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Asking patients about their gender identity: ‘Normalize’ the discussion and other recommendations
PORTLAND, ORE. –
“From the patient perspective, there’s nothing more awkward than having an awkward provider asking awkward questions,” Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said at the annual meeting of the Pacific Dermatologic Association.
In 2014, Sean Cahill, PhD, and Harvey Makadon, MD, published an article recommending the inclusion of sexual orientation and gender identity questions in electronic medical records, a practice that Dr. Yeung characterized as “the most patient-centered way to collect sexual orientation and gender identity information. The most important thing is to ask routinely on an intake form where they fill it out themselves. All electronic medical records have the capacity to do so.”
On the other hand, when asking new patients about their sexual orientation and gender identity in person, it’s important to normalize the discussion and ask in an inclusive way, said Dr. Yeung, who was the lead author on published recommendations on dermatologic care for LGBTQ persons published in the Journal of the American Academy of Dermatology. “For example, I always say, ‘I’m Howa Yeung. I use him pronouns,’ ” he said. “ ‘How should I address you?’ Then they will tell you. Allow people to lead the way.”
Other suggested tips in the JAAD article include to avoid using terms such as “sir” or “miss” until the patient’s gender identify is ascertained. Instead, use gender-neutral terms such as “they” or “the patient” when referring to new patients. Do not use the pronoun “it.” If a patient’s name does not match a name in the medical record, ask, “What is the name on your insurance/records?” and avoid assuming gender(s) of a patient’s partner or parents. Instead, consider asking, “Who did you bring with you today?” “Are you in a relationship?” “What are the names of your parents?”
Normalizing questions about the patient’s sexual history is also key. “I tell patients that I routinely ask about sexual history for patients with similar skin issues because it helps me provide the best care for them,” Dr. Yeung said. “I also discuss confidentiality and documentation.”
Dr. Yeung reported having no relevant disclosures.
PORTLAND, ORE. –
“From the patient perspective, there’s nothing more awkward than having an awkward provider asking awkward questions,” Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said at the annual meeting of the Pacific Dermatologic Association.
In 2014, Sean Cahill, PhD, and Harvey Makadon, MD, published an article recommending the inclusion of sexual orientation and gender identity questions in electronic medical records, a practice that Dr. Yeung characterized as “the most patient-centered way to collect sexual orientation and gender identity information. The most important thing is to ask routinely on an intake form where they fill it out themselves. All electronic medical records have the capacity to do so.”
On the other hand, when asking new patients about their sexual orientation and gender identity in person, it’s important to normalize the discussion and ask in an inclusive way, said Dr. Yeung, who was the lead author on published recommendations on dermatologic care for LGBTQ persons published in the Journal of the American Academy of Dermatology. “For example, I always say, ‘I’m Howa Yeung. I use him pronouns,’ ” he said. “ ‘How should I address you?’ Then they will tell you. Allow people to lead the way.”
Other suggested tips in the JAAD article include to avoid using terms such as “sir” or “miss” until the patient’s gender identify is ascertained. Instead, use gender-neutral terms such as “they” or “the patient” when referring to new patients. Do not use the pronoun “it.” If a patient’s name does not match a name in the medical record, ask, “What is the name on your insurance/records?” and avoid assuming gender(s) of a patient’s partner or parents. Instead, consider asking, “Who did you bring with you today?” “Are you in a relationship?” “What are the names of your parents?”
Normalizing questions about the patient’s sexual history is also key. “I tell patients that I routinely ask about sexual history for patients with similar skin issues because it helps me provide the best care for them,” Dr. Yeung said. “I also discuss confidentiality and documentation.”
Dr. Yeung reported having no relevant disclosures.
PORTLAND, ORE. –
“From the patient perspective, there’s nothing more awkward than having an awkward provider asking awkward questions,” Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said at the annual meeting of the Pacific Dermatologic Association.
In 2014, Sean Cahill, PhD, and Harvey Makadon, MD, published an article recommending the inclusion of sexual orientation and gender identity questions in electronic medical records, a practice that Dr. Yeung characterized as “the most patient-centered way to collect sexual orientation and gender identity information. The most important thing is to ask routinely on an intake form where they fill it out themselves. All electronic medical records have the capacity to do so.”
On the other hand, when asking new patients about their sexual orientation and gender identity in person, it’s important to normalize the discussion and ask in an inclusive way, said Dr. Yeung, who was the lead author on published recommendations on dermatologic care for LGBTQ persons published in the Journal of the American Academy of Dermatology. “For example, I always say, ‘I’m Howa Yeung. I use him pronouns,’ ” he said. “ ‘How should I address you?’ Then they will tell you. Allow people to lead the way.”
Other suggested tips in the JAAD article include to avoid using terms such as “sir” or “miss” until the patient’s gender identify is ascertained. Instead, use gender-neutral terms such as “they” or “the patient” when referring to new patients. Do not use the pronoun “it.” If a patient’s name does not match a name in the medical record, ask, “What is the name on your insurance/records?” and avoid assuming gender(s) of a patient’s partner or parents. Instead, consider asking, “Who did you bring with you today?” “Are you in a relationship?” “What are the names of your parents?”
Normalizing questions about the patient’s sexual history is also key. “I tell patients that I routinely ask about sexual history for patients with similar skin issues because it helps me provide the best care for them,” Dr. Yeung said. “I also discuss confidentiality and documentation.”
Dr. Yeung reported having no relevant disclosures.
AT PDA 2022
AML’s seasonal peak suggests viral or environmental etiology
Most diagnoses of acute myeloid leukemia (AML) are made during January. This finding strongly implies that seasonal factors, such as infectious agents or environmental triggers, influence the development or proliferation of the disease, which points to prevention opportunities. This was the conclusion of an international study led by a team from the Jiménez Díaz Foundation University Hospital Health Research Institute (IIS-FJD) in Madrid, in collaboration with colleagues from the University of Bristol, England. Their work was published in the British Journal of Haematology.
The study’s aim was to investigate the potential seasonal and long-term trends in AML diagnosis in an overall population and in subgroups according to sex and age. To do so, the researchers examined 26,472 cases of AML diagnosed in Spain between 2004 and 2015. They found seasonality in the diagnosis of this type of leukemia. This “could point to there being an underlying seasonal etiology at play,” noted one of the main authors of the study, Juan Manuel Alonso, MD, a physician in the IIS-FJD’s department of hematology and hemotherapy.
“The environmental triggers involved could be radiation, pollution, allergens, or infectious agents like viruses. We’re leaning toward viruses, because there are already distinct solid tumor and hematologic cancers that are caused by them and because, in the winter months, there’s an increased incidence of cancers due to viral infections,” Dr. Alonso said in an interview. “The etiological mechanism should be different from that exerted by chronic viral pressure, because here we’re dealing with an acute and aggressive disease that probably needs a short incubation period.”
Various hypotheses
In an interview, David Martínez, MD, a hematologist at La Fe University Hospital in Valencia, Spain, described the research as “an extremely well done and much-discussed study on AML, a disease that appears to be diagnosed more frequently at a certain time of year – namely, January.
“There’s no clear explanation for this finding,” Dr. Martínez said. “Several possible reasons have been put forward and are being talked about. The one that seems to hold the most water is the hypothesis that infectious agents and environmental factors may have a greater influence. This is because the idea that they’re involved in neoplastic diseases is nothing new. In fact, there are a lot of publications and a good amount of scientific evidence that link viral infections and environmental factors with the development of oncologic diseases.”
AML is a rare disease yet is responsible for many cancer-related deaths. Mutations that cause AML can occur due to an inherited mutant gene or exposure to certain carcinogens, such as chemotherapy, radiotherapy, ionizing radiation, tobacco, and benzene. These findings are broadly similar to those of a large U.S.-based study by Calip et al., who found a peak of adult AML diagnoses during December and January from 1992 to 2008. Previous smaller studies have provided conflicting evidence, likely due to lower power or to the use of less advanced statistical approaches.
Seasonal factors involved?
Demonstration of seasonal variation in the occurrence of AML would, firstly, provide supportive evidence of etiology by seasonal factors, such as infectious agents or environmental factors, and, secondly, focus research onto the etiologic role of such factors.
The current study used population-based data on cases of AML occurring in Spain from a nationwide hospital discharge registry for the years 2004 to 2015. “This is, to our knowledge, the largest study aimed at investigating the potential seasonal and long-term trends in AML incidence in an overall population and in subgroups according to sex and age while employing novel statistical models with serial dependence for discrete-valued time series,” wrote the researchers.
They extracted information from the register of each case about the date of admission, discharge date, the anonymous identifier for each patient, International Classification of Diseases (ICD)–9 codes, sex, and date of birth, from which they derived age groups as described for the at-risk population. For patients hospitalized on more than one occasion, only the record corresponding to their first diagnosis of AML was selected.
AML cases per month were standardized to months of equal length.
Age/sex-standardized monthly incidence rates of AML were calculated using the census of Spanish population in 2010 as a “standard” population. Age-standardized and sex-standardized monthly incidence rates of AML were calculated.
Nine separate time-series decompositions were performed as an initial exploratory analysis on the monthly incidence rates of AML using data for all cases and data for each sex and age group. Nine separate Poisson generalized linear autoregressive moving average (GLARMA) models were fitted to evaluate the temporal dynamics in AML incidence using data for all cases, and data for each sex and age group.
Long-term trend
A total of 26,472 patients with a first diagnosis of active AML were hospitalized in Spain and registered at the country’s Minimum Basic Data Set (CMBD) during 2004-2015. In the end, there were 26,475 patients in the study population; a greater proportion of cases were male (56.0%), and the median age at diagnosis was 67 years.
Seasonal and trend decomposition using Loess decomposition of the incidence rates observed in the overall population exhibited seasonal fluctuation with a peak in January. A slight upward trend was apparent from visual inspection with an upturn in early 2005 and a downturn at the end of 2013. As for the differences by sex groups and age groups, Dr. Alonso said, “For both sexes and in age groups 5-19, 20-49, and 50-64 years, we found that the results were identical to those found in the overall population.”
The final model included an upward linear long-term trend, as well as the variables monthly seasonality and December 2015. The estimated monthly long-term trend implies that the monthly incidence rates of AML diagnoses annually increased by 0.4% (95% confidence interval [CI], 0.2%-0.6%; P = .0011), given that the other covariates are held constant.
January displayed the highest incidence rate of AML, with a minimum average difference of 7%, when compared with February (95% CI, 2%-12%; P = .0143) and a maximum average difference of 16%, compared with November (95% CI, 11%-21%; P < .0001) and August (95% CI, 10%-21%; P < .0001).
The incidence rate of AML for December 2015 was 0.43 (95% CI, 0.34-0.54; P < .0001) times the average incidence rate for the rest of the study period.
Potential role of viruses
“We have to keep in mind that infectious agents (viral infections) and environmental factors (allergens) don’t disappear in the warmer months,” Dr. Martínez added. “There are just other viruses and different factors. We don’t know the role or the weight that each one of the factors has, either individually or specifically, in the development of AML. In addition, we know that AML is a very heterogeneous disease and that various factors, including genetic ones, can be involved in its etiopathogenesis.”
With respect to the stem cell theory in this leukemia, Dr. Alonso emphasized that, “in theory, the virus could fit into it with no problem. That said, any other environmental agent could also produce the described phenomenon where the rapid proliferation of quiescent leukemic stem cells is stimulated, thereby hastening the diagnosis.”
“Should the etiological factor be found,” Dr. Martínez noted, “we can try to reduce exposure and thereby decrease the incidence of AML. On the other hand, discovering how the environmental factor stimulates the proliferation of quiescent leukemic [stem] cells could enhance our knowledge about the regulation of that.”
As to whether there is evidence for the involvement of infections in other hematologic malignancies, Dr. Martínez reported, “This has already been seen. And this study shows other examples (Epstein-Barr virus and human T-cell lymphotropic virus type 1 with lymphomas), and there could also be Helicobacter pylori and lymphomas.”
