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Even small changes in fitness tied to lower mortality risk
Even relatively small changes in cardiorespiratory fitness (CRF) are associated with “considerable” impact on clinical symptoms and mortality risk among individuals with and without cardiovascular disease, new observational data in United States veterans suggest.
“We had a few surprises,” Peter Kokkinos, PhD, Robert Wood Johnson Medical School, New Brunswick, N. J., and the VA Medical Center, Washington, told this news organization. “First, the mortality risk was greatly attenuated in those who were moderate- and high-fit at baseline, despite a decline in fitness over time. In fact, in those with no CVD, the risk was not significantly elevated even when CRF declined by at least one MET [metabolic equivalent of task] for the moderate-fit and two or more METs for the high-fit group.”
“Second,” he said, “Our findings suggest that the impact of CRF on human health is not ephemeral, but rather carries a certain protection over time. Third, the changes in CRF necessary to impact mortality risk are relatively small (> 1.0 METs). This has a substantial clinical and public health significance.”
The study was published online in the Journal of the American College of Cardiology.
CRF up, mortality risk down
Dr. Kokkinos and colleagues analyzed data from 93,060 U.S. veterans; of these, 95% were men (mean age, 61.4 years) and 5% were women (mean age, 57.1 years). Overall, 72% of participants were White; 19.8%, African American; 5.2%, Hispanic; 1.9%, Native American, Asian, or Hawaiian; and 1.2%, unknown.
Participants were assigned to age-specific fitness quartiles based on peak METs achieved on a baseline exercise treadmill test (ETT). Each CRF quartile was stratified based on CRF changes (increase, decrease, no change) on the final ETT, with at least two ETT assessments at least 1 year apart.
The mean follow-up was 5.8 years (663,522 person-years), during which 18,302 deaths (19.7%) occurred, for an average annual mortality rate of 27.6 events per 1,000 person-years.
CRF was unchanged in 25.1% of the cohort, increased in 29.3%, and decreased in 45.6%. The trend was similar for those with and without CVD.
Significant differences were seen in all variables across CRF categories. In general, body weight, body mass index, CVD risk factors, and overall disease burden were progressively more unfavorable for those in the lowest CRF categories.
Conversely, medication use was progressively higher among those in low CRF categories.
After adjustment, higher CRF was inversely related to mortality risk for the entire cohort, with and without CVD. Cumulative survival rates across CRF categories declined progressively with increased fitness.
For patients with CVD (hazard ratio, 1.11), other significant predictors of all-cause mortality for patients were age (HR, 1.07), body mass index (HR, 0.98), chronic kidney disease (HR, 1.85), smoking (HR, 1.57), type 2 diabetes (HR, 1.42), hypertension (HR, 1.39), and cancers (HR, 1.37).
Generally, changes in CRF of at least 1.0 MET were associated with inverse and proportionate changes in mortality risk, regardless of baseline CRF status. For example, they note, a CRF decline of > 2.0 METs was associated with a 74% increased mortality risk for low-fit individuals with CVD, and a 69% increase for those without CVD.
A second analysis was done after excluding patients whose CRF declined and who died within 2 years of their last ETT, to account for the possibility that higher mortality rates and CRF declines were consequences of underlying disease (reverse causality). The association between changes in CRF and mortality risk persisted and remained similar to that observed in the entire cohort.
The authors add, “It is noteworthy that CRF increased by at least 1 MET in approximately 29% of the participants in the current study and decreased in approximately 46% of participants. This finding underscores the need to promote physical activity to maintain or increase CRF levels in middle-aged and older individuals.”
“Our findings make a persuasive argument that CRF is a strong and independent determinant of all-cause mortality risk, independent of genetic factors,” Dr. Kokkinos said. “We know that CRF is determined to some degree by genetic factors. However, improvements in aerobic capacity or CRF over time are largely the outcomes of regular engagement in aerobic activities of adequate intensity and volume.”
“Conversely,” he said, “a decline in CRF is likely the result of sedentary behavior, the onset of a chronic condition, or aging.”
If genetics were the sole contributor to mortality risk, then changes in CRF would not influence mortality risk, he concluded.
CRF impact “woefully underestimated”
Barry A. Franklin, PhD, past chair of both the American Heart Association’s Council on Physical Activity and Metabolism and the National Advocacy Committee, said the study substantiates previous smaller studies and is a “seminal” work.
“CRF is woefully underestimated as an index of health outcomes and survival,” said Dr. Franklin, director of preventive cardiology and cardiac rehabilitation at Beaumont Health in Royal Oak, Mich. “Moderate to vigorous physical activity should be regularly promoted by the medical community.”
Dr. Franklin’s recent review, published in Mayo Clinic Proceedings, provides evidence for other exercise benefits that clinicians may not be aware of, he noted. These include:
- Each 1 MET increase in CRF is generally associated with approximately 16% reduction in mortality.
- At any given risk factor profile or coronary calcium score, unfit people have 2-3 times the mortality as their fit counterparts.
- Fitness is inversely related to annual health care costs (each 1 MET increase in CRF is associated with approximately 6% lower annual health care costs).
- Physically active people hospitalized with acute coronary syndromes have better short-term outcomes (likely because of a phenomenon called ‘exercise preconditioning’).
- Fit people who undergo elective or emergent surgical procedures have better outcomes.
- Regular physical activity is a common characteristic in population subsets who routinely live into their 90s and to 100+.
Dr. Franklin had this advice for clinicians seeking to promote CRF increases of 1 MET or more among patients: “Sedentary people who embark on a walking program, who over time increase their walking speed to 3 mph or faster, invariably show at least a 1 MET increase in CRF during subsequent peak or symptom-limited treadmill testing.”
“Another general rule is that if an exercise program decreases heart rate at a given or fixed workload by about 10 beats per minute [bpm], the same treadmill workload that initially was accomplished at a heart rate of 120 bpm is now being accomplished at a heart rate of 110 bpm,” likely resulting in about a 1 MET increase in fitness.
“Accordingly,” he added, “a 20-bpm decrease would suggest a 2 MET increase in fitness!”
In a related editorial, Leonard A. Kaminsky, Ball State University, Muncie, Ind. and colleagues, write, “We agree with and believe the conclusion, reached by Kokkinos et al., bears repeating. We (again) call on both clinicians and public health professionals to adopt CRF as a key health indicator.”
“This should be done by coupling routine assessments of CRF with continued advocacy for promoting physical activity as an essential healthy lifestyle behavior,” they write.
No funding or relevant financial relationships were disclosed.
A version of this article first appeared on Medscape.com.
Even relatively small changes in cardiorespiratory fitness (CRF) are associated with “considerable” impact on clinical symptoms and mortality risk among individuals with and without cardiovascular disease, new observational data in United States veterans suggest.
“We had a few surprises,” Peter Kokkinos, PhD, Robert Wood Johnson Medical School, New Brunswick, N. J., and the VA Medical Center, Washington, told this news organization. “First, the mortality risk was greatly attenuated in those who were moderate- and high-fit at baseline, despite a decline in fitness over time. In fact, in those with no CVD, the risk was not significantly elevated even when CRF declined by at least one MET [metabolic equivalent of task] for the moderate-fit and two or more METs for the high-fit group.”
“Second,” he said, “Our findings suggest that the impact of CRF on human health is not ephemeral, but rather carries a certain protection over time. Third, the changes in CRF necessary to impact mortality risk are relatively small (> 1.0 METs). This has a substantial clinical and public health significance.”
The study was published online in the Journal of the American College of Cardiology.
CRF up, mortality risk down
Dr. Kokkinos and colleagues analyzed data from 93,060 U.S. veterans; of these, 95% were men (mean age, 61.4 years) and 5% were women (mean age, 57.1 years). Overall, 72% of participants were White; 19.8%, African American; 5.2%, Hispanic; 1.9%, Native American, Asian, or Hawaiian; and 1.2%, unknown.
Participants were assigned to age-specific fitness quartiles based on peak METs achieved on a baseline exercise treadmill test (ETT). Each CRF quartile was stratified based on CRF changes (increase, decrease, no change) on the final ETT, with at least two ETT assessments at least 1 year apart.
The mean follow-up was 5.8 years (663,522 person-years), during which 18,302 deaths (19.7%) occurred, for an average annual mortality rate of 27.6 events per 1,000 person-years.
CRF was unchanged in 25.1% of the cohort, increased in 29.3%, and decreased in 45.6%. The trend was similar for those with and without CVD.
Significant differences were seen in all variables across CRF categories. In general, body weight, body mass index, CVD risk factors, and overall disease burden were progressively more unfavorable for those in the lowest CRF categories.
Conversely, medication use was progressively higher among those in low CRF categories.
After adjustment, higher CRF was inversely related to mortality risk for the entire cohort, with and without CVD. Cumulative survival rates across CRF categories declined progressively with increased fitness.
For patients with CVD (hazard ratio, 1.11), other significant predictors of all-cause mortality for patients were age (HR, 1.07), body mass index (HR, 0.98), chronic kidney disease (HR, 1.85), smoking (HR, 1.57), type 2 diabetes (HR, 1.42), hypertension (HR, 1.39), and cancers (HR, 1.37).
Generally, changes in CRF of at least 1.0 MET were associated with inverse and proportionate changes in mortality risk, regardless of baseline CRF status. For example, they note, a CRF decline of > 2.0 METs was associated with a 74% increased mortality risk for low-fit individuals with CVD, and a 69% increase for those without CVD.
A second analysis was done after excluding patients whose CRF declined and who died within 2 years of their last ETT, to account for the possibility that higher mortality rates and CRF declines were consequences of underlying disease (reverse causality). The association between changes in CRF and mortality risk persisted and remained similar to that observed in the entire cohort.
The authors add, “It is noteworthy that CRF increased by at least 1 MET in approximately 29% of the participants in the current study and decreased in approximately 46% of participants. This finding underscores the need to promote physical activity to maintain or increase CRF levels in middle-aged and older individuals.”
“Our findings make a persuasive argument that CRF is a strong and independent determinant of all-cause mortality risk, independent of genetic factors,” Dr. Kokkinos said. “We know that CRF is determined to some degree by genetic factors. However, improvements in aerobic capacity or CRF over time are largely the outcomes of regular engagement in aerobic activities of adequate intensity and volume.”
“Conversely,” he said, “a decline in CRF is likely the result of sedentary behavior, the onset of a chronic condition, or aging.”
If genetics were the sole contributor to mortality risk, then changes in CRF would not influence mortality risk, he concluded.
CRF impact “woefully underestimated”
Barry A. Franklin, PhD, past chair of both the American Heart Association’s Council on Physical Activity and Metabolism and the National Advocacy Committee, said the study substantiates previous smaller studies and is a “seminal” work.
“CRF is woefully underestimated as an index of health outcomes and survival,” said Dr. Franklin, director of preventive cardiology and cardiac rehabilitation at Beaumont Health in Royal Oak, Mich. “Moderate to vigorous physical activity should be regularly promoted by the medical community.”
Dr. Franklin’s recent review, published in Mayo Clinic Proceedings, provides evidence for other exercise benefits that clinicians may not be aware of, he noted. These include:
- Each 1 MET increase in CRF is generally associated with approximately 16% reduction in mortality.
- At any given risk factor profile or coronary calcium score, unfit people have 2-3 times the mortality as their fit counterparts.
- Fitness is inversely related to annual health care costs (each 1 MET increase in CRF is associated with approximately 6% lower annual health care costs).
- Physically active people hospitalized with acute coronary syndromes have better short-term outcomes (likely because of a phenomenon called ‘exercise preconditioning’).
- Fit people who undergo elective or emergent surgical procedures have better outcomes.
- Regular physical activity is a common characteristic in population subsets who routinely live into their 90s and to 100+.
Dr. Franklin had this advice for clinicians seeking to promote CRF increases of 1 MET or more among patients: “Sedentary people who embark on a walking program, who over time increase their walking speed to 3 mph or faster, invariably show at least a 1 MET increase in CRF during subsequent peak or symptom-limited treadmill testing.”
“Another general rule is that if an exercise program decreases heart rate at a given or fixed workload by about 10 beats per minute [bpm], the same treadmill workload that initially was accomplished at a heart rate of 120 bpm is now being accomplished at a heart rate of 110 bpm,” likely resulting in about a 1 MET increase in fitness.
“Accordingly,” he added, “a 20-bpm decrease would suggest a 2 MET increase in fitness!”
In a related editorial, Leonard A. Kaminsky, Ball State University, Muncie, Ind. and colleagues, write, “We agree with and believe the conclusion, reached by Kokkinos et al., bears repeating. We (again) call on both clinicians and public health professionals to adopt CRF as a key health indicator.”
“This should be done by coupling routine assessments of CRF with continued advocacy for promoting physical activity as an essential healthy lifestyle behavior,” they write.
No funding or relevant financial relationships were disclosed.
A version of this article first appeared on Medscape.com.
Even relatively small changes in cardiorespiratory fitness (CRF) are associated with “considerable” impact on clinical symptoms and mortality risk among individuals with and without cardiovascular disease, new observational data in United States veterans suggest.
“We had a few surprises,” Peter Kokkinos, PhD, Robert Wood Johnson Medical School, New Brunswick, N. J., and the VA Medical Center, Washington, told this news organization. “First, the mortality risk was greatly attenuated in those who were moderate- and high-fit at baseline, despite a decline in fitness over time. In fact, in those with no CVD, the risk was not significantly elevated even when CRF declined by at least one MET [metabolic equivalent of task] for the moderate-fit and two or more METs for the high-fit group.”
“Second,” he said, “Our findings suggest that the impact of CRF on human health is not ephemeral, but rather carries a certain protection over time. Third, the changes in CRF necessary to impact mortality risk are relatively small (> 1.0 METs). This has a substantial clinical and public health significance.”
The study was published online in the Journal of the American College of Cardiology.
CRF up, mortality risk down
Dr. Kokkinos and colleagues analyzed data from 93,060 U.S. veterans; of these, 95% were men (mean age, 61.4 years) and 5% were women (mean age, 57.1 years). Overall, 72% of participants were White; 19.8%, African American; 5.2%, Hispanic; 1.9%, Native American, Asian, or Hawaiian; and 1.2%, unknown.
Participants were assigned to age-specific fitness quartiles based on peak METs achieved on a baseline exercise treadmill test (ETT). Each CRF quartile was stratified based on CRF changes (increase, decrease, no change) on the final ETT, with at least two ETT assessments at least 1 year apart.
The mean follow-up was 5.8 years (663,522 person-years), during which 18,302 deaths (19.7%) occurred, for an average annual mortality rate of 27.6 events per 1,000 person-years.
CRF was unchanged in 25.1% of the cohort, increased in 29.3%, and decreased in 45.6%. The trend was similar for those with and without CVD.
Significant differences were seen in all variables across CRF categories. In general, body weight, body mass index, CVD risk factors, and overall disease burden were progressively more unfavorable for those in the lowest CRF categories.
Conversely, medication use was progressively higher among those in low CRF categories.
After adjustment, higher CRF was inversely related to mortality risk for the entire cohort, with and without CVD. Cumulative survival rates across CRF categories declined progressively with increased fitness.
For patients with CVD (hazard ratio, 1.11), other significant predictors of all-cause mortality for patients were age (HR, 1.07), body mass index (HR, 0.98), chronic kidney disease (HR, 1.85), smoking (HR, 1.57), type 2 diabetes (HR, 1.42), hypertension (HR, 1.39), and cancers (HR, 1.37).
Generally, changes in CRF of at least 1.0 MET were associated with inverse and proportionate changes in mortality risk, regardless of baseline CRF status. For example, they note, a CRF decline of > 2.0 METs was associated with a 74% increased mortality risk for low-fit individuals with CVD, and a 69% increase for those without CVD.
A second analysis was done after excluding patients whose CRF declined and who died within 2 years of their last ETT, to account for the possibility that higher mortality rates and CRF declines were consequences of underlying disease (reverse causality). The association between changes in CRF and mortality risk persisted and remained similar to that observed in the entire cohort.
The authors add, “It is noteworthy that CRF increased by at least 1 MET in approximately 29% of the participants in the current study and decreased in approximately 46% of participants. This finding underscores the need to promote physical activity to maintain or increase CRF levels in middle-aged and older individuals.”
