Don’t miss type 1 diabetes in adults

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Mon, 09/25/2023 - 17:15

Approximately 4 in 10 cases of type 1 diabetes in adults are diagnosed at age 30 years and older, based on data from nearly 1,000 individuals.

New-onset type 1 diabetes in adults is often misdiagnosed as type 2 diabetes, which may lead to inappropriate care, wrote Michael Fang, PhD, of Johns Hopkins University, Baltimore, and colleagues.

Previous research suggests that more than half of type 1 diabetes cases develop in adults, but data on variations in clinical characteristics and age at diagnosis are limited, the researchers said. “Clarifying the burden of adult-onset type 1 diabetes in the general population may help reduce misdiagnosis.”

In a study published in Annals of Internal Medicine, the researchers identified 947 adults aged 18 years and older with newly diagnosed type 1 diabetes, by using data from the National Health Interview Survey between 2016 and 2022. The subjects’ mean age at the time of the survey was 49 years and 48% were women. The racial/ethnic distribution was 73% non-Hispanic White, 10% non-Hispanic Black, 12% Hispanic, 3%, non-Hispanic Asian, and 3% other race/ethnicity.

Overall, 37% of participants were diagnosed with type 1 diabetes after age 30 years, with an overall median age at diagnosis of 24 years.

Type 1 diabetes was diagnosed later in men than in women, at a median age of 27 years vs. 22 years, respectively, and later in racial/ethnic minorities than in non-Hispanic Whites, with a median age of 26-30 years versus 21 years, respectively.

Autoantibody and C-peptide tests are recommended to confirm type 1 diabetes in adults with a suspected diagnosis, but the best method to identify high-risk adults remains unclear, the researchers wrote in their discussion.

“Traditional markers used to differentiate type 1 and type 2 diabetes, such as body mass index, may have limited utility, especially because obesity is now common in the type 1 diabetes population,” they said. New tools combining clinical features and biomarkers may improve accuracy of diagnosis of type 1 diabetes in the adult population, but more research is needed.

The findings were limited by several factors including misclassification based on self-reports of diagnosis and age, the researchers noted. Other limitations included lack of data on diagnostic measures such as levels of autoantibodies, C-peptides, and other indicators of diabetes, as well as inexact subgroup estimates because of small sample sizes.

“We extended existing research by characterizing the age at diagnosis in a nationally representative sample and by documenting variation across race/ethnicity and clinical characteristics,” they said.

The study was supported by grants from the National Heart, Lung, and Blood Institute. The lead authors had no financial conflicts to disclose. Corresponding author Elizabeth Selvin, PhD, disclosed grants from NIH and FNIH, personal fees from Novo Nordisk, other financial relationships with Wolters Kluwer, and nonfinancial support from many pharmaceutical companies outside the current study; she also serves as deputy editor of Diabetes Care and a member of the editorial board of Diabetologia.

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Approximately 4 in 10 cases of type 1 diabetes in adults are diagnosed at age 30 years and older, based on data from nearly 1,000 individuals.

New-onset type 1 diabetes in adults is often misdiagnosed as type 2 diabetes, which may lead to inappropriate care, wrote Michael Fang, PhD, of Johns Hopkins University, Baltimore, and colleagues.

Previous research suggests that more than half of type 1 diabetes cases develop in adults, but data on variations in clinical characteristics and age at diagnosis are limited, the researchers said. “Clarifying the burden of adult-onset type 1 diabetes in the general population may help reduce misdiagnosis.”

In a study published in Annals of Internal Medicine, the researchers identified 947 adults aged 18 years and older with newly diagnosed type 1 diabetes, by using data from the National Health Interview Survey between 2016 and 2022. The subjects’ mean age at the time of the survey was 49 years and 48% were women. The racial/ethnic distribution was 73% non-Hispanic White, 10% non-Hispanic Black, 12% Hispanic, 3%, non-Hispanic Asian, and 3% other race/ethnicity.

Overall, 37% of participants were diagnosed with type 1 diabetes after age 30 years, with an overall median age at diagnosis of 24 years.

Type 1 diabetes was diagnosed later in men than in women, at a median age of 27 years vs. 22 years, respectively, and later in racial/ethnic minorities than in non-Hispanic Whites, with a median age of 26-30 years versus 21 years, respectively.

Autoantibody and C-peptide tests are recommended to confirm type 1 diabetes in adults with a suspected diagnosis, but the best method to identify high-risk adults remains unclear, the researchers wrote in their discussion.

“Traditional markers used to differentiate type 1 and type 2 diabetes, such as body mass index, may have limited utility, especially because obesity is now common in the type 1 diabetes population,” they said. New tools combining clinical features and biomarkers may improve accuracy of diagnosis of type 1 diabetes in the adult population, but more research is needed.

The findings were limited by several factors including misclassification based on self-reports of diagnosis and age, the researchers noted. Other limitations included lack of data on diagnostic measures such as levels of autoantibodies, C-peptides, and other indicators of diabetes, as well as inexact subgroup estimates because of small sample sizes.

“We extended existing research by characterizing the age at diagnosis in a nationally representative sample and by documenting variation across race/ethnicity and clinical characteristics,” they said.

The study was supported by grants from the National Heart, Lung, and Blood Institute. The lead authors had no financial conflicts to disclose. Corresponding author Elizabeth Selvin, PhD, disclosed grants from NIH and FNIH, personal fees from Novo Nordisk, other financial relationships with Wolters Kluwer, and nonfinancial support from many pharmaceutical companies outside the current study; she also serves as deputy editor of Diabetes Care and a member of the editorial board of Diabetologia.

Approximately 4 in 10 cases of type 1 diabetes in adults are diagnosed at age 30 years and older, based on data from nearly 1,000 individuals.

New-onset type 1 diabetes in adults is often misdiagnosed as type 2 diabetes, which may lead to inappropriate care, wrote Michael Fang, PhD, of Johns Hopkins University, Baltimore, and colleagues.

Previous research suggests that more than half of type 1 diabetes cases develop in adults, but data on variations in clinical characteristics and age at diagnosis are limited, the researchers said. “Clarifying the burden of adult-onset type 1 diabetes in the general population may help reduce misdiagnosis.”

In a study published in Annals of Internal Medicine, the researchers identified 947 adults aged 18 years and older with newly diagnosed type 1 diabetes, by using data from the National Health Interview Survey between 2016 and 2022. The subjects’ mean age at the time of the survey was 49 years and 48% were women. The racial/ethnic distribution was 73% non-Hispanic White, 10% non-Hispanic Black, 12% Hispanic, 3%, non-Hispanic Asian, and 3% other race/ethnicity.

Overall, 37% of participants were diagnosed with type 1 diabetes after age 30 years, with an overall median age at diagnosis of 24 years.

Type 1 diabetes was diagnosed later in men than in women, at a median age of 27 years vs. 22 years, respectively, and later in racial/ethnic minorities than in non-Hispanic Whites, with a median age of 26-30 years versus 21 years, respectively.

Autoantibody and C-peptide tests are recommended to confirm type 1 diabetes in adults with a suspected diagnosis, but the best method to identify high-risk adults remains unclear, the researchers wrote in their discussion.

“Traditional markers used to differentiate type 1 and type 2 diabetes, such as body mass index, may have limited utility, especially because obesity is now common in the type 1 diabetes population,” they said. New tools combining clinical features and biomarkers may improve accuracy of diagnosis of type 1 diabetes in the adult population, but more research is needed.

The findings were limited by several factors including misclassification based on self-reports of diagnosis and age, the researchers noted. Other limitations included lack of data on diagnostic measures such as levels of autoantibodies, C-peptides, and other indicators of diabetes, as well as inexact subgroup estimates because of small sample sizes.

“We extended existing research by characterizing the age at diagnosis in a nationally representative sample and by documenting variation across race/ethnicity and clinical characteristics,” they said.

The study was supported by grants from the National Heart, Lung, and Blood Institute. The lead authors had no financial conflicts to disclose. Corresponding author Elizabeth Selvin, PhD, disclosed grants from NIH and FNIH, personal fees from Novo Nordisk, other financial relationships with Wolters Kluwer, and nonfinancial support from many pharmaceutical companies outside the current study; she also serves as deputy editor of Diabetes Care and a member of the editorial board of Diabetologia.

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How targeted drugs can vanquish a virulent leukemia

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Fri, 10/06/2023 - 17:14

For patients with acute myeloid leukemia (AML), especially those who are older or have relapsed/refractory disease, standard chemotherapy treatments often fail to change their poor clinical trajectories. These days, however, a new era of targeted therapy is improving prognoses somewhat – and raising hopes that even bigger advancements are on the horizon.

“We went almost 3 decades with nothing, then all of a sudden we’ve had nine approvals in 5 or 6 years,” said Harvard Medical School, Boston, leukemia specialist Amir Fathi, MD, in an interview. “We’ve had a lot of advancement and a number of good options emerge.”

However, Dr. Fathi and other hematologists cautioned that the treatment landscape is becoming more complex to navigate. And they noted that prognoses for many older patients with AML remain grim. The expensive new treatments may only extend their lifespans by a matter of months, although some are surviving for years.

As the specialists explained, there are a variety of reasons why AML is especially difficult to treat.

“AML is one of the fastest growing human cancers, with tumor cell doubling times measured in mere hours in some patients. Therefore patients can present critically ill with white blood cell counts in the [hundreds of thousands of white blood cells per microliter instead of the normal range of 4,000-11,000]," said leukemia specialist Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y. “Because blood cells are found in every organ of the body, the sheer volume of rapidly growing cancer cells can overwhelm multiple organ systems in a very short amount of time. These rapid growing cells and the fact that the median age of diagnosis with AML is 67-70 years old makes this a clinically challenging cancer to treat. Chemotherapy strong enough to kill cancer cells run the risk of also harming the patient as well.”

Also, older patients often have comorbidities, and they face risks of infection from both the disease and its treatments, said AML specialist Nicole R. Grieselhuber, MD, PhD, of the Ohio State University, Columbus, in an interview.

Enter targeted therapy, which “has allowed individuals who previously were not candidates for cytotoxic chemotherapy because of their age or possible toxicities to receive effective therapy for AML,” Dr. Wang said. “Therapy directed at specific biological features of AML cells such as mutations (FLT3, IDH1, IDH2) or surface proteins (CD33) can augment the efficacy of conventional chemotherapy or in some cases (i.e., FLT3 inhibitors) be more effective than chemotherapy in controlling AML.”

Targeted therapy drugs “are expected to more selectively kill cancer cells and spare normal counterparts,” she added.

The FDA has approved nine targeted therapy drugs for AML in the last few years.

Retinoic acid and arsenic trioxide therapy for acute promyelocytic leukemia “has transformed this AML subtype into one of the most curable AML diseases,” Dr. Wang said. A 2017 long-term analysis of the drug combination found that complete remission was reached in 96% of 54 high-risk patients and 133 low-risk patients; the 5-year survival rate was 88%. (Some patients also received gemtuzumab ozogamicin, a CD33 antibody-drug conjugate.)

According to Dr. Wang, three FLT3 inhibitors have been approved for AML with the FLT3 mutation: midostaurin and quizartinib in the frontline setting in conjunction with intensive chemotherapy and gilteritinib for relapsed/refractory FLT3-mutant AML.

A 2017 study linked midostaurin plus chemotherapy to longer survival (hazard ratio for death = 0.78; P = .009), versus placebo plus chemotherapy, in patients aged 18-59. This year, a phase 3 randomized trial of quizartinib versus placebo linked the drug to longer survival median overall (31.9 months versus 15.1 months; P = .032) In a 2019 trial, patients who took gilteritinib had longer median overall survival (9.3 months versus 5.6 months; HR for death = 0.64; P < .001).

The success of these treatments “has led FLT3 mutant AML to be reclassified from a poor risk AML subtype to intermediate risk AML,” Dr. Wang said.

A 2022 report about FLT3 inhibitors cautioned, however, that “several drug resistance mechanisms have been identified” and added that “the benefit of FLT3 inhibitor maintenance therapy, either post chemotherapy or post transplant, remains controversial, although several studies are ongoing.”

Gemtuzumab ozogamicin is a monoclonal antibody connected to a chemotherapy drug, according to the American Cancer Society. “The addition of gemtuzumab ozogamicin to intensive chemotherapy has enhanced outcomes of favorable and intermediate risk disease,” Dr. Wang said.

Ivosidenib, olutasidenib, and enasidenib target the IDH1 or IDH2 genes in ADL. “These drugs seem to work by helping the leukemia cells mature (differentiate) into more normal cells,” according to the American Cancer Society. “Because of this, they are sometimes referred to as differentiation agents.”

In older adults, a combination treatment with venetoclax, a BCL-2 inhibitor, and a hypomethylating agent has become standard, Ohio State’s Dr. Grieselhuber said. The treatment is FDA approved.

There are caveats to targeted therapy in AML. The treatments can be enormously expensive, “and even patients with insurance are often shocked by the copay,” Dr. Grieselhuber said. It helps to work with pharmacists, social workers, or nurse navigators to help patients afford the treatments, she said.

Side effects vary by therapy and can include QT elongation and differentiation syndrome.

Most challenging of all, many AML patients still face shortened lifespans even if new treatments are available for them.

“Typically for older patients with AML, the lifespan of patients with therapy was 5-7 months and without therapy was 2-3 months,” Dr. Wang said. “Now, with regimens specifically designed for elderly and/or unfit subjects, many individuals are now routinely living more than a year: 14-18 months to 3-4 years.”

But “the vast majority of AML patients will still die of their disease with overall 5-year outcomes still less than 30% in all age categories,” she said. In addition, “fewer than 50% of AML patients are eligible for treatment with FDA-approved targeted therapies, as their disease biology does not express the mutation or protein needed for efficacy.”

Still, she said, “this represents a vast improvement.” And, she added, “in younger individuals, the combination of chemotherapy followed by allogeneic transplant has now permitted more of these individuals to be cured of their disease.” Dr. Grieselhuber noted that transplants are now considered appropriate even for patients in their 60s or early 70s, and they can be combined with targeted therapy.

Dr. Grieselhuber urged colleagues to keep in mind that quality-of-life preferences will play a role in some patient choices. For example, a elderly patient may reject burdensome infusion therapy and choose a pill instead, even if it has less efficacy. “There’s really no one-size-fits-all,” she said.

And, she added, it can be difficult to make choices about treatment because of the lack of randomized, head-to-head data regarding new therapies.

What’s on the horizon? Dr. Wang highlighted a novel class of targeted therapies called menin inhibitors for patients with NPM1-mutated AML, which she said accounts for one-third of patients with the disease. A treatment targeting disease in the 5%-10% patients with the KMT2A gene is also in the works, she said.

For now, Dr. Wang said it’s essential for clinicians “to perform timely comprehensive molecular and genomic tests on all AML patients at diagnosis and relapse to determine which individuals would benefit from targeted therapy versus cytotoxic chemotherapy. And participation in clinical trials at every stage of AML therapy can help accelerate clinical development of new agents for this disease.”

Dr. Fathi discloses relationships with Daiichi Sankyo, Pfizer, Rigel, Autolus, Amgen, Servier, Takeda, Orum, Menarini, Remix, AbbVie, Astellas, BMS, Ibsen, Gilead, Genentech, and AstraZeneca. Dr. Wang discloses ties with AbbVie, Astellas, BMS, CTI Biopharma, Daiichi Sankyo, Gilead, GSK, Johnson & Johnson, Kite, Kura, Novartis, Pfizer, Rigel, Sellas, and Sumitomo Pharma. Dr. Grieselhuber has no disclosures.

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For patients with acute myeloid leukemia (AML), especially those who are older or have relapsed/refractory disease, standard chemotherapy treatments often fail to change their poor clinical trajectories. These days, however, a new era of targeted therapy is improving prognoses somewhat – and raising hopes that even bigger advancements are on the horizon.

“We went almost 3 decades with nothing, then all of a sudden we’ve had nine approvals in 5 or 6 years,” said Harvard Medical School, Boston, leukemia specialist Amir Fathi, MD, in an interview. “We’ve had a lot of advancement and a number of good options emerge.”

However, Dr. Fathi and other hematologists cautioned that the treatment landscape is becoming more complex to navigate. And they noted that prognoses for many older patients with AML remain grim. The expensive new treatments may only extend their lifespans by a matter of months, although some are surviving for years.