Outside of hematology, human papillomavirus has been associated with cervical cancer, tobacco with lung cancer, sun with skin cancer, and diet with the development of some solid neoplasms.
“The study speaks about the concept of a latency period. To accept the idea that a factor or virus that’s more prevalent in winter produces, on its own, AML in a few weeks or months means accepting the idea of a very short latency period – something that’s not usually the case. For that, another explanation is given: An abnormal immune response or that a seasonal infectious agent can be capable of promoting leukemogenesis. These are also hypotheses to be explored in the future,” suggested Dr. Martínez.
New research network
Several potential limitations of this study should be considered. One limitation is that AML cases were obtained from the CMBD registry as defined by ICD-9, and no other AML classifications were available. Another limitation is that information on the date of onset of clinical symptoms was not available for analysis. In addition, a further limitation related to the source of their data may have led the researchers to underestimate the incidence rates of AML in older patients, as only hospitalized patients were captured in their study.
As for continuing the research, the results make it necessary to carry out complementary epidemiologic studies that will examine the association between seasonal risk factors and the increased diagnosis of AML during winter months.
To go forward, the first step would be to secure funding. For this purpose, a network is being put together featuring collaborators from other world-renowned research groups that are at the top of their respective disciplines. Through this network, they hope to be able to apply together for public research grants from countries in Europe and elsewhere as well as to establish collaborations with various companies in the private sector.
“This could open up new therapeutic avenues in the future, as we could try to force leukemic stem cells to divide, thereby reducing the resistance that the standard treatments usually demonstrate,” Dr. Alonso concluded.
Dr. Alonso received research funding from Incyte, Pfizer International, and Astellas Pharma outside the present work. Dr. Martínez disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of the article appeared on Medscape.com.
Most diagnoses of acute myeloid leukemia (AML) are made during January. This finding strongly implies that seasonal factors, such as infectious agents or environmental triggers, influence the development or proliferation of the disease, which points to prevention opportunities. This was the conclusion of an international study led by a team from the Jiménez Díaz Foundation University Hospital Health Research Institute (IIS-FJD) in Madrid, in collaboration with colleagues from the University of Bristol, England. Their work was published in the British Journal of Haematology.
The study’s aim was to investigate the potential seasonal and long-term trends in AML diagnosis in an overall population and in subgroups according to sex and age. To do so, the researchers examined 26,472 cases of AML diagnosed in Spain between 2004 and 2015. They found seasonality in the diagnosis of this type of leukemia. This “could point to there being an underlying seasonal etiology at play,” noted one of the main authors of the study, Juan Manuel Alonso, MD, a physician in the IIS-FJD’s department of hematology and hemotherapy.
“The environmental triggers involved could be radiation, pollution, allergens, or infectious agents like viruses. We’re leaning toward viruses, because there are already distinct solid tumor and hematologic cancers that are caused by them and because, in the winter months, there’s an increased incidence of cancers due to viral infections,” Dr. Alonso said in an interview. “The etiological mechanism should be different from that exerted by chronic viral pressure, because here we’re dealing with an acute and aggressive disease that probably needs a short incubation period.”
Various hypotheses
In an interview, David Martínez, MD, a hematologist at La Fe University Hospital in Valencia, Spain, described the research as “an extremely well done and much-discussed study on AML, a disease that appears to be diagnosed more frequently at a certain time of year – namely, January.
“There’s no clear explanation for this finding,” Dr. Martínez said. “Several possible reasons have been put forward and are being talked about. The one that seems to hold the most water is the hypothesis that infectious agents and environmental factors may have a greater influence. This is because the idea that they’re involved in neoplastic diseases is nothing new. In fact, there are a lot of publications and a good amount of scientific evidence that link viral infections and environmental factors with the development of oncologic diseases.”
AML is a rare disease yet is responsible for many cancer-related deaths. Mutations that cause AML can occur due to an inherited mutant gene or exposure to certain carcinogens, such as chemotherapy, radiotherapy, ionizing radiation, tobacco, and benzene. These findings are broadly similar to those of a large U.S.-based study by Calip et al., who found a peak of adult AML diagnoses during December and January from 1992 to 2008. Previous smaller studies have provided conflicting evidence, likely due to lower power or to the use of less advanced statistical approaches.
Seasonal factors involved?
Demonstration of seasonal variation in the occurrence of AML would, firstly, provide supportive evidence of etiology by seasonal factors, such as infectious agents or environmental factors, and, secondly, focus research onto the etiologic role of such factors.
The current study used population-based data on cases of AML occurring in Spain from a nationwide hospital discharge registry for the years 2004 to 2015. “This is, to our knowledge, the largest study aimed at investigating the potential seasonal and long-term trends in AML incidence in an overall population and in subgroups according to sex and age while employing novel statistical models with serial dependence for discrete-valued time series,” wrote the researchers.
They extracted information from the register of each case about the date of admission, discharge date, the anonymous identifier for each patient, International Classification of Diseases (ICD)–9 codes, sex, and date of birth, from which they derived age groups as described for the at-risk population. For patients hospitalized on more than one occasion, only the record corresponding to their first diagnosis of AML was selected.
AML cases per month were standardized to months of equal length.
Age/sex-standardized monthly incidence rates of AML were calculated using the census of Spanish population in 2010 as a “standard” population. Age-standardized and sex-standardized monthly incidence rates of AML were calculated.
Nine separate time-series decompositions were performed as an initial exploratory analysis on the monthly incidence rates of AML using data for all cases and data for each sex and age group. Nine separate Poisson generalized linear autoregressive moving average (GLARMA) models were fitted to evaluate the temporal dynamics in AML incidence using data for all cases, and data for each sex and age group.
Long-term trend
A total of 26,472 patients with a first diagnosis of active AML were hospitalized in Spain and registered at the country’s Minimum Basic Data Set (CMBD) during 2004-2015. In the end, there were 26,475 patients in the study population; a greater proportion of cases were male (56.0%), and the median age at diagnosis was 67 years.
Seasonal and trend decomposition using Loess decomposition of the incidence rates observed in the overall population exhibited seasonal fluctuation with a peak in January. A slight upward trend was apparent from visual inspection with an upturn in early 2005 and a downturn at the end of 2013. As for the differences by sex groups and age groups, Dr. Alonso said, “For both sexes and in age groups 5-19, 20-49, and 50-64 years, we found that the results were identical to those found in the overall population.”
The final model included an upward linear long-term trend, as well as the variables monthly seasonality and December 2015. The estimated monthly long-term trend implies that the monthly incidence rates of AML diagnoses annually increased by 0.4% (95% confidence interval [CI], 0.2%-0.6%; P = .0011), given that the other covariates are held constant.
January displayed the highest incidence rate of AML, with a minimum average difference of 7%, when compared with February (95% CI, 2%-12%; P = .0143) and a maximum average difference of 16%, compared with November (95% CI, 11%-21%; P < .0001) and August (95% CI, 10%-21%; P < .0001).
The incidence rate of AML for December 2015 was 0.43 (95% CI, 0.34-0.54; P < .0001) times the average incidence rate for the rest of the study period.
Potential role of viruses
“We have to keep in mind that infectious agents (viral infections) and environmental factors (allergens) don’t disappear in the warmer months,” Dr. Martínez added. “There are just other viruses and different factors. We don’t know the role or the weight that each one of the factors has, either individually or specifically, in the development of AML. In addition, we know that AML is a very heterogeneous disease and that various factors, including genetic ones, can be involved in its etiopathogenesis.”
With respect to the stem cell theory in this leukemia, Dr. Alonso emphasized that, “in theory, the virus could fit into it with no problem. That said, any other environmental agent could also produce the described phenomenon where the rapid proliferation of quiescent leukemic stem cells is stimulated, thereby hastening the diagnosis.”
“Should the etiological factor be found,” Dr. Martínez noted, “we can try to reduce exposure and thereby decrease the incidence of AML. On the other hand, discovering how the environmental factor stimulates the proliferation of quiescent leukemic [stem] cells could enhance our knowledge about the regulation of that.”
As to whether there is evidence for the involvement of infections in other hematologic malignancies, Dr. Martínez reported, “This has already been seen. And this study shows other examples (Epstein-Barr virus and human T-cell lymphotropic virus type 1 with lymphomas), and there could also be Helicobacter pylori and lymphomas.”
Outside of hematology, human papillomavirus has been associated with cervical cancer, tobacco with lung cancer, sun with skin cancer, and diet with the development of some solid neoplasms.
“The study speaks about the concept of a latency period. To accept the idea that a factor or virus that’s more prevalent in winter produces, on its own, AML in a few weeks or months means accepting the idea of a very short latency period – something that’s not usually the case. For that, another explanation is given: An abnormal immune response or that a seasonal infectious agent can be capable of promoting leukemogenesis. These are also hypotheses to be explored in the future,” suggested Dr. Martínez.
New research network
Several potential limitations of this study should be considered. One limitation is that AML cases were obtained from the CMBD registry as defined by ICD-9, and no other AML classifications were available. Another limitation is that information on the date of onset of clinical symptoms was not available for analysis. In addition, a further limitation related to the source of their data may have led the researchers to underestimate the incidence rates of AML in older patients, as only hospitalized patients were captured in their study.
As for continuing the research, the results make it necessary to carry out complementary epidemiologic studies that will examine the association between seasonal risk factors and the increased diagnosis of AML during winter months.
To go forward, the first step would be to secure funding. For this purpose, a network is being put together featuring collaborators from other world-renowned research groups that are at the top of their respective disciplines. Through this network, they hope to be able to apply together for public research grants from countries in Europe and elsewhere as well as to establish collaborations with various companies in the private sector.
“This could open up new therapeutic avenues in the future, as we could try to force leukemic stem cells to divide, thereby reducing the resistance that the standard treatments usually demonstrate,” Dr. Alonso concluded.
Dr. Alonso received research funding from Incyte, Pfizer International, and Astellas Pharma outside the present work. Dr. Martínez disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of the article appeared on Medscape.com.
Most diagnoses of acute myeloid leukemia (AML) are made during January. This finding strongly implies that seasonal factors, such as infectious agents or environmental triggers, influence the development or proliferation of the disease, which points to prevention opportunities. This was the conclusion of an international study led by a team from the Jiménez Díaz Foundation University Hospital Health Research Institute (IIS-FJD) in Madrid, in collaboration with colleagues from the University of Bristol, England. Their work was published in the British Journal of Haematology.
The study’s aim was to investigate the potential seasonal and long-term trends in AML diagnosis in an overall population and in subgroups according to sex and age. To do so, the researchers examined 26,472 cases of AML diagnosed in Spain between 2004 and 2015. They found seasonality in the diagnosis of this type of leukemia. This “could point to there being an underlying seasonal etiology at play,” noted one of the main authors of the study, Juan Manuel Alonso, MD, a physician in the IIS-FJD’s department of hematology and hemotherapy.
“The environmental triggers involved could be radiation, pollution, allergens, or infectious agents like viruses. We’re leaning toward viruses, because there are already distinct solid tumor and hematologic cancers that are caused by them and because, in the winter months, there’s an increased incidence of cancers due to viral infections,” Dr. Alonso said in an interview. “The etiological mechanism should be different from that exerted by chronic viral pressure, because here we’re dealing with an acute and aggressive disease that probably needs a short incubation period.”
Various hypotheses
In an interview, David Martínez, MD, a hematologist at La Fe University Hospital in Valencia, Spain, described the research as “an extremely well done and much-discussed study on AML, a disease that appears to be diagnosed more frequently at a certain time of year – namely, January.
