Long or irregular menstrual cycles in relatively young women are linked an increased risk of both prevalent and incident nonalcoholic fatty liver disease (NAFLD), according to a cross-sectional study that included data on more than 70,000 women.

“Our results indicate that menstrual irregularity, which is easier to diagnose and usually presented earlier than PCOS [polycystic ovary syndrome] highlights the possibility of identifying premenopausal women at risk of developing NAFLD,” reported a team of authors primarily from Sungkyunkwan University, Seoul, South Korea.

The study evaluated women aged younger than 40 years who were participating in the Kangbuk Samsung Health Study, which involves a comprehensive biennial health examination at health centers in South Korea. Of the 135,090 women enrolled over a 6-year period who had at least one follow-up examination, 72,092 were available for analysis after excluding for a sizable list of confounding factors such as liver disease and infections; exposure to steatogenic medications, such as corticosteroids; hysterectomy; and pregnancy.
 

NAFLD prevalence climbs with longer menses

Of these women, 36.378 (27.7%) had menstrual cycles of 26-30 days and were identified as the index group. The prevalence of NAFLD in this group was 5.8%. For those with a menstrual cycle of 31-39 days, the prevalence rate climbed to 7.2%. For those with a menstrual cycle of at least 40 days or too irregular to estimate, the prevalence was 9.7%. The prevalence was 7.1% for those with a menstrual cycle less than 21 days.

The results of this study were published in the Journal of Clinical Endocrinology & Metabolism.

In those without NAFLD at baseline who were then followed for a mean of 4.4 years, there were 4,524 incident cases of NAFLD. Incidence density was calculated per 103 patient-years. In the index group, the rate was 18.4. It climbed to 20.2 for those with a menstrual cycle of 31-39 days and then to 22.9 for those with a menstrual cycle of at least 40 days. For those with a cycle of fewer than 21 days, the rate was 26.8.

After adjusting for age, body mass index, insulin resistance, and other confounders, the hazard ratio for incident NAFLD for those with long or irregular menstrual cycles compared with the incident group corresponded with a 22% increased risk (HR, 1.22; 95% confidence interval, 1.14-1.31). When calculated in a time-dependent analysis, the risk of NAFLD was increased by almost 50% (HR, 1.49; 95% CI, 1.38-1.60).


 

Risk persists with PCOS exclusion

PCOS has previously been associated with increased risk of NAFLD, but the association between long or irregular menstrual cycles and NAFLD persisted after women with PCOS were excluded.

The mechanism that links menstrual irregularity with NAFLD is unclear, but the investigators said that estrogen exposure is implicated. In addition to a previously reported associated between low estradiol levels and antiestrogens such as tamoxifen with increased risk of NAFLD, they cited studies associating estrogen replacement therapy with a reduced risk of NAFLD. The role of estrogen in suppressing inflammation, oxidative stress, and insulin resistance are all activities that might link more regular menses with a reduced risk of NAFLD, the authors contended.

Women older than 40 years were excluded from this analysis to reduce the possibility of perimenopausal changes as a confounding factor.

Of study limitations acknowledged by the investigators, the presence of NAFLD was diagnosed on ultrasonography rather than histology. Information on sex hormone or prolactin levels was not captured in relation to NAFLD incidence, and the lack of exposure to estrogen replacement therapy and oral contraceptives was based on self-reports from the participants.

Still, the large study size and the consistency of results after adjustment for multiple risk factors argue that long and irregular menstrual cycles do identify women at risk for NAFLD. One implication is that irregular menses can be a marker for NAFLD risk.

“Our findings do not prove a causal relationship, but they show that long or irregular menstrual cycles were significantly associated with an increased risk of developing NAFLD,” said Seungho Ryu, MD, PhD, a professor at the Sungkyunkwan University. Senior author of this study, Dr. Ryu emphasized in an interview that the association “was not explained by obesity or any other risk factor for NAFLD.”
 

Lifestyle changes may lower risk

The message is that “young women with long or irregular menstrual cycles may benefit from lifestyle changes to reduce the risk of NAFLD,” Dr. Ryu stated.

The Study of Women’s Health Across the Nation, which was started in 1994, has not evaluated NAFLD, but it did show a relationship between longer menstrual cycles and more cardiometabolic risk factors, according to Nanette Santoro MD, professor and chair, department of obstetrics & gynecology, University of Colorado at Denver, Aurora.

This suggests that others are “thinking along the same lines,” but in discussing this study with this news organization, she characterized some of the design elements as well as some of the findings in this study as “peculiar.”

In addition to a “very, very narrow definition of regular cycles,” she questioned the consistent hazard ratio for NAFLD for those with long cycles relative to other types of irregular menses. Presuming that the group with longer cycles would have included at least some patients with undiagnosed PCOS, she was would have expected that the risk would have been highest in this group. While conceding that differences in body composition of Korean women is a potential explanation for this apparent discrepancy, “I would like to see confirmed in other samples of women with more detailed metabolic assessments to understand who is at risk,” she said.

Not least problematic for the strength of the conclusions, the hazard ratio for NAFLD among women with long or irregular menstrual cycles was “pretty low.” She described this as a level at which the risk “is very susceptible to confounding and unlikely to influence clinical practice.”

Anuja Dokras, MD, PHD, a professor of obstetrics and gynecology and director of the PCOS Center at the University of Pennsylvania, Philadelphia, also questioned whether undiagnosed PCOS might have skewed the data.

“There is increasing data on the association between PCOS and NAFLD. Irregular menses is a key criterion for PCOS, and PCOS is the commonest reason for anovulation,” she said. Dr. Dokras therefore considered it possible that patients with unrecognized PCOS were included in the study, weakening the claim that risk of NAFLD and long menstrual cycles remains significant after controlling for PCOS.

Dr. Ryu and coinvestigators, Dr. Santoro, and Dr. Dokras reported no potential conflicts of interest.

Long or irregular menstrual cycles in relatively young women are linked an increased risk of both prevalent and incident nonalcoholic fatty liver disease (NAFLD), according to a cross-sectional study that included data on more than 70,000 women.

“Our results indicate that menstrual irregularity, which is easier to diagnose and usually presented earlier than PCOS [polycystic ovary syndrome] highlights the possibility of identifying premenopausal women at risk of developing NAFLD,” reported a team of authors primarily from Sungkyunkwan University, Seoul, South Korea.

The study evaluated women aged younger than 40 years who were participating in the Kangbuk Samsung Health Study, which involves a comprehensive biennial health examination at health centers in South Korea. Of the 135,090 women enrolled over a 6-year period who had at least one follow-up examination, 72,092 were available for analysis after excluding for a sizable list of confounding factors such as liver disease and infections; exposure to steatogenic medications, such as corticosteroids; hysterectomy; and pregnancy.
 

NAFLD prevalence climbs with longer menses

Of these women, 36.378 (27.7%) had menstrual cycles of 26-30 days and were identified as the index group. The prevalence of NAFLD in this group was 5.8%. For those with a menstrual cycle of 31-39 days, the prevalence rate climbed to 7.2%. For those with a menstrual cycle of at least 40 days or too irregular to estimate, the prevalence was 9.7%. The prevalence was 7.1% for those with a menstrual cycle less than 21 days.

The results of this study were published in the Journal of Clinical Endocrinology & Metabolism.

In those without NAFLD at baseline who were then followed for a mean of 4.4 years, there were 4,524 incident cases of NAFLD. Incidence density was calculated per 103 patient-years. In the index group, the rate was 18.4. It climbed to 20.2 for those with a menstrual cycle of 31-39 days and then to 22.9 for those with a menstrual cycle of at least 40 days. For those with a cycle of fewer than 21 days, the rate was 26.8.

After adjusting for age, body mass index, insulin resistance, and other confounders, the hazard ratio for incident NAFLD for those with long or irregular menstrual cycles compared with the incident group corresponded with a 22% increased risk (HR, 1.22; 95% confidence interval, 1.14-1.31). When calculated in a time-dependent analysis, the risk of NAFLD was increased by almost 50% (HR, 1.49; 95% CI, 1.38-1.60).


 

Risk persists with PCOS exclusion

PCOS has previously been associated with increased risk of NAFLD, but the association between long or irregular menstrual cycles and NAFLD persisted after women with PCOS were excluded.

The mechanism that links menstrual irregularity with NAFLD is unclear, but the investigators said that estrogen exposure is implicated. In addition to a previously reported associated between low estradiol levels and antiestrogens such as tamoxifen with increased risk of NAFLD, they cited studies associating estrogen replacement therapy with a reduced risk of NAFLD. The role of estrogen in suppressing inflammation, oxidative stress, and insulin resistance are all activities that might link more regular menses with a reduced risk of NAFLD, the authors contended.

Women older than 40 years were excluded from this analysis to reduce the possibility of perimenopausal changes as a confounding factor.

Of study limitations acknowledged by the investigators, the presence of NAFLD was diagnosed on ultrasonography rather than histology. Information on sex hormone or prolactin levels was not captured in relation to NAFLD incidence, and the lack of exposure to estrogen replacement therapy and oral contraceptives was based on self-reports from the participants.

Still, the large study size and the consistency of results after adjustment for multiple risk factors argue that long and irregular menstrual cycles do identify women at risk for NAFLD. One implication is that irregular menses can be a marker for NAFLD risk.

“Our findings do not prove a causal relationship, but they show that long or irregular menstrual cycles were significantly associated with an increased risk of developing NAFLD,” said Seungho Ryu, MD, PhD, a professor at the Sungkyunkwan University. Senior author of this study, Dr. Ryu emphasized in an interview that the association “was not explained by obesity or any other risk factor for NAFLD.”
 

Lifestyle changes may lower risk

The message is that “young women with long or irregular menstrual cycles may benefit from lifestyle changes to reduce the risk of NAFLD,” Dr. Ryu stated.

The Study of Women’s Health Across the Nation, which was started in 1994, has not evaluated NAFLD, but it did show a relationship between longer menstrual cycles and more cardiometabolic risk factors, according to Nanette Santoro MD, professor and chair, department of obstetrics & gynecology, University of Colorado at Denver, Aurora.

This suggests that others are “thinking along the same lines,” but in discussing this study with this news organization, she characterized some of the design elements as well as some of the findings in this study as “peculiar.”

In addition to a “very, very narrow definition of regular cycles,” she questioned the consistent hazard ratio for NAFLD for those with long cycles relative to other types of irregular menses. Presuming that the group with longer cycles would have included at least some patients with undiagnosed PCOS, she was would have expected that the risk would have been highest in this group. While conceding that differences in body composition of Korean women is a potential explanation for this apparent discrepancy, “I would like to see confirmed in other samples of women with more detailed metabolic assessments to understand who is at risk,” she said.

Not least problematic for the strength of the conclusions, the hazard ratio for NAFLD among women with long or irregular menstrual cycles was “pretty low.” She described this as a level at which the risk “is very susceptible to confounding and unlikely to influence clinical practice.”

Anuja Dokras, MD, PHD, a professor of obstetrics and gynecology and director of the PCOS Center at the University of Pennsylvania, Philadelphia, also questioned whether undiagnosed PCOS might have skewed the data.

“There is increasing data on the association between PCOS and NAFLD. Irregular menses is a key criterion for PCOS, and PCOS is the commonest reason for anovulation,” she said. Dr. Dokras therefore considered it possible that patients with unrecognized PCOS were included in the study, weakening the claim that risk of NAFLD and long menstrual cycles remains significant after controlling for PCOS.

Dr. Ryu and coinvestigators, Dr. Santoro, and Dr. Dokras reported no potential conflicts of interest.

Long or irregular menstrual cycles in relatively young women are linked an increased risk of both prevalent and incident nonalcoholic fatty liver disease (NAFLD), according to a cross-sectional study that included data on more than 70,000 women.

“Our results indicate that menstrual irregularity, which is easier to diagnose and usually presented earlier than PCOS [polycystic ovary syndrome] highlights the possibility of identifying premenopausal women at risk of developing NAFLD,” reported a team of authors primarily from Sungkyunkwan University, Seoul, South Korea.

The study evaluated women aged younger than 40 years who were participating in the Kangbuk Samsung Health Study, which involves a comprehensive biennial health examination at health centers in South Korea. Of the 135,090 women enrolled over a 6-year period who had at least one follow-up examination, 72,092 were available for analysis after excluding for a sizable list of confounding factors such as liver disease and infections; exposure to steatogenic medications, such as corticosteroids; hysterectomy; and pregnancy.
 

NAFLD prevalence climbs with longer menses

Of these women, 36.378 (27.7%) had menstrual cycles of 26-30 days and were identified as the index group. The prevalence of NAFLD in this group was 5.8%. For those with a menstrual cycle of 31-39 days, the prevalence rate climbed to 7.2%. For those with a menstrual cycle of at least 40 days or too irregular to estimate, the prevalence was 9.7%. The prevalence was 7.1% for those with a menstrual cycle less than 21 days.

The results of this study were published in the Journal of Clinical Endocrinology & Metabolism.

In those without NAFLD at baseline who were then followed for a mean of 4.4 years, there were 4,524 incident cases of NAFLD. Incidence density was calculated per 103 patient-years. In the index group, the rate was 18.4. It climbed to 20.2 for those with a menstrual cycle of 31-39 days and then to 22.9 for those with a menstrual cycle of at least 40 days. For those with a cycle of fewer than 21 days, the rate was 26.8.

After adjusting for age, body mass index, insulin resistance, and other confounders, the hazard ratio for incident NAFLD for those with long or irregular menstrual cycles compared with the incident group corresponded with a 22% increased risk (HR, 1.22; 95% confidence interval, 1.14-1.31). When calculated in a time-dependent analysis, the risk of NAFLD was increased by almost 50% (HR, 1.49; 95% CI, 1.38-1.60).


 

Risk persists with PCOS exclusion

PCOS has previously been associated with increased risk of NAFLD, but the association between long or irregular menstrual cycles and NAFLD persisted after women with PCOS were excluded.

The mechanism that links menstrual irregularity with NAFLD is unclear, but the investigators said that estrogen exposure is implicated. In addition to a previously reported associated between low estradiol levels and antiestrogens such as tamoxifen with increased risk of NAFLD, they cited studies associating estrogen replacement therapy with a reduced risk of NAFLD. The role of estrogen in suppressing inflammation, oxidative stress, and insulin resistance are all activities that might link more regular menses with a reduced risk of NAFLD, the authors contended.

