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Menopause an independent risk factor for schizophrenia relapse
Investigators studied a cohort of close to 62,000 people with SSDs, stratifying individuals by sex and age, and found that starting between the ages of 45 and 50 years – when the menopausal transition is underway – women were more frequently hospitalized for psychosis, compared with men and women younger than 45 years.
In addition, the protective effect of antipsychotic medication was highest in women younger than 45 years and lowest in women aged 45 years or older, even at higher doses.
“Women with schizophrenia who are older than 45 are a vulnerable group for relapse, and higher doses of antipsychotics are not the answer,” lead author Iris Sommer, MD, PhD, professor, department of neuroscience, University Medical Center of Groningen, the Netherlands, told this news organization.
The study was published online in Schizophrenia Bulletin.
Vulnerable period
There is an association between estrogen levels and disease severity throughout the life stages of women with SSDs, with lower estrogen levels associated with psychosis, for example, during low estrogenic phases of the menstrual cycle, the investigators note.
“After menopause, estrogen levels remain low, which is associated with a deterioration in the clinical course; therefore, women with SSD have sex-specific psychiatric needs that differ according to their life stage,” they add.
“Estrogens inhibit an important liver enzyme (cytochrome P-450 [CYP1A2]), which leads to higher blood levels of several antipsychotics like olanzapine and clozapine,” said Dr. Sommer. In addition, estrogens make the stomach less acidic, “leading to easier resorption of medication.”
As a clinician, Dr. Sommer said that she has “often witnessed a worsening of symptoms [of psychosis] after menopause.” As a researcher, she “knew that estrogens can have ameliorating effects on brain health, especially in schizophrenia.”
She and her colleagues were motivated to research the issue because there is a “remarkable paucity” of quantitative data on a “vulnerable period that all women with schizophrenia will experience.”
Detailed, quantitative data
The researchers sought to provide “detailed, quantitative data on life-stage dependent clinical changes occurring in women with SSD, using an intra-individual design to prevent confounding.”
They drew on data from a nationwide, register-based cohort study of all hospitalized patients with SSD between 1972 and 2014 in Finland (n = 61,889), with follow-up from Jan. 1, 1996, to Dec. 31, 2017.
People were stratified according to age (younger than 45 years and 45 years or older), with the same person contributing person-time to both age groups. The cohort was also subdivided into 5-year age groups, starting at age 20 years and ending at age 69 years.
The primary outcome measure was relapse (that is, inpatient hospitalization because of psychosis).
The researchers focused specifically on monotherapies, excluding time periods when two or more antipsychotics were used concomitantly. They also looked at antipsychotic nonuse periods.
Antipsychotic monotherapies were categorized into defined daily doses per day (DDDs/d):
- less than 0.4
- 0.4 to 0.6
- 0.6 to 0.9
- 0.9 to less than 1.1
- 1.1 to less than 1.4
- 1.4 to less than 1.6
- 1.6 or more
The researchers restricted the main analyses to the four most frequently used oral antipsychotic monotherapies: clozapine, olanzapine, quetiapine, and risperidone.
The turning tide
The cohort consisted of more men than women (31,104 vs. 30,785, respectively), with a mean (standard deviation) age of 49.8 (16.6) years in women vs. 43.6 (14.8) in men.
Among both sexes, olanzapine was the most prescribed antipsychotic (roughly one-quarter of patients). In women, the next most common antipsychotic was risperidone, followed by quetiapine and clozapine, whereas in men, the second most common antipsychotic was clozapine, followed by risperidone and quetiapine.
When the researchers compared men and women younger than 45 years, there were “few consistent differences” in proportions hospitalized for psychosis.
Starting at age 45 years and continuing through the oldest age group (65-69 years), higher proportions of women were hospitalized for psychosis, compared with their male peers (all Ps < .00001).
Women 45 or older had significantly higher risk for relapse associated with standard dose use, compared with the other groups.
When the researchers compared men and women older and younger than 45 years, women younger than 45 years showed lower adjusted hazard ratios (aHRs) at doses between of 0.6-0.9 DDDs/d, whereas for doses over 1.1 DDDs/d, women aged 45 years or older showed “remarkably higher” aHRs, compared with women younger than 45 years and men aged 45 years or older, with a difference that increased with increasing dose.
In women, the efficacy of the antipsychotics was decreased at these DDDs/d.
“We ... showed that antipsychotic monotherapy is most effective in preventing relapse in women below 45, as compared to women above that age, and also as compared to men of all ages,” the authors summarize. But after age 45 years, “the tide seems to turn for women,” compared with younger women and with men of the same age group.
One of several study limitations was the use of age as an estimation of menopausal status, they note.
Don’t just raise the dose
Commenting on the research, Mary Seeman, MD, professor emerita, department of psychiatry, University of Toronto, noted the study corroborates her group’s findings regarding the effect of menopause on antipsychotic response.
“When the efficacy of previously effective antipsychotic doses wanes at menopause, raising the dose is not the treatment of choice because it increases the risk of weight gain, cardiovascular, and cerebrovascular events,” said Dr. Seeman, who was not involved with the current research.
“Changing to an antipsychotic that is less affected by estrogen loss may work better,” she continued, noting that amisulpride and aripiprazole “work well post menopause.”
Additional interventions may include changing to a depot or skin-patch antipsychotic that “obviates first-pass metabolism,” adding hormone replacement or a selective estrogen receptor modulator or including phytoestrogens (bioidenticals) in the diet.
The study yields research recommendations, including comparing the effectiveness of different antipsychotics in postmenopausal women with SSDs, recruiting pre- and postmenopausal women in trials of antipsychotic drugs, and stratifying by hormonal status when analyzing results of antipsychotic trials, Dr. Seeman said.
This work was supported by the Finnish Ministry of Social Affairs and Health through the developmental fund for Niuvanniemi Hospital and the Academy of Finland. The Dutch Medical Research Association supported Dr. Sommer. Dr. Sommer declares no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Seeman declares no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Investigators studied a cohort of close to 62,000 people with SSDs, stratifying individuals by sex and age, and found that starting between the ages of 45 and 50 years – when the menopausal transition is underway – women were more frequently hospitalized for psychosis, compared with men and women younger than 45 years.
In addition, the protective effect of antipsychotic medication was highest in women younger than 45 years and lowest in women aged 45 years or older, even at higher doses.
“Women with schizophrenia who are older than 45 are a vulnerable group for relapse, and higher doses of antipsychotics are not the answer,” lead author Iris Sommer, MD, PhD, professor, department of neuroscience, University Medical Center of Groningen, the Netherlands, told this news organization.
The study was published online in Schizophrenia Bulletin.
Vulnerable period
There is an association between estrogen levels and disease severity throughout the life stages of women with SSDs, with lower estrogen levels associated with psychosis, for example, during low estrogenic phases of the menstrual cycle, the investigators note.
“After menopause, estrogen levels remain low, which is associated with a deterioration in the clinical course; therefore, women with SSD have sex-specific psychiatric needs that differ according to their life stage,” they add.
“Estrogens inhibit an important liver enzyme (cytochrome P-450 [CYP1A2]), which leads to higher blood levels of several antipsychotics like olanzapine and clozapine,” said Dr. Sommer. In addition, estrogens make the stomach less acidic, “leading to easier resorption of medication.”
As a clinician, Dr. Sommer said that she has “often witnessed a worsening of symptoms [of psychosis] after menopause.” As a researcher, she “knew that estrogens can have ameliorating effects on brain health, especially in schizophrenia.”
She and her colleagues were motivated to research the issue because there is a “remarkable paucity” of quantitative data on a “vulnerable period that all women with schizophrenia will experience.”
Detailed, quantitative data
The researchers sought to provide “detailed, quantitative data on life-stage dependent clinical changes occurring in women with SSD, using an intra-individual design to prevent confounding.”
They drew on data from a nationwide, register-based cohort study of all hospitalized patients with SSD between 1972 and 2014 in Finland (n = 61,889), with follow-up from Jan. 1, 1996, to Dec. 31, 2017.
People were stratified according to age (younger than 45 years and 45 years or older), with the same person contributing person-time to both age groups. The cohort was also subdivided into 5-year age groups, starting at age 20 years and ending at age 69 years.
The primary outcome measure was relapse (that is, inpatient hospitalization because of psychosis).
The researchers focused specifically on monotherapies, excluding time periods when two or more antipsychotics were used concomitantly. They also looked at antipsychotic nonuse periods.
Antipsychotic monotherapies were categorized into defined daily doses per day (DDDs/d):
- less than 0.4
- 0.4 to 0.6
- 0.6 to 0.9
- 0.9 to less than 1.1
- 1.1 to less than 1.4
- 1.4 to less than 1.6
- 1.6 or more
The researchers restricted the main analyses to the four most frequently used oral antipsychotic monotherapies: clozapine, olanzapine, quetiapine, and risperidone.
The turning tide
The cohort consisted of more men than women (31,104 vs. 30,785, respectively), with a mean (standard deviation) age of 49.8 (16.6) years in women vs. 43.6 (14.8) in men.
Among both sexes, olanzapine was the most prescribed antipsychotic (roughly one-quarter of patients). In women, the next most common antipsychotic was risperidone, followed by quetiapine and clozapine, whereas in men, the second most common antipsychotic was clozapine, followed by risperidone and quetiapine.
When the researchers compared men and women younger than 45 years, there were “few consistent differences” in proportions hospitalized for psychosis.
Starting at age 45 years and continuing through the oldest age group (65-69 years), higher proportions of women were hospitalized for psychosis, compared with their male peers (all Ps < .00001).
Women 45 or older had significantly higher risk for relapse associated with standard dose use, compared with the other groups.
When the researchers compared men and women older and younger than 45 years, women younger than 45 years showed lower adjusted hazard ratios (aHRs) at doses between of 0.6-0.9 DDDs/d, whereas for doses over 1.1 DDDs/d, women aged 45 years or older showed “remarkably higher” aHRs, compared with women younger than 45 years and men aged 45 years or older, with a difference that increased with increasing dose.
In women, the efficacy of the antipsychotics was decreased at these DDDs/d.
“We ... showed that antipsychotic monotherapy is most effective in preventing relapse in women below 45, as compared to women above that age, and also as compared to men of all ages,” the authors summarize. But after age 45 years, “the tide seems to turn for women,” compared with younger women and with men of the same age group.
One of several study limitations was the use of age as an estimation of menopausal status, they note.
Don’t just raise the dose
Commenting on the research, Mary Seeman, MD, professor emerita, department of psychiatry, University of Toronto, noted the study corroborates her group’s findings regarding the effect of menopause on antipsychotic response.
“When the efficacy of previously effective antipsychotic doses wanes at menopause, raising the dose is not the treatment of choice because it increases the risk of weight gain, cardiovascular, and cerebrovascular events,” said Dr. Seeman, who was not involved with the current research.
“Changing to an antipsychotic that is less affected by estrogen loss may work better,” she continued, noting that amisulpride and aripiprazole “work well post menopause.”
Additional interventions may include changing to a depot or skin-patch antipsychotic that “obviates first-pass metabolism,” adding hormone replacement or a selective estrogen receptor modulator or including phytoestrogens (bioidenticals) in the diet.
The study yields research recommendations, including comparing the effectiveness of different antipsychotics in postmenopausal women with SSDs, recruiting pre- and postmenopausal women in trials of antipsychotic drugs, and stratifying by hormonal status when analyzing results of antipsychotic trials, Dr. Seeman said.
This work was supported by the Finnish Ministry of Social Affairs and Health through the developmental fund for Niuvanniemi Hospital and the Academy of Finland. The Dutch Medical Research Association supported Dr. Sommer. Dr. Sommer declares no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Seeman declares no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Investigators studied a cohort of close to 62,000 people with SSDs, stratifying individuals by sex and age, and found that starting between the ages of 45 and 50 years – when the menopausal transition is underway – women were more frequently hospitalized for psychosis, compared with men and women younger than 45 years.
In addition, the protective effect of antipsychotic medication was highest in women younger than 45 years and lowest in women aged 45 years or older, even at higher doses.
“Women with schizophrenia who are older than 45 are a vulnerable group for relapse, and higher doses of antipsychotics are not the answer,” lead author Iris Sommer, MD, PhD, professor, department of neuroscience, University Medical Center of Groningen, the Netherlands, told this news organization.
The study was published online in Schizophrenia Bulletin.
Vulnerable period
There is an association between estrogen levels and disease severity throughout the life stages of women with SSDs, with lower estrogen levels associated with psychosis, for example, during low estrogenic phases of the menstrual cycle, the investigators note.
“After menopause, estrogen levels remain low, which is associated with a deterioration in the clinical course; therefore, women with SSD have sex-specific psychiatric needs that differ according to their life stage,” they add.
“Estrogens inhibit an important liver enzyme (cytochrome P-450 [CYP1A2]), which leads to higher blood levels of several antipsychotics like olanzapine and clozapine,” said Dr. Sommer. In addition, estrogens make the stomach less acidic, “leading to easier resorption of medication.”
As a clinician, Dr. Sommer said that she has “often witnessed a worsening of symptoms [of psychosis] after menopause.” As a researcher, she “knew that estrogens can have ameliorating effects on brain health, especially in schizophrenia.”
She and her colleagues were motivated to research the issue because there is a “remarkable paucity” of quantitative data on a “vulnerable period that all women with schizophrenia will experience.”
Detailed, quantitative data
The researchers sought to provide “detailed, quantitative data on life-stage dependent clinical changes occurring in women with SSD, using an intra-individual design to prevent confounding.”
They drew on data from a nationwide, register-based cohort study of all hospitalized patients with SSD between 1972 and 2014 in Finland (n = 61,889), with follow-up from Jan. 1, 1996, to Dec. 31, 2017.
People were stratified according to age (younger than 45 years and 45 years or older), with the same person contributing person-time to both age groups. The cohort was also subdivided into 5-year age groups, starting at age 20 years and ending at age 69 years.
The primary outcome measure was relapse (that is, inpatient hospitalization because of psychosis).
The researchers focused specifically on monotherapies, excluding time periods when two or more antipsychotics were used concomitantly. They also looked at antipsychotic nonuse periods.
Antipsychotic monotherapies were categorized into defined daily doses per day (DDDs/d):
- less than 0.4
- 0.4 to 0.6
- 0.6 to 0.9
- 0.9 to less than 1.1
- 1.1 to less than 1.4
- 1.4 to less than 1.6
- 1.6 or more
The researchers restricted the main analyses to the four most frequently used oral antipsychotic monotherapies: clozapine, olanzapine, quetiapine, and risperidone.
The turning tide
The cohort consisted of more men than women (31,104 vs. 30,785, respectively), with a mean (standard deviation) age of 49.8 (16.6) years in women vs. 43.6 (14.8) in men.
Among both sexes, olanzapine was the most prescribed antipsychotic (roughly one-quarter of patients). In women, the next most common antipsychotic was risperidone, followed by quetiapine and clozapine, whereas in men, the second most common antipsychotic was clozapine, followed by risperidone and quetiapine.
When the researchers compared men and women younger than 45 years, there were “few consistent differences” in proportions hospitalized for psychosis.
Starting at age 45 years and continuing through the oldest age group (65-69 years), higher proportions of women were hospitalized for psychosis, compared with their male peers (all Ps < .00001).
Women 45 or older had significantly higher risk for relapse associated with standard dose use, compared with the other groups.
When the researchers compared men and women older and younger than 45 years, women younger than 45 years showed lower adjusted hazard ratios (aHRs) at doses between of 0.6-0.9 DDDs/d, whereas for doses over 1.1 DDDs/d, women aged 45 years or older showed “remarkably higher” aHRs, compared with women younger than 45 years and men aged 45 years or older, with a difference that increased with increasing dose.
In women, the efficacy of the antipsychotics was decreased at these DDDs/d.
“We ... showed that antipsychotic monotherapy is most effective in preventing relapse in women below 45, as compared to women above that age, and also as compared to men of all ages,” the authors summarize. But after age 45 years, “the tide seems to turn for women,” compared with younger women and with men of the same age group.
One of several study limitations was the use of age as an estimation of menopausal status, they note.
Don’t just raise the dose
Commenting on the research, Mary Seeman, MD, professor emerita, department of psychiatry, University of Toronto, noted the study corroborates her group’s findings regarding the effect of menopause on antipsychotic response.
