Cutaneous T-cell lymphoma (CTCL) is a diverse group of skin-homing T-cell neoplasms with a wide array of clinical presentations, immunohistopathologic subtypes, and prognoses. The age-adjusted incidence of CTCL in the United States is 6.4 per million individuals.¹ In the early stages of CTCL, the malignant lymphocytes are isolated to the skin, while more advanced disease involves metastatic spread to the lymphatic and peripheral blood compartments. Mycosis fungoides (MF) is the most common subtype of CTCL, comprising roughly 50% of all cases. The etiology of CTCL and MF remains poorly understood and no unifying driver mutation has been identified.² However, recent sequencing efforts have revealed recurrent genomics alterations primarily in 3 pathways: constitutive T-cell activation, resistance to apoptosis/cell-cycle dysregulation, and DNA structural/gene expression dysregulation.^3-8 These studies, among others, support the assertion that CTCL may be an epigenetic phenomenon.^9-14

Most patients with MF will experience an indolent course of skin-limited disease with a favorable prognosis and a 5-year survival rate of 88%.^15-17 A large study of patients with MF (N=525) followed for more than 40 years determined that approximately 20% of early-stage (IA-IIA) patients with MF progress to develop tumors, metastasis to the lymphatic tissue, and/or leukemic blood disease.¹⁸

Cutaneous T-cell lymphoma is a chronic disease, and most treatment responses are partial and short-lived. Allogenic hematopoietic transplantation is the only potentially curative option, and all other therapies are aimed at arresting progression and achieving remission.¹⁹ Skin-directed therapies include topical steroids, topical nitrogen mustard, phototherapy, and radiation. Systemic therapies such as oral retinoids, chemotherapy, and immunotherapy may be used alone or in combination with skin-directed therapies based on the overall disease stage and clinical presentation. Unfortunately, complete response (CR) to therapy is rare and fleeting, and most patients require multiple sequential treatments over their lifetimes.²⁰

Across all stages of CTCL, there is a therapeutic push to combination and immune-based therapies to achieve more durable responses. The imidazoquinolines are a family of toll-like receptor (TLR) agonists including imiquimod (TLR7) and resiquimod (TLR7 and TLR8). Imiquimod (IMQ) is a topical immunomodulator, which increases the local cytotoxic helper T-cell profile (T_H1 marked by IFN-α, tumor necrosis factor α, IL-1α, IL-6, and IL-8), thereby enhancing both humoral and innate immune responses targeting tumor cells.^21-23 Several small studies evaluating topical TLR agonists have documented efficacy in patients with early and advanced stages of CTCL.^24-34

Skin-directed chemotherapy using 5-fluorouracil (5-FU) has shown activity against many cutaneous malignancies. 5-Fluorouracil is an antimetabolite drug that inhibits thymidylate synthase, resulting in interrupted DNA and RNA synthesis and leading to an apoptotic cell death (Figure 1). It has been administered via intravenous, oral (prodrug), intralesional (IL), and topical routes with well-documented success in treating cutaneous squamous cell carcinoma, keratoacanthoma, basal cell carcinoma, and precancerous actinic keratosis.³⁵ As a topical, 5-FU has been shown to provide a good response in 6 patients with early MF.³⁶ In late-stage MF, 5-FU has been used in combination with methotrexate as an infusion.³⁷ We present a single-center case series of 9 patients with CTCL who received combination IL 5-FU and IMQ cream 5%.

Methods

Patient Selection—Patients were selected from our multidisciplinary CTCL subspecialty clinic at the Inova Schar Cancer Institute (Fairfax, Virginia). Patients with single to few recalcitrant CTCL plaques or tumors that were symptomatic or otherwise bothersome were included. All patients had at least 2 prior skin-directed therapies that failed, and many had advanced-stage disease requiring systemic therapy. All patients provided verbal consent.

Study Materials and Evaluations—Patients received IL injections of 5-FU 50 mg/mL. The volume injected was approximately 0.2 cc per cubic centimeter of lesion tissue. Injections were repeated at 2- to 3-week intervals until the target lesions achieved an acute hemorrhagic phase characterized by erosion, flattening, and crust formation. The total number of serial injections administered ranged from 1 to 5. The patients concomitantly treated all lesions with IMQ cream 5% daily for a duration of 2 to 3 months.

Medical photography and physical examination were performed every 2 to 3 weeks until the hemorrhagic phase resolved and treated sites re-epithelialized. Index lesions were assessed using the Composite Assessment of Index Lesion Severity (CAILS) score by a single investigator for all patients.³⁸ Scores were retrospectively assigned using the investigator’s detailed physical examination descriptions and extensive medical photography. Any hyperpigmentation was scored as residual disease, despite the fair interpretation of it as procedure-related postinflammatory dyspigmentation. Complete response was strictly defined as a CAILS score of 0. The patients were screened for possible systemic effects of IMQ, including the presence of fever, chills, fatigue, and myalgia. Patients were evaluated every 6 to 12 weeks as a standing follow-up.

Statistical Analysis—Reductions were calculated using local regression from baseline to the 4- to 7-week follow-up. Patients with multiple lesions had their CAILS score averaged at ea

Results

Nine patients aged 28 to 91 years (median age, 66 years) with CTCL stages IA to IVA2, who had lesions located throughout their body, achieved CR; 3 patients were female (Table 1). The most common phenotype was CD8⁺ (n=3). All patients had at least 2 prior skin-directed therapies at treatment sites that failed, and 1 patient had 7 prior treatments that failed. Prior treatments included a variety of modalities, including all standard-of-care options and enrollment in clinical trials. One patient died from pneumonia following CR (Table 2). Seven patients had previously received systemic therapy for CTCL, and 1 patient was stable on romidepsin during our study. In patients who received more than 1 injection of 5-FU—1 injection: 3 patients; 2 injections: 3 patients; 3 injections: 1 patient; 4 injections: 1 patient; 5 injections: 1 patient—injections were spaced by 2 to 3 weeks. There was 1 patient who initially had an inadequate dosing of IL 5-FU and was restarted 14 months later; this was the patient with 5 total injections. This occurred in one of the first patients in the study, who presented with a facial lesion. The investigator used approximately 0.02 cc per cubic centimeter (dose reduction of nearly 90%), which was inadequate and did not achieve the requisite hemorrhagic phase.

Treatment was well tolerated overall. In all cases, a hemorrhagic phase was achieved, characterized by erosion and crusting that was rated as mildly uncomfortable by 7 patients and moderately uncomfortable by 2 patients. In total, 15 lesions in all 9 patients achieved a CR within 24 weeks of the final injection. The longest treatment course required 12 weeks of therapy with IMQ and 5 IL injections of 5-FU. The fastest CR was achieved in patient 6 within 6 weeks following a single IL injection of 5-FU and 2 applications of IMQ. The average time to CR was 14.78 weeks (95% CI, 1.75-27.81)(Figure 2), and the time to CR ranged from 4 to 24 weeks. On average, patients achieved more than 50% reduction in CAILS score by 3.53 weeks (95% CI, 1.55-5.51) and nearly a 4-fold (74.7%) reduction at the time of initial follow-up (occurring at 4–7 weeks). By 7 weeks, patient 3 had the most modest improvement in CAILS score with a 2.75-fold reduction, while patient 5 had the largest decrease with a 5-fold reduction. Figure 3 shows representative clinical photographs of 2 patients before and after treatment, with all patients having similar results.

Comment

Cutaneous T-cell lymphoma is a chronic skin cancer with a pattern of limited response to therapy and frequent recurrence. Currently available skin-directed therapies function as temporizing measures rather than curative treatments. Immunotherapy offers the promise of lasting disease control even after cessation of treatment, as it may essentially awaken cutaneous immune surveillance to malignant lymphocytes.

Several small observational studies have evaluated topical IMQ and TLR agonist therapy in CTCL. The construct of prior reports varies widely, including many different pretreatments, dosing schemes, and follow-up periods.^24-33 Dosing intervals with IMQ ranged from daily to 3 times per week and treatment duration from 2 weeks to 1 year. Complete response rates from 50% to 100% were reported, and partial responses were observed in all but 1 patient, with recurrence-free follow-up ranging from 6 months to 8 years. Comparatively, combining IL 5-FU and IMQ appears to be at least as effective as IMQ alone or in other sequential treatments and combinations.^24-33

Resiquimod, an experimental TLR7/8 agonist, has shown promising results in CTCL. Rook et al³⁴ conducted a phase 1 trial of topical resiquimod in 12 early-stage patients with CTCL, all of whom responded to therapy. Two patients achieved CR, and 9 achieved a partial response, including 5 patients with the folliculotropic subtype. Interestingly, an abscopal effect was observed in 92% (11/12) of patients. Molecular evidence of reduction of the malignant clone was observed in 90% of patients via high-throughput sequencing of lesional tissue.³⁴ These exciting findings suggest that topical immune therapy with TLR agonists may achieve robust, sustained, and possibly global disease control in CTCL.

Topical therapies are limited by depth of absorption, which can present a barrier to using these treatments for thicker plaques and tumors. Combining IL and topical routes was critical in our study design. Having good clinical experience using IL 5-FU in nonmelanoma skin cancers, we hypothesized that IL 5-FU would achieve a cytotoxic response through the full depth of thicker lesions and erode the surface of these lesions to facilitate penetration of topical IMQ. We additionally hypothesized that the combination of mechanisms of action would lead to an additive or synergistic response (Figure 1). By first inducing apoptotic cell death via 5-FU, we hoped to spill malignant lymphocyte neoantigens. Coupling that antigen exposure with an enhanced T_H1-biased immune response driven by IMQ should facilitate tumor clearance and immune education against malignant T cells.

In our case series, all 15 lesions in 9 patients completely cleared, and no recurrences were observed at 26-month follow-up. No patients encountered any major adverse events, and the procedure was well tolerated by all.

Study Limitations—Limitations of this small study certainly exist. It is impossible to prove that our mechanistic theory is accurate given our strictly clinical assessment tools. We speculate that if our results had been achieved with IL 5-FU alone, future investigation with a prospective study using multiple treatment arms including a control would be warranted. Kannangara et al³⁶ reported the use of topical 5-FU for MF and the drug’s utility in either topical or IL routes for CTCL, which deserves further study. It is less likely that results were achieved exclusively by IMQ because of the rapid tissue breakdown observed in the acute hemorrhagic phase. This phenomenon is best explained by the sudden apoptosis caused by DNA intercalation from 5-FU. The follow-up period is not uniform because this was a rolling enrollment study. Follow-up will be ongoing, and we aim to assess all patients up to at least the 5-year point. A final limitation of this study is the purely clinical end point. In the future, pretreatment and posttreatment biopsies would be useful in assessing proof of histologic response, and high-throughput sequencing may be used to look for molecular clearance via liquid biopsy. Lastly, careful observation for possible abscopal effect using the Severity-Weighted Assessment Tool score would be interesting and potentially contributory to our understanding of the impact of topical immune therapy on cutaneous tumor surveillance.

Conclusion

Combination IL 5-FU and topical IMQ is a well-tolerated, effective, and durable therapy for recalcitrant thick plaques and tumors of CTCL. This treatment is convenient and cost-effective. The procedure is performed in less than 5 minutes in an outpatient dermatology clinic. All patients received full insurance coverage for both drug and procedure fees under Medicare and commercial carriers.

Cutaneous T-cell lymphoma (CTCL) is a diverse group of skin-homing T-cell neoplasms with a wide array of clinical presentations, immunohistopathologic subtypes, and prognoses. The age-adjusted incidence of CTCL in the United States is 6.4 per million individuals.¹ In the early stages of CTCL, the malignant lymphocytes are isolated to the skin, while more advanced disease involves metastatic spread to the lymphatic and peripheral blood compartments. Mycosis fungoides (MF) is the most common subtype of CTCL, comprising roughly 50% of all cases. The etiology of CTCL and MF remains poorly understood and no unifying driver mutation has been identified.² However, recent sequencing efforts have revealed recurrent genomics alterations primarily in 3 pathways: constitutive T-cell activation, resistance to apoptosis/cell-cycle dysregulation, and DNA structural/gene expression dysregulation.^3-8 These studies, among others, support the assertion that CTCL may be an epigenetic phenomenon.^9-14

Most patients with MF will experience an indolent course of skin-limited disease with a favorable prognosis and a 5-year survival rate of 88%.^15-17 A large study of patients with MF (N=525) followed for more than 40 years determined that approximately 20% of early-stage (IA-IIA) patients with MF progress to develop tumors, metastasis to the lymphatic tissue, and/or leukemic blood disease.¹⁸

Cutaneous T-cell lymphoma is a chronic disease, and most treatment responses are partial and short-lived. Allogenic hematopoietic transplantation is the only potentially curative option, and all other therapies are aimed at arresting progression and achieving remission.¹⁹ Skin-directed therapies include topical steroids, topical nitrogen mustard, phototherapy, and radiation. Systemic therapies such as oral retinoids, chemotherapy, and immunotherapy may be used alone or in combination with skin-directed therapies based on the overall disease stage and clinical presentation. Unfortunately, complete response (CR) to therapy is rare and fleeting, and most patients require multiple sequential treatments over their lifetimes.²⁰

Across all stages of CTCL, there is a therapeutic push to combination and immune-based therapies to achieve more durable responses. The imidazoquinolines are a family of toll-like receptor (TLR) agonists including imiquimod (TLR7) and resiquimod (TLR7 and TLR8). Imiquimod (IMQ) is a topical immunomodulator, which increases the local cytotoxic helper T-cell profile (T_H1 marked by IFN-α, tumor necrosis factor α, IL-1α, IL-6, and IL-8), thereby enhancing both humoral and innate immune responses targeting tumor cells.^21-23 Several small studies evaluating topical TLR agonists have documented efficacy in patients with early and advanced stages of CTCL.^24-34

Skin-directed chemotherapy using 5-fluorouracil (5-FU) has shown activity against many cutaneous malignancies. 5-Fluorouracil is an antimetabolite drug that inhibits thymidylate synthase, resulting in interrupted DNA and RNA synthesis and leading to an apoptotic cell death (Figure 1). It has been administered via intravenous, oral (prodrug), intralesional (IL), and topical routes with well-documented success in treating cutaneous squamous cell carcinoma, keratoacanthoma, basal cell carcinoma, and precancerous actinic keratosis.³⁵ As a topical, 5-FU has been shown to provide a good response in 6 patients with early MF.³⁶ In late-stage MF, 5-FU has been used in combination with methotrexate as an infusion.³⁷ We present a single-center case series of 9 patients with CTCL who received combination IL 5-FU and IMQ cream 5%.

Methods

Patient Selection—Patients were selected from our multidisciplinary CTCL subspecialty clinic at the Inova Schar Cancer Institute (Fairfax, Virginia). Patients with single to few recalcitrant CTCL plaques or tumors that were symptomatic or otherwise bothersome were included. All patients had at least 2 prior skin-directed therapies that failed, and many had advanced-stage disease requiring systemic therapy. All patients provided verbal consent.

Study Materials and Evaluations—Patients received IL injections of 5-FU 50 mg/mL. The volume injected was approximately 0.2 cc per cubic centimeter of lesion tissue. Injections were repeated at 2- to 3-week intervals until the target lesions achieved an acute hemorrhagic phase characterized by erosion, flattening, and crust formation. The total number of serial injections administered ranged from 1 to 5. The patients concomitantly treated all lesions with IMQ cream 5% daily for a duration of 2 to 3 months.

Medical photography and physical examination were performed every 2 to 3 weeks until the hemorrhagic phase resolved and treated sites re-epithelialized. Index lesions were assessed using the Composite Assessment of Index Lesion Severity (CAILS) score by a single investigator for all patients.³⁸ Scores were retrospectively assigned using the investigator’s detailed physical examination descriptions and extensive medical photography. Any hyperpigmentation was scored as residual disease, despite the fair interpretation of it as procedure-related postinflammatory dyspigmentation. Complete response was strictly defined as a CAILS score of 0. The patients were screened for possible systemic effects of IMQ, including the presence of fever, chills, fatigue, and myalgia. Patients were evaluated every 6 to 12 weeks as a standing follow-up.

Statistical Analysis—Reductions were calculated using local regression from baseline to the 4- to 7-week follow-up. Patients with multiple lesions had their CAILS score averaged at ea

Results

Nine patients aged 28 to 91 years (median age, 66 years) with CTCL stages IA to IVA2, who had lesions located throughout their body, achieved CR; 3 patients were female (Table 1). The most common phenotype was CD8⁺ (n=3). All patients had at least 2 prior skin-directed therapies at treatment sites that failed, and 1 patient had 7 prior treatments that failed. Prior treatments included a variety of modalities, including all standard-of-care options and enrollment in clinical trials. One patient died from pneumonia following CR (Table 2). Seven patients had previously received systemic therapy for CTCL, and 1 patient was stable on romidepsin during our study. In patients who received more than 1 injection of 5-FU—1 injection: 3 patients; 2 injections: 3 patients; 3 injections: 1 patient; 4 injections: 1 patient; 5 injections: 1 patient—injections were spaced by 2 to 3 weeks. There was 1 patient who initially had an inadequate dosing of IL 5-FU and was restarted 14 months later; this was the patient with 5 total injections. This occurred in one of the first patients in the study, who presented with a facial lesion. The investigator used approximately 0.02 cc per cubic centimeter (dose reduction of nearly 90%), which was inadequate and did not achieve the requisite hemorrhagic phase.

Treatment was well tolerated overall. In all cases, a hemorrhagic phase was achieved, characterized by erosion and crusting that was rated as mildly uncomfortable by 7 patients and moderately uncomfortable by 2 patients. In total, 15 lesions in all 9 patients achieved a CR within 24 weeks of the final injection. The longest treatment course required 12 weeks of therapy with IMQ and 5 IL injections of 5-FU. The fastest CR was achieved in patient 6 within 6 weeks following a single IL injection of 5-FU and 2 applications of IMQ. The average time to CR was 14.78 weeks (95% CI, 1.75-27.81)(Figure 2), and the time to CR ranged from 4 to 24 weeks. On average, patients achieved more than 50% reduction in CAILS score by 3.53 weeks (95% CI, 1.55-5.51) and nearly a 4-fold (74.7%) reduction at the time of initial follow-up (occurring at 4–7 weeks). By 7 weeks, patient 3 had the most modest improvement in CAILS score with a 2.75-fold reduction, while patient 5 had the largest decrease with a 5-fold reduction. Figure 3 shows representative clinical photographs of 2 patients before and after treatment, with all patients having similar results.

Comment

Cutaneous T-cell lymphoma is a chronic skin cancer with a pattern of limited response to therapy and frequent recurrence. Currently available skin-directed therapies function as temporizing measures rather than curative treatments. Immunotherapy offers the promise of lasting disease control even after cessation of treatment, as it may essentially awaken cutaneous immune surveillance to malignant lymphocytes.

Several small observational studies have evaluated topical IMQ and TLR agonist therapy in CTCL. The construct of prior reports varies widely, including many different pretreatments, dosing schemes, and follow-up periods.^24-33 Dosing intervals with IMQ ranged from daily to 3 times per week and treatment duration from 2 weeks to 1 year. Complete response rates from 50% to 100% were reported, and partial responses were observed in all but 1 patient, with recurrence-free follow-up ranging from 6 months to 8 years. Comparatively, combining IL 5-FU and IMQ appears to be at least as effective as IMQ alone or in other sequential treatments and combinations.^24-33

Resiquimod, an experimental TLR7/8 agonist, has shown promising results in CTCL. Rook et al³⁴ conducted a phase 1 trial of topical resiquimod in 12 early-stage patients with CTCL, all of whom responded to therapy. Two patients achieved CR, and 9 achieved a partial response, including 5 patients with the folliculotropic subtype. Interestingly, an abscopal effect was observed in 92% (11/12) of patients. Molecular evidence of reduction of the malignant clone was observed in 90% of patients via high-throughput sequencing of lesional tissue.³⁴ These exciting findings suggest that topical immune therapy with TLR agonists may achieve robust, sustained, and possibly global disease control in CTCL.

