Federal Practitioner

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disorder characterized by painful nodules, abscesses, and tunnels predominantly affecting intertriginous areas of the body.^1,2 The condition poses significant challenges in terms of diagnosis, treatment, and quality of life for affected individuals. Various systemic therapies have been explored to manage this debilitating condition, with the emergence of biologic agents offering hope for improved outcomes. In 2015, adalimumab (ADA) was the first biologic approved by the US Food and Drug Administration (FDA) for the treatment of HS, followed by secukinumab in 2023 and bimekizumab in 2024. However, the off-label use of other biologics and/or tumor necrosis factor inhibitors such as infliximab (IFX) has become common practice.³

Although these therapies have demonstrated promising results in the treatment of HS, their widespread use may be hindered by accessibility and cost barriers. Orenstein et al analyzed data from the IBM Explorys platform from 2015 to 2020 and found that only 1.8% of patients diagnosed with HS had been prescribed ADA or IFX.⁴ More recently, Garg et al examined IBM MarketScan and IBM US Medicaid data from 2015 to 2018 to evaluate trends in clinical care and treatment. The prevalence of ADA and IFX prescriptions among patients with HS ranged from 2.3% to 8.0% (ADA) and 0.7% to 0.9% (IFX) for patients with commercial insurance, and 1.4% to 4.8% (ADA) and 0.5% to 0.7% (IFX) for patients with Medicaid.⁵ Biologics are often expensive, and the high cost associated with these therapies has been identified as a significant barrier to access for patients with HS, particularly those who lack adequate insurance coverage or face financial constraints.⁶

Furthermore, these barriers, particularly the financial barriers, are potentially compounded by the demographics of patients most notably affected by HS. In the US, a disproportionate incidence of HS has been noted in specific groups and age ranges, including women, individuals aged 18 to 29 years, and Black individuals.⁴ Orenstein et al found a statistically significant difference in use of ADA and IFX biologics based on age, sex, and race.⁴

The aim of this study was to examine the use of 2 biologics (ADA and IFX) in the Veterans Health Administration (VHA), a unique population in which financial barriers are reduced due to the single-payer government health care system structure. This design allowed for improved isolation and evaluation of variation in ADA and/or IFX prescription rates by demographics and health-related factors among patients with HS. To our knowledge, no studies have analyzed these metrics within the VHA.

Methods

This retrospective, cross-sectional analysis of VHA patients used data from the US Department of Veterans Affairs (VA) Corporate Data Warehouse, a data repository that provides access to longitudinal national electronic health record data for all veterans receiving care through VHA facilities. This study received ethical approval from institutional review boards at the Minneapolis Veterans Affairs Health Care System and VA Salt Lake City Healthcare System. Patient information was deidentified, and patient consent was not required.

Patients with HS were identified using ≥ 1 International Classification of Diseases (ICD) diagnostic code: (ICD-9 [705.83] or ICD-10 [L73.2]) between January 1, 2011, and December 31, 2021. The study included patients aged ≥ 18 years as of January 1, 2011, with ≥ 2 patient encounters during the postdiagnosis follow-up period, and with ≥ 1 encounter 6 months postindex. Patients with a biologic prescription prior to HS diagnosis were excluded. For this study, the term biologics refers to ADA and/or IFX prescriptions, unless otherwise specified. Only ADA and IFX were included in this analysis because ADA, a tumor necrosis factor (TNF)-á inhibitor, was the only FDA-approved medication at the time of the search, and IFX is another common TNF-α inhibitor used for the treatment of HS.

Statistical Analysis

We calculated logistic regression using SAS 9.4 (SAS Institute, Cary, NC). For each variable, the univariate relationship with biologic prescriptions was examined first, followed by the multivariate relationship controlling for all other variables. The following variables were controlled for in the multivariate models and were chosen a priori: sex, age, race, ethnicity, US region, hospital setting, current or previous tobacco use, obesity (defined as body mass index [BMI] ≥ 30), and Charlson Comorbidity Index (CCI).⁷

Results

Using ICD codes, we identified 29,483 individuals with ≥ 1 HS diagnosis (Figure 1). Of those identified, 1537 patients (5.21%) had been prescribed ≥ 1 biologic. The cohort was predominantly White (60.56%), male (75.27%), obese (59.34%), and had a history of current or previous tobacco use (73.47%) (Table 1). There were significant adjusted differences in prescription rates among veterans with HS based on age, race, and BMI. Notably, there was an age-dependent reduction in the odds of being prescribed a biologic in patients with HS. Compared with patients aged 18 to 44 years, patients aged 45 to 64 years (adjusted odds ratio [aOR], 0.63; 95% CI, 0.54–0.74; P < .001) and patients aged ≥ 65 years (aOR, 0.36; 95% CI, 0.27–0.48; P < .001) had significantly lower odds of receiving a biologic prescription (Table 2). Compared with White patients with HS, Native Hawaiian (NH) or Pacific Islander (PI) patients were less likely to be prescribed a biologic (aOR, 0.23; 95% CI, 0.06–0.92; P = .04). Patients with obesity had significantly higher odds of receiving a biologic prescription compared with patients without obesity (aOR, 1.47; 95% CI, 1.27– 1.71; P < .001).

After adjusting for the variables listed in Table 1, there were no significant differences in biologic prescription rates for men compared with women (aOR, 0.97; 95% CI, 0.83-1.12; P = .68). We observed slight variations in biologic prescriptions between US regions (Midwest 5.0%, East 4.2%, South 5.8%, West 4.6%), none of which were significantly different in the fully adjusted model. No statistically significant differences were found in biologic prescriptions between urban and rural VA settings (5.4% vs 4.8%; aOR, 1.06; 95% CI, 0.90–1.24; P = .47). Tobacco use was not associated with the rate of biologic prescription receipt (aOR, 1.14; 95% CI, 0.97–1.34; P = .11). After adjusting for other variables (as outlined in Table 2), no significant differences were found between CCI of 0 and 1 (aOR, 0.97; 95% CI, 0.82–1.16; P = .77) or between CCI of 0 and 2 (aOR, 0.89; 95% CI, 0.74–1.07; P = .22).⁷

Discussion

The aim of the study was to ascertain potential discrepancies in biologic prescription patterns among patients with HS in the VHA by demographic and lifestyle behavior modifiers. Veteran cohorts are unique in composition, consisting predominantly of older White men within a single-payer health care system. The prevalence of biologic prescriptions in this population was low (5.2%), consistent with prior studies (1.8%–8.9%).^4,5

We found a significant difference in ADA/IFX prescription patterns between White patients and NH/PI patients (aOR, 0.23; 95% CI, 0.06-0.92; P = .04). Further replication of this result is needed due to the small number of NH/PI patients included in the study (n = 241). Notably, we did not find a significant difference in the odds of Black patients being prescribed a biologic compared with White patients (aOR, 1.07; 95% CI, 0.92–1.25; P = .38), consistent with prior studies.⁴

In line with prior studies, age was associated with the likelihood of receiving a biologic prescription.⁴ Using the multivariate model adjusting for variables listed in Table 1, including CCI, patients aged 45 to 64 years and > 64 years were less likely to be prescribed a biologic than patients aged 18 to 44 years. HS disease activity could be a potential confounding variable, as HS severity may subside in some people with increasing age or menopause.⁸

Because different regions in the US have different sociopolitical ideologies and governing legislation, we hypothesized that there may be dissimilarities in the prevalence rates of biologic prescribing across various US regions. However, no significant differences were found in prescription patterns among US regions or between rural and urban settings. Previous research has demonstrated discernible disparities in both dermatologic care and clinical outcomes based on hospital setting (ie, urban vs rural).^9-11

Tobacco use has been demonstrated to be associated with the development of HS.¹² In a large retrospective analysis, Garg et al reported increased odds of receiving a new HS diagnosis in known tobacco users (aOR, 1.9; 95% CI, 1.8–2.0).¹³ The extent to which tobacco use affects HS severity is less understood. While some studies have found an association between smoking and HS severity, other analyses have failed to find this association.^14,15 The effects of smoking cessation on the disease course of HS are unknown.¹⁶ This analysis, found no significant difference in prescriptions for biologics among patients with HS comparing current or previous tobacco users with nonusers.

There is a known positive correlation between increasing BMI and HS prevalence and severity that may be explained by the downstream effects of adipose tissue secretion of proinflammatory mediators and insulin resistance in the setting of chronic inflammation.¹² This analysis found that patients with HS and obesity were 1.47 times more likely to be prescribed a biologic than patients with HS without obesity, which may be confounded by increased HS severity among patients with obesity. The initial concern when analyzing tobacco use and obesity was that clinician bias may result in a decrease in the prevalence of biologic use in these demographics, which was not supported in this study.

Although we identified few disparities, the results demonstrated a substantial underutilization of biologic therapies (5.2%), similar to the other US civilian studies (1.8-8.9%).^4,5 While there is no current universal, standardized severity scoring system to evaluate HS (it is difficult to objectively define moderate to severe HS), estimates have shown that 40.3% to 65.8% of patients with HS have Hurley stage II or III.^17-19 Therefore, only a small percentage of patients with moderate to severe disease were prescribed the only FDA-approved medication during this time period. The persistence of this underutilization within a medical system that reduces financial barriers suggests that nonfinancial barriers have a notable role in the underutilization of biologics.

For instance, risk of adverse events, particularly lymphoma and infection, has been cited by patients as a reason to avoid biologics. Additionally, treatment fatigue reduced some patients’ willingness to try new treatments, as did lack of knowledge about treatment options.^6,20 Other reported barriers included the frequency of injections and fear of needles.⁶ Additionally, within the VA, ADA may require prior authorization at the local facility level.²¹ An established relationship with a dermatologist has been shown to significantly increase the odds of being prescribed a biologic medication in the face of these barriers.⁴ Future system-wide quality improvement initiatives could be implemented to identify patients with HS not followed by dermatology, with the goal of establishing care with a dermatologist.

Limitations

Limitations to this study include an inability to categorize HS disease severity and assess the degree to which disease severity confounded study findings, particularly in relation to tobacco use and obesity. The generalizability of this study is also limited because of the demographic characteristics of the veteran patient population, which is predominantly older, White, and male, whereas HS disproportionately affects younger, Black, and female individuals in the US.²² Despite these limitations, this study contributes valuable insights into the use of biologic therapies for veteran populations with HS using a national dataset.

Conclusions

This study was performed within a single-payer government medical system, likely reducing or removing the financial barriers that some patient populations may face when pursuing biologics for HS treatment. However, the prevalence of biologic use in this population was low overall (5.2%), suggesting that other factors play a role in the underutilization of biologics in HS. Consistent with previous studies, younger individuals were more likely to be prescribed a biologic, and no difference in prescription rates between Black and White patients was observed. Unlike previous studies, no significant difference in prescription rates between men and women was observed.

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disorder characterized by painful nodules, abscesses, and tunnels predominantly affecting intertriginous areas of the body.^1,2 The condition poses significant challenges in terms of diagnosis, treatment, and quality of life for affected individuals. Various systemic therapies have been explored to manage this debilitating condition, with the emergence of biologic agents offering hope for improved outcomes. In 2015, adalimumab (ADA) was the first biologic approved by the US Food and Drug Administration (FDA) for the treatment of HS, followed by secukinumab in 2023 and bimekizumab in 2024. However, the off-label use of other biologics and/or tumor necrosis factor inhibitors such as infliximab (IFX) has become common practice.³

Although these therapies have demonstrated promising results in the treatment of HS, their widespread use may be hindered by accessibility and cost barriers. Orenstein et al analyzed data from the IBM Explorys platform from 2015 to 2020 and found that only 1.8% of patients diagnosed with HS had been prescribed ADA or IFX.⁴ More recently, Garg et al examined IBM MarketScan and IBM US Medicaid data from 2015 to 2018 to evaluate trends in clinical care and treatment. The prevalence of ADA and IFX prescriptions among patients with HS ranged from 2.3% to 8.0% (ADA) and 0.7% to 0.9% (IFX) for patients with commercial insurance, and 1.4% to 4.8% (ADA) and 0.5% to 0.7% (IFX) for patients with Medicaid.⁵ Biologics are often expensive, and the high cost associated with these therapies has been identified as a significant barrier to access for patients with HS, particularly those who lack adequate insurance coverage or face financial constraints.⁶

Furthermore, these barriers, particularly the financial barriers, are potentially compounded by the demographics of patients most notably affected by HS. In the US, a disproportionate incidence of HS has been noted in specific groups and age ranges, including women, individuals aged 18 to 29 years, and Black individuals.⁴ Orenstein et al found a statistically significant difference in use of ADA and IFX biologics based on age, sex, and race.⁴

The aim of this study was to examine the use of 2 biologics (ADA and IFX) in the Veterans Health Administration (VHA), a unique population in which financial barriers are reduced due to the single-payer government health care system structure. This design allowed for improved isolation and evaluation of variation in ADA and/or IFX prescription rates by demographics and health-related factors among patients with HS. To our knowledge, no studies have analyzed these metrics within the VHA.

Methods

This retrospective, cross-sectional analysis of VHA patients used data from the US Department of Veterans Affairs (VA) Corporate Data Warehouse, a data repository that provides access to longitudinal national electronic health record data for all veterans receiving care through VHA facilities. This study received ethical approval from institutional review boards at the Minneapolis Veterans Affairs Health Care System and VA Salt Lake City Healthcare System. Patient information was deidentified, and patient consent was not required.

Patients with HS were identified using ≥ 1 International Classification of Diseases (ICD) diagnostic code: (ICD-9 [705.83] or ICD-10 [L73.2]) between January 1, 2011, and December 31, 2021. The study included patients aged ≥ 18 years as of January 1, 2011, with ≥ 2 patient encounters during the postdiagnosis follow-up period, and with ≥ 1 encounter 6 months postindex. Patients with a biologic prescription prior to HS diagnosis were excluded. For this study, the term biologics refers to ADA and/or IFX prescriptions, unless otherwise specified. Only ADA and IFX were included in this analysis because ADA, a tumor necrosis factor (TNF)-á inhibitor, was the only FDA-approved medication at the time of the search, and IFX is another common TNF-α inhibitor used for the treatment of HS.

