Background

IDH1 mutations are detected in 3-4% of MDS, nearly always with one or more co-mutations. Treatment with IDH1 inhibitor ivosidenib typically resulted in regression of the abnormal clone in 15 reported responders. However, in a few cases differentiation was restored from the abnormal clone. Here we report a durable MDS remission despite sustained proliferation of a clone with IDH1 and ZRSR2 mutations.

Case Presentation

A 49-year-old man developed severe neutropenia and macrocytic anemia in January 2019. Mild marrow dysplasia developed by March 2020 with IDH1 (31.1%) and splicing gene ZRSR2 (55.7%) mutations. In October 2022 biopsy showed MDS with 4% blasts, megakaryocytic/granulocytic hypoplasia, normal cytogenetics and 43% IDH1/89% ZRSR2. After azacytidine failure, ivosidenib was started in November 2023 following FDA approval. Within weeks ANCs increased from 170 to 1580 and hemoglobin from 7.9 to 11.6 with MCV 115, reticulocytes 1.72%. At 3 months a CBC was normal except for MCV 111. IDH1 and ZRSR2 were 36.4% and 71%. After 6 months, ANC was 2380, hemoglobin 14.7, MCV 108.6, reticulo-cytes 1.77%. IDH1 PCR showed a 33.1% allele frequency consistent with a clonal remission.

Discussion

IDH1 mutations in MDS/AML frequently co-occur with mutations in RNA splicing genes SRSF2 or ZRSR2. For ZRSR2, we previously reported that isolated mutations of this gene cause refractory macrocytic anemias without dysplasia, thus presenting as clonal cytopenias of undetermined significance (Fleischman et al., Leuk Res, 2017). In this MDS case, after ivosidenib treatment the ZRSR2 splicing defect sustained clonal dominance over polyclonal hematopoiesis while accounting for macrocytosis. Longitudinal data for two ivosidenib-treated IDH1/SRSF2 MDS cases are incomplete, but one case of IDH2/SRSF2 MDS treated with the inhibitor enasidenib similarly achieved complete remission without regression of the mutated clone for 12 months.

Conclusions

Following the FDA approval of ivosidenib, all cases of MDS should have DNA sequencing performed at diagnosis to identify IDH1 mutations. Treatment induces high rates of remission even when polyclonal hematopoiesis does not recover. Moreover, the restoration of hematopoietic differentiation by the abnormal clone provides unique insights into the clinical phenotype and fitness advantage conferred by the co-existing driver mutations.

Background

IDH1 mutations are detected in 3-4% of MDS, nearly always with one or more co-mutations. Treatment with IDH1 inhibitor ivosidenib typically resulted in regression of the abnormal clone in 15 reported responders. However, in a few cases differentiation was restored from the abnormal clone. Here we report a durable MDS remission despite sustained proliferation of a clone with IDH1 and ZRSR2 mutations.

Case Presentation

A 49-year-old man developed severe neutropenia and macrocytic anemia in January 2019. Mild marrow dysplasia developed by March 2020 with IDH1 (31.1%) and splicing gene ZRSR2 (55.7%) mutations. In October 2022 biopsy showed MDS with 4% blasts, megakaryocytic/granulocytic hypoplasia, normal cytogenetics and 43% IDH1/89% ZRSR2. After azacytidine failure, ivosidenib was started in November 2023 following FDA approval. Within weeks ANCs increased from 170 to 1580 and hemoglobin from 7.9 to 11.6 with MCV 115, reticulocytes 1.72%. At 3 months a CBC was normal except for MCV 111. IDH1 and ZRSR2 were 36.4% and 71%. After 6 months, ANC was 2380, hemoglobin 14.7, MCV 108.6, reticulo-cytes 1.77%. IDH1 PCR showed a 33.1% allele frequency consistent with a clonal remission.

Discussion

IDH1 mutations in MDS/AML frequently co-occur with mutations in RNA splicing genes SRSF2 or ZRSR2. For ZRSR2, we previously reported that isolated mutations of this gene cause refractory macrocytic anemias without dysplasia, thus presenting as clonal cytopenias of undetermined significance (Fleischman et al., Leuk Res, 2017). In this MDS case, after ivosidenib treatment the ZRSR2 splicing defect sustained clonal dominance over polyclonal hematopoiesis while accounting for macrocytosis. Longitudinal data for two ivosidenib-treated IDH1/SRSF2 MDS cases are incomplete, but one case of IDH2/SRSF2 MDS treated with the inhibitor enasidenib similarly achieved complete remission without regression of the mutated clone for 12 months.

Conclusions

Following the FDA approval of ivosidenib, all cases of MDS should have DNA sequencing performed at diagnosis to identify IDH1 mutations. Treatment induces high rates of remission even when polyclonal hematopoiesis does not recover. Moreover, the restoration of hematopoietic differentiation by the abnormal clone provides unique insights into the clinical phenotype and fitness advantage conferred by the co-existing driver mutations.

Background

IDH1 mutations are detected in 3-4% of MDS, nearly always with one or more co-mutations. Treatment with IDH1 inhibitor ivosidenib typically resulted in regression of the abnormal clone in 15 reported responders. However, in a few cases differentiation was restored from the abnormal clone. Here we report a durable MDS remission despite sustained proliferation of a clone with IDH1 and ZRSR2 mutations.

Case Presentation

A 49-year-old man developed severe neutropenia and macrocytic anemia in January 2019. Mild marrow dysplasia developed by March 2020 with IDH1 (31.1%) and splicing gene ZRSR2 (55.7%) mutations. In October 2022 biopsy showed MDS with 4% blasts, megakaryocytic/granulocytic hypoplasia, normal cytogenetics and 43% IDH1/89% ZRSR2. After azacytidine failure, ivosidenib was started in November 2023 following FDA approval. Within weeks ANCs increased from 170 to 1580 and hemoglobin from 7.9 to 11.6 with MCV 115, reticulocytes 1.72%. At 3 months a CBC was normal except for MCV 111. IDH1 and ZRSR2 were 36.4% and 71%. After 6 months, ANC was 2380, hemoglobin 14.7, MCV 108.6, reticulo-cytes 1.77%. IDH1 PCR showed a 33.1% allele frequency consistent with a clonal remission.

Discussion

IDH1 mutations in MDS/AML frequently co-occur with mutations in RNA splicing genes SRSF2 or ZRSR2. For ZRSR2, we previously reported that isolated mutations of this gene cause refractory macrocytic anemias without dysplasia, thus presenting as clonal cytopenias of undetermined significance (Fleischman et al., Leuk Res, 2017). In this MDS case, after ivosidenib treatment the ZRSR2 splicing defect sustained clonal dominance over polyclonal hematopoiesis while accounting for macrocytosis. Longitudinal data for two ivosidenib-treated IDH1/SRSF2 MDS cases are incomplete, but one case of IDH2/SRSF2 MDS treated with the inhibitor enasidenib similarly achieved complete remission without regression of the mutated clone for 12 months.

Conclusions

Following the FDA approval of ivosidenib, all cases of MDS should have DNA sequencing performed at diagnosis to identify IDH1 mutations. Treatment induces high rates of remission even when polyclonal hematopoiesis does not recover. Moreover, the restoration of hematopoietic differentiation by the abnormal clone provides unique insights into the clinical phenotype and fitness advantage conferred by the co-existing driver mutations.

Background

Over one-third of newly diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) cases are in people age ≥75. Although a potentially curable malignancy, older adults have a comparatively lower survival rate. This may be due to multiple factors including suboptimal management. In one study, up to 23% of patients age ≥80 did not receive any therapy for DLBCL. This age-related survival disparity is potentially magnified in patients who reside in rural areas. As there is no standard of care for this population, we speculate that there is wide variation in treatment practices which may influence outcomes. The purpose of this study is to describe treatment patterns and outcomes in in veterans age ≥80 with DLBCL by area of residence.

Methods

We conducted a retrospective study of veterans age ≥80 newly diagnosed with Stage II-IV DLBCL between 2006-2023 using the Veterans Affairs (VA) Cancer Registry System (VACRS). Patient, disease, and treatment variables were extracted from the VA Corporate Data Warehouse (CDW) and via chart review. Variables were compared amongst Veterans residing at urban vs. rural addresses.

Results

We evaluated a total of 181 Veterans. Most veterans resided in an urban area (60.2%). At least 18.8% of veterans failed to start lymphoma-directed therapy, but only 6.6% of veterans were not explicitly offered treatment per documentation. In total, 68.5% of veterans were offered a curative treatment regimen by their provider; curative treatment was more likely to be offered to urban patients (68.8% vs 61.5%, p=0.86). Pre-phase steroids and geriatric assessments prior to treatment were severely underutilized (2.8% and 0.6%). More urban veterans started treatment (75.2% vs 65.4%, p=0.38) and 40.9% started an anthracyclinecontaining regimen. Only 27.6% of veterans completed 6 total cycles of treatment. Only 37.6% of veterans achieved a complete response at end of treatment, although response was not reported in 46.4% of patients.

Conclusions

Most elderly veterans with DLBCL are being offered and started on a curative treatment regimen; however, most do not complete a full course of treatment. Although not statistically significant, more urban veterans were offered a curative regimen and received treatment. Wider adoption of pre-phase steroids and geriatric assessments could improve response outcomes.

Background

Over one-third of newly diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) cases are in people age ≥75. Although a potentially curable malignancy, older adults have a comparatively lower survival rate. This may be due to multiple factors including suboptimal management. In one study, up to 23% of patients age ≥80 did not receive any therapy for DLBCL. This age-related survival disparity is potentially magnified in patients who reside in rural areas. As there is no standard of care for this population, we speculate that there is wide variation in treatment practices which may influence outcomes. The purpose of this study is to describe treatment patterns and outcomes in in veterans age ≥80 with DLBCL by area of residence.