“When the efficacy of previously effective antipsychotic doses wanes at menopause, raising the dose is not the treatment of choice because it increases the risk of weight gain, cardiovascular, and cerebrovascular events,” said Dr. Seeman, who was not involved with the current research.
“Changing to an antipsychotic that is less affected by estrogen loss may work better,” she continued, noting that amisulpride and aripiprazole “work well post menopause.”
Additional interventions may include changing to a depot or skin-patch antipsychotic that “obviates first-pass metabolism,” adding hormone replacement or a selective estrogen receptor modulator or including phytoestrogens (bioidenticals) in the diet.
The study yields research recommendations, including comparing the effectiveness of different antipsychotics in postmenopausal women with SSDs, recruiting pre- and postmenopausal women in trials of antipsychotic drugs, and stratifying by hormonal status when analyzing results of antipsychotic trials, Dr. Seeman said.
This work was supported by the Finnish Ministry of Social Affairs and Health through the developmental fund for Niuvanniemi Hospital and the Academy of Finland. The Dutch Medical Research Association supported Dr. Sommer. Dr. Sommer declares no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Seeman declares no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM SCHIZOPHRENIA BULLETIN
Commentary: Potential new treatments in gastroesophageal adenocarcinoma, November 2022
The phase 2 FIGHT trial1 evaluated the role of bemarituzumab, an anti-FGFR2 antibody, in combination with chemotherapy during first-line treatment of advanced gastroesophageal adenocarcinoma. The primary endpoint of this trial was progression-free survival (PFS). This trial enrolled 155 patients with upper gastrointestinal tumors with FGFR2b overexpression (defined as at least 2+ by immunohistochemistry) or amplification on next-generation sequencing. About 30% of patients with HER2 nonpositive tumors (ie, those that would not qualify for treatment with the targeted agent trastuzumab) were eligible for participation. In the FIGHT trial, patients were randomized in a 1:1 ratio to receive either standard chemotherapy (folinic acid, fluorouracil, and oxaliplatin [FOLFOX]) or chemotherapy plus bemarituzumab. Patients in the experimental group were allowed to receive one dose of standard FOLFOX chemotherapy while biomarker testing was ongoing.
With a median follow-up time of 10.9 moths, PFS was numerically prolonged in the bemarituzumab group (9.5 vs 7.4 months), but it did not reach statistical significance (P = .073). Overall survival (OS) was improved in the experimental group (not reached vs 12.9 months; P = .027). With a longer follow-up of 12.5 months, in post hoc exploratory analysis, OS was significantly longer in the experimental group (19.2 vs 13.5 months; hazard ratio 0.60, P = .027). The rate of serious adverse events was similar between the two groups. However, it is important to note ocular toxicities associated with bemarituzumab treatment. Corneal adverse events were seen in 67% of patients in the experimental group, with 24% of patients experiencing grade 3 events. Moreover, 26% of patients discontinued bemarituzumab because of corneal adverse events.
Overall, this phase 2 trial demonstrated that FGFR2b is emerging as an important biomarker and target in patients with advanced gastroesophageal adenocarcinoma. Ongoing phase 3 trials (FORTITUDE-101 with FOLFOX [NCT05052801] and FORTITUDE-102 with FOLFOX and nivolumab [NCT05111626]) hopefully will confirm the early results seen in the FIGHT trial. Awareness and early attention to treatment-associated toxicities will be critical for the potential future incorporation of bemarituzumab into clinical practice.
A study by Ramos‐Santillan and colleagues explored whether the order of treatment modalities matter in the management of early-stage gastric cancer. Typically, perioperative chemotherapy (both neoadjuvant and adjuvant) is used during treatment of early-stage gastric cancer, which is usually defined as at least cT2N0 or cTxN+ disease. In this study, multivariable Cox regression analyses were performed on propensity score-matched cohorts. The study analyzed outcomes of 11,984 patients who were identified using the US National Cancer Database and treated between 2005 and 2014. The results revealed that patients who had stage I disease had better outcomes with upfront resection followed by adjuvant therapy. Patients with stage III disease did better with a neoadjuvant approach, whereas patients with stage II disease had similar outcomes regardless of chemotherapy timing. This research has the limitations inherent to the retrospective nature of the analysis and lack of prospective enrollment and controls. However, it does suggest that there may be a fraction of patients who should be treated with upfront resection. For incorporation of this change into standard practice, the question of therapy sequencing should be answered in a randomized prospective trial that incorporates the most updated systemic therapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel [FLOT]) into its design.
Chemotherapy continues to play a critical role during first-line treatment of advanced esophageal and gastric adenocarcinoma. Triple chemotherapy regimens have been known to have increased efficacy in this setting, but their use has been limited by associated toxicities. A study by Nguyen and colleagues evaluated the TCX regimen (paclitaxel, carboplatin, and capecitabine) during first-line treatment of advanced gastric cancer. This regimen is similar to other triple chemotherapy regimens, such as FLOT and DCF (docetaxel, cisplatin, and fluorouracil), which have proven activity in this disease. This prospective phase 2 trial enrolled 83 patients. The median PFS (9.3 months) and OS (17 months) compared favorably with historical references. The regimen had expected adverse events, with cytopenias and fatigue being the most frequently reported. On the basis of the reported safety and efficacy, TCX has potential to be used as a chemotherapy backbone in future trials, but larger trials are needed to confirm the phase 2 trial results.
References
Wainberg ZA, Enzinger PC, Kang YK, et al. Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): A randomised, double-blind, placebo-controlled, phase 2 study. Lancet Oncol. 2022 Oct 13. Doi: 10.1016/S1470-2045(22)00603-9
The phase 2 FIGHT trial1 evaluated the role of bemarituzumab, an anti-FGFR2 antibody, in combination with chemotherapy during first-line treatment of advanced gastroesophageal adenocarcinoma. The primary endpoint of this trial was progression-free survival (PFS). This trial enrolled 155 patients with upper gastrointestinal tumors with FGFR2b overexpression (defined as at least 2+ by immunohistochemistry) or amplification on next-generation sequencing. About 30% of patients with HER2 nonpositive tumors (ie, those that would not qualify for treatment with the targeted agent trastuzumab) were eligible for participation. In the FIGHT trial, patients were randomized in a 1:1 ratio to receive either standard chemotherapy (folinic acid, fluorouracil, and oxaliplatin [FOLFOX]) or chemotherapy plus bemarituzumab. Patients in the experimental group were allowed to receive one dose of standard FOLFOX chemotherapy while biomarker testing was ongoing.
With a median follow-up time of 10.9 moths, PFS was numerically prolonged in the bemarituzumab group (9.5 vs 7.4 months), but it did not reach statistical significance (P = .073). Overall survival (OS) was improved in the experimental group (not reached vs 12.9 months; P = .027). With a longer follow-up of 12.5 months, in post hoc exploratory analysis, OS was significantly longer in the experimental group (19.2 vs 13.5 months; hazard ratio 0.60, P = .027). The rate of serious adverse events was similar between the two groups. However, it is important to note ocular toxicities associated with bemarituzumab treatment. Corneal adverse events were seen in 67% of patients in the experimental group, with 24% of patients experiencing grade 3 events. Moreover, 26% of patients discontinued bemarituzumab because of corneal adverse events.
Overall, this phase 2 trial demonstrated that FGFR2b is emerging as an important biomarker and target in patients with advanced gastroesophageal adenocarcinoma. Ongoing phase 3 trials (FORTITUDE-101 with FOLFOX [NCT05052801] and FORTITUDE-102 with FOLFOX and nivolumab [NCT05111626]) hopefully will confirm the early results seen in the FIGHT trial. Awareness and early attention to treatment-associated toxicities will be critical for the potential future incorporation of bemarituzumab into clinical practice.
A study by Ramos‐Santillan and colleagues explored whether the order of treatment modalities matter in the management of early-stage gastric cancer. Typically, perioperative chemotherapy (both neoadjuvant and adjuvant) is used during treatment of early-stage gastric cancer, which is usually defined as at least cT2N0 or cTxN+ disease. In this study, multivariable Cox regression analyses were performed on propensity score-matched cohorts. The study analyzed outcomes of 11,984 patients who were identified using the US National Cancer Database and treated between 2005 and 2014. The results revealed that patients who had stage I disease had better outcomes with upfront resection followed by adjuvant therapy. Patients with stage III disease did better with a neoadjuvant approach, whereas patients with stage II disease had similar outcomes regardless of chemotherapy timing. This research has the limitations inherent to the retrospective nature of the analysis and lack of prospective enrollment and controls. However, it does suggest that there may be a fraction of patients who should be treated with upfront resection. For incorporation of this change into standard practice, the question of therapy sequencing should be answered in a randomized prospective trial that incorporates the most updated systemic therapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel [FLOT]) into its design.
Chemotherapy continues to play a critical role during first-line treatment of advanced esophageal and gastric adenocarcinoma. Triple chemotherapy regimens have been known to have increased efficacy in this setting, but their use has been limited by associated toxicities. A study by Nguyen and colleagues evaluated the TCX regimen (paclitaxel, carboplatin, and capecitabine) during first-line treatment of advanced gastric cancer. This regimen is similar to other triple chemotherapy regimens, such as FLOT and DCF (docetaxel, cisplatin, and fluorouracil), which have proven activity in this disease. This prospective phase 2 trial enrolled 83 patients. The median PFS (9.3 months) and OS (17 months) compared favorably with historical references. The regimen had expected adverse events, with cytopenias and fatigue being the most frequently reported. On the basis of the reported safety and efficacy, TCX has potential to be used as a chemotherapy backbone in future trials, but larger trials are needed to confirm the phase 2 trial results.
References
Wainberg ZA, Enzinger PC, Kang YK, et al. Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): A randomised, double-blind, placebo-controlled, phase 2 study. Lancet Oncol. 2022 Oct 13. Doi: 10.1016/S1470-2045(22)00603-9
The phase 2 FIGHT trial1 evaluated the role of bemarituzumab, an anti-FGFR2 antibody, in combination with chemotherapy during first-line treatment of advanced gastroesophageal adenocarcinoma. The primary endpoint of this trial was progression-free survival (PFS). This trial enrolled 155 patients with upper gastrointestinal tumors with FGFR2b overexpression (defined as at least 2+ by immunohistochemistry) or amplification on next-generation sequencing. About 30% of patients with HER2 nonpositive tumors (ie, those that would not qualify for treatment with the targeted agent trastuzumab) were eligible for participation. In the FIGHT trial, patients were randomized in a 1:1 ratio to receive either standard chemotherapy (folinic acid, fluorouracil, and oxaliplatin [FOLFOX]) or chemotherapy plus bemarituzumab. Patients in the experimental group were allowed to receive one dose of standard FOLFOX chemotherapy while biomarker testing was ongoing.
With a median follow-up time of 10.9 moths, PFS was numerically prolonged in the bemarituzumab group (9.5 vs 7.4 months), but it did not reach statistical significance (P = .073). Overall survival (OS) was improved in the experimental group (not reached vs 12.9 months; P = .027). With a longer follow-up of 12.5 months, in post hoc exploratory analysis, OS was significantly longer in the experimental group (19.2 vs 13.5 months; hazard ratio 0.60, P = .027). The rate of serious adverse events was similar between the two groups. However, it is important to note ocular toxicities associated with bemarituzumab treatment. Corneal adverse events were seen in 67% of patients in the experimental group, with 24% of patients experiencing grade 3 events. Moreover, 26% of patients discontinued bemarituzumab because of corneal adverse events.
Overall, this phase 2 trial demonstrated that FGFR2b is emerging as an important biomarker and target in patients with advanced gastroesophageal adenocarcinoma. Ongoing phase 3 trials (FORTITUDE-101 with FOLFOX [NCT05052801] and FORTITUDE-102 with FOLFOX and nivolumab [NCT05111626]) hopefully will confirm the early results seen in the FIGHT trial. Awareness and early attention to treatment-associated toxicities will be critical for the potential future incorporation of bemarituzumab into clinical practice.
A study by Ramos‐Santillan and colleagues explored whether the order of treatment modalities matter in the management of early-stage gastric cancer. Typically, perioperative chemotherapy (both neoadjuvant and adjuvant) is used during treatment of early-stage gastric cancer, which is usually defined as at least cT2N0 or cTxN+ disease. In this study, multivariable Cox regression analyses were performed on propensity score-matched cohorts. The study analyzed outcomes of 11,984 patients who were identified using the US National Cancer Database and treated between 2005 and 2014. The results revealed that patients who had stage I disease had better outcomes with upfront resection followed by adjuvant therapy. Patients with stage III disease did better with a neoadjuvant approach, whereas patients with stage II disease had similar outcomes regardless of chemotherapy timing. This research has the limitations inherent to the retrospective nature of the analysis and lack of prospective enrollment and controls. However, it does suggest that there may be a fraction of patients who should be treated with upfront resection. For incorporation of this change into standard practice, the question of therapy sequencing should be answered in a randomized prospective trial that incorporates the most updated systemic therapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel [FLOT]) into its design.
Chemotherapy continues to play a critical role during first-line treatment of advanced esophageal and gastric adenocarcinoma. Triple chemotherapy regimens have been known to have increased efficacy in this setting, but their use has been limited by associated toxicities. A study by Nguyen and colleagues evaluated the TCX regimen (paclitaxel, carboplatin, and capecitabine) during first-line treatment of advanced gastric cancer. This regimen is similar to other triple chemotherapy regimens, such as FLOT and DCF (docetaxel, cisplatin, and fluorouracil), which have proven activity in this disease. This prospective phase 2 trial enrolled 83 patients. The median PFS (9.3 months) and OS (17 months) compared favorably with historical references. The regimen had expected adverse events, with cytopenias and fatigue being the most frequently reported. On the basis of the reported safety and efficacy, TCX has potential to be used as a chemotherapy backbone in future trials, but larger trials are needed to confirm the phase 2 trial results.
References
Wainberg ZA, Enzinger PC, Kang YK, et al. Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): A randomised, double-blind, placebo-controlled, phase 2 study. Lancet Oncol. 2022 Oct 13. Doi: 10.1016/S1470-2045(22)00603-9
Commentary: Chemoradiotherapy in CRC, November 2022
Once again, I have been given the distinct honor of analyzing two of the most provocative studies in colorectal cancer this month for Clinical Edge. The first study I will examine was done by Khamzina and colleagues and attempts to define the optimal time to perform surgery after neoadjuvant chemoradiotherapy in locally advanced rectal cancer. In this retrospective analysis, 770 patients who received long-course chemoradiotherapy for rectal cancer followed by total mesorectal excision (TME) were analyzed by how long the interval was between completion of radiation and surgery. Patients were separated into two groups: 6-8 weeks (n = 502) vs >8 weeks (n = 268). Though the pathologic complete response rates and 5-year disease-free survival rates were not significantly different between the two groups, tumor regression grade was significantly better in the >8 weeks arm (P = .004). This result confirms many previous studies that demonstrate continued tumor shrinkage months after completion of chemoradiotherapy and may provide an explanation of why the OPRA trial demonstrated a higher TME-free rate in the chemoradiotherapy-then-chemotherapy arm than it did in the induction chemotherapy-then-chemoradiotherapy arm (53% vs 41%).
Schaefer and colleagues looked at the potential prognostic markers for efficacy of transarterial radioembolization (TARE) with 90Y resin microspheres in the treatment of liver-dominant metastatic colorectal cancer (mCRC). Their study evaluated 237 patients with liver-dominant mCRC from the prospective observational CIRSE Registry for SIR-Spheres Therapy (CIRT) study who were scheduled to receive TARE with 90Y resin microspheres. For these patients, the aspartate transaminase-to-platelet ratio index (APRI), international normalized ratio (INR), and albumin-bilirubin (ALBI) grade were measured prior to treatment to potentially detect values that might be associated with differential outcomes from TARE. An APRI > 0.40 independently predicted worse overall survival (OS) (hazard ratio [HR] 2.25; P < .0001), progression-free survival (PFS) (HR 1.42; P = .0416), and hepatic PFS (HR 1.50; P = .0207). The other independent predictors for worse OS and hepatic PFS were an INR value of < 1 (HR 1.66; P = .0091) and ALBI grade 3 (HR 5.29; P = .0075), respectively. It is very difficult to make much out of this study save to say that poorer liver function at baseline (at least with respect to APRI and ALBI) predicts worse outcomes after TARE, which is none too controversial an opinion. That said, APRI and ALBI may be able to provide an extra measure of granularity to determine who might be more of a marginal candidate for TARE than would categorization according to Child-Pugh score alone. Saving these patients from a potentially morbid procedure would be a significant benefit.