Statistical Analysis

We calculated logistic regression using SAS 9.4 (SAS Institute, Cary, NC). For each variable, the univariate relationship with biologic prescriptions was examined first, followed by the multivariate relationship controlling for all other variables. The following variables were controlled for in the multivariate models and were chosen a priori: sex, age, race, ethnicity, US region, hospital setting, current or previous tobacco use, obesity (defined as body mass index [BMI] ≥ 30), and Charlson Comorbidity Index (CCI).⁷

Results

Using ICD codes, we identified 29,483 individuals with ≥ 1 HS diagnosis (Figure 1). Of those identified, 1537 patients (5.21%) had been prescribed ≥ 1 biologic. The cohort was predominantly White (60.56%), male (75.27%), obese (59.34%), and had a history of current or previous tobacco use (73.47%) (Table 1). There were significant adjusted differences in prescription rates among veterans with HS based on age, race, and BMI. Notably, there was an age-dependent reduction in the odds of being prescribed a biologic in patients with HS. Compared with patients aged 18 to 44 years, patients aged 45 to 64 years (adjusted odds ratio [aOR], 0.63; 95% CI, 0.54–0.74; P < .001) and patients aged ≥ 65 years (aOR, 0.36; 95% CI, 0.27–0.48; P < .001) had significantly lower odds of receiving a biologic prescription (Table 2). Compared with White patients with HS, Native Hawaiian (NH) or Pacific Islander (PI) patients were less likely to be prescribed a biologic (aOR, 0.23; 95% CI, 0.06–0.92; P = .04). Patients with obesity had significantly higher odds of receiving a biologic prescription compared with patients without obesity (aOR, 1.47; 95% CI, 1.27– 1.71; P < .001).

After adjusting for the variables listed in Table 1, there were no significant differences in biologic prescription rates for men compared with women (aOR, 0.97; 95% CI, 0.83-1.12; P = .68). We observed slight variations in biologic prescriptions between US regions (Midwest 5.0%, East 4.2%, South 5.8%, West 4.6%), none of which were significantly different in the fully adjusted model. No statistically significant differences were found in biologic prescriptions between urban and rural VA settings (5.4% vs 4.8%; aOR, 1.06; 95% CI, 0.90–1.24; P = .47). Tobacco use was not associated with the rate of biologic prescription receipt (aOR, 1.14; 95% CI, 0.97–1.34; P = .11). After adjusting for other variables (as outlined in Table 2), no significant differences were found between CCI of 0 and 1 (aOR, 0.97; 95% CI, 0.82–1.16; P = .77) or between CCI of 0 and 2 (aOR, 0.89; 95% CI, 0.74–1.07; P = .22).⁷

Discussion

The aim of the study was to ascertain potential discrepancies in biologic prescription patterns among patients with HS in the VHA by demographic and lifestyle behavior modifiers. Veteran cohorts are unique in composition, consisting predominantly of older White men within a single-payer health care system. The prevalence of biologic prescriptions in this population was low (5.2%), consistent with prior studies (1.8%–8.9%).^4,5

We found a significant difference in ADA/IFX prescription patterns between White patients and NH/PI patients (aOR, 0.23; 95% CI, 0.06-0.92; P = .04). Further replication of this result is needed due to the small number of NH/PI patients included in the study (n = 241). Notably, we did not find a significant difference in the odds of Black patients being prescribed a biologic compared with White patients (aOR, 1.07; 95% CI, 0.92–1.25; P = .38), consistent with prior studies.⁴

In line with prior studies, age was associated with the likelihood of receiving a biologic prescription.⁴ Using the multivariate model adjusting for variables listed in Table 1, including CCI, patients aged 45 to 64 years and > 64 years were less likely to be prescribed a biologic than patients aged 18 to 44 years. HS disease activity could be a potential confounding variable, as HS severity may subside in some people with increasing age or menopause.⁸

Because different regions in the US have different sociopolitical ideologies and governing legislation, we hypothesized that there may be dissimilarities in the prevalence rates of biologic prescribing across various US regions. However, no significant differences were found in prescription patterns among US regions or between rural and urban settings. Previous research has demonstrated discernible disparities in both dermatologic care and clinical outcomes based on hospital setting (ie, urban vs rural).^9-11

Tobacco use has been demonstrated to be associated with the development of HS.¹² In a large retrospective analysis, Garg et al reported increased odds of receiving a new HS diagnosis in known tobacco users (aOR, 1.9; 95% CI, 1.8–2.0).¹³ The extent to which tobacco use affects HS severity is less understood. While some studies have found an association between smoking and HS severity, other analyses have failed to find this association.^14,15 The effects of smoking cessation on the disease course of HS are unknown.¹⁶ This analysis, found no significant difference in prescriptions for biologics among patients with HS comparing current or previous tobacco users with nonusers.

There is a known positive correlation between increasing BMI and HS prevalence and severity that may be explained by the downstream effects of adipose tissue secretion of proinflammatory mediators and insulin resistance in the setting of chronic inflammation.¹² This analysis found that patients with HS and obesity were 1.47 times more likely to be prescribed a biologic than patients with HS without obesity, which may be confounded by increased HS severity among patients with obesity. The initial concern when analyzing tobacco use and obesity was that clinician bias may result in a decrease in the prevalence of biologic use in these demographics, which was not supported in this study.

Although we identified few disparities, the results demonstrated a substantial underutilization of biologic therapies (5.2%), similar to the other US civilian studies (1.8-8.9%).^4,5 While there is no current universal, standardized severity scoring system to evaluate HS (it is difficult to objectively define moderate to severe HS), estimates have shown that 40.3% to 65.8% of patients with HS have Hurley stage II or III.^17-19 Therefore, only a small percentage of patients with moderate to severe disease were prescribed the only FDA-approved medication during this time period. The persistence of this underutilization within a medical system that reduces financial barriers suggests that nonfinancial barriers have a notable role in the underutilization of biologics.

For instance, risk of adverse events, particularly lymphoma and infection, has been cited by patients as a reason to avoid biologics. Additionally, treatment fatigue reduced some patients’ willingness to try new treatments, as did lack of knowledge about treatment options.^6,20 Other reported barriers included the frequency of injections and fear of needles.⁶ Additionally, within the VA, ADA may require prior authorization at the local facility level.²¹ An established relationship with a dermatologist has been shown to significantly increase the odds of being prescribed a biologic medication in the face of these barriers.⁴ Future system-wide quality improvement initiatives could be implemented to identify patients with HS not followed by dermatology, with the goal of establishing care with a dermatologist.

Limitations

Limitations to this study include an inability to categorize HS disease severity and assess the degree to which disease severity confounded study findings, particularly in relation to tobacco use and obesity. The generalizability of this study is also limited because of the demographic characteristics of the veteran patient population, which is predominantly older, White, and male, whereas HS disproportionately affects younger, Black, and female individuals in the US.²² Despite these limitations, this study contributes valuable insights into the use of biologic therapies for veteran populations with HS using a national dataset.

Conclusions

This study was performed within a single-payer government medical system, likely reducing or removing the financial barriers that some patient populations may face when pursuing biologics for HS treatment. However, the prevalence of biologic use in this population was low overall (5.2%), suggesting that other factors play a role in the underutilization of biologics in HS. Consistent with previous studies, younger individuals were more likely to be prescribed a biologic, and no difference in prescription rates between Black and White patients was observed. Unlike previous studies, no significant difference in prescription rates between men and women was observed.

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disorder characterized by painful nodules, abscesses, and tunnels predominantly affecting intertriginous areas of the body.^1,2 The condition poses significant challenges in terms of diagnosis, treatment, and quality of life for affected individuals. Various systemic therapies have been explored to manage this debilitating condition, with the emergence of biologic agents offering hope for improved outcomes. In 2015, adalimumab (ADA) was the first biologic approved by the US Food and Drug Administration (FDA) for the treatment of HS, followed by secukinumab in 2023 and bimekizumab in 2024. However, the off-label use of other biologics and/or tumor necrosis factor inhibitors such as infliximab (IFX) has become common practice.³

Although these therapies have demonstrated promising results in the treatment of HS, their widespread use may be hindered by accessibility and cost barriers. Orenstein et al analyzed data from the IBM Explorys platform from 2015 to 2020 and found that only 1.8% of patients diagnosed with HS had been prescribed ADA or IFX.⁴ More recently, Garg et al examined IBM MarketScan and IBM US Medicaid data from 2015 to 2018 to evaluate trends in clinical care and treatment. The prevalence of ADA and IFX prescriptions among patients with HS ranged from 2.3% to 8.0% (ADA) and 0.7% to 0.9% (IFX) for patients with commercial insurance, and 1.4% to 4.8% (ADA) and 0.5% to 0.7% (IFX) for patients with Medicaid.⁵ Biologics are often expensive, and the high cost associated with these therapies has been identified as a significant barrier to access for patients with HS, particularly those who lack adequate insurance coverage or face financial constraints.⁶

Furthermore, these barriers, particularly the financial barriers, are potentially compounded by the demographics of patients most notably affected by HS. In the US, a disproportionate incidence of HS has been noted in specific groups and age ranges, including women, individuals aged 18 to 29 years, and Black individuals.⁴ Orenstein et al found a statistically significant difference in use of ADA and IFX biologics based on age, sex, and race.⁴

The aim of this study was to examine the use of 2 biologics (ADA and IFX) in the Veterans Health Administration (VHA), a unique population in which financial barriers are reduced due to the single-payer government health care system structure. This design allowed for improved isolation and evaluation of variation in ADA and/or IFX prescription rates by demographics and health-related factors among patients with HS. To our knowledge, no studies have analyzed these metrics within the VHA.

Methods

This retrospective, cross-sectional analysis of VHA patients used data from the US Department of Veterans Affairs (VA) Corporate Data Warehouse, a data repository that provides access to longitudinal national electronic health record data for all veterans receiving care through VHA facilities. This study received ethical approval from institutional review boards at the Minneapolis Veterans Affairs Health Care System and VA Salt Lake City Healthcare System. Patient information was deidentified, and patient consent was not required.

Patients with HS were identified using ≥ 1 International Classification of Diseases (ICD) diagnostic code: (ICD-9 [705.83] or ICD-10 [L73.2]) between January 1, 2011, and December 31, 2021. The study included patients aged ≥ 18 years as of January 1, 2011, with ≥ 2 patient encounters during the postdiagnosis follow-up period, and with ≥ 1 encounter 6 months postindex. Patients with a biologic prescription prior to HS diagnosis were excluded. For this study, the term biologics refers to ADA and/or IFX prescriptions, unless otherwise specified. Only ADA and IFX were included in this analysis because ADA, a tumor necrosis factor (TNF)-á inhibitor, was the only FDA-approved medication at the time of the search, and IFX is another common TNF-α inhibitor used for the treatment of HS.

Statistical Analysis

We calculated logistic regression using SAS 9.4 (SAS Institute, Cary, NC). For each variable, the univariate relationship with biologic prescriptions was examined first, followed by the multivariate relationship controlling for all other variables. The following variables were controlled for in the multivariate models and were chosen a priori: sex, age, race, ethnicity, US region, hospital setting, current or previous tobacco use, obesity (defined as body mass index [BMI] ≥ 30), and Charlson Comorbidity Index (CCI).⁷

Results

Using ICD codes, we identified 29,483 individuals with ≥ 1 HS diagnosis (Figure 1). Of those identified, 1537 patients (5.21%) had been prescribed ≥ 1 biologic. The cohort was predominantly White (60.56%), male (75.27%), obese (59.34%), and had a history of current or previous tobacco use (73.47%) (Table 1). There were significant adjusted differences in prescription rates among veterans with HS based on age, race, and BMI. Notably, there was an age-dependent reduction in the odds of being prescribed a biologic in patients with HS. Compared with patients aged 18 to 44 years, patients aged 45 to 64 years (adjusted odds ratio [aOR], 0.63; 95% CI, 0.54–0.74; P < .001) and patients aged ≥ 65 years (aOR, 0.36; 95% CI, 0.27–0.48; P < .001) had significantly lower odds of receiving a biologic prescription (Table 2). Compared with White patients with HS, Native Hawaiian (NH) or Pacific Islander (PI) patients were less likely to be prescribed a biologic (aOR, 0.23; 95% CI, 0.06–0.92; P = .04). Patients with obesity had significantly higher odds of receiving a biologic prescription compared with patients without obesity (aOR, 1.47; 95% CI, 1.27– 1.71; P < .001).