As the specialists explained, there are a variety of reasons why AML is especially difficult to treat.

“AML is one of the fastest growing human cancers, with tumor cell doubling times measured in mere hours in some patients. Therefore patients can present critically ill with white blood cell counts in the [hundreds of thousands of white blood cells per microliter instead of the normal range of 4,000-11,000]," said leukemia specialist Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y. “Because blood cells are found in every organ of the body, the sheer volume of rapidly growing cancer cells can overwhelm multiple organ systems in a very short amount of time. These rapid growing cells and the fact that the median age of diagnosis with AML is 67-70 years old makes this a clinically challenging cancer to treat. Chemotherapy strong enough to kill cancer cells run the risk of also harming the patient as well.”

Also, older patients often have comorbidities, and they face risks of infection from both the disease and its treatments, said AML specialist Nicole R. Grieselhuber, MD, PhD, of the Ohio State University, Columbus, in an interview.

Enter targeted therapy, which “has allowed individuals who previously were not candidates for cytotoxic chemotherapy because of their age or possible toxicities to receive effective therapy for AML,” Dr. Wang said. “Therapy directed at specific biological features of AML cells such as mutations (FLT3, IDH1, IDH2) or surface proteins (CD33) can augment the efficacy of conventional chemotherapy or in some cases (i.e., FLT3 inhibitors) be more effective than chemotherapy in controlling AML.”

Targeted therapy drugs “are expected to more selectively kill cancer cells and spare normal counterparts,” she added.

The FDA has approved nine targeted therapy drugs for AML in the last few years.

Retinoic acid and arsenic trioxide therapy for acute promyelocytic leukemia “has transformed this AML subtype into one of the most curable AML diseases,” Dr. Wang said. A 2017 long-term analysis of the drug combination found that complete remission was reached in 96% of 54 high-risk patients and 133 low-risk patients; the 5-year survival rate was 88%. (Some patients also received gemtuzumab ozogamicin, a CD33 antibody-drug conjugate.)

According to Dr. Wang, three FLT3 inhibitors have been approved for AML with the FLT3 mutation: midostaurin and quizartinib in the frontline setting in conjunction with intensive chemotherapy and gilteritinib for relapsed/refractory FLT3-mutant AML.

A 2017 study linked midostaurin plus chemotherapy to longer survival (hazard ratio for death = 0.78; P = .009), versus placebo plus chemotherapy, in patients aged 18-59. This year, a phase 3 randomized trial of quizartinib versus placebo linked the drug to longer survival median overall (31.9 months versus 15.1 months; P = .032) In a 2019 trial, patients who took gilteritinib had longer median overall survival (9.3 months versus 5.6 months; HR for death = 0.64; P < .001).

The success of these treatments “has led FLT3 mutant AML to be reclassified from a poor risk AML subtype to intermediate risk AML,” Dr. Wang said.

A 2022 report about FLT3 inhibitors cautioned, however, that “several drug resistance mechanisms have been identified” and added that “the benefit of FLT3 inhibitor maintenance therapy, either post chemotherapy or post transplant, remains controversial, although several studies are ongoing.”

Gemtuzumab ozogamicin is a monoclonal antibody connected to a chemotherapy drug, according to the American Cancer Society. “The addition of gemtuzumab ozogamicin to intensive chemotherapy has enhanced outcomes of favorable and intermediate risk disease,” Dr. Wang said.

Ivosidenib, olutasidenib, and enasidenib target the IDH1 or IDH2 genes in ADL. “These drugs seem to work by helping the leukemia cells mature (differentiate) into more normal cells,” according to the American Cancer Society. “Because of this, they are sometimes referred to as differentiation agents.”

In older adults, a combination treatment with venetoclax, a BCL-2 inhibitor, and a hypomethylating agent has become standard, Ohio State’s Dr. Grieselhuber said. The treatment is FDA approved.

There are caveats to targeted therapy in AML. The treatments can be enormously expensive, “and even patients with insurance are often shocked by the copay,” Dr. Grieselhuber said. It helps to work with pharmacists, social workers, or nurse navigators to help patients afford the treatments, she said.

Side effects vary by therapy and can include QT elongation and differentiation syndrome.

Most challenging of all, many AML patients still face shortened lifespans even if new treatments are available for them.

“Typically for older patients with AML, the lifespan of patients with therapy was 5-7 months and without therapy was 2-3 months,” Dr. Wang said. “Now, with regimens specifically designed for elderly and/or unfit subjects, many individuals are now routinely living more than a year: 14-18 months to 3-4 years.”

But “the vast majority of AML patients will still die of their disease with overall 5-year outcomes still less than 30% in all age categories,” she said. In addition, “fewer than 50% of AML patients are eligible for treatment with FDA-approved targeted therapies, as their disease biology does not express the mutation or protein needed for efficacy.”

Still, she said, “this represents a vast improvement.” And, she added, “in younger individuals, the combination of chemotherapy followed by allogeneic transplant has now permitted more of these individuals to be cured of their disease.” Dr. Grieselhuber noted that transplants are now considered appropriate even for patients in their 60s or early 70s, and they can be combined with targeted therapy.

Dr. Grieselhuber urged colleagues to keep in mind that quality-of-life preferences will play a role in some patient choices. For example, a elderly patient may reject burdensome infusion therapy and choose a pill instead, even if it has less efficacy. “There’s really no one-size-fits-all,” she said.

And, she added, it can be difficult to make choices about treatment because of the lack of randomized, head-to-head data regarding new therapies.

What’s on the horizon? Dr. Wang highlighted a novel class of targeted therapies called menin inhibitors for patients with NPM1-mutated AML, which she said accounts for one-third of patients with the disease. A treatment targeting disease in the 5%-10% patients with the KMT2A gene is also in the works, she said.

For now, Dr. Wang said it’s essential for clinicians “to perform timely comprehensive molecular and genomic tests on all AML patients at diagnosis and relapse to determine which individuals would benefit from targeted therapy versus cytotoxic chemotherapy. And participation in clinical trials at every stage of AML therapy can help accelerate clinical development of new agents for this disease.”

Dr. Fathi discloses relationships with Daiichi Sankyo, Pfizer, Rigel, Autolus, Amgen, Servier, Takeda, Orum, Menarini, Remix, AbbVie, Astellas, BMS, Ibsen, Gilead, Genentech, and AstraZeneca. Dr. Wang discloses ties with AbbVie, Astellas, BMS, CTI Biopharma, Daiichi Sankyo, Gilead, GSK, Johnson & Johnson, Kite, Kura, Novartis, Pfizer, Rigel, Sellas, and Sumitomo Pharma. Dr. Grieselhuber has no disclosures.

For patients with acute myeloid leukemia (AML), especially those who are older or have relapsed/refractory disease, standard chemotherapy treatments often fail to change their poor clinical trajectories. These days, however, a new era of targeted therapy is improving prognoses somewhat – and raising hopes that even bigger advancements are on the horizon.

“We went almost 3 decades with nothing, then all of a sudden we’ve had nine approvals in 5 or 6 years,” said Harvard Medical School, Boston, leukemia specialist Amir Fathi, MD, in an interview. “We’ve had a lot of advancement and a number of good options emerge.”

However, Dr. Fathi and other hematologists cautioned that the treatment landscape is becoming more complex to navigate. And they noted that prognoses for many older patients with AML remain grim. The expensive new treatments may only extend their lifespans by a matter of months, although some are surviving for years.

As the specialists explained, there are a variety of reasons why AML is especially difficult to treat.

“AML is one of the fastest growing human cancers, with tumor cell doubling times measured in mere hours in some patients. Therefore patients can present critically ill with white blood cell counts in the [hundreds of thousands of white blood cells per microliter instead of the normal range of 4,000-11,000]," said leukemia specialist Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y. “Because blood cells are found in every organ of the body, the sheer volume of rapidly growing cancer cells can overwhelm multiple organ systems in a very short amount of time. These rapid growing cells and the fact that the median age of diagnosis with AML is 67-70 years old makes this a clinically challenging cancer to treat. Chemotherapy strong enough to kill cancer cells run the risk of also harming the patient as well.”

Also, older patients often have comorbidities, and they face risks of infection from both the disease and its treatments, said AML specialist Nicole R. Grieselhuber, MD, PhD, of the Ohio State University, Columbus, in an interview.

Enter targeted therapy, which “has allowed individuals who previously were not candidates for cytotoxic chemotherapy because of their age or possible toxicities to receive effective therapy for AML,” Dr. Wang said. “Therapy directed at specific biological features of AML cells such as mutations (FLT3, IDH1, IDH2) or surface proteins (CD33) can augment the efficacy of conventional chemotherapy or in some cases (i.e., FLT3 inhibitors) be more effective than chemotherapy in controlling AML.”

Targeted therapy drugs “are expected to more selectively kill cancer cells and spare normal counterparts,” she added.

The FDA has approved nine targeted therapy drugs for AML in the last few years.

Retinoic acid and arsenic trioxide therapy for acute promyelocytic leukemia “has transformed this AML subtype into one of the most curable AML diseases,” Dr. Wang said. A 2017 long-term analysis of the drug combination found that complete remission was reached in 96% of 54 high-risk patients and 133 low-risk patients; the 5-year survival rate was 88%. (Some patients also received gemtuzumab ozogamicin, a CD33 antibody-drug conjugate.)

According to Dr. Wang, three FLT3 inhibitors have been approved for AML with the FLT3 mutation: midostaurin and quizartinib in the frontline setting in conjunction with intensive chemotherapy and gilteritinib for relapsed/refractory FLT3-mutant AML.

A 2017 study linked midostaurin plus chemotherapy to longer survival (hazard ratio for death = 0.78; P = .009), versus placebo plus chemotherapy, in patients aged 18-59. This year, a phase 3 randomized trial of quizartinib versus placebo linked the drug to longer survival median overall (31.9 months versus 15.1 months; P = .032) In a 2019 trial, patients who took gilteritinib had longer median overall survival (9.3 months versus 5.6 months; HR for death = 0.64; P < .001).

The success of these treatments “has led FLT3 mutant AML to be reclassified from a poor risk AML subtype to intermediate risk AML,” Dr. Wang said.

A 2022 report about FLT3 inhibitors cautioned, however, that “several drug resistance mechanisms have been identified” and added that “the benefit of FLT3 inhibitor maintenance therapy, either post chemotherapy or post transplant, remains controversial, although several studies are ongoing.”

Gemtuzumab ozogamicin is a monoclonal antibody connected to a chemotherapy drug, according to the American Cancer Society. “The addition of gemtuzumab ozogamicin to intensive chemotherapy has enhanced outcomes of favorable and intermediate risk disease,” Dr. Wang said.

Ivosidenib, olutasidenib, and enasidenib target the IDH1 or IDH2 genes in ADL. “These drugs seem to work by helping the leukemia cells mature (differentiate) into more normal cells,” according to the American Cancer Society. “Because of this, they are sometimes referred to as differentiation agents.”

In older adults, a combination treatment with venetoclax, a BCL-2 inhibitor, and a hypomethylating agent has become standard, Ohio State’s Dr. Grieselhuber said. The treatment is FDA approved.

There are caveats to targeted therapy in AML. The treatments can be enormously expensive, “and even patients with insurance are often shocked by the copay,” Dr. Grieselhuber said. It helps to work with pharmacists, social workers, or nurse navigators to help patients afford the treatments, she said.

Side effects vary by therapy and can include QT elongation and differentiation syndrome.

Most challenging of all, many AML patients still face shortened lifespans even if new treatments are available for them.

“Typically for older patients with AML, the lifespan of patients with therapy was 5-7 months and without therapy was 2-3 months,” Dr. Wang said. “Now, with regimens specifically designed for elderly and/or unfit subjects, many individuals are now routinely living more than a year: 14-18 months to 3-4 years.”

But “the vast majority of AML patients will still die of their disease with overall 5-year outcomes still less than 30% in all age categories,” she said. In addition, “fewer than 50% of AML patients are eligible for treatment with FDA-approved targeted therapies, as their disease biology does not express the mutation or protein needed for efficacy.”

Still, she said, “this represents a vast improvement.” And, she added, “in younger individuals, the combination of chemotherapy followed by allogeneic transplant has now permitted more of these individuals to be cured of their disease.” Dr. Grieselhuber noted that transplants are now considered appropriate even for patients in their 60s or early 70s, and they can be combined with targeted therapy.

Dr. Grieselhuber urged colleagues to keep in mind that quality-of-life preferences will play a role in some patient choices. For example, a elderly patient may reject burdensome infusion therapy and choose a pill instead, even if it has less efficacy. “There’s really no one-size-fits-all,” she said.

And, she added, it can be difficult to make choices about treatment because of the lack of randomized, head-to-head data regarding new therapies.

What’s on the horizon? Dr. Wang highlighted a novel class of targeted therapies called menin inhibitors for patients with NPM1-mutated AML, which she said accounts for one-third of patients with the disease. A treatment targeting disease in the 5%-10% patients with the KMT2A gene is also in the works, she said.

For now, Dr. Wang said it’s essential for clinicians “to perform timely comprehensive molecular and genomic tests on all AML patients at diagnosis and relapse to determine which individuals would benefit from targeted therapy versus cytotoxic chemotherapy. And participation in clinical trials at every stage of AML therapy can help accelerate clinical development of new agents for this disease.”

Dr. Fathi discloses relationships with Daiichi Sankyo, Pfizer, Rigel, Autolus, Amgen, Servier, Takeda, Orum, Menarini, Remix, AbbVie, Astellas, BMS, Ibsen, Gilead, Genentech, and AstraZeneca. Dr. Wang discloses ties with AbbVie, Astellas, BMS, CTI Biopharma, Daiichi Sankyo, Gilead, GSK, Johnson & Johnson, Kite, Kura, Novartis, Pfizer, Rigel, Sellas, and Sumitomo Pharma. Dr. Grieselhuber has no disclosures.

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The ‘triple-G’ agonist for obesity management: Five things to know

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Mon, 09/25/2023 - 15:15

The complex pathophysiology of obesity requires a multidisciplinary approach that includes lifestyle and medical interventions for successful management. Antiobesity medications (AOMs) have emerged as a powerful and life-changing tool for many individuals with obesity who are unable to sustain long-term weight loss through lifestyle changes alone. As with other chronic diseases such as hypertension and hyperlipidemia, the goal of decades of research has been to develop antiobesity medications with long-term efficacy and safety. Recent groundbreaking findings from a phase 2 trial show immense potential for a new AOM.

Here are five things to know about the role of agonists in the management of obesity.

1. Gut hormone physiology informs the development of AOMs.

The three hormones associated with obesity or diabetes are glucagonlike peptide 1 (GLP-1)glucose-dependent insulinotropic peptide (GIP), and glucagon. GLP-1, a peptide released from the intestines in response to food ingestion, increases insulin production, reduces gut motility, and suppresses appetite. GIP is also an intestinal hormone that increases meal-stimulated insulin production and additionally facilitates lipolysis. Glucagon is known to increase hepatic glucose output but will also increase insulin secretion in the setting of hyperglycemia. Glucagon also promotes lipolysis.

Though these hormones are more commonly thought of as incretins, gut hormones that stimulate postprandial insulin secretion, their role in energy physiology is more diverse. Because of multiple mechanisms of action, incretins are increasingly referred to as nutrient-stimulated hormones (NuSH), a term which encompasses other peptides with therapeutic potential (e.g., amylin, oxyntomodulin, peptide tyrosine–tyrosine).

2. Studies have shown that NuSH therapies are highly effective AOMs.

In 2021 the Food and Drug Administration approved subcutaneous semaglutide 2.4 mg, a GLP-1 receptor agonist, for the treatment of obesity. Clinical trials demonstrating an average weight loss of 15% in patients taking semaglutide ushered in a new era of AOMs associated with significant weight loss that not only improve disease activity but also have the potential to achieve diabetes remission. Recent findings from the OASIS I trial demonstrated an average weight loss of 15.1% from baseline in patients treated with oral semaglutide for 68 weeks. Medical societies, including the American Diabetes Association and the American Association for the Study of Liver Diseases, recommend 10%-15% weight loss to fully treat weight-related comorbidities like type 2 diabetes and nonalcoholic fatty liver disease. In 2022, tirzepatide, a dual GLP-1 and GIP receptor agonist, demonstrated an average weight loss of 22.5% in phase 3 of the SURMOUNT-1 trial for obesity – a weight loss approaching that of some bariatric surgeries.