“There’s no clear explanation for this finding,” Dr. Martínez said. “Several possible reasons have been put forward and are being talked about. The one that seems to hold the most water is the hypothesis that infectious agents and environmental factors may have a greater influence. This is because the idea that they’re involved in neoplastic diseases is nothing new. In fact, there are a lot of publications and a good amount of scientific evidence that link viral infections and environmental factors with the development of oncologic diseases.”
AML is a rare disease yet is responsible for many cancer-related deaths. Mutations that cause AML can occur due to an inherited mutant gene or exposure to certain carcinogens, such as chemotherapy, radiotherapy, ionizing radiation, tobacco, and benzene. These findings are broadly similar to those of a large U.S.-based study by Calip et al., who found a peak of adult AML diagnoses during December and January from 1992 to 2008. Previous smaller studies have provided conflicting evidence, likely due to lower power or to the use of less advanced statistical approaches.
Seasonal factors involved?
Demonstration of seasonal variation in the occurrence of AML would, firstly, provide supportive evidence of etiology by seasonal factors, such as infectious agents or environmental factors, and, secondly, focus research onto the etiologic role of such factors.
The current study used population-based data on cases of AML occurring in Spain from a nationwide hospital discharge registry for the years 2004 to 2015. “This is, to our knowledge, the largest study aimed at investigating the potential seasonal and long-term trends in AML incidence in an overall population and in subgroups according to sex and age while employing novel statistical models with serial dependence for discrete-valued time series,” wrote the researchers.
They extracted information from the register of each case about the date of admission, discharge date, the anonymous identifier for each patient, International Classification of Diseases (ICD)–9 codes, sex, and date of birth, from which they derived age groups as described for the at-risk population. For patients hospitalized on more than one occasion, only the record corresponding to their first diagnosis of AML was selected.
AML cases per month were standardized to months of equal length.
Age/sex-standardized monthly incidence rates of AML were calculated using the census of Spanish population in 2010 as a “standard” population. Age-standardized and sex-standardized monthly incidence rates of AML were calculated.
Nine separate time-series decompositions were performed as an initial exploratory analysis on the monthly incidence rates of AML using data for all cases and data for each sex and age group. Nine separate Poisson generalized linear autoregressive moving average (GLARMA) models were fitted to evaluate the temporal dynamics in AML incidence using data for all cases, and data for each sex and age group.
Long-term trend
A total of 26,472 patients with a first diagnosis of active AML were hospitalized in Spain and registered at the country’s Minimum Basic Data Set (CMBD) during 2004-2015. In the end, there were 26,475 patients in the study population; a greater proportion of cases were male (56.0%), and the median age at diagnosis was 67 years.
Seasonal and trend decomposition using Loess decomposition of the incidence rates observed in the overall population exhibited seasonal fluctuation with a peak in January. A slight upward trend was apparent from visual inspection with an upturn in early 2005 and a downturn at the end of 2013. As for the differences by sex groups and age groups, Dr. Alonso said, “For both sexes and in age groups 5-19, 20-49, and 50-64 years, we found that the results were identical to those found in the overall population.”
The final model included an upward linear long-term trend, as well as the variables monthly seasonality and December 2015. The estimated monthly long-term trend implies that the monthly incidence rates of AML diagnoses annually increased by 0.4% (95% confidence interval [CI], 0.2%-0.6%; P = .0011), given that the other covariates are held constant.
January displayed the highest incidence rate of AML, with a minimum average difference of 7%, when compared with February (95% CI, 2%-12%; P = .0143) and a maximum average difference of 16%, compared with November (95% CI, 11%-21%; P < .0001) and August (95% CI, 10%-21%; P < .0001).
The incidence rate of AML for December 2015 was 0.43 (95% CI, 0.34-0.54; P < .0001) times the average incidence rate for the rest of the study period.
Potential role of viruses
“We have to keep in mind that infectious agents (viral infections) and environmental factors (allergens) don’t disappear in the warmer months,” Dr. Martínez added. “There are just other viruses and different factors. We don’t know the role or the weight that each one of the factors has, either individually or specifically, in the development of AML. In addition, we know that AML is a very heterogeneous disease and that various factors, including genetic ones, can be involved in its etiopathogenesis.”
With respect to the stem cell theory in this leukemia, Dr. Alonso emphasized that, “in theory, the virus could fit into it with no problem. That said, any other environmental agent could also produce the described phenomenon where the rapid proliferation of quiescent leukemic stem cells is stimulated, thereby hastening the diagnosis.”
“Should the etiological factor be found,” Dr. Martínez noted, “we can try to reduce exposure and thereby decrease the incidence of AML. On the other hand, discovering how the environmental factor stimulates the proliferation of quiescent leukemic [stem] cells could enhance our knowledge about the regulation of that.”
As to whether there is evidence for the involvement of infections in other hematologic malignancies, Dr. Martínez reported, “This has already been seen. And this study shows other examples (Epstein-Barr virus and human T-cell lymphotropic virus type 1 with lymphomas), and there could also be Helicobacter pylori and lymphomas.”
Outside of hematology, human papillomavirus has been associated with cervical cancer, tobacco with lung cancer, sun with skin cancer, and diet with the development of some solid neoplasms.
“The study speaks about the concept of a latency period. To accept the idea that a factor or virus that’s more prevalent in winter produces, on its own, AML in a few weeks or months means accepting the idea of a very short latency period – something that’s not usually the case. For that, another explanation is given: An abnormal immune response or that a seasonal infectious agent can be capable of promoting leukemogenesis. These are also hypotheses to be explored in the future,” suggested Dr. Martínez.
New research network
Several potential limitations of this study should be considered. One limitation is that AML cases were obtained from the CMBD registry as defined by ICD-9, and no other AML classifications were available. Another limitation is that information on the date of onset of clinical symptoms was not available for analysis. In addition, a further limitation related to the source of their data may have led the researchers to underestimate the incidence rates of AML in older patients, as only hospitalized patients were captured in their study.
As for continuing the research, the results make it necessary to carry out complementary epidemiologic studies that will examine the association between seasonal risk factors and the increased diagnosis of AML during winter months.
To go forward, the first step would be to secure funding. For this purpose, a network is being put together featuring collaborators from other world-renowned research groups that are at the top of their respective disciplines. Through this network, they hope to be able to apply together for public research grants from countries in Europe and elsewhere as well as to establish collaborations with various companies in the private sector.
“This could open up new therapeutic avenues in the future, as we could try to force leukemic stem cells to divide, thereby reducing the resistance that the standard treatments usually demonstrate,” Dr. Alonso concluded.
Dr. Alonso received research funding from Incyte, Pfizer International, and Astellas Pharma outside the present work. Dr. Martínez disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of the article appeared on Medscape.com.
FROM THE BRITISH JOURNAL OF HEMATOLOGY
Pediatricians at odds over gender-affirming care for trans kids
Some members of the American Academy of Pediatrics say its association leadership is blocking discussion about a resolution asking for a “rigorous systematic review” of gender-affirming care guidelines.
At issue is 2018 guidance that states children can undergo hormonal therapy after they are deemed appropriate candidates following a thorough mental health evaluation.
Critics say minors under age 18 may be getting “fast-tracked” to hormonal treatment too quickly or inappropriately and can end up regretting the decision and facing medical conditions like sterility.
Five AAP members, which has a total membership of around 67,000 pediatricians in the United States and Canada, this year penned Resolution 27, calling for a possible update of the guidelines following consultation with stakeholders that include mental health and medical clinicians, parents, and patients “with diverse views and experiences.”
Those members and others in written comments on a members-only website accuse the AAP of deliberately silencing debate on the issue and changing resolution rules. Any AAP member can submit a resolution for consideration by the group’s leadership at its annual policy meeting.
This year, the AAP sent an email to members stating it would not allow comments on resolutions that had not been “sponsored” by one of the group’s 66 chapters or 88 internal committees, councils, or sections.
That’s why comments were not allowed on Resolution 27, said Mark Del Monte, the AAP’s CEO. A second attempt to get sponsorship during the annual leadership forum, held earlier this month in Chicago, also failed, he noted. Mr. Del Monte told this news organization that changes to the resolution process are made every year and that no rule changes were directly associated with Resolution 27.
But one of the resolution’s authors said there was sponsorship when members first drafted the suggestion. Julia Mason, MD, a board member for the Society for Evidence-based Gender Medicine and a pediatrician in private practice in Gresham, Ore., says an AAP chapter president agreed to second Resolution 27 but backed off after attending a different AAP meeting. Dr. Mason did not name the member.
On Aug. 10, AAP President Moira Szilagyi, MD, PhD, wrote in a blog on the AAP website – after the AAP leadership meeting in Chicago – that the lack of sponsorship “meant no one was willing to support their proposal.”
The AAP Leadership Council’s 154 voting entities approved 48 resolutions at the meeting, all of which will be referred to the AAP Board of Directors for potential, but not definite, action as the Board only takes resolutions under advisement, Mr. Del Monte notes.
In an email allowing members to comment on a resolution (number 28) regarding education support for caring for transgender patients, 23 chose to support Resolution 27 instead.
“I am wholeheartedly in support of Resolution 27, which interestingly has been removed from the list of resolutions for member comment,” one comment read. “I can no longer trust the AAP to provide medical evidence-based education with regard to care for transgender individuals.”
“We don’t need a formal resolution to look at the evidence around the care of transgender young people. Evaluating the evidence behind our recommendations, which the unsponsored resolution called for, is a routine part of the Academy’s policy-writing process,” wrote Dr. Szilagyi in her blog.
Mr. Del Monte says that “the 2018 policy is under review now.”
So far, “the evidence that we have seen reinforces our policy that gender-affirming care is the correct approach,” Mr. Del Monte stresses. “It is supported by every mainstream medical society in the world and is the standard of care,” he maintains.
Among those societies is the World Professional Association for Transgender Health, which in the draft of its latest Standards of Care (SOC8) – the first new guidance on the issue for 10 years – reportedly lowers the age for “top surgery” to 15 years.
The final SOC8 will most likely be published to coincide with WPATH’s annual meeting in September in Montreal.
Opponents plan to protest outside the AAP’s annual meeting, in Anaheim in October, Dr. Mason says.
“I’m concerned that kids with a transient gender identity are being funneled into medicalization that does not serve them,” Dr. Mason says. “I am worried that the trans identity is valued over the possibility of desistance,” she adds, admitting that her goal is to have fewer children transition gender.
Last summer, AAP found itself in hot water on the same topic when it barred SEGM from having a booth at the AAP annual meeting in 2021, as reported by this news organization.
A version of this article first appeared on Medscape.com.
Some members of the American Academy of Pediatrics say its association leadership is blocking discussion about a resolution asking for a “rigorous systematic review” of gender-affirming care guidelines.
At issue is 2018 guidance that states children can undergo hormonal therapy after they are deemed appropriate candidates following a thorough mental health evaluation.
Critics say minors under age 18 may be getting “fast-tracked” to hormonal treatment too quickly or inappropriately and can end up regretting the decision and facing medical conditions like sterility.
Five AAP members, which has a total membership of around 67,000 pediatricians in the United States and Canada, this year penned Resolution 27, calling for a possible update of the guidelines following consultation with stakeholders that include mental health and medical clinicians, parents, and patients “with diverse views and experiences.”
Those members and others in written comments on a members-only website accuse the AAP of deliberately silencing debate on the issue and changing resolution rules. Any AAP member can submit a resolution for consideration by the group’s leadership at its annual policy meeting.
This year, the AAP sent an email to members stating it would not allow comments on resolutions that had not been “sponsored” by one of the group’s 66 chapters or 88 internal committees, councils, or sections.
That’s why comments were not allowed on Resolution 27, said Mark Del Monte, the AAP’s CEO. A second attempt to get sponsorship during the annual leadership forum, held earlier this month in Chicago, also failed, he noted. Mr. Del Monte told this news organization that changes to the resolution process are made every year and that no rule changes were directly associated with Resolution 27.