Women older than 40 years were excluded from this analysis to reduce the possibility of perimenopausal changes as a confounding factor.

Of study limitations acknowledged by the investigators, the presence of NAFLD was diagnosed on ultrasonography rather than histology. Information on sex hormone or prolactin levels was not captured in relation to NAFLD incidence, and the lack of exposure to estrogen replacement therapy and oral contraceptives was based on self-reports from the participants.

Still, the large study size and the consistency of results after adjustment for multiple risk factors argue that long and irregular menstrual cycles do identify women at risk for NAFLD. One implication is that irregular menses can be a marker for NAFLD risk.

“Our findings do not prove a causal relationship, but they show that long or irregular menstrual cycles were significantly associated with an increased risk of developing NAFLD,” said Seungho Ryu, MD, PhD, a professor at the Sungkyunkwan University. Senior author of this study, Dr. Ryu emphasized in an interview that the association “was not explained by obesity or any other risk factor for NAFLD.”
 

Lifestyle changes may lower risk

The message is that “young women with long or irregular menstrual cycles may benefit from lifestyle changes to reduce the risk of NAFLD,” Dr. Ryu stated.

The Study of Women’s Health Across the Nation, which was started in 1994, has not evaluated NAFLD, but it did show a relationship between longer menstrual cycles and more cardiometabolic risk factors, according to Nanette Santoro MD, professor and chair, department of obstetrics & gynecology, University of Colorado at Denver, Aurora.

This suggests that others are “thinking along the same lines,” but in discussing this study with this news organization, she characterized some of the design elements as well as some of the findings in this study as “peculiar.”

In addition to a “very, very narrow definition of regular cycles,” she questioned the consistent hazard ratio for NAFLD for those with long cycles relative to other types of irregular menses. Presuming that the group with longer cycles would have included at least some patients with undiagnosed PCOS, she was would have expected that the risk would have been highest in this group. While conceding that differences in body composition of Korean women is a potential explanation for this apparent discrepancy, “I would like to see confirmed in other samples of women with more detailed metabolic assessments to understand who is at risk,” she said.

Not least problematic for the strength of the conclusions, the hazard ratio for NAFLD among women with long or irregular menstrual cycles was “pretty low.” She described this as a level at which the risk “is very susceptible to confounding and unlikely to influence clinical practice.”

Anuja Dokras, MD, PHD, a professor of obstetrics and gynecology and director of the PCOS Center at the University of Pennsylvania, Philadelphia, also questioned whether undiagnosed PCOS might have skewed the data.

“There is increasing data on the association between PCOS and NAFLD. Irregular menses is a key criterion for PCOS, and PCOS is the commonest reason for anovulation,” she said. Dr. Dokras therefore considered it possible that patients with unrecognized PCOS were included in the study, weakening the claim that risk of NAFLD and long menstrual cycles remains significant after controlling for PCOS.

Dr. Ryu and coinvestigators, Dr. Santoro, and Dr. Dokras reported no potential conflicts of interest.

The rate of recurrence of the rare but aggressive skin cancer Merkel cell carcinoma (MCC) is markedly higher than that for invasive melanoma, squamous cell carcinoma, or basal cell carcinoma, and more than half of all patients with stage IV disease will have a recurrence within 1 year of definitive therapy, results of a new study show.

A study of 618 patients with MCC who were enrolled in a Seattle-based data repository shows that among all patients the 5-year recurrence rate was 40%. The risk of recurrence within the first year was 11% for patients with pathologic stage I disease, 33% for those with stage IIA/IIB disease, 45% for those with stage IIIB disease, and 58% for patients with pathologic stage IV MCC.

Approximately 95% of all recurrences happened within 3 years of the initial diagnosis, report Aubriana McEvoy, MD, from the University of Washington in Seattle, and colleagues.

“This cohort study indicates that the highest yield (and likely most cost-effective) time period for detecting MCC recurrence is 1-3 years after diagnosis,” they write in a study published online in JAMA Dermatology.

The estimated annual incidence of MCC in the United States in 2018 was 2,000 according to the American Cancer Society. The annual incidence rate is rising rapidly, however, and is estimated to reach 3,284 by 2025, McEvoy and colleagues write.

Although MCC is known to have high recurrence rates and is associated with a higher mortality rate than malignant melanoma, recurrence rate data are not captured by either the Surveillance, Epidemiology, and End Results (SEER) database or by the National Cancer Database. As a result, estimates of recurrence rates with MCC have been all over the map, ranging from 27% to 77%, depending on the population studied.

But as senior author Paul Nghiem, MD, PhD, professor and chair of dermatology at the University of Washington, Seattle, told this news organization, recurrence rates over time in their study were remarkably consistent.

“The biggest surprise to me was that, when we broke our nearly 20-year cohort into three 5- or 6-year chunks, every one of the groups had a 40% recurrence rate, within 1%. So we feel really confident that’s the right number,” he said.

Dr. Nghiem and colleagues report that, in contrast to patients with MCC, approximately 19% of patients with melanoma will have a recurrence, as will an estimated 5%-9% of patients with squamous cell carcinoma and 1%-10% of patients with basal cell carcinoma.

The fact that recurrence rates of MCC have remained stable over time despite presumed improvements in definitive therapy is disappointing, Dr. Nghiem acknowledged. He noted that it’s still unclear whether immunotherapy will have the same dramatic effect on survival rates for patients with MCC as it has for patients with malignant melanoma.

The high recurrence rates following definitive therapy for patients with early-stage disease was a novel finding, commented Shawn Demehri, MD, PhD, director of the high-risk skin cancer clinic at Massachusetts General Hospital in Boston.

“When you’re looking at patients with stage I or stage II, and they have definitive surgery but still have recurrences at a higher rate than melanoma, it brings home the point that these are among the most aggressive tumors of the skin,” he said in an interview.

The high recurrence rates seen with MCC are attributable to a variety of factors.

“This is a rare cancer of mostly older individuals with a lot of comorbidities, and also a cancer that, even though it is a primary cancer, might be detected a little later than even a melanoma primary tumor, just because of the nature of the neuroendocrine tumor cells,” he said.

Dr. Demehri was not involved in the study.
 

Prospective cohort

The study cohort consisted of 618 patients with MCC. The median age of the patients was 69, and 227 (37%) were women. The patients were enrolled within 6 months of their diagnosis in the prospective data repository from 2003 through 2019. Of this group, 223 had a recurrence of MCC.

As noted, there was a high risk of recurrence within 1 year, ranging from 11% for patients with pathologic stage I tumors to 58% for those with stage IV disease, and 95% of all recurrences occurred within 3 years of definitive therapy.

To get a better picture of the natural history of MCC recurrence, the investigators studied a cohort of patients with pathologically confirmed MCC who were prospectively enrolled from January 2003 through April 2019 in a data repository maintained at the University of Washington.

In addition to disease stage, factors associated with increased recurrence risk in univariable analyses include immunosuppression (hazard ratio, 2.4; P < .001), male sex (HR, 1.9; P < .001), known primary lesion among patients with clinically detectable nodal disease (HR, 2.3; P = .001), and older age (HR, 1.1, P = .06 for each 10-year increase).

Of the 187 patients in the cohort who died during the study, 121 died from MCC. At 4 years after diagnosis, MCC-specific survival rates were 95% for patients with pathologic stage I, 84% with stage IIA/IIB, 80% with stage IIIA, 58% with stage IIIB, and 41% with stage IV.

Evidence supports close monitoring within the first 3 years for patients with stage I-II MCC. Local recurrence within or adjacent to the primary tumor scar was associated with a 5-year MCC-specific survival rate of 85%, compared with 88% of patients with stage I or II disease who did not have recurrences.

“Because more than 90% of MCC recurrences arise within 3 years, it is appropriate to adjust surveillance intensity accordingly. Stage- and time-specific recurrence data can assist in appropriately focusing surveillance resources on patients and time intervals in which recurrence risk is highest,” the authors wrote.

“If you’re a patient who has not had your cancer come back for 3, 4, or 5 years, you can really cut down on the intensity of your follow-up and scans,” Dr. Nghiem said.

“We do now have two excellent blood tests that are working very well, and we have really good ways to detect the cancer coming back early, and that’s important, because we have potentially curative therapies that tend to work better if you catch the cancer early,” he said.

The study was supported by the National Institutes of Health. Dr. Nghiem reported personal fees and institutional support outside the study from several companies and patents for Merkel cell therapies with the University of Washington and University of Denmark. Dr. Demehri has disclosed no relevant financial relationships.

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

The rate of recurrence of the rare but aggressive skin cancer Merkel cell carcinoma (MCC) is markedly higher than that for invasive melanoma, squamous cell carcinoma, or basal cell carcinoma, and more than half of all patients with stage IV disease will have a recurrence within 1 year of definitive therapy, results of a new study show.

A study of 618 patients with MCC who were enrolled in a Seattle-based data repository shows that among all patients the 5-year recurrence rate was 40%. The risk of recurrence within the first year was 11% for patients with pathologic stage I disease, 33% for those with stage IIA/IIB disease, 45% for those with stage IIIB disease, and 58% for patients with pathologic stage IV MCC.

Approximately 95% of all recurrences happened within 3 years of the initial diagnosis, report Aubriana McEvoy, MD, from the University of Washington in Seattle, and colleagues.

“This cohort study indicates that the highest yield (and likely most cost-effective) time period for detecting MCC recurrence is 1-3 years after diagnosis,” they write in a study published online in JAMA Dermatology.

The estimated annual incidence of MCC in the United States in 2018 was 2,000 according to the American Cancer Society. The annual incidence rate is rising rapidly, however, and is estimated to reach 3,284 by 2025, McEvoy and colleagues write.

Although MCC is known to have high recurrence rates and is associated with a higher mortality rate than malignant melanoma, recurrence rate data are not captured by either the Surveillance, Epidemiology, and End Results (SEER) database or by the National Cancer Database. As a result, estimates of recurrence rates with MCC have been all over the map, ranging from 27% to 77%, depending on the population studied.

But as senior author Paul Nghiem, MD, PhD, professor and chair of dermatology at the University of Washington, Seattle, told this news organization, recurrence rates over time in their study were remarkably consistent.

“The biggest surprise to me was that, when we broke our nearly 20-year cohort into three 5- or 6-year chunks, every one of the groups had a 40% recurrence rate, within 1%. So we feel really confident that’s the right number,” he said.

Dr. Nghiem and colleagues report that, in contrast to patients with MCC, approximately 19% of patients with melanoma will have a recurrence, as will an estimated 5%-9% of patients with squamous cell carcinoma and 1%-10% of patients with basal cell carcinoma.

The fact that recurrence rates of MCC have remained stable over time despite presumed improvements in definitive therapy is disappointing, Dr. Nghiem acknowledged. He noted that it’s still unclear whether immunotherapy will have the same dramatic effect on survival rates for patients with MCC as it has for patients with malignant melanoma.

The high recurrence rates following definitive therapy for patients with early-stage disease was a novel finding, commented Shawn Demehri, MD, PhD, director of the high-risk skin cancer clinic at Massachusetts General Hospital in Boston.

“When you’re looking at patients with stage I or stage II, and they have definitive surgery but still have recurrences at a higher rate than melanoma, it brings home the point that these are among the most aggressive tumors of the skin,” he said in an interview.

The high recurrence rates seen with MCC are attributable to a variety of factors.

“This is a rare cancer of mostly older individuals with a lot of comorbidities, and also a cancer that, even though it is a primary cancer, might be detected a little later than even a melanoma primary tumor, just because of the nature of the neuroendocrine tumor cells,” he said.

Dr. Demehri was not involved in the study.
 

Prospective cohort

The study cohort consisted of 618 patients with MCC. The median age of the patients was 69, and 227 (37%) were women. The patients were enrolled within 6 months of their diagnosis in the prospective data repository from 2003 through 2019. Of this group, 223 had a recurrence of MCC.

As noted, there was a high risk of recurrence within 1 year, ranging from 11% for patients with pathologic stage I tumors to 58% for those with stage IV disease, and 95% of all recurrences occurred within 3 years of definitive therapy.

To get a better picture of the natural history of MCC recurrence, the investigators studied a cohort of patients with pathologically confirmed MCC who were prospectively enrolled from January 2003 through April 2019 in a data repository maintained at the University of Washington.

In addition to disease stage, factors associated with increased recurrence risk in univariable analyses include immunosuppression (hazard ratio, 2.4; P < .001), male sex (HR, 1.9; P < .001), known primary lesion among patients with clinically detectable nodal disease (HR, 2.3; P = .001), and older age (HR, 1.1, P = .06 for each 10-year increase).

Of the 187 patients in the cohort who died during the study, 121 died from MCC. At 4 years after diagnosis, MCC-specific survival rates were 95% for patients with pathologic stage I, 84% with stage IIA/IIB, 80% with stage IIIA, 58% with stage IIIB, and 41% with stage IV.

Evidence supports close monitoring within the first 3 years for patients with stage I-II MCC. Local recurrence within or adjacent to the primary tumor scar was associated with a 5-year MCC-specific survival rate of 85%, compared with 88% of patients with stage I or II disease who did not have recurrences.

“Because more than 90% of MCC recurrences arise within 3 years, it is appropriate to adjust surveillance intensity accordingly. Stage- and time-specific recurrence data can assist in appropriately focusing surveillance resources on patients and time intervals in which recurrence risk is highest,” the authors wrote.

“If you’re a patient who has not had your cancer come back for 3, 4, or 5 years, you can really cut down on the intensity of your follow-up and scans,” Dr. Nghiem said.

“We do now have two excellent blood tests that are working very well, and we have really good ways to detect the cancer coming back early, and that’s important, because we have potentially curative therapies that tend to work better if you catch the cancer early,” he said.

The study was supported by the National Institutes of Health. Dr. Nghiem reported personal fees and institutional support outside the study from several companies and patents for Merkel cell therapies with the University of Washington and University of Denmark. Dr. Demehri has disclosed no relevant financial relationships.

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

The rate of recurrence of the rare but aggressive skin cancer Merkel cell carcinoma (MCC) is markedly higher than that for invasive melanoma, squamous cell carcinoma, or basal cell carcinoma, and more than half of all patients with stage IV disease will have a recurrence within 1 year of definitive therapy, results of a new study show.