3. Clinical trial data show that the novel triple agonist retatrutide induces significant weight loss.

Preclinical studies on the newest NuSH therapy, triple GLP-1–GIP–glucagon receptor agonist retatrutide, showed predominant activity at the GIP receptor, with less GLP-1– and glucagon-receptor agonism than that of endogenous GLP-1 and GIP. Results from a phase 2 trial published in June 2023 showed a weight loss of 24% at 48 weeks in adults with obesity treated with retatrutide, which is the greatest weight loss reported in an obesity trial so far. Moreover, for the first time in obesity pharmacotherapy research, 100% of participants achieved clinically significant weight loss (defined as ≥ 5% of baseline weight).

4. Retatrutide may improve lipid metabolism.

In the phase 2 trial, retatrutide reduced low-density lipoprotein cholesterol levels by approximately 20%. This degree of reduced plasma LDL-C is dramatic in weight loss studies. Typically, weight loss significantly reduces triglyceride levels, increases high-density lipoprotein cholesterol levels, and has a modest effect on LDL-C reduction of about 5%.

A 20% reduction in LDL-C with retatrutide is hypothesis generating. Preclinical studies have shown glucagon to be an important regulator of proprotein convertase subtilisin/kexin type 9 degradation, with the lack of glucagon resulting in increased PCSK9 levels, decreased LDL receptors, and increased plasma LDL; conversely, treatment with glucagon decreased plasma LDL.

5. The long-term safety of retatrutide still needs to be determined.

In the 48-week phase 2 trial, retatrutide was observed to have a side-effect profile largely similar to other NuSH therapies (e.g., semaglutide 2.4 mg, tirzepatide), with a predominance of gastrointestinal symptoms including nausea, diarrhea, vomiting, and constipation. However, side effects potentially unique to retatrutide also emerged. Cutaneous hyperesthesia and skin sensitivity were reported in 7% of participants in the retatrutide group vs. 1% in the placebo group; none of these effects were associated with physical skin findings. Of note, 17 out of 198 (9%) participants in the retatrutide group developed cardiac arrhythmia vs. two out of 70 (3%) in the placebo group. There was no consistent pattern of arrhythmia type (e.g., supraventricular, ventricular) observed, and some of these events were reported as “palpitations” or “increased heart rate” without further detail. Phase 3 clinical trial data will provide further insight into the long-term safety of retatrutide.

Dr. Tchang is assistant professor of clinical medicine, division of endocrinology, Weill Cornell Medicine and physician, department of medicine, New York-Presbyterian/Weill Cornell Medical Center, both in New York. She has disclosed ties with Gelesis and Novo Nordisk.

A version of this article appeared on Medscape.com.

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The complex pathophysiology of obesity requires a multidisciplinary approach that includes lifestyle and medical interventions for successful management. Antiobesity medications (AOMs) have emerged as a powerful and life-changing tool for many individuals with obesity who are unable to sustain long-term weight loss through lifestyle changes alone. As with other chronic diseases such as hypertension and hyperlipidemia, the goal of decades of research has been to develop antiobesity medications with long-term efficacy and safety. Recent groundbreaking findings from a phase 2 trial show immense potential for a new AOM.

Here are five things to know about the role of agonists in the management of obesity.

1. Gut hormone physiology informs the development of AOMs.

The three hormones associated with obesity or diabetes are glucagonlike peptide 1 (GLP-1)glucose-dependent insulinotropic peptide (GIP), and glucagon. GLP-1, a peptide released from the intestines in response to food ingestion, increases insulin production, reduces gut motility, and suppresses appetite. GIP is also an intestinal hormone that increases meal-stimulated insulin production and additionally facilitates lipolysis. Glucagon is known to increase hepatic glucose output but will also increase insulin secretion in the setting of hyperglycemia. Glucagon also promotes lipolysis.

Though these hormones are more commonly thought of as incretins, gut hormones that stimulate postprandial insulin secretion, their role in energy physiology is more diverse. Because of multiple mechanisms of action, incretins are increasingly referred to as nutrient-stimulated hormones (NuSH), a term which encompasses other peptides with therapeutic potential (e.g., amylin, oxyntomodulin, peptide tyrosine–tyrosine).

2. Studies have shown that NuSH therapies are highly effective AOMs.

In 2021 the Food and Drug Administration approved subcutaneous semaglutide 2.4 mg, a GLP-1 receptor agonist, for the treatment of obesity. Clinical trials demonstrating an average weight loss of 15% in patients taking semaglutide ushered in a new era of AOMs associated with significant weight loss that not only improve disease activity but also have the potential to achieve diabetes remission. Recent findings from the OASIS I trial demonstrated an average weight loss of 15.1% from baseline in patients treated with oral semaglutide for 68 weeks. Medical societies, including the American Diabetes Association and the American Association for the Study of Liver Diseases, recommend 10%-15% weight loss to fully treat weight-related comorbidities like type 2 diabetes and nonalcoholic fatty liver disease. In 2022, tirzepatide, a dual GLP-1 and GIP receptor agonist, demonstrated an average weight loss of 22.5% in phase 3 of the SURMOUNT-1 trial for obesity – a weight loss approaching that of some bariatric surgeries.

3. Clinical trial data show that the novel triple agonist retatrutide induces significant weight loss.

Preclinical studies on the newest NuSH therapy, triple GLP-1–GIP–glucagon receptor agonist retatrutide, showed predominant activity at the GIP receptor, with less GLP-1– and glucagon-receptor agonism than that of endogenous GLP-1 and GIP. Results from a phase 2 trial published in June 2023 showed a weight loss of 24% at 48 weeks in adults with obesity treated with retatrutide, which is the greatest weight loss reported in an obesity trial so far. Moreover, for the first time in obesity pharmacotherapy research, 100% of participants achieved clinically significant weight loss (defined as ≥ 5% of baseline weight).

4. Retatrutide may improve lipid metabolism.

In the phase 2 trial, retatrutide reduced low-density lipoprotein cholesterol levels by approximately 20%. This degree of reduced plasma LDL-C is dramatic in weight loss studies. Typically, weight loss significantly reduces triglyceride levels, increases high-density lipoprotein cholesterol levels, and has a modest effect on LDL-C reduction of about 5%.

A 20% reduction in LDL-C with retatrutide is hypothesis generating. Preclinical studies have shown glucagon to be an important regulator of proprotein convertase subtilisin/kexin type 9 degradation, with the lack of glucagon resulting in increased PCSK9 levels, decreased LDL receptors, and increased plasma LDL; conversely, treatment with glucagon decreased plasma LDL.

5. The long-term safety of retatrutide still needs to be determined.

In the 48-week phase 2 trial, retatrutide was observed to have a side-effect profile largely similar to other NuSH therapies (e.g., semaglutide 2.4 mg, tirzepatide), with a predominance of gastrointestinal symptoms including nausea, diarrhea, vomiting, and constipation. However, side effects potentially unique to retatrutide also emerged. Cutaneous hyperesthesia and skin sensitivity were reported in 7% of participants in the retatrutide group vs. 1% in the placebo group; none of these effects were associated with physical skin findings. Of note, 17 out of 198 (9%) participants in the retatrutide group developed cardiac arrhythmia vs. two out of 70 (3%) in the placebo group. There was no consistent pattern of arrhythmia type (e.g., supraventricular, ventricular) observed, and some of these events were reported as “palpitations” or “increased heart rate” without further detail. Phase 3 clinical trial data will provide further insight into the long-term safety of retatrutide.

Dr. Tchang is assistant professor of clinical medicine, division of endocrinology, Weill Cornell Medicine and physician, department of medicine, New York-Presbyterian/Weill Cornell Medical Center, both in New York. She has disclosed ties with Gelesis and Novo Nordisk.

A version of this article appeared on Medscape.com.

The complex pathophysiology of obesity requires a multidisciplinary approach that includes lifestyle and medical interventions for successful management. Antiobesity medications (AOMs) have emerged as a powerful and life-changing tool for many individuals with obesity who are unable to sustain long-term weight loss through lifestyle changes alone. As with other chronic diseases such as hypertension and hyperlipidemia, the goal of decades of research has been to develop antiobesity medications with long-term efficacy and safety. Recent groundbreaking findings from a phase 2 trial show immense potential for a new AOM.

Here are five things to know about the role of agonists in the management of obesity.

1. Gut hormone physiology informs the development of AOMs.

The three hormones associated with obesity or diabetes are glucagonlike peptide 1 (GLP-1)glucose-dependent insulinotropic peptide (GIP), and glucagon. GLP-1, a peptide released from the intestines in response to food ingestion, increases insulin production, reduces gut motility, and suppresses appetite. GIP is also an intestinal hormone that increases meal-stimulated insulin production and additionally facilitates lipolysis. Glucagon is known to increase hepatic glucose output but will also increase insulin secretion in the setting of hyperglycemia. Glucagon also promotes lipolysis.

Though these hormones are more commonly thought of as incretins, gut hormones that stimulate postprandial insulin secretion, their role in energy physiology is more diverse. Because of multiple mechanisms of action, incretins are increasingly referred to as nutrient-stimulated hormones (NuSH), a term which encompasses other peptides with therapeutic potential (e.g., amylin, oxyntomodulin, peptide tyrosine–tyrosine).

2. Studies have shown that NuSH therapies are highly effective AOMs.

In 2021 the Food and Drug Administration approved subcutaneous semaglutide 2.4 mg, a GLP-1 receptor agonist, for the treatment of obesity. Clinical trials demonstrating an average weight loss of 15% in patients taking semaglutide ushered in a new era of AOMs associated with significant weight loss that not only improve disease activity but also have the potential to achieve diabetes remission. Recent findings from the OASIS I trial demonstrated an average weight loss of 15.1% from baseline in patients treated with oral semaglutide for 68 weeks. Medical societies, including the American Diabetes Association and the American Association for the Study of Liver Diseases, recommend 10%-15% weight loss to fully treat weight-related comorbidities like type 2 diabetes and nonalcoholic fatty liver disease. In 2022, tirzepatide, a dual GLP-1 and GIP receptor agonist, demonstrated an average weight loss of 22.5% in phase 3 of the SURMOUNT-1 trial for obesity – a weight loss approaching that of some bariatric surgeries.

3. Clinical trial data show that the novel triple agonist retatrutide induces significant weight loss.

Preclinical studies on the newest NuSH therapy, triple GLP-1–GIP–glucagon receptor agonist retatrutide, showed predominant activity at the GIP receptor, with less GLP-1– and glucagon-receptor agonism than that of endogenous GLP-1 and GIP. Results from a phase 2 trial published in June 2023 showed a weight loss of 24% at 48 weeks in adults with obesity treated with retatrutide, which is the greatest weight loss reported in an obesity trial so far. Moreover, for the first time in obesity pharmacotherapy research, 100% of participants achieved clinically significant weight loss (defined as ≥ 5% of baseline weight).

4. Retatrutide may improve lipid metabolism.

In the phase 2 trial, retatrutide reduced low-density lipoprotein cholesterol levels by approximately 20%. This degree of reduced plasma LDL-C is dramatic in weight loss studies. Typically, weight loss significantly reduces triglyceride levels, increases high-density lipoprotein cholesterol levels, and has a modest effect on LDL-C reduction of about 5%.

A 20% reduction in LDL-C with retatrutide is hypothesis generating. Preclinical studies have shown glucagon to be an important regulator of proprotein convertase subtilisin/kexin type 9 degradation, with the lack of glucagon resulting in increased PCSK9 levels, decreased LDL receptors, and increased plasma LDL; conversely, treatment with glucagon decreased plasma LDL.

5. The long-term safety of retatrutide still needs to be determined.

In the 48-week phase 2 trial, retatrutide was observed to have a side-effect profile largely similar to other NuSH therapies (e.g., semaglutide 2.4 mg, tirzepatide), with a predominance of gastrointestinal symptoms including nausea, diarrhea, vomiting, and constipation. However, side effects potentially unique to retatrutide also emerged. Cutaneous hyperesthesia and skin sensitivity were reported in 7% of participants in the retatrutide group vs. 1% in the placebo group; none of these effects were associated with physical skin findings. Of note, 17 out of 198 (9%) participants in the retatrutide group developed cardiac arrhythmia vs. two out of 70 (3%) in the placebo group. There was no consistent pattern of arrhythmia type (e.g., supraventricular, ventricular) observed, and some of these events were reported as “palpitations” or “increased heart rate” without further detail. Phase 3 clinical trial data will provide further insight into the long-term safety of retatrutide.

Dr. Tchang is assistant professor of clinical medicine, division of endocrinology, Weill Cornell Medicine and physician, department of medicine, New York-Presbyterian/Weill Cornell Medical Center, both in New York. She has disclosed ties with Gelesis and Novo Nordisk.

A version of this article appeared on Medscape.com.

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Have early-onset cancer cases soared? Not so fast, experts say

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Changed
Mon, 09/25/2023 - 12:24

In early September, startling cancer research findings hit the news.

A study press release headline touted a “global surge” in new cancer cases among younger people over the past 3 decades.

Many major news outlets parroted the “striking” finding. “Cancer cases in under-50s worldwide up nearly 80% in 3 decades, study finds,” The Guardian reported.

The analysis, published in BMJ Oncology, plumbed data from the Global Burden of Disease 2019 study to determine changes in cancer incidence and deaths among people aged 15-49 years across 204 countries.

The team found that, between 1990 and 2019, global cancer cases in this younger group had increased by almost 80% and cancer deaths had risen by nearly 28%. The authors flagged diet, alcohol, and tobacco as “the main risk factors” underlying the early-onset cancer trend.

But the analysis was deeply flawed, experts said. It failed to account for population growth and age.

The global population has increased by 46% between 1990 and 2019, but the study calculations are “based on absolute numbers rather than age-standardized rates,” said Montserrat García-Closas, MD, MPH, PhD, professor of epidemiology at the Institute of Cancer Research, London, who weighed in on the findings via the U.K.-based Science Media Centre. That means “these numbers do not account for changes in demographics such as increases in population size or aging of the population.”

The study researchers reported 1.82 million early-onset cancer cases in 1990 and 3.26 million global cases in 2019, which led to the reported increase of 79.1%.

Similarly, the authors calculated the change in cancer deaths globally using absolute, not population or age-adjusted, numbers: 0.83 million cancer deaths in 1990 and 1.06 million in 2019 led to the reported increase of 27.7%.

But when population growth is considered, the story changes dramatically. The population-adjusted calculations indicate that the global incidence of early-onset cancers only rose about 6% over the past 30 years while cancer deaths actually fell 25% in that time, according to calculations done by Medscape using the study’s supplemental data.

Experts commenting via the BMJ website also noted the flawed calculations. “Epidemic news, but no epidemic of cancer,” Henrik Møller, MD, lead epidemiologist for the Danish Clinical Registries, and colleagues wrote, highlighting the “misleading” 79% figure. When accounting for population growth in Nordic countries, Dr. Møller and colleagues found a 1% average annual increase in the cancer incidence rate and a 2.5% decrease in the cancer mortality rate.

This news organization reached out to the study’s corresponding authors, Kefeng Ding and Xue Li, to ask why they used absolute numbers instead of population-adjusted numbers for their calculations, but they did not respond in time for publication.

In their analysis, however, the researchers did note that “the study still has several limitations” that could affect the results, such as variations in the quality and availability of data provided by different countries.

The study, for instance, compared the Solomon Islands with the other 203 nations and concluded that the Solomons had the highest age-standardized death rate for early-onset cancer (82.9 per 100,000). However, this tiny South Pacific nation, whose population is scattered across 350 islands, did not start collecting cancer data until 2008 and founded its first oncology unit in 2019.

The authors also reported the “sharpest increases” in cancer cases diagnosed between 1990 and 2019 in the United Arab Emirates (1,127.6%), Qatar (1,089.5%), and Saudi Arabia (896.0%); however, those numbers do not seem possible, given population growth during that time, and may instead reflect reporting or other changes in those countries.

Although the overarching conclusion may be misleading, some of the numbers ring true, especially for breast cancer. The researchers found that the incidence of early breast cancer increased nearly 18% – from 11.2 to 13.2 per 100,000 – between 1990 and 2019.

This increase is “consistent with what is happening” in the United Kingdom, said Stephen Duffy of Queen Mary University of London, also weighing in via the Science Media Centre. Since the United Kingdom does not routinely screen women under 50, this rise “is not due to increased diagnostic activity.”