But one of the resolution’s authors said there was sponsorship when members first drafted the suggestion. Julia Mason, MD, a board member for the Society for Evidence-based Gender Medicine and a pediatrician in private practice in Gresham, Ore., says an AAP chapter president agreed to second Resolution 27 but backed off after attending a different AAP meeting. Dr. Mason did not name the member.
On Aug. 10, AAP President Moira Szilagyi, MD, PhD, wrote in a blog on the AAP website – after the AAP leadership meeting in Chicago – that the lack of sponsorship “meant no one was willing to support their proposal.”
The AAP Leadership Council’s 154 voting entities approved 48 resolutions at the meeting, all of which will be referred to the AAP Board of Directors for potential, but not definite, action as the Board only takes resolutions under advisement, Mr. Del Monte notes.
In an email allowing members to comment on a resolution (number 28) regarding education support for caring for transgender patients, 23 chose to support Resolution 27 instead.
“I am wholeheartedly in support of Resolution 27, which interestingly has been removed from the list of resolutions for member comment,” one comment read. “I can no longer trust the AAP to provide medical evidence-based education with regard to care for transgender individuals.”
“We don’t need a formal resolution to look at the evidence around the care of transgender young people. Evaluating the evidence behind our recommendations, which the unsponsored resolution called for, is a routine part of the Academy’s policy-writing process,” wrote Dr. Szilagyi in her blog.
Mr. Del Monte says that “the 2018 policy is under review now.”
So far, “the evidence that we have seen reinforces our policy that gender-affirming care is the correct approach,” Mr. Del Monte stresses. “It is supported by every mainstream medical society in the world and is the standard of care,” he maintains.
Among those societies is the World Professional Association for Transgender Health, which in the draft of its latest Standards of Care (SOC8) – the first new guidance on the issue for 10 years – reportedly lowers the age for “top surgery” to 15 years.
The final SOC8 will most likely be published to coincide with WPATH’s annual meeting in September in Montreal.
Opponents plan to protest outside the AAP’s annual meeting, in Anaheim in October, Dr. Mason says.
“I’m concerned that kids with a transient gender identity are being funneled into medicalization that does not serve them,” Dr. Mason says. “I am worried that the trans identity is valued over the possibility of desistance,” she adds, admitting that her goal is to have fewer children transition gender.
Last summer, AAP found itself in hot water on the same topic when it barred SEGM from having a booth at the AAP annual meeting in 2021, as reported by this news organization.
A version of this article first appeared on Medscape.com.
Some members of the American Academy of Pediatrics say its association leadership is blocking discussion about a resolution asking for a “rigorous systematic review” of gender-affirming care guidelines.
At issue is 2018 guidance that states children can undergo hormonal therapy after they are deemed appropriate candidates following a thorough mental health evaluation.
Critics say minors under age 18 may be getting “fast-tracked” to hormonal treatment too quickly or inappropriately and can end up regretting the decision and facing medical conditions like sterility.
Five AAP members, which has a total membership of around 67,000 pediatricians in the United States and Canada, this year penned Resolution 27, calling for a possible update of the guidelines following consultation with stakeholders that include mental health and medical clinicians, parents, and patients “with diverse views and experiences.”
Those members and others in written comments on a members-only website accuse the AAP of deliberately silencing debate on the issue and changing resolution rules. Any AAP member can submit a resolution for consideration by the group’s leadership at its annual policy meeting.
This year, the AAP sent an email to members stating it would not allow comments on resolutions that had not been “sponsored” by one of the group’s 66 chapters or 88 internal committees, councils, or sections.
That’s why comments were not allowed on Resolution 27, said Mark Del Monte, the AAP’s CEO. A second attempt to get sponsorship during the annual leadership forum, held earlier this month in Chicago, also failed, he noted. Mr. Del Monte told this news organization that changes to the resolution process are made every year and that no rule changes were directly associated with Resolution 27.
But one of the resolution’s authors said there was sponsorship when members first drafted the suggestion. Julia Mason, MD, a board member for the Society for Evidence-based Gender Medicine and a pediatrician in private practice in Gresham, Ore., says an AAP chapter president agreed to second Resolution 27 but backed off after attending a different AAP meeting. Dr. Mason did not name the member.
On Aug. 10, AAP President Moira Szilagyi, MD, PhD, wrote in a blog on the AAP website – after the AAP leadership meeting in Chicago – that the lack of sponsorship “meant no one was willing to support their proposal.”
The AAP Leadership Council’s 154 voting entities approved 48 resolutions at the meeting, all of which will be referred to the AAP Board of Directors for potential, but not definite, action as the Board only takes resolutions under advisement, Mr. Del Monte notes.
In an email allowing members to comment on a resolution (number 28) regarding education support for caring for transgender patients, 23 chose to support Resolution 27 instead.
“I am wholeheartedly in support of Resolution 27, which interestingly has been removed from the list of resolutions for member comment,” one comment read. “I can no longer trust the AAP to provide medical evidence-based education with regard to care for transgender individuals.”
“We don’t need a formal resolution to look at the evidence around the care of transgender young people. Evaluating the evidence behind our recommendations, which the unsponsored resolution called for, is a routine part of the Academy’s policy-writing process,” wrote Dr. Szilagyi in her blog.
Mr. Del Monte says that “the 2018 policy is under review now.”
So far, “the evidence that we have seen reinforces our policy that gender-affirming care is the correct approach,” Mr. Del Monte stresses. “It is supported by every mainstream medical society in the world and is the standard of care,” he maintains.
Among those societies is the World Professional Association for Transgender Health, which in the draft of its latest Standards of Care (SOC8) – the first new guidance on the issue for 10 years – reportedly lowers the age for “top surgery” to 15 years.
The final SOC8 will most likely be published to coincide with WPATH’s annual meeting in September in Montreal.
Opponents plan to protest outside the AAP’s annual meeting, in Anaheim in October, Dr. Mason says.
“I’m concerned that kids with a transient gender identity are being funneled into medicalization that does not serve them,” Dr. Mason says. “I am worried that the trans identity is valued over the possibility of desistance,” she adds, admitting that her goal is to have fewer children transition gender.
Last summer, AAP found itself in hot water on the same topic when it barred SEGM from having a booth at the AAP annual meeting in 2021, as reported by this news organization.
A version of this article first appeared on Medscape.com.
Estrogen replacement therapy in endometrial cancer survivors
In the United States, uterine cancer is the fourth most common cancer among women, behind breast, lung/bronchus, and colorectal cancer. There are expected to be almost 66,000 new cases of uterine cancer in 2022.1 The majority of uterine cancers are endometrioid in histology and tend to be low grade, diagnosed at an early stage, and have a good prognosis. While our molecular understanding of endometrial cancers (EC) has changed significantly in recent years, low-grade endometrioid adenocarcinomas have historically been described as type 1 ECs. Type 1 ECs are typically caused by excess estrogen exposure (often unopposed or lacking progesterone protection) and are preceded by endometrial hyperplasia. Excess estrogen can come from exogenous sources (such as unopposed estrogen replacement therapy or tamoxifen, a commonly used treatment in estrogen receptor–positive breast cancer that acts as an estrogen agonist in the endometrium in postmenopausal patients) or endogenous ones (such as obesity).
Peripheral adipose tissue converts androgens into estrogens; paired with the decreased levels of sex hormone–binding globulin seen in obesity, there is more unbound or free serum estrogen (specifically estradiol) in obese women. Estrogen acts on the endometrium to cause proliferation and, if unopposed or imbalanced in relation to progesterone exposure, can ultimately lead to hyperplasia and malignancy.
If excess and unopposed estrogen exposure are major risk factors for the development of EC, is it safe to consider estrogen replacement therapy (ERT) in patients after EC treatment?
The short answer is the data are limited, but in a patient with a history of low-risk early-stage EC who undergoes appropriate counseling, it is likely safe to consider ERT.
Among EC survivors, there has been only one prospective randomized controlled trial that assessed the effect of recurrence rate and survival in women on ERT after EC treatment.2 Patients with stage I or occult stage II endometrial adenocarcinoma treated with at least a total hysterectomy and bilateral salpingo-oophorectomy were randomized to ERT versus placebo for 3 years of treatment, with therapy starting once recovered and within 20 weeks after surgery. Trial participation required an indication for ERT, such as vasomotor symptoms, vaginal atrophy, or increased risk of cardiovascular disease or osteoporosis.
The trial accrued 1,236 patients, falling short of its goal of 2,108 patients after enrollment decreased following the publication of the Women’s Health Initiative results in 2002. This publication prompted a review of the ERT study protocol that found that between decreased accrual and lower than expected recurrence rate, goal accrual would be impossible. Of those enrolled, participants were overwhelmingly white (84%-85%), 41-70 years old (80%-82%), and had stage IA or IB disease (88%). Median follow-up was almost 3 years.
Twenty-six (2.1%) patients experienced cancer recurrence, with similar rates in both groups. Three-year progression-free and overall survival were high overall among all study participants (94.8% and 96.5%). Unfortunately, because the study was closed early, definitive conclusions about the noninferiority of ERT versus placebo regarding oncologic outcomes in early-stage endometrial adenocarcinoma could not be made.
A subsequent meta-analysis looked at the effect of hormone therapy (HT) on recurrence rate in EC survivors.3 Five observational studies were included along with the previously discussed randomized controlled trial. Among 1,975 participants across six studies, there were cancer recurrences in 19 of 896 (2.1%) HT users and 64 of 1,079 (5.9%) controls. HT did not negatively affect cancer recurrence or overall survival. There was significant heterogeneity between studies as to dosing, duration, and type of HT given (some used estrogen-only replacement, others used estrogen and progesterone replacement, and some used both estrogen only and the combination of estrogen and progesterone replacement). Among the five nonrandomized studies included, a protective effect of combined HT on EC recurrence was noted. One study included patients with stage III disease, but only four patients received HT in this cohort.
Given the data we have, ERT does not appear to significantly affect oncologic outcomes in low-risk, early-stage EC survivors. We do not have data to support this same assertion in more advanced, high-risk disease. Before initiation of any ERT in an EC survivor, there should be a detailed discussion to weigh the risks and benefits of starting therapy. The goal of treatment should be to use the lowest dose of ERT possible to treat symptoms, with planned surveillance visits for symptom check-in and assessment of readiness to start tapering treatment.
Footnote: vaginal estrogen therapy
There are no randomized trials assessing the safety of vaginal estrogen preparations or their effect on oncologic outcomes in EC survivors. Observational data from the Women’s Health Initiative showed no increased risk of endometrial cancer in patients who used vaginal estrogen with an intact uterus.4 A recently published retrospective study among 244 gynecologic cancer survivors found low rates of disease recurrence and adverse outcomes among women who used vaginal estrogen for genitourinary symptoms.5 Among EC survivors, the incidence of recurrence was 2.4% for patients with stage I/II disease and 4.3% for stage III/IV disease, with a median follow-up of 80.2 months. While there appears to be some systemic absorption with vaginal estrogen use, this can be quite challenging to measure because of the current sensitivity of serum estradiol and estrone assays. Given the significantly lower serum levels with vaginal estrogen preparations compared with ERT, vaginal estrogen use appears to be safe in EC survivors.
Dr. Tucker is assistant professor of gynecologic oncology at the University of North Carolina at Chapel Hill.
References
1. Cancer Stat Facts: Uterine Cancer. National Cancer Institute: Surveillance, Epidemiology, and End Results Program. Accessed 12 Aug. 2022. https://seer.cancer.gov/statfacts/html/corp.html.