After adjusting for the variables listed in Table 1, there were no significant differences in biologic prescription rates for men compared with women (aOR, 0.97; 95% CI, 0.83-1.12; P = .68). We observed slight variations in biologic prescriptions between US regions (Midwest 5.0%, East 4.2%, South 5.8%, West 4.6%), none of which were significantly different in the fully adjusted model. No statistically significant differences were found in biologic prescriptions between urban and rural VA settings (5.4% vs 4.8%; aOR, 1.06; 95% CI, 0.90–1.24; P = .47). Tobacco use was not associated with the rate of biologic prescription receipt (aOR, 1.14; 95% CI, 0.97–1.34; P = .11). After adjusting for other variables (as outlined in Table 2), no significant differences were found between CCI of 0 and 1 (aOR, 0.97; 95% CI, 0.82–1.16; P = .77) or between CCI of 0 and 2 (aOR, 0.89; 95% CI, 0.74–1.07; P = .22).⁷

Discussion

The aim of the study was to ascertain potential discrepancies in biologic prescription patterns among patients with HS in the VHA by demographic and lifestyle behavior modifiers. Veteran cohorts are unique in composition, consisting predominantly of older White men within a single-payer health care system. The prevalence of biologic prescriptions in this population was low (5.2%), consistent with prior studies (1.8%–8.9%).^4,5

We found a significant difference in ADA/IFX prescription patterns between White patients and NH/PI patients (aOR, 0.23; 95% CI, 0.06-0.92; P = .04). Further replication of this result is needed due to the small number of NH/PI patients included in the study (n = 241). Notably, we did not find a significant difference in the odds of Black patients being prescribed a biologic compared with White patients (aOR, 1.07; 95% CI, 0.92–1.25; P = .38), consistent with prior studies.⁴

In line with prior studies, age was associated with the likelihood of receiving a biologic prescription.⁴ Using the multivariate model adjusting for variables listed in Table 1, including CCI, patients aged 45 to 64 years and > 64 years were less likely to be prescribed a biologic than patients aged 18 to 44 years. HS disease activity could be a potential confounding variable, as HS severity may subside in some people with increasing age or menopause.⁸

Because different regions in the US have different sociopolitical ideologies and governing legislation, we hypothesized that there may be dissimilarities in the prevalence rates of biologic prescribing across various US regions. However, no significant differences were found in prescription patterns among US regions or between rural and urban settings. Previous research has demonstrated discernible disparities in both dermatologic care and clinical outcomes based on hospital setting (ie, urban vs rural).^9-11

Tobacco use has been demonstrated to be associated with the development of HS.¹² In a large retrospective analysis, Garg et al reported increased odds of receiving a new HS diagnosis in known tobacco users (aOR, 1.9; 95% CI, 1.8–2.0).¹³ The extent to which tobacco use affects HS severity is less understood. While some studies have found an association between smoking and HS severity, other analyses have failed to find this association.^14,15 The effects of smoking cessation on the disease course of HS are unknown.¹⁶ This analysis, found no significant difference in prescriptions for biologics among patients with HS comparing current or previous tobacco users with nonusers.

There is a known positive correlation between increasing BMI and HS prevalence and severity that may be explained by the downstream effects of adipose tissue secretion of proinflammatory mediators and insulin resistance in the setting of chronic inflammation.¹² This analysis found that patients with HS and obesity were 1.47 times more likely to be prescribed a biologic than patients with HS without obesity, which may be confounded by increased HS severity among patients with obesity. The initial concern when analyzing tobacco use and obesity was that clinician bias may result in a decrease in the prevalence of biologic use in these demographics, which was not supported in this study.

Although we identified few disparities, the results demonstrated a substantial underutilization of biologic therapies (5.2%), similar to the other US civilian studies (1.8-8.9%).^4,5 While there is no current universal, standardized severity scoring system to evaluate HS (it is difficult to objectively define moderate to severe HS), estimates have shown that 40.3% to 65.8% of patients with HS have Hurley stage II or III.^17-19 Therefore, only a small percentage of patients with moderate to severe disease were prescribed the only FDA-approved medication during this time period. The persistence of this underutilization within a medical system that reduces financial barriers suggests that nonfinancial barriers have a notable role in the underutilization of biologics.

For instance, risk of adverse events, particularly lymphoma and infection, has been cited by patients as a reason to avoid biologics. Additionally, treatment fatigue reduced some patients’ willingness to try new treatments, as did lack of knowledge about treatment options.^6,20 Other reported barriers included the frequency of injections and fear of needles.⁶ Additionally, within the VA, ADA may require prior authorization at the local facility level.²¹ An established relationship with a dermatologist has been shown to significantly increase the odds of being prescribed a biologic medication in the face of these barriers.⁴ Future system-wide quality improvement initiatives could be implemented to identify patients with HS not followed by dermatology, with the goal of establishing care with a dermatologist.

Limitations

Limitations to this study include an inability to categorize HS disease severity and assess the degree to which disease severity confounded study findings, particularly in relation to tobacco use and obesity. The generalizability of this study is also limited because of the demographic characteristics of the veteran patient population, which is predominantly older, White, and male, whereas HS disproportionately affects younger, Black, and female individuals in the US.²² Despite these limitations, this study contributes valuable insights into the use of biologic therapies for veteran populations with HS using a national dataset.

Conclusions

This study was performed within a single-payer government medical system, likely reducing or removing the financial barriers that some patient populations may face when pursuing biologics for HS treatment. However, the prevalence of biologic use in this population was low overall (5.2%), suggesting that other factors play a role in the underutilization of biologics in HS. Consistent with previous studies, younger individuals were more likely to be prescribed a biologic, and no difference in prescription rates between Black and White patients was observed. Unlike previous studies, no significant difference in prescription rates between men and women was observed.

TOPLINE:

An artificial intelligence (AI) model, developed using stool images, accurately assessed whether a patient’s bowel preparation was sufficient for colonoscopy. The best version of the model achieved an area under the receiver operating characteristic curve (AUC) of 0.95, accuracy of 0.90, sensitivity of 0.93, and specificity of 0.86.

METHODOLOGY:

• Patients often need help during bowel preparation for colonoscopy, which increases staff workload; up to 20%-25% of colonoscopies are reported to be inadequately prepared. Researchers developed and tested an AI tool (AI-PREPOO) using stool images to assess whether patients were ready for colonoscopy.
• They conducted a multicenter observational study in Japan between 2022 and 2023 that included 37 patients scheduled for colonoscopy (median age, 57 years; 45.9% women).
• After starting consumption of a 2-liter polyethylene glycol solution, patients used smartphones to take photos of their stool in the toilet after each bowel movement and uploaded the images to a secure web server.
• The images were divided into training and test sets. Images were classified as “ready” for colonoscopy when the stool was clear or light yellow and watery with no solid content.
• Four image-recognition models based on different deep learning architectures were developed using transfer learning to classify readiness for colonoscopy.

TAKEAWAY:

• Researchers collected 282 stool images, with 141 classified as ready and 141 as not ready. Of these, 224 images were used for training (the number augmented to 2240 images) and 58 for testing.
• All four AI-PREPOO models showed high performance, with AUCs ranging from 0.92 to 0.95; pairwise differences in AUCs were not significant.
• The AI-PREPOO 1 model, based on the MobileNetV3-Small architecture, showed the most balanced performance, with an AUC of 0.95, accuracy of 0.90, sensitivity of 0.93, and specificity of 0.86 on the test set.
• During colonoscopy, all patients had a Boston Bowel Preparation Scale score of 6 or higher, indicating that “ready” images corresponded to an adequately prepared bowel.

IN PRACTICE:

“If implemented as a mobile application, our model would allow patients to quickly and independently assess bowel preparation adequacy, reducing reliance on nurses and alleviating embarrassment associated with sharing stool images. This approach could also lessen nurses’ workload by minimizing unnecessary inquiries and preventing excessive or insufficient bowel preparation due to uncertainty,” the authors wrote.

SOURCE:

This study was led by Kosuke Kojima, Graduate School of Medical and Dental Sciences, Niigata University in Niigata, Japan. It was published online in the Journal of Gastroenterology and Hepatology.

LIMITATIONS:

The small dataset limited generalizability and increased the risk for overfitting. In real-world practice, stool images might vary in lighting, angle, focus, zoom, and background; thus, a larger and more diverse dataset was needed. The model lacked external validation in an independent or prospective cohort.

DISCLOSURES:

This study received support from the Japanese Foundation for Research and Promotion of Endoscopy. The authors reported having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

An artificial intelligence (AI) model, developed using stool images, accurately assessed whether a patient’s bowel preparation was sufficient for colonoscopy. The best version of the model achieved an area under the receiver operating characteristic curve (AUC) of 0.95, accuracy of 0.90, sensitivity of 0.93, and specificity of 0.86.

METHODOLOGY:

• Patients often need help during bowel preparation for colonoscopy, which increases staff workload; up to 20%-25% of colonoscopies are reported to be inadequately prepared. Researchers developed and tested an AI tool (AI-PREPOO) using stool images to assess whether patients were ready for colonoscopy.
• They conducted a multicenter observational study in Japan between 2022 and 2023 that included 37 patients scheduled for colonoscopy (median age, 57 years; 45.9% women).
• After starting consumption of a 2-liter polyethylene glycol solution, patients used smartphones to take photos of their stool in the toilet after each bowel movement and uploaded the images to a secure web server.
• The images were divided into training and test sets. Images were classified as “ready” for colonoscopy when the stool was clear or light yellow and watery with no solid content.
• Four image-recognition models based on different deep learning architectures were developed using transfer learning to classify readiness for colonoscopy.

TAKEAWAY:

• Researchers collected 282 stool images, with 141 classified as ready and 141 as not ready. Of these, 224 images were used for training (the number augmented to 2240 images) and 58 for testing.
• All four AI-PREPOO models showed high performance, with AUCs ranging from 0.92 to 0.95; pairwise differences in AUCs were not significant.
• The AI-PREPOO 1 model, based on the MobileNetV3-Small architecture, showed the most balanced performance, with an AUC of 0.95, accuracy of 0.90, sensitivity of 0.93, and specificity of 0.86 on the test set.
• During colonoscopy, all patients had a Boston Bowel Preparation Scale score of 6 or higher, indicating that “ready” images corresponded to an adequately prepared bowel.

IN PRACTICE:

“If implemented as a mobile application, our model would allow patients to quickly and independently assess bowel preparation adequacy, reducing reliance on nurses and alleviating embarrassment associated with sharing stool images. This approach could also lessen nurses’ workload by minimizing unnecessary inquiries and preventing excessive or insufficient bowel preparation due to uncertainty,” the authors wrote.

SOURCE:

This study was led by Kosuke Kojima, Graduate School of Medical and Dental Sciences, Niigata University in Niigata, Japan. It was published online in the Journal of Gastroenterology and Hepatology.

LIMITATIONS:

The small dataset limited generalizability and increased the risk for overfitting. In real-world practice, stool images might vary in lighting, angle, focus, zoom, and background; thus, a larger and more diverse dataset was needed. The model lacked external validation in an independent or prospective cohort.

DISCLOSURES:

This study received support from the Japanese Foundation for Research and Promotion of Endoscopy. The authors reported having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

An artificial intelligence (AI) model, developed using stool images, accurately assessed whether a patient’s bowel preparation was sufficient for colonoscopy. The best version of the model achieved an area under the receiver operating characteristic curve (AUC) of 0.95, accuracy of 0.90, sensitivity of 0.93, and specificity of 0.86.

METHODOLOGY:

• Patients often need help during bowel preparation for colonoscopy, which increases staff workload; up to 20%-25% of colonoscopies are reported to be inadequately prepared. Researchers developed and tested an AI tool (AI-PREPOO) using stool images to assess whether patients were ready for colonoscopy.
• They conducted a multicenter observational study in Japan between 2022 and 2023 that included 37 patients scheduled for colonoscopy (median age, 57 years; 45.9% women).
• After starting consumption of a 2-liter polyethylene glycol solution, patients used smartphones to take photos of their stool in the toilet after each bowel movement and uploaded the images to a secure web server.
• The images were divided into training and test sets. Images were classified as “ready” for colonoscopy when the stool was clear or light yellow and watery with no solid content.
• Four image-recognition models based on different deep learning architectures were developed using transfer learning to classify readiness for colonoscopy.

TAKEAWAY:

• Researchers collected 282 stool images, with 141 classified as ready and 141 as not ready. Of these, 224 images were used for training (the number augmented to 2240 images) and 58 for testing.
• All four AI-PREPOO models showed high performance, with AUCs ranging from 0.92 to 0.95; pairwise differences in AUCs were not significant.
• The AI-PREPOO 1 model, based on the MobileNetV3-Small architecture, showed the most balanced performance, with an AUC of 0.95, accuracy of 0.90, sensitivity of 0.93, and specificity of 0.86 on the test set.
• During colonoscopy, all patients had a Boston Bowel Preparation Scale score of 6 or higher, indicating that “ready” images corresponded to an adequately prepared bowel.

IN PRACTICE:

“If implemented as a mobile application, our model would allow patients to quickly and independently assess bowel preparation adequacy, reducing reliance on nurses and alleviating embarrassment associated with sharing stool images. This approach could also lessen nurses’ workload by minimizing unnecessary inquiries and preventing excessive or insufficient bowel preparation due to uncertainty,” the authors wrote.

SOURCE:

This study was led by Kosuke Kojima, Graduate School of Medical and Dental Sciences, Niigata University in Niigata, Japan. It was published online in the Journal of Gastroenterology and Hepatology.

LIMITATIONS:

The small dataset limited generalizability and increased the risk for overfitting. In real-world practice, stool images might vary in lighting, angle, focus, zoom, and background; thus, a larger and more diverse dataset was needed. The model lacked external validation in an independent or prospective cohort.

DISCLOSURES:

This study received support from the Japanese Foundation for Research and Promotion of Endoscopy. The authors reported having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

France has authorized Ricimed, the first antibody-based treatment specifically indicated for acute ricin intoxication, providing clinicians with a targeted option beyond supportive care for exposure to one of the most lethal naturally occurring toxins.

Fabentech is a French biopharmaceutical company specializing in medical countermeasures against biological threats and infectious diseases.

The polyclonal antibody technology used in the development of Ricimed has received marketing authorization in France as a treatment for ricin poisoning. Ricin is a highly toxic natural substance that can cause death within hours to a few days of exposure.

Supported by the Ministry of Armed Forces and Veterans Affairs (Directorate General of Armaments [DGA] and Armed Forces Health Service) in France, Ricimed is the first approved antidote for ricin poisoning, a condition for which treatment was previously limited to supportive measures alone.

Historical Incident

One incident, in particular, remains etched in espionage history. On September 7, 1978 in London during the Cold War, Bulgarian dissident writer Georgi Markov, living in exile, was struck by the umbrella of a passer-by while waiting at a bus stop. He felt a slight sting. Four days later, he died in the hospital due to a sudden and unexplained illness. An autopsy revealed that he had been poisoned by a tiny metal pellet implanted at the tip of an umbrella containing ricin, a lethal toxin. The legend of the “Bulgarian umbrella,” later invoked in other assassination attempts, was born.