“Our findings make a persuasive argument that CRF is a strong and independent determinant of all-cause mortality risk, independent of genetic factors,” Dr. Kokkinos said. “We know that CRF is determined to some degree by genetic factors. However, improvements in aerobic capacity or CRF over time are largely the outcomes of regular engagement in aerobic activities of adequate intensity and volume.”
“Conversely,” he said, “a decline in CRF is likely the result of sedentary behavior, the onset of a chronic condition, or aging.”
If genetics were the sole contributor to mortality risk, then changes in CRF would not influence mortality risk, he concluded.
CRF impact “woefully underestimated”
Barry A. Franklin, PhD, past chair of both the American Heart Association’s Council on Physical Activity and Metabolism and the National Advocacy Committee, said the study substantiates previous smaller studies and is a “seminal” work.
“CRF is woefully underestimated as an index of health outcomes and survival,” said Dr. Franklin, director of preventive cardiology and cardiac rehabilitation at Beaumont Health in Royal Oak, Mich. “Moderate to vigorous physical activity should be regularly promoted by the medical community.”
Dr. Franklin’s recent review, published in Mayo Clinic Proceedings, provides evidence for other exercise benefits that clinicians may not be aware of, he noted. These include:
- Each 1 MET increase in CRF is generally associated with approximately 16% reduction in mortality.
- At any given risk factor profile or coronary calcium score, unfit people have 2-3 times the mortality as their fit counterparts.
- Fitness is inversely related to annual health care costs (each 1 MET increase in CRF is associated with approximately 6% lower annual health care costs).
- Physically active people hospitalized with acute coronary syndromes have better short-term outcomes (likely because of a phenomenon called ‘exercise preconditioning’).
- Fit people who undergo elective or emergent surgical procedures have better outcomes.
- Regular physical activity is a common characteristic in population subsets who routinely live into their 90s and to 100+.
Dr. Franklin had this advice for clinicians seeking to promote CRF increases of 1 MET or more among patients: “Sedentary people who embark on a walking program, who over time increase their walking speed to 3 mph or faster, invariably show at least a 1 MET increase in CRF during subsequent peak or symptom-limited treadmill testing.”
“Another general rule is that if an exercise program decreases heart rate at a given or fixed workload by about 10 beats per minute [bpm], the same treadmill workload that initially was accomplished at a heart rate of 120 bpm is now being accomplished at a heart rate of 110 bpm,” likely resulting in about a 1 MET increase in fitness.
“Accordingly,” he added, “a 20-bpm decrease would suggest a 2 MET increase in fitness!”
In a related editorial, Leonard A. Kaminsky, Ball State University, Muncie, Ind. and colleagues, write, “We agree with and believe the conclusion, reached by Kokkinos et al., bears repeating. We (again) call on both clinicians and public health professionals to adopt CRF as a key health indicator.”
“This should be done by coupling routine assessments of CRF with continued advocacy for promoting physical activity as an essential healthy lifestyle behavior,” they write.
No funding or relevant financial relationships were disclosed.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Sports-related sudden cardiac arrest ‘extremely’ rare in women
Sports-related sudden cardiac arrest (Sr-SCA) appears to be extremely rare in women, compared with men, despite similar characteristics and circumstances of occurrence, data from three European population-based registries suggest.
“Our study shows that cardiac arrest during sports activities is up to 13 times less frequent in women, which means that the risk of sports-related cardiac arrest is substantially lower in women than in men. This tighter risk is consistent across all age subgroups and registries,” Orianne Weizman, MD, MPH, Université Paris Cité, said in an interview.
“Even if it is a nonconsensual suggestion, the question of risk-adapted screening in women must be asked,” Dr. Weizman and colleagues propose.
Their study was published online in the Journal of the American College of Cardiology.
Annual incidence
Among 34,826 cases of SCA in the registries that occurred in adults between 2006 and 2017, 760 (2.2%) were related to sports, and the vast majority occurred in men (706, 92.9%). Only 54 (7.1%) occurred in women.
Overall, the average annual incidence of Sr-SCA in women was 0.19 per million, compared with 2.63 per million in men (P < .0001).
When extrapolating to the total European population and accounting for age and sex, this translates into 98 expected cases of Sr-SCA each year in women versus 1,350 cases annually in men.
The average age of Sr-SCA was similar in women and men (59 years). Most cases occurred during moderate-vigorous physical activity, although data on the types of sports and time spent on sports per week or month were not defined.
However, the investigators note that women with Sr-SCA were more likely than men to be engaged in light or moderate physical activity at the time of arrest (17.5% vs. 4.2%) – suggesting a potential higher propensity for women to present with SCA at moderate workloads.
The incidence of Sr-SCA increased only slightly in postmenopausal women, while there was an 8-fold increase in men aged 60-74 years, relative to peers younger than 40 years.
History of heart disease was relatively uncommon in both men and women. Previous myocardial infarction was the most frequent preexisting condition in men (26.8%), whereas nonischemic heart disease (cardiomyopathy and valvular heart disease) was more frequent among women (29.0%).
Cardiovascular risk factors were frequently present in both men and women, with at least one factor present in two-thirds of the patients, regardless of sex.
Pulseless electrical activity and asystole were more common in women than in men (40.7% vs. 19.1%), as has been shown in previous studies of resuscitation from SCA in the general population. Ventricular tachycardia or fibrillation was the initial rhythm in 80.9% of men and 59.3% of women.
The cause of SCA was MI in 31.4% of women and 29.0% of men. Other cases were related to dilated cardiomyopathy (5.6% in women, 1.8% in men) or hypertrophic cardiomyopathy (1.9% in women, 1.3% in men). Electrical heart disease was found in two women (3.7%) and 15 men (2.1%).
In most cases (86%), one or more witnesses were present and assisted after the collapse. There was no significant difference between men and women in bystander response, time to defibrillation, and survival, which approached 60% at hospital discharge with early bystander cardiorespiratory resuscitation and automatic external defibrillator use.
A limitation of the study is a predominantly White European population, meaning that the findings may not be extrapolated to other populations.
Tailored screening?
“These findings raise questions about the causes of this extremely low risk, which are not yet clear, and the extent to which we should revise our pre-sport screening methods,” Dr. Weizman told this news organization.
“We suggest that extensive, routinely conducted screening in women would not be cost-effective because of the extremely rare incidence of serious events,” Dr. Weizman said.
What’s lacking, however, is sport-specific data on whether specific activities (endurance or resistance) would be more risky for women. Further information, particularly on the sports at highest risk for Sr-SCA in women, is needed to propose tailor-made screening algorithms, Dr. Weizman noted.
The value of preparticipation screening for occult heart disease beyond the history and physical examination has been debated, with some organizations recommending electrocardiogram in addition to baseline assessments.
But this can lead to false-positives, “with the anxiety and cost associated with additional testing,” Anne Curtis, MD, State University of New York at Buffalo, Buffalo General Medical Center, and Jan Tijssen, PhD, University of Amsterdam, write in a linked editorial.
Currently, the American Heart Association recommends screening before sports participation, with a focused personal and family history and physical examination.
Dr. Curtis told this news organization that the U.S. guidelines “should stay as they are, but if one were to change them, it would be important to recognize that male athletes are much more likely to suffer arrhythmic events during sports than female athletes.”
“That to me means that female athletes in particular should not need to have ECGs prior to sports participation unless the history and physical examination detects a potential problem that needs further investigation,” Dr. Curtis said.
“Both women and men should be screened for cardiovascular risk factors during routine primary care, with appropriate interventions for hypertension, hyperlipidemia, smoking, and other risk factors,” Dr. Curtis and Dr. Tijssen advise in their editorial.
“In asymptomatic individuals who wish to become more active, in most cases they should be given the green light to proceed, starting slow and increasing intensity/duration over time, without specific additional testing. This advice is particularly relevant for women, given the findings of the current and prior studies,” they add.
This research was funded by Horizon 2020 and COST Action PARQ, supported by the European Cooperation in Science and Technology. Additional support was provided by INSERM, University of Paris, Assistance Publique-Hôpitaux de Paris, Fondation Coeur et Artères, Global Heart Watch, Fédération Française de Cardiologie, Société Française de Cardiologie, Fondation Recherche Medicale, as well as unrestricted grants from industrial partners. The authors and Dr. Tijssen have declared no relevant financial relationships. Dr. Curtis has disclosed relationships with Janssen several pharmaceutical companies.
A version of this article first appeared on Medscape.com.
Sports-related sudden cardiac arrest (Sr-SCA) appears to be extremely rare in women, compared with men, despite similar characteristics and circumstances of occurrence, data from three European population-based registries suggest.
“Our study shows that cardiac arrest during sports activities is up to 13 times less frequent in women, which means that the risk of sports-related cardiac arrest is substantially lower in women than in men. This tighter risk is consistent across all age subgroups and registries,” Orianne Weizman, MD, MPH, Université Paris Cité, said in an interview.
“Even if it is a nonconsensual suggestion, the question of risk-adapted screening in women must be asked,” Dr. Weizman and colleagues propose.
Their study was published online in the Journal of the American College of Cardiology.
Annual incidence
Among 34,826 cases of SCA in the registries that occurred in adults between 2006 and 2017, 760 (2.2%) were related to sports, and the vast majority occurred in men (706, 92.9%). Only 54 (7.1%) occurred in women.
Overall, the average annual incidence of Sr-SCA in women was 0.19 per million, compared with 2.63 per million in men (P < .0001).
When extrapolating to the total European population and accounting for age and sex, this translates into 98 expected cases of Sr-SCA each year in women versus 1,350 cases annually in men.
The average age of Sr-SCA was similar in women and men (59 years). Most cases occurred during moderate-vigorous physical activity, although data on the types of sports and time spent on sports per week or month were not defined.
However, the investigators note that women with Sr-SCA were more likely than men to be engaged in light or moderate physical activity at the time of arrest (17.5% vs. 4.2%) – suggesting a potential higher propensity for women to present with SCA at moderate workloads.
The incidence of Sr-SCA increased only slightly in postmenopausal women, while there was an 8-fold increase in men aged 60-74 years, relative to peers younger than 40 years.
History of heart disease was relatively uncommon in both men and women. Previous myocardial infarction was the most frequent preexisting condition in men (26.8%), whereas nonischemic heart disease (cardiomyopathy and valvular heart disease) was more frequent among women (29.0%).
Cardiovascular risk factors were frequently present in both men and women, with at least one factor present in two-thirds of the patients, regardless of sex.
Pulseless electrical activity and asystole were more common in women than in men (40.7% vs. 19.1%), as has been shown in previous studies of resuscitation from SCA in the general population. Ventricular tachycardia or fibrillation was the initial rhythm in 80.9% of men and 59.3% of women.
The cause of SCA was MI in 31.4% of women and 29.0% of men. Other cases were related to dilated cardiomyopathy (5.6% in women, 1.8% in men) or hypertrophic cardiomyopathy (1.9% in women, 1.3% in men). Electrical heart disease was found in two women (3.7%) and 15 men (2.1%).
In most cases (86%), one or more witnesses were present and assisted after the collapse. There was no significant difference between men and women in bystander response, time to defibrillation, and survival, which approached 60% at hospital discharge with early bystander cardiorespiratory resuscitation and automatic external defibrillator use.
A limitation of the study is a predominantly White European population, meaning that the findings may not be extrapolated to other populations.
Tailored screening?
“These findings raise questions about the causes of this extremely low risk, which are not yet clear, and the extent to which we should revise our pre-sport screening methods,” Dr. Weizman told this news organization.
“We suggest that extensive, routinely conducted screening in women would not be cost-effective because of the extremely rare incidence of serious events,” Dr. Weizman said.
What’s lacking, however, is sport-specific data on whether specific activities (endurance or resistance) would be more risky for women. Further information, particularly on the sports at highest risk for Sr-SCA in women, is needed to propose tailor-made screening algorithms, Dr. Weizman noted.
The value of preparticipation screening for occult heart disease beyond the history and physical examination has been debated, with some organizations recommending electrocardiogram in addition to baseline assessments.
But this can lead to false-positives, “with the anxiety and cost associated with additional testing,” Anne Curtis, MD, State University of New York at Buffalo, Buffalo General Medical Center, and Jan Tijssen, PhD, University of Amsterdam, write in a linked editorial.
Currently, the American Heart Association recommends screening before sports participation, with a focused personal and family history and physical examination.
Dr. Curtis told this news organization that the U.S. guidelines “should stay as they are, but if one were to change them, it would be important to recognize that male athletes are much more likely to suffer arrhythmic events during sports than female athletes.”
“That to me means that female athletes in particular should not need to have ECGs prior to sports participation unless the history and physical examination detects a potential problem that needs further investigation,” Dr. Curtis said.
“Both women and men should be screened for cardiovascular risk factors during routine primary care, with appropriate interventions for hypertension, hyperlipidemia, smoking, and other risk factors,” Dr. Curtis and Dr. Tijssen advise in their editorial.
“In asymptomatic individuals who wish to become more active, in most cases they should be given the green light to proceed, starting slow and increasing intensity/duration over time, without specific additional testing. This advice is particularly relevant for women, given the findings of the current and prior studies,” they add.
This research was funded by Horizon 2020 and COST Action PARQ, supported by the European Cooperation in Science and Technology. Additional support was provided by INSERM, University of Paris, Assistance Publique-Hôpitaux de Paris, Fondation Coeur et Artères, Global Heart Watch, Fédération Française de Cardiologie, Société Française de Cardiologie, Fondation Recherche Medicale, as well as unrestricted grants from industrial partners. The authors and Dr. Tijssen have declared no relevant financial relationships. Dr. Curtis has disclosed relationships with Janssen several pharmaceutical companies.
A version of this article first appeared on Medscape.com.
Sports-related sudden cardiac arrest (Sr-SCA) appears to be extremely rare in women, compared with men, despite similar characteristics and circumstances of occurrence, data from three European population-based registries suggest.
“Our study shows that cardiac arrest during sports activities is up to 13 times less frequent in women, which means that the risk of sports-related cardiac arrest is substantially lower in women than in men. This tighter risk is consistent across all age subgroups and registries,” Orianne Weizman, MD, MPH, Université Paris Cité, said in an interview.
“Even if it is a nonconsensual suggestion, the question of risk-adapted screening in women must be asked,” Dr. Weizman and colleagues propose.
Their study was published online in the Journal of the American College of Cardiology.
Annual incidence
Among 34,826 cases of SCA in the registries that occurred in adults between 2006 and 2017, 760 (2.2%) were related to sports, and the vast majority occurred in men (706, 92.9%). Only 54 (7.1%) occurred in women.
Overall, the average annual incidence of Sr-SCA in women was 0.19 per million, compared with 2.63 per million in men (P < .0001).
When extrapolating to the total European population and accounting for age and sex, this translates into 98 expected cases of Sr-SCA each year in women versus 1,350 cases annually in men.
The average age of Sr-SCA was similar in women and men (59 years). Most cases occurred during moderate-vigorous physical activity, although data on the types of sports and time spent on sports per week or month were not defined.
However, the investigators note that women with Sr-SCA were more likely than men to be engaged in light or moderate physical activity at the time of arrest (17.5% vs. 4.2%) – suggesting a potential higher propensity for women to present with SCA at moderate workloads.
The incidence of Sr-SCA increased only slightly in postmenopausal women, while there was an 8-fold increase in men aged 60-74 years, relative to peers younger than 40 years.
History of heart disease was relatively uncommon in both men and women. Previous myocardial infarction was the most frequent preexisting condition in men (26.8%), whereas nonischemic heart disease (cardiomyopathy and valvular heart disease) was more frequent among women (29.0%).
Cardiovascular risk factors were frequently present in both men and women, with at least one factor present in two-thirds of the patients, regardless of sex.
Pulseless electrical activity and asystole were more common in women than in men (40.7% vs. 19.1%), as has been shown in previous studies of resuscitation from SCA in the general population. Ventricular tachycardia or fibrillation was the initial rhythm in 80.9% of men and 59.3% of women.
The cause of SCA was MI in 31.4% of women and 29.0% of men. Other cases were related to dilated cardiomyopathy (5.6% in women, 1.8% in men) or hypertrophic cardiomyopathy (1.9% in women, 1.3% in men). Electrical heart disease was found in two women (3.7%) and 15 men (2.1%).
In most cases (86%), one or more witnesses were present and assisted after the collapse. There was no significant difference between men and women in bystander response, time to defibrillation, and survival, which approached 60% at hospital discharge with early bystander cardiorespiratory resuscitation and automatic external defibrillator use.
