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30% of docs say they don’t want own kids 5-11 to get COVID vaccine
A Medscape
Among physician respondents who have children in that age group, 30% said they would not want their children to be vaccinated; 9% were unsure. For nurses/advanced practice registered nurses (APRNs), more (45%) said they did not want their kids to get the COVID-19 vaccine; 13% were unsure. Among pharmacists, 31% said they would not get them vaccinated and 9% were unsure.
Clinicians were more likely to want vaccinations for their kids 5-11 than were 510 consumers polled by WebMD at the same time. Overall, 49% of the consumers who had kids that age did not want them to get the COVID-19 vaccine.
On November 2, Centers for Disease Control and Prevention (CDC) Director Rochelle P. Walensky, MD, MPH, endorsed the CDC Advisory Committee on Immunization Practices’ recommendation that children 5-11 be vaccinated with the Pfizer-BioNTech pediatric vaccine. That decision expanded vaccine recommendations to about 28 million children in the United States.
The CDC states that, in clinical trials, the Pfizer vaccine had more than 90% efficacy in preventing laboratory-confirmed COVID-19 infection in children 5 to 15 years old, and that the immune response in children ages 5-15 equaled the immune response in people 16 to 25 years old.
The Medscape poll, fielded from November 3 to November 11, included 325 physicians, 793 nurses/APRNs, and 151 pharmacists.
How safe is the vaccine?
Clinicians were asked how confident they were that the vaccine is safe for that age group, and 66% of physicians, 52% of nurses/APRNs, and 66% of pharmacists said they were somewhat or very confident.
Among consumers overall in the WebMD poll, 56% said they were confident or somewhat confident that the vaccine is safe in that age group.
Among adolescents and young adults, rare cases of myocarditis and pericarditis in adolescents and young adults have been reported. According to the CDC, “[I]n one study, the risk of myocarditis after the second dose of Pfizer-BioNTech in the week following vaccination was around 54 cases per million doses administered to males ages 12-17 years.”
Known and potential benefits of COVID-19 vaccination outweigh the risks, including the possible risk for myocarditis or pericarditis, the CDC states.
Across clinician types, women edged out their male counterparts on confidence in the vaccine’ s safety: 71% vs 65% among physicians, 55% vs 45% among nurses/APRNs, and 68% vs 60% among pharmacists.
Among both physicians and nurses, younger physicians (under 45) tended to have greater confidence in the vaccine’ s safety: 72% vs 64% (physicians), 54% vs 51% (nurses/APRNs), and 71% vs 59% (pharmacists).
The difference in confidence was clear between vaccinated and unvaccinated physicians. All of the unvaccinated physicians who responded to the poll said they had no confidence in the vaccine for kids. Among unvaccinated nurses/APRNs, 2% were somewhat confident in the vaccine for kids under 12.
Knowledge about smaller dosage
The clinicians were asked about whether they were aware, before reading the poll question, that the Pfizer vaccine for children and the proposed Moderna vaccine for children in this age group (5-11) would have a different dosage.
The dose for kids 5-11 is 10 micrograms rather than 30 micrograms for people at least 12 years old. Children 5-11 receive a second dose 21 days or more after their first shot. The formulation comes with an orange cap, and a smaller needle is used.
Knowledge on the lower dose was highest among pharmacists (91% said they knew), followed by physicians (84%) and nurses (79%).
The poll also asked whether the COVID-19 vaccine should be added to the list of childhood immunizations. Responses varied widely and uncertainty was evident.
Notably, female physicians were more likely to say it should be added to the list of immunizations than were their male counterparts: 46% vs 35% (physicians), 26% vs 22% (nurses/APRNs), and 33% vs 30% (pharmacists).
A version of this article first appeared on Medscape.com.
A Medscape
Among physician respondents who have children in that age group, 30% said they would not want their children to be vaccinated; 9% were unsure. For nurses/advanced practice registered nurses (APRNs), more (45%) said they did not want their kids to get the COVID-19 vaccine; 13% were unsure. Among pharmacists, 31% said they would not get them vaccinated and 9% were unsure.
Clinicians were more likely to want vaccinations for their kids 5-11 than were 510 consumers polled by WebMD at the same time. Overall, 49% of the consumers who had kids that age did not want them to get the COVID-19 vaccine.
On November 2, Centers for Disease Control and Prevention (CDC) Director Rochelle P. Walensky, MD, MPH, endorsed the CDC Advisory Committee on Immunization Practices’ recommendation that children 5-11 be vaccinated with the Pfizer-BioNTech pediatric vaccine. That decision expanded vaccine recommendations to about 28 million children in the United States.
The CDC states that, in clinical trials, the Pfizer vaccine had more than 90% efficacy in preventing laboratory-confirmed COVID-19 infection in children 5 to 15 years old, and that the immune response in children ages 5-15 equaled the immune response in people 16 to 25 years old.
The Medscape poll, fielded from November 3 to November 11, included 325 physicians, 793 nurses/APRNs, and 151 pharmacists.
How safe is the vaccine?
Clinicians were asked how confident they were that the vaccine is safe for that age group, and 66% of physicians, 52% of nurses/APRNs, and 66% of pharmacists said they were somewhat or very confident.
Among consumers overall in the WebMD poll, 56% said they were confident or somewhat confident that the vaccine is safe in that age group.
Among adolescents and young adults, rare cases of myocarditis and pericarditis in adolescents and young adults have been reported. According to the CDC, “[I]n one study, the risk of myocarditis after the second dose of Pfizer-BioNTech in the week following vaccination was around 54 cases per million doses administered to males ages 12-17 years.”
Known and potential benefits of COVID-19 vaccination outweigh the risks, including the possible risk for myocarditis or pericarditis, the CDC states.
Across clinician types, women edged out their male counterparts on confidence in the vaccine’ s safety: 71% vs 65% among physicians, 55% vs 45% among nurses/APRNs, and 68% vs 60% among pharmacists.
Among both physicians and nurses, younger physicians (under 45) tended to have greater confidence in the vaccine’ s safety: 72% vs 64% (physicians), 54% vs 51% (nurses/APRNs), and 71% vs 59% (pharmacists).
The difference in confidence was clear between vaccinated and unvaccinated physicians. All of the unvaccinated physicians who responded to the poll said they had no confidence in the vaccine for kids. Among unvaccinated nurses/APRNs, 2% were somewhat confident in the vaccine for kids under 12.
Knowledge about smaller dosage
The clinicians were asked about whether they were aware, before reading the poll question, that the Pfizer vaccine for children and the proposed Moderna vaccine for children in this age group (5-11) would have a different dosage.
The dose for kids 5-11 is 10 micrograms rather than 30 micrograms for people at least 12 years old. Children 5-11 receive a second dose 21 days or more after their first shot. The formulation comes with an orange cap, and a smaller needle is used.
Knowledge on the lower dose was highest among pharmacists (91% said they knew), followed by physicians (84%) and nurses (79%).
The poll also asked whether the COVID-19 vaccine should be added to the list of childhood immunizations. Responses varied widely and uncertainty was evident.
Notably, female physicians were more likely to say it should be added to the list of immunizations than were their male counterparts: 46% vs 35% (physicians), 26% vs 22% (nurses/APRNs), and 33% vs 30% (pharmacists).
A version of this article first appeared on Medscape.com.
A Medscape
Among physician respondents who have children in that age group, 30% said they would not want their children to be vaccinated; 9% were unsure. For nurses/advanced practice registered nurses (APRNs), more (45%) said they did not want their kids to get the COVID-19 vaccine; 13% were unsure. Among pharmacists, 31% said they would not get them vaccinated and 9% were unsure.
Clinicians were more likely to want vaccinations for their kids 5-11 than were 510 consumers polled by WebMD at the same time. Overall, 49% of the consumers who had kids that age did not want them to get the COVID-19 vaccine.
On November 2, Centers for Disease Control and Prevention (CDC) Director Rochelle P. Walensky, MD, MPH, endorsed the CDC Advisory Committee on Immunization Practices’ recommendation that children 5-11 be vaccinated with the Pfizer-BioNTech pediatric vaccine. That decision expanded vaccine recommendations to about 28 million children in the United States.
The CDC states that, in clinical trials, the Pfizer vaccine had more than 90% efficacy in preventing laboratory-confirmed COVID-19 infection in children 5 to 15 years old, and that the immune response in children ages 5-15 equaled the immune response in people 16 to 25 years old.
The Medscape poll, fielded from November 3 to November 11, included 325 physicians, 793 nurses/APRNs, and 151 pharmacists.
How safe is the vaccine?
Clinicians were asked how confident they were that the vaccine is safe for that age group, and 66% of physicians, 52% of nurses/APRNs, and 66% of pharmacists said they were somewhat or very confident.
Among consumers overall in the WebMD poll, 56% said they were confident or somewhat confident that the vaccine is safe in that age group.
Among adolescents and young adults, rare cases of myocarditis and pericarditis in adolescents and young adults have been reported. According to the CDC, “[I]n one study, the risk of myocarditis after the second dose of Pfizer-BioNTech in the week following vaccination was around 54 cases per million doses administered to males ages 12-17 years.”
Known and potential benefits of COVID-19 vaccination outweigh the risks, including the possible risk for myocarditis or pericarditis, the CDC states.
Across clinician types, women edged out their male counterparts on confidence in the vaccine’ s safety: 71% vs 65% among physicians, 55% vs 45% among nurses/APRNs, and 68% vs 60% among pharmacists.
Among both physicians and nurses, younger physicians (under 45) tended to have greater confidence in the vaccine’ s safety: 72% vs 64% (physicians), 54% vs 51% (nurses/APRNs), and 71% vs 59% (pharmacists).
The difference in confidence was clear between vaccinated and unvaccinated physicians. All of the unvaccinated physicians who responded to the poll said they had no confidence in the vaccine for kids. Among unvaccinated nurses/APRNs, 2% were somewhat confident in the vaccine for kids under 12.
Knowledge about smaller dosage
The clinicians were asked about whether they were aware, before reading the poll question, that the Pfizer vaccine for children and the proposed Moderna vaccine for children in this age group (5-11) would have a different dosage.
The dose for kids 5-11 is 10 micrograms rather than 30 micrograms for people at least 12 years old. Children 5-11 receive a second dose 21 days or more after their first shot. The formulation comes with an orange cap, and a smaller needle is used.
Knowledge on the lower dose was highest among pharmacists (91% said they knew), followed by physicians (84%) and nurses (79%).
The poll also asked whether the COVID-19 vaccine should be added to the list of childhood immunizations. Responses varied widely and uncertainty was evident.
Notably, female physicians were more likely to say it should be added to the list of immunizations than were their male counterparts: 46% vs 35% (physicians), 26% vs 22% (nurses/APRNs), and 33% vs 30% (pharmacists).
A version of this article first appeared on Medscape.com.
Treating unexplained infertility – avoiding trial and error
Physicians who care for women having difficulty conceiving must understand the devastation their patients feel while knowing how to define infertility, when (and when not) to advise an evaluation, and offer evidence-based treatment options. Analogous to a mother desiring an antibiotic prescription for her child’s common cold, infertility patients can be desperate for an evaluation and treatment, despite the lack of an indication. This month’s article addresses the diagnosis and management of unexplained infertility.
The chronological age of a woman is the leading prognostic factor for successful reproduction. The definition of infertility remains 1 year of an inability to conceive in a couple who have no demonstrable risk factors, such as ovulation dysfunction, prior infertility, or known male factor. In women less than age 30, monthly fecundity rates are between 20% and 37% during the first 3 months of trying to conceive. The chance of success increases to 80% after 1 year and 90% after 2 years of trying to conceive, according to the American Society of Reproductive Medicine. Nevertheless, following unsuccessful attempts at conception by a couple, the physician should offer an evaluation based on the woman’s age – 1 year for women less than age 35, 6 months for women aged 35-39, and 3 months for women aged 40 and older. Testing can be initiated earlier if there are predisposing factors impairing fertility.
The basic infertility evaluation consists of a thorough history of the couple, a review of medical records, and an assessment of ovulation, fallopian tube patency, and sperm parameters on analysis. In the interest of efficiency, given that couples are typically anxious, these three areas can be evaluated within 1 month. In years past, a diagnostic laparoscopy was considered the gold standard of necessity to provide the diagnosis of exclusion, that is, unexplained infertility. This surgical procedure has fallen out of favor given the low diagnostic yield in a woman with a normal hysterosalpingogram, pelvic ultrasound, and no risk for a pelvic factor; for example, prior abdominal myomectomy, bowel surgery, or strong suspicion for endometriosis based on symptoms including significant pelvic pain affecting activities of daily living.
Initial laboratory testing should be judiciously ordered by recommending only those that will affect management, that is, prenatal labs to assess immunity to rubella and varicella along with a baseline thyroid-stimulating hormone, CBC, blood type, and Rh and antibody screen. In a woman with monthly ovulatory menstrual cycles and no signs of hirsutism or galactorrhea, the clinical utility of obtaining follicle-stimulating hormone, luteinizing hormone (LH), estradiol, prolactin, total and free testosterone, and dehydroepiandrosterone lack evidence. Further, a random anti-Müllerian hormone (without prior chemotherapy, radiation, or ovarian surgery) lacks value as the natural pregnancy rate does not appear to be affected, although low AMH has been associated with an increased risk for miscarriage.
Although not typically screened, measles can cause significant complications in pregnancy including an increased risk of maternal hospitalization and pneumonia, as well as miscarriage, stillbirth, low birth weight, and increased risk of preterm delivery.
Education is an important tool to guide patients and begins with an explanation of urine LH timed intercourse. From the onset of the LH surge, the oocyte is released in 24-36 hours, i.e., the actual day of ovulation is estimated to be the day after the urine LH surge. The “fertile window” appears to be the 5 days before plus the day of ovulation but the highest chance of conception occurs within the 2 days before and including the day of ovulation.
Empiric treatment may be offered when no demonstrable etiology has been identified, lifestyle factors have been addressed (for example, elevated female body mass index, tobacco use by the couple), and medical conditions have been optimized. Reproductive capability declines with continued attempts at conception such that, by 2 years, the approximate monthly fecundity rate is 3%-4%.
The first-line treatment of unexplained infertility is clomiphene citrate (CC) with intrauterine insemination. Letrozole, while not Food and Drug Administration approved for infertility treatment, has been shown in multiple studies to be equally effective as CC and to have a good safety profile. In a recent study, the cumulative live-birth rate over three cycles with CC and IUI, compared with expectant management was 31% versus 9%, respectively. Further, multiple studies failed to show a difference in pregnancy outcomes when comparing CC and IUI with letrozole and IUI.
It is vital to note that, for women who ovulate, studies do not support the use of CC without the addition of intrauterine insemination (IUI). The monthly fecundity rate of a cycle of CC without IUI is similar to natural conception attempts with urine LH timed intercourse, that is, without ovarian stimulation.