Methods

We conducted a retrospective study of veterans age ≥80 newly diagnosed with Stage II-IV DLBCL between 2006-2023 using the Veterans Affairs (VA) Cancer Registry System (VACRS). Patient, disease, and treatment variables were extracted from the VA Corporate Data Warehouse (CDW) and via chart review. Variables were compared amongst Veterans residing at urban vs. rural addresses.

Results

We evaluated a total of 181 Veterans. Most veterans resided in an urban area (60.2%). At least 18.8% of veterans failed to start lymphoma-directed therapy, but only 6.6% of veterans were not explicitly offered treatment per documentation. In total, 68.5% of veterans were offered a curative treatment regimen by their provider; curative treatment was more likely to be offered to urban patients (68.8% vs 61.5%, p=0.86). Pre-phase steroids and geriatric assessments prior to treatment were severely underutilized (2.8% and 0.6%). More urban veterans started treatment (75.2% vs 65.4%, p=0.38) and 40.9% started an anthracyclinecontaining regimen. Only 27.6% of veterans completed 6 total cycles of treatment. Only 37.6% of veterans achieved a complete response at end of treatment, although response was not reported in 46.4% of patients.

Conclusions

Most elderly veterans with DLBCL are being offered and started on a curative treatment regimen; however, most do not complete a full course of treatment. Although not statistically significant, more urban veterans were offered a curative regimen and received treatment. Wider adoption of pre-phase steroids and geriatric assessments could improve response outcomes.

Background

Over one-third of newly diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) cases are in people age ≥75. Although a potentially curable malignancy, older adults have a comparatively lower survival rate. This may be due to multiple factors including suboptimal management. In one study, up to 23% of patients age ≥80 did not receive any therapy for DLBCL. This age-related survival disparity is potentially magnified in patients who reside in rural areas. As there is no standard of care for this population, we speculate that there is wide variation in treatment practices which may influence outcomes. The purpose of this study is to describe treatment patterns and outcomes in in veterans age ≥80 with DLBCL by area of residence.

Methods

We conducted a retrospective study of veterans age ≥80 newly diagnosed with Stage II-IV DLBCL between 2006-2023 using the Veterans Affairs (VA) Cancer Registry System (VACRS). Patient, disease, and treatment variables were extracted from the VA Corporate Data Warehouse (CDW) and via chart review. Variables were compared amongst Veterans residing at urban vs. rural addresses.

Results

We evaluated a total of 181 Veterans. Most veterans resided in an urban area (60.2%). At least 18.8% of veterans failed to start lymphoma-directed therapy, but only 6.6% of veterans were not explicitly offered treatment per documentation. In total, 68.5% of veterans were offered a curative treatment regimen by their provider; curative treatment was more likely to be offered to urban patients (68.8% vs 61.5%, p=0.86). Pre-phase steroids and geriatric assessments prior to treatment were severely underutilized (2.8% and 0.6%). More urban veterans started treatment (75.2% vs 65.4%, p=0.38) and 40.9% started an anthracyclinecontaining regimen. Only 27.6% of veterans completed 6 total cycles of treatment. Only 37.6% of veterans achieved a complete response at end of treatment, although response was not reported in 46.4% of patients.

Conclusions

Most elderly veterans with DLBCL are being offered and started on a curative treatment regimen; however, most do not complete a full course of treatment. Although not statistically significant, more urban veterans were offered a curative regimen and received treatment. Wider adoption of pre-phase steroids and geriatric assessments could improve response outcomes.

Background

Melanoma is a malignant type of skin cancer and is the fifth most common type of cancer in the United States. The purpose of this study is to determine how demographic information such as race and gender may influence mortality rates in melanoma patients. To date, no previous studies have analyzed epidemiological trends in melanoma mortality using the CDC Wonder database. However, previous literature has suggested that non-Hispanic Whites have the highest mortality rate.

Methods

CDC Wonder is a database that contains mortality and demographic information for various pathologies. Melanoma cases were specified using the ICD-10 code C43. Patients over the age of 35 were considered for this study. Mortality rates were generated based on gender, race, and a combination of both variables. Data analysis involved finding the rates and 95% confidence intervals for the crude and age-adjusted mortality rate (AAMR) per 100,000. Joinpoint regression analysis was also used.

Results

Several differences in the age-adjusted mortality rate were observed. In every year from 1999 to 2022, the non-Hispanic White group (NH White) had the highest mortality rate, whereas all other races had similar rates. Meanwhile, when stratifying by both race and gender, it appears that NH White males have the highest rate in mortality. In 2022, the mortality rate for NH White males was 8.8 per 100,000, whereas the second highest rate belonged to the NH White female group (4 per 100,000). All other racial and gender combinations had similar mortality rates. The trends in mortality rates did not fluctuate much from the years 1999-2022. No significant deviation in mortality trends were seen after the start of the COVID-19 pandemic.

Conclusions

This data corroborates with the results from previous studies. It also indicates that certain demographics that may be at greater risk for mortality, and that the mortality rates have remained relatively stable. The mortality rate for melanoma may vary by race and gender. More specifically, NH White males may be susceptible to higher mortality rates compared to other demographic groups. Future research on cancer staging and treatment modality received could help explain these differences.

Background

Melanoma is a malignant type of skin cancer and is the fifth most common type of cancer in the United States. The purpose of this study is to determine how demographic information such as race and gender may influence mortality rates in melanoma patients. To date, no previous studies have analyzed epidemiological trends in melanoma mortality using the CDC Wonder database. However, previous literature has suggested that non-Hispanic Whites have the highest mortality rate.

Methods

CDC Wonder is a database that contains mortality and demographic information for various pathologies. Melanoma cases were specified using the ICD-10 code C43. Patients over the age of 35 were considered for this study. Mortality rates were generated based on gender, race, and a combination of both variables. Data analysis involved finding the rates and 95% confidence intervals for the crude and age-adjusted mortality rate (AAMR) per 100,000. Joinpoint regression analysis was also used.

Results

Several differences in the age-adjusted mortality rate were observed. In every year from 1999 to 2022, the non-Hispanic White group (NH White) had the highest mortality rate, whereas all other races had similar rates. Meanwhile, when stratifying by both race and gender, it appears that NH White males have the highest rate in mortality. In 2022, the mortality rate for NH White males was 8.8 per 100,000, whereas the second highest rate belonged to the NH White female group (4 per 100,000). All other racial and gender combinations had similar mortality rates. The trends in mortality rates did not fluctuate much from the years 1999-2022. No significant deviation in mortality trends were seen after the start of the COVID-19 pandemic.

Conclusions

This data corroborates with the results from previous studies. It also indicates that certain demographics that may be at greater risk for mortality, and that the mortality rates have remained relatively stable. The mortality rate for melanoma may vary by race and gender. More specifically, NH White males may be susceptible to higher mortality rates compared to other demographic groups. Future research on cancer staging and treatment modality received could help explain these differences.

Background

Melanoma is a malignant type of skin cancer and is the fifth most common type of cancer in the United States. The purpose of this study is to determine how demographic information such as race and gender may influence mortality rates in melanoma patients. To date, no previous studies have analyzed epidemiological trends in melanoma mortality using the CDC Wonder database. However, previous literature has suggested that non-Hispanic Whites have the highest mortality rate.

Methods

CDC Wonder is a database that contains mortality and demographic information for various pathologies. Melanoma cases were specified using the ICD-10 code C43. Patients over the age of 35 were considered for this study. Mortality rates were generated based on gender, race, and a combination of both variables. Data analysis involved finding the rates and 95% confidence intervals for the crude and age-adjusted mortality rate (AAMR) per 100,000. Joinpoint regression analysis was also used.

Results

Several differences in the age-adjusted mortality rate were observed. In every year from 1999 to 2022, the non-Hispanic White group (NH White) had the highest mortality rate, whereas all other races had similar rates. Meanwhile, when stratifying by both race and gender, it appears that NH White males have the highest rate in mortality. In 2022, the mortality rate for NH White males was 8.8 per 100,000, whereas the second highest rate belonged to the NH White female group (4 per 100,000). All other racial and gender combinations had similar mortality rates. The trends in mortality rates did not fluctuate much from the years 1999-2022. No significant deviation in mortality trends were seen after the start of the COVID-19 pandemic.

Conclusions

This data corroborates with the results from previous studies. It also indicates that certain demographics that may be at greater risk for mortality, and that the mortality rates have remained relatively stable. The mortality rate for melanoma may vary by race and gender. More specifically, NH White males may be susceptible to higher mortality rates compared to other demographic groups. Future research on cancer staging and treatment modality received could help explain these differences.

Black Friday is coming up. Although it seems (fortunately) to have lost some of its insanity since the pandemic, it’s still a huge shopping day for those who want to spend their day off in hand-to-hand combat at a Walmart. For me it’s a good day not to leave my house at all.

Following Black Friday we have Cyber Monday, where people go online to start buying stuff, presumably using business WiFi when they’re back at work. In spite of the apparent contradiction of having an online shopping day when people are at their jobs, it’s shamelessly promoted by the online retail giants.

Sandwiched between them is the quieter Small Business Saturday, started in 2010 by American Express and since gradually taking hold here and across the pond. The idea is to support the smaller local, perhaps family-owned, stores of varying kinds. Politicians love to talk about small businesses, calling them the backbone of the economy, promising to support them, etc.

I have no issue with that. I agree with it. I try to support my smaller, local places whenever I can. I’m glad AMEX started it, and that it’s taken off.

So why don’t we have a campaign to support small medical practices? Aren’t we small businesses, too? I’m the only doctor at my place, that’s about as small as you can get.

Like other small businesses, I don’t have the resources to advertise, aside from a simple website. At the same time I can’t drive too far without seeing a billboard, or hearing a radio ad, for one of the large local healthcare systems promising better convenience and care than that of their competitors.