Darren Brenner, MD, associate professor in oncology at the University of Calgary (Alta.), said in an interview he agreed that the breast cancer trends look accurate.

In a 2020 study, Brenner and colleagues found that breast cancer diagnoses in women under 40 had increased significantly between 2000 and 2015, at a rate of 0.66% per year. “Given that breast cancer at a younger age is associated with worse outcomes, the results are troubling,” Brenner and colleagues concluded at the time.

The experts commenting via Science Media Centre reported no conflicts of interest.

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

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In early September, startling cancer research findings hit the news.

A study press release headline touted a “global surge” in new cancer cases among younger people over the past 3 decades.

Many major news outlets parroted the “striking” finding. “Cancer cases in under-50s worldwide up nearly 80% in 3 decades, study finds,” The Guardian reported.

The analysis, published in BMJ Oncology, plumbed data from the Global Burden of Disease 2019 study to determine changes in cancer incidence and deaths among people aged 15-49 years across 204 countries.

The team found that, between 1990 and 2019, global cancer cases in this younger group had increased by almost 80% and cancer deaths had risen by nearly 28%. The authors flagged diet, alcohol, and tobacco as “the main risk factors” underlying the early-onset cancer trend.

But the analysis was deeply flawed, experts said. It failed to account for population growth and age.

The global population has increased by 46% between 1990 and 2019, but the study calculations are “based on absolute numbers rather than age-standardized rates,” said Montserrat García-Closas, MD, MPH, PhD, professor of epidemiology at the Institute of Cancer Research, London, who weighed in on the findings via the U.K.-based Science Media Centre. That means “these numbers do not account for changes in demographics such as increases in population size or aging of the population.”

The study researchers reported 1.82 million early-onset cancer cases in 1990 and 3.26 million global cases in 2019, which led to the reported increase of 79.1%.

Similarly, the authors calculated the change in cancer deaths globally using absolute, not population or age-adjusted, numbers: 0.83 million cancer deaths in 1990 and 1.06 million in 2019 led to the reported increase of 27.7%.

But when population growth is considered, the story changes dramatically. The population-adjusted calculations indicate that the global incidence of early-onset cancers only rose about 6% over the past 30 years while cancer deaths actually fell 25% in that time, according to calculations done by Medscape using the study’s supplemental data.

Experts commenting via the BMJ website also noted the flawed calculations. “Epidemic news, but no epidemic of cancer,” Henrik Møller, MD, lead epidemiologist for the Danish Clinical Registries, and colleagues wrote, highlighting the “misleading” 79% figure. When accounting for population growth in Nordic countries, Dr. Møller and colleagues found a 1% average annual increase in the cancer incidence rate and a 2.5% decrease in the cancer mortality rate.

This news organization reached out to the study’s corresponding authors, Kefeng Ding and Xue Li, to ask why they used absolute numbers instead of population-adjusted numbers for their calculations, but they did not respond in time for publication.

In their analysis, however, the researchers did note that “the study still has several limitations” that could affect the results, such as variations in the quality and availability of data provided by different countries.

The study, for instance, compared the Solomon Islands with the other 203 nations and concluded that the Solomons had the highest age-standardized death rate for early-onset cancer (82.9 per 100,000). However, this tiny South Pacific nation, whose population is scattered across 350 islands, did not start collecting cancer data until 2008 and founded its first oncology unit in 2019.

The authors also reported the “sharpest increases” in cancer cases diagnosed between 1990 and 2019 in the United Arab Emirates (1,127.6%), Qatar (1,089.5%), and Saudi Arabia (896.0%); however, those numbers do not seem possible, given population growth during that time, and may instead reflect reporting or other changes in those countries.

Although the overarching conclusion may be misleading, some of the numbers ring true, especially for breast cancer. The researchers found that the incidence of early breast cancer increased nearly 18% – from 11.2 to 13.2 per 100,000 – between 1990 and 2019.

This increase is “consistent with what is happening” in the United Kingdom, said Stephen Duffy of Queen Mary University of London, also weighing in via the Science Media Centre. Since the United Kingdom does not routinely screen women under 50, this rise “is not due to increased diagnostic activity.”

Darren Brenner, MD, associate professor in oncology at the University of Calgary (Alta.), said in an interview he agreed that the breast cancer trends look accurate.

In a 2020 study, Brenner and colleagues found that breast cancer diagnoses in women under 40 had increased significantly between 2000 and 2015, at a rate of 0.66% per year. “Given that breast cancer at a younger age is associated with worse outcomes, the results are troubling,” Brenner and colleagues concluded at the time.

The experts commenting via Science Media Centre reported no conflicts of interest.

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

In early September, startling cancer research findings hit the news.

A study press release headline touted a “global surge” in new cancer cases among younger people over the past 3 decades.

Many major news outlets parroted the “striking” finding. “Cancer cases in under-50s worldwide up nearly 80% in 3 decades, study finds,” The Guardian reported.

The analysis, published in BMJ Oncology, plumbed data from the Global Burden of Disease 2019 study to determine changes in cancer incidence and deaths among people aged 15-49 years across 204 countries.

The team found that, between 1990 and 2019, global cancer cases in this younger group had increased by almost 80% and cancer deaths had risen by nearly 28%. The authors flagged diet, alcohol, and tobacco as “the main risk factors” underlying the early-onset cancer trend.

But the analysis was deeply flawed, experts said. It failed to account for population growth and age.

The global population has increased by 46% between 1990 and 2019, but the study calculations are “based on absolute numbers rather than age-standardized rates,” said Montserrat García-Closas, MD, MPH, PhD, professor of epidemiology at the Institute of Cancer Research, London, who weighed in on the findings via the U.K.-based Science Media Centre. That means “these numbers do not account for changes in demographics such as increases in population size or aging of the population.”

The study researchers reported 1.82 million early-onset cancer cases in 1990 and 3.26 million global cases in 2019, which led to the reported increase of 79.1%.

Similarly, the authors calculated the change in cancer deaths globally using absolute, not population or age-adjusted, numbers: 0.83 million cancer deaths in 1990 and 1.06 million in 2019 led to the reported increase of 27.7%.

But when population growth is considered, the story changes dramatically. The population-adjusted calculations indicate that the global incidence of early-onset cancers only rose about 6% over the past 30 years while cancer deaths actually fell 25% in that time, according to calculations done by Medscape using the study’s supplemental data.

Experts commenting via the BMJ website also noted the flawed calculations. “Epidemic news, but no epidemic of cancer,” Henrik Møller, MD, lead epidemiologist for the Danish Clinical Registries, and colleagues wrote, highlighting the “misleading” 79% figure. When accounting for population growth in Nordic countries, Dr. Møller and colleagues found a 1% average annual increase in the cancer incidence rate and a 2.5% decrease in the cancer mortality rate.

This news organization reached out to the study’s corresponding authors, Kefeng Ding and Xue Li, to ask why they used absolute numbers instead of population-adjusted numbers for their calculations, but they did not respond in time for publication.

In their analysis, however, the researchers did note that “the study still has several limitations” that could affect the results, such as variations in the quality and availability of data provided by different countries.

The study, for instance, compared the Solomon Islands with the other 203 nations and concluded that the Solomons had the highest age-standardized death rate for early-onset cancer (82.9 per 100,000). However, this tiny South Pacific nation, whose population is scattered across 350 islands, did not start collecting cancer data until 2008 and founded its first oncology unit in 2019.

The authors also reported the “sharpest increases” in cancer cases diagnosed between 1990 and 2019 in the United Arab Emirates (1,127.6%), Qatar (1,089.5%), and Saudi Arabia (896.0%); however, those numbers do not seem possible, given population growth during that time, and may instead reflect reporting or other changes in those countries.

Although the overarching conclusion may be misleading, some of the numbers ring true, especially for breast cancer. The researchers found that the incidence of early breast cancer increased nearly 18% – from 11.2 to 13.2 per 100,000 – between 1990 and 2019.

This increase is “consistent with what is happening” in the United Kingdom, said Stephen Duffy of Queen Mary University of London, also weighing in via the Science Media Centre. Since the United Kingdom does not routinely screen women under 50, this rise “is not due to increased diagnostic activity.”

Darren Brenner, MD, associate professor in oncology at the University of Calgary (Alta.), said in an interview he agreed that the breast cancer trends look accurate.

In a 2020 study, Brenner and colleagues found that breast cancer diagnoses in women under 40 had increased significantly between 2000 and 2015, at a rate of 0.66% per year. “Given that breast cancer at a younger age is associated with worse outcomes, the results are troubling,” Brenner and colleagues concluded at the time.

The experts commenting via Science Media Centre reported no conflicts of interest.

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

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As U.S. syphilis cases rise, those at the epicenter scramble

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Tue, 09/26/2023 - 13:19

It was just a routine checkup – or so she thought. But this time, Marnina Miller’s love interest came along. The pair headed to an STD clinic in Houston, where Ms. Miller worked, to get tested for syphilis and HIV. With an already compromised immune system because of an HIV diagnosis 9 years ago, it is critical for Ms. Miller to ensure she is clear of any other diseases. She tested negative for syphilis. Her partner, on the other hand, tested positive for latent (or stage 3) syphilis. 

Syphilis has been on the rise in the United States for more than 2 decades. From 2017 to 2021, the number of cases shot up 75% (to 176,713), according to the Centers for Disease Control and Prevention. Houston – the fourth-largest city in the United States – seems to be at the epicenter. Between 2019 and 2022, there was a 128% rise in syphilis cases there, particularly among women and people of color, according to the Houston Health Department. This summer, drugmaker Pfizer reported a widespread shortage of the antibiotic penicillin, which is used to cure early-stage syphilis and treat latent syphilis. 

“I was immediately scared,” Ms. Miller said. “I was nervous about what that meant for me because we did kiss before. And, although I am openly living with HIV, there is little education around syphilis and how it is contracted.”

The Houston Health Department has been warning Houstonites to take this public health crisis seriously by practicing safe sex and getting tested if they’re sexually active. There has also been a ninefold increase in congenital syphilis in Houston and Harris County, Tex. To help curb the spread, residents can now get free testing for sexually transmitted diseases at Houston health clinics. 

“It is crucial for pregnant women to seek prenatal care and syphilis testing to protect themselves from an infection that could result in the deaths of their babies,” said Marlene McNeese Ward, deputy assistant director of the Houston Health Department’s Bureau of HIV/STI and Viral Hepatitis Prevention. She said a pregnant woman needs to get tested for syphilis three times during her pregnancy.

There are four stages of syphilis: primary, secondary, latent, and tertiary. Oral, anal, and vaginal sex are some of the ways the disease can spread. Some people who contract syphilis never have symptoms and could have the disease for years without knowing.

Penicillin can cure both syphilis and congenital syphilis. The antibiotic cannot reverse damage done to organs via infection, especially if the disease has greatly progressed before treatment. 

Sergino Nicolas, MD, creates TikTok videos and Instagram reels to raise awareness about the outbreak. The Pittsburgh-based emergency medical doctor said there is often a “nonchalant” attitude toward STDs among some people in their 20s and 30s. Being unaware of the consequences of syphilis could drive that attitude. “With thoughts like ‘I can just get treated,’ I think there is danger in that, because when you have these infections, [irreversible] complications can occur,” he said.

Preconceived notions among this age group that oral sex is a safer alternative to vaginal or anal sex is also common, Dr. Nicolas said. “Any time you might have infected secretions or be exposed to mucosa, including the vaginal mucosa, that can result in spreading the infection.”

Women of color have been particularly impacted by the outbreak. Syphilis has a wide range of signs and symptoms, and that could play a major role, Dr. Nicolas said. Lack of education on the dangers of unprotected sex, particularly with multiple sexual partners, could be another reason, as this increases rates of yeast infections and STDs, he said.

Another potential factor: Sexually explicit music and entertainment can also cloud judgment on whether to engage in sexual activity, Dr. Nicolas said. Younger generations can especially fall prey to this. “There have been new artists over the past few months that have really been pushing for ‘female empowerment’ in a sense,” he said. “At the same time, they can also push a narrative more so pertaining to promiscuity, which could result in certain psychological effects” that could lead to unsafe sex practices.

Public health activists in Houston are spreading the word on the importance of getting tested for STDs. Kevin Anderson is the founder of the T.R.U.T.H. Project, a Houston-based nonprofit that educates and mobilizes LGBTQ communities of color through social arts that promote sexual, mental, and physical health.

While celebrating its 10th anniversary, T.R.U.T.H. Project is creatively promoting syphilis education and awareness. The organization’s recent events have included an open-mic night called “Heart and Soul,” with free STD testing on site for attendees. It also hosted a sex-positive night aiming to educate attendees about STDs and safe sex practices. Self-love, self-care, and self-awareness of one’s body is one of the group’s most prominent messages. “If something feels or looks different, love yourself enough to be proactive in following up to find out what’s going on – because avoidance leads to outbreaks,” Mr. Anderson said.

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

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It was just a routine checkup – or so she thought. But this time, Marnina Miller’s love interest came along. The pair headed to an STD clinic in Houston, where Ms. Miller worked, to get tested for syphilis and HIV. With an already compromised immune system because of an HIV diagnosis 9 years ago, it is critical for Ms. Miller to ensure she is clear of any other diseases. She tested negative for syphilis. Her partner, on the other hand, tested positive for latent (or stage 3) syphilis. 

Syphilis has been on the rise in the United States for more than 2 decades. From 2017 to 2021, the number of cases shot up 75% (to 176,713), according to the Centers for Disease Control and Prevention. Houston – the fourth-largest city in the United States – seems to be at the epicenter. Between 2019 and 2022, there was a 128% rise in syphilis cases there, particularly among women and people of color, according to the Houston Health Department. This summer, drugmaker Pfizer reported a widespread shortage of the antibiotic penicillin, which is used to cure early-stage syphilis and treat latent syphilis. 

“I was immediately scared,” Ms. Miller said. “I was nervous about what that meant for me because we did kiss before. And, although I am openly living with HIV, there is little education around syphilis and how it is contracted.”

The Houston Health Department has been warning Houstonites to take this public health crisis seriously by practicing safe sex and getting tested if they’re sexually active. There has also been a ninefold increase in congenital syphilis in Houston and Harris County, Tex. To help curb the spread, residents can now get free testing for sexually transmitted diseases at Houston health clinics. 

“It is crucial for pregnant women to seek prenatal care and syphilis testing to protect themselves from an infection that could result in the deaths of their babies,” said Marlene McNeese Ward, deputy assistant director of the Houston Health Department’s Bureau of HIV/STI and Viral Hepatitis Prevention. She said a pregnant woman needs to get tested for syphilis three times during her pregnancy.

There are four stages of syphilis: primary, secondary, latent, and tertiary. Oral, anal, and vaginal sex are some of the ways the disease can spread. Some people who contract syphilis never have symptoms and could have the disease for years without knowing.

Penicillin can cure both syphilis and congenital syphilis. The antibiotic cannot reverse damage done to organs via infection, especially if the disease has greatly progressed before treatment. 

Sergino Nicolas, MD, creates TikTok videos and Instagram reels to raise awareness about the outbreak. The Pittsburgh-based emergency medical doctor said there is often a “nonchalant” attitude toward STDs among some people in their 20s and 30s. Being unaware of the consequences of syphilis could drive that attitude. “With thoughts like ‘I can just get treated,’ I think there is danger in that, because when you have these infections, [irreversible] complications can occur,” he said.

Preconceived notions among this age group that oral sex is a safer alternative to vaginal or anal sex is also common, Dr. Nicolas said. “Any time you might have infected secretions or be exposed to mucosa, including the vaginal mucosa, that can result in spreading the infection.”

Women of color have been particularly impacted by the outbreak. Syphilis has a wide range of signs and symptoms, and that could play a major role, Dr. Nicolas said. Lack of education on the dangers of unprotected sex, particularly with multiple sexual partners, could be another reason, as this increases rates of yeast infections and STDs, he said.

Another potential factor: Sexually explicit music and entertainment can also cloud judgment on whether to engage in sexual activity, Dr. Nicolas said. Younger generations can especially fall prey to this. “There have been new artists over the past few months that have really been pushing for ‘female empowerment’ in a sense,” he said. “At the same time, they can also push a narrative more so pertaining to promiscuity, which could result in certain psychological effects” that could lead to unsafe sex practices.