Topical therapies are limited by depth of absorption, which can present a barrier to using these treatments for thicker plaques and tumors. Combining IL and topical routes was critical in our study design. Having good clinical experience using IL 5-FU in nonmelanoma skin cancers, we hypothesized that IL 5-FU would achieve a cytotoxic response through the full depth of thicker lesions and erode the surface of these lesions to facilitate penetration of topical IMQ. We additionally hypothesized that the combination of mechanisms of action would lead to an additive or synergistic response (Figure 1). By first inducing apoptotic cell death via 5-FU, we hoped to spill malignant lymphocyte neoantigens. Coupling that antigen exposure with an enhanced T_H1-biased immune response driven by IMQ should facilitate tumor clearance and immune education against malignant T cells.

In our case series, all 15 lesions in 9 patients completely cleared, and no recurrences were observed at 26-month follow-up. No patients encountered any major adverse events, and the procedure was well tolerated by all.

Study Limitations—Limitations of this small study certainly exist. It is impossible to prove that our mechanistic theory is accurate given our strictly clinical assessment tools. We speculate that if our results had been achieved with IL 5-FU alone, future investigation with a prospective study using multiple treatment arms including a control would be warranted. Kannangara et al³⁶ reported the use of topical 5-FU for MF and the drug’s utility in either topical or IL routes for CTCL, which deserves further study. It is less likely that results were achieved exclusively by IMQ because of the rapid tissue breakdown observed in the acute hemorrhagic phase. This phenomenon is best explained by the sudden apoptosis caused by DNA intercalation from 5-FU. The follow-up period is not uniform because this was a rolling enrollment study. Follow-up will be ongoing, and we aim to assess all patients up to at least the 5-year point. A final limitation of this study is the purely clinical end point. In the future, pretreatment and posttreatment biopsies would be useful in assessing proof of histologic response, and high-throughput sequencing may be used to look for molecular clearance via liquid biopsy. Lastly, careful observation for possible abscopal effect using the Severity-Weighted Assessment Tool score would be interesting and potentially contributory to our understanding of the impact of topical immune therapy on cutaneous tumor surveillance.

Conclusion

Combination IL 5-FU and topical IMQ is a well-tolerated, effective, and durable therapy for recalcitrant thick plaques and tumors of CTCL. This treatment is convenient and cost-effective. The procedure is performed in less than 5 minutes in an outpatient dermatology clinic. All patients received full insurance coverage for both drug and procedure fees under Medicare and commercial carriers.

Cutaneous T-cell lymphoma (CTCL) is a diverse group of skin-homing T-cell neoplasms with a wide array of clinical presentations, immunohistopathologic subtypes, and prognoses. The age-adjusted incidence of CTCL in the United States is 6.4 per million individuals.¹ In the early stages of CTCL, the malignant lymphocytes are isolated to the skin, while more advanced disease involves metastatic spread to the lymphatic and peripheral blood compartments. Mycosis fungoides (MF) is the most common subtype of CTCL, comprising roughly 50% of all cases. The etiology of CTCL and MF remains poorly understood and no unifying driver mutation has been identified.² However, recent sequencing efforts have revealed recurrent genomics alterations primarily in 3 pathways: constitutive T-cell activation, resistance to apoptosis/cell-cycle dysregulation, and DNA structural/gene expression dysregulation.^3-8 These studies, among others, support the assertion that CTCL may be an epigenetic phenomenon.^9-14

Most patients with MF will experience an indolent course of skin-limited disease with a favorable prognosis and a 5-year survival rate of 88%.^15-17 A large study of patients with MF (N=525) followed for more than 40 years determined that approximately 20% of early-stage (IA-IIA) patients with MF progress to develop tumors, metastasis to the lymphatic tissue, and/or leukemic blood disease.¹⁸

Cutaneous T-cell lymphoma is a chronic disease, and most treatment responses are partial and short-lived. Allogenic hematopoietic transplantation is the only potentially curative option, and all other therapies are aimed at arresting progression and achieving remission.¹⁹ Skin-directed therapies include topical steroids, topical nitrogen mustard, phototherapy, and radiation. Systemic therapies such as oral retinoids, chemotherapy, and immunotherapy may be used alone or in combination with skin-directed therapies based on the overall disease stage and clinical presentation. Unfortunately, complete response (CR) to therapy is rare and fleeting, and most patients require multiple sequential treatments over their lifetimes.²⁰

Across all stages of CTCL, there is a therapeutic push to combination and immune-based therapies to achieve more durable responses. The imidazoquinolines are a family of toll-like receptor (TLR) agonists including imiquimod (TLR7) and resiquimod (TLR7 and TLR8). Imiquimod (IMQ) is a topical immunomodulator, which increases the local cytotoxic helper T-cell profile (T_H1 marked by IFN-α, tumor necrosis factor α, IL-1α, IL-6, and IL-8), thereby enhancing both humoral and innate immune responses targeting tumor cells.^21-23 Several small studies evaluating topical TLR agonists have documented efficacy in patients with early and advanced stages of CTCL.^24-34

Skin-directed chemotherapy using 5-fluorouracil (5-FU) has shown activity against many cutaneous malignancies. 5-Fluorouracil is an antimetabolite drug that inhibits thymidylate synthase, resulting in interrupted DNA and RNA synthesis and leading to an apoptotic cell death (Figure 1). It has been administered via intravenous, oral (prodrug), intralesional (IL), and topical routes with well-documented success in treating cutaneous squamous cell carcinoma, keratoacanthoma, basal cell carcinoma, and precancerous actinic keratosis.³⁵ As a topical, 5-FU has been shown to provide a good response in 6 patients with early MF.³⁶ In late-stage MF, 5-FU has been used in combination with methotrexate as an infusion.³⁷ We present a single-center case series of 9 patients with CTCL who received combination IL 5-FU and IMQ cream 5%.

Methods

Patient Selection—Patients were selected from our multidisciplinary CTCL subspecialty clinic at the Inova Schar Cancer Institute (Fairfax, Virginia). Patients with single to few recalcitrant CTCL plaques or tumors that were symptomatic or otherwise bothersome were included. All patients had at least 2 prior skin-directed therapies that failed, and many had advanced-stage disease requiring systemic therapy. All patients provided verbal consent.

Study Materials and Evaluations—Patients received IL injections of 5-FU 50 mg/mL. The volume injected was approximately 0.2 cc per cubic centimeter of lesion tissue. Injections were repeated at 2- to 3-week intervals until the target lesions achieved an acute hemorrhagic phase characterized by erosion, flattening, and crust formation. The total number of serial injections administered ranged from 1 to 5. The patients concomitantly treated all lesions with IMQ cream 5% daily for a duration of 2 to 3 months.

Medical photography and physical examination were performed every 2 to 3 weeks until the hemorrhagic phase resolved and treated sites re-epithelialized. Index lesions were assessed using the Composite Assessment of Index Lesion Severity (CAILS) score by a single investigator for all patients.³⁸ Scores were retrospectively assigned using the investigator’s detailed physical examination descriptions and extensive medical photography. Any hyperpigmentation was scored as residual disease, despite the fair interpretation of it as procedure-related postinflammatory dyspigmentation. Complete response was strictly defined as a CAILS score of 0. The patients were screened for possible systemic effects of IMQ, including the presence of fever, chills, fatigue, and myalgia. Patients were evaluated every 6 to 12 weeks as a standing follow-up.

Statistical Analysis—Reductions were calculated using local regression from baseline to the 4- to 7-week follow-up. Patients with multiple lesions had their CAILS score averaged at ea

Results

Nine patients aged 28 to 91 years (median age, 66 years) with CTCL stages IA to IVA2, who had lesions located throughout their body, achieved CR; 3 patients were female (Table 1). The most common phenotype was CD8⁺ (n=3). All patients had at least 2 prior skin-directed therapies at treatment sites that failed, and 1 patient had 7 prior treatments that failed. Prior treatments included a variety of modalities, including all standard-of-care options and enrollment in clinical trials. One patient died from pneumonia following CR (Table 2). Seven patients had previously received systemic therapy for CTCL, and 1 patient was stable on romidepsin during our study. In patients who received more than 1 injection of 5-FU—1 injection: 3 patients; 2 injections: 3 patients; 3 injections: 1 patient; 4 injections: 1 patient; 5 injections: 1 patient—injections were spaced by 2 to 3 weeks. There was 1 patient who initially had an inadequate dosing of IL 5-FU and was restarted 14 months later; this was the patient with 5 total injections. This occurred in one of the first patients in the study, who presented with a facial lesion. The investigator used approximately 0.02 cc per cubic centimeter (dose reduction of nearly 90%), which was inadequate and did not achieve the requisite hemorrhagic phase.

Treatment was well tolerated overall. In all cases, a hemorrhagic phase was achieved, characterized by erosion and crusting that was rated as mildly uncomfortable by 7 patients and moderately uncomfortable by 2 patients. In total, 15 lesions in all 9 patients achieved a CR within 24 weeks of the final injection. The longest treatment course required 12 weeks of therapy with IMQ and 5 IL injections of 5-FU. The fastest CR was achieved in patient 6 within 6 weeks following a single IL injection of 5-FU and 2 applications of IMQ. The average time to CR was 14.78 weeks (95% CI, 1.75-27.81)(Figure 2), and the time to CR ranged from 4 to 24 weeks. On average, patients achieved more than 50% reduction in CAILS score by 3.53 weeks (95% CI, 1.55-5.51) and nearly a 4-fold (74.7%) reduction at the time of initial follow-up (occurring at 4–7 weeks). By 7 weeks, patient 3 had the most modest improvement in CAILS score with a 2.75-fold reduction, while patient 5 had the largest decrease with a 5-fold reduction. Figure 3 shows representative clinical photographs of 2 patients before and after treatment, with all patients having similar results.

Comment

Cutaneous T-cell lymphoma is a chronic skin cancer with a pattern of limited response to therapy and frequent recurrence. Currently available skin-directed therapies function as temporizing measures rather than curative treatments. Immunotherapy offers the promise of lasting disease control even after cessation of treatment, as it may essentially awaken cutaneous immune surveillance to malignant lymphocytes.

Several small observational studies have evaluated topical IMQ and TLR agonist therapy in CTCL. The construct of prior reports varies widely, including many different pretreatments, dosing schemes, and follow-up periods.^24-33 Dosing intervals with IMQ ranged from daily to 3 times per week and treatment duration from 2 weeks to 1 year. Complete response rates from 50% to 100% were reported, and partial responses were observed in all but 1 patient, with recurrence-free follow-up ranging from 6 months to 8 years. Comparatively, combining IL 5-FU and IMQ appears to be at least as effective as IMQ alone or in other sequential treatments and combinations.^24-33

Resiquimod, an experimental TLR7/8 agonist, has shown promising results in CTCL. Rook et al³⁴ conducted a phase 1 trial of topical resiquimod in 12 early-stage patients with CTCL, all of whom responded to therapy. Two patients achieved CR, and 9 achieved a partial response, including 5 patients with the folliculotropic subtype. Interestingly, an abscopal effect was observed in 92% (11/12) of patients. Molecular evidence of reduction of the malignant clone was observed in 90% of patients via high-throughput sequencing of lesional tissue.³⁴ These exciting findings suggest that topical immune therapy with TLR agonists may achieve robust, sustained, and possibly global disease control in CTCL.

Topical therapies are limited by depth of absorption, which can present a barrier to using these treatments for thicker plaques and tumors. Combining IL and topical routes was critical in our study design. Having good clinical experience using IL 5-FU in nonmelanoma skin cancers, we hypothesized that IL 5-FU would achieve a cytotoxic response through the full depth of thicker lesions and erode the surface of these lesions to facilitate penetration of topical IMQ. We additionally hypothesized that the combination of mechanisms of action would lead to an additive or synergistic response (Figure 1). By first inducing apoptotic cell death via 5-FU, we hoped to spill malignant lymphocyte neoantigens. Coupling that antigen exposure with an enhanced T_H1-biased immune response driven by IMQ should facilitate tumor clearance and immune education against malignant T cells.

In our case series, all 15 lesions in 9 patients completely cleared, and no recurrences were observed at 26-month follow-up. No patients encountered any major adverse events, and the procedure was well tolerated by all.

Study Limitations—Limitations of this small study certainly exist. It is impossible to prove that our mechanistic theory is accurate given our strictly clinical assessment tools. We speculate that if our results had been achieved with IL 5-FU alone, future investigation with a prospective study using multiple treatment arms including a control would be warranted. Kannangara et al³⁶ reported the use of topical 5-FU for MF and the drug’s utility in either topical or IL routes for CTCL, which deserves further study. It is less likely that results were achieved exclusively by IMQ because of the rapid tissue breakdown observed in the acute hemorrhagic phase. This phenomenon is best explained by the sudden apoptosis caused by DNA intercalation from 5-FU. The follow-up period is not uniform because this was a rolling enrollment study. Follow-up will be ongoing, and we aim to assess all patients up to at least the 5-year point. A final limitation of this study is the purely clinical end point. In the future, pretreatment and posttreatment biopsies would be useful in assessing proof of histologic response, and high-throughput sequencing may be used to look for molecular clearance via liquid biopsy. Lastly, careful observation for possible abscopal effect using the Severity-Weighted Assessment Tool score would be interesting and potentially contributory to our understanding of the impact of topical immune therapy on cutaneous tumor surveillance.

Conclusion

Combination IL 5-FU and topical IMQ is a well-tolerated, effective, and durable therapy for recalcitrant thick plaques and tumors of CTCL. This treatment is convenient and cost-effective. The procedure is performed in less than 5 minutes in an outpatient dermatology clinic. All patients received full insurance coverage for both drug and procedure fees under Medicare and commercial carriers.

Introduction

The professional activity of physicians has traditionally consisted of patient care, teaching/education, and research in varying proportions. These aims, especially education and research, have traditionally been achieved in academic health settings. However, involvement with industry can afford all physicians an opportunity to increase patient referrals, gain exposure to colleagues through a variety of educational opportunities, and participate in meaningful research projects they could not initiate independently. This article will discuss a variety of ways that gastroenterologists can engage with industry to achieve a mutually beneficial relationship.

How to initiate relationships with industry

Here are several ways to initiate a collaboration with industry. A few of the most common ways are to become a site investigator of a multicenter device or pharmaceutical trial, participate as a member of a speaker’s bureau, or obtain training on a new technology and subsequently incorporate it into your clinical practice. To find out what trials are enrolling and looking for additional sites or new studies that are being planned, I would suggest contacting the company’s local representative and have them put you in touch the appropriate personnel in the clinical trials division. For individuals who become involved in trials, this can be a great way to improve your understanding of how to design and conduct clinical trials as well as gain exposure to colleagues with similar clinical and research interests. Some of my closest long-term collaborators and friends have been individuals who I initially met as part of industry trials at investigator meetings. Another approach is to participate in a speaker’s bureau, which can be an excellent way to improve one’s presentation skills as well as gain knowledge with respect to a specific disease state. It is also a great way to network, meet colleagues, and develop a local and regional reputation as a content expert on a specific topic. Methods to find out about such opportunities include touring the exhibit halls during educational meetings and reading scientific journals to identify new products that are launching. I have found these sorts of opportunities can significantly increase topic-based referrals. Finally, obtaining training on a new diagnostic or therapeutic technology (usually through an industry-sponsored course) can allow individuals an opportunity to offer a unique or distinctive service to their community. In addition, as further clinical expertise is gained, the relationship can be expanded to offer local, regional, or even national training courses to colleagues via either on-site or virtual courses. Similarly, opportunities to speak about or demonstrate the technology/technique at educational courses may also follow.

Navigating and expanding the relationship

Once an individual establishes a relationship with a company or has established a reputation as a key opinion leader, additional opportunities for engagement may become available. These include serving as a consultant, becoming a member of an advisory board, participating or directing educational courses for trainees/practitioners, or serving as the principal investigator of a future clinical trial. Serving as a consultant can be quite rewarding as it can highlight clinical needs, identify where product improvement can be achieved, and focus where research and development funds should be directed. Serving on the advisory board can afford an even higher level of influence where corporate strategy can be influenced. Such input is particularly impactful with smaller companies looking to enter a new field or expand a limited market share. There are also a variety of educational opportunities offered by industry including local, regional, and national courses that focus on utilizing a new technology or education concerning a specific disease state. These courses can be held locally at the physician’s clinical site or off site to attract the desired target audience. Finally, being involved in research studies, especially early-stage projects, can be critical as many small companies have limited capital, and it is essential for them to design studies with appropriate endpoints that will ideally achieve both regulatory approval as well as payor coverage. Of note, in addition to relationships directly involving industry, the American Gastroenterological Association Center for GI Innovation and Technology (CGIT) also offers the opportunity to be part of key opinion leader meetings arranged and organized by the AGA. This may allow for some individuals to participate who may be restricted from direct relationships with industry partners. The industry services offered by the CGIT also include clinical trial design and registry management services.

Entrepreneurship/intellectual property

A less commonly explored opportunity with industry involves the development of one’s own intellectual property. Some of the most impactful technologies in my advanced endoscopy clinical practice have been developed from the ideas of gastroenterology colleagues that have been successfully commercialized. These include radiofrequency ablation technology to treat Barrett’s esophagus and the development of lumen-apposing stents. There are several options for physicians with an idea for an innovation. These can include working with a university technology transfer department if they are in an academic setting, creation of their own company, or collaborating with industry to develop the device through a licensing/royalty agreement. The AGA CGIT offers extensive resources to physicians with new ideas on how to secure their intellectual property as well as to evaluate the feasibility of the aforementioned options to choose which may be most appropriate for them.

Important caveats

It is important that physicians with industry relations be aware of their local institutional policies. Some institutions may prohibit such activities while others may limit the types of relationships or the amount of income that can be received. It is the physician’s responsibility to be aware of their institution’s guidelines prior to formalizing industry agreements. If intellectual property is involved, it is essential to know the specific rules regarding physician remuneration, especially pertaining to royalty or equity agreements. Furthermore, with regard to presentations and publications, it is required to acknowledge industry relations and potential conflicts of interest. Failure to do so may adversely affect an individual’s reputation as well as lead to additional consequences such as the potential for retraction of publications or restrictions regarding future educational speaking opportunities. In addition, key opinion leaders often consult for several companies that may be in competition with each other. Therefore, it is essential that there is no disclosure of confidential proprietary information among companies. Finally, the financial incentives resulting from industry collaboration should never influence physician judgment when interpreting or speaking about data regarding product efficacy or safety.

Conclusions

In summary, there are numerous opportunities for physicians to collaborate with industry. These relationships can be very rewarding and can serve to expedite the introduction of new diagnostic or treatment modalities and provide the opportunity to network and interact with colleagues as well as to participate in important research that improves clinical practice. The nature of these relationships should always be transparent, and it is the physician’s responsibility to ensure that the types of relationships that are engaged in are permitted by their employer. Over the course of my career, I have participated in nearly all forms of these relationships and have seen that participation lead to important publications, changes in corporate strategy, the fostering of acquisitions, and the rapid development and utilization of new endoscopic technologies. It is my personal belief than industry relationships can improve professional satisfaction, enhance one’s brand, and most importantly, expedite clinical innovation to improve patient care.

