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Early PCSK9 inhibition in AMI yields plaque regression
When the PCSK9 inhibitor alirocumab is added to high-intensity statins soon after an acute myocardial infarction (AMI), the reduction in atheroma volume is doubled at 12 months, compared with placebo, while other key signs of plaque stabilization, such as fibrous cap thickness, are also significantly and substantially improved, according to the results of the PACMAN-AMI trial.
The study is consistent with other PCSK9 inhibitor trials, supporting the concept that “we should be seeking very low levels of LDL-C in high-risk patients,” reported Lorenz Räber, MD, PhD, of Bern (Switz.) University Hospital, at the annual scientific sessions of the American College of Cardiology.
The low LCL-C target, the data from PACMAN-AMI suggest, is below 50 mg/dL, but even lower is better. When displayed graphically, the improvements in remodeling characteristics “get very steep” as levels descend below a 50 mg/dL threshold, Dr. Räber reported. This was true regardless of study arm.
In PACMAN-AMI, 300 AMI patients (with either ST-elevation or non-ST-elevaion) were randomized to 150 mg alirocumab or placebo administered by subcutaneous injection within 24 hours after an urgent percutaneous intervention (PCI) and stent placement. All patients received their assigned therapy on top of a high-intensity statin in the form of 20 mg of rosuvastatin daily.
Primary outcome was atheroma volume
The primary endpoint was atheroma volume as determined by intravenous ultrasound (IVUS), but the secondary endpoints of maximum lipid core burden, as determined by near infrared spectroscopy (NIRS), and fibrous cap thickness, as determined by optical coherence tomography (OCT), were also adequately powered, according to Dr. Räber.
The imaging measures taken at baseline were repeated in exactly the same spot after 52 weeks on treatment.
For the primary outcome of atheroma volume, the mean 2.1% reduction among those randomized to alirocumab was more than double the 0.9% reduction in the placebo group (P = .001).
The mean reduction in lipid core volume based on a maximum lipid core burden index was also more than doubled (-79.42 vs. -37.60 maxLCBI4mm; P = .006). The increase in fibrous cap thickness was not quite twofold greater but very close (62.67 vs. 33.19 mcm; P = .001).
From baseline, the relative reductions in LDL-C, which were reached about 4 weeks after starting treatment and maintained over the course of the study, were greater in the group randomized to alirocumab (-84.8% vs. -50.7%). This was expected, but the more important finding was a near linear relationship between reductions of LDL-C and each of these endpoints regardless of treatment, fully explaining the advantage of alirocumab, according to Dr. Räber.
For the addition of alirocumab, “these findings indicate incremental coronary plaque regression, lipid core reduction, and plaque stabilization, and provide a mechanistic rationale in favor of early initiation of very intensive LDL-C lower in the setting of an acute MI,” he said.
The results of the PACMAN-AMI trial were published simultaneously at the time of the ACC presentation.
Results consistent with earlier trials
Alirocumab was well tolerated. Injection site reactions (6.1% vs. 3.3%) and general allergic reactions (3.4% vs. 0%) were more common on alirocumab, but there were no significant differences between the arms of this study for serious adverse events. There were slightly more neurocognitive events (2.0 vs. 0%) and abnormal alanine transferase levels (0.7% vs. 0%) in the alirocumab group.
The data are generally consistent with two previously published trials with another PCSK9 inhibitor, according to Dr. Räber. In the randomized GLAGOV trial published more than 5 years ago, evolocumab also produced about a 1% absolute reduction (P < .001) in plaque volume at the end of 78 weeks of follow-up relative to placebo.
However, that trial was limited to patients with coronary artery disease without a recent cardiovascular event. The more recent HUYGENS trial, which was presented virtually at the 2021 annual meeting of the European Society of Cardiology meeting and has not yet been published, looked at one of the endpoints also evaluated in PACMAN-AMI. In that study of 161 randomized NSTEMI patients, there was also about a doubling of fibrous cap thickness (42.7 vs. 21.5 mcm) for the PCSK9 inhibitor relative to placebo.
Clinical endpoints were not compared in either the PACMAN-AMI or HUYGENS trial.
PACMAN-AMI confirms plaque stabilization
Nevertheless, the message of plaque stabilization is important, according to Anthony N. DeMaria, MD, Founding Director of the Sulpizio Cardiovascular Center at the University of San Diego. Although he acknowledged that a 1% absolute reduction in mean plaque volume might “make you want to yawn,” he argued that this is a misreading of important changes observed in plaque physiology.
“What we have now is evidence that very low lipid levels result in plaque remodeling. The plaques might not get a whole lot smaller, but the changes are important,” he said, noting, for example, that a thicker fibrous cap and increased plaque stability “clearly plays a role in reducing risk of subsequent events.”
“You cannot help but be impressed by the relationship of lipid lowering and the favorable effect on remodeling,” he added.
The data associating PCSK9 inhibitors with protection from cardiovascular events is already extensive, according to Michael J. Blaha, MD, Director of Clinical Research for Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University, Baltimore, but he called PACMAN-ACS “an extremely relevant study.”
“This provides more evidence of the mechanism of benefit, which I think is extremely important when talking to patients about the goals of therapy,” he said.
PACMAN-AMI provided a very simple take home message for Pamela B. Morris, MD, Director of Preventive Cardiology, Medical University of South Carolina, Charleston.
“This study shows that if you get LCL-C under 50 mg/dL regardless of treatment, there is a favorable remodeling effect,” Dr. Morris said. In AMI patients, the data confirm “go early and go low,” she added. “You should do whatever is necessary [go get to these lower targets].”
Dr. Räber has financial relationships with Abbott, Amgen, AstraZeneca, Boston Scientific, Biotronik, Canon, Heartflow, Medtronic, Occlutech, Regeneron, Sanofi, and Vifor. Dr. Blaha reports financial relationships with Akcea, Amgen, Bayer, Inozyme, Kaleido, Kowa, Medimmune, Novartis, Novo Nordisk, Regeneron, Roche, Sanofi, Siemens, and 89Bio. Dr. DeMaria reports no potential conflicts of interest. Dr. Morris reports a financial relationship with Amgen. The investigator-initiated trial received research grants from Infraredx, Regeneron, and Sanofi.
When the PCSK9 inhibitor alirocumab is added to high-intensity statins soon after an acute myocardial infarction (AMI), the reduction in atheroma volume is doubled at 12 months, compared with placebo, while other key signs of plaque stabilization, such as fibrous cap thickness, are also significantly and substantially improved, according to the results of the PACMAN-AMI trial.
The study is consistent with other PCSK9 inhibitor trials, supporting the concept that “we should be seeking very low levels of LDL-C in high-risk patients,” reported Lorenz Räber, MD, PhD, of Bern (Switz.) University Hospital, at the annual scientific sessions of the American College of Cardiology.
The low LCL-C target, the data from PACMAN-AMI suggest, is below 50 mg/dL, but even lower is better. When displayed graphically, the improvements in remodeling characteristics “get very steep” as levels descend below a 50 mg/dL threshold, Dr. Räber reported. This was true regardless of study arm.
In PACMAN-AMI, 300 AMI patients (with either ST-elevation or non-ST-elevaion) were randomized to 150 mg alirocumab or placebo administered by subcutaneous injection within 24 hours after an urgent percutaneous intervention (PCI) and stent placement. All patients received their assigned therapy on top of a high-intensity statin in the form of 20 mg of rosuvastatin daily.
Primary outcome was atheroma volume
The primary endpoint was atheroma volume as determined by intravenous ultrasound (IVUS), but the secondary endpoints of maximum lipid core burden, as determined by near infrared spectroscopy (NIRS), and fibrous cap thickness, as determined by optical coherence tomography (OCT), were also adequately powered, according to Dr. Räber.
The imaging measures taken at baseline were repeated in exactly the same spot after 52 weeks on treatment.
For the primary outcome of atheroma volume, the mean 2.1% reduction among those randomized to alirocumab was more than double the 0.9% reduction in the placebo group (P = .001).
The mean reduction in lipid core volume based on a maximum lipid core burden index was also more than doubled (-79.42 vs. -37.60 maxLCBI4mm; P = .006). The increase in fibrous cap thickness was not quite twofold greater but very close (62.67 vs. 33.19 mcm; P = .001).
From baseline, the relative reductions in LDL-C, which were reached about 4 weeks after starting treatment and maintained over the course of the study, were greater in the group randomized to alirocumab (-84.8% vs. -50.7%). This was expected, but the more important finding was a near linear relationship between reductions of LDL-C and each of these endpoints regardless of treatment, fully explaining the advantage of alirocumab, according to Dr. Räber.
For the addition of alirocumab, “these findings indicate incremental coronary plaque regression, lipid core reduction, and plaque stabilization, and provide a mechanistic rationale in favor of early initiation of very intensive LDL-C lower in the setting of an acute MI,” he said.
The results of the PACMAN-AMI trial were published simultaneously at the time of the ACC presentation.
Results consistent with earlier trials
Alirocumab was well tolerated. Injection site reactions (6.1% vs. 3.3%) and general allergic reactions (3.4% vs. 0%) were more common on alirocumab, but there were no significant differences between the arms of this study for serious adverse events. There were slightly more neurocognitive events (2.0 vs. 0%) and abnormal alanine transferase levels (0.7% vs. 0%) in the alirocumab group.
The data are generally consistent with two previously published trials with another PCSK9 inhibitor, according to Dr. Räber. In the randomized GLAGOV trial published more than 5 years ago, evolocumab also produced about a 1% absolute reduction (P < .001) in plaque volume at the end of 78 weeks of follow-up relative to placebo.
However, that trial was limited to patients with coronary artery disease without a recent cardiovascular event. The more recent HUYGENS trial, which was presented virtually at the 2021 annual meeting of the European Society of Cardiology meeting and has not yet been published, looked at one of the endpoints also evaluated in PACMAN-AMI. In that study of 161 randomized NSTEMI patients, there was also about a doubling of fibrous cap thickness (42.7 vs. 21.5 mcm) for the PCSK9 inhibitor relative to placebo.
Clinical endpoints were not compared in either the PACMAN-AMI or HUYGENS trial.
PACMAN-AMI confirms plaque stabilization
Nevertheless, the message of plaque stabilization is important, according to Anthony N. DeMaria, MD, Founding Director of the Sulpizio Cardiovascular Center at the University of San Diego. Although he acknowledged that a 1% absolute reduction in mean plaque volume might “make you want to yawn,” he argued that this is a misreading of important changes observed in plaque physiology.
“What we have now is evidence that very low lipid levels result in plaque remodeling. The plaques might not get a whole lot smaller, but the changes are important,” he said, noting, for example, that a thicker fibrous cap and increased plaque stability “clearly plays a role in reducing risk of subsequent events.”
“You cannot help but be impressed by the relationship of lipid lowering and the favorable effect on remodeling,” he added.
The data associating PCSK9 inhibitors with protection from cardiovascular events is already extensive, according to Michael J. Blaha, MD, Director of Clinical Research for Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University, Baltimore, but he called PACMAN-ACS “an extremely relevant study.”
“This provides more evidence of the mechanism of benefit, which I think is extremely important when talking to patients about the goals of therapy,” he said.
PACMAN-AMI provided a very simple take home message for Pamela B. Morris, MD, Director of Preventive Cardiology, Medical University of South Carolina, Charleston.
“This study shows that if you get LCL-C under 50 mg/dL regardless of treatment, there is a favorable remodeling effect,” Dr. Morris said. In AMI patients, the data confirm “go early and go low,” she added. “You should do whatever is necessary [go get to these lower targets].”
Dr. Räber has financial relationships with Abbott, Amgen, AstraZeneca, Boston Scientific, Biotronik, Canon, Heartflow, Medtronic, Occlutech, Regeneron, Sanofi, and Vifor. Dr. Blaha reports financial relationships with Akcea, Amgen, Bayer, Inozyme, Kaleido, Kowa, Medimmune, Novartis, Novo Nordisk, Regeneron, Roche, Sanofi, Siemens, and 89Bio. Dr. DeMaria reports no potential conflicts of interest. Dr. Morris reports a financial relationship with Amgen. The investigator-initiated trial received research grants from Infraredx, Regeneron, and Sanofi.
When the PCSK9 inhibitor alirocumab is added to high-intensity statins soon after an acute myocardial infarction (AMI), the reduction in atheroma volume is doubled at 12 months, compared with placebo, while other key signs of plaque stabilization, such as fibrous cap thickness, are also significantly and substantially improved, according to the results of the PACMAN-AMI trial.
The study is consistent with other PCSK9 inhibitor trials, supporting the concept that “we should be seeking very low levels of LDL-C in high-risk patients,” reported Lorenz Räber, MD, PhD, of Bern (Switz.) University Hospital, at the annual scientific sessions of the American College of Cardiology.
The low LCL-C target, the data from PACMAN-AMI suggest, is below 50 mg/dL, but even lower is better. When displayed graphically, the improvements in remodeling characteristics “get very steep” as levels descend below a 50 mg/dL threshold, Dr. Räber reported. This was true regardless of study arm.
In PACMAN-AMI, 300 AMI patients (with either ST-elevation or non-ST-elevaion) were randomized to 150 mg alirocumab or placebo administered by subcutaneous injection within 24 hours after an urgent percutaneous intervention (PCI) and stent placement. All patients received their assigned therapy on top of a high-intensity statin in the form of 20 mg of rosuvastatin daily.
Primary outcome was atheroma volume
The primary endpoint was atheroma volume as determined by intravenous ultrasound (IVUS), but the secondary endpoints of maximum lipid core burden, as determined by near infrared spectroscopy (NIRS), and fibrous cap thickness, as determined by optical coherence tomography (OCT), were also adequately powered, according to Dr. Räber.
The imaging measures taken at baseline were repeated in exactly the same spot after 52 weeks on treatment.
For the primary outcome of atheroma volume, the mean 2.1% reduction among those randomized to alirocumab was more than double the 0.9% reduction in the placebo group (P = .001).
The mean reduction in lipid core volume based on a maximum lipid core burden index was also more than doubled (-79.42 vs. -37.60 maxLCBI4mm; P = .006). The increase in fibrous cap thickness was not quite twofold greater but very close (62.67 vs. 33.19 mcm; P = .001).