Public health activists in Houston are spreading the word on the importance of getting tested for STDs. Kevin Anderson is the founder of the T.R.U.T.H. Project, a Houston-based nonprofit that educates and mobilizes LGBTQ communities of color through social arts that promote sexual, mental, and physical health.

While celebrating its 10th anniversary, T.R.U.T.H. Project is creatively promoting syphilis education and awareness. The organization’s recent events have included an open-mic night called “Heart and Soul,” with free STD testing on site for attendees. It also hosted a sex-positive night aiming to educate attendees about STDs and safe sex practices. Self-love, self-care, and self-awareness of one’s body is one of the group’s most prominent messages. “If something feels or looks different, love yourself enough to be proactive in following up to find out what’s going on – because avoidance leads to outbreaks,” Mr. Anderson said.

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

It was just a routine checkup – or so she thought. But this time, Marnina Miller’s love interest came along. The pair headed to an STD clinic in Houston, where Ms. Miller worked, to get tested for syphilis and HIV. With an already compromised immune system because of an HIV diagnosis 9 years ago, it is critical for Ms. Miller to ensure she is clear of any other diseases. She tested negative for syphilis. Her partner, on the other hand, tested positive for latent (or stage 3) syphilis. 

Syphilis has been on the rise in the United States for more than 2 decades. From 2017 to 2021, the number of cases shot up 75% (to 176,713), according to the Centers for Disease Control and Prevention. Houston – the fourth-largest city in the United States – seems to be at the epicenter. Between 2019 and 2022, there was a 128% rise in syphilis cases there, particularly among women and people of color, according to the Houston Health Department. This summer, drugmaker Pfizer reported a widespread shortage of the antibiotic penicillin, which is used to cure early-stage syphilis and treat latent syphilis. 

“I was immediately scared,” Ms. Miller said. “I was nervous about what that meant for me because we did kiss before. And, although I am openly living with HIV, there is little education around syphilis and how it is contracted.”

The Houston Health Department has been warning Houstonites to take this public health crisis seriously by practicing safe sex and getting tested if they’re sexually active. There has also been a ninefold increase in congenital syphilis in Houston and Harris County, Tex. To help curb the spread, residents can now get free testing for sexually transmitted diseases at Houston health clinics. 

“It is crucial for pregnant women to seek prenatal care and syphilis testing to protect themselves from an infection that could result in the deaths of their babies,” said Marlene McNeese Ward, deputy assistant director of the Houston Health Department’s Bureau of HIV/STI and Viral Hepatitis Prevention. She said a pregnant woman needs to get tested for syphilis three times during her pregnancy.

There are four stages of syphilis: primary, secondary, latent, and tertiary. Oral, anal, and vaginal sex are some of the ways the disease can spread. Some people who contract syphilis never have symptoms and could have the disease for years without knowing.

Penicillin can cure both syphilis and congenital syphilis. The antibiotic cannot reverse damage done to organs via infection, especially if the disease has greatly progressed before treatment. 

Sergino Nicolas, MD, creates TikTok videos and Instagram reels to raise awareness about the outbreak. The Pittsburgh-based emergency medical doctor said there is often a “nonchalant” attitude toward STDs among some people in their 20s and 30s. Being unaware of the consequences of syphilis could drive that attitude. “With thoughts like ‘I can just get treated,’ I think there is danger in that, because when you have these infections, [irreversible] complications can occur,” he said.

Preconceived notions among this age group that oral sex is a safer alternative to vaginal or anal sex is also common, Dr. Nicolas said. “Any time you might have infected secretions or be exposed to mucosa, including the vaginal mucosa, that can result in spreading the infection.”

Women of color have been particularly impacted by the outbreak. Syphilis has a wide range of signs and symptoms, and that could play a major role, Dr. Nicolas said. Lack of education on the dangers of unprotected sex, particularly with multiple sexual partners, could be another reason, as this increases rates of yeast infections and STDs, he said.

Another potential factor: Sexually explicit music and entertainment can also cloud judgment on whether to engage in sexual activity, Dr. Nicolas said. Younger generations can especially fall prey to this. “There have been new artists over the past few months that have really been pushing for ‘female empowerment’ in a sense,” he said. “At the same time, they can also push a narrative more so pertaining to promiscuity, which could result in certain psychological effects” that could lead to unsafe sex practices.

Public health activists in Houston are spreading the word on the importance of getting tested for STDs. Kevin Anderson is the founder of the T.R.U.T.H. Project, a Houston-based nonprofit that educates and mobilizes LGBTQ communities of color through social arts that promote sexual, mental, and physical health.

While celebrating its 10th anniversary, T.R.U.T.H. Project is creatively promoting syphilis education and awareness. The organization’s recent events have included an open-mic night called “Heart and Soul,” with free STD testing on site for attendees. It also hosted a sex-positive night aiming to educate attendees about STDs and safe sex practices. Self-love, self-care, and self-awareness of one’s body is one of the group’s most prominent messages. “If something feels or looks different, love yourself enough to be proactive in following up to find out what’s going on – because avoidance leads to outbreaks,” Mr. Anderson said.

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

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Worm pulled from woman’s brain in case that ‘stunned’

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Tue, 10/03/2023 - 13:09

When they started the open biopsy, surgeons didn’t know what they were going to find, but they certainly didn’t expect this.

The stringlike worm was five-sixteenths of an inch long, was alive, and wiggled.

“It stunned everyone in that operating theater,” Sanjaya Senanayake, MBBS, an associate professor of infectious disease at Australian National University, Canberra, and senior author of the case report, said in an interview. “When you operate on a brain, you don’t expect to find anything alive.”

The parasitic worm was about half the width of a dime. Helminths like it can usually be seen with the naked eye but are often found in the intestines after being transmitted by soil and infecting the gastrointestinal tract. But this one made it into a woman’s brain in a first-of-its-kind case reported in the journal Emerging Infectious Diseases).

“We weren’t suspecting a worm at all,” Dr. Senanayake said. “There was something abnormal there. Was it going to be granulomatous lesion? Was it going to be cancer? Who knows, but it needed to be biopsied, and a worm was the last thing at the back of anyone’s mind,” he said.
 

A year of inexplicable symptoms

The 64-year-old woman was diagnosed with pneumonia and had a high white blood cell count, low hemoglobin, high platelets, and a very high C-reactive protein of 102 mg/L.

She hadn’t fully recovered from her illness when the abdominal pain and diarrhea started. And then she had a dry cough and night sweats.

After 3 weeks of discomfort, she was admitted to the hospital. She had a history of diabetes, hypothyroidism, and depression, and doctors began looking for answers to her acute illness.

They tested for autoimmune diseases and parasitic infections and prescribed prednisolone to help ease symptoms.

But 3 weeks later, her fever and cough persisted, and she was readmitted to the hospital. Doctors ordered more tests, and her eosinophils were still high, plus there were lesions on her liver, spleen, and lungs.

But tests were negative for bacterial, fungal, and mycobacterial cultures. Her stools showed no evidence of parasites.

She was prescribed mycophenolate and then ivermectin in case her tests for roundworm were a false negative. Doctors suspected Strongyloides, but lesions remained on her spleen even as the liver and lung lesions improved.

Reducing the prednisolone dose affected respiratory symptoms, so by January 2022, a year after initial symptoms began, the medical team added the monoclonal antibody mepolizumab. But her symptoms worsened, and she developed forgetfulness and more depression.

After a brain MRI revealed a right frontal lobe lesion, the team recommended an open biopsy and discovered the worm. The specimen was Ophidascaris robertsi, the intestinal roundworm typically of the carpet python. Never before seen in a human, the only other animals in its life cycle are small marsupials or mammals consumed by pythons.
 

A snake’s bug

Although this is the first case of an Ophidascaris infection in a human, other cases could occur, warn the doctors in their case report.

The best guess for how the patient contracted the infection was by inadvertently consuming larval eggs on wild vegetation that she collected near her home to eat. She lived near a lake known to be home to carpet pythons, so the eggs could have been on the plants she collected or on her hands or kitchen equipment.

“If you’re foraging or using native grasses or plants in recipes, it would be a good idea to cook those instead of having a salad,” Dr. Senanayake said. “That would make the chance of getting something really rare even less likely.”

It’s unclear how or why the worm, which usually stays in the gut, made its way into the patient’s brain, but her long course of immunosuppressing drugs may have played a role, the team points out. “If the normal immune barriers are reduced, then it’s easier for the parasite to move around between organ systems,” Dr. Senanayake said.

Doctors also wondered if she may have been getting re-infected when she went home between hospital admissions. After removing the worm, she received 4 weeks of treatment with albendazole to eliminate any other possible larvae in other organs, especially since Ophidascaris larvae have been known to survive for long periods – more than 4 years in laboratory rats. “The hope is that she’s been cured of this parasitic infection,” Dr. Senanayake said.

As people around the world contend with the global COVID pandemic, they might not realize that new infections are arising around the world every year, he explained.
 

 

 

Novel parasitic infections

“The reality is that 30 new infections appeared in the last 30 years, and three-quarters of them are zoonotic, animal infections spilling over into the human world,” Dr. Senanayake said.

Though some of that number is the result of improved surveillance and diagnostics, a real increase has been occurring as human settlements continue expanding.

“This is just a reflection of how burgeoning human populations are encroaching upon animal habitats, and we’re getting more interactions between humans and wild animals, domestic animals and wild animals, and humans and natural flora, which is increasing the risk of this type of infection being recognized,” he explained.

The Ophidascaris worm found in this instance is in other snake species in different continents around the world, too. “Awareness of this case will hopefully lead to the diagnosis and treatment of other cases,” Dr. Senanayake added.

Though it’s certainly surprising to find this particular parasite in a human, finding a zoonotic organism in a person isn’t that strange, according to Janet Foley, DVM, PhD, a professor of veterinary medicine at the University of California, Davis. This is especially true if the usual host is closely related to humans, like primates, or spends a lot of time around them, like rats.

“There are still a lot of parasites and diseases out there in wildlife that haven’t been discovered, and we don’t know the risk,” said Dr. Foley. “But still, the risk would have to be low, generally, or we would see more human cases.”

In the United States, the roundworm common in raccoon feces is Baylisascaris procyonis and can be dangerous for people. “There have been deaths in people exposed to these worms, which do seem to prefer to travel to a human brain,” Dr. Foley said.

A 2016 Centers for Disease Control and Prevention report described seven U.S. cases identified between May 2013 and December 2015, including six that caused central nervous system disease. Another case report in 2018 involved a toddler who had eaten dirt and animal feces in his backyard.

And this past June, an Emerging Infectious Diseases case report described a B. procyonis infection in a 7-year-old with autism spectrum disorder and a history of pica. He had put material in his mouth from the ground near a tree where epidemiologists later found raccoon feces.

Still, Dr. Senanayake cautions against people jumping to conclusions about parasitic infections when they experience symptoms that aren’t otherwise immediately explainable.

The typical person who develops forgetfulness, depression, and a fever probably doesn’t have a worm in their brain or need an immediate MRI, he pointed out. “There may be other cases out there, but common things happen commonly, and this is likely to be rare,” Dr. Senanayake said.

This case demonstrates the challenge in picking a course of treatment when the differential diagnoses for hypereosinophilic syndromes is so broad.
 

Tricky hypereosinophilic syndromes

One of those differentials for the syndromes is parasitic infections, for which treatment would be antiparasitic agents, but another differential is an autoimmune condition that would call for immunosuppression.

“Obviously, as with this case, you don’t want to give someone immunosuppressive treatment if they’ve got a parasite, so you want to look really hard for a parasite before you start them on immunosuppressive treatment for an immunological condition,” Dr. Senanayake said.

But all the blood tests for different antibodies came back negative for parasites, “and this parasite was simply difficult to find until they pulled it from her brain,” he said.

Infectious disease physicians are always looking for the unusual and exotic, Dr. Senanayake explained. But it’s important to exclude the common, easy things first, he added. It’s after exhausting all the likely culprits that “you have to start really thinking laterally and putting resources into unusual tests.”

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

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When they started the open biopsy, surgeons didn’t know what they were going to find, but they certainly didn’t expect this.

The stringlike worm was five-sixteenths of an inch long, was alive, and wiggled.

“It stunned everyone in that operating theater,” Sanjaya Senanayake, MBBS, an associate professor of infectious disease at Australian National University, Canberra, and senior author of the case report, said in an interview. “When you operate on a brain, you don’t expect to find anything alive.”

The parasitic worm was about half the width of a dime. Helminths like it can usually be seen with the naked eye but are often found in the intestines after being transmitted by soil and infecting the gastrointestinal tract. But this one made it into a woman’s brain in a first-of-its-kind case reported in the journal Emerging Infectious Diseases).

“We weren’t suspecting a worm at all,” Dr. Senanayake said. “There was something abnormal there. Was it going to be granulomatous lesion? Was it going to be cancer? Who knows, but it needed to be biopsied, and a worm was the last thing at the back of anyone’s mind,” he said.
 

A year of inexplicable symptoms

The 64-year-old woman was diagnosed with pneumonia and had a high white blood cell count, low hemoglobin, high platelets, and a very high C-reactive protein of 102 mg/L.

She hadn’t fully recovered from her illness when the abdominal pain and diarrhea started. And then she had a dry cough and night sweats.

After 3 weeks of discomfort, she was admitted to the hospital. She had a history of diabetes, hypothyroidism, and depression, and doctors began looking for answers to her acute illness.

They tested for autoimmune diseases and parasitic infections and prescribed prednisolone to help ease symptoms.

But 3 weeks later, her fever and cough persisted, and she was readmitted to the hospital. Doctors ordered more tests, and her eosinophils were still high, plus there were lesions on her liver, spleen, and lungs.

But tests were negative for bacterial, fungal, and mycobacterial cultures. Her stools showed no evidence of parasites.

She was prescribed mycophenolate and then ivermectin in case her tests for roundworm were a false negative. Doctors suspected Strongyloides, but lesions remained on her spleen even as the liver and lung lesions improved.

Reducing the prednisolone dose affected respiratory symptoms, so by January 2022, a year after initial symptoms began, the medical team added the monoclonal antibody mepolizumab. But her symptoms worsened, and she developed forgetfulness and more depression.

After a brain MRI revealed a right frontal lobe lesion, the team recommended an open biopsy and discovered the worm. The specimen was Ophidascaris robertsi, the intestinal roundworm typically of the carpet python. Never before seen in a human, the only other animals in its life cycle are small marsupials or mammals consumed by pythons.
 

A snake’s bug

Although this is the first case of an Ophidascaris infection in a human, other cases could occur, warn the doctors in their case report.

The best guess for how the patient contracted the infection was by inadvertently consuming larval eggs on wild vegetation that she collected near her home to eat. She lived near a lake known to be home to carpet pythons, so the eggs could have been on the plants she collected or on her hands or kitchen equipment.

“If you’re foraging or using native grasses or plants in recipes, it would be a good idea to cook those instead of having a salad,” Dr. Senanayake said. “That would make the chance of getting something really rare even less likely.”

It’s unclear how or why the worm, which usually stays in the gut, made its way into the patient’s brain, but her long course of immunosuppressing drugs may have played a role, the team points out. “If the normal immune barriers are reduced, then it’s easier for the parasite to move around between organ systems,” Dr. Senanayake said.

Doctors also wondered if she may have been getting re-infected when she went home between hospital admissions. After removing the worm, she received 4 weeks of treatment with albendazole to eliminate any other possible larvae in other organs, especially since Ophidascaris larvae have been known to survive for long periods – more than 4 years in laboratory rats. “The hope is that she’s been cured of this parasitic infection,” Dr. Senanayake said.

As people around the world contend with the global COVID pandemic, they might not realize that new infections are arising around the world every year, he explained.
 

 

 

Novel parasitic infections

“The reality is that 30 new infections appeared in the last 30 years, and three-quarters of them are zoonotic, animal infections spilling over into the human world,” Dr. Senanayake said.

Though some of that number is the result of improved surveillance and diagnostics, a real increase has been occurring as human settlements continue expanding.

“This is just a reflection of how burgeoning human populations are encroaching upon animal habitats, and we’re getting more interactions between humans and wild animals, domestic animals and wild animals, and humans and natural flora, which is increasing the risk of this type of infection being recognized,” he explained.

The Ophidascaris worm found in this instance is in other snake species in different continents around the world, too. “Awareness of this case will hopefully lead to the diagnosis and treatment of other cases,” Dr. Senanayake added.