A study of 618 patients with MCC who were enrolled in a Seattle-based data repository shows that among all patients the 5-year recurrence rate was 40%. The risk of recurrence within the first year was 11% for patients with pathologic stage I disease, 33% for those with stage IIA/IIB disease, 45% for those with stage IIIB disease, and 58% for patients with pathologic stage IV MCC.

Approximately 95% of all recurrences happened within 3 years of the initial diagnosis, report Aubriana McEvoy, MD, from the University of Washington in Seattle, and colleagues.

“This cohort study indicates that the highest yield (and likely most cost-effective) time period for detecting MCC recurrence is 1-3 years after diagnosis,” they write in a study published online in JAMA Dermatology.

The estimated annual incidence of MCC in the United States in 2018 was 2,000 according to the American Cancer Society. The annual incidence rate is rising rapidly, however, and is estimated to reach 3,284 by 2025, McEvoy and colleagues write.

Although MCC is known to have high recurrence rates and is associated with a higher mortality rate than malignant melanoma, recurrence rate data are not captured by either the Surveillance, Epidemiology, and End Results (SEER) database or by the National Cancer Database. As a result, estimates of recurrence rates with MCC have been all over the map, ranging from 27% to 77%, depending on the population studied.

But as senior author Paul Nghiem, MD, PhD, professor and chair of dermatology at the University of Washington, Seattle, told this news organization, recurrence rates over time in their study were remarkably consistent.

“The biggest surprise to me was that, when we broke our nearly 20-year cohort into three 5- or 6-year chunks, every one of the groups had a 40% recurrence rate, within 1%. So we feel really confident that’s the right number,” he said.

Dr. Nghiem and colleagues report that, in contrast to patients with MCC, approximately 19% of patients with melanoma will have a recurrence, as will an estimated 5%-9% of patients with squamous cell carcinoma and 1%-10% of patients with basal cell carcinoma.

The fact that recurrence rates of MCC have remained stable over time despite presumed improvements in definitive therapy is disappointing, Dr. Nghiem acknowledged. He noted that it’s still unclear whether immunotherapy will have the same dramatic effect on survival rates for patients with MCC as it has for patients with malignant melanoma.

The high recurrence rates following definitive therapy for patients with early-stage disease was a novel finding, commented Shawn Demehri, MD, PhD, director of the high-risk skin cancer clinic at Massachusetts General Hospital in Boston.

“When you’re looking at patients with stage I or stage II, and they have definitive surgery but still have recurrences at a higher rate than melanoma, it brings home the point that these are among the most aggressive tumors of the skin,” he said in an interview.

The high recurrence rates seen with MCC are attributable to a variety of factors.

“This is a rare cancer of mostly older individuals with a lot of comorbidities, and also a cancer that, even though it is a primary cancer, might be detected a little later than even a melanoma primary tumor, just because of the nature of the neuroendocrine tumor cells,” he said.

Dr. Demehri was not involved in the study.
 

Prospective cohort

The study cohort consisted of 618 patients with MCC. The median age of the patients was 69, and 227 (37%) were women. The patients were enrolled within 6 months of their diagnosis in the prospective data repository from 2003 through 2019. Of this group, 223 had a recurrence of MCC.

As noted, there was a high risk of recurrence within 1 year, ranging from 11% for patients with pathologic stage I tumors to 58% for those with stage IV disease, and 95% of all recurrences occurred within 3 years of definitive therapy.

To get a better picture of the natural history of MCC recurrence, the investigators studied a cohort of patients with pathologically confirmed MCC who were prospectively enrolled from January 2003 through April 2019 in a data repository maintained at the University of Washington.

In addition to disease stage, factors associated with increased recurrence risk in univariable analyses include immunosuppression (hazard ratio, 2.4; P < .001), male sex (HR, 1.9; P < .001), known primary lesion among patients with clinically detectable nodal disease (HR, 2.3; P = .001), and older age (HR, 1.1, P = .06 for each 10-year increase).

Of the 187 patients in the cohort who died during the study, 121 died from MCC. At 4 years after diagnosis, MCC-specific survival rates were 95% for patients with pathologic stage I, 84% with stage IIA/IIB, 80% with stage IIIA, 58% with stage IIIB, and 41% with stage IV.

Evidence supports close monitoring within the first 3 years for patients with stage I-II MCC. Local recurrence within or adjacent to the primary tumor scar was associated with a 5-year MCC-specific survival rate of 85%, compared with 88% of patients with stage I or II disease who did not have recurrences.

“Because more than 90% of MCC recurrences arise within 3 years, it is appropriate to adjust surveillance intensity accordingly. Stage- and time-specific recurrence data can assist in appropriately focusing surveillance resources on patients and time intervals in which recurrence risk is highest,” the authors wrote.

“If you’re a patient who has not had your cancer come back for 3, 4, or 5 years, you can really cut down on the intensity of your follow-up and scans,” Dr. Nghiem said.

“We do now have two excellent blood tests that are working very well, and we have really good ways to detect the cancer coming back early, and that’s important, because we have potentially curative therapies that tend to work better if you catch the cancer early,” he said.

The study was supported by the National Institutes of Health. Dr. Nghiem reported personal fees and institutional support outside the study from several companies and patents for Merkel cell therapies with the University of Washington and University of Denmark. Dr. Demehri has disclosed no relevant financial relationships.

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

PHOENIX – In a 15-month phase 4 trial, an inexpensive intervention that can be explained in a single office visit reduced severe exacerbations and improved asthma control in patient populations that suffer disproportionately from the disease. This easy-to-implement strategy achieved benefits similar to those from previous studies that prompted new treatment recommendations for moderate-to-severe asthma.

The findings were reported Feb. 26 in the Late-Breaking Oral Abstracts session at the American Academy of Allergy, Asthma, and Immunology (AAAAI) 2022 Meeting, coinciding with publication in the New England Journal of Medicine.

Black and Latino patients are under-represented in asthma research trials yet visit the emergency room and die from asthma-related complications at more than twice the rates of their White counterparts. Prior efforts to reduce this burden “have been expensive, difficult, and mostly unsuccessful,” Juan-Carlos Cardet, MD, MPH, assistant professor of internal medicine at the University of South Florida, Tampa, told attendees.

Dr. Cardet and his colleagues, led by principal investigator Elliot Israel, MD, of Brigham & Women’s Hospital, Boston, Mass., designed a study with input and financial support from the Patient-Centered Outcomes Research Institute (PCORI). The trial recruited 603 Black and 598 Latino adults with moderate-to-severe asthma. About a fifth were current or former smokers, and many lived in smoking environments. All had poorly controlled asthma or at least one severe asthma attack in the previous year. Each participant held prescriptions for daily inhaled corticosteroids (ICS) with or without long-acting beta-agonists.

Current guidelines recommend daily ICS in all but the mildest asthma cases, yet adherence is poor. Patients generally take medicine when they perceive a need, and since asthma is episodic, “most people don’t like to take controller therapy for asthma,” Dr. Cardet told this news organization in advance of his meeting presentation. Rather, many asthma patients use quick-relief therapies, such as albuterol or nebulizers, on an as-needed basis.

Prior research showed that clinical outcomes can improve with a strategy called Single Maintenance and Reliever Therapy (SMART). In this approach, an ICS (budesonide) is combined with a long-acting beta-agonist (formoterol) into a single inhaler so that patients automatically receive inhaled steroids whenever they treat their symptoms with quick-relief medication. The ICS-formoterol strategy looked promising in studies published more than a decade ago, and those results have prompted an update in national treatment guidelines, but “it’s been difficult to get [the strategy] into the clinic,” Dr. Cardet told this news organization. “FDA cautions against as-needed use of ICS-formoterol. That’s a big reason. Insurance companies won’t pay for it.”

Unlike the SMART studies, which asked participants to replace their usual controller and rescue therapies with the all-in-one inhaler, Black and Latino patients in the new trial were told to continue with their usual asthma care. On top of usual care, half of the participants were randomly assigned to receive one-time instruction around use of a controller medication (beclomethasone; Qvar) supplied by study investigators. “Essentially we told them to keep doing what your doctor tells you to do, but whenever you use a puff of rescue therapy, puff yourself with this Qvar, and if you use the nebulizer, puff yourself five times with the Qvar,” Dr. Cardet said.

This approach, called Patient Activated Reliever-Triggered Inhaled Corticosteroid (PARTICS), was explained to patients through a video in English and Spanish. “All of this we instructed in a single study visit,” Dr. Cardet said.

The PARTICS intervention reduced severe asthma exacerbations by 15% (0.13 exacerbations per patient per year) – on par with the estimated 0.12 exacerbations per patient annualized reduction with SMART. In addition, the PARTICS group had:

• better asthma control (3.4-point increase on the Asthma Control Test, vs. a 2.5-point increase in the usual-care group);
• improved quality of life (0.12-point increase on the Asthma Symptom Utility Index, vs. a 0.08-point increase in the usual-care group);
• fewer self-reported days lost from work, school, and usual activities (13.4 days, vs. 16.8 days in the usual-care group).

Addressing long-standing challenges with controller therapy compliance, this was a real-world strategy “to get more inhaled steroids in [asthma patients] on a regular basis,” Brian Vickery, MD, director of the Food Allergy Center at Emory University + Children’s Healthcare of Atlanta, said during the meeting session Q&A. Dr. Vickery was not involved in the study. “And you see an effect size that rivaled previous studies, which suggests to me that the improvement is in the inhaled steroid component and not necessarily the long-acting beta-agonist.”

The study team hopes these results can be implemented on a health care system level. “If it stays just in a journal, it’s not going to do anything. We want to help people. We want to bring it to clinic,” Dr. Cardet said in an interview.

The study was supported by a Patient-Centered Outcomes Research Institute (PCORI) award to Israel and by grants from the National Institute of Allergy and Infectious Diseases and the American Lung Association–American Academy of Allergy, Asthma, and Immunology to Dr. Cardet. QVAR and QVAR RediHaler inhalers were provided free of charge, and funding for the AssistRx pharmacy was provided by Teva Pharmaceuticals. NIOX VERO devices for measuring exhaled nitric oxide were provided free of charge by Circassia Pharmaceuticals. Dr. Cardet reported honoraria from AstraZeneca and Genentech for work in advisory boards and from GlaxoSmithKline for educational lectures on asthma, all unrelated to the AAAAI presentation. Dr. Vickery has disclosed no relevant financial relationships.

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

PHOENIX – In a 15-month phase 4 trial, an inexpensive intervention that can be explained in a single office visit reduced severe exacerbations and improved asthma control in patient populations that suffer disproportionately from the disease. This easy-to-implement strategy achieved benefits similar to those from previous studies that prompted new treatment recommendations for moderate-to-severe asthma.

The findings were reported Feb. 26 in the Late-Breaking Oral Abstracts session at the American Academy of Allergy, Asthma, and Immunology (AAAAI) 2022 Meeting, coinciding with publication in the New England Journal of Medicine.

Black and Latino patients are under-represented in asthma research trials yet visit the emergency room and die from asthma-related complications at more than twice the rates of their White counterparts. Prior efforts to reduce this burden “have been expensive, difficult, and mostly unsuccessful,” Juan-Carlos Cardet, MD, MPH, assistant professor of internal medicine at the University of South Florida, Tampa, told attendees.

Dr. Cardet and his colleagues, led by principal investigator Elliot Israel, MD, of Brigham & Women’s Hospital, Boston, Mass., designed a study with input and financial support from the Patient-Centered Outcomes Research Institute (PCORI). The trial recruited 603 Black and 598 Latino adults with moderate-to-severe asthma. About a fifth were current or former smokers, and many lived in smoking environments. All had poorly controlled asthma or at least one severe asthma attack in the previous year. Each participant held prescriptions for daily inhaled corticosteroids (ICS) with or without long-acting beta-agonists.

Current guidelines recommend daily ICS in all but the mildest asthma cases, yet adherence is poor. Patients generally take medicine when they perceive a need, and since asthma is episodic, “most people don’t like to take controller therapy for asthma,” Dr. Cardet told this news organization in advance of his meeting presentation. Rather, many asthma patients use quick-relief therapies, such as albuterol or nebulizers, on an as-needed basis.

Prior research showed that clinical outcomes can improve with a strategy called Single Maintenance and Reliever Therapy (SMART). In this approach, an ICS (budesonide) is combined with a long-acting beta-agonist (formoterol) into a single inhaler so that patients automatically receive inhaled steroids whenever they treat their symptoms with quick-relief medication. The ICS-formoterol strategy looked promising in studies published more than a decade ago, and those results have prompted an update in national treatment guidelines, but “it’s been difficult to get [the strategy] into the clinic,” Dr. Cardet told this news organization. “FDA cautions against as-needed use of ICS-formoterol. That’s a big reason. Insurance companies won’t pay for it.”

Unlike the SMART studies, which asked participants to replace their usual controller and rescue therapies with the all-in-one inhaler, Black and Latino patients in the new trial were told to continue with their usual asthma care. On top of usual care, half of the participants were randomly assigned to receive one-time instruction around use of a controller medication (beclomethasone; Qvar) supplied by study investigators. “Essentially we told them to keep doing what your doctor tells you to do, but whenever you use a puff of rescue therapy, puff yourself with this Qvar, and if you use the nebulizer, puff yourself five times with the Qvar,” Dr. Cardet said.

This approach, called Patient Activated Reliever-Triggered Inhaled Corticosteroid (PARTICS), was explained to patients through a video in English and Spanish. “All of this we instructed in a single study visit,” Dr. Cardet said.

The PARTICS intervention reduced severe asthma exacerbations by 15% (0.13 exacerbations per patient per year) – on par with the estimated 0.12 exacerbations per patient annualized reduction with SMART. In addition, the PARTICS group had:

• better asthma control (3.4-point increase on the Asthma Control Test, vs. a 2.5-point increase in the usual-care group);
• improved quality of life (0.12-point increase on the Asthma Symptom Utility Index, vs. a 0.08-point increase in the usual-care group);
• fewer self-reported days lost from work, school, and usual activities (13.4 days, vs. 16.8 days in the usual-care group).

Addressing long-standing challenges with controller therapy compliance, this was a real-world strategy “to get more inhaled steroids in [asthma patients] on a regular basis,” Brian Vickery, MD, director of the Food Allergy Center at Emory University + Children’s Healthcare of Atlanta, said during the meeting session Q&A. Dr. Vickery was not involved in the study. “And you see an effect size that rivaled previous studies, which suggests to me that the improvement is in the inhaled steroid component and not necessarily the long-acting beta-agonist.”