2. Barakat RR et al. J Clin Oncol. 2006;24(4):587-92.
3. Shim SH et al. Eur J Cancer. 2014;50(9):1628-37.
4. Crandall CJ et al. Menopause. 2018 Jan;25(1):11-20.
5. Chambers LM et al. Int J Gynecol Cancer. 2020 Apr;30(4):515-24.
In the United States, uterine cancer is the fourth most common cancer among women, behind breast, lung/bronchus, and colorectal cancer. There are expected to be almost 66,000 new cases of uterine cancer in 2022.1 The majority of uterine cancers are endometrioid in histology and tend to be low grade, diagnosed at an early stage, and have a good prognosis. While our molecular understanding of endometrial cancers (EC) has changed significantly in recent years, low-grade endometrioid adenocarcinomas have historically been described as type 1 ECs. Type 1 ECs are typically caused by excess estrogen exposure (often unopposed or lacking progesterone protection) and are preceded by endometrial hyperplasia. Excess estrogen can come from exogenous sources (such as unopposed estrogen replacement therapy or tamoxifen, a commonly used treatment in estrogen receptor–positive breast cancer that acts as an estrogen agonist in the endometrium in postmenopausal patients) or endogenous ones (such as obesity).
Peripheral adipose tissue converts androgens into estrogens; paired with the decreased levels of sex hormone–binding globulin seen in obesity, there is more unbound or free serum estrogen (specifically estradiol) in obese women. Estrogen acts on the endometrium to cause proliferation and, if unopposed or imbalanced in relation to progesterone exposure, can ultimately lead to hyperplasia and malignancy.
If excess and unopposed estrogen exposure are major risk factors for the development of EC, is it safe to consider estrogen replacement therapy (ERT) in patients after EC treatment?
The short answer is the data are limited, but in a patient with a history of low-risk early-stage EC who undergoes appropriate counseling, it is likely safe to consider ERT.
Among EC survivors, there has been only one prospective randomized controlled trial that assessed the effect of recurrence rate and survival in women on ERT after EC treatment.2 Patients with stage I or occult stage II endometrial adenocarcinoma treated with at least a total hysterectomy and bilateral salpingo-oophorectomy were randomized to ERT versus placebo for 3 years of treatment, with therapy starting once recovered and within 20 weeks after surgery. Trial participation required an indication for ERT, such as vasomotor symptoms, vaginal atrophy, or increased risk of cardiovascular disease or osteoporosis.
The trial accrued 1,236 patients, falling short of its goal of 2,108 patients after enrollment decreased following the publication of the Women’s Health Initiative results in 2002. This publication prompted a review of the ERT study protocol that found that between decreased accrual and lower than expected recurrence rate, goal accrual would be impossible. Of those enrolled, participants were overwhelmingly white (84%-85%), 41-70 years old (80%-82%), and had stage IA or IB disease (88%). Median follow-up was almost 3 years.
Twenty-six (2.1%) patients experienced cancer recurrence, with similar rates in both groups. Three-year progression-free and overall survival were high overall among all study participants (94.8% and 96.5%). Unfortunately, because the study was closed early, definitive conclusions about the noninferiority of ERT versus placebo regarding oncologic outcomes in early-stage endometrial adenocarcinoma could not be made.
A subsequent meta-analysis looked at the effect of hormone therapy (HT) on recurrence rate in EC survivors.3 Five observational studies were included along with the previously discussed randomized controlled trial. Among 1,975 participants across six studies, there were cancer recurrences in 19 of 896 (2.1%) HT users and 64 of 1,079 (5.9%) controls. HT did not negatively affect cancer recurrence or overall survival. There was significant heterogeneity between studies as to dosing, duration, and type of HT given (some used estrogen-only replacement, others used estrogen and progesterone replacement, and some used both estrogen only and the combination of estrogen and progesterone replacement). Among the five nonrandomized studies included, a protective effect of combined HT on EC recurrence was noted. One study included patients with stage III disease, but only four patients received HT in this cohort.
Given the data we have, ERT does not appear to significantly affect oncologic outcomes in low-risk, early-stage EC survivors. We do not have data to support this same assertion in more advanced, high-risk disease. Before initiation of any ERT in an EC survivor, there should be a detailed discussion to weigh the risks and benefits of starting therapy. The goal of treatment should be to use the lowest dose of ERT possible to treat symptoms, with planned surveillance visits for symptom check-in and assessment of readiness to start tapering treatment.
Footnote: vaginal estrogen therapy
There are no randomized trials assessing the safety of vaginal estrogen preparations or their effect on oncologic outcomes in EC survivors. Observational data from the Women’s Health Initiative showed no increased risk of endometrial cancer in patients who used vaginal estrogen with an intact uterus.4 A recently published retrospective study among 244 gynecologic cancer survivors found low rates of disease recurrence and adverse outcomes among women who used vaginal estrogen for genitourinary symptoms.5 Among EC survivors, the incidence of recurrence was 2.4% for patients with stage I/II disease and 4.3% for stage III/IV disease, with a median follow-up of 80.2 months. While there appears to be some systemic absorption with vaginal estrogen use, this can be quite challenging to measure because of the current sensitivity of serum estradiol and estrone assays. Given the significantly lower serum levels with vaginal estrogen preparations compared with ERT, vaginal estrogen use appears to be safe in EC survivors.
Dr. Tucker is assistant professor of gynecologic oncology at the University of North Carolina at Chapel Hill.
References
1. Cancer Stat Facts: Uterine Cancer. National Cancer Institute: Surveillance, Epidemiology, and End Results Program. Accessed 12 Aug. 2022. https://seer.cancer.gov/statfacts/html/corp.html.
2. Barakat RR et al. J Clin Oncol. 2006;24(4):587-92.
3. Shim SH et al. Eur J Cancer. 2014;50(9):1628-37.
4. Crandall CJ et al. Menopause. 2018 Jan;25(1):11-20.
5. Chambers LM et al. Int J Gynecol Cancer. 2020 Apr;30(4):515-24.
In the United States, uterine cancer is the fourth most common cancer among women, behind breast, lung/bronchus, and colorectal cancer. There are expected to be almost 66,000 new cases of uterine cancer in 2022.1 The majority of uterine cancers are endometrioid in histology and tend to be low grade, diagnosed at an early stage, and have a good prognosis. While our molecular understanding of endometrial cancers (EC) has changed significantly in recent years, low-grade endometrioid adenocarcinomas have historically been described as type 1 ECs. Type 1 ECs are typically caused by excess estrogen exposure (often unopposed or lacking progesterone protection) and are preceded by endometrial hyperplasia. Excess estrogen can come from exogenous sources (such as unopposed estrogen replacement therapy or tamoxifen, a commonly used treatment in estrogen receptor–positive breast cancer that acts as an estrogen agonist in the endometrium in postmenopausal patients) or endogenous ones (such as obesity).
Peripheral adipose tissue converts androgens into estrogens; paired with the decreased levels of sex hormone–binding globulin seen in obesity, there is more unbound or free serum estrogen (specifically estradiol) in obese women. Estrogen acts on the endometrium to cause proliferation and, if unopposed or imbalanced in relation to progesterone exposure, can ultimately lead to hyperplasia and malignancy.
If excess and unopposed estrogen exposure are major risk factors for the development of EC, is it safe to consider estrogen replacement therapy (ERT) in patients after EC treatment?
The short answer is the data are limited, but in a patient with a history of low-risk early-stage EC who undergoes appropriate counseling, it is likely safe to consider ERT.
Among EC survivors, there has been only one prospective randomized controlled trial that assessed the effect of recurrence rate and survival in women on ERT after EC treatment.2 Patients with stage I or occult stage II endometrial adenocarcinoma treated with at least a total hysterectomy and bilateral salpingo-oophorectomy were randomized to ERT versus placebo for 3 years of treatment, with therapy starting once recovered and within 20 weeks after surgery. Trial participation required an indication for ERT, such as vasomotor symptoms, vaginal atrophy, or increased risk of cardiovascular disease or osteoporosis.
The trial accrued 1,236 patients, falling short of its goal of 2,108 patients after enrollment decreased following the publication of the Women’s Health Initiative results in 2002. This publication prompted a review of the ERT study protocol that found that between decreased accrual and lower than expected recurrence rate, goal accrual would be impossible. Of those enrolled, participants were overwhelmingly white (84%-85%), 41-70 years old (80%-82%), and had stage IA or IB disease (88%). Median follow-up was almost 3 years.
Twenty-six (2.1%) patients experienced cancer recurrence, with similar rates in both groups. Three-year progression-free and overall survival were high overall among all study participants (94.8% and 96.5%). Unfortunately, because the study was closed early, definitive conclusions about the noninferiority of ERT versus placebo regarding oncologic outcomes in early-stage endometrial adenocarcinoma could not be made.
A subsequent meta-analysis looked at the effect of hormone therapy (HT) on recurrence rate in EC survivors.3 Five observational studies were included along with the previously discussed randomized controlled trial. Among 1,975 participants across six studies, there were cancer recurrences in 19 of 896 (2.1%) HT users and 64 of 1,079 (5.9%) controls. HT did not negatively affect cancer recurrence or overall survival. There was significant heterogeneity between studies as to dosing, duration, and type of HT given (some used estrogen-only replacement, others used estrogen and progesterone replacement, and some used both estrogen only and the combination of estrogen and progesterone replacement). Among the five nonrandomized studies included, a protective effect of combined HT on EC recurrence was noted. One study included patients with stage III disease, but only four patients received HT in this cohort.
Given the data we have, ERT does not appear to significantly affect oncologic outcomes in low-risk, early-stage EC survivors. We do not have data to support this same assertion in more advanced, high-risk disease. Before initiation of any ERT in an EC survivor, there should be a detailed discussion to weigh the risks and benefits of starting therapy. The goal of treatment should be to use the lowest dose of ERT possible to treat symptoms, with planned surveillance visits for symptom check-in and assessment of readiness to start tapering treatment.
Footnote: vaginal estrogen therapy
There are no randomized trials assessing the safety of vaginal estrogen preparations or their effect on oncologic outcomes in EC survivors. Observational data from the Women’s Health Initiative showed no increased risk of endometrial cancer in patients who used vaginal estrogen with an intact uterus.4 A recently published retrospective study among 244 gynecologic cancer survivors found low rates of disease recurrence and adverse outcomes among women who used vaginal estrogen for genitourinary symptoms.5 Among EC survivors, the incidence of recurrence was 2.4% for patients with stage I/II disease and 4.3% for stage III/IV disease, with a median follow-up of 80.2 months. While there appears to be some systemic absorption with vaginal estrogen use, this can be quite challenging to measure because of the current sensitivity of serum estradiol and estrone assays. Given the significantly lower serum levels with vaginal estrogen preparations compared with ERT, vaginal estrogen use appears to be safe in EC survivors.
Dr. Tucker is assistant professor of gynecologic oncology at the University of North Carolina at Chapel Hill.
References
1. Cancer Stat Facts: Uterine Cancer. National Cancer Institute: Surveillance, Epidemiology, and End Results Program. Accessed 12 Aug. 2022. https://seer.cancer.gov/statfacts/html/corp.html.
2. Barakat RR et al. J Clin Oncol. 2006;24(4):587-92.
3. Shim SH et al. Eur J Cancer. 2014;50(9):1628-37.
4. Crandall CJ et al. Menopause. 2018 Jan;25(1):11-20.
5. Chambers LM et al. Int J Gynecol Cancer. 2020 Apr;30(4):515-24.
Annual PSA screening important for Black men
, new data suggest.
The data come from a review of 45,834 veterans (aged 55-69 years) who had been diagnosed with prostate cancer. About one-third of these men self-identified as non-Hispanic Black, and the rest were White.
During the study period (2004-2017), 2,465 men (5.4%) died of the disease.
The review found that annual prostate-specific antigen (PSA) screening significantly reduced the risk of dying from prostate cancer among Black men but not White men.
The study was published online in JAMA Oncology.
“These results may be biologically plausible because a shorter screening interval may be valuable for detecting aggressive disease, which is more common in Black men,” say investigators, led by University of California, San Diego, radiation oncology resident Michael Sherer, MD.