Dr. Muthusamy is professor of clinical medicine at the University of California, Los Angeles, and medical director of endoscopy, UCLA Health System. He disclosed ties with Medtronic, Boston Scientific, Motus GI, Endogastric Solutions, and Capsovision.

Introduction

The professional activity of physicians has traditionally consisted of patient care, teaching/education, and research in varying proportions. These aims, especially education and research, have traditionally been achieved in academic health settings. However, involvement with industry can afford all physicians an opportunity to increase patient referrals, gain exposure to colleagues through a variety of educational opportunities, and participate in meaningful research projects they could not initiate independently. This article will discuss a variety of ways that gastroenterologists can engage with industry to achieve a mutually beneficial relationship.

How to initiate relationships with industry

Here are several ways to initiate a collaboration with industry. A few of the most common ways are to become a site investigator of a multicenter device or pharmaceutical trial, participate as a member of a speaker’s bureau, or obtain training on a new technology and subsequently incorporate it into your clinical practice. To find out what trials are enrolling and looking for additional sites or new studies that are being planned, I would suggest contacting the company’s local representative and have them put you in touch the appropriate personnel in the clinical trials division. For individuals who become involved in trials, this can be a great way to improve your understanding of how to design and conduct clinical trials as well as gain exposure to colleagues with similar clinical and research interests. Some of my closest long-term collaborators and friends have been individuals who I initially met as part of industry trials at investigator meetings. Another approach is to participate in a speaker’s bureau, which can be an excellent way to improve one’s presentation skills as well as gain knowledge with respect to a specific disease state. It is also a great way to network, meet colleagues, and develop a local and regional reputation as a content expert on a specific topic. Methods to find out about such opportunities include touring the exhibit halls during educational meetings and reading scientific journals to identify new products that are launching. I have found these sorts of opportunities can significantly increase topic-based referrals. Finally, obtaining training on a new diagnostic or therapeutic technology (usually through an industry-sponsored course) can allow individuals an opportunity to offer a unique or distinctive service to their community. In addition, as further clinical expertise is gained, the relationship can be expanded to offer local, regional, or even national training courses to colleagues via either on-site or virtual courses. Similarly, opportunities to speak about or demonstrate the technology/technique at educational courses may also follow.

Navigating and expanding the relationship

Once an individual establishes a relationship with a company or has established a reputation as a key opinion leader, additional opportunities for engagement may become available. These include serving as a consultant, becoming a member of an advisory board, participating or directing educational courses for trainees/practitioners, or serving as the principal investigator of a future clinical trial. Serving as a consultant can be quite rewarding as it can highlight clinical needs, identify where product improvement can be achieved, and focus where research and development funds should be directed. Serving on the advisory board can afford an even higher level of influence where corporate strategy can be influenced. Such input is particularly impactful with smaller companies looking to enter a new field or expand a limited market share. There are also a variety of educational opportunities offered by industry including local, regional, and national courses that focus on utilizing a new technology or education concerning a specific disease state. These courses can be held locally at the physician’s clinical site or off site to attract the desired target audience. Finally, being involved in research studies, especially early-stage projects, can be critical as many small companies have limited capital, and it is essential for them to design studies with appropriate endpoints that will ideally achieve both regulatory approval as well as payor coverage. Of note, in addition to relationships directly involving industry, the American Gastroenterological Association Center for GI Innovation and Technology (CGIT) also offers the opportunity to be part of key opinion leader meetings arranged and organized by the AGA. This may allow for some individuals to participate who may be restricted from direct relationships with industry partners. The industry services offered by the CGIT also include clinical trial design and registry management services.

Entrepreneurship/intellectual property

A less commonly explored opportunity with industry involves the development of one’s own intellectual property. Some of the most impactful technologies in my advanced endoscopy clinical practice have been developed from the ideas of gastroenterology colleagues that have been successfully commercialized. These include radiofrequency ablation technology to treat Barrett’s esophagus and the development of lumen-apposing stents. There are several options for physicians with an idea for an innovation. These can include working with a university technology transfer department if they are in an academic setting, creation of their own company, or collaborating with industry to develop the device through a licensing/royalty agreement. The AGA CGIT offers extensive resources to physicians with new ideas on how to secure their intellectual property as well as to evaluate the feasibility of the aforementioned options to choose which may be most appropriate for them.

Important caveats

It is important that physicians with industry relations be aware of their local institutional policies. Some institutions may prohibit such activities while others may limit the types of relationships or the amount of income that can be received. It is the physician’s responsibility to be aware of their institution’s guidelines prior to formalizing industry agreements. If intellectual property is involved, it is essential to know the specific rules regarding physician remuneration, especially pertaining to royalty or equity agreements. Furthermore, with regard to presentations and publications, it is required to acknowledge industry relations and potential conflicts of interest. Failure to do so may adversely affect an individual’s reputation as well as lead to additional consequences such as the potential for retraction of publications or restrictions regarding future educational speaking opportunities. In addition, key opinion leaders often consult for several companies that may be in competition with each other. Therefore, it is essential that there is no disclosure of confidential proprietary information among companies. Finally, the financial incentives resulting from industry collaboration should never influence physician judgment when interpreting or speaking about data regarding product efficacy or safety.

Conclusions

In summary, there are numerous opportunities for physicians to collaborate with industry. These relationships can be very rewarding and can serve to expedite the introduction of new diagnostic or treatment modalities and provide the opportunity to network and interact with colleagues as well as to participate in important research that improves clinical practice. The nature of these relationships should always be transparent, and it is the physician’s responsibility to ensure that the types of relationships that are engaged in are permitted by their employer. Over the course of my career, I have participated in nearly all forms of these relationships and have seen that participation lead to important publications, changes in corporate strategy, the fostering of acquisitions, and the rapid development and utilization of new endoscopic technologies. It is my personal belief than industry relationships can improve professional satisfaction, enhance one’s brand, and most importantly, expedite clinical innovation to improve patient care.

Dr. Muthusamy is professor of clinical medicine at the University of California, Los Angeles, and medical director of endoscopy, UCLA Health System. He disclosed ties with Medtronic, Boston Scientific, Motus GI, Endogastric Solutions, and Capsovision.

Introduction

The professional activity of physicians has traditionally consisted of patient care, teaching/education, and research in varying proportions. These aims, especially education and research, have traditionally been achieved in academic health settings. However, involvement with industry can afford all physicians an opportunity to increase patient referrals, gain exposure to colleagues through a variety of educational opportunities, and participate in meaningful research projects they could not initiate independently. This article will discuss a variety of ways that gastroenterologists can engage with industry to achieve a mutually beneficial relationship.

How to initiate relationships with industry

Here are several ways to initiate a collaboration with industry. A few of the most common ways are to become a site investigator of a multicenter device or pharmaceutical trial, participate as a member of a speaker’s bureau, or obtain training on a new technology and subsequently incorporate it into your clinical practice. To find out what trials are enrolling and looking for additional sites or new studies that are being planned, I would suggest contacting the company’s local representative and have them put you in touch the appropriate personnel in the clinical trials division. For individuals who become involved in trials, this can be a great way to improve your understanding of how to design and conduct clinical trials as well as gain exposure to colleagues with similar clinical and research interests. Some of my closest long-term collaborators and friends have been individuals who I initially met as part of industry trials at investigator meetings. Another approach is to participate in a speaker’s bureau, which can be an excellent way to improve one’s presentation skills as well as gain knowledge with respect to a specific disease state. It is also a great way to network, meet colleagues, and develop a local and regional reputation as a content expert on a specific topic. Methods to find out about such opportunities include touring the exhibit halls during educational meetings and reading scientific journals to identify new products that are launching. I have found these sorts of opportunities can significantly increase topic-based referrals. Finally, obtaining training on a new diagnostic or therapeutic technology (usually through an industry-sponsored course) can allow individuals an opportunity to offer a unique or distinctive service to their community. In addition, as further clinical expertise is gained, the relationship can be expanded to offer local, regional, or even national training courses to colleagues via either on-site or virtual courses. Similarly, opportunities to speak about or demonstrate the technology/technique at educational courses may also follow.

Navigating and expanding the relationship

Once an individual establishes a relationship with a company or has established a reputation as a key opinion leader, additional opportunities for engagement may become available. These include serving as a consultant, becoming a member of an advisory board, participating or directing educational courses for trainees/practitioners, or serving as the principal investigator of a future clinical trial. Serving as a consultant can be quite rewarding as it can highlight clinical needs, identify where product improvement can be achieved, and focus where research and development funds should be directed. Serving on the advisory board can afford an even higher level of influence where corporate strategy can be influenced. Such input is particularly impactful with smaller companies looking to enter a new field or expand a limited market share. There are also a variety of educational opportunities offered by industry including local, regional, and national courses that focus on utilizing a new technology or education concerning a specific disease state. These courses can be held locally at the physician’s clinical site or off site to attract the desired target audience. Finally, being involved in research studies, especially early-stage projects, can be critical as many small companies have limited capital, and it is essential for them to design studies with appropriate endpoints that will ideally achieve both regulatory approval as well as payor coverage. Of note, in addition to relationships directly involving industry, the American Gastroenterological Association Center for GI Innovation and Technology (CGIT) also offers the opportunity to be part of key opinion leader meetings arranged and organized by the AGA. This may allow for some individuals to participate who may be restricted from direct relationships with industry partners. The industry services offered by the CGIT also include clinical trial design and registry management services.

Entrepreneurship/intellectual property

A less commonly explored opportunity with industry involves the development of one’s own intellectual property. Some of the most impactful technologies in my advanced endoscopy clinical practice have been developed from the ideas of gastroenterology colleagues that have been successfully commercialized. These include radiofrequency ablation technology to treat Barrett’s esophagus and the development of lumen-apposing stents. There are several options for physicians with an idea for an innovation. These can include working with a university technology transfer department if they are in an academic setting, creation of their own company, or collaborating with industry to develop the device through a licensing/royalty agreement. The AGA CGIT offers extensive resources to physicians with new ideas on how to secure their intellectual property as well as to evaluate the feasibility of the aforementioned options to choose which may be most appropriate for them.

Important caveats

It is important that physicians with industry relations be aware of their local institutional policies. Some institutions may prohibit such activities while others may limit the types of relationships or the amount of income that can be received. It is the physician’s responsibility to be aware of their institution’s guidelines prior to formalizing industry agreements. If intellectual property is involved, it is essential to know the specific rules regarding physician remuneration, especially pertaining to royalty or equity agreements. Furthermore, with regard to presentations and publications, it is required to acknowledge industry relations and potential conflicts of interest. Failure to do so may adversely affect an individual’s reputation as well as lead to additional consequences such as the potential for retraction of publications or restrictions regarding future educational speaking opportunities. In addition, key opinion leaders often consult for several companies that may be in competition with each other. Therefore, it is essential that there is no disclosure of confidential proprietary information among companies. Finally, the financial incentives resulting from industry collaboration should never influence physician judgment when interpreting or speaking about data regarding product efficacy or safety.

Conclusions

In summary, there are numerous opportunities for physicians to collaborate with industry. These relationships can be very rewarding and can serve to expedite the introduction of new diagnostic or treatment modalities and provide the opportunity to network and interact with colleagues as well as to participate in important research that improves clinical practice. The nature of these relationships should always be transparent, and it is the physician’s responsibility to ensure that the types of relationships that are engaged in are permitted by their employer. Over the course of my career, I have participated in nearly all forms of these relationships and have seen that participation lead to important publications, changes in corporate strategy, the fostering of acquisitions, and the rapid development and utilization of new endoscopic technologies. It is my personal belief than industry relationships can improve professional satisfaction, enhance one’s brand, and most importantly, expedite clinical innovation to improve patient care.

Dr. Muthusamy is professor of clinical medicine at the University of California, Los Angeles, and medical director of endoscopy, UCLA Health System. He disclosed ties with Medtronic, Boston Scientific, Motus GI, Endogastric Solutions, and Capsovision.

More than half of emergency department visits from U.S. patients with cancer are potentially preventable, a new analysis suggests.

Overall, researchers found that 18.3 million (52%) ED visits among patients with cancer between 2012 and 2019 were potentially avoidable. Pain was the most common reason for such a visit. Notably, the number of potentially preventable ED visits documented each year increased over the study period.

“These findings highlight the need for cancer care programs to implement evidence-based interventions to better manage cancer treatment complications, such as uncontrolled pain, in outpatient and ambulatory settings,” said the authors, led by Amir Alishahi Tabriz, MD, PhD, MPH, department of health outcomes and behavior, Moffitt Cancer Center, Tampa.

Authors of an accompanying editorial agree, noting that “patients at risk for having uncontrolled pain could potentially be identified earlier, and steps could be taken that would address their pain and help prevent acute care visits.”

The study and the editorial were published online Jan. 19, 2022, in JAMA Network Open.

Patients with cancer experience a range of side effects from their cancer and treatment. Many such problems can be managed in the ambulatory setting but are often managed in the ED, which is far from optimal for patients with cancer from both a complications and cost perspective. Still, little is known about whether ED visits among patients with cancer are avoidable.

To better understand unnecessary emergency care use by these patients, Dr. Tabriz and colleagues evaluated trends and characteristics of potentially preventable ED visits among adults with cancer who had an ED visit between 2012 and 2019. The authors used the Centers for Medicare & Medicaid Services definition for a potentially preventable ED visit among patients receiving chemotherapy.

Among the 35.5 million ED visits made by patients with cancer during the study period, 18.3 million (52%) were identified as potentially preventable. Nearly 5.8 million of these visits (21%) were classified as being of “high acuity,” and almost 30% resulted in unplanned hospitalizations.

Pain was the most common reason for potentially preventable ED visits, accounting for 37% of these visits.

The absolute number of potentially preventable ED visits among cancer patients increased from about 1.8 million in 2012 to 3.2 million in 2019. The number of patients who visited the ED because of pain more than doubled, from roughly 1.2 million in 2012 to 2.4 million in 2019.

“The disproportionate increase in the number of ED visits by patients with cancer has put a substantial burden on EDs that are already operating at peak capacity” and “reinforces the need for cancer care programs to devise innovative ways to manage complications associated with cancer treatment in the outpatient and ambulatory settings,” Dr. Tabriz and coauthors wrote.

The increase could be an “unintended” consequence of efforts to decrease overall opioid administration in response to the opioid epidemic, Dr. Tabriz and colleagues noted. For example, the authors point to a recent study that found that about half of patients with cancer who had severe pain did not receive outpatient opioids in the week before visiting the ED.

“Even access to outpatient care does not mean patients can get the care they need outside an ED,” wrote editorialists Erek Majka, MD, with Summerlin Hospital, Las Vegas, and N. Seth Trueger, MD, MPH, with Northwestern University, Chicago. Thus, “it is no surprise that patients are sent to the ED if the alternatives do not have the staff or diagnostic and therapeutic capabilities the patients need.”

Overall, however, the “goal is not to eliminate ED visits for their own sake; rather, the goal is better care of patients with cancer, and secondarily, in a manner that is cost-effective,” Dr. Majka and Dr. Trueger explained.

No specific funding for the study was reported. The authors disclosed no relevant financial relationships. Dr. Trueger is digital media editor of JAMA Network Open, but he was not involved in decisions regarding review of the manuscript or its acceptance.

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

More than half of emergency department visits from U.S. patients with cancer are potentially preventable, a new analysis suggests.

Overall, researchers found that 18.3 million (52%) ED visits among patients with cancer between 2012 and 2019 were potentially avoidable. Pain was the most common reason for such a visit. Notably, the number of potentially preventable ED visits documented each year increased over the study period.

“These findings highlight the need for cancer care programs to implement evidence-based interventions to better manage cancer treatment complications, such as uncontrolled pain, in outpatient and ambulatory settings,” said the authors, led by Amir Alishahi Tabriz, MD, PhD, MPH, department of health outcomes and behavior, Moffitt Cancer Center, Tampa.

Authors of an accompanying editorial agree, noting that “patients at risk for having uncontrolled pain could potentially be identified earlier, and steps could be taken that would address their pain and help prevent acute care visits.”

The study and the editorial were published online Jan. 19, 2022, in JAMA Network Open.

Patients with cancer experience a range of side effects from their cancer and treatment. Many such problems can be managed in the ambulatory setting but are often managed in the ED, which is far from optimal for patients with cancer from both a complications and cost perspective. Still, little is known about whether ED visits among patients with cancer are avoidable.

To better understand unnecessary emergency care use by these patients, Dr. Tabriz and colleagues evaluated trends and characteristics of potentially preventable ED visits among adults with cancer who had an ED visit between 2012 and 2019. The authors used the Centers for Medicare & Medicaid Services definition for a potentially preventable ED visit among patients receiving chemotherapy.

Among the 35.5 million ED visits made by patients with cancer during the study period, 18.3 million (52%) were identified as potentially preventable. Nearly 5.8 million of these visits (21%) were classified as being of “high acuity,” and almost 30% resulted in unplanned hospitalizations.

Pain was the most common reason for potentially preventable ED visits, accounting for 37% of these visits.

The absolute number of potentially preventable ED visits among cancer patients increased from about 1.8 million in 2012 to 3.2 million in 2019. The number of patients who visited the ED because of pain more than doubled, from roughly 1.2 million in 2012 to 2.4 million in 2019.

“The disproportionate increase in the number of ED visits by patients with cancer has put a substantial burden on EDs that are already operating at peak capacity” and “reinforces the need for cancer care programs to devise innovative ways to manage complications associated with cancer treatment in the outpatient and ambulatory settings,” Dr. Tabriz and coauthors wrote.

The increase could be an “unintended” consequence of efforts to decrease overall opioid administration in response to the opioid epidemic, Dr. Tabriz and colleagues noted. For example, the authors point to a recent study that found that about half of patients with cancer who had severe pain did not receive outpatient opioids in the week before visiting the ED.

“Even access to outpatient care does not mean patients can get the care they need outside an ED,” wrote editorialists Erek Majka, MD, with Summerlin Hospital, Las Vegas, and N. Seth Trueger, MD, MPH, with Northwestern University, Chicago. Thus, “it is no surprise that patients are sent to the ED if the alternatives do not have the staff or diagnostic and therapeutic capabilities the patients need.”

Overall, however, the “goal is not to eliminate ED visits for their own sake; rather, the goal is better care of patients with cancer, and secondarily, in a manner that is cost-effective,” Dr. Majka and Dr. Trueger explained.

No specific funding for the study was reported. The authors disclosed no relevant financial relationships. Dr. Trueger is digital media editor of JAMA Network Open, but he was not involved in decisions regarding review of the manuscript or its acceptance.

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

More than half of emergency department visits from U.S. patients with cancer are potentially preventable, a new analysis suggests.

Overall, researchers found that 18.3 million (52%) ED visits among patients with cancer between 2012 and 2019 were potentially avoidable. Pain was the most common reason for such a visit. Notably, the number of potentially preventable ED visits documented each year increased over the study period.

“These findings highlight the need for cancer care programs to implement evidence-based interventions to better manage cancer treatment complications, such as uncontrolled pain, in outpatient and ambulatory settings,” said the authors, led by Amir Alishahi Tabriz, MD, PhD, MPH, department of health outcomes and behavior, Moffitt Cancer Center, Tampa.