Recommendations (along with the level of evidence) from ASRM guidelines
- 1. Natural cycle, that is, without ovarian stimulation, timed with IUI is equivalent to expectant management (strong)
- 2. CC or letrozole with timed intercourse is no more effective than a natural cycle (good)
- 3. Pregnancy rates using gonadotropins with timed intercourse have not been shown to be superior to oral ovarian stimulating medications but risks multiple gestation (insufficient)
- 4. CC plus standard-dose gonadotropins results in higher pregnancy rates, there is good evidence for an increased risk of multiple gestation (fair)
- 5. Treatment with gonadotropins alone with IUI is superior to CC or letrozole with IUI; the risk of a multiple gestation rate remains significant (insufficient)
- 6. IUI can be performed between 0 and 36 hours following human chorionic gonadotropin trigger and performing one IUI in a cycle has equivalent success as two (fair)
- 7. Immediate IVF in women older than 38 years may be associated with a higher pregnancy rate and shorter time to pregnancy, compared with ovarian stimulation/IUI cycles before IVF (good)
Conclusion
It is recommended that couples with unexplained infertility initially undergo a course (typically three or four cycles) of ovarian stimulation with IUI using oral agents (CC or letrozole). For those unsuccessful with ovarian stimulation and IUI treatments with oral agents, in vitro fertilization is recommended rather than ovarian stimulation and IUI with gonadotropins to reduce the risk of a multiple gestation.
Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. Email him at [email protected].
Physicians who care for women having difficulty conceiving must understand the devastation their patients feel while knowing how to define infertility, when (and when not) to advise an evaluation, and offer evidence-based treatment options. Analogous to a mother desiring an antibiotic prescription for her child’s common cold, infertility patients can be desperate for an evaluation and treatment, despite the lack of an indication. This month’s article addresses the diagnosis and management of unexplained infertility.
The chronological age of a woman is the leading prognostic factor for successful reproduction. The definition of infertility remains 1 year of an inability to conceive in a couple who have no demonstrable risk factors, such as ovulation dysfunction, prior infertility, or known male factor. In women less than age 30, monthly fecundity rates are between 20% and 37% during the first 3 months of trying to conceive. The chance of success increases to 80% after 1 year and 90% after 2 years of trying to conceive, according to the American Society of Reproductive Medicine. Nevertheless, following unsuccessful attempts at conception by a couple, the physician should offer an evaluation based on the woman’s age – 1 year for women less than age 35, 6 months for women aged 35-39, and 3 months for women aged 40 and older. Testing can be initiated earlier if there are predisposing factors impairing fertility.
The basic infertility evaluation consists of a thorough history of the couple, a review of medical records, and an assessment of ovulation, fallopian tube patency, and sperm parameters on analysis. In the interest of efficiency, given that couples are typically anxious, these three areas can be evaluated within 1 month. In years past, a diagnostic laparoscopy was considered the gold standard of necessity to provide the diagnosis of exclusion, that is, unexplained infertility. This surgical procedure has fallen out of favor given the low diagnostic yield in a woman with a normal hysterosalpingogram, pelvic ultrasound, and no risk for a pelvic factor; for example, prior abdominal myomectomy, bowel surgery, or strong suspicion for endometriosis based on symptoms including significant pelvic pain affecting activities of daily living.
Initial laboratory testing should be judiciously ordered by recommending only those that will affect management, that is, prenatal labs to assess immunity to rubella and varicella along with a baseline thyroid-stimulating hormone, CBC, blood type, and Rh and antibody screen. In a woman with monthly ovulatory menstrual cycles and no signs of hirsutism or galactorrhea, the clinical utility of obtaining follicle-stimulating hormone, luteinizing hormone (LH), estradiol, prolactin, total and free testosterone, and dehydroepiandrosterone lack evidence. Further, a random anti-Müllerian hormone (without prior chemotherapy, radiation, or ovarian surgery) lacks value as the natural pregnancy rate does not appear to be affected, although low AMH has been associated with an increased risk for miscarriage.
Although not typically screened, measles can cause significant complications in pregnancy including an increased risk of maternal hospitalization and pneumonia, as well as miscarriage, stillbirth, low birth weight, and increased risk of preterm delivery.
Education is an important tool to guide patients and begins with an explanation of urine LH timed intercourse. From the onset of the LH surge, the oocyte is released in 24-36 hours, i.e., the actual day of ovulation is estimated to be the day after the urine LH surge. The “fertile window” appears to be the 5 days before plus the day of ovulation but the highest chance of conception occurs within the 2 days before and including the day of ovulation.
Empiric treatment may be offered when no demonstrable etiology has been identified, lifestyle factors have been addressed (for example, elevated female body mass index, tobacco use by the couple), and medical conditions have been optimized. Reproductive capability declines with continued attempts at conception such that, by 2 years, the approximate monthly fecundity rate is 3%-4%.
The first-line treatment of unexplained infertility is clomiphene citrate (CC) with intrauterine insemination. Letrozole, while not Food and Drug Administration approved for infertility treatment, has been shown in multiple studies to be equally effective as CC and to have a good safety profile. In a recent study, the cumulative live-birth rate over three cycles with CC and IUI, compared with expectant management was 31% versus 9%, respectively. Further, multiple studies failed to show a difference in pregnancy outcomes when comparing CC and IUI with letrozole and IUI.
It is vital to note that, for women who ovulate, studies do not support the use of CC without the addition of intrauterine insemination (IUI). The monthly fecundity rate of a cycle of CC without IUI is similar to natural conception attempts with urine LH timed intercourse, that is, without ovarian stimulation.
Recommendations (along with the level of evidence) from ASRM guidelines
- 1. Natural cycle, that is, without ovarian stimulation, timed with IUI is equivalent to expectant management (strong)
- 2. CC or letrozole with timed intercourse is no more effective than a natural cycle (good)
- 3. Pregnancy rates using gonadotropins with timed intercourse have not been shown to be superior to oral ovarian stimulating medications but risks multiple gestation (insufficient)
- 4. CC plus standard-dose gonadotropins results in higher pregnancy rates, there is good evidence for an increased risk of multiple gestation (fair)
- 5. Treatment with gonadotropins alone with IUI is superior to CC or letrozole with IUI; the risk of a multiple gestation rate remains significant (insufficient)
- 6. IUI can be performed between 0 and 36 hours following human chorionic gonadotropin trigger and performing one IUI in a cycle has equivalent success as two (fair)
- 7. Immediate IVF in women older than 38 years may be associated with a higher pregnancy rate and shorter time to pregnancy, compared with ovarian stimulation/IUI cycles before IVF (good)
Conclusion
It is recommended that couples with unexplained infertility initially undergo a course (typically three or four cycles) of ovarian stimulation with IUI using oral agents (CC or letrozole). For those unsuccessful with ovarian stimulation and IUI treatments with oral agents, in vitro fertilization is recommended rather than ovarian stimulation and IUI with gonadotropins to reduce the risk of a multiple gestation.
Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. Email him at [email protected].
Physicians who care for women having difficulty conceiving must understand the devastation their patients feel while knowing how to define infertility, when (and when not) to advise an evaluation, and offer evidence-based treatment options. Analogous to a mother desiring an antibiotic prescription for her child’s common cold, infertility patients can be desperate for an evaluation and treatment, despite the lack of an indication. This month’s article addresses the diagnosis and management of unexplained infertility.
The chronological age of a woman is the leading prognostic factor for successful reproduction. The definition of infertility remains 1 year of an inability to conceive in a couple who have no demonstrable risk factors, such as ovulation dysfunction, prior infertility, or known male factor. In women less than age 30, monthly fecundity rates are between 20% and 37% during the first 3 months of trying to conceive. The chance of success increases to 80% after 1 year and 90% after 2 years of trying to conceive, according to the American Society of Reproductive Medicine. Nevertheless, following unsuccessful attempts at conception by a couple, the physician should offer an evaluation based on the woman’s age – 1 year for women less than age 35, 6 months for women aged 35-39, and 3 months for women aged 40 and older. Testing can be initiated earlier if there are predisposing factors impairing fertility.
The basic infertility evaluation consists of a thorough history of the couple, a review of medical records, and an assessment of ovulation, fallopian tube patency, and sperm parameters on analysis. In the interest of efficiency, given that couples are typically anxious, these three areas can be evaluated within 1 month. In years past, a diagnostic laparoscopy was considered the gold standard of necessity to provide the diagnosis of exclusion, that is, unexplained infertility. This surgical procedure has fallen out of favor given the low diagnostic yield in a woman with a normal hysterosalpingogram, pelvic ultrasound, and no risk for a pelvic factor; for example, prior abdominal myomectomy, bowel surgery, or strong suspicion for endometriosis based on symptoms including significant pelvic pain affecting activities of daily living.
Initial laboratory testing should be judiciously ordered by recommending only those that will affect management, that is, prenatal labs to assess immunity to rubella and varicella along with a baseline thyroid-stimulating hormone, CBC, blood type, and Rh and antibody screen. In a woman with monthly ovulatory menstrual cycles and no signs of hirsutism or galactorrhea, the clinical utility of obtaining follicle-stimulating hormone, luteinizing hormone (LH), estradiol, prolactin, total and free testosterone, and dehydroepiandrosterone lack evidence. Further, a random anti-Müllerian hormone (without prior chemotherapy, radiation, or ovarian surgery) lacks value as the natural pregnancy rate does not appear to be affected, although low AMH has been associated with an increased risk for miscarriage.
Although not typically screened, measles can cause significant complications in pregnancy including an increased risk of maternal hospitalization and pneumonia, as well as miscarriage, stillbirth, low birth weight, and increased risk of preterm delivery.
Education is an important tool to guide patients and begins with an explanation of urine LH timed intercourse. From the onset of the LH surge, the oocyte is released in 24-36 hours, i.e., the actual day of ovulation is estimated to be the day after the urine LH surge. The “fertile window” appears to be the 5 days before plus the day of ovulation but the highest chance of conception occurs within the 2 days before and including the day of ovulation.
Empiric treatment may be offered when no demonstrable etiology has been identified, lifestyle factors have been addressed (for example, elevated female body mass index, tobacco use by the couple), and medical conditions have been optimized. Reproductive capability declines with continued attempts at conception such that, by 2 years, the approximate monthly fecundity rate is 3%-4%.
The first-line treatment of unexplained infertility is clomiphene citrate (CC) with intrauterine insemination. Letrozole, while not Food and Drug Administration approved for infertility treatment, has been shown in multiple studies to be equally effective as CC and to have a good safety profile. In a recent study, the cumulative live-birth rate over three cycles with CC and IUI, compared with expectant management was 31% versus 9%, respectively. Further, multiple studies failed to show a difference in pregnancy outcomes when comparing CC and IUI with letrozole and IUI.
It is vital to note that, for women who ovulate, studies do not support the use of CC without the addition of intrauterine insemination (IUI). The monthly fecundity rate of a cycle of CC without IUI is similar to natural conception attempts with urine LH timed intercourse, that is, without ovarian stimulation.
Recommendations (along with the level of evidence) from ASRM guidelines
- 1. Natural cycle, that is, without ovarian stimulation, timed with IUI is equivalent to expectant management (strong)
- 2. CC or letrozole with timed intercourse is no more effective than a natural cycle (good)
- 3. Pregnancy rates using gonadotropins with timed intercourse have not been shown to be superior to oral ovarian stimulating medications but risks multiple gestation (insufficient)
- 4. CC plus standard-dose gonadotropins results in higher pregnancy rates, there is good evidence for an increased risk of multiple gestation (fair)
- 5. Treatment with gonadotropins alone with IUI is superior to CC or letrozole with IUI; the risk of a multiple gestation rate remains significant (insufficient)
- 6. IUI can be performed between 0 and 36 hours following human chorionic gonadotropin trigger and performing one IUI in a cycle has equivalent success as two (fair)
- 7. Immediate IVF in women older than 38 years may be associated with a higher pregnancy rate and shorter time to pregnancy, compared with ovarian stimulation/IUI cycles before IVF (good)
Conclusion
It is recommended that couples with unexplained infertility initially undergo a course (typically three or four cycles) of ovarian stimulation with IUI using oral agents (CC or letrozole). For those unsuccessful with ovarian stimulation and IUI treatments with oral agents, in vitro fertilization is recommended rather than ovarian stimulation and IUI with gonadotropins to reduce the risk of a multiple gestation.
Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. Email him at [email protected].
COVID-19 mortality risk factors: An unexpected finding
Schizophrenia and severe mood and anxiety disorders are associated with a significantly lower risk of COVID-19 but are tied to a two- to fourfold increased risk of death from the virus, new research shows.
The study results held after the researchers controlled for other risk factors, and they contradict an earlier study that showed no increased mortality risk associated with mood or anxiety disorders. The findings come as the overall number of deaths in the United States approaches 800,000.
“These patients were less likely to be infected because they were probably less exposed, but once they have the infection, they are more prone to worse outcomes,” lead author Antonio L. Teixeira, MD, PhD, professor of psychiatry with McGovern Medical School at the University of Texas Health Science Center at Houston, said in an interview.
The study was published online Nov. 23 in JAMA Network Open.
Unexpected finding
Researchers analyzed electronic health records for 2.5 million adults with private health insurance who were tested for COVID-19 in 2020.
The overall positivity rate for the entire cohort was 11.91%, and patients with severe psychiatric illness fell below that rate. Positivity rates were 9.86% for people with schizophrenia or mood disorders and 11.17% among those with anxiety disorder.
Despite their lower positivity rate, patients with schizophrenia had the highest odds of death from COVID-19 after adjustment for age, race, body mass index, and comorbidities (aOR, 3.74; 95% confidence interval, 2.66-5.24).
Those results were not very surprising, Dr. Teixeira said, as earlier studies have reported similar findings. However,
Patients with mood disorders were nearly three times as likely to die (aOR, 2.76; 95% CI, 2.00-3.81), and those with anxiety disorders had more than double the mortality risk (aOR, 2.34; 95% CI, 1.68-3.27).
“We were expecting some increase, but there was strong evidence in those populations as well,” he said. “We were especially surprised at the data on patients with anxiety disorders.”
An outstanding question
These findings contradict a study published Jan. 27, 2021, in JAMA Psychiatry, that showed no significant increase in mortality risk among those with mood or anxiety disorders.
Study methodology and timing might explain some of the differences, Katlyn Nemani, MD, a research assistant professor of psychiatry at New York University, who led that earlier study, said in an interview.
Dr. Nemani’s study had a smaller study sample, examined mortality over a 30-day period after a positive COVID-19 test, and was limited to the peak of the pandemic in New York, between March and May 2020. Dr. Teixeira’s team examined a full year of data and assessed mortality for 7 days following a positive test.
“It is possible patients with some psychiatric disorders were less likely to receive or successfully respond to treatment for severe COVD-19 which evolved during the course of the pandemic,” Dr. Nemani said, adding that it’s also possible that differences in mortality in the days following infection became attenuated over time.
While a meta-analysis published in July and reported by this news organization at that time did show higher COVID-19 mortality among patients with mood disorders, the risk was far lower than that reported in this new study. That report, which included 33 studies in 22 countries, also found no increase in risk among those with anxiety disorder.
In October, the Centers for Disease Control and Prevention added mood disorders to the list of medical conditions that increase the risk for more severe COVID-19. Schizophrenia was already on that list.
“The outstanding question is what underlies this increased risk,” Dr. Nemani said. “Future studies focused on immune-mediated mechanisms and other potential explanations will help guide targeted interventions to reduce morbidity and mortality in this vulnerable population.”
Funding for the study was not disclosed. Dr. Teixeira and Dr. Nemani report no conflicts of interest.
A version of this article first appeared on Medscape.com.