I’m certainly not in a position to offer extended or weekend hours — I mean, I could, but I also have my own sanity to keep. But at the same time small practices may know their patients better than Huge Medicine Inc. We don’t have as many patients, and the staff turnover at small places is usually lower.

No one, though, is going to stand up for us, AMEX included (outside of cosmetic services, doctor visit charges are probably a tiny fraction of credit card company charges). Even our own organizations, like the AMA and others, won’t (at least not too much). They might pay lip service to us, but the reality is that most of their members work for large healthcare systems. Those groups probably make some big donations to them, too. So the last thing they want to do is tick them off.

I’m not against large groups. They have capabilities I don’t, like the ability to run research trials and have subspecialists. Even the best of us in solo practice needs someone better to refer to, such as an epileptologist, Parkinsonologist, neuromuscular disease-ologist, When I can’t help a patient any further those are the doctors I turn to, and, believe me, I appreciate them.

But it sometimes seems odd that, in a world where financial companies and public figures often stress their support for small business, those of us in the small medical practice are forgotten.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

Black Friday is coming up. Although it seems (fortunately) to have lost some of its insanity since the pandemic, it’s still a huge shopping day for those who want to spend their day off in hand-to-hand combat at a Walmart. For me it’s a good day not to leave my house at all.

Following Black Friday we have Cyber Monday, where people go online to start buying stuff, presumably using business WiFi when they’re back at work. In spite of the apparent contradiction of having an online shopping day when people are at their jobs, it’s shamelessly promoted by the online retail giants.

Sandwiched between them is the quieter Small Business Saturday, started in 2010 by American Express and since gradually taking hold here and across the pond. The idea is to support the smaller local, perhaps family-owned, stores of varying kinds. Politicians love to talk about small businesses, calling them the backbone of the economy, promising to support them, etc.

I have no issue with that. I agree with it. I try to support my smaller, local places whenever I can. I’m glad AMEX started it, and that it’s taken off.

So why don’t we have a campaign to support small medical practices? Aren’t we small businesses, too? I’m the only doctor at my place, that’s about as small as you can get.

Like other small businesses, I don’t have the resources to advertise, aside from a simple website. At the same time I can’t drive too far without seeing a billboard, or hearing a radio ad, for one of the large local healthcare systems promising better convenience and care than that of their competitors.

I’m certainly not in a position to offer extended or weekend hours — I mean, I could, but I also have my own sanity to keep. But at the same time small practices may know their patients better than Huge Medicine Inc. We don’t have as many patients, and the staff turnover at small places is usually lower.

No one, though, is going to stand up for us, AMEX included (outside of cosmetic services, doctor visit charges are probably a tiny fraction of credit card company charges). Even our own organizations, like the AMA and others, won’t (at least not too much). They might pay lip service to us, but the reality is that most of their members work for large healthcare systems. Those groups probably make some big donations to them, too. So the last thing they want to do is tick them off.

I’m not against large groups. They have capabilities I don’t, like the ability to run research trials and have subspecialists. Even the best of us in solo practice needs someone better to refer to, such as an epileptologist, Parkinsonologist, neuromuscular disease-ologist, When I can’t help a patient any further those are the doctors I turn to, and, believe me, I appreciate them.

But it sometimes seems odd that, in a world where financial companies and public figures often stress their support for small business, those of us in the small medical practice are forgotten.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

Black Friday is coming up. Although it seems (fortunately) to have lost some of its insanity since the pandemic, it’s still a huge shopping day for those who want to spend their day off in hand-to-hand combat at a Walmart. For me it’s a good day not to leave my house at all.

Following Black Friday we have Cyber Monday, where people go online to start buying stuff, presumably using business WiFi when they’re back at work. In spite of the apparent contradiction of having an online shopping day when people are at their jobs, it’s shamelessly promoted by the online retail giants.

Sandwiched between them is the quieter Small Business Saturday, started in 2010 by American Express and since gradually taking hold here and across the pond. The idea is to support the smaller local, perhaps family-owned, stores of varying kinds. Politicians love to talk about small businesses, calling them the backbone of the economy, promising to support them, etc.

I have no issue with that. I agree with it. I try to support my smaller, local places whenever I can. I’m glad AMEX started it, and that it’s taken off.

So why don’t we have a campaign to support small medical practices? Aren’t we small businesses, too? I’m the only doctor at my place, that’s about as small as you can get.

Like other small businesses, I don’t have the resources to advertise, aside from a simple website. At the same time I can’t drive too far without seeing a billboard, or hearing a radio ad, for one of the large local healthcare systems promising better convenience and care than that of their competitors.

I’m certainly not in a position to offer extended or weekend hours — I mean, I could, but I also have my own sanity to keep. But at the same time small practices may know their patients better than Huge Medicine Inc. We don’t have as many patients, and the staff turnover at small places is usually lower.

No one, though, is going to stand up for us, AMEX included (outside of cosmetic services, doctor visit charges are probably a tiny fraction of credit card company charges). Even our own organizations, like the AMA and others, won’t (at least not too much). They might pay lip service to us, but the reality is that most of their members work for large healthcare systems. Those groups probably make some big donations to them, too. So the last thing they want to do is tick them off.

I’m not against large groups. They have capabilities I don’t, like the ability to run research trials and have subspecialists. Even the best of us in solo practice needs someone better to refer to, such as an epileptologist, Parkinsonologist, neuromuscular disease-ologist, When I can’t help a patient any further those are the doctors I turn to, and, believe me, I appreciate them.

But it sometimes seems odd that, in a world where financial companies and public figures often stress their support for small business, those of us in the small medical practice are forgotten.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

This transcript has been edited for clarity. 

New updated COVID vaccines are now available, but who can get them, who should get them, and when? Two updated mRNA COVID vaccines, one by Moderna and the other by Pfizer, have been authorized or approved by the US Food and Drug Administration (FDA) for those aged 6 months or older.

Both vaccines target Omicron’s KP.2 strain of the JN.1 lineage. An updated protein-based version by Novavax, also directed at JN.1, has been authorized, but only for those aged 12 years or older. 

The Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices recommends a dose of the 2024-2025 updated COVID vaccine for everyone aged 6 months or older. This includes people who have never been vaccinated against COVID, those who have been vaccinated, as well as people with previous COVID infection. 

The big question is when, and FDA and CDC have set some parameters. For mRNA updated vaccines, patients should wait at least 2 months after their last dose of any COVID vaccine before getting a dose of the updated vaccine.

If the patient has recently had COVID, the wait time is even longer: Patients can wait 3 months after a COVID infection to be vaccinated, but they don’t have to. FDA’s instructions for the Novavax version are not as straightforward. People can get an updated Novavax dose at least 2 months after their last mRNA COVID vaccine dose, or at least 2 months after completing a Novavax two-dose primary series. Those two Novavax doses should be given at least 3 weeks apart. 

Patients can personalize their vaccine plan. They will have the greatest protection in the first few weeks to months after a vaccine, after which antibodies tend to wane. It is a good idea to time vaccination so that protection peaks at big events like weddings and major meetings.

If patients decide to wait, they run the risk of getting a COVID infection. Also keep in mind which variants are circulating and the amount of local activity. Right now, there is a lot of COVID going around, and most of it is related to JN.1, the target of this year’s updated vaccine. If patients decide to wait, they should avoid crowded indoor settings or wear a high-quality mask for some protection. 

Here’s the bottom line: Most people (more than 95%) have some degree of COVID protection from previous infection, vaccination, or both. But if they haven’t recently had COVID infection and didn’t get a dose of last year’s vaccine, they are sitting ducks for getting sick without updated protection. The best way to stay well is to get a dose of the updated vaccine as soon as possible. This is especially true for those in high-risk groups or who are near someone who is high risk. 

Two thirds of COVID hospitalizations are in those aged 65 or older. Hospitalization rates are highest for those aged 75 or older and among infants under 6 months of age. These babies are too young to be vaccinated, but maternal vaccination during pregnancy and breastfeeding can help protect them. 

We’re still seeing racial and ethnic disparities in COVID-related hospitalizations, which are highest among American Indians, Alaska Natives, and Black populations. People with immunocompromising conditions, those with chronic medical conditions, and people living in long-term care facilities are also at greater risk. Unlike last year, additional mRNA doses are not recommended for those aged 65 or older at this time, but that could change.

Since 2020, we’ve come a long way in our fight against COVID, but the battle is still on. In 2023, nearly a million people were hospitalized from COVID. More than 75,000 died. COVID vaccines help protect us from severe disease, hospitalization, and death. 

Let’s face it — we all have booster fatigue, but COVID is now endemic. It’s here to stay, and it’s much safer to update antibody protection with vaccination than with infection. Another benefit of getting vaccinated is that it decreases the chance of getting long COVID. The uptake of last year’s COVID vaccine was abysmal; only about 23% of adults and 14% of children received it.

But this is a new year and a new vaccine. Please make sure your patients understand that the virus has changed a lot. Antibodies we built from previous infection and previous vaccination don’t work as well against these new variants. Antibody levels wane over time, so even if they missed the last few vaccine doses without getting sick, they really should consider getting a dose of this new vaccine. The 2024-2025 updated COVID vaccine is the best way to catch up, update their immunity, and keep them protected. 

Furthermore, we are now entering respiratory virus season, which means we need to think about, recommend, and administer three shots if indicated: COVID, flu, and RSV. Now is the time. Patients can get all three at the same time, in the same visit, if they choose to do so. 

Your recommendation as a physician is powerful. Adults and children who receive a healthcare provider recommendation are more likely to get vaccinated.

Dr. Fryhofer is an adjunct clinical associate professor of medicine, Emory University School of Medicine, Atlanta, Georgia. She reported conflicts of interest with the American Medical Association, the Medical Association of Atlanta, the American College of Physicians, and Medscape.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

New updated COVID vaccines are now available, but who can get them, who should get them, and when? Two updated mRNA COVID vaccines, one by Moderna and the other by Pfizer, have been authorized or approved by the US Food and Drug Administration (FDA) for those aged 6 months or older.