A limitation of the study is a predominantly White European population, meaning that the findings may not be extrapolated to other populations.
Tailored screening?
“These findings raise questions about the causes of this extremely low risk, which are not yet clear, and the extent to which we should revise our pre-sport screening methods,” Dr. Weizman told this news organization.
“We suggest that extensive, routinely conducted screening in women would not be cost-effective because of the extremely rare incidence of serious events,” Dr. Weizman said.
What’s lacking, however, is sport-specific data on whether specific activities (endurance or resistance) would be more risky for women. Further information, particularly on the sports at highest risk for Sr-SCA in women, is needed to propose tailor-made screening algorithms, Dr. Weizman noted.
The value of preparticipation screening for occult heart disease beyond the history and physical examination has been debated, with some organizations recommending electrocardiogram in addition to baseline assessments.
But this can lead to false-positives, “with the anxiety and cost associated with additional testing,” Anne Curtis, MD, State University of New York at Buffalo, Buffalo General Medical Center, and Jan Tijssen, PhD, University of Amsterdam, write in a linked editorial.
Currently, the American Heart Association recommends screening before sports participation, with a focused personal and family history and physical examination.
Dr. Curtis told this news organization that the U.S. guidelines “should stay as they are, but if one were to change them, it would be important to recognize that male athletes are much more likely to suffer arrhythmic events during sports than female athletes.”
“That to me means that female athletes in particular should not need to have ECGs prior to sports participation unless the history and physical examination detects a potential problem that needs further investigation,” Dr. Curtis said.
“Both women and men should be screened for cardiovascular risk factors during routine primary care, with appropriate interventions for hypertension, hyperlipidemia, smoking, and other risk factors,” Dr. Curtis and Dr. Tijssen advise in their editorial.
“In asymptomatic individuals who wish to become more active, in most cases they should be given the green light to proceed, starting slow and increasing intensity/duration over time, without specific additional testing. This advice is particularly relevant for women, given the findings of the current and prior studies,” they add.
This research was funded by Horizon 2020 and COST Action PARQ, supported by the European Cooperation in Science and Technology. Additional support was provided by INSERM, University of Paris, Assistance Publique-Hôpitaux de Paris, Fondation Coeur et Artères, Global Heart Watch, Fédération Française de Cardiologie, Société Française de Cardiologie, Fondation Recherche Medicale, as well as unrestricted grants from industrial partners. The authors and Dr. Tijssen have declared no relevant financial relationships. Dr. Curtis has disclosed relationships with Janssen several pharmaceutical companies.
A version of this article first appeared on Medscape.com.
Tooth loss and diabetes together hasten mental decline
most specifically in those 65-74 years of age, new findings suggest.
The data come from a 12-year follow-up of older adults in a nationally representative U.S. survey.
“From a clinical perspective, our study demonstrates the importance of improving access to dental health care and integrating primary dental and medical care. Health care professionals and family caregivers should pay close attention to the cognitive status of diabetic older adults with poor oral health status,” lead author Bei Wu, PhD, of New York University, said in an interview. Dr. Wu is the Dean’s Professor in Global Health and codirector of the NYU Aging Incubator.
Moreover, said Dr. Wu: “For individuals with both poor oral health and diabetes, regular dental visits should be encouraged in addition to adherence to the diabetes self-care protocol.”
Diabetes has long been recognized as a risk factor for cognitive decline, but the findings have been inconsistent for different age groups. Tooth loss has also been linked to cognitive decline and dementia, as well as diabetes.
The mechanisms aren’t entirely clear, but “co-occurring diabetes and poor oral health may increase the risk for dementia, possibly via the potentially interrelated pathways of chronic inflammation and cardiovascular risk factors,” Dr. Wu said.
The new study, published in the Journal of Dental Research, is the first to examine the relationships between all three conditions by age group.
Diabetes, edentulism, and cognitive decline
The data came from a total of 9,948 participants in the Health and Retirement Study (HRS) from 2006 to 2018. At baseline, 5,440 participants were aged 65-74 years, 3,300 were aged 75-84, and 1,208 were aged 85 years or older.
They were assessed every 2 years using the 35-point Telephone Survey for Cognitive Status, which included tests of immediate and delayed word recall, repeated subtracting by 7, counting backward from 20, naming objects, and naming the president and vice president of the U.S. As might be expected, the youngest group scored the highest, averaging 23 points, while the oldest group scored lowest, at 18.5 points.
Participants were also asked if they had ever been told by a doctor that they have diabetes. Another question was: “Have you lost all of your upper and lower natural permanent teeth?”
The condition of having no teeth is known as edentulism.
The percentages of participants who reported having both diabetes and edentulism were 6.0%, 6.7%, and 5.0% for those aged 65-74 years, 75-84 years, and 85 years or older, respectively. The proportions with neither of those conditions were 63.5%, 60.4%, and 58.3% in those three age groups, respectively (P < .001).
Compared with their counterparts with neither diabetes nor edentulism at baseline, older adults with both conditions aged 65-74 years (P < .001) and aged 75-84 years had worse cognitive function (P < .001).
In terms of the rate of cognitive decline, compared with those with neither condition from the same age cohort, older adults aged 65-74 years with both conditions declined at a higher rate (P < .001).
Having diabetes alone led to accelerated cognitive decline in older adults aged 65-74 years (P < .001). Having edentulism alone led to accelerated decline in older adults aged 65-74 years (P < .001) and older adults aged 75-84 years (P < 0.01).
“Our study finds the co-occurrence of diabetes and edentulism led to a worse cognitive function and a faster cognitive decline in older adults aged 65-74 years,” say Wu and colleagues.
Study limitations: Better data needed
The study has several limitations, most of them due to the data source. For example, while the HRS collects detailed information on cognitive status, edentulism is its only measure of oral health. There were no data on whether individuals had replacements such as dentures or implants that would affect their ability to eat, which could influence other health factors.
“I have made repeated appeals for federal funding to collect more oral health-related information in large national surveys,” Dr. Wu told this news organization.
Similarly, assessments of diabetes status such as hemoglobin A1c were only available for small subsets and not sufficient to demonstrate statistical significance, she explained.
Dr. Wu suggested that both oral health and cognitive screening might be included in the “Welcome to Medicare” preventive visit. In addition, “Oral hygiene practice should also be highlighted to improve cognitive health. Developing dental care interventions and programs are needed for reducing the societal cost of dementia.”
The study was partially supported by the National Institutes of Health. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
most specifically in those 65-74 years of age, new findings suggest.
The data come from a 12-year follow-up of older adults in a nationally representative U.S. survey.
“From a clinical perspective, our study demonstrates the importance of improving access to dental health care and integrating primary dental and medical care. Health care professionals and family caregivers should pay close attention to the cognitive status of diabetic older adults with poor oral health status,” lead author Bei Wu, PhD, of New York University, said in an interview. Dr. Wu is the Dean’s Professor in Global Health and codirector of the NYU Aging Incubator.
Moreover, said Dr. Wu: “For individuals with both poor oral health and diabetes, regular dental visits should be encouraged in addition to adherence to the diabetes self-care protocol.”
Diabetes has long been recognized as a risk factor for cognitive decline, but the findings have been inconsistent for different age groups. Tooth loss has also been linked to cognitive decline and dementia, as well as diabetes.
The mechanisms aren’t entirely clear, but “co-occurring diabetes and poor oral health may increase the risk for dementia, possibly via the potentially interrelated pathways of chronic inflammation and cardiovascular risk factors,” Dr. Wu said.
The new study, published in the Journal of Dental Research, is the first to examine the relationships between all three conditions by age group.
Diabetes, edentulism, and cognitive decline
The data came from a total of 9,948 participants in the Health and Retirement Study (HRS) from 2006 to 2018. At baseline, 5,440 participants were aged 65-74 years, 3,300 were aged 75-84, and 1,208 were aged 85 years or older.
They were assessed every 2 years using the 35-point Telephone Survey for Cognitive Status, which included tests of immediate and delayed word recall, repeated subtracting by 7, counting backward from 20, naming objects, and naming the president and vice president of the U.S. As might be expected, the youngest group scored the highest, averaging 23 points, while the oldest group scored lowest, at 18.5 points.
Participants were also asked if they had ever been told by a doctor that they have diabetes. Another question was: “Have you lost all of your upper and lower natural permanent teeth?”
The condition of having no teeth is known as edentulism.
The percentages of participants who reported having both diabetes and edentulism were 6.0%, 6.7%, and 5.0% for those aged 65-74 years, 75-84 years, and 85 years or older, respectively. The proportions with neither of those conditions were 63.5%, 60.4%, and 58.3% in those three age groups, respectively (P < .001).
Compared with their counterparts with neither diabetes nor edentulism at baseline, older adults with both conditions aged 65-74 years (P < .001) and aged 75-84 years had worse cognitive function (P < .001).
In terms of the rate of cognitive decline, compared with those with neither condition from the same age cohort, older adults aged 65-74 years with both conditions declined at a higher rate (P < .001).
Having diabetes alone led to accelerated cognitive decline in older adults aged 65-74 years (P < .001). Having edentulism alone led to accelerated decline in older adults aged 65-74 years (P < .001) and older adults aged 75-84 years (P < 0.01).
“Our study finds the co-occurrence of diabetes and edentulism led to a worse cognitive function and a faster cognitive decline in older adults aged 65-74 years,” say Wu and colleagues.
Study limitations: Better data needed
The study has several limitations, most of them due to the data source. For example, while the HRS collects detailed information on cognitive status, edentulism is its only measure of oral health. There were no data on whether individuals had replacements such as dentures or implants that would affect their ability to eat, which could influence other health factors.
“I have made repeated appeals for federal funding to collect more oral health-related information in large national surveys,” Dr. Wu told this news organization.
Similarly, assessments of diabetes status such as hemoglobin A1c were only available for small subsets and not sufficient to demonstrate statistical significance, she explained.
Dr. Wu suggested that both oral health and cognitive screening might be included in the “Welcome to Medicare” preventive visit. In addition, “Oral hygiene practice should also be highlighted to improve cognitive health. Developing dental care interventions and programs are needed for reducing the societal cost of dementia.”
The study was partially supported by the National Institutes of Health. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
most specifically in those 65-74 years of age, new findings suggest.
The data come from a 12-year follow-up of older adults in a nationally representative U.S. survey.
“From a clinical perspective, our study demonstrates the importance of improving access to dental health care and integrating primary dental and medical care. Health care professionals and family caregivers should pay close attention to the cognitive status of diabetic older adults with poor oral health status,” lead author Bei Wu, PhD, of New York University, said in an interview. Dr. Wu is the Dean’s Professor in Global Health and codirector of the NYU Aging Incubator.
Moreover, said Dr. Wu: “For individuals with both poor oral health and diabetes, regular dental visits should be encouraged in addition to adherence to the diabetes self-care protocol.”
Diabetes has long been recognized as a risk factor for cognitive decline, but the findings have been inconsistent for different age groups. Tooth loss has also been linked to cognitive decline and dementia, as well as diabetes.
The mechanisms aren’t entirely clear, but “co-occurring diabetes and poor oral health may increase the risk for dementia, possibly via the potentially interrelated pathways of chronic inflammation and cardiovascular risk factors,” Dr. Wu said.
The new study, published in the Journal of Dental Research, is the first to examine the relationships between all three conditions by age group.
Diabetes, edentulism, and cognitive decline
The data came from a total of 9,948 participants in the Health and Retirement Study (HRS) from 2006 to 2018. At baseline, 5,440 participants were aged 65-74 years, 3,300 were aged 75-84, and 1,208 were aged 85 years or older.
They were assessed every 2 years using the 35-point Telephone Survey for Cognitive Status, which included tests of immediate and delayed word recall, repeated subtracting by 7, counting backward from 20, naming objects, and naming the president and vice president of the U.S. As might be expected, the youngest group scored the highest, averaging 23 points, while the oldest group scored lowest, at 18.5 points.
Participants were also asked if they had ever been told by a doctor that they have diabetes. Another question was: “Have you lost all of your upper and lower natural permanent teeth?”
The condition of having no teeth is known as edentulism.
The percentages of participants who reported having both diabetes and edentulism were 6.0%, 6.7%, and 5.0% for those aged 65-74 years, 75-84 years, and 85 years or older, respectively. The proportions with neither of those conditions were 63.5%, 60.4%, and 58.3% in those three age groups, respectively (P < .001).
Compared with their counterparts with neither diabetes nor edentulism at baseline, older adults with both conditions aged 65-74 years (P < .001) and aged 75-84 years had worse cognitive function (P < .001).
In terms of the rate of cognitive decline, compared with those with neither condition from the same age cohort, older adults aged 65-74 years with both conditions declined at a higher rate (P < .001).
Having diabetes alone led to accelerated cognitive decline in older adults aged 65-74 years (P < .001). Having edentulism alone led to accelerated decline in older adults aged 65-74 years (P < .001) and older adults aged 75-84 years (P < 0.01).
“Our study finds the co-occurrence of diabetes and edentulism led to a worse cognitive function and a faster cognitive decline in older adults aged 65-74 years,” say Wu and colleagues.
Study limitations: Better data needed
The study has several limitations, most of them due to the data source. For example, while the HRS collects detailed information on cognitive status, edentulism is its only measure of oral health. There were no data on whether individuals had replacements such as dentures or implants that would affect their ability to eat, which could influence other health factors.
“I have made repeated appeals for federal funding to collect more oral health-related information in large national surveys,” Dr. Wu told this news organization.
Similarly, assessments of diabetes status such as hemoglobin A1c were only available for small subsets and not sufficient to demonstrate statistical significance, she explained.
Dr. Wu suggested that both oral health and cognitive screening might be included in the “Welcome to Medicare” preventive visit. In addition, “Oral hygiene practice should also be highlighted to improve cognitive health. Developing dental care interventions and programs are needed for reducing the societal cost of dementia.”
The study was partially supported by the National Institutes of Health. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF DENTAL RESEARCH
Celebrity death finally solved – with locks of hair
This transcript has been edited for clarity.
I’m going to open this week with a case.
A 56-year-old musician presents with diffuse abdominal pain, cramping, and jaundice. His medical history is notable for years of diffuse abdominal complaints, characterized by disabling bouts of diarrhea.
In addition to the jaundice, this acute illness was accompanied by fever as well as diffuse edema and ascites. The patient underwent several abdominal paracenteses to drain excess fluid. One consulting physician administered alcohol to relieve pain, to little avail.
The patient succumbed to his illness. An autopsy showed diffuse liver injury, as well as papillary necrosis of the kidneys. Notably, the nerves of his auditory canal were noted to be thickened, along with the bony part of the skull, consistent with Paget disease of the bone and explaining, potentially, why the talented musician had gone deaf at such a young age.
An interesting note on social history: The patient had apparently developed some feelings for the niece of that doctor who prescribed alcohol. Her name was Therese, perhaps mistranscribed as Elise, and it seems that he may have written this song for her.
We’re talking about this paper in Current Biology, by Tristan Begg and colleagues, which gives us a look into the very genome of what some would argue is the world’s greatest composer.
The ability to extract DNA from older specimens has transformed the fields of anthropology, archaeology, and history, and now, perhaps, musicology as well.
The researchers identified eight locks of hair in private and public collections, all attributed to the maestro.
Four of the samples had an intact chain of custody from the time the hair was cut. DNA sequencing on these four and an additional one of the eight locks came from the same individual, a male of European heritage.
The three locks with less documentation came from three other unrelated individuals. Interestingly, analysis of one of those hair samples – the so-called Hiller Lock – had shown high levels of lead, leading historians to speculate that lead poisoning could account for some of Beethoven’s symptoms.
DNA analysis of that hair reveals it to have come from a woman likely of North African, Middle Eastern, or Jewish ancestry. We can no longer presume that plumbism was involved in Beethoven’s death. Beethoven’s ancestry turns out to be less exotic and maps quite well to ethnic German populations today.
In fact, there are van Beethovens alive as we speak, primarily in Belgium. Genealogic records suggest that these van Beethovens share a common ancestor with the virtuoso composer, a man by the name of Aert van Beethoven.
But the DNA reveals a scandal.
The Y-chromosome that Beethoven inherited was not Aert van Beethoven’s. Questions of Beethoven’s paternity have been raised before, but this evidence strongly suggests an extramarital paternity event, at least in the generations preceding his birth. That’s right – Beethoven may not have been a Beethoven.