Schizophrenia and severe mood and anxiety disorders are associated with a significantly lower risk of COVID-19 but are tied to a two- to fourfold increased risk of death from the virus, new research shows.
The study results held after the researchers controlled for other risk factors, and they contradict an earlier study that showed no increased mortality risk associated with mood or anxiety disorders. The findings come as the overall number of deaths in the United States approaches 800,000.
“These patients were less likely to be infected because they were probably less exposed, but once they have the infection, they are more prone to worse outcomes,” lead author Antonio L. Teixeira, MD, PhD, professor of psychiatry with McGovern Medical School at the University of Texas Health Science Center at Houston, said in an interview.
The study was published online Nov. 23 in JAMA Network Open.
Unexpected finding
Researchers analyzed electronic health records for 2.5 million adults with private health insurance who were tested for COVID-19 in 2020.
The overall positivity rate for the entire cohort was 11.91%, and patients with severe psychiatric illness fell below that rate. Positivity rates were 9.86% for people with schizophrenia or mood disorders and 11.17% among those with anxiety disorder.
Despite their lower positivity rate, patients with schizophrenia had the highest odds of death from COVID-19 after adjustment for age, race, body mass index, and comorbidities (aOR, 3.74; 95% confidence interval, 2.66-5.24).
Those results were not very surprising, Dr. Teixeira said, as earlier studies have reported similar findings. However,
Patients with mood disorders were nearly three times as likely to die (aOR, 2.76; 95% CI, 2.00-3.81), and those with anxiety disorders had more than double the mortality risk (aOR, 2.34; 95% CI, 1.68-3.27).
“We were expecting some increase, but there was strong evidence in those populations as well,” he said. “We were especially surprised at the data on patients with anxiety disorders.”
An outstanding question
These findings contradict a study published Jan. 27, 2021, in JAMA Psychiatry, that showed no significant increase in mortality risk among those with mood or anxiety disorders.
Study methodology and timing might explain some of the differences, Katlyn Nemani, MD, a research assistant professor of psychiatry at New York University, who led that earlier study, said in an interview.
Dr. Nemani’s study had a smaller study sample, examined mortality over a 30-day period after a positive COVID-19 test, and was limited to the peak of the pandemic in New York, between March and May 2020. Dr. Teixeira’s team examined a full year of data and assessed mortality for 7 days following a positive test.
“It is possible patients with some psychiatric disorders were less likely to receive or successfully respond to treatment for severe COVD-19 which evolved during the course of the pandemic,” Dr. Nemani said, adding that it’s also possible that differences in mortality in the days following infection became attenuated over time.
While a meta-analysis published in July and reported by this news organization at that time did show higher COVID-19 mortality among patients with mood disorders, the risk was far lower than that reported in this new study. That report, which included 33 studies in 22 countries, also found no increase in risk among those with anxiety disorder.
In October, the Centers for Disease Control and Prevention added mood disorders to the list of medical conditions that increase the risk for more severe COVID-19. Schizophrenia was already on that list.
“The outstanding question is what underlies this increased risk,” Dr. Nemani said. “Future studies focused on immune-mediated mechanisms and other potential explanations will help guide targeted interventions to reduce morbidity and mortality in this vulnerable population.”
Funding for the study was not disclosed. Dr. Teixeira and Dr. Nemani report no conflicts of interest.
A version of this article first appeared on Medscape.com.
Schizophrenia and severe mood and anxiety disorders are associated with a significantly lower risk of COVID-19 but are tied to a two- to fourfold increased risk of death from the virus, new research shows.
The study results held after the researchers controlled for other risk factors, and they contradict an earlier study that showed no increased mortality risk associated with mood or anxiety disorders. The findings come as the overall number of deaths in the United States approaches 800,000.
“These patients were less likely to be infected because they were probably less exposed, but once they have the infection, they are more prone to worse outcomes,” lead author Antonio L. Teixeira, MD, PhD, professor of psychiatry with McGovern Medical School at the University of Texas Health Science Center at Houston, said in an interview.
The study was published online Nov. 23 in JAMA Network Open.
Unexpected finding
Researchers analyzed electronic health records for 2.5 million adults with private health insurance who were tested for COVID-19 in 2020.
The overall positivity rate for the entire cohort was 11.91%, and patients with severe psychiatric illness fell below that rate. Positivity rates were 9.86% for people with schizophrenia or mood disorders and 11.17% among those with anxiety disorder.
Despite their lower positivity rate, patients with schizophrenia had the highest odds of death from COVID-19 after adjustment for age, race, body mass index, and comorbidities (aOR, 3.74; 95% confidence interval, 2.66-5.24).
Those results were not very surprising, Dr. Teixeira said, as earlier studies have reported similar findings. However,
Patients with mood disorders were nearly three times as likely to die (aOR, 2.76; 95% CI, 2.00-3.81), and those with anxiety disorders had more than double the mortality risk (aOR, 2.34; 95% CI, 1.68-3.27).
“We were expecting some increase, but there was strong evidence in those populations as well,” he said. “We were especially surprised at the data on patients with anxiety disorders.”
An outstanding question
These findings contradict a study published Jan. 27, 2021, in JAMA Psychiatry, that showed no significant increase in mortality risk among those with mood or anxiety disorders.
Study methodology and timing might explain some of the differences, Katlyn Nemani, MD, a research assistant professor of psychiatry at New York University, who led that earlier study, said in an interview.
Dr. Nemani’s study had a smaller study sample, examined mortality over a 30-day period after a positive COVID-19 test, and was limited to the peak of the pandemic in New York, between March and May 2020. Dr. Teixeira’s team examined a full year of data and assessed mortality for 7 days following a positive test.
“It is possible patients with some psychiatric disorders were less likely to receive or successfully respond to treatment for severe COVD-19 which evolved during the course of the pandemic,” Dr. Nemani said, adding that it’s also possible that differences in mortality in the days following infection became attenuated over time.
While a meta-analysis published in July and reported by this news organization at that time did show higher COVID-19 mortality among patients with mood disorders, the risk was far lower than that reported in this new study. That report, which included 33 studies in 22 countries, also found no increase in risk among those with anxiety disorder.
In October, the Centers for Disease Control and Prevention added mood disorders to the list of medical conditions that increase the risk for more severe COVID-19. Schizophrenia was already on that list.
“The outstanding question is what underlies this increased risk,” Dr. Nemani said. “Future studies focused on immune-mediated mechanisms and other potential explanations will help guide targeted interventions to reduce morbidity and mortality in this vulnerable population.”
Funding for the study was not disclosed. Dr. Teixeira and Dr. Nemani report no conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
New blood test may detect preclinical Alzheimer’s years in advance
, early research suggests.
Analysis of two studies showed the test (AlzoSure Predict), which uses less than 1 ml of blood, had numerous benefits compared with other blood tests that track AD pathology.
“We believe this has the potential to radically improve early stratification and identification of patients for trials 6 years in advance of a diagnosis, which can potentially enable more rapid and efficient approvals of therapies,” Paul Kinnon, CEO of Diadem, the test’s manufacturer, said in an interview.
The findings were presented at the 14th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
Positive “discovery” results
P53, which is present in both the brain and elsewhere in the body, “is one of the most targeted proteins” for drug development in cancer and other conditions, said Mr. Kinnon.
The current blood test measures a derivative of P53 (U-p53AZ). Previous research suggests this derivative, which affects amyloid and oxidative stress, is also implicated in AD pathogenesis.
Researchers used blood samples from patients aged 60 years and older from the Australia Imaging, Biomarkers, and Lifestyles (AIBL) study who had various levels of cognitive function.
They analyzed samples at multiple timepoints over a 10-year period, “so we know when the marker is most accurate at predicting decline,” Mr. Kinnon said.
The first of two studies was considered a “discovery” study and included blood samples from 224 patients.
Results showed the test predicted decline from mild cognitive impairment (MCI) to AD at the end of 6 years, with an area under the curve (AUC) greater than 90%.
These results are “massive,” said Mr. Kinnon. “It’s the most accurate test I’ve seen anywhere for predicting decline of a patient.”
The test can also accurately classify a patient’s stage of cognition, he added. “Not only does it allow us to predict 6 years in advance, it also tells us if the patient has SMC [subjective memory complaints], MCI, or AD with a 95% certainty,” Mr. Kinnon said.
He noted that test sensitivity was higher than results found from traditional methods that are currently being used. The positive predictive value (PPV) and negative predictive value (NPV), which were at 90% or more, were “absolutely fantastic,” said Mr. Kinnon.
“Better than expected” results
In the second “validation” study, investigators examined samples from a completely different group of 482 patients. The “very compelling” results showed AUCs over 90%, PPVs over 90%, and “very high” NPVs, Mr. Kinnon said.
“These are great data, better than we expected,” he added.
However, he noted the test is “very specific” for decline to AD and not to other dementias.
In addition, Mr. Kinnon noted the test does not monitor levels of amyloid beta or tau, which accumulate at a later stage of AD. “Amyloid and tau tell you you’ve got it. We’re there way before those concentrations become detectable,” he said.
Identifying patients who will progress to AD years before they have symptoms gives them time to make medical decisions. These patients may also try treatments at an earlier stage of the disease, when these therapies are most likely to be helpful, said Mr. Kinnon.
In addition, using the test could speed up the approval of prospective drug treatments for AD. Currently, pharmaceutical companies enroll thousands of patients into a clinical study “and they don’t know which ones will have AD,” Mr. Kinnon noted.
“This test tells you these are the ones who are going to progress and should go into the study, and these are the ones that aren’t. So it makes the studies statistically relevant and accurate,” he said.
Investigators can also use the test to monitor patients during a study instead of relying on expensive PET scans and painful and costly spinal fluid taps, he added.
Previous surveys and market research have shown that neurologists and general practitioners “want a blood test to screen patients early, to help educate and inform patients,” said Mr. Kinnon.
Further results that will include biobank data on more than 1,000 patients in the United States and Europe are due for completion toward the end of this year.
The company is currently in negotiations to bring the product to North America, Europe, and elsewhere. “Our goal is to have it on the market by the middle of next year in multiple regions,” Mr. Kinnon said.
Encouraging, preliminary
Commenting on the findings, Percy Griffin, PhD, MSc, director of scientific engagement at the Alzheimer’s Association, said “it’s exciting” to see development of novel ways for detecting or predicting AD.
“There is an urgent need for simple, inexpensive, noninvasive, and accessible early detection tools for Alzheimer’s, such as a blood test,” he said.
However, Dr. Griffin cautioned the test is still in the early stages of development and has not been tested extensively in large, diverse clinical trials.
In addition, although the test predicts whether a person will progress, it does not predict when the person will progress, he added.
“These preliminary results are encouraging, but further validation is needed before this test can be implemented widely,” he said.
Technologies that facilitate the early detection and intervention before significant loss of brain cells from AD “would be game-changing” for individuals, families, and the healthcare system, Dr. Griffin concluded.
A version of this article first appeared on Medscape.com.
, early research suggests.
Analysis of two studies showed the test (AlzoSure Predict), which uses less than 1 ml of blood, had numerous benefits compared with other blood tests that track AD pathology.
“We believe this has the potential to radically improve early stratification and identification of patients for trials 6 years in advance of a diagnosis, which can potentially enable more rapid and efficient approvals of therapies,” Paul Kinnon, CEO of Diadem, the test’s manufacturer, said in an interview.
The findings were presented at the 14th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
Positive “discovery” results
P53, which is present in both the brain and elsewhere in the body, “is one of the most targeted proteins” for drug development in cancer and other conditions, said Mr. Kinnon.
The current blood test measures a derivative of P53 (U-p53AZ). Previous research suggests this derivative, which affects amyloid and oxidative stress, is also implicated in AD pathogenesis.
Researchers used blood samples from patients aged 60 years and older from the Australia Imaging, Biomarkers, and Lifestyles (AIBL) study who had various levels of cognitive function.
They analyzed samples at multiple timepoints over a 10-year period, “so we know when the marker is most accurate at predicting decline,” Mr. Kinnon said.
The first of two studies was considered a “discovery” study and included blood samples from 224 patients.
Results showed the test predicted decline from mild cognitive impairment (MCI) to AD at the end of 6 years, with an area under the curve (AUC) greater than 90%.
These results are “massive,” said Mr. Kinnon. “It’s the most accurate test I’ve seen anywhere for predicting decline of a patient.”
The test can also accurately classify a patient’s stage of cognition, he added. “Not only does it allow us to predict 6 years in advance, it also tells us if the patient has SMC [subjective memory complaints], MCI, or AD with a 95% certainty,” Mr. Kinnon said.
He noted that test sensitivity was higher than results found from traditional methods that are currently being used. The positive predictive value (PPV) and negative predictive value (NPV), which were at 90% or more, were “absolutely fantastic,” said Mr. Kinnon.
“Better than expected” results
In the second “validation” study, investigators examined samples from a completely different group of 482 patients. The “very compelling” results showed AUCs over 90%, PPVs over 90%, and “very high” NPVs, Mr. Kinnon said.
“These are great data, better than we expected,” he added.
However, he noted the test is “very specific” for decline to AD and not to other dementias.
In addition, Mr. Kinnon noted the test does not monitor levels of amyloid beta or tau, which accumulate at a later stage of AD. “Amyloid and tau tell you you’ve got it. We’re there way before those concentrations become detectable,” he said.
Identifying patients who will progress to AD years before they have symptoms gives them time to make medical decisions. These patients may also try treatments at an earlier stage of the disease, when these therapies are most likely to be helpful, said Mr. Kinnon.
In addition, using the test could speed up the approval of prospective drug treatments for AD. Currently, pharmaceutical companies enroll thousands of patients into a clinical study “and they don’t know which ones will have AD,” Mr. Kinnon noted.
“This test tells you these are the ones who are going to progress and should go into the study, and these are the ones that aren’t. So it makes the studies statistically relevant and accurate,” he said.
Investigators can also use the test to monitor patients during a study instead of relying on expensive PET scans and painful and costly spinal fluid taps, he added.
Previous surveys and market research have shown that neurologists and general practitioners “want a blood test to screen patients early, to help educate and inform patients,” said Mr. Kinnon.
Further results that will include biobank data on more than 1,000 patients in the United States and Europe are due for completion toward the end of this year.
The company is currently in negotiations to bring the product to North America, Europe, and elsewhere. “Our goal is to have it on the market by the middle of next year in multiple regions,” Mr. Kinnon said.
Encouraging, preliminary
Commenting on the findings, Percy Griffin, PhD, MSc, director of scientific engagement at the Alzheimer’s Association, said “it’s exciting” to see development of novel ways for detecting or predicting AD.
“There is an urgent need for simple, inexpensive, noninvasive, and accessible early detection tools for Alzheimer’s, such as a blood test,” he said.
However, Dr. Griffin cautioned the test is still in the early stages of development and has not been tested extensively in large, diverse clinical trials.
In addition, although the test predicts whether a person will progress, it does not predict when the person will progress, he added.
“These preliminary results are encouraging, but further validation is needed before this test can be implemented widely,” he said.
Technologies that facilitate the early detection and intervention before significant loss of brain cells from AD “would be game-changing” for individuals, families, and the healthcare system, Dr. Griffin concluded.
A version of this article first appeared on Medscape.com.
, early research suggests.