Since then, although Markov remains the only known individual to have been killed by ricin poisoning, this theoretically extremely toxic substance, which can be manufactured relatively easily from castor beans, a widely available plant, has continued to fascinate authors of thrillers and spy novels.

Numerous works of fiction depict characters who succumb to ricin poisoning. The toxin is notably portrayed as a favored weapon of the main character in the hit television series Breaking Bad.

However, ricin is not confined to the realm of science fiction. For several years, authorities in various countries have feared that extremist groups could carry out attacks using ricin. The threat has been taken particularly seriously since 2018, when a clandestine ricin laboratory operated by members of the Islamic State was dismantled in Germany. Since then, several similar attack plots have been thwarted.

This context triggered a race among major powers to develop an effective antidote as quickly as possible. In this effort, Fabentech has risen to a challenge.

“Having demonstrated its ability to target and then neutralize ricin before it causes irreparable damage, Ricimed is a treatment that works based on polyclonal antibodies and compensates for the absence of a vaccine or specific treatment,” Fabentech said in a press release.

The polyclonal antibody technology used by Fabentech offers potential for the development of antidotes against bioterrorist attacks and for the treatment of many infectious diseases.

Ricimed contributed to the deployment of a European health shield against intentional biological threats in France.

Military Backing

Speaking to Le Figaro, France’s oldest national newspaper, Fabentech CEO Sébastien Iva explained that ricin disrupts the body by halting cell function, while noting several other drug candidates in development at the firm.

Typically, the lungs sustain fatal damage. Our treatment interrupts this toxic process. In animals administered the antidote, we observed pulmonary function recovery, allowing survival.

Given that the possibility of terrorist attacks using ricin is considered a national security issue, Fabentech benefited from the support by the Ministry of the Armed Forces and the DGA and lasted nearly a decade of research and development work.

The granting of marketing authorisation was also supported by the French Armed Forces and welcomed by the French Minister of the Armed Forces, Catherine Vautrin, who previously served as France’s Minister of Labour, Health, and Solidarity.

“Supporting the development of companies in France capable of manufacturing antidotes against certain biological agents helps guarantee the operational superiority of our armed forces. Developing and producing such drugs when they do not yet exist on the market is also serving the nation and the public interest,” she said.

Although the threat posed by ricin remains hypothetical, Fabentech reports a strong interest from potential clients, with many countries seeking protection against possible bioterrorist attacks.

The DGA had already placed an order for several doses of Ricimed for deployment in France. For optimal effectiveness, the antidote must be administered within 6 hours of poisoning. Iva confirmed that multiple countries had already expressed interest in acquiring the antidote.

This story was translated from JIM, part of the Medscape Professional Network.

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

France has authorized Ricimed, the first antibody-based treatment specifically indicated for acute ricin intoxication, providing clinicians with a targeted option beyond supportive care for exposure to one of the most lethal naturally occurring toxins.

Fabentech is a French biopharmaceutical company specializing in medical countermeasures against biological threats and infectious diseases.

The polyclonal antibody technology used in the development of Ricimed has received marketing authorization in France as a treatment for ricin poisoning. Ricin is a highly toxic natural substance that can cause death within hours to a few days of exposure.

Supported by the Ministry of Armed Forces and Veterans Affairs (Directorate General of Armaments [DGA] and Armed Forces Health Service) in France, Ricimed is the first approved antidote for ricin poisoning, a condition for which treatment was previously limited to supportive measures alone.

Historical Incident

One incident, in particular, remains etched in espionage history. On September 7, 1978 in London during the Cold War, Bulgarian dissident writer Georgi Markov, living in exile, was struck by the umbrella of a passer-by while waiting at a bus stop. He felt a slight sting. Four days later, he died in the hospital due to a sudden and unexplained illness. An autopsy revealed that he had been poisoned by a tiny metal pellet implanted at the tip of an umbrella containing ricin, a lethal toxin. The legend of the “Bulgarian umbrella,” later invoked in other assassination attempts, was born.

Since then, although Markov remains the only known individual to have been killed by ricin poisoning, this theoretically extremely toxic substance, which can be manufactured relatively easily from castor beans, a widely available plant, has continued to fascinate authors of thrillers and spy novels.

Numerous works of fiction depict characters who succumb to ricin poisoning. The toxin is notably portrayed as a favored weapon of the main character in the hit television series Breaking Bad.

However, ricin is not confined to the realm of science fiction. For several years, authorities in various countries have feared that extremist groups could carry out attacks using ricin. The threat has been taken particularly seriously since 2018, when a clandestine ricin laboratory operated by members of the Islamic State was dismantled in Germany. Since then, several similar attack plots have been thwarted.

This context triggered a race among major powers to develop an effective antidote as quickly as possible. In this effort, Fabentech has risen to a challenge.

“Having demonstrated its ability to target and then neutralize ricin before it causes irreparable damage, Ricimed is a treatment that works based on polyclonal antibodies and compensates for the absence of a vaccine or specific treatment,” Fabentech said in a press release.

The polyclonal antibody technology used by Fabentech offers potential for the development of antidotes against bioterrorist attacks and for the treatment of many infectious diseases.

Ricimed contributed to the deployment of a European health shield against intentional biological threats in France.

Military Backing

Speaking to Le Figaro, France’s oldest national newspaper, Fabentech CEO Sébastien Iva explained that ricin disrupts the body by halting cell function, while noting several other drug candidates in development at the firm.

Typically, the lungs sustain fatal damage. Our treatment interrupts this toxic process. In animals administered the antidote, we observed pulmonary function recovery, allowing survival.

Given that the possibility of terrorist attacks using ricin is considered a national security issue, Fabentech benefited from the support by the Ministry of the Armed Forces and the DGA and lasted nearly a decade of research and development work.

The granting of marketing authorisation was also supported by the French Armed Forces and welcomed by the French Minister of the Armed Forces, Catherine Vautrin, who previously served as France’s Minister of Labour, Health, and Solidarity.

“Supporting the development of companies in France capable of manufacturing antidotes against certain biological agents helps guarantee the operational superiority of our armed forces. Developing and producing such drugs when they do not yet exist on the market is also serving the nation and the public interest,” she said.

Although the threat posed by ricin remains hypothetical, Fabentech reports a strong interest from potential clients, with many countries seeking protection against possible bioterrorist attacks.

The DGA had already placed an order for several doses of Ricimed for deployment in France. For optimal effectiveness, the antidote must be administered within 6 hours of poisoning. Iva confirmed that multiple countries had already expressed interest in acquiring the antidote.

This story was translated from JIM, part of the Medscape Professional Network.

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

France has authorized Ricimed, the first antibody-based treatment specifically indicated for acute ricin intoxication, providing clinicians with a targeted option beyond supportive care for exposure to one of the most lethal naturally occurring toxins.

Fabentech is a French biopharmaceutical company specializing in medical countermeasures against biological threats and infectious diseases.

The polyclonal antibody technology used in the development of Ricimed has received marketing authorization in France as a treatment for ricin poisoning. Ricin is a highly toxic natural substance that can cause death within hours to a few days of exposure.

Supported by the Ministry of Armed Forces and Veterans Affairs (Directorate General of Armaments [DGA] and Armed Forces Health Service) in France, Ricimed is the first approved antidote for ricin poisoning, a condition for which treatment was previously limited to supportive measures alone.

Historical Incident

One incident, in particular, remains etched in espionage history. On September 7, 1978 in London during the Cold War, Bulgarian dissident writer Georgi Markov, living in exile, was struck by the umbrella of a passer-by while waiting at a bus stop. He felt a slight sting. Four days later, he died in the hospital due to a sudden and unexplained illness. An autopsy revealed that he had been poisoned by a tiny metal pellet implanted at the tip of an umbrella containing ricin, a lethal toxin. The legend of the “Bulgarian umbrella,” later invoked in other assassination attempts, was born.

Since then, although Markov remains the only known individual to have been killed by ricin poisoning, this theoretically extremely toxic substance, which can be manufactured relatively easily from castor beans, a widely available plant, has continued to fascinate authors of thrillers and spy novels.

Numerous works of fiction depict characters who succumb to ricin poisoning. The toxin is notably portrayed as a favored weapon of the main character in the hit television series Breaking Bad.

However, ricin is not confined to the realm of science fiction. For several years, authorities in various countries have feared that extremist groups could carry out attacks using ricin. The threat has been taken particularly seriously since 2018, when a clandestine ricin laboratory operated by members of the Islamic State was dismantled in Germany. Since then, several similar attack plots have been thwarted.

This context triggered a race among major powers to develop an effective antidote as quickly as possible. In this effort, Fabentech has risen to a challenge.

“Having demonstrated its ability to target and then neutralize ricin before it causes irreparable damage, Ricimed is a treatment that works based on polyclonal antibodies and compensates for the absence of a vaccine or specific treatment,” Fabentech said in a press release.

The polyclonal antibody technology used by Fabentech offers potential for the development of antidotes against bioterrorist attacks and for the treatment of many infectious diseases.

Ricimed contributed to the deployment of a European health shield against intentional biological threats in France.

Military Backing

Speaking to Le Figaro, France’s oldest national newspaper, Fabentech CEO Sébastien Iva explained that ricin disrupts the body by halting cell function, while noting several other drug candidates in development at the firm.

Typically, the lungs sustain fatal damage. Our treatment interrupts this toxic process. In animals administered the antidote, we observed pulmonary function recovery, allowing survival.

Given that the possibility of terrorist attacks using ricin is considered a national security issue, Fabentech benefited from the support by the Ministry of the Armed Forces and the DGA and lasted nearly a decade of research and development work.

The granting of marketing authorisation was also supported by the French Armed Forces and welcomed by the French Minister of the Armed Forces, Catherine Vautrin, who previously served as France’s Minister of Labour, Health, and Solidarity.

“Supporting the development of companies in France capable of manufacturing antidotes against certain biological agents helps guarantee the operational superiority of our armed forces. Developing and producing such drugs when they do not yet exist on the market is also serving the nation and the public interest,” she said.

Although the threat posed by ricin remains hypothetical, Fabentech reports a strong interest from potential clients, with many countries seeking protection against possible bioterrorist attacks.

The DGA had already placed an order for several doses of Ricimed for deployment in France. For optimal effectiveness, the antidote must be administered within 6 hours of poisoning. Iva confirmed that multiple countries had already expressed interest in acquiring the antidote.

This story was translated from JIM, part of the Medscape Professional Network.

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

TOPLINE:

Veterans with dementia experienced significant reductions in time spent at home following emergency department (ED) visits, with a mean of 21.7 days away from home within 180 days of the index visit. ED admission was the strongest predictor of extended time away from home, followed by high frailty, an unmarried status, and lack of housing.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using Department of Veterans Affairs (VA) and Centers for Medicare & Medicaid Services administrative data of 51,707 veterans with dementia (mean age, 79.9 years; 97.6% men; 52.2% married individuals; 73% White individuals) who had an eligible Veterans Health Administration ED visit between October 2016 and September 2018.
• The primary outcome was home time, defined as days alive and not spent in institutional care settings during the 180 days following the index ED visit; secondary outcomes included ED revisits within 30 days of the index visit and 30-day mortality.

TAKEAWAY:

• Veterans experienced a mean of 21.7 days away from home within 180 days after the ED visit; 4.5% never returned home, and 18.2% spent the entire 180-day follow-up period at home. Patients admitted from the ED spent a mean of 34.2 days away from home within 180 days, whereas those discharged directly spent a mean of 13.6 days.
• ED admission had the strongest association with increased days away from home (rate ratio [RR], 3.18), followed by patient factors such as unhoused status (RR, 1.50), very high frailty (RR, 1.27), unmarried status — never married (RR, 1.24) or divorced, separated, or widowed (RR, 1.24) — and depression (RR, 1.13).
• Compared with the overall cohort, veterans with psychiatric concerns had the highest risk for extended time away from home (RR, 1.31), followed by those with nonspecific concerns and geriatric syndromes.
• Among all participants, 27.6% had a 30-day ED revisit, and 4% died within 30 days of the index visit. An admission was associated with a lower likelihood of a 30-day ED revisit (hazard ratio [HR], 0.75) but an increased likelihood of 30-day mortality (HR, 4.87).

IN PRACTICE:

"Home time offers a promising, patient-centered measure to align emergency care with patients' and care partners' goals and preferences to remain at home," the authors wrote. However, they emphasized that "refining its application — particularly in accounting for index hospitalizations and long-term care transitions — is critical to accurately capturing quality of care and long-term well-being."

SOURCE:

The study was led by Justine Seidenfeld, MD, MHs, Durham Veterans Affairs Health Care System, Durham, North Carolina. It was published online on December 29, 2025, in JAMA Network Open.

LIMITATIONS:

The study population of veterans aged 65-66 years may have had incomplete dementia confirmation as Medicare data were limited, and the predominantly male cohort limited generalizability. Marriage status served as an imperfect proxy for social and care partner support. The varying severity of dementia among participants could not be fully assessed using VA administrative data. Additionally, some highly emergent ED visits may have been inadvertently included if patients were not properly triaged, and very low-acuity visits could not be reliably identified due to the lack of validated approaches.

DISCLOSURES:

The study was supported by the National Institute on Aging-Veterans Affairs Mentored Physician and Clinical Psychologist Scientist Award in Alzheimer's Disease (AD) and AD-Related Dementias, a project grant from the National Institute on Aging, and a grant from the Veterans Affairs Office of Health Systems Research, Center of Innovation to Accelerate Discovery and Practice Transformation at the Durham VA Health Care System. Several authors reported receiving grants, personal fees, and payments for literature reviews from or serving as consultants for various organizations. Detailed disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Veterans with dementia experienced significant reductions in time spent at home following emergency department (ED) visits, with a mean of 21.7 days away from home within 180 days of the index visit. ED admission was the strongest predictor of extended time away from home, followed by high frailty, an unmarried status, and lack of housing.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using Department of Veterans Affairs (VA) and Centers for Medicare & Medicaid Services administrative data of 51,707 veterans with dementia (mean age, 79.9 years; 97.6% men; 52.2% married individuals; 73% White individuals) who had an eligible Veterans Health Administration ED visit between October 2016 and September 2018.
• The primary outcome was home time, defined as days alive and not spent in institutional care settings during the 180 days following the index ED visit; secondary outcomes included ED revisits within 30 days of the index visit and 30-day mortality.