With five locks now essentially certain to have come from Beethoven himself, the authors could use DNA analysis to try to explain three significant health problems he experienced throughout his life and death: his hearing loss, his terrible gastrointestinal issues, and his liver failure.
Let’s start with the most disappointing results, explanations for his hearing loss. No genetic cause was forthcoming, though the authors note that they have little to go on in regard to the genetic risk for otosclerosis, to which his hearing loss has often been attributed. Lead poisoning is, of course, possible here, though this report focuses only on genetics – there was no testing for lead – and as I mentioned, the lock that was strongly lead-positive in prior studies is almost certainly inauthentic.
What about his lifelong GI complaints? Some have suggested celiac disease or lactose intolerance as explanations. These can essentially be ruled out by the genetic analysis, which shows no risk alleles for celiac disease and the presence of the lactase-persistence gene which confers the ability to metabolize lactose throughout one’s life. IBS is harder to assess genetically, but for what it’s worth, he scored quite low on a polygenic risk score for the condition, in just the 9th percentile of risk. We should probably be looking elsewhere to explain the GI distress.
The genetic information bore much more fruit in regard to his liver disease. Remember that Beethoven’s autopsy showed cirrhosis. His polygenic risk score for liver cirrhosis puts him in the 96th percentile of risk. He was also heterozygous for two variants that can cause hereditary hemochromatosis. The risk for cirrhosis among those with these variants is increased by the use of alcohol. And historical accounts are quite clear that Beethoven consumed more than his share.
But it wasn’t just Beethoven’s DNA in these hair follicles. Analysis of a follicle from later in his life revealed the unmistakable presence of hepatitis B virus. Endemic in Europe at the time, this was a common cause of liver failure and is likely to have contributed to, if not directly caused, Beethoven’s demise.
It’s hard to read these results and not marvel at the fact that, two centuries after his death, our fascination with Beethoven has led us to probe every corner of his life – his letters, his writings, his medical records, and now his very DNA. What are we actually looking for? Is it relevant to us today what caused his hearing loss? His stomach troubles? Even his death? Will it help any patients in the future? I propose that what we are actually trying to understand is something ineffable: Genius of magnitude that is rarely seen in one or many lifetimes. And our scientific tools, as sharp as they may have become, are still far too blunt to probe the depths of that transcendence.
In any case, friends, no more of these sounds. Let us sing more cheerful songs, more full of joy.
For Medscape, I’m Perry Wilson.
Dr. Wilson is associate professor, department of medicine, and director, Clinical and Translational Research Accelerator, at Yale University, New Haven, Conn. He reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
I’m going to open this week with a case.
A 56-year-old musician presents with diffuse abdominal pain, cramping, and jaundice. His medical history is notable for years of diffuse abdominal complaints, characterized by disabling bouts of diarrhea.
In addition to the jaundice, this acute illness was accompanied by fever as well as diffuse edema and ascites. The patient underwent several abdominal paracenteses to drain excess fluid. One consulting physician administered alcohol to relieve pain, to little avail.
The patient succumbed to his illness. An autopsy showed diffuse liver injury, as well as papillary necrosis of the kidneys. Notably, the nerves of his auditory canal were noted to be thickened, along with the bony part of the skull, consistent with Paget disease of the bone and explaining, potentially, why the talented musician had gone deaf at such a young age.
An interesting note on social history: The patient had apparently developed some feelings for the niece of that doctor who prescribed alcohol. Her name was Therese, perhaps mistranscribed as Elise, and it seems that he may have written this song for her.
We’re talking about this paper in Current Biology, by Tristan Begg and colleagues, which gives us a look into the very genome of what some would argue is the world’s greatest composer.
The ability to extract DNA from older specimens has transformed the fields of anthropology, archaeology, and history, and now, perhaps, musicology as well.
The researchers identified eight locks of hair in private and public collections, all attributed to the maestro.
Four of the samples had an intact chain of custody from the time the hair was cut. DNA sequencing on these four and an additional one of the eight locks came from the same individual, a male of European heritage.
The three locks with less documentation came from three other unrelated individuals. Interestingly, analysis of one of those hair samples – the so-called Hiller Lock – had shown high levels of lead, leading historians to speculate that lead poisoning could account for some of Beethoven’s symptoms.
DNA analysis of that hair reveals it to have come from a woman likely of North African, Middle Eastern, or Jewish ancestry. We can no longer presume that plumbism was involved in Beethoven’s death. Beethoven’s ancestry turns out to be less exotic and maps quite well to ethnic German populations today.
In fact, there are van Beethovens alive as we speak, primarily in Belgium. Genealogic records suggest that these van Beethovens share a common ancestor with the virtuoso composer, a man by the name of Aert van Beethoven.
But the DNA reveals a scandal.
The Y-chromosome that Beethoven inherited was not Aert van Beethoven’s. Questions of Beethoven’s paternity have been raised before, but this evidence strongly suggests an extramarital paternity event, at least in the generations preceding his birth. That’s right – Beethoven may not have been a Beethoven.
With five locks now essentially certain to have come from Beethoven himself, the authors could use DNA analysis to try to explain three significant health problems he experienced throughout his life and death: his hearing loss, his terrible gastrointestinal issues, and his liver failure.
Let’s start with the most disappointing results, explanations for his hearing loss. No genetic cause was forthcoming, though the authors note that they have little to go on in regard to the genetic risk for otosclerosis, to which his hearing loss has often been attributed. Lead poisoning is, of course, possible here, though this report focuses only on genetics – there was no testing for lead – and as I mentioned, the lock that was strongly lead-positive in prior studies is almost certainly inauthentic.
What about his lifelong GI complaints? Some have suggested celiac disease or lactose intolerance as explanations. These can essentially be ruled out by the genetic analysis, which shows no risk alleles for celiac disease and the presence of the lactase-persistence gene which confers the ability to metabolize lactose throughout one’s life. IBS is harder to assess genetically, but for what it’s worth, he scored quite low on a polygenic risk score for the condition, in just the 9th percentile of risk. We should probably be looking elsewhere to explain the GI distress.
The genetic information bore much more fruit in regard to his liver disease. Remember that Beethoven’s autopsy showed cirrhosis. His polygenic risk score for liver cirrhosis puts him in the 96th percentile of risk. He was also heterozygous for two variants that can cause hereditary hemochromatosis. The risk for cirrhosis among those with these variants is increased by the use of alcohol. And historical accounts are quite clear that Beethoven consumed more than his share.
But it wasn’t just Beethoven’s DNA in these hair follicles. Analysis of a follicle from later in his life revealed the unmistakable presence of hepatitis B virus. Endemic in Europe at the time, this was a common cause of liver failure and is likely to have contributed to, if not directly caused, Beethoven’s demise.
It’s hard to read these results and not marvel at the fact that, two centuries after his death, our fascination with Beethoven has led us to probe every corner of his life – his letters, his writings, his medical records, and now his very DNA. What are we actually looking for? Is it relevant to us today what caused his hearing loss? His stomach troubles? Even his death? Will it help any patients in the future? I propose that what we are actually trying to understand is something ineffable: Genius of magnitude that is rarely seen in one or many lifetimes. And our scientific tools, as sharp as they may have become, are still far too blunt to probe the depths of that transcendence.
In any case, friends, no more of these sounds. Let us sing more cheerful songs, more full of joy.
For Medscape, I’m Perry Wilson.
Dr. Wilson is associate professor, department of medicine, and director, Clinical and Translational Research Accelerator, at Yale University, New Haven, Conn. He reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
I’m going to open this week with a case.
A 56-year-old musician presents with diffuse abdominal pain, cramping, and jaundice. His medical history is notable for years of diffuse abdominal complaints, characterized by disabling bouts of diarrhea.
In addition to the jaundice, this acute illness was accompanied by fever as well as diffuse edema and ascites. The patient underwent several abdominal paracenteses to drain excess fluid. One consulting physician administered alcohol to relieve pain, to little avail.
The patient succumbed to his illness. An autopsy showed diffuse liver injury, as well as papillary necrosis of the kidneys. Notably, the nerves of his auditory canal were noted to be thickened, along with the bony part of the skull, consistent with Paget disease of the bone and explaining, potentially, why the talented musician had gone deaf at such a young age.
An interesting note on social history: The patient had apparently developed some feelings for the niece of that doctor who prescribed alcohol. Her name was Therese, perhaps mistranscribed as Elise, and it seems that he may have written this song for her.
We’re talking about this paper in Current Biology, by Tristan Begg and colleagues, which gives us a look into the very genome of what some would argue is the world’s greatest composer.
The ability to extract DNA from older specimens has transformed the fields of anthropology, archaeology, and history, and now, perhaps, musicology as well.
The researchers identified eight locks of hair in private and public collections, all attributed to the maestro.
Four of the samples had an intact chain of custody from the time the hair was cut. DNA sequencing on these four and an additional one of the eight locks came from the same individual, a male of European heritage.
The three locks with less documentation came from three other unrelated individuals. Interestingly, analysis of one of those hair samples – the so-called Hiller Lock – had shown high levels of lead, leading historians to speculate that lead poisoning could account for some of Beethoven’s symptoms.
DNA analysis of that hair reveals it to have come from a woman likely of North African, Middle Eastern, or Jewish ancestry. We can no longer presume that plumbism was involved in Beethoven’s death. Beethoven’s ancestry turns out to be less exotic and maps quite well to ethnic German populations today.
In fact, there are van Beethovens alive as we speak, primarily in Belgium. Genealogic records suggest that these van Beethovens share a common ancestor with the virtuoso composer, a man by the name of Aert van Beethoven.
But the DNA reveals a scandal.
The Y-chromosome that Beethoven inherited was not Aert van Beethoven’s. Questions of Beethoven’s paternity have been raised before, but this evidence strongly suggests an extramarital paternity event, at least in the generations preceding his birth. That’s right – Beethoven may not have been a Beethoven.
With five locks now essentially certain to have come from Beethoven himself, the authors could use DNA analysis to try to explain three significant health problems he experienced throughout his life and death: his hearing loss, his terrible gastrointestinal issues, and his liver failure.
Let’s start with the most disappointing results, explanations for his hearing loss. No genetic cause was forthcoming, though the authors note that they have little to go on in regard to the genetic risk for otosclerosis, to which his hearing loss has often been attributed. Lead poisoning is, of course, possible here, though this report focuses only on genetics – there was no testing for lead – and as I mentioned, the lock that was strongly lead-positive in prior studies is almost certainly inauthentic.
What about his lifelong GI complaints? Some have suggested celiac disease or lactose intolerance as explanations. These can essentially be ruled out by the genetic analysis, which shows no risk alleles for celiac disease and the presence of the lactase-persistence gene which confers the ability to metabolize lactose throughout one’s life. IBS is harder to assess genetically, but for what it’s worth, he scored quite low on a polygenic risk score for the condition, in just the 9th percentile of risk. We should probably be looking elsewhere to explain the GI distress.
The genetic information bore much more fruit in regard to his liver disease. Remember that Beethoven’s autopsy showed cirrhosis. His polygenic risk score for liver cirrhosis puts him in the 96th percentile of risk. He was also heterozygous for two variants that can cause hereditary hemochromatosis. The risk for cirrhosis among those with these variants is increased by the use of alcohol. And historical accounts are quite clear that Beethoven consumed more than his share.
But it wasn’t just Beethoven’s DNA in these hair follicles. Analysis of a follicle from later in his life revealed the unmistakable presence of hepatitis B virus. Endemic in Europe at the time, this was a common cause of liver failure and is likely to have contributed to, if not directly caused, Beethoven’s demise.
It’s hard to read these results and not marvel at the fact that, two centuries after his death, our fascination with Beethoven has led us to probe every corner of his life – his letters, his writings, his medical records, and now his very DNA. What are we actually looking for? Is it relevant to us today what caused his hearing loss? His stomach troubles? Even his death? Will it help any patients in the future? I propose that what we are actually trying to understand is something ineffable: Genius of magnitude that is rarely seen in one or many lifetimes. And our scientific tools, as sharp as they may have become, are still far too blunt to probe the depths of that transcendence.
In any case, friends, no more of these sounds. Let us sing more cheerful songs, more full of joy.
For Medscape, I’m Perry Wilson.
Dr. Wilson is associate professor, department of medicine, and director, Clinical and Translational Research Accelerator, at Yale University, New Haven, Conn. He reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
Nurse makes millions selling her licensing exam study sheets
Ms. Beggs, 28, sells one-page study sheets or bundles of sheets, sometimes with colorful drawings, conversation bubbles and underlining, that boil down concepts for particular conditions into easy-to-understand language.
The biggest seller on Ms. Beggs’ online marketplace Etsy site, RNExplained, is a bundle of study guides covering eight core nursing classes. The notes range in price from $2 to $150. More than 70,000 customers have bought the $60 bundle, according to the website.
Ms. Beggs’ business developed in a “very unintentional” way when COVID hit with just months left in her nursing program at Mount Saint Mary’s University, Los Angeles, she told this news organization.
Classes had switched to Zoom, and she had no one to study with as she prepared to take her board exams.
“The best way I know how to study is to teach things out loud. But because I had nobody to teach out loud to, I would literally teach them to the wall,” Ms. Beggs said. “I would record myself so I could play it back and teach myself these topics that were hard for me to understand.”
Just for fun, she says, she posted them on TikTok and the responses started flowing in, with followers asking where she was selling the sheets. She now has more than 660,000 TikTok followers and 9 million likes.
Ms. Beggs said that every sheet highlights a condition, and she has made 308 of them.
Traditional classroom lessons typically teach one medical condition in 5-6 pages, Ms. Beggs said. “I go straight to the point.”
One reviewer on Ms. Beggs’ Etsy site appreciated the handwritten notes, calling them “simplified and concise.” Another commented: “Definitely helped me pass my last exam.”
Ms. Beggs says that her notes may seem simple, but each page represents comprehensive research.
“I have to go through not just one source of information to make sure my information is factual,” Ms. Beggs says. “What you teach in California might be a little different than what you teach in Florida. It’s very meticulous. The lab values will be a little different everywhere you go.”
She acknowledges her competition, noting that there are many other study guides for the NCLEX and nursing courses.
Nursing groups weigh in
Dawn Kappel, spokesperson for the National Council of State Boards of Nursing, which oversees NCLEX, said in an interview that “NCSBN has no issue with the current content of Stephanee Beggs’ business venture.”
For many students, the study guides will be helpful, especially for visual learners, said Carole Kenner, PhD, RN, dean and professor in the School of Nursing and Health Sciences at The College of New Jersey.
But for students “who are less confident in their knowledge, I would want to see a lot more in-depth explanation and rationale,” Dr. Kenner said.
“Since the NCLEX is moving to more cased-based scenarios, the next-gen unfolding cases, you really have to understand a lot of the rationale.”
The notes remind Dr. Kenner of traditional flash cards. “I don’t think it will work for all students, but even the fanciest of onsite review courses are useful to everyone,” she said.
‘Not cutting corners’
As an emergency nurse, Ms. Beggs said, “I have the experience as a nurse to show people that what you are learning will be seen in real life.”
“The way I teach my brand is not to take shortcuts. I love to teach to understand rather than teaching to memorize for an exam.”
She said she sees her guides as a supplement to learning, not a replacement.
“It’s not cutting corners,” she says. “I condense a medical condition that could take a very long time to understand and break it into layman’s terms.”
Ms. Beggs said when people hear about the $2 million, they often ask her whether she plans to give up her shifts in the emergency department for the more lucrative venture.
The answer is no, at least not yet.
“Aside from teaching, I genuinely love being at the bedside,” Ms. Beggs said. “I don’t foresee myself leaving that for good for as long as I can handle both.” She acknowledged, though, that her business now takes up most of her time.
“I love everything about both aspects, so it’s hard for me to choose.”
A version of this article first appeared on Medscape.com.
Ms. Beggs, 28, sells one-page study sheets or bundles of sheets, sometimes with colorful drawings, conversation bubbles and underlining, that boil down concepts for particular conditions into easy-to-understand language.
The biggest seller on Ms. Beggs’ online marketplace Etsy site, RNExplained, is a bundle of study guides covering eight core nursing classes. The notes range in price from $2 to $150. More than 70,000 customers have bought the $60 bundle, according to the website.
Ms. Beggs’ business developed in a “very unintentional” way when COVID hit with just months left in her nursing program at Mount Saint Mary’s University, Los Angeles, she told this news organization.
