Federal Practitioner

The antiseptic methenamine hippurate (MH) is known to sterilize urine and has been suggested to be of use in preventing urinary tract infections (UTIs), but firm evidence has so far been lacking. Now researchers led by clinicians and scientists from Newcastle-upon-Tyne, England, have provided the ALTAR trial (Alternative to Prophylactic Antibiotics for the Treatment of Recurrent UTIs in Women).

Daily low-dose antibiotics as recommended by current guidelines for prophylactic treatment of recurrent UTI have been linked to antibiotic resistance. Using MH as an alternative could play an important role in helping to tackle the global problem of increasing antibiotic resistance, the team said.
 

Study details

They recruited 240 women aged 18 or over with recurrent UTIs requiring prophylactic treatment from eight secondary care urology and urogynecology centers in the United Kingdom from June 2016 to June 2018. Women were randomized to receive MH or daily low-dose antibiotics for 12 months, with follow up for a further 6 months beyond that.

Before trial entry the women had experienced an average of more than six UTI episodes per year. During the 12-month treatment period, in the modified intention-to-treat population, there were 90 symptomatic, antibiotic-treated UTI episodes reported over 101 person-years of follow-up in the antibiotic group, and 141 episodes over 102 person-years in the MH group.

This yielded a UTI rate of 0.89 episodes per person-year in the antibiotic group, compared with 1.38 in the MH group, an absolute difference of 0.49 episodes per person-year. In the 6-month posttreatment follow-up period, the UTI incidence rate was 1.19 episodes per person-year in the antibiotic prophylaxis group versus 1.72 in the MH group, an absolute difference of 0.53.

Before the trial, a patient and public involvement group had predefined the noninferiority margin as one episode of UTI per person-year. The small difference between the two groups was less than this, confirming noninferiority of MH to antibiotic prophylaxis in this setting. This finding was consistent across the modified intention-to-treat, strict intention-to-treat, per protocol, and modified per protocol (post hoc) analyses.

Thus the ALTAR results showed that MH was no worse than antibiotics at preventing UTIs, and MH was also associated with reduced antibiotic consumption.

The vast majority of participants were over 90% adherent with the allocated treatment. Patient satisfaction was generally high and rates of adverse events and adverse reactions generally low, and both were comparable between treatment groups. Adverse reactions were reported by 34/142 (24%) in the antibiotic group and 35/127 (28%) in the MH group, and most reactions were mild. In the antibiotic group there were two serious adverse reactions (severe abdominal pain and raised alanine transaminase), whereas six participants in the MH group reported an episode of febrile UTI and four were admitted to hospital because of UTI.
 

Substantial global health care problem

At least 50% and up to 80% of all women have at least one acute UTI in their lifetime, most often uncomplicated acute cystitis. About a quarter of them go on to suffer recurrent infection, defined as three or more repeat infections in the past year, or two infections in the preceding 6 months. Frequent recurrences thus represent “a substantial global health care problem,” the authors say.

Guidelines from the United Kingdom, Europe, and the United States acknowledge the need for preventive strategies and strongly recommend the use of daily, low-dose antibiotics as standard prophylactic treatment. However, the United Kingdom’s antimicrobial resistance strategy recommends a “strong focus on infection prevention,” and aims to reduce antimicrobial use in humans by 15% before 2024.

“To achieve that, exploration of nonantibiotic preventive treatments in common conditions such as UTI is essential,” the team said.

MH is one such nonantibiotic treatment. It is bactericidal and works by denaturing bacterial proteins and nucleic acids. Although previous Cochrane systematic reviews had concluded that it could be effective for preventing UTI, further large trials were needed.

“This trial adds to the evidence base for the use of MH for prophylactic treatment in adult women with recurrent UTI. Although the MH group had a 55% higher rate of UTI episodes than the antibiotics group, the absolute difference was just 0.49 UTI episodes per year, which has limited clinical consequence,” the team concluded.
 

Results could ‘support a change in practice’

In older patients, particularly, the risks of long-term antibiotic prophylaxis might outweigh the benefits, and the authors said that their results “could support a change in practice in terms of preventive treatments for recurrent UTI and provide patients and clinicians with a credible alternative to daily antibiotics, giving them the confidence to pursue strategies that avoid long-term antibiotic use.”

They acknowledged limitations of the study, including that treatment allocation was not masked, crossover between arms was allowed, and differences in antibiotics prescribed may have affected the results. In addition, data regarding long-term safety of MH are scarce.

However, they said that the trial accurately represented the broad range of women with recurrent UTI, and that its results “might encourage patients and clinicians to consider MH as a first line treatment for UTI prevention in women.”

In a linked editorial, scientists from the Institute for Evidence-Based Healthcare at Bond University in Queensland, Australia, commented: “Although the results need cautious interpretation, they align with others, and this new research increases the confidence with which MH can be offered as an option to women needing prophylaxis against recurrent urinary tract infection.”

References

Harding C et al. Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, noninferiority trial. BMJ 2022 Mar 9;376:e068229.

Hoffmann TC et al. Methenamine hippurate for recurrent urinary tract infections. BMJ 2022 Mar 9;376:o533.

A version of this article first appeared on Medscape.co.uk.

The antiseptic methenamine hippurate (MH) is known to sterilize urine and has been suggested to be of use in preventing urinary tract infections (UTIs), but firm evidence has so far been lacking. Now researchers led by clinicians and scientists from Newcastle-upon-Tyne, England, have provided the ALTAR trial (Alternative to Prophylactic Antibiotics for the Treatment of Recurrent UTIs in Women).

Daily low-dose antibiotics as recommended by current guidelines for prophylactic treatment of recurrent UTI have been linked to antibiotic resistance. Using MH as an alternative could play an important role in helping to tackle the global problem of increasing antibiotic resistance, the team said.
 

Study details

They recruited 240 women aged 18 or over with recurrent UTIs requiring prophylactic treatment from eight secondary care urology and urogynecology centers in the United Kingdom from June 2016 to June 2018. Women were randomized to receive MH or daily low-dose antibiotics for 12 months, with follow up for a further 6 months beyond that.

Before trial entry the women had experienced an average of more than six UTI episodes per year. During the 12-month treatment period, in the modified intention-to-treat population, there were 90 symptomatic, antibiotic-treated UTI episodes reported over 101 person-years of follow-up in the antibiotic group, and 141 episodes over 102 person-years in the MH group.

This yielded a UTI rate of 0.89 episodes per person-year in the antibiotic group, compared with 1.38 in the MH group, an absolute difference of 0.49 episodes per person-year. In the 6-month posttreatment follow-up period, the UTI incidence rate was 1.19 episodes per person-year in the antibiotic prophylaxis group versus 1.72 in the MH group, an absolute difference of 0.53.

Before the trial, a patient and public involvement group had predefined the noninferiority margin as one episode of UTI per person-year. The small difference between the two groups was less than this, confirming noninferiority of MH to antibiotic prophylaxis in this setting. This finding was consistent across the modified intention-to-treat, strict intention-to-treat, per protocol, and modified per protocol (post hoc) analyses.

Thus the ALTAR results showed that MH was no worse than antibiotics at preventing UTIs, and MH was also associated with reduced antibiotic consumption.

The vast majority of participants were over 90% adherent with the allocated treatment. Patient satisfaction was generally high and rates of adverse events and adverse reactions generally low, and both were comparable between treatment groups. Adverse reactions were reported by 34/142 (24%) in the antibiotic group and 35/127 (28%) in the MH group, and most reactions were mild. In the antibiotic group there were two serious adverse reactions (severe abdominal pain and raised alanine transaminase), whereas six participants in the MH group reported an episode of febrile UTI and four were admitted to hospital because of UTI.
 

Substantial global health care problem

At least 50% and up to 80% of all women have at least one acute UTI in their lifetime, most often uncomplicated acute cystitis. About a quarter of them go on to suffer recurrent infection, defined as three or more repeat infections in the past year, or two infections in the preceding 6 months. Frequent recurrences thus represent “a substantial global health care problem,” the authors say.

Guidelines from the United Kingdom, Europe, and the United States acknowledge the need for preventive strategies and strongly recommend the use of daily, low-dose antibiotics as standard prophylactic treatment. However, the United Kingdom’s antimicrobial resistance strategy recommends a “strong focus on infection prevention,” and aims to reduce antimicrobial use in humans by 15% before 2024.

“To achieve that, exploration of nonantibiotic preventive treatments in common conditions such as UTI is essential,” the team said.

MH is one such nonantibiotic treatment. It is bactericidal and works by denaturing bacterial proteins and nucleic acids. Although previous Cochrane systematic reviews had concluded that it could be effective for preventing UTI, further large trials were needed.

“This trial adds to the evidence base for the use of MH for prophylactic treatment in adult women with recurrent UTI. Although the MH group had a 55% higher rate of UTI episodes than the antibiotics group, the absolute difference was just 0.49 UTI episodes per year, which has limited clinical consequence,” the team concluded.
 

Results could ‘support a change in practice’

In older patients, particularly, the risks of long-term antibiotic prophylaxis might outweigh the benefits, and the authors said that their results “could support a change in practice in terms of preventive treatments for recurrent UTI and provide patients and clinicians with a credible alternative to daily antibiotics, giving them the confidence to pursue strategies that avoid long-term antibiotic use.”

They acknowledged limitations of the study, including that treatment allocation was not masked, crossover between arms was allowed, and differences in antibiotics prescribed may have affected the results. In addition, data regarding long-term safety of MH are scarce.

However, they said that the trial accurately represented the broad range of women with recurrent UTI, and that its results “might encourage patients and clinicians to consider MH as a first line treatment for UTI prevention in women.”

In a linked editorial, scientists from the Institute for Evidence-Based Healthcare at Bond University in Queensland, Australia, commented: “Although the results need cautious interpretation, they align with others, and this new research increases the confidence with which MH can be offered as an option to women needing prophylaxis against recurrent urinary tract infection.”

References

Harding C et al. Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, noninferiority trial. BMJ 2022 Mar 9;376:e068229.

Hoffmann TC et al. Methenamine hippurate for recurrent urinary tract infections. BMJ 2022 Mar 9;376:o533.

A version of this article first appeared on Medscape.co.uk.

The antiseptic methenamine hippurate (MH) is known to sterilize urine and has been suggested to be of use in preventing urinary tract infections (UTIs), but firm evidence has so far been lacking. Now researchers led by clinicians and scientists from Newcastle-upon-Tyne, England, have provided the ALTAR trial (Alternative to Prophylactic Antibiotics for the Treatment of Recurrent UTIs in Women).

Daily low-dose antibiotics as recommended by current guidelines for prophylactic treatment of recurrent UTI have been linked to antibiotic resistance. Using MH as an alternative could play an important role in helping to tackle the global problem of increasing antibiotic resistance, the team said.
 

Study details

They recruited 240 women aged 18 or over with recurrent UTIs requiring prophylactic treatment from eight secondary care urology and urogynecology centers in the United Kingdom from June 2016 to June 2018. Women were randomized to receive MH or daily low-dose antibiotics for 12 months, with follow up for a further 6 months beyond that.

Before trial entry the women had experienced an average of more than six UTI episodes per year. During the 12-month treatment period, in the modified intention-to-treat population, there were 90 symptomatic, antibiotic-treated UTI episodes reported over 101 person-years of follow-up in the antibiotic group, and 141 episodes over 102 person-years in the MH group.

This yielded a UTI rate of 0.89 episodes per person-year in the antibiotic group, compared with 1.38 in the MH group, an absolute difference of 0.49 episodes per person-year. In the 6-month posttreatment follow-up period, the UTI incidence rate was 1.19 episodes per person-year in the antibiotic prophylaxis group versus 1.72 in the MH group, an absolute difference of 0.53.

Before the trial, a patient and public involvement group had predefined the noninferiority margin as one episode of UTI per person-year. The small difference between the two groups was less than this, confirming noninferiority of MH to antibiotic prophylaxis in this setting. This finding was consistent across the modified intention-to-treat, strict intention-to-treat, per protocol, and modified per protocol (post hoc) analyses.

Thus the ALTAR results showed that MH was no worse than antibiotics at preventing UTIs, and MH was also associated with reduced antibiotic consumption.

The vast majority of participants were over 90% adherent with the allocated treatment. Patient satisfaction was generally high and rates of adverse events and adverse reactions generally low, and both were comparable between treatment groups. Adverse reactions were reported by 34/142 (24%) in the antibiotic group and 35/127 (28%) in the MH group, and most reactions were mild. In the antibiotic group there were two serious adverse reactions (severe abdominal pain and raised alanine transaminase), whereas six participants in the MH group reported an episode of febrile UTI and four were admitted to hospital because of UTI.
 

Substantial global health care problem

At least 50% and up to 80% of all women have at least one acute UTI in their lifetime, most often uncomplicated acute cystitis. About a quarter of them go on to suffer recurrent infection, defined as three or more repeat infections in the past year, or two infections in the preceding 6 months. Frequent recurrences thus represent “a substantial global health care problem,” the authors say.

Guidelines from the United Kingdom, Europe, and the United States acknowledge the need for preventive strategies and strongly recommend the use of daily, low-dose antibiotics as standard prophylactic treatment. However, the United Kingdom’s antimicrobial resistance strategy recommends a “strong focus on infection prevention,” and aims to reduce antimicrobial use in humans by 15% before 2024.

“To achieve that, exploration of nonantibiotic preventive treatments in common conditions such as UTI is essential,” the team said.

MH is one such nonantibiotic treatment. It is bactericidal and works by denaturing bacterial proteins and nucleic acids. Although previous Cochrane systematic reviews had concluded that it could be effective for preventing UTI, further large trials were needed.

“This trial adds to the evidence base for the use of MH for prophylactic treatment in adult women with recurrent UTI. Although the MH group had a 55% higher rate of UTI episodes than the antibiotics group, the absolute difference was just 0.49 UTI episodes per year, which has limited clinical consequence,” the team concluded.
 

Results could ‘support a change in practice’

In older patients, particularly, the risks of long-term antibiotic prophylaxis might outweigh the benefits, and the authors said that their results “could support a change in practice in terms of preventive treatments for recurrent UTI and provide patients and clinicians with a credible alternative to daily antibiotics, giving them the confidence to pursue strategies that avoid long-term antibiotic use.”

