults should have greater access to noncombustible alternatives.
A version of this article first appeared on WebMD.com.
FDA okays cancer drugs faster than EMA. But at what cost?
Over the past decade, the U.S. Food and Drug Administration has approved new cancer drugs twice as fast as the European Medicines Agency (EMA), often using accelerated pathways, a new analysis shows.
Between 2010 and 2019, the FDA approved almost all oncology therapies ahead of the EMA. Drugs entered the United States market about 8 months (241 days) before European market authorization.
“The faster FDA approval process potentially provides earlier access to potentially life-prolonging medications for patients with cancer in the United States,” Ali Raza Khaki, MD, department of oncology, Stanford (Calif.) University School of Medicine, told this news organization. “On the surface, this is a good thing. However, it comes with limitations.”
Earlier drug approval often means greater uncertainty about an agent’s benefit – most notably, whether it will improve a patient’s survival or quality of life. Dr. Khaki pointed to a study published in JAMA Internal Medicine, which found that only 19 of 93 (20%) cancer drugs that had been recently approved through the FDA’s accelerated approval pathway demonstrated an improvement in overall survival.
In the new study, published online in JAMA Network Open, Dr. Khaki and colleagues found that among the 89 cancer drugs approved in the United States and Europe between January 2010 and December 2019, the FDA approved 85 (95%) before European authorization and four (5%) after.
The researchers found that the median FDA review time was half that of the EMA’s (200 vs. 426 days). Furthermore, 64 new drug applications (72%) were submitted to the FDA first, compared with 21 (23%) to the EMA.
Of the drugs approved through an accelerated pathway, three were ultimately pulled from the U.S. market, compared with one in Europe.
“These early drug approvals that later lead to withdrawal expose many more patients to toxicity, including financial toxicity, given the high cost of cancer medications,” Dr. Khaki commented.
In addition, 35 oncology therapies (39%) were approved by the FDA before trial results were published, compared with only eight (9%) by the EMA. Although FDA drug labels contain some information about efficacy and toxicity, scientific publications often have much more, including details about study populations and toxicities.
“Without this information, providers may be limited in their knowledge about patient selection, clinical benefit, and optimal toxicity management,” Dr. Khaki said.
Jeff Allen PhD, president and CEO of the nonprofit Friends of Cancer Research, who wasn’t involved in the study, believes that an FDA approval before publication shouldn’t be “particularly concerning.”
“Peer-reviewed publication is an important component of validating and communicating scientific findings, but the processes and time lines for individual journals can be highly variable,” he said. “I don’t think we would want to see a situation where potential beneficial treatments are held up due to unrelated publication processes.”
The author of an invited commentary in JAMA Network Open had a different take on the study findings.
“A tempting interpretation” of this study is that the FDA is a “superior agency for expedited review times that bring cancer drugs to patients earlier,” Kristina Jenei, BSN, MSc, with the University of British Columbia School of Population and Public Health, writes. In addition, the fact that more drugs were pulled from the market after approval in the United States than in Europe could be interpreted to mean that the system is working as it should.
Although the speed of FDA reviews and the number of subsequent approvals have increased over time, the proportion of cancer drugs that improve survival has declined. In addition, because the FDA’s follow-up of postmarketing studies has been “inconsistent,” a substantial number of cancer drugs that were approved through accelerated pathways have remained on the market for years without confirmation of their benefit.
Although regulatory agencies must balance earlier patient access to novel treatments with evidence that the therapies are effective and safe, “faster review times and approvals are not cause for celebration; better patient outcomes are,” Ms. Jenei writes. “In other words, quality over quantity.”
The study was supported by the National Cancer Institute. Dr. Khaki reported stock ownership from Merck and stock ownership from Sanofi outside the submitted work. Dr. Allen and Ms. Jenei have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Over the past decade, the U.S. Food and Drug Administration has approved new cancer drugs twice as fast as the European Medicines Agency (EMA), often using accelerated pathways, a new analysis shows.
Between 2010 and 2019, the FDA approved almost all oncology therapies ahead of the EMA. Drugs entered the United States market about 8 months (241 days) before European market authorization.
“The faster FDA approval process potentially provides earlier access to potentially life-prolonging medications for patients with cancer in the United States,” Ali Raza Khaki, MD, department of oncology, Stanford (Calif.) University School of Medicine, told this news organization. “On the surface, this is a good thing. However, it comes with limitations.”
Earlier drug approval often means greater uncertainty about an agent’s benefit – most notably, whether it will improve a patient’s survival or quality of life. Dr. Khaki pointed to a study published in JAMA Internal Medicine, which found that only 19 of 93 (20%) cancer drugs that had been recently approved through the FDA’s accelerated approval pathway demonstrated an improvement in overall survival.
In the new study, published online in JAMA Network Open, Dr. Khaki and colleagues found that among the 89 cancer drugs approved in the United States and Europe between January 2010 and December 2019, the FDA approved 85 (95%) before European authorization and four (5%) after.
The researchers found that the median FDA review time was half that of the EMA’s (200 vs. 426 days). Furthermore, 64 new drug applications (72%) were submitted to the FDA first, compared with 21 (23%) to the EMA.
Of the drugs approved through an accelerated pathway, three were ultimately pulled from the U.S. market, compared with one in Europe.
“These early drug approvals that later lead to withdrawal expose many more patients to toxicity, including financial toxicity, given the high cost of cancer medications,” Dr. Khaki commented.
In addition, 35 oncology therapies (39%) were approved by the FDA before trial results were published, compared with only eight (9%) by the EMA. Although FDA drug labels contain some information about efficacy and toxicity, scientific publications often have much more, including details about study populations and toxicities.
“Without this information, providers may be limited in their knowledge about patient selection, clinical benefit, and optimal toxicity management,” Dr. Khaki said.
Jeff Allen PhD, president and CEO of the nonprofit Friends of Cancer Research, who wasn’t involved in the study, believes that an FDA approval before publication shouldn’t be “particularly concerning.”
“Peer-reviewed publication is an important component of validating and communicating scientific findings, but the processes and time lines for individual journals can be highly variable,” he said. “I don’t think we would want to see a situation where potential beneficial treatments are held up due to unrelated publication processes.”
The author of an invited commentary in JAMA Network Open had a different take on the study findings.
“A tempting interpretation” of this study is that the FDA is a “superior agency for expedited review times that bring cancer drugs to patients earlier,” Kristina Jenei, BSN, MSc, with the University of British Columbia School of Population and Public Health, writes. In addition, the fact that more drugs were pulled from the market after approval in the United States than in Europe could be interpreted to mean that the system is working as it should.
Although the speed of FDA reviews and the number of subsequent approvals have increased over time, the proportion of cancer drugs that improve survival has declined. In addition, because the FDA’s follow-up of postmarketing studies has been “inconsistent,” a substantial number of cancer drugs that were approved through accelerated pathways have remained on the market for years without confirmation of their benefit.
Although regulatory agencies must balance earlier patient access to novel treatments with evidence that the therapies are effective and safe, “faster review times and approvals are not cause for celebration; better patient outcomes are,” Ms. Jenei writes. “In other words, quality over quantity.”
The study was supported by the National Cancer Institute. Dr. Khaki reported stock ownership from Merck and stock ownership from Sanofi outside the submitted work. Dr. Allen and Ms. Jenei have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Over the past decade, the U.S. Food and Drug Administration has approved new cancer drugs twice as fast as the European Medicines Agency (EMA), often using accelerated pathways, a new analysis shows.
Between 2010 and 2019, the FDA approved almost all oncology therapies ahead of the EMA. Drugs entered the United States market about 8 months (241 days) before European market authorization.
“The faster FDA approval process potentially provides earlier access to potentially life-prolonging medications for patients with cancer in the United States,” Ali Raza Khaki, MD, department of oncology, Stanford (Calif.) University School of Medicine, told this news organization. “On the surface, this is a good thing. However, it comes with limitations.”
Earlier drug approval often means greater uncertainty about an agent’s benefit – most notably, whether it will improve a patient’s survival or quality of life. Dr. Khaki pointed to a study published in JAMA Internal Medicine, which found that only 19 of 93 (20%) cancer drugs that had been recently approved through the FDA’s accelerated approval pathway demonstrated an improvement in overall survival.
In the new study, published online in JAMA Network Open, Dr. Khaki and colleagues found that among the 89 cancer drugs approved in the United States and Europe between January 2010 and December 2019, the FDA approved 85 (95%) before European authorization and four (5%) after.
The researchers found that the median FDA review time was half that of the EMA’s (200 vs. 426 days). Furthermore, 64 new drug applications (72%) were submitted to the FDA first, compared with 21 (23%) to the EMA.
Of the drugs approved through an accelerated pathway, three were ultimately pulled from the U.S. market, compared with one in Europe.
“These early drug approvals that later lead to withdrawal expose many more patients to toxicity, including financial toxicity, given the high cost of cancer medications,” Dr. Khaki commented.
In addition, 35 oncology therapies (39%) were approved by the FDA before trial results were published, compared with only eight (9%) by the EMA. Although FDA drug labels contain some information about efficacy and toxicity, scientific publications often have much more, including details about study populations and toxicities.
“Without this information, providers may be limited in their knowledge about patient selection, clinical benefit, and optimal toxicity management,” Dr. Khaki said.
Jeff Allen PhD, president and CEO of the nonprofit Friends of Cancer Research, who wasn’t involved in the study, believes that an FDA approval before publication shouldn’t be “particularly concerning.”
“Peer-reviewed publication is an important component of validating and communicating scientific findings, but the processes and time lines for individual journals can be highly variable,” he said. “I don’t think we would want to see a situation where potential beneficial treatments are held up due to unrelated publication processes.”
The author of an invited commentary in JAMA Network Open had a different take on the study findings.
“A tempting interpretation” of this study is that the FDA is a “superior agency for expedited review times that bring cancer drugs to patients earlier,” Kristina Jenei, BSN, MSc, with the University of British Columbia School of Population and Public Health, writes. In addition, the fact that more drugs were pulled from the market after approval in the United States than in Europe could be interpreted to mean that the system is working as it should.
Although the speed of FDA reviews and the number of subsequent approvals have increased over time, the proportion of cancer drugs that improve survival has declined. In addition, because the FDA’s follow-up of postmarketing studies has been “inconsistent,” a substantial number of cancer drugs that were approved through accelerated pathways have remained on the market for years without confirmation of their benefit.
Although regulatory agencies must balance earlier patient access to novel treatments with evidence that the therapies are effective and safe, “faster review times and approvals are not cause for celebration; better patient outcomes are,” Ms. Jenei writes. “In other words, quality over quantity.”
The study was supported by the National Cancer Institute. Dr. Khaki reported stock ownership from Merck and stock ownership from Sanofi outside the submitted work. Dr. Allen and Ms. Jenei have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
COVID-19 Pandemic stress affected ovulation, not menstruation
ATLANTA – Disturbances in ovulation that didn’t produce any actual changes in the menstrual cycle of women were extremely common during the first year of the COVID-19 pandemic and were linked to emotional stress, according to the findings of an “experiment of nature” that allowed for comparison with women a decade earlier.