Analysis of two studies showed the test (AlzoSure Predict), which uses less than 1 ml of blood, had numerous benefits compared with other blood tests that track AD pathology.
“We believe this has the potential to radically improve early stratification and identification of patients for trials 6 years in advance of a diagnosis, which can potentially enable more rapid and efficient approvals of therapies,” Paul Kinnon, CEO of Diadem, the test’s manufacturer, said in an interview.
The findings were presented at the 14th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
Positive “discovery” results
P53, which is present in both the brain and elsewhere in the body, “is one of the most targeted proteins” for drug development in cancer and other conditions, said Mr. Kinnon.
The current blood test measures a derivative of P53 (U-p53AZ). Previous research suggests this derivative, which affects amyloid and oxidative stress, is also implicated in AD pathogenesis.
Researchers used blood samples from patients aged 60 years and older from the Australia Imaging, Biomarkers, and Lifestyles (AIBL) study who had various levels of cognitive function.
They analyzed samples at multiple timepoints over a 10-year period, “so we know when the marker is most accurate at predicting decline,” Mr. Kinnon said.
The first of two studies was considered a “discovery” study and included blood samples from 224 patients.
Results showed the test predicted decline from mild cognitive impairment (MCI) to AD at the end of 6 years, with an area under the curve (AUC) greater than 90%.
These results are “massive,” said Mr. Kinnon. “It’s the most accurate test I’ve seen anywhere for predicting decline of a patient.”
The test can also accurately classify a patient’s stage of cognition, he added. “Not only does it allow us to predict 6 years in advance, it also tells us if the patient has SMC [subjective memory complaints], MCI, or AD with a 95% certainty,” Mr. Kinnon said.
He noted that test sensitivity was higher than results found from traditional methods that are currently being used. The positive predictive value (PPV) and negative predictive value (NPV), which were at 90% or more, were “absolutely fantastic,” said Mr. Kinnon.
“Better than expected” results
In the second “validation” study, investigators examined samples from a completely different group of 482 patients. The “very compelling” results showed AUCs over 90%, PPVs over 90%, and “very high” NPVs, Mr. Kinnon said.
“These are great data, better than we expected,” he added.
However, he noted the test is “very specific” for decline to AD and not to other dementias.
In addition, Mr. Kinnon noted the test does not monitor levels of amyloid beta or tau, which accumulate at a later stage of AD. “Amyloid and tau tell you you’ve got it. We’re there way before those concentrations become detectable,” he said.
Identifying patients who will progress to AD years before they have symptoms gives them time to make medical decisions. These patients may also try treatments at an earlier stage of the disease, when these therapies are most likely to be helpful, said Mr. Kinnon.
In addition, using the test could speed up the approval of prospective drug treatments for AD. Currently, pharmaceutical companies enroll thousands of patients into a clinical study “and they don’t know which ones will have AD,” Mr. Kinnon noted.
“This test tells you these are the ones who are going to progress and should go into the study, and these are the ones that aren’t. So it makes the studies statistically relevant and accurate,” he said.
Investigators can also use the test to monitor patients during a study instead of relying on expensive PET scans and painful and costly spinal fluid taps, he added.
Previous surveys and market research have shown that neurologists and general practitioners “want a blood test to screen patients early, to help educate and inform patients,” said Mr. Kinnon.
Further results that will include biobank data on more than 1,000 patients in the United States and Europe are due for completion toward the end of this year.
The company is currently in negotiations to bring the product to North America, Europe, and elsewhere. “Our goal is to have it on the market by the middle of next year in multiple regions,” Mr. Kinnon said.
Encouraging, preliminary
Commenting on the findings, Percy Griffin, PhD, MSc, director of scientific engagement at the Alzheimer’s Association, said “it’s exciting” to see development of novel ways for detecting or predicting AD.
“There is an urgent need for simple, inexpensive, noninvasive, and accessible early detection tools for Alzheimer’s, such as a blood test,” he said.
However, Dr. Griffin cautioned the test is still in the early stages of development and has not been tested extensively in large, diverse clinical trials.
In addition, although the test predicts whether a person will progress, it does not predict when the person will progress, he added.
“These preliminary results are encouraging, but further validation is needed before this test can be implemented widely,” he said.
Technologies that facilitate the early detection and intervention before significant loss of brain cells from AD “would be game-changing” for individuals, families, and the healthcare system, Dr. Griffin concluded.
A version of this article first appeared on Medscape.com.
FROM CTAD21
Headache is a common post–COVID-19 complaint
The Centers for Disease Control and Prevention has identified it as a sentinel symptom of COVID-19 disease. “A lot of the recommendations surrounding post-COVID headache is that if you identify a patient who has headaches associated with fever, and myalgia, and other systemic symptoms, the specificity of a COVID-19 diagnosis goes up. So [COVID-19] is a really important feature to look out for in patients with headache,” Deena Kuruvilla, MD, said during a presentation on post–COVID-19 headache at the 2021 Scottsdale Headache Symposium.
Estimates of the prevalence of headache in COVID-19 range widely, from 6.5% to 71%, but Dr. Kuruvilla has plenty of personal experience with it. “During my stint on the inpatient neurology service during the peak of COVID, I saw patients with headache being one of the most frequent complaints, [along with] dizziness, stroke, and seizure among many other neurological manifestations,” said Dr. Kuruvilla, director of the Westport (Conn.) Headache Institute.
One meta-analysis showed that 47% of patients with COVID-19 complain of headache within 30 days of diagnosis, and this drops to around 10% at 60-90 days, and around 8% at 180 days.
A survey of 3,458 patients, published in the Journal of Headache Pain, found that migraine is the most common type of post–COVID-19 headache phenotype, and patients reporting anosmia-ageusia were more likely to have post–COVID-19 headache (odds ratio [OR], 5.39; 95% confidence interval, 1.66-17.45).
A case-control study of post–COVID-19 headache patients with and without a history of migraine found that those with a history of migraine were more likely to have post–COVID-19 symptoms (OR, 1.70; P < .001) and fatigue (OR, 2.89; P = .008). “Interestingly, they found no difference in headache as post-COVID symptoms in people who had a history of migraine compared with people without a history of migraine,” said Dr. Kuruvilla.
Headache and COVID-19: What is the connection?
Several mechanisms have been proposed for direct invasion of the central nervous system, either via infection through the angiotensin-converting enzyme 2 (ACE-2) receptor, which is expressed in brain regions including the motor cortex, the posterior cingulate cortex, and the olfactory bulb, among other locations. Another potential mechanism is direct entry through the olfactory nerve and the associated olfactory epithelium. There are various potential mechanisms for spread among the peripheral nervous system, and the blood-brain barrier can be compromised by infection of vascular endothelial cells. According to the literature, neuronal damage seems to occur directly from viral damage rather than from the immune response, said Dr. Kuruvilla.
The virus may also gain entry to the CNS indirectly, as a result of hypoxia and metabolic disturbances, as well as dehydration and systematic inflammation. The cytokine storm associated with COVID-19 infection can activate C-reactive protein and calcitonin gene-related peptide (CGRP), which plays a key role in migraine pathology. The CGRP receptor antagonist vazegepant is being studied in a phase 2 clinical trial for the treatment of COVID-19–related lung inflammation.
Testing and treatment
“If I see patients with new headache, worsening headache from their baseline, or headache with systemic symptoms, I often consider screening them for COVID. If that screening is positive, I proceed with PCR testing. I also consider an MRI of the brain with and without gadolinium just to rule out any secondary causes for headache,” said Dr. Kuruvilla, noting that she has diagnosed patients with venous sinus thrombosis, ischemic stroke, and meningitis following COVID-19.
The existing literature suggests that lumbar puncture in patients with SARS-CoV-2 typically returns normal results, but Dr. Kuruvilla proceeds with it anyway with viral, bacterial, fungal, and autoimmune studies to rule out potential secondary causes for headache.
There are few studies on how to treat post–COVID-19 headache, and the general recommendation is that headache phenotype should drive treatment decisions.
In a case series, three patients with persistent headache following mild COVID-19 infection were treated with onabotulinumtoxinA and amitriptyline. They had daily headaches, along with post–COVID-19 symptoms including fatigue and insomnia. After treatment, each patient converted to episodic headaches.
One retrospective study of 37 patients found that a 5-day course of indomethacin 50 mg twice per day and pantoprazole 40 mg once per day was associated with a 50% or greater improvement in headache on the third day in 36 of the 37 patients. Five patients were free of pain by day 5.
A common problem
Neurologists have been involved in the treatment of COVID-19 since the beginning, and post–COVID-19 headache has added another layer. “It’s been a remarkably common clinical problem. And the fact that it’s actually reached the level of headache specialist actually shows that in some cases, it’s really quite a significant problem, in both its severity and persistence. So I think it’s a very, very significant issue,” said Andrew Charles, MD, professor of neurology at the University of California, Los Angeles, and director of the UCLA Goldberg Migraine Program.
Dr. Kuruvilla also discussed the question of whether neurological damage is due to direct damage from the virus, or indirect damage from an immune response. This was debated during the Q&A session following Dr. Kuruvilla’s talk, and it was pointed out that headache is a frequent side effect of the Pfizer and Moderna vaccines.
“It’s a huge open question about how much is direct invasion or damage or not even damage, but just change in function with the viral infection, as opposed to inflammation. The fact that very often the response to the vaccine is similar to what you see with COVID suggests that at least some component of it is inflammation. I wouldn’t commit to one mechanism or the other, but I’d say that it’s possible that it’s really both,” said Dr. Charles.
Dr. Kuruvilla has consulted for Cefaly, Neurolief, Theranica, Now What Media, and KX advisors. She has been on the speakers bureau for Abbvie/Allergan, Amgen/Novartis, and Lilly. She has been on advisory boards for Abbvie/Allergan, Lilly, Theranica, and Amgen/Novartis. Dr. Charles has no relevant financial disclosures.
The Centers for Disease Control and Prevention has identified it as a sentinel symptom of COVID-19 disease. “A lot of the recommendations surrounding post-COVID headache is that if you identify a patient who has headaches associated with fever, and myalgia, and other systemic symptoms, the specificity of a COVID-19 diagnosis goes up. So [COVID-19] is a really important feature to look out for in patients with headache,” Deena Kuruvilla, MD, said during a presentation on post–COVID-19 headache at the 2021 Scottsdale Headache Symposium.
Estimates of the prevalence of headache in COVID-19 range widely, from 6.5% to 71%, but Dr. Kuruvilla has plenty of personal experience with it. “During my stint on the inpatient neurology service during the peak of COVID, I saw patients with headache being one of the most frequent complaints, [along with] dizziness, stroke, and seizure among many other neurological manifestations,” said Dr. Kuruvilla, director of the Westport (Conn.) Headache Institute.
One meta-analysis showed that 47% of patients with COVID-19 complain of headache within 30 days of diagnosis, and this drops to around 10% at 60-90 days, and around 8% at 180 days.
A survey of 3,458 patients, published in the Journal of Headache Pain, found that migraine is the most common type of post–COVID-19 headache phenotype, and patients reporting anosmia-ageusia were more likely to have post–COVID-19 headache (odds ratio [OR], 5.39; 95% confidence interval, 1.66-17.45).
A case-control study of post–COVID-19 headache patients with and without a history of migraine found that those with a history of migraine were more likely to have post–COVID-19 symptoms (OR, 1.70; P < .001) and fatigue (OR, 2.89; P = .008). “Interestingly, they found no difference in headache as post-COVID symptoms in people who had a history of migraine compared with people without a history of migraine,” said Dr. Kuruvilla.
Headache and COVID-19: What is the connection?
Several mechanisms have been proposed for direct invasion of the central nervous system, either via infection through the angiotensin-converting enzyme 2 (ACE-2) receptor, which is expressed in brain regions including the motor cortex, the posterior cingulate cortex, and the olfactory bulb, among other locations. Another potential mechanism is direct entry through the olfactory nerve and the associated olfactory epithelium. There are various potential mechanisms for spread among the peripheral nervous system, and the blood-brain barrier can be compromised by infection of vascular endothelial cells. According to the literature, neuronal damage seems to occur directly from viral damage rather than from the immune response, said Dr. Kuruvilla.
The virus may also gain entry to the CNS indirectly, as a result of hypoxia and metabolic disturbances, as well as dehydration and systematic inflammation. The cytokine storm associated with COVID-19 infection can activate C-reactive protein and calcitonin gene-related peptide (CGRP), which plays a key role in migraine pathology. The CGRP receptor antagonist vazegepant is being studied in a phase 2 clinical trial for the treatment of COVID-19–related lung inflammation.
Testing and treatment
“If I see patients with new headache, worsening headache from their baseline, or headache with systemic symptoms, I often consider screening them for COVID. If that screening is positive, I proceed with PCR testing. I also consider an MRI of the brain with and without gadolinium just to rule out any secondary causes for headache,” said Dr. Kuruvilla, noting that she has diagnosed patients with venous sinus thrombosis, ischemic stroke, and meningitis following COVID-19.
The existing literature suggests that lumbar puncture in patients with SARS-CoV-2 typically returns normal results, but Dr. Kuruvilla proceeds with it anyway with viral, bacterial, fungal, and autoimmune studies to rule out potential secondary causes for headache.
There are few studies on how to treat post–COVID-19 headache, and the general recommendation is that headache phenotype should drive treatment decisions.
In a case series, three patients with persistent headache following mild COVID-19 infection were treated with onabotulinumtoxinA and amitriptyline. They had daily headaches, along with post–COVID-19 symptoms including fatigue and insomnia. After treatment, each patient converted to episodic headaches.
One retrospective study of 37 patients found that a 5-day course of indomethacin 50 mg twice per day and pantoprazole 40 mg once per day was associated with a 50% or greater improvement in headache on the third day in 36 of the 37 patients. Five patients were free of pain by day 5.
A common problem
Neurologists have been involved in the treatment of COVID-19 since the beginning, and post–COVID-19 headache has added another layer. “It’s been a remarkably common clinical problem. And the fact that it’s actually reached the level of headache specialist actually shows that in some cases, it’s really quite a significant problem, in both its severity and persistence. So I think it’s a very, very significant issue,” said Andrew Charles, MD, professor of neurology at the University of California, Los Angeles, and director of the UCLA Goldberg Migraine Program.
Dr. Kuruvilla also discussed the question of whether neurological damage is due to direct damage from the virus, or indirect damage from an immune response. This was debated during the Q&A session following Dr. Kuruvilla’s talk, and it was pointed out that headache is a frequent side effect of the Pfizer and Moderna vaccines.
“It’s a huge open question about how much is direct invasion or damage or not even damage, but just change in function with the viral infection, as opposed to inflammation. The fact that very often the response to the vaccine is similar to what you see with COVID suggests that at least some component of it is inflammation. I wouldn’t commit to one mechanism or the other, but I’d say that it’s possible that it’s really both,” said Dr. Charles.
Dr. Kuruvilla has consulted for Cefaly, Neurolief, Theranica, Now What Media, and KX advisors. She has been on the speakers bureau for Abbvie/Allergan, Amgen/Novartis, and Lilly. She has been on advisory boards for Abbvie/Allergan, Lilly, Theranica, and Amgen/Novartis. Dr. Charles has no relevant financial disclosures.