TAKEAWAY:

• Veterans experienced a mean of 21.7 days away from home within 180 days after the ED visit; 4.5% never returned home, and 18.2% spent the entire 180-day follow-up period at home. Patients admitted from the ED spent a mean of 34.2 days away from home within 180 days, whereas those discharged directly spent a mean of 13.6 days.
• ED admission had the strongest association with increased days away from home (rate ratio [RR], 3.18), followed by patient factors such as unhoused status (RR, 1.50), very high frailty (RR, 1.27), unmarried status — never married (RR, 1.24) or divorced, separated, or widowed (RR, 1.24) — and depression (RR, 1.13).
• Compared with the overall cohort, veterans with psychiatric concerns had the highest risk for extended time away from home (RR, 1.31), followed by those with nonspecific concerns and geriatric syndromes.
• Among all participants, 27.6% had a 30-day ED revisit, and 4% died within 30 days of the index visit. An admission was associated with a lower likelihood of a 30-day ED revisit (hazard ratio [HR], 0.75) but an increased likelihood of 30-day mortality (HR, 4.87).

IN PRACTICE:

"Home time offers a promising, patient-centered measure to align emergency care with patients' and care partners' goals and preferences to remain at home," the authors wrote. However, they emphasized that "refining its application — particularly in accounting for index hospitalizations and long-term care transitions — is critical to accurately capturing quality of care and long-term well-being."

SOURCE:

The study was led by Justine Seidenfeld, MD, MHs, Durham Veterans Affairs Health Care System, Durham, North Carolina. It was published online on December 29, 2025, in JAMA Network Open.

LIMITATIONS:

The study population of veterans aged 65-66 years may have had incomplete dementia confirmation as Medicare data were limited, and the predominantly male cohort limited generalizability. Marriage status served as an imperfect proxy for social and care partner support. The varying severity of dementia among participants could not be fully assessed using VA administrative data. Additionally, some highly emergent ED visits may have been inadvertently included if patients were not properly triaged, and very low-acuity visits could not be reliably identified due to the lack of validated approaches.

DISCLOSURES:

The study was supported by the National Institute on Aging-Veterans Affairs Mentored Physician and Clinical Psychologist Scientist Award in Alzheimer's Disease (AD) and AD-Related Dementias, a project grant from the National Institute on Aging, and a grant from the Veterans Affairs Office of Health Systems Research, Center of Innovation to Accelerate Discovery and Practice Transformation at the Durham VA Health Care System. Several authors reported receiving grants, personal fees, and payments for literature reviews from or serving as consultants for various organizations. Detailed disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Veterans with dementia experienced significant reductions in time spent at home following emergency department (ED) visits, with a mean of 21.7 days away from home within 180 days of the index visit. ED admission was the strongest predictor of extended time away from home, followed by high frailty, an unmarried status, and lack of housing.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using Department of Veterans Affairs (VA) and Centers for Medicare & Medicaid Services administrative data of 51,707 veterans with dementia (mean age, 79.9 years; 97.6% men; 52.2% married individuals; 73% White individuals) who had an eligible Veterans Health Administration ED visit between October 2016 and September 2018.
• The primary outcome was home time, defined as days alive and not spent in institutional care settings during the 180 days following the index ED visit; secondary outcomes included ED revisits within 30 days of the index visit and 30-day mortality.

TAKEAWAY:

• Veterans experienced a mean of 21.7 days away from home within 180 days after the ED visit; 4.5% never returned home, and 18.2% spent the entire 180-day follow-up period at home. Patients admitted from the ED spent a mean of 34.2 days away from home within 180 days, whereas those discharged directly spent a mean of 13.6 days.
• ED admission had the strongest association with increased days away from home (rate ratio [RR], 3.18), followed by patient factors such as unhoused status (RR, 1.50), very high frailty (RR, 1.27), unmarried status — never married (RR, 1.24) or divorced, separated, or widowed (RR, 1.24) — and depression (RR, 1.13).
• Compared with the overall cohort, veterans with psychiatric concerns had the highest risk for extended time away from home (RR, 1.31), followed by those with nonspecific concerns and geriatric syndromes.
• Among all participants, 27.6% had a 30-day ED revisit, and 4% died within 30 days of the index visit. An admission was associated with a lower likelihood of a 30-day ED revisit (hazard ratio [HR], 0.75) but an increased likelihood of 30-day mortality (HR, 4.87).

IN PRACTICE:

"Home time offers a promising, patient-centered measure to align emergency care with patients' and care partners' goals and preferences to remain at home," the authors wrote. However, they emphasized that "refining its application — particularly in accounting for index hospitalizations and long-term care transitions — is critical to accurately capturing quality of care and long-term well-being."

SOURCE:

The study was led by Justine Seidenfeld, MD, MHs, Durham Veterans Affairs Health Care System, Durham, North Carolina. It was published online on December 29, 2025, in JAMA Network Open.

LIMITATIONS:

The study population of veterans aged 65-66 years may have had incomplete dementia confirmation as Medicare data were limited, and the predominantly male cohort limited generalizability. Marriage status served as an imperfect proxy for social and care partner support. The varying severity of dementia among participants could not be fully assessed using VA administrative data. Additionally, some highly emergent ED visits may have been inadvertently included if patients were not properly triaged, and very low-acuity visits could not be reliably identified due to the lack of validated approaches.

DISCLOSURES:

The study was supported by the National Institute on Aging-Veterans Affairs Mentored Physician and Clinical Psychologist Scientist Award in Alzheimer's Disease (AD) and AD-Related Dementias, a project grant from the National Institute on Aging, and a grant from the Veterans Affairs Office of Health Systems Research, Center of Innovation to Accelerate Discovery and Practice Transformation at the Durham VA Health Care System. Several authors reported receiving grants, personal fees, and payments for literature reviews from or serving as consultants for various organizations. Detailed disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

A new analysis found that high-deductible health plans were associated with worse overall survival and cancer-specific survival among cancer survivors. High-deductible plans, however, were not associated with worse overall survival among adults without a history of cancer.

METHODOLOGY:

• Previous studies have linked high-deductible health plans with decreased or delayed health utilization among cancer survivors and higher out-of-pocket costs. However, it’s not clear whether these plans influence cancer outcomes.
• In a cross-sectional study, researchers analyzed data from 147,254 respondents (aged 18 to 84 years) in the National Health Interview Survey from 2011 to 2018 and identified individuals with high-deductible plans — 2331 cancer survivors and 37,473 people without a history of cancer.
• The researchers acquired linked mortality files from the National Death Index, which included data on mortality events through the end of 2019.
• High-deductible health plans were identified through survey responses and defined as plans with yearly deductibles of at least $1200-$1350 for individuals or at least $2400-$2700 for families.
• The primary endpoints included overall survival and cancer-specific survival. Researchers adjusted for insurance status, marital status, sex, comorbidities, education, household income, geographic region, cancer site, and time since diagnosis.

TAKEAWAY:

• Among cancer survivors, having a high-deductible health plan was associated with worse overall survival (hazard ratio [HR], 1.46) and cancer-specific survival (HR, 1.34). However, sensitivity analyses incorporating time since diagnosis slightly attenuated the cancer-specific survival association (HR, 1.20; 95% CI, 0.92-1.55).
• Among adults without a history of cancer, having a high-deductible health plan was not associated with significantly worse overall survival (HR, 1.08; 95% CI, 0.96-1.21).
• General concerns over finances, worry about medical bills, cost-related delays, or forgone care, as well as cost-related underuse of medications were significant mediators of the associations between high-deductible health plan status and mortality outcomes among cancer survivors.
• High-deductible health plan status was also associated with worse cancer-specific survival among cancer survivors with incomes at least 400% of the federal poverty level (HR, 1.65; P for interaction = .03).

IN PRACTICE:

“These data suggest that insurance coverage that financially discourages medical care may financially discourage necessary care and ultimately worsen cancer outcomes,” the study authors wrote. “This danger appears to be unique to cancer survivors, as [high-deductible health plans] were not associated with survival among adults without a cancer history.”

SOURCE:

The study, led by Justin M. Barnes, MD, MS, Department of Radiation Oncology, Mayo Clinic in Rochester, Minnesota, was published online on January 29 in JAMA Network Open.

LIMITATIONS:

High-deductible health plan status was self-reported and may have been inaccurate for some individuals, with more than half of consumers being unsure about their annual deductible amount. The study lacked specific plan details and exact deductible amounts, and high-deductible health plan status was based on a single time point during survey participation. Additionally, researchers lacked information about cancer stage, cancer-directed therapies, recurrences, or complications, and cancer mortality could be from cancers diagnosed after survey participation.

DISCLOSURES:

Meera Ragavan, MD, MPH, disclosed receiving personal fees from Trial Library and AstraZeneca and grants from Merck, outside the submitted work. Other authors reported receiving personal fees from Costs of Care during the study. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

A new analysis found that high-deductible health plans were associated with worse overall survival and cancer-specific survival among cancer survivors. High-deductible plans, however, were not associated with worse overall survival among adults without a history of cancer.

METHODOLOGY:

• Previous studies have linked high-deductible health plans with decreased or delayed health utilization among cancer survivors and higher out-of-pocket costs. However, it’s not clear whether these plans influence cancer outcomes.
• In a cross-sectional study, researchers analyzed data from 147,254 respondents (aged 18 to 84 years) in the National Health Interview Survey from 2011 to 2018 and identified individuals with high-deductible plans — 2331 cancer survivors and 37,473 people without a history of cancer.
• The researchers acquired linked mortality files from the National Death Index, which included data on mortality events through the end of 2019.
• High-deductible health plans were identified through survey responses and defined as plans with yearly deductibles of at least $1200-$1350 for individuals or at least $2400-$2700 for families.
• The primary endpoints included overall survival and cancer-specific survival. Researchers adjusted for insurance status, marital status, sex, comorbidities, education, household income, geographic region, cancer site, and time since diagnosis.

TAKEAWAY:

• Among cancer survivors, having a high-deductible health plan was associated with worse overall survival (hazard ratio [HR], 1.46) and cancer-specific survival (HR, 1.34). However, sensitivity analyses incorporating time since diagnosis slightly attenuated the cancer-specific survival association (HR, 1.20; 95% CI, 0.92-1.55).
• Among adults without a history of cancer, having a high-deductible health plan was not associated with significantly worse overall survival (HR, 1.08; 95% CI, 0.96-1.21).
• General concerns over finances, worry about medical bills, cost-related delays, or forgone care, as well as cost-related underuse of medications were significant mediators of the associations between high-deductible health plan status and mortality outcomes among cancer survivors.
• High-deductible health plan status was also associated with worse cancer-specific survival among cancer survivors with incomes at least 400% of the federal poverty level (HR, 1.65; P for interaction = .03).

IN PRACTICE:

“These data suggest that insurance coverage that financially discourages medical care may financially discourage necessary care and ultimately worsen cancer outcomes,” the study authors wrote. “This danger appears to be unique to cancer survivors, as [high-deductible health plans] were not associated with survival among adults without a cancer history.”

SOURCE:

The study, led by Justin M. Barnes, MD, MS, Department of Radiation Oncology, Mayo Clinic in Rochester, Minnesota, was published online on January 29 in JAMA Network Open.

LIMITATIONS:

High-deductible health plan status was self-reported and may have been inaccurate for some individuals, with more than half of consumers being unsure about their annual deductible amount. The study lacked specific plan details and exact deductible amounts, and high-deductible health plan status was based on a single time point during survey participation. Additionally, researchers lacked information about cancer stage, cancer-directed therapies, recurrences, or complications, and cancer mortality could be from cancers diagnosed after survey participation.

DISCLOSURES:

Meera Ragavan, MD, MPH, disclosed receiving personal fees from Trial Library and AstraZeneca and grants from Merck, outside the submitted work. Other authors reported receiving personal fees from Costs of Care during the study. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

A new analysis found that high-deductible health plans were associated with worse overall survival and cancer-specific survival among cancer survivors. High-deductible plans, however, were not associated with worse overall survival among adults without a history of cancer.

METHODOLOGY:

• Previous studies have linked high-deductible health plans with decreased or delayed health utilization among cancer survivors and higher out-of-pocket costs. However, it’s not clear whether these plans influence cancer outcomes.
• In a cross-sectional study, researchers analyzed data from 147,254 respondents (aged 18 to 84 years) in the National Health Interview Survey from 2011 to 2018 and identified individuals with high-deductible plans — 2331 cancer survivors and 37,473 people without a history of cancer.
• The researchers acquired linked mortality files from the National Death Index, which included data on mortality events through the end of 2019.
• High-deductible health plans were identified through survey responses and defined as plans with yearly deductibles of at least $1200-$1350 for individuals or at least $2400-$2700 for families.
• The primary endpoints included overall survival and cancer-specific survival. Researchers adjusted for insurance status, marital status, sex, comorbidities, education, household income, geographic region, cancer site, and time since diagnosis.

TAKEAWAY:

• Among cancer survivors, having a high-deductible health plan was associated with worse overall survival (hazard ratio [HR], 1.46) and cancer-specific survival (HR, 1.34). However, sensitivity analyses incorporating time since diagnosis slightly attenuated the cancer-specific survival association (HR, 1.20; 95% CI, 0.92-1.55).
• Among adults without a history of cancer, having a high-deductible health plan was not associated with significantly worse overall survival (HR, 1.08; 95% CI, 0.96-1.21).
• General concerns over finances, worry about medical bills, cost-related delays, or forgone care, as well as cost-related underuse of medications were significant mediators of the associations between high-deductible health plan status and mortality outcomes among cancer survivors.
• High-deductible health plan status was also associated with worse cancer-specific survival among cancer survivors with incomes at least 400% of the federal poverty level (HR, 1.65; P for interaction = .03).