Findings from two studies of reproductive-age women, one conducted in 2006-2008 and the other in 2020-2021, were presented by Jerilynn C. Prior, MD, at the annual meeting of the Endocrine Society.
The comparison of the two time periods yielded several novel findings. “I was taught in medical school that when women don’t eat enough they lose their period. But what we now understand is there’s a graded response to various stressors, acting through the hypothalamus in a common pathway. There is a gradation of disturbances, some of which are subclinical or not obvious,” said Dr. Prior, professor of endocrinology and metabolism at the University of British Columbia, Vancouver.
Moreover, women’s menstrual cycle lengths didn’t differ across the two time periods, despite a dramatic 63% decrement in normal ovulatory function related to increased depression, anxiety, and outside stresses that the women reported in diaries.
“Assuming that regular cycles need normal ovulation is something we should just get out of our minds. It changes our concept about what’s normal if we only know about the cycle length,” she observed.
It will be critical going forward to see whether the ovulatory disturbances have resolved as the pandemic has shifted “because there’s strong evidence that ovulatory disturbances, even with normal cycle length, are related to bone loss and some evidence it’s related to early heart attacks, breast and endometrial cancers,” Dr. Prior said during a press conference.
Asked to comment, session moderator Genevieve Neal-Perry, MD, PhD, told this news organization: “I think what we can take away is that stress itself is a modifier of the way the brain and the gonads communicate with each other, and that then has an impact on ovulatory function.”
Dr. Neal-Perry noted that the association of stress and ovulatory disruption has been reported in various ways previously, but “clearly it doesn’t affect everyone. What we don’t know is who is most susceptible. There have been some studies showing a genetic predisposition and a genetic anomaly that actually makes them more susceptible to the impact of stress on the reproductive system.”
But the lack of data on weight change in the study cohorts is a limitation. “To me one of the more important questions was what was going on with weight. Just looking at a static number doesn’t tell you whether there were changes. We know that weight gain or weight loss can stress the reproductive axis,” noted Dr. Neal-Parry of the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill.
‘Experiment of nature’ revealed invisible effect of pandemic stress
The women in both cohorts of the Menstruation Ovulation Study (MOS) were healthy volunteers aged 19-35 years recruited from the metropolitan Vancouver region. All were menstruating monthly and none were taking hormonal birth control. Recruitment for the second cohort had begun just prior to the March 2020 COVID-19 pandemic lockdown.
Interviewer-administered questionnaires (CaMos) covering demographics, socioeconomic status, and reproductive history, and daily diaries kept by the women (menstrual cycle diary) were identical for both cohorts.
Assessments of ovulation differed for the two studies but were cross-validated. For the earlier time period, ovulation was assessed by a threefold increase in follicular-to-luteal urinary progesterone (PdG). For the pandemic-era study, the validated quantitative basal temperature (QBT) method was used.
There were 301 women in the earlier cohort and 125 during the pandemic. Both were an average age of about 29 years and had a body mass index of about 24.3 kg/m2 (within the normal range). The pandemic cohort was more racially/ethnically diverse than the earlier one and more in-line with recent census data.
More of the women were nulliparous during the pandemic than earlier (92.7% vs. 80.4%; P = .002).
The distribution of menstrual cycle lengths didn’t differ, with both cohorts averaging about 30 days (P = .893). However, while 90% of the women in the earlier cohort ovulated normally, only 37% did during the pandemic, a highly significant difference (P < .0001).
Thus, during the pandemic, 63% of women had “silent ovulatory disturbances,” either with short luteal phases after ovulation or no ovulation, compared with just 10% in the earlier cohort, “which is remarkable, unbelievable actually,” Dr. Prior remarked.
The difference wasn’t explained by any of the demographic information collected either, including socioeconomic status, lifestyle, or reproductive history variables.
And it wasn’t because of COVID-19 vaccination, as the vaccine wasn’t available when most of the women were recruited, and of the 79 who were recruited during vaccine availability, only two received a COVID-19 vaccine during the study (and both had normal ovulation).
Employment changes, caring responsibilities, and worry likely causes
The information from the diaries was more revealing. Several diary components were far more common during the pandemic, including negative mood (feeling depressed or anxious, sleep problems, and outside stresses), self-worth, interest in sex, energy level, and appetite. All were significantly different between the two cohorts (P < .001) and between those with and without ovulatory disturbances.
“So menstrual cycle lengths and long cycles didn’t differ, but there was a much higher prevalence of silent or subclinical ovulatory disturbances, and these were related to the increased stresses that women recorded in their diaries. This means that the estrogen levels were pretty close to normal but the progesterone levels were remarkably decreased,” Dr. Prior said.
Interestingly, reported menstrual cramps were also significantly more common during the pandemic and associated with ovulatory disruption.
“That is a new observation because previously we’ve always thought that you needed to ovulate in order to even have cramps,” she commented.
Asked whether COVID-19 itself might have played a role, Dr. Prior said no woman in the study tested positive for the virus or had long COVID.
“As far as I’m aware, it was the changes in employment … and caring for elders and worry about illness in somebody you loved that was related,” she said.
Asked what she thinks the result would be if the study were conducted now, she said: “I don’t know. We’re still in a stressful time with inflation and not complete recovery, so probably the issue is still very present.”
Dr. Prior and Dr. Neal-Perry have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ATLANTA – Disturbances in ovulation that didn’t produce any actual changes in the menstrual cycle of women were extremely common during the first year of the COVID-19 pandemic and were linked to emotional stress, according to the findings of an “experiment of nature” that allowed for comparison with women a decade earlier.
Findings from two studies of reproductive-age women, one conducted in 2006-2008 and the other in 2020-2021, were presented by Jerilynn C. Prior, MD, at the annual meeting of the Endocrine Society.
The comparison of the two time periods yielded several novel findings. “I was taught in medical school that when women don’t eat enough they lose their period. But what we now understand is there’s a graded response to various stressors, acting through the hypothalamus in a common pathway. There is a gradation of disturbances, some of which are subclinical or not obvious,” said Dr. Prior, professor of endocrinology and metabolism at the University of British Columbia, Vancouver.
Moreover, women’s menstrual cycle lengths didn’t differ across the two time periods, despite a dramatic 63% decrement in normal ovulatory function related to increased depression, anxiety, and outside stresses that the women reported in diaries.
“Assuming that regular cycles need normal ovulation is something we should just get out of our minds. It changes our concept about what’s normal if we only know about the cycle length,” she observed.
It will be critical going forward to see whether the ovulatory disturbances have resolved as the pandemic has shifted “because there’s strong evidence that ovulatory disturbances, even with normal cycle length, are related to bone loss and some evidence it’s related to early heart attacks, breast and endometrial cancers,” Dr. Prior said during a press conference.
Asked to comment, session moderator Genevieve Neal-Perry, MD, PhD, told this news organization: “I think what we can take away is that stress itself is a modifier of the way the brain and the gonads communicate with each other, and that then has an impact on ovulatory function.”
Dr. Neal-Perry noted that the association of stress and ovulatory disruption has been reported in various ways previously, but “clearly it doesn’t affect everyone. What we don’t know is who is most susceptible. There have been some studies showing a genetic predisposition and a genetic anomaly that actually makes them more susceptible to the impact of stress on the reproductive system.”
But the lack of data on weight change in the study cohorts is a limitation. “To me one of the more important questions was what was going on with weight. Just looking at a static number doesn’t tell you whether there were changes. We know that weight gain or weight loss can stress the reproductive axis,” noted Dr. Neal-Parry of the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill.
‘Experiment of nature’ revealed invisible effect of pandemic stress
The women in both cohorts of the Menstruation Ovulation Study (MOS) were healthy volunteers aged 19-35 years recruited from the metropolitan Vancouver region. All were menstruating monthly and none were taking hormonal birth control. Recruitment for the second cohort had begun just prior to the March 2020 COVID-19 pandemic lockdown.
Interviewer-administered questionnaires (CaMos) covering demographics, socioeconomic status, and reproductive history, and daily diaries kept by the women (menstrual cycle diary) were identical for both cohorts.
Assessments of ovulation differed for the two studies but were cross-validated. For the earlier time period, ovulation was assessed by a threefold increase in follicular-to-luteal urinary progesterone (PdG). For the pandemic-era study, the validated quantitative basal temperature (QBT) method was used.
There were 301 women in the earlier cohort and 125 during the pandemic. Both were an average age of about 29 years and had a body mass index of about 24.3 kg/m2 (within the normal range). The pandemic cohort was more racially/ethnically diverse than the earlier one and more in-line with recent census data.
More of the women were nulliparous during the pandemic than earlier (92.7% vs. 80.4%; P = .002).
The distribution of menstrual cycle lengths didn’t differ, with both cohorts averaging about 30 days (P = .893). However, while 90% of the women in the earlier cohort ovulated normally, only 37% did during the pandemic, a highly significant difference (P < .0001).
Thus, during the pandemic, 63% of women had “silent ovulatory disturbances,” either with short luteal phases after ovulation or no ovulation, compared with just 10% in the earlier cohort, “which is remarkable, unbelievable actually,” Dr. Prior remarked.
The difference wasn’t explained by any of the demographic information collected either, including socioeconomic status, lifestyle, or reproductive history variables.
And it wasn’t because of COVID-19 vaccination, as the vaccine wasn’t available when most of the women were recruited, and of the 79 who were recruited during vaccine availability, only two received a COVID-19 vaccine during the study (and both had normal ovulation).
Employment changes, caring responsibilities, and worry likely causes
The information from the diaries was more revealing. Several diary components were far more common during the pandemic, including negative mood (feeling depressed or anxious, sleep problems, and outside stresses), self-worth, interest in sex, energy level, and appetite. All were significantly different between the two cohorts (P < .001) and between those with and without ovulatory disturbances.
“So menstrual cycle lengths and long cycles didn’t differ, but there was a much higher prevalence of silent or subclinical ovulatory disturbances, and these were related to the increased stresses that women recorded in their diaries. This means that the estrogen levels were pretty close to normal but the progesterone levels were remarkably decreased,” Dr. Prior said.
Interestingly, reported menstrual cramps were also significantly more common during the pandemic and associated with ovulatory disruption.
“That is a new observation because previously we’ve always thought that you needed to ovulate in order to even have cramps,” she commented.
Asked whether COVID-19 itself might have played a role, Dr. Prior said no woman in the study tested positive for the virus or had long COVID.
“As far as I’m aware, it was the changes in employment … and caring for elders and worry about illness in somebody you loved that was related,” she said.
Asked what she thinks the result would be if the study were conducted now, she said: “I don’t know. We’re still in a stressful time with inflation and not complete recovery, so probably the issue is still very present.”