Though it’s certainly surprising to find this particular parasite in a human, finding a zoonotic organism in a person isn’t that strange, according to Janet Foley, DVM, PhD, a professor of veterinary medicine at the University of California, Davis. This is especially true if the usual host is closely related to humans, like primates, or spends a lot of time around them, like rats.

“There are still a lot of parasites and diseases out there in wildlife that haven’t been discovered, and we don’t know the risk,” said Dr. Foley. “But still, the risk would have to be low, generally, or we would see more human cases.”

In the United States, the roundworm common in raccoon feces is Baylisascaris procyonis and can be dangerous for people. “There have been deaths in people exposed to these worms, which do seem to prefer to travel to a human brain,” Dr. Foley said.

A 2016 Centers for Disease Control and Prevention report described seven U.S. cases identified between May 2013 and December 2015, including six that caused central nervous system disease. Another case report in 2018 involved a toddler who had eaten dirt and animal feces in his backyard.

And this past June, an Emerging Infectious Diseases case report described a B. procyonis infection in a 7-year-old with autism spectrum disorder and a history of pica. He had put material in his mouth from the ground near a tree where epidemiologists later found raccoon feces.

Still, Dr. Senanayake cautions against people jumping to conclusions about parasitic infections when they experience symptoms that aren’t otherwise immediately explainable.

The typical person who develops forgetfulness, depression, and a fever probably doesn’t have a worm in their brain or need an immediate MRI, he pointed out. “There may be other cases out there, but common things happen commonly, and this is likely to be rare,” Dr. Senanayake said.

This case demonstrates the challenge in picking a course of treatment when the differential diagnoses for hypereosinophilic syndromes is so broad.
 

Tricky hypereosinophilic syndromes

One of those differentials for the syndromes is parasitic infections, for which treatment would be antiparasitic agents, but another differential is an autoimmune condition that would call for immunosuppression.

“Obviously, as with this case, you don’t want to give someone immunosuppressive treatment if they’ve got a parasite, so you want to look really hard for a parasite before you start them on immunosuppressive treatment for an immunological condition,” Dr. Senanayake said.

But all the blood tests for different antibodies came back negative for parasites, “and this parasite was simply difficult to find until they pulled it from her brain,” he said.

Infectious disease physicians are always looking for the unusual and exotic, Dr. Senanayake explained. But it’s important to exclude the common, easy things first, he added. It’s after exhausting all the likely culprits that “you have to start really thinking laterally and putting resources into unusual tests.”

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

When they started the open biopsy, surgeons didn’t know what they were going to find, but they certainly didn’t expect this.

The stringlike worm was five-sixteenths of an inch long, was alive, and wiggled.

“It stunned everyone in that operating theater,” Sanjaya Senanayake, MBBS, an associate professor of infectious disease at Australian National University, Canberra, and senior author of the case report, said in an interview. “When you operate on a brain, you don’t expect to find anything alive.”

The parasitic worm was about half the width of a dime. Helminths like it can usually be seen with the naked eye but are often found in the intestines after being transmitted by soil and infecting the gastrointestinal tract. But this one made it into a woman’s brain in a first-of-its-kind case reported in the journal Emerging Infectious Diseases).

“We weren’t suspecting a worm at all,” Dr. Senanayake said. “There was something abnormal there. Was it going to be granulomatous lesion? Was it going to be cancer? Who knows, but it needed to be biopsied, and a worm was the last thing at the back of anyone’s mind,” he said.
 

A year of inexplicable symptoms

The 64-year-old woman was diagnosed with pneumonia and had a high white blood cell count, low hemoglobin, high platelets, and a very high C-reactive protein of 102 mg/L.

She hadn’t fully recovered from her illness when the abdominal pain and diarrhea started. And then she had a dry cough and night sweats.

After 3 weeks of discomfort, she was admitted to the hospital. She had a history of diabetes, hypothyroidism, and depression, and doctors began looking for answers to her acute illness.

They tested for autoimmune diseases and parasitic infections and prescribed prednisolone to help ease symptoms.

But 3 weeks later, her fever and cough persisted, and she was readmitted to the hospital. Doctors ordered more tests, and her eosinophils were still high, plus there were lesions on her liver, spleen, and lungs.

But tests were negative for bacterial, fungal, and mycobacterial cultures. Her stools showed no evidence of parasites.

She was prescribed mycophenolate and then ivermectin in case her tests for roundworm were a false negative. Doctors suspected Strongyloides, but lesions remained on her spleen even as the liver and lung lesions improved.

Reducing the prednisolone dose affected respiratory symptoms, so by January 2022, a year after initial symptoms began, the medical team added the monoclonal antibody mepolizumab. But her symptoms worsened, and she developed forgetfulness and more depression.

After a brain MRI revealed a right frontal lobe lesion, the team recommended an open biopsy and discovered the worm. The specimen was Ophidascaris robertsi, the intestinal roundworm typically of the carpet python. Never before seen in a human, the only other animals in its life cycle are small marsupials or mammals consumed by pythons.
 

A snake’s bug

Although this is the first case of an Ophidascaris infection in a human, other cases could occur, warn the doctors in their case report.

The best guess for how the patient contracted the infection was by inadvertently consuming larval eggs on wild vegetation that she collected near her home to eat. She lived near a lake known to be home to carpet pythons, so the eggs could have been on the plants she collected or on her hands or kitchen equipment.

“If you’re foraging or using native grasses or plants in recipes, it would be a good idea to cook those instead of having a salad,” Dr. Senanayake said. “That would make the chance of getting something really rare even less likely.”

It’s unclear how or why the worm, which usually stays in the gut, made its way into the patient’s brain, but her long course of immunosuppressing drugs may have played a role, the team points out. “If the normal immune barriers are reduced, then it’s easier for the parasite to move around between organ systems,” Dr. Senanayake said.

Doctors also wondered if she may have been getting re-infected when she went home between hospital admissions. After removing the worm, she received 4 weeks of treatment with albendazole to eliminate any other possible larvae in other organs, especially since Ophidascaris larvae have been known to survive for long periods – more than 4 years in laboratory rats. “The hope is that she’s been cured of this parasitic infection,” Dr. Senanayake said.

As people around the world contend with the global COVID pandemic, they might not realize that new infections are arising around the world every year, he explained.
 

 

 

Novel parasitic infections

“The reality is that 30 new infections appeared in the last 30 years, and three-quarters of them are zoonotic, animal infections spilling over into the human world,” Dr. Senanayake said.

Though some of that number is the result of improved surveillance and diagnostics, a real increase has been occurring as human settlements continue expanding.

“This is just a reflection of how burgeoning human populations are encroaching upon animal habitats, and we’re getting more interactions between humans and wild animals, domestic animals and wild animals, and humans and natural flora, which is increasing the risk of this type of infection being recognized,” he explained.

The Ophidascaris worm found in this instance is in other snake species in different continents around the world, too. “Awareness of this case will hopefully lead to the diagnosis and treatment of other cases,” Dr. Senanayake added.

Though it’s certainly surprising to find this particular parasite in a human, finding a zoonotic organism in a person isn’t that strange, according to Janet Foley, DVM, PhD, a professor of veterinary medicine at the University of California, Davis. This is especially true if the usual host is closely related to humans, like primates, or spends a lot of time around them, like rats.

“There are still a lot of parasites and diseases out there in wildlife that haven’t been discovered, and we don’t know the risk,” said Dr. Foley. “But still, the risk would have to be low, generally, or we would see more human cases.”

In the United States, the roundworm common in raccoon feces is Baylisascaris procyonis and can be dangerous for people. “There have been deaths in people exposed to these worms, which do seem to prefer to travel to a human brain,” Dr. Foley said.

A 2016 Centers for Disease Control and Prevention report described seven U.S. cases identified between May 2013 and December 2015, including six that caused central nervous system disease. Another case report in 2018 involved a toddler who had eaten dirt and animal feces in his backyard.

And this past June, an Emerging Infectious Diseases case report described a B. procyonis infection in a 7-year-old with autism spectrum disorder and a history of pica. He had put material in his mouth from the ground near a tree where epidemiologists later found raccoon feces.

Still, Dr. Senanayake cautions against people jumping to conclusions about parasitic infections when they experience symptoms that aren’t otherwise immediately explainable.

The typical person who develops forgetfulness, depression, and a fever probably doesn’t have a worm in their brain or need an immediate MRI, he pointed out. “There may be other cases out there, but common things happen commonly, and this is likely to be rare,” Dr. Senanayake said.

This case demonstrates the challenge in picking a course of treatment when the differential diagnoses for hypereosinophilic syndromes is so broad.
 

Tricky hypereosinophilic syndromes

One of those differentials for the syndromes is parasitic infections, for which treatment would be antiparasitic agents, but another differential is an autoimmune condition that would call for immunosuppression.

“Obviously, as with this case, you don’t want to give someone immunosuppressive treatment if they’ve got a parasite, so you want to look really hard for a parasite before you start them on immunosuppressive treatment for an immunological condition,” Dr. Senanayake said.

But all the blood tests for different antibodies came back negative for parasites, “and this parasite was simply difficult to find until they pulled it from her brain,” he said.

Infectious disease physicians are always looking for the unusual and exotic, Dr. Senanayake explained. But it’s important to exclude the common, easy things first, he added. It’s after exhausting all the likely culprits that “you have to start really thinking laterally and putting resources into unusual tests.”

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

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Paxlovid weaker against current COVID-19 variants

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Thu, 10/05/2023 - 20:33

A real-world study published in  JAMA Open Network found that Pfizer’s COVID-19 antiviral Paxlovid is now less effective at preventing hospitalization or death in high-risk patients, compared with earlier studies. But when looking at death alone, the antiviral was still highly effective. 

Paxlovid was about 37% effective at preventing death or hospitalization in high-risk patients, compared with no treatment. The study also looked at the antiviral Lagevrio, made by Merck, and found it was about 41% effective. In preventing death alone, Paxlovid was about 84% effective, compared with no treatment, and Lagevrio was about 77% effective.

The investigators, of the University of North Carolina at Chapel Hill and the Cleveland Clinic, examined electronic health records of 68,867 patients at hospitals in Cleveland and Florida who were diagnosed with COVID from April 1, 2022, to Feb. 20, 2023.

For Paxlovid, the effectiveness against death and hospitalization was lower than the effectiveness rate of about 86% found in clinical trials in 2021, according to Bloomberg

The difference in effectiveness in the real-world and clinical studies may have occurred because the early studies were conducted with unvaccinated people. Also, the virus has evolved since those first studies, Bloomberg reported. 

The researchers said Paxlovid and Lagevrio are recommended for use because they reduce hospitalization and death among high-risk patients who get COVID, even taking recent Omicron subvariants into account.

“These findings suggest that the use of either nirmatrelvir (Paxlovid) or molnupiravir (Lagevrio) is associated with reductions in mortality and hospitalization in patients infected with Omicron, regardless of age, race and ethnicity, virus strain, vaccination status, previous infection status, or coexisting conditions,” the researchers wrote. “Both drugs can, therefore, be used to treat nonhospitalized patients who are at high risk of progressing to severe COVID-19.”

Both drugs should be taken within 5 days of the onset of COVID symptoms.

The study was supported by the National Institutes of Health. Three coauthors reported conflicts of interest with various companies and organizations.

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

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A real-world study published in  JAMA Open Network found that Pfizer’s COVID-19 antiviral Paxlovid is now less effective at preventing hospitalization or death in high-risk patients, compared with earlier studies. But when looking at death alone, the antiviral was still highly effective. 

Paxlovid was about 37% effective at preventing death or hospitalization in high-risk patients, compared with no treatment. The study also looked at the antiviral Lagevrio, made by Merck, and found it was about 41% effective. In preventing death alone, Paxlovid was about 84% effective, compared with no treatment, and Lagevrio was about 77% effective.

The investigators, of the University of North Carolina at Chapel Hill and the Cleveland Clinic, examined electronic health records of 68,867 patients at hospitals in Cleveland and Florida who were diagnosed with COVID from April 1, 2022, to Feb. 20, 2023.

For Paxlovid, the effectiveness against death and hospitalization was lower than the effectiveness rate of about 86% found in clinical trials in 2021, according to Bloomberg

The difference in effectiveness in the real-world and clinical studies may have occurred because the early studies were conducted with unvaccinated people. Also, the virus has evolved since those first studies, Bloomberg reported. 

The researchers said Paxlovid and Lagevrio are recommended for use because they reduce hospitalization and death among high-risk patients who get COVID, even taking recent Omicron subvariants into account.

“These findings suggest that the use of either nirmatrelvir (Paxlovid) or molnupiravir (Lagevrio) is associated with reductions in mortality and hospitalization in patients infected with Omicron, regardless of age, race and ethnicity, virus strain, vaccination status, previous infection status, or coexisting conditions,” the researchers wrote. “Both drugs can, therefore, be used to treat nonhospitalized patients who are at high risk of progressing to severe COVID-19.”

Both drugs should be taken within 5 days of the onset of COVID symptoms.

The study was supported by the National Institutes of Health. Three coauthors reported conflicts of interest with various companies and organizations.

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

A real-world study published in  JAMA Open Network found that Pfizer’s COVID-19 antiviral Paxlovid is now less effective at preventing hospitalization or death in high-risk patients, compared with earlier studies. But when looking at death alone, the antiviral was still highly effective. 

Paxlovid was about 37% effective at preventing death or hospitalization in high-risk patients, compared with no treatment. The study also looked at the antiviral Lagevrio, made by Merck, and found it was about 41% effective. In preventing death alone, Paxlovid was about 84% effective, compared with no treatment, and Lagevrio was about 77% effective.

The investigators, of the University of North Carolina at Chapel Hill and the Cleveland Clinic, examined electronic health records of 68,867 patients at hospitals in Cleveland and Florida who were diagnosed with COVID from April 1, 2022, to Feb. 20, 2023.

For Paxlovid, the effectiveness against death and hospitalization was lower than the effectiveness rate of about 86% found in clinical trials in 2021, according to Bloomberg

The difference in effectiveness in the real-world and clinical studies may have occurred because the early studies were conducted with unvaccinated people. Also, the virus has evolved since those first studies, Bloomberg reported. 

The researchers said Paxlovid and Lagevrio are recommended for use because they reduce hospitalization and death among high-risk patients who get COVID, even taking recent Omicron subvariants into account.

“These findings suggest that the use of either nirmatrelvir (Paxlovid) or molnupiravir (Lagevrio) is associated with reductions in mortality and hospitalization in patients infected with Omicron, regardless of age, race and ethnicity, virus strain, vaccination status, previous infection status, or coexisting conditions,” the researchers wrote. “Both drugs can, therefore, be used to treat nonhospitalized patients who are at high risk of progressing to severe COVID-19.”

Both drugs should be taken within 5 days of the onset of COVID symptoms.

The study was supported by the National Institutes of Health. Three coauthors reported conflicts of interest with various companies and organizations.

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

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Babies conceived during winter/spring may be at higher risk for cerebral palsy

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Fri, 09/29/2023 - 11:18

 

TOPLINE:

Cerebral palsy (CP) affects 1-4 per 1,000 live births in the United States. A new cohort study found children conceived during the winter and spring months appear to have a slightly higher risk for developing CP than those conceived during the summer. Fall months carried about the same or only slightly higher risk of CP than summer months.

METHODOLOGY:

  • Researchers examined data from nearly 4.5 million live births registered in California between 2007 and 2015, exploring if the season of conception could serve as an indicator of exposure to environmental risk factors.
  • For instance, infants conceived in winter months may have higher exposure to viruses like influenza. In California, agricultural pesticides are most often applied in summer months, when pregnant people would be in their first or second trimester and receive their most exposure to the fine particulates, the authors hypothesize.
  • Almost 4,700 babies in the study population were diagnosed with CP. Researchers also considered the role of preterm birth as a potential mediating factor, and adjusted for sociodemographic characteristics such as maternal age, race, education, smoking during pregnancy, and body mass index.

TAKEAWAY:

  • The study found that children conceived in winter and spring had a 9% (95% confidence interval, 1.01-1.19) to 10% (95% CI, 1.02-1.20) higher risk of developing CP than those conceived in the summer.
  • Children conceived in January, February, or May carried a 15% higher risk, compared with babies conceived in July.
  • The risk was more pronounced among mothers with low education levels or living in neighborhoods where residents have high rates of unemployment, single-parent households, multiunit households, and lower rates of high school graduates.