They acknowledged limitations of the study, including that treatment allocation was not masked, crossover between arms was allowed, and differences in antibiotics prescribed may have affected the results. In addition, data regarding long-term safety of MH are scarce.

However, they said that the trial accurately represented the broad range of women with recurrent UTI, and that its results “might encourage patients and clinicians to consider MH as a first line treatment for UTI prevention in women.”

In a linked editorial, scientists from the Institute for Evidence-Based Healthcare at Bond University in Queensland, Australia, commented: “Although the results need cautious interpretation, they align with others, and this new research increases the confidence with which MH can be offered as an option to women needing prophylaxis against recurrent urinary tract infection.”

References

Harding C et al. Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, noninferiority trial. BMJ 2022 Mar 9;376:e068229.

Hoffmann TC et al. Methenamine hippurate for recurrent urinary tract infections. BMJ 2022 Mar 9;376:o533.

A version of this article first appeared on Medscape.co.uk.

Adults with a congenital heart defect (CHD) are at increased risk for serious illness and death when hospitalized with COVID-19, making vaccination and other preventive measures even important in this population, say researchers with the Centers for Disease Control and Prevention.

“We found that hospitalized patients with heart defects are up to twice as likely to have critical outcomes of COVID-19 illness (admission to the intensive care unit, use of a ventilator to help with breathing, or death) compared to hospitalized COVID-19 patients without heart defects,” Karrie Downing, MPH, epidemiologist, with the CDC’s National Center on Birth Defects and Developmental Disabilities, said in an interview.

“Additionally, we learned that people with hearts defects who were older or who also had other conditions like heart failure, pulmonary hypertension, Down syndrome, diabetes, or obesity were the most likely to have critical COVID-19 illness, but children and adults with heart defects without these other conditions were still at increased risk,” Ms. Downing said.

The message for health care providers is clear: “Encourage your patients with heart defects to get vaccinated and discuss with your patients the need for other preventive measures to avoid infection that may progress to severe COVID-19 illness,” Ms. Downing added.

The study was published online March 7, 2022, in Circulation.

The researchers analyzed data on 235,638 patients hospitalized with COVID-19 between March 2020 and January 2021, including 421 (0.2%) with CHD. Most CHD patients were older than 30 years (73%) and 61% were men, with 55% non-Hispanic white, 19% Hispanic and 16% non-Hispanic Black.

Overall, 68% of CHD patients had at least one comorbidity, as did 59% of patients without CHD.

Rates of ICU admission were higher in the CHD group (54% vs. 43%), as were rates of invasive mechanical ventilation (24% vs. 15%) and in-hospital death (11% vs. 7%).

After accounting for patient characteristics, ICU admission, invasive mechanical ventilation and death were more prevalent among COVID-19 patients with rather than without CHD, with adjusted prevalence ratios of 1.4, 1.8 and 2.0, respectively.

When stratified by high-risk characteristics, prevalence estimates for ICU admission, invasive mechanical ventilation and death remained higher among patients with COVID-19 and CHD across nearly all strata, including younger age groups and those without heart failure, pulmonary hypertension, Down syndrome, diabetes, or obesity, the researchers reported.

Ms. Downing said more work is needed to identify why the clinical course of COVID-19 disease results in admission to the ICU, the need for a ventilator, or death for some hospitalized patients with CHD and not for others.

“There could be a number of social, environmental, economic, medical, and genetic factors playing a role. But staying up to date with COVID-19 vaccines and following preventive measures for COVID-19 are effective ways to reduce the risk of severe illness from COVID-19,” Ms. Downing said.

The study had no specific funding. The authors reported no relevant disclosures.

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

Adults with a congenital heart defect (CHD) are at increased risk for serious illness and death when hospitalized with COVID-19, making vaccination and other preventive measures even important in this population, say researchers with the Centers for Disease Control and Prevention.

“We found that hospitalized patients with heart defects are up to twice as likely to have critical outcomes of COVID-19 illness (admission to the intensive care unit, use of a ventilator to help with breathing, or death) compared to hospitalized COVID-19 patients without heart defects,” Karrie Downing, MPH, epidemiologist, with the CDC’s National Center on Birth Defects and Developmental Disabilities, said in an interview.

“Additionally, we learned that people with hearts defects who were older or who also had other conditions like heart failure, pulmonary hypertension, Down syndrome, diabetes, or obesity were the most likely to have critical COVID-19 illness, but children and adults with heart defects without these other conditions were still at increased risk,” Ms. Downing said.

The message for health care providers is clear: “Encourage your patients with heart defects to get vaccinated and discuss with your patients the need for other preventive measures to avoid infection that may progress to severe COVID-19 illness,” Ms. Downing added.

The study was published online March 7, 2022, in Circulation.

The researchers analyzed data on 235,638 patients hospitalized with COVID-19 between March 2020 and January 2021, including 421 (0.2%) with CHD. Most CHD patients were older than 30 years (73%) and 61% were men, with 55% non-Hispanic white, 19% Hispanic and 16% non-Hispanic Black.

Overall, 68% of CHD patients had at least one comorbidity, as did 59% of patients without CHD.

Rates of ICU admission were higher in the CHD group (54% vs. 43%), as were rates of invasive mechanical ventilation (24% vs. 15%) and in-hospital death (11% vs. 7%).

After accounting for patient characteristics, ICU admission, invasive mechanical ventilation and death were more prevalent among COVID-19 patients with rather than without CHD, with adjusted prevalence ratios of 1.4, 1.8 and 2.0, respectively.

When stratified by high-risk characteristics, prevalence estimates for ICU admission, invasive mechanical ventilation and death remained higher among patients with COVID-19 and CHD across nearly all strata, including younger age groups and those without heart failure, pulmonary hypertension, Down syndrome, diabetes, or obesity, the researchers reported.

Ms. Downing said more work is needed to identify why the clinical course of COVID-19 disease results in admission to the ICU, the need for a ventilator, or death for some hospitalized patients with CHD and not for others.

“There could be a number of social, environmental, economic, medical, and genetic factors playing a role. But staying up to date with COVID-19 vaccines and following preventive measures for COVID-19 are effective ways to reduce the risk of severe illness from COVID-19,” Ms. Downing said.

The study had no specific funding. The authors reported no relevant disclosures.

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

Adults with a congenital heart defect (CHD) are at increased risk for serious illness and death when hospitalized with COVID-19, making vaccination and other preventive measures even important in this population, say researchers with the Centers for Disease Control and Prevention.

“We found that hospitalized patients with heart defects are up to twice as likely to have critical outcomes of COVID-19 illness (admission to the intensive care unit, use of a ventilator to help with breathing, or death) compared to hospitalized COVID-19 patients without heart defects,” Karrie Downing, MPH, epidemiologist, with the CDC’s National Center on Birth Defects and Developmental Disabilities, said in an interview.

“Additionally, we learned that people with hearts defects who were older or who also had other conditions like heart failure, pulmonary hypertension, Down syndrome, diabetes, or obesity were the most likely to have critical COVID-19 illness, but children and adults with heart defects without these other conditions were still at increased risk,” Ms. Downing said.

The message for health care providers is clear: “Encourage your patients with heart defects to get vaccinated and discuss with your patients the need for other preventive measures to avoid infection that may progress to severe COVID-19 illness,” Ms. Downing added.

The study was published online March 7, 2022, in Circulation.

The researchers analyzed data on 235,638 patients hospitalized with COVID-19 between March 2020 and January 2021, including 421 (0.2%) with CHD. Most CHD patients were older than 30 years (73%) and 61% were men, with 55% non-Hispanic white, 19% Hispanic and 16% non-Hispanic Black.

Overall, 68% of CHD patients had at least one comorbidity, as did 59% of patients without CHD.

Rates of ICU admission were higher in the CHD group (54% vs. 43%), as were rates of invasive mechanical ventilation (24% vs. 15%) and in-hospital death (11% vs. 7%).

After accounting for patient characteristics, ICU admission, invasive mechanical ventilation and death were more prevalent among COVID-19 patients with rather than without CHD, with adjusted prevalence ratios of 1.4, 1.8 and 2.0, respectively.

When stratified by high-risk characteristics, prevalence estimates for ICU admission, invasive mechanical ventilation and death remained higher among patients with COVID-19 and CHD across nearly all strata, including younger age groups and those without heart failure, pulmonary hypertension, Down syndrome, diabetes, or obesity, the researchers reported.

Ms. Downing said more work is needed to identify why the clinical course of COVID-19 disease results in admission to the ICU, the need for a ventilator, or death for some hospitalized patients with CHD and not for others.

“There could be a number of social, environmental, economic, medical, and genetic factors playing a role. But staying up to date with COVID-19 vaccines and following preventive measures for COVID-19 are effective ways to reduce the risk of severe illness from COVID-19,” Ms. Downing said.

The study had no specific funding. The authors reported no relevant disclosures.

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

People taking immunosuppressive drugs benefit significantly from SARS-CoV-2 vaccines approved in the United States to prevent and reduce the severity of COVID-19, according to the first study to quantify the vaccines’ real-world effectiveness in this population.

Researchers’ analysis of the electronic medical records of more than 150,000 people in the University of Michigan’s health care system showed that even after becoming fully vaccinated, immunosuppressed individuals remain at higher risk for COVID-19 than are vaccinated people in the wider population who aren’t receiving immunosuppressive therapy. However, they still derive benefit from vaccination, particularly when bolstered with a booster dose.

BrianAJackson/Thinkstock

The study, published online in Annals of the Rheumatic Diseases, also claims to be the first to show that the Moderna (mRNA-1273) vaccine is as effective as the Pfizer-BioNTech (BNT162b2) vaccine for people taking immunosuppressants.

“Booster doses are effective and important for individuals on immunosuppressants,” corresponding author Lili Zhao, PhD, a research associate professor in biostatistics at the University of Michigan, Ann Arbor, said in an interview. “Previous studies focused mostly on the Pfizer vaccine, whereas our study is the first that also investigates the Moderna vaccine in a large, immunosuppressed population.”

The epidemiologic study included 154,519 fully vaccinated and unvaccinated adults in the Michigan Medicine electronic health record database. Participants were considered fully vaccinated if they were within 2 weeks of having received a second dose of the Pfizer-BioNTech and Moderna vaccines or the single-dose Johnson & Johnson (Ad26.COV2.S) vaccine. The study population included 5,536 immunosuppressed patients; of those, 4,283 were fully vaccinated, and 1,253 were unvaccinated.

The researchers focused on data collected from Jan. 1 to Dec. 7, 2021, so the study doesn’t cover the Omicron variant. “The conclusions for immunosuppressed individuals are likely to remain the same during the Omicron period,” Dr. Zhao said. “We are currently investigating this.” Johnson & Johnson paused production of its vaccine in February.

The researchers found that, among unvaccinated individuals, the immunosuppressed group had about a 40% higher risk of infection than did the immunocompetent patients (hazard ratio, 1.398; 95% confidence interval, 1.068-1.829; P = .0075) but a similar risk of COVID-19 hospitalization (HR, 0.951; 95% CI, 0.435-2.080; P = .9984). For the fully vaccinated, the gap was significantly wider: Immunosuppressed patients had more than double the risk of infection (HR, 2.173; 95% CI, 1.690-2.794; P < .0001) and almost five times the risk of hospitalization (HR, 4.861; 95% CI, 2.238-10.56; P < .0001), compared with immunocompetent patients.

However, among immunosuppressed individuals, the vaccinations significantly lowered risks, compared with not being vaccinated. There was a statistically significant 45% lower risk of infection (HR, 0.550; 95% CI, 0.387-0.781; P = .001) and similarly lower risk of hospitalization that did not reach statistical significance (HR, 0.534; 95% CI, 0.196-1.452; P = .3724).

When those immunosuppressed patients received a booster dose, their protection against COVID-19 improved, compared with their immunosuppressed counterparts who didn’t get a booster, with a 58% lower risk of infection after adjustment for age, gender, race, and Charlson Comorbidity Index (adjusted HR, 0.42; 95% CI, 0.24-0.76; P = .0037). The study included nearly 4 months of data after the Centers for Disease Control and Prevention recommended a booster dose of the Moderna and Pfizer-BioNTech vaccines for immunocompromised individuals in August 2021. Among the immunosuppressed patients, 38.5% had received a booster dose.

There also was no apparent difference in the effectiveness between the Moderna and Pfizer-BioNTech vaccines, with adjusted hazard ratios showing 41%-48% lower risk of infection. Too few individuals in the study were vaccinated with the Johnson & Johnson vaccine to enable a sufficiently powered calculation of its effectiveness.

Other studies reach similar conclusions

The study findings fall into line with other studies of patient populations on immunosuppressants. A retrospective cohort study of Veterans Affairs patients with inflammatory bowel disease who were taking immunosuppressants, published in Gastroenterology, found that full vaccination with either Moderna and Pfizer-BioNTech vaccines was about 80% effective. Another retrospective cohort study of data from the National COVID Cohort Collaborative, published in JAMA Internal Medicine, reported that full vaccination significantly reduced the risk of COVID-19 breakthrough infection regardless of immune status. Immunosuppressed patients in this study had higher rates of breakthrough infections than immunocompetent patients, but the disparities were in line with what Dr. Zhao and the University of Michigan researchers reported.

A review of 23 studies of COVID-19 vaccinations, published in Lancet Global Health, found that immunocompromised people – 1,722 of whom were included in the studies – had lower rates of producing antibodies after two vaccine doses than did immunocompetent people, ranging from 27% to 92%, depending on the nature of their immunocompromised status, compared with 99% for the immunocompetent.
 

Strengths and limitations

One strength of the Michigan study is the quality of data, which were drawn from the Michigan Medicine electronic health record, Dr. Zhao said. “So, we know who received the vaccine and who didn’t. We also have access to data on patient health conditions, such as comorbidities, in addition to demographic variables (age, gender, and race), which were controlled in making fair comparisons between immunosuppressants and immunocompetent groups.”