Dr. Prior and Dr. Neal-Perry have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ATLANTA – Disturbances in ovulation that didn’t produce any actual changes in the menstrual cycle of women were extremely common during the first year of the COVID-19 pandemic and were linked to emotional stress, according to the findings of an “experiment of nature” that allowed for comparison with women a decade earlier.
Findings from two studies of reproductive-age women, one conducted in 2006-2008 and the other in 2020-2021, were presented by Jerilynn C. Prior, MD, at the annual meeting of the Endocrine Society.
The comparison of the two time periods yielded several novel findings. “I was taught in medical school that when women don’t eat enough they lose their period. But what we now understand is there’s a graded response to various stressors, acting through the hypothalamus in a common pathway. There is a gradation of disturbances, some of which are subclinical or not obvious,” said Dr. Prior, professor of endocrinology and metabolism at the University of British Columbia, Vancouver.
Moreover, women’s menstrual cycle lengths didn’t differ across the two time periods, despite a dramatic 63% decrement in normal ovulatory function related to increased depression, anxiety, and outside stresses that the women reported in diaries.
“Assuming that regular cycles need normal ovulation is something we should just get out of our minds. It changes our concept about what’s normal if we only know about the cycle length,” she observed.
It will be critical going forward to see whether the ovulatory disturbances have resolved as the pandemic has shifted “because there’s strong evidence that ovulatory disturbances, even with normal cycle length, are related to bone loss and some evidence it’s related to early heart attacks, breast and endometrial cancers,” Dr. Prior said during a press conference.
Asked to comment, session moderator Genevieve Neal-Perry, MD, PhD, told this news organization: “I think what we can take away is that stress itself is a modifier of the way the brain and the gonads communicate with each other, and that then has an impact on ovulatory function.”
Dr. Neal-Perry noted that the association of stress and ovulatory disruption has been reported in various ways previously, but “clearly it doesn’t affect everyone. What we don’t know is who is most susceptible. There have been some studies showing a genetic predisposition and a genetic anomaly that actually makes them more susceptible to the impact of stress on the reproductive system.”
But the lack of data on weight change in the study cohorts is a limitation. “To me one of the more important questions was what was going on with weight. Just looking at a static number doesn’t tell you whether there were changes. We know that weight gain or weight loss can stress the reproductive axis,” noted Dr. Neal-Parry of the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill.
‘Experiment of nature’ revealed invisible effect of pandemic stress
The women in both cohorts of the Menstruation Ovulation Study (MOS) were healthy volunteers aged 19-35 years recruited from the metropolitan Vancouver region. All were menstruating monthly and none were taking hormonal birth control. Recruitment for the second cohort had begun just prior to the March 2020 COVID-19 pandemic lockdown.
Interviewer-administered questionnaires (CaMos) covering demographics, socioeconomic status, and reproductive history, and daily diaries kept by the women (menstrual cycle diary) were identical for both cohorts.
Assessments of ovulation differed for the two studies but were cross-validated. For the earlier time period, ovulation was assessed by a threefold increase in follicular-to-luteal urinary progesterone (PdG). For the pandemic-era study, the validated quantitative basal temperature (QBT) method was used.
There were 301 women in the earlier cohort and 125 during the pandemic. Both were an average age of about 29 years and had a body mass index of about 24.3 kg/m2 (within the normal range). The pandemic cohort was more racially/ethnically diverse than the earlier one and more in-line with recent census data.
More of the women were nulliparous during the pandemic than earlier (92.7% vs. 80.4%; P = .002).
The distribution of menstrual cycle lengths didn’t differ, with both cohorts averaging about 30 days (P = .893). However, while 90% of the women in the earlier cohort ovulated normally, only 37% did during the pandemic, a highly significant difference (P < .0001).
Thus, during the pandemic, 63% of women had “silent ovulatory disturbances,” either with short luteal phases after ovulation or no ovulation, compared with just 10% in the earlier cohort, “which is remarkable, unbelievable actually,” Dr. Prior remarked.
The difference wasn’t explained by any of the demographic information collected either, including socioeconomic status, lifestyle, or reproductive history variables.
And it wasn’t because of COVID-19 vaccination, as the vaccine wasn’t available when most of the women were recruited, and of the 79 who were recruited during vaccine availability, only two received a COVID-19 vaccine during the study (and both had normal ovulation).
Employment changes, caring responsibilities, and worry likely causes
The information from the diaries was more revealing. Several diary components were far more common during the pandemic, including negative mood (feeling depressed or anxious, sleep problems, and outside stresses), self-worth, interest in sex, energy level, and appetite. All were significantly different between the two cohorts (P < .001) and between those with and without ovulatory disturbances.
“So menstrual cycle lengths and long cycles didn’t differ, but there was a much higher prevalence of silent or subclinical ovulatory disturbances, and these were related to the increased stresses that women recorded in their diaries. This means that the estrogen levels were pretty close to normal but the progesterone levels were remarkably decreased,” Dr. Prior said.
Interestingly, reported menstrual cramps were also significantly more common during the pandemic and associated with ovulatory disruption.
“That is a new observation because previously we’ve always thought that you needed to ovulate in order to even have cramps,” she commented.
Asked whether COVID-19 itself might have played a role, Dr. Prior said no woman in the study tested positive for the virus or had long COVID.
“As far as I’m aware, it was the changes in employment … and caring for elders and worry about illness in somebody you loved that was related,” she said.
Asked what she thinks the result would be if the study were conducted now, she said: “I don’t know. We’re still in a stressful time with inflation and not complete recovery, so probably the issue is still very present.”
Dr. Prior and Dr. Neal-Perry have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ENDO 2022
HPV vaccination with Cervarix ‘unmasks’ cervical lesions from non-vax strains
Vaccines against human papillomavirus have been hailed as a success: they have been shown to decrease the incidence of cervical lesions associated with the HPV types that are in the vaccine.
However,
An expert not involved in the research said the new data “tell us to be a little bit careful.” Although the HPV types not included in the vaccine are rarer and less aggressive, they can still cause cancer.
The data come from the Costa Rica HPV Vaccine Trial, which involved more than 10,000 women aged 18-25 years. The HPV vaccine used in the trial was Cervarix, from GlaxoSmithKline. It covers the two leading causes of cervical cancer, HPV-16 and -18, and provides partial protection against three other genotypes.
After a follow-up of 11 years, among vaccinated women, there was an excess of precancerous cervical lesions caused by genotypes not included in the vaccine, resulting in negative vaccine efficacy for those HPV variants.
The increase wasn’t enough to offset the overall benefit of vaccination when all genotypes were considered, said the researchers, led by Jaimie Shing, PhD, a postdoctoral research fellow at the National Cancer Institute in Bethesda, Md.
Vaccinated women “still had long-term absolute reductions in high-grade lesions,” they pointed out.
The net protection “remained considerable, emphasizing the importance of HPV vaccination for cervical cancer prevention,” the team concluded.
The findings were published online in The Lancet Oncology.
The results are likely the first evidence to date of “clinical unmasking” with HPV vaccination, meaning that protection against the strains covered by the vaccine leaves women more prone to attack from other carcinogenic HPV variants.
This phenomenon “could attenuate long-term reductions in high-grade disease following successful implementation of HPV vaccination programs,” the investigators commented.
Highlighting a need for caution
The take-home message from the trial is that “we have to be careful,” said Marc Steben, MD, co-President of HPV Global Action and a professor at the University of Montreal.
He noted that the Cervarix HPV vaccine used in the trial is not the vaccine that is used now in developed nations.
The current standard HPV vaccine is Gardasil 9 (Merck), which offers broader coverage against nine HPV types (types 6, 11, 16, 18, 31, 33, 45, 52, and 58).
There are 12 main carcinogenic HPV genotypes, so unmasking of other strains is still possible with Gardasil 9, he said.
There is another issue, Dr. Steben added. The success of HPV vaccinations - a nearly 90% reduction in invasive cervical cancer in women who are vaccinated at a young age – has led to questions about the future role of routine cervical cancer screening.
“Some people are saying that if we achieve 90% coverage, we might” eliminate community transmission and no longer need to screen, he said.
These trial results “tell us to be a little bit careful,” Dr. Steben continued. Those HPV types that are less aggressive and rarer than HPV-16 and -18 “can still cause cancer and might be there and surprise us. It could take more time than we thought” to get to the point where screening can be eliminated.
“There might be a little problem if we stop too early,” he said.
Study details
During the period 2004-2005, the investigators randomly assigned 3,727 women aged 18-25 years to receive Cervarix and 3,739 to a control group that received the hepatitis A vaccine; after 4 years, the control group also received Cervarix and exited the study. They were replaced by an unvaccinated control group of 2,836 women. The new control group and the original HPV vaccine group were followed for an additional 7 years.
In years 7-11 of the trial, the investigators found 9.2 additional cervical intraepithelial neoplasias of grade 2 or worse (CIN2+) from HPV types not covered by Cervarix per 1,000 vaccinated women in comparison with unvaccinated participants. This corresponds to –71.2% negative vaccine efficacy against CIN2+ lesions of HPV types not covered by the vaccine.
There were 8.3 additional CIN3+ lesions from nontargeted HPV strains per 1,000 vaccinated women in comparison with unvaccinated participants, which corresponds to –135% negative vaccine efficacy.
Overall, however, there was a net benefit of vaccination, with 27 fewer CIN2+ lesions when all HPV genotypes – vaccine covered or not – were considered per 1,000 vaccinated women over the entire 11 years of follow-up.
There were also 8.7 fewer CIN3+ lesions across all genotypes per 1,000 vaccinated women, but the benefit was not statistically significant.
Among the study limits, the team was unable to evaluate the effect of clinical unmasking on cervical cancer, because women were treated for high-grade cervical lesions before cases could progress to cervical cancer.
The trial was funded by the National Cancer Institute and the National Institutes of Health Office of Research on Women’s Health. GlaxoSmithKline provided the Cervarix vaccine and supported aspects of the trial. Two authors are named inventors on U.S. government–owned HPV vaccine patents with expired licenses to GlaxoSmithKline and Merck. Dr. Steben is an adviser/speaker for many companies, including GlaxoSmithKline and Merck.
A version of this article first appeared on Medscape.com.
Vaccines against human papillomavirus have been hailed as a success: they have been shown to decrease the incidence of cervical lesions associated with the HPV types that are in the vaccine.
However,
An expert not involved in the research said the new data “tell us to be a little bit careful.” Although the HPV types not included in the vaccine are rarer and less aggressive, they can still cause cancer.
The data come from the Costa Rica HPV Vaccine Trial, which involved more than 10,000 women aged 18-25 years. The HPV vaccine used in the trial was Cervarix, from GlaxoSmithKline. It covers the two leading causes of cervical cancer, HPV-16 and -18, and provides partial protection against three other genotypes.
After a follow-up of 11 years, among vaccinated women, there was an excess of precancerous cervical lesions caused by genotypes not included in the vaccine, resulting in negative vaccine efficacy for those HPV variants.