From baseline, the relative reductions in LDL-C, which were reached about 4 weeks after starting treatment and maintained over the course of the study, were greater in the group randomized to alirocumab (-84.8% vs. -50.7%). This was expected, but the more important finding was a near linear relationship between reductions of LDL-C and each of these endpoints regardless of treatment, fully explaining the advantage of alirocumab, according to Dr. Räber.
For the addition of alirocumab, “these findings indicate incremental coronary plaque regression, lipid core reduction, and plaque stabilization, and provide a mechanistic rationale in favor of early initiation of very intensive LDL-C lower in the setting of an acute MI,” he said.
The results of the PACMAN-AMI trial were published simultaneously at the time of the ACC presentation.
Results consistent with earlier trials
Alirocumab was well tolerated. Injection site reactions (6.1% vs. 3.3%) and general allergic reactions (3.4% vs. 0%) were more common on alirocumab, but there were no significant differences between the arms of this study for serious adverse events. There were slightly more neurocognitive events (2.0 vs. 0%) and abnormal alanine transferase levels (0.7% vs. 0%) in the alirocumab group.
The data are generally consistent with two previously published trials with another PCSK9 inhibitor, according to Dr. Räber. In the randomized GLAGOV trial published more than 5 years ago, evolocumab also produced about a 1% absolute reduction (P < .001) in plaque volume at the end of 78 weeks of follow-up relative to placebo.
However, that trial was limited to patients with coronary artery disease without a recent cardiovascular event. The more recent HUYGENS trial, which was presented virtually at the 2021 annual meeting of the European Society of Cardiology meeting and has not yet been published, looked at one of the endpoints also evaluated in PACMAN-AMI. In that study of 161 randomized NSTEMI patients, there was also about a doubling of fibrous cap thickness (42.7 vs. 21.5 mcm) for the PCSK9 inhibitor relative to placebo.
Clinical endpoints were not compared in either the PACMAN-AMI or HUYGENS trial.
PACMAN-AMI confirms plaque stabilization
Nevertheless, the message of plaque stabilization is important, according to Anthony N. DeMaria, MD, Founding Director of the Sulpizio Cardiovascular Center at the University of San Diego. Although he acknowledged that a 1% absolute reduction in mean plaque volume might “make you want to yawn,” he argued that this is a misreading of important changes observed in plaque physiology.
“What we have now is evidence that very low lipid levels result in plaque remodeling. The plaques might not get a whole lot smaller, but the changes are important,” he said, noting, for example, that a thicker fibrous cap and increased plaque stability “clearly plays a role in reducing risk of subsequent events.”
“You cannot help but be impressed by the relationship of lipid lowering and the favorable effect on remodeling,” he added.
The data associating PCSK9 inhibitors with protection from cardiovascular events is already extensive, according to Michael J. Blaha, MD, Director of Clinical Research for Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University, Baltimore, but he called PACMAN-ACS “an extremely relevant study.”
“This provides more evidence of the mechanism of benefit, which I think is extremely important when talking to patients about the goals of therapy,” he said.
PACMAN-AMI provided a very simple take home message for Pamela B. Morris, MD, Director of Preventive Cardiology, Medical University of South Carolina, Charleston.
“This study shows that if you get LCL-C under 50 mg/dL regardless of treatment, there is a favorable remodeling effect,” Dr. Morris said. In AMI patients, the data confirm “go early and go low,” she added. “You should do whatever is necessary [go get to these lower targets].”
Dr. Räber has financial relationships with Abbott, Amgen, AstraZeneca, Boston Scientific, Biotronik, Canon, Heartflow, Medtronic, Occlutech, Regeneron, Sanofi, and Vifor. Dr. Blaha reports financial relationships with Akcea, Amgen, Bayer, Inozyme, Kaleido, Kowa, Medimmune, Novartis, Novo Nordisk, Regeneron, Roche, Sanofi, Siemens, and 89Bio. Dr. DeMaria reports no potential conflicts of interest. Dr. Morris reports a financial relationship with Amgen. The investigator-initiated trial received research grants from Infraredx, Regeneron, and Sanofi.
FROM ACC 2022
FDA approves leadless, single-chamber pacemaker system
The Food and Drug Administration has granted approval to Abbott’s Aveir leadless, single-chamber pacemaker system for patients with bradycardia.
In a press release, Abbott said the device has a unique mapping capability that allows interventionists implanting the device to measure electrical signals within the heart to determine the correct placement before final implantation. Aveir is implanted directly into the right ventricle via a catheter.
The company also said Aveir has a battery life that’s up to twice as long as other commercially available leadless pacemakers when following International Association for Standardization (ISO) standard settings. And the device can be retrieved if necessary, the press release said.
“Leadless pacemakers address known complications associated with traditional pacemakers,” Rahul Doshi, MD, director of electrophysiology at Honor Health in Scottsdale, Ariz., said in the press release. “In addition, the Aveir leadless pacemaker brings unique innovations we’ve been seeking, such as the ability to ensure electrical performance before we commit to placement.”
Investigators of the LEADLESS II phase 2 study reported last year on what they called “key design improvements” of the Aveir device compared to the first leadless pacemaker, the discontinued Nanostim. They included a 12% longer battery life, a shorter and wider form factor, a modified docking button that allows for retrievability, a modified delivery system, and an application-specific integrated circuit chip that can support a dual-chamber pacing system in the future.
The study reported that 96% of the 200 enrolled patients met the primary safety endpoint of no serious device-related adverse events at 6 weeks after implantation. A similar percentage achieved therapeutic pacing and sensing amplitude.
The study also reported that interventionists accurately positioned Aveir the first time or with a single repositioning in 96% of cases.
The Food and Drug Administration has granted approval to Abbott’s Aveir leadless, single-chamber pacemaker system for patients with bradycardia.
In a press release, Abbott said the device has a unique mapping capability that allows interventionists implanting the device to measure electrical signals within the heart to determine the correct placement before final implantation. Aveir is implanted directly into the right ventricle via a catheter.
The company also said Aveir has a battery life that’s up to twice as long as other commercially available leadless pacemakers when following International Association for Standardization (ISO) standard settings. And the device can be retrieved if necessary, the press release said.
“Leadless pacemakers address known complications associated with traditional pacemakers,” Rahul Doshi, MD, director of electrophysiology at Honor Health in Scottsdale, Ariz., said in the press release. “In addition, the Aveir leadless pacemaker brings unique innovations we’ve been seeking, such as the ability to ensure electrical performance before we commit to placement.”
Investigators of the LEADLESS II phase 2 study reported last year on what they called “key design improvements” of the Aveir device compared to the first leadless pacemaker, the discontinued Nanostim. They included a 12% longer battery life, a shorter and wider form factor, a modified docking button that allows for retrievability, a modified delivery system, and an application-specific integrated circuit chip that can support a dual-chamber pacing system in the future.
The study reported that 96% of the 200 enrolled patients met the primary safety endpoint of no serious device-related adverse events at 6 weeks after implantation. A similar percentage achieved therapeutic pacing and sensing amplitude.
The study also reported that interventionists accurately positioned Aveir the first time or with a single repositioning in 96% of cases.
The Food and Drug Administration has granted approval to Abbott’s Aveir leadless, single-chamber pacemaker system for patients with bradycardia.
In a press release, Abbott said the device has a unique mapping capability that allows interventionists implanting the device to measure electrical signals within the heart to determine the correct placement before final implantation. Aveir is implanted directly into the right ventricle via a catheter.
The company also said Aveir has a battery life that’s up to twice as long as other commercially available leadless pacemakers when following International Association for Standardization (ISO) standard settings. And the device can be retrieved if necessary, the press release said.
“Leadless pacemakers address known complications associated with traditional pacemakers,” Rahul Doshi, MD, director of electrophysiology at Honor Health in Scottsdale, Ariz., said in the press release. “In addition, the Aveir leadless pacemaker brings unique innovations we’ve been seeking, such as the ability to ensure electrical performance before we commit to placement.”
Investigators of the LEADLESS II phase 2 study reported last year on what they called “key design improvements” of the Aveir device compared to the first leadless pacemaker, the discontinued Nanostim. They included a 12% longer battery life, a shorter and wider form factor, a modified docking button that allows for retrievability, a modified delivery system, and an application-specific integrated circuit chip that can support a dual-chamber pacing system in the future.
The study reported that 96% of the 200 enrolled patients met the primary safety endpoint of no serious device-related adverse events at 6 weeks after implantation. A similar percentage achieved therapeutic pacing and sensing amplitude.
The study also reported that interventionists accurately positioned Aveir the first time or with a single repositioning in 96% of cases.
More evidence that COVID ‘brain fog’ is biologically based
Researchers found elevated levels of CSF immune activation and immunovascular markers in individuals with cognitive postacute sequelae of SARS-CoV-2 infection (PASC). Patients whose cognitive symptoms developed during the acute phase of COVID-19 had the highest levels of brain inflammation.
The findings add to a growing body of evidence that suggests the condition often referred to as “brain fog” has a neurologic basis, said lead author Joanna Hellmuth, MD, MHS, assistant professor of neurology at the University of California, San Francisco Weill Institute of Neurosciences and the UCSF Memory and Aging Center.
The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
Inflammatory response
There are no effective diagnostic tests or treatments for cognitive PASC, which prompted the investigators to study inflammation in patients with the condition. Initial findings were reported earlier in 2022, which showed abnormalities in the CSF in 77% of patients with cognitive impairment. Patients without cognitive impairments had normal CSF.
Extending that work in this new study, researchers studied patients from the Long-term Impact of Infection With Novel Coronavirus (LIINC) study with confirmed SARS-CoV-2 infection who were not hospitalized. They conducted 2-hour neurocognitive interviews and identified 23 people with new, persistent cognitive symptoms (cognitive PASC) and 10 with no cognitive symptoms who served as controls.
All participants underwent additional neurologic examination and neuropsychological testing, and half agreed to a lumbar puncture to allow researchers to collect CSF samples. The CSF was collected a median of 10.2 months after initial COVID symptoms began.
Participants with cognitive PASC had higher median levels of CSF acute phase reactants C-reactive protein (0.007 mg/L vs. 0.000 mg/L; P =.004) and serum amyloid A (0.001 mg/L vs. 0.000 mg/L; P = .001), compared with COVID controls.
The PASC group also had elevated levels of CSF immune activation markers interferon gamma–inducible protein (IP-10), interleukin-8, and immunovascular markers vascular endothelial growth factor-C and VEGFR-1, although the differences with the control group were not statistically significant.
The timing of the onset of cognitive problems was also associated with higher levels of immune activation and immunovascular markers. Patients with brain fog that developed during the acute phase of COVID-19 had higher levels of CSF VEGF-C, compared with patients whose cognitive symptoms developed more than a month after initial COVID symptoms (173 pg/mL vs. 99 pg/mL; P = .048) and COVID controls (79 pg/mL; P = .048).
Acute onset cognitive PASC participants had higher CSF levels of IP-10 (P = .030), IL-8 (P = .048), placental growth factor (P = .030) and intercellular adhesion molecule-1 (P = .045), compared with COVID controls.
Researchers believe these new findings could mean that intrathecal immune activation and endothelial activation/dysfunction may contribute to cognitive PASC and that the mechanisms involved may be different in patients with acute cognitive PASC versus those with delayed onset.
“Our data suggests that perhaps in these people with more acute cognitive changes they don’t have the return to homeostasis,” Dr. Hellmuth said, while patients with delayed onset cognitive PASC had levels more in line with COVID patients who had no cognitive issues.
Moving the needle forward
Commenting on the findings, William Schaffner, MD, professor of infectious diseases, Vanderbilt University Medical Center, Nashville, Tenn., said that, while the study doesn’t rule out a possible psychological basis for cognitive PASC, it adds more weight to the biological argument.
“When you have nonspecific symptoms for which specific tests are unavailable,” Dr. Schaffner explained, “there is a natural question that always comes up: Is this principally a biologically induced phenomenon or psychological? This moves the needle substantially in the direction of a biological phenomenon.”
Another important element to the study, Dr. Schaffner said, is that the patients involved had mild COVID.
“Not every patient with long COVID symptoms had been hospitalized with severe disease,” he said. “There are inflammatory phenomenon in various organ systems such that even if the inflammatory response in the lung was not severe enough to get you into the hospital, there were inflammatory responses in other organ systems that could persist once the acute infection resolved.”
Although the small size of the study is a limitation, Dr. Schaffner said that shouldn’t minimize the importance of these findings.
“That it’s small doesn’t diminish its value,” he said. “The next step forward might be to try to associate the markers more specifically with COVID. The more precise we can be, the more convincing the story will become.”
The study was funded by the National Institutes of Health. Dr. Hellmuth received grant support from the National Institutes of Health/National Institute of Mental Health supporting this work and personal fees for medical-legal consultation outside of the submitted work. Dr. Schaffner disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Researchers found elevated levels of CSF immune activation and immunovascular markers in individuals with cognitive postacute sequelae of SARS-CoV-2 infection (PASC). Patients whose cognitive symptoms developed during the acute phase of COVID-19 had the highest levels of brain inflammation.
The findings add to a growing body of evidence that suggests the condition often referred to as “brain fog” has a neurologic basis, said lead author Joanna Hellmuth, MD, MHS, assistant professor of neurology at the University of California, San Francisco Weill Institute of Neurosciences and the UCSF Memory and Aging Center.
The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
Inflammatory response
There are no effective diagnostic tests or treatments for cognitive PASC, which prompted the investigators to study inflammation in patients with the condition. Initial findings were reported earlier in 2022, which showed abnormalities in the CSF in 77% of patients with cognitive impairment. Patients without cognitive impairments had normal CSF.
Extending that work in this new study, researchers studied patients from the Long-term Impact of Infection With Novel Coronavirus (LIINC) study with confirmed SARS-CoV-2 infection who were not hospitalized. They conducted 2-hour neurocognitive interviews and identified 23 people with new, persistent cognitive symptoms (cognitive PASC) and 10 with no cognitive symptoms who served as controls.
All participants underwent additional neurologic examination and neuropsychological testing, and half agreed to a lumbar puncture to allow researchers to collect CSF samples. The CSF was collected a median of 10.2 months after initial COVID symptoms began.
Participants with cognitive PASC had higher median levels of CSF acute phase reactants C-reactive protein (0.007 mg/L vs. 0.000 mg/L; P =.004) and serum amyloid A (0.001 mg/L vs. 0.000 mg/L; P = .001), compared with COVID controls.