Both vaccines target Omicron’s KP.2 strain of the JN.1 lineage. An updated protein-based version by Novavax, also directed at JN.1, has been authorized, but only for those aged 12 years or older. 

The Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices recommends a dose of the 2024-2025 updated COVID vaccine for everyone aged 6 months or older. This includes people who have never been vaccinated against COVID, those who have been vaccinated, as well as people with previous COVID infection. 

The big question is when, and FDA and CDC have set some parameters. For mRNA updated vaccines, patients should wait at least 2 months after their last dose of any COVID vaccine before getting a dose of the updated vaccine.

If the patient has recently had COVID, the wait time is even longer: Patients can wait 3 months after a COVID infection to be vaccinated, but they don’t have to. FDA’s instructions for the Novavax version are not as straightforward. People can get an updated Novavax dose at least 2 months after their last mRNA COVID vaccine dose, or at least 2 months after completing a Novavax two-dose primary series. Those two Novavax doses should be given at least 3 weeks apart. 

Patients can personalize their vaccine plan. They will have the greatest protection in the first few weeks to months after a vaccine, after which antibodies tend to wane. It is a good idea to time vaccination so that protection peaks at big events like weddings and major meetings.

If patients decide to wait, they run the risk of getting a COVID infection. Also keep in mind which variants are circulating and the amount of local activity. Right now, there is a lot of COVID going around, and most of it is related to JN.1, the target of this year’s updated vaccine. If patients decide to wait, they should avoid crowded indoor settings or wear a high-quality mask for some protection. 

Here’s the bottom line: Most people (more than 95%) have some degree of COVID protection from previous infection, vaccination, or both. But if they haven’t recently had COVID infection and didn’t get a dose of last year’s vaccine, they are sitting ducks for getting sick without updated protection. The best way to stay well is to get a dose of the updated vaccine as soon as possible. This is especially true for those in high-risk groups or who are near someone who is high risk. 

Two thirds of COVID hospitalizations are in those aged 65 or older. Hospitalization rates are highest for those aged 75 or older and among infants under 6 months of age. These babies are too young to be vaccinated, but maternal vaccination during pregnancy and breastfeeding can help protect them. 

We’re still seeing racial and ethnic disparities in COVID-related hospitalizations, which are highest among American Indians, Alaska Natives, and Black populations. People with immunocompromising conditions, those with chronic medical conditions, and people living in long-term care facilities are also at greater risk. Unlike last year, additional mRNA doses are not recommended for those aged 65 or older at this time, but that could change.

Since 2020, we’ve come a long way in our fight against COVID, but the battle is still on. In 2023, nearly a million people were hospitalized from COVID. More than 75,000 died. COVID vaccines help protect us from severe disease, hospitalization, and death. 

Let’s face it — we all have booster fatigue, but COVID is now endemic. It’s here to stay, and it’s much safer to update antibody protection with vaccination than with infection. Another benefit of getting vaccinated is that it decreases the chance of getting long COVID. The uptake of last year’s COVID vaccine was abysmal; only about 23% of adults and 14% of children received it.

But this is a new year and a new vaccine. Please make sure your patients understand that the virus has changed a lot. Antibodies we built from previous infection and previous vaccination don’t work as well against these new variants. Antibody levels wane over time, so even if they missed the last few vaccine doses without getting sick, they really should consider getting a dose of this new vaccine. The 2024-2025 updated COVID vaccine is the best way to catch up, update their immunity, and keep them protected. 

Furthermore, we are now entering respiratory virus season, which means we need to think about, recommend, and administer three shots if indicated: COVID, flu, and RSV. Now is the time. Patients can get all three at the same time, in the same visit, if they choose to do so. 

Your recommendation as a physician is powerful. Adults and children who receive a healthcare provider recommendation are more likely to get vaccinated.

Dr. Fryhofer is an adjunct clinical associate professor of medicine, Emory University School of Medicine, Atlanta, Georgia. She reported conflicts of interest with the American Medical Association, the Medical Association of Atlanta, the American College of Physicians, and Medscape.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

New updated COVID vaccines are now available, but who can get them, who should get them, and when? Two updated mRNA COVID vaccines, one by Moderna and the other by Pfizer, have been authorized or approved by the US Food and Drug Administration (FDA) for those aged 6 months or older.

Both vaccines target Omicron’s KP.2 strain of the JN.1 lineage. An updated protein-based version by Novavax, also directed at JN.1, has been authorized, but only for those aged 12 years or older. 

The Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices recommends a dose of the 2024-2025 updated COVID vaccine for everyone aged 6 months or older. This includes people who have never been vaccinated against COVID, those who have been vaccinated, as well as people with previous COVID infection. 

The big question is when, and FDA and CDC have set some parameters. For mRNA updated vaccines, patients should wait at least 2 months after their last dose of any COVID vaccine before getting a dose of the updated vaccine.

If the patient has recently had COVID, the wait time is even longer: Patients can wait 3 months after a COVID infection to be vaccinated, but they don’t have to. FDA’s instructions for the Novavax version are not as straightforward. People can get an updated Novavax dose at least 2 months after their last mRNA COVID vaccine dose, or at least 2 months after completing a Novavax two-dose primary series. Those two Novavax doses should be given at least 3 weeks apart. 

Patients can personalize their vaccine plan. They will have the greatest protection in the first few weeks to months after a vaccine, after which antibodies tend to wane. It is a good idea to time vaccination so that protection peaks at big events like weddings and major meetings.

If patients decide to wait, they run the risk of getting a COVID infection. Also keep in mind which variants are circulating and the amount of local activity. Right now, there is a lot of COVID going around, and most of it is related to JN.1, the target of this year’s updated vaccine. If patients decide to wait, they should avoid crowded indoor settings or wear a high-quality mask for some protection. 

Here’s the bottom line: Most people (more than 95%) have some degree of COVID protection from previous infection, vaccination, or both. But if they haven’t recently had COVID infection and didn’t get a dose of last year’s vaccine, they are sitting ducks for getting sick without updated protection. The best way to stay well is to get a dose of the updated vaccine as soon as possible. This is especially true for those in high-risk groups or who are near someone who is high risk. 

Two thirds of COVID hospitalizations are in those aged 65 or older. Hospitalization rates are highest for those aged 75 or older and among infants under 6 months of age. These babies are too young to be vaccinated, but maternal vaccination during pregnancy and breastfeeding can help protect them. 

We’re still seeing racial and ethnic disparities in COVID-related hospitalizations, which are highest among American Indians, Alaska Natives, and Black populations. People with immunocompromising conditions, those with chronic medical conditions, and people living in long-term care facilities are also at greater risk. Unlike last year, additional mRNA doses are not recommended for those aged 65 or older at this time, but that could change.

Since 2020, we’ve come a long way in our fight against COVID, but the battle is still on. In 2023, nearly a million people were hospitalized from COVID. More than 75,000 died. COVID vaccines help protect us from severe disease, hospitalization, and death. 

Let’s face it — we all have booster fatigue, but COVID is now endemic. It’s here to stay, and it’s much safer to update antibody protection with vaccination than with infection. Another benefit of getting vaccinated is that it decreases the chance of getting long COVID. The uptake of last year’s COVID vaccine was abysmal; only about 23% of adults and 14% of children received it.

But this is a new year and a new vaccine. Please make sure your patients understand that the virus has changed a lot. Antibodies we built from previous infection and previous vaccination don’t work as well against these new variants. Antibody levels wane over time, so even if they missed the last few vaccine doses without getting sick, they really should consider getting a dose of this new vaccine. The 2024-2025 updated COVID vaccine is the best way to catch up, update their immunity, and keep them protected. 

Furthermore, we are now entering respiratory virus season, which means we need to think about, recommend, and administer three shots if indicated: COVID, flu, and RSV. Now is the time. Patients can get all three at the same time, in the same visit, if they choose to do so. 

Your recommendation as a physician is powerful. Adults and children who receive a healthcare provider recommendation are more likely to get vaccinated.

Dr. Fryhofer is an adjunct clinical associate professor of medicine, Emory University School of Medicine, Atlanta, Georgia. She reported conflicts of interest with the American Medical Association, the Medical Association of Atlanta, the American College of Physicians, and Medscape.

A version of this article first appeared on Medscape.com.

TOPLINE:

The presence of an operational classification of drug interactions (ORCA) class 3 or 4 drug-drug interactions (DDIs) did not increase the risk for colchicine-related gastrointestinal adverse events or modify the effect of colchicine on death or hospitalization caused by COVID-19 infection in ambulatory patients.

METHODOLOGY:

• This secondary analysis of the COLCORONA trial aimed to evaluate if a potential DDI of colchicine was associated with changes in its pharmacokinetics or modified its clinical safety and efficacy in patients with COVID-19.
• Overall, 4432 ambulatory patients with COVID-19 (median age, 54 years; 54% women) were randomly assigned to receive colchicine 0.5 mg twice daily for 3 days and then 0.5 mg once daily for 27 days (n = 2205) or a placebo (n = 2227).
• All the participants had at least one high-risk criterion such as age ≥ 70 years, diabetes, heart failure, systolic blood pressure ≥ 150 mm Hg, respiratory disease, coronary disease, body temperature ≥ 38.4 °C within the last 48 hours, dyspnea, bicytopenia, pancytopenia, or high neutrophil count with low lymphocyte count.
• The medications that could interact with colchicine were determined and categorized under ORCA classes 1 (contraindicated), 2 (provisionally contraindicated), 3 (conditional use), or 4 (minimal risk).
• The primary outcome was any gastrointestinal adverse event assessed over a 30-day follow-up period.