Alfred Kim, MD, PhD, an assistant professor of internal medicine and rheumatology at Washington University in St. Louis, who was not involved with the study, credited Dr. Zhao and associates for delivering the first data that specifically quantified COVID-19 risk reduction in a large study population. Although he noted that the large sample size and the design reduced the chances of confounding and were strengths, he said in an interview that “lumping” the patients taking immunosuppressive drugs into one group was a weakness of the study.

“Clearly, there are certain medications (B-cell depleters, mycophenolate, for example) that carry the greatest risk of poor antibody responses post vaccination,” he said. “One would have to guess that the greatest risk of breakthrough infections continues to be in those patients taking these high-risk medications.”

Another possible problem, which the authors acknowledged, is spotty SARS-CoV-2 testing of study participants – “a systemic issue,” Dr. Kim noted.

“The easiest and most durable way to reduce the risk of getting COVID-19 is through vaccination, period,” he said. “Now we have infection-rates data from a real-world study cohort to prove this. Furthermore, boosting clearly provides additional benefit to this population.”

The National Institute of Allergy and Infectious Diseases provided funding for the study. Dr. Zhao, Dr. Zhao’s coauthors, and Kim disclosed no relevant financial relationships.

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

People taking immunosuppressive drugs benefit significantly from SARS-CoV-2 vaccines approved in the United States to prevent and reduce the severity of COVID-19, according to the first study to quantify the vaccines’ real-world effectiveness in this population.

Researchers’ analysis of the electronic medical records of more than 150,000 people in the University of Michigan’s health care system showed that even after becoming fully vaccinated, immunosuppressed individuals remain at higher risk for COVID-19 than are vaccinated people in the wider population who aren’t receiving immunosuppressive therapy. However, they still derive benefit from vaccination, particularly when bolstered with a booster dose.

BrianAJackson/Thinkstock

The study, published online in Annals of the Rheumatic Diseases, also claims to be the first to show that the Moderna (mRNA-1273) vaccine is as effective as the Pfizer-BioNTech (BNT162b2) vaccine for people taking immunosuppressants.

“Booster doses are effective and important for individuals on immunosuppressants,” corresponding author Lili Zhao, PhD, a research associate professor in biostatistics at the University of Michigan, Ann Arbor, said in an interview. “Previous studies focused mostly on the Pfizer vaccine, whereas our study is the first that also investigates the Moderna vaccine in a large, immunosuppressed population.”

The epidemiologic study included 154,519 fully vaccinated and unvaccinated adults in the Michigan Medicine electronic health record database. Participants were considered fully vaccinated if they were within 2 weeks of having received a second dose of the Pfizer-BioNTech and Moderna vaccines or the single-dose Johnson & Johnson (Ad26.COV2.S) vaccine. The study population included 5,536 immunosuppressed patients; of those, 4,283 were fully vaccinated, and 1,253 were unvaccinated.

The researchers focused on data collected from Jan. 1 to Dec. 7, 2021, so the study doesn’t cover the Omicron variant. “The conclusions for immunosuppressed individuals are likely to remain the same during the Omicron period,” Dr. Zhao said. “We are currently investigating this.” Johnson & Johnson paused production of its vaccine in February.

The researchers found that, among unvaccinated individuals, the immunosuppressed group had about a 40% higher risk of infection than did the immunocompetent patients (hazard ratio, 1.398; 95% confidence interval, 1.068-1.829; P = .0075) but a similar risk of COVID-19 hospitalization (HR, 0.951; 95% CI, 0.435-2.080; P = .9984). For the fully vaccinated, the gap was significantly wider: Immunosuppressed patients had more than double the risk of infection (HR, 2.173; 95% CI, 1.690-2.794; P < .0001) and almost five times the risk of hospitalization (HR, 4.861; 95% CI, 2.238-10.56; P < .0001), compared with immunocompetent patients.

However, among immunosuppressed individuals, the vaccinations significantly lowered risks, compared with not being vaccinated. There was a statistically significant 45% lower risk of infection (HR, 0.550; 95% CI, 0.387-0.781; P = .001) and similarly lower risk of hospitalization that did not reach statistical significance (HR, 0.534; 95% CI, 0.196-1.452; P = .3724).

When those immunosuppressed patients received a booster dose, their protection against COVID-19 improved, compared with their immunosuppressed counterparts who didn’t get a booster, with a 58% lower risk of infection after adjustment for age, gender, race, and Charlson Comorbidity Index (adjusted HR, 0.42; 95% CI, 0.24-0.76; P = .0037). The study included nearly 4 months of data after the Centers for Disease Control and Prevention recommended a booster dose of the Moderna and Pfizer-BioNTech vaccines for immunocompromised individuals in August 2021. Among the immunosuppressed patients, 38.5% had received a booster dose.

There also was no apparent difference in the effectiveness between the Moderna and Pfizer-BioNTech vaccines, with adjusted hazard ratios showing 41%-48% lower risk of infection. Too few individuals in the study were vaccinated with the Johnson & Johnson vaccine to enable a sufficiently powered calculation of its effectiveness.

Other studies reach similar conclusions

The study findings fall into line with other studies of patient populations on immunosuppressants. A retrospective cohort study of Veterans Affairs patients with inflammatory bowel disease who were taking immunosuppressants, published in Gastroenterology, found that full vaccination with either Moderna and Pfizer-BioNTech vaccines was about 80% effective. Another retrospective cohort study of data from the National COVID Cohort Collaborative, published in JAMA Internal Medicine, reported that full vaccination significantly reduced the risk of COVID-19 breakthrough infection regardless of immune status. Immunosuppressed patients in this study had higher rates of breakthrough infections than immunocompetent patients, but the disparities were in line with what Dr. Zhao and the University of Michigan researchers reported.

A review of 23 studies of COVID-19 vaccinations, published in Lancet Global Health, found that immunocompromised people – 1,722 of whom were included in the studies – had lower rates of producing antibodies after two vaccine doses than did immunocompetent people, ranging from 27% to 92%, depending on the nature of their immunocompromised status, compared with 99% for the immunocompetent.
 

Strengths and limitations

One strength of the Michigan study is the quality of data, which were drawn from the Michigan Medicine electronic health record, Dr. Zhao said. “So, we know who received the vaccine and who didn’t. We also have access to data on patient health conditions, such as comorbidities, in addition to demographic variables (age, gender, and race), which were controlled in making fair comparisons between immunosuppressants and immunocompetent groups.”

Alfred Kim, MD, PhD, an assistant professor of internal medicine and rheumatology at Washington University in St. Louis, who was not involved with the study, credited Dr. Zhao and associates for delivering the first data that specifically quantified COVID-19 risk reduction in a large study population. Although he noted that the large sample size and the design reduced the chances of confounding and were strengths, he said in an interview that “lumping” the patients taking immunosuppressive drugs into one group was a weakness of the study.

“Clearly, there are certain medications (B-cell depleters, mycophenolate, for example) that carry the greatest risk of poor antibody responses post vaccination,” he said. “One would have to guess that the greatest risk of breakthrough infections continues to be in those patients taking these high-risk medications.”

Another possible problem, which the authors acknowledged, is spotty SARS-CoV-2 testing of study participants – “a systemic issue,” Dr. Kim noted.

“The easiest and most durable way to reduce the risk of getting COVID-19 is through vaccination, period,” he said. “Now we have infection-rates data from a real-world study cohort to prove this. Furthermore, boosting clearly provides additional benefit to this population.”

The National Institute of Allergy and Infectious Diseases provided funding for the study. Dr. Zhao, Dr. Zhao’s coauthors, and Kim disclosed no relevant financial relationships.

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

People taking immunosuppressive drugs benefit significantly from SARS-CoV-2 vaccines approved in the United States to prevent and reduce the severity of COVID-19, according to the first study to quantify the vaccines’ real-world effectiveness in this population.

Researchers’ analysis of the electronic medical records of more than 150,000 people in the University of Michigan’s health care system showed that even after becoming fully vaccinated, immunosuppressed individuals remain at higher risk for COVID-19 than are vaccinated people in the wider population who aren’t receiving immunosuppressive therapy. However, they still derive benefit from vaccination, particularly when bolstered with a booster dose.

BrianAJackson/Thinkstock

The study, published online in Annals of the Rheumatic Diseases, also claims to be the first to show that the Moderna (mRNA-1273) vaccine is as effective as the Pfizer-BioNTech (BNT162b2) vaccine for people taking immunosuppressants.

“Booster doses are effective and important for individuals on immunosuppressants,” corresponding author Lili Zhao, PhD, a research associate professor in biostatistics at the University of Michigan, Ann Arbor, said in an interview. “Previous studies focused mostly on the Pfizer vaccine, whereas our study is the first that also investigates the Moderna vaccine in a large, immunosuppressed population.”

The epidemiologic study included 154,519 fully vaccinated and unvaccinated adults in the Michigan Medicine electronic health record database. Participants were considered fully vaccinated if they were within 2 weeks of having received a second dose of the Pfizer-BioNTech and Moderna vaccines or the single-dose Johnson & Johnson (Ad26.COV2.S) vaccine. The study population included 5,536 immunosuppressed patients; of those, 4,283 were fully vaccinated, and 1,253 were unvaccinated.

The researchers focused on data collected from Jan. 1 to Dec. 7, 2021, so the study doesn’t cover the Omicron variant. “The conclusions for immunosuppressed individuals are likely to remain the same during the Omicron period,” Dr. Zhao said. “We are currently investigating this.” Johnson & Johnson paused production of its vaccine in February.

The researchers found that, among unvaccinated individuals, the immunosuppressed group had about a 40% higher risk of infection than did the immunocompetent patients (hazard ratio, 1.398; 95% confidence interval, 1.068-1.829; P = .0075) but a similar risk of COVID-19 hospitalization (HR, 0.951; 95% CI, 0.435-2.080; P = .9984). For the fully vaccinated, the gap was significantly wider: Immunosuppressed patients had more than double the risk of infection (HR, 2.173; 95% CI, 1.690-2.794; P < .0001) and almost five times the risk of hospitalization (HR, 4.861; 95% CI, 2.238-10.56; P < .0001), compared with immunocompetent patients.

However, among immunosuppressed individuals, the vaccinations significantly lowered risks, compared with not being vaccinated. There was a statistically significant 45% lower risk of infection (HR, 0.550; 95% CI, 0.387-0.781; P = .001) and similarly lower risk of hospitalization that did not reach statistical significance (HR, 0.534; 95% CI, 0.196-1.452; P = .3724).

When those immunosuppressed patients received a booster dose, their protection against COVID-19 improved, compared with their immunosuppressed counterparts who didn’t get a booster, with a 58% lower risk of infection after adjustment for age, gender, race, and Charlson Comorbidity Index (adjusted HR, 0.42; 95% CI, 0.24-0.76; P = .0037). The study included nearly 4 months of data after the Centers for Disease Control and Prevention recommended a booster dose of the Moderna and Pfizer-BioNTech vaccines for immunocompromised individuals in August 2021. Among the immunosuppressed patients, 38.5% had received a booster dose.

There also was no apparent difference in the effectiveness between the Moderna and Pfizer-BioNTech vaccines, with adjusted hazard ratios showing 41%-48% lower risk of infection. Too few individuals in the study were vaccinated with the Johnson & Johnson vaccine to enable a sufficiently powered calculation of its effectiveness.

Other studies reach similar conclusions

The study findings fall into line with other studies of patient populations on immunosuppressants. A retrospective cohort study of Veterans Affairs patients with inflammatory bowel disease who were taking immunosuppressants, published in Gastroenterology, found that full vaccination with either Moderna and Pfizer-BioNTech vaccines was about 80% effective. Another retrospective cohort study of data from the National COVID Cohort Collaborative, published in JAMA Internal Medicine, reported that full vaccination significantly reduced the risk of COVID-19 breakthrough infection regardless of immune status. Immunosuppressed patients in this study had higher rates of breakthrough infections than immunocompetent patients, but the disparities were in line with what Dr. Zhao and the University of Michigan researchers reported.

A review of 23 studies of COVID-19 vaccinations, published in Lancet Global Health, found that immunocompromised people – 1,722 of whom were included in the studies – had lower rates of producing antibodies after two vaccine doses than did immunocompetent people, ranging from 27% to 92%, depending on the nature of their immunocompromised status, compared with 99% for the immunocompetent.
 

Strengths and limitations

One strength of the Michigan study is the quality of data, which were drawn from the Michigan Medicine electronic health record, Dr. Zhao said. “So, we know who received the vaccine and who didn’t. We also have access to data on patient health conditions, such as comorbidities, in addition to demographic variables (age, gender, and race), which were controlled in making fair comparisons between immunosuppressants and immunocompetent groups.”

Alfred Kim, MD, PhD, an assistant professor of internal medicine and rheumatology at Washington University in St. Louis, who was not involved with the study, credited Dr. Zhao and associates for delivering the first data that specifically quantified COVID-19 risk reduction in a large study population. Although he noted that the large sample size and the design reduced the chances of confounding and were strengths, he said in an interview that “lumping” the patients taking immunosuppressive drugs into one group was a weakness of the study.

“Clearly, there are certain medications (B-cell depleters, mycophenolate, for example) that carry the greatest risk of poor antibody responses post vaccination,” he said. “One would have to guess that the greatest risk of breakthrough infections continues to be in those patients taking these high-risk medications.”

Another possible problem, which the authors acknowledged, is spotty SARS-CoV-2 testing of study participants – “a systemic issue,” Dr. Kim noted.

“The easiest and most durable way to reduce the risk of getting COVID-19 is through vaccination, period,” he said. “Now we have infection-rates data from a real-world study cohort to prove this. Furthermore, boosting clearly provides additional benefit to this population.”

The National Institute of Allergy and Infectious Diseases provided funding for the study. Dr. Zhao, Dr. Zhao’s coauthors, and Kim disclosed no relevant financial relationships.

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

Heavy drinking during early adulthood may raise the risk for alcohol-related cancers, even after drinking stops or decreases in middle age, according to a new study from Australia.

Although alcohol is a known risk factor for cancer, people generally do not expect their heavy drinking in early adulthood to affect their cancer risk many years later, lead author Harindra Jayasekara, MBBS, MD, PhD, with Cancer Council Victoria and University of Melbourne, said in an interview. But in this analysis, “we found evidence consistent with early initiation and chronic progression of carcinogenesis linked to alcohol and its toxic metabolites.”