The PASC group also had elevated levels of CSF immune activation markers interferon gamma–inducible protein (IP-10), interleukin-8, and immunovascular markers vascular endothelial growth factor-C and VEGFR-1, although the differences with the control group were not statistically significant.
The timing of the onset of cognitive problems was also associated with higher levels of immune activation and immunovascular markers. Patients with brain fog that developed during the acute phase of COVID-19 had higher levels of CSF VEGF-C, compared with patients whose cognitive symptoms developed more than a month after initial COVID symptoms (173 pg/mL vs. 99 pg/mL; P = .048) and COVID controls (79 pg/mL; P = .048).
Acute onset cognitive PASC participants had higher CSF levels of IP-10 (P = .030), IL-8 (P = .048), placental growth factor (P = .030) and intercellular adhesion molecule-1 (P = .045), compared with COVID controls.
Researchers believe these new findings could mean that intrathecal immune activation and endothelial activation/dysfunction may contribute to cognitive PASC and that the mechanisms involved may be different in patients with acute cognitive PASC versus those with delayed onset.
“Our data suggests that perhaps in these people with more acute cognitive changes they don’t have the return to homeostasis,” Dr. Hellmuth said, while patients with delayed onset cognitive PASC had levels more in line with COVID patients who had no cognitive issues.
Moving the needle forward
Commenting on the findings, William Schaffner, MD, professor of infectious diseases, Vanderbilt University Medical Center, Nashville, Tenn., said that, while the study doesn’t rule out a possible psychological basis for cognitive PASC, it adds more weight to the biological argument.
“When you have nonspecific symptoms for which specific tests are unavailable,” Dr. Schaffner explained, “there is a natural question that always comes up: Is this principally a biologically induced phenomenon or psychological? This moves the needle substantially in the direction of a biological phenomenon.”
Another important element to the study, Dr. Schaffner said, is that the patients involved had mild COVID.
“Not every patient with long COVID symptoms had been hospitalized with severe disease,” he said. “There are inflammatory phenomenon in various organ systems such that even if the inflammatory response in the lung was not severe enough to get you into the hospital, there were inflammatory responses in other organ systems that could persist once the acute infection resolved.”
Although the small size of the study is a limitation, Dr. Schaffner said that shouldn’t minimize the importance of these findings.
“That it’s small doesn’t diminish its value,” he said. “The next step forward might be to try to associate the markers more specifically with COVID. The more precise we can be, the more convincing the story will become.”
The study was funded by the National Institutes of Health. Dr. Hellmuth received grant support from the National Institutes of Health/National Institute of Mental Health supporting this work and personal fees for medical-legal consultation outside of the submitted work. Dr. Schaffner disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Researchers found elevated levels of CSF immune activation and immunovascular markers in individuals with cognitive postacute sequelae of SARS-CoV-2 infection (PASC). Patients whose cognitive symptoms developed during the acute phase of COVID-19 had the highest levels of brain inflammation.
The findings add to a growing body of evidence that suggests the condition often referred to as “brain fog” has a neurologic basis, said lead author Joanna Hellmuth, MD, MHS, assistant professor of neurology at the University of California, San Francisco Weill Institute of Neurosciences and the UCSF Memory and Aging Center.
The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
Inflammatory response
There are no effective diagnostic tests or treatments for cognitive PASC, which prompted the investigators to study inflammation in patients with the condition. Initial findings were reported earlier in 2022, which showed abnormalities in the CSF in 77% of patients with cognitive impairment. Patients without cognitive impairments had normal CSF.
Extending that work in this new study, researchers studied patients from the Long-term Impact of Infection With Novel Coronavirus (LIINC) study with confirmed SARS-CoV-2 infection who were not hospitalized. They conducted 2-hour neurocognitive interviews and identified 23 people with new, persistent cognitive symptoms (cognitive PASC) and 10 with no cognitive symptoms who served as controls.
All participants underwent additional neurologic examination and neuropsychological testing, and half agreed to a lumbar puncture to allow researchers to collect CSF samples. The CSF was collected a median of 10.2 months after initial COVID symptoms began.
Participants with cognitive PASC had higher median levels of CSF acute phase reactants C-reactive protein (0.007 mg/L vs. 0.000 mg/L; P =.004) and serum amyloid A (0.001 mg/L vs. 0.000 mg/L; P = .001), compared with COVID controls.
The PASC group also had elevated levels of CSF immune activation markers interferon gamma–inducible protein (IP-10), interleukin-8, and immunovascular markers vascular endothelial growth factor-C and VEGFR-1, although the differences with the control group were not statistically significant.
The timing of the onset of cognitive problems was also associated with higher levels of immune activation and immunovascular markers. Patients with brain fog that developed during the acute phase of COVID-19 had higher levels of CSF VEGF-C, compared with patients whose cognitive symptoms developed more than a month after initial COVID symptoms (173 pg/mL vs. 99 pg/mL; P = .048) and COVID controls (79 pg/mL; P = .048).
Acute onset cognitive PASC participants had higher CSF levels of IP-10 (P = .030), IL-8 (P = .048), placental growth factor (P = .030) and intercellular adhesion molecule-1 (P = .045), compared with COVID controls.
Researchers believe these new findings could mean that intrathecal immune activation and endothelial activation/dysfunction may contribute to cognitive PASC and that the mechanisms involved may be different in patients with acute cognitive PASC versus those with delayed onset.
“Our data suggests that perhaps in these people with more acute cognitive changes they don’t have the return to homeostasis,” Dr. Hellmuth said, while patients with delayed onset cognitive PASC had levels more in line with COVID patients who had no cognitive issues.
Moving the needle forward
Commenting on the findings, William Schaffner, MD, professor of infectious diseases, Vanderbilt University Medical Center, Nashville, Tenn., said that, while the study doesn’t rule out a possible psychological basis for cognitive PASC, it adds more weight to the biological argument.
“When you have nonspecific symptoms for which specific tests are unavailable,” Dr. Schaffner explained, “there is a natural question that always comes up: Is this principally a biologically induced phenomenon or psychological? This moves the needle substantially in the direction of a biological phenomenon.”
Another important element to the study, Dr. Schaffner said, is that the patients involved had mild COVID.
“Not every patient with long COVID symptoms had been hospitalized with severe disease,” he said. “There are inflammatory phenomenon in various organ systems such that even if the inflammatory response in the lung was not severe enough to get you into the hospital, there were inflammatory responses in other organ systems that could persist once the acute infection resolved.”
Although the small size of the study is a limitation, Dr. Schaffner said that shouldn’t minimize the importance of these findings.
“That it’s small doesn’t diminish its value,” he said. “The next step forward might be to try to associate the markers more specifically with COVID. The more precise we can be, the more convincing the story will become.”
The study was funded by the National Institutes of Health. Dr. Hellmuth received grant support from the National Institutes of Health/National Institute of Mental Health supporting this work and personal fees for medical-legal consultation outside of the submitted work. Dr. Schaffner disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAN 2022
Postmenopausal women may benefit from vaginal estradiol for treatment of symptoms
Vaginal estradiol tablets promoted significant changes in the vaginal microbiota in postmenopausal women compared with vaginal moisturizer or placebo, but reduction in bothersome symptoms were similar, based on data from 144 individuals.
“In the Menopause Strategies–Finding Lasting Answers and Health (MsFLASH) trial network’s Vaginal Health Trial of treatment for moderate to severe vaginal symptoms of menopause, there were no significant differences in reduction of vaginal symptoms among women using the estradiol vaginal tablet or vaginal moisturizer compared to women using the placebo regimen; all three groups had a reduction in vaginal symptoms,” lead author Sujatha Srinivasan, PhD, of the Fred Hutchinson Cancer Center, Seattle, said in an interview.
“However, the impact of these treatments on the vaginal microenvironment are poorly understood,” she said.
In a study published in JAMA Network Open, Dr. Srinivasan and colleagues conducted a secondary analysis to examine the effects of estradiol or a low-pH vaginal moisturizer on the vaginal microbiota, metabolome, and pH after 12 weeks of treatment vs. a low-pH placebo.
“Changes, or lack thereof, in the vaginal microenvironment might have implications beyond symptoms, and might be linked to risk for cervical cancer, genital infections, or other outcomes, though our study did not evaluate those associations,” Dr. Srinivasan said in an interview. Dr. Srinivasan’s comments were corroborated by coauthor Caroline M. Mitchell, MD, of Massachusetts General Hospital, Boston.
The study population included postmenopausal women with moderate to severe genitourinary symptoms who were enrolled in a randomized, controlled trial between April 2016 and February 2017. The average age of the women was 61 years, and 90% were White. The women were randomized to 10 mcg vaginal estradiol plus placebo gel, placebo tablet plus vaginal moisturizer, or a dual placebo.
The primary outcome in the original study was a change in the reported most bothersome symptoms (MBS) selected by the participants at the time of study enrollment; these included pain with penetration, vaginal dryness, and vulvovaginal irritation, itching, and pain. The main outcomes in the secondary analysis were changes in the diversity and composition of the vaginal microbiota, changes in the metabolome, and pH. Microbiota diversity was calculated via the Shannon Diversity Index (SDI).
After 12 weeks, the bacterial microbiota were dominated by Lactobacillus and Bifidobacterium in 80% of the estradiol group, 36% of the moisturizer group, and 26% of the placebo group (P < .001).
In addition, diversity analysis showed significant changes in bacterial composition in women in the estradiol group compared with the placebo group, but no significant differences between the moisturizer and placebo groups.
The composition of vaginal fluid small molecule metabolites changed significantly in 90 of 171 metabolites measured in the estradiol group from baseline to 12 weeks. Changes in the moisturizer and placebo groups were not significant.
Vaginal pH among women in the estradiol group was significantly lower than placebo at 12 weeks, with a median of 5 vs. 6 (P = .005). No significant difference in pH occurred for women in the moisturizer group. “However, pH significantly decreased over 12 weeks within each treatment group, reflecting the low-pH formulations of both the moisturizer and the placebo,” the researchers wrote.
Overall, women with high-diversity bacterial communities at baseline showed a greater median change in pH compared with women with low-diversity communities (median change of −1 vs. −0.3, P = .007).
Improvement in MBS symptoms by at least 2 points occurred in 53% of the estradiol group, 44% of the moisturizer group, and 49% of the placebo group. The similarity in severe symptom improvement among the groups confirms the lack of a causal association between microbiota and postmenopausal vaginal symptom severity, the researchers wrote.
“This study demonstrated that a decrease in vaginal pH alone was insufficient to change the vaginal microbiota,” Dr. Srinivasan said. “While the changes with estrogen were somewhat expected, the observation that low-pH vaginal products don’t change the vaginal microbiota is contrary to some expectations, and suggests that “low-pH” products may not be as helpful as their marketing claims,” she added. “A vaginal microbiota with an abundance of lactobacilli, a vaginal microenvironment with high concentrations of lactate, and a low vaginal pH is associated with health in premenopausal women. We also know that such a microenvironment is typically associated with low inflammation,” said Dr. Srinivasan. “At this time, we don’t have specific information as to how this is beneficial to postmenopausal women,” she noted. However, “If we extrapolate from the data on premenopausal women, the data from this secondary analysis suggests that vaginal estradiol may have positive impacts on the vaginal microenvironment regardless of impact on symptoms,” she said.
“Future areas of investigation should focus on understanding potential benefits of a Lactobacillus-dominant microbiota in postmenopausal women,” Dr. Srinivasan said.
The study findings were limited by several factors including the relatively small number of participants, and collection of data samples at only three time periods, as well as the lack of data on whether the observed changes are durable over longer treatment times, the researchers noted.
“The need to increase participant diversity in studies of postmenopausal women is highlighted by our finding that the 6 Black women in our analysis were all categorized in the low-diversity subgroup; data from premenopausal women suggest that Black women have diverse bacterial communities,” they added.
However, the results suggest that “a significant decrease in pH over the course of a trial may not reflect the same underlying biological processes among different interventions, and thus, lowering pH should not be a primary goal,” they concluded.
Estradiol may have limited clinical impact
“For postmenopausal women with dyspareunia, vaginal dryness, and/or burning/itching/irritation, the question of appropriate treatment is common,” Constance Bohon, MD, a gynecologist in private practice in Washington, said in an interview. “It is helpful to have a study that focuses on the benefit of a moisturizer as compared with vaginal estrogen for these women,” she said.
Dr. Bohon said she was not surprised with the benefits of the moisturizer for dyspareunia and vaginal dryness. “What did surprise me was that the complaint of vaginal itch, burn, or irritation was not significantly improved in the vaginal estrogen group compared with the moisturizer group. I assumed that estrogen would have been more beneficial in this group because these symptoms are more likely to be caused by a vaginal infection that would not be improved with moisturizer alone,” she said. “I expected that the change in the vaginal flora to increase Lactobacillus would have had a greater impact on an infection than the moisturizer, which did not significantly change the flora.”
For clinicians, the take-home message is that, for these patients, use of a moisturizer may be sufficient, Dr. Bohon said.
“Additional research should be done to assess each issue,” she noted. “For example, in the women who have pain with sex, what is the frequency of intercourse?” she asked. Other research should address the questions of whether women who have intercourse at least once a week have less dyspareunia than those who have less frequent sex, and whether a lubricant decreases dyspareunia as well as a moisturizer or vaginal estrogen, she added.
The study was supported by the National Institutes of Health. Dr. Srinivasan disclosed personal fees from Lupin unrelated to the current study. Dr. Bohon had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.
Vaginal estradiol tablets promoted significant changes in the vaginal microbiota in postmenopausal women compared with vaginal moisturizer or placebo, but reduction in bothersome symptoms were similar, based on data from 144 individuals.
“In the Menopause Strategies–Finding Lasting Answers and Health (MsFLASH) trial network’s Vaginal Health Trial of treatment for moderate to severe vaginal symptoms of menopause, there were no significant differences in reduction of vaginal symptoms among women using the estradiol vaginal tablet or vaginal moisturizer compared to women using the placebo regimen; all three groups had a reduction in vaginal symptoms,” lead author Sujatha Srinivasan, PhD, of the Fred Hutchinson Cancer Center, Seattle, said in an interview.