Authors of an accompanying editorial agree, noting that “patients at risk for having uncontrolled pain could potentially be identified earlier, and steps could be taken that would address their pain and help prevent acute care visits.”

The study and the editorial were published online Jan. 19, 2022, in JAMA Network Open.

Patients with cancer experience a range of side effects from their cancer and treatment. Many such problems can be managed in the ambulatory setting but are often managed in the ED, which is far from optimal for patients with cancer from both a complications and cost perspective. Still, little is known about whether ED visits among patients with cancer are avoidable.

To better understand unnecessary emergency care use by these patients, Dr. Tabriz and colleagues evaluated trends and characteristics of potentially preventable ED visits among adults with cancer who had an ED visit between 2012 and 2019. The authors used the Centers for Medicare & Medicaid Services definition for a potentially preventable ED visit among patients receiving chemotherapy.

Among the 35.5 million ED visits made by patients with cancer during the study period, 18.3 million (52%) were identified as potentially preventable. Nearly 5.8 million of these visits (21%) were classified as being of “high acuity,” and almost 30% resulted in unplanned hospitalizations.

Pain was the most common reason for potentially preventable ED visits, accounting for 37% of these visits.

The absolute number of potentially preventable ED visits among cancer patients increased from about 1.8 million in 2012 to 3.2 million in 2019. The number of patients who visited the ED because of pain more than doubled, from roughly 1.2 million in 2012 to 2.4 million in 2019.

“The disproportionate increase in the number of ED visits by patients with cancer has put a substantial burden on EDs that are already operating at peak capacity” and “reinforces the need for cancer care programs to devise innovative ways to manage complications associated with cancer treatment in the outpatient and ambulatory settings,” Dr. Tabriz and coauthors wrote.

The increase could be an “unintended” consequence of efforts to decrease overall opioid administration in response to the opioid epidemic, Dr. Tabriz and colleagues noted. For example, the authors point to a recent study that found that about half of patients with cancer who had severe pain did not receive outpatient opioids in the week before visiting the ED.

“Even access to outpatient care does not mean patients can get the care they need outside an ED,” wrote editorialists Erek Majka, MD, with Summerlin Hospital, Las Vegas, and N. Seth Trueger, MD, MPH, with Northwestern University, Chicago. Thus, “it is no surprise that patients are sent to the ED if the alternatives do not have the staff or diagnostic and therapeutic capabilities the patients need.”

Overall, however, the “goal is not to eliminate ED visits for their own sake; rather, the goal is better care of patients with cancer, and secondarily, in a manner that is cost-effective,” Dr. Majka and Dr. Trueger explained.

No specific funding for the study was reported. The authors disclosed no relevant financial relationships. Dr. Trueger is digital media editor of JAMA Network Open, but he was not involved in decisions regarding review of the manuscript or its acceptance.

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

ORLANDO – Research on pigmentary disorders has entered an overdue era of increased attention, resulting in more treatment options and the promise of improved quality of life for patients, a panel of experts said in a session on this topic at the ODAC Dermatology, Aesthetic & Surgical Conference.

The arrival of ruxolitinib cream, a topical JAK inhibitor – and oral JAK inhibitors, including ritlecitinib, a JAK3/TEC (tyrosine kinase expressed in hepatocellular carcinoma) inhibitor in clinical trials – is a welcome development for treatment of vitiligo, said John E. Harris, MD, PhD, chair of dermatology and director of the Vitiligo Clinic and Research Center at the University of Massachusetts, Worcester. Also in the pipeline is a kit for melanocyte-keratinocyte transplantation, which involves transplanting epidermal cells from one part of the body to another. This can be a challenging procedure but a kit would make it easier for a wider range of practitioners. (Topical ruxolitinib was approved by the Food and Drug Administration for treating nonsegmental vitiligo in July, 2022.)

“In the last 10 years, it’s just blown up and people care about vitiligo now,” Dr. Harris said, noting that vitiligo is more than a cosmetic issue, like gray hair or wrinkles. “Vitiligo is an autoimmune disease and now is being treated as such.”

Nada Elbuluk, MD, MSc, associate professor of dermatology at the University of Southern California, Los Angeles, said she’s pleased at the increasing availability of treatment options for hyperpigmentation, aside from hydroquinone, which is associated with an increased risk of adverse effects.

“We have more and more nonhydroquinone agents ... which is really nice because it expands our treatment armamentarium and what we can use to cycle people off of hydroquinone,” she said.

Some of these options include tranexamic acid and products containing azelaic acid or vitamin C.

Iltefat H. Hamzavi, MD, senior staff physician at Henry Ford Health System, Detroit, said that pigmentary disorders are receiving the recognition they deserve.

“I’m excited just about the intersection of society and science, the awareness that pigmentary abnormalities mean something, and they mean something across our society,” he said.

Dr. Elbuluk said that hyperpigmentation has “profound effects on quality of life” for patients.

“They are often more bothered by the darkening of the skin than the primary process that caused it,” she said. “It’s not uncommon that the chief complaint will say ‘dark spots’ and I walk in a room and it’s a patient who has acne. They don’t even say they’re here for acne. They just put ‘dark spots’ [down] because that’s what bothers them. That’s what lasts for so long after the acne is gone.”

The experts offered suggestions for managing these cases. Among her tips, Dr. Elbuluk said that for hyperpigmentation, physicians should not be afraid to biopsy the face – but suggested small, 2-millimeter specimens. In addition, “you can get common conditions in uncommon places,” she noted. “If you see something that looks like melasma off the face, it actually could be, so keep that in your differential.”

Dr. Hamzavi, who spoke about hypopigmentation disorders, said clinicians need to use an algorithm for diagnosis, considering features such as localized or diffuse, scale or no scale, as well as patient history, and other factors. For instance, a hypopigmented area that is localized and has a reddish central papule might lead a clinician to a diagnosis of hypopigmented sarcoidosis.

Using the algorithms, “you actually have to categorize these and then use your own experience. ... All of these elements can help you become a really good taxonomist – ultimately that’s what physicians are.”

He said it’s also important to know when it’s time to reconsider a diagnosis, such as when patients do not respond to traditional treatments. “If they don’t respond, re-categorize,” he said.

Speaking about vitiligo, Dr. Harris said it’s crucial to differentiate active vitiligo from inactive vitiligo and if it’s active, steps need to be taken to keep it from worsening..

Four signs of active vitiligo are a “confetti” pattern of clustered tiny macules of depigmentation, which will coalesce quickly into huge patches; tri-chrome vitiligo that includes a hypopigmented zone; linear areas of depigmentation (Koebner’s phenomenon) that look like scratches on the skin; and inflammatory vitiligo, with an erythematous ring around the edges of a depigmented area.

Dr. Harris disclosed ties with Incyte, Pfizer, Abbvie, Genzyme/Sanofi and other companies. Dr. Elbuluk disclosed ties with Avita, Incyte, Beiersdorf, and other companies. Dr. Hamzavi disclosed ties with AbbVie, Pfizer, Incyte, and other companies.

ORLANDO – Research on pigmentary disorders has entered an overdue era of increased attention, resulting in more treatment options and the promise of improved quality of life for patients, a panel of experts said in a session on this topic at the ODAC Dermatology, Aesthetic & Surgical Conference.

The arrival of ruxolitinib cream, a topical JAK inhibitor – and oral JAK inhibitors, including ritlecitinib, a JAK3/TEC (tyrosine kinase expressed in hepatocellular carcinoma) inhibitor in clinical trials – is a welcome development for treatment of vitiligo, said John E. Harris, MD, PhD, chair of dermatology and director of the Vitiligo Clinic and Research Center at the University of Massachusetts, Worcester. Also in the pipeline is a kit for melanocyte-keratinocyte transplantation, which involves transplanting epidermal cells from one part of the body to another. This can be a challenging procedure but a kit would make it easier for a wider range of practitioners. (Topical ruxolitinib was approved by the Food and Drug Administration for treating nonsegmental vitiligo in July, 2022.)

“In the last 10 years, it’s just blown up and people care about vitiligo now,” Dr. Harris said, noting that vitiligo is more than a cosmetic issue, like gray hair or wrinkles. “Vitiligo is an autoimmune disease and now is being treated as such.”

Nada Elbuluk, MD, MSc, associate professor of dermatology at the University of Southern California, Los Angeles, said she’s pleased at the increasing availability of treatment options for hyperpigmentation, aside from hydroquinone, which is associated with an increased risk of adverse effects.

“We have more and more nonhydroquinone agents ... which is really nice because it expands our treatment armamentarium and what we can use to cycle people off of hydroquinone,” she said.

Some of these options include tranexamic acid and products containing azelaic acid or vitamin C.

Iltefat H. Hamzavi, MD, senior staff physician at Henry Ford Health System, Detroit, said that pigmentary disorders are receiving the recognition they deserve.

“I’m excited just about the intersection of society and science, the awareness that pigmentary abnormalities mean something, and they mean something across our society,” he said.

Dr. Elbuluk said that hyperpigmentation has “profound effects on quality of life” for patients.

“They are often more bothered by the darkening of the skin than the primary process that caused it,” she said. “It’s not uncommon that the chief complaint will say ‘dark spots’ and I walk in a room and it’s a patient who has acne. They don’t even say they’re here for acne. They just put ‘dark spots’ [down] because that’s what bothers them. That’s what lasts for so long after the acne is gone.”

The experts offered suggestions for managing these cases. Among her tips, Dr. Elbuluk said that for hyperpigmentation, physicians should not be afraid to biopsy the face – but suggested small, 2-millimeter specimens. In addition, “you can get common conditions in uncommon places,” she noted. “If you see something that looks like melasma off the face, it actually could be, so keep that in your differential.”

Dr. Hamzavi, who spoke about hypopigmentation disorders, said clinicians need to use an algorithm for diagnosis, considering features such as localized or diffuse, scale or no scale, as well as patient history, and other factors. For instance, a hypopigmented area that is localized and has a reddish central papule might lead a clinician to a diagnosis of hypopigmented sarcoidosis.

Using the algorithms, “you actually have to categorize these and then use your own experience. ... All of these elements can help you become a really good taxonomist – ultimately that’s what physicians are.”

He said it’s also important to know when it’s time to reconsider a diagnosis, such as when patients do not respond to traditional treatments. “If they don’t respond, re-categorize,” he said.

Speaking about vitiligo, Dr. Harris said it’s crucial to differentiate active vitiligo from inactive vitiligo and if it’s active, steps need to be taken to keep it from worsening..

Four signs of active vitiligo are a “confetti” pattern of clustered tiny macules of depigmentation, which will coalesce quickly into huge patches; tri-chrome vitiligo that includes a hypopigmented zone; linear areas of depigmentation (Koebner’s phenomenon) that look like scratches on the skin; and inflammatory vitiligo, with an erythematous ring around the edges of a depigmented area.

Dr. Harris disclosed ties with Incyte, Pfizer, Abbvie, Genzyme/Sanofi and other companies. Dr. Elbuluk disclosed ties with Avita, Incyte, Beiersdorf, and other companies. Dr. Hamzavi disclosed ties with AbbVie, Pfizer, Incyte, and other companies.

ORLANDO – Research on pigmentary disorders has entered an overdue era of increased attention, resulting in more treatment options and the promise of improved quality of life for patients, a panel of experts said in a session on this topic at the ODAC Dermatology, Aesthetic & Surgical Conference.

The arrival of ruxolitinib cream, a topical JAK inhibitor – and oral JAK inhibitors, including ritlecitinib, a JAK3/TEC (tyrosine kinase expressed in hepatocellular carcinoma) inhibitor in clinical trials – is a welcome development for treatment of vitiligo, said John E. Harris, MD, PhD, chair of dermatology and director of the Vitiligo Clinic and Research Center at the University of Massachusetts, Worcester. Also in the pipeline is a kit for melanocyte-keratinocyte transplantation, which involves transplanting epidermal cells from one part of the body to another. This can be a challenging procedure but a kit would make it easier for a wider range of practitioners. (Topical ruxolitinib was approved by the Food and Drug Administration for treating nonsegmental vitiligo in July, 2022.)

“In the last 10 years, it’s just blown up and people care about vitiligo now,” Dr. Harris said, noting that vitiligo is more than a cosmetic issue, like gray hair or wrinkles. “Vitiligo is an autoimmune disease and now is being treated as such.”

Nada Elbuluk, MD, MSc, associate professor of dermatology at the University of Southern California, Los Angeles, said she’s pleased at the increasing availability of treatment options for hyperpigmentation, aside from hydroquinone, which is associated with an increased risk of adverse effects.

“We have more and more nonhydroquinone agents ... which is really nice because it expands our treatment armamentarium and what we can use to cycle people off of hydroquinone,” she said.

Some of these options include tranexamic acid and products containing azelaic acid or vitamin C.

Iltefat H. Hamzavi, MD, senior staff physician at Henry Ford Health System, Detroit, said that pigmentary disorders are receiving the recognition they deserve.

“I’m excited just about the intersection of society and science, the awareness that pigmentary abnormalities mean something, and they mean something across our society,” he said.

Dr. Elbuluk said that hyperpigmentation has “profound effects on quality of life” for patients.

“They are often more bothered by the darkening of the skin than the primary process that caused it,” she said. “It’s not uncommon that the chief complaint will say ‘dark spots’ and I walk in a room and it’s a patient who has acne. They don’t even say they’re here for acne. They just put ‘dark spots’ [down] because that’s what bothers them. That’s what lasts for so long after the acne is gone.”

The experts offered suggestions for managing these cases. Among her tips, Dr. Elbuluk said that for hyperpigmentation, physicians should not be afraid to biopsy the face – but suggested small, 2-millimeter specimens. In addition, “you can get common conditions in uncommon places,” she noted. “If you see something that looks like melasma off the face, it actually could be, so keep that in your differential.”

Dr. Hamzavi, who spoke about hypopigmentation disorders, said clinicians need to use an algorithm for diagnosis, considering features such as localized or diffuse, scale or no scale, as well as patient history, and other factors. For instance, a hypopigmented area that is localized and has a reddish central papule might lead a clinician to a diagnosis of hypopigmented sarcoidosis.

Using the algorithms, “you actually have to categorize these and then use your own experience. ... All of these elements can help you become a really good taxonomist – ultimately that’s what physicians are.”

He said it’s also important to know when it’s time to reconsider a diagnosis, such as when patients do not respond to traditional treatments. “If they don’t respond, re-categorize,” he said.

Speaking about vitiligo, Dr. Harris said it’s crucial to differentiate active vitiligo from inactive vitiligo and if it’s active, steps need to be taken to keep it from worsening..

Four signs of active vitiligo are a “confetti” pattern of clustered tiny macules of depigmentation, which will coalesce quickly into huge patches; tri-chrome vitiligo that includes a hypopigmented zone; linear areas of depigmentation (Koebner’s phenomenon) that look like scratches on the skin; and inflammatory vitiligo, with an erythematous ring around the edges of a depigmented area.

Dr. Harris disclosed ties with Incyte, Pfizer, Abbvie, Genzyme/Sanofi and other companies. Dr. Elbuluk disclosed ties with Avita, Incyte, Beiersdorf, and other companies. Dr. Hamzavi disclosed ties with AbbVie, Pfizer, Incyte, and other companies.

Most patients with end-stage hepatocellular carcinoma experience pain, but when it’s severe, how best to control the pain is debatable. A number of studies, including one recently presented at the ASCO Gastrointestinal Cancers Symposium 2023, shows that low-dose radiotherapy can improve pain, and in this case, even improve survival.

The study, conducted by Laura Dawson, MD, a radiation oncologist with the Princess Margaret Cancer Center, Toronto, was conducted in 66 patients with painful hepatocellular carcinoma or liver metastases. They were randomized to receive either palliative radiotherapy (single fraction 8 gray) or standard pain control. Sixty-three percent of patients treated with radiotherapy reported significant improvements in mild pain compared with 28% of patients who received standard pain control (P = .03).

Currently, palliative radiotherapy to control pain in late stage cancer may be an option for some patients with other types of advanced cancer, but in liver cancer, there is little data to support its routine use in patients with terminal hepatocellular carcinoma. “Several prior studies have shown radiation therapy may be delivered safely and that it may help patients with hepatic cancer pain,” Dr. Dawson said. But the previous studies have mostly been single-arm, she said, and many lacked patient-reported outcomes.

In liver cancer, existing therapies are largely inadequate for pain relief, especially for moderate to severe pain. Systemic therapy isn’t effective for rapid pain relief. And, for a subset of patients with end-stage liver cancer, standard pain control with acetaminophen, steroids, and narcotics either is not effective or cannot be tolerated because of underlying cirrhosis or poor liver function due to the cancer.

Although not clinically significant, palliative radiotherapy improved 3-month survival (51%) compared with patients who received best supportive care (33%, P = .07). “Interestingly, there was a trend for improved survival in those patients who received radiation with a 3-month survival of 51% versus 33% of those who received best supportive care. Clearly, the study was not powered for this, but it is very intriguing and hopefully sets the stage for future clinical trials.”

In this study, “simple radiotherapy was used and could consist of two beams, opposed or oblique parallel pair, or simple intensity modulated radiation. This is available with any medical linear accelerator or any cancer center,” Dr. Dawson said. “A single dose of radiation therapy with an antiemetic is a low-cost simple palliative intervention for patients with analgesia-refractory hepatic pain from cancer.”
 

New data reported at ASCO GI

The Dawson et al. study included 66 patients with liver cancer who had pain scores of at least 4. They had pain that was specific to the liver and they were unsuitable for or refractory to other therapies with no other planned therapies, such as immunotherapy. Their pain was refractory to standard treatments. Of the patients, 43 had liver metastasis from cancers that originated in the colon (12), breast (5), pancreas (4), lung (3), hepatocellular carcinoma (23), or other sites (19).

At 59%, more than half of patients had ECOG performance status of 2 or 3, suggesting the cancer had progressed to the extent that they were confined to a bed or chair for more than half of their waking hours (level 3) or they were capable of self-care but unable to work (level 2). Of the 66 patients, 42 patients completed 1-month assessments and of these, 67% of 24 patients receiving palliative radiotherapy (21% had no increase in opioids) and 22% of 18 patients receiving best supportive care (with no increase in opioids) reported improvements in their worst pain levels.

The primary endpoint – the proportion of patients with a clinically important improvement in pain 1 month after therapy – was met. “There was a significant improvement in all pain endpoints from baseline to one month, with more patients who received radiotherapy reporting clinically important reduction of pain (a reduction by 2 or more on the 0 to 10 scale). The primary endpoint was pain – worst pain, and 67% of those patients who had radiation reported an improvement in their pain at worst in the past 24 hours versus 22% treated with best supportive care, with a P value .004,” Dr. Dawson said.

Adverse events of at least grade 2 or higher occurred 30 days after radiotherapy, affecting 58% of patients compared with 33% of patients who did not receive the treatment. Adverse events at grade 3 or higher were uncommon.

Dr. Dawson reports institutional research funding from Merck.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
 

Most patients with end-stage hepatocellular carcinoma experience pain, but when it’s severe, how best to control the pain is debatable. A number of studies, including one recently presented at the ASCO Gastrointestinal Cancers Symposium 2023, shows that low-dose radiotherapy can improve pain, and in this case, even improve survival.

The study, conducted by Laura Dawson, MD, a radiation oncologist with the Princess Margaret Cancer Center, Toronto, was conducted in 66 patients with painful hepatocellular carcinoma or liver metastases. They were randomized to receive either palliative radiotherapy (single fraction 8 gray) or standard pain control. Sixty-three percent of patients treated with radiotherapy reported significant improvements in mild pain compared with 28% of patients who received standard pain control (P = .03).