IN PRACTICE:

The researchers noted that possible explanations for the seasonal link to CP risk may include the prevalence of maternal infections during pregnancy, variations in exposure to pesticides, and seasonal patterns for air pollution. “Investigating seasonal variations in disease occurrence can provide clues about etiologically relevant factors.”

SOURCE:

Lead author Haoran Zhou, MPH, Yale University, New Haven, Conn., and colleagues published their findings online in JAMA Network Open. The study was partly supported by a grant from the American Academy for Cerebral Palsy and Developmental Medicine.

LIMITATIONS:

The study may not have fully captured all children with CP in the cohort due to the possibility of misclassification. The findings may not be generalizable beyond California. The overall increased risk associated with the season of conception was relatively small, suggesting family planning strategies may not need to change based on these findings. The exact mechanisms involving potential environmental factors need further investigation.

DISCLOSURES:

The authors reported no relevant financial relationships.

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

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TOPLINE:

Cerebral palsy (CP) affects 1-4 per 1,000 live births in the United States. A new cohort study found children conceived during the winter and spring months appear to have a slightly higher risk for developing CP than those conceived during the summer. Fall months carried about the same or only slightly higher risk of CP than summer months.

METHODOLOGY:

  • Researchers examined data from nearly 4.5 million live births registered in California between 2007 and 2015, exploring if the season of conception could serve as an indicator of exposure to environmental risk factors.
  • For instance, infants conceived in winter months may have higher exposure to viruses like influenza. In California, agricultural pesticides are most often applied in summer months, when pregnant people would be in their first or second trimester and receive their most exposure to the fine particulates, the authors hypothesize.
  • Almost 4,700 babies in the study population were diagnosed with CP. Researchers also considered the role of preterm birth as a potential mediating factor, and adjusted for sociodemographic characteristics such as maternal age, race, education, smoking during pregnancy, and body mass index.

TAKEAWAY:

  • The study found that children conceived in winter and spring had a 9% (95% confidence interval, 1.01-1.19) to 10% (95% CI, 1.02-1.20) higher risk of developing CP than those conceived in the summer.
  • Children conceived in January, February, or May carried a 15% higher risk, compared with babies conceived in July.
  • The risk was more pronounced among mothers with low education levels or living in neighborhoods where residents have high rates of unemployment, single-parent households, multiunit households, and lower rates of high school graduates.

IN PRACTICE:

The researchers noted that possible explanations for the seasonal link to CP risk may include the prevalence of maternal infections during pregnancy, variations in exposure to pesticides, and seasonal patterns for air pollution. “Investigating seasonal variations in disease occurrence can provide clues about etiologically relevant factors.”

SOURCE:

Lead author Haoran Zhou, MPH, Yale University, New Haven, Conn., and colleagues published their findings online in JAMA Network Open. The study was partly supported by a grant from the American Academy for Cerebral Palsy and Developmental Medicine.

LIMITATIONS:

The study may not have fully captured all children with CP in the cohort due to the possibility of misclassification. The findings may not be generalizable beyond California. The overall increased risk associated with the season of conception was relatively small, suggesting family planning strategies may not need to change based on these findings. The exact mechanisms involving potential environmental factors need further investigation.

DISCLOSURES:

The authors reported no relevant financial relationships.

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

 

TOPLINE:

Cerebral palsy (CP) affects 1-4 per 1,000 live births in the United States. A new cohort study found children conceived during the winter and spring months appear to have a slightly higher risk for developing CP than those conceived during the summer. Fall months carried about the same or only slightly higher risk of CP than summer months.

METHODOLOGY:

  • Researchers examined data from nearly 4.5 million live births registered in California between 2007 and 2015, exploring if the season of conception could serve as an indicator of exposure to environmental risk factors.
  • For instance, infants conceived in winter months may have higher exposure to viruses like influenza. In California, agricultural pesticides are most often applied in summer months, when pregnant people would be in their first or second trimester and receive their most exposure to the fine particulates, the authors hypothesize.
  • Almost 4,700 babies in the study population were diagnosed with CP. Researchers also considered the role of preterm birth as a potential mediating factor, and adjusted for sociodemographic characteristics such as maternal age, race, education, smoking during pregnancy, and body mass index.

TAKEAWAY:

  • The study found that children conceived in winter and spring had a 9% (95% confidence interval, 1.01-1.19) to 10% (95% CI, 1.02-1.20) higher risk of developing CP than those conceived in the summer.
  • Children conceived in January, February, or May carried a 15% higher risk, compared with babies conceived in July.
  • The risk was more pronounced among mothers with low education levels or living in neighborhoods where residents have high rates of unemployment, single-parent households, multiunit households, and lower rates of high school graduates.

IN PRACTICE:

The researchers noted that possible explanations for the seasonal link to CP risk may include the prevalence of maternal infections during pregnancy, variations in exposure to pesticides, and seasonal patterns for air pollution. “Investigating seasonal variations in disease occurrence can provide clues about etiologically relevant factors.”

SOURCE:

Lead author Haoran Zhou, MPH, Yale University, New Haven, Conn., and colleagues published their findings online in JAMA Network Open. The study was partly supported by a grant from the American Academy for Cerebral Palsy and Developmental Medicine.

LIMITATIONS:

The study may not have fully captured all children with CP in the cohort due to the possibility of misclassification. The findings may not be generalizable beyond California. The overall increased risk associated with the season of conception was relatively small, suggesting family planning strategies may not need to change based on these findings. The exact mechanisms involving potential environmental factors need further investigation.

DISCLOSURES:

The authors reported no relevant financial relationships.

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

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Thread lifts an option for noninvasive facial tightening

Article Type
Changed
Mon, 09/25/2023 - 09:52

The use of absorbable threads to improve skin laxity is safe and effective, but their long-term aesthetic effects remain unclear, according to Catherine M. DiGiorgio, MD, MS.

In the 1990s, clinicians used nonabsorbable sutures for thread lifts, including polypropylene-barbed threads, which caused adverse events ranging from extrusion and migration to thread expulsion, dimpling, granuloma formation, and prolonged pain, Dr. DiGiorgio, a laser and cosmetic dermatologist who practices in Boston, said at the annual Masters of Aesthetics Symposium. As a result, the Food and Drug Administration withdrew its approval of contour thread aesthetic procedures in 2009. Since then, the development of absorbable threads made from a hybrid of poly-l-lactic acid (PLLA) and polyglycolide/l-lactide (PLGA), and from polydioxanone (PDO) has led to renewed interest in thread lift procedures.

Dr. DiGiorgio
Dr. Catherine M. DiGiorgio

While a surgical facelift remains the gold standard, “we have some options to offer patients for noninvasive tightening,” Dr. DiGiorgio said. “We have devices that provide minimal downtime and are less costly, but results are inconsistent. Thread lifts, or suspension sutures, also have minimal downtime and are less costly, but the [results are] subtle and not long lasting.”

PLGA/PLLA threads consist of an 18% PLGA and 82% PLLA monofilament with bidirectional cones that shift the tissue. They are available in 8, 12, or 16 cones spaced 5-8 mm apart on either side of a 2-cm central cone-free area. “There is a 12-cm, 23-gauge needle on either side of the thread, to allow for insertion,” she explained. “These cones stimulate types I and II collagen, which results in collagenesis. The skin encapsulates the cones, resulting in lasting volume and contour.”

PDO threads, meanwhile, are biodegradable by hydrolysis over 4-8 months. They are inserted with a cannula or a needle and vary based on length, diameter, twined vs. braided, coned vs. barbed, and twisted vs. smooth. “The barbed PDO threads are what I use the most,” Dr. DiGiorgio said. “They provide slight tissue repositioning by anchoring and gripping.”

In 2019, researchers in Korea published results of a study that evaluated the collagen-producing effects of powdered PDO injection, compared with PLLA injection, in a murine model. They found that while both PDO and PLLA induced granulomatous reactions and collagen formation, PDO resulted in slightly more collagen formation than PLLA.

Dr. DiGiorgio, who transitioned to using PDO threads after first using the PLLA/PLGA threads, said that both are effective. “I find PDO threads to be easier. They’re less costly for me, they’re less costly for the patient, and the results are about equivalent.”

Absorbable threads are indicated for the cheek, jawline, neck, lips, forehead, and brow. She finds them most useful “for the lower face, below the nasolabial fold down to the jawline, for improvement of the jowls,” she said. “I don’t think they really work on the neck.”

As with any cosmetic procedure, patient selection is key. According to Dr. DiGiorgio, the patient should have specific and segmental areas of facial laxity amenable to lifting and recontouring along a straight-line vector, adequate dermal thickness, and appropriate expectations for the level of correction. “I like to re-volumize with filler before performing thread lifts to make sure that volume is restored, because you can’t really provide lift to someone with significant volume loss,” she said.
 

 

 

Procedural tips

Prior to the procedure, Dr. DiGiorgio marks the area to be treated while the patient is seated upright and holding a mirror. Then, she pulls back the amount of skin laxity the thread is going to correct. The plane of insertion for barbed threads is at the superficial musculoaponeurotic system (SMAS), and she typically uses 3-4 threads on each side of the face.

“How do you know you’re in the right plane?” If the patient is experiencing significant pain, “you’re too deep, and it’s not going to work,” she said. “You can see if the thread is too superficial as you do more of these.”

After the procedure she asks the patient to sit up prior to trimming the threads. “I take a look in the mirror with them and have them smile and make funny faces to see if there is any dimpling or crimpling, which is probably the most common side effect,” she said. “If I see that, I will pull the thread immediately, so we don’t have a problem. It’s a little uncomfortable to pull the thread but not more uncomfortable than the procedure itself, but I think it’s worth doing to avoid having a dimple or a crimple that can last up to a year.”



In her clinical experience, thread lifts last about 8-10 months. “I find that my patients will come in about once a year for this procedure, and the treated area feels tight afterward,” Dr. DiGiorgio said. “I think that sensation of feeling tight also provides satisfaction to the patient. Results are very subtle. It’s tissue repositioning; it is not a facelift. There’s not really any downtime, but further studies are required to see if threads are safe and effective in the long-term.”

In an interview after the meeting, she noted that the learning curve for thread lifts is variable, as with any new procedure a physician chooses to add to his or her practice. “It’s important to see these patients in follow-up 2 weeks after the procedure consistently, especially when someone first starts performing the procedure,” she recommended. “These patients are usually coming in to see me for other treatments, so I see them at regular 3-month intervals regardless. You begin to get a feel for what angles work and why and how to optimize the results. As with any procedure, the more experience you have performing the procedure will result in improved outcomes and improved management.”

Dr. DiGiorgio disclosed that she has been an advisory board member for Quthero and she holds stock options in the company. She is a consultant for Revelle and has received equipment from Acclaro.

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The use of absorbable threads to improve skin laxity is safe and effective, but their long-term aesthetic effects remain unclear, according to Catherine M. DiGiorgio, MD, MS.

In the 1990s, clinicians used nonabsorbable sutures for thread lifts, including polypropylene-barbed threads, which caused adverse events ranging from extrusion and migration to thread expulsion, dimpling, granuloma formation, and prolonged pain, Dr. DiGiorgio, a laser and cosmetic dermatologist who practices in Boston, said at the annual Masters of Aesthetics Symposium. As a result, the Food and Drug Administration withdrew its approval of contour thread aesthetic procedures in 2009. Since then, the development of absorbable threads made from a hybrid of poly-l-lactic acid (PLLA) and polyglycolide/l-lactide (PLGA), and from polydioxanone (PDO) has led to renewed interest in thread lift procedures.

Dr. DiGiorgio
Dr. Catherine M. DiGiorgio

While a surgical facelift remains the gold standard, “we have some options to offer patients for noninvasive tightening,” Dr. DiGiorgio said. “We have devices that provide minimal downtime and are less costly, but results are inconsistent. Thread lifts, or suspension sutures, also have minimal downtime and are less costly, but the [results are] subtle and not long lasting.”

PLGA/PLLA threads consist of an 18% PLGA and 82% PLLA monofilament with bidirectional cones that shift the tissue. They are available in 8, 12, or 16 cones spaced 5-8 mm apart on either side of a 2-cm central cone-free area. “There is a 12-cm, 23-gauge needle on either side of the thread, to allow for insertion,” she explained. “These cones stimulate types I and II collagen, which results in collagenesis. The skin encapsulates the cones, resulting in lasting volume and contour.”

PDO threads, meanwhile, are biodegradable by hydrolysis over 4-8 months. They are inserted with a cannula or a needle and vary based on length, diameter, twined vs. braided, coned vs. barbed, and twisted vs. smooth. “The barbed PDO threads are what I use the most,” Dr. DiGiorgio said. “They provide slight tissue repositioning by anchoring and gripping.”

In 2019, researchers in Korea published results of a study that evaluated the collagen-producing effects of powdered PDO injection, compared with PLLA injection, in a murine model. They found that while both PDO and PLLA induced granulomatous reactions and collagen formation, PDO resulted in slightly more collagen formation than PLLA.

Dr. DiGiorgio, who transitioned to using PDO threads after first using the PLLA/PLGA threads, said that both are effective. “I find PDO threads to be easier. They’re less costly for me, they’re less costly for the patient, and the results are about equivalent.”

Absorbable threads are indicated for the cheek, jawline, neck, lips, forehead, and brow. She finds them most useful “for the lower face, below the nasolabial fold down to the jawline, for improvement of the jowls,” she said. “I don’t think they really work on the neck.”

As with any cosmetic procedure, patient selection is key. According to Dr. DiGiorgio, the patient should have specific and segmental areas of facial laxity amenable to lifting and recontouring along a straight-line vector, adequate dermal thickness, and appropriate expectations for the level of correction. “I like to re-volumize with filler before performing thread lifts to make sure that volume is restored, because you can’t really provide lift to someone with significant volume loss,” she said.
 

 

 

Procedural tips

Prior to the procedure, Dr. DiGiorgio marks the area to be treated while the patient is seated upright and holding a mirror. Then, she pulls back the amount of skin laxity the thread is going to correct. The plane of insertion for barbed threads is at the superficial musculoaponeurotic system (SMAS), and she typically uses 3-4 threads on each side of the face.

“How do you know you’re in the right plane?” If the patient is experiencing significant pain, “you’re too deep, and it’s not going to work,” she said. “You can see if the thread is too superficial as you do more of these.”

After the procedure she asks the patient to sit up prior to trimming the threads. “I take a look in the mirror with them and have them smile and make funny faces to see if there is any dimpling or crimpling, which is probably the most common side effect,” she said. “If I see that, I will pull the thread immediately, so we don’t have a problem. It’s a little uncomfortable to pull the thread but not more uncomfortable than the procedure itself, but I think it’s worth doing to avoid having a dimple or a crimple that can last up to a year.”



In her clinical experience, thread lifts last about 8-10 months. “I find that my patients will come in about once a year for this procedure, and the treated area feels tight afterward,” Dr. DiGiorgio said. “I think that sensation of feeling tight also provides satisfaction to the patient. Results are very subtle. It’s tissue repositioning; it is not a facelift. There’s not really any downtime, but further studies are required to see if threads are safe and effective in the long-term.”

In an interview after the meeting, she noted that the learning curve for thread lifts is variable, as with any new procedure a physician chooses to add to his or her practice. “It’s important to see these patients in follow-up 2 weeks after the procedure consistently, especially when someone first starts performing the procedure,” she recommended. “These patients are usually coming in to see me for other treatments, so I see them at regular 3-month intervals regardless. You begin to get a feel for what angles work and why and how to optimize the results. As with any procedure, the more experience you have performing the procedure will result in improved outcomes and improved management.”

Dr. DiGiorgio disclosed that she has been an advisory board member for Quthero and she holds stock options in the company. She is a consultant for Revelle and has received equipment from Acclaro.

The use of absorbable threads to improve skin laxity is safe and effective, but their long-term aesthetic effects remain unclear, according to Catherine M. DiGiorgio, MD, MS.

In the 1990s, clinicians used nonabsorbable sutures for thread lifts, including polypropylene-barbed threads, which caused adverse events ranging from extrusion and migration to thread expulsion, dimpling, granuloma formation, and prolonged pain, Dr. DiGiorgio, a laser and cosmetic dermatologist who practices in Boston, said at the annual Masters of Aesthetics Symposium. As a result, the Food and Drug Administration withdrew its approval of contour thread aesthetic procedures in 2009. Since then, the development of absorbable threads made from a hybrid of poly-l-lactic acid (PLLA) and polyglycolide/l-lactide (PLGA), and from polydioxanone (PDO) has led to renewed interest in thread lift procedures.