Courtesy Debora Cartagena, USCDCP

Impact on cancer risk

For men, relative to lifetime abstention, heavy drinking trajectories were associated with an increased risk for alcohol-related cancer overall.

The strongest associations were for the early decreasing heavy trajectory (hazard ratio, 1.75) and the late decreasing heavy trajectory (HR, 1.94), with the increasing heavy trajectory not far behind (HR, 1.45).

The strength of these associations did not change appreciably in analyses excluding current smokers at baseline.

Among men, the early decreasing heavy and late decreasing heavy intake trajectories were similarly associated with an increased risk for colorectal cancer (HR, 1.56 for early, and HR, 1.74 for late). The corresponding HR for the increasing heavy trajectory was 1.36.

For women, compared with lifetime abstention, the alcohol intake trajectory classified as increasing moderate (30-59 g/day) was associated with a greater risk for alcohol-related cancer overall (HR, 1.25). The strength of this association weakened slightly when current smokers were excluded.

Compared with lifetime abstention, the increasing moderate trajectory in women was similarly associated with an increased risk for breast cancer (HR, 1.30) and colorectal cancer (HR, 1.23).

The 2018 World Cancer Research Fund and American Institute for Cancer Research global cancer prevention recommendation on alcohol is to “avoid any alcohol,” study investigator Julie Bassett, PhD, MSc, with Cancer Council Victoria, said in an interview. “As much as it is important to limit alcohol intake during middle age to prevent cancer, we have shown that limiting intake during early adulthood is also important.”
 

‘Striking’ findings

Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services at the Addiction Institute of Mount Sinai in New York, said it is “striking” that heavy drinking in early adulthood led to an increased risk for alcohol-related cancers, even among people who drank much less in middle age.

“We’ve known for decades that alcohol is not harmless, but this data adds to the growing body of literature regarding the significant dangers of heavy drinking during early adulthood,” said Dr. Brennan, who wasn’t involved in the study.

Dr. Brennan cautioned, however, that the authors studied alcohol-related cancers, and “there are likely many other [cancer] risk factors that were not analyzed in this dataset.”

Nevertheless, this evidence helps counter the “troubling narrative” that “it is somehow normal and safe to drink excessively in young adulthood.”

“It is most certainly not safe,” Dr. Brennan told this news organization . “We see in this study that drinking excessively in young adulthood can raise the risk of cancer much later in life.”

The study had no commercial funding. Dr. Bassett, Dr. Jayasekara, and Dr. Brennan have disclosed no relevant financial relationships.

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

Heavy drinking during early adulthood may raise the risk for alcohol-related cancers, even after drinking stops or decreases in middle age, according to a new study from Australia.

Although alcohol is a known risk factor for cancer, people generally do not expect their heavy drinking in early adulthood to affect their cancer risk many years later, lead author Harindra Jayasekara, MBBS, MD, PhD, with Cancer Council Victoria and University of Melbourne, said in an interview. But in this analysis, “we found evidence consistent with early initiation and chronic progression of carcinogenesis linked to alcohol and its toxic metabolites.”

Courtesy Debora Cartagena, USCDCP

Impact on cancer risk

For men, relative to lifetime abstention, heavy drinking trajectories were associated with an increased risk for alcohol-related cancer overall.

The strongest associations were for the early decreasing heavy trajectory (hazard ratio, 1.75) and the late decreasing heavy trajectory (HR, 1.94), with the increasing heavy trajectory not far behind (HR, 1.45).

The strength of these associations did not change appreciably in analyses excluding current smokers at baseline.

Among men, the early decreasing heavy and late decreasing heavy intake trajectories were similarly associated with an increased risk for colorectal cancer (HR, 1.56 for early, and HR, 1.74 for late). The corresponding HR for the increasing heavy trajectory was 1.36.

For women, compared with lifetime abstention, the alcohol intake trajectory classified as increasing moderate (30-59 g/day) was associated with a greater risk for alcohol-related cancer overall (HR, 1.25). The strength of this association weakened slightly when current smokers were excluded.

Compared with lifetime abstention, the increasing moderate trajectory in women was similarly associated with an increased risk for breast cancer (HR, 1.30) and colorectal cancer (HR, 1.23).

The 2018 World Cancer Research Fund and American Institute for Cancer Research global cancer prevention recommendation on alcohol is to “avoid any alcohol,” study investigator Julie Bassett, PhD, MSc, with Cancer Council Victoria, said in an interview. “As much as it is important to limit alcohol intake during middle age to prevent cancer, we have shown that limiting intake during early adulthood is also important.”
 

‘Striking’ findings

Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services at the Addiction Institute of Mount Sinai in New York, said it is “striking” that heavy drinking in early adulthood led to an increased risk for alcohol-related cancers, even among people who drank much less in middle age.

“We’ve known for decades that alcohol is not harmless, but this data adds to the growing body of literature regarding the significant dangers of heavy drinking during early adulthood,” said Dr. Brennan, who wasn’t involved in the study.

Dr. Brennan cautioned, however, that the authors studied alcohol-related cancers, and “there are likely many other [cancer] risk factors that were not analyzed in this dataset.”

Nevertheless, this evidence helps counter the “troubling narrative” that “it is somehow normal and safe to drink excessively in young adulthood.”

“It is most certainly not safe,” Dr. Brennan told this news organization . “We see in this study that drinking excessively in young adulthood can raise the risk of cancer much later in life.”

The study had no commercial funding. Dr. Bassett, Dr. Jayasekara, and Dr. Brennan have disclosed no relevant financial relationships.

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

Heavy drinking during early adulthood may raise the risk for alcohol-related cancers, even after drinking stops or decreases in middle age, according to a new study from Australia.

Although alcohol is a known risk factor for cancer, people generally do not expect their heavy drinking in early adulthood to affect their cancer risk many years later, lead author Harindra Jayasekara, MBBS, MD, PhD, with Cancer Council Victoria and University of Melbourne, said in an interview. But in this analysis, “we found evidence consistent with early initiation and chronic progression of carcinogenesis linked to alcohol and its toxic metabolites.”

Courtesy Debora Cartagena, USCDCP

Impact on cancer risk

For men, relative to lifetime abstention, heavy drinking trajectories were associated with an increased risk for alcohol-related cancer overall.

The strongest associations were for the early decreasing heavy trajectory (hazard ratio, 1.75) and the late decreasing heavy trajectory (HR, 1.94), with the increasing heavy trajectory not far behind (HR, 1.45).

The strength of these associations did not change appreciably in analyses excluding current smokers at baseline.

Among men, the early decreasing heavy and late decreasing heavy intake trajectories were similarly associated with an increased risk for colorectal cancer (HR, 1.56 for early, and HR, 1.74 for late). The corresponding HR for the increasing heavy trajectory was 1.36.

For women, compared with lifetime abstention, the alcohol intake trajectory classified as increasing moderate (30-59 g/day) was associated with a greater risk for alcohol-related cancer overall (HR, 1.25). The strength of this association weakened slightly when current smokers were excluded.

Compared with lifetime abstention, the increasing moderate trajectory in women was similarly associated with an increased risk for breast cancer (HR, 1.30) and colorectal cancer (HR, 1.23).

The 2018 World Cancer Research Fund and American Institute for Cancer Research global cancer prevention recommendation on alcohol is to “avoid any alcohol,” study investigator Julie Bassett, PhD, MSc, with Cancer Council Victoria, said in an interview. “As much as it is important to limit alcohol intake during middle age to prevent cancer, we have shown that limiting intake during early adulthood is also important.”
 

‘Striking’ findings

Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services at the Addiction Institute of Mount Sinai in New York, said it is “striking” that heavy drinking in early adulthood led to an increased risk for alcohol-related cancers, even among people who drank much less in middle age.

“We’ve known for decades that alcohol is not harmless, but this data adds to the growing body of literature regarding the significant dangers of heavy drinking during early adulthood,” said Dr. Brennan, who wasn’t involved in the study.

Dr. Brennan cautioned, however, that the authors studied alcohol-related cancers, and “there are likely many other [cancer] risk factors that were not analyzed in this dataset.”

Nevertheless, this evidence helps counter the “troubling narrative” that “it is somehow normal and safe to drink excessively in young adulthood.”

“It is most certainly not safe,” Dr. Brennan told this news organization . “We see in this study that drinking excessively in young adulthood can raise the risk of cancer much later in life.”

The study had no commercial funding. Dr. Bassett, Dr. Jayasekara, and Dr. Brennan have disclosed no relevant financial relationships.

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

More than 170 million Americans – or about half of U.S. adults – were exposed to harmful levels of lead as children, according to a new study published in the Proceedings of the National Academy of Sciences.

In addition, the researchers found, 90% of children born in the United States between 1951 and 1980 had blood-lead levels higher than the Centers for Disease Control and Prevention threshold. On average, early childhood exposure to lead resulted in a 2.6-point drop in IQ per person.

“Most of what we think of as the Lost Generation and the Greatest Generation and Baby Boomers had a moderate amount of lead exposure,” Matt Hauer, PhD, one of the coauthors and an assistant professor of sociology at Florida State University, Tallahassee, said in a statement.

“Generation X was exposed to very high amounts of lead, and now Millennials and the generation following them have been exposed to very low amounts of lead,” he said.

The findings were “infuriating” because scientists have long known that lead exposure is harmful, Michael McFarland, PhD, coauthor and an associate professor of sociology at Florida State University, Tallahassee, told The Associated Press.

The research team analyzed blood-lead levels, census data, and the use of leaded gasoline to understand how widespread early childhood lead exposure was in the United States between 1940 and 2015. They looked mostly at exposure caused by leaded gasoline, which was the dominant form of exposure between the 1940s and 1980s.

They estimated that half of the U.S. adult population in 2015 had been exposed to lead levels that surpassed 5 micrograms per deciliter, which was the CDC threshold at the time. More than 54 million had been exposed to levels above 15 micrograms per deciliter, and 4.5 million were exposed to 30 micrograms per deciliter – or six times the threshold.

They found that estimated lead-linked deficits were greatest for the 21 million people born between 1966 and 1970, who had an average 5.9-point drop in IQ per person.

The United States has put in place tougher regulations to protect Americans from lead poisoning in recent decades, particularly from gasoline. The study team found that blood-lead levels were considerably lower than 5 micrograms per deciliter among those born since 2001.

At the same time, the public health effects of childhood exposure for older generations will last for years to come.

“Childhood lead exposure is not just here and now. It’s going to impact your lifelong health,” Abheet Solomon, a senior program manager at the United Nations Children’s Fund, told the AP.

Childhood lead exposure is known to affect the development of mental skills, and it raises the risk of hypertension, kidney damage, and heart disease. It has been linked to harm in pregnant women and developing children.

“The more tragic part is that we keep making the same … mistakes again,” Bruce Lanphear, MD, a health sciences professor at Simon Fraser University in Vancouver, B.C., told the AP.

Dr. Lanphear’s research on lead exposure has found loss of mental skills and IQ as well.

“First it was lead, then it was air pollution. Now it’s PFAS chemicals and phthalates (chemicals used to make plastics more durable),” he said. “And we can’t stop long enough to ask ourselves should we be regulating chemicals differently.”

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

More than 170 million Americans – or about half of U.S. adults – were exposed to harmful levels of lead as children, according to a new study published in the Proceedings of the National Academy of Sciences.

In addition, the researchers found, 90% of children born in the United States between 1951 and 1980 had blood-lead levels higher than the Centers for Disease Control and Prevention threshold. On average, early childhood exposure to lead resulted in a 2.6-point drop in IQ per person.

“Most of what we think of as the Lost Generation and the Greatest Generation and Baby Boomers had a moderate amount of lead exposure,” Matt Hauer, PhD, one of the coauthors and an assistant professor of sociology at Florida State University, Tallahassee, said in a statement.

“Generation X was exposed to very high amounts of lead, and now Millennials and the generation following them have been exposed to very low amounts of lead,” he said.

The findings were “infuriating” because scientists have long known that lead exposure is harmful, Michael McFarland, PhD, coauthor and an associate professor of sociology at Florida State University, Tallahassee, told The Associated Press.

The research team analyzed blood-lead levels, census data, and the use of leaded gasoline to understand how widespread early childhood lead exposure was in the United States between 1940 and 2015. They looked mostly at exposure caused by leaded gasoline, which was the dominant form of exposure between the 1940s and 1980s.

They estimated that half of the U.S. adult population in 2015 had been exposed to lead levels that surpassed 5 micrograms per deciliter, which was the CDC threshold at the time. More than 54 million had been exposed to levels above 15 micrograms per deciliter, and 4.5 million were exposed to 30 micrograms per deciliter – or six times the threshold.

They found that estimated lead-linked deficits were greatest for the 21 million people born between 1966 and 1970, who had an average 5.9-point drop in IQ per person.

The United States has put in place tougher regulations to protect Americans from lead poisoning in recent decades, particularly from gasoline. The study team found that blood-lead levels were considerably lower than 5 micrograms per deciliter among those born since 2001.

At the same time, the public health effects of childhood exposure for older generations will last for years to come.

“Childhood lead exposure is not just here and now. It’s going to impact your lifelong health,” Abheet Solomon, a senior program manager at the United Nations Children’s Fund, told the AP.

Childhood lead exposure is known to affect the development of mental skills, and it raises the risk of hypertension, kidney damage, and heart disease. It has been linked to harm in pregnant women and developing children.

“The more tragic part is that we keep making the same … mistakes again,” Bruce Lanphear, MD, a health sciences professor at Simon Fraser University in Vancouver, B.C., told the AP.

Dr. Lanphear’s research on lead exposure has found loss of mental skills and IQ as well.

“First it was lead, then it was air pollution. Now it’s PFAS chemicals and phthalates (chemicals used to make plastics more durable),” he said. “And we can’t stop long enough to ask ourselves should we be regulating chemicals differently.”

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

More than 170 million Americans – or about half of U.S. adults – were exposed to harmful levels of lead as children, according to a new study published in the Proceedings of the National Academy of Sciences.