Currently, palliative radiotherapy to control pain in late stage cancer may be an option for some patients with other types of advanced cancer, but in liver cancer, there is little data to support its routine use in patients with terminal hepatocellular carcinoma. “Several prior studies have shown radiation therapy may be delivered safely and that it may help patients with hepatic cancer pain,” Dr. Dawson said. But the previous studies have mostly been single-arm, she said, and many lacked patient-reported outcomes.

In liver cancer, existing therapies are largely inadequate for pain relief, especially for moderate to severe pain. Systemic therapy isn’t effective for rapid pain relief. And, for a subset of patients with end-stage liver cancer, standard pain control with acetaminophen, steroids, and narcotics either is not effective or cannot be tolerated because of underlying cirrhosis or poor liver function due to the cancer.

Although not clinically significant, palliative radiotherapy improved 3-month survival (51%) compared with patients who received best supportive care (33%, P = .07). “Interestingly, there was a trend for improved survival in those patients who received radiation with a 3-month survival of 51% versus 33% of those who received best supportive care. Clearly, the study was not powered for this, but it is very intriguing and hopefully sets the stage for future clinical trials.”

In this study, “simple radiotherapy was used and could consist of two beams, opposed or oblique parallel pair, or simple intensity modulated radiation. This is available with any medical linear accelerator or any cancer center,” Dr. Dawson said. “A single dose of radiation therapy with an antiemetic is a low-cost simple palliative intervention for patients with analgesia-refractory hepatic pain from cancer.”
 

New data reported at ASCO GI

The Dawson et al. study included 66 patients with liver cancer who had pain scores of at least 4. They had pain that was specific to the liver and they were unsuitable for or refractory to other therapies with no other planned therapies, such as immunotherapy. Their pain was refractory to standard treatments. Of the patients, 43 had liver metastasis from cancers that originated in the colon (12), breast (5), pancreas (4), lung (3), hepatocellular carcinoma (23), or other sites (19).

At 59%, more than half of patients had ECOG performance status of 2 or 3, suggesting the cancer had progressed to the extent that they were confined to a bed or chair for more than half of their waking hours (level 3) or they were capable of self-care but unable to work (level 2). Of the 66 patients, 42 patients completed 1-month assessments and of these, 67% of 24 patients receiving palliative radiotherapy (21% had no increase in opioids) and 22% of 18 patients receiving best supportive care (with no increase in opioids) reported improvements in their worst pain levels.

The primary endpoint – the proportion of patients with a clinically important improvement in pain 1 month after therapy – was met. “There was a significant improvement in all pain endpoints from baseline to one month, with more patients who received radiotherapy reporting clinically important reduction of pain (a reduction by 2 or more on the 0 to 10 scale). The primary endpoint was pain – worst pain, and 67% of those patients who had radiation reported an improvement in their pain at worst in the past 24 hours versus 22% treated with best supportive care, with a P value .004,” Dr. Dawson said.

Adverse events of at least grade 2 or higher occurred 30 days after radiotherapy, affecting 58% of patients compared with 33% of patients who did not receive the treatment. Adverse events at grade 3 or higher were uncommon.

Dr. Dawson reports institutional research funding from Merck.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
 

Most patients with end-stage hepatocellular carcinoma experience pain, but when it’s severe, how best to control the pain is debatable. A number of studies, including one recently presented at the ASCO Gastrointestinal Cancers Symposium 2023, shows that low-dose radiotherapy can improve pain, and in this case, even improve survival.

The study, conducted by Laura Dawson, MD, a radiation oncologist with the Princess Margaret Cancer Center, Toronto, was conducted in 66 patients with painful hepatocellular carcinoma or liver metastases. They were randomized to receive either palliative radiotherapy (single fraction 8 gray) or standard pain control. Sixty-three percent of patients treated with radiotherapy reported significant improvements in mild pain compared with 28% of patients who received standard pain control (P = .03).

Currently, palliative radiotherapy to control pain in late stage cancer may be an option for some patients with other types of advanced cancer, but in liver cancer, there is little data to support its routine use in patients with terminal hepatocellular carcinoma. “Several prior studies have shown radiation therapy may be delivered safely and that it may help patients with hepatic cancer pain,” Dr. Dawson said. But the previous studies have mostly been single-arm, she said, and many lacked patient-reported outcomes.

In liver cancer, existing therapies are largely inadequate for pain relief, especially for moderate to severe pain. Systemic therapy isn’t effective for rapid pain relief. And, for a subset of patients with end-stage liver cancer, standard pain control with acetaminophen, steroids, and narcotics either is not effective or cannot be tolerated because of underlying cirrhosis or poor liver function due to the cancer.

Although not clinically significant, palliative radiotherapy improved 3-month survival (51%) compared with patients who received best supportive care (33%, P = .07). “Interestingly, there was a trend for improved survival in those patients who received radiation with a 3-month survival of 51% versus 33% of those who received best supportive care. Clearly, the study was not powered for this, but it is very intriguing and hopefully sets the stage for future clinical trials.”

In this study, “simple radiotherapy was used and could consist of two beams, opposed or oblique parallel pair, or simple intensity modulated radiation. This is available with any medical linear accelerator or any cancer center,” Dr. Dawson said. “A single dose of radiation therapy with an antiemetic is a low-cost simple palliative intervention for patients with analgesia-refractory hepatic pain from cancer.”
 

New data reported at ASCO GI

The Dawson et al. study included 66 patients with liver cancer who had pain scores of at least 4. They had pain that was specific to the liver and they were unsuitable for or refractory to other therapies with no other planned therapies, such as immunotherapy. Their pain was refractory to standard treatments. Of the patients, 43 had liver metastasis from cancers that originated in the colon (12), breast (5), pancreas (4), lung (3), hepatocellular carcinoma (23), or other sites (19).

At 59%, more than half of patients had ECOG performance status of 2 or 3, suggesting the cancer had progressed to the extent that they were confined to a bed or chair for more than half of their waking hours (level 3) or they were capable of self-care but unable to work (level 2). Of the 66 patients, 42 patients completed 1-month assessments and of these, 67% of 24 patients receiving palliative radiotherapy (21% had no increase in opioids) and 22% of 18 patients receiving best supportive care (with no increase in opioids) reported improvements in their worst pain levels.

The primary endpoint – the proportion of patients with a clinically important improvement in pain 1 month after therapy – was met. “There was a significant improvement in all pain endpoints from baseline to one month, with more patients who received radiotherapy reporting clinically important reduction of pain (a reduction by 2 or more on the 0 to 10 scale). The primary endpoint was pain – worst pain, and 67% of those patients who had radiation reported an improvement in their pain at worst in the past 24 hours versus 22% treated with best supportive care, with a P value .004,” Dr. Dawson said.

Adverse events of at least grade 2 or higher occurred 30 days after radiotherapy, affecting 58% of patients compared with 33% of patients who did not receive the treatment. Adverse events at grade 3 or higher were uncommon.

Dr. Dawson reports institutional research funding from Merck.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
 

According to an article in the Wall Street Journal (Mosbergen D. 2023 Jan 16), physicians-in-training in several parts of the country are attempting to unionize. The Committee of Interns and Residents (CIR), a union representing about 15% of the 140,000 residents and fellows in the United States reports that it has been adding chapters at an accelerated rate since the pandemic began.

Most of the 1,400 residents at Palo Alto–based Stanford Medicine recently voted to unionize seeking better compensation and improved working conditions including more accommodations for residents with disabilities or who are breastfeeding. At the University of Illinois at Chicago, house officers are also exploring an association with CIR hoping that collective bargaining might help them get “better pay and working conditions that could alleviate some burnout and stress.”

Although physicians have been hesitant to organize themselves around workplace concerns, nurses have a more robust history of unionizing and taking action. Recently, the nurses at two of New York’s largest medical centers went on a strike for 3 days that ended after the medical centers agreed to their primary demand of hiring more nurses and committing to set more workable nurse to patient ratios.

In an unusual but historic incident of workplace activism, the residents and interns at the then notoriously decrepit Boston City Hospital staged a “heal-in” in 1967 during which they admitted more patients (all with legitimate conditions for admission) than the hospital could handle. While more pay was included in their demands (interns were being paid $3,600/year and senior residents $7,500/year), the primary complaint of the house officers focused on patient health and safety issues. The crisis this work action triggered finally brought into sharp focus the city’s failure to care for its most needy citizens and over time, changes have been made (TIME Magazine. U.S. edition. Jun 21;91:25).

Having spent some time at the Boston City Hospital as a medical student in the 1960s I can attest to the deplorable conditions. While you might not be washing your hands and instruments in rusty sinks or having to brush flaking paint off your patients’ cribs, you may be experiencing working conditions that are threatening the health and safety of you, your coworkers, and not least of all your patients. Staffing shortages, clunky electronic health record systems that are adding hours of work to your day, screen after screen of data entry tasks that prevent you from meeting your patients eye-to-eye, and piles of prior authorization requests clogging your inbox to name just a few.

Who can you complain to, other than your coworkers? The patients brought their problems to you; it doesn’t seem fair to add to their burden by sharing your own. Maybe it’s time to think about joining a union to strengthen your voice and create some change.

But “union” and “strike” don’t sound very professional and certainly not coming from the mouths of folks who have chosen to be caregivers. However, things have changed. Most of us are employees now. We need to finally accept that role and begin acting like employees working under stressful and unhealthy conditions. Does the word “burnout” make the notion of unionizing any more palatable?

The American Medical Association’s code of ethics wisely discourages physicians from engaging in actions that withhold medical care. However, the Boston City Hospital house officers provided just one example of a work action that can draw attention to the problem while still providing care to the patients in our trust.

Simply, joining our voices can be a powerful force in the war of words and images. Patients don’t like the impersonalization that has come with the current crop of electronic health record systems and the tortuous phone trees they must navigate just to talk to a human voice any more than we do. Instead of complaining to the patients, we should explain to them that the working conditions we must endure have the same roots as the things they don’t like about coming to see us.

I hope your situation still allows you to have an effective voice. If it doesn’t maybe it’s time to consider unionizing. However, if asking for more pay is anywhere near the top of your grievance list, I don’t want to join your union because you are doomed to failure on the public relations battlefield.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

According to an article in the Wall Street Journal (Mosbergen D. 2023 Jan 16), physicians-in-training in several parts of the country are attempting to unionize. The Committee of Interns and Residents (CIR), a union representing about 15% of the 140,000 residents and fellows in the United States reports that it has been adding chapters at an accelerated rate since the pandemic began.

Most of the 1,400 residents at Palo Alto–based Stanford Medicine recently voted to unionize seeking better compensation and improved working conditions including more accommodations for residents with disabilities or who are breastfeeding. At the University of Illinois at Chicago, house officers are also exploring an association with CIR hoping that collective bargaining might help them get “better pay and working conditions that could alleviate some burnout and stress.”

Although physicians have been hesitant to organize themselves around workplace concerns, nurses have a more robust history of unionizing and taking action. Recently, the nurses at two of New York’s largest medical centers went on a strike for 3 days that ended after the medical centers agreed to their primary demand of hiring more nurses and committing to set more workable nurse to patient ratios.

In an unusual but historic incident of workplace activism, the residents and interns at the then notoriously decrepit Boston City Hospital staged a “heal-in” in 1967 during which they admitted more patients (all with legitimate conditions for admission) than the hospital could handle. While more pay was included in their demands (interns were being paid $3,600/year and senior residents $7,500/year), the primary complaint of the house officers focused on patient health and safety issues. The crisis this work action triggered finally brought into sharp focus the city’s failure to care for its most needy citizens and over time, changes have been made (TIME Magazine. U.S. edition. Jun 21;91:25).

Having spent some time at the Boston City Hospital as a medical student in the 1960s I can attest to the deplorable conditions. While you might not be washing your hands and instruments in rusty sinks or having to brush flaking paint off your patients’ cribs, you may be experiencing working conditions that are threatening the health and safety of you, your coworkers, and not least of all your patients. Staffing shortages, clunky electronic health record systems that are adding hours of work to your day, screen after screen of data entry tasks that prevent you from meeting your patients eye-to-eye, and piles of prior authorization requests clogging your inbox to name just a few.

Who can you complain to, other than your coworkers? The patients brought their problems to you; it doesn’t seem fair to add to their burden by sharing your own. Maybe it’s time to think about joining a union to strengthen your voice and create some change.

But “union” and “strike” don’t sound very professional and certainly not coming from the mouths of folks who have chosen to be caregivers. However, things have changed. Most of us are employees now. We need to finally accept that role and begin acting like employees working under stressful and unhealthy conditions. Does the word “burnout” make the notion of unionizing any more palatable?

The American Medical Association’s code of ethics wisely discourages physicians from engaging in actions that withhold medical care. However, the Boston City Hospital house officers provided just one example of a work action that can draw attention to the problem while still providing care to the patients in our trust.

Simply, joining our voices can be a powerful force in the war of words and images. Patients don’t like the impersonalization that has come with the current crop of electronic health record systems and the tortuous phone trees they must navigate just to talk to a human voice any more than we do. Instead of complaining to the patients, we should explain to them that the working conditions we must endure have the same roots as the things they don’t like about coming to see us.

I hope your situation still allows you to have an effective voice. If it doesn’t maybe it’s time to consider unionizing. However, if asking for more pay is anywhere near the top of your grievance list, I don’t want to join your union because you are doomed to failure on the public relations battlefield.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

According to an article in the Wall Street Journal (Mosbergen D. 2023 Jan 16), physicians-in-training in several parts of the country are attempting to unionize. The Committee of Interns and Residents (CIR), a union representing about 15% of the 140,000 residents and fellows in the United States reports that it has been adding chapters at an accelerated rate since the pandemic began.

Most of the 1,400 residents at Palo Alto–based Stanford Medicine recently voted to unionize seeking better compensation and improved working conditions including more accommodations for residents with disabilities or who are breastfeeding. At the University of Illinois at Chicago, house officers are also exploring an association with CIR hoping that collective bargaining might help them get “better pay and working conditions that could alleviate some burnout and stress.”

Although physicians have been hesitant to organize themselves around workplace concerns, nurses have a more robust history of unionizing and taking action. Recently, the nurses at two of New York’s largest medical centers went on a strike for 3 days that ended after the medical centers agreed to their primary demand of hiring more nurses and committing to set more workable nurse to patient ratios.

In an unusual but historic incident of workplace activism, the residents and interns at the then notoriously decrepit Boston City Hospital staged a “heal-in” in 1967 during which they admitted more patients (all with legitimate conditions for admission) than the hospital could handle. While more pay was included in their demands (interns were being paid $3,600/year and senior residents $7,500/year), the primary complaint of the house officers focused on patient health and safety issues. The crisis this work action triggered finally brought into sharp focus the city’s failure to care for its most needy citizens and over time, changes have been made (TIME Magazine. U.S. edition. Jun 21;91:25).

Having spent some time at the Boston City Hospital as a medical student in the 1960s I can attest to the deplorable conditions. While you might not be washing your hands and instruments in rusty sinks or having to brush flaking paint off your patients’ cribs, you may be experiencing working conditions that are threatening the health and safety of you, your coworkers, and not least of all your patients. Staffing shortages, clunky electronic health record systems that are adding hours of work to your day, screen after screen of data entry tasks that prevent you from meeting your patients eye-to-eye, and piles of prior authorization requests clogging your inbox to name just a few.

Who can you complain to, other than your coworkers? The patients brought their problems to you; it doesn’t seem fair to add to their burden by sharing your own. Maybe it’s time to think about joining a union to strengthen your voice and create some change.

But “union” and “strike” don’t sound very professional and certainly not coming from the mouths of folks who have chosen to be caregivers. However, things have changed. Most of us are employees now. We need to finally accept that role and begin acting like employees working under stressful and unhealthy conditions. Does the word “burnout” make the notion of unionizing any more palatable?

The American Medical Association’s code of ethics wisely discourages physicians from engaging in actions that withhold medical care. However, the Boston City Hospital house officers provided just one example of a work action that can draw attention to the problem while still providing care to the patients in our trust.

Simply, joining our voices can be a powerful force in the war of words and images. Patients don’t like the impersonalization that has come with the current crop of electronic health record systems and the tortuous phone trees they must navigate just to talk to a human voice any more than we do. Instead of complaining to the patients, we should explain to them that the working conditions we must endure have the same roots as the things they don’t like about coming to see us.

I hope your situation still allows you to have an effective voice. If it doesn’t maybe it’s time to consider unionizing. However, if asking for more pay is anywhere near the top of your grievance list, I don’t want to join your union because you are doomed to failure on the public relations battlefield.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Topical cannabidiol (CBD) oil appeared to lower pain scores and reduce painkiller use vs. standard treatment in patients with digital ulcers due to systemic sclerosis, a small new study finds. Patients who received the treatment also showed signs of more healing.

The study, published in Advances in Skin & Wound Care, is far from definitive since it’s retrospective and tracked only 45 patients. But the findings add to other research suggesting dermatologic benefits from the topical use of CBD, an ingredient in cannabis that’s widely available and doesn’t cause people to become high or become addicted.

Anatoliy Sizov/Getty Images

“This is a good first step in trying to address scleroderma digital ulcer pain and healing,” University of Colorado rheumatologist Melissa Griffith, MD, said in an interview. “Digital ulcers cause great impact on quality of life, daily activities of living, and pain, so we are always looking for new, effective tools.”

According to Dr. Griffith, digital ulcers occur in scleroderma due to Raynaud’s phenomenon with reversible vasospasm. “Unlike patients with primary Raynaud’s phenomenon, patients will develop ischemia of digits, leading to digital ulcers due to the vasculopathy or vascular remodeling that occurs in scleroderma,” she said.

Current treatments include removal of causative drugs/toxins and warmth, rest, and pain control, although “no trials exist to compare the scleroderma digital ulcer or digital ischemia treatments to each other,” Dr. Griffith said.

Therapy for vasospasm begins with calcium channel blockers such as amlodipine and nifedipine, she said, followed by phosphodiesterase type 5 inhibitors such as sildenafil or endothelin receptor antagonist medications such as bosentan. “If these fail, we use an IV option – epoprostenol. Other options are sympathectomy surgery, Botox, digital nerve blocks, biofeedback, and SSRIs,” she said. “These treatments work fairly well in most patients, but there are patients who break through these therapies and have ongoing digital ischemia, leading to digital ulcers, pain, infections, acro-osteolysis, and auto-amputation. There is definitely room to improve on our current treatment paradigm.”

For the new study, researchers in Italy led by Amelia Spinella, MD, PhD, of University Hospital of Modena, retrospectively tracked 45 patients with systemic sclerosis and at least one digital ulcer (40 women; average age, 53 years) who were treated in 2019. All patients’ ulcers were resistant to opioid therapy at the maximum tolerated dose, and all had undergone periodic iloprost infusion every 30-40 days. Based on each patient’s clinical situation, they had received calcium-channel blockers, phosphodiesterase type 5 inhibitors (sildenafil), and/or endothelin receptor antagonists (bosentan or macitentan). The researchers noted that all patients underwent surgical debridement regularly following wound bed preparation procedures and received advanced dressings (alginate, hydrocolloid, hydrofiber, hydrogel, and polyurethane foam or film). Of the 45 patients, 25 treated their wounds daily over the course of a month by administering four drops of a preparation of 10% CBD oil in acidic form and 90% hemp oil over the wound bed and perilesional skin and then covering it with a nonadhesive cloth.