Once again, I have been given the distinct honor of analyzing two of the most provocative studies in colorectal cancer this month for Clinical Edge. The first study I will examine was done by Khamzina and colleagues and attempts to define the optimal time to perform surgery after neoadjuvant chemoradiotherapy in locally advanced rectal cancer. In this retrospective analysis, 770 patients who received long-course chemoradiotherapy for rectal cancer followed by total mesorectal excision (TME) were analyzed by how long the interval was between completion of radiation and surgery. Patients were separated into two groups: 6-8 weeks (n = 502) vs >8 weeks (n = 268). Though the pathologic complete response rates and 5-year disease-free survival rates were not significantly different between the two groups, tumor regression grade was significantly better in the >8 weeks arm (P = .004). This result confirms many previous studies that demonstrate continued tumor shrinkage months after completion of chemoradiotherapy and may provide an explanation of why the OPRA trial demonstrated a higher TME-free rate in the chemoradiotherapy-then-chemotherapy arm than it did in the induction chemotherapy-then-chemoradiotherapy arm (53% vs 41%).
Schaefer and colleagues looked at the potential prognostic markers for efficacy of transarterial radioembolization (TARE) with 90Y resin microspheres in the treatment of liver-dominant metastatic colorectal cancer (mCRC). Their study evaluated 237 patients with liver-dominant mCRC from the prospective observational CIRSE Registry for SIR-Spheres Therapy (CIRT) study who were scheduled to receive TARE with 90Y resin microspheres. For these patients, the aspartate transaminase-to-platelet ratio index (APRI), international normalized ratio (INR), and albumin-bilirubin (ALBI) grade were measured prior to treatment to potentially detect values that might be associated with differential outcomes from TARE. An APRI > 0.40 independently predicted worse overall survival (OS) (hazard ratio [HR] 2.25; P < .0001), progression-free survival (PFS) (HR 1.42; P = .0416), and hepatic PFS (HR 1.50; P = .0207). The other independent predictors for worse OS and hepatic PFS were an INR value of < 1 (HR 1.66; P = .0091) and ALBI grade 3 (HR 5.29; P = .0075), respectively. It is very difficult to make much out of this study save to say that poorer liver function at baseline (at least with respect to APRI and ALBI) predicts worse outcomes after TARE, which is none too controversial an opinion. That said, APRI and ALBI may be able to provide an extra measure of granularity to determine who might be more of a marginal candidate for TARE than would categorization according to Child-Pugh score alone. Saving these patients from a potentially morbid procedure would be a significant benefit.
Once again, I have been given the distinct honor of analyzing two of the most provocative studies in colorectal cancer this month for Clinical Edge. The first study I will examine was done by Khamzina and colleagues and attempts to define the optimal time to perform surgery after neoadjuvant chemoradiotherapy in locally advanced rectal cancer. In this retrospective analysis, 770 patients who received long-course chemoradiotherapy for rectal cancer followed by total mesorectal excision (TME) were analyzed by how long the interval was between completion of radiation and surgery. Patients were separated into two groups: 6-8 weeks (n = 502) vs >8 weeks (n = 268). Though the pathologic complete response rates and 5-year disease-free survival rates were not significantly different between the two groups, tumor regression grade was significantly better in the >8 weeks arm (P = .004). This result confirms many previous studies that demonstrate continued tumor shrinkage months after completion of chemoradiotherapy and may provide an explanation of why the OPRA trial demonstrated a higher TME-free rate in the chemoradiotherapy-then-chemotherapy arm than it did in the induction chemotherapy-then-chemoradiotherapy arm (53% vs 41%).
Schaefer and colleagues looked at the potential prognostic markers for efficacy of transarterial radioembolization (TARE) with 90Y resin microspheres in the treatment of liver-dominant metastatic colorectal cancer (mCRC). Their study evaluated 237 patients with liver-dominant mCRC from the prospective observational CIRSE Registry for SIR-Spheres Therapy (CIRT) study who were scheduled to receive TARE with 90Y resin microspheres. For these patients, the aspartate transaminase-to-platelet ratio index (APRI), international normalized ratio (INR), and albumin-bilirubin (ALBI) grade were measured prior to treatment to potentially detect values that might be associated with differential outcomes from TARE. An APRI > 0.40 independently predicted worse overall survival (OS) (hazard ratio [HR] 2.25; P < .0001), progression-free survival (PFS) (HR 1.42; P = .0416), and hepatic PFS (HR 1.50; P = .0207). The other independent predictors for worse OS and hepatic PFS were an INR value of < 1 (HR 1.66; P = .0091) and ALBI grade 3 (HR 5.29; P = .0075), respectively. It is very difficult to make much out of this study save to say that poorer liver function at baseline (at least with respect to APRI and ALBI) predicts worse outcomes after TARE, which is none too controversial an opinion. That said, APRI and ALBI may be able to provide an extra measure of granularity to determine who might be more of a marginal candidate for TARE than would categorization according to Child-Pugh score alone. Saving these patients from a potentially morbid procedure would be a significant benefit.
AGA News – November 2022
Vaccine recommendations for your patients with IBD
It’s cold and flu season – are your patients with inflammatory bowel disease (IBD) properly informed about increased risk of infections?
It is especially important for patients with IBD to receive the flu vaccine every year. With IBD, you can only get the shot (and not the spray in the nose).
The AGA GI Patient Center provides additional recommendations about vaccines in adults with IBD. Talk to your patients with IBD about what vaccines are needed for their treatment regimen, age and sex.
Review vaccines and vaccine-preventable diseases the patient had when first diagnosed with IBD, no matter the age and continue discussing vaccines during regular health care visits.
Give patients vaccine(s) for infections they are not immune as soon as possible.
Make sure patients are up to date or receive any live vaccines prior to starting some immunosuppressive treatments, such as biologics.
Help drive HCV testing, treatment, and eradication
AGA has been working with the Centers for Medicare & Medicaid Services and the Centers for Disease Control and Prevention to help drive the national priority for hepatitis C virus (HCV) testing, treatment and eradication.
Updates to QPP measure 400
In July 2022, CMS contacted AGA to modify measure 400 – to update the coverage for one-time screening for HCV to include a referral for treatment for patients with positive antibodies. CMS also advised that confirmation of eradication is a priority and we have started working with the CDC to modify AGA’s sustained virologic response measure for future consideration in the Quality Payment Program.
The modifications to measure 400 have been drafted and given the substantial changes to the measure specification, the measure needs to be retested and submitted to the National Quality Forum for consideration by the Measures Application Partnership. The CMS contractor for this project, Mathematica, will be leading this testing initiative and selected test sites will qualify for up to $2,000 to participate.
Additionally, there will be a second phase of testing to use deidentified patient-level data to assess the measure’s validity and reliability, which will be contracted separately. Our hope is that testing sites recruited for the first phase of testing will stay on through the second phase.
Participants in the second phase of testing are expected to have at least 2 years of patient data available containing data elements needed to calculate the measure. Ideally, each of the participating clinicians at the prospective testing sites would see at least 40 confirmed HCV-positive cases annually.
Vaccine recommendations for your patients with IBD
It’s cold and flu season – are your patients with inflammatory bowel disease (IBD) properly informed about increased risk of infections?
It is especially important for patients with IBD to receive the flu vaccine every year. With IBD, you can only get the shot (and not the spray in the nose).
The AGA GI Patient Center provides additional recommendations about vaccines in adults with IBD. Talk to your patients with IBD about what vaccines are needed for their treatment regimen, age and sex.
Review vaccines and vaccine-preventable diseases the patient had when first diagnosed with IBD, no matter the age and continue discussing vaccines during regular health care visits.
Give patients vaccine(s) for infections they are not immune as soon as possible.
Make sure patients are up to date or receive any live vaccines prior to starting some immunosuppressive treatments, such as biologics.
Help drive HCV testing, treatment, and eradication
AGA has been working with the Centers for Medicare & Medicaid Services and the Centers for Disease Control and Prevention to help drive the national priority for hepatitis C virus (HCV) testing, treatment and eradication.
Updates to QPP measure 400
In July 2022, CMS contacted AGA to modify measure 400 – to update the coverage for one-time screening for HCV to include a referral for treatment for patients with positive antibodies. CMS also advised that confirmation of eradication is a priority and we have started working with the CDC to modify AGA’s sustained virologic response measure for future consideration in the Quality Payment Program.
The modifications to measure 400 have been drafted and given the substantial changes to the measure specification, the measure needs to be retested and submitted to the National Quality Forum for consideration by the Measures Application Partnership. The CMS contractor for this project, Mathematica, will be leading this testing initiative and selected test sites will qualify for up to $2,000 to participate.
Additionally, there will be a second phase of testing to use deidentified patient-level data to assess the measure’s validity and reliability, which will be contracted separately. Our hope is that testing sites recruited for the first phase of testing will stay on through the second phase.
Participants in the second phase of testing are expected to have at least 2 years of patient data available containing data elements needed to calculate the measure. Ideally, each of the participating clinicians at the prospective testing sites would see at least 40 confirmed HCV-positive cases annually.
Vaccine recommendations for your patients with IBD
It’s cold and flu season – are your patients with inflammatory bowel disease (IBD) properly informed about increased risk of infections?
It is especially important for patients with IBD to receive the flu vaccine every year. With IBD, you can only get the shot (and not the spray in the nose).
The AGA GI Patient Center provides additional recommendations about vaccines in adults with IBD. Talk to your patients with IBD about what vaccines are needed for their treatment regimen, age and sex.
Review vaccines and vaccine-preventable diseases the patient had when first diagnosed with IBD, no matter the age and continue discussing vaccines during regular health care visits.
Give patients vaccine(s) for infections they are not immune as soon as possible.
Make sure patients are up to date or receive any live vaccines prior to starting some immunosuppressive treatments, such as biologics.
Help drive HCV testing, treatment, and eradication
AGA has been working with the Centers for Medicare & Medicaid Services and the Centers for Disease Control and Prevention to help drive the national priority for hepatitis C virus (HCV) testing, treatment and eradication.
Updates to QPP measure 400
In July 2022, CMS contacted AGA to modify measure 400 – to update the coverage for one-time screening for HCV to include a referral for treatment for patients with positive antibodies. CMS also advised that confirmation of eradication is a priority and we have started working with the CDC to modify AGA’s sustained virologic response measure for future consideration in the Quality Payment Program.
The modifications to measure 400 have been drafted and given the substantial changes to the measure specification, the measure needs to be retested and submitted to the National Quality Forum for consideration by the Measures Application Partnership. The CMS contractor for this project, Mathematica, will be leading this testing initiative and selected test sites will qualify for up to $2,000 to participate.
Additionally, there will be a second phase of testing to use deidentified patient-level data to assess the measure’s validity and reliability, which will be contracted separately. Our hope is that testing sites recruited for the first phase of testing will stay on through the second phase.
Participants in the second phase of testing are expected to have at least 2 years of patient data available containing data elements needed to calculate the measure. Ideally, each of the participating clinicians at the prospective testing sites would see at least 40 confirmed HCV-positive cases annually.
Commentary: COVID-19, Tenosynovitis, and RA, November 2022
Multiple studies have emphasized the potential for severe COVID-19 outcomes in patients with rheumatic disease, including patients with rheumatoid arthritis (RA). Because these studies often group together patients with different diseases, medications, and manifestations, differences in outcomes between patients with these conditions may be difficult to tease out.
Figueroa-Parra and colleagues performed a retrospective cohort study comparing people with RA who developed COVID-19 to those who did not have RA to examine the effect of RA characteristics, such as interstitial lung disease (ILD), serostatus, and bone erosions, on COVID-19 outcomes. Patients with RA, particularly those with seropositive RA, bone erosions, and RA-associated ILD, had approximately twofold (or higher) risk for severe COVID-19 outcomes, such as mortality or mechanical ventilation, than did those without RA. However, there was no difference in outcomes seen between patients with RA who were seropositive compared with those who were seronegative, with or without bone erosions, or with or without ILD. The mechanism by which RA phenotypes and their treatment affect this risk remains unclear.
Li and colleagues also looked at COVID-19 outcomes in patients with RA according to vaccination status using a UK primary care database. Among unvaccinated patients, the risk for SARS-CoV-2 infection and hospitalization or mortality because of COVID-19 were modestly higher in people with RA. Among vaccinated patients, there was no increased risk for breakthrough infection, COVID-19 hospitalization, or mortality observed in patients with RA over 3 or 6 months of follow-up, with a slight increase over 9 months of follow-up. Overall, both studies support prior research suggesting a higher risk for more severe COVID-19 in patients with RA, as well as potential mitigation with vaccination.
Predictors of RA course and severity are of great interest in determining the optimal therapy to reduce joint damage and prevent RA progression while also minimizing the adverse effects of treatment. Early disease course has been shown to be important in several studies. Giollo and colleagues compared patients with "difficult-to-treat RA," ie, RA that is resistant to multiple biologic disease-modifying antirheumatic drugs (bDMARD) or targeted synthetic DMARD (tsDMARD), with those without in an inception cohort study and found that early difficult management as well as delay of methotrexate initiation was associated with persistent inflammatory symptoms. This finding does not show a causative relationship between methotrexate and protection from the development of refractory RA but does lend support for early aggressive treatment in patients with a high inflammatory burden.
Conversely, Parisi and colleagues performed a subanalysis of the STARTER study of patients with RA in clinical remission to evaluate the impact of different therapies. The STARTER study had shown an association between ultrasound detection of tenosynovitis and RA flares. Of the more than 250 patients completing the study, ultrasound evidence of tenosynovitis was better controlled in patients on combination bDMARD and conventional synthetic DMARD (csDMARD) therapy than in those on csDMARDs monotherapy, with a trend toward reduction in flares in patients on combination therapy. Given the relatively small effect, it is not clear that combination therapy is associated with deeper remission, but, as suggested in prior studies, ultrasound evidence of tenosynovitis may be worthwhile considering prior to tapering therapy.
Multiple studies have emphasized the potential for severe COVID-19 outcomes in patients with rheumatic disease, including patients with rheumatoid arthritis (RA). Because these studies often group together patients with different diseases, medications, and manifestations, differences in outcomes between patients with these conditions may be difficult to tease out.
Figueroa-Parra and colleagues performed a retrospective cohort study comparing people with RA who developed COVID-19 to those who did not have RA to examine the effect of RA characteristics, such as interstitial lung disease (ILD), serostatus, and bone erosions, on COVID-19 outcomes. Patients with RA, particularly those with seropositive RA, bone erosions, and RA-associated ILD, had approximately twofold (or higher) risk for severe COVID-19 outcomes, such as mortality or mechanical ventilation, than did those without RA. However, there was no difference in outcomes seen between patients with RA who were seropositive compared with those who were seronegative, with or without bone erosions, or with or without ILD. The mechanism by which RA phenotypes and their treatment affect this risk remains unclear.
Li and colleagues also looked at COVID-19 outcomes in patients with RA according to vaccination status using a UK primary care database. Among unvaccinated patients, the risk for SARS-CoV-2 infection and hospitalization or mortality because of COVID-19 were modestly higher in people with RA. Among vaccinated patients, there was no increased risk for breakthrough infection, COVID-19 hospitalization, or mortality observed in patients with RA over 3 or 6 months of follow-up, with a slight increase over 9 months of follow-up. Overall, both studies support prior research suggesting a higher risk for more severe COVID-19 in patients with RA, as well as potential mitigation with vaccination.
Predictors of RA course and severity are of great interest in determining the optimal therapy to reduce joint damage and prevent RA progression while also minimizing the adverse effects of treatment. Early disease course has been shown to be important in several studies. Giollo and colleagues compared patients with "difficult-to-treat RA," ie, RA that is resistant to multiple biologic disease-modifying antirheumatic drugs (bDMARD) or targeted synthetic DMARD (tsDMARD), with those without in an inception cohort study and found that early difficult management as well as delay of methotrexate initiation was associated with persistent inflammatory symptoms. This finding does not show a causative relationship between methotrexate and protection from the development of refractory RA but does lend support for early aggressive treatment in patients with a high inflammatory burden.