The study team hopes these results can be implemented on a health care system level. “If it stays just in a journal, it’s not going to do anything. We want to help people. We want to bring it to clinic,” Dr. Cardet said in an interview.

The study was supported by a Patient-Centered Outcomes Research Institute (PCORI) award to Israel and by grants from the National Institute of Allergy and Infectious Diseases and the American Lung Association–American Academy of Allergy, Asthma, and Immunology to Dr. Cardet. QVAR and QVAR RediHaler inhalers were provided free of charge, and funding for the AssistRx pharmacy was provided by Teva Pharmaceuticals. NIOX VERO devices for measuring exhaled nitric oxide were provided free of charge by Circassia Pharmaceuticals. Dr. Cardet reported honoraria from AstraZeneca and Genentech for work in advisory boards and from GlaxoSmithKline for educational lectures on asthma, all unrelated to the AAAAI presentation. Dr. Vickery has disclosed no relevant financial relationships.

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

PHOENIX – In a 15-month phase 4 trial, an inexpensive intervention that can be explained in a single office visit reduced severe exacerbations and improved asthma control in patient populations that suffer disproportionately from the disease. This easy-to-implement strategy achieved benefits similar to those from previous studies that prompted new treatment recommendations for moderate-to-severe asthma.

The findings were reported Feb. 26 in the Late-Breaking Oral Abstracts session at the American Academy of Allergy, Asthma, and Immunology (AAAAI) 2022 Meeting, coinciding with publication in the New England Journal of Medicine.

Black and Latino patients are under-represented in asthma research trials yet visit the emergency room and die from asthma-related complications at more than twice the rates of their White counterparts. Prior efforts to reduce this burden “have been expensive, difficult, and mostly unsuccessful,” Juan-Carlos Cardet, MD, MPH, assistant professor of internal medicine at the University of South Florida, Tampa, told attendees.

Dr. Cardet and his colleagues, led by principal investigator Elliot Israel, MD, of Brigham & Women’s Hospital, Boston, Mass., designed a study with input and financial support from the Patient-Centered Outcomes Research Institute (PCORI). The trial recruited 603 Black and 598 Latino adults with moderate-to-severe asthma. About a fifth were current or former smokers, and many lived in smoking environments. All had poorly controlled asthma or at least one severe asthma attack in the previous year. Each participant held prescriptions for daily inhaled corticosteroids (ICS) with or without long-acting beta-agonists.

Current guidelines recommend daily ICS in all but the mildest asthma cases, yet adherence is poor. Patients generally take medicine when they perceive a need, and since asthma is episodic, “most people don’t like to take controller therapy for asthma,” Dr. Cardet told this news organization in advance of his meeting presentation. Rather, many asthma patients use quick-relief therapies, such as albuterol or nebulizers, on an as-needed basis.

Prior research showed that clinical outcomes can improve with a strategy called Single Maintenance and Reliever Therapy (SMART). In this approach, an ICS (budesonide) is combined with a long-acting beta-agonist (formoterol) into a single inhaler so that patients automatically receive inhaled steroids whenever they treat their symptoms with quick-relief medication. The ICS-formoterol strategy looked promising in studies published more than a decade ago, and those results have prompted an update in national treatment guidelines, but “it’s been difficult to get [the strategy] into the clinic,” Dr. Cardet told this news organization. “FDA cautions against as-needed use of ICS-formoterol. That’s a big reason. Insurance companies won’t pay for it.”

Unlike the SMART studies, which asked participants to replace their usual controller and rescue therapies with the all-in-one inhaler, Black and Latino patients in the new trial were told to continue with their usual asthma care. On top of usual care, half of the participants were randomly assigned to receive one-time instruction around use of a controller medication (beclomethasone; Qvar) supplied by study investigators. “Essentially we told them to keep doing what your doctor tells you to do, but whenever you use a puff of rescue therapy, puff yourself with this Qvar, and if you use the nebulizer, puff yourself five times with the Qvar,” Dr. Cardet said.

This approach, called Patient Activated Reliever-Triggered Inhaled Corticosteroid (PARTICS), was explained to patients through a video in English and Spanish. “All of this we instructed in a single study visit,” Dr. Cardet said.

The PARTICS intervention reduced severe asthma exacerbations by 15% (0.13 exacerbations per patient per year) – on par with the estimated 0.12 exacerbations per patient annualized reduction with SMART. In addition, the PARTICS group had:

• better asthma control (3.4-point increase on the Asthma Control Test, vs. a 2.5-point increase in the usual-care group);
• improved quality of life (0.12-point increase on the Asthma Symptom Utility Index, vs. a 0.08-point increase in the usual-care group);
• fewer self-reported days lost from work, school, and usual activities (13.4 days, vs. 16.8 days in the usual-care group).

Addressing long-standing challenges with controller therapy compliance, this was a real-world strategy “to get more inhaled steroids in [asthma patients] on a regular basis,” Brian Vickery, MD, director of the Food Allergy Center at Emory University + Children’s Healthcare of Atlanta, said during the meeting session Q&A. Dr. Vickery was not involved in the study. “And you see an effect size that rivaled previous studies, which suggests to me that the improvement is in the inhaled steroid component and not necessarily the long-acting beta-agonist.”

The study team hopes these results can be implemented on a health care system level. “If it stays just in a journal, it’s not going to do anything. We want to help people. We want to bring it to clinic,” Dr. Cardet said in an interview.

The study was supported by a Patient-Centered Outcomes Research Institute (PCORI) award to Israel and by grants from the National Institute of Allergy and Infectious Diseases and the American Lung Association–American Academy of Allergy, Asthma, and Immunology to Dr. Cardet. QVAR and QVAR RediHaler inhalers were provided free of charge, and funding for the AssistRx pharmacy was provided by Teva Pharmaceuticals. NIOX VERO devices for measuring exhaled nitric oxide were provided free of charge by Circassia Pharmaceuticals. Dr. Cardet reported honoraria from AstraZeneca and Genentech for work in advisory boards and from GlaxoSmithKline for educational lectures on asthma, all unrelated to the AAAAI presentation. Dr. Vickery has disclosed no relevant financial relationships.

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

Imagine a time when RSV doesn’t rage through the community each year. That time would result from decades of research that uncovered RSV’s secrets and explained the only partly successful initial vaccines and prophylactic interventions (for example, palivizumab). 

Key discovery: The original RSV antigen target, RSV’s fusion (F) protein, is suboptimal despite having been associated with RSV attachment to and breaching of host cell membranes. 
Some amazing work showed that having antibodies block the F-protein was like putting up a shield to protect against an arrow only after the arrow had already struck its target. Indeed, the F-protein evolves only after the attachment/breach. The preattachment/breach version (prefusion protein) sits on the virus surface and is like a loaded bow with an arrow in place. The prefusion protein changes configuration when RSV contacts host cells to uncoil and release the “arrow,” creating the entry point for RSV nucleic acids.

Nirsevimab was created to glom onto the prefusion protein and prevent it from uncoiling/releasing its “arrow,” the critical event in RSV infecting a cell. So, it is not surprising that it works better than palivizumab, which targets the fusion protein.

The prefusion protein is also the target of newer vaccine candidates, including one that showed 87% efficacy against RSV challenge in adults (think of mother getting this vaccine and endowing newborns with antiprefusion antibodies; N Engl J Med. 2022;386:2377-86).

The time when RSV is not an annual scourge is closer than ever.

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.

Imagine a time when RSV doesn’t rage through the community each year. That time would result from decades of research that uncovered RSV’s secrets and explained the only partly successful initial vaccines and prophylactic interventions (for example, palivizumab). 

Key discovery: The original RSV antigen target, RSV’s fusion (F) protein, is suboptimal despite having been associated with RSV attachment to and breaching of host cell membranes. 
Some amazing work showed that having antibodies block the F-protein was like putting up a shield to protect against an arrow only after the arrow had already struck its target. Indeed, the F-protein evolves only after the attachment/breach. The preattachment/breach version (prefusion protein) sits on the virus surface and is like a loaded bow with an arrow in place. The prefusion protein changes configuration when RSV contacts host cells to uncoil and release the “arrow,” creating the entry point for RSV nucleic acids.

Nirsevimab was created to glom onto the prefusion protein and prevent it from uncoiling/releasing its “arrow,” the critical event in RSV infecting a cell. So, it is not surprising that it works better than palivizumab, which targets the fusion protein.

The prefusion protein is also the target of newer vaccine candidates, including one that showed 87% efficacy against RSV challenge in adults (think of mother getting this vaccine and endowing newborns with antiprefusion antibodies; N Engl J Med. 2022;386:2377-86).

The time when RSV is not an annual scourge is closer than ever.

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.

Imagine a time when RSV doesn’t rage through the community each year. That time would result from decades of research that uncovered RSV’s secrets and explained the only partly successful initial vaccines and prophylactic interventions (for example, palivizumab). 

Key discovery: The original RSV antigen target, RSV’s fusion (F) protein, is suboptimal despite having been associated with RSV attachment to and breaching of host cell membranes. 
Some amazing work showed that having antibodies block the F-protein was like putting up a shield to protect against an arrow only after the arrow had already struck its target. Indeed, the F-protein evolves only after the attachment/breach. The preattachment/breach version (prefusion protein) sits on the virus surface and is like a loaded bow with an arrow in place. The prefusion protein changes configuration when RSV contacts host cells to uncoil and release the “arrow,” creating the entry point for RSV nucleic acids.

Nirsevimab was created to glom onto the prefusion protein and prevent it from uncoiling/releasing its “arrow,” the critical event in RSV infecting a cell. So, it is not surprising that it works better than palivizumab, which targets the fusion protein.

The prefusion protein is also the target of newer vaccine candidates, including one that showed 87% efficacy against RSV challenge in adults (think of mother getting this vaccine and endowing newborns with antiprefusion antibodies; N Engl J Med. 2022;386:2377-86).

The time when RSV is not an annual scourge is closer than ever.

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.

Medtronic and the American Society for Gastrointestinal Endoscopy (ASGE) are working to provide colorectal cancer (CRC) screening technologies to low-income and underserved communities across the United States, with support from Amazon Web Services (AWS).

Through the Medtronic Health Equity Assistance Program for colon cancer screening, the company will donate 50 GI Genius intelligent endoscopy modules to endoscopy centers across the country.

The Medtronic program will provide selected facilities with GI Genius modules at no cost, so they can be used to assist colonoscopy procedures, a spokesperson for Medtronic told this news organization.

These procedures include screening, diagnostic, or surveillance colonoscopy, and coverage can vary from Medicare, Medicaid, and private insurers.

The use of GI Genius during such procedures does not affect the cost or coverage of the procedure; it simply ensures they receive improved polyp detection compared to non–artificial intelligence (AI)-assisted procedures, the spokesperson explained.

The U.S. Food and Drug Administration authorized GI Genius in April 2021. The system uses AI to improve detection of colorectal polyps or suspected tumors in real time during colonoscopies.

In the pivotal clinical trial, the combination of standard colonoscopy and the GI Genius module identified laboratory-confirmed adenomas or carcinomas in 54.8% patients, compared with 40.4% of patients who underwent colonoscopy alone – an improvement of 14%.
 

Addressing gaps in screening

CRC remains the third most common and third deadliest cancer among adults in the United States. However, when caught early, certain types of CRC have a 5-year survival rate of up to 91%.

Donation of 50 GI Genius systems to endoscopy centers in low-income and underserved areas could potentially benefit more than 350,000 patients over 3 years, Medtronic said in a news release.

“Addressing gaps in colorectal cancer screening is complex. We know that Black adults are more likely to be diagnosed and subsequently die from this disease. There are also disparities in screenings among different groups, including adults in rural communities,” ASGE President Douglas K. Rex, MD, said in the release.

“Colonoscopy is critical in preventing colorectal cancer, and as the global leader in gastrointestinal endoscopy, ASGE is working together with Medtronic to ensure that providers receive screening technology and are able to use them in communities where they are most needed,” Dr. Rex added.

ASGE is independently leading the application and selection process for the devices. To apply, visit the ASGE program website. Initial recipients will be announced in March 2022 during Colorectal Cancer Awareness Month. 

AWS is providing the computing credits to fund the program and continues to work with Medtronic on health equity.

“Individual health outcomes should not depend on socioeconomic status, race, ethnicity, or neighborhood,” Maggie Carter, global lead for social impact at AWS, said in the release.

“We are pleased to support Medtronic and ASGE as part of AWS’ recently launched health equity program to help these organizations bring effective screening tools to the communities that need them most,” said Ms. Carter.

“The crisis of health inequities cannot be solved without expanding access to health care technologies that put people first,” added Geoff Martha, Medtronic chairman and chief executive officer.

“We must begin with local efforts that consider the needs of the community. This program is an important step towards ensuring that our powerful technologies help reduce disparities, improve care, and enhance patient outcomes,” Mr. Martha said.

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

Medtronic and the American Society for Gastrointestinal Endoscopy (ASGE) are working to provide colorectal cancer (CRC) screening technologies to low-income and underserved communities across the United States, with support from Amazon Web Services (AWS).

Through the Medtronic Health Equity Assistance Program for colon cancer screening, the company will donate 50 GI Genius intelligent endoscopy modules to endoscopy centers across the country.

The Medtronic program will provide selected facilities with GI Genius modules at no cost, so they can be used to assist colonoscopy procedures, a spokesperson for Medtronic told this news organization.

These procedures include screening, diagnostic, or surveillance colonoscopy, and coverage can vary from Medicare, Medicaid, and private insurers.

The use of GI Genius during such procedures does not affect the cost or coverage of the procedure; it simply ensures they receive improved polyp detection compared to non–artificial intelligence (AI)-assisted procedures, the spokesperson explained.

The U.S. Food and Drug Administration authorized GI Genius in April 2021. The system uses AI to improve detection of colorectal polyps or suspected tumors in real time during colonoscopies.

In the pivotal clinical trial, the combination of standard colonoscopy and the GI Genius module identified laboratory-confirmed adenomas or carcinomas in 54.8% patients, compared with 40.4% of patients who underwent colonoscopy alone – an improvement of 14%.
 

Addressing gaps in screening

CRC remains the third most common and third deadliest cancer among adults in the United States. However, when caught early, certain types of CRC have a 5-year survival rate of up to 91%.