The increase wasn’t enough to offset the overall benefit of vaccination when all genotypes were considered, said the researchers, led by Jaimie Shing, PhD, a postdoctoral research fellow at the National Cancer Institute in Bethesda, Md.
Vaccinated women “still had long-term absolute reductions in high-grade lesions,” they pointed out.
The net protection “remained considerable, emphasizing the importance of HPV vaccination for cervical cancer prevention,” the team concluded.
The findings were published online in The Lancet Oncology.
The results are likely the first evidence to date of “clinical unmasking” with HPV vaccination, meaning that protection against the strains covered by the vaccine leaves women more prone to attack from other carcinogenic HPV variants.
This phenomenon “could attenuate long-term reductions in high-grade disease following successful implementation of HPV vaccination programs,” the investigators commented.
Highlighting a need for caution
The take-home message from the trial is that “we have to be careful,” said Marc Steben, MD, co-President of HPV Global Action and a professor at the University of Montreal.
He noted that the Cervarix HPV vaccine used in the trial is not the vaccine that is used now in developed nations.
The current standard HPV vaccine is Gardasil 9 (Merck), which offers broader coverage against nine HPV types (types 6, 11, 16, 18, 31, 33, 45, 52, and 58).
There are 12 main carcinogenic HPV genotypes, so unmasking of other strains is still possible with Gardasil 9, he said.
There is another issue, Dr. Steben added. The success of HPV vaccinations - a nearly 90% reduction in invasive cervical cancer in women who are vaccinated at a young age – has led to questions about the future role of routine cervical cancer screening.
“Some people are saying that if we achieve 90% coverage, we might” eliminate community transmission and no longer need to screen, he said.
These trial results “tell us to be a little bit careful,” Dr. Steben continued. Those HPV types that are less aggressive and rarer than HPV-16 and -18 “can still cause cancer and might be there and surprise us. It could take more time than we thought” to get to the point where screening can be eliminated.
“There might be a little problem if we stop too early,” he said.
Study details
During the period 2004-2005, the investigators randomly assigned 3,727 women aged 18-25 years to receive Cervarix and 3,739 to a control group that received the hepatitis A vaccine; after 4 years, the control group also received Cervarix and exited the study. They were replaced by an unvaccinated control group of 2,836 women. The new control group and the original HPV vaccine group were followed for an additional 7 years.
In years 7-11 of the trial, the investigators found 9.2 additional cervical intraepithelial neoplasias of grade 2 or worse (CIN2+) from HPV types not covered by Cervarix per 1,000 vaccinated women in comparison with unvaccinated participants. This corresponds to –71.2% negative vaccine efficacy against CIN2+ lesions of HPV types not covered by the vaccine.
There were 8.3 additional CIN3+ lesions from nontargeted HPV strains per 1,000 vaccinated women in comparison with unvaccinated participants, which corresponds to –135% negative vaccine efficacy.
Overall, however, there was a net benefit of vaccination, with 27 fewer CIN2+ lesions when all HPV genotypes – vaccine covered or not – were considered per 1,000 vaccinated women over the entire 11 years of follow-up.
There were also 8.7 fewer CIN3+ lesions across all genotypes per 1,000 vaccinated women, but the benefit was not statistically significant.
Among the study limits, the team was unable to evaluate the effect of clinical unmasking on cervical cancer, because women were treated for high-grade cervical lesions before cases could progress to cervical cancer.
The trial was funded by the National Cancer Institute and the National Institutes of Health Office of Research on Women’s Health. GlaxoSmithKline provided the Cervarix vaccine and supported aspects of the trial. Two authors are named inventors on U.S. government–owned HPV vaccine patents with expired licenses to GlaxoSmithKline and Merck. Dr. Steben is an adviser/speaker for many companies, including GlaxoSmithKline and Merck.
A version of this article first appeared on Medscape.com.
Vaccines against human papillomavirus have been hailed as a success: they have been shown to decrease the incidence of cervical lesions associated with the HPV types that are in the vaccine.
However,
An expert not involved in the research said the new data “tell us to be a little bit careful.” Although the HPV types not included in the vaccine are rarer and less aggressive, they can still cause cancer.
The data come from the Costa Rica HPV Vaccine Trial, which involved more than 10,000 women aged 18-25 years. The HPV vaccine used in the trial was Cervarix, from GlaxoSmithKline. It covers the two leading causes of cervical cancer, HPV-16 and -18, and provides partial protection against three other genotypes.
After a follow-up of 11 years, among vaccinated women, there was an excess of precancerous cervical lesions caused by genotypes not included in the vaccine, resulting in negative vaccine efficacy for those HPV variants.
The increase wasn’t enough to offset the overall benefit of vaccination when all genotypes were considered, said the researchers, led by Jaimie Shing, PhD, a postdoctoral research fellow at the National Cancer Institute in Bethesda, Md.
Vaccinated women “still had long-term absolute reductions in high-grade lesions,” they pointed out.
The net protection “remained considerable, emphasizing the importance of HPV vaccination for cervical cancer prevention,” the team concluded.
The findings were published online in The Lancet Oncology.
The results are likely the first evidence to date of “clinical unmasking” with HPV vaccination, meaning that protection against the strains covered by the vaccine leaves women more prone to attack from other carcinogenic HPV variants.
This phenomenon “could attenuate long-term reductions in high-grade disease following successful implementation of HPV vaccination programs,” the investigators commented.
Highlighting a need for caution
The take-home message from the trial is that “we have to be careful,” said Marc Steben, MD, co-President of HPV Global Action and a professor at the University of Montreal.
He noted that the Cervarix HPV vaccine used in the trial is not the vaccine that is used now in developed nations.
The current standard HPV vaccine is Gardasil 9 (Merck), which offers broader coverage against nine HPV types (types 6, 11, 16, 18, 31, 33, 45, 52, and 58).
There are 12 main carcinogenic HPV genotypes, so unmasking of other strains is still possible with Gardasil 9, he said.
There is another issue, Dr. Steben added. The success of HPV vaccinations - a nearly 90% reduction in invasive cervical cancer in women who are vaccinated at a young age – has led to questions about the future role of routine cervical cancer screening.
“Some people are saying that if we achieve 90% coverage, we might” eliminate community transmission and no longer need to screen, he said.
These trial results “tell us to be a little bit careful,” Dr. Steben continued. Those HPV types that are less aggressive and rarer than HPV-16 and -18 “can still cause cancer and might be there and surprise us. It could take more time than we thought” to get to the point where screening can be eliminated.
“There might be a little problem if we stop too early,” he said.
Study details
During the period 2004-2005, the investigators randomly assigned 3,727 women aged 18-25 years to receive Cervarix and 3,739 to a control group that received the hepatitis A vaccine; after 4 years, the control group also received Cervarix and exited the study. They were replaced by an unvaccinated control group of 2,836 women. The new control group and the original HPV vaccine group were followed for an additional 7 years.
In years 7-11 of the trial, the investigators found 9.2 additional cervical intraepithelial neoplasias of grade 2 or worse (CIN2+) from HPV types not covered by Cervarix per 1,000 vaccinated women in comparison with unvaccinated participants. This corresponds to –71.2% negative vaccine efficacy against CIN2+ lesions of HPV types not covered by the vaccine.
There were 8.3 additional CIN3+ lesions from nontargeted HPV strains per 1,000 vaccinated women in comparison with unvaccinated participants, which corresponds to –135% negative vaccine efficacy.
Overall, however, there was a net benefit of vaccination, with 27 fewer CIN2+ lesions when all HPV genotypes – vaccine covered or not – were considered per 1,000 vaccinated women over the entire 11 years of follow-up.
There were also 8.7 fewer CIN3+ lesions across all genotypes per 1,000 vaccinated women, but the benefit was not statistically significant.
Among the study limits, the team was unable to evaluate the effect of clinical unmasking on cervical cancer, because women were treated for high-grade cervical lesions before cases could progress to cervical cancer.
The trial was funded by the National Cancer Institute and the National Institutes of Health Office of Research on Women’s Health. GlaxoSmithKline provided the Cervarix vaccine and supported aspects of the trial. Two authors are named inventors on U.S. government–owned HPV vaccine patents with expired licenses to GlaxoSmithKline and Merck. Dr. Steben is an adviser/speaker for many companies, including GlaxoSmithKline and Merck.
A version of this article first appeared on Medscape.com.
FROM THE LANCET ONCOLOGY
What’s the best time of day to exercise? It depends on your goals
For most of us, the “best” time of day to work out is simple: When we can.
Maybe that’s before or after work. Or when the gym offers free daycare. Or when our favorite instructor teaches our favorite class.
That’s why we call it a “routine.” And if the results are the same, it’s hard to imagine changing it up.
But what if the results aren’t the same?
They may not be, according to a new study from a research team at Skidmore College in Saratoga Springs, N.Y.
Women who worked out in the morning lost more fat, while those who trained in the evening gained more upper-body strength and power. As for men, the performance improvements were similar no matter when they exercised. But those who did so in the evening had a significant drop in blood pressure, among other benefits.
The study is part of a growing body of research showing different results for different times of day among different populations. As it turns out, when you exercise can ultimately have a big effect, not just on strength and fat loss, but also heart health, mood, and quality of sleep.
An accidental discovery
The original goal of the Skidmore study was to test a unique fitness program with a group of healthy, fit, and extremely active adults in early middle age.
The program includes four workouts a week, each with a different focus: strength, steady-pace endurance, high-intensity intervals, and flexibility (traditional stretching combined with yoga and Pilates exercises).
But because the group was so large – 27 women and 20 men completed the 3-month program – they had to split them into morning and evening workout groups.
It wasn’t until researchers looked at the results that they saw the differences between morning and evening exercise, says lead author Paul Arciero, PhD.
Dr. Arciero stressed that participants in every group got leaner and stronger. But the women who worked out in the morning got much bigger reductions in body fat and body-fat percentage than the evening group. Meanwhile, women in the evening group got much bigger gains in upper-body strength, power, and muscular endurance than their morning counterparts.
Among the men, the evening group had significantly larger improvements in blood pressure, cholesterol levels, and the percentage of fat they burned for energy, along with a bigger drop in feelings of fatigue.
Strategic timing for powerful results
Some of these findings are consistent with previous research. For example, a study published in 2021 showed that the ability to exert high effort and express strength and power peaks in the late afternoon, about the same time that your core body temperature is at its highest point.
On the other hand, you’ll probably perform better in the morning when the activity requires a lot of skill and coordination or depends on strategic decision-making.
The findings apply to both men and women.
Performance aside, exercise timing might offer strong health benefits for men with type 2 diabetes, or at high risk for it.
A study showed that men who exercised between 3 p.m. and 6 p.m. saw dramatic improvements in blood sugar management and insulin sensitivity, compared to a group that worked out between 8 a.m. and 10 a.m.
They also lost more fat during the 12-week program, even though they were doing the exact same workouts.