“However, the impact of these treatments on the vaginal microenvironment are poorly understood,” she said.
In a study published in JAMA Network Open, Dr. Srinivasan and colleagues conducted a secondary analysis to examine the effects of estradiol or a low-pH vaginal moisturizer on the vaginal microbiota, metabolome, and pH after 12 weeks of treatment vs. a low-pH placebo.
“Changes, or lack thereof, in the vaginal microenvironment might have implications beyond symptoms, and might be linked to risk for cervical cancer, genital infections, or other outcomes, though our study did not evaluate those associations,” Dr. Srinivasan said in an interview. Dr. Srinivasan’s comments were corroborated by coauthor Caroline M. Mitchell, MD, of Massachusetts General Hospital, Boston.
The study population included postmenopausal women with moderate to severe genitourinary symptoms who were enrolled in a randomized, controlled trial between April 2016 and February 2017. The average age of the women was 61 years, and 90% were White. The women were randomized to 10 mcg vaginal estradiol plus placebo gel, placebo tablet plus vaginal moisturizer, or a dual placebo.
The primary outcome in the original study was a change in the reported most bothersome symptoms (MBS) selected by the participants at the time of study enrollment; these included pain with penetration, vaginal dryness, and vulvovaginal irritation, itching, and pain. The main outcomes in the secondary analysis were changes in the diversity and composition of the vaginal microbiota, changes in the metabolome, and pH. Microbiota diversity was calculated via the Shannon Diversity Index (SDI).
After 12 weeks, the bacterial microbiota were dominated by Lactobacillus and Bifidobacterium in 80% of the estradiol group, 36% of the moisturizer group, and 26% of the placebo group (P < .001).
In addition, diversity analysis showed significant changes in bacterial composition in women in the estradiol group compared with the placebo group, but no significant differences between the moisturizer and placebo groups.
The composition of vaginal fluid small molecule metabolites changed significantly in 90 of 171 metabolites measured in the estradiol group from baseline to 12 weeks. Changes in the moisturizer and placebo groups were not significant.
Vaginal pH among women in the estradiol group was significantly lower than placebo at 12 weeks, with a median of 5 vs. 6 (P = .005). No significant difference in pH occurred for women in the moisturizer group. “However, pH significantly decreased over 12 weeks within each treatment group, reflecting the low-pH formulations of both the moisturizer and the placebo,” the researchers wrote.
Overall, women with high-diversity bacterial communities at baseline showed a greater median change in pH compared with women with low-diversity communities (median change of −1 vs. −0.3, P = .007).
Improvement in MBS symptoms by at least 2 points occurred in 53% of the estradiol group, 44% of the moisturizer group, and 49% of the placebo group. The similarity in severe symptom improvement among the groups confirms the lack of a causal association between microbiota and postmenopausal vaginal symptom severity, the researchers wrote.
“This study demonstrated that a decrease in vaginal pH alone was insufficient to change the vaginal microbiota,” Dr. Srinivasan said. “While the changes with estrogen were somewhat expected, the observation that low-pH vaginal products don’t change the vaginal microbiota is contrary to some expectations, and suggests that “low-pH” products may not be as helpful as their marketing claims,” she added. “A vaginal microbiota with an abundance of lactobacilli, a vaginal microenvironment with high concentrations of lactate, and a low vaginal pH is associated with health in premenopausal women. We also know that such a microenvironment is typically associated with low inflammation,” said Dr. Srinivasan. “At this time, we don’t have specific information as to how this is beneficial to postmenopausal women,” she noted. However, “If we extrapolate from the data on premenopausal women, the data from this secondary analysis suggests that vaginal estradiol may have positive impacts on the vaginal microenvironment regardless of impact on symptoms,” she said.
“Future areas of investigation should focus on understanding potential benefits of a Lactobacillus-dominant microbiota in postmenopausal women,” Dr. Srinivasan said.
The study findings were limited by several factors including the relatively small number of participants, and collection of data samples at only three time periods, as well as the lack of data on whether the observed changes are durable over longer treatment times, the researchers noted.
“The need to increase participant diversity in studies of postmenopausal women is highlighted by our finding that the 6 Black women in our analysis were all categorized in the low-diversity subgroup; data from premenopausal women suggest that Black women have diverse bacterial communities,” they added.
However, the results suggest that “a significant decrease in pH over the course of a trial may not reflect the same underlying biological processes among different interventions, and thus, lowering pH should not be a primary goal,” they concluded.
Estradiol may have limited clinical impact
“For postmenopausal women with dyspareunia, vaginal dryness, and/or burning/itching/irritation, the question of appropriate treatment is common,” Constance Bohon, MD, a gynecologist in private practice in Washington, said in an interview. “It is helpful to have a study that focuses on the benefit of a moisturizer as compared with vaginal estrogen for these women,” she said.
Dr. Bohon said she was not surprised with the benefits of the moisturizer for dyspareunia and vaginal dryness. “What did surprise me was that the complaint of vaginal itch, burn, or irritation was not significantly improved in the vaginal estrogen group compared with the moisturizer group. I assumed that estrogen would have been more beneficial in this group because these symptoms are more likely to be caused by a vaginal infection that would not be improved with moisturizer alone,” she said. “I expected that the change in the vaginal flora to increase Lactobacillus would have had a greater impact on an infection than the moisturizer, which did not significantly change the flora.”
For clinicians, the take-home message is that, for these patients, use of a moisturizer may be sufficient, Dr. Bohon said.
“Additional research should be done to assess each issue,” she noted. “For example, in the women who have pain with sex, what is the frequency of intercourse?” she asked. Other research should address the questions of whether women who have intercourse at least once a week have less dyspareunia than those who have less frequent sex, and whether a lubricant decreases dyspareunia as well as a moisturizer or vaginal estrogen, she added.
The study was supported by the National Institutes of Health. Dr. Srinivasan disclosed personal fees from Lupin unrelated to the current study. Dr. Bohon had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.
Vaginal estradiol tablets promoted significant changes in the vaginal microbiota in postmenopausal women compared with vaginal moisturizer or placebo, but reduction in bothersome symptoms were similar, based on data from 144 individuals.
“In the Menopause Strategies–Finding Lasting Answers and Health (MsFLASH) trial network’s Vaginal Health Trial of treatment for moderate to severe vaginal symptoms of menopause, there were no significant differences in reduction of vaginal symptoms among women using the estradiol vaginal tablet or vaginal moisturizer compared to women using the placebo regimen; all three groups had a reduction in vaginal symptoms,” lead author Sujatha Srinivasan, PhD, of the Fred Hutchinson Cancer Center, Seattle, said in an interview.
“However, the impact of these treatments on the vaginal microenvironment are poorly understood,” she said.
In a study published in JAMA Network Open, Dr. Srinivasan and colleagues conducted a secondary analysis to examine the effects of estradiol or a low-pH vaginal moisturizer on the vaginal microbiota, metabolome, and pH after 12 weeks of treatment vs. a low-pH placebo.
“Changes, or lack thereof, in the vaginal microenvironment might have implications beyond symptoms, and might be linked to risk for cervical cancer, genital infections, or other outcomes, though our study did not evaluate those associations,” Dr. Srinivasan said in an interview. Dr. Srinivasan’s comments were corroborated by coauthor Caroline M. Mitchell, MD, of Massachusetts General Hospital, Boston.
The study population included postmenopausal women with moderate to severe genitourinary symptoms who were enrolled in a randomized, controlled trial between April 2016 and February 2017. The average age of the women was 61 years, and 90% were White. The women were randomized to 10 mcg vaginal estradiol plus placebo gel, placebo tablet plus vaginal moisturizer, or a dual placebo.
The primary outcome in the original study was a change in the reported most bothersome symptoms (MBS) selected by the participants at the time of study enrollment; these included pain with penetration, vaginal dryness, and vulvovaginal irritation, itching, and pain. The main outcomes in the secondary analysis were changes in the diversity and composition of the vaginal microbiota, changes in the metabolome, and pH. Microbiota diversity was calculated via the Shannon Diversity Index (SDI).
After 12 weeks, the bacterial microbiota were dominated by Lactobacillus and Bifidobacterium in 80% of the estradiol group, 36% of the moisturizer group, and 26% of the placebo group (P < .001).
In addition, diversity analysis showed significant changes in bacterial composition in women in the estradiol group compared with the placebo group, but no significant differences between the moisturizer and placebo groups.
The composition of vaginal fluid small molecule metabolites changed significantly in 90 of 171 metabolites measured in the estradiol group from baseline to 12 weeks. Changes in the moisturizer and placebo groups were not significant.
Vaginal pH among women in the estradiol group was significantly lower than placebo at 12 weeks, with a median of 5 vs. 6 (P = .005). No significant difference in pH occurred for women in the moisturizer group. “However, pH significantly decreased over 12 weeks within each treatment group, reflecting the low-pH formulations of both the moisturizer and the placebo,” the researchers wrote.
Overall, women with high-diversity bacterial communities at baseline showed a greater median change in pH compared with women with low-diversity communities (median change of −1 vs. −0.3, P = .007).
Improvement in MBS symptoms by at least 2 points occurred in 53% of the estradiol group, 44% of the moisturizer group, and 49% of the placebo group. The similarity in severe symptom improvement among the groups confirms the lack of a causal association between microbiota and postmenopausal vaginal symptom severity, the researchers wrote.
“This study demonstrated that a decrease in vaginal pH alone was insufficient to change the vaginal microbiota,” Dr. Srinivasan said. “While the changes with estrogen were somewhat expected, the observation that low-pH vaginal products don’t change the vaginal microbiota is contrary to some expectations, and suggests that “low-pH” products may not be as helpful as their marketing claims,” she added. “A vaginal microbiota with an abundance of lactobacilli, a vaginal microenvironment with high concentrations of lactate, and a low vaginal pH is associated with health in premenopausal women. We also know that such a microenvironment is typically associated with low inflammation,” said Dr. Srinivasan. “At this time, we don’t have specific information as to how this is beneficial to postmenopausal women,” she noted. However, “If we extrapolate from the data on premenopausal women, the data from this secondary analysis suggests that vaginal estradiol may have positive impacts on the vaginal microenvironment regardless of impact on symptoms,” she said.
“Future areas of investigation should focus on understanding potential benefits of a Lactobacillus-dominant microbiota in postmenopausal women,” Dr. Srinivasan said.
The study findings were limited by several factors including the relatively small number of participants, and collection of data samples at only three time periods, as well as the lack of data on whether the observed changes are durable over longer treatment times, the researchers noted.
“The need to increase participant diversity in studies of postmenopausal women is highlighted by our finding that the 6 Black women in our analysis were all categorized in the low-diversity subgroup; data from premenopausal women suggest that Black women have diverse bacterial communities,” they added.
However, the results suggest that “a significant decrease in pH over the course of a trial may not reflect the same underlying biological processes among different interventions, and thus, lowering pH should not be a primary goal,” they concluded.
Estradiol may have limited clinical impact
“For postmenopausal women with dyspareunia, vaginal dryness, and/or burning/itching/irritation, the question of appropriate treatment is common,” Constance Bohon, MD, a gynecologist in private practice in Washington, said in an interview. “It is helpful to have a study that focuses on the benefit of a moisturizer as compared with vaginal estrogen for these women,” she said.
Dr. Bohon said she was not surprised with the benefits of the moisturizer for dyspareunia and vaginal dryness. “What did surprise me was that the complaint of vaginal itch, burn, or irritation was not significantly improved in the vaginal estrogen group compared with the moisturizer group. I assumed that estrogen would have been more beneficial in this group because these symptoms are more likely to be caused by a vaginal infection that would not be improved with moisturizer alone,” she said. “I expected that the change in the vaginal flora to increase Lactobacillus would have had a greater impact on an infection than the moisturizer, which did not significantly change the flora.”
For clinicians, the take-home message is that, for these patients, use of a moisturizer may be sufficient, Dr. Bohon said.
“Additional research should be done to assess each issue,” she noted. “For example, in the women who have pain with sex, what is the frequency of intercourse?” she asked. Other research should address the questions of whether women who have intercourse at least once a week have less dyspareunia than those who have less frequent sex, and whether a lubricant decreases dyspareunia as well as a moisturizer or vaginal estrogen, she added.
The study was supported by the National Institutes of Health. Dr. Srinivasan disclosed personal fees from Lupin unrelated to the current study. Dr. Bohon had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.
FROM JAMA NETWORK OPEN
It’s a gimmick
March 30 was National Doctor’s Day, which resulted in my getting all kinds of generic emails from pharmaceutical reps, market research places, insurance companies, and the two hospitals I’m on staff at.
They all had similar meaningless platitudes thanking me for what I do, reassuring me that I’m appreciated, that I make the world a better place, yadda yadda yadda. The hospital even said I could swing by the medical staff office and pick up an “appreciation bag,” which I’m told contained a T-shirt, bottle of hand sanitizer, and a few other trinkets.
Spare me.
I’m not looking for any of that. In fact, I really don’t care.
Wishing me a “Happy Doctors Day” after spending the other 364 days denying my claims, refusing to cover tests or medications for my patients who need them (I don’t order these things for the hell of it, you know), telling me that I’m bringing down your Press Ganey scores, complaining about the copay that I have no control over, yelling at my staff for doing their jobs ... is pretty damn hollow.
It’s kind of like Mother’s Day: If you’re a jackass to your mom most of the year, sending her flowers on a Sunday in May doesn’t make it all right.
People also seem to forget that, in a small practice, my awesome staff is an extension of myself. Mistreating them, then wishing me a “Happy Doctor’s Day,” is also worthless.
I still like what I do. All the hassles from insurance companies, various administrators, the occasional angry patient … after all these years, they put a dent in it, but I still have no regrets about the course I’ve chosen. They can’t take away the happiness I get from helping those who need me.
It’s a job I love that’s allowed me to support my family and work with two wonderful staff members I’d never have met otherwise.
And that’s all I need.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
March 30 was National Doctor’s Day, which resulted in my getting all kinds of generic emails from pharmaceutical reps, market research places, insurance companies, and the two hospitals I’m on staff at.
They all had similar meaningless platitudes thanking me for what I do, reassuring me that I’m appreciated, that I make the world a better place, yadda yadda yadda. The hospital even said I could swing by the medical staff office and pick up an “appreciation bag,” which I’m told contained a T-shirt, bottle of hand sanitizer, and a few other trinkets.