TAKEAWAY:

• Among all the participants, 1% received medications with an ORCA class 2 interaction, 14% with a class 3 interaction, and 13% with a class 4 interaction; rosuvastatin (12%) and atorvastatin (10%) were the most common interacting medications.
• The odds of any gastrointestinal adverse event were 1.80 times and 1.68 times higher in the colchicine arm than in the placebo arm among those without and with a DDI, respectively, with the effect of colchicine being consistent regardless of the presence of drug interactions (P = .69 for interaction).
• Similarly, DDIs did not influence the effect of colchicine on combined risk for COVID-19 hospitalization or mortality (P = .80 for interaction).

IN PRACTICE:

“Once potential DDIs have been identified through screening, they must be tested,” Hemalkumar B. Mehta, PhD, and G. Caleb Alexander, MD, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, wrote in an invited commentary published online in JAMA Network Open. “Theoretical DDIs may not translate into real-world harms,” they added.

SOURCE:

The study was led by Lama S. Alfehaid, PharmD, of Brigham and Women’s Hospital, Boston. It was published online in JAMA Network Open.

LIMITATIONS:

This study focused on the medications used by participants at baseline, which may not have captured all potential DDIs. The findings did not provide information on rare adverse events, such as rhabdomyolysis, which usually occur months after initiating drug therapy. Furthermore, all the study participants had confirmed SARS-CoV-2 infection, which may have increased their susceptibility to adverse reactions associated with the use of colchicine.

DISCLOSURES:

Some authors were supported by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute, American Heart Association, and other sources. The authors also declared serving on advisory boards or on the board of directors; receiving personal fees, grants, research support, or speaking fees; or having other ties with many pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The presence of an operational classification of drug interactions (ORCA) class 3 or 4 drug-drug interactions (DDIs) did not increase the risk for colchicine-related gastrointestinal adverse events or modify the effect of colchicine on death or hospitalization caused by COVID-19 infection in ambulatory patients.

METHODOLOGY:

• This secondary analysis of the COLCORONA trial aimed to evaluate if a potential DDI of colchicine was associated with changes in its pharmacokinetics or modified its clinical safety and efficacy in patients with COVID-19.
• Overall, 4432 ambulatory patients with COVID-19 (median age, 54 years; 54% women) were randomly assigned to receive colchicine 0.5 mg twice daily for 3 days and then 0.5 mg once daily for 27 days (n = 2205) or a placebo (n = 2227).
• All the participants had at least one high-risk criterion such as age ≥ 70 years, diabetes, heart failure, systolic blood pressure ≥ 150 mm Hg, respiratory disease, coronary disease, body temperature ≥ 38.4 °C within the last 48 hours, dyspnea, bicytopenia, pancytopenia, or high neutrophil count with low lymphocyte count.
• The medications that could interact with colchicine were determined and categorized under ORCA classes 1 (contraindicated), 2 (provisionally contraindicated), 3 (conditional use), or 4 (minimal risk).
• The primary outcome was any gastrointestinal adverse event assessed over a 30-day follow-up period.

TAKEAWAY:

• Among all the participants, 1% received medications with an ORCA class 2 interaction, 14% with a class 3 interaction, and 13% with a class 4 interaction; rosuvastatin (12%) and atorvastatin (10%) were the most common interacting medications.
• The odds of any gastrointestinal adverse event were 1.80 times and 1.68 times higher in the colchicine arm than in the placebo arm among those without and with a DDI, respectively, with the effect of colchicine being consistent regardless of the presence of drug interactions (P = .69 for interaction).
• Similarly, DDIs did not influence the effect of colchicine on combined risk for COVID-19 hospitalization or mortality (P = .80 for interaction).

IN PRACTICE:

“Once potential DDIs have been identified through screening, they must be tested,” Hemalkumar B. Mehta, PhD, and G. Caleb Alexander, MD, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, wrote in an invited commentary published online in JAMA Network Open. “Theoretical DDIs may not translate into real-world harms,” they added.

SOURCE:

The study was led by Lama S. Alfehaid, PharmD, of Brigham and Women’s Hospital, Boston. It was published online in JAMA Network Open.

LIMITATIONS:

This study focused on the medications used by participants at baseline, which may not have captured all potential DDIs. The findings did not provide information on rare adverse events, such as rhabdomyolysis, which usually occur months after initiating drug therapy. Furthermore, all the study participants had confirmed SARS-CoV-2 infection, which may have increased their susceptibility to adverse reactions associated with the use of colchicine.

DISCLOSURES:

Some authors were supported by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute, American Heart Association, and other sources. The authors also declared serving on advisory boards or on the board of directors; receiving personal fees, grants, research support, or speaking fees; or having other ties with many pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The presence of an operational classification of drug interactions (ORCA) class 3 or 4 drug-drug interactions (DDIs) did not increase the risk for colchicine-related gastrointestinal adverse events or modify the effect of colchicine on death or hospitalization caused by COVID-19 infection in ambulatory patients.

METHODOLOGY:

• This secondary analysis of the COLCORONA trial aimed to evaluate if a potential DDI of colchicine was associated with changes in its pharmacokinetics or modified its clinical safety and efficacy in patients with COVID-19.
• Overall, 4432 ambulatory patients with COVID-19 (median age, 54 years; 54% women) were randomly assigned to receive colchicine 0.5 mg twice daily for 3 days and then 0.5 mg once daily for 27 days (n = 2205) or a placebo (n = 2227).
• All the participants had at least one high-risk criterion such as age ≥ 70 years, diabetes, heart failure, systolic blood pressure ≥ 150 mm Hg, respiratory disease, coronary disease, body temperature ≥ 38.4 °C within the last 48 hours, dyspnea, bicytopenia, pancytopenia, or high neutrophil count with low lymphocyte count.
• The medications that could interact with colchicine were determined and categorized under ORCA classes 1 (contraindicated), 2 (provisionally contraindicated), 3 (conditional use), or 4 (minimal risk).
• The primary outcome was any gastrointestinal adverse event assessed over a 30-day follow-up period.

TAKEAWAY:

• Among all the participants, 1% received medications with an ORCA class 2 interaction, 14% with a class 3 interaction, and 13% with a class 4 interaction; rosuvastatin (12%) and atorvastatin (10%) were the most common interacting medications.
• The odds of any gastrointestinal adverse event were 1.80 times and 1.68 times higher in the colchicine arm than in the placebo arm among those without and with a DDI, respectively, with the effect of colchicine being consistent regardless of the presence of drug interactions (P = .69 for interaction).
• Similarly, DDIs did not influence the effect of colchicine on combined risk for COVID-19 hospitalization or mortality (P = .80 for interaction).

IN PRACTICE:

“Once potential DDIs have been identified through screening, they must be tested,” Hemalkumar B. Mehta, PhD, and G. Caleb Alexander, MD, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, wrote in an invited commentary published online in JAMA Network Open. “Theoretical DDIs may not translate into real-world harms,” they added.

SOURCE:

The study was led by Lama S. Alfehaid, PharmD, of Brigham and Women’s Hospital, Boston. It was published online in JAMA Network Open.

LIMITATIONS:

This study focused on the medications used by participants at baseline, which may not have captured all potential DDIs. The findings did not provide information on rare adverse events, such as rhabdomyolysis, which usually occur months after initiating drug therapy. Furthermore, all the study participants had confirmed SARS-CoV-2 infection, which may have increased their susceptibility to adverse reactions associated with the use of colchicine.

DISCLOSURES:

Some authors were supported by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute, American Heart Association, and other sources. The authors also declared serving on advisory boards or on the board of directors; receiving personal fees, grants, research support, or speaking fees; or having other ties with many pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

I suspect that many of you have seen or read about a recent study regarding the “long COVID” enigma. The investigators surveyed the records of more than 4000 pediatric patients who had been infected and nearly 1400 who had not. The researchers then developed models in which 14 symptoms were more common in previous SARS-CoV2–infected individuals in all age groups, compared with the uninfected. There were four additional symptoms in children only and three additional symptoms in the adolescents.

Using these data, the investigators created research indices that “correlated with poor overall health and quality of life” and emphasized “neurocognitive, pain, and gastrointestinal symptoms in school-age children” and a “change or loss in smell or taste, pain, and fatigue/malaise-related symptoms in adolescents.”

So now thanks to these investigators we have research indices for characterizing PASC (post-acute sequelae of SARS-CoV-2, aka. long COVID). What should we to do with them? I’m not sure these results move us any further if our goal is finding something to help patients who believe, or have been told, that they have long COVID.

Even to a non-statistician like myself there appear to be some problems with this study. In an editorial accompanying this study, Suchitra Rao, MBBS, MSCS in the Department of Pediatrics, University of Colorado School of Medicine, Aurora, noted the study has the potential for ascertainment bias. For example, the researchers’ subject recruitment procedure resulted in a higher “proportion of neurocognitive/behavioral manifestations” may have skewed the results.

Also, some of the patient evaluations were not done at a consistent interval after the initial infection, which could result in recall bias. And, more importantly, because there were no baseline measurements to determine preinfection status, the investigators had no way of determining to what degree the patients’ underlying conditions may have reflected the quality of life scores.

Although I wouldn’t consider it a bias, I wonder if the investigators have a preconceived vision of what long COVID is going to look like once it is better understood. The fact that they undertook this project suggests that they believe the truth about the phenomenon will be discoverable using data based on collections of vague symptoms.

Or, do the researchers share my vision of long COVID that if it exists it will be something akin to the burst of Parkinson’s disease seen decades later in survivors of the 1918-1920 flu pandemic. Or, maybe it is something like post-polio syndrome, in which survivors in childhood develop atrophy and muscle weakness as they age. Do the researchers believe that COVID survivors are harboring some remnant of SARS-CoV-2 or its genome inside their bodies ticking like a time bomb ready to surface in the future? Think shingles.