Train consistently, sleep well
When you exercise can affect your sleep quality in many ways, said neuroscientist Jennifer Heisz, PhD, of McMaster University, Hamilton, Ont.
First, she said, “exercise helps you fall asleep faster and sleep deeper at night.” (The only exception is if you exercise so intensely or so close to bedtime that your heart rate is still elevated.)
Second, “exercising at a consistent time every day helps regulate the body’s circadian rhythms.” It doesn’t matter if the exercise is in the morning, evening, or anywhere in between. As long as it’s predictable, it will help you fall asleep and wake up at the same times.
Outdoor exercise is even better, she said. The sun is the most powerful regulator of the circadian clock and works in tandem with physical activity.
Third, exercising at specific times can help you overcome jet lag or adjust to an earlier or later shift at work.
“Exercising at 7 a.m. or between 1 and 4 p.m. helps your circadian clock to ‘fall back’ in time, making it easier to wake up earlier,” Dr. Heisz said. If you need to train your body to wake up later in the morning, try working out between 7 p.m. and 10 p.m.
All exercise is good, but the right timing can make it even better
“The best time to exercise is when you can fit it in,” Dr. Arciero said. “You’ve got to choose the time that fits your lifestyle best.”
But context matters, he noted.
“For someone needing to achieve an improvement in their risk for cardiometabolic disease,” his study shows an advantage to working out later in the day, especially for men. If you’re more focused on building upper-body strength and power, you’ll probably get better results from training in the afternoon or evening.
And for fat loss, the Skidmore study shows better results for women who did morning workouts.
And if you’re still not sure? Try sleeping on it – preferably after your workout.
A version of this article first appeared on WebMD.com.
For most of us, the “best” time of day to work out is simple: When we can.
Maybe that’s before or after work. Or when the gym offers free daycare. Or when our favorite instructor teaches our favorite class.
That’s why we call it a “routine.” And if the results are the same, it’s hard to imagine changing it up.
But what if the results aren’t the same?
They may not be, according to a new study from a research team at Skidmore College in Saratoga Springs, N.Y.
Women who worked out in the morning lost more fat, while those who trained in the evening gained more upper-body strength and power. As for men, the performance improvements were similar no matter when they exercised. But those who did so in the evening had a significant drop in blood pressure, among other benefits.
The study is part of a growing body of research showing different results for different times of day among different populations. As it turns out, when you exercise can ultimately have a big effect, not just on strength and fat loss, but also heart health, mood, and quality of sleep.
An accidental discovery
The original goal of the Skidmore study was to test a unique fitness program with a group of healthy, fit, and extremely active adults in early middle age.
The program includes four workouts a week, each with a different focus: strength, steady-pace endurance, high-intensity intervals, and flexibility (traditional stretching combined with yoga and Pilates exercises).
But because the group was so large – 27 women and 20 men completed the 3-month program – they had to split them into morning and evening workout groups.
It wasn’t until researchers looked at the results that they saw the differences between morning and evening exercise, says lead author Paul Arciero, PhD.
Dr. Arciero stressed that participants in every group got leaner and stronger. But the women who worked out in the morning got much bigger reductions in body fat and body-fat percentage than the evening group. Meanwhile, women in the evening group got much bigger gains in upper-body strength, power, and muscular endurance than their morning counterparts.
Among the men, the evening group had significantly larger improvements in blood pressure, cholesterol levels, and the percentage of fat they burned for energy, along with a bigger drop in feelings of fatigue.
Strategic timing for powerful results
Some of these findings are consistent with previous research. For example, a study published in 2021 showed that the ability to exert high effort and express strength and power peaks in the late afternoon, about the same time that your core body temperature is at its highest point.
On the other hand, you’ll probably perform better in the morning when the activity requires a lot of skill and coordination or depends on strategic decision-making.
The findings apply to both men and women.
Performance aside, exercise timing might offer strong health benefits for men with type 2 diabetes, or at high risk for it.
A study showed that men who exercised between 3 p.m. and 6 p.m. saw dramatic improvements in blood sugar management and insulin sensitivity, compared to a group that worked out between 8 a.m. and 10 a.m.
They also lost more fat during the 12-week program, even though they were doing the exact same workouts.
Train consistently, sleep well
When you exercise can affect your sleep quality in many ways, said neuroscientist Jennifer Heisz, PhD, of McMaster University, Hamilton, Ont.
First, she said, “exercise helps you fall asleep faster and sleep deeper at night.” (The only exception is if you exercise so intensely or so close to bedtime that your heart rate is still elevated.)
Second, “exercising at a consistent time every day helps regulate the body’s circadian rhythms.” It doesn’t matter if the exercise is in the morning, evening, or anywhere in between. As long as it’s predictable, it will help you fall asleep and wake up at the same times.
Outdoor exercise is even better, she said. The sun is the most powerful regulator of the circadian clock and works in tandem with physical activity.
Third, exercising at specific times can help you overcome jet lag or adjust to an earlier or later shift at work.
“Exercising at 7 a.m. or between 1 and 4 p.m. helps your circadian clock to ‘fall back’ in time, making it easier to wake up earlier,” Dr. Heisz said. If you need to train your body to wake up later in the morning, try working out between 7 p.m. and 10 p.m.
All exercise is good, but the right timing can make it even better
“The best time to exercise is when you can fit it in,” Dr. Arciero said. “You’ve got to choose the time that fits your lifestyle best.”
But context matters, he noted.
“For someone needing to achieve an improvement in their risk for cardiometabolic disease,” his study shows an advantage to working out later in the day, especially for men. If you’re more focused on building upper-body strength and power, you’ll probably get better results from training in the afternoon or evening.
And for fat loss, the Skidmore study shows better results for women who did morning workouts.
And if you’re still not sure? Try sleeping on it – preferably after your workout.
A version of this article first appeared on WebMD.com.
For most of us, the “best” time of day to work out is simple: When we can.
Maybe that’s before or after work. Or when the gym offers free daycare. Or when our favorite instructor teaches our favorite class.
That’s why we call it a “routine.” And if the results are the same, it’s hard to imagine changing it up.
But what if the results aren’t the same?
They may not be, according to a new study from a research team at Skidmore College in Saratoga Springs, N.Y.
Women who worked out in the morning lost more fat, while those who trained in the evening gained more upper-body strength and power. As for men, the performance improvements were similar no matter when they exercised. But those who did so in the evening had a significant drop in blood pressure, among other benefits.
The study is part of a growing body of research showing different results for different times of day among different populations. As it turns out, when you exercise can ultimately have a big effect, not just on strength and fat loss, but also heart health, mood, and quality of sleep.
An accidental discovery
The original goal of the Skidmore study was to test a unique fitness program with a group of healthy, fit, and extremely active adults in early middle age.
The program includes four workouts a week, each with a different focus: strength, steady-pace endurance, high-intensity intervals, and flexibility (traditional stretching combined with yoga and Pilates exercises).
But because the group was so large – 27 women and 20 men completed the 3-month program – they had to split them into morning and evening workout groups.
It wasn’t until researchers looked at the results that they saw the differences between morning and evening exercise, says lead author Paul Arciero, PhD.
Dr. Arciero stressed that participants in every group got leaner and stronger. But the women who worked out in the morning got much bigger reductions in body fat and body-fat percentage than the evening group. Meanwhile, women in the evening group got much bigger gains in upper-body strength, power, and muscular endurance than their morning counterparts.
Among the men, the evening group had significantly larger improvements in blood pressure, cholesterol levels, and the percentage of fat they burned for energy, along with a bigger drop in feelings of fatigue.
Strategic timing for powerful results
Some of these findings are consistent with previous research. For example, a study published in 2021 showed that the ability to exert high effort and express strength and power peaks in the late afternoon, about the same time that your core body temperature is at its highest point.
On the other hand, you’ll probably perform better in the morning when the activity requires a lot of skill and coordination or depends on strategic decision-making.
The findings apply to both men and women.
Performance aside, exercise timing might offer strong health benefits for men with type 2 diabetes, or at high risk for it.
A study showed that men who exercised between 3 p.m. and 6 p.m. saw dramatic improvements in blood sugar management and insulin sensitivity, compared to a group that worked out between 8 a.m. and 10 a.m.
They also lost more fat during the 12-week program, even though they were doing the exact same workouts.
Train consistently, sleep well
When you exercise can affect your sleep quality in many ways, said neuroscientist Jennifer Heisz, PhD, of McMaster University, Hamilton, Ont.
First, she said, “exercise helps you fall asleep faster and sleep deeper at night.” (The only exception is if you exercise so intensely or so close to bedtime that your heart rate is still elevated.)
Second, “exercising at a consistent time every day helps regulate the body’s circadian rhythms.” It doesn’t matter if the exercise is in the morning, evening, or anywhere in between. As long as it’s predictable, it will help you fall asleep and wake up at the same times.
Outdoor exercise is even better, she said. The sun is the most powerful regulator of the circadian clock and works in tandem with physical activity.
Third, exercising at specific times can help you overcome jet lag or adjust to an earlier or later shift at work.
“Exercising at 7 a.m. or between 1 and 4 p.m. helps your circadian clock to ‘fall back’ in time, making it easier to wake up earlier,” Dr. Heisz said. If you need to train your body to wake up later in the morning, try working out between 7 p.m. and 10 p.m.
All exercise is good, but the right timing can make it even better
“The best time to exercise is when you can fit it in,” Dr. Arciero said. “You’ve got to choose the time that fits your lifestyle best.”
But context matters, he noted.
“For someone needing to achieve an improvement in their risk for cardiometabolic disease,” his study shows an advantage to working out later in the day, especially for men. If you’re more focused on building upper-body strength and power, you’ll probably get better results from training in the afternoon or evening.
And for fat loss, the Skidmore study shows better results for women who did morning workouts.
And if you’re still not sure? Try sleeping on it – preferably after your workout.
A version of this article first appeared on WebMD.com.
FROM FRONTIERS IN PHYSIOLOGY
To predict mortality, you need a leg to stand on
Storks everywhere, rejoice.
According to the findings, people in middle age and older who couldn’t perform the 10-second standing test were nearly four times as likely to die of any cause – heart attacks, strokes, cancer, and more – in the coming years than those who could, well, stand the test of time.
Claudio Gil Araújo, MD, PhD, research director of the Exercise Medicine Clinic-CLINIMEX in Rio de Janeiro, who led the study, called the results “awesome!”
“As a physician who has worked with cardiac patients for over 4 decades, I was very impressed in finding out that, for those between 51 and 75 years of age, it is riskier for survival to not complete the 10-second one-leg standing test than to have been diagnosed as having coronary artery disease or in being hypertensive” or having abnormal cholesterol, Dr. Araújo said in an interview.
The findings appeared in the British Journal of Sports Medicine.
Researchers have known for at least a half century that balance and mortality are connected. One reason is falls: Worldwide, nearly 700,000 people each year die as a result of a fall, according to the World Health Organization, and more than 37 million falls annually require medical attention. But as the new study indicates, falls aren’t the only problem.