Conversely, Parisi and colleagues performed a subanalysis of the STARTER study of patients with RA in clinical remission to evaluate the impact of different therapies. The STARTER study had shown an association between ultrasound detection of tenosynovitis and RA flares. Of the more than 250 patients completing the study, ultrasound evidence of tenosynovitis was better controlled in patients on combination bDMARD and conventional synthetic DMARD (csDMARD) therapy than in those on csDMARDs monotherapy, with a trend toward reduction in flares in patients on combination therapy. Given the relatively small effect, it is not clear that combination therapy is associated with deeper remission, but, as suggested in prior studies, ultrasound evidence of tenosynovitis may be worthwhile considering prior to tapering therapy.
Multiple studies have emphasized the potential for severe COVID-19 outcomes in patients with rheumatic disease, including patients with rheumatoid arthritis (RA). Because these studies often group together patients with different diseases, medications, and manifestations, differences in outcomes between patients with these conditions may be difficult to tease out.
Figueroa-Parra and colleagues performed a retrospective cohort study comparing people with RA who developed COVID-19 to those who did not have RA to examine the effect of RA characteristics, such as interstitial lung disease (ILD), serostatus, and bone erosions, on COVID-19 outcomes. Patients with RA, particularly those with seropositive RA, bone erosions, and RA-associated ILD, had approximately twofold (or higher) risk for severe COVID-19 outcomes, such as mortality or mechanical ventilation, than did those without RA. However, there was no difference in outcomes seen between patients with RA who were seropositive compared with those who were seronegative, with or without bone erosions, or with or without ILD. The mechanism by which RA phenotypes and their treatment affect this risk remains unclear.
Li and colleagues also looked at COVID-19 outcomes in patients with RA according to vaccination status using a UK primary care database. Among unvaccinated patients, the risk for SARS-CoV-2 infection and hospitalization or mortality because of COVID-19 were modestly higher in people with RA. Among vaccinated patients, there was no increased risk for breakthrough infection, COVID-19 hospitalization, or mortality observed in patients with RA over 3 or 6 months of follow-up, with a slight increase over 9 months of follow-up. Overall, both studies support prior research suggesting a higher risk for more severe COVID-19 in patients with RA, as well as potential mitigation with vaccination.
Predictors of RA course and severity are of great interest in determining the optimal therapy to reduce joint damage and prevent RA progression while also minimizing the adverse effects of treatment. Early disease course has been shown to be important in several studies. Giollo and colleagues compared patients with "difficult-to-treat RA," ie, RA that is resistant to multiple biologic disease-modifying antirheumatic drugs (bDMARD) or targeted synthetic DMARD (tsDMARD), with those without in an inception cohort study and found that early difficult management as well as delay of methotrexate initiation was associated with persistent inflammatory symptoms. This finding does not show a causative relationship between methotrexate and protection from the development of refractory RA but does lend support for early aggressive treatment in patients with a high inflammatory burden.
Conversely, Parisi and colleagues performed a subanalysis of the STARTER study of patients with RA in clinical remission to evaluate the impact of different therapies. The STARTER study had shown an association between ultrasound detection of tenosynovitis and RA flares. Of the more than 250 patients completing the study, ultrasound evidence of tenosynovitis was better controlled in patients on combination bDMARD and conventional synthetic DMARD (csDMARD) therapy than in those on csDMARDs monotherapy, with a trend toward reduction in flares in patients on combination therapy. Given the relatively small effect, it is not clear that combination therapy is associated with deeper remission, but, as suggested in prior studies, ultrasound evidence of tenosynovitis may be worthwhile considering prior to tapering therapy.
Study uncovers two molecular subgroups of cervical cancer
Scientists have discovered that cervical cancer can be divided into two distinct molecular subgroups – one far more aggressive than the other – offering hope of better understanding and treatment of the disease.
In the United Kingdom, there are over 3,000 new case of cervical cancer, with around 850 deaths each year. It is almost always caused by the human papillomavirus (HPV), and vaccination against this virus has successfully reduced the incidence of cervical cancer – in fact, the reduction has been by 87% among women in their 20s in England who were offered the vaccine when they were aged 12-13 years as part of the U.K. HPV vaccination program.
“Despite major steps forward in preventing cervical cancer, many women still die from the disease,” said Tim Fenton, MD, associate professor in cancer biology, School of Cancer Sciences Centre for Cancer Immunology, University of Southampton (England), and coauthor of the new study.
Two distinct subgroups
In the new study, published in Nature Communications, researchers described their breakthrough findings as a “major step forward” in understanding the disease, and said they provided a “tantalizing new clue” in determining the best treatments for individual patients.
For the observational study - part of the largest ‘omics’ study of its kind – researchers led by scientists at University College London and the University of Southampton began by applying a multiomics approach to identify combinations of molecular markers and characteristics associated with the biological processes involved in cervical cancer cells. The integrated multiomic analysis of 643 cervical squamous cell carcinomas (CSCC) – the most common histological variant of cervical cancer – represented patient populations from the United States, Europe, and sub-Saharan Africa.
To begin with they analysed and compared DNA, RNA, proteins, and metabolites in 236 CSCC cases in a publicly available U.S. database. They found that U.S. cancers fell into two distinct “omics” subgroups, which they named C1 and C2. After further investigation, the researchers identified that C1 tumors contained a much higher number of cytotoxic T cells. “The findings suggested that patients with C1 tumors would have a stronger immune response within the tumor micro-environment,” they said.
Weaker antitumor immune response
To determine if the two sub-types affect patients with cervical cancer in different ways, the team, which also included researchers from the University of Kent, the University of Cambridge, Oslo University Hospital, the University of Bergen (Norway), and the University of Innsbruck (Austria) derived molecular profiles and looked at clinical outcomes of a further 313 CSCC cases from Norway and Austria.
The researchers found that, just as in the US cohort, nearly a quarter of patients fell into the C2 subtype, and that again C1 tumors contained far more killer T cells than C2 tumors. “Importantly, the data also showed C2 was far more clinically aggressive with worse outcomes for patients,” the authors said.
Patients with C2 tumors were more than twice as likely (hazard ratio, 2.32) to die from their cervical cancer at any point during the follow-up period – up to 21 years – than those with C1 tumors. In terms of 5-year disease-specific survival, the rates were 79% survival for C1 and 66% survival for C2, the authors pointed out.
They highlighted that the difference in outcomes between patients with C1 and C2 tumors was very similar across the US and European cohorts.
Kerry Chester, PhD, professor of molecular medicine at UCL Cancer Institute, and coauthor, said: “Inclusion of patient cohorts in Norway and Austria, for which highly detailed clinical information was available to complement the molecular data, were key factors in the success of the study.”
Analyzing a further cohort of 94 Ugandan CSCC cases, the team found that C2 tumors were much more common than C1 tumors in patients who were also HIV-positive, “underlining the link to a weaker antitumor immune response” in this group.
Molecular subtyping offers better prognostic information
Cervical cancer can be caused by at least 12 different ‘high-risk’ HPV types, and there have been conflicting reports as to whether the HPV type present in a cervical cancer influences the prognosis for the patient. CSCCs can now also be categorized into two subtypes, C1 and C2, the authors explained, among which C1 tumors have a more favorable outcome.
“Although HPV16 is more likely to cause C1 tumors and HPV18 C2 tumors, HPV type is not an independent predictor of prognosis, suggesting it is the tumor type rather than the causative HPV type that is critical for the disease outcome,” they highlighted.
“Intriguingly, the C1/C2 grouping appeared to be more informative than the type of HPV present,” they added. “While certain HPV types were found more commonly in either C1 or C2 tumors, prognosis was linked to the group to which the tumor could be assigned, rather than the HPV type it contained.”
The reason that HPV16 and other alpha-9 HPV types have been associated with more favorable outcomes was possibly that these viruses are “more likely to cause C1-type tumors”, the authors suggested. Although larger numbers are needed for robust within-stage comparisons of C1 and C2 tumors, “we observe a clear trend in the survival rates between C1 and C2 by stage”, they said.
Taking molecular (C1/C2) subtyping into account may allow for more “accurate prognostication” than current staging and potentially different clinical management of patients with C1 versus C2 tumors, the authors said. This could include the identification of patients at risk of relapse who may require further adjuvant therapy after completion of up-front therapy.
New therapeutic targets
Dr. Fenton highlighted that the study findings suggested that determining whether a patient has a C1 or a C2 cervical cancer could help in planning their treatment, since it appeared to provide “additional prognostic information beyond that gained from clinical staging”. Given the differences in the antitumor immune response observed in C1 and C2 tumors, this classification might also be useful in predicting which patients are likely to benefit from emerging immunotherapy drugs, he said.
The study findings also found that CSCC can develop along “two trajectories” associated with differing clinical behavior that can be identified using defined gene expression or DNA methylation signatures, and this may guide “improved clinical management of cervical cancer patients”, they said.
“This collaborative multidisciplinary research is a major step forward in our understanding of cervical cancer,” said Dr. Chester. “Through careful molecular profiling and genetic analysis of cervical cancer tumors we have gained valuable new insight into the tumor microenvironment and factors potentially making the cancer less aggressive in some patients.”
The authors expressed hope that their study findings will stimulate functional studies of genes and their role in cervical cancer pathogenesis, potentially enabling identification of new therapeutic targets.
The study was funded by Debbie Fund (a UCL postgraduate research scholarship), Rosetrees Trust, Cancer Research UK, the Biotechnology and Biosciences Research Council, the Royal Society, and the Global Challenges Doctoral Centre at the University of Kent, MRC, PCUK, BBSRC, TUF, Orchid, and the UCLH BRC. The authors declared no competing interests.
A version of this article first appeared on Medscape UK.
Scientists have discovered that cervical cancer can be divided into two distinct molecular subgroups – one far more aggressive than the other – offering hope of better understanding and treatment of the disease.
In the United Kingdom, there are over 3,000 new case of cervical cancer, with around 850 deaths each year. It is almost always caused by the human papillomavirus (HPV), and vaccination against this virus has successfully reduced the incidence of cervical cancer – in fact, the reduction has been by 87% among women in their 20s in England who were offered the vaccine when they were aged 12-13 years as part of the U.K. HPV vaccination program.
“Despite major steps forward in preventing cervical cancer, many women still die from the disease,” said Tim Fenton, MD, associate professor in cancer biology, School of Cancer Sciences Centre for Cancer Immunology, University of Southampton (England), and coauthor of the new study.
Two distinct subgroups
In the new study, published in Nature Communications, researchers described their breakthrough findings as a “major step forward” in understanding the disease, and said they provided a “tantalizing new clue” in determining the best treatments for individual patients.
For the observational study - part of the largest ‘omics’ study of its kind – researchers led by scientists at University College London and the University of Southampton began by applying a multiomics approach to identify combinations of molecular markers and characteristics associated with the biological processes involved in cervical cancer cells. The integrated multiomic analysis of 643 cervical squamous cell carcinomas (CSCC) – the most common histological variant of cervical cancer – represented patient populations from the United States, Europe, and sub-Saharan Africa.
To begin with they analysed and compared DNA, RNA, proteins, and metabolites in 236 CSCC cases in a publicly available U.S. database. They found that U.S. cancers fell into two distinct “omics” subgroups, which they named C1 and C2. After further investigation, the researchers identified that C1 tumors contained a much higher number of cytotoxic T cells. “The findings suggested that patients with C1 tumors would have a stronger immune response within the tumor micro-environment,” they said.
Weaker antitumor immune response
To determine if the two sub-types affect patients with cervical cancer in different ways, the team, which also included researchers from the University of Kent, the University of Cambridge, Oslo University Hospital, the University of Bergen (Norway), and the University of Innsbruck (Austria) derived molecular profiles and looked at clinical outcomes of a further 313 CSCC cases from Norway and Austria.
The researchers found that, just as in the US cohort, nearly a quarter of patients fell into the C2 subtype, and that again C1 tumors contained far more killer T cells than C2 tumors. “Importantly, the data also showed C2 was far more clinically aggressive with worse outcomes for patients,” the authors said.
Patients with C2 tumors were more than twice as likely (hazard ratio, 2.32) to die from their cervical cancer at any point during the follow-up period – up to 21 years – than those with C1 tumors. In terms of 5-year disease-specific survival, the rates were 79% survival for C1 and 66% survival for C2, the authors pointed out.
They highlighted that the difference in outcomes between patients with C1 and C2 tumors was very similar across the US and European cohorts.
Kerry Chester, PhD, professor of molecular medicine at UCL Cancer Institute, and coauthor, said: “Inclusion of patient cohorts in Norway and Austria, for which highly detailed clinical information was available to complement the molecular data, were key factors in the success of the study.”
Analyzing a further cohort of 94 Ugandan CSCC cases, the team found that C2 tumors were much more common than C1 tumors in patients who were also HIV-positive, “underlining the link to a weaker antitumor immune response” in this group.
Molecular subtyping offers better prognostic information
Cervical cancer can be caused by at least 12 different ‘high-risk’ HPV types, and there have been conflicting reports as to whether the HPV type present in a cervical cancer influences the prognosis for the patient. CSCCs can now also be categorized into two subtypes, C1 and C2, the authors explained, among which C1 tumors have a more favorable outcome.
“Although HPV16 is more likely to cause C1 tumors and HPV18 C2 tumors, HPV type is not an independent predictor of prognosis, suggesting it is the tumor type rather than the causative HPV type that is critical for the disease outcome,” they highlighted.
“Intriguingly, the C1/C2 grouping appeared to be more informative than the type of HPV present,” they added. “While certain HPV types were found more commonly in either C1 or C2 tumors, prognosis was linked to the group to which the tumor could be assigned, rather than the HPV type it contained.”
The reason that HPV16 and other alpha-9 HPV types have been associated with more favorable outcomes was possibly that these viruses are “more likely to cause C1-type tumors”, the authors suggested. Although larger numbers are needed for robust within-stage comparisons of C1 and C2 tumors, “we observe a clear trend in the survival rates between C1 and C2 by stage”, they said.
Taking molecular (C1/C2) subtyping into account may allow for more “accurate prognostication” than current staging and potentially different clinical management of patients with C1 versus C2 tumors, the authors said. This could include the identification of patients at risk of relapse who may require further adjuvant therapy after completion of up-front therapy.
New therapeutic targets
Dr. Fenton highlighted that the study findings suggested that determining whether a patient has a C1 or a C2 cervical cancer could help in planning their treatment, since it appeared to provide “additional prognostic information beyond that gained from clinical staging”. Given the differences in the antitumor immune response observed in C1 and C2 tumors, this classification might also be useful in predicting which patients are likely to benefit from emerging immunotherapy drugs, he said.
The study findings also found that CSCC can develop along “two trajectories” associated with differing clinical behavior that can be identified using defined gene expression or DNA methylation signatures, and this may guide “improved clinical management of cervical cancer patients”, they said.
“This collaborative multidisciplinary research is a major step forward in our understanding of cervical cancer,” said Dr. Chester. “Through careful molecular profiling and genetic analysis of cervical cancer tumors we have gained valuable new insight into the tumor microenvironment and factors potentially making the cancer less aggressive in some patients.”
The authors expressed hope that their study findings will stimulate functional studies of genes and their role in cervical cancer pathogenesis, potentially enabling identification of new therapeutic targets.
The study was funded by Debbie Fund (a UCL postgraduate research scholarship), Rosetrees Trust, Cancer Research UK, the Biotechnology and Biosciences Research Council, the Royal Society, and the Global Challenges Doctoral Centre at the University of Kent, MRC, PCUK, BBSRC, TUF, Orchid, and the UCLH BRC. The authors declared no competing interests.
A version of this article first appeared on Medscape UK.
Scientists have discovered that cervical cancer can be divided into two distinct molecular subgroups – one far more aggressive than the other – offering hope of better understanding and treatment of the disease.
In the United Kingdom, there are over 3,000 new case of cervical cancer, with around 850 deaths each year. It is almost always caused by the human papillomavirus (HPV), and vaccination against this virus has successfully reduced the incidence of cervical cancer – in fact, the reduction has been by 87% among women in their 20s in England who were offered the vaccine when they were aged 12-13 years as part of the U.K. HPV vaccination program.
“Despite major steps forward in preventing cervical cancer, many women still die from the disease,” said Tim Fenton, MD, associate professor in cancer biology, School of Cancer Sciences Centre for Cancer Immunology, University of Southampton (England), and coauthor of the new study.