Spare me.
I’m not looking for any of that. In fact, I really don’t care.
Wishing me a “Happy Doctors Day” after spending the other 364 days denying my claims, refusing to cover tests or medications for my patients who need them (I don’t order these things for the hell of it, you know), telling me that I’m bringing down your Press Ganey scores, complaining about the copay that I have no control over, yelling at my staff for doing their jobs ... is pretty damn hollow.
It’s kind of like Mother’s Day: If you’re a jackass to your mom most of the year, sending her flowers on a Sunday in May doesn’t make it all right.
People also seem to forget that, in a small practice, my awesome staff is an extension of myself. Mistreating them, then wishing me a “Happy Doctor’s Day,” is also worthless.
I still like what I do. All the hassles from insurance companies, various administrators, the occasional angry patient … after all these years, they put a dent in it, but I still have no regrets about the course I’ve chosen. They can’t take away the happiness I get from helping those who need me.
It’s a job I love that’s allowed me to support my family and work with two wonderful staff members I’d never have met otherwise.
And that’s all I need.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
March 30 was National Doctor’s Day, which resulted in my getting all kinds of generic emails from pharmaceutical reps, market research places, insurance companies, and the two hospitals I’m on staff at.
They all had similar meaningless platitudes thanking me for what I do, reassuring me that I’m appreciated, that I make the world a better place, yadda yadda yadda. The hospital even said I could swing by the medical staff office and pick up an “appreciation bag,” which I’m told contained a T-shirt, bottle of hand sanitizer, and a few other trinkets.
Spare me.
I’m not looking for any of that. In fact, I really don’t care.
Wishing me a “Happy Doctors Day” after spending the other 364 days denying my claims, refusing to cover tests or medications for my patients who need them (I don’t order these things for the hell of it, you know), telling me that I’m bringing down your Press Ganey scores, complaining about the copay that I have no control over, yelling at my staff for doing their jobs ... is pretty damn hollow.
It’s kind of like Mother’s Day: If you’re a jackass to your mom most of the year, sending her flowers on a Sunday in May doesn’t make it all right.
People also seem to forget that, in a small practice, my awesome staff is an extension of myself. Mistreating them, then wishing me a “Happy Doctor’s Day,” is also worthless.
I still like what I do. All the hassles from insurance companies, various administrators, the occasional angry patient … after all these years, they put a dent in it, but I still have no regrets about the course I’ve chosen. They can’t take away the happiness I get from helping those who need me.
It’s a job I love that’s allowed me to support my family and work with two wonderful staff members I’d never have met otherwise.
And that’s all I need.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Early puberty cases among girls surged during pandemic
Overwhelming numbers of early puberty cases among girls have been reported during the pandemic, according a report copublished by the Washington Post and The Fuller Project.
Early puberty is uncommon, affecting about 1 in every 5,000 to 10,000 children, with cases about 10 times higher in girls than boys. But since the pandemic started, doctors and parents around the world have noted a substantial surge in early puberty.
In some cases, girls as young as 5 have begun developing breasts and girls younger than 8 have started menstruation.
“I noticed that quite a few of my [girl patients] got their period after a lockdown,” Adiaha Spinks-Franklin, MD, a pediatrician at Texas Children’s Hospital, Houston, told the news outlets.
The condition, also called precocious puberty, is defined as puberty-related changes earlier than normal or expected, which starts around age 8 for girls and age 9 for boys. It can sometimes be caused by genetic syndromes, central nervous system issues, or tumors on the ovaries, adrenal glands, pituitary gland, or brain.
Pediatricians across the world have reported more precocious puberty cases, the news outlets reported, including in the United States, India, Italy, and Turkey.
A recent study found that more than 300 girls were referred to five pediatric endocrinology centers in Italy between March and September 2020, as opposed to 140 referrals during the same time period in 2019.
In another study, a Turkish pediatric endocrinology clinic reported 58 cases during the first year of the pandemic, as compared with 66 total cases during the 3 previous years.
Early puberty tends to mean there are other mental and physical issues, though in most cases, an exact cause can’t be found. Doctors have tied the current uptick to the stress of the pandemic and lockdowns, including reduced physical activity and increased consumption of unhealthy food, which are things linked to a higher risk of early puberty.
“I think it’s directly related to the amount of stress that the children have gone through,” Vaishakhi Rustagi, MD, a pediatric endocrinologist in Delhi, India, told the news outlets.
In a typical year, Dr. Rustagi sees about 20 patients with early puberty. Since mid-2020, she’s seen more than 300 girls with the condition. Imaging scans and ultrasounds haven’t found tumors, and the cause has been mostly unidentifiable, though Dr. Rustagi attributed it to stress and grief.
“These children have lost family members,” she said.
Early puberty is known to increase depression, eating disorders, substance abuse, and antisocial behavior, the news outlets reported.
The main treatment for the condition, a form of hormone therapy known as gonadotropin-releasing hormone analogue therapy, is known to work very well. But some patients and families may not seek treatment because of a lack of awareness or stigmas that come with menstruation.
A version of this article first appeared on WebMD.com.
Overwhelming numbers of early puberty cases among girls have been reported during the pandemic, according a report copublished by the Washington Post and The Fuller Project.
Early puberty is uncommon, affecting about 1 in every 5,000 to 10,000 children, with cases about 10 times higher in girls than boys. But since the pandemic started, doctors and parents around the world have noted a substantial surge in early puberty.
In some cases, girls as young as 5 have begun developing breasts and girls younger than 8 have started menstruation.
“I noticed that quite a few of my [girl patients] got their period after a lockdown,” Adiaha Spinks-Franklin, MD, a pediatrician at Texas Children’s Hospital, Houston, told the news outlets.
The condition, also called precocious puberty, is defined as puberty-related changes earlier than normal or expected, which starts around age 8 for girls and age 9 for boys. It can sometimes be caused by genetic syndromes, central nervous system issues, or tumors on the ovaries, adrenal glands, pituitary gland, or brain.
Pediatricians across the world have reported more precocious puberty cases, the news outlets reported, including in the United States, India, Italy, and Turkey.
A recent study found that more than 300 girls were referred to five pediatric endocrinology centers in Italy between March and September 2020, as opposed to 140 referrals during the same time period in 2019.
In another study, a Turkish pediatric endocrinology clinic reported 58 cases during the first year of the pandemic, as compared with 66 total cases during the 3 previous years.
Early puberty tends to mean there are other mental and physical issues, though in most cases, an exact cause can’t be found. Doctors have tied the current uptick to the stress of the pandemic and lockdowns, including reduced physical activity and increased consumption of unhealthy food, which are things linked to a higher risk of early puberty.
“I think it’s directly related to the amount of stress that the children have gone through,” Vaishakhi Rustagi, MD, a pediatric endocrinologist in Delhi, India, told the news outlets.
In a typical year, Dr. Rustagi sees about 20 patients with early puberty. Since mid-2020, she’s seen more than 300 girls with the condition. Imaging scans and ultrasounds haven’t found tumors, and the cause has been mostly unidentifiable, though Dr. Rustagi attributed it to stress and grief.
“These children have lost family members,” she said.
Early puberty is known to increase depression, eating disorders, substance abuse, and antisocial behavior, the news outlets reported.
The main treatment for the condition, a form of hormone therapy known as gonadotropin-releasing hormone analogue therapy, is known to work very well. But some patients and families may not seek treatment because of a lack of awareness or stigmas that come with menstruation.
A version of this article first appeared on WebMD.com.
Overwhelming numbers of early puberty cases among girls have been reported during the pandemic, according a report copublished by the Washington Post and The Fuller Project.
Early puberty is uncommon, affecting about 1 in every 5,000 to 10,000 children, with cases about 10 times higher in girls than boys. But since the pandemic started, doctors and parents around the world have noted a substantial surge in early puberty.
In some cases, girls as young as 5 have begun developing breasts and girls younger than 8 have started menstruation.
“I noticed that quite a few of my [girl patients] got their period after a lockdown,” Adiaha Spinks-Franklin, MD, a pediatrician at Texas Children’s Hospital, Houston, told the news outlets.
The condition, also called precocious puberty, is defined as puberty-related changes earlier than normal or expected, which starts around age 8 for girls and age 9 for boys. It can sometimes be caused by genetic syndromes, central nervous system issues, or tumors on the ovaries, adrenal glands, pituitary gland, or brain.
Pediatricians across the world have reported more precocious puberty cases, the news outlets reported, including in the United States, India, Italy, and Turkey.
A recent study found that more than 300 girls were referred to five pediatric endocrinology centers in Italy between March and September 2020, as opposed to 140 referrals during the same time period in 2019.
In another study, a Turkish pediatric endocrinology clinic reported 58 cases during the first year of the pandemic, as compared with 66 total cases during the 3 previous years.
Early puberty tends to mean there are other mental and physical issues, though in most cases, an exact cause can’t be found. Doctors have tied the current uptick to the stress of the pandemic and lockdowns, including reduced physical activity and increased consumption of unhealthy food, which are things linked to a higher risk of early puberty.
“I think it’s directly related to the amount of stress that the children have gone through,” Vaishakhi Rustagi, MD, a pediatric endocrinologist in Delhi, India, told the news outlets.
In a typical year, Dr. Rustagi sees about 20 patients with early puberty. Since mid-2020, she’s seen more than 300 girls with the condition. Imaging scans and ultrasounds haven’t found tumors, and the cause has been mostly unidentifiable, though Dr. Rustagi attributed it to stress and grief.
“These children have lost family members,” she said.
Early puberty is known to increase depression, eating disorders, substance abuse, and antisocial behavior, the news outlets reported.
The main treatment for the condition, a form of hormone therapy known as gonadotropin-releasing hormone analogue therapy, is known to work very well. But some patients and families may not seek treatment because of a lack of awareness or stigmas that come with menstruation.
A version of this article first appeared on WebMD.com.
CDC recommends hep B vaccination for most adults
It also added that adults aged 60 years or older without known risk factors for hepatitis B may get vaccinated.
The agency earlier recommended the vaccination for all infants and children under the age of 19 years and for adults aged 60 years or older with known risk factors.
The CDC said it wants to expand vaccinations because, after decades of progress, the number of new hepatitis B infections is increasing among adults. Acute hepatitis B infections among adults lead to chronic hepatitis B disease in an estimated 2%-6% of cases, and can result in cirrhosis, liver cancer, and death.
Among adults aged 40-49 years, the rate of cases increased from 1.9 per 100,000 people in 2011 to 2.7 per 100,000 in 2019. Among adults aged 50-59 years, the rate increased during this period from 1.1 to 1.6 per 100,000.
Most adults aren’t vaccinated. Among adults aged 19 years or older, only 30.0% reported that they’d received at least the three recommended doses of the vaccine. The rate was 40.3% for adults aged 19-49 years, and 19.1% for adults aged 50 years or older.
Hepatitis B infection rates are particularly elevated among African Americans.
Even among adults with chronic liver disease, the vaccination rate is only 33.0%. And, among travelers to countries where the virus has been endemic since 1995, only 38.9% were vaccinated.
In a 2018 survey of internal medicine and family physicians, 68% said their patients had not told them about risk factors, making it difficult to assess whether the patients needed the vaccine according to the recommendations at the time. These risk factors include injection drug use, incarceration, and multiple sex partners, experiences the patients may not have been willing to discuss.
CDC researchers calculated that universal adult hepatitis B vaccination would cost $153,000 for every quality-adjusted life-year (QALY) gained. For adults aged 19-59 years, a QALY would cost $117,000 because infections are more prevalent in that age group.
The CDC specified that it intends its new guidelines to prompt physicians to offer the vaccine to adults aged 60 years or older rather than wait for them to request it.
The Food and Drug Administration has approved both three-dose and two-dose hepatitis B vaccines, with evidence showing similar seroprotection and adverse events.
People who have already completed their vaccination or have a history of hepatitis B infection should only receive additional vaccinations in specific cases, as detailed in the CDC’s 2018 recommendations.
A version of this article first appeared on Medscape.com.
It also added that adults aged 60 years or older without known risk factors for hepatitis B may get vaccinated.
The agency earlier recommended the vaccination for all infants and children under the age of 19 years and for adults aged 60 years or older with known risk factors.
The CDC said it wants to expand vaccinations because, after decades of progress, the number of new hepatitis B infections is increasing among adults. Acute hepatitis B infections among adults lead to chronic hepatitis B disease in an estimated 2%-6% of cases, and can result in cirrhosis, liver cancer, and death.
Among adults aged 40-49 years, the rate of cases increased from 1.9 per 100,000 people in 2011 to 2.7 per 100,000 in 2019. Among adults aged 50-59 years, the rate increased during this period from 1.1 to 1.6 per 100,000.
Most adults aren’t vaccinated. Among adults aged 19 years or older, only 30.0% reported that they’d received at least the three recommended doses of the vaccine. The rate was 40.3% for adults aged 19-49 years, and 19.1% for adults aged 50 years or older.
Hepatitis B infection rates are particularly elevated among African Americans.
Even among adults with chronic liver disease, the vaccination rate is only 33.0%. And, among travelers to countries where the virus has been endemic since 1995, only 38.9% were vaccinated.
In a 2018 survey of internal medicine and family physicians, 68% said their patients had not told them about risk factors, making it difficult to assess whether the patients needed the vaccine according to the recommendations at the time. These risk factors include injection drug use, incarceration, and multiple sex partners, experiences the patients may not have been willing to discuss.
CDC researchers calculated that universal adult hepatitis B vaccination would cost $153,000 for every quality-adjusted life-year (QALY) gained. For adults aged 19-59 years, a QALY would cost $117,000 because infections are more prevalent in that age group.
The CDC specified that it intends its new guidelines to prompt physicians to offer the vaccine to adults aged 60 years or older rather than wait for them to request it.
The Food and Drug Administration has approved both three-dose and two-dose hepatitis B vaccines, with evidence showing similar seroprotection and adverse events.
People who have already completed their vaccination or have a history of hepatitis B infection should only receive additional vaccinations in specific cases, as detailed in the CDC’s 2018 recommendations.
A version of this article first appeared on Medscape.com.
It also added that adults aged 60 years or older without known risk factors for hepatitis B may get vaccinated.
The agency earlier recommended the vaccination for all infants and children under the age of 19 years and for adults aged 60 years or older with known risk factors.