The Centers for Disease Control and Prevention has identified it as a sentinel symptom of COVID-19 disease. “A lot of the recommendations surrounding post-COVID headache is that if you identify a patient who has headaches associated with fever, and myalgia, and other systemic symptoms, the specificity of a COVID-19 diagnosis goes up. So [COVID-19] is a really important feature to look out for in patients with headache,” Deena Kuruvilla, MD, said during a presentation on post–COVID-19 headache at the 2021 Scottsdale Headache Symposium.
Estimates of the prevalence of headache in COVID-19 range widely, from 6.5% to 71%, but Dr. Kuruvilla has plenty of personal experience with it. “During my stint on the inpatient neurology service during the peak of COVID, I saw patients with headache being one of the most frequent complaints, [along with] dizziness, stroke, and seizure among many other neurological manifestations,” said Dr. Kuruvilla, director of the Westport (Conn.) Headache Institute.
One meta-analysis showed that 47% of patients with COVID-19 complain of headache within 30 days of diagnosis, and this drops to around 10% at 60-90 days, and around 8% at 180 days.
A survey of 3,458 patients, published in the Journal of Headache Pain, found that migraine is the most common type of post–COVID-19 headache phenotype, and patients reporting anosmia-ageusia were more likely to have post–COVID-19 headache (odds ratio [OR], 5.39; 95% confidence interval, 1.66-17.45).
A case-control study of post–COVID-19 headache patients with and without a history of migraine found that those with a history of migraine were more likely to have post–COVID-19 symptoms (OR, 1.70; P < .001) and fatigue (OR, 2.89; P = .008). “Interestingly, they found no difference in headache as post-COVID symptoms in people who had a history of migraine compared with people without a history of migraine,” said Dr. Kuruvilla.
Headache and COVID-19: What is the connection?
Several mechanisms have been proposed for direct invasion of the central nervous system, either via infection through the angiotensin-converting enzyme 2 (ACE-2) receptor, which is expressed in brain regions including the motor cortex, the posterior cingulate cortex, and the olfactory bulb, among other locations. Another potential mechanism is direct entry through the olfactory nerve and the associated olfactory epithelium. There are various potential mechanisms for spread among the peripheral nervous system, and the blood-brain barrier can be compromised by infection of vascular endothelial cells. According to the literature, neuronal damage seems to occur directly from viral damage rather than from the immune response, said Dr. Kuruvilla.
The virus may also gain entry to the CNS indirectly, as a result of hypoxia and metabolic disturbances, as well as dehydration and systematic inflammation. The cytokine storm associated with COVID-19 infection can activate C-reactive protein and calcitonin gene-related peptide (CGRP), which plays a key role in migraine pathology. The CGRP receptor antagonist vazegepant is being studied in a phase 2 clinical trial for the treatment of COVID-19–related lung inflammation.
Testing and treatment
“If I see patients with new headache, worsening headache from their baseline, or headache with systemic symptoms, I often consider screening them for COVID. If that screening is positive, I proceed with PCR testing. I also consider an MRI of the brain with and without gadolinium just to rule out any secondary causes for headache,” said Dr. Kuruvilla, noting that she has diagnosed patients with venous sinus thrombosis, ischemic stroke, and meningitis following COVID-19.
The existing literature suggests that lumbar puncture in patients with SARS-CoV-2 typically returns normal results, but Dr. Kuruvilla proceeds with it anyway with viral, bacterial, fungal, and autoimmune studies to rule out potential secondary causes for headache.
There are few studies on how to treat post–COVID-19 headache, and the general recommendation is that headache phenotype should drive treatment decisions.
In a case series, three patients with persistent headache following mild COVID-19 infection were treated with onabotulinumtoxinA and amitriptyline. They had daily headaches, along with post–COVID-19 symptoms including fatigue and insomnia. After treatment, each patient converted to episodic headaches.
One retrospective study of 37 patients found that a 5-day course of indomethacin 50 mg twice per day and pantoprazole 40 mg once per day was associated with a 50% or greater improvement in headache on the third day in 36 of the 37 patients. Five patients were free of pain by day 5.
A common problem
Neurologists have been involved in the treatment of COVID-19 since the beginning, and post–COVID-19 headache has added another layer. “It’s been a remarkably common clinical problem. And the fact that it’s actually reached the level of headache specialist actually shows that in some cases, it’s really quite a significant problem, in both its severity and persistence. So I think it’s a very, very significant issue,” said Andrew Charles, MD, professor of neurology at the University of California, Los Angeles, and director of the UCLA Goldberg Migraine Program.
Dr. Kuruvilla also discussed the question of whether neurological damage is due to direct damage from the virus, or indirect damage from an immune response. This was debated during the Q&A session following Dr. Kuruvilla’s talk, and it was pointed out that headache is a frequent side effect of the Pfizer and Moderna vaccines.
“It’s a huge open question about how much is direct invasion or damage or not even damage, but just change in function with the viral infection, as opposed to inflammation. The fact that very often the response to the vaccine is similar to what you see with COVID suggests that at least some component of it is inflammation. I wouldn’t commit to one mechanism or the other, but I’d say that it’s possible that it’s really both,” said Dr. Charles.
Dr. Kuruvilla has consulted for Cefaly, Neurolief, Theranica, Now What Media, and KX advisors. She has been on the speakers bureau for Abbvie/Allergan, Amgen/Novartis, and Lilly. She has been on advisory boards for Abbvie/Allergan, Lilly, Theranica, and Amgen/Novartis. Dr. Charles has no relevant financial disclosures.
FROM 2021 SCOTTSDALE HEADACHE SYMPOSIUM
Psychiatrist’s killer gets life in prison
A patient has been sentenced to life in prison 4 years after brutally murdering his psychiatrist.
According to news reports, Umar Dutt, then age 21, went to the office of psychiatrist Achutha Reddy, MD, in Wichita, Kan., on Sept. 19, 2017, aiming to hold the doctor hostage. Dr. Reddy’s office manager reportedly heard noise coming from the closed office and after entering, found Mr. Dutt assaulting the 57-year-old Dr. Reddy.
She intervened, and Dr. Reddy fled the building, but Mr. Dutt followed him and ultimately stabbed the physician more than 160 times. Mr. Dutt than ran over Dr. Reddy’s body.
The patient was arrested that day elsewhere and initially entered a “not guilty” plea in Sedgwick County District Court in 2019. Mr. Dutt was held in the county jail on a $1 million bond.
In September 2021, he changed his plea to guilty. He was sentenced on Nov. 9.
He received credit for time served of 4 years. The prosecutors and defense attorneys and the judge recommended that Mr. Dutt serve his sentence at Larned Correctional Mental Health Facility because of a history of mental illness.
KWCH reports that the Kansas Department of Corrections will ultimately decide where Mr. Dutt will be incarcerated.
Dr. Reddy left behind a wife and three children.
At Mr. Dutt’s sentencing hearing, Dr. Reddy’s widow, Beena Reddy, MD, a Wichita-based anesthesiologist, reportedly told the court: “My children and I have been devastated by Achutha’s death. Our stability, our security, our peace of mind, has been destroyed by the premeditated, evil actions of Umar Dutt.”
A version of this article first appeared on Medscape.com.
A patient has been sentenced to life in prison 4 years after brutally murdering his psychiatrist.
According to news reports, Umar Dutt, then age 21, went to the office of psychiatrist Achutha Reddy, MD, in Wichita, Kan., on Sept. 19, 2017, aiming to hold the doctor hostage. Dr. Reddy’s office manager reportedly heard noise coming from the closed office and after entering, found Mr. Dutt assaulting the 57-year-old Dr. Reddy.
She intervened, and Dr. Reddy fled the building, but Mr. Dutt followed him and ultimately stabbed the physician more than 160 times. Mr. Dutt than ran over Dr. Reddy’s body.
The patient was arrested that day elsewhere and initially entered a “not guilty” plea in Sedgwick County District Court in 2019. Mr. Dutt was held in the county jail on a $1 million bond.
In September 2021, he changed his plea to guilty. He was sentenced on Nov. 9.
He received credit for time served of 4 years. The prosecutors and defense attorneys and the judge recommended that Mr. Dutt serve his sentence at Larned Correctional Mental Health Facility because of a history of mental illness.
KWCH reports that the Kansas Department of Corrections will ultimately decide where Mr. Dutt will be incarcerated.
Dr. Reddy left behind a wife and three children.
At Mr. Dutt’s sentencing hearing, Dr. Reddy’s widow, Beena Reddy, MD, a Wichita-based anesthesiologist, reportedly told the court: “My children and I have been devastated by Achutha’s death. Our stability, our security, our peace of mind, has been destroyed by the premeditated, evil actions of Umar Dutt.”
A version of this article first appeared on Medscape.com.
A patient has been sentenced to life in prison 4 years after brutally murdering his psychiatrist.
According to news reports, Umar Dutt, then age 21, went to the office of psychiatrist Achutha Reddy, MD, in Wichita, Kan., on Sept. 19, 2017, aiming to hold the doctor hostage. Dr. Reddy’s office manager reportedly heard noise coming from the closed office and after entering, found Mr. Dutt assaulting the 57-year-old Dr. Reddy.
She intervened, and Dr. Reddy fled the building, but Mr. Dutt followed him and ultimately stabbed the physician more than 160 times. Mr. Dutt than ran over Dr. Reddy’s body.
The patient was arrested that day elsewhere and initially entered a “not guilty” plea in Sedgwick County District Court in 2019. Mr. Dutt was held in the county jail on a $1 million bond.
In September 2021, he changed his plea to guilty. He was sentenced on Nov. 9.
He received credit for time served of 4 years. The prosecutors and defense attorneys and the judge recommended that Mr. Dutt serve his sentence at Larned Correctional Mental Health Facility because of a history of mental illness.
KWCH reports that the Kansas Department of Corrections will ultimately decide where Mr. Dutt will be incarcerated.
Dr. Reddy left behind a wife and three children.
At Mr. Dutt’s sentencing hearing, Dr. Reddy’s widow, Beena Reddy, MD, a Wichita-based anesthesiologist, reportedly told the court: “My children and I have been devastated by Achutha’s death. Our stability, our security, our peace of mind, has been destroyed by the premeditated, evil actions of Umar Dutt.”
A version of this article first appeared on Medscape.com.
Daily aspirin linked to increased risk of heart failure
Daily aspirin is associated with new onset heart failure independent of other risk factors, according to data derived from a database with follow-up from more than 30,000 patients who did not have HF when they were enrolled.
These data are not relevant to primary or secondary prevention of cardiovascular events but “refer only to starting aspirin for secondary prevention of HF in patients at high risk of HF or with symptomatic HF,” according to the senior investigator, Jan A. Staessen, MD, PhD, professor emeritus at the University of Leuven (Belgium).
In data from 30,827 patients at risk for HF enrolled in six observational studies, the hazard ratio (HR) for developing HF among those taking daily aspirin at baseline relative to those who were not was 1.26 (P ≤ .001) over 5.3 years of follow-up. In the 22,690 patients without a prior history cardiovascular disease (CVD), the HF risk increase for exposure to daily aspirin was about the same (HR 1.27; P = .001).
This study was launched because multiple conflicting studies have made the relationship between aspirin and HF risk unclear, according to the multinational team of authors, whose finding were published in ESC Heart Failure.
In principle, HF is recognized as a prothrombotic condition for which an antithrombotic therapy such as aspirin would be expected to have a protective role, but the investigators pointed out that the evidence is mixed. In a population-based Danish study of 12,277 patients with new-onset HF, for example, there was no relationship seen between aspirin use and a reduction in the composite outcome of all-cause mortality, myocardial infarction, or stroke.
Aspirin use linked to HF admissions
“Interestingly, this study reported that aspirin use was associated with an increased risk of readmissions for HF,” wrote the authors of the newly published data. “Uncertainty on aspirin use has been reflected in current guideline recommendations,” they added.
The population studied was drawn from the HOMAGE database, which has collated data on 46,437 participants in 21 studies. After the exclusion of studies with patients who already had HF as well as studies without information on HF incidence over time, six studies with 30,827 participants provided the basis for this analysis.
One study, ASCOT, which was randomized and blinded, served as the derivation data set. The remaining five studies, FLEMENGHO, HEALTH ABC, HULL LIFE LAB, PREDICTOR, and PROSPER, served as the validation data set.
In addition to identifying participants as aspirin users or nonusers at baseline, all of the studies had detailed baseline data on a wide variety of patient characteristics and risk factors, such as body mass index, blood cholesterol levels, blood glucose concentrations, blood pressure, and creatinine.
No patient in any trial was on an antithrombotic therapy other than aspirin at baseline.
Of the minority of patients with CVD at baseline, more than 80% had coronary heart disease. Only 2.8% of the total population had a prior myocardial infarction. In the study population overall, most (86%) had hypertension, and there was a sizeable proportion with diabetes (22%). The average age was 67 years, and 34% were women.
HF incidence on aspirin: 14.5/1000 person-years
Overall, the incidence rate of HF per 1,000 person-years for the entire population before adjustment was 14.5 in the group on daily aspirin versus 5.9 in the non-aspirin group. These absolute rates were lower in the discovery data set than in the validation set, but the relative differences in HF incidence rates for those who were versus those who were not on aspirin at baseline were similar.
Numerous sensitivity analyses supported the basic conclusions. This not only included one omitting patients with a history of CVD, but another that excluded patients who developed HF within the first 2 years. Stratified analyses looking for overall consistency across variables showed increased risk of new onset heart failure among those taking daily aspirin regardless of relative age, body weight, or blood pressure levels.
The most important limitation of this study was that it evaluated data taken from studies not originally designed to test the study hypothesis. In addition, only baseline data were available, so the drugs that patients took over the course of follow-up are unknown. However, the authors believe these data have a clinical message.
Given the consistency of these results, “our observations suggest that aspirin should be prescribed with caution in patients at risk of HF or having HF,” the investigators concluded.
“If such treatment is initiated in these patients, use low-dose aspirin,” Dr. Staessen told this news organization.
Aspirin for CVD versus HF risk
Many patients take low-dose aspirin to prevent the types of cardiovascular events, such as MI, that lead to heart failure. In attempting to address a controversy regarding aspirin and risk of new onset heart failure, it appears to create another regarding CVD risk reduction.
Deepak L. Bhatt, MD, executive director of Interventional Cardiovascular Programs at Brigham and Women’s Health, Boston, expressed some reluctance in applying these data to routine practice.
“It is important to emphasize that this pooled analysis draws upon six observational studies, not randomized trials of aspirin,” Dr. Bhatt said.
He called these findings “provocative,” but he said they “would need to be confirmed in databases of already completed randomized trials of aspirin versus a control before being actionable.” For Dr. Bhatt, one obstacle to a change in practice based on these data is that, “to my knowledge, no such signal [of a relationship between aspirin and incident heart failure] exists in the cumulative randomized data.”
Dr. Staessen reports no potential conflicts of interest for this study. Dr. Bhatt has a financial relationship with a large number of pharmaceutical companies, including PLx Pharma, for which he performs aspirin-related research.
Daily aspirin is associated with new onset heart failure independent of other risk factors, according to data derived from a database with follow-up from more than 30,000 patients who did not have HF when they were enrolled.