Two distinct subgroups
In the new study, published in Nature Communications, researchers described their breakthrough findings as a “major step forward” in understanding the disease, and said they provided a “tantalizing new clue” in determining the best treatments for individual patients.
For the observational study - part of the largest ‘omics’ study of its kind – researchers led by scientists at University College London and the University of Southampton began by applying a multiomics approach to identify combinations of molecular markers and characteristics associated with the biological processes involved in cervical cancer cells. The integrated multiomic analysis of 643 cervical squamous cell carcinomas (CSCC) – the most common histological variant of cervical cancer – represented patient populations from the United States, Europe, and sub-Saharan Africa.
To begin with they analysed and compared DNA, RNA, proteins, and metabolites in 236 CSCC cases in a publicly available U.S. database. They found that U.S. cancers fell into two distinct “omics” subgroups, which they named C1 and C2. After further investigation, the researchers identified that C1 tumors contained a much higher number of cytotoxic T cells. “The findings suggested that patients with C1 tumors would have a stronger immune response within the tumor micro-environment,” they said.
Weaker antitumor immune response
To determine if the two sub-types affect patients with cervical cancer in different ways, the team, which also included researchers from the University of Kent, the University of Cambridge, Oslo University Hospital, the University of Bergen (Norway), and the University of Innsbruck (Austria) derived molecular profiles and looked at clinical outcomes of a further 313 CSCC cases from Norway and Austria.
The researchers found that, just as in the US cohort, nearly a quarter of patients fell into the C2 subtype, and that again C1 tumors contained far more killer T cells than C2 tumors. “Importantly, the data also showed C2 was far more clinically aggressive with worse outcomes for patients,” the authors said.
Patients with C2 tumors were more than twice as likely (hazard ratio, 2.32) to die from their cervical cancer at any point during the follow-up period – up to 21 years – than those with C1 tumors. In terms of 5-year disease-specific survival, the rates were 79% survival for C1 and 66% survival for C2, the authors pointed out.
They highlighted that the difference in outcomes between patients with C1 and C2 tumors was very similar across the US and European cohorts.
Kerry Chester, PhD, professor of molecular medicine at UCL Cancer Institute, and coauthor, said: “Inclusion of patient cohorts in Norway and Austria, for which highly detailed clinical information was available to complement the molecular data, were key factors in the success of the study.”
Analyzing a further cohort of 94 Ugandan CSCC cases, the team found that C2 tumors were much more common than C1 tumors in patients who were also HIV-positive, “underlining the link to a weaker antitumor immune response” in this group.
Molecular subtyping offers better prognostic information
Cervical cancer can be caused by at least 12 different ‘high-risk’ HPV types, and there have been conflicting reports as to whether the HPV type present in a cervical cancer influences the prognosis for the patient. CSCCs can now also be categorized into two subtypes, C1 and C2, the authors explained, among which C1 tumors have a more favorable outcome.
“Although HPV16 is more likely to cause C1 tumors and HPV18 C2 tumors, HPV type is not an independent predictor of prognosis, suggesting it is the tumor type rather than the causative HPV type that is critical for the disease outcome,” they highlighted.
“Intriguingly, the C1/C2 grouping appeared to be more informative than the type of HPV present,” they added. “While certain HPV types were found more commonly in either C1 or C2 tumors, prognosis was linked to the group to which the tumor could be assigned, rather than the HPV type it contained.”
The reason that HPV16 and other alpha-9 HPV types have been associated with more favorable outcomes was possibly that these viruses are “more likely to cause C1-type tumors”, the authors suggested. Although larger numbers are needed for robust within-stage comparisons of C1 and C2 tumors, “we observe a clear trend in the survival rates between C1 and C2 by stage”, they said.
Taking molecular (C1/C2) subtyping into account may allow for more “accurate prognostication” than current staging and potentially different clinical management of patients with C1 versus C2 tumors, the authors said. This could include the identification of patients at risk of relapse who may require further adjuvant therapy after completion of up-front therapy.
New therapeutic targets
Dr. Fenton highlighted that the study findings suggested that determining whether a patient has a C1 or a C2 cervical cancer could help in planning their treatment, since it appeared to provide “additional prognostic information beyond that gained from clinical staging”. Given the differences in the antitumor immune response observed in C1 and C2 tumors, this classification might also be useful in predicting which patients are likely to benefit from emerging immunotherapy drugs, he said.
The study findings also found that CSCC can develop along “two trajectories” associated with differing clinical behavior that can be identified using defined gene expression or DNA methylation signatures, and this may guide “improved clinical management of cervical cancer patients”, they said.
“This collaborative multidisciplinary research is a major step forward in our understanding of cervical cancer,” said Dr. Chester. “Through careful molecular profiling and genetic analysis of cervical cancer tumors we have gained valuable new insight into the tumor microenvironment and factors potentially making the cancer less aggressive in some patients.”
The authors expressed hope that their study findings will stimulate functional studies of genes and their role in cervical cancer pathogenesis, potentially enabling identification of new therapeutic targets.
The study was funded by Debbie Fund (a UCL postgraduate research scholarship), Rosetrees Trust, Cancer Research UK, the Biotechnology and Biosciences Research Council, the Royal Society, and the Global Challenges Doctoral Centre at the University of Kent, MRC, PCUK, BBSRC, TUF, Orchid, and the UCLH BRC. The authors declared no competing interests.
A version of this article first appeared on Medscape UK.
FROM NATURE COMMUNICATIONS
Major U.S. GI societies issue strategic plan on environmental sustainability
according to a new joint strategic plan published simultaneously in Gastroenterology, Gastrointestinal Endoscopy, American Journal of Gastroenterology, and Hepatology.
The plan outlines numerous strategic goals and objectives across clinical care, education, research, and industry to support sustainable practices. With first author Heiko Pohl, MD, a gastroenterologist and hepatologist at the Veterans Affairs Medical Center in White River Junction, Vermont, and professor of medicine at the Geisel School of Medicine at Dartmouth, Hanover, N.H., the joint statement includes task force members from the American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy.
“It is clear that the evolving climate crisis, with its deleterious effects on planetary ecosystems, also poses harm to the health of humankind,” the authors wrote in Gastroenterology.
“Climate change affects many social and environmental determinants of health, including water and food security, shelter, physical activity, and accessible health care,” they added. These changes influence gastrointestinal practice (for example, increased risk of obesity and fatty liver disease, disruption of the microbiome, compromised gut immune function).
At the same time, health care delivery contributes to climate change and greenhouse gas emissions worldwide, they wrote. As a procedure-intensive specialty, digestive health care adds to the health care carbon footprint through single-use supplies and high levels of waste.
“As is the case for the impact of climate change by and on health care systems, there is a vicious cycle whereby climate change negatively impacts individual digestive health, which accelerates specialized health care activity, which further contributes to the climate crisis,” the authors wrote.
The multisociety task force noted the transition to a more sustainable model will be challenging and require major modification of current habits in practice. However, the long-term effects “will promote health, save cost, and ... correspond with a broader shared vision of planetary health,” they wrote.
The strategic plan covers seven domains: clinical settings, education, research, society efforts, intersociety efforts, industry, and advocacy. Each domain has specific initiatives for 2023 to 2027. Years 1 and 2 are conceived as a period of self-assessment and planning, followed by implementation and assessment during years 3-5.
In the plan, clinical settings would assess the carbon footprint and waste within all areas of practice and identify low-carbon and low-waste alternatives, such as immediate, short-term, and long-term solutions. This involves creating a framework for GI practices to develop sustainability metrics and offer affordable testing and treatment alternatives with a favorable environmental impact.
Through education, the societies would raise awareness and share sustainability practices with health care leadership, practitioners, and patients regarding the interactions among climate change, digestive health, and health care services. This would include discussions about the professional and ethical implications of old and new patterns of shared resource utilization.
The societies also support raising and allocating resources for research related to the intersections of climate change, digestive health, and health care, with an emphasis on vulnerable groups. This would encourage the inclusion of environmental considerations in research proposals.
At the GI society level, the groups suggest assessing and monitoring the current environmental impact of society-related activities. This entails identifying and implementing measures that would decrease the carbon footprint and reduce waste, as well as track financial costs and savings and environmental benefits from efforts included in a sustainability model.
At the intersociety level, the U.S. groups would collaborate with national and international GI and hepatology societies to support sustainability efforts and use validated metrics to evaluate their efforts. The multisociety plan has received endorsements from nearly two-dozen groups, including the Crohn’s & Colitis Foundation, World Endoscopy Organization, and World Gastroenterology Organisation.
The plan calls for engagement with GI- and hepatology-focused industry and pharmaceutical partners to develop environmentally friendly products, publish information on carbon footprint implications, and promote options for recycling.
Through advocacy efforts, the societies would also identify and incorporate principles of sustainable health care among the goals of relevant political action committees, as well as leverage collaborative advocacy efforts with national and international health care and research agencies, political leaders, and payors.
“We are grateful that several other GI organizations have endorsed our plan, which reflects the importance and timeliness of the opportunity to work together and share best practices to overcome the burden of climate change on digestive health and help mitigate the environmental impact of GI practice,” the authors concluded.
The authors did not declare a funding source for the report. Several of the authors declared financial relationships with pharmaceutical companies, serving as a consultant or receiving research funding.
according to a new joint strategic plan published simultaneously in Gastroenterology, Gastrointestinal Endoscopy, American Journal of Gastroenterology, and Hepatology.
The plan outlines numerous strategic goals and objectives across clinical care, education, research, and industry to support sustainable practices. With first author Heiko Pohl, MD, a gastroenterologist and hepatologist at the Veterans Affairs Medical Center in White River Junction, Vermont, and professor of medicine at the Geisel School of Medicine at Dartmouth, Hanover, N.H., the joint statement includes task force members from the American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy.
“It is clear that the evolving climate crisis, with its deleterious effects on planetary ecosystems, also poses harm to the health of humankind,” the authors wrote in Gastroenterology.
“Climate change affects many social and environmental determinants of health, including water and food security, shelter, physical activity, and accessible health care,” they added. These changes influence gastrointestinal practice (for example, increased risk of obesity and fatty liver disease, disruption of the microbiome, compromised gut immune function).
At the same time, health care delivery contributes to climate change and greenhouse gas emissions worldwide, they wrote. As a procedure-intensive specialty, digestive health care adds to the health care carbon footprint through single-use supplies and high levels of waste.
“As is the case for the impact of climate change by and on health care systems, there is a vicious cycle whereby climate change negatively impacts individual digestive health, which accelerates specialized health care activity, which further contributes to the climate crisis,” the authors wrote.
The multisociety task force noted the transition to a more sustainable model will be challenging and require major modification of current habits in practice. However, the long-term effects “will promote health, save cost, and ... correspond with a broader shared vision of planetary health,” they wrote.
The strategic plan covers seven domains: clinical settings, education, research, society efforts, intersociety efforts, industry, and advocacy. Each domain has specific initiatives for 2023 to 2027. Years 1 and 2 are conceived as a period of self-assessment and planning, followed by implementation and assessment during years 3-5.
In the plan, clinical settings would assess the carbon footprint and waste within all areas of practice and identify low-carbon and low-waste alternatives, such as immediate, short-term, and long-term solutions. This involves creating a framework for GI practices to develop sustainability metrics and offer affordable testing and treatment alternatives with a favorable environmental impact.
Through education, the societies would raise awareness and share sustainability practices with health care leadership, practitioners, and patients regarding the interactions among climate change, digestive health, and health care services. This would include discussions about the professional and ethical implications of old and new patterns of shared resource utilization.
The societies also support raising and allocating resources for research related to the intersections of climate change, digestive health, and health care, with an emphasis on vulnerable groups. This would encourage the inclusion of environmental considerations in research proposals.
At the GI society level, the groups suggest assessing and monitoring the current environmental impact of society-related activities. This entails identifying and implementing measures that would decrease the carbon footprint and reduce waste, as well as track financial costs and savings and environmental benefits from efforts included in a sustainability model.
At the intersociety level, the U.S. groups would collaborate with national and international GI and hepatology societies to support sustainability efforts and use validated metrics to evaluate their efforts. The multisociety plan has received endorsements from nearly two-dozen groups, including the Crohn’s & Colitis Foundation, World Endoscopy Organization, and World Gastroenterology Organisation.
The plan calls for engagement with GI- and hepatology-focused industry and pharmaceutical partners to develop environmentally friendly products, publish information on carbon footprint implications, and promote options for recycling.
Through advocacy efforts, the societies would also identify and incorporate principles of sustainable health care among the goals of relevant political action committees, as well as leverage collaborative advocacy efforts with national and international health care and research agencies, political leaders, and payors.
“We are grateful that several other GI organizations have endorsed our plan, which reflects the importance and timeliness of the opportunity to work together and share best practices to overcome the burden of climate change on digestive health and help mitigate the environmental impact of GI practice,” the authors concluded.
The authors did not declare a funding source for the report. Several of the authors declared financial relationships with pharmaceutical companies, serving as a consultant or receiving research funding.
according to a new joint strategic plan published simultaneously in Gastroenterology, Gastrointestinal Endoscopy, American Journal of Gastroenterology, and Hepatology.
The plan outlines numerous strategic goals and objectives across clinical care, education, research, and industry to support sustainable practices. With first author Heiko Pohl, MD, a gastroenterologist and hepatologist at the Veterans Affairs Medical Center in White River Junction, Vermont, and professor of medicine at the Geisel School of Medicine at Dartmouth, Hanover, N.H., the joint statement includes task force members from the American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy.
“It is clear that the evolving climate crisis, with its deleterious effects on planetary ecosystems, also poses harm to the health of humankind,” the authors wrote in Gastroenterology.
“Climate change affects many social and environmental determinants of health, including water and food security, shelter, physical activity, and accessible health care,” they added. These changes influence gastrointestinal practice (for example, increased risk of obesity and fatty liver disease, disruption of the microbiome, compromised gut immune function).
At the same time, health care delivery contributes to climate change and greenhouse gas emissions worldwide, they wrote. As a procedure-intensive specialty, digestive health care adds to the health care carbon footprint through single-use supplies and high levels of waste.
“As is the case for the impact of climate change by and on health care systems, there is a vicious cycle whereby climate change negatively impacts individual digestive health, which accelerates specialized health care activity, which further contributes to the climate crisis,” the authors wrote.
The multisociety task force noted the transition to a more sustainable model will be challenging and require major modification of current habits in practice. However, the long-term effects “will promote health, save cost, and ... correspond with a broader shared vision of planetary health,” they wrote.
The strategic plan covers seven domains: clinical settings, education, research, society efforts, intersociety efforts, industry, and advocacy. Each domain has specific initiatives for 2023 to 2027. Years 1 and 2 are conceived as a period of self-assessment and planning, followed by implementation and assessment during years 3-5.
In the plan, clinical settings would assess the carbon footprint and waste within all areas of practice and identify low-carbon and low-waste alternatives, such as immediate, short-term, and long-term solutions. This involves creating a framework for GI practices to develop sustainability metrics and offer affordable testing and treatment alternatives with a favorable environmental impact.
Through education, the societies would raise awareness and share sustainability practices with health care leadership, practitioners, and patients regarding the interactions among climate change, digestive health, and health care services. This would include discussions about the professional and ethical implications of old and new patterns of shared resource utilization.
The societies also support raising and allocating resources for research related to the intersections of climate change, digestive health, and health care, with an emphasis on vulnerable groups. This would encourage the inclusion of environmental considerations in research proposals.
At the GI society level, the groups suggest assessing and monitoring the current environmental impact of society-related activities. This entails identifying and implementing measures that would decrease the carbon footprint and reduce waste, as well as track financial costs and savings and environmental benefits from efforts included in a sustainability model.
At the intersociety level, the U.S. groups would collaborate with national and international GI and hepatology societies to support sustainability efforts and use validated metrics to evaluate their efforts. The multisociety plan has received endorsements from nearly two-dozen groups, including the Crohn’s & Colitis Foundation, World Endoscopy Organization, and World Gastroenterology Organisation.
The plan calls for engagement with GI- and hepatology-focused industry and pharmaceutical partners to develop environmentally friendly products, publish information on carbon footprint implications, and promote options for recycling.
Through advocacy efforts, the societies would also identify and incorporate principles of sustainable health care among the goals of relevant political action committees, as well as leverage collaborative advocacy efforts with national and international health care and research agencies, political leaders, and payors.