Donation of 50 GI Genius systems to endoscopy centers in low-income and underserved areas could potentially benefit more than 350,000 patients over 3 years, Medtronic said in a news release.

“Addressing gaps in colorectal cancer screening is complex. We know that Black adults are more likely to be diagnosed and subsequently die from this disease. There are also disparities in screenings among different groups, including adults in rural communities,” ASGE President Douglas K. Rex, MD, said in the release.

“Colonoscopy is critical in preventing colorectal cancer, and as the global leader in gastrointestinal endoscopy, ASGE is working together with Medtronic to ensure that providers receive screening technology and are able to use them in communities where they are most needed,” Dr. Rex added.

ASGE is independently leading the application and selection process for the devices. To apply, visit the ASGE program website. Initial recipients will be announced in March 2022 during Colorectal Cancer Awareness Month. 

AWS is providing the computing credits to fund the program and continues to work with Medtronic on health equity.

“Individual health outcomes should not depend on socioeconomic status, race, ethnicity, or neighborhood,” Maggie Carter, global lead for social impact at AWS, said in the release.

“We are pleased to support Medtronic and ASGE as part of AWS’ recently launched health equity program to help these organizations bring effective screening tools to the communities that need them most,” said Ms. Carter.

“The crisis of health inequities cannot be solved without expanding access to health care technologies that put people first,” added Geoff Martha, Medtronic chairman and chief executive officer.

“We must begin with local efforts that consider the needs of the community. This program is an important step towards ensuring that our powerful technologies help reduce disparities, improve care, and enhance patient outcomes,” Mr. Martha said.

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

Medtronic and the American Society for Gastrointestinal Endoscopy (ASGE) are working to provide colorectal cancer (CRC) screening technologies to low-income and underserved communities across the United States, with support from Amazon Web Services (AWS).

Through the Medtronic Health Equity Assistance Program for colon cancer screening, the company will donate 50 GI Genius intelligent endoscopy modules to endoscopy centers across the country.

The Medtronic program will provide selected facilities with GI Genius modules at no cost, so they can be used to assist colonoscopy procedures, a spokesperson for Medtronic told this news organization.

These procedures include screening, diagnostic, or surveillance colonoscopy, and coverage can vary from Medicare, Medicaid, and private insurers.

The use of GI Genius during such procedures does not affect the cost or coverage of the procedure; it simply ensures they receive improved polyp detection compared to non–artificial intelligence (AI)-assisted procedures, the spokesperson explained.

The U.S. Food and Drug Administration authorized GI Genius in April 2021. The system uses AI to improve detection of colorectal polyps or suspected tumors in real time during colonoscopies.

In the pivotal clinical trial, the combination of standard colonoscopy and the GI Genius module identified laboratory-confirmed adenomas or carcinomas in 54.8% patients, compared with 40.4% of patients who underwent colonoscopy alone – an improvement of 14%.
 

Addressing gaps in screening

CRC remains the third most common and third deadliest cancer among adults in the United States. However, when caught early, certain types of CRC have a 5-year survival rate of up to 91%.

Donation of 50 GI Genius systems to endoscopy centers in low-income and underserved areas could potentially benefit more than 350,000 patients over 3 years, Medtronic said in a news release.

“Addressing gaps in colorectal cancer screening is complex. We know that Black adults are more likely to be diagnosed and subsequently die from this disease. There are also disparities in screenings among different groups, including adults in rural communities,” ASGE President Douglas K. Rex, MD, said in the release.

“Colonoscopy is critical in preventing colorectal cancer, and as the global leader in gastrointestinal endoscopy, ASGE is working together with Medtronic to ensure that providers receive screening technology and are able to use them in communities where they are most needed,” Dr. Rex added.

ASGE is independently leading the application and selection process for the devices. To apply, visit the ASGE program website. Initial recipients will be announced in March 2022 during Colorectal Cancer Awareness Month. 

AWS is providing the computing credits to fund the program and continues to work with Medtronic on health equity.

“Individual health outcomes should not depend on socioeconomic status, race, ethnicity, or neighborhood,” Maggie Carter, global lead for social impact at AWS, said in the release.

“We are pleased to support Medtronic and ASGE as part of AWS’ recently launched health equity program to help these organizations bring effective screening tools to the communities that need them most,” said Ms. Carter.

“The crisis of health inequities cannot be solved without expanding access to health care technologies that put people first,” added Geoff Martha, Medtronic chairman and chief executive officer.

“We must begin with local efforts that consider the needs of the community. This program is an important step towards ensuring that our powerful technologies help reduce disparities, improve care, and enhance patient outcomes,” Mr. Martha said.

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

Early results from a new study show a significant correlation between tic severity and social media use during the COVID pandemic in adolescents with a preexisting tic disorder.

The findings should help answer questions surrounding a recent increase in tic disorders, lead author Jessica Frey, MD, a movement disorders fellow at the University of Florida, Gainesville, told this news organization.

University of Florida

“We’re trying to learn why there are new-onset explosive tic disorders [or] functional tic disorders, and to find ways to educate patients, parents, and the general public about what Tourette syndrome looks like – and how we can help patients have a better quality of life,” Dr. Frey said.

The findings will be presented at the American Academy of Neurology 2022 annual meeting in April.
 

‘Robust’ increase

A neurologic disorder that causes sudden repetitive involuntary muscle movements and sounds, Tourette syndrome typically develops in childhood, worsens in adolescence, and improves or completely disappears in adulthood, Dr. Frey noted.

The condition is often negatively portrayed in films, showing people using obscene gestures or vulgar language, she said. Although social media can be an “empowering tool” for tic sufferers, it is unregulated and can be a vehicle for “false information,” she added.

Dr. Frey noted that during the pandemic there has been a “robust” increase in use by teens of social media, particularly TikTok. At the same time, there have been reports of teen girls experiencing “explosive tic onset” that mimics videos from TikTok influencers.

The new analysis included 20 teens with a tic disorder, ranging in age from 11 to 21 years (average age, 16 years). About 45% of participants identified as male, 45% as female, and 10% as nonbinary.

The nature of the tic disorder varied widely among participants. Some had experienced tics for many years, while others only developed tics during the pandemic.

Participants completed a detailed survey, part of which inquired about where they received information about tics, such as from a doctor, media, parents, or teachers.

They were also asked to rank various social media platforms, including Tik Tok, Facebook, and YouTube on a five-point Likert scale as an information source about tics.

In addition, the survey inquired about tic severity and frequency, quality of life, and whether the pandemic or social media affected respondents’ tics.
 

Worsens quality of life

Results showed 65% of respondents used social media at least four to five times per day for an average of 5.6 hours per day. Approximately 90% reported increased use of social media during COVID.

Only 5% of participants reported using social media to provide information about tics.

About half of respondents indicated social media adversely affected their tics, and 85% said their tic frequency worsened during COVID.

Dr. Frey noted that because teens had to attend school virtually, that may have led to increased hours spent online.

There was no significant correlation between social media use and self-reported frequency of tics since the onset of COVID (Pearson correlation coefficient [R], –0.0055, P = .982).

However, there was a statistically significant correlation between social media use and tic severity (R, –0.496, P = .026) and quality of life (R, –0.447, P = .048).

These results suggest teenagers did not develop more tics, but rather the tics they already had worsened and affected their quality of life, Dr. Frey noted. She added that teens sometimes injure themselves while experiencing tics.

The full study has now enrolled 50 participants, and investigators anticipate that number to go up to 80. “We’re hoping to see more patterns emerge when we have a larger cohort of data available,” said Dr. Frey.

Asking parents to weigh in on the impact of social media on their child’s tic condition would be “a great idea for a follow-up study,” she added.
 

Symptoms exacerbated

Commenting on the findings, Tamara Pringsheim, MD, professor in the department of clinical neurosciences, psychiatry, pediatrics, and community health sciences at the University of Calgary (Alta.), said she also has noticed the impact of increased social media use on young patients with tics during the pandemic.

“Many young people report that seeing other people with tics, or ticlike behaviors, can exacerbate their own symptoms,” said Dr. Pringsheim, who is the university’s program lead on Tourette and pediatric movement disorders.

She noted a principle of the Comprehensive Behavioral Intervention for Tics, which is a nonpharmacologic technique demonstrated to reduce tic severity, is to identify antecedents or triggers for tics, and to learn to manage them. It might be a good idea to remind young patients of this principle, said Dr. Pringsheim, who was not associated with the current research.

“I suggest to young people who report specific social media content as a trigger for symptoms to recognize the effect of the exposure on their symptoms and make an informed choice about what they view and how much time they spend on social media,” she added.

The study did not receive any outside funding support. Dr. Frey has disclosed no relevant financial relationships.

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

Early results from a new study show a significant correlation between tic severity and social media use during the COVID pandemic in adolescents with a preexisting tic disorder.

The findings should help answer questions surrounding a recent increase in tic disorders, lead author Jessica Frey, MD, a movement disorders fellow at the University of Florida, Gainesville, told this news organization.

University of Florida

“We’re trying to learn why there are new-onset explosive tic disorders [or] functional tic disorders, and to find ways to educate patients, parents, and the general public about what Tourette syndrome looks like – and how we can help patients have a better quality of life,” Dr. Frey said.

The findings will be presented at the American Academy of Neurology 2022 annual meeting in April.
 

‘Robust’ increase

A neurologic disorder that causes sudden repetitive involuntary muscle movements and sounds, Tourette syndrome typically develops in childhood, worsens in adolescence, and improves or completely disappears in adulthood, Dr. Frey noted.

The condition is often negatively portrayed in films, showing people using obscene gestures or vulgar language, she said. Although social media can be an “empowering tool” for tic sufferers, it is unregulated and can be a vehicle for “false information,” she added.

Dr. Frey noted that during the pandemic there has been a “robust” increase in use by teens of social media, particularly TikTok. At the same time, there have been reports of teen girls experiencing “explosive tic onset” that mimics videos from TikTok influencers.

The new analysis included 20 teens with a tic disorder, ranging in age from 11 to 21 years (average age, 16 years). About 45% of participants identified as male, 45% as female, and 10% as nonbinary.

The nature of the tic disorder varied widely among participants. Some had experienced tics for many years, while others only developed tics during the pandemic.

Participants completed a detailed survey, part of which inquired about where they received information about tics, such as from a doctor, media, parents, or teachers.

They were also asked to rank various social media platforms, including Tik Tok, Facebook, and YouTube on a five-point Likert scale as an information source about tics.

In addition, the survey inquired about tic severity and frequency, quality of life, and whether the pandemic or social media affected respondents’ tics.
 

Worsens quality of life

Results showed 65% of respondents used social media at least four to five times per day for an average of 5.6 hours per day. Approximately 90% reported increased use of social media during COVID.

Only 5% of participants reported using social media to provide information about tics.

About half of respondents indicated social media adversely affected their tics, and 85% said their tic frequency worsened during COVID.

Dr. Frey noted that because teens had to attend school virtually, that may have led to increased hours spent online.

There was no significant correlation between social media use and self-reported frequency of tics since the onset of COVID (Pearson correlation coefficient [R], –0.0055, P = .982).

However, there was a statistically significant correlation between social media use and tic severity (R, –0.496, P = .026) and quality of life (R, –0.447, P = .048).

These results suggest teenagers did not develop more tics, but rather the tics they already had worsened and affected their quality of life, Dr. Frey noted. She added that teens sometimes injure themselves while experiencing tics.

The full study has now enrolled 50 participants, and investigators anticipate that number to go up to 80. “We’re hoping to see more patterns emerge when we have a larger cohort of data available,” said Dr. Frey.

Asking parents to weigh in on the impact of social media on their child’s tic condition would be “a great idea for a follow-up study,” she added.
 

Symptoms exacerbated

Commenting on the findings, Tamara Pringsheim, MD, professor in the department of clinical neurosciences, psychiatry, pediatrics, and community health sciences at the University of Calgary (Alta.), said she also has noticed the impact of increased social media use on young patients with tics during the pandemic.

“Many young people report that seeing other people with tics, or ticlike behaviors, can exacerbate their own symptoms,” said Dr. Pringsheim, who is the university’s program lead on Tourette and pediatric movement disorders.

She noted a principle of the Comprehensive Behavioral Intervention for Tics, which is a nonpharmacologic technique demonstrated to reduce tic severity, is to identify antecedents or triggers for tics, and to learn to manage them. It might be a good idea to remind young patients of this principle, said Dr. Pringsheim, who was not associated with the current research.

“I suggest to young people who report specific social media content as a trigger for symptoms to recognize the effect of the exposure on their symptoms and make an informed choice about what they view and how much time they spend on social media,” she added.

The study did not receive any outside funding support. Dr. Frey has disclosed no relevant financial relationships.

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

Early results from a new study show a significant correlation between tic severity and social media use during the COVID pandemic in adolescents with a preexisting tic disorder.

The findings should help answer questions surrounding a recent increase in tic disorders, lead author Jessica Frey, MD, a movement disorders fellow at the University of Florida, Gainesville, told this news organization.

University of Florida

“We’re trying to learn why there are new-onset explosive tic disorders [or] functional tic disorders, and to find ways to educate patients, parents, and the general public about what Tourette syndrome looks like – and how we can help patients have a better quality of life,” Dr. Frey said.

The findings will be presented at the American Academy of Neurology 2022 annual meeting in April.
 

‘Robust’ increase

A neurologic disorder that causes sudden repetitive involuntary muscle movements and sounds, Tourette syndrome typically develops in childhood, worsens in adolescence, and improves or completely disappears in adulthood, Dr. Frey noted.

The condition is often negatively portrayed in films, showing people using obscene gestures or vulgar language, she said. Although social media can be an “empowering tool” for tic sufferers, it is unregulated and can be a vehicle for “false information,” she added.

Dr. Frey noted that during the pandemic there has been a “robust” increase in use by teens of social media, particularly TikTok. At the same time, there have been reports of teen girls experiencing “explosive tic onset” that mimics videos from TikTok influencers.

The new analysis included 20 teens with a tic disorder, ranging in age from 11 to 21 years (average age, 16 years). About 45% of participants identified as male, 45% as female, and 10% as nonbinary.

The nature of the tic disorder varied widely among participants. Some had experienced tics for many years, while others only developed tics during the pandemic.

Participants completed a detailed survey, part of which inquired about where they received information about tics, such as from a doctor, media, parents, or teachers.