Dr. Araújo and colleagues have been working on ways to improve balance and strength as people age. In addition to the one-legged standing test, they have previously shown that the ability to rise from a sitting position on the floor is also a strong predictor of longevity.
For the new study, the researchers assessed 1,702 people in Brazil (68% men) aged 51-75 years who had been participating in an ongoing exercise study that began there in 1994.
Three tries to succeed
Starting in 2008, the team introduced the standing test, which involves balancing on one leg and placing the other foot at the back weight-bearing limb for support. People get three tries to maintain that posture for at least 10 seconds.
Not surprisingly, the ability to perform the test dropped with age. Although 20% of people in the study overall were unable to stand on one leg for 10 seconds, that figure rose to about 70% for those aged 76-80 years, and nearly 90% for those aged 81-85, according to the researchers. Of the two dozen 85-year-olds in the study, only two were able to complete the standing test, Dr. Araújo told this news organization.
At roughly age 70, half of people could not complete the 10-second test.
Over an average of 7 years of follow-up, 17.5% of people who could not manage the 10-second stand had died, compared with 4.5% of those who could last that long, the study found.
After accounting for age and many other risk factors, such as diabetes, body mass index, and a history of heart disease, people who were unable to complete the standing test were 84% more likely to die from any cause over the study period than their peers with better one-legged static balance (95% confidence interval, 1.23-2.78; P < .001).
The researchers said their study was limited by its lack of diversity – all the participants were relatively affluent Brazilians – and the inability to control for a history of falls and physical activity. But they said the size of the cohort, the long follow-up period, and their use of sophistical statistical methods helped mitigate the shortcomings.
Although low aerobic fitness is a marker of poor health, much less attention has been paid to nonaerobic fitness – things like balance, flexibility, and muscle strength and power, Dr. Araújo said.
“We are accumulating evidence that these three components of nonaerobic physical fitness are potentially relevant for good health and even more relevant for survival in older subjects,” Dr. Araújo said. Poor nonaerobic fitness, which is normally but not always associated with a sedentary lifestyle, “is the background of most cases of frailty, and being frail is strongly associated with a poor quality of life, less physical activity and exercise, and so on. It’s a bad circle.”
Dr. Araújo’s group has been using the standing test in their clinic for more than a dozen years and have seen gains in their patients. “Patients are often unaware that they are unable to sustain 10 seconds standing one legged. After this simple evaluation, they are much more prone to engage in balance training,” he said.
For now, the researchers don’t have data to show that improving static balance or performance on the standing test can affect survival, a “quite attractive” possibility, he added. But balance can be substantially improved through training.
“After only a few sessions, an improvement can be perceived, and this influences quality of life,” Dr. Araújo said. “And this is exactly what we do with the patients that we evaluated and for those that are attending our medically supervised exercise program.”
George A. Kuchel, MD, CM, FRCP, professor and Travelers Chair in Geriatrics and Gerontology at the University of Connecticut, Farmington, called the research “well done” and said the results “make perfect sense, since we have known for a long time that muscle strength is an important determinant of health, independence, and survival.”
Identifying frail patients quickly, simply, and reliably in the clinical setting is a pressing need, Dr. Kuchel, director of the UConn Center on Aging, said in an interview. The 10-second test “has considerable appeal” for this purpose.
“This could be, or rather should be, of great interest to all busy clinicians who see older adults in primary care or consultative capacities,” Dr. Kuchel added. “I hate to be nihilistic as regards what is possible in the context of really busy clinical practices, but even the minute or so that this takes to do may very well be too much for busy clinicians to do.”
Dr. Araújo and Dr. Kuchel reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Storks everywhere, rejoice.
According to the findings, people in middle age and older who couldn’t perform the 10-second standing test were nearly four times as likely to die of any cause – heart attacks, strokes, cancer, and more – in the coming years than those who could, well, stand the test of time.
Claudio Gil Araújo, MD, PhD, research director of the Exercise Medicine Clinic-CLINIMEX in Rio de Janeiro, who led the study, called the results “awesome!”
“As a physician who has worked with cardiac patients for over 4 decades, I was very impressed in finding out that, for those between 51 and 75 years of age, it is riskier for survival to not complete the 10-second one-leg standing test than to have been diagnosed as having coronary artery disease or in being hypertensive” or having abnormal cholesterol, Dr. Araújo said in an interview.
The findings appeared in the British Journal of Sports Medicine.
Researchers have known for at least a half century that balance and mortality are connected. One reason is falls: Worldwide, nearly 700,000 people each year die as a result of a fall, according to the World Health Organization, and more than 37 million falls annually require medical attention. But as the new study indicates, falls aren’t the only problem.
Dr. Araújo and colleagues have been working on ways to improve balance and strength as people age. In addition to the one-legged standing test, they have previously shown that the ability to rise from a sitting position on the floor is also a strong predictor of longevity.
For the new study, the researchers assessed 1,702 people in Brazil (68% men) aged 51-75 years who had been participating in an ongoing exercise study that began there in 1994.
Three tries to succeed
Starting in 2008, the team introduced the standing test, which involves balancing on one leg and placing the other foot at the back weight-bearing limb for support. People get three tries to maintain that posture for at least 10 seconds.
Not surprisingly, the ability to perform the test dropped with age. Although 20% of people in the study overall were unable to stand on one leg for 10 seconds, that figure rose to about 70% for those aged 76-80 years, and nearly 90% for those aged 81-85, according to the researchers. Of the two dozen 85-year-olds in the study, only two were able to complete the standing test, Dr. Araújo told this news organization.
At roughly age 70, half of people could not complete the 10-second test.
Over an average of 7 years of follow-up, 17.5% of people who could not manage the 10-second stand had died, compared with 4.5% of those who could last that long, the study found.
After accounting for age and many other risk factors, such as diabetes, body mass index, and a history of heart disease, people who were unable to complete the standing test were 84% more likely to die from any cause over the study period than their peers with better one-legged static balance (95% confidence interval, 1.23-2.78; P < .001).
The researchers said their study was limited by its lack of diversity – all the participants were relatively affluent Brazilians – and the inability to control for a history of falls and physical activity. But they said the size of the cohort, the long follow-up period, and their use of sophistical statistical methods helped mitigate the shortcomings.
Although low aerobic fitness is a marker of poor health, much less attention has been paid to nonaerobic fitness – things like balance, flexibility, and muscle strength and power, Dr. Araújo said.
“We are accumulating evidence that these three components of nonaerobic physical fitness are potentially relevant for good health and even more relevant for survival in older subjects,” Dr. Araújo said. Poor nonaerobic fitness, which is normally but not always associated with a sedentary lifestyle, “is the background of most cases of frailty, and being frail is strongly associated with a poor quality of life, less physical activity and exercise, and so on. It’s a bad circle.”
Dr. Araújo’s group has been using the standing test in their clinic for more than a dozen years and have seen gains in their patients. “Patients are often unaware that they are unable to sustain 10 seconds standing one legged. After this simple evaluation, they are much more prone to engage in balance training,” he said.
For now, the researchers don’t have data to show that improving static balance or performance on the standing test can affect survival, a “quite attractive” possibility, he added. But balance can be substantially improved through training.
“After only a few sessions, an improvement can be perceived, and this influences quality of life,” Dr. Araújo said. “And this is exactly what we do with the patients that we evaluated and for those that are attending our medically supervised exercise program.”
George A. Kuchel, MD, CM, FRCP, professor and Travelers Chair in Geriatrics and Gerontology at the University of Connecticut, Farmington, called the research “well done” and said the results “make perfect sense, since we have known for a long time that muscle strength is an important determinant of health, independence, and survival.”
Identifying frail patients quickly, simply, and reliably in the clinical setting is a pressing need, Dr. Kuchel, director of the UConn Center on Aging, said in an interview. The 10-second test “has considerable appeal” for this purpose.
“This could be, or rather should be, of great interest to all busy clinicians who see older adults in primary care or consultative capacities,” Dr. Kuchel added. “I hate to be nihilistic as regards what is possible in the context of really busy clinical practices, but even the minute or so that this takes to do may very well be too much for busy clinicians to do.”
Dr. Araújo and Dr. Kuchel reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Storks everywhere, rejoice.
According to the findings, people in middle age and older who couldn’t perform the 10-second standing test were nearly four times as likely to die of any cause – heart attacks, strokes, cancer, and more – in the coming years than those who could, well, stand the test of time.
Claudio Gil Araújo, MD, PhD, research director of the Exercise Medicine Clinic-CLINIMEX in Rio de Janeiro, who led the study, called the results “awesome!”
“As a physician who has worked with cardiac patients for over 4 decades, I was very impressed in finding out that, for those between 51 and 75 years of age, it is riskier for survival to not complete the 10-second one-leg standing test than to have been diagnosed as having coronary artery disease or in being hypertensive” or having abnormal cholesterol, Dr. Araújo said in an interview.
The findings appeared in the British Journal of Sports Medicine.
Researchers have known for at least a half century that balance and mortality are connected. One reason is falls: Worldwide, nearly 700,000 people each year die as a result of a fall, according to the World Health Organization, and more than 37 million falls annually require medical attention. But as the new study indicates, falls aren’t the only problem.
Dr. Araújo and colleagues have been working on ways to improve balance and strength as people age. In addition to the one-legged standing test, they have previously shown that the ability to rise from a sitting position on the floor is also a strong predictor of longevity.
For the new study, the researchers assessed 1,702 people in Brazil (68% men) aged 51-75 years who had been participating in an ongoing exercise study that began there in 1994.
Three tries to succeed
Starting in 2008, the team introduced the standing test, which involves balancing on one leg and placing the other foot at the back weight-bearing limb for support. People get three tries to maintain that posture for at least 10 seconds.
Not surprisingly, the ability to perform the test dropped with age. Although 20% of people in the study overall were unable to stand on one leg for 10 seconds, that figure rose to about 70% for those aged 76-80 years, and nearly 90% for those aged 81-85, according to the researchers. Of the two dozen 85-year-olds in the study, only two were able to complete the standing test, Dr. Araújo told this news organization.
At roughly age 70, half of people could not complete the 10-second test.
Over an average of 7 years of follow-up, 17.5% of people who could not manage the 10-second stand had died, compared with 4.5% of those who could last that long, the study found.
After accounting for age and many other risk factors, such as diabetes, body mass index, and a history of heart disease, people who were unable to complete the standing test were 84% more likely to die from any cause over the study period than their peers with better one-legged static balance (95% confidence interval, 1.23-2.78; P < .001).
The researchers said their study was limited by its lack of diversity – all the participants were relatively affluent Brazilians – and the inability to control for a history of falls and physical activity. But they said the size of the cohort, the long follow-up period, and their use of sophistical statistical methods helped mitigate the shortcomings.
Although low aerobic fitness is a marker of poor health, much less attention has been paid to nonaerobic fitness – things like balance, flexibility, and muscle strength and power, Dr. Araújo said.