IN PRACTICE:

“These data suggest that insurance coverage that financially discourages medical care may financially discourage necessary care and ultimately worsen cancer outcomes,” the study authors wrote. “This danger appears to be unique to cancer survivors, as [high-deductible health plans] were not associated with survival among adults without a cancer history.”

SOURCE:

The study, led by Justin M. Barnes, MD, MS, Department of Radiation Oncology, Mayo Clinic in Rochester, Minnesota, was published online on January 29 in JAMA Network Open.

LIMITATIONS:

High-deductible health plan status was self-reported and may have been inaccurate for some individuals, with more than half of consumers being unsure about their annual deductible amount. The study lacked specific plan details and exact deductible amounts, and high-deductible health plan status was based on a single time point during survey participation. Additionally, researchers lacked information about cancer stage, cancer-directed therapies, recurrences, or complications, and cancer mortality could be from cancers diagnosed after survey participation.

DISCLOSURES:

Meera Ragavan, MD, MPH, disclosed receiving personal fees from Trial Library and AstraZeneca and grants from Merck, outside the submitted work. Other authors reported receiving personal fees from Costs of Care during the study. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Adding aminopeptidase N and polymeric immunoglobin receptor to a plasma biomarker panel of carbohydrate antigen 19-9 (CA19-9) and thrombospondin 2 (THBS2) enhanced the detection of early-stage pancreatic ductal adenocarcinoma (PDAC). At 95% specificity, the four-marker panel achieved more than 87% sensitivity for early-stage and more than 91% sensitivity for disease at any stage in two independent phase II studies. But prospective validation is required to ascertain clinical applicability.

METHODOLOGY:

• PDAC is associated with high mortality, but markedly improved survival is observed with early detection. Biomarkers such as CA19-9 are widely used to monitor PDAC treatment response but lack sensitivity and specificity for early-stage disease and can be influenced by patients’ genetics. A phase 2 study found THBS2 complements CA19‑9, with higher THBS2 levels linked to poorer prognosis in late-stage disease. This study uses phase 1 and 2 analyses to identify additional plasma biomarkers to improve early detection of PDAC.
• In phase 1 discovery, researchers used pooled plasma from 2 centers (University of Pennsylvania [Penn] and Mayo Clinic [Mayo]) to create representative samples for healthy control, chronic pancreatitis, early-stage PDAC (stage I/II), mid-stage PDAC (stage III), and late-stage PDAC.
• Plasma pools underwent abundant-protein depletion and were analyzed by two complementary mass spectrometry workflows; proteins consistently elevated in early PDAC (aminopeptidase N and polymeric immunoglobin receptor) were prioritized.
• Phase 2 validation measured CA19-9, THBS2, aminopeptidase N, and polymeric immunoglobin receptor levels by enzyme-linked immunosorbent assay in two blinded retrospective cohorts (Penn, n = 135; Mayo, n = 537). Overall, the Penn cohort included 59 patients with PDAC, 47 healthy control individuals, and 29 control patients with diseases (chronic pancreatitis, pancreatic cysts, pancreatic intraepithelial neoplasia, and intraductal papillary mucinous neoplasms). The Mayo cohort included 197 patients with PDAC, 140 healthy control individuals, and 200 control patients with diseases (intraductal papillary mucinous neoplasms, pancreatic neuroendocrine tumors, and chronic pancreatitis).
• Investigators developed univariate and multivariable logistic regression models to evaluate each marker alone and in combinations (2-, 3-, and 4-marker panels) for discriminating patients with PDAC from healthy control individuals and from control patients with diseases. Model performance was assessed using receiver-operating characteristic (ROC) curves and area under the ROC curve (AUC), and bootstrap methods were used to estimate 95% CIs.

TAKEAWAY:

• Comparing the performances of single markers for patients with stage I/II PDAC vs healthy control individuals, no single marker could outperform CA19-9 alone (AUC = 0.90 in both Penn and Mayo cohorts). Two-marker models (CA19-9 plus one marker) vs CA19-9 alone improved AUCs for both early- and all-stage PDACs in both cohorts.
• Looking at multivariable panels for patients with stage I/II PDAC vs healthy control individuals, the 3-marker panel of CA19-9/THBS2/ aminopeptidase N outperformed the other three-marker models, with AUCs of 0.96 (Penn) and 0.97 (Mayo). The 4-marker panel of CA19-9/THBS2/aminopeptidase N /polymeric immunoglobin receptor was the strongest performing panel with AUCs of 0.96 (Penn) and 0.97 (Mayo).
• In the Mayo cohort, the 4-marker panel (CA19-9/THBS2/aminopeptidase N/polymeric immunoglobin receptor) achieved AUCs of 0.87 and 0.91 for patients with stage I/II PDAC vs control patients with diseases and patients with stages I-IV PDAC vs control patients with diseases, respectively.
• At a specificity of 95%, “a plasma biomarker panel composed of CA19-9 (≥ 35 U/mL), THBS2 (≥ 42 ng/mL), aminopeptidase N (≥ 2995 ng/mL), and polymeric immunoglobin receptor (≥ 1800 ng/mL) yielded a sensitivity of 91.94% for all stages and 87.53% for early stage I/II PDAC detection,” the authors wrote.

IN PRACTICE:

“A panel composed of CA19-9/THBS2/aminopeptidase N/polymeric immunoglobin receptor may be suitable for early detection of PDAC based on results showing a high sensitivity and specificity in the larger Mayo phase II cohort but would require prediagnostic cohorts for verification,” the authors of the study wrote.

SOURCE:

The study, led by Brianna M. Krusen, Institute for Regenerative Medicine, Perelman School of Medicine at Penn, Philadelphia, was published online in Clinical Cancer Research.

LIMITATIONS:

The biomarker panel was evaluated on samples drawn at the time of diagnosis and has not yet been assessed in prediagnostic or high‑risk surveillance cohorts, which are necessary to establish its clinical performance.

DISCLOSURES:

The study was supported by the Penn Pancreatic Cancer Research Center, A Love for Life, and National Institutes of Health (NIH) Grant. Several authors reported receiving grants and other support from the NIH and various other sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Adding aminopeptidase N and polymeric immunoglobin receptor to a plasma biomarker panel of carbohydrate antigen 19-9 (CA19-9) and thrombospondin 2 (THBS2) enhanced the detection of early-stage pancreatic ductal adenocarcinoma (PDAC). At 95% specificity, the four-marker panel achieved more than 87% sensitivity for early-stage and more than 91% sensitivity for disease at any stage in two independent phase II studies. But prospective validation is required to ascertain clinical applicability.

METHODOLOGY:

• PDAC is associated with high mortality, but markedly improved survival is observed with early detection. Biomarkers such as CA19-9 are widely used to monitor PDAC treatment response but lack sensitivity and specificity for early-stage disease and can be influenced by patients’ genetics. A phase 2 study found THBS2 complements CA19‑9, with higher THBS2 levels linked to poorer prognosis in late-stage disease. This study uses phase 1 and 2 analyses to identify additional plasma biomarkers to improve early detection of PDAC.
• In phase 1 discovery, researchers used pooled plasma from 2 centers (University of Pennsylvania [Penn] and Mayo Clinic [Mayo]) to create representative samples for healthy control, chronic pancreatitis, early-stage PDAC (stage I/II), mid-stage PDAC (stage III), and late-stage PDAC.
• Plasma pools underwent abundant-protein depletion and were analyzed by two complementary mass spectrometry workflows; proteins consistently elevated in early PDAC (aminopeptidase N and polymeric immunoglobin receptor) were prioritized.
• Phase 2 validation measured CA19-9, THBS2, aminopeptidase N, and polymeric immunoglobin receptor levels by enzyme-linked immunosorbent assay in two blinded retrospective cohorts (Penn, n = 135; Mayo, n = 537). Overall, the Penn cohort included 59 patients with PDAC, 47 healthy control individuals, and 29 control patients with diseases (chronic pancreatitis, pancreatic cysts, pancreatic intraepithelial neoplasia, and intraductal papillary mucinous neoplasms). The Mayo cohort included 197 patients with PDAC, 140 healthy control individuals, and 200 control patients with diseases (intraductal papillary mucinous neoplasms, pancreatic neuroendocrine tumors, and chronic pancreatitis).
• Investigators developed univariate and multivariable logistic regression models to evaluate each marker alone and in combinations (2-, 3-, and 4-marker panels) for discriminating patients with PDAC from healthy control individuals and from control patients with diseases. Model performance was assessed using receiver-operating characteristic (ROC) curves and area under the ROC curve (AUC), and bootstrap methods were used to estimate 95% CIs.

TAKEAWAY:

• Comparing the performances of single markers for patients with stage I/II PDAC vs healthy control individuals, no single marker could outperform CA19-9 alone (AUC = 0.90 in both Penn and Mayo cohorts). Two-marker models (CA19-9 plus one marker) vs CA19-9 alone improved AUCs for both early- and all-stage PDACs in both cohorts.
• Looking at multivariable panels for patients with stage I/II PDAC vs healthy control individuals, the 3-marker panel of CA19-9/THBS2/ aminopeptidase N outperformed the other three-marker models, with AUCs of 0.96 (Penn) and 0.97 (Mayo). The 4-marker panel of CA19-9/THBS2/aminopeptidase N /polymeric immunoglobin receptor was the strongest performing panel with AUCs of 0.96 (Penn) and 0.97 (Mayo).
• In the Mayo cohort, the 4-marker panel (CA19-9/THBS2/aminopeptidase N/polymeric immunoglobin receptor) achieved AUCs of 0.87 and 0.91 for patients with stage I/II PDAC vs control patients with diseases and patients with stages I-IV PDAC vs control patients with diseases, respectively.
• At a specificity of 95%, “a plasma biomarker panel composed of CA19-9 (≥ 35 U/mL), THBS2 (≥ 42 ng/mL), aminopeptidase N (≥ 2995 ng/mL), and polymeric immunoglobin receptor (≥ 1800 ng/mL) yielded a sensitivity of 91.94% for all stages and 87.53% for early stage I/II PDAC detection,” the authors wrote.

IN PRACTICE:

“A panel composed of CA19-9/THBS2/aminopeptidase N/polymeric immunoglobin receptor may be suitable for early detection of PDAC based on results showing a high sensitivity and specificity in the larger Mayo phase II cohort but would require prediagnostic cohorts for verification,” the authors of the study wrote.

SOURCE:

The study, led by Brianna M. Krusen, Institute for Regenerative Medicine, Perelman School of Medicine at Penn, Philadelphia, was published online in Clinical Cancer Research.

LIMITATIONS:

The biomarker panel was evaluated on samples drawn at the time of diagnosis and has not yet been assessed in prediagnostic or high‑risk surveillance cohorts, which are necessary to establish its clinical performance.

DISCLOSURES:

The study was supported by the Penn Pancreatic Cancer Research Center, A Love for Life, and National Institutes of Health (NIH) Grant. Several authors reported receiving grants and other support from the NIH and various other sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Adding aminopeptidase N and polymeric immunoglobin receptor to a plasma biomarker panel of carbohydrate antigen 19-9 (CA19-9) and thrombospondin 2 (THBS2) enhanced the detection of early-stage pancreatic ductal adenocarcinoma (PDAC). At 95% specificity, the four-marker panel achieved more than 87% sensitivity for early-stage and more than 91% sensitivity for disease at any stage in two independent phase II studies. But prospective validation is required to ascertain clinical applicability.

METHODOLOGY:

• PDAC is associated with high mortality, but markedly improved survival is observed with early detection. Biomarkers such as CA19-9 are widely used to monitor PDAC treatment response but lack sensitivity and specificity for early-stage disease and can be influenced by patients’ genetics. A phase 2 study found THBS2 complements CA19‑9, with higher THBS2 levels linked to poorer prognosis in late-stage disease. This study uses phase 1 and 2 analyses to identify additional plasma biomarkers to improve early detection of PDAC.
• In phase 1 discovery, researchers used pooled plasma from 2 centers (University of Pennsylvania [Penn] and Mayo Clinic [Mayo]) to create representative samples for healthy control, chronic pancreatitis, early-stage PDAC (stage I/II), mid-stage PDAC (stage III), and late-stage PDAC.
• Plasma pools underwent abundant-protein depletion and were analyzed by two complementary mass spectrometry workflows; proteins consistently elevated in early PDAC (aminopeptidase N and polymeric immunoglobin receptor) were prioritized.
• Phase 2 validation measured CA19-9, THBS2, aminopeptidase N, and polymeric immunoglobin receptor levels by enzyme-linked immunosorbent assay in two blinded retrospective cohorts (Penn, n = 135; Mayo, n = 537). Overall, the Penn cohort included 59 patients with PDAC, 47 healthy control individuals, and 29 control patients with diseases (chronic pancreatitis, pancreatic cysts, pancreatic intraepithelial neoplasia, and intraductal papillary mucinous neoplasms). The Mayo cohort included 197 patients with PDAC, 140 healthy control individuals, and 200 control patients with diseases (intraductal papillary mucinous neoplasms, pancreatic neuroendocrine tumors, and chronic pancreatitis).
• Investigators developed univariate and multivariable logistic regression models to evaluate each marker alone and in combinations (2-, 3-, and 4-marker panels) for discriminating patients with PDAC from healthy control individuals and from control patients with diseases. Model performance was assessed using receiver-operating characteristic (ROC) curves and area under the ROC curve (AUC), and bootstrap methods were used to estimate 95% CIs.