They were also asked to rank various social media platforms, including Tik Tok, Facebook, and YouTube on a five-point Likert scale as an information source about tics.

In addition, the survey inquired about tic severity and frequency, quality of life, and whether the pandemic or social media affected respondents’ tics.
 

Worsens quality of life

Results showed 65% of respondents used social media at least four to five times per day for an average of 5.6 hours per day. Approximately 90% reported increased use of social media during COVID.

Only 5% of participants reported using social media to provide information about tics.

About half of respondents indicated social media adversely affected their tics, and 85% said their tic frequency worsened during COVID.

Dr. Frey noted that because teens had to attend school virtually, that may have led to increased hours spent online.

There was no significant correlation between social media use and self-reported frequency of tics since the onset of COVID (Pearson correlation coefficient [R], –0.0055, P = .982).

However, there was a statistically significant correlation between social media use and tic severity (R, –0.496, P = .026) and quality of life (R, –0.447, P = .048).

These results suggest teenagers did not develop more tics, but rather the tics they already had worsened and affected their quality of life, Dr. Frey noted. She added that teens sometimes injure themselves while experiencing tics.

The full study has now enrolled 50 participants, and investigators anticipate that number to go up to 80. “We’re hoping to see more patterns emerge when we have a larger cohort of data available,” said Dr. Frey.

Asking parents to weigh in on the impact of social media on their child’s tic condition would be “a great idea for a follow-up study,” she added.
 

Symptoms exacerbated

Commenting on the findings, Tamara Pringsheim, MD, professor in the department of clinical neurosciences, psychiatry, pediatrics, and community health sciences at the University of Calgary (Alta.), said she also has noticed the impact of increased social media use on young patients with tics during the pandemic.

“Many young people report that seeing other people with tics, or ticlike behaviors, can exacerbate their own symptoms,” said Dr. Pringsheim, who is the university’s program lead on Tourette and pediatric movement disorders.

She noted a principle of the Comprehensive Behavioral Intervention for Tics, which is a nonpharmacologic technique demonstrated to reduce tic severity, is to identify antecedents or triggers for tics, and to learn to manage them. It might be a good idea to remind young patients of this principle, said Dr. Pringsheim, who was not associated with the current research.

“I suggest to young people who report specific social media content as a trigger for symptoms to recognize the effect of the exposure on their symptoms and make an informed choice about what they view and how much time they spend on social media,” she added.

The study did not receive any outside funding support. Dr. Frey has disclosed no relevant financial relationships.

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

Infectious disease specialist and humanitarian, Paul Edward Farmer, MD, PhD, who cofounded Partners In Health, died suddenly on Feb. 21. To celebrate his life, this news organization interviewed Serena Koenig, MD, MPH, who met Dr. Farmer when she was an internal medicine resident at Brigham and Women’s Hospital. Dr. Koenig had worked closely with Dr. Farmer ever since they met.

Q. Can you please share one of your best memories of Dr. Farmer?

Dr. Serena Koenig: There are so many memories it is hard to choose. One that was very formative for me occurred during one of my first trips to Haiti, in 2001. Paul and some other incredible colleagues at Partners IN Health (PIH) had started the HIV Equity Initiative, which was one of the first programs in the world to provide free, comprehensive treatment for HIV. This was at the time when millions of people in Africa were dying of HIV and many experts said it was not feasible to treat HIV in a poor country, because it was too complicated and expensive. Paul took me on some home visits with patients who had what he called the Lazarus effect, coming back from death’s door from advanced AIDS to vigorous health on antiretroviral therapy. I had just started working in Haiti with Paul and PIH, and I felt the enormous magnitude of what he was doing.

Q. What aspects of him and his work do you find most admirable?

Dr. Koenig: I most admired Paul’s humanity, his belief that every person matters and has the right to high-quality health care, and his vision of global health equity.

He said: “The idea that some lives matter less is the root of all that is wrong with the world.” Paul lived this philosophy. He has spoken extensively about harms of socialization for scarcity on behalf of those who are poor, leading policy makers to decisions regarding the feasibility of treating some diseases, but not others.

He said in an interview with the Harvard Gazette in 2018: “The most compelling thing to fight socialization for scarcity on behalf of others is health system strengthening. Health systems that integrate prevention and quality care.”

A few weeks ago, I asked him his thoughts about the high-level resources we have invested in some patients who have needed specialty care over the years, and he said: “No way that we should waste all of our emotional energy responding only to those constant, nagging critics that it’s not cost effective, not feasible, not sustainable, not even prudent. Because you know what they would have done if it was their child or family member.”
 

Q. When did you first meet Dr. Farmer, and what inspired you to work with him?

Dr. Koenig: When I was an internal medicine resident at the Brigham, Paul and I bonded over the care of one of my clinic patients who I followed very closely, and who was admitted to his inpatient service.

Like everyone else who has worked with Paul, I was touched by his kindness and warmth.

A couple of years later, he asked me to help him raise money to bring a young man named Wilnot from Haiti to the Brigham for an aortic valve replacement. After we raised the money, he asked me to go to Haiti to help Wilnot get his medical visa and to escort him to Boston.

That short trip to Haiti had an enormous impact on my life. I was shattered to see the poverty that the people of Haiti were enduring – and in a country a short plane flight from Miami.

Shortly after this, Paul asked me to help him find treatment for another patient, a young boy named John, who presented with neck masses that were later diagnosed as nasopharyngeal carcinoma.

It took us some time to make the diagnosis and then to arrange free care at Mass General.

When I returned to Haiti with two PIH colleagues to help John get a visa and escort him back to Boston, we found that John’s condition was much worse. We ended up medically evacuating him to Boston, because he was too sick for a commercial flight.

Tracy Kidder wrote about this heartbreaking experience in the book “Mountains Beyond Mountains.”

Throughout all of these experiences, I was deeply impressed with Paul’s commitment to do whatever it took to provide the best care for patients, as if they were members of his own family. He said “Tout Moun Se Moun” (Haitian Creole for “every person is a person”), and I could tell that he meant it.
 

Q. How did you collaborate with him professionally?

Dr. Koenig: I spent the first few years after residency working with Paul and Partners In Health. Initially, I served as a liaison between PIH in Haiti and the Brigham, bringing several more patients to Boston for care, and arranging specialty surgical trips to Haiti.

Later, when HIV funding became available from the Global Fund for HIV, Tuberculosis, and Malaria, I moved to rural Haiti to provide treatment for patients with HIV and/or TB at one of the first PIH expansion sites. We treated many patients with advanced stages of HIV and/or TB, and many of them recovered remarkably quickly with antiretroviral therapy.

When I returned to Boston to complete an infectious disease fellowship I switched my focus to conducting clinical research to improve HIV and TB treatment outcomes. Paul emailed his mentor and friend, Jean “Bill” Pape, the director of a Haitian NGO called GHESKIO (Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections), which is an internationally celebrated center of excellence in HIV-related research and clinical care, to ask if I could collaborate with them.

Ever since that time, I have been based between the Brigham’s division of global health equity, which was led by Paul, and GHESKIO.

Paul was very supportive of our research, which aims to improve health service delivery and treatment regimens for HIV and TB.
 

Q. What lessons do you think other physicians can learn from him?

Dr. Koenig: As Joia Mukherjee, chief medical officer of Partners In Health, has said, Paul left us a roadmap. He wrote many books, and he was very eloquent in expressing his philosophy about equity and justice in numerous interviews. This is relevant not only for international sites, but in the United States as well, with our major disparities in health outcomes by race, geography, and socioeconomic status.

No one will be able to replace Paul, but he left us with a vision of what is achievable.

Dr. Koenig is associate physician, Brigham and Women’s Hospital, Boston, with faculty appointments in the divisions of global health equity and infectious diseases. She is also associate professor at Harvard Medical School.

Infectious disease specialist and humanitarian, Paul Edward Farmer, MD, PhD, who cofounded Partners In Health, died suddenly on Feb. 21. To celebrate his life, this news organization interviewed Serena Koenig, MD, MPH, who met Dr. Farmer when she was an internal medicine resident at Brigham and Women’s Hospital. Dr. Koenig had worked closely with Dr. Farmer ever since they met.

Q. Can you please share one of your best memories of Dr. Farmer?

Dr. Serena Koenig: There are so many memories it is hard to choose. One that was very formative for me occurred during one of my first trips to Haiti, in 2001. Paul and some other incredible colleagues at Partners IN Health (PIH) had started the HIV Equity Initiative, which was one of the first programs in the world to provide free, comprehensive treatment for HIV. This was at the time when millions of people in Africa were dying of HIV and many experts said it was not feasible to treat HIV in a poor country, because it was too complicated and expensive. Paul took me on some home visits with patients who had what he called the Lazarus effect, coming back from death’s door from advanced AIDS to vigorous health on antiretroviral therapy. I had just started working in Haiti with Paul and PIH, and I felt the enormous magnitude of what he was doing.

Q. What aspects of him and his work do you find most admirable?

Dr. Koenig: I most admired Paul’s humanity, his belief that every person matters and has the right to high-quality health care, and his vision of global health equity.

He said: “The idea that some lives matter less is the root of all that is wrong with the world.” Paul lived this philosophy. He has spoken extensively about harms of socialization for scarcity on behalf of those who are poor, leading policy makers to decisions regarding the feasibility of treating some diseases, but not others.

He said in an interview with the Harvard Gazette in 2018: “The most compelling thing to fight socialization for scarcity on behalf of others is health system strengthening. Health systems that integrate prevention and quality care.”

A few weeks ago, I asked him his thoughts about the high-level resources we have invested in some patients who have needed specialty care over the years, and he said: “No way that we should waste all of our emotional energy responding only to those constant, nagging critics that it’s not cost effective, not feasible, not sustainable, not even prudent. Because you know what they would have done if it was their child or family member.”
 

Q. When did you first meet Dr. Farmer, and what inspired you to work with him?

Dr. Koenig: When I was an internal medicine resident at the Brigham, Paul and I bonded over the care of one of my clinic patients who I followed very closely, and who was admitted to his inpatient service.

Like everyone else who has worked with Paul, I was touched by his kindness and warmth.

A couple of years later, he asked me to help him raise money to bring a young man named Wilnot from Haiti to the Brigham for an aortic valve replacement. After we raised the money, he asked me to go to Haiti to help Wilnot get his medical visa and to escort him to Boston.

That short trip to Haiti had an enormous impact on my life. I was shattered to see the poverty that the people of Haiti were enduring – and in a country a short plane flight from Miami.

Shortly after this, Paul asked me to help him find treatment for another patient, a young boy named John, who presented with neck masses that were later diagnosed as nasopharyngeal carcinoma.

It took us some time to make the diagnosis and then to arrange free care at Mass General.

When I returned to Haiti with two PIH colleagues to help John get a visa and escort him back to Boston, we found that John’s condition was much worse. We ended up medically evacuating him to Boston, because he was too sick for a commercial flight.

Tracy Kidder wrote about this heartbreaking experience in the book “Mountains Beyond Mountains.”

Throughout all of these experiences, I was deeply impressed with Paul’s commitment to do whatever it took to provide the best care for patients, as if they were members of his own family. He said “Tout Moun Se Moun” (Haitian Creole for “every person is a person”), and I could tell that he meant it.
 

Q. How did you collaborate with him professionally?

Dr. Koenig: I spent the first few years after residency working with Paul and Partners In Health. Initially, I served as a liaison between PIH in Haiti and the Brigham, bringing several more patients to Boston for care, and arranging specialty surgical trips to Haiti.

Later, when HIV funding became available from the Global Fund for HIV, Tuberculosis, and Malaria, I moved to rural Haiti to provide treatment for patients with HIV and/or TB at one of the first PIH expansion sites. We treated many patients with advanced stages of HIV and/or TB, and many of them recovered remarkably quickly with antiretroviral therapy.

When I returned to Boston to complete an infectious disease fellowship I switched my focus to conducting clinical research to improve HIV and TB treatment outcomes. Paul emailed his mentor and friend, Jean “Bill” Pape, the director of a Haitian NGO called GHESKIO (Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections), which is an internationally celebrated center of excellence in HIV-related research and clinical care, to ask if I could collaborate with them.

Ever since that time, I have been based between the Brigham’s division of global health equity, which was led by Paul, and GHESKIO.

Paul was very supportive of our research, which aims to improve health service delivery and treatment regimens for HIV and TB.
 

Q. What lessons do you think other physicians can learn from him?

Dr. Koenig: As Joia Mukherjee, chief medical officer of Partners In Health, has said, Paul left us a roadmap. He wrote many books, and he was very eloquent in expressing his philosophy about equity and justice in numerous interviews. This is relevant not only for international sites, but in the United States as well, with our major disparities in health outcomes by race, geography, and socioeconomic status.

No one will be able to replace Paul, but he left us with a vision of what is achievable.

Dr. Koenig is associate physician, Brigham and Women’s Hospital, Boston, with faculty appointments in the divisions of global health equity and infectious diseases. She is also associate professor at Harvard Medical School.

Infectious disease specialist and humanitarian, Paul Edward Farmer, MD, PhD, who cofounded Partners In Health, died suddenly on Feb. 21. To celebrate his life, this news organization interviewed Serena Koenig, MD, MPH, who met Dr. Farmer when she was an internal medicine resident at Brigham and Women’s Hospital. Dr. Koenig had worked closely with Dr. Farmer ever since they met.

Q. Can you please share one of your best memories of Dr. Farmer?

Dr. Serena Koenig: There are so many memories it is hard to choose. One that was very formative for me occurred during one of my first trips to Haiti, in 2001. Paul and some other incredible colleagues at Partners IN Health (PIH) had started the HIV Equity Initiative, which was one of the first programs in the world to provide free, comprehensive treatment for HIV. This was at the time when millions of people in Africa were dying of HIV and many experts said it was not feasible to treat HIV in a poor country, because it was too complicated and expensive. Paul took me on some home visits with patients who had what he called the Lazarus effect, coming back from death’s door from advanced AIDS to vigorous health on antiretroviral therapy. I had just started working in Haiti with Paul and PIH, and I felt the enormous magnitude of what he was doing.

Q. What aspects of him and his work do you find most admirable?

Dr. Koenig: I most admired Paul’s humanity, his belief that every person matters and has the right to high-quality health care, and his vision of global health equity.

He said: “The idea that some lives matter less is the root of all that is wrong with the world.” Paul lived this philosophy. He has spoken extensively about harms of socialization for scarcity on behalf of those who are poor, leading policy makers to decisions regarding the feasibility of treating some diseases, but not others.