In addition, the researchers found, 90% of children born in the United States between 1951 and 1980 had blood-lead levels higher than the Centers for Disease Control and Prevention threshold. On average, early childhood exposure to lead resulted in a 2.6-point drop in IQ per person.

“Most of what we think of as the Lost Generation and the Greatest Generation and Baby Boomers had a moderate amount of lead exposure,” Matt Hauer, PhD, one of the coauthors and an assistant professor of sociology at Florida State University, Tallahassee, said in a statement.

“Generation X was exposed to very high amounts of lead, and now Millennials and the generation following them have been exposed to very low amounts of lead,” he said.

The findings were “infuriating” because scientists have long known that lead exposure is harmful, Michael McFarland, PhD, coauthor and an associate professor of sociology at Florida State University, Tallahassee, told The Associated Press.

The research team analyzed blood-lead levels, census data, and the use of leaded gasoline to understand how widespread early childhood lead exposure was in the United States between 1940 and 2015. They looked mostly at exposure caused by leaded gasoline, which was the dominant form of exposure between the 1940s and 1980s.

They estimated that half of the U.S. adult population in 2015 had been exposed to lead levels that surpassed 5 micrograms per deciliter, which was the CDC threshold at the time. More than 54 million had been exposed to levels above 15 micrograms per deciliter, and 4.5 million were exposed to 30 micrograms per deciliter – or six times the threshold.

They found that estimated lead-linked deficits were greatest for the 21 million people born between 1966 and 1970, who had an average 5.9-point drop in IQ per person.

The United States has put in place tougher regulations to protect Americans from lead poisoning in recent decades, particularly from gasoline. The study team found that blood-lead levels were considerably lower than 5 micrograms per deciliter among those born since 2001.

At the same time, the public health effects of childhood exposure for older generations will last for years to come.

“Childhood lead exposure is not just here and now. It’s going to impact your lifelong health,” Abheet Solomon, a senior program manager at the United Nations Children’s Fund, told the AP.

Childhood lead exposure is known to affect the development of mental skills, and it raises the risk of hypertension, kidney damage, and heart disease. It has been linked to harm in pregnant women and developing children.

“The more tragic part is that we keep making the same … mistakes again,” Bruce Lanphear, MD, a health sciences professor at Simon Fraser University in Vancouver, B.C., told the AP.

Dr. Lanphear’s research on lead exposure has found loss of mental skills and IQ as well.

“First it was lead, then it was air pollution. Now it’s PFAS chemicals and phthalates (chemicals used to make plastics more durable),” he said. “And we can’t stop long enough to ask ourselves should we be regulating chemicals differently.”

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

Giving patients and their providers genetic test results for kidney failure risk promotes positive behavioral change that could decrease an individual’s likelihood of developing chronic kidney disease (CKD) and end-stage renal failure (ESRF), a new pilot study suggests.

“Disclosing APOL1 genetic testing results to patients of African ancestry with hypertension and their clinicians was associated with a greater reduction in systolic blood pressure [SBP], increased kidney disease screening, and positive self-reported behavior change in those with high-risk genotypes,” Girish Nadkarni, MD, MPH, Icahn Mount Sinai School of Medicine, New York, and colleagues reported.

“These two measurements – the change in blood pressure and increased kidney function tests – act as hallmarks for detecting beneficial lifestyle change,” Dr. Nadkarni noted in a statement from his institution.

“For many years, researchers have wondered whether reporting APOL1 genetic test results would help improve clinical management. This is the first pragmatic randomized clinical trial to test this out [and] these results suggest we are headed in the right direction,” he added.

The study was published online March 4, 2022, in JAMA Network Open.
 

A quarter of those with high-risk genotype changed medication behavior

High-risk APOL1 genotypes confer a 5- to 10-fold increased risk for CKD and ESRF caused by hypertension and are found in one out of seven individuals of African ancestry. People of African ancestry also have the highest age-adjusted prevalence of high BP and the lowest rates of BP control, Dr. Nadkarni and colleagues wrote.

They studied a total of 2,050 patients of African ancestry with hypertension but without CKD who were randomized to undergo either immediate APOL1 testing (intervention group) or delayed APOL1 testing (control group).

“Patients randomly assigned to the intervention group received APOL1 genetic testing results from trained staff [while] their clinicians received results through clinical decision support in electronic health records,” the investigators explained.

Control patients received results after 12 months of follow-up. The mean age of the cohort was 53 years and almost two-thirds were female. Mean baseline SBP was significantly higher in patients with high-risk APOL1 genotypes, at 137 mm Hg, compared with those with low-risk APOL1 genotypes, at 134 mm Hg (P = .003), and controls, at 133 mm Hg (P = .001), the authors reported. 

At 3 months, “all groups had some decrease in SBP,” Dr. Nadkarni and colleagues observed.

However, patients with high-risk APOL1 genotypes had a significantly greater decrease in SBP, at 6 mm Hg, compared with a mean decrease of 3 mm Hg for those with low-risk APOL1 genotypes (P = .004) as well as controls (P = .01). At 12 months, there was no significant difference in SBP or change in SBP from baseline to 12 months between the three groups.

“All three groups showed a significant increase in the rate of urine protein testing over time,” the authors added.

Again, however, the most significant increase in urine protein testing over time was seen in patients with high-risk APOL1 genotypes, with a 12% increase from baseline, compared with a 6% increase for patients with low-risk APOL1 genotypes and a 7% increase among controls. The difference was significant only between patients with high-risk APOL1 genotypes and controls (P = .01).

Significantly more patients with high-risk APOL1 genotypes, at 59%, reported making positive lifestyle changes as reflected in better dietary and exercise habits after receiving their test results than did those with low-risk APOL1 genotypes, at 37% (P < .001).

Moreover, 24% of those with high-risk genotypes reported that receiving test results changed how they take their BP medication, compared with only 10% of those with low-risk genotypes.

More high-risk genotype carriers also reported taking their medications more often, at 10%, compared with 5% of low-risk genotype carriers (P = .005).

On the other hand, more patients with the high-risk genotype, at 27%, worried that they would develop kidney problems than low-risk carriers, at 17% (P < .001). Although investigators did offer patients the opportunity to speak with a genetic counselor at no cost, none chose to do so, the authors noted.
 

Small improvements

As the investigators emphasized, the magnitude of BP improvement seen in high-risk APOL1 carriers was small. However, they did not provide specific BP target recommendations or BP-lowering strategies, which, had they done so, may have brought BP down to a greater degree.

Health behavior changes were similarly small and may not have been clinically that meaningful.

Still, “results suggest that the trial clearly influenced those who received positive results and may have had some positive effects on other patients,” Dr. Nadkarni concluded.

Dr. Nadkarni is a cofounder of and has equity in Renalytx, and has been a member of the scientific advisory board and received personal fees from the company. He is also a cofounder of Pensieve Health.

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

Giving patients and their providers genetic test results for kidney failure risk promotes positive behavioral change that could decrease an individual’s likelihood of developing chronic kidney disease (CKD) and end-stage renal failure (ESRF), a new pilot study suggests.

“Disclosing APOL1 genetic testing results to patients of African ancestry with hypertension and their clinicians was associated with a greater reduction in systolic blood pressure [SBP], increased kidney disease screening, and positive self-reported behavior change in those with high-risk genotypes,” Girish Nadkarni, MD, MPH, Icahn Mount Sinai School of Medicine, New York, and colleagues reported.

“These two measurements – the change in blood pressure and increased kidney function tests – act as hallmarks for detecting beneficial lifestyle change,” Dr. Nadkarni noted in a statement from his institution.

“For many years, researchers have wondered whether reporting APOL1 genetic test results would help improve clinical management. This is the first pragmatic randomized clinical trial to test this out [and] these results suggest we are headed in the right direction,” he added.

The study was published online March 4, 2022, in JAMA Network Open.
 

A quarter of those with high-risk genotype changed medication behavior

High-risk APOL1 genotypes confer a 5- to 10-fold increased risk for CKD and ESRF caused by hypertension and are found in one out of seven individuals of African ancestry. People of African ancestry also have the highest age-adjusted prevalence of high BP and the lowest rates of BP control, Dr. Nadkarni and colleagues wrote.

They studied a total of 2,050 patients of African ancestry with hypertension but without CKD who were randomized to undergo either immediate APOL1 testing (intervention group) or delayed APOL1 testing (control group).

“Patients randomly assigned to the intervention group received APOL1 genetic testing results from trained staff [while] their clinicians received results through clinical decision support in electronic health records,” the investigators explained.

Control patients received results after 12 months of follow-up. The mean age of the cohort was 53 years and almost two-thirds were female. Mean baseline SBP was significantly higher in patients with high-risk APOL1 genotypes, at 137 mm Hg, compared with those with low-risk APOL1 genotypes, at 134 mm Hg (P = .003), and controls, at 133 mm Hg (P = .001), the authors reported. 

At 3 months, “all groups had some decrease in SBP,” Dr. Nadkarni and colleagues observed.

However, patients with high-risk APOL1 genotypes had a significantly greater decrease in SBP, at 6 mm Hg, compared with a mean decrease of 3 mm Hg for those with low-risk APOL1 genotypes (P = .004) as well as controls (P = .01). At 12 months, there was no significant difference in SBP or change in SBP from baseline to 12 months between the three groups.

“All three groups showed a significant increase in the rate of urine protein testing over time,” the authors added.

Again, however, the most significant increase in urine protein testing over time was seen in patients with high-risk APOL1 genotypes, with a 12% increase from baseline, compared with a 6% increase for patients with low-risk APOL1 genotypes and a 7% increase among controls. The difference was significant only between patients with high-risk APOL1 genotypes and controls (P = .01).

Significantly more patients with high-risk APOL1 genotypes, at 59%, reported making positive lifestyle changes as reflected in better dietary and exercise habits after receiving their test results than did those with low-risk APOL1 genotypes, at 37% (P < .001).

Moreover, 24% of those with high-risk genotypes reported that receiving test results changed how they take their BP medication, compared with only 10% of those with low-risk genotypes.

More high-risk genotype carriers also reported taking their medications more often, at 10%, compared with 5% of low-risk genotype carriers (P = .005).

On the other hand, more patients with the high-risk genotype, at 27%, worried that they would develop kidney problems than low-risk carriers, at 17% (P < .001). Although investigators did offer patients the opportunity to speak with a genetic counselor at no cost, none chose to do so, the authors noted.
 

Small improvements

As the investigators emphasized, the magnitude of BP improvement seen in high-risk APOL1 carriers was small. However, they did not provide specific BP target recommendations or BP-lowering strategies, which, had they done so, may have brought BP down to a greater degree.

Health behavior changes were similarly small and may not have been clinically that meaningful.

Still, “results suggest that the trial clearly influenced those who received positive results and may have had some positive effects on other patients,” Dr. Nadkarni concluded.

Dr. Nadkarni is a cofounder of and has equity in Renalytx, and has been a member of the scientific advisory board and received personal fees from the company. He is also a cofounder of Pensieve Health.

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

Giving patients and their providers genetic test results for kidney failure risk promotes positive behavioral change that could decrease an individual’s likelihood of developing chronic kidney disease (CKD) and end-stage renal failure (ESRF), a new pilot study suggests.

“Disclosing APOL1 genetic testing results to patients of African ancestry with hypertension and their clinicians was associated with a greater reduction in systolic blood pressure [SBP], increased kidney disease screening, and positive self-reported behavior change in those with high-risk genotypes,” Girish Nadkarni, MD, MPH, Icahn Mount Sinai School of Medicine, New York, and colleagues reported.

“These two measurements – the change in blood pressure and increased kidney function tests – act as hallmarks for detecting beneficial lifestyle change,” Dr. Nadkarni noted in a statement from his institution.

“For many years, researchers have wondered whether reporting APOL1 genetic test results would help improve clinical management. This is the first pragmatic randomized clinical trial to test this out [and] these results suggest we are headed in the right direction,” he added.

The study was published online March 4, 2022, in JAMA Network Open.
 

A quarter of those with high-risk genotype changed medication behavior

High-risk APOL1 genotypes confer a 5- to 10-fold increased risk for CKD and ESRF caused by hypertension and are found in one out of seven individuals of African ancestry. People of African ancestry also have the highest age-adjusted prevalence of high BP and the lowest rates of BP control, Dr. Nadkarni and colleagues wrote.

They studied a total of 2,050 patients of African ancestry with hypertension but without CKD who were randomized to undergo either immediate APOL1 testing (intervention group) or delayed APOL1 testing (control group).

“Patients randomly assigned to the intervention group received APOL1 genetic testing results from trained staff [while] their clinicians received results through clinical decision support in electronic health records,” the investigators explained.

Control patients received results after 12 months of follow-up. The mean age of the cohort was 53 years and almost two-thirds were female. Mean baseline SBP was significantly higher in patients with high-risk APOL1 genotypes, at 137 mm Hg, compared with those with low-risk APOL1 genotypes, at 134 mm Hg (P = .003), and controls, at 133 mm Hg (P = .001), the authors reported. 

At 3 months, “all groups had some decrease in SBP,” Dr. Nadkarni and colleagues observed.

However, patients with high-risk APOL1 genotypes had a significantly greater decrease in SBP, at 6 mm Hg, compared with a mean decrease of 3 mm Hg for those with low-risk APOL1 genotypes (P = .004) as well as controls (P = .01). At 12 months, there was no significant difference in SBP or change in SBP from baseline to 12 months between the three groups.

“All three groups showed a significant increase in the rate of urine protein testing over time,” the authors added.

Again, however, the most significant increase in urine protein testing over time was seen in patients with high-risk APOL1 genotypes, with a 12% increase from baseline, compared with a 6% increase for patients with low-risk APOL1 genotypes and a 7% increase among controls. The difference was significant only between patients with high-risk APOL1 genotypes and controls (P = .01).

Significantly more patients with high-risk APOL1 genotypes, at 59%, reported making positive lifestyle changes as reflected in better dietary and exercise habits after receiving their test results than did those with low-risk APOL1 genotypes, at 37% (P < .001).

Moreover, 24% of those with high-risk genotypes reported that receiving test results changed how they take their BP medication, compared with only 10% of those with low-risk genotypes.