Classes had switched to Zoom, and she had no one to study with as she prepared to take her board exams.
“The best way I know how to study is to teach things out loud. But because I had nobody to teach out loud to, I would literally teach them to the wall,” Ms. Beggs said. “I would record myself so I could play it back and teach myself these topics that were hard for me to understand.”
Just for fun, she says, she posted them on TikTok and the responses started flowing in, with followers asking where she was selling the sheets. She now has more than 660,000 TikTok followers and 9 million likes.
Ms. Beggs said that every sheet highlights a condition, and she has made 308 of them.
Traditional classroom lessons typically teach one medical condition in 5-6 pages, Ms. Beggs said. “I go straight to the point.”
One reviewer on Ms. Beggs’ Etsy site appreciated the handwritten notes, calling them “simplified and concise.” Another commented: “Definitely helped me pass my last exam.”
Ms. Beggs says that her notes may seem simple, but each page represents comprehensive research.
“I have to go through not just one source of information to make sure my information is factual,” Ms. Beggs says. “What you teach in California might be a little different than what you teach in Florida. It’s very meticulous. The lab values will be a little different everywhere you go.”
She acknowledges her competition, noting that there are many other study guides for the NCLEX and nursing courses.
Nursing groups weigh in
Dawn Kappel, spokesperson for the National Council of State Boards of Nursing, which oversees NCLEX, said in an interview that “NCSBN has no issue with the current content of Stephanee Beggs’ business venture.”
For many students, the study guides will be helpful, especially for visual learners, said Carole Kenner, PhD, RN, dean and professor in the School of Nursing and Health Sciences at The College of New Jersey.
But for students “who are less confident in their knowledge, I would want to see a lot more in-depth explanation and rationale,” Dr. Kenner said.
“Since the NCLEX is moving to more cased-based scenarios, the next-gen unfolding cases, you really have to understand a lot of the rationale.”
The notes remind Dr. Kenner of traditional flash cards. “I don’t think it will work for all students, but even the fanciest of onsite review courses are useful to everyone,” she said.
‘Not cutting corners’
As an emergency nurse, Ms. Beggs said, “I have the experience as a nurse to show people that what you are learning will be seen in real life.”
“The way I teach my brand is not to take shortcuts. I love to teach to understand rather than teaching to memorize for an exam.”
She said she sees her guides as a supplement to learning, not a replacement.
“It’s not cutting corners,” she says. “I condense a medical condition that could take a very long time to understand and break it into layman’s terms.”
Ms. Beggs said when people hear about the $2 million, they often ask her whether she plans to give up her shifts in the emergency department for the more lucrative venture.
The answer is no, at least not yet.
“Aside from teaching, I genuinely love being at the bedside,” Ms. Beggs said. “I don’t foresee myself leaving that for good for as long as I can handle both.” She acknowledged, though, that her business now takes up most of her time.
“I love everything about both aspects, so it’s hard for me to choose.”
A version of this article first appeared on Medscape.com.
Ms. Beggs, 28, sells one-page study sheets or bundles of sheets, sometimes with colorful drawings, conversation bubbles and underlining, that boil down concepts for particular conditions into easy-to-understand language.
The biggest seller on Ms. Beggs’ online marketplace Etsy site, RNExplained, is a bundle of study guides covering eight core nursing classes. The notes range in price from $2 to $150. More than 70,000 customers have bought the $60 bundle, according to the website.
Ms. Beggs’ business developed in a “very unintentional” way when COVID hit with just months left in her nursing program at Mount Saint Mary’s University, Los Angeles, she told this news organization.
Classes had switched to Zoom, and she had no one to study with as she prepared to take her board exams.
“The best way I know how to study is to teach things out loud. But because I had nobody to teach out loud to, I would literally teach them to the wall,” Ms. Beggs said. “I would record myself so I could play it back and teach myself these topics that were hard for me to understand.”
Just for fun, she says, she posted them on TikTok and the responses started flowing in, with followers asking where she was selling the sheets. She now has more than 660,000 TikTok followers and 9 million likes.
Ms. Beggs said that every sheet highlights a condition, and she has made 308 of them.
Traditional classroom lessons typically teach one medical condition in 5-6 pages, Ms. Beggs said. “I go straight to the point.”
One reviewer on Ms. Beggs’ Etsy site appreciated the handwritten notes, calling them “simplified and concise.” Another commented: “Definitely helped me pass my last exam.”
Ms. Beggs says that her notes may seem simple, but each page represents comprehensive research.
“I have to go through not just one source of information to make sure my information is factual,” Ms. Beggs says. “What you teach in California might be a little different than what you teach in Florida. It’s very meticulous. The lab values will be a little different everywhere you go.”
She acknowledges her competition, noting that there are many other study guides for the NCLEX and nursing courses.
Nursing groups weigh in
Dawn Kappel, spokesperson for the National Council of State Boards of Nursing, which oversees NCLEX, said in an interview that “NCSBN has no issue with the current content of Stephanee Beggs’ business venture.”
For many students, the study guides will be helpful, especially for visual learners, said Carole Kenner, PhD, RN, dean and professor in the School of Nursing and Health Sciences at The College of New Jersey.
But for students “who are less confident in their knowledge, I would want to see a lot more in-depth explanation and rationale,” Dr. Kenner said.
“Since the NCLEX is moving to more cased-based scenarios, the next-gen unfolding cases, you really have to understand a lot of the rationale.”
The notes remind Dr. Kenner of traditional flash cards. “I don’t think it will work for all students, but even the fanciest of onsite review courses are useful to everyone,” she said.
‘Not cutting corners’
As an emergency nurse, Ms. Beggs said, “I have the experience as a nurse to show people that what you are learning will be seen in real life.”
“The way I teach my brand is not to take shortcuts. I love to teach to understand rather than teaching to memorize for an exam.”
She said she sees her guides as a supplement to learning, not a replacement.
“It’s not cutting corners,” she says. “I condense a medical condition that could take a very long time to understand and break it into layman’s terms.”
Ms. Beggs said when people hear about the $2 million, they often ask her whether she plans to give up her shifts in the emergency department for the more lucrative venture.
The answer is no, at least not yet.
“Aside from teaching, I genuinely love being at the bedside,” Ms. Beggs said. “I don’t foresee myself leaving that for good for as long as I can handle both.” She acknowledged, though, that her business now takes up most of her time.
“I love everything about both aspects, so it’s hard for me to choose.”
A version of this article first appeared on Medscape.com.
FDA expands evinacumab approval to younger kids with HoFH
The U.S. Food and Drug Administration has expanded the indicated age range for evinacumab-dgnb (Evkeeza, Regeneron Pharmaceuticals), which was approved 2 years ago as an adjunct to other lipid-lowering therapies for homozygous familial hypercholesterolemia (HoFH) in patients aged 12 and older.
The antibody-based agent’s indication now also covers patients aged 5-11 years with the rare genetic disorder, Regeneron announced. It blocks angiopoietin-like 3 (ANGPTL3), inhibiting lipoprotein lipase and endothelial lipase, thereby cutting LDL-cholesterol levels by mechanisms not directly involving the LDL receptor.
The expanded indication is based on a study that saw a 48% drop in LDL-cholesterol levels over 24 weeks, the primary endpoint, across 20 HoFH patients aged 5-11 years who received evinacumab-dgnb on top of maximally tolerated standard lipid-modifying therapy, the company reports.
Levels of apolipoprotein B, non-HDL cholesterol, and total cholesterol also fell significantly in the trial, which was completed in January.
The drug’s efficacy and safety resembled those of a previously reported larger study of patients with HoFH aged 12 years and older (mean age about 40 years) that led to its initial approval.
“The safety and effectiveness of Evkeeza have not been established in patients with other causes of hypercholesterolemia, including those with heterozygous familial hypercholesterolemia,” the company states. Nor is it known whether the drug affects clinical outcomes.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has expanded the indicated age range for evinacumab-dgnb (Evkeeza, Regeneron Pharmaceuticals), which was approved 2 years ago as an adjunct to other lipid-lowering therapies for homozygous familial hypercholesterolemia (HoFH) in patients aged 12 and older.
The antibody-based agent’s indication now also covers patients aged 5-11 years with the rare genetic disorder, Regeneron announced. It blocks angiopoietin-like 3 (ANGPTL3), inhibiting lipoprotein lipase and endothelial lipase, thereby cutting LDL-cholesterol levels by mechanisms not directly involving the LDL receptor.
The expanded indication is based on a study that saw a 48% drop in LDL-cholesterol levels over 24 weeks, the primary endpoint, across 20 HoFH patients aged 5-11 years who received evinacumab-dgnb on top of maximally tolerated standard lipid-modifying therapy, the company reports.
Levels of apolipoprotein B, non-HDL cholesterol, and total cholesterol also fell significantly in the trial, which was completed in January.
The drug’s efficacy and safety resembled those of a previously reported larger study of patients with HoFH aged 12 years and older (mean age about 40 years) that led to its initial approval.
“The safety and effectiveness of Evkeeza have not been established in patients with other causes of hypercholesterolemia, including those with heterozygous familial hypercholesterolemia,” the company states. Nor is it known whether the drug affects clinical outcomes.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has expanded the indicated age range for evinacumab-dgnb (Evkeeza, Regeneron Pharmaceuticals), which was approved 2 years ago as an adjunct to other lipid-lowering therapies for homozygous familial hypercholesterolemia (HoFH) in patients aged 12 and older.
The antibody-based agent’s indication now also covers patients aged 5-11 years with the rare genetic disorder, Regeneron announced. It blocks angiopoietin-like 3 (ANGPTL3), inhibiting lipoprotein lipase and endothelial lipase, thereby cutting LDL-cholesterol levels by mechanisms not directly involving the LDL receptor.
The expanded indication is based on a study that saw a 48% drop in LDL-cholesterol levels over 24 weeks, the primary endpoint, across 20 HoFH patients aged 5-11 years who received evinacumab-dgnb on top of maximally tolerated standard lipid-modifying therapy, the company reports.
Levels of apolipoprotein B, non-HDL cholesterol, and total cholesterol also fell significantly in the trial, which was completed in January.
The drug’s efficacy and safety resembled those of a previously reported larger study of patients with HoFH aged 12 years and older (mean age about 40 years) that led to its initial approval.
“The safety and effectiveness of Evkeeza have not been established in patients with other causes of hypercholesterolemia, including those with heterozygous familial hypercholesterolemia,” the company states. Nor is it known whether the drug affects clinical outcomes.
A version of this article first appeared on Medscape.com.
The air up there: Oxygen could be a bit overrated
Into thin, but healthy, air
Human civilization has essentially been built on proximity to water. Ancient civilizations in Mesopotamia, Egypt, Greece, China, and India were all intimately connected to either rivers or the ocean. Even today, with all our technology, about a third of Earth’s 8 billion people live within 100 vertical meters of sea level, and the median person lives at an elevation of just 200 meters.
All things considered, one might imagine life is pretty tough for the 2 million people living at an elevation of 4,500 meters (nearly 15,000 feet). Not too many Wal-Marts or McDonalds up there. Oh, and not much air either. And for most of us not named Spongebob, air is good.
Or is it? That’s the question posed by a new study. After all, the researchers said, people living at high altitudes, where the air has only 11% effective oxygen instead of the 21% we have at low altitude, have significantly lower rates of metabolic disorders such as diabetes and heart diseases. Maybe breathing isn’t all it’s cracked up to be.
To find out, the researchers placed a group of mice in environments with either 11% oxygen or 8% oxygen. This netted them a bunch of very tired mice. Hey, sudden altitude gain doesn’t go too well for us either, but after 3 weeks, all the mice in the hypoxic environments had regained their normal movement and were behaving as any mouse would.
While the critters seemed normal on the outside, a closer examination found the truth. Their metabolism had been permanently altered, and their blood sugar and weight went down and never bounced back up. Further examination through PET scans showed that the hypoxic mice’s organs showed an increase in glucose metabolism and that brown fat and skeletal muscles reduced the amount of sugar they used.
This goes against the prevailing assumption about hypoxic conditions, the researchers said, since it was previously theorized that the body simply burned more glucose in response to having less oxygen. And while that’s true, our organs also conspicuously use less glucose. Currently, many athletes use hypoxic environments to train, but these new data suggest that people with metabolic disorders also would see benefits from living in low-oxygen environments.
Do you know what this means? All we have to do to stop diabetes is take civilization and push it somewhere else. This can’t possibly end badly.
Sleep survey: The restless majority
Newsflash! This just in: Nobody is sleeping well.
When we go to bed, our goal is to get rest, right? Sorry America, but you’re falling short. In a recent survey conducted by OnePoll for Purple Mattress, almost two-thirds of the 2,011 participants considered themselves restless sleepers.
Not surprised. So what’s keeping us up?
Snoring partners (20%) and anxiety (26%) made the list, but the award for top complaint goes to body pain. Back pain was most prevalent, reported by 36% of respondents, followed by neck pain (33%) and shoulder pain (24%). No wonder, then, that only 10% of the group reported feeling well rested when they woke up.
Do you ever blame your tiredness on sleeping funny? Well, we all kind of sleep funny, and yet we’re still not sleeping well.
The largest proportion of people like to sleep on their side (48%), compared with 18% on their back and 17% on their stomach. The main reasons to choose certain positions were to ease soreness or sleep better, both at 28%. The largest share of participants (47%) reported sleeping in a “yearner” position, while 40% lay on their stomachs in the “free faller” position, and 39% reported using the “soldier” position.
Regardless of the method people use to get to sleep or the position they’re in, the goal is always the same. We’re all just trying to figure out what’s the right one for us.
Seen a UFO recently? Don’t blame COVID
First of all, because we know you’re going to be thinking it in a minute, no, we did not make this up. With COVID-19 still hanging around, there’s no need for fabrication on our part.
The pandemic, clearly, has caused humans to do some strange things over the last 3 years, but what about some of the more, shall we say … eccentric behavior that people were already exhibiting before COVID found its way into our lives?
If, like R. Chase Cockrell, PhD, of the University of Vermont and associates at the Center for UFO Studies, you were wondering if the pandemic affected UFO reporting, then wonder no more. After all, with all that extra time being spent outdoors back in 2020 and all the additional anxiety, surely somebody must have seen something.
The investigators started with the basics by analyzing data from the National UFO Reporting Center and the Mutual UFO Network. Sightings did increase by about 600 in each database during 2020, compared with 2018 and 2019, but not because of the pandemic.
That’s right, we can’t pin this one on our good friend SARS-CoV-2. Further analysis showed that the launches of SpaceX Starlink satellites – sometimes as many as 60 at a time – probably caused the increase in UFO sightings, which means that our favorite billionaire, Elon Musk, is to blame. Yup, the genial Mr. Muskellunge did something that even a global pandemic couldn’t, and yet we vaccinate for COVID.
Next week on tenuous connections: A new study links the 2020 presidential election to increased emergency department visits for external hemorrhoids.
See? That’s fabrication. We made that up.
This article was updated 5/15/23.
Into thin, but healthy, air
Human civilization has essentially been built on proximity to water. Ancient civilizations in Mesopotamia, Egypt, Greece, China, and India were all intimately connected to either rivers or the ocean. Even today, with all our technology, about a third of Earth’s 8 billion people live within 100 vertical meters of sea level, and the median person lives at an elevation of just 200 meters.
All things considered, one might imagine life is pretty tough for the 2 million people living at an elevation of 4,500 meters (nearly 15,000 feet). Not too many Wal-Marts or McDonalds up there. Oh, and not much air either. And for most of us not named Spongebob, air is good.
Or is it? That’s the question posed by a new study. After all, the researchers said, people living at high altitudes, where the air has only 11% effective oxygen instead of the 21% we have at low altitude, have significantly lower rates of metabolic disorders such as diabetes and heart diseases. Maybe breathing isn’t all it’s cracked up to be.
To find out, the researchers placed a group of mice in environments with either 11% oxygen or 8% oxygen. This netted them a bunch of very tired mice. Hey, sudden altitude gain doesn’t go too well for us either, but after 3 weeks, all the mice in the hypoxic environments had regained their normal movement and were behaving as any mouse would.
While the critters seemed normal on the outside, a closer examination found the truth. Their metabolism had been permanently altered, and their blood sugar and weight went down and never bounced back up. Further examination through PET scans showed that the hypoxic mice’s organs showed an increase in glucose metabolism and that brown fat and skeletal muscles reduced the amount of sugar they used.