TAKEAWAY:

• Comparing the performances of single markers for patients with stage I/II PDAC vs healthy control individuals, no single marker could outperform CA19-9 alone (AUC = 0.90 in both Penn and Mayo cohorts). Two-marker models (CA19-9 plus one marker) vs CA19-9 alone improved AUCs for both early- and all-stage PDACs in both cohorts.
• Looking at multivariable panels for patients with stage I/II PDAC vs healthy control individuals, the 3-marker panel of CA19-9/THBS2/ aminopeptidase N outperformed the other three-marker models, with AUCs of 0.96 (Penn) and 0.97 (Mayo). The 4-marker panel of CA19-9/THBS2/aminopeptidase N /polymeric immunoglobin receptor was the strongest performing panel with AUCs of 0.96 (Penn) and 0.97 (Mayo).
• In the Mayo cohort, the 4-marker panel (CA19-9/THBS2/aminopeptidase N/polymeric immunoglobin receptor) achieved AUCs of 0.87 and 0.91 for patients with stage I/II PDAC vs control patients with diseases and patients with stages I-IV PDAC vs control patients with diseases, respectively.
• At a specificity of 95%, “a plasma biomarker panel composed of CA19-9 (≥ 35 U/mL), THBS2 (≥ 42 ng/mL), aminopeptidase N (≥ 2995 ng/mL), and polymeric immunoglobin receptor (≥ 1800 ng/mL) yielded a sensitivity of 91.94% for all stages and 87.53% for early stage I/II PDAC detection,” the authors wrote.

IN PRACTICE:

“A panel composed of CA19-9/THBS2/aminopeptidase N/polymeric immunoglobin receptor may be suitable for early detection of PDAC based on results showing a high sensitivity and specificity in the larger Mayo phase II cohort but would require prediagnostic cohorts for verification,” the authors of the study wrote.

SOURCE:

The study, led by Brianna M. Krusen, Institute for Regenerative Medicine, Perelman School of Medicine at Penn, Philadelphia, was published online in Clinical Cancer Research.

LIMITATIONS:

The biomarker panel was evaluated on samples drawn at the time of diagnosis and has not yet been assessed in prediagnostic or high‑risk surveillance cohorts, which are necessary to establish its clinical performance.

DISCLOSURES:

The study was supported by the Penn Pancreatic Cancer Research Center, A Love for Life, and National Institutes of Health (NIH) Grant. Several authors reported receiving grants and other support from the NIH and various other sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

New research sheds light on how chronic heavy alcohol use may contribute to colorectal cancer (CRC) development and how quitting may lower the risk for precancerous colorectal adenomas.

In a large US cancer screening trial, current heavy drinkers — with an average lifetime alcohol intake of 14 or more drinks per week — had a 25% higher risk for CRC and an almost twofold higher risk for rectal cancer than light drinkers averaging less than one drink per week.

When the research team further considered drinking consistency, steady heavy drinking throughout adulthood was associated with a 91% higher risk for CRC than consistent light drinking. 

Additionally, no increased risk for CRC was found among former drinkers, and former drinkers were less likely than light drinkers to develop nonadvanced colorectal adenomas.

This analysis “adds to the growing amount of concerning literature showing that chronic heavy alcohol use can potentially contribute to colorectal cancer development,” Benjamin H. Levy III, MD, gastroenterologist and clinical associate of medicine at UChicago Medicine in Chicago, who wasn’t involved in the study, told Medscape Medical News.

The study’s co-senior author, Erikka Loftfield, PhD, MPH, also noted that the study “provides new evidence indicating that drinking cessation, compared to consistent light drinking, may lower adenoma risk.”

Current cancer prevention guidelines recommend limiting alcohol intake or ideally not drinking at all, and “our findings do not change this advice,” said Loftfield, with the National Cancer Institute (NCI) in Bethesda, Maryland. 

The study was published online on January 26 in the journal Cancer.

Addressing a Data Gap

Alcoholic beverages are classified as carcinogenic to humans and are causally associated with CRC, Loftfield told Medscape Medical News. However, much of the evidence for this comes from cohort studies that only measure recent drinking patterns, generally among older adults, at study baseline. Fewer studies have looked at how drinking over a person’s lifetime and alcohol consumption patterns relate to colorectal adenoma and CRC risk, she explained.

To address these gaps, Loftfield and colleagues leveraged data on alcohol intake gathered as part of the NCI’s Prostate, Long, Colorectal, and Ovarian Cancer Screening Trial.

Average lifetime alcohol intake was calculated as drinks per week from age 18 through study baseline, and drinking patterns were further classified based on consistency and intensity over time. 

During 20 years of follow-up, 1679 incident CRC cases occurred among 88,092 study participants. In multivariable-adjusted analyses, current heavy drinkers had a higher risk for CRC than those averaging less than one drink per week (hazard ratio [HR], 1.25), with the strongest association observed for rectal cancer (HR, 1.95).

“The increase in rectal cancer risk for heavy drinkers seen in this 20-year observational study was especially concerning,” Levy told Medscape Medical News.

What About Moderate Drinking?

Perhaps counterintuitively, moderate current drinkers (those consuming an average of 7 to less than 14 drinks per week) had a lower risk for CRC (HR, 0.79), especially distal colon cancer (HR, 0.64), than light drinkers.

Loftfield said that research in rodents suggests moderate alcohol intake may reduce inflammation and lower DNA damage, but it’s possible that the observed inverse association is due to residual confounding by unmeasured or poorly measured confounders, such as socioeconomic status.

She said it’s also important to note that the inverse association of moderate alcohol intake was strongest for distal colon cancer and in the screening arm of the trial. Those in the screening arm who screened positive with flexible sigmoidoscopy had polyps removed and were referred for colonoscopy during the trial period, making screening a potential intervention as well.

“Screening with flexible sigmoidoscopy has previously been found to decrease CRC incidence, specifically distal colon cancer, in this population. Thus, it is possible that better adherence to screening among moderate drinkers over the course of follow-up contributed to this finding,” Loftfield explained.

When looking at consistency of drinking, her team found that current drinkers who were consistent heavy drinkers throughout adulthood had a higher risk for CRC than consistent light drinkers (HR, 1.91).

Separate analyses of incident colorectal adenomas were directionally consistent with the CRC findings. These analyses included 12,327 participants with a negative baseline sigmoidoscopy, among whom 812 adenomas were detected on repeat screening.

Compared with current light drinkers, former drinkers had significantly lower odds of nonadvanced adenomas (odds ratio [OR], 0.58), but no significant association was observed for advanced adenomas (OR, 1.08; 95% CI, 0.62-1.90). The authors cautioned, however, that overall adenoma case numbers were limited, and estimates for advanced lesions were imprecise.

Educating Patients

Reached for comment, William Dahut, chief scientific officer for the American Cancer Society, told Medscape Medical News that this “very well done, large perspective study clearly demonstrates the significant increased risk of colorectal cancer for those that are heavy drinkers.”

He noted that the nearly twofold increased risk for rectal cancer among heavy drinkers “makes biological sense because the rectum is the area of the body where the toxins produced by alcohol potentially spend the most period of time.” 

Heavy drinkers are at the highest risk, Dahut said, and “for them, screenings are particularly important.”

Even with this growing body of evidence, Levy noted that many patients in America and worldwide “have not been educated yet about the potential carcinogenic dangers of chronic alcohol use.”

Levy recommended that physicians get “accurate social histories about alcohol use” and “spend several minutes educating patients about their increased risk of cancer and liver problems from heavy alcohol use.”

Dahut encouraged health providers to tell patients that the risk for CRC from alcohol is also based on one’s lifetime alcohol consumption, “not simply what they had last weekend.”

Overall, this important research study, along with the Surgeon General’s recent publication about Alcohol and Cancer Risk, will hopefully “encourage physicians to have important conversations about alcohol reduction with their patients,” Levy said. 

The study had no commercial funding. Loftfield, Dahult, and Levy reported no relevant disclosures.

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

New research sheds light on how chronic heavy alcohol use may contribute to colorectal cancer (CRC) development and how quitting may lower the risk for precancerous colorectal adenomas.

In a large US cancer screening trial, current heavy drinkers — with an average lifetime alcohol intake of 14 or more drinks per week — had a 25% higher risk for CRC and an almost twofold higher risk for rectal cancer than light drinkers averaging less than one drink per week.

When the research team further considered drinking consistency, steady heavy drinking throughout adulthood was associated with a 91% higher risk for CRC than consistent light drinking. 

Additionally, no increased risk for CRC was found among former drinkers, and former drinkers were less likely than light drinkers to develop nonadvanced colorectal adenomas.

This analysis “adds to the growing amount of concerning literature showing that chronic heavy alcohol use can potentially contribute to colorectal cancer development,” Benjamin H. Levy III, MD, gastroenterologist and clinical associate of medicine at UChicago Medicine in Chicago, who wasn’t involved in the study, told Medscape Medical News.

The study’s co-senior author, Erikka Loftfield, PhD, MPH, also noted that the study “provides new evidence indicating that drinking cessation, compared to consistent light drinking, may lower adenoma risk.”

Current cancer prevention guidelines recommend limiting alcohol intake or ideally not drinking at all, and “our findings do not change this advice,” said Loftfield, with the National Cancer Institute (NCI) in Bethesda, Maryland. 

The study was published online on January 26 in the journal Cancer.

Addressing a Data Gap

Alcoholic beverages are classified as carcinogenic to humans and are causally associated with CRC, Loftfield told Medscape Medical News. However, much of the evidence for this comes from cohort studies that only measure recent drinking patterns, generally among older adults, at study baseline. Fewer studies have looked at how drinking over a person’s lifetime and alcohol consumption patterns relate to colorectal adenoma and CRC risk, she explained.

To address these gaps, Loftfield and colleagues leveraged data on alcohol intake gathered as part of the NCI’s Prostate, Long, Colorectal, and Ovarian Cancer Screening Trial.

Average lifetime alcohol intake was calculated as drinks per week from age 18 through study baseline, and drinking patterns were further classified based on consistency and intensity over time. 

During 20 years of follow-up, 1679 incident CRC cases occurred among 88,092 study participants. In multivariable-adjusted analyses, current heavy drinkers had a higher risk for CRC than those averaging less than one drink per week (hazard ratio [HR], 1.25), with the strongest association observed for rectal cancer (HR, 1.95).

“The increase in rectal cancer risk for heavy drinkers seen in this 20-year observational study was especially concerning,” Levy told Medscape Medical News.

What About Moderate Drinking?

Perhaps counterintuitively, moderate current drinkers (those consuming an average of 7 to less than 14 drinks per week) had a lower risk for CRC (HR, 0.79), especially distal colon cancer (HR, 0.64), than light drinkers.

Loftfield said that research in rodents suggests moderate alcohol intake may reduce inflammation and lower DNA damage, but it’s possible that the observed inverse association is due to residual confounding by unmeasured or poorly measured confounders, such as socioeconomic status.

She said it’s also important to note that the inverse association of moderate alcohol intake was strongest for distal colon cancer and in the screening arm of the trial. Those in the screening arm who screened positive with flexible sigmoidoscopy had polyps removed and were referred for colonoscopy during the trial period, making screening a potential intervention as well.

“Screening with flexible sigmoidoscopy has previously been found to decrease CRC incidence, specifically distal colon cancer, in this population. Thus, it is possible that better adherence to screening among moderate drinkers over the course of follow-up contributed to this finding,” Loftfield explained.

When looking at consistency of drinking, her team found that current drinkers who were consistent heavy drinkers throughout adulthood had a higher risk for CRC than consistent light drinkers (HR, 1.91).

Separate analyses of incident colorectal adenomas were directionally consistent with the CRC findings. These analyses included 12,327 participants with a negative baseline sigmoidoscopy, among whom 812 adenomas were detected on repeat screening.

Compared with current light drinkers, former drinkers had significantly lower odds of nonadvanced adenomas (odds ratio [OR], 0.58), but no significant association was observed for advanced adenomas (OR, 1.08; 95% CI, 0.62-1.90). The authors cautioned, however, that overall adenoma case numbers were limited, and estimates for advanced lesions were imprecise.

Educating Patients

Reached for comment, William Dahut, chief scientific officer for the American Cancer Society, told Medscape Medical News that this “very well done, large perspective study clearly demonstrates the significant increased risk of colorectal cancer for those that are heavy drinkers.”

He noted that the nearly twofold increased risk for rectal cancer among heavy drinkers “makes biological sense because the rectum is the area of the body where the toxins produced by alcohol potentially spend the most period of time.” 

Heavy drinkers are at the highest risk, Dahut said, and “for them, screenings are particularly important.”

Even with this growing body of evidence, Levy noted that many patients in America and worldwide “have not been educated yet about the potential carcinogenic dangers of chronic alcohol use.”

Levy recommended that physicians get “accurate social histories about alcohol use” and “spend several minutes educating patients about their increased risk of cancer and liver problems from heavy alcohol use.”

Dahut encouraged health providers to tell patients that the risk for CRC from alcohol is also based on one’s lifetime alcohol consumption, “not simply what they had last weekend.”

Overall, this important research study, along with the Surgeon General’s recent publication about Alcohol and Cancer Risk, will hopefully “encourage physicians to have important conversations about alcohol reduction with their patients,” Levy said. 

The study had no commercial funding. Loftfield, Dahult, and Levy reported no relevant disclosures.

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

New research sheds light on how chronic heavy alcohol use may contribute to colorectal cancer (CRC) development and how quitting may lower the risk for precancerous colorectal adenomas.

In a large US cancer screening trial, current heavy drinkers — with an average lifetime alcohol intake of 14 or more drinks per week — had a 25% higher risk for CRC and an almost twofold higher risk for rectal cancer than light drinkers averaging less than one drink per week.

When the research team further considered drinking consistency, steady heavy drinking throughout adulthood was associated with a 91% higher risk for CRC than consistent light drinking. 

Additionally, no increased risk for CRC was found among former drinkers, and former drinkers were less likely than light drinkers to develop nonadvanced colorectal adenomas.