More high-risk genotype carriers also reported taking their medications more often, at 10%, compared with 5% of low-risk genotype carriers (P = .005).

On the other hand, more patients with the high-risk genotype, at 27%, worried that they would develop kidney problems than low-risk carriers, at 17% (P < .001). Although investigators did offer patients the opportunity to speak with a genetic counselor at no cost, none chose to do so, the authors noted.
 

Small improvements

As the investigators emphasized, the magnitude of BP improvement seen in high-risk APOL1 carriers was small. However, they did not provide specific BP target recommendations or BP-lowering strategies, which, had they done so, may have brought BP down to a greater degree.

Health behavior changes were similarly small and may not have been clinically that meaningful.

Still, “results suggest that the trial clearly influenced those who received positive results and may have had some positive effects on other patients,” Dr. Nadkarni concluded.

Dr. Nadkarni is a cofounder of and has equity in Renalytx, and has been a member of the scientific advisory board and received personal fees from the company. He is also a cofounder of Pensieve Health.

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

Patients with low-risk differentiated thyroid cancer (DTC) undergoing thyroidectomy show no improvements in outcomes with the use of postoperative radioiodine ablation compared to those who do not receive this therapy, suggesting these patients can be spared the previously common treatment.

The study’s take-home message for clinicians should be to “stop systematic radioiodine ablation administration in low-risk thyroid cancer patients,” lead author Sophie Leboulleux, MD, PhD, said in an interview.

The results were first reported at ENDO 2021 and have now been published in the New England Journal of Medicine by Dr. Leboulleux, of the department of nuclear medicine and endocrine oncology, Gustave Roussy Cancer Institute, Villejuif, France, and colleagues.

While American Thyroid Association (ATA) guidelines already indicate that radioiodine ablation is not routinely recommended after thyroidectomy for patients with low-risk thyroid cancer, the guidance is only a “weak recommendation,” supported by “low-quality evidence.”  

However, the new findings should give that level of evidence a much-needed boost, said one expert. “I think the main contribution of this paper is to change the evidence level to ‘high quality,’ therefore making the recommendation ‘strong,’ rather than ‘weak,’ ” David S. Cooper, MD, said in an interview.

Dr. Cooper, professor of medicine and radiology at Johns Hopkins University, Baltimore, wrote an editorial that accompanies Dr. Leboulleux’s study.

The ability to safely spare patients the radioiodine ablation step after thyroidectomy has important benefits in terms of cost and convenience, Dr. Cooper stressed.
 

ESTIMABL2 trial

The new findings are from the prospective, randomized, phase 3 Essai Stimulation Ablation 2 (ESTIMABL2) trial, in which 730 patients at 35 centers in France with low-risk DTC scheduled to undergo thyroidectomy were enrolled between May 2013 and March 2017.

Patients were randomized to receive either postoperative radioiodine ablation (1.1 GBq) after injections of recombinant human thyrotropin (n = 363) or no postoperative radioiodine (n = 367).

Patients were a mean age of 52 years and 83% were women. About 96% had papillary tumors, and pathological tumor node (pTN) stages were mostly pT1b thyroid with a nodal status of N0 or Nx (81.1%). It is these patients in particular in whom retrospective studies of the use of radioiodine ablation have yielded inconsistent results, Dr. Leboulleux and colleagues noted. Hence, their decision to look at this prospectively.

Outcomes were based on the groups’ rates of events, defined as the presence of abnormal foci of radioiodine uptake on whole-body scanning that required treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or increased levels of thyroglobulin or thyroglobulin antibodies.

After a 3-year follow-up, the rates of having no events in both groups were very high – and nearly identical – at 95.6% among those receiving no radioiodine ablation and 95.9% in the radioiodine group, for a between-group difference of –0.3 percentage points, which met the criteria for noninferiority for the no-radioiodine group.

Likewise, the events that did occur were nearly equally split between the no-radioiodine group (16 events, 4.4%) and the radioiodine group (15 events, 4.1%).

Among patients who had events, subsequent treatments, including surgery, radioiodine administration, or both, were necessary for four patients in the no-radioiodine group and 10 in the radioiodine group, and additional treatments were not necessary for the other patients who experienced events.

There were no differences between those who did and did not experience events in terms of molecular alterations, and 50 of the tumors had BRAF mutations, with no significant differences between groups.

Of the adverse events that occurred in 30 patients, none were determined to be related to treatment, and there were no thyroid-related deaths.

The recurrence rates align with the rates observed overall with low-risk thyroid cancer, the authors noted. 

“We observed that less than 5% of the patients in the two groups had events that included abnormal findings on whole-body scanning or neck ultrasonography or elevated levels of thyroglobulin or thyroglobulin antibodies during the first 3 years of follow-up,” they reported.

“This rate is concordant with the definition of low-risk thyroid cancer, and our trial showed that the risk of events was not higher in the absence of postoperative administration of radioiodine.”
 

Patients spared costs, work losses

Dr. Cooper elaborated on the advantages, for patients, of avoiding radioiodine ablation.

For one thing, the recombinant human TSH that is necessary to prepare for radioiodine therapy is very expensive, ranging from $2,000 to $3,000, with patients often having a copay, he explained.

“Patients usually have to take time off work, which is also an expense to society and to them if they don’t get paid for days that they don’t work,” Dr. Cooper added.

A possible study limitation is the question of whether 3 years is an ample follow-up period to detect events. However, Dr. Cooper said he considers the period to be sufficient.

“As the authors point out, most recurrences of thyroid cancer are detected within the first 3-5 years of initial treatment, so ... the 3-year window is still clinically relevant,” he said.

Regarding the study’s inclusion of centers only in France, Dr. Cooper added, “I do not think that this is a study limitation. There is nothing specific about the French population that would lead me to conclude that the results were not generalizable to all populations with low-risk papillary thyroid cancer.”
 

Some continue radioiodine use, but lobectomies add to decline

Despite the mounting evidence of the lack of benefit of radioiodine ablation in low-risk patients, some centers, particularly in Europe, continue the practice, which was standard in the treatment of DTC until relatively recently.

“[While] U.S. guidelines changed in 2015 in favor of no radioiodine in low-risk differentiated thyroid cancer patients, this study should help to change European guidelines,” Dr. Leboulleux said. “The results will help to change practice both in the U.S. and in Europe.”

In addition to awareness of guidelines and new evidence, another reason for the decline in radioiodine ablation for low-risk DTC is the increasing use of thyroid lobectomy, which does not involve the use of radioiodine ablation, rather than total thyroidectomy, Dr. Cooper noted.

“The [new] NEJM paper will hopefully decrease the inappropriate use of radioiodine in low-risk patients even further,” he concluded.

The study received support from the French Ministry of Health through a grant from the National Cancer Institute. The authors have reported no relevant financial relationships.

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

Patients with low-risk differentiated thyroid cancer (DTC) undergoing thyroidectomy show no improvements in outcomes with the use of postoperative radioiodine ablation compared to those who do not receive this therapy, suggesting these patients can be spared the previously common treatment.

The study’s take-home message for clinicians should be to “stop systematic radioiodine ablation administration in low-risk thyroid cancer patients,” lead author Sophie Leboulleux, MD, PhD, said in an interview.

The results were first reported at ENDO 2021 and have now been published in the New England Journal of Medicine by Dr. Leboulleux, of the department of nuclear medicine and endocrine oncology, Gustave Roussy Cancer Institute, Villejuif, France, and colleagues.

While American Thyroid Association (ATA) guidelines already indicate that radioiodine ablation is not routinely recommended after thyroidectomy for patients with low-risk thyroid cancer, the guidance is only a “weak recommendation,” supported by “low-quality evidence.”  

However, the new findings should give that level of evidence a much-needed boost, said one expert. “I think the main contribution of this paper is to change the evidence level to ‘high quality,’ therefore making the recommendation ‘strong,’ rather than ‘weak,’ ” David S. Cooper, MD, said in an interview.

Dr. Cooper, professor of medicine and radiology at Johns Hopkins University, Baltimore, wrote an editorial that accompanies Dr. Leboulleux’s study.

The ability to safely spare patients the radioiodine ablation step after thyroidectomy has important benefits in terms of cost and convenience, Dr. Cooper stressed.
 

ESTIMABL2 trial

The new findings are from the prospective, randomized, phase 3 Essai Stimulation Ablation 2 (ESTIMABL2) trial, in which 730 patients at 35 centers in France with low-risk DTC scheduled to undergo thyroidectomy were enrolled between May 2013 and March 2017.

Patients were randomized to receive either postoperative radioiodine ablation (1.1 GBq) after injections of recombinant human thyrotropin (n = 363) or no postoperative radioiodine (n = 367).

Patients were a mean age of 52 years and 83% were women. About 96% had papillary tumors, and pathological tumor node (pTN) stages were mostly pT1b thyroid with a nodal status of N0 or Nx (81.1%). It is these patients in particular in whom retrospective studies of the use of radioiodine ablation have yielded inconsistent results, Dr. Leboulleux and colleagues noted. Hence, their decision to look at this prospectively.

Outcomes were based on the groups’ rates of events, defined as the presence of abnormal foci of radioiodine uptake on whole-body scanning that required treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or increased levels of thyroglobulin or thyroglobulin antibodies.

After a 3-year follow-up, the rates of having no events in both groups were very high – and nearly identical – at 95.6% among those receiving no radioiodine ablation and 95.9% in the radioiodine group, for a between-group difference of –0.3 percentage points, which met the criteria for noninferiority for the no-radioiodine group.

Likewise, the events that did occur were nearly equally split between the no-radioiodine group (16 events, 4.4%) and the radioiodine group (15 events, 4.1%).

Among patients who had events, subsequent treatments, including surgery, radioiodine administration, or both, were necessary for four patients in the no-radioiodine group and 10 in the radioiodine group, and additional treatments were not necessary for the other patients who experienced events.

There were no differences between those who did and did not experience events in terms of molecular alterations, and 50 of the tumors had BRAF mutations, with no significant differences between groups.

Of the adverse events that occurred in 30 patients, none were determined to be related to treatment, and there were no thyroid-related deaths.

The recurrence rates align with the rates observed overall with low-risk thyroid cancer, the authors noted. 

“We observed that less than 5% of the patients in the two groups had events that included abnormal findings on whole-body scanning or neck ultrasonography or elevated levels of thyroglobulin or thyroglobulin antibodies during the first 3 years of follow-up,” they reported.

“This rate is concordant with the definition of low-risk thyroid cancer, and our trial showed that the risk of events was not higher in the absence of postoperative administration of radioiodine.”
 

Patients spared costs, work losses

Dr. Cooper elaborated on the advantages, for patients, of avoiding radioiodine ablation.

For one thing, the recombinant human TSH that is necessary to prepare for radioiodine therapy is very expensive, ranging from $2,000 to $3,000, with patients often having a copay, he explained.

“Patients usually have to take time off work, which is also an expense to society and to them if they don’t get paid for days that they don’t work,” Dr. Cooper added.

A possible study limitation is the question of whether 3 years is an ample follow-up period to detect events. However, Dr. Cooper said he considers the period to be sufficient.

“As the authors point out, most recurrences of thyroid cancer are detected within the first 3-5 years of initial treatment, so ... the 3-year window is still clinically relevant,” he said.

Regarding the study’s inclusion of centers only in France, Dr. Cooper added, “I do not think that this is a study limitation. There is nothing specific about the French population that would lead me to conclude that the results were not generalizable to all populations with low-risk papillary thyroid cancer.”
 

Some continue radioiodine use, but lobectomies add to decline

Despite the mounting evidence of the lack of benefit of radioiodine ablation in low-risk patients, some centers, particularly in Europe, continue the practice, which was standard in the treatment of DTC until relatively recently.

“[While] U.S. guidelines changed in 2015 in favor of no radioiodine in low-risk differentiated thyroid cancer patients, this study should help to change European guidelines,” Dr. Leboulleux said. “The results will help to change practice both in the U.S. and in Europe.”

In addition to awareness of guidelines and new evidence, another reason for the decline in radioiodine ablation for low-risk DTC is the increasing use of thyroid lobectomy, which does not involve the use of radioiodine ablation, rather than total thyroidectomy, Dr. Cooper noted.

“The [new] NEJM paper will hopefully decrease the inappropriate use of radioiodine in low-risk patients even further,” he concluded.

The study received support from the French Ministry of Health through a grant from the National Cancer Institute. The authors have reported no relevant financial relationships.

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

Patients with low-risk differentiated thyroid cancer (DTC) undergoing thyroidectomy show no improvements in outcomes with the use of postoperative radioiodine ablation compared to those who do not receive this therapy, suggesting these patients can be spared the previously common treatment.

The study’s take-home message for clinicians should be to “stop systematic radioiodine ablation administration in low-risk thyroid cancer patients,” lead author Sophie Leboulleux, MD, PhD, said in an interview.

The results were first reported at ENDO 2021 and have now been published in the New England Journal of Medicine by Dr. Leboulleux, of the department of nuclear medicine and endocrine oncology, Gustave Roussy Cancer Institute, Villejuif, France, and colleagues.

While American Thyroid Association (ATA) guidelines already indicate that radioiodine ablation is not routinely recommended after thyroidectomy for patients with low-risk thyroid cancer, the guidance is only a “weak recommendation,” supported by “low-quality evidence.”  

However, the new findings should give that level of evidence a much-needed boost, said one expert. “I think the main contribution of this paper is to change the evidence level to ‘high quality,’ therefore making the recommendation ‘strong,’ rather than ‘weak,’ ” David S. Cooper, MD, said in an interview.

Dr. Cooper, professor of medicine and radiology at Johns Hopkins University, Baltimore, wrote an editorial that accompanies Dr. Leboulleux’s study.

The ability to safely spare patients the radioiodine ablation step after thyroidectomy has important benefits in terms of cost and convenience, Dr. Cooper stressed.
 

ESTIMABL2 trial

The new findings are from the prospective, randomized, phase 3 Essai Stimulation Ablation 2 (ESTIMABL2) trial, in which 730 patients at 35 centers in France with low-risk DTC scheduled to undergo thyroidectomy were enrolled between May 2013 and March 2017.