I suspect that there are some folks who may or not share my ticking time bomb vision, but who, like me, wonder if there is really such a thing as long COVID – at least one in the form characterized by the work of these investigators. Unfortunately, the $1 billion the National Institutes of Health has invested in the Researching COVID to Enhance Recovery (RECOVER) initiative is not going to discover delayed sequelae until time is ready to tell us. What researchers are looking at now is a collection of patients, some who were not well to begin with but now describe a collection of vague symptoms, some of which are unique to COVID, but most are not. The loss of taste and smell being the one notable and important exception.

It is easy to understand why patients and their physicians would like to have a diagnosis like “long COVID” to at least validate their symptoms that up until now have eluded explanation or remedy. Not surprisingly, they may feel that, if researchers can’t find a cure, let’s at least have something we can lay the blame on.

A major flaw in this current attempt to characterize long COVID is the lack of a true control group. Yes, the subjects the researchers labeled as “uninfected” lived contemporaneously with the patients unfortunate enough to have acquired the virus. However, this illness was mysterious from its first appearance, continued to be more frightening as we struggled to learn more about it, and was clumsily managed in a way that turned our way of life upside down. This was particularly true for school-age children. It unmasked previously unsuspected underlying conditions and quickly acquired a poorly documented reputation for having a “long” variety.

Of course the “uninfected” also lived through these same tumultuous times. But knowing that you harbored, and may still harbor, this mysterious invader moves the infected and their families into a whole new level of concern and anxiety the rest of us who were more fortunate don’t share.

We must not ignore the fact that patients and their caregivers may receive some comfort when they have something to blame for their symptoms. However, we must shift our focus away from blame hunting, which up to this point has been fruitless. Instead, we must invest our energies into helping those struggling with long COVID find a manageable pathway toward improvement. Each patient should be treated as an individual and not part of a group with similar symptoms cobbled together with data acquired under a cloud of bias.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

I suspect that many of you have seen or read about a recent study regarding the “long COVID” enigma. The investigators surveyed the records of more than 4000 pediatric patients who had been infected and nearly 1400 who had not. The researchers then developed models in which 14 symptoms were more common in previous SARS-CoV2–infected individuals in all age groups, compared with the uninfected. There were four additional symptoms in children only and three additional symptoms in the adolescents.

Using these data, the investigators created research indices that “correlated with poor overall health and quality of life” and emphasized “neurocognitive, pain, and gastrointestinal symptoms in school-age children” and a “change or loss in smell or taste, pain, and fatigue/malaise-related symptoms in adolescents.”

So now thanks to these investigators we have research indices for characterizing PASC (post-acute sequelae of SARS-CoV-2, aka. long COVID). What should we to do with them? I’m not sure these results move us any further if our goal is finding something to help patients who believe, or have been told, that they have long COVID.

Even to a non-statistician like myself there appear to be some problems with this study. In an editorial accompanying this study, Suchitra Rao, MBBS, MSCS in the Department of Pediatrics, University of Colorado School of Medicine, Aurora, noted the study has the potential for ascertainment bias. For example, the researchers’ subject recruitment procedure resulted in a higher “proportion of neurocognitive/behavioral manifestations” may have skewed the results.

Also, some of the patient evaluations were not done at a consistent interval after the initial infection, which could result in recall bias. And, more importantly, because there were no baseline measurements to determine preinfection status, the investigators had no way of determining to what degree the patients’ underlying conditions may have reflected the quality of life scores.

Although I wouldn’t consider it a bias, I wonder if the investigators have a preconceived vision of what long COVID is going to look like once it is better understood. The fact that they undertook this project suggests that they believe the truth about the phenomenon will be discoverable using data based on collections of vague symptoms.

Or, do the researchers share my vision of long COVID that if it exists it will be something akin to the burst of Parkinson’s disease seen decades later in survivors of the 1918-1920 flu pandemic. Or, maybe it is something like post-polio syndrome, in which survivors in childhood develop atrophy and muscle weakness as they age. Do the researchers believe that COVID survivors are harboring some remnant of SARS-CoV-2 or its genome inside their bodies ticking like a time bomb ready to surface in the future? Think shingles.

I suspect that there are some folks who may or not share my ticking time bomb vision, but who, like me, wonder if there is really such a thing as long COVID – at least one in the form characterized by the work of these investigators. Unfortunately, the $1 billion the National Institutes of Health has invested in the Researching COVID to Enhance Recovery (RECOVER) initiative is not going to discover delayed sequelae until time is ready to tell us. What researchers are looking at now is a collection of patients, some who were not well to begin with but now describe a collection of vague symptoms, some of which are unique to COVID, but most are not. The loss of taste and smell being the one notable and important exception.

It is easy to understand why patients and their physicians would like to have a diagnosis like “long COVID” to at least validate their symptoms that up until now have eluded explanation or remedy. Not surprisingly, they may feel that, if researchers can’t find a cure, let’s at least have something we can lay the blame on.

A major flaw in this current attempt to characterize long COVID is the lack of a true control group. Yes, the subjects the researchers labeled as “uninfected” lived contemporaneously with the patients unfortunate enough to have acquired the virus. However, this illness was mysterious from its first appearance, continued to be more frightening as we struggled to learn more about it, and was clumsily managed in a way that turned our way of life upside down. This was particularly true for school-age children. It unmasked previously unsuspected underlying conditions and quickly acquired a poorly documented reputation for having a “long” variety.

Of course the “uninfected” also lived through these same tumultuous times. But knowing that you harbored, and may still harbor, this mysterious invader moves the infected and their families into a whole new level of concern and anxiety the rest of us who were more fortunate don’t share.

We must not ignore the fact that patients and their caregivers may receive some comfort when they have something to blame for their symptoms. However, we must shift our focus away from blame hunting, which up to this point has been fruitless. Instead, we must invest our energies into helping those struggling with long COVID find a manageable pathway toward improvement. Each patient should be treated as an individual and not part of a group with similar symptoms cobbled together with data acquired under a cloud of bias.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

I suspect that many of you have seen or read about a recent study regarding the “long COVID” enigma. The investigators surveyed the records of more than 4000 pediatric patients who had been infected and nearly 1400 who had not. The researchers then developed models in which 14 symptoms were more common in previous SARS-CoV2–infected individuals in all age groups, compared with the uninfected. There were four additional symptoms in children only and three additional symptoms in the adolescents.

Using these data, the investigators created research indices that “correlated with poor overall health and quality of life” and emphasized “neurocognitive, pain, and gastrointestinal symptoms in school-age children” and a “change or loss in smell or taste, pain, and fatigue/malaise-related symptoms in adolescents.”

So now thanks to these investigators we have research indices for characterizing PASC (post-acute sequelae of SARS-CoV-2, aka. long COVID). What should we to do with them? I’m not sure these results move us any further if our goal is finding something to help patients who believe, or have been told, that they have long COVID.

Even to a non-statistician like myself there appear to be some problems with this study. In an editorial accompanying this study, Suchitra Rao, MBBS, MSCS in the Department of Pediatrics, University of Colorado School of Medicine, Aurora, noted the study has the potential for ascertainment bias. For example, the researchers’ subject recruitment procedure resulted in a higher “proportion of neurocognitive/behavioral manifestations” may have skewed the results.

Also, some of the patient evaluations were not done at a consistent interval after the initial infection, which could result in recall bias. And, more importantly, because there were no baseline measurements to determine preinfection status, the investigators had no way of determining to what degree the patients’ underlying conditions may have reflected the quality of life scores.

Although I wouldn’t consider it a bias, I wonder if the investigators have a preconceived vision of what long COVID is going to look like once it is better understood. The fact that they undertook this project suggests that they believe the truth about the phenomenon will be discoverable using data based on collections of vague symptoms.

Or, do the researchers share my vision of long COVID that if it exists it will be something akin to the burst of Parkinson’s disease seen decades later in survivors of the 1918-1920 flu pandemic. Or, maybe it is something like post-polio syndrome, in which survivors in childhood develop atrophy and muscle weakness as they age. Do the researchers believe that COVID survivors are harboring some remnant of SARS-CoV-2 or its genome inside their bodies ticking like a time bomb ready to surface in the future? Think shingles.

I suspect that there are some folks who may or not share my ticking time bomb vision, but who, like me, wonder if there is really such a thing as long COVID – at least one in the form characterized by the work of these investigators. Unfortunately, the $1 billion the National Institutes of Health has invested in the Researching COVID to Enhance Recovery (RECOVER) initiative is not going to discover delayed sequelae until time is ready to tell us. What researchers are looking at now is a collection of patients, some who were not well to begin with but now describe a collection of vague symptoms, some of which are unique to COVID, but most are not. The loss of taste and smell being the one notable and important exception.

It is easy to understand why patients and their physicians would like to have a diagnosis like “long COVID” to at least validate their symptoms that up until now have eluded explanation or remedy. Not surprisingly, they may feel that, if researchers can’t find a cure, let’s at least have something we can lay the blame on.

A major flaw in this current attempt to characterize long COVID is the lack of a true control group. Yes, the subjects the researchers labeled as “uninfected” lived contemporaneously with the patients unfortunate enough to have acquired the virus. However, this illness was mysterious from its first appearance, continued to be more frightening as we struggled to learn more about it, and was clumsily managed in a way that turned our way of life upside down. This was particularly true for school-age children. It unmasked previously unsuspected underlying conditions and quickly acquired a poorly documented reputation for having a “long” variety.

Of course the “uninfected” also lived through these same tumultuous times. But knowing that you harbored, and may still harbor, this mysterious invader moves the infected and their families into a whole new level of concern and anxiety the rest of us who were more fortunate don’t share.

We must not ignore the fact that patients and their caregivers may receive some comfort when they have something to blame for their symptoms. However, we must shift our focus away from blame hunting, which up to this point has been fruitless. Instead, we must invest our energies into helping those struggling with long COVID find a manageable pathway toward improvement. Each patient should be treated as an individual and not part of a group with similar symptoms cobbled together with data acquired under a cloud of bias.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

TOPLINE:

In systemic sclerosis, Raynaud phenomenon is more severe at both high and low temperature extremes, according to new research.