This goes against the prevailing assumption about hypoxic conditions, the researchers said, since it was previously theorized that the body simply burned more glucose in response to having less oxygen. And while that’s true, our organs also conspicuously use less glucose. Currently, many athletes use hypoxic environments to train, but these new data suggest that people with metabolic disorders also would see benefits from living in low-oxygen environments.
Do you know what this means? All we have to do to stop diabetes is take civilization and push it somewhere else. This can’t possibly end badly.
Sleep survey: The restless majority
Newsflash! This just in: Nobody is sleeping well.
When we go to bed, our goal is to get rest, right? Sorry America, but you’re falling short. In a recent survey conducted by OnePoll for Purple Mattress, almost two-thirds of the 2,011 participants considered themselves restless sleepers.
Not surprised. So what’s keeping us up?
Snoring partners (20%) and anxiety (26%) made the list, but the award for top complaint goes to body pain. Back pain was most prevalent, reported by 36% of respondents, followed by neck pain (33%) and shoulder pain (24%). No wonder, then, that only 10% of the group reported feeling well rested when they woke up.
Do you ever blame your tiredness on sleeping funny? Well, we all kind of sleep funny, and yet we’re still not sleeping well.
The largest proportion of people like to sleep on their side (48%), compared with 18% on their back and 17% on their stomach. The main reasons to choose certain positions were to ease soreness or sleep better, both at 28%. The largest share of participants (47%) reported sleeping in a “yearner” position, while 40% lay on their stomachs in the “free faller” position, and 39% reported using the “soldier” position.
Regardless of the method people use to get to sleep or the position they’re in, the goal is always the same. We’re all just trying to figure out what’s the right one for us.
Seen a UFO recently? Don’t blame COVID
First of all, because we know you’re going to be thinking it in a minute, no, we did not make this up. With COVID-19 still hanging around, there’s no need for fabrication on our part.
The pandemic, clearly, has caused humans to do some strange things over the last 3 years, but what about some of the more, shall we say … eccentric behavior that people were already exhibiting before COVID found its way into our lives?
If, like R. Chase Cockrell, PhD, of the University of Vermont and associates at the Center for UFO Studies, you were wondering if the pandemic affected UFO reporting, then wonder no more. After all, with all that extra time being spent outdoors back in 2020 and all the additional anxiety, surely somebody must have seen something.
The investigators started with the basics by analyzing data from the National UFO Reporting Center and the Mutual UFO Network. Sightings did increase by about 600 in each database during 2020, compared with 2018 and 2019, but not because of the pandemic.
That’s right, we can’t pin this one on our good friend SARS-CoV-2. Further analysis showed that the launches of SpaceX Starlink satellites – sometimes as many as 60 at a time – probably caused the increase in UFO sightings, which means that our favorite billionaire, Elon Musk, is to blame. Yup, the genial Mr. Muskellunge did something that even a global pandemic couldn’t, and yet we vaccinate for COVID.
Next week on tenuous connections: A new study links the 2020 presidential election to increased emergency department visits for external hemorrhoids.
See? That’s fabrication. We made that up.
This article was updated 5/15/23.
Into thin, but healthy, air
Human civilization has essentially been built on proximity to water. Ancient civilizations in Mesopotamia, Egypt, Greece, China, and India were all intimately connected to either rivers or the ocean. Even today, with all our technology, about a third of Earth’s 8 billion people live within 100 vertical meters of sea level, and the median person lives at an elevation of just 200 meters.
All things considered, one might imagine life is pretty tough for the 2 million people living at an elevation of 4,500 meters (nearly 15,000 feet). Not too many Wal-Marts or McDonalds up there. Oh, and not much air either. And for most of us not named Spongebob, air is good.
Or is it? That’s the question posed by a new study. After all, the researchers said, people living at high altitudes, where the air has only 11% effective oxygen instead of the 21% we have at low altitude, have significantly lower rates of metabolic disorders such as diabetes and heart diseases. Maybe breathing isn’t all it’s cracked up to be.
To find out, the researchers placed a group of mice in environments with either 11% oxygen or 8% oxygen. This netted them a bunch of very tired mice. Hey, sudden altitude gain doesn’t go too well for us either, but after 3 weeks, all the mice in the hypoxic environments had regained their normal movement and were behaving as any mouse would.
While the critters seemed normal on the outside, a closer examination found the truth. Their metabolism had been permanently altered, and their blood sugar and weight went down and never bounced back up. Further examination through PET scans showed that the hypoxic mice’s organs showed an increase in glucose metabolism and that brown fat and skeletal muscles reduced the amount of sugar they used.
This goes against the prevailing assumption about hypoxic conditions, the researchers said, since it was previously theorized that the body simply burned more glucose in response to having less oxygen. And while that’s true, our organs also conspicuously use less glucose. Currently, many athletes use hypoxic environments to train, but these new data suggest that people with metabolic disorders also would see benefits from living in low-oxygen environments.
Do you know what this means? All we have to do to stop diabetes is take civilization and push it somewhere else. This can’t possibly end badly.
Sleep survey: The restless majority
Newsflash! This just in: Nobody is sleeping well.
When we go to bed, our goal is to get rest, right? Sorry America, but you’re falling short. In a recent survey conducted by OnePoll for Purple Mattress, almost two-thirds of the 2,011 participants considered themselves restless sleepers.
Not surprised. So what’s keeping us up?
Snoring partners (20%) and anxiety (26%) made the list, but the award for top complaint goes to body pain. Back pain was most prevalent, reported by 36% of respondents, followed by neck pain (33%) and shoulder pain (24%). No wonder, then, that only 10% of the group reported feeling well rested when they woke up.
Do you ever blame your tiredness on sleeping funny? Well, we all kind of sleep funny, and yet we’re still not sleeping well.
The largest proportion of people like to sleep on their side (48%), compared with 18% on their back and 17% on their stomach. The main reasons to choose certain positions were to ease soreness or sleep better, both at 28%. The largest share of participants (47%) reported sleeping in a “yearner” position, while 40% lay on their stomachs in the “free faller” position, and 39% reported using the “soldier” position.
Regardless of the method people use to get to sleep or the position they’re in, the goal is always the same. We’re all just trying to figure out what’s the right one for us.
Seen a UFO recently? Don’t blame COVID
First of all, because we know you’re going to be thinking it in a minute, no, we did not make this up. With COVID-19 still hanging around, there’s no need for fabrication on our part.
The pandemic, clearly, has caused humans to do some strange things over the last 3 years, but what about some of the more, shall we say … eccentric behavior that people were already exhibiting before COVID found its way into our lives?
If, like R. Chase Cockrell, PhD, of the University of Vermont and associates at the Center for UFO Studies, you were wondering if the pandemic affected UFO reporting, then wonder no more. After all, with all that extra time being spent outdoors back in 2020 and all the additional anxiety, surely somebody must have seen something.
The investigators started with the basics by analyzing data from the National UFO Reporting Center and the Mutual UFO Network. Sightings did increase by about 600 in each database during 2020, compared with 2018 and 2019, but not because of the pandemic.
That’s right, we can’t pin this one on our good friend SARS-CoV-2. Further analysis showed that the launches of SpaceX Starlink satellites – sometimes as many as 60 at a time – probably caused the increase in UFO sightings, which means that our favorite billionaire, Elon Musk, is to blame. Yup, the genial Mr. Muskellunge did something that even a global pandemic couldn’t, and yet we vaccinate for COVID.
Next week on tenuous connections: A new study links the 2020 presidential election to increased emergency department visits for external hemorrhoids.
See? That’s fabrication. We made that up.
This article was updated 5/15/23.
LAA closure device shown safe in groups omitted in trials
WASHINGTON – Left atrial appendage closure can be performed safely and effectively in older patients, those with end-stage renal disease, and likely others not included in the pivotal clinical trials, according to a series of new studies, including a late-breaker, presented on the both older and newer Watchman devices at the Cardiovascular Research Technologies conference.
In the case of the late-breaking clinical trial report, which included more than 60,000 patients, the goal was to look at the safety of the Watchman FLX, which is the newest of the devices in real-world practice, according to Samir R. Kapadia, MD, chairman of the department of cardiovascular medicine at the Cleveland Clinic.
In the SURPASS registry, the number of patients discharged on the Watchman FLX climbed from zero in August 2020, when data accrual began, to 66,894 by March 2022. For the current analysis, 45-day follow-up was available for 61,963 patients and 1-year follow-up was available for 18,233.
Based on this number of patients treated by more than 2,300 clinicians at more than 740 sites, the SURPASS registry establishes that Watchman FLX “can be accomplished safely with clinical outcomes similar to pivotal trials at 45 days and 1 year,” Dr. Kapadia reported.
No surprises found in real-world outcome
At 7 days or hospital discharge (whichever came last), the rate of all-cause death was 0.18%, the rate of ischemic stroke was 0.13%, and there were no systemic emboli. By 45 days, the rate of all-cause death (0.84%) and stroke of any kind (0.32%) remained less than 1% and there were still no systemic emboli. Major bleeding events, of which about one-third occurred during hospitalization, had reached 3.34% by day 45.
By 1 year, all-cause mortality had risen to 8.3%, the stroke rate was 1.6%, and major bleeding reached 6.7%. The rate of systemic emboli remained very low (0.1%). The rates of death and stroke rose at a slow but steady rate throughout the 1-year follow-up. In contrast, major bleeding events rose steeply in the first 90 days and were followed by a much slower accrual subsequently.
At 1 year, 84.4% of patients had a complete seal. Leaks ≤ 3 mm were observed in 12.1%. The remaining leaks were larger, but just 0.7% had a leak > 5 mm.
Relative to the first-generation Watchman, the Watchman FLX has numerous design changes, including a shorter profile, more struts, and a reduced metal exposure. Most of these changes were performed to make the device easier to deploy.
When the SURPASS data are compared to the pivotal trials with Watchman FLX or to the Ewolution and National Cardiovascular Data (NCD) registries, which were created to monitor efficacy and safety with the earlier generation Watchman, the outcomes are similar or, in many cases, numerically favorable for such outcomes as bleeding and rates of stroke.
In addition to providing reassurance for the real-world safety of Watchman FLX, Dr. Kapadia said that these data establish reasonable benchmarks for centers tracking in-hospital and 1-year outcomes.
Dr. Kapadia also reported that outcomes overall in SURPASS were similar in women and men with the exception of major bleeding, a finding common to other interventional studies.
The late-breaker panelists generally agreed that SURPASS provides a robust set of data by which to be reassured, but David J. Cohen, MD, director of Clinical and Outcomes Research at the Cardiovascular Research Foundation in New York, said that he thinks the rate of bleeding is unnecessarily high.
“You really need to figure out a way to get the rate of bleeding at 45 days down,” Dr. Cohen said. He called for studies of anticoagulation in the post-procedural period that offer a better benefit-to-risk ratio.
Elderly patients benefit equally from Watchman
Yet, Watchman devices are generally regarded as a success story, and this has led investigators to evaluate safety in patients not well represented or explicitly excluded from clinical trials, such as the elderly and those with end-stage renal disease (ESRD). New data derived from experience in both of these groups were presented at the conference, which was sponsored by MedStar Heart & Vascular Institute.
To tease out the relative safety of Watchman in octogenarians, Samian Sulaiman, MD, a cardiology fellow at West Virginia University Heart and Vascular Institute, Morgantown, performed a competing risk analysis to study the relative benefit of Watchman devices after controlling for the greater overall risk of complications in the elderly.
In raw data comparisons of those 80 years of age or older to those younger in published trials, the not-surprising result is that overall rates of death and ischemic events are far higher in the elderly, according to Dr. Sulaiman, but it’s an “unfair comparison,” he said.
“It is easy to mistakenly conclude that left atrial appendage closure is associated with worse outcomes, but older patients have far higher rates of these events independent of other factors,” Dr. Sulaiman noted.
In fact, in his comparison of 472 older patients to 1,404 younger patients, the seal rates at 45 days, 6 months, and 12 months are almost identical. Moreover, after the extensive adjustments performed for competing risk analysis, the rates of death, stroke, and bleeding were also almost identical for those 80 years or older whether or not they received a Watchman.
Although he acknowledged the risk for residual confounding, Dr. Sulaiman concluded that elderly patients derive about the same benefits as younger patients from the Watchman. He concluded age alone should not be a factor in selecting candidates for this device.
ESRD is not Watchman contraindication
A similar point was made about ESRD based on analysis of 237 patients who received either an earlier generation Watchman or the Watchman FLX. Initiated in Spain, the study was amended to collect data from centers elsewhere in Europe, the United States, and Australia.
Successful implantation was achieved in 99.2% of the patients, reported Armando Perez de Prado, MD, PhD, head of interventional cardiology at the University of Leon, Spain.
After a median follow-up of 480 days, stroke or transient ischemic attacks were observed in 3.1%, leaks > 5 mm were observed in 1.4%, and systemic emboli were observed in 0.9%. Major bleeding (BARC > 2) occurred in 13.3%.
Although the all-cause mortality over the period of follow-up was high (37.4%), most of the deaths (61.2%) were of noncardiovascular origin, according to Dr. Sulaiman. He said mortality and adverse events linked to the Watchman appeared to be roughly comparable to those seen in patients with ESRD.
“The Watchman device for patients on hemodialysis with nonvalvular atrial fibrillation is an effective and safe intervention to prevent embolic events,” he said. However, he also cautioned these the ESRD and the accompanying comorbidities place these patients at high risk of a limited life expectancy.
“Given the high mortality rate of this population, proper selection of candidates is paramount to ensure the optimal clinical benefit,” he cautioned.
Dr. Samir reported no potential conflicts of interest but stated that this study was funded by Boston Scientific. Dr. Cohen reported financial ties with Abbott Vascular, Boston Scientific, Corvia Medical, Edwards Lifesciences, Impulse Dynamics, MyoKardia, Phillips, Svelte, V-Wave, and Zoll. Dr. Sulaiman reported no potential conflicts of interest. Dr. Perez de Prado reported no potential conflicts of interest but stated that this study was funded by Boston Scientific.
WASHINGTON – Left atrial appendage closure can be performed safely and effectively in older patients, those with end-stage renal disease, and likely others not included in the pivotal clinical trials, according to a series of new studies, including a late-breaker, presented on the both older and newer Watchman devices at the Cardiovascular Research Technologies conference.
In the case of the late-breaking clinical trial report, which included more than 60,000 patients, the goal was to look at the safety of the Watchman FLX, which is the newest of the devices in real-world practice, according to Samir R. Kapadia, MD, chairman of the department of cardiovascular medicine at the Cleveland Clinic.
In the SURPASS registry, the number of patients discharged on the Watchman FLX climbed from zero in August 2020, when data accrual began, to 66,894 by March 2022. For the current analysis, 45-day follow-up was available for 61,963 patients and 1-year follow-up was available for 18,233.
Based on this number of patients treated by more than 2,300 clinicians at more than 740 sites, the SURPASS registry establishes that Watchman FLX “can be accomplished safely with clinical outcomes similar to pivotal trials at 45 days and 1 year,” Dr. Kapadia reported.
No surprises found in real-world outcome
At 7 days or hospital discharge (whichever came last), the rate of all-cause death was 0.18%, the rate of ischemic stroke was 0.13%, and there were no systemic emboli. By 45 days, the rate of all-cause death (0.84%) and stroke of any kind (0.32%) remained less than 1% and there were still no systemic emboli. Major bleeding events, of which about one-third occurred during hospitalization, had reached 3.34% by day 45.
By 1 year, all-cause mortality had risen to 8.3%, the stroke rate was 1.6%, and major bleeding reached 6.7%. The rate of systemic emboli remained very low (0.1%). The rates of death and stroke rose at a slow but steady rate throughout the 1-year follow-up. In contrast, major bleeding events rose steeply in the first 90 days and were followed by a much slower accrual subsequently.
At 1 year, 84.4% of patients had a complete seal. Leaks ≤ 3 mm were observed in 12.1%. The remaining leaks were larger, but just 0.7% had a leak > 5 mm.
Relative to the first-generation Watchman, the Watchman FLX has numerous design changes, including a shorter profile, more struts, and a reduced metal exposure. Most of these changes were performed to make the device easier to deploy.