“Basal wound-related pain NRS [numeric rating scale] scores decreased from 8.4 (standard deviation [SD], 0.8) at the baseline (T0) to 6.0 (SD, 0.82) after 1 month of CBD treatment (T1; P < .0001),” the researchers reported. “Across the same time period, volitional incident pain NRS scores decreased from 9.32 (SD, 0.75; T0) to 6.8 (SD, 1.12; T1; P < .0001). In addition, mean total hours of sleep per night increased from 2.56 (SD, 1.28) to 5.67 (SD, 0.85) hours (P < .0001).” Twelve of the 25 needed additional painkiller therapy.

Complete digital ulcer healing occurred by the end of the study in 18 of 25 (72%) CBD-treated patients, compared with 6 of 20 (30%) control patients.

In contrast, the control group didn’t see any significant improvement in wound-related pain, volitional incident pain, or sleep. All needed additional painkiller therapy. Six developed ulcer infections and received antibiotics.

No significant adverse effects were reported, although 28% of those in the CBD oil group said they had mild effects such as itch and perilesional erythema.

The authors of the new study called for larger, randomized controlled, multicenter trials to confirm the benefit of CBD topical treatment.

In recent years, researchers have devoted more attention to topical CBD as a treatment for skin conditions. While limited, the evidence suggests they “may be effective for the treatment of various inflammatory skin disorders,” researchers wrote in a 2022 report. “Although promising, additional research is necessary to evaluate efficacy and to determine dosing, safety, and long-term treatment guidelines.”

Dr. Griffith, who did not take part in the new study but is familiar with its findings, said she was especially surprised by the hint that topical CBD improves healing in addition to relieving symptoms. “I thought only pain would be affected. This is a great outcome if it can be replicated.”

As for future research, she said “there are difficulties with reproducing this at a big scale in the U.S. given CBD commercial variability. The big issue is the standardization of CBD extraction and production. It is really hard for us as physicians to know what patients are getting. Some online CBD orders contain THC [the major psychoactive ingredient of cannabis] > 0.3% or no CBD at all.”

Still, she said, “physicians and patients may consider this when standard therapies are not working or causing too many adverse effects,” especially since “the downsides here seem fairly minimal – at worst itchiness and redness that did not prevent patients from continuing in the study.”

No details about study funding were provided. The authors and Dr. Griffith report no disclosures.

Topical cannabidiol (CBD) oil appeared to lower pain scores and reduce painkiller use vs. standard treatment in patients with digital ulcers due to systemic sclerosis, a small new study finds. Patients who received the treatment also showed signs of more healing.

The study, published in Advances in Skin & Wound Care, is far from definitive since it’s retrospective and tracked only 45 patients. But the findings add to other research suggesting dermatologic benefits from the topical use of CBD, an ingredient in cannabis that’s widely available and doesn’t cause people to become high or become addicted.

Anatoliy Sizov/Getty Images

“This is a good first step in trying to address scleroderma digital ulcer pain and healing,” University of Colorado rheumatologist Melissa Griffith, MD, said in an interview. “Digital ulcers cause great impact on quality of life, daily activities of living, and pain, so we are always looking for new, effective tools.”

According to Dr. Griffith, digital ulcers occur in scleroderma due to Raynaud’s phenomenon with reversible vasospasm. “Unlike patients with primary Raynaud’s phenomenon, patients will develop ischemia of digits, leading to digital ulcers due to the vasculopathy or vascular remodeling that occurs in scleroderma,” she said.

Current treatments include removal of causative drugs/toxins and warmth, rest, and pain control, although “no trials exist to compare the scleroderma digital ulcer or digital ischemia treatments to each other,” Dr. Griffith said.

Therapy for vasospasm begins with calcium channel blockers such as amlodipine and nifedipine, she said, followed by phosphodiesterase type 5 inhibitors such as sildenafil or endothelin receptor antagonist medications such as bosentan. “If these fail, we use an IV option – epoprostenol. Other options are sympathectomy surgery, Botox, digital nerve blocks, biofeedback, and SSRIs,” she said. “These treatments work fairly well in most patients, but there are patients who break through these therapies and have ongoing digital ischemia, leading to digital ulcers, pain, infections, acro-osteolysis, and auto-amputation. There is definitely room to improve on our current treatment paradigm.”

For the new study, researchers in Italy led by Amelia Spinella, MD, PhD, of University Hospital of Modena, retrospectively tracked 45 patients with systemic sclerosis and at least one digital ulcer (40 women; average age, 53 years) who were treated in 2019. All patients’ ulcers were resistant to opioid therapy at the maximum tolerated dose, and all had undergone periodic iloprost infusion every 30-40 days. Based on each patient’s clinical situation, they had received calcium-channel blockers, phosphodiesterase type 5 inhibitors (sildenafil), and/or endothelin receptor antagonists (bosentan or macitentan). The researchers noted that all patients underwent surgical debridement regularly following wound bed preparation procedures and received advanced dressings (alginate, hydrocolloid, hydrofiber, hydrogel, and polyurethane foam or film). Of the 45 patients, 25 treated their wounds daily over the course of a month by administering four drops of a preparation of 10% CBD oil in acidic form and 90% hemp oil over the wound bed and perilesional skin and then covering it with a nonadhesive cloth.

“Basal wound-related pain NRS [numeric rating scale] scores decreased from 8.4 (standard deviation [SD], 0.8) at the baseline (T0) to 6.0 (SD, 0.82) after 1 month of CBD treatment (T1; P < .0001),” the researchers reported. “Across the same time period, volitional incident pain NRS scores decreased from 9.32 (SD, 0.75; T0) to 6.8 (SD, 1.12; T1; P < .0001). In addition, mean total hours of sleep per night increased from 2.56 (SD, 1.28) to 5.67 (SD, 0.85) hours (P < .0001).” Twelve of the 25 needed additional painkiller therapy.

Complete digital ulcer healing occurred by the end of the study in 18 of 25 (72%) CBD-treated patients, compared with 6 of 20 (30%) control patients.

In contrast, the control group didn’t see any significant improvement in wound-related pain, volitional incident pain, or sleep. All needed additional painkiller therapy. Six developed ulcer infections and received antibiotics.

No significant adverse effects were reported, although 28% of those in the CBD oil group said they had mild effects such as itch and perilesional erythema.

The authors of the new study called for larger, randomized controlled, multicenter trials to confirm the benefit of CBD topical treatment.

In recent years, researchers have devoted more attention to topical CBD as a treatment for skin conditions. While limited, the evidence suggests they “may be effective for the treatment of various inflammatory skin disorders,” researchers wrote in a 2022 report. “Although promising, additional research is necessary to evaluate efficacy and to determine dosing, safety, and long-term treatment guidelines.”

Dr. Griffith, who did not take part in the new study but is familiar with its findings, said she was especially surprised by the hint that topical CBD improves healing in addition to relieving symptoms. “I thought only pain would be affected. This is a great outcome if it can be replicated.”

As for future research, she said “there are difficulties with reproducing this at a big scale in the U.S. given CBD commercial variability. The big issue is the standardization of CBD extraction and production. It is really hard for us as physicians to know what patients are getting. Some online CBD orders contain THC [the major psychoactive ingredient of cannabis] > 0.3% or no CBD at all.”

Still, she said, “physicians and patients may consider this when standard therapies are not working or causing too many adverse effects,” especially since “the downsides here seem fairly minimal – at worst itchiness and redness that did not prevent patients from continuing in the study.”

No details about study funding were provided. The authors and Dr. Griffith report no disclosures.

Topical cannabidiol (CBD) oil appeared to lower pain scores and reduce painkiller use vs. standard treatment in patients with digital ulcers due to systemic sclerosis, a small new study finds. Patients who received the treatment also showed signs of more healing.

The study, published in Advances in Skin & Wound Care, is far from definitive since it’s retrospective and tracked only 45 patients. But the findings add to other research suggesting dermatologic benefits from the topical use of CBD, an ingredient in cannabis that’s widely available and doesn’t cause people to become high or become addicted.

Anatoliy Sizov/Getty Images

“This is a good first step in trying to address scleroderma digital ulcer pain and healing,” University of Colorado rheumatologist Melissa Griffith, MD, said in an interview. “Digital ulcers cause great impact on quality of life, daily activities of living, and pain, so we are always looking for new, effective tools.”

According to Dr. Griffith, digital ulcers occur in scleroderma due to Raynaud’s phenomenon with reversible vasospasm. “Unlike patients with primary Raynaud’s phenomenon, patients will develop ischemia of digits, leading to digital ulcers due to the vasculopathy or vascular remodeling that occurs in scleroderma,” she said.

Current treatments include removal of causative drugs/toxins and warmth, rest, and pain control, although “no trials exist to compare the scleroderma digital ulcer or digital ischemia treatments to each other,” Dr. Griffith said.

Therapy for vasospasm begins with calcium channel blockers such as amlodipine and nifedipine, she said, followed by phosphodiesterase type 5 inhibitors such as sildenafil or endothelin receptor antagonist medications such as bosentan. “If these fail, we use an IV option – epoprostenol. Other options are sympathectomy surgery, Botox, digital nerve blocks, biofeedback, and SSRIs,” she said. “These treatments work fairly well in most patients, but there are patients who break through these therapies and have ongoing digital ischemia, leading to digital ulcers, pain, infections, acro-osteolysis, and auto-amputation. There is definitely room to improve on our current treatment paradigm.”

For the new study, researchers in Italy led by Amelia Spinella, MD, PhD, of University Hospital of Modena, retrospectively tracked 45 patients with systemic sclerosis and at least one digital ulcer (40 women; average age, 53 years) who were treated in 2019. All patients’ ulcers were resistant to opioid therapy at the maximum tolerated dose, and all had undergone periodic iloprost infusion every 30-40 days. Based on each patient’s clinical situation, they had received calcium-channel blockers, phosphodiesterase type 5 inhibitors (sildenafil), and/or endothelin receptor antagonists (bosentan or macitentan). The researchers noted that all patients underwent surgical debridement regularly following wound bed preparation procedures and received advanced dressings (alginate, hydrocolloid, hydrofiber, hydrogel, and polyurethane foam or film). Of the 45 patients, 25 treated their wounds daily over the course of a month by administering four drops of a preparation of 10% CBD oil in acidic form and 90% hemp oil over the wound bed and perilesional skin and then covering it with a nonadhesive cloth.

“Basal wound-related pain NRS [numeric rating scale] scores decreased from 8.4 (standard deviation [SD], 0.8) at the baseline (T0) to 6.0 (SD, 0.82) after 1 month of CBD treatment (T1; P < .0001),” the researchers reported. “Across the same time period, volitional incident pain NRS scores decreased from 9.32 (SD, 0.75; T0) to 6.8 (SD, 1.12; T1; P < .0001). In addition, mean total hours of sleep per night increased from 2.56 (SD, 1.28) to 5.67 (SD, 0.85) hours (P < .0001).” Twelve of the 25 needed additional painkiller therapy.

Complete digital ulcer healing occurred by the end of the study in 18 of 25 (72%) CBD-treated patients, compared with 6 of 20 (30%) control patients.

In contrast, the control group didn’t see any significant improvement in wound-related pain, volitional incident pain, or sleep. All needed additional painkiller therapy. Six developed ulcer infections and received antibiotics.

No significant adverse effects were reported, although 28% of those in the CBD oil group said they had mild effects such as itch and perilesional erythema.

The authors of the new study called for larger, randomized controlled, multicenter trials to confirm the benefit of CBD topical treatment.

In recent years, researchers have devoted more attention to topical CBD as a treatment for skin conditions. While limited, the evidence suggests they “may be effective for the treatment of various inflammatory skin disorders,” researchers wrote in a 2022 report. “Although promising, additional research is necessary to evaluate efficacy and to determine dosing, safety, and long-term treatment guidelines.”

Dr. Griffith, who did not take part in the new study but is familiar with its findings, said she was especially surprised by the hint that topical CBD improves healing in addition to relieving symptoms. “I thought only pain would be affected. This is a great outcome if it can be replicated.”

As for future research, she said “there are difficulties with reproducing this at a big scale in the U.S. given CBD commercial variability. The big issue is the standardization of CBD extraction and production. It is really hard for us as physicians to know what patients are getting. Some online CBD orders contain THC [the major psychoactive ingredient of cannabis] > 0.3% or no CBD at all.”

Still, she said, “physicians and patients may consider this when standard therapies are not working or causing too many adverse effects,” especially since “the downsides here seem fairly minimal – at worst itchiness and redness that did not prevent patients from continuing in the study.”

No details about study funding were provided. The authors and Dr. Griffith report no disclosures.

Amid growing concern among the public, psychiatrists, and other mental health professionals, the Canadian government is seeking to delay the legalization of its proposed medical assistance in dying (MAID) for mental illness law that is slated to pass on March 17.

Canada already has the largest number of deaths by MAID of any nation, with 10,064 in 2021, a 32% increase from 2020. With the addition of serious mental illness (SMI) as an eligible category, the country is on track to have the most liberal assisted-death policy in the world.

Concerns about the additional number of patients who could become eligible for MAID, and a lack of evidence-backed standards from disability rights groups, mental health advocates, First Nations leaders, psychiatrists, and other mental health providers, seems to have led the Canadian government to give the proposed law some sober second thought.

“Listening to experts and Canadians, we believe this date needs to be temporarily delayed,” said David Lametti, Canada’s minister of Justice and attorney general of Canada; Jean-Yves Duclos, minister of Health; and  Carolyn Bennett, minister of Mental Health and Addictions, in a Dec. 15, 2022, joint statement.

Canada’s Parliament – which approved the expansion – will now have to vote on whether to okay a pause on the legislation.

However, the Canadian Psychiatric Association has not been calling for a delay in the proposed legislation. In a November 2021 statement, the CPA  said it “does not take a position on the legality or morality of MAID,” but added that to deny MAID to people with mental illness was discriminatory, and that, as it was the law, it must be followed.

“CPA has not taken a position about MAID,” the association’s president Gary Chaimowitz, MBChB, told this news organization. “We know this is coming and our organization is trying to get its members ready for what will be most likely the ability of people with mental conditions to be able to request MAID,” said Dr. Chaimowitz, who is also head of forensic psychiatry at St. Joseph’s Healthcare and a professor of psychiatry at McMaster University, both in Hamilton, Ont.

Dr. Chaimowitz acknowledges that “a majority of psychiatrists do not want to be involved in anything to do with MAID.”

“The idea, certainly in psychiatry, is to get people well and we’ve been taught that people dying from a major mental disorder is something that we’re trained to prevent,” he added.
 

A ‘clinical option’

Assisted medical death is especially fraught in psychiatry, said Rebecca Brendel, MD, president of the American Psychiatric Association. She noted a 25-year life expectancy gap between people with SMI and those who do not have such conditions.

“As a profession we have very serious obligations to advance treatment so that a person with serious mental illness can live [a] full, productive, and healthy [life],” Dr. Brendel, associate director of the Center for Bioethics at Harvard Medical School in Boston, said in an interview.

Under the Canadian proposal, psychiatrists would be allowed to suggest MAID as a “clinical option.”

Harold Braswell, PhD, a fellow with The Hastings Center, a bioethics research institute, calls that problematic.

“It’s not neutral to suggest to someone that it would be theoretically reasonable to end their lives,” Dr. Braswell, associate professor at the Albert Gnaegi Center for Health Care Ethics at Saint Louis University, told this news organization.

It also creates a double standard in the treatment of suicidal ideation, in which suicide prevention is absolute for some, but encouraging it as a possibility for others, he added.  

“To have that come from an authority figure is something that’s very harsh and, in my opinion, very potentially destructive,” especially for vulnerable groups, like First Nations people, who already have elevated rates of suicide, said Dr. Braswell.
 

Fierce debate

Since 2016, Canada has allowed MAID for medical conditions and diseases that will not improve and in cases where the evidence shows that medical providers can accurately predict the condition will not improve.

However, in 2019, a Quebec court ruled that the law unconstitutionally barred euthanasia in people who were not terminally ill. In March 2021, Canada’s criminal code was amended to allow MAID for people whose natural death was not “reasonably foreseeable,” but it excluded SMI for a period of 2 years, ending in March 2023.

The 2-year stay was intended to allow for study and to give mental health providers and MAID assessors time to develop standards.

The federal government charged a 12-member expert panel with determining how to safely allow MAID for SMI. In its final report released in May 2022 it recommended that standards be developed. 

The panel acknowledged that for many conditions it may be impossible to make predictions about whether an individual might improve. However, it did not mention SMI.

In those cases, when MAID is requested, “establishing incurability and irreversibility on the basis of the evolution and response to past interventions is necessary,” the panel noted, adding that these are the criteria used by psychiatrists assessing euthanasia requests in the Netherlands and Belgium.

But the notion that mental illness can be irremediable has been fiercely debated.

Soon after the expert report was released, the Center for Addiction and Mental Health in Toronto noted on its website that there are currently  “no agreed upon standards for psychiatrists or other health care practitioners to use to determine if a person’s mental illness is ‘grievous and irremediable’ for the purposes of MAID.” 

Dr. Chaimowitz acknowledged that “there’s no agreed-upon definition of incurability” in mental illness. Some psychiatrists “will argue that there’s always another treatment that can be attempted,” he said, adding that there has been a lack of consensus on irremediability among CPA members.
 

Protecting vulnerable populations

Matt Wynia, MD, MPH, FACP, director of the Center for Bioethics and Humanities at the University of Colorado at Denver, Aurora, said the question of irremediability is crucial. “Most people with mental illness do get better, especially if they’re in treatment,” Dr. Wynia said.

For MAID assessors it may be difficult to know when someone has tried all possible treatments, especially given the wide array of options, including psychedelics, said Dr. Wynia.

Dr. Braswell said there is not enough evidence that mental illness is incurable. With SMI, “there’s a lot more potential for the causes of the individual’s suffering to be ameliorated. By offering MAID, you’re going to kill people who might have been able to get out of this through other nonlethal means.”

Currently, MAID is provided for an irremediable medical condition, “in other words, a condition that will not improve and that we can predict will not improve,” said Karandeep S. Gaind, MD, chief of psychiatry at Toronto’s Humber River Hospital and physician chair of the hospital’s MAID team.

“If that’s the premise, then I think we cannot provide MAID for sole mental illness,” Dr. Gaind said. “Because we can’t honestly make those predictions” with mental illness, he added.

Dr. Gaind does not support MAID for mental illness and believes that it will put the vulnerable – including those living in poverty – at particular risk.

With the proposed expansion, MAID is “now becoming something which is being sought as a way to escape a painful life rather than to avoid a painful death,” said Dr. Gaind, who is also a past president of the CPA.

One member of the federal government’s expert panel – Ellen Cohen, who had a psychiatric condition – wrote in The Globe and Mail that she quit early on when it became apparent that the panel was not seriously considering her own experiences or the possibility that poverty and lack of access to care or social supports could strongly influence a request for MAID.
 

Social determinants of suffering

People with mental illness often are without homes, have substance use disorders, have been stigmatized and discriminated against, and have poor social supports, said Dr. Wynia. “You worry that it’s all of those things that are making them want to end their lives,” he said.

The Daily Mail ran a story in December 2022 about a 65-year-old Canadian who said he’d applied for MAID solely because of fears that his disability benefits for various chronic health conditions were being cut off and that he didn’t want to live in poverty.

A 51-year-old Ontario woman with multiple chemical sensitivities was granted MAID after she said she could not find housing that could keep her safe, according to an August report by CTV News.