“Given that Black men are younger at diagnosis and have worse prostate cancer survival compared with White men,” more intensive screening recommendations “may benefit Black patients,” they write.
The study “conclusions are reasonable,” said Christopher Wallis, MD, PhD, a urologic oncologist at Mount Sinai Hospital in Toronto, when asked for comment.
Annual screening may well have “a greater potential to benefit” Black men, he said. “While we would ideally see randomized data supporting this, those data are unlikely to ever be forthcoming. Thus, this study provides a strong rationale to support the recommendations from many guideline panels (including those from the American Urological Association) that Black men, in the context of shared decision-making, may benefit more from PSA-based prostate cancer screening than the population at large,” he added.
Overall, the findings could help inform screening discussions with Black men, the investigators comments. In its most recent guidance, the U.S. Preventive Services Task Force recommends shared decision-making regarding PSA screening for men aged 55-69 years.
Similar screening frequency
For their study, the team reviewed Veterans Health Administration data to assess PSA screening patterns – which they categorized as no screening, less than annual screening, or annual screening – in the 5 years leading up to diagnosis.
They then correlated screening behaviors with the subsequent risk of dying from prostate cancer.
Overall, the reduction in risk of prostate cancer–specific mortality (PCSM) associated with screening was similar among Black men (subdistribution hazard ratio, 0.56; P = .001) and White men (sHR, 0.58; P = .001).
However, on multivariable regression, annual screening, in comparison with some screening, was associated with a significant reduction in the risk of dying from prostate cancer only among Black men (sHR, 0.65; P = .02), not among White men (sHR, 0.91; P = .35).
The cumulative incidence of PCSM among Black men was 4.7% with annual screening but 7.3% with only some screening.
Among White men, the cumulative incidence of PCSM with annual screening was 5.9% vs. 6.9% with less than annual screening.
Screening frequency was similar between Black men and White men. Black men were younger on average (61.8 vs. 63.1 years) and had slightly higher PSA levels at diagnosis but were not more likely to have regional or metastatic disease.
No funding was reported for this study. The investigators have disclosed no relevant financial relationships. Dr. Wallis has received personal fees from Janssen Canada.
A version of this article first appeared on Medscape.com.
, new data suggest.
The data come from a review of 45,834 veterans (aged 55-69 years) who had been diagnosed with prostate cancer. About one-third of these men self-identified as non-Hispanic Black, and the rest were White.
During the study period (2004-2017), 2,465 men (5.4%) died of the disease.
The review found that annual prostate-specific antigen (PSA) screening significantly reduced the risk of dying from prostate cancer among Black men but not White men.
The study was published online in JAMA Oncology.
“These results may be biologically plausible because a shorter screening interval may be valuable for detecting aggressive disease, which is more common in Black men,” say investigators, led by University of California, San Diego, radiation oncology resident Michael Sherer, MD.
“Given that Black men are younger at diagnosis and have worse prostate cancer survival compared with White men,” more intensive screening recommendations “may benefit Black patients,” they write.
The study “conclusions are reasonable,” said Christopher Wallis, MD, PhD, a urologic oncologist at Mount Sinai Hospital in Toronto, when asked for comment.
Annual screening may well have “a greater potential to benefit” Black men, he said. “While we would ideally see randomized data supporting this, those data are unlikely to ever be forthcoming. Thus, this study provides a strong rationale to support the recommendations from many guideline panels (including those from the American Urological Association) that Black men, in the context of shared decision-making, may benefit more from PSA-based prostate cancer screening than the population at large,” he added.
Overall, the findings could help inform screening discussions with Black men, the investigators comments. In its most recent guidance, the U.S. Preventive Services Task Force recommends shared decision-making regarding PSA screening for men aged 55-69 years.
Similar screening frequency
For their study, the team reviewed Veterans Health Administration data to assess PSA screening patterns – which they categorized as no screening, less than annual screening, or annual screening – in the 5 years leading up to diagnosis.
They then correlated screening behaviors with the subsequent risk of dying from prostate cancer.
Overall, the reduction in risk of prostate cancer–specific mortality (PCSM) associated with screening was similar among Black men (subdistribution hazard ratio, 0.56; P = .001) and White men (sHR, 0.58; P = .001).
However, on multivariable regression, annual screening, in comparison with some screening, was associated with a significant reduction in the risk of dying from prostate cancer only among Black men (sHR, 0.65; P = .02), not among White men (sHR, 0.91; P = .35).
The cumulative incidence of PCSM among Black men was 4.7% with annual screening but 7.3% with only some screening.
Among White men, the cumulative incidence of PCSM with annual screening was 5.9% vs. 6.9% with less than annual screening.
Screening frequency was similar between Black men and White men. Black men were younger on average (61.8 vs. 63.1 years) and had slightly higher PSA levels at diagnosis but were not more likely to have regional or metastatic disease.
No funding was reported for this study. The investigators have disclosed no relevant financial relationships. Dr. Wallis has received personal fees from Janssen Canada.
A version of this article first appeared on Medscape.com.
, new data suggest.
The data come from a review of 45,834 veterans (aged 55-69 years) who had been diagnosed with prostate cancer. About one-third of these men self-identified as non-Hispanic Black, and the rest were White.
During the study period (2004-2017), 2,465 men (5.4%) died of the disease.
The review found that annual prostate-specific antigen (PSA) screening significantly reduced the risk of dying from prostate cancer among Black men but not White men.
The study was published online in JAMA Oncology.
“These results may be biologically plausible because a shorter screening interval may be valuable for detecting aggressive disease, which is more common in Black men,” say investigators, led by University of California, San Diego, radiation oncology resident Michael Sherer, MD.
“Given that Black men are younger at diagnosis and have worse prostate cancer survival compared with White men,” more intensive screening recommendations “may benefit Black patients,” they write.
The study “conclusions are reasonable,” said Christopher Wallis, MD, PhD, a urologic oncologist at Mount Sinai Hospital in Toronto, when asked for comment.
Annual screening may well have “a greater potential to benefit” Black men, he said. “While we would ideally see randomized data supporting this, those data are unlikely to ever be forthcoming. Thus, this study provides a strong rationale to support the recommendations from many guideline panels (including those from the American Urological Association) that Black men, in the context of shared decision-making, may benefit more from PSA-based prostate cancer screening than the population at large,” he added.
Overall, the findings could help inform screening discussions with Black men, the investigators comments. In its most recent guidance, the U.S. Preventive Services Task Force recommends shared decision-making regarding PSA screening for men aged 55-69 years.
Similar screening frequency
For their study, the team reviewed Veterans Health Administration data to assess PSA screening patterns – which they categorized as no screening, less than annual screening, or annual screening – in the 5 years leading up to diagnosis.
They then correlated screening behaviors with the subsequent risk of dying from prostate cancer.
Overall, the reduction in risk of prostate cancer–specific mortality (PCSM) associated with screening was similar among Black men (subdistribution hazard ratio, 0.56; P = .001) and White men (sHR, 0.58; P = .001).
However, on multivariable regression, annual screening, in comparison with some screening, was associated with a significant reduction in the risk of dying from prostate cancer only among Black men (sHR, 0.65; P = .02), not among White men (sHR, 0.91; P = .35).
The cumulative incidence of PCSM among Black men was 4.7% with annual screening but 7.3% with only some screening.
Among White men, the cumulative incidence of PCSM with annual screening was 5.9% vs. 6.9% with less than annual screening.
Screening frequency was similar between Black men and White men. Black men were younger on average (61.8 vs. 63.1 years) and had slightly higher PSA levels at diagnosis but were not more likely to have regional or metastatic disease.
No funding was reported for this study. The investigators have disclosed no relevant financial relationships. Dr. Wallis has received personal fees from Janssen Canada.
A version of this article first appeared on Medscape.com.
FROM JAMA ONCOLOGY
Hidradenitis Suppurativa Guidelines
Mechanistic link between herpes virus, Alzheimer’s revealed?
, new research suggests.
“Our results suggest one pathway to Alzheimer’s disease, caused by a VZV infection which creates inflammatory triggers that awaken HSV in the brain,” lead author Dana Cairns, PhD, research associate, department of biomedical engineering at Tufts University, Boston, said in a news release.
The findings were published online in Journal of Alzheimer’s Disease.
‘One-two punch’
Previous research has suggested a correlation between HSV-1 and AD and involvement of VZV. However, the sequence of events that the viruses create to set the disease in motion has been unclear.
“We think we now have evidence of those events,” co–senior author David Kaplan, PhD, chair of the department of biomedical engineering at Tufts, said in the release.
Working with co–senior author Ruth Itzhaki, PhD, University of Oxford, United Kingdom, the researchers infected human-induced neural stem cells (hiNSCs) and 3D brain tissue models with HSV-1 and/or VZV. Dr. Itzhaki was one of the first to hypothesize a connection between herpes virus and AD.
The investigators found that HSV-1 infection of hiNSCs induces amyloid-beta and P-tau accumulation: the main components of AD plaques and neurofibrillary tangles, respectively.
On the other hand, VZV infection of cultured hiNSCs did not lead to amyloid-beta and P-tau accumulation but instead resulted in gliosis and increased levels of proinflammatory cytokines.
“Strikingly,” VZV infection of cells quiescently infected with HSV-1 caused reactivation of HSV-1, leading to AD-like changes, including amyloid-beta and P-tau accumulation, the investigators report.
This suggests that VZV is unlikely to be a direct cause of AD but rather acts indirectly via reactivation of HSV-1, they add.
Similar findings emerged in similar experiments using 3D human brain tissue models.
“It’s a one-two punch of two viruses that are very common and usually harmless, but the lab studies suggest that if a new exposure to VZV wakes up dormant HSV-1, they could cause trouble,” Dr. Cairns said.
The researchers note that vaccination against VZV has been shown previously to reduce risk for dementia. It is possible, they add, that the vaccine is helping to stop the cycle of viral reactivation, inflammation, and neuronal damage.
‘A first step’
Heather M. Snyder, PhD, vice president of Medical & Scientific Relations at the Alzheimer’s Association, said that the study “is using artificial systems with the goal of more clearly and more deeply understanding” the assessed associations.
She added that although it is a first step, it may provide valuable direction for follow-up research.
“This is preliminary work that first needs replication, validation, and further development to understand if any association that is uncovered between viruses and Alzheimer’s/dementia has a mechanistic link,” said Dr. Snyder.
She noted that several past studies have sought to help the research field better understand the links between different viruses and Alzheimer’s and other forms of dementia.
“There have been some challenges in evaluating these associations in our current model systems or in individuals for a number of reasons,” said Dr. Snyder.
However, “the COVID-19 pandemic has created an opportunity to examine and investigate the relationships between different viruses and Alzheimer’s and other dementias by following individuals in more common and well-established ways,” she added.
She reported that her organization is “leading and working with a large global network of studies and investigators to address some of these questions” from during and after the COVID pandemic.
“The lessons we learn and share may inform our understanding of how other viruses are, or are not, connected to Alzheimer’s and other dementia,” Dr. Snyder said.
More information on the Alzheimer’s Association International Cohort Study of Chronic Neurological Sequelae of SARS-CoV-2 is available online.
The study was funded by the National Institutes of Health. Dr. Cairns, Dr. Kaplan, Dr. Itzhaki, and Dr. Snyder have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
“Our results suggest one pathway to Alzheimer’s disease, caused by a VZV infection which creates inflammatory triggers that awaken HSV in the brain,” lead author Dana Cairns, PhD, research associate, department of biomedical engineering at Tufts University, Boston, said in a news release.
The findings were published online in Journal of Alzheimer’s Disease.
‘One-two punch’
Previous research has suggested a correlation between HSV-1 and AD and involvement of VZV. However, the sequence of events that the viruses create to set the disease in motion has been unclear.
“We think we now have evidence of those events,” co–senior author David Kaplan, PhD, chair of the department of biomedical engineering at Tufts, said in the release.