“We are grateful that several other GI organizations have endorsed our plan, which reflects the importance and timeliness of the opportunity to work together and share best practices to overcome the burden of climate change on digestive health and help mitigate the environmental impact of GI practice,” the authors concluded.
The authors did not declare a funding source for the report. Several of the authors declared financial relationships with pharmaceutical companies, serving as a consultant or receiving research funding.
FROM GASTROENTEROLOGY
Latiglutenase reduces symptoms in celiac patients exposed to gluten
according to a new study published in Gastroenterology.
Latiglutenase led to 95% gluten degradation in the stomach, as indicated by measurements of gluten-immunogenic peptides in urine, wrote Joseph A. Murray, MD, a gastroenterologist at the Mayo Clinic, Rochester, Minn., and Jack A. Syage, PhD, CEO and cofounder of ImmunogenX Inc., Newport Beach, Calif., and colleagues on behalf of the CeliacShield Study Group.
For patients with celiac disease, the only available treatment is a life-long gluten-free diet (GFD). Low levels of gluten exposure can lead to ongoing inflammation and the risk of complications, and about half of patients continue to experience moderate to severe symptoms.
“Although a GFD can reduce symptoms and intestinal damage, the diet is neither easy nor readily achievable by many patients and, furthermore, can be lacking in essential nutrients,” the authors wrote.
In a randomized, double-blind, placebo-controlled gluten challenge study, the research team assessed the efficacy and safety of a 1,200-mg dose of IMGX003, formerly known as ALV003. The dual-enzyme supplementation therapy was “designed to mitigate the impact of gluten exposure in patients who are attempting to adhere to a GFD.”
The phase 2 trial was conducted at the Mayo Clinic with adult patients (aged 18-80 years) who had physician-diagnosed and biopsy-confirmed celiac disease, followed a GFD for more than 1 year, and had histologically well-controlled disease. During the study, they were exposed to 2 g of gluten per day for 6 weeks.
The primary endpoint focused on the change in the ratio of villus height to crypt depth. The “secondary endpoints included density of intraepithelial lymphocytes and symptom severity. Additional endpoints included serology and gluten-immunogenic peptides in urine.”
Among the 50 patients randomized, 43 completed the study, with 21 assigned to the IMGX003 group. About 74% of the participants were women; the mean age of all participants was 43.8 years.
Overall, the mean change in the ratio of villus height to crypt depth was –0.04 for IMGX003, compared with –0.35 for placebo. In addition, the mean change in the density of intraepithelial lymphocytes for IMGX003 was 9.8, compared with 24.8 for placebo. Based on the ratio of the means for both groups, the researchers estimated an 88% reduction of change in villus height to crypt depth and a 60% reduction of change in intraepithelial lymphocytes.
The mean changes, or worsening from baseline, in symptom severity for IMGX003 vs. placebo were 0.22 vs. 1.63 for abdominal pain, 0.96 vs. 3.29 for bloating, 0.02 vs. 3.2 for tiredness, and 0.64 vs. 2.27 for nonstool composite. The calculated symptom reduction values were 93% for abdominal pain, 53% for bloating, 99% for tiredness, and 70% for nonstool composite.
The mean change from baseline for symptom severity was evaluated over three 2-week periods, and the percent changes showed consistent reduction of symptom worsening during that time. Based on the effect size and trend significance, the P values were .014 for abdominal pain, .030 for bloating, .002 for tiredness, and < . 001 for nonstool composite.
The mean change in gluten-immunogenic peptides in urine (GIP) relative to baseline was 0.59 for IMGX003, compared with 11.53 for placebo. The researchers estimated an efficacy of gluten degradation in vivo of 95%.
“Measurement of GIP in urine demonstrated the purported mechanism of action of IMGX003, namely, degradation of gluten in the stomach, thereby preventing the triggering of the immunogenic autoimmune response,” the authors wrote. “Targeting gluten by degrading the immunogenic peptides before absorption minimizes or abrogates the cascading innate and adaptive immune responses that characterize the inflammatory response to gluten in CeD [celiac disease].”
The study was sponsored by ImmunogenX Inc., and partially funded by a grant from the National Center for Complementary and Integrative Health. The project was further supported by grants from the National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors reported receiving grants from numerous funders, including ImmunogenX, and some reported being a cofounder, stockholder, or board director of the company.
From the perspective of patients affected by other chronic GI diseases requiring constant treatment with drugs, the life of celiac patients must appear “a piece of cake” (pun intended). But this is not the case. In fact, the burden of following a gluten-free diet (GFD) can profoundly impact their quality of life. Furthermore, a substantial portion of patients trying their best on a GFD do not experience full clinical and histologic remission, mainly because of ongoing involuntary gluten ingestion. Therefore, it’s not surprising that several lines of research have been actively trying to address this unmet need.
In this phase 2 trial, the proprietary enzyme combination called IMGX003 (latiglutenase) was investigated for safety and efficacy. IMGX003 can digest gluten in the stomach, thus preventing its intact entry into the small intestine where it would trigger the immune reaction leading to the villi destruction. The study did indeed demonstrate that administering it to patients on GFD exposed to 2 grams of gluten daily (roughly the equivalent of half a slice of wheat bread) effectively reduced both the mucosal damage and symptom severity. Is this good news for patients with celiac? You bet it is! While not replacing the need for a GFD, having a safe drug that adds a substantial layer of protection to inadvertent gluten exposure or the so-called “cross-contamination” is surely to be welcome by them.
If and once approved for use, IMGX003 could be taken sporadically by patients on GFD: For instance, while eating out in “new” places, traveling, going to parties, or for younger patients, when having sleepovers, birthday celebrations, and so on. With the caveat, not to be forgotten, that this is not meant to be a wonder drug eliminating the need for vigilance; we still need to wait patiently for science to advance further for that.
Stefano Guandalini, MD, AGAF, is professor emeritus of pediatrics at the University of Chicago and director emeritus of the University of Chicago Celiac Disease Center. He declares no relevant conflicts of interest.
From the perspective of patients affected by other chronic GI diseases requiring constant treatment with drugs, the life of celiac patients must appear “a piece of cake” (pun intended). But this is not the case. In fact, the burden of following a gluten-free diet (GFD) can profoundly impact their quality of life. Furthermore, a substantial portion of patients trying their best on a GFD do not experience full clinical and histologic remission, mainly because of ongoing involuntary gluten ingestion. Therefore, it’s not surprising that several lines of research have been actively trying to address this unmet need.
In this phase 2 trial, the proprietary enzyme combination called IMGX003 (latiglutenase) was investigated for safety and efficacy. IMGX003 can digest gluten in the stomach, thus preventing its intact entry into the small intestine where it would trigger the immune reaction leading to the villi destruction. The study did indeed demonstrate that administering it to patients on GFD exposed to 2 grams of gluten daily (roughly the equivalent of half a slice of wheat bread) effectively reduced both the mucosal damage and symptom severity. Is this good news for patients with celiac? You bet it is! While not replacing the need for a GFD, having a safe drug that adds a substantial layer of protection to inadvertent gluten exposure or the so-called “cross-contamination” is surely to be welcome by them.
If and once approved for use, IMGX003 could be taken sporadically by patients on GFD: For instance, while eating out in “new” places, traveling, going to parties, or for younger patients, when having sleepovers, birthday celebrations, and so on. With the caveat, not to be forgotten, that this is not meant to be a wonder drug eliminating the need for vigilance; we still need to wait patiently for science to advance further for that.
Stefano Guandalini, MD, AGAF, is professor emeritus of pediatrics at the University of Chicago and director emeritus of the University of Chicago Celiac Disease Center. He declares no relevant conflicts of interest.
From the perspective of patients affected by other chronic GI diseases requiring constant treatment with drugs, the life of celiac patients must appear “a piece of cake” (pun intended). But this is not the case. In fact, the burden of following a gluten-free diet (GFD) can profoundly impact their quality of life. Furthermore, a substantial portion of patients trying their best on a GFD do not experience full clinical and histologic remission, mainly because of ongoing involuntary gluten ingestion. Therefore, it’s not surprising that several lines of research have been actively trying to address this unmet need.
In this phase 2 trial, the proprietary enzyme combination called IMGX003 (latiglutenase) was investigated for safety and efficacy. IMGX003 can digest gluten in the stomach, thus preventing its intact entry into the small intestine where it would trigger the immune reaction leading to the villi destruction. The study did indeed demonstrate that administering it to patients on GFD exposed to 2 grams of gluten daily (roughly the equivalent of half a slice of wheat bread) effectively reduced both the mucosal damage and symptom severity. Is this good news for patients with celiac? You bet it is! While not replacing the need for a GFD, having a safe drug that adds a substantial layer of protection to inadvertent gluten exposure or the so-called “cross-contamination” is surely to be welcome by them.
If and once approved for use, IMGX003 could be taken sporadically by patients on GFD: For instance, while eating out in “new” places, traveling, going to parties, or for younger patients, when having sleepovers, birthday celebrations, and so on. With the caveat, not to be forgotten, that this is not meant to be a wonder drug eliminating the need for vigilance; we still need to wait patiently for science to advance further for that.
Stefano Guandalini, MD, AGAF, is professor emeritus of pediatrics at the University of Chicago and director emeritus of the University of Chicago Celiac Disease Center. He declares no relevant conflicts of interest.
according to a new study published in Gastroenterology.
Latiglutenase led to 95% gluten degradation in the stomach, as indicated by measurements of gluten-immunogenic peptides in urine, wrote Joseph A. Murray, MD, a gastroenterologist at the Mayo Clinic, Rochester, Minn., and Jack A. Syage, PhD, CEO and cofounder of ImmunogenX Inc., Newport Beach, Calif., and colleagues on behalf of the CeliacShield Study Group.
For patients with celiac disease, the only available treatment is a life-long gluten-free diet (GFD). Low levels of gluten exposure can lead to ongoing inflammation and the risk of complications, and about half of patients continue to experience moderate to severe symptoms.
“Although a GFD can reduce symptoms and intestinal damage, the diet is neither easy nor readily achievable by many patients and, furthermore, can be lacking in essential nutrients,” the authors wrote.
In a randomized, double-blind, placebo-controlled gluten challenge study, the research team assessed the efficacy and safety of a 1,200-mg dose of IMGX003, formerly known as ALV003. The dual-enzyme supplementation therapy was “designed to mitigate the impact of gluten exposure in patients who are attempting to adhere to a GFD.”
The phase 2 trial was conducted at the Mayo Clinic with adult patients (aged 18-80 years) who had physician-diagnosed and biopsy-confirmed celiac disease, followed a GFD for more than 1 year, and had histologically well-controlled disease. During the study, they were exposed to 2 g of gluten per day for 6 weeks.
The primary endpoint focused on the change in the ratio of villus height to crypt depth. The “secondary endpoints included density of intraepithelial lymphocytes and symptom severity. Additional endpoints included serology and gluten-immunogenic peptides in urine.”
Among the 50 patients randomized, 43 completed the study, with 21 assigned to the IMGX003 group. About 74% of the participants were women; the mean age of all participants was 43.8 years.
Overall, the mean change in the ratio of villus height to crypt depth was –0.04 for IMGX003, compared with –0.35 for placebo. In addition, the mean change in the density of intraepithelial lymphocytes for IMGX003 was 9.8, compared with 24.8 for placebo. Based on the ratio of the means for both groups, the researchers estimated an 88% reduction of change in villus height to crypt depth and a 60% reduction of change in intraepithelial lymphocytes.
The mean changes, or worsening from baseline, in symptom severity for IMGX003 vs. placebo were 0.22 vs. 1.63 for abdominal pain, 0.96 vs. 3.29 for bloating, 0.02 vs. 3.2 for tiredness, and 0.64 vs. 2.27 for nonstool composite. The calculated symptom reduction values were 93% for abdominal pain, 53% for bloating, 99% for tiredness, and 70% for nonstool composite.
The mean change from baseline for symptom severity was evaluated over three 2-week periods, and the percent changes showed consistent reduction of symptom worsening during that time. Based on the effect size and trend significance, the P values were .014 for abdominal pain, .030 for bloating, .002 for tiredness, and < . 001 for nonstool composite.
The mean change in gluten-immunogenic peptides in urine (GIP) relative to baseline was 0.59 for IMGX003, compared with 11.53 for placebo. The researchers estimated an efficacy of gluten degradation in vivo of 95%.
“Measurement of GIP in urine demonstrated the purported mechanism of action of IMGX003, namely, degradation of gluten in the stomach, thereby preventing the triggering of the immunogenic autoimmune response,” the authors wrote. “Targeting gluten by degrading the immunogenic peptides before absorption minimizes or abrogates the cascading innate and adaptive immune responses that characterize the inflammatory response to gluten in CeD [celiac disease].”
The study was sponsored by ImmunogenX Inc., and partially funded by a grant from the National Center for Complementary and Integrative Health. The project was further supported by grants from the National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors reported receiving grants from numerous funders, including ImmunogenX, and some reported being a cofounder, stockholder, or board director of the company.
according to a new study published in Gastroenterology.
Latiglutenase led to 95% gluten degradation in the stomach, as indicated by measurements of gluten-immunogenic peptides in urine, wrote Joseph A. Murray, MD, a gastroenterologist at the Mayo Clinic, Rochester, Minn., and Jack A. Syage, PhD, CEO and cofounder of ImmunogenX Inc., Newport Beach, Calif., and colleagues on behalf of the CeliacShield Study Group.
For patients with celiac disease, the only available treatment is a life-long gluten-free diet (GFD). Low levels of gluten exposure can lead to ongoing inflammation and the risk of complications, and about half of patients continue to experience moderate to severe symptoms.
“Although a GFD can reduce symptoms and intestinal damage, the diet is neither easy nor readily achievable by many patients and, furthermore, can be lacking in essential nutrients,” the authors wrote.
In a randomized, double-blind, placebo-controlled gluten challenge study, the research team assessed the efficacy and safety of a 1,200-mg dose of IMGX003, formerly known as ALV003. The dual-enzyme supplementation therapy was “designed to mitigate the impact of gluten exposure in patients who are attempting to adhere to a GFD.”
The phase 2 trial was conducted at the Mayo Clinic with adult patients (aged 18-80 years) who had physician-diagnosed and biopsy-confirmed celiac disease, followed a GFD for more than 1 year, and had histologically well-controlled disease. During the study, they were exposed to 2 g of gluten per day for 6 weeks.
The primary endpoint focused on the change in the ratio of villus height to crypt depth. The “secondary endpoints included density of intraepithelial lymphocytes and symptom severity. Additional endpoints included serology and gluten-immunogenic peptides in urine.”
Among the 50 patients randomized, 43 completed the study, with 21 assigned to the IMGX003 group. About 74% of the participants were women; the mean age of all participants was 43.8 years.
Overall, the mean change in the ratio of villus height to crypt depth was –0.04 for IMGX003, compared with –0.35 for placebo. In addition, the mean change in the density of intraepithelial lymphocytes for IMGX003 was 9.8, compared with 24.8 for placebo. Based on the ratio of the means for both groups, the researchers estimated an 88% reduction of change in villus height to crypt depth and a 60% reduction of change in intraepithelial lymphocytes.
The mean changes, or worsening from baseline, in symptom severity for IMGX003 vs. placebo were 0.22 vs. 1.63 for abdominal pain, 0.96 vs. 3.29 for bloating, 0.02 vs. 3.2 for tiredness, and 0.64 vs. 2.27 for nonstool composite. The calculated symptom reduction values were 93% for abdominal pain, 53% for bloating, 99% for tiredness, and 70% for nonstool composite.
The mean change from baseline for symptom severity was evaluated over three 2-week periods, and the percent changes showed consistent reduction of symptom worsening during that time. Based on the effect size and trend significance, the P values were .014 for abdominal pain, .030 for bloating, .002 for tiredness, and < . 001 for nonstool composite.
The mean change in gluten-immunogenic peptides in urine (GIP) relative to baseline was 0.59 for IMGX003, compared with 11.53 for placebo. The researchers estimated an efficacy of gluten degradation in vivo of 95%.
“Measurement of GIP in urine demonstrated the purported mechanism of action of IMGX003, namely, degradation of gluten in the stomach, thereby preventing the triggering of the immunogenic autoimmune response,” the authors wrote. “Targeting gluten by degrading the immunogenic peptides before absorption minimizes or abrogates the cascading innate and adaptive immune responses that characterize the inflammatory response to gluten in CeD [celiac disease].”