He said in an interview with the Harvard Gazette in 2018: “The most compelling thing to fight socialization for scarcity on behalf of others is health system strengthening. Health systems that integrate prevention and quality care.”

A few weeks ago, I asked him his thoughts about the high-level resources we have invested in some patients who have needed specialty care over the years, and he said: “No way that we should waste all of our emotional energy responding only to those constant, nagging critics that it’s not cost effective, not feasible, not sustainable, not even prudent. Because you know what they would have done if it was their child or family member.”
 

Q. When did you first meet Dr. Farmer, and what inspired you to work with him?

Dr. Koenig: When I was an internal medicine resident at the Brigham, Paul and I bonded over the care of one of my clinic patients who I followed very closely, and who was admitted to his inpatient service.

Like everyone else who has worked with Paul, I was touched by his kindness and warmth.

A couple of years later, he asked me to help him raise money to bring a young man named Wilnot from Haiti to the Brigham for an aortic valve replacement. After we raised the money, he asked me to go to Haiti to help Wilnot get his medical visa and to escort him to Boston.

That short trip to Haiti had an enormous impact on my life. I was shattered to see the poverty that the people of Haiti were enduring – and in a country a short plane flight from Miami.

Shortly after this, Paul asked me to help him find treatment for another patient, a young boy named John, who presented with neck masses that were later diagnosed as nasopharyngeal carcinoma.

It took us some time to make the diagnosis and then to arrange free care at Mass General.

When I returned to Haiti with two PIH colleagues to help John get a visa and escort him back to Boston, we found that John’s condition was much worse. We ended up medically evacuating him to Boston, because he was too sick for a commercial flight.

Tracy Kidder wrote about this heartbreaking experience in the book “Mountains Beyond Mountains.”

Throughout all of these experiences, I was deeply impressed with Paul’s commitment to do whatever it took to provide the best care for patients, as if they were members of his own family. He said “Tout Moun Se Moun” (Haitian Creole for “every person is a person”), and I could tell that he meant it.
 

Q. How did you collaborate with him professionally?

Dr. Koenig: I spent the first few years after residency working with Paul and Partners In Health. Initially, I served as a liaison between PIH in Haiti and the Brigham, bringing several more patients to Boston for care, and arranging specialty surgical trips to Haiti.

Later, when HIV funding became available from the Global Fund for HIV, Tuberculosis, and Malaria, I moved to rural Haiti to provide treatment for patients with HIV and/or TB at one of the first PIH expansion sites. We treated many patients with advanced stages of HIV and/or TB, and many of them recovered remarkably quickly with antiretroviral therapy.

When I returned to Boston to complete an infectious disease fellowship I switched my focus to conducting clinical research to improve HIV and TB treatment outcomes. Paul emailed his mentor and friend, Jean “Bill” Pape, the director of a Haitian NGO called GHESKIO (Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections), which is an internationally celebrated center of excellence in HIV-related research and clinical care, to ask if I could collaborate with them.

Ever since that time, I have been based between the Brigham’s division of global health equity, which was led by Paul, and GHESKIO.

Paul was very supportive of our research, which aims to improve health service delivery and treatment regimens for HIV and TB.
 

Q. What lessons do you think other physicians can learn from him?

Dr. Koenig: As Joia Mukherjee, chief medical officer of Partners In Health, has said, Paul left us a roadmap. He wrote many books, and he was very eloquent in expressing his philosophy about equity and justice in numerous interviews. This is relevant not only for international sites, but in the United States as well, with our major disparities in health outcomes by race, geography, and socioeconomic status.

No one will be able to replace Paul, but he left us with a vision of what is achievable.

Dr. Koenig is associate physician, Brigham and Women’s Hospital, Boston, with faculty appointments in the divisions of global health equity and infectious diseases. She is also associate professor at Harvard Medical School.

Survival after in-hospital cardiac arrest was roughly one-third lower in patients with COVID-19 infections compared to uninfected patients, based on data from nearly 25,000 individuals.

Survival rates of less than 3% were reported in the United States and China for patients who suffered in-hospital cardiac arrest (IHCA) while infected with COVID-19 early in the pandemic, but the data came from small, single-center studies in overwhelmed hospitals, wrote Saket Girotra, MD, of the University of Iowa, Iowa City, and fellow American Heart Association Get With the Guidelines–Resuscitation Investigators. Whether these early reports reflect the broader experience of patients with COVID-19 in hospitals in the United States remains unknown.

In a study published as a research letter in JAMA Network Open, the researchers reviewed data from the American Heart Association Get With the Guidelines–Resuscitation registry. The registry collects detailed information on patients aged 18 years and older who experience cardiac arrest at participating hospitals in the United States. The study population included 24,915 patients aged 18 years and older from 286 hospitals who experienced IHCA during March–December 2020. The mean age of the patients was 64.7 years; 61.1% were White, 24.8% were Black, 3.8% were of other race or ethnicity, and 10.3% were of unknown race or ethnicity.

The primary outcomes were survival to discharge and return of spontaneous circulation (ROSC) for at least 20 minutes.

A total of 5,916 patients (23.7%) had suspected or confirmed COVID-19 infections, and infected patients were more likely to be younger, male, and Black. Patients with COVID-19 infections also were significantly more likely than noninfected patients to have nonshockable rhythm, pneumonia, respiratory insufficiency, or sepsis, and to be on mechanical ventilation or vasopressors when the IHCA occurred, the researchers noted.

Survival rates to hospital discharge were 11.9% for COVID-19 patients, compared with 23.5% for noninfected patients (adjusted relative risk, 0.65; P < .001). ROSC was 53.7% and 63.6%, for infected and noninfected patients, respectively (aRR, 0.86; P < .001).

COVID-19 patients also were more likely than noninfected patients to receive delayed defibrillation, the researchers said. “Although delays in resuscitation, especially defibrillation, may have contributed to lower survival, the negative association of COVID-19 with survival in this study was consistent across subgroups, including patients who received timely treatment with defibrillation and epinephrine.”

The extremely low survival rate in early pandemic studies likely reflected the overwhelming burden on health systems at the time, the researchers said in their discussion.

The study findings were limited by several factors, including potential confounding from unmeasured variables, the use of a quality improvement registry that may not reflect nonparticipating hospitals, and potential false-positive COVID-19 cases. However, the result support findings from recent studies of multiple centers and extend clinical knowledge by comparing infected and noninfected patients from a larger group of hospitals than previously studied, the researchers said.

“We believe that these data will be relevant to health care providers and hospital administrators as the COVID-19 pandemic continues,” they concluded.
 

Think beyond COVID-19 for cardiac care

“Early during the pandemic, questions were raised whether COVID-19 patients should be treated with CPR,” Dr. Girotra said in an interview. “This was because initial studies had found a dismal survival of 0%-3% in COVID patients treated with CPR. The potential of transmitting the virus to health care professionals during CPR further heightened these concerns. We wanted to know whether the poor survival reported in these initial studies were broadly representative.”

Dr. Girotra said that some of the study findings were surprising. “We found that of all patients with IHCA in 2020 in our study, one in four were suspected or confirmed to have COVID-19 infection. We were surprised by the magnitude of COVID’s impact on the cardiac arrest incidence.”

The implications for clinical decision-making are to think outside of COVID-19 infection, said Dr. Girotra. In the current study, “Although overall survival of cardiac arrest in COVID-positive patients was 30% lower, compared to non-COVID patients, it was not as poor as previously reported. COVID-19 infection alone should not be considered the sole factor for making decisions regarding CPR.

“Over the past 2 decades, we have experienced large gains in survival for in-hospital cardiac arrest. However, the COVID-19 pandemic has eroded these gains,” said Dr. Girotra. “Future studies are needed to monitor the impact of any new variants on cardiac arrest care,” as well as studies “to see whether we return to the prepandemic levels of IHCA survival once the pandemic recedes.”

Dr. Girotra has no relevant financial disclosures.

Survival after in-hospital cardiac arrest was roughly one-third lower in patients with COVID-19 infections compared to uninfected patients, based on data from nearly 25,000 individuals.

Survival rates of less than 3% were reported in the United States and China for patients who suffered in-hospital cardiac arrest (IHCA) while infected with COVID-19 early in the pandemic, but the data came from small, single-center studies in overwhelmed hospitals, wrote Saket Girotra, MD, of the University of Iowa, Iowa City, and fellow American Heart Association Get With the Guidelines–Resuscitation Investigators. Whether these early reports reflect the broader experience of patients with COVID-19 in hospitals in the United States remains unknown.

In a study published as a research letter in JAMA Network Open, the researchers reviewed data from the American Heart Association Get With the Guidelines–Resuscitation registry. The registry collects detailed information on patients aged 18 years and older who experience cardiac arrest at participating hospitals in the United States. The study population included 24,915 patients aged 18 years and older from 286 hospitals who experienced IHCA during March–December 2020. The mean age of the patients was 64.7 years; 61.1% were White, 24.8% were Black, 3.8% were of other race or ethnicity, and 10.3% were of unknown race or ethnicity.

The primary outcomes were survival to discharge and return of spontaneous circulation (ROSC) for at least 20 minutes.

A total of 5,916 patients (23.7%) had suspected or confirmed COVID-19 infections, and infected patients were more likely to be younger, male, and Black. Patients with COVID-19 infections also were significantly more likely than noninfected patients to have nonshockable rhythm, pneumonia, respiratory insufficiency, or sepsis, and to be on mechanical ventilation or vasopressors when the IHCA occurred, the researchers noted.

Survival rates to hospital discharge were 11.9% for COVID-19 patients, compared with 23.5% for noninfected patients (adjusted relative risk, 0.65; P < .001). ROSC was 53.7% and 63.6%, for infected and noninfected patients, respectively (aRR, 0.86; P < .001).

COVID-19 patients also were more likely than noninfected patients to receive delayed defibrillation, the researchers said. “Although delays in resuscitation, especially defibrillation, may have contributed to lower survival, the negative association of COVID-19 with survival in this study was consistent across subgroups, including patients who received timely treatment with defibrillation and epinephrine.”

The extremely low survival rate in early pandemic studies likely reflected the overwhelming burden on health systems at the time, the researchers said in their discussion.

The study findings were limited by several factors, including potential confounding from unmeasured variables, the use of a quality improvement registry that may not reflect nonparticipating hospitals, and potential false-positive COVID-19 cases. However, the result support findings from recent studies of multiple centers and extend clinical knowledge by comparing infected and noninfected patients from a larger group of hospitals than previously studied, the researchers said.

“We believe that these data will be relevant to health care providers and hospital administrators as the COVID-19 pandemic continues,” they concluded.
 

Think beyond COVID-19 for cardiac care

“Early during the pandemic, questions were raised whether COVID-19 patients should be treated with CPR,” Dr. Girotra said in an interview. “This was because initial studies had found a dismal survival of 0%-3% in COVID patients treated with CPR. The potential of transmitting the virus to health care professionals during CPR further heightened these concerns. We wanted to know whether the poor survival reported in these initial studies were broadly representative.”

Dr. Girotra said that some of the study findings were surprising. “We found that of all patients with IHCA in 2020 in our study, one in four were suspected or confirmed to have COVID-19 infection. We were surprised by the magnitude of COVID’s impact on the cardiac arrest incidence.”

The implications for clinical decision-making are to think outside of COVID-19 infection, said Dr. Girotra. In the current study, “Although overall survival of cardiac arrest in COVID-positive patients was 30% lower, compared to non-COVID patients, it was not as poor as previously reported. COVID-19 infection alone should not be considered the sole factor for making decisions regarding CPR.

“Over the past 2 decades, we have experienced large gains in survival for in-hospital cardiac arrest. However, the COVID-19 pandemic has eroded these gains,” said Dr. Girotra. “Future studies are needed to monitor the impact of any new variants on cardiac arrest care,” as well as studies “to see whether we return to the prepandemic levels of IHCA survival once the pandemic recedes.”

Dr. Girotra has no relevant financial disclosures.

Survival after in-hospital cardiac arrest was roughly one-third lower in patients with COVID-19 infections compared to uninfected patients, based on data from nearly 25,000 individuals.

Survival rates of less than 3% were reported in the United States and China for patients who suffered in-hospital cardiac arrest (IHCA) while infected with COVID-19 early in the pandemic, but the data came from small, single-center studies in overwhelmed hospitals, wrote Saket Girotra, MD, of the University of Iowa, Iowa City, and fellow American Heart Association Get With the Guidelines–Resuscitation Investigators. Whether these early reports reflect the broader experience of patients with COVID-19 in hospitals in the United States remains unknown.

In a study published as a research letter in JAMA Network Open, the researchers reviewed data from the American Heart Association Get With the Guidelines–Resuscitation registry. The registry collects detailed information on patients aged 18 years and older who experience cardiac arrest at participating hospitals in the United States. The study population included 24,915 patients aged 18 years and older from 286 hospitals who experienced IHCA during March–December 2020. The mean age of the patients was 64.7 years; 61.1% were White, 24.8% were Black, 3.8% were of other race or ethnicity, and 10.3% were of unknown race or ethnicity.

The primary outcomes were survival to discharge and return of spontaneous circulation (ROSC) for at least 20 minutes.

A total of 5,916 patients (23.7%) had suspected or confirmed COVID-19 infections, and infected patients were more likely to be younger, male, and Black. Patients with COVID-19 infections also were significantly more likely than noninfected patients to have nonshockable rhythm, pneumonia, respiratory insufficiency, or sepsis, and to be on mechanical ventilation or vasopressors when the IHCA occurred, the researchers noted.

Survival rates to hospital discharge were 11.9% for COVID-19 patients, compared with 23.5% for noninfected patients (adjusted relative risk, 0.65; P < .001). ROSC was 53.7% and 63.6%, for infected and noninfected patients, respectively (aRR, 0.86; P < .001).

COVID-19 patients also were more likely than noninfected patients to receive delayed defibrillation, the researchers said. “Although delays in resuscitation, especially defibrillation, may have contributed to lower survival, the negative association of COVID-19 with survival in this study was consistent across subgroups, including patients who received timely treatment with defibrillation and epinephrine.”

The extremely low survival rate in early pandemic studies likely reflected the overwhelming burden on health systems at the time, the researchers said in their discussion.