The CDC said it wants to expand vaccinations because, after decades of progress, the number of new hepatitis B infections is increasing among adults. Acute hepatitis B infections among adults lead to chronic hepatitis B disease in an estimated 2%-6% of cases, and can result in cirrhosis, liver cancer, and death.
Among adults aged 40-49 years, the rate of cases increased from 1.9 per 100,000 people in 2011 to 2.7 per 100,000 in 2019. Among adults aged 50-59 years, the rate increased during this period from 1.1 to 1.6 per 100,000.
Most adults aren’t vaccinated. Among adults aged 19 years or older, only 30.0% reported that they’d received at least the three recommended doses of the vaccine. The rate was 40.3% for adults aged 19-49 years, and 19.1% for adults aged 50 years or older.
Hepatitis B infection rates are particularly elevated among African Americans.
Even among adults with chronic liver disease, the vaccination rate is only 33.0%. And, among travelers to countries where the virus has been endemic since 1995, only 38.9% were vaccinated.
In a 2018 survey of internal medicine and family physicians, 68% said their patients had not told them about risk factors, making it difficult to assess whether the patients needed the vaccine according to the recommendations at the time. These risk factors include injection drug use, incarceration, and multiple sex partners, experiences the patients may not have been willing to discuss.
CDC researchers calculated that universal adult hepatitis B vaccination would cost $153,000 for every quality-adjusted life-year (QALY) gained. For adults aged 19-59 years, a QALY would cost $117,000 because infections are more prevalent in that age group.
The CDC specified that it intends its new guidelines to prompt physicians to offer the vaccine to adults aged 60 years or older rather than wait for them to request it.
The Food and Drug Administration has approved both three-dose and two-dose hepatitis B vaccines, with evidence showing similar seroprotection and adverse events.
People who have already completed their vaccination or have a history of hepatitis B infection should only receive additional vaccinations in specific cases, as detailed in the CDC’s 2018 recommendations.
A version of this article first appeared on Medscape.com.
FROM THE MMWR
Asking hard questions during office visits can improve patient outcomes
Screening patients for social needs and referring patients to resources should be a routine part of cancer care, said a physician who presented a study on the social needs of patients at the Society of Gynecologic Oncology’s 2022 Annual Meeting on Women’s Cancer held in March.
The study, by Anna L. Beavis, MD, MPH, a gynecologic oncologist with the Johns Hopkins Kelly Gynecologic Oncology Service, Baltimore, identified social needs, such as financial assistance and housing insecurity, among a group of 373 patients who completed a written assessment during regular office visits.
The patients were asked about food and housing insecurities, utility and transportation needs, and financial assistance. For some patients these are such dire issues, they actually affect patient outcomes.
While the results were limited to a single urban population and may not be generalizable to other populations, Dr. Beavis said the findings are noteworthy because for physicians, these are tangible items that can be addressed to improve patient outcomes.
“The greatest obstacle is not asking the questions, it’s in ensuring there are acceptable and effective mechanisms for referrals to resources. It is important to have a plan in place to refer patients to resources before beginning a screening program,” she said.
In an interview, Dr. Beavis said that screening and referring patients to resources should be a routine part of cancer care. In this study, 92% of patients completed the questionnaire in her office and the process doesn’t slow her clinic down, she said.
“Our findings demonstrate that social needs are prevalent, and screening for them should be a routine part of the standard of care for cancer patients,” Dr. Beavis said. “Social needs are also actionable for us as physicians, because we can address tangible, individual-level needs, such as food insecurity and transportation, through the provision of resources. These needs stand in contrast to the social determinants of health, which are community-level and require changes on a much larger scale through policy decisions.”
Of the 373 patients in the study group, 74 patients were identified as having at least one social need. Fifty-seven percent asked for a referral to a partner organization for resource assistance. Fifty-eight percent of the study group were White and 42% identified as patients of color, including Black, Asian, Hispanic, American Indian/Alaska Native, and multiple/other races.
“We’ve begun to assess patient satisfaction and have found that patients feel these questions are important – plus, they’re comfortable answering them,” she said.
Dr. Beavis’ study was funded by a grant from the American Cancer Society and Pfizer Global Medical Grants under the Addressing Racial Disparities in Cancer Care Competitive Grant Program.
Screening patients for social needs and referring patients to resources should be a routine part of cancer care, said a physician who presented a study on the social needs of patients at the Society of Gynecologic Oncology’s 2022 Annual Meeting on Women’s Cancer held in March.
The study, by Anna L. Beavis, MD, MPH, a gynecologic oncologist with the Johns Hopkins Kelly Gynecologic Oncology Service, Baltimore, identified social needs, such as financial assistance and housing insecurity, among a group of 373 patients who completed a written assessment during regular office visits.
The patients were asked about food and housing insecurities, utility and transportation needs, and financial assistance. For some patients these are such dire issues, they actually affect patient outcomes.
While the results were limited to a single urban population and may not be generalizable to other populations, Dr. Beavis said the findings are noteworthy because for physicians, these are tangible items that can be addressed to improve patient outcomes.
“The greatest obstacle is not asking the questions, it’s in ensuring there are acceptable and effective mechanisms for referrals to resources. It is important to have a plan in place to refer patients to resources before beginning a screening program,” she said.
In an interview, Dr. Beavis said that screening and referring patients to resources should be a routine part of cancer care. In this study, 92% of patients completed the questionnaire in her office and the process doesn’t slow her clinic down, she said.
“Our findings demonstrate that social needs are prevalent, and screening for them should be a routine part of the standard of care for cancer patients,” Dr. Beavis said. “Social needs are also actionable for us as physicians, because we can address tangible, individual-level needs, such as food insecurity and transportation, through the provision of resources. These needs stand in contrast to the social determinants of health, which are community-level and require changes on a much larger scale through policy decisions.”
Of the 373 patients in the study group, 74 patients were identified as having at least one social need. Fifty-seven percent asked for a referral to a partner organization for resource assistance. Fifty-eight percent of the study group were White and 42% identified as patients of color, including Black, Asian, Hispanic, American Indian/Alaska Native, and multiple/other races.
“We’ve begun to assess patient satisfaction and have found that patients feel these questions are important – plus, they’re comfortable answering them,” she said.
Dr. Beavis’ study was funded by a grant from the American Cancer Society and Pfizer Global Medical Grants under the Addressing Racial Disparities in Cancer Care Competitive Grant Program.
Screening patients for social needs and referring patients to resources should be a routine part of cancer care, said a physician who presented a study on the social needs of patients at the Society of Gynecologic Oncology’s 2022 Annual Meeting on Women’s Cancer held in March.
The study, by Anna L. Beavis, MD, MPH, a gynecologic oncologist with the Johns Hopkins Kelly Gynecologic Oncology Service, Baltimore, identified social needs, such as financial assistance and housing insecurity, among a group of 373 patients who completed a written assessment during regular office visits.
The patients were asked about food and housing insecurities, utility and transportation needs, and financial assistance. For some patients these are such dire issues, they actually affect patient outcomes.
While the results were limited to a single urban population and may not be generalizable to other populations, Dr. Beavis said the findings are noteworthy because for physicians, these are tangible items that can be addressed to improve patient outcomes.
“The greatest obstacle is not asking the questions, it’s in ensuring there are acceptable and effective mechanisms for referrals to resources. It is important to have a plan in place to refer patients to resources before beginning a screening program,” she said.
In an interview, Dr. Beavis said that screening and referring patients to resources should be a routine part of cancer care. In this study, 92% of patients completed the questionnaire in her office and the process doesn’t slow her clinic down, she said.
“Our findings demonstrate that social needs are prevalent, and screening for them should be a routine part of the standard of care for cancer patients,” Dr. Beavis said. “Social needs are also actionable for us as physicians, because we can address tangible, individual-level needs, such as food insecurity and transportation, through the provision of resources. These needs stand in contrast to the social determinants of health, which are community-level and require changes on a much larger scale through policy decisions.”
Of the 373 patients in the study group, 74 patients were identified as having at least one social need. Fifty-seven percent asked for a referral to a partner organization for resource assistance. Fifty-eight percent of the study group were White and 42% identified as patients of color, including Black, Asian, Hispanic, American Indian/Alaska Native, and multiple/other races.
“We’ve begun to assess patient satisfaction and have found that patients feel these questions are important – plus, they’re comfortable answering them,” she said.
Dr. Beavis’ study was funded by a grant from the American Cancer Society and Pfizer Global Medical Grants under the Addressing Racial Disparities in Cancer Care Competitive Grant Program.
FROM SGO 2022
First COVID-19 human challenge study provides insights
A small droplet that contains the coronavirus can infect someone with COVID-19, according to recent results from the first COVID-19 human challenge study, which were published in Nature Medicine.
Human challenge trials deliberately infect healthy volunteers to understand how an infection occurs and develops. In the first human challenge study for COVID-19, people were infected with the SARS-CoV-2 virus to better understand what has happened during the pandemic.
“Really, there’s no other type of study where you can do that, because normally, patients only come to your attention if they have developed symptoms, and so you miss all of those preceding days when the infection is brewing,” Christopher Chiu, MD, PhD, the lead study author and an infectious disease doctor and immunologist at Imperial College London, told CNN.
Starting in March 2021, Dr. Chiu and colleagues carefully selected 36 volunteers aged 18-30 years who didn’t have any risk factors for severe COVID-19, such as being overweight or having kidney, liver, heart, lung or blood problems. Participants also signed an extensive informed consent form, CNN reported.
The researchers conducted the trial in phases for safety. The first 10 participants who were infected received remdesivir, the antiviral drug, to reduce their chances of progressing to severe COVID-19. The research team also had monoclonal antibodies on hand in case any volunteers developed more severe symptoms. Ultimately, the researchers said, remdesivir was unnecessary, and they didn’t need to use the antibodies.
As part of the study, the participants had a small droplet of fluid that contained the original coronavirus strain inserted into their nose through a long tube. They stayed at London’s Royal Free Hospital for 2 weeks and were monitored by doctors 24 hours a day in rooms that had special air flow to keep the virus from spreading.
Of the 36 participants, 18 became infected, including two who never developed symptoms. The others had mild cases with symptoms such as congestion, sneezing, stuffy nose, and sore throat. Some also had headaches, muscle and joint pain, fatigue, and fever.
About 83% of participants who contracted COVID-19 lost their sense of smell to some degree, and nine people couldn’t smell at all. The symptom improved for most participants within 90 days, though one person still hadn’t fully regained their sense of smell about six months after the study ended.
The research team reported several other findings:
- Small amounts of the virus can make someone sick. About 10 mcm, or the amount in a single droplet that someone sneezes or coughs, can lead to infection.
- About 40 hours after the virus was inserted into a participant’s nose, the virus could be detected in the back of the throat.
- It took about 58 hours for the virus to appear on swabs from the nose, where the viral load eventually increased even more.
- COVID-19 has a short incubation period. It takes about 2 days after infection for someone to begin shedding the virus to others.
- People become contagious and shed high amounts of the virus before they show symptoms.
- In addition, infected people can shed high levels of the virus even if they don’t develop any symptoms.
- The study volunteers shed the virus for about 6 days on average, though some shed the virus for up to 12 days, even if they didn’t have symptoms.
- Lateral flow tests, which are used for rapid at-home tests, work well when an infected person is contagious. These tests could diagnose infection before 70%-80% of the viable virus had been generated.
The findings emphasized the importance of contagious people covering their mouth and nose when sick to protect others, Dr. Chiu told CNN.
None of the study volunteers developed lung issues as part of their infection, CNN reported. Dr. Chiu said that’s likely because they were young, healthy and received tiny amounts of the virus. All of the participants will be followed for a year to monitor for potential long-term effects.
Throughout the study, the research team also conducted cognitive tests to check the participants’ short-term memory and reaction time. The researchers are still analyzing the data, but the results “will really be informative,” Dr. Chiu told CNN.
Now the research team will conduct another human challenge trial, which will include vaccinated people who will be infected with the Delta variant. The researchers intend to study participants’ immune responses, which could provide valuable insights about new variants and vaccines.
“While there are differences in transmissibility due to the emergence of variants, such as Delta and Omicron, fundamentally, this is the same disease and the same factors will be responsible for protecting it,” Dr. Chiu said in a statement.
The research team will also study the 18 participants who didn’t get sick in the first human challenge trial. They didn’t develop antibodies, Dr. Chiu told CNN, despite receiving the same dose of the virus as those who got sick.
Before the study, all of the participants were screened for antibodies to other viruses, such as the original SARS virus. That means the volunteers weren’t cross-protected, and other factors may play into why some people don’t contract COVID-19. Future studies could help researchers provide better advice about protection if new variants emerge or a future pandemic occurs.
“There are lots of other things that help protect us,” Dr. Chiu said. “There are barriers in the nose. There are different kinds of proteins and things which are very ancient, primordial, protective systems ... and we’re really interested in trying to understand what those are.”
A version of this article first appeared on WebMD.com.
A small droplet that contains the coronavirus can infect someone with COVID-19, according to recent results from the first COVID-19 human challenge study, which were published in Nature Medicine.
Human challenge trials deliberately infect healthy volunteers to understand how an infection occurs and develops. In the first human challenge study for COVID-19, people were infected with the SARS-CoV-2 virus to better understand what has happened during the pandemic.
“Really, there’s no other type of study where you can do that, because normally, patients only come to your attention if they have developed symptoms, and so you miss all of those preceding days when the infection is brewing,” Christopher Chiu, MD, PhD, the lead study author and an infectious disease doctor and immunologist at Imperial College London, told CNN.
Starting in March 2021, Dr. Chiu and colleagues carefully selected 36 volunteers aged 18-30 years who didn’t have any risk factors for severe COVID-19, such as being overweight or having kidney, liver, heart, lung or blood problems. Participants also signed an extensive informed consent form, CNN reported.
The researchers conducted the trial in phases for safety. The first 10 participants who were infected received remdesivir, the antiviral drug, to reduce their chances of progressing to severe COVID-19. The research team also had monoclonal antibodies on hand in case any volunteers developed more severe symptoms. Ultimately, the researchers said, remdesivir was unnecessary, and they didn’t need to use the antibodies.