This analysis “adds to the growing amount of concerning literature showing that chronic heavy alcohol use can potentially contribute to colorectal cancer development,” Benjamin H. Levy III, MD, gastroenterologist and clinical associate of medicine at UChicago Medicine in Chicago, who wasn’t involved in the study, told Medscape Medical News.

The study’s co-senior author, Erikka Loftfield, PhD, MPH, also noted that the study “provides new evidence indicating that drinking cessation, compared to consistent light drinking, may lower adenoma risk.”

Current cancer prevention guidelines recommend limiting alcohol intake or ideally not drinking at all, and “our findings do not change this advice,” said Loftfield, with the National Cancer Institute (NCI) in Bethesda, Maryland. 

The study was published online on January 26 in the journal Cancer.

Addressing a Data Gap

Alcoholic beverages are classified as carcinogenic to humans and are causally associated with CRC, Loftfield told Medscape Medical News. However, much of the evidence for this comes from cohort studies that only measure recent drinking patterns, generally among older adults, at study baseline. Fewer studies have looked at how drinking over a person’s lifetime and alcohol consumption patterns relate to colorectal adenoma and CRC risk, she explained.

To address these gaps, Loftfield and colleagues leveraged data on alcohol intake gathered as part of the NCI’s Prostate, Long, Colorectal, and Ovarian Cancer Screening Trial.

Average lifetime alcohol intake was calculated as drinks per week from age 18 through study baseline, and drinking patterns were further classified based on consistency and intensity over time. 

During 20 years of follow-up, 1679 incident CRC cases occurred among 88,092 study participants. In multivariable-adjusted analyses, current heavy drinkers had a higher risk for CRC than those averaging less than one drink per week (hazard ratio [HR], 1.25), with the strongest association observed for rectal cancer (HR, 1.95).

“The increase in rectal cancer risk for heavy drinkers seen in this 20-year observational study was especially concerning,” Levy told Medscape Medical News.

What About Moderate Drinking?

Perhaps counterintuitively, moderate current drinkers (those consuming an average of 7 to less than 14 drinks per week) had a lower risk for CRC (HR, 0.79), especially distal colon cancer (HR, 0.64), than light drinkers.

Loftfield said that research in rodents suggests moderate alcohol intake may reduce inflammation and lower DNA damage, but it’s possible that the observed inverse association is due to residual confounding by unmeasured or poorly measured confounders, such as socioeconomic status.

She said it’s also important to note that the inverse association of moderate alcohol intake was strongest for distal colon cancer and in the screening arm of the trial. Those in the screening arm who screened positive with flexible sigmoidoscopy had polyps removed and were referred for colonoscopy during the trial period, making screening a potential intervention as well.

“Screening with flexible sigmoidoscopy has previously been found to decrease CRC incidence, specifically distal colon cancer, in this population. Thus, it is possible that better adherence to screening among moderate drinkers over the course of follow-up contributed to this finding,” Loftfield explained.

When looking at consistency of drinking, her team found that current drinkers who were consistent heavy drinkers throughout adulthood had a higher risk for CRC than consistent light drinkers (HR, 1.91).

Separate analyses of incident colorectal adenomas were directionally consistent with the CRC findings. These analyses included 12,327 participants with a negative baseline sigmoidoscopy, among whom 812 adenomas were detected on repeat screening.

Compared with current light drinkers, former drinkers had significantly lower odds of nonadvanced adenomas (odds ratio [OR], 0.58), but no significant association was observed for advanced adenomas (OR, 1.08; 95% CI, 0.62-1.90). The authors cautioned, however, that overall adenoma case numbers were limited, and estimates for advanced lesions were imprecise.

Educating Patients

Reached for comment, William Dahut, chief scientific officer for the American Cancer Society, told Medscape Medical News that this “very well done, large perspective study clearly demonstrates the significant increased risk of colorectal cancer for those that are heavy drinkers.”

He noted that the nearly twofold increased risk for rectal cancer among heavy drinkers “makes biological sense because the rectum is the area of the body where the toxins produced by alcohol potentially spend the most period of time.” 

Heavy drinkers are at the highest risk, Dahut said, and “for them, screenings are particularly important.”

Even with this growing body of evidence, Levy noted that many patients in America and worldwide “have not been educated yet about the potential carcinogenic dangers of chronic alcohol use.”

Levy recommended that physicians get “accurate social histories about alcohol use” and “spend several minutes educating patients about their increased risk of cancer and liver problems from heavy alcohol use.”

Dahut encouraged health providers to tell patients that the risk for CRC from alcohol is also based on one’s lifetime alcohol consumption, “not simply what they had last weekend.”

Overall, this important research study, along with the Surgeon General’s recent publication about Alcohol and Cancer Risk, will hopefully “encourage physicians to have important conversations about alcohol reduction with their patients,” Levy said. 

The study had no commercial funding. Loftfield, Dahult, and Levy reported no relevant disclosures.

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

TOPLINE:

New research examining recreational physical activity’s relationship with breast tissue composition, oxidative stress, and inflammation in adolescent girls revealed potential pathways for cancer risk reduction.

METHODOLOGY:

• Recent research shows 12-22% lower risk for breast cancer among highly active women, but the biological mechanisms explaining this remain unclear. Breast tissue composition, particularly mammographic density, is one of the strongest predictors of breast cancer risk, and breast tissue composition tracks across the life course.
• Researchers analyzed data from a population-based urban cohort of 191 Black/African American and Hispanic (Dominican) adolescent girls aged 11-20 years.
• Participants reported organized and unorganized recreational physical activity in the past week, categorized as none, < 2 hours, or ≥ 2 hours.
• Optical spectroscopy measured breast tissue composition through chromophores that are positively (percent water content and percent collagen content) or negatively (percent lipid content) correlated with mammographic breast density.
• Analysis included urinary concentrations of 15-F2-isoprostane for oxidative stress and blood biomarkers of inflammation including TNF-alpha, interleukin-6, and high-sensitivity C-reactive protein.

TAKEAWAY:

• Fifty-one percent of adolescent girls reported no past-week engagement in any type of recreational physical activity, with 73% reporting no participation in organized activities and 66% reporting no participation in unorganized activities.
• Girls engaging in at least 2 hours of organized recreational physical activity vs none showed lower percent water content in breast tissue (beta coefficient, -0.41; 95% CI, -0.77 to -0.05) and lower urinary concentrations of 15-F2-isoprostane (beta coefficient, -0.50; 95% CI, -0.95 to -0.05).
• Higher urinary concentrations of 15-F2-isoprostane were associated with higher percent collagen content in breast tissue (beta coefficient, 0.15; 95% CI, 0.00-0.31).
• No associations were found between recreational physical activity and inflammatory biomarkers, and these biomarkers showed no association with breast tissue composition after adjusting for percent body fat.

IN PRACTICE:

“These findings support that recreational physical activity is associated with breast tissue composition and oxidative stress in adolescent girls, independent of body fat. Additional longitudinal research is needed to understand the implications of these findings regarding subsequent breast cancer risk,” the authors of the study wrote.

SOURCE:

The study was led by Rebecca D. Kehm, PhD, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City. It was published online in Breast Cancer Research.

LIMITATIONS:

Recreational physical activity was assessed using self-reported data capturing only a 1-week timeframe, which may not fully reflect habitual patterns and is susceptible to measurement error. The cross-sectional nature of the analysis prevented establishing temporal relationships or causal inferences. The relatively small sample size limited statistical power, though researchers were able to detect modest associations. The findings may not be generalizable to populations with different demographics or higher levels of physical activity because recreational physical activity was notably low in this cohort. Additionally, while several validated biomarkers were examined, other mechanisms such as hormonal regulation and insulin sensitivity may also be important for understanding the relationship between adolescent physical activity and breast cancer risk.

DISCLOSURES:

The study received support from the National Institute of Environmental Health Sciences through grants U01ES026122 and P30ES009089, as well as grant ROICA263024 from the National Cancer Institute.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

New research examining recreational physical activity’s relationship with breast tissue composition, oxidative stress, and inflammation in adolescent girls revealed potential pathways for cancer risk reduction.

METHODOLOGY:

• Recent research shows 12-22% lower risk for breast cancer among highly active women, but the biological mechanisms explaining this remain unclear. Breast tissue composition, particularly mammographic density, is one of the strongest predictors of breast cancer risk, and breast tissue composition tracks across the life course.
• Researchers analyzed data from a population-based urban cohort of 191 Black/African American and Hispanic (Dominican) adolescent girls aged 11-20 years.
• Participants reported organized and unorganized recreational physical activity in the past week, categorized as none, < 2 hours, or ≥ 2 hours.
• Optical spectroscopy measured breast tissue composition through chromophores that are positively (percent water content and percent collagen content) or negatively (percent lipid content) correlated with mammographic breast density.
• Analysis included urinary concentrations of 15-F2-isoprostane for oxidative stress and blood biomarkers of inflammation including TNF-alpha, interleukin-6, and high-sensitivity C-reactive protein.

TAKEAWAY:

• Fifty-one percent of adolescent girls reported no past-week engagement in any type of recreational physical activity, with 73% reporting no participation in organized activities and 66% reporting no participation in unorganized activities.
• Girls engaging in at least 2 hours of organized recreational physical activity vs none showed lower percent water content in breast tissue (beta coefficient, -0.41; 95% CI, -0.77 to -0.05) and lower urinary concentrations of 15-F2-isoprostane (beta coefficient, -0.50; 95% CI, -0.95 to -0.05).
• Higher urinary concentrations of 15-F2-isoprostane were associated with higher percent collagen content in breast tissue (beta coefficient, 0.15; 95% CI, 0.00-0.31).
• No associations were found between recreational physical activity and inflammatory biomarkers, and these biomarkers showed no association with breast tissue composition after adjusting for percent body fat.

IN PRACTICE:

“These findings support that recreational physical activity is associated with breast tissue composition and oxidative stress in adolescent girls, independent of body fat. Additional longitudinal research is needed to understand the implications of these findings regarding subsequent breast cancer risk,” the authors of the study wrote.

SOURCE:

The study was led by Rebecca D. Kehm, PhD, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City. It was published online in Breast Cancer Research.

LIMITATIONS:

Recreational physical activity was assessed using self-reported data capturing only a 1-week timeframe, which may not fully reflect habitual patterns and is susceptible to measurement error. The cross-sectional nature of the analysis prevented establishing temporal relationships or causal inferences. The relatively small sample size limited statistical power, though researchers were able to detect modest associations. The findings may not be generalizable to populations with different demographics or higher levels of physical activity because recreational physical activity was notably low in this cohort. Additionally, while several validated biomarkers were examined, other mechanisms such as hormonal regulation and insulin sensitivity may also be important for understanding the relationship between adolescent physical activity and breast cancer risk.

DISCLOSURES:

The study received support from the National Institute of Environmental Health Sciences through grants U01ES026122 and P30ES009089, as well as grant ROICA263024 from the National Cancer Institute.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

New research examining recreational physical activity’s relationship with breast tissue composition, oxidative stress, and inflammation in adolescent girls revealed potential pathways for cancer risk reduction.

METHODOLOGY:

• Recent research shows 12-22% lower risk for breast cancer among highly active women, but the biological mechanisms explaining this remain unclear. Breast tissue composition, particularly mammographic density, is one of the strongest predictors of breast cancer risk, and breast tissue composition tracks across the life course.
• Researchers analyzed data from a population-based urban cohort of 191 Black/African American and Hispanic (Dominican) adolescent girls aged 11-20 years.
• Participants reported organized and unorganized recreational physical activity in the past week, categorized as none, < 2 hours, or ≥ 2 hours.
• Optical spectroscopy measured breast tissue composition through chromophores that are positively (percent water content and percent collagen content) or negatively (percent lipid content) correlated with mammographic breast density.
• Analysis included urinary concentrations of 15-F2-isoprostane for oxidative stress and blood biomarkers of inflammation including TNF-alpha, interleukin-6, and high-sensitivity C-reactive protein.

TAKEAWAY:

• Fifty-one percent of adolescent girls reported no past-week engagement in any type of recreational physical activity, with 73% reporting no participation in organized activities and 66% reporting no participation in unorganized activities.
• Girls engaging in at least 2 hours of organized recreational physical activity vs none showed lower percent water content in breast tissue (beta coefficient, -0.41; 95% CI, -0.77 to -0.05) and lower urinary concentrations of 15-F2-isoprostane (beta coefficient, -0.50; 95% CI, -0.95 to -0.05).
• Higher urinary concentrations of 15-F2-isoprostane were associated with higher percent collagen content in breast tissue (beta coefficient, 0.15; 95% CI, 0.00-0.31).
• No associations were found between recreational physical activity and inflammatory biomarkers, and these biomarkers showed no association with breast tissue composition after adjusting for percent body fat.

IN PRACTICE:

“These findings support that recreational physical activity is associated with breast tissue composition and oxidative stress in adolescent girls, independent of body fat. Additional longitudinal research is needed to understand the implications of these findings regarding subsequent breast cancer risk,” the authors of the study wrote.

SOURCE:

The study was led by Rebecca D. Kehm, PhD, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City. It was published online in Breast Cancer Research.

LIMITATIONS:

Recreational physical activity was assessed using self-reported data capturing only a 1-week timeframe, which may not fully reflect habitual patterns and is susceptible to measurement error. The cross-sectional nature of the analysis prevented establishing temporal relationships or causal inferences. The relatively small sample size limited statistical power, though researchers were able to detect modest associations. The findings may not be generalizable to populations with different demographics or higher levels of physical activity because recreational physical activity was notably low in this cohort. Additionally, while several validated biomarkers were examined, other mechanisms such as hormonal regulation and insulin sensitivity may also be important for understanding the relationship between adolescent physical activity and breast cancer risk.

DISCLOSURES:

The study received support from the National Institute of Environmental Health Sciences through grants U01ES026122 and P30ES009089, as well as grant ROICA263024 from the National Cancer Institute.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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