These data are not relevant to primary or secondary prevention of cardiovascular events but “refer only to starting aspirin for secondary prevention of HF in patients at high risk of HF or with symptomatic HF,” according to the senior investigator, Jan A. Staessen, MD, PhD, professor emeritus at the University of Leuven (Belgium).
In data from 30,827 patients at risk for HF enrolled in six observational studies, the hazard ratio (HR) for developing HF among those taking daily aspirin at baseline relative to those who were not was 1.26 (P ≤ .001) over 5.3 years of follow-up. In the 22,690 patients without a prior history cardiovascular disease (CVD), the HF risk increase for exposure to daily aspirin was about the same (HR 1.27; P = .001).
This study was launched because multiple conflicting studies have made the relationship between aspirin and HF risk unclear, according to the multinational team of authors, whose finding were published in ESC Heart Failure.
In principle, HF is recognized as a prothrombotic condition for which an antithrombotic therapy such as aspirin would be expected to have a protective role, but the investigators pointed out that the evidence is mixed. In a population-based Danish study of 12,277 patients with new-onset HF, for example, there was no relationship seen between aspirin use and a reduction in the composite outcome of all-cause mortality, myocardial infarction, or stroke.
Aspirin use linked to HF admissions
“Interestingly, this study reported that aspirin use was associated with an increased risk of readmissions for HF,” wrote the authors of the newly published data. “Uncertainty on aspirin use has been reflected in current guideline recommendations,” they added.
The population studied was drawn from the HOMAGE database, which has collated data on 46,437 participants in 21 studies. After the exclusion of studies with patients who already had HF as well as studies without information on HF incidence over time, six studies with 30,827 participants provided the basis for this analysis.
One study, ASCOT, which was randomized and blinded, served as the derivation data set. The remaining five studies, FLEMENGHO, HEALTH ABC, HULL LIFE LAB, PREDICTOR, and PROSPER, served as the validation data set.
In addition to identifying participants as aspirin users or nonusers at baseline, all of the studies had detailed baseline data on a wide variety of patient characteristics and risk factors, such as body mass index, blood cholesterol levels, blood glucose concentrations, blood pressure, and creatinine.
No patient in any trial was on an antithrombotic therapy other than aspirin at baseline.
Of the minority of patients with CVD at baseline, more than 80% had coronary heart disease. Only 2.8% of the total population had a prior myocardial infarction. In the study population overall, most (86%) had hypertension, and there was a sizeable proportion with diabetes (22%). The average age was 67 years, and 34% were women.
HF incidence on aspirin: 14.5/1000 person-years
Overall, the incidence rate of HF per 1,000 person-years for the entire population before adjustment was 14.5 in the group on daily aspirin versus 5.9 in the non-aspirin group. These absolute rates were lower in the discovery data set than in the validation set, but the relative differences in HF incidence rates for those who were versus those who were not on aspirin at baseline were similar.
Numerous sensitivity analyses supported the basic conclusions. This not only included one omitting patients with a history of CVD, but another that excluded patients who developed HF within the first 2 years. Stratified analyses looking for overall consistency across variables showed increased risk of new onset heart failure among those taking daily aspirin regardless of relative age, body weight, or blood pressure levels.
The most important limitation of this study was that it evaluated data taken from studies not originally designed to test the study hypothesis. In addition, only baseline data were available, so the drugs that patients took over the course of follow-up are unknown. However, the authors believe these data have a clinical message.
Given the consistency of these results, “our observations suggest that aspirin should be prescribed with caution in patients at risk of HF or having HF,” the investigators concluded.
“If such treatment is initiated in these patients, use low-dose aspirin,” Dr. Staessen told this news organization.
Aspirin for CVD versus HF risk
Many patients take low-dose aspirin to prevent the types of cardiovascular events, such as MI, that lead to heart failure. In attempting to address a controversy regarding aspirin and risk of new onset heart failure, it appears to create another regarding CVD risk reduction.
Deepak L. Bhatt, MD, executive director of Interventional Cardiovascular Programs at Brigham and Women’s Health, Boston, expressed some reluctance in applying these data to routine practice.
“It is important to emphasize that this pooled analysis draws upon six observational studies, not randomized trials of aspirin,” Dr. Bhatt said.
He called these findings “provocative,” but he said they “would need to be confirmed in databases of already completed randomized trials of aspirin versus a control before being actionable.” For Dr. Bhatt, one obstacle to a change in practice based on these data is that, “to my knowledge, no such signal [of a relationship between aspirin and incident heart failure] exists in the cumulative randomized data.”
Dr. Staessen reports no potential conflicts of interest for this study. Dr. Bhatt has a financial relationship with a large number of pharmaceutical companies, including PLx Pharma, for which he performs aspirin-related research.
Daily aspirin is associated with new onset heart failure independent of other risk factors, according to data derived from a database with follow-up from more than 30,000 patients who did not have HF when they were enrolled.
These data are not relevant to primary or secondary prevention of cardiovascular events but “refer only to starting aspirin for secondary prevention of HF in patients at high risk of HF or with symptomatic HF,” according to the senior investigator, Jan A. Staessen, MD, PhD, professor emeritus at the University of Leuven (Belgium).
In data from 30,827 patients at risk for HF enrolled in six observational studies, the hazard ratio (HR) for developing HF among those taking daily aspirin at baseline relative to those who were not was 1.26 (P ≤ .001) over 5.3 years of follow-up. In the 22,690 patients without a prior history cardiovascular disease (CVD), the HF risk increase for exposure to daily aspirin was about the same (HR 1.27; P = .001).
This study was launched because multiple conflicting studies have made the relationship between aspirin and HF risk unclear, according to the multinational team of authors, whose finding were published in ESC Heart Failure.
In principle, HF is recognized as a prothrombotic condition for which an antithrombotic therapy such as aspirin would be expected to have a protective role, but the investigators pointed out that the evidence is mixed. In a population-based Danish study of 12,277 patients with new-onset HF, for example, there was no relationship seen between aspirin use and a reduction in the composite outcome of all-cause mortality, myocardial infarction, or stroke.
Aspirin use linked to HF admissions
“Interestingly, this study reported that aspirin use was associated with an increased risk of readmissions for HF,” wrote the authors of the newly published data. “Uncertainty on aspirin use has been reflected in current guideline recommendations,” they added.
The population studied was drawn from the HOMAGE database, which has collated data on 46,437 participants in 21 studies. After the exclusion of studies with patients who already had HF as well as studies without information on HF incidence over time, six studies with 30,827 participants provided the basis for this analysis.
One study, ASCOT, which was randomized and blinded, served as the derivation data set. The remaining five studies, FLEMENGHO, HEALTH ABC, HULL LIFE LAB, PREDICTOR, and PROSPER, served as the validation data set.
In addition to identifying participants as aspirin users or nonusers at baseline, all of the studies had detailed baseline data on a wide variety of patient characteristics and risk factors, such as body mass index, blood cholesterol levels, blood glucose concentrations, blood pressure, and creatinine.
No patient in any trial was on an antithrombotic therapy other than aspirin at baseline.
Of the minority of patients with CVD at baseline, more than 80% had coronary heart disease. Only 2.8% of the total population had a prior myocardial infarction. In the study population overall, most (86%) had hypertension, and there was a sizeable proportion with diabetes (22%). The average age was 67 years, and 34% were women.
HF incidence on aspirin: 14.5/1000 person-years
Overall, the incidence rate of HF per 1,000 person-years for the entire population before adjustment was 14.5 in the group on daily aspirin versus 5.9 in the non-aspirin group. These absolute rates were lower in the discovery data set than in the validation set, but the relative differences in HF incidence rates for those who were versus those who were not on aspirin at baseline were similar.
Numerous sensitivity analyses supported the basic conclusions. This not only included one omitting patients with a history of CVD, but another that excluded patients who developed HF within the first 2 years. Stratified analyses looking for overall consistency across variables showed increased risk of new onset heart failure among those taking daily aspirin regardless of relative age, body weight, or blood pressure levels.
The most important limitation of this study was that it evaluated data taken from studies not originally designed to test the study hypothesis. In addition, only baseline data were available, so the drugs that patients took over the course of follow-up are unknown. However, the authors believe these data have a clinical message.
Given the consistency of these results, “our observations suggest that aspirin should be prescribed with caution in patients at risk of HF or having HF,” the investigators concluded.
“If such treatment is initiated in these patients, use low-dose aspirin,” Dr. Staessen told this news organization.
Aspirin for CVD versus HF risk
Many patients take low-dose aspirin to prevent the types of cardiovascular events, such as MI, that lead to heart failure. In attempting to address a controversy regarding aspirin and risk of new onset heart failure, it appears to create another regarding CVD risk reduction.
Deepak L. Bhatt, MD, executive director of Interventional Cardiovascular Programs at Brigham and Women’s Health, Boston, expressed some reluctance in applying these data to routine practice.
“It is important to emphasize that this pooled analysis draws upon six observational studies, not randomized trials of aspirin,” Dr. Bhatt said.
He called these findings “provocative,” but he said they “would need to be confirmed in databases of already completed randomized trials of aspirin versus a control before being actionable.” For Dr. Bhatt, one obstacle to a change in practice based on these data is that, “to my knowledge, no such signal [of a relationship between aspirin and incident heart failure] exists in the cumulative randomized data.”
Dr. Staessen reports no potential conflicts of interest for this study. Dr. Bhatt has a financial relationship with a large number of pharmaceutical companies, including PLx Pharma, for which he performs aspirin-related research.
FROM JACC HEART FAILURE
MRI before tongue carcinoma biopsy may be more reliable than other radiologic methods
Tongue squamous cell carcinomas are one of the most common oral cancers yet one of the most difficult to successfully treat. Getting an accurate measure of the depth of the tumor is critical to determining a patient’s prognosis and currently CT, MRI, and ultrasound are used to determine the depth and location of the tumor.
“Several studies have reported a significant relationship between radiological depth of invasion measured on MRI and pathological depth of invasion in the tongue squamous cell carcinoma. To the best of our knowledge, this is the first study on MRI divided into ‘before biopsy’ and ‘after incision biopsy,’ ” Hiroyuki Harada, DDS, PhD, of Tokyo Medical and Dental University, and colleagues wrote.
The issue of depth of invasion is so critical to determining metastasis to neck lymph nodes that in 2017 it was added to the AJCC Cancer Staging Manual.
This retrospective Japanese study included 128 patients with tongue carcinoma who underwent glossectomy between 2006 and 2019. The researchers evaluated which radiologic depth of invasion measurement – MRI before or after biopsy and ultrasound – was the most agreeable to clinical depth of invasion.
All the participants had undergone ultrasound, while 18 had undergone MRI before biopsy and 110 had undergone MRI after biopsy. The coefficients of determination were 0.664, 0.891, and 0.422 respectively, suggesting that calculating radiologic depth of invasion using MRI before biopsy was the most reliable radiologic method. MRI before biopsy slightly overestimated clinical depth of tumor invasion, MRI after biopsy severely overestimated the clinical measurement, and ultrasound slightly underestimated the clinical depth of tumor invasion.
Ultrasound is often preferred because of its easy use, yet measuring ulcerous lesions is difficult with ultrasound. But with MRI, there is no upper limit of measured value, but tongue movement during the procedure can make getting accurate images during the procedure difficult.
“The advantage of the MRI is that the image is acquired in the tongue’s resting position and that there is no upper limit of the measured value. The disadvantages include difficult detection of superficial tumors, influence of metal artifacts, and movement of the tongue,” the authors wrote. “Biopsy may lead to edema or hemorrhage and subsequent overestimation of tumor size and invasion depth in MRI.”
A small Canadian study published in 2016 in the Journal of Otolaryngology–Head & Neck Surgery, found a strong correlation between clinical, pathological, and MRI measurements of depth of invasion in oral tongue SCC. Meanwhile, a 2017 U.K. study published in the British Journal of Oral and Maxillofacial Surgery found that the accuracy of clinical staging in oral SCC did not differ whether the biopsy was taken before or after MRI. While a good radiologic-pathological tumor thickness correlation has been reported in 2018 in the American Journal of Neuroradiology, tongue carcinoma often shows exophytic or ulcerous lesions, which are difficult to measure with MRI, CT, or ultrasound.
The authors suggested that further studies are needed to determine the effects on MRI of postbiopsy tongue inflammation. Limitations of the study included the small number of cases with MRI before biopsy.
The authors declared no conflicts of interest.
Tongue squamous cell carcinomas are one of the most common oral cancers yet one of the most difficult to successfully treat. Getting an accurate measure of the depth of the tumor is critical to determining a patient’s prognosis and currently CT, MRI, and ultrasound are used to determine the depth and location of the tumor.
“Several studies have reported a significant relationship between radiological depth of invasion measured on MRI and pathological depth of invasion in the tongue squamous cell carcinoma. To the best of our knowledge, this is the first study on MRI divided into ‘before biopsy’ and ‘after incision biopsy,’ ” Hiroyuki Harada, DDS, PhD, of Tokyo Medical and Dental University, and colleagues wrote.
The issue of depth of invasion is so critical to determining metastasis to neck lymph nodes that in 2017 it was added to the AJCC Cancer Staging Manual.
This retrospective Japanese study included 128 patients with tongue carcinoma who underwent glossectomy between 2006 and 2019. The researchers evaluated which radiologic depth of invasion measurement – MRI before or after biopsy and ultrasound – was the most agreeable to clinical depth of invasion.
All the participants had undergone ultrasound, while 18 had undergone MRI before biopsy and 110 had undergone MRI after biopsy. The coefficients of determination were 0.664, 0.891, and 0.422 respectively, suggesting that calculating radiologic depth of invasion using MRI before biopsy was the most reliable radiologic method. MRI before biopsy slightly overestimated clinical depth of tumor invasion, MRI after biopsy severely overestimated the clinical measurement, and ultrasound slightly underestimated the clinical depth of tumor invasion.
Ultrasound is often preferred because of its easy use, yet measuring ulcerous lesions is difficult with ultrasound. But with MRI, there is no upper limit of measured value, but tongue movement during the procedure can make getting accurate images during the procedure difficult.
“The advantage of the MRI is that the image is acquired in the tongue’s resting position and that there is no upper limit of the measured value. The disadvantages include difficult detection of superficial tumors, influence of metal artifacts, and movement of the tongue,” the authors wrote. “Biopsy may lead to edema or hemorrhage and subsequent overestimation of tumor size and invasion depth in MRI.”
A small Canadian study published in 2016 in the Journal of Otolaryngology–Head & Neck Surgery, found a strong correlation between clinical, pathological, and MRI measurements of depth of invasion in oral tongue SCC. Meanwhile, a 2017 U.K. study published in the British Journal of Oral and Maxillofacial Surgery found that the accuracy of clinical staging in oral SCC did not differ whether the biopsy was taken before or after MRI. While a good radiologic-pathological tumor thickness correlation has been reported in 2018 in the American Journal of Neuroradiology, tongue carcinoma often shows exophytic or ulcerous lesions, which are difficult to measure with MRI, CT, or ultrasound.
The authors suggested that further studies are needed to determine the effects on MRI of postbiopsy tongue inflammation. Limitations of the study included the small number of cases with MRI before biopsy.
The authors declared no conflicts of interest.