The study was sponsored by ImmunogenX Inc., and partially funded by a grant from the National Center for Complementary and Integrative Health. The project was further supported by grants from the National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors reported receiving grants from numerous funders, including ImmunogenX, and some reported being a cofounder, stockholder, or board director of the company.
FROM GASTROENTEROLOGY
Younger doctors call for more attention to patients with disabilities
As an undergraduate student at Northeastern University in Boston, Meghan Chin spent her summers working for a day program in Rhode Island. Her charges were adults with various forms of intellectual and developmental disabilities (IDD).
“I was very much a caretaker,” Ms. Chin, now 29, said. “It was everything from helping them get dressed in the morning to getting them to medical appointments.”
During one such visit Ms. Chin got a lesson about how health care looks from the viewpoint of someone with an IDD.
The patient was a woman in her 60s and she was having gastrointestinal issues; symptoms she could have articulated, if asked. “She was perfectly capable of telling a clinician where it hurt, how long she had experienced the problem, and what she had done or not done to alleviate it,” Ms. Chin said.
And of comprehending a response. But she was not given the opportunity.
“She would explain what was going on to the clinician,” Ms. Chin recalled. “And the clinician would turn to me and answer. It was this weird three-way conversation – as if she wasn’t even there in the room with us.”
Ms. Chin was incensed at the rude and disrespectful way the patient had been treated. But her charge didn’t seem upset or surprised. Just resigned. “Sadly, she had become used to this,” Ms. Chin said.
For the young aide, however, the experience was searing. “It didn’t seem right to me,” Ms. Chin said. “That’s why, when I went to medical school, I knew I wanted to do better for this population.”
Serendipity led her to Georgetown University, Washington, where she met Kim Bullock, MD, one of the country’s leading advocates for improved health care delivery to those with IDDs.
Dr. Bullock, an associate professor of family medicine, seeks to create better training and educational opportunities for medical students who will likely encounter patients with these disabilities in their practices.
When Dr. Bullock heard Ms. Chin’s story about the patient being ignored, she was not surprised.
“This is not an unusual or unique situation,” said Dr. Bullock, who is also director of Georgetown’s community health division and a faculty member of the university’s Center for Excellence for Developmental Disabilities. “In fact, it’s quite common and is part of what spurred my own interest in educating pre-med and medical students about effective communication techniques, particularly when addressing neurodiverse patients.”
More than 13% of Americans, or roughly 44 million people, have some form of disability, according to the National Institute on Disability at the University of New Hampshire, a figure that does not include those who are institutionalized. The Centers for Disease Control and Prevention estimates that 17% of children aged 3-17 years have a developmental disability.
Even so, many physicians feel ill-prepared to care for disabled patients. A survey of physicians, published in the journal Health Affairs, found that some lacked the resources and training to properly care for patients with disabilities, or that they struggled to coordinate care for such individuals. Some said they did not know which types of accessible equipment, like adjustable tables and chair scales, were needed or how to use them. And some said they actively try to avoid treating patients with disabilities.
Don’t assume
The first step at correcting the problem, Dr. Bullock said, is to not assume that all IDD patients are incapable of communicating. By talking not to the patient but to their caregiver or spouse or child, as the clinician did with Ms. Chin years ago, “we are taking away their agency, their autonomy to speak for and about themselves.”
Change involves altering physicians’ attitudes and assumptions toward this population, through education. But how?
“The medical school curriculum is tight as it is,” Dr. Bullock acknowledged. “There’s a lot of things students have to learn. People wonder: where we will add this?”
Her suggestion: Incorporate IDD all along the way, through programs or experiences that will enable medical students to see such patients “not as something separate, but as people that have special needs just as other populations have.”
Case in point: Operation House Call, a program in Massachusetts designed to support young health care professionals, by building “confidence, interest, and sensitivity” toward individuals with IDD.
Eight medical and allied health schools, including those at Harvard Medical School and Yale School of Nursing, participate in the program, the centerpiece of which is time spent by teams of medical students in the homes of families with neurodiverse members. “It’s transformational,” said Susan Feeney, DNP, NP-C, director of adult gerontology and family nurse practitioner programs at the graduate school of nursing at the University of Massachusetts, Worcester. “They spend a few hours at the homes of these families, have this interaction with them, and journal about their experiences.”
Dr. Feeney described as “transformational” the experience of the students after getting to know these families. “They all come back profoundly changed,” she told this news organization. “As a medical or health care professional, you meet people in an artificial environment of the clinic and hospital. Here, they become human, like you. It takes the stigma away.”
One area of medicine in which this is an exception is pediatrics, where interaction with children with IDD and their families is common – and close. “They’re going to be much more attuned to this,” Dr. Feeney said. “The problem is primary care or internal medicine. Once these children get into their mid and later 20s, and they need a practitioner to talk to about adult concerns.”
And with adulthood come other medical needs, as the physical demands of age fall no less heavily on individuals with IDDs than those without. For example: “Neurodiverse people get pregnant,” Dr. Bullock said. They also can get heart disease as they age; or require the care of a rheumatologist, a neurologist, an orthopedic surgeon, or any other medical specialty.
Generation gap
Fortunately, the next generation of physicians may be more open to this more inclusionary approach toward a widely misunderstood population.
Like Ms. Chin, Sarah Bdeir had experience with this population prior to beginning her training in medicine. She had volunteered at a school for people with IDD.
“It was one of the best experiences I’ve ever had,” Ms. Bdeir, now 23 and a first-year medical student at Wayne State University, Detroit, said. She found that the neurodiverse individuals she worked with had as many abilities as disabilities. “They are capable of learning, but they do it differently,” she said. “You have to adjust to the way they learn. And you have to step out of your own box.”
Ms. Bdeir also heard about Dr. Bullock’s work and is assisting her in a research project on how to better improve nutritional education for people with IDDs. And although she said it may take time for curriculum boards at medical schools to integrate this kind of training into their programs, she believes they will, in part because the rising cohort of medical students today have an eagerness to engage with and learn more about IDD patients.
As does Ms. Chin.
“When I talk to my peers about this, they’re very receptive,” Ms. Chin said. “They want to learn how to better support the IDD population. And they will learn. I believe in my generation of future doctors.”
A version of this article first appeared on Medscape.com.
As an undergraduate student at Northeastern University in Boston, Meghan Chin spent her summers working for a day program in Rhode Island. Her charges were adults with various forms of intellectual and developmental disabilities (IDD).
“I was very much a caretaker,” Ms. Chin, now 29, said. “It was everything from helping them get dressed in the morning to getting them to medical appointments.”
During one such visit Ms. Chin got a lesson about how health care looks from the viewpoint of someone with an IDD.
The patient was a woman in her 60s and she was having gastrointestinal issues; symptoms she could have articulated, if asked. “She was perfectly capable of telling a clinician where it hurt, how long she had experienced the problem, and what she had done or not done to alleviate it,” Ms. Chin said.
And of comprehending a response. But she was not given the opportunity.
“She would explain what was going on to the clinician,” Ms. Chin recalled. “And the clinician would turn to me and answer. It was this weird three-way conversation – as if she wasn’t even there in the room with us.”
Ms. Chin was incensed at the rude and disrespectful way the patient had been treated. But her charge didn’t seem upset or surprised. Just resigned. “Sadly, she had become used to this,” Ms. Chin said.
For the young aide, however, the experience was searing. “It didn’t seem right to me,” Ms. Chin said. “That’s why, when I went to medical school, I knew I wanted to do better for this population.”
Serendipity led her to Georgetown University, Washington, where she met Kim Bullock, MD, one of the country’s leading advocates for improved health care delivery to those with IDDs.
Dr. Bullock, an associate professor of family medicine, seeks to create better training and educational opportunities for medical students who will likely encounter patients with these disabilities in their practices.
When Dr. Bullock heard Ms. Chin’s story about the patient being ignored, she was not surprised.
“This is not an unusual or unique situation,” said Dr. Bullock, who is also director of Georgetown’s community health division and a faculty member of the university’s Center for Excellence for Developmental Disabilities. “In fact, it’s quite common and is part of what spurred my own interest in educating pre-med and medical students about effective communication techniques, particularly when addressing neurodiverse patients.”
More than 13% of Americans, or roughly 44 million people, have some form of disability, according to the National Institute on Disability at the University of New Hampshire, a figure that does not include those who are institutionalized. The Centers for Disease Control and Prevention estimates that 17% of children aged 3-17 years have a developmental disability.
Even so, many physicians feel ill-prepared to care for disabled patients. A survey of physicians, published in the journal Health Affairs, found that some lacked the resources and training to properly care for patients with disabilities, or that they struggled to coordinate care for such individuals. Some said they did not know which types of accessible equipment, like adjustable tables and chair scales, were needed or how to use them. And some said they actively try to avoid treating patients with disabilities.
Don’t assume
The first step at correcting the problem, Dr. Bullock said, is to not assume that all IDD patients are incapable of communicating. By talking not to the patient but to their caregiver or spouse or child, as the clinician did with Ms. Chin years ago, “we are taking away their agency, their autonomy to speak for and about themselves.”
Change involves altering physicians’ attitudes and assumptions toward this population, through education. But how?
“The medical school curriculum is tight as it is,” Dr. Bullock acknowledged. “There’s a lot of things students have to learn. People wonder: where we will add this?”
Her suggestion: Incorporate IDD all along the way, through programs or experiences that will enable medical students to see such patients “not as something separate, but as people that have special needs just as other populations have.”
Case in point: Operation House Call, a program in Massachusetts designed to support young health care professionals, by building “confidence, interest, and sensitivity” toward individuals with IDD.
Eight medical and allied health schools, including those at Harvard Medical School and Yale School of Nursing, participate in the program, the centerpiece of which is time spent by teams of medical students in the homes of families with neurodiverse members. “It’s transformational,” said Susan Feeney, DNP, NP-C, director of adult gerontology and family nurse practitioner programs at the graduate school of nursing at the University of Massachusetts, Worcester. “They spend a few hours at the homes of these families, have this interaction with them, and journal about their experiences.”
Dr. Feeney described as “transformational” the experience of the students after getting to know these families. “They all come back profoundly changed,” she told this news organization. “As a medical or health care professional, you meet people in an artificial environment of the clinic and hospital. Here, they become human, like you. It takes the stigma away.”
One area of medicine in which this is an exception is pediatrics, where interaction with children with IDD and their families is common – and close. “They’re going to be much more attuned to this,” Dr. Feeney said. “The problem is primary care or internal medicine. Once these children get into their mid and later 20s, and they need a practitioner to talk to about adult concerns.”
And with adulthood come other medical needs, as the physical demands of age fall no less heavily on individuals with IDDs than those without. For example: “Neurodiverse people get pregnant,” Dr. Bullock said. They also can get heart disease as they age; or require the care of a rheumatologist, a neurologist, an orthopedic surgeon, or any other medical specialty.
Generation gap
Fortunately, the next generation of physicians may be more open to this more inclusionary approach toward a widely misunderstood population.
Like Ms. Chin, Sarah Bdeir had experience with this population prior to beginning her training in medicine. She had volunteered at a school for people with IDD.
“It was one of the best experiences I’ve ever had,” Ms. Bdeir, now 23 and a first-year medical student at Wayne State University, Detroit, said. She found that the neurodiverse individuals she worked with had as many abilities as disabilities. “They are capable of learning, but they do it differently,” she said. “You have to adjust to the way they learn. And you have to step out of your own box.”
Ms. Bdeir also heard about Dr. Bullock’s work and is assisting her in a research project on how to better improve nutritional education for people with IDDs. And although she said it may take time for curriculum boards at medical schools to integrate this kind of training into their programs, she believes they will, in part because the rising cohort of medical students today have an eagerness to engage with and learn more about IDD patients.
As does Ms. Chin.
“When I talk to my peers about this, they’re very receptive,” Ms. Chin said. “They want to learn how to better support the IDD population. And they will learn. I believe in my generation of future doctors.”
A version of this article first appeared on Medscape.com.
As an undergraduate student at Northeastern University in Boston, Meghan Chin spent her summers working for a day program in Rhode Island. Her charges were adults with various forms of intellectual and developmental disabilities (IDD).
“I was very much a caretaker,” Ms. Chin, now 29, said. “It was everything from helping them get dressed in the morning to getting them to medical appointments.”
During one such visit Ms. Chin got a lesson about how health care looks from the viewpoint of someone with an IDD.
The patient was a woman in her 60s and she was having gastrointestinal issues; symptoms she could have articulated, if asked. “She was perfectly capable of telling a clinician where it hurt, how long she had experienced the problem, and what she had done or not done to alleviate it,” Ms. Chin said.
And of comprehending a response. But she was not given the opportunity.
“She would explain what was going on to the clinician,” Ms. Chin recalled. “And the clinician would turn to me and answer. It was this weird three-way conversation – as if she wasn’t even there in the room with us.”
Ms. Chin was incensed at the rude and disrespectful way the patient had been treated. But her charge didn’t seem upset or surprised. Just resigned. “Sadly, she had become used to this,” Ms. Chin said.
For the young aide, however, the experience was searing. “It didn’t seem right to me,” Ms. Chin said. “That’s why, when I went to medical school, I knew I wanted to do better for this population.”
Serendipity led her to Georgetown University, Washington, where she met Kim Bullock, MD, one of the country’s leading advocates for improved health care delivery to those with IDDs.
Dr. Bullock, an associate professor of family medicine, seeks to create better training and educational opportunities for medical students who will likely encounter patients with these disabilities in their practices.
When Dr. Bullock heard Ms. Chin’s story about the patient being ignored, she was not surprised.
“This is not an unusual or unique situation,” said Dr. Bullock, who is also director of Georgetown’s community health division and a faculty member of the university’s Center for Excellence for Developmental Disabilities. “In fact, it’s quite common and is part of what spurred my own interest in educating pre-med and medical students about effective communication techniques, particularly when addressing neurodiverse patients.”
More than 13% of Americans, or roughly 44 million people, have some form of disability, according to the National Institute on Disability at the University of New Hampshire, a figure that does not include those who are institutionalized. The Centers for Disease Control and Prevention estimates that 17% of children aged 3-17 years have a developmental disability.
Even so, many physicians feel ill-prepared to care for disabled patients. A survey of physicians, published in the journal Health Affairs, found that some lacked the resources and training to properly care for patients with disabilities, or that they struggled to coordinate care for such individuals. Some said they did not know which types of accessible equipment, like adjustable tables and chair scales, were needed or how to use them. And some said they actively try to avoid treating patients with disabilities.
Don’t assume
The first step at correcting the problem, Dr. Bullock said, is to not assume that all IDD patients are incapable of communicating. By talking not to the patient but to their caregiver or spouse or child, as the clinician did with Ms. Chin years ago, “we are taking away their agency, their autonomy to speak for and about themselves.”
Change involves altering physicians’ attitudes and assumptions toward this population, through education. But how?
“The medical school curriculum is tight as it is,” Dr. Bullock acknowledged. “There’s a lot of things students have to learn. People wonder: where we will add this?”
Her suggestion: Incorporate IDD all along the way, through programs or experiences that will enable medical students to see such patients “not as something separate, but as people that have special needs just as other populations have.”
Case in point: Operation House Call, a program in Massachusetts designed to support young health care professionals, by building “confidence, interest, and sensitivity” toward individuals with IDD.
Eight medical and allied health schools, including those at Harvard Medical School and Yale School of Nursing, participate in the program, the centerpiece of which is time spent by teams of medical students in the homes of families with neurodiverse members. “It’s transformational,” said Susan Feeney, DNP, NP-C, director of adult gerontology and family nurse practitioner programs at the graduate school of nursing at the University of Massachusetts, Worcester. “They spend a few hours at the homes of these families, have this interaction with them, and journal about their experiences.”
Dr. Feeney described as “transformational” the experience of the students after getting to know these families. “They all come back profoundly changed,” she told this news organization. “As a medical or health care professional, you meet people in an artificial environment of the clinic and hospital. Here, they become human, like you. It takes the stigma away.”
One area of medicine in which this is an exception is pediatrics, where interaction with children with IDD and their families is common – and close. “They’re going to be much more attuned to this,” Dr. Feeney said. “The problem is primary care or internal medicine. Once these children get into their mid and later 20s, and they need a practitioner to talk to about adult concerns.”