“We are accumulating evidence that these three components of nonaerobic physical fitness are potentially relevant for good health and even more relevant for survival in older subjects,” Dr. Araújo said. Poor nonaerobic fitness, which is normally but not always associated with a sedentary lifestyle, “is the background of most cases of frailty, and being frail is strongly associated with a poor quality of life, less physical activity and exercise, and so on. It’s a bad circle.”
Dr. Araújo’s group has been using the standing test in their clinic for more than a dozen years and have seen gains in their patients. “Patients are often unaware that they are unable to sustain 10 seconds standing one legged. After this simple evaluation, they are much more prone to engage in balance training,” he said.
For now, the researchers don’t have data to show that improving static balance or performance on the standing test can affect survival, a “quite attractive” possibility, he added. But balance can be substantially improved through training.
“After only a few sessions, an improvement can be perceived, and this influences quality of life,” Dr. Araújo said. “And this is exactly what we do with the patients that we evaluated and for those that are attending our medically supervised exercise program.”
George A. Kuchel, MD, CM, FRCP, professor and Travelers Chair in Geriatrics and Gerontology at the University of Connecticut, Farmington, called the research “well done” and said the results “make perfect sense, since we have known for a long time that muscle strength is an important determinant of health, independence, and survival.”
Identifying frail patients quickly, simply, and reliably in the clinical setting is a pressing need, Dr. Kuchel, director of the UConn Center on Aging, said in an interview. The 10-second test “has considerable appeal” for this purpose.
“This could be, or rather should be, of great interest to all busy clinicians who see older adults in primary care or consultative capacities,” Dr. Kuchel added. “I hate to be nihilistic as regards what is possible in the context of really busy clinical practices, but even the minute or so that this takes to do may very well be too much for busy clinicians to do.”
Dr. Araújo and Dr. Kuchel reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE BRITISH JOURNAL OF SPORTS MEDICINE
Updates in aspirin use, aducanumab, and CKD diagnostic criteria in geriatric medicine
I selected these topics as they were among the most discussed by my colleagues in geriatric medicine and inquired about by my primary care patients in geriatric medicine clinic. I hope that these updates provide primary care clinicians who care for older adults with more context and background information regarding new Alzheimer’s disease therapy to better answer patient inquiries, and to feel empowered to deprescribe aspirin and reframe the diagnostic criteria of chronic kidney disease (CKD).
Aspirin for primary prevention
It was welcome news in the geriatrics community when the United States Preventive Services Task Force updated their guidelines in April 2022 to recommend against the initiation of aspirin for primary prevention in adults aged 60 or older. This recommendation was based on studies that found that net benefits of CVD prevention in older adults are outweighed by risk of bleeding.1
The risk of bleeding increases with age and can occur in individuals without common risk factors for bleeding, such as prior gastrointestinal bleeding, peptic ulcer disease, concurrent NSAID use, or corticosteroid use.
While it may be easier to not initiate aspirin for primary prevention, deprescribing aspirin for patients who have been on aspirin long term for primary prevention presents more of a challenge. Modeling data from the USPTSF suggest stopping aspirin at age 75 for those taking aspirin for primary prevention.2
Behavioral change, particularly for patients who have been on aspirin for decades, can be difficult. A 2021 study by Green et al. found that language that resonates the most with older adults when deprescribing emphasized the side effects rather than statements such as “this will not help you” or “do not need anymore.”3
Aducanumab for mild cognitive impairment and mild Alzheimer’s dementia
One of the most discussed topics this past year is the Food and Drug Administration approval of aducanumab (brand name Aduhelm) in June 2021. Aducanumab is the first approved disease-modifying therapy for Alzheimer’s disease and the first drug approved for the treatment of Alzheimer’s disease since 2003. Aducanumab is an antiamyloid monoclonal antibody that was developed to reduce amyloid plaque in the brain, one of the features of Alzheimer’s disease pathology.
Uptake of aducanumab by dementia providers has been limited for several reasons. Firstly, the clinical significance of the drug remains in question. ENGAGE and EMERGE were the two main randomized clinical trials that studied the effect of aducanumab on amyloid burden and clinical stages of dementia over 18 months. While both studies demonstrated that aducanumab reduced amyloid burden based on neuroimaging and in cerebrospinal fluid, the ENGAGE trial found no difference in the stage of dementia. The EMERGE trial did note a small, statistically significant difference in stage of dementia, however the participants of the EMERGE trial had a faster rate of progression of dementia than the placebo participants in the ENGAGE trial, which could have contributed to the difference detected.4
Additionally, exclusion criteria for both trials call into question the generalizability of this study. Participants over age 85, with CKD, prior stroke, or transient ischemic attacks, or on anticoagulation were excluded. One of the drivers for the exclusion criteria is the increased risk of macro and microhemorrhages.
Thirty-five percent of research participants were incidentally noted to have brain edema, an abnormality called amyloid-related imaging abnormality or ARIA-E, that necessitated serial monitoring with brain MRIs. It is also important to highlight that inclusion of African American, Hispanic, and Latinx participants in these studies was less than 5%, despite a higher incidence of Alzheimer’s disease in these populations.5
Lastly, economic implications for the U.S. health care system with increased uptake of aducanumab could be enormous. Originally quoted at $56,000 yearly, Biogen, the maker of aducanumab, recently reduced annual costs to $28,200 per patient.
In April 2022, CMS released a statement that antiamyloid monoclonal antibodies and related services, including PET scans, would be covered under Medicare for those with mild cognitive impairment and mild Alzheimer’s dementia with confirmed presence of amyloid. A study by Mafi et al. estimated that aducanumab could cost Medicare between $7 billion and $37.4 billion annually based on lower and upper bound estimates of eligible Medicare beneficiaries.6
Overdiagnosis of CKD in older adults
The current diagnostic criteria of CKD, which is based on an estimated glomerular filtration rate (eGFR) of less than 60, has been up for debate, as glomerular filtration rate (GFR) physiologically decreases with age. Fixed thresholds can lead to underdiagnosis of CKD in younger adults and overdiagnosis of CKD in older adults. Age-adapted thresholds for the diagnosis of CKD have been proposed, with the suggestion of an eGFR threshold of 45mL/min/1.73 m2 for adults aged 65 and older.7
The clinical implication of using an age-adapted eGFR threshold definition was investigated in a 2021 cohort study by Liu et al.8 In this study, outcomes of adults diagnosed with CKD using a fixed threshold versus age-adapted threshold were compared with a healthy cohort.
A fixed threshold led to a 60% higher incidence of CKD diagnosis. However, incidence of renal failure and all-cause mortality in older adults with an eGFR between 45-59 /min/1.73 m2 with normal or mild albuminuria was of similar magnitude to the healthy cohort at 5 years of follow-up.
These findings support the use of age-adapted thresholds for the diagnosis of CKD in older adults, as an earlier diagnosis of mild CKD does not equate to clinical benefits, but could lead to harms of unnecessary interventions and patient anxiety.
Dr. Mengru “Ruru” Wang is a geriatrician and internist at the University of Washington, Seattle. She practices full-spectrum medicine, seeing patients in primary care, nursing homes, and acute care. Dr. Wang has no disclosures related to this piece.
References
1. Selak Vet al. Predicting bleeding risk to guide aspirin use for the primary prevention of cardiovascular disease: A cohort study. Ann Intern Med. 2019;170(6):357-68. doi: 10.7326/M18-2808.
2. US Preventive Services Task Force. Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement. JAMA. 2022;327(16):1577-84. doi: 10.1001/jama.2022.4983.
3. Green AR et al. Assessment of patient-preferred language to achieve goal-aligned deprescribing in older adults. JAMA Netw Open. 2021;4(4):e212633. doi: 10.1001/jamanetworkopen.2021.2633.
4. Oh ES. Use of anti-amyloid therapy for Alzheimer’s disease in clinical practice. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at American Geriatrics Society Meeting, 2022. Orlando.
5. Amjad H. Issues of Access and Marginalization. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at: American Geriatrics Society Meeting, 2022. Orlando.
6. Mafi JN et al. Estimated annual spending on aducanumab in the U.S. Medicare program. JAMA Health Forum. 2022;3(1):e214495. doi: 10.1001/jamahealthforum.2021.4495.
7. Delanaye P et al. CKD: A call for an age-adapted definition. J Am Soc Nephrol. 2019;30(10):1785-1805. doi: 10.1681/ASN.2019030238.
8. Liu Pet al. Accounting for age in the definition of chronic kidney disease. JAMA Intern Med. 2021;181(10):1359-66. doi: 10.1001/jamainternmed.2021.4813.
I selected these topics as they were among the most discussed by my colleagues in geriatric medicine and inquired about by my primary care patients in geriatric medicine clinic. I hope that these updates provide primary care clinicians who care for older adults with more context and background information regarding new Alzheimer’s disease therapy to better answer patient inquiries, and to feel empowered to deprescribe aspirin and reframe the diagnostic criteria of chronic kidney disease (CKD).
Aspirin for primary prevention
It was welcome news in the geriatrics community when the United States Preventive Services Task Force updated their guidelines in April 2022 to recommend against the initiation of aspirin for primary prevention in adults aged 60 or older. This recommendation was based on studies that found that net benefits of CVD prevention in older adults are outweighed by risk of bleeding.1
The risk of bleeding increases with age and can occur in individuals without common risk factors for bleeding, such as prior gastrointestinal bleeding, peptic ulcer disease, concurrent NSAID use, or corticosteroid use.
While it may be easier to not initiate aspirin for primary prevention, deprescribing aspirin for patients who have been on aspirin long term for primary prevention presents more of a challenge. Modeling data from the USPTSF suggest stopping aspirin at age 75 for those taking aspirin for primary prevention.2
Behavioral change, particularly for patients who have been on aspirin for decades, can be difficult. A 2021 study by Green et al. found that language that resonates the most with older adults when deprescribing emphasized the side effects rather than statements such as “this will not help you” or “do not need anymore.”3
Aducanumab for mild cognitive impairment and mild Alzheimer’s dementia
One of the most discussed topics this past year is the Food and Drug Administration approval of aducanumab (brand name Aduhelm) in June 2021. Aducanumab is the first approved disease-modifying therapy for Alzheimer’s disease and the first drug approved for the treatment of Alzheimer’s disease since 2003. Aducanumab is an antiamyloid monoclonal antibody that was developed to reduce amyloid plaque in the brain, one of the features of Alzheimer’s disease pathology.