Patients were randomized to receive either postoperative radioiodine ablation (1.1 GBq) after injections of recombinant human thyrotropin (n = 363) or no postoperative radioiodine (n = 367).

Patients were a mean age of 52 years and 83% were women. About 96% had papillary tumors, and pathological tumor node (pTN) stages were mostly pT1b thyroid with a nodal status of N0 or Nx (81.1%). It is these patients in particular in whom retrospective studies of the use of radioiodine ablation have yielded inconsistent results, Dr. Leboulleux and colleagues noted. Hence, their decision to look at this prospectively.

Outcomes were based on the groups’ rates of events, defined as the presence of abnormal foci of radioiodine uptake on whole-body scanning that required treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or increased levels of thyroglobulin or thyroglobulin antibodies.

After a 3-year follow-up, the rates of having no events in both groups were very high – and nearly identical – at 95.6% among those receiving no radioiodine ablation and 95.9% in the radioiodine group, for a between-group difference of –0.3 percentage points, which met the criteria for noninferiority for the no-radioiodine group.

Likewise, the events that did occur were nearly equally split between the no-radioiodine group (16 events, 4.4%) and the radioiodine group (15 events, 4.1%).

Among patients who had events, subsequent treatments, including surgery, radioiodine administration, or both, were necessary for four patients in the no-radioiodine group and 10 in the radioiodine group, and additional treatments were not necessary for the other patients who experienced events.

There were no differences between those who did and did not experience events in terms of molecular alterations, and 50 of the tumors had BRAF mutations, with no significant differences between groups.

Of the adverse events that occurred in 30 patients, none were determined to be related to treatment, and there were no thyroid-related deaths.

The recurrence rates align with the rates observed overall with low-risk thyroid cancer, the authors noted. 

“We observed that less than 5% of the patients in the two groups had events that included abnormal findings on whole-body scanning or neck ultrasonography or elevated levels of thyroglobulin or thyroglobulin antibodies during the first 3 years of follow-up,” they reported.

“This rate is concordant with the definition of low-risk thyroid cancer, and our trial showed that the risk of events was not higher in the absence of postoperative administration of radioiodine.”
 

Patients spared costs, work losses

Dr. Cooper elaborated on the advantages, for patients, of avoiding radioiodine ablation.

For one thing, the recombinant human TSH that is necessary to prepare for radioiodine therapy is very expensive, ranging from $2,000 to $3,000, with patients often having a copay, he explained.

“Patients usually have to take time off work, which is also an expense to society and to them if they don’t get paid for days that they don’t work,” Dr. Cooper added.

A possible study limitation is the question of whether 3 years is an ample follow-up period to detect events. However, Dr. Cooper said he considers the period to be sufficient.

“As the authors point out, most recurrences of thyroid cancer are detected within the first 3-5 years of initial treatment, so ... the 3-year window is still clinically relevant,” he said.

Regarding the study’s inclusion of centers only in France, Dr. Cooper added, “I do not think that this is a study limitation. There is nothing specific about the French population that would lead me to conclude that the results were not generalizable to all populations with low-risk papillary thyroid cancer.”
 

Some continue radioiodine use, but lobectomies add to decline

Despite the mounting evidence of the lack of benefit of radioiodine ablation in low-risk patients, some centers, particularly in Europe, continue the practice, which was standard in the treatment of DTC until relatively recently.

“[While] U.S. guidelines changed in 2015 in favor of no radioiodine in low-risk differentiated thyroid cancer patients, this study should help to change European guidelines,” Dr. Leboulleux said. “The results will help to change practice both in the U.S. and in Europe.”

In addition to awareness of guidelines and new evidence, another reason for the decline in radioiodine ablation for low-risk DTC is the increasing use of thyroid lobectomy, which does not involve the use of radioiodine ablation, rather than total thyroidectomy, Dr. Cooper noted.

“The [new] NEJM paper will hopefully decrease the inappropriate use of radioiodine in low-risk patients even further,” he concluded.

The study received support from the French Ministry of Health through a grant from the National Cancer Institute. The authors have reported no relevant financial relationships.

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

LAS VEGAS – Is the relationship between major depressive disorder and the development of cancer, cardiovascular disease, and other medical conditions a coincidence, or is there more at play?

According to Charles B. Nemeroff, MD, PhD, a host of circumstances potentially underlies this association, including treatment of the medical disorder itself.

Courtesy University of Texas, Austin

“The best example of that is probably the use of interferon-alpha for the treatment of malignant melanoma,” Dr. Nemeroff, professor and chair of the department of psychiatry and behavioral sciences at the University of Texas at Austin, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “Many patients treated with interferon-alpha ended up with very severe depression, including several documented suicides. Another possibility of the relationship between depression and medical disorders is that treating a patient for depression could result in a medical disorder. The best example of this is the use of 20 mg of olanzapine to augment the effects of an antidepressant, resulting in a 50-pound weight gain and the development of type 2 diabetes and metabolic syndrome. Both of those scenarios are well understood.”

Then there’s the behavioral aspects of the relationship, he continued, in which patients adopt the mindset that “I’m depressed. I don’t want to exercise. I’m a couch potato. I have been gaining a lot of weight. It’s bad for my heart.”

Converging biology is another possibility. “Is it possible that the biology of depression is linked to the biology of other disorders?” asked Dr. Nemeroff, who directs the university’s Institute for Early Life Adversity Research. “We can talk about this in relation to thyroid disease, a well known cause of depression, but we can also talk about the relationship to other disorders. There’s amazing epidemiologic evidence that patients with PTSD are much more likely to develop Alzheimer’s disease than patients without PTSD.”

Psychosocial issues also play a role. He recalled seeing patient in a clinic for the underserved who had underlying severe ulcerative colitis and anemia and couldn’t afford medical treatment. “The patient had a low hemoglobin, so it was impossible to distinguish between that and whether they had a primary depressive disorder or not,” he said.

In a study that explored the relationship between major depression and cancer, Dr. Nemeroff and colleagues found that the prevalence was highest in those with pancreatic cancer (50%), followed by oropharyngeal (40%), colon (13-25%), breast (18-25%), and gynecologic (23%), and Hodgkin’s lymphoma (17%) (Arch Gen Psychiatry 1995;52[2]:89-99). “Not all cancers have the same rate of depression,” he said. “One of the central questions is, not so much is the cancer patient depressed, but is depression a risk factor for developing cancer? The answer is a resounding yes. But what we don’t know is if you treat the depression aggressively, can you reduce that risk of either developing cancer or the progression of cancer?”

Dr. Nemeroff spotlighted several studies largely from the oncology literature, including a prospective survival analysis of 578 women with early-stage breast cancer (Lancet 1999;354:1331-6). After 5 years, 395 were alive and without relapse, 50 were alive with relapse, and 133 had died. The researchers found a significantly increased risk of death from all causes by 5 years in women with a high depression score (HR 3.59). There was a significantly increased risk of relapse or death at 5 years in women with high scores on helplessness and hopelessness measures.

In an analysis of the association between breast cancer and traumatic events, women who had severe stress or a traumatic event had lower rates of disease-free intervals (J Psychosomatic Res 2007;63:233-9). Another study by the same investigators found that a decrease in depression symptoms is associated with longer survival in patients with metastatic breast cancer (J Clin Oncol 2010;29:413-20). The median survival was 53.6 months for women with decreasing depression scores over 1 year and 25.1 months for women with increasing depression scores.

A more recent study of cervical cancer patients found that those exposed to psychological stress had an increased risk of cancer-specific mortality (HR 1.33) (Cancer Res 2019;79:3965-72). The association was mainly driven by distress experienced within 1 year before or after diagnosis (HR 1.30) but not afterward (HR 1.12). In addition, data from the large longitudinal Nurses’ Health Study II found that women with high PTSD symptoms had a twofold greater risk of ovarian cancer compared with women who had no trauma exposure (Cancer Res 2019;79:5113-20).

Authors of a separate study analyzed data from the Women’s Health Initiative to examine if depression precedes the development of a cancer diagnosis. They found that depression 3 years before a diagnosis of breast cancer was associated with all-cause mortality (HR 1.35) (Cancer 2017;123[16]:3107-15). Meanwhile, among women with late-stage breast cancer, newly developed depression at year 3 was significantly associated with all-cause mortality (HR 2.0) and breast cancer-specific mortality (HR 2.42). “That’s a pretty amazing finding,” Dr. Nemeroff said. “We have to think about depression as a systemic illness. What is depression doing that’s creating a fertile environment for cancer or worsening of cancer?”

He then discussed the risk of suicide in patients who are newly diagnosed with cancer. “No one ever talks about this, and I can’t get anybody to support research in this area,” he said. In one of the first studies on the topic, researchers conducted a case-control study of Medicare patients and determined risk of suicide among those with cancer was 2.3-fold higher compared with controls, even after adjustment for psychiatric illness and the risk of dying within a year (J Clin Oncol 2008;26[29]:4720-4). More recently, authors of a large population-based study in England found that the overall standardized mortality ratio for suicide was 1.20 (JAMA Psychiatry 2019;76[1]51-60). The risk was highest among patients with mesothelioma, with a 4.51-fold risk, followed by pancreatic (3.89-fold), esophageal (2.65-fold), lung (2.57-fold), and stomach cancer (2.20-fold). “They reported that the first 6 months after the diagnosis is associated with an increased risk of suicide – unrelated to prognosis,” Dr. Nemeroff said.

A separate analysis of SEER data from 1973-2014 and comprising more than 8.6 million cancer patients found that newly diagnosed cancer patients are 4.4 times more likely to die from suicide than patients in the same age group without cancer (Nat Commun 2019;10[1]:207). The highest risk was in lung cancer, followed by head and neck, testes, bladder, and Hodgkin’s lymphoma.

According to Dr. Nemeroff, the association between depression and the risk of certain forms of cancer or with a poor cancer prognosis “may have to do with immune function. Depression is associated with a change in inflammatory markers that very likely control the microenvironment of the tumor.” For example, he said, if the depressed environment is associated with a marked increase in tumor necrosis factor, interleukin 6, and other inflammatory markers, “that probably contributes to the body’s ability to fight disease. Ironically, depression is associated with an increase in inflammation but a decreased in T cell function. Remember, there are two fundamental types of immunity: the antibody response and the cellular response. What’s odd about depression is that there’s an increase in inflammatory markers but a decrease in the ability of T cells to function in terms of cellular immunity.”

Dr. Nemeroff disclosed that he has served as a consultant and/or scientific adviser for numerous pharmaceutical companies. He has received research and grant support from the National Institutes of Health.

LAS VEGAS – Is the relationship between major depressive disorder and the development of cancer, cardiovascular disease, and other medical conditions a coincidence, or is there more at play?

According to Charles B. Nemeroff, MD, PhD, a host of circumstances potentially underlies this association, including treatment of the medical disorder itself.

Courtesy University of Texas, Austin

“The best example of that is probably the use of interferon-alpha for the treatment of malignant melanoma,” Dr. Nemeroff, professor and chair of the department of psychiatry and behavioral sciences at the University of Texas at Austin, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “Many patients treated with interferon-alpha ended up with very severe depression, including several documented suicides. Another possibility of the relationship between depression and medical disorders is that treating a patient for depression could result in a medical disorder. The best example of this is the use of 20 mg of olanzapine to augment the effects of an antidepressant, resulting in a 50-pound weight gain and the development of type 2 diabetes and metabolic syndrome. Both of those scenarios are well understood.”

Then there’s the behavioral aspects of the relationship, he continued, in which patients adopt the mindset that “I’m depressed. I don’t want to exercise. I’m a couch potato. I have been gaining a lot of weight. It’s bad for my heart.”

Converging biology is another possibility. “Is it possible that the biology of depression is linked to the biology of other disorders?” asked Dr. Nemeroff, who directs the university’s Institute for Early Life Adversity Research. “We can talk about this in relation to thyroid disease, a well known cause of depression, but we can also talk about the relationship to other disorders. There’s amazing epidemiologic evidence that patients with PTSD are much more likely to develop Alzheimer’s disease than patients without PTSD.”

Psychosocial issues also play a role. He recalled seeing patient in a clinic for the underserved who had underlying severe ulcerative colitis and anemia and couldn’t afford medical treatment. “The patient had a low hemoglobin, so it was impossible to distinguish between that and whether they had a primary depressive disorder or not,” he said.

In a study that explored the relationship between major depression and cancer, Dr. Nemeroff and colleagues found that the prevalence was highest in those with pancreatic cancer (50%), followed by oropharyngeal (40%), colon (13-25%), breast (18-25%), and gynecologic (23%), and Hodgkin’s lymphoma (17%) (Arch Gen Psychiatry 1995;52[2]:89-99). “Not all cancers have the same rate of depression,” he said. “One of the central questions is, not so much is the cancer patient depressed, but is depression a risk factor for developing cancer? The answer is a resounding yes. But what we don’t know is if you treat the depression aggressively, can you reduce that risk of either developing cancer or the progression of cancer?”

Dr. Nemeroff spotlighted several studies largely from the oncology literature, including a prospective survival analysis of 578 women with early-stage breast cancer (Lancet 1999;354:1331-6). After 5 years, 395 were alive and without relapse, 50 were alive with relapse, and 133 had died. The researchers found a significantly increased risk of death from all causes by 5 years in women with a high depression score (HR 3.59). There was a significantly increased risk of relapse or death at 5 years in women with high scores on helplessness and hopelessness measures.

In an analysis of the association between breast cancer and traumatic events, women who had severe stress or a traumatic event had lower rates of disease-free intervals (J Psychosomatic Res 2007;63:233-9). Another study by the same investigators found that a decrease in depression symptoms is associated with longer survival in patients with metastatic breast cancer (J Clin Oncol 2010;29:413-20). The median survival was 53.6 months for women with decreasing depression scores over 1 year and 25.1 months for women with increasing depression scores.

A more recent study of cervical cancer patients found that those exposed to psychological stress had an increased risk of cancer-specific mortality (HR 1.33) (Cancer Res 2019;79:3965-72). The association was mainly driven by distress experienced within 1 year before or after diagnosis (HR 1.30) but not afterward (HR 1.12). In addition, data from the large longitudinal Nurses’ Health Study II found that women with high PTSD symptoms had a twofold greater risk of ovarian cancer compared with women who had no trauma exposure (Cancer Res 2019;79:5113-20).