Working with co–senior author Ruth Itzhaki, PhD, University of Oxford, United Kingdom, the researchers infected human-induced neural stem cells (hiNSCs) and 3D brain tissue models with HSV-1 and/or VZV. Dr. Itzhaki was one of the first to hypothesize a connection between herpes virus and AD.
The investigators found that HSV-1 infection of hiNSCs induces amyloid-beta and P-tau accumulation: the main components of AD plaques and neurofibrillary tangles, respectively.
On the other hand, VZV infection of cultured hiNSCs did not lead to amyloid-beta and P-tau accumulation but instead resulted in gliosis and increased levels of proinflammatory cytokines.
“Strikingly,” VZV infection of cells quiescently infected with HSV-1 caused reactivation of HSV-1, leading to AD-like changes, including amyloid-beta and P-tau accumulation, the investigators report.
This suggests that VZV is unlikely to be a direct cause of AD but rather acts indirectly via reactivation of HSV-1, they add.
Similar findings emerged in similar experiments using 3D human brain tissue models.
“It’s a one-two punch of two viruses that are very common and usually harmless, but the lab studies suggest that if a new exposure to VZV wakes up dormant HSV-1, they could cause trouble,” Dr. Cairns said.
The researchers note that vaccination against VZV has been shown previously to reduce risk for dementia. It is possible, they add, that the vaccine is helping to stop the cycle of viral reactivation, inflammation, and neuronal damage.
‘A first step’
Heather M. Snyder, PhD, vice president of Medical & Scientific Relations at the Alzheimer’s Association, said that the study “is using artificial systems with the goal of more clearly and more deeply understanding” the assessed associations.
She added that although it is a first step, it may provide valuable direction for follow-up research.
“This is preliminary work that first needs replication, validation, and further development to understand if any association that is uncovered between viruses and Alzheimer’s/dementia has a mechanistic link,” said Dr. Snyder.
She noted that several past studies have sought to help the research field better understand the links between different viruses and Alzheimer’s and other forms of dementia.
“There have been some challenges in evaluating these associations in our current model systems or in individuals for a number of reasons,” said Dr. Snyder.
However, “the COVID-19 pandemic has created an opportunity to examine and investigate the relationships between different viruses and Alzheimer’s and other dementias by following individuals in more common and well-established ways,” she added.
She reported that her organization is “leading and working with a large global network of studies and investigators to address some of these questions” from during and after the COVID pandemic.
“The lessons we learn and share may inform our understanding of how other viruses are, or are not, connected to Alzheimer’s and other dementia,” Dr. Snyder said.
More information on the Alzheimer’s Association International Cohort Study of Chronic Neurological Sequelae of SARS-CoV-2 is available online.
The study was funded by the National Institutes of Health. Dr. Cairns, Dr. Kaplan, Dr. Itzhaki, and Dr. Snyder have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
“Our results suggest one pathway to Alzheimer’s disease, caused by a VZV infection which creates inflammatory triggers that awaken HSV in the brain,” lead author Dana Cairns, PhD, research associate, department of biomedical engineering at Tufts University, Boston, said in a news release.
The findings were published online in Journal of Alzheimer’s Disease.
‘One-two punch’
Previous research has suggested a correlation between HSV-1 and AD and involvement of VZV. However, the sequence of events that the viruses create to set the disease in motion has been unclear.
“We think we now have evidence of those events,” co–senior author David Kaplan, PhD, chair of the department of biomedical engineering at Tufts, said in the release.
Working with co–senior author Ruth Itzhaki, PhD, University of Oxford, United Kingdom, the researchers infected human-induced neural stem cells (hiNSCs) and 3D brain tissue models with HSV-1 and/or VZV. Dr. Itzhaki was one of the first to hypothesize a connection between herpes virus and AD.
The investigators found that HSV-1 infection of hiNSCs induces amyloid-beta and P-tau accumulation: the main components of AD plaques and neurofibrillary tangles, respectively.
On the other hand, VZV infection of cultured hiNSCs did not lead to amyloid-beta and P-tau accumulation but instead resulted in gliosis and increased levels of proinflammatory cytokines.
“Strikingly,” VZV infection of cells quiescently infected with HSV-1 caused reactivation of HSV-1, leading to AD-like changes, including amyloid-beta and P-tau accumulation, the investigators report.
This suggests that VZV is unlikely to be a direct cause of AD but rather acts indirectly via reactivation of HSV-1, they add.
Similar findings emerged in similar experiments using 3D human brain tissue models.
“It’s a one-two punch of two viruses that are very common and usually harmless, but the lab studies suggest that if a new exposure to VZV wakes up dormant HSV-1, they could cause trouble,” Dr. Cairns said.
The researchers note that vaccination against VZV has been shown previously to reduce risk for dementia. It is possible, they add, that the vaccine is helping to stop the cycle of viral reactivation, inflammation, and neuronal damage.
‘A first step’
Heather M. Snyder, PhD, vice president of Medical & Scientific Relations at the Alzheimer’s Association, said that the study “is using artificial systems with the goal of more clearly and more deeply understanding” the assessed associations.
She added that although it is a first step, it may provide valuable direction for follow-up research.
“This is preliminary work that first needs replication, validation, and further development to understand if any association that is uncovered between viruses and Alzheimer’s/dementia has a mechanistic link,” said Dr. Snyder.
She noted that several past studies have sought to help the research field better understand the links between different viruses and Alzheimer’s and other forms of dementia.
“There have been some challenges in evaluating these associations in our current model systems or in individuals for a number of reasons,” said Dr. Snyder.
However, “the COVID-19 pandemic has created an opportunity to examine and investigate the relationships between different viruses and Alzheimer’s and other dementias by following individuals in more common and well-established ways,” she added.
She reported that her organization is “leading and working with a large global network of studies and investigators to address some of these questions” from during and after the COVID pandemic.
“The lessons we learn and share may inform our understanding of how other viruses are, or are not, connected to Alzheimer’s and other dementia,” Dr. Snyder said.
More information on the Alzheimer’s Association International Cohort Study of Chronic Neurological Sequelae of SARS-CoV-2 is available online.
The study was funded by the National Institutes of Health. Dr. Cairns, Dr. Kaplan, Dr. Itzhaki, and Dr. Snyder have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF ALZHEIMER’S DISEASE
Oncologists’ wealth and debt: COVID had little impact
concludes the latest Medscape Oncologist Wealth & Debt Report 2022.
Comparing the findings with those in the larger Medscape Physician Wealth & Debt Report 2022, which surveyed more than 13,000 physicians in 29 specialties, the findings for oncologists show how they compare with those who chose other paths in medicine.
Oncologists’ income rose, on average, by 2% in the past year and now stands at an average of $411,000 annually, up from $403,000 in the 2021 report.
This puts oncologists in the top third of specialties, with plastic surgeons again in the top slot (with average income of $576,000 in 2022).
One-fifth (20%) of oncologists surveyed reported a family worth of more than $5 million, which represents substantial family wealth, the report comments.
However, 22% of oncologists reported that their family net worth was less than $500,000, and another 10% estimated that it to fall between $500,000 and $1 million.
For comparison, the average U.S. family net worth is about $749,000, according to data from the Federal Reserve.
Most live ‘within their means’
Most oncologists (94%) and also most (94%) of all of the physicians surveyed said that they live within or below their means.
How does one do this? Just paying off credit cards each month and contributing enough to a 401(k) account to receive an employer match does not meet this standard, said Joel Greenwald MD, CFP, a wealth management advisor for physicians. To live within or below your means, you also need to be saving at least 20% toward retirement, pay down student loans, contribute to your kids’ college savings, and set aside rainy day cash, he explained.
When physicians were asked about their favorite cost-cutting tactics, replies included bringing lunch to work, keeping a car for 15 years, and carrying out their own household maintenance and repairs. One doctor described a “24-hour rule” when it comes to shopping: “Revisit the desired purchase after 24 hours to see if it’s still desired.”
But how well do these tactics go down with ‘the other half’ and the rest of the household? Two-thirds (66%) of oncologists, and a similar proportion of all physicians, said that they argue with their significant other about spending. This appears to be high in comparison with the finding from a recent survey that across the United States, about one in four couples (25%) argue about money at least once a month.
Regarding spending, the top expense among oncologists was for childcare (16%), private tuition for offspring (14%), mortgage on a second home (14%), college tuition for offspring (14%), and a car lease (12%).
Around 17% of oncologists reported that they are still paying off their own college or medical school loans. For this statistic, they are about in the middle of all specialties.
The report notes that freeing oneself from medical school debt is very costly. Physicians in the United States pay an average of $356,000-$440,000, about half of which is interest.
Little change over 2021
The COVID pandemic had much less of an impact on physicians than it had on the general population when it comes to keeping up with payments, and most physicians were not affected. Only 3% of oncologists said they fell behind with payments for mortgage; 6% fell behind with payments for other bills.
In comparison, nearly half (46%) of Americans missed one or more payments of rent or mortgage because of COVID, according to a 2021 industry survey.
Over the past year, most oncologists (70%) did not change their spending habits, and only 11% cut expenses by deferring or refinancing loans. Also, most oncologists (75%) avoided major financial loses. Only 8% reported financial losses because of problems at their medical practice.
However, a slightly higher percentage of oncologists reported a stock or company investment that had turned sour in 2022 (37%) in comparison with 2021 (28%).
A version of this article first appeared on Medscape.com.
concludes the latest Medscape Oncologist Wealth & Debt Report 2022.
Comparing the findings with those in the larger Medscape Physician Wealth & Debt Report 2022, which surveyed more than 13,000 physicians in 29 specialties, the findings for oncologists show how they compare with those who chose other paths in medicine.
Oncologists’ income rose, on average, by 2% in the past year and now stands at an average of $411,000 annually, up from $403,000 in the 2021 report.
This puts oncologists in the top third of specialties, with plastic surgeons again in the top slot (with average income of $576,000 in 2022).
One-fifth (20%) of oncologists surveyed reported a family worth of more than $5 million, which represents substantial family wealth, the report comments.
However, 22% of oncologists reported that their family net worth was less than $500,000, and another 10% estimated that it to fall between $500,000 and $1 million.
For comparison, the average U.S. family net worth is about $749,000, according to data from the Federal Reserve.
Most live ‘within their means’
Most oncologists (94%) and also most (94%) of all of the physicians surveyed said that they live within or below their means.
How does one do this? Just paying off credit cards each month and contributing enough to a 401(k) account to receive an employer match does not meet this standard, said Joel Greenwald MD, CFP, a wealth management advisor for physicians. To live within or below your means, you also need to be saving at least 20% toward retirement, pay down student loans, contribute to your kids’ college savings, and set aside rainy day cash, he explained.
When physicians were asked about their favorite cost-cutting tactics, replies included bringing lunch to work, keeping a car for 15 years, and carrying out their own household maintenance and repairs. One doctor described a “24-hour rule” when it comes to shopping: “Revisit the desired purchase after 24 hours to see if it’s still desired.”
But how well do these tactics go down with ‘the other half’ and the rest of the household? Two-thirds (66%) of oncologists, and a similar proportion of all physicians, said that they argue with their significant other about spending. This appears to be high in comparison with the finding from a recent survey that across the United States, about one in four couples (25%) argue about money at least once a month.
Regarding spending, the top expense among oncologists was for childcare (16%), private tuition for offspring (14%), mortgage on a second home (14%), college tuition for offspring (14%), and a car lease (12%).
Around 17% of oncologists reported that they are still paying off their own college or medical school loans. For this statistic, they are about in the middle of all specialties.
The report notes that freeing oneself from medical school debt is very costly. Physicians in the United States pay an average of $356,000-$440,000, about half of which is interest.
Little change over 2021
The COVID pandemic had much less of an impact on physicians than it had on the general population when it comes to keeping up with payments, and most physicians were not affected. Only 3% of oncologists said they fell behind with payments for mortgage; 6% fell behind with payments for other bills.