The study findings were limited by several factors, including potential confounding from unmeasured variables, the use of a quality improvement registry that may not reflect nonparticipating hospitals, and potential false-positive COVID-19 cases. However, the result support findings from recent studies of multiple centers and extend clinical knowledge by comparing infected and noninfected patients from a larger group of hospitals than previously studied, the researchers said.

“We believe that these data will be relevant to health care providers and hospital administrators as the COVID-19 pandemic continues,” they concluded.
 

Think beyond COVID-19 for cardiac care

“Early during the pandemic, questions were raised whether COVID-19 patients should be treated with CPR,” Dr. Girotra said in an interview. “This was because initial studies had found a dismal survival of 0%-3% in COVID patients treated with CPR. The potential of transmitting the virus to health care professionals during CPR further heightened these concerns. We wanted to know whether the poor survival reported in these initial studies were broadly representative.”

Dr. Girotra said that some of the study findings were surprising. “We found that of all patients with IHCA in 2020 in our study, one in four were suspected or confirmed to have COVID-19 infection. We were surprised by the magnitude of COVID’s impact on the cardiac arrest incidence.”

The implications for clinical decision-making are to think outside of COVID-19 infection, said Dr. Girotra. In the current study, “Although overall survival of cardiac arrest in COVID-positive patients was 30% lower, compared to non-COVID patients, it was not as poor as previously reported. COVID-19 infection alone should not be considered the sole factor for making decisions regarding CPR.

“Over the past 2 decades, we have experienced large gains in survival for in-hospital cardiac arrest. However, the COVID-19 pandemic has eroded these gains,” said Dr. Girotra. “Future studies are needed to monitor the impact of any new variants on cardiac arrest care,” as well as studies “to see whether we return to the prepandemic levels of IHCA survival once the pandemic recedes.”

Dr. Girotra has no relevant financial disclosures.

A 64-year-old woman is evaluated for fever, diarrhea, and abdominal pain. She was diagnosed with Clostridioides difficile 2 months ago and completed a 10-day course of vancomycin. Her stool toxin test is positive for Clostridioides difficile (C. diff). Based on the most recent Infectious Diseases Society of America (IDSA) guidelines, what would be the preferred therapy?

A) Metronidazole

B) Fidaxomicin + bezlotoxumab

C) Vancomycin

D) Fecal microbiota transplant

The recommendations from the 2021 guidelines would be to treat with fidaxomicin and add bezlotoxumab.¹ The guidelines highlight the following changes:

• In patients with an initial Clostridioides difficile infections (CDI) fidaxomicin is preferred over vancomycin.
• In patients with a recurrent CDI episode, fidaxomicin is favored over vancomycin. For patients with multiple recurrences, vancomycin in a tapered and pulsed regimen, vancomycin followed by rifaximin, and fecal microbiota transplantation are options in addition to fidaxomicin.
• Addition of bezlotoxumab to standard of care antibiotics is recommended for recurrence of CDI within the first 6 months over standard of care antibiotics alone

The feasibility of these recommendations is up for debate. The cost of a course of fidaxomicin is $2,800, and the cost of bezlotoxumab is about $4,500. Cost effectiveness studies that helped drive the recommendations show a savings by reducing future hospitalizations for C. diff.² Unfortunately, this enthusiasm is not shared by many insurance companies for outpatient treatment.

Knee osteoarthritis

I will save you the excitement of the new acromegaly guidelines and focus on something we see all the time: knee osteoarthritis. The American Academy of Orthopedic Surgeons has released guidelines for this condition.³ The useful points I found were as follows:

• Topical application of nonsteroidal anti-inflammatory drugs (e.g., diclofenac) should be used to improve function and quality of life in patients with knee osteoarthritis.
• Exercise routines (i.e, supervised, unsupervised, and/or aquatic) are recommended versus no exercise for improving pain and function in patients with knee osteoarthritis.
• Not recommended is the use of oral narcotics (including tramadol), as they are not effective at improving pain or function, and their use results in a significant increased risk of adverse events.
• Not recommended for routine use in symptomatic knee osteoarthritis is intra-articular injection of hyaluronic acid.

I was happy to see topical NSAIDS recommended, as they are a much safer option in older patients than oral NSAIDS (which were also recommended). The recommendation against narcotics, including tramadol, is a shift from the recommendation of tramadol in the 2013 guidelines.⁴ Acetaminophen was enthusiastically recommended, and is still worth a try.

Sexually transmitted infections

• The dosing for the treatment of gonorrhea has increased to 500 mg of ceftriaxone (was 250 mg in 2015 guidelines), with a dose of 1 gram for patients who weigh more than 150 kg.
• Chlamydia infections should be treated with a 7-day course of doxycycline as the preferred antibiotic, except in pregnant women (where azithromycin is recommended).
• Herpes simplex virus 2 recurrences can be treated with twice-daily dosing of 800 mg of acyclovir for 5 days, or acyclovir 800 mg three times a day for 2 days. The shortest course for recurrence is famciclovir 1 gram twice a day for 1 day.
• The Centers for Disease Control and Prevention has removed the recommendation for avoidance of alcohol when taking metronidazole.

I hope these highlights of guidelines for common issues we see are helpful!

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. Johnson S et al. Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused update guidelines on management of Clostridioides difficile Infection in adults. Clin Infect Dis. 2021 Sep 7;73(5):e1029-e1044.

2. Pabhu VS et al. Cost-effectiveness of bezlotoxumab compared with placebo for the prevention of recurrent Clostridium difficile infection. Clin Infect Dis. 2018 Feb 1;66(3):355-62.

3. American Academy of Orthopaedic Surgeons: Management of osteoarthritis of the knee (non-arthroplasty) – Evidence-based clinical practice guideline (2021 Aug 31. https://www.aaos.org/oak3cpg).

4. Jevsevar DS. Treatment of osteoarthritis of the knee: Evidence-based guideline, 2nd edition. J Am Acad Orthop Surg. 2013: Sep;21(9):571-6.

5. Sexually transmitted infections treatment guidelines, 2021 recommendations and reports. MMWR 2021 Jul 23;70(4):1-187.

A 64-year-old woman is evaluated for fever, diarrhea, and abdominal pain. She was diagnosed with Clostridioides difficile 2 months ago and completed a 10-day course of vancomycin. Her stool toxin test is positive for Clostridioides difficile (C. diff). Based on the most recent Infectious Diseases Society of America (IDSA) guidelines, what would be the preferred therapy?

A) Metronidazole

B) Fidaxomicin + bezlotoxumab

C) Vancomycin

D) Fecal microbiota transplant

The recommendations from the 2021 guidelines would be to treat with fidaxomicin and add bezlotoxumab.¹ The guidelines highlight the following changes:

• In patients with an initial Clostridioides difficile infections (CDI) fidaxomicin is preferred over vancomycin.
• In patients with a recurrent CDI episode, fidaxomicin is favored over vancomycin. For patients with multiple recurrences, vancomycin in a tapered and pulsed regimen, vancomycin followed by rifaximin, and fecal microbiota transplantation are options in addition to fidaxomicin.
• Addition of bezlotoxumab to standard of care antibiotics is recommended for recurrence of CDI within the first 6 months over standard of care antibiotics alone

The feasibility of these recommendations is up for debate. The cost of a course of fidaxomicin is $2,800, and the cost of bezlotoxumab is about $4,500. Cost effectiveness studies that helped drive the recommendations show a savings by reducing future hospitalizations for C. diff.² Unfortunately, this enthusiasm is not shared by many insurance companies for outpatient treatment.

Knee osteoarthritis

I will save you the excitement of the new acromegaly guidelines and focus on something we see all the time: knee osteoarthritis. The American Academy of Orthopedic Surgeons has released guidelines for this condition.³ The useful points I found were as follows:

• Topical application of nonsteroidal anti-inflammatory drugs (e.g., diclofenac) should be used to improve function and quality of life in patients with knee osteoarthritis.
• Exercise routines (i.e, supervised, unsupervised, and/or aquatic) are recommended versus no exercise for improving pain and function in patients with knee osteoarthritis.
• Not recommended is the use of oral narcotics (including tramadol), as they are not effective at improving pain or function, and their use results in a significant increased risk of adverse events.
• Not recommended for routine use in symptomatic knee osteoarthritis is intra-articular injection of hyaluronic acid.

I was happy to see topical NSAIDS recommended, as they are a much safer option in older patients than oral NSAIDS (which were also recommended). The recommendation against narcotics, including tramadol, is a shift from the recommendation of tramadol in the 2013 guidelines.⁴ Acetaminophen was enthusiastically recommended, and is still worth a try.

Sexually transmitted infections

• The dosing for the treatment of gonorrhea has increased to 500 mg of ceftriaxone (was 250 mg in 2015 guidelines), with a dose of 1 gram for patients who weigh more than 150 kg.
• Chlamydia infections should be treated with a 7-day course of doxycycline as the preferred antibiotic, except in pregnant women (where azithromycin is recommended).
• Herpes simplex virus 2 recurrences can be treated with twice-daily dosing of 800 mg of acyclovir for 5 days, or acyclovir 800 mg three times a day for 2 days. The shortest course for recurrence is famciclovir 1 gram twice a day for 1 day.
• The Centers for Disease Control and Prevention has removed the recommendation for avoidance of alcohol when taking metronidazole.

I hope these highlights of guidelines for common issues we see are helpful!

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. Johnson S et al. Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused update guidelines on management of Clostridioides difficile Infection in adults. Clin Infect Dis. 2021 Sep 7;73(5):e1029-e1044.

2. Pabhu VS et al. Cost-effectiveness of bezlotoxumab compared with placebo for the prevention of recurrent Clostridium difficile infection. Clin Infect Dis. 2018 Feb 1;66(3):355-62.

3. American Academy of Orthopaedic Surgeons: Management of osteoarthritis of the knee (non-arthroplasty) – Evidence-based clinical practice guideline (2021 Aug 31. https://www.aaos.org/oak3cpg).

4. Jevsevar DS. Treatment of osteoarthritis of the knee: Evidence-based guideline, 2nd edition. J Am Acad Orthop Surg. 2013: Sep;21(9):571-6.

5. Sexually transmitted infections treatment guidelines, 2021 recommendations and reports. MMWR 2021 Jul 23;70(4):1-187.

A 64-year-old woman is evaluated for fever, diarrhea, and abdominal pain. She was diagnosed with Clostridioides difficile 2 months ago and completed a 10-day course of vancomycin. Her stool toxin test is positive for Clostridioides difficile (C. diff). Based on the most recent Infectious Diseases Society of America (IDSA) guidelines, what would be the preferred therapy?

A) Metronidazole

B) Fidaxomicin + bezlotoxumab

C) Vancomycin

D) Fecal microbiota transplant

The recommendations from the 2021 guidelines would be to treat with fidaxomicin and add bezlotoxumab.¹ The guidelines highlight the following changes:

• In patients with an initial Clostridioides difficile infections (CDI) fidaxomicin is preferred over vancomycin.
• In patients with a recurrent CDI episode, fidaxomicin is favored over vancomycin. For patients with multiple recurrences, vancomycin in a tapered and pulsed regimen, vancomycin followed by rifaximin, and fecal microbiota transplantation are options in addition to fidaxomicin.
• Addition of bezlotoxumab to standard of care antibiotics is recommended for recurrence of CDI within the first 6 months over standard of care antibiotics alone

The feasibility of these recommendations is up for debate. The cost of a course of fidaxomicin is $2,800, and the cost of bezlotoxumab is about $4,500. Cost effectiveness studies that helped drive the recommendations show a savings by reducing future hospitalizations for C. diff.² Unfortunately, this enthusiasm is not shared by many insurance companies for outpatient treatment.

Knee osteoarthritis

I will save you the excitement of the new acromegaly guidelines and focus on something we see all the time: knee osteoarthritis. The American Academy of Orthopedic Surgeons has released guidelines for this condition.³ The useful points I found were as follows:

• Topical application of nonsteroidal anti-inflammatory drugs (e.g., diclofenac) should be used to improve function and quality of life in patients with knee osteoarthritis.
• Exercise routines (i.e, supervised, unsupervised, and/or aquatic) are recommended versus no exercise for improving pain and function in patients with knee osteoarthritis.
• Not recommended is the use of oral narcotics (including tramadol), as they are not effective at improving pain or function, and their use results in a significant increased risk of adverse events.
• Not recommended for routine use in symptomatic knee osteoarthritis is intra-articular injection of hyaluronic acid.

I was happy to see topical NSAIDS recommended, as they are a much safer option in older patients than oral NSAIDS (which were also recommended). The recommendation against narcotics, including tramadol, is a shift from the recommendation of tramadol in the 2013 guidelines.⁴ Acetaminophen was enthusiastically recommended, and is still worth a try.

Sexually transmitted infections

• The dosing for the treatment of gonorrhea has increased to 500 mg of ceftriaxone (was 250 mg in 2015 guidelines), with a dose of 1 gram for patients who weigh more than 150 kg.
• Chlamydia infections should be treated with a 7-day course of doxycycline as the preferred antibiotic, except in pregnant women (where azithromycin is recommended).
• Herpes simplex virus 2 recurrences can be treated with twice-daily dosing of 800 mg of acyclovir for 5 days, or acyclovir 800 mg three times a day for 2 days. The shortest course for recurrence is famciclovir 1 gram twice a day for 1 day.
• The Centers for Disease Control and Prevention has removed the recommendation for avoidance of alcohol when taking metronidazole.

I hope these highlights of guidelines for common issues we see are helpful!

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. Johnson S et al. Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused update guidelines on management of Clostridioides difficile Infection in adults. Clin Infect Dis. 2021 Sep 7;73(5):e1029-e1044.

2. Pabhu VS et al. Cost-effectiveness of bezlotoxumab compared with placebo for the prevention of recurrent Clostridium difficile infection. Clin Infect Dis. 2018 Feb 1;66(3):355-62.

3. American Academy of Orthopaedic Surgeons: Management of osteoarthritis of the knee (non-arthroplasty) – Evidence-based clinical practice guideline (2021 Aug 31. https://www.aaos.org/oak3cpg).

4. Jevsevar DS. Treatment of osteoarthritis of the knee: Evidence-based guideline, 2nd edition. J Am Acad Orthop Surg. 2013: Sep;21(9):571-6.

5. Sexually transmitted infections treatment guidelines, 2021 recommendations and reports. MMWR 2021 Jul 23;70(4):1-187.