BACKGROUND:

• Raynaud phenomenon, a condition that causes decreased blood flow to extremities, occurs in about 95% of individuals with systemic sclerosis.
• Episodes of Raynaud phenomenon can be triggered by cold exposure and ambient temperature changes.
• In severe cases, it can cause permanent damage to tissues of the fingers and toes.

METHODOLOGY:

• Researchers analyzed data from 2243 participants with Raynaud phenomenon secondary to systemic sclerosis from the Scleroderma Patient-centered Intervention Network (SPIN) Cohort.
• Participants completed past-week Raynaud phenomenon severity assessments using a 0-10 numerical rating scale at enrollment and every 3 months.
• The study included data from 20,233 Raynaud phenomenon severity assessments between April 15, 2014, and August 1, 2023.
• Researchers used average daily temperature from a weather site close to the participant’s recruiting center and mapped these ambient temperature changes to Raynaud’s phenomenon outcomes.

TAKEAWAY:

• Raynaud’s phenomenon severity was highest at –25 °C (–13 °F), with assessment scores at 6.8 points out of 10.0, and lowest at 25 °C (77 °F), with scores at 2.6.
• Severity scores increased again at temperatures above 35 °C (95 °F), reaching a high of 5.6 out of 10 at 40 °C (104 °F).
• This spike at higher temperatures is presumably due to air conditioning, the authors said.
• In an accompanying commentary, Cutolo et al. posited that increased sweating and hypotension could also lead to a relative hypovolemic state in patients, causing Raynaud-like symptoms.

IN PRACTICE:

“Temperature-related variations in Raynaud’s phenomenon severity scores should be considered in clinical trials to account for normal within-season temperature fluctuations, enhancing the accuracy of treatment outcomes,” wrote Cutolo and colleagues in their commentary.

SOURCE:

The study was led by Gabrielle Virgili-Gervais, MSc, McGill University Health Centre in Montreal, Quebec, Canada. It was published online on August 28 in The Lancet Rheumatology. The accompanying commentary, also published on August 28, was authored by Maurizio Cutolo, MD, and Elvis Hysa, MD, both of University of Genova, Italy, as well as Vanessa Smith, MD, PhD, of Ghent University in Ghent, Belgium.

LIMITATIONS:

The lower number of assessments at extreme temperatures (–25 °C and 40 °C) may affect the robustness of the findings at these ranges. The study did not account for vasodilator use, which could influence participants’ response to temperature. The study also did not account for other potential confounding factors such as sex, smoking status, psychosocial factors, and comorbid conditions like cardiovascular disease.

DISCLOSURES:

A variety of scleroderma-related patient advocacy groups helped to fund research on the SPIN cohort, in addition to the Canadian Institutes of Health Research, the Arthritis Society, the Lady Davis Institute for Medical Research of the Jewish General Hospital, the Jewish General Hospital Foundation, and McGill University. Two authors reported having financial ties with pharmaceutical companies. Dr. Cutolo, Dr. Smith, and Dr. Hysa had no disclosures.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

In systemic sclerosis, Raynaud phenomenon is more severe at both high and low temperature extremes, according to new research.

BACKGROUND:

• Raynaud phenomenon, a condition that causes decreased blood flow to extremities, occurs in about 95% of individuals with systemic sclerosis.
• Episodes of Raynaud phenomenon can be triggered by cold exposure and ambient temperature changes.
• In severe cases, it can cause permanent damage to tissues of the fingers and toes.

METHODOLOGY:

• Researchers analyzed data from 2243 participants with Raynaud phenomenon secondary to systemic sclerosis from the Scleroderma Patient-centered Intervention Network (SPIN) Cohort.
• Participants completed past-week Raynaud phenomenon severity assessments using a 0-10 numerical rating scale at enrollment and every 3 months.
• The study included data from 20,233 Raynaud phenomenon severity assessments between April 15, 2014, and August 1, 2023.
• Researchers used average daily temperature from a weather site close to the participant’s recruiting center and mapped these ambient temperature changes to Raynaud’s phenomenon outcomes.

TAKEAWAY:

• Raynaud’s phenomenon severity was highest at –25 °C (–13 °F), with assessment scores at 6.8 points out of 10.0, and lowest at 25 °C (77 °F), with scores at 2.6.
• Severity scores increased again at temperatures above 35 °C (95 °F), reaching a high of 5.6 out of 10 at 40 °C (104 °F).
• This spike at higher temperatures is presumably due to air conditioning, the authors said.
• In an accompanying commentary, Cutolo et al. posited that increased sweating and hypotension could also lead to a relative hypovolemic state in patients, causing Raynaud-like symptoms.

IN PRACTICE:

“Temperature-related variations in Raynaud’s phenomenon severity scores should be considered in clinical trials to account for normal within-season temperature fluctuations, enhancing the accuracy of treatment outcomes,” wrote Cutolo and colleagues in their commentary.

SOURCE:

The study was led by Gabrielle Virgili-Gervais, MSc, McGill University Health Centre in Montreal, Quebec, Canada. It was published online on August 28 in The Lancet Rheumatology. The accompanying commentary, also published on August 28, was authored by Maurizio Cutolo, MD, and Elvis Hysa, MD, both of University of Genova, Italy, as well as Vanessa Smith, MD, PhD, of Ghent University in Ghent, Belgium.

LIMITATIONS:

The lower number of assessments at extreme temperatures (–25 °C and 40 °C) may affect the robustness of the findings at these ranges. The study did not account for vasodilator use, which could influence participants’ response to temperature. The study also did not account for other potential confounding factors such as sex, smoking status, psychosocial factors, and comorbid conditions like cardiovascular disease.

DISCLOSURES:

A variety of scleroderma-related patient advocacy groups helped to fund research on the SPIN cohort, in addition to the Canadian Institutes of Health Research, the Arthritis Society, the Lady Davis Institute for Medical Research of the Jewish General Hospital, the Jewish General Hospital Foundation, and McGill University. Two authors reported having financial ties with pharmaceutical companies. Dr. Cutolo, Dr. Smith, and Dr. Hysa had no disclosures.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

In systemic sclerosis, Raynaud phenomenon is more severe at both high and low temperature extremes, according to new research.

BACKGROUND:

• Raynaud phenomenon, a condition that causes decreased blood flow to extremities, occurs in about 95% of individuals with systemic sclerosis.
• Episodes of Raynaud phenomenon can be triggered by cold exposure and ambient temperature changes.
• In severe cases, it can cause permanent damage to tissues of the fingers and toes.

METHODOLOGY:

• Researchers analyzed data from 2243 participants with Raynaud phenomenon secondary to systemic sclerosis from the Scleroderma Patient-centered Intervention Network (SPIN) Cohort.
• Participants completed past-week Raynaud phenomenon severity assessments using a 0-10 numerical rating scale at enrollment and every 3 months.
• The study included data from 20,233 Raynaud phenomenon severity assessments between April 15, 2014, and August 1, 2023.
• Researchers used average daily temperature from a weather site close to the participant’s recruiting center and mapped these ambient temperature changes to Raynaud’s phenomenon outcomes.

TAKEAWAY:

• Raynaud’s phenomenon severity was highest at –25 °C (–13 °F), with assessment scores at 6.8 points out of 10.0, and lowest at 25 °C (77 °F), with scores at 2.6.
• Severity scores increased again at temperatures above 35 °C (95 °F), reaching a high of 5.6 out of 10 at 40 °C (104 °F).
• This spike at higher temperatures is presumably due to air conditioning, the authors said.
• In an accompanying commentary, Cutolo et al. posited that increased sweating and hypotension could also lead to a relative hypovolemic state in patients, causing Raynaud-like symptoms.

IN PRACTICE:

“Temperature-related variations in Raynaud’s phenomenon severity scores should be considered in clinical trials to account for normal within-season temperature fluctuations, enhancing the accuracy of treatment outcomes,” wrote Cutolo and colleagues in their commentary.

SOURCE:

The study was led by Gabrielle Virgili-Gervais, MSc, McGill University Health Centre in Montreal, Quebec, Canada. It was published online on August 28 in The Lancet Rheumatology. The accompanying commentary, also published on August 28, was authored by Maurizio Cutolo, MD, and Elvis Hysa, MD, both of University of Genova, Italy, as well as Vanessa Smith, MD, PhD, of Ghent University in Ghent, Belgium.

LIMITATIONS:

The lower number of assessments at extreme temperatures (–25 °C and 40 °C) may affect the robustness of the findings at these ranges. The study did not account for vasodilator use, which could influence participants’ response to temperature. The study also did not account for other potential confounding factors such as sex, smoking status, psychosocial factors, and comorbid conditions like cardiovascular disease.

DISCLOSURES:

A variety of scleroderma-related patient advocacy groups helped to fund research on the SPIN cohort, in addition to the Canadian Institutes of Health Research, the Arthritis Society, the Lady Davis Institute for Medical Research of the Jewish General Hospital, the Jewish General Hospital Foundation, and McGill University. Two authors reported having financial ties with pharmaceutical companies. Dr. Cutolo, Dr. Smith, and Dr. Hysa had no disclosures.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

In a recent study, patients with multiple sclerosis (MS) had half the rate of amyloid beta pathology versus matched controls without MS, supporting authors’ suspicion that MS may protect against Alzheimer’s disease. Understanding how MS does this may drive new treatment strategies, said the authors of the study, which was published online in Annals of Neurology. Regarding current treatments, they added, the availability of new disease-modifying Alzheimer’s disease therapies increases the importance of early diagnosis in cognitively impaired people including those with MS.

Confirmatory Studies Needed

“Replication and confirmation of these findings, including in studies representative of the real-world Alzheimer’s population in race/ethnicity and sex/gender, are needed before any clinical implications can be drawn,” said Claire Sexton, DPhil, Alzheimer’s Association senior director of scientific programs and outreach. She was not involved with the study but was asked to comment.