Tarek Rajji, MD, chief of the Adult Neurodevelopment and Geriatric Psychiatry Division at CAMH, said social determinants of health need to be considered in standards created to guide MAID for mental illness.

“We’re very mindful of the fact that the suffering, that is, the grievousness that the person is living with, in the context of mental illness, many times is due to the social determinants of their illness and the social determinants of their suffering,” Dr. Rajji said.

Many are also concerned that it will be difficult to separate out suicidality from sheer hopelessness.

The CPA has advised a group that’s working on developing guidelines for MAID in SMI and is also developing a curriculum for mental health providers, Dr. Chaimowitz said. As part of that, there will be a process to ensure that someone who is actively suicidal is not granted MAID.

“I do not believe that it’s contemplated that MAID is going to accelerate or facilitate suicidal ideation,” he said. Someone who is suicidal will be referred to treatment, said Dr. Chaimowitz.

“People with depression often feel hopeless,” and may refuse treatments that have worked in the past, countered Dr. Gaind. Some of his patients “are absolutely convinced that nothing will help,” he said.
 

Troublesome cases

The expert panel said in its final report that “it is not possible to provide fixed rules for how many attempts at interventions, how many types of interventions, and over how much time,” are necessary to establish “irreversibility” of mental illness.

Dr. Chaimowitz said MAID will not be offered to anyone “refusing treatment for their condition without any good reason.” They will be “unlikely to meet criteria for incurable,” as they will have needed to avail themselves of the array of treatments available, he said. 

That would be similar to rules in Belgium and the Netherlands, which allow euthanasia for psychiatric conditions. 

An estimated 100-300 psychiatric patients receive euthanasia each year in those countries, according to a 2021 commentary in Psychiatric Times (Jun 7;38[6]) by Mark S. Komrad, MD, a Towson, Maryland-based psychiatrist.

There are still troublesome cases. 

As previously reported by this news organization, many in Belgium were distressed recently at the news that a 23-year-old woman who had survived a terrorist attack, Shanti De Corte, requested and was granted euthanasia.

As the deadline for implementation of MAID grew closer, calls for delay grew louder, especially given the lack of concrete standards for providers.

During the waning months of 2022, Dr. Gaind – who said he was suspended from CPA for “unprofessional interactions” and allegedly misrepresenting CPA’s processes and governance matters – announced the launch of a new organization, the Society of Canadian Psychiatry, in November calling for a delay in MAID of at least 1 year so that evidence-based safeguards could be implemented. The petition has been signed by more than 200 psychiatrists, along with several dozen physicians, MAID assessors, and individuals with mental illness and family members.

The Association of Chairs of Psychiatry in Canada, the Canadian Association for Suicide Prevention, the Council of Canadians with Disabilities, a group of indigenous leaders, and the Ontario Association for ACT and FACT, psychiatrists who provide care to individuals with severe mental illness, among other groups, joined the call for a delay.

In its December announcement, the Canadian federal ministers said a factor in seeking a delay was that standards guiding clinicians would not be delivered until at least February – too close to when applications would be opened.

Upon hearing about the federal government’s intentions, the chair of the expert panel, Mona Gupta, MD, told The Canadian Press that she did not think it was necessary to put off implementation because necessary safeguards were already in place.

Dr. Chaimowitz awaits the standards but is optimistic that for mental illness, “the process will be tightly controlled, closely monitored, and open to scrutiny,” he said.

Dr. Braswell is not convinced. The concern is that adding people with mental illness is “going to overload the capacity of the government to monitor this practice,” he said.
 

Is the United States next?

Although Canada and the United States share a border, it’s unlikely that U.S. states will allow aid in dying for nonterminal illness, much less for psychiatric conditions any time soon, said Dr. Braswell and others.

Ten states – California, Colorado, Hawaii, Maine, Montana, New Jersey, New Mexico, Oregon, Vermont, and Washington – have laws allowing assistance in dying, but for terminal illness only.

In 2016, the APA adopted the American Medical Association policy on medical euthanasia, stating, “that a psychiatrist should not prescribe or administer any intervention to a nonterminally ill person for the purpose of causing death.”

Dr. Brendel said the field is acutely aware that people with mental illness do suffer, but that more work needs to be done – and is being done – on “distinguishing wishes to hasten death or end one’s life from these historical or traditional notions that any premature death is a suicide.”

There is also increasing discussion within the medical community, not just psychiatry, about a physician’s duty to relieve suffering, said Dr. Wynia. “There’s debate basically about whether we stand for preserving life essentially at all costs and never being involved in the taking of life, or whether we stand for reduction of suffering and being the advocate for the patients that we serve,” he said.

“Those are both legitimate,” said Dr. Wynia, adding, “there are good reasons to want both of those to be true.”

“I suspect that 20 years from now we will still be having conversations about how physicians, how psychiatrists ought to participate in preserving life and in shepherding death,” said Dr. Brendel.

But to Dr. Gaind, the debate is not just esoteric, it’s a soon-to-be reality in Canada. “When we’re providing death to people who aren’t dying, to me that’s like providing what amounts to a wrongful death,” he said.

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

Amid growing concern among the public, psychiatrists, and other mental health professionals, the Canadian government is seeking to delay the legalization of its proposed medical assistance in dying (MAID) for mental illness law that is slated to pass on March 17.

Canada already has the largest number of deaths by MAID of any nation, with 10,064 in 2021, a 32% increase from 2020. With the addition of serious mental illness (SMI) as an eligible category, the country is on track to have the most liberal assisted-death policy in the world.

Concerns about the additional number of patients who could become eligible for MAID, and a lack of evidence-backed standards from disability rights groups, mental health advocates, First Nations leaders, psychiatrists, and other mental health providers, seems to have led the Canadian government to give the proposed law some sober second thought.

“Listening to experts and Canadians, we believe this date needs to be temporarily delayed,” said David Lametti, Canada’s minister of Justice and attorney general of Canada; Jean-Yves Duclos, minister of Health; and  Carolyn Bennett, minister of Mental Health and Addictions, in a Dec. 15, 2022, joint statement.

Canada’s Parliament – which approved the expansion – will now have to vote on whether to okay a pause on the legislation.

However, the Canadian Psychiatric Association has not been calling for a delay in the proposed legislation. In a November 2021 statement, the CPA  said it “does not take a position on the legality or morality of MAID,” but added that to deny MAID to people with mental illness was discriminatory, and that, as it was the law, it must be followed.

“CPA has not taken a position about MAID,” the association’s president Gary Chaimowitz, MBChB, told this news organization. “We know this is coming and our organization is trying to get its members ready for what will be most likely the ability of people with mental conditions to be able to request MAID,” said Dr. Chaimowitz, who is also head of forensic psychiatry at St. Joseph’s Healthcare and a professor of psychiatry at McMaster University, both in Hamilton, Ont.

Dr. Chaimowitz acknowledges that “a majority of psychiatrists do not want to be involved in anything to do with MAID.”

“The idea, certainly in psychiatry, is to get people well and we’ve been taught that people dying from a major mental disorder is something that we’re trained to prevent,” he added.
 

A ‘clinical option’

Assisted medical death is especially fraught in psychiatry, said Rebecca Brendel, MD, president of the American Psychiatric Association. She noted a 25-year life expectancy gap between people with SMI and those who do not have such conditions.

“As a profession we have very serious obligations to advance treatment so that a person with serious mental illness can live [a] full, productive, and healthy [life],” Dr. Brendel, associate director of the Center for Bioethics at Harvard Medical School in Boston, said in an interview.

Under the Canadian proposal, psychiatrists would be allowed to suggest MAID as a “clinical option.”

Harold Braswell, PhD, a fellow with The Hastings Center, a bioethics research institute, calls that problematic.

“It’s not neutral to suggest to someone that it would be theoretically reasonable to end their lives,” Dr. Braswell, associate professor at the Albert Gnaegi Center for Health Care Ethics at Saint Louis University, told this news organization.

It also creates a double standard in the treatment of suicidal ideation, in which suicide prevention is absolute for some, but encouraging it as a possibility for others, he added.  

“To have that come from an authority figure is something that’s very harsh and, in my opinion, very potentially destructive,” especially for vulnerable groups, like First Nations people, who already have elevated rates of suicide, said Dr. Braswell.
 

Fierce debate

Since 2016, Canada has allowed MAID for medical conditions and diseases that will not improve and in cases where the evidence shows that medical providers can accurately predict the condition will not improve.

However, in 2019, a Quebec court ruled that the law unconstitutionally barred euthanasia in people who were not terminally ill. In March 2021, Canada’s criminal code was amended to allow MAID for people whose natural death was not “reasonably foreseeable,” but it excluded SMI for a period of 2 years, ending in March 2023.

The 2-year stay was intended to allow for study and to give mental health providers and MAID assessors time to develop standards.

The federal government charged a 12-member expert panel with determining how to safely allow MAID for SMI. In its final report released in May 2022 it recommended that standards be developed. 

The panel acknowledged that for many conditions it may be impossible to make predictions about whether an individual might improve. However, it did not mention SMI.

In those cases, when MAID is requested, “establishing incurability and irreversibility on the basis of the evolution and response to past interventions is necessary,” the panel noted, adding that these are the criteria used by psychiatrists assessing euthanasia requests in the Netherlands and Belgium.

But the notion that mental illness can be irremediable has been fiercely debated.

Soon after the expert report was released, the Center for Addiction and Mental Health in Toronto noted on its website that there are currently  “no agreed upon standards for psychiatrists or other health care practitioners to use to determine if a person’s mental illness is ‘grievous and irremediable’ for the purposes of MAID.” 

Dr. Chaimowitz acknowledged that “there’s no agreed-upon definition of incurability” in mental illness. Some psychiatrists “will argue that there’s always another treatment that can be attempted,” he said, adding that there has been a lack of consensus on irremediability among CPA members.
 

Protecting vulnerable populations

Matt Wynia, MD, MPH, FACP, director of the Center for Bioethics and Humanities at the University of Colorado at Denver, Aurora, said the question of irremediability is crucial. “Most people with mental illness do get better, especially if they’re in treatment,” Dr. Wynia said.

For MAID assessors it may be difficult to know when someone has tried all possible treatments, especially given the wide array of options, including psychedelics, said Dr. Wynia.

Dr. Braswell said there is not enough evidence that mental illness is incurable. With SMI, “there’s a lot more potential for the causes of the individual’s suffering to be ameliorated. By offering MAID, you’re going to kill people who might have been able to get out of this through other nonlethal means.”

Currently, MAID is provided for an irremediable medical condition, “in other words, a condition that will not improve and that we can predict will not improve,” said Karandeep S. Gaind, MD, chief of psychiatry at Toronto’s Humber River Hospital and physician chair of the hospital’s MAID team.

“If that’s the premise, then I think we cannot provide MAID for sole mental illness,” Dr. Gaind said. “Because we can’t honestly make those predictions” with mental illness, he added.

Dr. Gaind does not support MAID for mental illness and believes that it will put the vulnerable – including those living in poverty – at particular risk.

With the proposed expansion, MAID is “now becoming something which is being sought as a way to escape a painful life rather than to avoid a painful death,” said Dr. Gaind, who is also a past president of the CPA.

One member of the federal government’s expert panel – Ellen Cohen, who had a psychiatric condition – wrote in The Globe and Mail that she quit early on when it became apparent that the panel was not seriously considering her own experiences or the possibility that poverty and lack of access to care or social supports could strongly influence a request for MAID.
 

Social determinants of suffering

People with mental illness often are without homes, have substance use disorders, have been stigmatized and discriminated against, and have poor social supports, said Dr. Wynia. “You worry that it’s all of those things that are making them want to end their lives,” he said.

The Daily Mail ran a story in December 2022 about a 65-year-old Canadian who said he’d applied for MAID solely because of fears that his disability benefits for various chronic health conditions were being cut off and that he didn’t want to live in poverty.

A 51-year-old Ontario woman with multiple chemical sensitivities was granted MAID after she said she could not find housing that could keep her safe, according to an August report by CTV News.

Tarek Rajji, MD, chief of the Adult Neurodevelopment and Geriatric Psychiatry Division at CAMH, said social determinants of health need to be considered in standards created to guide MAID for mental illness.

“We’re very mindful of the fact that the suffering, that is, the grievousness that the person is living with, in the context of mental illness, many times is due to the social determinants of their illness and the social determinants of their suffering,” Dr. Rajji said.

Many are also concerned that it will be difficult to separate out suicidality from sheer hopelessness.

The CPA has advised a group that’s working on developing guidelines for MAID in SMI and is also developing a curriculum for mental health providers, Dr. Chaimowitz said. As part of that, there will be a process to ensure that someone who is actively suicidal is not granted MAID.

“I do not believe that it’s contemplated that MAID is going to accelerate or facilitate suicidal ideation,” he said. Someone who is suicidal will be referred to treatment, said Dr. Chaimowitz.

“People with depression often feel hopeless,” and may refuse treatments that have worked in the past, countered Dr. Gaind. Some of his patients “are absolutely convinced that nothing will help,” he said.
 

Troublesome cases

The expert panel said in its final report that “it is not possible to provide fixed rules for how many attempts at interventions, how many types of interventions, and over how much time,” are necessary to establish “irreversibility” of mental illness.

Dr. Chaimowitz said MAID will not be offered to anyone “refusing treatment for their condition without any good reason.” They will be “unlikely to meet criteria for incurable,” as they will have needed to avail themselves of the array of treatments available, he said. 

That would be similar to rules in Belgium and the Netherlands, which allow euthanasia for psychiatric conditions. 

An estimated 100-300 psychiatric patients receive euthanasia each year in those countries, according to a 2021 commentary in Psychiatric Times (Jun 7;38[6]) by Mark S. Komrad, MD, a Towson, Maryland-based psychiatrist.

There are still troublesome cases. 

As previously reported by this news organization, many in Belgium were distressed recently at the news that a 23-year-old woman who had survived a terrorist attack, Shanti De Corte, requested and was granted euthanasia.

As the deadline for implementation of MAID grew closer, calls for delay grew louder, especially given the lack of concrete standards for providers.

During the waning months of 2022, Dr. Gaind – who said he was suspended from CPA for “unprofessional interactions” and allegedly misrepresenting CPA’s processes and governance matters – announced the launch of a new organization, the Society of Canadian Psychiatry, in November calling for a delay in MAID of at least 1 year so that evidence-based safeguards could be implemented. The petition has been signed by more than 200 psychiatrists, along with several dozen physicians, MAID assessors, and individuals with mental illness and family members.

The Association of Chairs of Psychiatry in Canada, the Canadian Association for Suicide Prevention, the Council of Canadians with Disabilities, a group of indigenous leaders, and the Ontario Association for ACT and FACT, psychiatrists who provide care to individuals with severe mental illness, among other groups, joined the call for a delay.

In its December announcement, the Canadian federal ministers said a factor in seeking a delay was that standards guiding clinicians would not be delivered until at least February – too close to when applications would be opened.

Upon hearing about the federal government’s intentions, the chair of the expert panel, Mona Gupta, MD, told The Canadian Press that she did not think it was necessary to put off implementation because necessary safeguards were already in place.

Dr. Chaimowitz awaits the standards but is optimistic that for mental illness, “the process will be tightly controlled, closely monitored, and open to scrutiny,” he said.

Dr. Braswell is not convinced. The concern is that adding people with mental illness is “going to overload the capacity of the government to monitor this practice,” he said.
 

Is the United States next?

Although Canada and the United States share a border, it’s unlikely that U.S. states will allow aid in dying for nonterminal illness, much less for psychiatric conditions any time soon, said Dr. Braswell and others.

Ten states – California, Colorado, Hawaii, Maine, Montana, New Jersey, New Mexico, Oregon, Vermont, and Washington – have laws allowing assistance in dying, but for terminal illness only.

In 2016, the APA adopted the American Medical Association policy on medical euthanasia, stating, “that a psychiatrist should not prescribe or administer any intervention to a nonterminally ill person for the purpose of causing death.”

Dr. Brendel said the field is acutely aware that people with mental illness do suffer, but that more work needs to be done – and is being done – on “distinguishing wishes to hasten death or end one’s life from these historical or traditional notions that any premature death is a suicide.”

There is also increasing discussion within the medical community, not just psychiatry, about a physician’s duty to relieve suffering, said Dr. Wynia. “There’s debate basically about whether we stand for preserving life essentially at all costs and never being involved in the taking of life, or whether we stand for reduction of suffering and being the advocate for the patients that we serve,” he said.

“Those are both legitimate,” said Dr. Wynia, adding, “there are good reasons to want both of those to be true.”

“I suspect that 20 years from now we will still be having conversations about how physicians, how psychiatrists ought to participate in preserving life and in shepherding death,” said Dr. Brendel.

But to Dr. Gaind, the debate is not just esoteric, it’s a soon-to-be reality in Canada. “When we’re providing death to people who aren’t dying, to me that’s like providing what amounts to a wrongful death,” he said.

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

Amid growing concern among the public, psychiatrists, and other mental health professionals, the Canadian government is seeking to delay the legalization of its proposed medical assistance in dying (MAID) for mental illness law that is slated to pass on March 17.

Canada already has the largest number of deaths by MAID of any nation, with 10,064 in 2021, a 32% increase from 2020. With the addition of serious mental illness (SMI) as an eligible category, the country is on track to have the most liberal assisted-death policy in the world.

Concerns about the additional number of patients who could become eligible for MAID, and a lack of evidence-backed standards from disability rights groups, mental health advocates, First Nations leaders, psychiatrists, and other mental health providers, seems to have led the Canadian government to give the proposed law some sober second thought.

“Listening to experts and Canadians, we believe this date needs to be temporarily delayed,” said David Lametti, Canada’s minister of Justice and attorney general of Canada; Jean-Yves Duclos, minister of Health; and  Carolyn Bennett, minister of Mental Health and Addictions, in a Dec. 15, 2022, joint statement.

Canada’s Parliament – which approved the expansion – will now have to vote on whether to okay a pause on the legislation.

However, the Canadian Psychiatric Association has not been calling for a delay in the proposed legislation. In a November 2021 statement, the CPA  said it “does not take a position on the legality or morality of MAID,” but added that to deny MAID to people with mental illness was discriminatory, and that, as it was the law, it must be followed.

“CPA has not taken a position about MAID,” the association’s president Gary Chaimowitz, MBChB, told this news organization. “We know this is coming and our organization is trying to get its members ready for what will be most likely the ability of people with mental conditions to be able to request MAID,” said Dr. Chaimowitz, who is also head of forensic psychiatry at St. Joseph’s Healthcare and a professor of psychiatry at McMaster University, both in Hamilton, Ont.

Dr. Chaimowitz acknowledges that “a majority of psychiatrists do not want to be involved in anything to do with MAID.”

“The idea, certainly in psychiatry, is to get people well and we’ve been taught that people dying from a major mental disorder is something that we’re trained to prevent,” he added.
 

A ‘clinical option’

Assisted medical death is especially fraught in psychiatry, said Rebecca Brendel, MD, president of the American Psychiatric Association. She noted a 25-year life expectancy gap between people with SMI and those who do not have such conditions.

“As a profession we have very serious obligations to advance treatment so that a person with serious mental illness can live [a] full, productive, and healthy [life],” Dr. Brendel, associate director of the Center for Bioethics at Harvard Medical School in Boston, said in an interview.

Under the Canadian proposal, psychiatrists would be allowed to suggest MAID as a “clinical option.”

Harold Braswell, PhD, a fellow with The Hastings Center, a bioethics research institute, calls that problematic.