Dr. DiGiorgio
Dr. Catherine M. DiGiorgio

While a surgical facelift remains the gold standard, “we have some options to offer patients for noninvasive tightening,” Dr. DiGiorgio said. “We have devices that provide minimal downtime and are less costly, but results are inconsistent. Thread lifts, or suspension sutures, also have minimal downtime and are less costly, but the [results are] subtle and not long lasting.”

PLGA/PLLA threads consist of an 18% PLGA and 82% PLLA monofilament with bidirectional cones that shift the tissue. They are available in 8, 12, or 16 cones spaced 5-8 mm apart on either side of a 2-cm central cone-free area. “There is a 12-cm, 23-gauge needle on either side of the thread, to allow for insertion,” she explained. “These cones stimulate types I and II collagen, which results in collagenesis. The skin encapsulates the cones, resulting in lasting volume and contour.”

PDO threads, meanwhile, are biodegradable by hydrolysis over 4-8 months. They are inserted with a cannula or a needle and vary based on length, diameter, twined vs. braided, coned vs. barbed, and twisted vs. smooth. “The barbed PDO threads are what I use the most,” Dr. DiGiorgio said. “They provide slight tissue repositioning by anchoring and gripping.”

In 2019, researchers in Korea published results of a study that evaluated the collagen-producing effects of powdered PDO injection, compared with PLLA injection, in a murine model. They found that while both PDO and PLLA induced granulomatous reactions and collagen formation, PDO resulted in slightly more collagen formation than PLLA.

Dr. DiGiorgio, who transitioned to using PDO threads after first using the PLLA/PLGA threads, said that both are effective. “I find PDO threads to be easier. They’re less costly for me, they’re less costly for the patient, and the results are about equivalent.”

Absorbable threads are indicated for the cheek, jawline, neck, lips, forehead, and brow. She finds them most useful “for the lower face, below the nasolabial fold down to the jawline, for improvement of the jowls,” she said. “I don’t think they really work on the neck.”

As with any cosmetic procedure, patient selection is key. According to Dr. DiGiorgio, the patient should have specific and segmental areas of facial laxity amenable to lifting and recontouring along a straight-line vector, adequate dermal thickness, and appropriate expectations for the level of correction. “I like to re-volumize with filler before performing thread lifts to make sure that volume is restored, because you can’t really provide lift to someone with significant volume loss,” she said.
 

 

 

Procedural tips

Prior to the procedure, Dr. DiGiorgio marks the area to be treated while the patient is seated upright and holding a mirror. Then, she pulls back the amount of skin laxity the thread is going to correct. The plane of insertion for barbed threads is at the superficial musculoaponeurotic system (SMAS), and she typically uses 3-4 threads on each side of the face.

“How do you know you’re in the right plane?” If the patient is experiencing significant pain, “you’re too deep, and it’s not going to work,” she said. “You can see if the thread is too superficial as you do more of these.”

After the procedure she asks the patient to sit up prior to trimming the threads. “I take a look in the mirror with them and have them smile and make funny faces to see if there is any dimpling or crimpling, which is probably the most common side effect,” she said. “If I see that, I will pull the thread immediately, so we don’t have a problem. It’s a little uncomfortable to pull the thread but not more uncomfortable than the procedure itself, but I think it’s worth doing to avoid having a dimple or a crimple that can last up to a year.”



In her clinical experience, thread lifts last about 8-10 months. “I find that my patients will come in about once a year for this procedure, and the treated area feels tight afterward,” Dr. DiGiorgio said. “I think that sensation of feeling tight also provides satisfaction to the patient. Results are very subtle. It’s tissue repositioning; it is not a facelift. There’s not really any downtime, but further studies are required to see if threads are safe and effective in the long-term.”

In an interview after the meeting, she noted that the learning curve for thread lifts is variable, as with any new procedure a physician chooses to add to his or her practice. “It’s important to see these patients in follow-up 2 weeks after the procedure consistently, especially when someone first starts performing the procedure,” she recommended. “These patients are usually coming in to see me for other treatments, so I see them at regular 3-month intervals regardless. You begin to get a feel for what angles work and why and how to optimize the results. As with any procedure, the more experience you have performing the procedure will result in improved outcomes and improved management.”

Dr. DiGiorgio disclosed that she has been an advisory board member for Quthero and she holds stock options in the company. She is a consultant for Revelle and has received equipment from Acclaro.

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Are vitamin D levels key to canagliflozin’s fracture risk?

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Changed
Mon, 09/25/2023 - 09:52

Vitamin D deficiency appears to render people more vulnerable to canagliflozin’s adverse effects on bone health, whereas vitamin D3 supplementation appears protective of individuals with vitamin D deficiency.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are beneficial for treating type 2 diabetes and reducing cardiovascular and kidney disease risk. However, some, but not all, trial data have linked the SLGT2 inhibitor canagliflozin to increased fracture risk. That particular agent has been reported to accelerate loss of bone mineral density, which could contribute to fracture risk. Other drugs in the class have also been implicated in worsening markers of bone health.



The new findings, from a small study of Amish adults with vitamin D deficiency (≤ 20 ng/mL) but without diabetes or osteoporosis, suggest that physicians consider screening for vitamin D deficiency prior to prescribing SGLT2 inhibitor. Alternatively, these patients can simply be prescribed safe, inexpensive, OTC vitamin D supplements without being screening, Zhinous Shahidzadeh Yazdi, MD, of the division of endocrinology, diabetes, and nutrition at the University of Maryland, Baltimore, and colleagues wrote.

“Something as simple as OTC vitamin D might protect against bone fractures caused by chronic multiyear treatment with a drug,” study lead author Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, said in an interview.

In the study, published in the Journal of Clinical Endocrinology and Metabolism, 11 adults with vitamin D deficiency underwent two canagliflozin challenge protocols of 300 mg/d for 5 days, once before and once after vitamin D3 supplementation (either 50,000 IU per week or twice weekly for body mass index < 30 kg/m2 or ≥ 30 kg/m2, respectively), to achieve 25(OH)D of at least 30 ng/mL.

When the participants were vitamin D deficient, canagliflozin significantly decreased 1,25(OH)2D levels by 31.3%, from 43.8 pg/mL on day 1 to 29.1 pg/mL on day 3 (P = .0003). In contrast, after receiving the vitamin D3 supplements, canagliflozin reduced mean 1,25(OH)2D levels by a nonsignificant 9.3%, from 45 pg/mL on day 1 to 41 pg/mL on day 3 (P = .3).

“Thus, [vitamin D3] supplementation provided statistically significant protection from the adverse effect of canagliflozin to decrease mean plasma levels of 1,25(OH)2D (P = .04),” Yazdi and colleagues wrote.

Similarly, when the participants were vitamin D deficient, canagliflozin was associated with a significant 36.2% increase in mean parathyroid hormone (PTH) levels, from 47.5 pg/mL on day 1 to 58.5 pg/mL on day 6 (P = .0009). In contrast, after vitamin D3 supplementation, the increase in PTH was far less, from 48.4 pg/mL on day 1 to 53.3 pg/mL on day 6 (P = .02).

Therefore, the supplementation “significantly decreased the magnitude of the canagliflozin-induced increase in mean levels of PTH (P = .005),” they wrote.

Also, in the vitamin D deficient state, canagliflozin significantly increased mean serum phosphorous on day 3 in comparison with day 1 (P = .007), while after supplementation, that change was also insignificant (P = .8).

“We are saying that SGLT2 inhibitors, when superimposed on vitamin D deficiency, is bad for bone health. This group of people have two important risk factors – vitamin D deficiency and SGLT2 inhibitors – and are distinct from the general population of people who are not vitamin D deficient,” Dr. Taylor noted.

The findings “raise interesting questions about how to proceed,” he said in an interview, since “the gold standard study – in this case, a fracture prevention study – will never be done because it would cost more than $100 million. Vitamin D costs only $10-$20 per year, and at appropriate doses, is extremely safe. At worst, vitamin D supplements are unnecessary. At best, vitamin D supplements can protect some patients against a serious drug toxicity, bone fracture.”

The study was funded by the National Institutes of Health. Dr. Taylor serves as a consultant for Ionis Pharmaceuticals and receives an inventor’s share of royalties from the National Institute of Diabetes, Digestive, and Kidney Diseases for metreleptin as a treatment for generalized lipodystrophy. Dr. Yazdi disclosed no relevant financial relationships.

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

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Vitamin D deficiency appears to render people more vulnerable to canagliflozin’s adverse effects on bone health, whereas vitamin D3 supplementation appears protective of individuals with vitamin D deficiency.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are beneficial for treating type 2 diabetes and reducing cardiovascular and kidney disease risk. However, some, but not all, trial data have linked the SLGT2 inhibitor canagliflozin to increased fracture risk. That particular agent has been reported to accelerate loss of bone mineral density, which could contribute to fracture risk. Other drugs in the class have also been implicated in worsening markers of bone health.



The new findings, from a small study of Amish adults with vitamin D deficiency (≤ 20 ng/mL) but without diabetes or osteoporosis, suggest that physicians consider screening for vitamin D deficiency prior to prescribing SGLT2 inhibitor. Alternatively, these patients can simply be prescribed safe, inexpensive, OTC vitamin D supplements without being screening, Zhinous Shahidzadeh Yazdi, MD, of the division of endocrinology, diabetes, and nutrition at the University of Maryland, Baltimore, and colleagues wrote.

“Something as simple as OTC vitamin D might protect against bone fractures caused by chronic multiyear treatment with a drug,” study lead author Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, said in an interview.

In the study, published in the Journal of Clinical Endocrinology and Metabolism, 11 adults with vitamin D deficiency underwent two canagliflozin challenge protocols of 300 mg/d for 5 days, once before and once after vitamin D3 supplementation (either 50,000 IU per week or twice weekly for body mass index < 30 kg/m2 or ≥ 30 kg/m2, respectively), to achieve 25(OH)D of at least 30 ng/mL.

When the participants were vitamin D deficient, canagliflozin significantly decreased 1,25(OH)2D levels by 31.3%, from 43.8 pg/mL on day 1 to 29.1 pg/mL on day 3 (P = .0003). In contrast, after receiving the vitamin D3 supplements, canagliflozin reduced mean 1,25(OH)2D levels by a nonsignificant 9.3%, from 45 pg/mL on day 1 to 41 pg/mL on day 3 (P = .3).

“Thus, [vitamin D3] supplementation provided statistically significant protection from the adverse effect of canagliflozin to decrease mean plasma levels of 1,25(OH)2D (P = .04),” Yazdi and colleagues wrote.

Similarly, when the participants were vitamin D deficient, canagliflozin was associated with a significant 36.2% increase in mean parathyroid hormone (PTH) levels, from 47.5 pg/mL on day 1 to 58.5 pg/mL on day 6 (P = .0009). In contrast, after vitamin D3 supplementation, the increase in PTH was far less, from 48.4 pg/mL on day 1 to 53.3 pg/mL on day 6 (P = .02).

Therefore, the supplementation “significantly decreased the magnitude of the canagliflozin-induced increase in mean levels of PTH (P = .005),” they wrote.

Also, in the vitamin D deficient state, canagliflozin significantly increased mean serum phosphorous on day 3 in comparison with day 1 (P = .007), while after supplementation, that change was also insignificant (P = .8).

“We are saying that SGLT2 inhibitors, when superimposed on vitamin D deficiency, is bad for bone health. This group of people have two important risk factors – vitamin D deficiency and SGLT2 inhibitors – and are distinct from the general population of people who are not vitamin D deficient,” Dr. Taylor noted.

The findings “raise interesting questions about how to proceed,” he said in an interview, since “the gold standard study – in this case, a fracture prevention study – will never be done because it would cost more than $100 million. Vitamin D costs only $10-$20 per year, and at appropriate doses, is extremely safe. At worst, vitamin D supplements are unnecessary. At best, vitamin D supplements can protect some patients against a serious drug toxicity, bone fracture.”

The study was funded by the National Institutes of Health. Dr. Taylor serves as a consultant for Ionis Pharmaceuticals and receives an inventor’s share of royalties from the National Institute of Diabetes, Digestive, and Kidney Diseases for metreleptin as a treatment for generalized lipodystrophy. Dr. Yazdi disclosed no relevant financial relationships.

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

Vitamin D deficiency appears to render people more vulnerable to canagliflozin’s adverse effects on bone health, whereas vitamin D3 supplementation appears protective of individuals with vitamin D deficiency.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are beneficial for treating type 2 diabetes and reducing cardiovascular and kidney disease risk. However, some, but not all, trial data have linked the SLGT2 inhibitor canagliflozin to increased fracture risk. That particular agent has been reported to accelerate loss of bone mineral density, which could contribute to fracture risk. Other drugs in the class have also been implicated in worsening markers of bone health.



The new findings, from a small study of Amish adults with vitamin D deficiency (≤ 20 ng/mL) but without diabetes or osteoporosis, suggest that physicians consider screening for vitamin D deficiency prior to prescribing SGLT2 inhibitor. Alternatively, these patients can simply be prescribed safe, inexpensive, OTC vitamin D supplements without being screening, Zhinous Shahidzadeh Yazdi, MD, of the division of endocrinology, diabetes, and nutrition at the University of Maryland, Baltimore, and colleagues wrote.

“Something as simple as OTC vitamin D might protect against bone fractures caused by chronic multiyear treatment with a drug,” study lead author Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, said in an interview.

In the study, published in the Journal of Clinical Endocrinology and Metabolism, 11 adults with vitamin D deficiency underwent two canagliflozin challenge protocols of 300 mg/d for 5 days, once before and once after vitamin D3 supplementation (either 50,000 IU per week or twice weekly for body mass index < 30 kg/m2 or ≥ 30 kg/m2, respectively), to achieve 25(OH)D of at least 30 ng/mL.

When the participants were vitamin D deficient, canagliflozin significantly decreased 1,25(OH)2D levels by 31.3%, from 43.8 pg/mL on day 1 to 29.1 pg/mL on day 3 (P = .0003). In contrast, after receiving the vitamin D3 supplements, canagliflozin reduced mean 1,25(OH)2D levels by a nonsignificant 9.3%, from 45 pg/mL on day 1 to 41 pg/mL on day 3 (P = .3).

“Thus, [vitamin D3] supplementation provided statistically significant protection from the adverse effect of canagliflozin to decrease mean plasma levels of 1,25(OH)2D (P = .04),” Yazdi and colleagues wrote.

Similarly, when the participants were vitamin D deficient, canagliflozin was associated with a significant 36.2% increase in mean parathyroid hormone (PTH) levels, from 47.5 pg/mL on day 1 to 58.5 pg/mL on day 6 (P = .0009). In contrast, after vitamin D3 supplementation, the increase in PTH was far less, from 48.4 pg/mL on day 1 to 53.3 pg/mL on day 6 (P = .02).

Therefore, the supplementation “significantly decreased the magnitude of the canagliflozin-induced increase in mean levels of PTH (P = .005),” they wrote.

Also, in the vitamin D deficient state, canagliflozin significantly increased mean serum phosphorous on day 3 in comparison with day 1 (P = .007), while after supplementation, that change was also insignificant (P = .8).

“We are saying that SGLT2 inhibitors, when superimposed on vitamin D deficiency, is bad for bone health. This group of people have two important risk factors – vitamin D deficiency and SGLT2 inhibitors – and are distinct from the general population of people who are not vitamin D deficient,” Dr. Taylor noted.

The findings “raise interesting questions about how to proceed,” he said in an interview, since “the gold standard study – in this case, a fracture prevention study – will never be done because it would cost more than $100 million. Vitamin D costs only $10-$20 per year, and at appropriate doses, is extremely safe. At worst, vitamin D supplements are unnecessary. At best, vitamin D supplements can protect some patients against a serious drug toxicity, bone fracture.”

The study was funded by the National Institutes of Health. Dr. Taylor serves as a consultant for Ionis Pharmaceuticals and receives an inventor’s share of royalties from the National Institute of Diabetes, Digestive, and Kidney Diseases for metreleptin as a treatment for generalized lipodystrophy. Dr. Yazdi disclosed no relevant financial relationships.

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

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