The study’s most important immediate implication, said Dr. Sexton, is that it “opens the door to questions about why MS may be associated with Alzheimer’s risk.”

Alzheimer's Association

Anecdotal Observation

Although life expectancy for people with MS is increasing, the authors, led by Matthew R. Brier, MD, PhD, an assistant professor at Washington University in St. Louis, Missouri, said they have seen no concomitant rise in Alzheimer’s disease dementia among their patients with MS. This anecdotal observation fueled their hypothesis that Alzheimer’s disease pathology occurs less frequently in this population.

To test their hypothesis, the investigators sequentially enrolled 100 patients with MS (age 60 years or older), along with 300 non-MS controls matched for age, sex, apolipoprotein E (apoE) proteotype, and cognitive status. All participants underwent the Mini-Mental State Examination (MMSE) and PrecivityAD2 (C2N Diagnostics) blood testing.

Washngton University

Possible Explanations

The authors hypothesized that the lower rate of amyloid pathology observed in their patients with MS may stem from the following possibly overlapping mechanisms:

• MS components, such as persistent perilesional immune activity, may inhibit amyloid beta deposition or facilitate its clearance.
• Exposure to MS drugs may impact Alzheimer’s disease pathology. Most study patients with MS were exposed to beta interferons or glatiramer acetate, the authors noted, and 39 had switched to high-efficacy medications such as B-cell depleting therapies and natalizumab.
• MS’s genetic signature may protect against AD.

“Investigating these ideas would advance our understanding of the relationship between MS and Alzheimer’s, and potentially inform avenues for treatment,” said Dr. Sexton. In this regard, the Alzheimer’s Association has funded an ongoing study examining a drug currently used to promote myelin formation in individuals with MS in genetically engineered Alzheimer’s-like mice. Additional Association-funded studies that examine inflammation also may improve understanding of the mechanisms that may link these diseases, said Dr. Sexton. 

The study authors added that unusual cases, such as a study patient who had high amyloid burden by PET but negative APS2 and tau PET, also may shed light on interactions between MS, amyloid pathology, and tau pathology.

Limitations of the present study include the fact that plasma Alzheimer’s disease biomarkers are potentially affected by other conditions as well, according to a study published in Nature Medicine. Additional shortcomings include the MS cohort’s relatively small size and lack of diagnostic confirmation by cerebrospinal fluid. Although MMSE scores among patients with MS were slightly lower, the authors added, this disparity would lead one to expect more, not less, amyloid pathology among these patients if their cognitive impairment resulted from Alzheimer’s disease.

Dr. Sexton reported no relevant financial interests.

The study was supported by the Hope Center for Neurological Disorders at Washington University in St. Louis and by C2N Diagnostics. Washington University in St. Louis holds equity in C2N Diagnostics and may receive royalties resulting from use of PrecivityAD2.

In a recent study, patients with multiple sclerosis (MS) had half the rate of amyloid beta pathology versus matched controls without MS, supporting authors’ suspicion that MS may protect against Alzheimer’s disease. Understanding how MS does this may drive new treatment strategies, said the authors of the study, which was published online in Annals of Neurology. Regarding current treatments, they added, the availability of new disease-modifying Alzheimer’s disease therapies increases the importance of early diagnosis in cognitively impaired people including those with MS.

Confirmatory Studies Needed

“Replication and confirmation of these findings, including in studies representative of the real-world Alzheimer’s population in race/ethnicity and sex/gender, are needed before any clinical implications can be drawn,” said Claire Sexton, DPhil, Alzheimer’s Association senior director of scientific programs and outreach. She was not involved with the study but was asked to comment.

The study’s most important immediate implication, said Dr. Sexton, is that it “opens the door to questions about why MS may be associated with Alzheimer’s risk.”

Alzheimer's Association

Anecdotal Observation

Although life expectancy for people with MS is increasing, the authors, led by Matthew R. Brier, MD, PhD, an assistant professor at Washington University in St. Louis, Missouri, said they have seen no concomitant rise in Alzheimer’s disease dementia among their patients with MS. This anecdotal observation fueled their hypothesis that Alzheimer’s disease pathology occurs less frequently in this population.

To test their hypothesis, the investigators sequentially enrolled 100 patients with MS (age 60 years or older), along with 300 non-MS controls matched for age, sex, apolipoprotein E (apoE) proteotype, and cognitive status. All participants underwent the Mini-Mental State Examination (MMSE) and PrecivityAD2 (C2N Diagnostics) blood testing.

Washngton University

Possible Explanations

The authors hypothesized that the lower rate of amyloid pathology observed in their patients with MS may stem from the following possibly overlapping mechanisms:

• MS components, such as persistent perilesional immune activity, may inhibit amyloid beta deposition or facilitate its clearance.
• Exposure to MS drugs may impact Alzheimer’s disease pathology. Most study patients with MS were exposed to beta interferons or glatiramer acetate, the authors noted, and 39 had switched to high-efficacy medications such as B-cell depleting therapies and natalizumab.
• MS’s genetic signature may protect against AD.

“Investigating these ideas would advance our understanding of the relationship between MS and Alzheimer’s, and potentially inform avenues for treatment,” said Dr. Sexton. In this regard, the Alzheimer’s Association has funded an ongoing study examining a drug currently used to promote myelin formation in individuals with MS in genetically engineered Alzheimer’s-like mice. Additional Association-funded studies that examine inflammation also may improve understanding of the mechanisms that may link these diseases, said Dr. Sexton. 

The study authors added that unusual cases, such as a study patient who had high amyloid burden by PET but negative APS2 and tau PET, also may shed light on interactions between MS, amyloid pathology, and tau pathology.

Limitations of the present study include the fact that plasma Alzheimer’s disease biomarkers are potentially affected by other conditions as well, according to a study published in Nature Medicine. Additional shortcomings include the MS cohort’s relatively small size and lack of diagnostic confirmation by cerebrospinal fluid. Although MMSE scores among patients with MS were slightly lower, the authors added, this disparity would lead one to expect more, not less, amyloid pathology among these patients if their cognitive impairment resulted from Alzheimer’s disease.

Dr. Sexton reported no relevant financial interests.

The study was supported by the Hope Center for Neurological Disorders at Washington University in St. Louis and by C2N Diagnostics. Washington University in St. Louis holds equity in C2N Diagnostics and may receive royalties resulting from use of PrecivityAD2.

In a recent study, patients with multiple sclerosis (MS) had half the rate of amyloid beta pathology versus matched controls without MS, supporting authors’ suspicion that MS may protect against Alzheimer’s disease. Understanding how MS does this may drive new treatment strategies, said the authors of the study, which was published online in Annals of Neurology. Regarding current treatments, they added, the availability of new disease-modifying Alzheimer’s disease therapies increases the importance of early diagnosis in cognitively impaired people including those with MS.

Confirmatory Studies Needed

“Replication and confirmation of these findings, including in studies representative of the real-world Alzheimer’s population in race/ethnicity and sex/gender, are needed before any clinical implications can be drawn,” said Claire Sexton, DPhil, Alzheimer’s Association senior director of scientific programs and outreach. She was not involved with the study but was asked to comment.

The study’s most important immediate implication, said Dr. Sexton, is that it “opens the door to questions about why MS may be associated with Alzheimer’s risk.”

Alzheimer's Association

Anecdotal Observation

Although life expectancy for people with MS is increasing, the authors, led by Matthew R. Brier, MD, PhD, an assistant professor at Washington University in St. Louis, Missouri, said they have seen no concomitant rise in Alzheimer’s disease dementia among their patients with MS. This anecdotal observation fueled their hypothesis that Alzheimer’s disease pathology occurs less frequently in this population.

To test their hypothesis, the investigators sequentially enrolled 100 patients with MS (age 60 years or older), along with 300 non-MS controls matched for age, sex, apolipoprotein E (apoE) proteotype, and cognitive status. All participants underwent the Mini-Mental State Examination (MMSE) and PrecivityAD2 (C2N Diagnostics) blood testing.

Washngton University

Possible Explanations

The authors hypothesized that the lower rate of amyloid pathology observed in their patients with MS may stem from the following possibly overlapping mechanisms:

• MS components, such as persistent perilesional immune activity, may inhibit amyloid beta deposition or facilitate its clearance.
• Exposure to MS drugs may impact Alzheimer’s disease pathology. Most study patients with MS were exposed to beta interferons or glatiramer acetate, the authors noted, and 39 had switched to high-efficacy medications such as B-cell depleting therapies and natalizumab.
• MS’s genetic signature may protect against AD.

“Investigating these ideas would advance our understanding of the relationship between MS and Alzheimer’s, and potentially inform avenues for treatment,” said Dr. Sexton. In this regard, the Alzheimer’s Association has funded an ongoing study examining a drug currently used to promote myelin formation in individuals with MS in genetically engineered Alzheimer’s-like mice. Additional Association-funded studies that examine inflammation also may improve understanding of the mechanisms that may link these diseases, said Dr. Sexton. 

The study authors added that unusual cases, such as a study patient who had high amyloid burden by PET but negative APS2 and tau PET, also may shed light on interactions between MS, amyloid pathology, and tau pathology.

Limitations of the present study include the fact that plasma Alzheimer’s disease biomarkers are potentially affected by other conditions as well, according to a study published in Nature Medicine. Additional shortcomings include the MS cohort’s relatively small size and lack of diagnostic confirmation by cerebrospinal fluid. Although MMSE scores among patients with MS were slightly lower, the authors added, this disparity would lead one to expect more, not less, amyloid pathology among these patients if their cognitive impairment resulted from Alzheimer’s disease.

Dr. Sexton reported no relevant financial interests.

The study was supported by the Hope Center for Neurological Disorders at Washington University in St. Louis and by C2N Diagnostics. Washington University in St. Louis holds equity in C2N Diagnostics and may receive royalties resulting from use of PrecivityAD2.