When the SURPASS data are compared to the pivotal trials with Watchman FLX or to the Ewolution and National Cardiovascular Data (NCD) registries, which were created to monitor efficacy and safety with the earlier generation Watchman, the outcomes are similar or, in many cases, numerically favorable for such outcomes as bleeding and rates of stroke.
In addition to providing reassurance for the real-world safety of Watchman FLX, Dr. Kapadia said that these data establish reasonable benchmarks for centers tracking in-hospital and 1-year outcomes.
Dr. Kapadia also reported that outcomes overall in SURPASS were similar in women and men with the exception of major bleeding, a finding common to other interventional studies.
The late-breaker panelists generally agreed that SURPASS provides a robust set of data by which to be reassured, but David J. Cohen, MD, director of Clinical and Outcomes Research at the Cardiovascular Research Foundation in New York, said that he thinks the rate of bleeding is unnecessarily high.
“You really need to figure out a way to get the rate of bleeding at 45 days down,” Dr. Cohen said. He called for studies of anticoagulation in the post-procedural period that offer a better benefit-to-risk ratio.
Elderly patients benefit equally from Watchman
Yet, Watchman devices are generally regarded as a success story, and this has led investigators to evaluate safety in patients not well represented or explicitly excluded from clinical trials, such as the elderly and those with end-stage renal disease (ESRD). New data derived from experience in both of these groups were presented at the conference, which was sponsored by MedStar Heart & Vascular Institute.
To tease out the relative safety of Watchman in octogenarians, Samian Sulaiman, MD, a cardiology fellow at West Virginia University Heart and Vascular Institute, Morgantown, performed a competing risk analysis to study the relative benefit of Watchman devices after controlling for the greater overall risk of complications in the elderly.
In raw data comparisons of those 80 years of age or older to those younger in published trials, the not-surprising result is that overall rates of death and ischemic events are far higher in the elderly, according to Dr. Sulaiman, but it’s an “unfair comparison,” he said.
“It is easy to mistakenly conclude that left atrial appendage closure is associated with worse outcomes, but older patients have far higher rates of these events independent of other factors,” Dr. Sulaiman noted.
In fact, in his comparison of 472 older patients to 1,404 younger patients, the seal rates at 45 days, 6 months, and 12 months are almost identical. Moreover, after the extensive adjustments performed for competing risk analysis, the rates of death, stroke, and bleeding were also almost identical for those 80 years or older whether or not they received a Watchman.
Although he acknowledged the risk for residual confounding, Dr. Sulaiman concluded that elderly patients derive about the same benefits as younger patients from the Watchman. He concluded age alone should not be a factor in selecting candidates for this device.
ESRD is not Watchman contraindication
A similar point was made about ESRD based on analysis of 237 patients who received either an earlier generation Watchman or the Watchman FLX. Initiated in Spain, the study was amended to collect data from centers elsewhere in Europe, the United States, and Australia.
Successful implantation was achieved in 99.2% of the patients, reported Armando Perez de Prado, MD, PhD, head of interventional cardiology at the University of Leon, Spain.
After a median follow-up of 480 days, stroke or transient ischemic attacks were observed in 3.1%, leaks > 5 mm were observed in 1.4%, and systemic emboli were observed in 0.9%. Major bleeding (BARC > 2) occurred in 13.3%.
Although the all-cause mortality over the period of follow-up was high (37.4%), most of the deaths (61.2%) were of noncardiovascular origin, according to Dr. Sulaiman. He said mortality and adverse events linked to the Watchman appeared to be roughly comparable to those seen in patients with ESRD.
“The Watchman device for patients on hemodialysis with nonvalvular atrial fibrillation is an effective and safe intervention to prevent embolic events,” he said. However, he also cautioned these the ESRD and the accompanying comorbidities place these patients at high risk of a limited life expectancy.
“Given the high mortality rate of this population, proper selection of candidates is paramount to ensure the optimal clinical benefit,” he cautioned.
Dr. Samir reported no potential conflicts of interest but stated that this study was funded by Boston Scientific. Dr. Cohen reported financial ties with Abbott Vascular, Boston Scientific, Corvia Medical, Edwards Lifesciences, Impulse Dynamics, MyoKardia, Phillips, Svelte, V-Wave, and Zoll. Dr. Sulaiman reported no potential conflicts of interest. Dr. Perez de Prado reported no potential conflicts of interest but stated that this study was funded by Boston Scientific.
WASHINGTON – Left atrial appendage closure can be performed safely and effectively in older patients, those with end-stage renal disease, and likely others not included in the pivotal clinical trials, according to a series of new studies, including a late-breaker, presented on the both older and newer Watchman devices at the Cardiovascular Research Technologies conference.
In the case of the late-breaking clinical trial report, which included more than 60,000 patients, the goal was to look at the safety of the Watchman FLX, which is the newest of the devices in real-world practice, according to Samir R. Kapadia, MD, chairman of the department of cardiovascular medicine at the Cleveland Clinic.
In the SURPASS registry, the number of patients discharged on the Watchman FLX climbed from zero in August 2020, when data accrual began, to 66,894 by March 2022. For the current analysis, 45-day follow-up was available for 61,963 patients and 1-year follow-up was available for 18,233.
Based on this number of patients treated by more than 2,300 clinicians at more than 740 sites, the SURPASS registry establishes that Watchman FLX “can be accomplished safely with clinical outcomes similar to pivotal trials at 45 days and 1 year,” Dr. Kapadia reported.
No surprises found in real-world outcome
At 7 days or hospital discharge (whichever came last), the rate of all-cause death was 0.18%, the rate of ischemic stroke was 0.13%, and there were no systemic emboli. By 45 days, the rate of all-cause death (0.84%) and stroke of any kind (0.32%) remained less than 1% and there were still no systemic emboli. Major bleeding events, of which about one-third occurred during hospitalization, had reached 3.34% by day 45.
By 1 year, all-cause mortality had risen to 8.3%, the stroke rate was 1.6%, and major bleeding reached 6.7%. The rate of systemic emboli remained very low (0.1%). The rates of death and stroke rose at a slow but steady rate throughout the 1-year follow-up. In contrast, major bleeding events rose steeply in the first 90 days and were followed by a much slower accrual subsequently.
At 1 year, 84.4% of patients had a complete seal. Leaks ≤ 3 mm were observed in 12.1%. The remaining leaks were larger, but just 0.7% had a leak > 5 mm.
Relative to the first-generation Watchman, the Watchman FLX has numerous design changes, including a shorter profile, more struts, and a reduced metal exposure. Most of these changes were performed to make the device easier to deploy.
When the SURPASS data are compared to the pivotal trials with Watchman FLX or to the Ewolution and National Cardiovascular Data (NCD) registries, which were created to monitor efficacy and safety with the earlier generation Watchman, the outcomes are similar or, in many cases, numerically favorable for such outcomes as bleeding and rates of stroke.
In addition to providing reassurance for the real-world safety of Watchman FLX, Dr. Kapadia said that these data establish reasonable benchmarks for centers tracking in-hospital and 1-year outcomes.
Dr. Kapadia also reported that outcomes overall in SURPASS were similar in women and men with the exception of major bleeding, a finding common to other interventional studies.
The late-breaker panelists generally agreed that SURPASS provides a robust set of data by which to be reassured, but David J. Cohen, MD, director of Clinical and Outcomes Research at the Cardiovascular Research Foundation in New York, said that he thinks the rate of bleeding is unnecessarily high.
“You really need to figure out a way to get the rate of bleeding at 45 days down,” Dr. Cohen said. He called for studies of anticoagulation in the post-procedural period that offer a better benefit-to-risk ratio.
Elderly patients benefit equally from Watchman
Yet, Watchman devices are generally regarded as a success story, and this has led investigators to evaluate safety in patients not well represented or explicitly excluded from clinical trials, such as the elderly and those with end-stage renal disease (ESRD). New data derived from experience in both of these groups were presented at the conference, which was sponsored by MedStar Heart & Vascular Institute.
To tease out the relative safety of Watchman in octogenarians, Samian Sulaiman, MD, a cardiology fellow at West Virginia University Heart and Vascular Institute, Morgantown, performed a competing risk analysis to study the relative benefit of Watchman devices after controlling for the greater overall risk of complications in the elderly.
In raw data comparisons of those 80 years of age or older to those younger in published trials, the not-surprising result is that overall rates of death and ischemic events are far higher in the elderly, according to Dr. Sulaiman, but it’s an “unfair comparison,” he said.
“It is easy to mistakenly conclude that left atrial appendage closure is associated with worse outcomes, but older patients have far higher rates of these events independent of other factors,” Dr. Sulaiman noted.
In fact, in his comparison of 472 older patients to 1,404 younger patients, the seal rates at 45 days, 6 months, and 12 months are almost identical. Moreover, after the extensive adjustments performed for competing risk analysis, the rates of death, stroke, and bleeding were also almost identical for those 80 years or older whether or not they received a Watchman.
Although he acknowledged the risk for residual confounding, Dr. Sulaiman concluded that elderly patients derive about the same benefits as younger patients from the Watchman. He concluded age alone should not be a factor in selecting candidates for this device.
ESRD is not Watchman contraindication
A similar point was made about ESRD based on analysis of 237 patients who received either an earlier generation Watchman or the Watchman FLX. Initiated in Spain, the study was amended to collect data from centers elsewhere in Europe, the United States, and Australia.
Successful implantation was achieved in 99.2% of the patients, reported Armando Perez de Prado, MD, PhD, head of interventional cardiology at the University of Leon, Spain.
After a median follow-up of 480 days, stroke or transient ischemic attacks were observed in 3.1%, leaks > 5 mm were observed in 1.4%, and systemic emboli were observed in 0.9%. Major bleeding (BARC > 2) occurred in 13.3%.
Although the all-cause mortality over the period of follow-up was high (37.4%), most of the deaths (61.2%) were of noncardiovascular origin, according to Dr. Sulaiman. He said mortality and adverse events linked to the Watchman appeared to be roughly comparable to those seen in patients with ESRD.
“The Watchman device for patients on hemodialysis with nonvalvular atrial fibrillation is an effective and safe intervention to prevent embolic events,” he said. However, he also cautioned these the ESRD and the accompanying comorbidities place these patients at high risk of a limited life expectancy.
“Given the high mortality rate of this population, proper selection of candidates is paramount to ensure the optimal clinical benefit,” he cautioned.
Dr. Samir reported no potential conflicts of interest but stated that this study was funded by Boston Scientific. Dr. Cohen reported financial ties with Abbott Vascular, Boston Scientific, Corvia Medical, Edwards Lifesciences, Impulse Dynamics, MyoKardia, Phillips, Svelte, V-Wave, and Zoll. Dr. Sulaiman reported no potential conflicts of interest. Dr. Perez de Prado reported no potential conflicts of interest but stated that this study was funded by Boston Scientific.
AT CRT 2023
After the Match: Next steps for new residents, unmatched
Medical school graduates around the US took to social media after last week's Match Day to share their joy ― or explore their options if they did not match.
Take this post March 19 on Twitter: “I went unmatched this year; looking for research position at any institute for internal medicine.”
including an international medical graduate who matched into his chosen specialty after multiple disappointments.
“I’ve waited for this email for 8 years,” Sahil Bawa, MD, posted on Twitter on March 13. A few days later, when he learned about his residency position, he posted: “I’m beyond grateful. Will be moving to Alabama soon #familymedicine.”
Dr. Bawa, who matched into UAB Medicine Selma (Ala.), graduated from medical school in India in 2014. He said in an interview that he has visited the United States periodically since then to pass medical tests, obtain letters of recommendation, and participate in research.
Over the years he watched his Indian colleagues give up on becoming American doctors, find alternative careers, or resolve to practice in their native country. But he held onto the few success stories he saw on social media. “There were always one to two every year. It kept me going. If they can do it, I can do it.”
International medical graduates (IMGs) like Dr. Bawa applied in record numbers to Match2023, according to the National Resident Matching Program (NRMP), which announced the results on March 13 of its main residency match and the Supplemental Offer and Acceptance Program (SOAP) for unfilled positions or unmatched applicants.
Overall, 48,156 total applicants registered for the match, which was driven by the increase of non-U.S. IMG applicants and U.S. DO seniors over the past year, NRMP stated in its release. U.S. MD seniors had a match rate of nearly 94%, and U.S. DO seniors, nearly 92%. U.S. IMGs had a match rate of nearly 68%, an “all-time high,” and non-U.S. IMGs, nearly 60%, NRMP stated.
Three specialties that filled all of their 30 or more available positions were orthopedic surgery, plastic surgery (integrated), radiology – diagnostic, and thoracic surgery. Specialties with 30 or more positions that filled with the highest percentage of U.S. MD and DO seniors were plastic surgery (integrated), internal medicine-pediatrics, ob.gyn., and orthopedic surgery.
The number of available primary care positions increased slightly, NRMP reported. Considering “a serious and growing shortage of primary care physicians across the U.S.,” there were 571 more primary care positions than 2022. That’s an increase of about 3% over last year and 17% over the past 5 years. Primary care positions filled at a rate of 94%, which remained steady from 2022.
NRMP also pointed out specialties with increases in the number of positions filled by U.S. MD seniors of more than 10% and 10 positions in the past 5 years: anesthesiology, child neurology, interventional radiology, neurology, pathology, physical medicine and rehabilitation, plastic surgery (integrated), psychiatry, radiology-diagnostic, transitional year, and vascular surgery.
Bryan Carmody, MD, MPH, a pediatric nephrologist known for his medical school commentaries, said in an interview that the most competitive specialties he noted in 2023 were radiology, pathology, and neurology.
“The surgical specialties are always competitive, so it wasn’t a surprise that orthopedics, plastic surgery, and thoracic surgery filled all of their positions. But I was surprised to see diagnostic radiology fill every single one of their positions in the match. And although pathology and neurology aren’t typically considered extremely competitive specialties, they filled over 99% of their positions in the Match this year.”
On Dr. Carmody’s blog about the winners and losers of Match Day, he said that despite the record number of primary care positions offered, family medicine programs suffered. “Only 89% of family medicine programs filled in the Match, and graduating U.S. MD and DO students only filled a little more than half of all the available positions,” he wrote.
For a record number of applicants that match each year, and “the most favorable ratio in the past 2 decades” of applicants-to-positions in 2023, there are still a lot unmatched, Dr. Carmody said. “It’s a tough thing to talk about. The reality is the number of residency positions should be determined by the number of physicians needed.”
One student, Asim Ansari, didn’t match into a traditional residency or through SOAP. It was his fifth attempt. He was serving a transitional-year residency at Merit Health Wesley in Hattiesburg, Miss., and when he didn’t match, he accepted a child and adolescent psychiatry fellowship at the University of Kansas Medical Center, Kansas City.
He said he was “relieved and excited” to have found a program in his chosen specialty. Still, in 2 years, Mr. Ansari must again try to match into a traditional psychiatry residency.
Meanwhile, Dr. Bawa will prepare for his 3-year residency in Alabama after completing his interim research year in the surgery department at Wayne State University, Detroit, in May.
Despite his years in limbo, Dr. Bawa said, “I have no regrets, no complaints. I am still very happy.”
A version of this article originally appeared on Medscape.com.
Medical school graduates around the US took to social media after last week's Match Day to share their joy ― or explore their options if they did not match.
Take this post March 19 on Twitter: “I went unmatched this year; looking for research position at any institute for internal medicine.”
including an international medical graduate who matched into his chosen specialty after multiple disappointments.
“I’ve waited for this email for 8 years,” Sahil Bawa, MD, posted on Twitter on March 13. A few days later, when he learned about his residency position, he posted: “I’m beyond grateful. Will be moving to Alabama soon #familymedicine.”
Dr. Bawa, who matched into UAB Medicine Selma (Ala.), graduated from medical school in India in 2014. He said in an interview that he has visited the United States periodically since then to pass medical tests, obtain letters of recommendation, and participate in research.
Over the years he watched his Indian colleagues give up on becoming American doctors, find alternative careers, or resolve to practice in their native country. But he held onto the few success stories he saw on social media. “There were always one to two every year. It kept me going. If they can do it, I can do it.”
International medical graduates (IMGs) like Dr. Bawa applied in record numbers to Match2023, according to the National Resident Matching Program (NRMP), which announced the results on March 13 of its main residency match and the Supplemental Offer and Acceptance Program (SOAP) for unfilled positions or unmatched applicants.