And with adulthood come other medical needs, as the physical demands of age fall no less heavily on individuals with IDDs than those without. For example: “Neurodiverse people get pregnant,” Dr. Bullock said. They also can get heart disease as they age; or require the care of a rheumatologist, a neurologist, an orthopedic surgeon, or any other medical specialty.
Generation gap
Fortunately, the next generation of physicians may be more open to this more inclusionary approach toward a widely misunderstood population.
Like Ms. Chin, Sarah Bdeir had experience with this population prior to beginning her training in medicine. She had volunteered at a school for people with IDD.
“It was one of the best experiences I’ve ever had,” Ms. Bdeir, now 23 and a first-year medical student at Wayne State University, Detroit, said. She found that the neurodiverse individuals she worked with had as many abilities as disabilities. “They are capable of learning, but they do it differently,” she said. “You have to adjust to the way they learn. And you have to step out of your own box.”
Ms. Bdeir also heard about Dr. Bullock’s work and is assisting her in a research project on how to better improve nutritional education for people with IDDs. And although she said it may take time for curriculum boards at medical schools to integrate this kind of training into their programs, she believes they will, in part because the rising cohort of medical students today have an eagerness to engage with and learn more about IDD patients.
As does Ms. Chin.
“When I talk to my peers about this, they’re very receptive,” Ms. Chin said. “They want to learn how to better support the IDD population. And they will learn. I believe in my generation of future doctors.”
A version of this article first appeared on Medscape.com.
Novel YouTube study detects colonoscopy misinformation, guides better content creation
Don’t just sit there. Post something.
To combat misinformation about colonoscopy, health care providers (HCPs) should engage more with social media platforms and create accurate, engaging educational videos, according to investigators.
An assessment of top-ranking YouTube videos about colonoscopy by both lay people and HCPs revealed numerous inaccuracies, which have potentially contributed to public hesitancy to undergo appropriate screening, reported lead author Austin L. Chiang, MD, MPH, of Thomas Jefferson University Hospitals, Philadelphia, and colleagues.
“The prevalence and predictors of misinformation among contents on social media platforms such as YouTube with regard to colonoscopy remain unknown,” the investigators wrote in Gastro Hep Advances. They noted that previous research characterized YouTube as a “suboptimal” resource for information about colonoscopy, although those studies did not use validated instruments.
For the present cohort study, Dr. Chiang and colleagues performed a YouTube search for “colonoscopy” on Nov. 21, 2020. Results with more than 250,000 views were included in the analysis, netting 69 videos. Of these, 39 were posted by lay people, while the remaining 30 were posted by HCPs.
Three board-certified gastroenterologists measured video quality with two validated instruments for evaluating consumer health information: DISCERN and the Patient Education Material Assessment Tool (PEMAT) understandability score. Any video with a DISCERN score less than 2 or a PEMAT score less than 50% was deemed “inaccurate or of low scientific quality per established standards.” The investigators also scored likelihood of recommending a video to a patient on a 5-point Likert scale.
More than half of the videos were low quality based on DISCERN (52.2%) and PEMAT (59.4%) criteria. Videos that featured an HCP scored significantly higher on both scales, while videos created by HCPs were more likely to meet minimum-quality criteria and be recommended to patients.
Specifically, only 20.5% of videos created by laypeople made the grade, compared with 66.7% (PMAT) and 83.3% (DISCERN) of videos made by HCPs, depending on the quality instrument. It therefore follows that an HCP creator was the greatest predictive factor for a high-quality video, according to the area under the receiving operating characteristic curve.
“Our analysis demonstrates a disturbing proportion of inaccuracies and poor scientific quality information among the most viewed YouTube videos around colonoscopy using validated instruments for consumer information,” the investigators wrote.
Types of misinformation varied. Some of the videos contradicted current recommendations and intentionally overstated colonoscopy risk, while others called for screening every year.
“Although it is disheartening to imagine the influence of these inaccurate videos on millions of people, it may be helpful to learn from them and dissect why they have succeeded in attracting viewers,” the investigators wrote.
So which videos had the most views? To put it bluntly, it was the funny, “gross” stuff. The top-ranking colonoscopy videos featured comedians talking about their colonoscopies or had shocking footage, like worms wiggling during an endoscopic exam of a patient with a parasitic infection.
How to create better content
While these acts may be hard to follow for the average gastroenterologist-YouTuber, Dr. Chiang and colleagues did detect one video characteristic that should be avoided: complexity. Multivariate analysis showed that endoscopic footage was a negative effect modifier for clarity and understandability.
“The main challenge of any video content is striking a balance between brevity and accuracy/comprehensiveness,” the investigators wrote. “When describing endoscopic videos to lay audiences, gastroenterologists must be careful to provide appropriate clinical context and use wording that is concise and easily comprehended.”
More broadly, the investigators called for a three-pronged approach to combat misinformation by creating better content.
First, they advised HCPs to increase participation on social media channels, with a focus on promoting health equity among at-risk and non–English-speaking audiences. Second, they asked professional societies such as the American Gastroenterological Association to assist HCPs with the fundamentals of content creation, including techniques in storytelling and videography. Finally, they proposed HCPs partner with lay creators, following a common strategy in traditional media in which celebrities share scientifically grounded medical information.
“Although the prevalence of inaccurate colonoscopy videos is concerning, an understanding of existing health misinformation and a proactive approach to cultivate professional content creation may help provide patients with high-quality information to help achieve colorectal cancer screening targets and improve health outcomes,” the investigators concluded.
The study was partially funded by the National Institutes of Health. Dr. Chiang is an employee of Medtronic and holds a seat on the YouTube Health Advisory Board. The other investigators disclosed no competing interests.
The advent of social media ushered in the promise of a new age of information democratization. Unfortunately, the reality of increasingly accessible information – including misinformation – has disabused us of the notion that this increased accessibility is an unalloyed good. “Fake news” abounds, and in an era in which “truth” seems to be in the eye of the beholder – or influencer – medical misinformation appetizingly presented to the public is a particular hazard to public health. This is one of the first studies to offer an objective description of the medical information landscape as it pertains to the field of gastroenterology.
There is a tension between accessibility and quality of information within social media, the modern public forum. This study highlights that tension and serves both as a call-to-arms and a guide for experts on how to displace the amateurs and hucksters who are confusing those who’ve come to the forum not for entertainment but for information.
Jason M. Brown, MD, is assistant professor and Grady site fellowship director, division of digestive diseases, Emory University School of Medicine, Atlanta. Dr. Brown reported no relevant conflicts of interest.
The advent of social media ushered in the promise of a new age of information democratization. Unfortunately, the reality of increasingly accessible information – including misinformation – has disabused us of the notion that this increased accessibility is an unalloyed good. “Fake news” abounds, and in an era in which “truth” seems to be in the eye of the beholder – or influencer – medical misinformation appetizingly presented to the public is a particular hazard to public health. This is one of the first studies to offer an objective description of the medical information landscape as it pertains to the field of gastroenterology.
There is a tension between accessibility and quality of information within social media, the modern public forum. This study highlights that tension and serves both as a call-to-arms and a guide for experts on how to displace the amateurs and hucksters who are confusing those who’ve come to the forum not for entertainment but for information.
Jason M. Brown, MD, is assistant professor and Grady site fellowship director, division of digestive diseases, Emory University School of Medicine, Atlanta. Dr. Brown reported no relevant conflicts of interest.
The advent of social media ushered in the promise of a new age of information democratization. Unfortunately, the reality of increasingly accessible information – including misinformation – has disabused us of the notion that this increased accessibility is an unalloyed good. “Fake news” abounds, and in an era in which “truth” seems to be in the eye of the beholder – or influencer – medical misinformation appetizingly presented to the public is a particular hazard to public health. This is one of the first studies to offer an objective description of the medical information landscape as it pertains to the field of gastroenterology.
There is a tension between accessibility and quality of information within social media, the modern public forum. This study highlights that tension and serves both as a call-to-arms and a guide for experts on how to displace the amateurs and hucksters who are confusing those who’ve come to the forum not for entertainment but for information.
Jason M. Brown, MD, is assistant professor and Grady site fellowship director, division of digestive diseases, Emory University School of Medicine, Atlanta. Dr. Brown reported no relevant conflicts of interest.
Don’t just sit there. Post something.
To combat misinformation about colonoscopy, health care providers (HCPs) should engage more with social media platforms and create accurate, engaging educational videos, according to investigators.
An assessment of top-ranking YouTube videos about colonoscopy by both lay people and HCPs revealed numerous inaccuracies, which have potentially contributed to public hesitancy to undergo appropriate screening, reported lead author Austin L. Chiang, MD, MPH, of Thomas Jefferson University Hospitals, Philadelphia, and colleagues.
“The prevalence and predictors of misinformation among contents on social media platforms such as YouTube with regard to colonoscopy remain unknown,” the investigators wrote in Gastro Hep Advances. They noted that previous research characterized YouTube as a “suboptimal” resource for information about colonoscopy, although those studies did not use validated instruments.
For the present cohort study, Dr. Chiang and colleagues performed a YouTube search for “colonoscopy” on Nov. 21, 2020. Results with more than 250,000 views were included in the analysis, netting 69 videos. Of these, 39 were posted by lay people, while the remaining 30 were posted by HCPs.
Three board-certified gastroenterologists measured video quality with two validated instruments for evaluating consumer health information: DISCERN and the Patient Education Material Assessment Tool (PEMAT) understandability score. Any video with a DISCERN score less than 2 or a PEMAT score less than 50% was deemed “inaccurate or of low scientific quality per established standards.” The investigators also scored likelihood of recommending a video to a patient on a 5-point Likert scale.
More than half of the videos were low quality based on DISCERN (52.2%) and PEMAT (59.4%) criteria. Videos that featured an HCP scored significantly higher on both scales, while videos created by HCPs were more likely to meet minimum-quality criteria and be recommended to patients.
Specifically, only 20.5% of videos created by laypeople made the grade, compared with 66.7% (PMAT) and 83.3% (DISCERN) of videos made by HCPs, depending on the quality instrument. It therefore follows that an HCP creator was the greatest predictive factor for a high-quality video, according to the area under the receiving operating characteristic curve.
“Our analysis demonstrates a disturbing proportion of inaccuracies and poor scientific quality information among the most viewed YouTube videos around colonoscopy using validated instruments for consumer information,” the investigators wrote.
Types of misinformation varied. Some of the videos contradicted current recommendations and intentionally overstated colonoscopy risk, while others called for screening every year.
“Although it is disheartening to imagine the influence of these inaccurate videos on millions of people, it may be helpful to learn from them and dissect why they have succeeded in attracting viewers,” the investigators wrote.
So which videos had the most views? To put it bluntly, it was the funny, “gross” stuff. The top-ranking colonoscopy videos featured comedians talking about their colonoscopies or had shocking footage, like worms wiggling during an endoscopic exam of a patient with a parasitic infection.
How to create better content
While these acts may be hard to follow for the average gastroenterologist-YouTuber, Dr. Chiang and colleagues did detect one video characteristic that should be avoided: complexity. Multivariate analysis showed that endoscopic footage was a negative effect modifier for clarity and understandability.
“The main challenge of any video content is striking a balance between brevity and accuracy/comprehensiveness,” the investigators wrote. “When describing endoscopic videos to lay audiences, gastroenterologists must be careful to provide appropriate clinical context and use wording that is concise and easily comprehended.”
More broadly, the investigators called for a three-pronged approach to combat misinformation by creating better content.
First, they advised HCPs to increase participation on social media channels, with a focus on promoting health equity among at-risk and non–English-speaking audiences. Second, they asked professional societies such as the American Gastroenterological Association to assist HCPs with the fundamentals of content creation, including techniques in storytelling and videography. Finally, they proposed HCPs partner with lay creators, following a common strategy in traditional media in which celebrities share scientifically grounded medical information.
“Although the prevalence of inaccurate colonoscopy videos is concerning, an understanding of existing health misinformation and a proactive approach to cultivate professional content creation may help provide patients with high-quality information to help achieve colorectal cancer screening targets and improve health outcomes,” the investigators concluded.
The study was partially funded by the National Institutes of Health. Dr. Chiang is an employee of Medtronic and holds a seat on the YouTube Health Advisory Board. The other investigators disclosed no competing interests.
Don’t just sit there. Post something.
To combat misinformation about colonoscopy, health care providers (HCPs) should engage more with social media platforms and create accurate, engaging educational videos, according to investigators.
An assessment of top-ranking YouTube videos about colonoscopy by both lay people and HCPs revealed numerous inaccuracies, which have potentially contributed to public hesitancy to undergo appropriate screening, reported lead author Austin L. Chiang, MD, MPH, of Thomas Jefferson University Hospitals, Philadelphia, and colleagues.
“The prevalence and predictors of misinformation among contents on social media platforms such as YouTube with regard to colonoscopy remain unknown,” the investigators wrote in Gastro Hep Advances. They noted that previous research characterized YouTube as a “suboptimal” resource for information about colonoscopy, although those studies did not use validated instruments.
For the present cohort study, Dr. Chiang and colleagues performed a YouTube search for “colonoscopy” on Nov. 21, 2020. Results with more than 250,000 views were included in the analysis, netting 69 videos. Of these, 39 were posted by lay people, while the remaining 30 were posted by HCPs.
Three board-certified gastroenterologists measured video quality with two validated instruments for evaluating consumer health information: DISCERN and the Patient Education Material Assessment Tool (PEMAT) understandability score. Any video with a DISCERN score less than 2 or a PEMAT score less than 50% was deemed “inaccurate or of low scientific quality per established standards.” The investigators also scored likelihood of recommending a video to a patient on a 5-point Likert scale.
More than half of the videos were low quality based on DISCERN (52.2%) and PEMAT (59.4%) criteria. Videos that featured an HCP scored significantly higher on both scales, while videos created by HCPs were more likely to meet minimum-quality criteria and be recommended to patients.
Specifically, only 20.5% of videos created by laypeople made the grade, compared with 66.7% (PMAT) and 83.3% (DISCERN) of videos made by HCPs, depending on the quality instrument. It therefore follows that an HCP creator was the greatest predictive factor for a high-quality video, according to the area under the receiving operating characteristic curve.
“Our analysis demonstrates a disturbing proportion of inaccuracies and poor scientific quality information among the most viewed YouTube videos around colonoscopy using validated instruments for consumer information,” the investigators wrote.
Types of misinformation varied. Some of the videos contradicted current recommendations and intentionally overstated colonoscopy risk, while others called for screening every year.
“Although it is disheartening to imagine the influence of these inaccurate videos on millions of people, it may be helpful to learn from them and dissect why they have succeeded in attracting viewers,” the investigators wrote.
So which videos had the most views? To put it bluntly, it was the funny, “gross” stuff. The top-ranking colonoscopy videos featured comedians talking about their colonoscopies or had shocking footage, like worms wiggling during an endoscopic exam of a patient with a parasitic infection.
How to create better content
While these acts may be hard to follow for the average gastroenterologist-YouTuber, Dr. Chiang and colleagues did detect one video characteristic that should be avoided: complexity. Multivariate analysis showed that endoscopic footage was a negative effect modifier for clarity and understandability.
“The main challenge of any video content is striking a balance between brevity and accuracy/comprehensiveness,” the investigators wrote. “When describing endoscopic videos to lay audiences, gastroenterologists must be careful to provide appropriate clinical context and use wording that is concise and easily comprehended.”
More broadly, the investigators called for a three-pronged approach to combat misinformation by creating better content.
First, they advised HCPs to increase participation on social media channels, with a focus on promoting health equity among at-risk and non–English-speaking audiences. Second, they asked professional societies such as the American Gastroenterological Association to assist HCPs with the fundamentals of content creation, including techniques in storytelling and videography. Finally, they proposed HCPs partner with lay creators, following a common strategy in traditional media in which celebrities share scientifically grounded medical information.
“Although the prevalence of inaccurate colonoscopy videos is concerning, an understanding of existing health misinformation and a proactive approach to cultivate professional content creation may help provide patients with high-quality information to help achieve colorectal cancer screening targets and improve health outcomes,” the investigators concluded.
The study was partially funded by the National Institutes of Health. Dr. Chiang is an employee of Medtronic and holds a seat on the YouTube Health Advisory Board. The other investigators disclosed no competing interests.
FROM GASTRO HEP ADVANCES