As part of the study, the participants had a small droplet of fluid that contained the original coronavirus strain inserted into their nose through a long tube. They stayed at London’s Royal Free Hospital for 2 weeks and were monitored by doctors 24 hours a day in rooms that had special air flow to keep the virus from spreading.
Of the 36 participants, 18 became infected, including two who never developed symptoms. The others had mild cases with symptoms such as congestion, sneezing, stuffy nose, and sore throat. Some also had headaches, muscle and joint pain, fatigue, and fever.
About 83% of participants who contracted COVID-19 lost their sense of smell to some degree, and nine people couldn’t smell at all. The symptom improved for most participants within 90 days, though one person still hadn’t fully regained their sense of smell about six months after the study ended.
The research team reported several other findings:
- Small amounts of the virus can make someone sick. About 10 mcm, or the amount in a single droplet that someone sneezes or coughs, can lead to infection.
- About 40 hours after the virus was inserted into a participant’s nose, the virus could be detected in the back of the throat.
- It took about 58 hours for the virus to appear on swabs from the nose, where the viral load eventually increased even more.
- COVID-19 has a short incubation period. It takes about 2 days after infection for someone to begin shedding the virus to others.
- People become contagious and shed high amounts of the virus before they show symptoms.
- In addition, infected people can shed high levels of the virus even if they don’t develop any symptoms.
- The study volunteers shed the virus for about 6 days on average, though some shed the virus for up to 12 days, even if they didn’t have symptoms.
- Lateral flow tests, which are used for rapid at-home tests, work well when an infected person is contagious. These tests could diagnose infection before 70%-80% of the viable virus had been generated.
The findings emphasized the importance of contagious people covering their mouth and nose when sick to protect others, Dr. Chiu told CNN.
None of the study volunteers developed lung issues as part of their infection, CNN reported. Dr. Chiu said that’s likely because they were young, healthy and received tiny amounts of the virus. All of the participants will be followed for a year to monitor for potential long-term effects.
Throughout the study, the research team also conducted cognitive tests to check the participants’ short-term memory and reaction time. The researchers are still analyzing the data, but the results “will really be informative,” Dr. Chiu told CNN.
Now the research team will conduct another human challenge trial, which will include vaccinated people who will be infected with the Delta variant. The researchers intend to study participants’ immune responses, which could provide valuable insights about new variants and vaccines.
“While there are differences in transmissibility due to the emergence of variants, such as Delta and Omicron, fundamentally, this is the same disease and the same factors will be responsible for protecting it,” Dr. Chiu said in a statement.
The research team will also study the 18 participants who didn’t get sick in the first human challenge trial. They didn’t develop antibodies, Dr. Chiu told CNN, despite receiving the same dose of the virus as those who got sick.
Before the study, all of the participants were screened for antibodies to other viruses, such as the original SARS virus. That means the volunteers weren’t cross-protected, and other factors may play into why some people don’t contract COVID-19. Future studies could help researchers provide better advice about protection if new variants emerge or a future pandemic occurs.
“There are lots of other things that help protect us,” Dr. Chiu said. “There are barriers in the nose. There are different kinds of proteins and things which are very ancient, primordial, protective systems ... and we’re really interested in trying to understand what those are.”
A version of this article first appeared on WebMD.com.
A small droplet that contains the coronavirus can infect someone with COVID-19, according to recent results from the first COVID-19 human challenge study, which were published in Nature Medicine.
Human challenge trials deliberately infect healthy volunteers to understand how an infection occurs and develops. In the first human challenge study for COVID-19, people were infected with the SARS-CoV-2 virus to better understand what has happened during the pandemic.
“Really, there’s no other type of study where you can do that, because normally, patients only come to your attention if they have developed symptoms, and so you miss all of those preceding days when the infection is brewing,” Christopher Chiu, MD, PhD, the lead study author and an infectious disease doctor and immunologist at Imperial College London, told CNN.
Starting in March 2021, Dr. Chiu and colleagues carefully selected 36 volunteers aged 18-30 years who didn’t have any risk factors for severe COVID-19, such as being overweight or having kidney, liver, heart, lung or blood problems. Participants also signed an extensive informed consent form, CNN reported.
The researchers conducted the trial in phases for safety. The first 10 participants who were infected received remdesivir, the antiviral drug, to reduce their chances of progressing to severe COVID-19. The research team also had monoclonal antibodies on hand in case any volunteers developed more severe symptoms. Ultimately, the researchers said, remdesivir was unnecessary, and they didn’t need to use the antibodies.
As part of the study, the participants had a small droplet of fluid that contained the original coronavirus strain inserted into their nose through a long tube. They stayed at London’s Royal Free Hospital for 2 weeks and were monitored by doctors 24 hours a day in rooms that had special air flow to keep the virus from spreading.
Of the 36 participants, 18 became infected, including two who never developed symptoms. The others had mild cases with symptoms such as congestion, sneezing, stuffy nose, and sore throat. Some also had headaches, muscle and joint pain, fatigue, and fever.
About 83% of participants who contracted COVID-19 lost their sense of smell to some degree, and nine people couldn’t smell at all. The symptom improved for most participants within 90 days, though one person still hadn’t fully regained their sense of smell about six months after the study ended.
The research team reported several other findings:
- Small amounts of the virus can make someone sick. About 10 mcm, or the amount in a single droplet that someone sneezes or coughs, can lead to infection.
- About 40 hours after the virus was inserted into a participant’s nose, the virus could be detected in the back of the throat.
- It took about 58 hours for the virus to appear on swabs from the nose, where the viral load eventually increased even more.
- COVID-19 has a short incubation period. It takes about 2 days after infection for someone to begin shedding the virus to others.
- People become contagious and shed high amounts of the virus before they show symptoms.
- In addition, infected people can shed high levels of the virus even if they don’t develop any symptoms.
- The study volunteers shed the virus for about 6 days on average, though some shed the virus for up to 12 days, even if they didn’t have symptoms.
- Lateral flow tests, which are used for rapid at-home tests, work well when an infected person is contagious. These tests could diagnose infection before 70%-80% of the viable virus had been generated.
The findings emphasized the importance of contagious people covering their mouth and nose when sick to protect others, Dr. Chiu told CNN.
None of the study volunteers developed lung issues as part of their infection, CNN reported. Dr. Chiu said that’s likely because they were young, healthy and received tiny amounts of the virus. All of the participants will be followed for a year to monitor for potential long-term effects.
Throughout the study, the research team also conducted cognitive tests to check the participants’ short-term memory and reaction time. The researchers are still analyzing the data, but the results “will really be informative,” Dr. Chiu told CNN.
Now the research team will conduct another human challenge trial, which will include vaccinated people who will be infected with the Delta variant. The researchers intend to study participants’ immune responses, which could provide valuable insights about new variants and vaccines.
“While there are differences in transmissibility due to the emergence of variants, such as Delta and Omicron, fundamentally, this is the same disease and the same factors will be responsible for protecting it,” Dr. Chiu said in a statement.
The research team will also study the 18 participants who didn’t get sick in the first human challenge trial. They didn’t develop antibodies, Dr. Chiu told CNN, despite receiving the same dose of the virus as those who got sick.
Before the study, all of the participants were screened for antibodies to other viruses, such as the original SARS virus. That means the volunteers weren’t cross-protected, and other factors may play into why some people don’t contract COVID-19. Future studies could help researchers provide better advice about protection if new variants emerge or a future pandemic occurs.
“There are lots of other things that help protect us,” Dr. Chiu said. “There are barriers in the nose. There are different kinds of proteins and things which are very ancient, primordial, protective systems ... and we’re really interested in trying to understand what those are.”
A version of this article first appeared on WebMD.com.
FROM NATURE MEDICINE
U.S. hospitals warned about potential Russian cyberattacks
as a result of the invasion of Ukraine and the U.S. and Western countermeasures against the aggressor nation.
The day after President Biden announced that the war had begun, the American Hospital Association (AHA) issued an alert to hospitals. The cybersecurity division of the Department of Health and Human Services (HHS), known as HC3, joined AHA with another public warning to the healthcare system on March 1. The federal government’s Cybersecurity & Infrastructure Security Agency (CISA) issued a “Shield’s Up” alert to private industry, supporting Biden’s March 21 statement about the need to improve domestic cybersecurity.
CISA warned that the Russian invasion of Ukraine could lead to “malicious cyber activity against the U.S. homeland, including as a response to the unprecedented economic costs imposed on Russia by the U.S. and our allies and partners.” The agency noted that the Russian government is currently exploring options for cyberattacks.
John Riggi, the AHA’s national advisor for cybersecurity and risk, and a former senior executive in the FBI’s cyber division, said in an interview, “We are not aware of any cyberattacks related to the current conflict [in Ukraine]. We don’t know of any specific credible threats targeted against U.S. healthcare from the Russian government.”
He added that there have been reports of Russian hackers searching U.S. health IT security systems for weaknesses.
Criminal gangs remain a threat
Besides the Russian government, Mr. Riggi said, Russian criminal gangs are another threat to U.S. hospitals and other healthcare providers. Of particular concern, he noted, is the Conti gang, which “has a history of conducting ransomware attacks against U.S. healthcare and the Irish health system.”
On February 25, said Mr. Riggi, the Conti group announced plans “to retaliate against the West for what they viewed as potential cyber aggression by the West against the Russian federation.”
Sophisticated hacker groups like the Conti gang that operate under the protection of the Russian government have “caused the greatest amount of disruption and have cost the most in terms of recovery and lost business,” Mac McMillan, CEO of CynergisTek, a cybersecurity consulting firm, told this news organization.
However, he said, the current threat is greater for two reasons: first, it will likely come directly from the Russian military intelligence service; and second, there are indications that the malware will be more destructive than ransomware. Two new types of malware identified by HC3 — HermeticWiper and WhisperGate — are designed to wipe out the data in their targets’ systems, rather than just encrypting it and disrupting access to data until a ransom is paid.
The Russian military intelligence service, known as the GRU, is extremely capable and dangerous, Mr. McMillan said. He doubts that many healthcare systems, even if they are fairly well prepared, could withstand an attack from this source. And he fully believes that the attack, when it comes, will aim to wipe out data in victims’ systems in order to create as much chaos and disruption as possible in the United States.
Hospitals better prepared, but still have gaps
Like Mr. Riggi, Mr. McMillan said that the healthcare industry is better prepared for cyberattacks now than it was in 2017, when the NotPetya assault on Ukraine’s online infrastructure created considerable collateral damage in the United States. However, he said, hospitals still have a long way to go before they can counter and/or recover from a dedicated Russian government cyberattack.
The NotPetya malware, Mr. Riggi said, was of the destructive variety. “That digital virus spread uncontrollably across the globe like a biological virus. All the organizations and institutions that had contact with Ukraine became infected.”
According to an indictment of six GRU officers that the Department of Justice announced in December 2020, NotPetya disrupted operations at a major pharmaceutical company, subsequently revealed to be Merck, and hospitals and other medical facilities in the Heritage Valley Health System in Pennsylvania. In addition, it temporarily shut down the transcription services of Nuance Communications, which lost $98 million as a result. Merck received $1.4 billion from an insurer to cover its NotPetya loss, Bloomberg reported.
That incident prompted the AHA to urge hospitals to use “geo-fencing” to block online communications with Ukraine and neighboring countries. However, Mr. Riggi said, that solution is not too effective because hackers commonly use proxy servers in other countries to forward their malware to the intended target.
The AHA alert included a list of actions that hospitals and health systems could take to reduce their vulnerability to Russian hacking. Besides geo-fencing, the AHA suggested that hospitals:
- Heighten staff awareness of the increased risk of receiving malware-laden phishing emails;
- Identify all international and third-party mission-critical, clinical, and operational services and technology and put in place business continuity plans and downtime procedures;
- Check the redundancy, resiliency, and security of the organization’s network and data backups;
- Document, update, and practice the organization’s incident response plan.
Hospitals increasingly targeted
In recent years, Mr. Riggi noted, hospitals have invested much more in cybersecurity than before, and hospital executives have told him that this is now one of their top priorities, along with COVID-19 and workforce issues. This has been not only because of NotPetya, but also because healthcare facilities are being increasingly attacked by foreign ransomware gangs, he says.
The hospitals’ biggest vulnerabilities, he said, are phishing emails, remote desktop access, and unpatched vulnerabilities, in that order. It’s not easy to remedy the latter, he observed, because hospital networks can include up to 100,000 connected medical devices and other computers that can access the network, both within and outside the hospital.
“With the new work-at-home environment, you may have thousands of employees who are using the network outside the traditional perimeter of the organization,” he pointed out. “There’s no longer that standard firewall that protects everything.” In addition, he said, hospitals also have to depend on vendors to develop patches and implement them.
In Mr. McMillan’s view, the healthcare industry is a decade behind the financial industry and other sectors in cybersecurity. Among other things, he says, “half of our hospitals still don’t have active monitoring on their networks. They don’t have privileged access on their networks. A bunch don’t have segmentation or endpoint protection. There are so many things that hospitals don’t have that they need to fend off these attacks — they’re better off than they were in 2017, but they still aren’t where they need to be.”
Physician practices also at risk
Employed physicians, naturally, are in danger of losing access to their electronic health records if their hospital’s network goes down as the result of a cyberattack, he notes. Many community doctors also use the EHR of a local hospital, and they’d be similarly affected, Mr. Riggi noted.
Physician practices might be saved if the attack were directed at the hospital and they could still connect to the EHR through a cloud provider, Mr. McMillan said. But Mr. Riggi stressed that practices still need a plan for their doctors to keep working if they lose access to a hospital EHR.
“The other possibility is that the practice could be targeted,” he added. “As hospitals become more hardened, often these hackers are looking for the weak link. The practices could become victims of increased targeting. And the practice becomes the conduit for malware to go from its system to the hospital and infect the hospital system.”
Hackers can hit service suppliers
Hospitals’ mission-critical service suppliers may also be targeted by Russian hackers and others, or they may be the accidental victims of a cyberattack elsewhere, Mr. Riggi noted. In the case of Nuance, he said, the disruption in transcription services affected thousands of U.S. healthcare providers who were unable to access their transcribed notes. This not only harmed patient care, but also meant that hospitals couldn’t fully bill for their services.
Another type of service supplier, he said, was struck with a ransomware attack last year. This was a cloud-based service that operated linear accelerators used in radiation oncology. “So radiation oncology and cancer treatment for patients across the U.S. was disrupted, and radiation oncology was delayed for some patients up to 3 weeks.”