In comparison, nearly half (46%) of Americans missed one or more payments of rent or mortgage because of COVID, according to a 2021 industry survey.
Over the past year, most oncologists (70%) did not change their spending habits, and only 11% cut expenses by deferring or refinancing loans. Also, most oncologists (75%) avoided major financial loses. Only 8% reported financial losses because of problems at their medical practice.
However, a slightly higher percentage of oncologists reported a stock or company investment that had turned sour in 2022 (37%) in comparison with 2021 (28%).
A version of this article first appeared on Medscape.com.
concludes the latest Medscape Oncologist Wealth & Debt Report 2022.
Comparing the findings with those in the larger Medscape Physician Wealth & Debt Report 2022, which surveyed more than 13,000 physicians in 29 specialties, the findings for oncologists show how they compare with those who chose other paths in medicine.
Oncologists’ income rose, on average, by 2% in the past year and now stands at an average of $411,000 annually, up from $403,000 in the 2021 report.
This puts oncologists in the top third of specialties, with plastic surgeons again in the top slot (with average income of $576,000 in 2022).
One-fifth (20%) of oncologists surveyed reported a family worth of more than $5 million, which represents substantial family wealth, the report comments.
However, 22% of oncologists reported that their family net worth was less than $500,000, and another 10% estimated that it to fall between $500,000 and $1 million.
For comparison, the average U.S. family net worth is about $749,000, according to data from the Federal Reserve.
Most live ‘within their means’
Most oncologists (94%) and also most (94%) of all of the physicians surveyed said that they live within or below their means.
How does one do this? Just paying off credit cards each month and contributing enough to a 401(k) account to receive an employer match does not meet this standard, said Joel Greenwald MD, CFP, a wealth management advisor for physicians. To live within or below your means, you also need to be saving at least 20% toward retirement, pay down student loans, contribute to your kids’ college savings, and set aside rainy day cash, he explained.
When physicians were asked about their favorite cost-cutting tactics, replies included bringing lunch to work, keeping a car for 15 years, and carrying out their own household maintenance and repairs. One doctor described a “24-hour rule” when it comes to shopping: “Revisit the desired purchase after 24 hours to see if it’s still desired.”
But how well do these tactics go down with ‘the other half’ and the rest of the household? Two-thirds (66%) of oncologists, and a similar proportion of all physicians, said that they argue with their significant other about spending. This appears to be high in comparison with the finding from a recent survey that across the United States, about one in four couples (25%) argue about money at least once a month.
Regarding spending, the top expense among oncologists was for childcare (16%), private tuition for offspring (14%), mortgage on a second home (14%), college tuition for offspring (14%), and a car lease (12%).
Around 17% of oncologists reported that they are still paying off their own college or medical school loans. For this statistic, they are about in the middle of all specialties.
The report notes that freeing oneself from medical school debt is very costly. Physicians in the United States pay an average of $356,000-$440,000, about half of which is interest.
Little change over 2021
The COVID pandemic had much less of an impact on physicians than it had on the general population when it comes to keeping up with payments, and most physicians were not affected. Only 3% of oncologists said they fell behind with payments for mortgage; 6% fell behind with payments for other bills.
In comparison, nearly half (46%) of Americans missed one or more payments of rent or mortgage because of COVID, according to a 2021 industry survey.
Over the past year, most oncologists (70%) did not change their spending habits, and only 11% cut expenses by deferring or refinancing loans. Also, most oncologists (75%) avoided major financial loses. Only 8% reported financial losses because of problems at their medical practice.
However, a slightly higher percentage of oncologists reported a stock or company investment that had turned sour in 2022 (37%) in comparison with 2021 (28%).
A version of this article first appeared on Medscape.com.
IV nutrition becoming the norm for athletes despite no evidence it works
In their editorial, published online in the British Journal of Sports Medicine, experts urged the “food first” and “no needle” messages – that are taught in sports nutrition courses around the world – need to be amplified among all athletes and their support teams to “stop this trend in its tracks”.
The international group of authors, including experts from St Mary’s University, London; University College London; and University of Bath (England), who regularly interact with professional team players in European and American leagues and their support teams, said they have become increasingly aware of the practice.
Although it’s not known exactly how common the practice is, they pointed out that, anecdotally, some players are hooked up to intravenous nutrition drips as often as every week as part of a pre- or postgame routine.
‘Drip-bars’ easily accessible but devoid of regulation
Intravenous nutrition has traditionally been reserved for serious clinical conditions – such as anaemia – symptoms caused by nutrient deficiencies, or to correct severe dehydration caused by marathon running in, for example, a desert.
A ban on needle use by athletes at the Olympic Games has been in place for all recent Games except for appropriate medical use, and where a therapeutic use exemption is obtained, explained the authors.
However, “so-called ‘drip bars’ and concierge IV nutrition services are now easily accessible,” they said. These claim to boost health and performance, restore hydration, and speed up recovery, by offering a menu of B vitamins, amino acids, glutathione, vitamin C, and electrolytes, and potentially boosting levels beyond any therapeutic range.
However, they are “devoid of regulation” and for players or practitioners there is no official guidance on their use.
Physical and reputational risks
Bypassing the gut-liver axis risks nutrient toxicity warned the authors, and “appears foolhardy” unless there is a “significant clinical rationale.” They highlighted that they had noted vitamin B6 and vitamin B12 levels often “beyond the measurement range of the laboratory” in a subgroup of professional players. They pointed out how long-term effects of too much vitamin B6 include peripheral neuropathy, and that athletes regularly receiving parenteral iron “risk liver disease.”
“Given that the long-term effects of supratherapeutic doses of B vitamins and other nutrients are unknown in athletes, it does not appear to be worth the risk, especially given the lack of evidence-based benefits,” they said. They added that there is also the risk related to venous access, including “infection and thromboembolic complications.”
Additionally, a shift away from “what works” according to scientific standards to that which is “unproven” puts the reputation of sport at risk, and also puts athletes at risk of antidoping violation, they cautioned.
Figures on the prevalence of intravenous nutrition need to be gathered in tandem with governing bodies and players’ associations in the professional leagues providing guidance on the potential risks of intravenous nutrition use, recommended the authors.
The ‘food first’ and ‘no needle’ messages need to be amplified among all athletes and multidisciplinary support teams, they emphasised, to avoid what was previously a ‘last resort’ treatment becoming “normal without scientific evidence of benefit”.
A version of this article first appeared on Medscape UK.
In their editorial, published online in the British Journal of Sports Medicine, experts urged the “food first” and “no needle” messages – that are taught in sports nutrition courses around the world – need to be amplified among all athletes and their support teams to “stop this trend in its tracks”.
The international group of authors, including experts from St Mary’s University, London; University College London; and University of Bath (England), who regularly interact with professional team players in European and American leagues and their support teams, said they have become increasingly aware of the practice.
Although it’s not known exactly how common the practice is, they pointed out that, anecdotally, some players are hooked up to intravenous nutrition drips as often as every week as part of a pre- or postgame routine.
‘Drip-bars’ easily accessible but devoid of regulation
Intravenous nutrition has traditionally been reserved for serious clinical conditions – such as anaemia – symptoms caused by nutrient deficiencies, or to correct severe dehydration caused by marathon running in, for example, a desert.
A ban on needle use by athletes at the Olympic Games has been in place for all recent Games except for appropriate medical use, and where a therapeutic use exemption is obtained, explained the authors.
However, “so-called ‘drip bars’ and concierge IV nutrition services are now easily accessible,” they said. These claim to boost health and performance, restore hydration, and speed up recovery, by offering a menu of B vitamins, amino acids, glutathione, vitamin C, and electrolytes, and potentially boosting levels beyond any therapeutic range.
However, they are “devoid of regulation” and for players or practitioners there is no official guidance on their use.
Physical and reputational risks
Bypassing the gut-liver axis risks nutrient toxicity warned the authors, and “appears foolhardy” unless there is a “significant clinical rationale.” They highlighted that they had noted vitamin B6 and vitamin B12 levels often “beyond the measurement range of the laboratory” in a subgroup of professional players. They pointed out how long-term effects of too much vitamin B6 include peripheral neuropathy, and that athletes regularly receiving parenteral iron “risk liver disease.”
“Given that the long-term effects of supratherapeutic doses of B vitamins and other nutrients are unknown in athletes, it does not appear to be worth the risk, especially given the lack of evidence-based benefits,” they said. They added that there is also the risk related to venous access, including “infection and thromboembolic complications.”
Additionally, a shift away from “what works” according to scientific standards to that which is “unproven” puts the reputation of sport at risk, and also puts athletes at risk of antidoping violation, they cautioned.
Figures on the prevalence of intravenous nutrition need to be gathered in tandem with governing bodies and players’ associations in the professional leagues providing guidance on the potential risks of intravenous nutrition use, recommended the authors.
The ‘food first’ and ‘no needle’ messages need to be amplified among all athletes and multidisciplinary support teams, they emphasised, to avoid what was previously a ‘last resort’ treatment becoming “normal without scientific evidence of benefit”.
A version of this article first appeared on Medscape UK.
In their editorial, published online in the British Journal of Sports Medicine, experts urged the “food first” and “no needle” messages – that are taught in sports nutrition courses around the world – need to be amplified among all athletes and their support teams to “stop this trend in its tracks”.
The international group of authors, including experts from St Mary’s University, London; University College London; and University of Bath (England), who regularly interact with professional team players in European and American leagues and their support teams, said they have become increasingly aware of the practice.
Although it’s not known exactly how common the practice is, they pointed out that, anecdotally, some players are hooked up to intravenous nutrition drips as often as every week as part of a pre- or postgame routine.
‘Drip-bars’ easily accessible but devoid of regulation
Intravenous nutrition has traditionally been reserved for serious clinical conditions – such as anaemia – symptoms caused by nutrient deficiencies, or to correct severe dehydration caused by marathon running in, for example, a desert.
A ban on needle use by athletes at the Olympic Games has been in place for all recent Games except for appropriate medical use, and where a therapeutic use exemption is obtained, explained the authors.
However, “so-called ‘drip bars’ and concierge IV nutrition services are now easily accessible,” they said. These claim to boost health and performance, restore hydration, and speed up recovery, by offering a menu of B vitamins, amino acids, glutathione, vitamin C, and electrolytes, and potentially boosting levels beyond any therapeutic range.
However, they are “devoid of regulation” and for players or practitioners there is no official guidance on their use.
Physical and reputational risks
Bypassing the gut-liver axis risks nutrient toxicity warned the authors, and “appears foolhardy” unless there is a “significant clinical rationale.” They highlighted that they had noted vitamin B6 and vitamin B12 levels often “beyond the measurement range of the laboratory” in a subgroup of professional players. They pointed out how long-term effects of too much vitamin B6 include peripheral neuropathy, and that athletes regularly receiving parenteral iron “risk liver disease.”
“Given that the long-term effects of supratherapeutic doses of B vitamins and other nutrients are unknown in athletes, it does not appear to be worth the risk, especially given the lack of evidence-based benefits,” they said. They added that there is also the risk related to venous access, including “infection and thromboembolic complications.”
Additionally, a shift away from “what works” according to scientific standards to that which is “unproven” puts the reputation of sport at risk, and also puts athletes at risk of antidoping violation, they cautioned.
Figures on the prevalence of intravenous nutrition need to be gathered in tandem with governing bodies and players’ associations in the professional leagues providing guidance on the potential risks of intravenous nutrition use, recommended the authors.
The ‘food first’ and ‘no needle’ messages need to be amplified among all athletes and multidisciplinary support teams, they emphasised, to avoid what was previously a ‘last resort’ treatment becoming “normal without scientific evidence of benefit”.
A version of this article first appeared on Medscape UK.
FROM THE BRITISH JOURNAL OF SPORTS MEDICINE