Tongue squamous cell carcinomas are one of the most common oral cancers yet one of the most difficult to successfully treat. Getting an accurate measure of the depth of the tumor is critical to determining a patient’s prognosis and currently CT, MRI, and ultrasound are used to determine the depth and location of the tumor.
“Several studies have reported a significant relationship between radiological depth of invasion measured on MRI and pathological depth of invasion in the tongue squamous cell carcinoma. To the best of our knowledge, this is the first study on MRI divided into ‘before biopsy’ and ‘after incision biopsy,’ ” Hiroyuki Harada, DDS, PhD, of Tokyo Medical and Dental University, and colleagues wrote.
The issue of depth of invasion is so critical to determining metastasis to neck lymph nodes that in 2017 it was added to the AJCC Cancer Staging Manual.
This retrospective Japanese study included 128 patients with tongue carcinoma who underwent glossectomy between 2006 and 2019. The researchers evaluated which radiologic depth of invasion measurement – MRI before or after biopsy and ultrasound – was the most agreeable to clinical depth of invasion.
All the participants had undergone ultrasound, while 18 had undergone MRI before biopsy and 110 had undergone MRI after biopsy. The coefficients of determination were 0.664, 0.891, and 0.422 respectively, suggesting that calculating radiologic depth of invasion using MRI before biopsy was the most reliable radiologic method. MRI before biopsy slightly overestimated clinical depth of tumor invasion, MRI after biopsy severely overestimated the clinical measurement, and ultrasound slightly underestimated the clinical depth of tumor invasion.
Ultrasound is often preferred because of its easy use, yet measuring ulcerous lesions is difficult with ultrasound. But with MRI, there is no upper limit of measured value, but tongue movement during the procedure can make getting accurate images during the procedure difficult.
“The advantage of the MRI is that the image is acquired in the tongue’s resting position and that there is no upper limit of the measured value. The disadvantages include difficult detection of superficial tumors, influence of metal artifacts, and movement of the tongue,” the authors wrote. “Biopsy may lead to edema or hemorrhage and subsequent overestimation of tumor size and invasion depth in MRI.”
A small Canadian study published in 2016 in the Journal of Otolaryngology–Head & Neck Surgery, found a strong correlation between clinical, pathological, and MRI measurements of depth of invasion in oral tongue SCC. Meanwhile, a 2017 U.K. study published in the British Journal of Oral and Maxillofacial Surgery found that the accuracy of clinical staging in oral SCC did not differ whether the biopsy was taken before or after MRI. While a good radiologic-pathological tumor thickness correlation has been reported in 2018 in the American Journal of Neuroradiology, tongue carcinoma often shows exophytic or ulcerous lesions, which are difficult to measure with MRI, CT, or ultrasound.
The authors suggested that further studies are needed to determine the effects on MRI of postbiopsy tongue inflammation. Limitations of the study included the small number of cases with MRI before biopsy.
The authors declared no conflicts of interest.
FROM SCIENTIFIC REPORTS
AAN issues ethical guidance on controversial Alzheimer’s drug
The statement includes ethical considerations and recommendations for informed consent, and the AAN notes that neurologists should ensure that patients understand all of the issues and uncertainties surrounding the use of aducanumab.
“Neurologists and other clinicians want to provide the best care to patients and families, particularly for a disease that is as challenging as Alzheimer’s. We hope that this statement can be a guide for clinicians in communicating with patients and families in order to carefully consider decisions about the use of aducanumab,” said lead author Winston Chiong, MD, PhD, University of California San Francisco Memory and Aging Center, and a member of the AAN’s Ethics, Law, and Humanities Committee.
The statement was published online Nov. 17 in Neurology.
Open, honest communication
The Food and Drug Administration approved the antiamyloid agent aducanumab based on two studies that were both stopped prematurely for futility. In subsequent post hoc analyses of the available data, one of those studies indicated a statistically significant, albeit small, benefit with high-dose aducanumab, while the other study continued to show no benefit.
The clinical importance of the small statistical benefit in the single trial for daily function is unclear, and aducanumab was also associated with brain inflammation and brain bleeds in more than one-third of patients who received the FDA-approved dose, which requires regular brain MRI monitoring.
All of this should be communicated to patients, the AAN advises.
Patients should know that while aducanumab reduces beta-amyloid plaques in the brain that are markers of Alzheimer’s disease, it remains unclear whether this provides any meaningful benefit.
The AAN adds that it is equally important to tell patients and families that aducanumab does not restore cognitive function and that there is insufficient data to offer it to people with moderate or advanced dementia or to those without evidence of beta-amyloid plaques.
It’s important to note that very few participants in the aducanumab trials were Hispanic, Black, or Indigenous.
“Informed consent conversations with patients of populations underrepresented in clinical trials should include disclosure about the absence of safety and efficacy data in these groups,” the authors noted.
‘New territory’ for neurologists
“There are two aspects of aducanumab that are relatively new territory for us as neurologists,” Dr. Chiong said. One is the controversy about the evidence for the drug. “In the statement, we’ve tried to help clinicians communicate the uncertainty over aducanumab’s risks and potential benefits,” Dr. Chiong said. The other is the high cost of the drug and how it will be covered.
Aducanumab has a price tag of $56,000 per year, which does not include the cost of infusing the drug, required repeat imaging, and medical management.
The AAN estimates annual costs of prescribing aducanumab may top $100,000 per year. With Medicare generally covering 80%, patients and families must be told that the full costs of treatment may not be covered.
“Regarding cost, we probably don’t think often enough about what prescribing a drug means for an individual patient’s finances and for the health system,” said Dr. Chiong. “In particular, when patients are in Medicare we might assume their health care costs will be sufficiently covered, but because aducanumab is so expensive its use is likely to impose very significant costs on individual patients as well as to the Medicare program,” Dr. Chiong said.
“It is understandable why a new drug for Alzheimer’s disease generates so much interest, because while its approval has been controversial, it still offers a glimmer of hope to patients and their families,” AAN President Orly Avitzur, MD, said in a news release. “By using ethical principles to create this position statement, the American Academy of Neurology aims to help neurologists and other physicians transparently counsel patients and their families with a goal of providing the highest quality patient-centered care,” Dr. Avitzur said.
This statement was approved by the Ethics, Law, and Humanities Committee, a joint committee of the AAN, American Neurological Association, and Child Neurology Society.
This research had no targeted funding. Dr. Chiong has received personal compensation for serving on the Neuroethics Working Group of the National Institutes of Health BRAIN Initiative, and his institution has received research support from the National Institutes of Health. A complete list of author disclosures is available with the original article.
A version of this article first appeared on Medscape.com.
The statement includes ethical considerations and recommendations for informed consent, and the AAN notes that neurologists should ensure that patients understand all of the issues and uncertainties surrounding the use of aducanumab.
“Neurologists and other clinicians want to provide the best care to patients and families, particularly for a disease that is as challenging as Alzheimer’s. We hope that this statement can be a guide for clinicians in communicating with patients and families in order to carefully consider decisions about the use of aducanumab,” said lead author Winston Chiong, MD, PhD, University of California San Francisco Memory and Aging Center, and a member of the AAN’s Ethics, Law, and Humanities Committee.
The statement was published online Nov. 17 in Neurology.
Open, honest communication
The Food and Drug Administration approved the antiamyloid agent aducanumab based on two studies that were both stopped prematurely for futility. In subsequent post hoc analyses of the available data, one of those studies indicated a statistically significant, albeit small, benefit with high-dose aducanumab, while the other study continued to show no benefit.
The clinical importance of the small statistical benefit in the single trial for daily function is unclear, and aducanumab was also associated with brain inflammation and brain bleeds in more than one-third of patients who received the FDA-approved dose, which requires regular brain MRI monitoring.
All of this should be communicated to patients, the AAN advises.
Patients should know that while aducanumab reduces beta-amyloid plaques in the brain that are markers of Alzheimer’s disease, it remains unclear whether this provides any meaningful benefit.
The AAN adds that it is equally important to tell patients and families that aducanumab does not restore cognitive function and that there is insufficient data to offer it to people with moderate or advanced dementia or to those without evidence of beta-amyloid plaques.
It’s important to note that very few participants in the aducanumab trials were Hispanic, Black, or Indigenous.
“Informed consent conversations with patients of populations underrepresented in clinical trials should include disclosure about the absence of safety and efficacy data in these groups,” the authors noted.
‘New territory’ for neurologists
“There are two aspects of aducanumab that are relatively new territory for us as neurologists,” Dr. Chiong said. One is the controversy about the evidence for the drug. “In the statement, we’ve tried to help clinicians communicate the uncertainty over aducanumab’s risks and potential benefits,” Dr. Chiong said. The other is the high cost of the drug and how it will be covered.
Aducanumab has a price tag of $56,000 per year, which does not include the cost of infusing the drug, required repeat imaging, and medical management.
The AAN estimates annual costs of prescribing aducanumab may top $100,000 per year. With Medicare generally covering 80%, patients and families must be told that the full costs of treatment may not be covered.
“Regarding cost, we probably don’t think often enough about what prescribing a drug means for an individual patient’s finances and for the health system,” said Dr. Chiong. “In particular, when patients are in Medicare we might assume their health care costs will be sufficiently covered, but because aducanumab is so expensive its use is likely to impose very significant costs on individual patients as well as to the Medicare program,” Dr. Chiong said.
“It is understandable why a new drug for Alzheimer’s disease generates so much interest, because while its approval has been controversial, it still offers a glimmer of hope to patients and their families,” AAN President Orly Avitzur, MD, said in a news release. “By using ethical principles to create this position statement, the American Academy of Neurology aims to help neurologists and other physicians transparently counsel patients and their families with a goal of providing the highest quality patient-centered care,” Dr. Avitzur said.
This statement was approved by the Ethics, Law, and Humanities Committee, a joint committee of the AAN, American Neurological Association, and Child Neurology Society.
This research had no targeted funding. Dr. Chiong has received personal compensation for serving on the Neuroethics Working Group of the National Institutes of Health BRAIN Initiative, and his institution has received research support from the National Institutes of Health. A complete list of author disclosures is available with the original article.
A version of this article first appeared on Medscape.com.
The statement includes ethical considerations and recommendations for informed consent, and the AAN notes that neurologists should ensure that patients understand all of the issues and uncertainties surrounding the use of aducanumab.
“Neurologists and other clinicians want to provide the best care to patients and families, particularly for a disease that is as challenging as Alzheimer’s. We hope that this statement can be a guide for clinicians in communicating with patients and families in order to carefully consider decisions about the use of aducanumab,” said lead author Winston Chiong, MD, PhD, University of California San Francisco Memory and Aging Center, and a member of the AAN’s Ethics, Law, and Humanities Committee.
The statement was published online Nov. 17 in Neurology.
Open, honest communication
The Food and Drug Administration approved the antiamyloid agent aducanumab based on two studies that were both stopped prematurely for futility. In subsequent post hoc analyses of the available data, one of those studies indicated a statistically significant, albeit small, benefit with high-dose aducanumab, while the other study continued to show no benefit.
The clinical importance of the small statistical benefit in the single trial for daily function is unclear, and aducanumab was also associated with brain inflammation and brain bleeds in more than one-third of patients who received the FDA-approved dose, which requires regular brain MRI monitoring.
All of this should be communicated to patients, the AAN advises.
Patients should know that while aducanumab reduces beta-amyloid plaques in the brain that are markers of Alzheimer’s disease, it remains unclear whether this provides any meaningful benefit.
The AAN adds that it is equally important to tell patients and families that aducanumab does not restore cognitive function and that there is insufficient data to offer it to people with moderate or advanced dementia or to those without evidence of beta-amyloid plaques.
It’s important to note that very few participants in the aducanumab trials were Hispanic, Black, or Indigenous.
“Informed consent conversations with patients of populations underrepresented in clinical trials should include disclosure about the absence of safety and efficacy data in these groups,” the authors noted.
‘New territory’ for neurologists
“There are two aspects of aducanumab that are relatively new territory for us as neurologists,” Dr. Chiong said. One is the controversy about the evidence for the drug. “In the statement, we’ve tried to help clinicians communicate the uncertainty over aducanumab’s risks and potential benefits,” Dr. Chiong said. The other is the high cost of the drug and how it will be covered.
Aducanumab has a price tag of $56,000 per year, which does not include the cost of infusing the drug, required repeat imaging, and medical management.
The AAN estimates annual costs of prescribing aducanumab may top $100,000 per year. With Medicare generally covering 80%, patients and families must be told that the full costs of treatment may not be covered.
“Regarding cost, we probably don’t think often enough about what prescribing a drug means for an individual patient’s finances and for the health system,” said Dr. Chiong. “In particular, when patients are in Medicare we might assume their health care costs will be sufficiently covered, but because aducanumab is so expensive its use is likely to impose very significant costs on individual patients as well as to the Medicare program,” Dr. Chiong said.
“It is understandable why a new drug for Alzheimer’s disease generates so much interest, because while its approval has been controversial, it still offers a glimmer of hope to patients and their families,” AAN President Orly Avitzur, MD, said in a news release. “By using ethical principles to create this position statement, the American Academy of Neurology aims to help neurologists and other physicians transparently counsel patients and their families with a goal of providing the highest quality patient-centered care,” Dr. Avitzur said.
This statement was approved by the Ethics, Law, and Humanities Committee, a joint committee of the AAN, American Neurological Association, and Child Neurology Society.
This research had no targeted funding. Dr. Chiong has received personal compensation for serving on the Neuroethics Working Group of the National Institutes of Health BRAIN Initiative, and his institution has received research support from the National Institutes of Health. A complete list of author disclosures is available with the original article.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Validity of commercial serologic tests for dermatomyositis still questionable
, according to Jeffrey P. Callen, MD.
That’s because the validity and reproducibility of testing in commercial laboratories remain questionable, Dr. Callen, professor of medicine and chief of the division of dermatology at the University of Louisville, Ky., said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “The testing in research laboratories is not widely available and the results are often delayed by weeks to months,” he said.
In addition, while the associations between antibody results and risks of malignancy or pulmonary disease are “statistically valid,” he said, “there are patients with disease in whom antibodies are not present and those without associated disease in whom the testing was positive.” For example, there are patients positive for anti–transition initiation factor (TIF)-1gamma but don’t have a malignancy, “and the ones with anti-MDA-5 tend to have pulmonary disease, but there are patients with anti-MDA-5 who don’t have pulmonary disease.”
Compared with patients with systemic lupus erythematosus, patients with dermatomyositis tend to have more itching and they tend of have fewer serologic abnormalities, such as anti-Ro/SS-A antibody, “but there is overlap,” Dr. Callen said. “The reason to differentiate cutaneous lupus erythematosus from dermatomyositis is because we think that patients who have amyopathic dermatomyositis still have an increased risk of having or developing an internal malignancy,” he added. Another differentiating point that is substantive is the presence of Gottron papules.
In a recent development related to antibody testing, researchers demonstrated that the IgG2 isotype of anti-TIF-1gamma antibodies is a biomarker of cancer and mortality in adult dermatomyositis.
According to population-based studies, about 20%-25% of dermatomyositis patients have had, have, or will develop a cancer (Lancet 2001;357: 96-100). Amyopathic dermatomyositis patients may also have cancer. Polymyositis patients generally have lower rates and their risk of subsequent malignancy is much closer to that of the general population, suggesting that the presence of the association is due to a “diagnostic suspicion bias,” Dr. Callen said.