Uptake of aducanumab by dementia providers has been limited for several reasons. Firstly, the clinical significance of the drug remains in question. ENGAGE and EMERGE were the two main randomized clinical trials that studied the effect of aducanumab on amyloid burden and clinical stages of dementia over 18 months. While both studies demonstrated that aducanumab reduced amyloid burden based on neuroimaging and in cerebrospinal fluid, the ENGAGE trial found no difference in the stage of dementia. The EMERGE trial did note a small, statistically significant difference in stage of dementia, however the participants of the EMERGE trial had a faster rate of progression of dementia than the placebo participants in the ENGAGE trial, which could have contributed to the difference detected.4
Additionally, exclusion criteria for both trials call into question the generalizability of this study. Participants over age 85, with CKD, prior stroke, or transient ischemic attacks, or on anticoagulation were excluded. One of the drivers for the exclusion criteria is the increased risk of macro and microhemorrhages.
Thirty-five percent of research participants were incidentally noted to have brain edema, an abnormality called amyloid-related imaging abnormality or ARIA-E, that necessitated serial monitoring with brain MRIs. It is also important to highlight that inclusion of African American, Hispanic, and Latinx participants in these studies was less than 5%, despite a higher incidence of Alzheimer’s disease in these populations.5
Lastly, economic implications for the U.S. health care system with increased uptake of aducanumab could be enormous. Originally quoted at $56,000 yearly, Biogen, the maker of aducanumab, recently reduced annual costs to $28,200 per patient.
In April 2022, CMS released a statement that antiamyloid monoclonal antibodies and related services, including PET scans, would be covered under Medicare for those with mild cognitive impairment and mild Alzheimer’s dementia with confirmed presence of amyloid. A study by Mafi et al. estimated that aducanumab could cost Medicare between $7 billion and $37.4 billion annually based on lower and upper bound estimates of eligible Medicare beneficiaries.6
Overdiagnosis of CKD in older adults
The current diagnostic criteria of CKD, which is based on an estimated glomerular filtration rate (eGFR) of less than 60, has been up for debate, as glomerular filtration rate (GFR) physiologically decreases with age. Fixed thresholds can lead to underdiagnosis of CKD in younger adults and overdiagnosis of CKD in older adults. Age-adapted thresholds for the diagnosis of CKD have been proposed, with the suggestion of an eGFR threshold of 45mL/min/1.73 m2 for adults aged 65 and older.7
The clinical implication of using an age-adapted eGFR threshold definition was investigated in a 2021 cohort study by Liu et al.8 In this study, outcomes of adults diagnosed with CKD using a fixed threshold versus age-adapted threshold were compared with a healthy cohort.
A fixed threshold led to a 60% higher incidence of CKD diagnosis. However, incidence of renal failure and all-cause mortality in older adults with an eGFR between 45-59 /min/1.73 m2 with normal or mild albuminuria was of similar magnitude to the healthy cohort at 5 years of follow-up.
These findings support the use of age-adapted thresholds for the diagnosis of CKD in older adults, as an earlier diagnosis of mild CKD does not equate to clinical benefits, but could lead to harms of unnecessary interventions and patient anxiety.
Dr. Mengru “Ruru” Wang is a geriatrician and internist at the University of Washington, Seattle. She practices full-spectrum medicine, seeing patients in primary care, nursing homes, and acute care. Dr. Wang has no disclosures related to this piece.
References
1. Selak Vet al. Predicting bleeding risk to guide aspirin use for the primary prevention of cardiovascular disease: A cohort study. Ann Intern Med. 2019;170(6):357-68. doi: 10.7326/M18-2808.
2. US Preventive Services Task Force. Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement. JAMA. 2022;327(16):1577-84. doi: 10.1001/jama.2022.4983.
3. Green AR et al. Assessment of patient-preferred language to achieve goal-aligned deprescribing in older adults. JAMA Netw Open. 2021;4(4):e212633. doi: 10.1001/jamanetworkopen.2021.2633.
4. Oh ES. Use of anti-amyloid therapy for Alzheimer’s disease in clinical practice. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at American Geriatrics Society Meeting, 2022. Orlando.
5. Amjad H. Issues of Access and Marginalization. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at: American Geriatrics Society Meeting, 2022. Orlando.
6. Mafi JN et al. Estimated annual spending on aducanumab in the U.S. Medicare program. JAMA Health Forum. 2022;3(1):e214495. doi: 10.1001/jamahealthforum.2021.4495.
7. Delanaye P et al. CKD: A call for an age-adapted definition. J Am Soc Nephrol. 2019;30(10):1785-1805. doi: 10.1681/ASN.2019030238.
8. Liu Pet al. Accounting for age in the definition of chronic kidney disease. JAMA Intern Med. 2021;181(10):1359-66. doi: 10.1001/jamainternmed.2021.4813.
I selected these topics as they were among the most discussed by my colleagues in geriatric medicine and inquired about by my primary care patients in geriatric medicine clinic. I hope that these updates provide primary care clinicians who care for older adults with more context and background information regarding new Alzheimer’s disease therapy to better answer patient inquiries, and to feel empowered to deprescribe aspirin and reframe the diagnostic criteria of chronic kidney disease (CKD).
Aspirin for primary prevention
It was welcome news in the geriatrics community when the United States Preventive Services Task Force updated their guidelines in April 2022 to recommend against the initiation of aspirin for primary prevention in adults aged 60 or older. This recommendation was based on studies that found that net benefits of CVD prevention in older adults are outweighed by risk of bleeding.1
The risk of bleeding increases with age and can occur in individuals without common risk factors for bleeding, such as prior gastrointestinal bleeding, peptic ulcer disease, concurrent NSAID use, or corticosteroid use.
While it may be easier to not initiate aspirin for primary prevention, deprescribing aspirin for patients who have been on aspirin long term for primary prevention presents more of a challenge. Modeling data from the USPTSF suggest stopping aspirin at age 75 for those taking aspirin for primary prevention.2
Behavioral change, particularly for patients who have been on aspirin for decades, can be difficult. A 2021 study by Green et al. found that language that resonates the most with older adults when deprescribing emphasized the side effects rather than statements such as “this will not help you” or “do not need anymore.”3
Aducanumab for mild cognitive impairment and mild Alzheimer’s dementia
One of the most discussed topics this past year is the Food and Drug Administration approval of aducanumab (brand name Aduhelm) in June 2021. Aducanumab is the first approved disease-modifying therapy for Alzheimer’s disease and the first drug approved for the treatment of Alzheimer’s disease since 2003. Aducanumab is an antiamyloid monoclonal antibody that was developed to reduce amyloid plaque in the brain, one of the features of Alzheimer’s disease pathology.
Uptake of aducanumab by dementia providers has been limited for several reasons. Firstly, the clinical significance of the drug remains in question. ENGAGE and EMERGE were the two main randomized clinical trials that studied the effect of aducanumab on amyloid burden and clinical stages of dementia over 18 months. While both studies demonstrated that aducanumab reduced amyloid burden based on neuroimaging and in cerebrospinal fluid, the ENGAGE trial found no difference in the stage of dementia. The EMERGE trial did note a small, statistically significant difference in stage of dementia, however the participants of the EMERGE trial had a faster rate of progression of dementia than the placebo participants in the ENGAGE trial, which could have contributed to the difference detected.4
Additionally, exclusion criteria for both trials call into question the generalizability of this study. Participants over age 85, with CKD, prior stroke, or transient ischemic attacks, or on anticoagulation were excluded. One of the drivers for the exclusion criteria is the increased risk of macro and microhemorrhages.
Thirty-five percent of research participants were incidentally noted to have brain edema, an abnormality called amyloid-related imaging abnormality or ARIA-E, that necessitated serial monitoring with brain MRIs. It is also important to highlight that inclusion of African American, Hispanic, and Latinx participants in these studies was less than 5%, despite a higher incidence of Alzheimer’s disease in these populations.5
Lastly, economic implications for the U.S. health care system with increased uptake of aducanumab could be enormous. Originally quoted at $56,000 yearly, Biogen, the maker of aducanumab, recently reduced annual costs to $28,200 per patient.
In April 2022, CMS released a statement that antiamyloid monoclonal antibodies and related services, including PET scans, would be covered under Medicare for those with mild cognitive impairment and mild Alzheimer’s dementia with confirmed presence of amyloid. A study by Mafi et al. estimated that aducanumab could cost Medicare between $7 billion and $37.4 billion annually based on lower and upper bound estimates of eligible Medicare beneficiaries.6
Overdiagnosis of CKD in older adults
The current diagnostic criteria of CKD, which is based on an estimated glomerular filtration rate (eGFR) of less than 60, has been up for debate, as glomerular filtration rate (GFR) physiologically decreases with age. Fixed thresholds can lead to underdiagnosis of CKD in younger adults and overdiagnosis of CKD in older adults. Age-adapted thresholds for the diagnosis of CKD have been proposed, with the suggestion of an eGFR threshold of 45mL/min/1.73 m2 for adults aged 65 and older.7
The clinical implication of using an age-adapted eGFR threshold definition was investigated in a 2021 cohort study by Liu et al.8 In this study, outcomes of adults diagnosed with CKD using a fixed threshold versus age-adapted threshold were compared with a healthy cohort.
A fixed threshold led to a 60% higher incidence of CKD diagnosis. However, incidence of renal failure and all-cause mortality in older adults with an eGFR between 45-59 /min/1.73 m2 with normal or mild albuminuria was of similar magnitude to the healthy cohort at 5 years of follow-up.
These findings support the use of age-adapted thresholds for the diagnosis of CKD in older adults, as an earlier diagnosis of mild CKD does not equate to clinical benefits, but could lead to harms of unnecessary interventions and patient anxiety.
Dr. Mengru “Ruru” Wang is a geriatrician and internist at the University of Washington, Seattle. She practices full-spectrum medicine, seeing patients in primary care, nursing homes, and acute care. Dr. Wang has no disclosures related to this piece.
References
1. Selak Vet al. Predicting bleeding risk to guide aspirin use for the primary prevention of cardiovascular disease: A cohort study. Ann Intern Med. 2019;170(6):357-68. doi: 10.7326/M18-2808.
2. US Preventive Services Task Force. Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement. JAMA. 2022;327(16):1577-84. doi: 10.1001/jama.2022.4983.
3. Green AR et al. Assessment of patient-preferred language to achieve goal-aligned deprescribing in older adults. JAMA Netw Open. 2021;4(4):e212633. doi: 10.1001/jamanetworkopen.2021.2633.
4. Oh ES. Use of anti-amyloid therapy for Alzheimer’s disease in clinical practice. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at American Geriatrics Society Meeting, 2022. Orlando.
5. Amjad H. Issues of Access and Marginalization. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at: American Geriatrics Society Meeting, 2022. Orlando.
6. Mafi JN et al. Estimated annual spending on aducanumab in the U.S. Medicare program. JAMA Health Forum. 2022;3(1):e214495. doi: 10.1001/jamahealthforum.2021.4495.
7. Delanaye P et al. CKD: A call for an age-adapted definition. J Am Soc Nephrol. 2019;30(10):1785-1805. doi: 10.1681/ASN.2019030238.
8. Liu Pet al. Accounting for age in the definition of chronic kidney disease. JAMA Intern Med. 2021;181(10):1359-66. doi: 10.1001/jamainternmed.2021.4813.