Overall, 48,156 total applicants registered for the match, which was driven by the increase of non-U.S. IMG applicants and U.S. DO seniors over the past year, NRMP stated in its release. U.S. MD seniors had a match rate of nearly 94%, and U.S. DO seniors, nearly 92%. U.S. IMGs had a match rate of nearly 68%, an “all-time high,” and non-U.S. IMGs, nearly 60%, NRMP stated.
Three specialties that filled all of their 30 or more available positions were orthopedic surgery, plastic surgery (integrated), radiology – diagnostic, and thoracic surgery. Specialties with 30 or more positions that filled with the highest percentage of U.S. MD and DO seniors were plastic surgery (integrated), internal medicine-pediatrics, ob.gyn., and orthopedic surgery.
The number of available primary care positions increased slightly, NRMP reported. Considering “a serious and growing shortage of primary care physicians across the U.S.,” there were 571 more primary care positions than 2022. That’s an increase of about 3% over last year and 17% over the past 5 years. Primary care positions filled at a rate of 94%, which remained steady from 2022.
NRMP also pointed out specialties with increases in the number of positions filled by U.S. MD seniors of more than 10% and 10 positions in the past 5 years: anesthesiology, child neurology, interventional radiology, neurology, pathology, physical medicine and rehabilitation, plastic surgery (integrated), psychiatry, radiology-diagnostic, transitional year, and vascular surgery.
Bryan Carmody, MD, MPH, a pediatric nephrologist known for his medical school commentaries, said in an interview that the most competitive specialties he noted in 2023 were radiology, pathology, and neurology.
“The surgical specialties are always competitive, so it wasn’t a surprise that orthopedics, plastic surgery, and thoracic surgery filled all of their positions. But I was surprised to see diagnostic radiology fill every single one of their positions in the match. And although pathology and neurology aren’t typically considered extremely competitive specialties, they filled over 99% of their positions in the Match this year.”
On Dr. Carmody’s blog about the winners and losers of Match Day, he said that despite the record number of primary care positions offered, family medicine programs suffered. “Only 89% of family medicine programs filled in the Match, and graduating U.S. MD and DO students only filled a little more than half of all the available positions,” he wrote.
For a record number of applicants that match each year, and “the most favorable ratio in the past 2 decades” of applicants-to-positions in 2023, there are still a lot unmatched, Dr. Carmody said. “It’s a tough thing to talk about. The reality is the number of residency positions should be determined by the number of physicians needed.”
One student, Asim Ansari, didn’t match into a traditional residency or through SOAP. It was his fifth attempt. He was serving a transitional-year residency at Merit Health Wesley in Hattiesburg, Miss., and when he didn’t match, he accepted a child and adolescent psychiatry fellowship at the University of Kansas Medical Center, Kansas City.
He said he was “relieved and excited” to have found a program in his chosen specialty. Still, in 2 years, Mr. Ansari must again try to match into a traditional psychiatry residency.
Meanwhile, Dr. Bawa will prepare for his 3-year residency in Alabama after completing his interim research year in the surgery department at Wayne State University, Detroit, in May.
Despite his years in limbo, Dr. Bawa said, “I have no regrets, no complaints. I am still very happy.”
A version of this article originally appeared on Medscape.com.
Medical school graduates around the US took to social media after last week's Match Day to share their joy ― or explore their options if they did not match.
Take this post March 19 on Twitter: “I went unmatched this year; looking for research position at any institute for internal medicine.”
including an international medical graduate who matched into his chosen specialty after multiple disappointments.
“I’ve waited for this email for 8 years,” Sahil Bawa, MD, posted on Twitter on March 13. A few days later, when he learned about his residency position, he posted: “I’m beyond grateful. Will be moving to Alabama soon #familymedicine.”
Dr. Bawa, who matched into UAB Medicine Selma (Ala.), graduated from medical school in India in 2014. He said in an interview that he has visited the United States periodically since then to pass medical tests, obtain letters of recommendation, and participate in research.
Over the years he watched his Indian colleagues give up on becoming American doctors, find alternative careers, or resolve to practice in their native country. But he held onto the few success stories he saw on social media. “There were always one to two every year. It kept me going. If they can do it, I can do it.”
International medical graduates (IMGs) like Dr. Bawa applied in record numbers to Match2023, according to the National Resident Matching Program (NRMP), which announced the results on March 13 of its main residency match and the Supplemental Offer and Acceptance Program (SOAP) for unfilled positions or unmatched applicants.
Overall, 48,156 total applicants registered for the match, which was driven by the increase of non-U.S. IMG applicants and U.S. DO seniors over the past year, NRMP stated in its release. U.S. MD seniors had a match rate of nearly 94%, and U.S. DO seniors, nearly 92%. U.S. IMGs had a match rate of nearly 68%, an “all-time high,” and non-U.S. IMGs, nearly 60%, NRMP stated.
Three specialties that filled all of their 30 or more available positions were orthopedic surgery, plastic surgery (integrated), radiology – diagnostic, and thoracic surgery. Specialties with 30 or more positions that filled with the highest percentage of U.S. MD and DO seniors were plastic surgery (integrated), internal medicine-pediatrics, ob.gyn., and orthopedic surgery.
The number of available primary care positions increased slightly, NRMP reported. Considering “a serious and growing shortage of primary care physicians across the U.S.,” there were 571 more primary care positions than 2022. That’s an increase of about 3% over last year and 17% over the past 5 years. Primary care positions filled at a rate of 94%, which remained steady from 2022.
NRMP also pointed out specialties with increases in the number of positions filled by U.S. MD seniors of more than 10% and 10 positions in the past 5 years: anesthesiology, child neurology, interventional radiology, neurology, pathology, physical medicine and rehabilitation, plastic surgery (integrated), psychiatry, radiology-diagnostic, transitional year, and vascular surgery.
Bryan Carmody, MD, MPH, a pediatric nephrologist known for his medical school commentaries, said in an interview that the most competitive specialties he noted in 2023 were radiology, pathology, and neurology.
“The surgical specialties are always competitive, so it wasn’t a surprise that orthopedics, plastic surgery, and thoracic surgery filled all of their positions. But I was surprised to see diagnostic radiology fill every single one of their positions in the match. And although pathology and neurology aren’t typically considered extremely competitive specialties, they filled over 99% of their positions in the Match this year.”
On Dr. Carmody’s blog about the winners and losers of Match Day, he said that despite the record number of primary care positions offered, family medicine programs suffered. “Only 89% of family medicine programs filled in the Match, and graduating U.S. MD and DO students only filled a little more than half of all the available positions,” he wrote.
For a record number of applicants that match each year, and “the most favorable ratio in the past 2 decades” of applicants-to-positions in 2023, there are still a lot unmatched, Dr. Carmody said. “It’s a tough thing to talk about. The reality is the number of residency positions should be determined by the number of physicians needed.”
One student, Asim Ansari, didn’t match into a traditional residency or through SOAP. It was his fifth attempt. He was serving a transitional-year residency at Merit Health Wesley in Hattiesburg, Miss., and when he didn’t match, he accepted a child and adolescent psychiatry fellowship at the University of Kansas Medical Center, Kansas City.
He said he was “relieved and excited” to have found a program in his chosen specialty. Still, in 2 years, Mr. Ansari must again try to match into a traditional psychiatry residency.
Meanwhile, Dr. Bawa will prepare for his 3-year residency in Alabama after completing his interim research year in the surgery department at Wayne State University, Detroit, in May.
Despite his years in limbo, Dr. Bawa said, “I have no regrets, no complaints. I am still very happy.”
A version of this article originally appeared on Medscape.com.
Old-school printer helps scientists quickly spot bacteria in blood
When a bacterial infection reaches the bloodstream, every second is critical. The person’s life is on the line. Yet blood tests to identify bacteria take hours to days. While waiting, doctors often prescribe broad-spectrum antibiotics in hopes of killing whatever bug may be at fault.
Someday soon, that wait time could shrink significantly, allowing health care providers to more quickly zero in on the best antibiotic for each infection – thanks to an innovation from Stanford (Calif.) University that identifies bacteria in seconds.
The cutting-edge method relies on old-school tech: an inkjet printer similar the kind you might have at home – except this one has been modified to print blood instead of ink.
The very small sample size – each drop is two trillionths of a liter, or about a billion times smaller than a raindrop – make spotting bacteria easier. Smaller samples mean fewer cells, so lab techs can more swiftly separate the bacterial spectra from other components, like red blood cells and white blood cells.
To boost efficiency even more, the researchers added gold nanoparticles, which attach to the bacteria, serving like antennas to focus the light. Machine learning – a type of artificial intelligence – helps interpret the spectrum of light and identify which fingerprint goes with which bacteria.
“It kind of wound up being this really interesting historical period where we could put the pieces together from different technologies, including nanophotonics, printing, and artificial intelligence, to help accelerate identification of bacteria in these complex samples,” says study author Jennifer Dionne, PhD, associate professor of materials science and engineering at Stanford.
Compare that to blood culture testing in hospitals, where it takes days for bacterial cells to grow and multiply inside a large machine that looks like a refrigerator. For some bacteria, like the kinds that cause tuberculosis, cultures take weeks.
Then further testing is needed to identify which antibiotics will quell the infection. The new technology from Stanford could accelerate this process, too.
“The promise of our technique is that you don’t need to have a culture of cells to put the antibiotic on top,” says Dr. Dionne. “What we’re finding is that from the Raman scattering, we can use that to identify – even without incubating with antibiotics – which drug the bacteria would respond to, and that’s really exciting.”
If patients can receive the antibiotic best suited for their infection, they will likely have better outcomes.
“Blood cultures can typically take 48-72 hours to come back, and then you base your clinical decisions and adjusting antibiotics based on those blood cultures,” says Richard Watkins, MD, an infectious disease physician and professor of medicine at the Northeastern Ohio Universities, Rootstown. Dr. Watkins was not involved in the study.
“Sometimes, despite your best guess, you’re wrong,” Dr. Watkins says, “and obviously, the patient could have an adverse outcome. So, if you can diagnose the pathogen sooner, that is ideal. Whatever technology enables clinicians to do that is definitely progress and a step forward.”
On a global scale, this technology could help reduce the overuse of broad-spectrum antibiotics, which contributes to antimicrobial resistance, an emerging health threat, says Dr. Dionne.
The team is working to develop the technology further into an instrument the size of a shoebox and, with further testing, commercialize the product. That could take a few years.
This technology has potential beyond bloodstream infections, too. It could be used to identify bacteria in other fluids, such as in wastewater or contaminated food.
A version of this article originally appeared on WebMD.com.
When a bacterial infection reaches the bloodstream, every second is critical. The person’s life is on the line. Yet blood tests to identify bacteria take hours to days. While waiting, doctors often prescribe broad-spectrum antibiotics in hopes of killing whatever bug may be at fault.
Someday soon, that wait time could shrink significantly, allowing health care providers to more quickly zero in on the best antibiotic for each infection – thanks to an innovation from Stanford (Calif.) University that identifies bacteria in seconds.
The cutting-edge method relies on old-school tech: an inkjet printer similar the kind you might have at home – except this one has been modified to print blood instead of ink.
The very small sample size – each drop is two trillionths of a liter, or about a billion times smaller than a raindrop – make spotting bacteria easier. Smaller samples mean fewer cells, so lab techs can more swiftly separate the bacterial spectra from other components, like red blood cells and white blood cells.
To boost efficiency even more, the researchers added gold nanoparticles, which attach to the bacteria, serving like antennas to focus the light. Machine learning – a type of artificial intelligence – helps interpret the spectrum of light and identify which fingerprint goes with which bacteria.
“It kind of wound up being this really interesting historical period where we could put the pieces together from different technologies, including nanophotonics, printing, and artificial intelligence, to help accelerate identification of bacteria in these complex samples,” says study author Jennifer Dionne, PhD, associate professor of materials science and engineering at Stanford.
Compare that to blood culture testing in hospitals, where it takes days for bacterial cells to grow and multiply inside a large machine that looks like a refrigerator. For some bacteria, like the kinds that cause tuberculosis, cultures take weeks.
Then further testing is needed to identify which antibiotics will quell the infection. The new technology from Stanford could accelerate this process, too.
“The promise of our technique is that you don’t need to have a culture of cells to put the antibiotic on top,” says Dr. Dionne. “What we’re finding is that from the Raman scattering, we can use that to identify – even without incubating with antibiotics – which drug the bacteria would respond to, and that’s really exciting.”
If patients can receive the antibiotic best suited for their infection, they will likely have better outcomes.
“Blood cultures can typically take 48-72 hours to come back, and then you base your clinical decisions and adjusting antibiotics based on those blood cultures,” says Richard Watkins, MD, an infectious disease physician and professor of medicine at the Northeastern Ohio Universities, Rootstown. Dr. Watkins was not involved in the study.
“Sometimes, despite your best guess, you’re wrong,” Dr. Watkins says, “and obviously, the patient could have an adverse outcome. So, if you can diagnose the pathogen sooner, that is ideal. Whatever technology enables clinicians to do that is definitely progress and a step forward.”
On a global scale, this technology could help reduce the overuse of broad-spectrum antibiotics, which contributes to antimicrobial resistance, an emerging health threat, says Dr. Dionne.
The team is working to develop the technology further into an instrument the size of a shoebox and, with further testing, commercialize the product. That could take a few years.
This technology has potential beyond bloodstream infections, too. It could be used to identify bacteria in other fluids, such as in wastewater or contaminated food.
A version of this article originally appeared on WebMD.com.
When a bacterial infection reaches the bloodstream, every second is critical. The person’s life is on the line. Yet blood tests to identify bacteria take hours to days. While waiting, doctors often prescribe broad-spectrum antibiotics in hopes of killing whatever bug may be at fault.
Someday soon, that wait time could shrink significantly, allowing health care providers to more quickly zero in on the best antibiotic for each infection – thanks to an innovation from Stanford (Calif.) University that identifies bacteria in seconds.
The cutting-edge method relies on old-school tech: an inkjet printer similar the kind you might have at home – except this one has been modified to print blood instead of ink.
The very small sample size – each drop is two trillionths of a liter, or about a billion times smaller than a raindrop – make spotting bacteria easier. Smaller samples mean fewer cells, so lab techs can more swiftly separate the bacterial spectra from other components, like red blood cells and white blood cells.
To boost efficiency even more, the researchers added gold nanoparticles, which attach to the bacteria, serving like antennas to focus the light. Machine learning – a type of artificial intelligence – helps interpret the spectrum of light and identify which fingerprint goes with which bacteria.
“It kind of wound up being this really interesting historical period where we could put the pieces together from different technologies, including nanophotonics, printing, and artificial intelligence, to help accelerate identification of bacteria in these complex samples,” says study author Jennifer Dionne, PhD, associate professor of materials science and engineering at Stanford.
Compare that to blood culture testing in hospitals, where it takes days for bacterial cells to grow and multiply inside a large machine that looks like a refrigerator. For some bacteria, like the kinds that cause tuberculosis, cultures take weeks.
Then further testing is needed to identify which antibiotics will quell the infection. The new technology from Stanford could accelerate this process, too.
“The promise of our technique is that you don’t need to have a culture of cells to put the antibiotic on top,” says Dr. Dionne. “What we’re finding is that from the Raman scattering, we can use that to identify – even without incubating with antibiotics – which drug the bacteria would respond to, and that’s really exciting.”
If patients can receive the antibiotic best suited for their infection, they will likely have better outcomes.
“Blood cultures can typically take 48-72 hours to come back, and then you base your clinical decisions and adjusting antibiotics based on those blood cultures,” says Richard Watkins, MD, an infectious disease physician and professor of medicine at the Northeastern Ohio Universities, Rootstown. Dr. Watkins was not involved in the study.
“Sometimes, despite your best guess, you’re wrong,” Dr. Watkins says, “and obviously, the patient could have an adverse outcome. So, if you can diagnose the pathogen sooner, that is ideal. Whatever technology enables clinicians to do that is definitely progress and a step forward.”
On a global scale, this technology could help reduce the overuse of broad-spectrum antibiotics, which contributes to antimicrobial resistance, an emerging health threat, says Dr. Dionne.
The team is working to develop the technology further into an instrument the size of a shoebox and, with further testing, commercialize the product. That could take a few years.
This technology has potential beyond bloodstream infections, too. It could be used to identify bacteria in other fluids, such as in wastewater or contaminated food.
A version of this article originally appeared on WebMD.com.