A large-scale multicenter cohort study that set out to identify the risk factors and prognosis of patients with cancer-associated myositis found that ovarian cancer seems to be overrepresented. The only serologic abnormality that was statistically significant was anti-TIF-1gamma antibody (P less than .001). Patients with cancer-associated myositis also have less overall survival compared with those with non–cancer-associated myositis (P = .004), with malignancy being the primary cause of death (P less than .001).
In what is believed to be the largest study of its kind, Dr. Callen and colleagues retrospectively examined the prevalence of malignancy and screening practices in 400 dermatomyositis patients. Of the 400 patients, 48 (12%) had malignancies, and 21 cancers (40%) were diagnosed within 1 year of the dermatomyositis diagnosis. Both classic dermatomyositis and amyopathic dermatomyositis were associated with cancer, and 27 patients (6.8%) had a cancer at the time of diagnosis. Of those, 59% were asymptomatic; their cancers were discovered with CT scans, suggesting that “blind” screening is effective in identifying cancers in DM patients.
Dr. Callen’s malignancy evaluation includes chest x-ray, CT of the chest and abdomen, stool Hematest in all dermatomyositis patients; a mammogram, pelvic ultrasound and/or CT of the pelvis in women; and age, race or ethnicity-related testing. “I generally reevaluate patients annually for 3 years, because data from epidemiologic studies suggest that after 3 years [from the initial diagnosis], the rates of malignancy return toward normal,” he said. “I also evaluate any new symptom that might be suggestive of malignancy. The remaining issue is how to handle a patient in remission for several years, but who develops a relapse. What I do is perform another malignancy assessment.”
According to results from a meta-analysis of risk factors and systematic review of screening approaches, factors that increase malignancy risk include dermatomyositis subtype (risk ratio, 2.21), older age (weighted mean difference 11.19), male gender (RR, 1.53), dysphagia (RR, 2.09), cutaneous necrosis (RR, 2.73), and positive anti-TIF-1gamma (RR, 4.41).
Factors associated with a decreased risk of malignancy include polymyositis (RR, 0.49), clinically amyopathic dermatomyositis subtypes (RR, 0.44), Raynaud’s phenomenon (RR, 0.61), interstitial lung disease (RR, 0.49), very high serum creatine kinase (WMD –1189.96) or lactate dehydrogenase levels (WMD –336.53), and anti-Jo1 (RR, 0.45) or anti-EJ (RR, 0.17) positivity.
The analysis also found that CT scanning of the thorax, abdomen and pelvis appeared to yield a high proportion of underlying asymptomatic cancers. Limited evidence relating to the utility of tumor markers and 18F-FDG PET/CT was available.
As for treatment, the use of tofacitinib for cutaneous lesions of dermatomyositis has been suggested in various studies. In a recent open-label study of 10 patients with dermatomyositis who took extended release the JAK inhibitor tofacitinib 11 mg daily for 12 weeks, half experienced moderate improvement in disease activity, and the other half experienced minimal improvement. JAK inhibitors have been used in patients with juvenile dermatomyositis.
Dr. Callen’s treatment approach with dermatomyositis patients includes recommendations for sunscreens and protective clothing, plus assessment of vitamin D levels. “I will use topical emollients, corticosteroids, and calcineurin inhibitors,” he said. “Antimalarials might be used. I generally reach for methotrexate or mycophenolate mofetil relatively early. IVIG has also been studied.” Off-label therapies that have been used include dapsone, thalidomide, leflunomide, sirolimus, chlorambucil, etanercept, infliximab, rituximab, apremilast, tofacitinib, lenabasum, and low-dose naltrexone.
Dr. Callen disclosed that he is a consultant to Genentech and is a member of the safety monitoring committee for Principia Biopharma. He holds equity in Celgene, Pfizer, 3M, Johnson & Johnson, Merck, Abbott Laboratories, AbbVie, Procter & Gamble, Gilead, Allergen, and Amgen.
MedscapeLive and this news organization are owned by the same parent company.
, according to Jeffrey P. Callen, MD.
That’s because the validity and reproducibility of testing in commercial laboratories remain questionable, Dr. Callen, professor of medicine and chief of the division of dermatology at the University of Louisville, Ky., said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “The testing in research laboratories is not widely available and the results are often delayed by weeks to months,” he said.
In addition, while the associations between antibody results and risks of malignancy or pulmonary disease are “statistically valid,” he said, “there are patients with disease in whom antibodies are not present and those without associated disease in whom the testing was positive.” For example, there are patients positive for anti–transition initiation factor (TIF)-1gamma but don’t have a malignancy, “and the ones with anti-MDA-5 tend to have pulmonary disease, but there are patients with anti-MDA-5 who don’t have pulmonary disease.”
Compared with patients with systemic lupus erythematosus, patients with dermatomyositis tend to have more itching and they tend of have fewer serologic abnormalities, such as anti-Ro/SS-A antibody, “but there is overlap,” Dr. Callen said. “The reason to differentiate cutaneous lupus erythematosus from dermatomyositis is because we think that patients who have amyopathic dermatomyositis still have an increased risk of having or developing an internal malignancy,” he added. Another differentiating point that is substantive is the presence of Gottron papules.
In a recent development related to antibody testing, researchers demonstrated that the IgG2 isotype of anti-TIF-1gamma antibodies is a biomarker of cancer and mortality in adult dermatomyositis.
According to population-based studies, about 20%-25% of dermatomyositis patients have had, have, or will develop a cancer (Lancet 2001;357: 96-100). Amyopathic dermatomyositis patients may also have cancer. Polymyositis patients generally have lower rates and their risk of subsequent malignancy is much closer to that of the general population, suggesting that the presence of the association is due to a “diagnostic suspicion bias,” Dr. Callen said.
A large-scale multicenter cohort study that set out to identify the risk factors and prognosis of patients with cancer-associated myositis found that ovarian cancer seems to be overrepresented. The only serologic abnormality that was statistically significant was anti-TIF-1gamma antibody (P less than .001). Patients with cancer-associated myositis also have less overall survival compared with those with non–cancer-associated myositis (P = .004), with malignancy being the primary cause of death (P less than .001).
In what is believed to be the largest study of its kind, Dr. Callen and colleagues retrospectively examined the prevalence of malignancy and screening practices in 400 dermatomyositis patients. Of the 400 patients, 48 (12%) had malignancies, and 21 cancers (40%) were diagnosed within 1 year of the dermatomyositis diagnosis. Both classic dermatomyositis and amyopathic dermatomyositis were associated with cancer, and 27 patients (6.8%) had a cancer at the time of diagnosis. Of those, 59% were asymptomatic; their cancers were discovered with CT scans, suggesting that “blind” screening is effective in identifying cancers in DM patients.
Dr. Callen’s malignancy evaluation includes chest x-ray, CT of the chest and abdomen, stool Hematest in all dermatomyositis patients; a mammogram, pelvic ultrasound and/or CT of the pelvis in women; and age, race or ethnicity-related testing. “I generally reevaluate patients annually for 3 years, because data from epidemiologic studies suggest that after 3 years [from the initial diagnosis], the rates of malignancy return toward normal,” he said. “I also evaluate any new symptom that might be suggestive of malignancy. The remaining issue is how to handle a patient in remission for several years, but who develops a relapse. What I do is perform another malignancy assessment.”
According to results from a meta-analysis of risk factors and systematic review of screening approaches, factors that increase malignancy risk include dermatomyositis subtype (risk ratio, 2.21), older age (weighted mean difference 11.19), male gender (RR, 1.53), dysphagia (RR, 2.09), cutaneous necrosis (RR, 2.73), and positive anti-TIF-1gamma (RR, 4.41).
Factors associated with a decreased risk of malignancy include polymyositis (RR, 0.49), clinically amyopathic dermatomyositis subtypes (RR, 0.44), Raynaud’s phenomenon (RR, 0.61), interstitial lung disease (RR, 0.49), very high serum creatine kinase (WMD –1189.96) or lactate dehydrogenase levels (WMD –336.53), and anti-Jo1 (RR, 0.45) or anti-EJ (RR, 0.17) positivity.
The analysis also found that CT scanning of the thorax, abdomen and pelvis appeared to yield a high proportion of underlying asymptomatic cancers. Limited evidence relating to the utility of tumor markers and 18F-FDG PET/CT was available.
As for treatment, the use of tofacitinib for cutaneous lesions of dermatomyositis has been suggested in various studies. In a recent open-label study of 10 patients with dermatomyositis who took extended release the JAK inhibitor tofacitinib 11 mg daily for 12 weeks, half experienced moderate improvement in disease activity, and the other half experienced minimal improvement. JAK inhibitors have been used in patients with juvenile dermatomyositis.
Dr. Callen’s treatment approach with dermatomyositis patients includes recommendations for sunscreens and protective clothing, plus assessment of vitamin D levels. “I will use topical emollients, corticosteroids, and calcineurin inhibitors,” he said. “Antimalarials might be used. I generally reach for methotrexate or mycophenolate mofetil relatively early. IVIG has also been studied.” Off-label therapies that have been used include dapsone, thalidomide, leflunomide, sirolimus, chlorambucil, etanercept, infliximab, rituximab, apremilast, tofacitinib, lenabasum, and low-dose naltrexone.
Dr. Callen disclosed that he is a consultant to Genentech and is a member of the safety monitoring committee for Principia Biopharma. He holds equity in Celgene, Pfizer, 3M, Johnson & Johnson, Merck, Abbott Laboratories, AbbVie, Procter & Gamble, Gilead, Allergen, and Amgen.
MedscapeLive and this news organization are owned by the same parent company.
, according to Jeffrey P. Callen, MD.
That’s because the validity and reproducibility of testing in commercial laboratories remain questionable, Dr. Callen, professor of medicine and chief of the division of dermatology at the University of Louisville, Ky., said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “The testing in research laboratories is not widely available and the results are often delayed by weeks to months,” he said.
In addition, while the associations between antibody results and risks of malignancy or pulmonary disease are “statistically valid,” he said, “there are patients with disease in whom antibodies are not present and those without associated disease in whom the testing was positive.” For example, there are patients positive for anti–transition initiation factor (TIF)-1gamma but don’t have a malignancy, “and the ones with anti-MDA-5 tend to have pulmonary disease, but there are patients with anti-MDA-5 who don’t have pulmonary disease.”
Compared with patients with systemic lupus erythematosus, patients with dermatomyositis tend to have more itching and they tend of have fewer serologic abnormalities, such as anti-Ro/SS-A antibody, “but there is overlap,” Dr. Callen said. “The reason to differentiate cutaneous lupus erythematosus from dermatomyositis is because we think that patients who have amyopathic dermatomyositis still have an increased risk of having or developing an internal malignancy,” he added. Another differentiating point that is substantive is the presence of Gottron papules.
In a recent development related to antibody testing, researchers demonstrated that the IgG2 isotype of anti-TIF-1gamma antibodies is a biomarker of cancer and mortality in adult dermatomyositis.
According to population-based studies, about 20%-25% of dermatomyositis patients have had, have, or will develop a cancer (Lancet 2001;357: 96-100). Amyopathic dermatomyositis patients may also have cancer. Polymyositis patients generally have lower rates and their risk of subsequent malignancy is much closer to that of the general population, suggesting that the presence of the association is due to a “diagnostic suspicion bias,” Dr. Callen said.
A large-scale multicenter cohort study that set out to identify the risk factors and prognosis of patients with cancer-associated myositis found that ovarian cancer seems to be overrepresented. The only serologic abnormality that was statistically significant was anti-TIF-1gamma antibody (P less than .001). Patients with cancer-associated myositis also have less overall survival compared with those with non–cancer-associated myositis (P = .004), with malignancy being the primary cause of death (P less than .001).
In what is believed to be the largest study of its kind, Dr. Callen and colleagues retrospectively examined the prevalence of malignancy and screening practices in 400 dermatomyositis patients. Of the 400 patients, 48 (12%) had malignancies, and 21 cancers (40%) were diagnosed within 1 year of the dermatomyositis diagnosis. Both classic dermatomyositis and amyopathic dermatomyositis were associated with cancer, and 27 patients (6.8%) had a cancer at the time of diagnosis. Of those, 59% were asymptomatic; their cancers were discovered with CT scans, suggesting that “blind” screening is effective in identifying cancers in DM patients.
Dr. Callen’s malignancy evaluation includes chest x-ray, CT of the chest and abdomen, stool Hematest in all dermatomyositis patients; a mammogram, pelvic ultrasound and/or CT of the pelvis in women; and age, race or ethnicity-related testing. “I generally reevaluate patients annually for 3 years, because data from epidemiologic studies suggest that after 3 years [from the initial diagnosis], the rates of malignancy return toward normal,” he said. “I also evaluate any new symptom that might be suggestive of malignancy. The remaining issue is how to handle a patient in remission for several years, but who develops a relapse. What I do is perform another malignancy assessment.”
According to results from a meta-analysis of risk factors and systematic review of screening approaches, factors that increase malignancy risk include dermatomyositis subtype (risk ratio, 2.21), older age (weighted mean difference 11.19), male gender (RR, 1.53), dysphagia (RR, 2.09), cutaneous necrosis (RR, 2.73), and positive anti-TIF-1gamma (RR, 4.41).
Factors associated with a decreased risk of malignancy include polymyositis (RR, 0.49), clinically amyopathic dermatomyositis subtypes (RR, 0.44), Raynaud’s phenomenon (RR, 0.61), interstitial lung disease (RR, 0.49), very high serum creatine kinase (WMD –1189.96) or lactate dehydrogenase levels (WMD –336.53), and anti-Jo1 (RR, 0.45) or anti-EJ (RR, 0.17) positivity.
The analysis also found that CT scanning of the thorax, abdomen and pelvis appeared to yield a high proportion of underlying asymptomatic cancers. Limited evidence relating to the utility of tumor markers and 18F-FDG PET/CT was available.
As for treatment, the use of tofacitinib for cutaneous lesions of dermatomyositis has been suggested in various studies. In a recent open-label study of 10 patients with dermatomyositis who took extended release the JAK inhibitor tofacitinib 11 mg daily for 12 weeks, half experienced moderate improvement in disease activity, and the other half experienced minimal improvement. JAK inhibitors have been used in patients with juvenile dermatomyositis.
Dr. Callen’s treatment approach with dermatomyositis patients includes recommendations for sunscreens and protective clothing, plus assessment of vitamin D levels. “I will use topical emollients, corticosteroids, and calcineurin inhibitors,” he said. “Antimalarials might be used. I generally reach for methotrexate or mycophenolate mofetil relatively early. IVIG has also been studied.” Off-label therapies that have been used include dapsone, thalidomide, leflunomide, sirolimus, chlorambucil, etanercept, infliximab, rituximab, apremilast, tofacitinib, lenabasum, and low-dose naltrexone.
Dr. Callen disclosed that he is a consultant to Genentech and is a member of the safety monitoring committee for Principia Biopharma. He holds equity in Celgene, Pfizer, 3M, Johnson & Johnson, Merck, Abbott Laboratories, AbbVie, Procter & Gamble, Gilead, Allergen, and Amgen.
MedscapeLive and this news organization are owned by the same parent company.
FROM THE MEDSCAPELIVE LAS VEGAS DERMATOLOGY SEMINAR