More recently, another cloud-based service called Kronos was struck by ransomware. Because of this incident, payroll and timekeeping services were disrupted across several industries, including healthcare.
A version of this article first appeared on Medscape.com.
as a result of the invasion of Ukraine and the U.S. and Western countermeasures against the aggressor nation.
The day after President Biden announced that the war had begun, the American Hospital Association (AHA) issued an alert to hospitals. The cybersecurity division of the Department of Health and Human Services (HHS), known as HC3, joined AHA with another public warning to the healthcare system on March 1. The federal government’s Cybersecurity & Infrastructure Security Agency (CISA) issued a “Shield’s Up” alert to private industry, supporting Biden’s March 21 statement about the need to improve domestic cybersecurity.
CISA warned that the Russian invasion of Ukraine could lead to “malicious cyber activity against the U.S. homeland, including as a response to the unprecedented economic costs imposed on Russia by the U.S. and our allies and partners.” The agency noted that the Russian government is currently exploring options for cyberattacks.
John Riggi, the AHA’s national advisor for cybersecurity and risk, and a former senior executive in the FBI’s cyber division, said in an interview, “We are not aware of any cyberattacks related to the current conflict [in Ukraine]. We don’t know of any specific credible threats targeted against U.S. healthcare from the Russian government.”
He added that there have been reports of Russian hackers searching U.S. health IT security systems for weaknesses.
Criminal gangs remain a threat
Besides the Russian government, Mr. Riggi said, Russian criminal gangs are another threat to U.S. hospitals and other healthcare providers. Of particular concern, he noted, is the Conti gang, which “has a history of conducting ransomware attacks against U.S. healthcare and the Irish health system.”
On February 25, said Mr. Riggi, the Conti group announced plans “to retaliate against the West for what they viewed as potential cyber aggression by the West against the Russian federation.”
Sophisticated hacker groups like the Conti gang that operate under the protection of the Russian government have “caused the greatest amount of disruption and have cost the most in terms of recovery and lost business,” Mac McMillan, CEO of CynergisTek, a cybersecurity consulting firm, told this news organization.
However, he said, the current threat is greater for two reasons: first, it will likely come directly from the Russian military intelligence service; and second, there are indications that the malware will be more destructive than ransomware. Two new types of malware identified by HC3 — HermeticWiper and WhisperGate — are designed to wipe out the data in their targets’ systems, rather than just encrypting it and disrupting access to data until a ransom is paid.
The Russian military intelligence service, known as the GRU, is extremely capable and dangerous, Mr. McMillan said. He doubts that many healthcare systems, even if they are fairly well prepared, could withstand an attack from this source. And he fully believes that the attack, when it comes, will aim to wipe out data in victims’ systems in order to create as much chaos and disruption as possible in the United States.
Hospitals better prepared, but still have gaps
Like Mr. Riggi, Mr. McMillan said that the healthcare industry is better prepared for cyberattacks now than it was in 2017, when the NotPetya assault on Ukraine’s online infrastructure created considerable collateral damage in the United States. However, he said, hospitals still have a long way to go before they can counter and/or recover from a dedicated Russian government cyberattack.
The NotPetya malware, Mr. Riggi said, was of the destructive variety. “That digital virus spread uncontrollably across the globe like a biological virus. All the organizations and institutions that had contact with Ukraine became infected.”
According to an indictment of six GRU officers that the Department of Justice announced in December 2020, NotPetya disrupted operations at a major pharmaceutical company, subsequently revealed to be Merck, and hospitals and other medical facilities in the Heritage Valley Health System in Pennsylvania. In addition, it temporarily shut down the transcription services of Nuance Communications, which lost $98 million as a result. Merck received $1.4 billion from an insurer to cover its NotPetya loss, Bloomberg reported.
That incident prompted the AHA to urge hospitals to use “geo-fencing” to block online communications with Ukraine and neighboring countries. However, Mr. Riggi said, that solution is not too effective because hackers commonly use proxy servers in other countries to forward their malware to the intended target.
The AHA alert included a list of actions that hospitals and health systems could take to reduce their vulnerability to Russian hacking. Besides geo-fencing, the AHA suggested that hospitals:
- Heighten staff awareness of the increased risk of receiving malware-laden phishing emails;
- Identify all international and third-party mission-critical, clinical, and operational services and technology and put in place business continuity plans and downtime procedures;
- Check the redundancy, resiliency, and security of the organization’s network and data backups;
- Document, update, and practice the organization’s incident response plan.
Hospitals increasingly targeted
In recent years, Mr. Riggi noted, hospitals have invested much more in cybersecurity than before, and hospital executives have told him that this is now one of their top priorities, along with COVID-19 and workforce issues. This has been not only because of NotPetya, but also because healthcare facilities are being increasingly attacked by foreign ransomware gangs, he says.
The hospitals’ biggest vulnerabilities, he said, are phishing emails, remote desktop access, and unpatched vulnerabilities, in that order. It’s not easy to remedy the latter, he observed, because hospital networks can include up to 100,000 connected medical devices and other computers that can access the network, both within and outside the hospital.
“With the new work-at-home environment, you may have thousands of employees who are using the network outside the traditional perimeter of the organization,” he pointed out. “There’s no longer that standard firewall that protects everything.” In addition, he said, hospitals also have to depend on vendors to develop patches and implement them.
In Mr. McMillan’s view, the healthcare industry is a decade behind the financial industry and other sectors in cybersecurity. Among other things, he says, “half of our hospitals still don’t have active monitoring on their networks. They don’t have privileged access on their networks. A bunch don’t have segmentation or endpoint protection. There are so many things that hospitals don’t have that they need to fend off these attacks — they’re better off than they were in 2017, but they still aren’t where they need to be.”
Physician practices also at risk
Employed physicians, naturally, are in danger of losing access to their electronic health records if their hospital’s network goes down as the result of a cyberattack, he notes. Many community doctors also use the EHR of a local hospital, and they’d be similarly affected, Mr. Riggi noted.
Physician practices might be saved if the attack were directed at the hospital and they could still connect to the EHR through a cloud provider, Mr. McMillan said. But Mr. Riggi stressed that practices still need a plan for their doctors to keep working if they lose access to a hospital EHR.
“The other possibility is that the practice could be targeted,” he added. “As hospitals become more hardened, often these hackers are looking for the weak link. The practices could become victims of increased targeting. And the practice becomes the conduit for malware to go from its system to the hospital and infect the hospital system.”
Hackers can hit service suppliers
Hospitals’ mission-critical service suppliers may also be targeted by Russian hackers and others, or they may be the accidental victims of a cyberattack elsewhere, Mr. Riggi noted. In the case of Nuance, he said, the disruption in transcription services affected thousands of U.S. healthcare providers who were unable to access their transcribed notes. This not only harmed patient care, but also meant that hospitals couldn’t fully bill for their services.
Another type of service supplier, he said, was struck with a ransomware attack last year. This was a cloud-based service that operated linear accelerators used in radiation oncology. “So radiation oncology and cancer treatment for patients across the U.S. was disrupted, and radiation oncology was delayed for some patients up to 3 weeks.”
More recently, another cloud-based service called Kronos was struck by ransomware. Because of this incident, payroll and timekeeping services were disrupted across several industries, including healthcare.
A version of this article first appeared on Medscape.com.
as a result of the invasion of Ukraine and the U.S. and Western countermeasures against the aggressor nation.
The day after President Biden announced that the war had begun, the American Hospital Association (AHA) issued an alert to hospitals. The cybersecurity division of the Department of Health and Human Services (HHS), known as HC3, joined AHA with another public warning to the healthcare system on March 1. The federal government’s Cybersecurity & Infrastructure Security Agency (CISA) issued a “Shield’s Up” alert to private industry, supporting Biden’s March 21 statement about the need to improve domestic cybersecurity.
CISA warned that the Russian invasion of Ukraine could lead to “malicious cyber activity against the U.S. homeland, including as a response to the unprecedented economic costs imposed on Russia by the U.S. and our allies and partners.” The agency noted that the Russian government is currently exploring options for cyberattacks.
John Riggi, the AHA’s national advisor for cybersecurity and risk, and a former senior executive in the FBI’s cyber division, said in an interview, “We are not aware of any cyberattacks related to the current conflict [in Ukraine]. We don’t know of any specific credible threats targeted against U.S. healthcare from the Russian government.”
He added that there have been reports of Russian hackers searching U.S. health IT security systems for weaknesses.
Criminal gangs remain a threat
Besides the Russian government, Mr. Riggi said, Russian criminal gangs are another threat to U.S. hospitals and other healthcare providers. Of particular concern, he noted, is the Conti gang, which “has a history of conducting ransomware attacks against U.S. healthcare and the Irish health system.”
On February 25, said Mr. Riggi, the Conti group announced plans “to retaliate against the West for what they viewed as potential cyber aggression by the West against the Russian federation.”
Sophisticated hacker groups like the Conti gang that operate under the protection of the Russian government have “caused the greatest amount of disruption and have cost the most in terms of recovery and lost business,” Mac McMillan, CEO of CynergisTek, a cybersecurity consulting firm, told this news organization.
However, he said, the current threat is greater for two reasons: first, it will likely come directly from the Russian military intelligence service; and second, there are indications that the malware will be more destructive than ransomware. Two new types of malware identified by HC3 — HermeticWiper and WhisperGate — are designed to wipe out the data in their targets’ systems, rather than just encrypting it and disrupting access to data until a ransom is paid.
The Russian military intelligence service, known as the GRU, is extremely capable and dangerous, Mr. McMillan said. He doubts that many healthcare systems, even if they are fairly well prepared, could withstand an attack from this source. And he fully believes that the attack, when it comes, will aim to wipe out data in victims’ systems in order to create as much chaos and disruption as possible in the United States.
Hospitals better prepared, but still have gaps
Like Mr. Riggi, Mr. McMillan said that the healthcare industry is better prepared for cyberattacks now than it was in 2017, when the NotPetya assault on Ukraine’s online infrastructure created considerable collateral damage in the United States. However, he said, hospitals still have a long way to go before they can counter and/or recover from a dedicated Russian government cyberattack.
The NotPetya malware, Mr. Riggi said, was of the destructive variety. “That digital virus spread uncontrollably across the globe like a biological virus. All the organizations and institutions that had contact with Ukraine became infected.”
According to an indictment of six GRU officers that the Department of Justice announced in December 2020, NotPetya disrupted operations at a major pharmaceutical company, subsequently revealed to be Merck, and hospitals and other medical facilities in the Heritage Valley Health System in Pennsylvania. In addition, it temporarily shut down the transcription services of Nuance Communications, which lost $98 million as a result. Merck received $1.4 billion from an insurer to cover its NotPetya loss, Bloomberg reported.
That incident prompted the AHA to urge hospitals to use “geo-fencing” to block online communications with Ukraine and neighboring countries. However, Mr. Riggi said, that solution is not too effective because hackers commonly use proxy servers in other countries to forward their malware to the intended target.
The AHA alert included a list of actions that hospitals and health systems could take to reduce their vulnerability to Russian hacking. Besides geo-fencing, the AHA suggested that hospitals:
- Heighten staff awareness of the increased risk of receiving malware-laden phishing emails;
- Identify all international and third-party mission-critical, clinical, and operational services and technology and put in place business continuity plans and downtime procedures;
- Check the redundancy, resiliency, and security of the organization’s network and data backups;
- Document, update, and practice the organization’s incident response plan.
Hospitals increasingly targeted
In recent years, Mr. Riggi noted, hospitals have invested much more in cybersecurity than before, and hospital executives have told him that this is now one of their top priorities, along with COVID-19 and workforce issues. This has been not only because of NotPetya, but also because healthcare facilities are being increasingly attacked by foreign ransomware gangs, he says.
The hospitals’ biggest vulnerabilities, he said, are phishing emails, remote desktop access, and unpatched vulnerabilities, in that order. It’s not easy to remedy the latter, he observed, because hospital networks can include up to 100,000 connected medical devices and other computers that can access the network, both within and outside the hospital.
“With the new work-at-home environment, you may have thousands of employees who are using the network outside the traditional perimeter of the organization,” he pointed out. “There’s no longer that standard firewall that protects everything.” In addition, he said, hospitals also have to depend on vendors to develop patches and implement them.
In Mr. McMillan’s view, the healthcare industry is a decade behind the financial industry and other sectors in cybersecurity. Among other things, he says, “half of our hospitals still don’t have active monitoring on their networks. They don’t have privileged access on their networks. A bunch don’t have segmentation or endpoint protection. There are so many things that hospitals don’t have that they need to fend off these attacks — they’re better off than they were in 2017, but they still aren’t where they need to be.”
Physician practices also at risk
Employed physicians, naturally, are in danger of losing access to their electronic health records if their hospital’s network goes down as the result of a cyberattack, he notes. Many community doctors also use the EHR of a local hospital, and they’d be similarly affected, Mr. Riggi noted.
Physician practices might be saved if the attack were directed at the hospital and they could still connect to the EHR through a cloud provider, Mr. McMillan said. But Mr. Riggi stressed that practices still need a plan for their doctors to keep working if they lose access to a hospital EHR.
“The other possibility is that the practice could be targeted,” he added. “As hospitals become more hardened, often these hackers are looking for the weak link. The practices could become victims of increased targeting. And the practice becomes the conduit for malware to go from its system to the hospital and infect the hospital system.”
Hackers can hit service suppliers
Hospitals’ mission-critical service suppliers may also be targeted by Russian hackers and others, or they may be the accidental victims of a cyberattack elsewhere, Mr. Riggi noted. In the case of Nuance, he said, the disruption in transcription services affected thousands of U.S. healthcare providers who were unable to access their transcribed notes. This not only harmed patient care, but also meant that hospitals couldn’t fully bill for their services.
Another type of service supplier, he said, was struck with a ransomware attack last year. This was a cloud-based service that operated linear accelerators used in radiation oncology. “So radiation oncology and cancer treatment for patients across the U.S. was disrupted, and radiation oncology was delayed for some patients up to 3 weeks.”
More recently, another cloud-based service called Kronos was struck by ransomware. Because of this incident, payroll and timekeeping services were disrupted across several industries, including healthcare.
A version of this article first appeared on Medscape.com.