Authors of a separate study analyzed data from the Women’s Health Initiative to examine if depression precedes the development of a cancer diagnosis. They found that depression 3 years before a diagnosis of breast cancer was associated with all-cause mortality (HR 1.35) (Cancer 2017;123[16]:3107-15). Meanwhile, among women with late-stage breast cancer, newly developed depression at year 3 was significantly associated with all-cause mortality (HR 2.0) and breast cancer-specific mortality (HR 2.42). “That’s a pretty amazing finding,” Dr. Nemeroff said. “We have to think about depression as a systemic illness. What is depression doing that’s creating a fertile environment for cancer or worsening of cancer?”

He then discussed the risk of suicide in patients who are newly diagnosed with cancer. “No one ever talks about this, and I can’t get anybody to support research in this area,” he said. In one of the first studies on the topic, researchers conducted a case-control study of Medicare patients and determined risk of suicide among those with cancer was 2.3-fold higher compared with controls, even after adjustment for psychiatric illness and the risk of dying within a year (J Clin Oncol 2008;26[29]:4720-4). More recently, authors of a large population-based study in England found that the overall standardized mortality ratio for suicide was 1.20 (JAMA Psychiatry 2019;76[1]51-60). The risk was highest among patients with mesothelioma, with a 4.51-fold risk, followed by pancreatic (3.89-fold), esophageal (2.65-fold), lung (2.57-fold), and stomach cancer (2.20-fold). “They reported that the first 6 months after the diagnosis is associated with an increased risk of suicide – unrelated to prognosis,” Dr. Nemeroff said.

A separate analysis of SEER data from 1973-2014 and comprising more than 8.6 million cancer patients found that newly diagnosed cancer patients are 4.4 times more likely to die from suicide than patients in the same age group without cancer (Nat Commun 2019;10[1]:207). The highest risk was in lung cancer, followed by head and neck, testes, bladder, and Hodgkin’s lymphoma.

According to Dr. Nemeroff, the association between depression and the risk of certain forms of cancer or with a poor cancer prognosis “may have to do with immune function. Depression is associated with a change in inflammatory markers that very likely control the microenvironment of the tumor.” For example, he said, if the depressed environment is associated with a marked increase in tumor necrosis factor, interleukin 6, and other inflammatory markers, “that probably contributes to the body’s ability to fight disease. Ironically, depression is associated with an increase in inflammation but a decreased in T cell function. Remember, there are two fundamental types of immunity: the antibody response and the cellular response. What’s odd about depression is that there’s an increase in inflammatory markers but a decrease in the ability of T cells to function in terms of cellular immunity.”

Dr. Nemeroff disclosed that he has served as a consultant and/or scientific adviser for numerous pharmaceutical companies. He has received research and grant support from the National Institutes of Health.

LAS VEGAS – Is the relationship between major depressive disorder and the development of cancer, cardiovascular disease, and other medical conditions a coincidence, or is there more at play?

According to Charles B. Nemeroff, MD, PhD, a host of circumstances potentially underlies this association, including treatment of the medical disorder itself.

Courtesy University of Texas, Austin

“The best example of that is probably the use of interferon-alpha for the treatment of malignant melanoma,” Dr. Nemeroff, professor and chair of the department of psychiatry and behavioral sciences at the University of Texas at Austin, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “Many patients treated with interferon-alpha ended up with very severe depression, including several documented suicides. Another possibility of the relationship between depression and medical disorders is that treating a patient for depression could result in a medical disorder. The best example of this is the use of 20 mg of olanzapine to augment the effects of an antidepressant, resulting in a 50-pound weight gain and the development of type 2 diabetes and metabolic syndrome. Both of those scenarios are well understood.”

Then there’s the behavioral aspects of the relationship, he continued, in which patients adopt the mindset that “I’m depressed. I don’t want to exercise. I’m a couch potato. I have been gaining a lot of weight. It’s bad for my heart.”

Converging biology is another possibility. “Is it possible that the biology of depression is linked to the biology of other disorders?” asked Dr. Nemeroff, who directs the university’s Institute for Early Life Adversity Research. “We can talk about this in relation to thyroid disease, a well known cause of depression, but we can also talk about the relationship to other disorders. There’s amazing epidemiologic evidence that patients with PTSD are much more likely to develop Alzheimer’s disease than patients without PTSD.”

Psychosocial issues also play a role. He recalled seeing patient in a clinic for the underserved who had underlying severe ulcerative colitis and anemia and couldn’t afford medical treatment. “The patient had a low hemoglobin, so it was impossible to distinguish between that and whether they had a primary depressive disorder or not,” he said.

In a study that explored the relationship between major depression and cancer, Dr. Nemeroff and colleagues found that the prevalence was highest in those with pancreatic cancer (50%), followed by oropharyngeal (40%), colon (13-25%), breast (18-25%), and gynecologic (23%), and Hodgkin’s lymphoma (17%) (Arch Gen Psychiatry 1995;52[2]:89-99). “Not all cancers have the same rate of depression,” he said. “One of the central questions is, not so much is the cancer patient depressed, but is depression a risk factor for developing cancer? The answer is a resounding yes. But what we don’t know is if you treat the depression aggressively, can you reduce that risk of either developing cancer or the progression of cancer?”

Dr. Nemeroff spotlighted several studies largely from the oncology literature, including a prospective survival analysis of 578 women with early-stage breast cancer (Lancet 1999;354:1331-6). After 5 years, 395 were alive and without relapse, 50 were alive with relapse, and 133 had died. The researchers found a significantly increased risk of death from all causes by 5 years in women with a high depression score (HR 3.59). There was a significantly increased risk of relapse or death at 5 years in women with high scores on helplessness and hopelessness measures.

In an analysis of the association between breast cancer and traumatic events, women who had severe stress or a traumatic event had lower rates of disease-free intervals (J Psychosomatic Res 2007;63:233-9). Another study by the same investigators found that a decrease in depression symptoms is associated with longer survival in patients with metastatic breast cancer (J Clin Oncol 2010;29:413-20). The median survival was 53.6 months for women with decreasing depression scores over 1 year and 25.1 months for women with increasing depression scores.

A more recent study of cervical cancer patients found that those exposed to psychological stress had an increased risk of cancer-specific mortality (HR 1.33) (Cancer Res 2019;79:3965-72). The association was mainly driven by distress experienced within 1 year before or after diagnosis (HR 1.30) but not afterward (HR 1.12). In addition, data from the large longitudinal Nurses’ Health Study II found that women with high PTSD symptoms had a twofold greater risk of ovarian cancer compared with women who had no trauma exposure (Cancer Res 2019;79:5113-20).

Authors of a separate study analyzed data from the Women’s Health Initiative to examine if depression precedes the development of a cancer diagnosis. They found that depression 3 years before a diagnosis of breast cancer was associated with all-cause mortality (HR 1.35) (Cancer 2017;123[16]:3107-15). Meanwhile, among women with late-stage breast cancer, newly developed depression at year 3 was significantly associated with all-cause mortality (HR 2.0) and breast cancer-specific mortality (HR 2.42). “That’s a pretty amazing finding,” Dr. Nemeroff said. “We have to think about depression as a systemic illness. What is depression doing that’s creating a fertile environment for cancer or worsening of cancer?”

He then discussed the risk of suicide in patients who are newly diagnosed with cancer. “No one ever talks about this, and I can’t get anybody to support research in this area,” he said. In one of the first studies on the topic, researchers conducted a case-control study of Medicare patients and determined risk of suicide among those with cancer was 2.3-fold higher compared with controls, even after adjustment for psychiatric illness and the risk of dying within a year (J Clin Oncol 2008;26[29]:4720-4). More recently, authors of a large population-based study in England found that the overall standardized mortality ratio for suicide was 1.20 (JAMA Psychiatry 2019;76[1]51-60). The risk was highest among patients with mesothelioma, with a 4.51-fold risk, followed by pancreatic (3.89-fold), esophageal (2.65-fold), lung (2.57-fold), and stomach cancer (2.20-fold). “They reported that the first 6 months after the diagnosis is associated with an increased risk of suicide – unrelated to prognosis,” Dr. Nemeroff said.

A separate analysis of SEER data from 1973-2014 and comprising more than 8.6 million cancer patients found that newly diagnosed cancer patients are 4.4 times more likely to die from suicide than patients in the same age group without cancer (Nat Commun 2019;10[1]:207). The highest risk was in lung cancer, followed by head and neck, testes, bladder, and Hodgkin’s lymphoma.

According to Dr. Nemeroff, the association between depression and the risk of certain forms of cancer or with a poor cancer prognosis “may have to do with immune function. Depression is associated with a change in inflammatory markers that very likely control the microenvironment of the tumor.” For example, he said, if the depressed environment is associated with a marked increase in tumor necrosis factor, interleukin 6, and other inflammatory markers, “that probably contributes to the body’s ability to fight disease. Ironically, depression is associated with an increase in inflammation but a decreased in T cell function. Remember, there are two fundamental types of immunity: the antibody response and the cellular response. What’s odd about depression is that there’s an increase in inflammatory markers but a decrease in the ability of T cells to function in terms of cellular immunity.”

Dr. Nemeroff disclosed that he has served as a consultant and/or scientific adviser for numerous pharmaceutical companies. He has received research and grant support from the National Institutes of Health.

Owning an outdoor cat as a child is associated with an increased risk of psychotic experiences in adulthood – but only in males, new research suggests.

Investigators found male children who owned cats that went outside had a small, but significantly increased, risk of psychotic experiences in adulthood, compared with their counterparts who had no cat during childhood or who had an indoor cat.

Courtesy McGill University

The suspected culprit is not the cat itself but rather exposure to Toxoplasma gondii, a common parasite carried by rodents and sometimes found in cat feces. The study adds to a growing evidence showing exposure to T. gondii may be a risk factor for schizophrenia and other psychotic disorders.

“These are small pieces of evidence but it’s interesting to consider that there might be combinations of risk factors at play,” lead author Vincent Paquin, MD, psychiatry resident at McGill University, Montreal, said in an interview.

“And even if the magnitude of the risk is small at the individual level,” he added, “cats and Toxoplasma gondii are so present in our society that if we add up all these small potential effects then it becomes a potential public health question.”

The study was published online Jan. 30, 2022, in the Journal of Psychiatric Research.
 

Inconsistent evidence

T. gondii infects about 30% of the human population and is usually transmitted by cats. Most infections are asymptomatic, but T. gondii can cause toxoplasmosis in humans, which has been linked to increased risk of schizophrenia, suicide attempts, and more recently, mild cognitive impairment.

Although some studies show an association between cat ownership and increased risk of mental illness, the research findings have been inconsistent.

“The evidence has been mixed about the association between cat ownership and psychosis expression, so our approach was to consider whether specific factors or combinations of factors could explain this mixed evidence,” Dr. Paquin said.

For the study, 2206 individuals aged 18-40 years completed the Community Assessment of Psychic Experiences (CAPE-42) and a questionnaire to gather information about cat ownership at any time between birth and age 13 and if the cats lived exclusively indoors (nonhunting) or if they were allowed outside (rodent hunting).

Participants were also asked about the number of residential moves between birth and age 15, date and place of birth, lifetime history of head trauma, and tobacco smoking history.

Rodent-hunting cat ownership was associated with higher risk of psychosis in male participants, compared with owning no cat or a nonhunting cat. When the investigators added head trauma and residential moves to rodent-hunting cat ownership, psychosis risk was elevated in both men and women.

Independent of cat ownership, younger age, moving more than three times as a child, a history of head trauma, and being a smoker were all associated with higher psychosis risk.

Courtesy McGill University

The study wasn’t designed to explore potential biological mechanisms to explain the sex differences in psychosis risk seen among rodent-hunting cat owners, but “one possible explanation based on the animal model literature is that the neurobiological effects of parasitic exposure may be greater with male sex,” senior author Suzanne King, PhD, professor of psychiatry at McGill, said in an interview.

The new study is part of a larger, long-term project called EnviroGen, led by Dr. King, examining the environmental and genetic risk factors for schizophrenia.
 

Need for replication

Commenting on the findings, E. Fuller Torrey, MD, who was among the first researchers to identify a link between cat ownership, T. gondii infection, and schizophrenia, said the study is “an interesting addition to the studies of cat ownership in childhood as a risk factor for psychosis.”

Of the approximately 10 published studies on the topic, about half suggest a link between cat ownership and psychosis later in life, said Dr. Torrey, associate director for research at the Stanley Medical Research Institute in Rockville, Md.

“The Canadian study is interesting in that it is the first study that separates exposure to permanently indoor cats from cats that are allowed to go outdoors, and the results were positive only for outdoor cats,” Dr. Torrey said.

The study has limitations, Dr. Torrey added, including its retrospective design and the use of a self-report questionnaire to assess psychotic experiences in adulthood.

Also commenting on findings, James Kirkbride, PhD, professor of psychiatric and social epidemiology, University College London, noted the same limitations.

Dr. Kirkbride is the lead author of a 2017 study that showed no link between cat ownership and serious mental illness that included nearly 5,000 people born in 1991 or 1992 and followed until age 18. In this study, there was no link between psychosis and cat ownership during pregnancy or at ages 4 or 10 years.

“Researchers have long been fascinated with the idea that cat ownership may affect mental health. This paper may have them chasing their own tail,” Dr. Kirkbride said.

“Evidence of any association is limited to certain subgroups without a strong theoretical basis for why this may be the case,” he added. “The retrospective and cross-sectional nature of the survey also raise the possibility that the results are impacted by differential recall bias, as well as the broader issues of chance and unobserved confounding.”

Dr. King noted that recall bias is a limitation the researchers highlighted in their study, but “considering the exposures are relatively objective and factual, we do not believe the potential for recall bias is substantial.”

“Nonetheless, we strongly believe that replication of our results in prospective, population-representative cohorts will be crucial to making firmer conclusions,” he added.

The study was funded by grants from the Quebec Health Research Fund. The study authors and Dr. Kirkbride disclosed no relevant financial relationships.

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