“It’s not neutral to suggest to someone that it would be theoretically reasonable to end their lives,” Dr. Braswell, associate professor at the Albert Gnaegi Center for Health Care Ethics at Saint Louis University, told this news organization.

It also creates a double standard in the treatment of suicidal ideation, in which suicide prevention is absolute for some, but encouraging it as a possibility for others, he added.  

“To have that come from an authority figure is something that’s very harsh and, in my opinion, very potentially destructive,” especially for vulnerable groups, like First Nations people, who already have elevated rates of suicide, said Dr. Braswell.
 

Fierce debate

Since 2016, Canada has allowed MAID for medical conditions and diseases that will not improve and in cases where the evidence shows that medical providers can accurately predict the condition will not improve.

However, in 2019, a Quebec court ruled that the law unconstitutionally barred euthanasia in people who were not terminally ill. In March 2021, Canada’s criminal code was amended to allow MAID for people whose natural death was not “reasonably foreseeable,” but it excluded SMI for a period of 2 years, ending in March 2023.

The 2-year stay was intended to allow for study and to give mental health providers and MAID assessors time to develop standards.

The federal government charged a 12-member expert panel with determining how to safely allow MAID for SMI. In its final report released in May 2022 it recommended that standards be developed. 

The panel acknowledged that for many conditions it may be impossible to make predictions about whether an individual might improve. However, it did not mention SMI.

In those cases, when MAID is requested, “establishing incurability and irreversibility on the basis of the evolution and response to past interventions is necessary,” the panel noted, adding that these are the criteria used by psychiatrists assessing euthanasia requests in the Netherlands and Belgium.

But the notion that mental illness can be irremediable has been fiercely debated.

Soon after the expert report was released, the Center for Addiction and Mental Health in Toronto noted on its website that there are currently  “no agreed upon standards for psychiatrists or other health care practitioners to use to determine if a person’s mental illness is ‘grievous and irremediable’ for the purposes of MAID.” 

Dr. Chaimowitz acknowledged that “there’s no agreed-upon definition of incurability” in mental illness. Some psychiatrists “will argue that there’s always another treatment that can be attempted,” he said, adding that there has been a lack of consensus on irremediability among CPA members.
 

Protecting vulnerable populations

Matt Wynia, MD, MPH, FACP, director of the Center for Bioethics and Humanities at the University of Colorado at Denver, Aurora, said the question of irremediability is crucial. “Most people with mental illness do get better, especially if they’re in treatment,” Dr. Wynia said.

For MAID assessors it may be difficult to know when someone has tried all possible treatments, especially given the wide array of options, including psychedelics, said Dr. Wynia.

Dr. Braswell said there is not enough evidence that mental illness is incurable. With SMI, “there’s a lot more potential for the causes of the individual’s suffering to be ameliorated. By offering MAID, you’re going to kill people who might have been able to get out of this through other nonlethal means.”

Currently, MAID is provided for an irremediable medical condition, “in other words, a condition that will not improve and that we can predict will not improve,” said Karandeep S. Gaind, MD, chief of psychiatry at Toronto’s Humber River Hospital and physician chair of the hospital’s MAID team.

“If that’s the premise, then I think we cannot provide MAID for sole mental illness,” Dr. Gaind said. “Because we can’t honestly make those predictions” with mental illness, he added.

Dr. Gaind does not support MAID for mental illness and believes that it will put the vulnerable – including those living in poverty – at particular risk.

With the proposed expansion, MAID is “now becoming something which is being sought as a way to escape a painful life rather than to avoid a painful death,” said Dr. Gaind, who is also a past president of the CPA.

One member of the federal government’s expert panel – Ellen Cohen, who had a psychiatric condition – wrote in The Globe and Mail that she quit early on when it became apparent that the panel was not seriously considering her own experiences or the possibility that poverty and lack of access to care or social supports could strongly influence a request for MAID.
 

Social determinants of suffering

People with mental illness often are without homes, have substance use disorders, have been stigmatized and discriminated against, and have poor social supports, said Dr. Wynia. “You worry that it’s all of those things that are making them want to end their lives,” he said.

The Daily Mail ran a story in December 2022 about a 65-year-old Canadian who said he’d applied for MAID solely because of fears that his disability benefits for various chronic health conditions were being cut off and that he didn’t want to live in poverty.

A 51-year-old Ontario woman with multiple chemical sensitivities was granted MAID after she said she could not find housing that could keep her safe, according to an August report by CTV News.

Tarek Rajji, MD, chief of the Adult Neurodevelopment and Geriatric Psychiatry Division at CAMH, said social determinants of health need to be considered in standards created to guide MAID for mental illness.

“We’re very mindful of the fact that the suffering, that is, the grievousness that the person is living with, in the context of mental illness, many times is due to the social determinants of their illness and the social determinants of their suffering,” Dr. Rajji said.

Many are also concerned that it will be difficult to separate out suicidality from sheer hopelessness.

The CPA has advised a group that’s working on developing guidelines for MAID in SMI and is also developing a curriculum for mental health providers, Dr. Chaimowitz said. As part of that, there will be a process to ensure that someone who is actively suicidal is not granted MAID.

“I do not believe that it’s contemplated that MAID is going to accelerate or facilitate suicidal ideation,” he said. Someone who is suicidal will be referred to treatment, said Dr. Chaimowitz.

“People with depression often feel hopeless,” and may refuse treatments that have worked in the past, countered Dr. Gaind. Some of his patients “are absolutely convinced that nothing will help,” he said.
 

Troublesome cases

The expert panel said in its final report that “it is not possible to provide fixed rules for how many attempts at interventions, how many types of interventions, and over how much time,” are necessary to establish “irreversibility” of mental illness.

Dr. Chaimowitz said MAID will not be offered to anyone “refusing treatment for their condition without any good reason.” They will be “unlikely to meet criteria for incurable,” as they will have needed to avail themselves of the array of treatments available, he said. 

That would be similar to rules in Belgium and the Netherlands, which allow euthanasia for psychiatric conditions. 

An estimated 100-300 psychiatric patients receive euthanasia each year in those countries, according to a 2021 commentary in Psychiatric Times (Jun 7;38[6]) by Mark S. Komrad, MD, a Towson, Maryland-based psychiatrist.

There are still troublesome cases. 

As previously reported by this news organization, many in Belgium were distressed recently at the news that a 23-year-old woman who had survived a terrorist attack, Shanti De Corte, requested and was granted euthanasia.

As the deadline for implementation of MAID grew closer, calls for delay grew louder, especially given the lack of concrete standards for providers.

During the waning months of 2022, Dr. Gaind – who said he was suspended from CPA for “unprofessional interactions” and allegedly misrepresenting CPA’s processes and governance matters – announced the launch of a new organization, the Society of Canadian Psychiatry, in November calling for a delay in MAID of at least 1 year so that evidence-based safeguards could be implemented. The petition has been signed by more than 200 psychiatrists, along with several dozen physicians, MAID assessors, and individuals with mental illness and family members.

The Association of Chairs of Psychiatry in Canada, the Canadian Association for Suicide Prevention, the Council of Canadians with Disabilities, a group of indigenous leaders, and the Ontario Association for ACT and FACT, psychiatrists who provide care to individuals with severe mental illness, among other groups, joined the call for a delay.

In its December announcement, the Canadian federal ministers said a factor in seeking a delay was that standards guiding clinicians would not be delivered until at least February – too close to when applications would be opened.

Upon hearing about the federal government’s intentions, the chair of the expert panel, Mona Gupta, MD, told The Canadian Press that she did not think it was necessary to put off implementation because necessary safeguards were already in place.

Dr. Chaimowitz awaits the standards but is optimistic that for mental illness, “the process will be tightly controlled, closely monitored, and open to scrutiny,” he said.

Dr. Braswell is not convinced. The concern is that adding people with mental illness is “going to overload the capacity of the government to monitor this practice,” he said.
 

Is the United States next?

Although Canada and the United States share a border, it’s unlikely that U.S. states will allow aid in dying for nonterminal illness, much less for psychiatric conditions any time soon, said Dr. Braswell and others.

Ten states – California, Colorado, Hawaii, Maine, Montana, New Jersey, New Mexico, Oregon, Vermont, and Washington – have laws allowing assistance in dying, but for terminal illness only.

In 2016, the APA adopted the American Medical Association policy on medical euthanasia, stating, “that a psychiatrist should not prescribe or administer any intervention to a nonterminally ill person for the purpose of causing death.”

Dr. Brendel said the field is acutely aware that people with mental illness do suffer, but that more work needs to be done – and is being done – on “distinguishing wishes to hasten death or end one’s life from these historical or traditional notions that any premature death is a suicide.”

There is also increasing discussion within the medical community, not just psychiatry, about a physician’s duty to relieve suffering, said Dr. Wynia. “There’s debate basically about whether we stand for preserving life essentially at all costs and never being involved in the taking of life, or whether we stand for reduction of suffering and being the advocate for the patients that we serve,” he said.

“Those are both legitimate,” said Dr. Wynia, adding, “there are good reasons to want both of those to be true.”

“I suspect that 20 years from now we will still be having conversations about how physicians, how psychiatrists ought to participate in preserving life and in shepherding death,” said Dr. Brendel.

But to Dr. Gaind, the debate is not just esoteric, it’s a soon-to-be reality in Canada. “When we’re providing death to people who aren’t dying, to me that’s like providing what amounts to a wrongful death,” he said.

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

For Tammy Rainey, finding a health care provider who knows about gender-affirming care has been a challenge in the rural northern Mississippi town where she lives.

As a transgender woman, Ms. Rainey needs the hormone estrogen, which allows her to physically transition by developing more feminine features. But when she asked her doctor for an estrogen prescription, he said he couldn’t provide that type of care.

“He’s generally a good guy and doesn’t act prejudiced. He gets my name and pronouns right,” said Ms. Rainey. “But when I asked him about hormones, he said, ‘I just don’t feel like I know enough about that. I don’t want to get involved in that.’ ”

So Ms. Rainey drives around 170 miles round trip every 6 months to get a supply of estrogen from a clinic in Memphis, Tenn., to take home with her.

The obstacles Ms. Rainey overcomes to access care illustrate a type of medical inequity that transgender people who live in the rural United States often face: A general lack of education about trans-related care among small-town health professionals who might also be reluctant to learn.

“Medical communities across the country are seeing clearly that there is a knowledge gap in the provision of gender-affirming care,” said Morissa Ladinsky, MD, a pediatrician who co-leads the Youth Multidisciplinary Gender Team at the University of Alabama–Birmingham (UAB).

Accurately counting the number of transgender people in rural America is hindered by a lack of U.S. census data and uniform state data. However, the Movement Advancement Project, a nonprofit organization that advocates for LGBTQ+ issues, used 2014-17 Centers for Disease Control and Prevention data from selected ZIP codes in 35 states to estimate that roughly one in six transgender adults in the United States live in a rural area. When that report was released in 2019, there were an estimated 1.4 million transgender people 13 and older nationwide. That number is now at least 1.6 million, according to the Williams Institute, a nonprofit think tank at the UCLA School of Law.

One in three trans people in rural areas experienced discrimination by a health care provider in the year leading up to the 2015 U.S. Transgender Survey Report, according to an analysis by MAP. A third of all trans individuals report having to teach their doctors about their health care needs to receive appropriate care, and 62% worry about being negatively judged by a health care provider because of their sexual orientation or gender identity, according to data collected by the Williams Institute and other organizations.

A lack of local rural providers knowledgeable in trans care can mean long drives to gender-affirming clinics in metropolitan areas. Rural trans people are three times as likely as are all transgender adults to travel 25-49 miles for routine care.

In Colorado, for example, many trans people outside Denver struggle to find proper care. Those who do have a trans-inclusive provider are more likely to receive wellness exams, less likely to delay care due to discrimination, and less likely to attempt suicide, according to results from the Colorado Transgender Health Survey published in 2018.

Much of the lack of care experienced by trans people is linked to insufficient education on LGBTQ+ health in medical schools across the country. In 2014, the Association of American Medical Colleges, which represents 170 accredited medical schools in the United States and Canada, released its first curriculum guidelines on caring for LGBTQ+ patients. As of 2018, 76% of medical schools included LGBTQ health themes in their curriculum, with half providing three or fewer classes on this topic.

Perhaps because of this, almost 77% of students from 10 medical schools in New England felt “not competent” or “somewhat not competent” in treating gender minority patients, according to a 2018 pilot study. Another paper, published last year, found that even clinicians who work in trans-friendly clinics lack knowledge about hormones, gender-affirming surgical options, and how to use appropriate pronouns and trans-inclusive language.

Throughout medical school, trans care was only briefly mentioned in endocrinology class, said Justin Bailey, MD, who received his medical degree from UAB in 2021 and is now a resident there. “I don’t want to say the wrong thing or use the wrong pronouns, so I was hesitant and a little bit tepid in my approach to interviewing and treating this population of patients,” he said.

On top of insufficient medical school education, some practicing doctors don’t take the time to teach themselves about trans people, said Kathie Moehlig, founder of TransFamily Support Services, a nonprofit organization that offers a range of services to transgender people and their families. They are very well intentioned yet uneducated when it comes to transgender care, she said.

Some medical schools, like the one at UAB, have pushed for change. Since 2017, Dr. Ladinsky and her colleagues have worked to include trans people in their standardized patient program, which gives medical students hands-on experience and feedback by interacting with “patients” in simulated clinical environments.

For example, a trans individual acting as a patient will simulate acid reflux by pretending to have pain in their stomach and chest. Then, over the course of the examination, they will reveal that they are transgender.

In the early years of this program, some students’ bedside manner would change once the patient’s gender identity was revealed, said Elaine Stephens, a trans woman who participates in UAB’s standardized patient program. “Sometimes they would immediately start asking about sexual activity,” Stephens said.

Since UAB launched its program, students’ reactions have improved significantly, she said.

This progress is being replicated by other medical schools, said Ms. Moehlig. “But it’s a slow start, and these are large institutions that take a long time to move forward.”

Advocates also are working outside medical schools to improve care in rural areas. In Colorado, the nonprofit Extension for Community Health Outcomes, or ECHO Colorado, has been offering monthly virtual classes on gender-affirming care to rural providers since 2020. The classes became so popular that the organization created a 4-week boot camp in 2021 for providers to learn about hormone therapy management, proper terminologies, surgical options, and supporting patients’ mental health.

For many years, doctors failed to recognize the need to learn about gender-affirming care, said Caroline Kirsch, DO, director of osteopathic education at the University of Wyoming Family Medicine Residency Program–Casper. In Casper, this led to “a number of patients traveling to Colorado to access care, which is a large burden for them financially,” said Dr. Kirsch, who has participated in the ECHO Colorado program.

“Things that haven’t been as well taught historically in medical school are things that I think many physicians feel anxious about initially,” she said. “The earlier you learn about this type of care in your career, the more likely you are to see its potential and be less anxious about it.”

Educating more providers about trans-related care has become increasingly vital in recent years as gender-affirming clinics nationwide experience a rise in harassment and threats. For instance, Vanderbilt University Medical Center’s Clinic for Transgender Health became the target of far-right hate on social media last year. After growing pressure from Tennessee’s Republican lawmakers, the clinic paused gender-affirmation surgeries on patients younger than 18, potentially leaving many trans individuals without necessary care.

Stephens hopes to see more medical schools include coursework on trans health care. She also wishes for doctors to treat trans people as they would any other patient.

“Just provide quality health care,” she tells the medical students at UAB. “We need health care like everyone else does.”
 

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

For Tammy Rainey, finding a health care provider who knows about gender-affirming care has been a challenge in the rural northern Mississippi town where she lives.

As a transgender woman, Ms. Rainey needs the hormone estrogen, which allows her to physically transition by developing more feminine features. But when she asked her doctor for an estrogen prescription, he said he couldn’t provide that type of care.

“He’s generally a good guy and doesn’t act prejudiced. He gets my name and pronouns right,” said Ms. Rainey. “But when I asked him about hormones, he said, ‘I just don’t feel like I know enough about that. I don’t want to get involved in that.’ ”

So Ms. Rainey drives around 170 miles round trip every 6 months to get a supply of estrogen from a clinic in Memphis, Tenn., to take home with her.

The obstacles Ms. Rainey overcomes to access care illustrate a type of medical inequity that transgender people who live in the rural United States often face: A general lack of education about trans-related care among small-town health professionals who might also be reluctant to learn.

“Medical communities across the country are seeing clearly that there is a knowledge gap in the provision of gender-affirming care,” said Morissa Ladinsky, MD, a pediatrician who co-leads the Youth Multidisciplinary Gender Team at the University of Alabama–Birmingham (UAB).

Accurately counting the number of transgender people in rural America is hindered by a lack of U.S. census data and uniform state data. However, the Movement Advancement Project, a nonprofit organization that advocates for LGBTQ+ issues, used 2014-17 Centers for Disease Control and Prevention data from selected ZIP codes in 35 states to estimate that roughly one in six transgender adults in the United States live in a rural area. When that report was released in 2019, there were an estimated 1.4 million transgender people 13 and older nationwide. That number is now at least 1.6 million, according to the Williams Institute, a nonprofit think tank at the UCLA School of Law.

One in three trans people in rural areas experienced discrimination by a health care provider in the year leading up to the 2015 U.S. Transgender Survey Report, according to an analysis by MAP. A third of all trans individuals report having to teach their doctors about their health care needs to receive appropriate care, and 62% worry about being negatively judged by a health care provider because of their sexual orientation or gender identity, according to data collected by the Williams Institute and other organizations.

A lack of local rural providers knowledgeable in trans care can mean long drives to gender-affirming clinics in metropolitan areas. Rural trans people are three times as likely as are all transgender adults to travel 25-49 miles for routine care.

In Colorado, for example, many trans people outside Denver struggle to find proper care. Those who do have a trans-inclusive provider are more likely to receive wellness exams, less likely to delay care due to discrimination, and less likely to attempt suicide, according to results from the Colorado Transgender Health Survey published in 2018.

Much of the lack of care experienced by trans people is linked to insufficient education on LGBTQ+ health in medical schools across the country. In 2014, the Association of American Medical Colleges, which represents 170 accredited medical schools in the United States and Canada, released its first curriculum guidelines on caring for LGBTQ+ patients. As of 2018, 76% of medical schools included LGBTQ health themes in their curriculum, with half providing three or fewer classes on this topic.

Perhaps because of this, almost 77% of students from 10 medical schools in New England felt “not competent” or “somewhat not competent” in treating gender minority patients, according to a 2018 pilot study. Another paper, published last year, found that even clinicians who work in trans-friendly clinics lack knowledge about hormones, gender-affirming surgical options, and how to use appropriate pronouns and trans-inclusive language.

Throughout medical school, trans care was only briefly mentioned in endocrinology class, said Justin Bailey, MD, who received his medical degree from UAB in 2021 and is now a resident there. “I don’t want to say the wrong thing or use the wrong pronouns, so I was hesitant and a little bit tepid in my approach to interviewing and treating this population of patients,” he said.

On top of insufficient medical school education, some practicing doctors don’t take the time to teach themselves about trans people, said Kathie Moehlig, founder of TransFamily Support Services, a nonprofit organization that offers a range of services to transgender people and their families. They are very well intentioned yet uneducated when it comes to transgender care, she said.

Some medical schools, like the one at UAB, have pushed for change. Since 2017, Dr. Ladinsky and her colleagues have worked to include trans people in their standardized patient program, which gives medical students hands-on experience and feedback by interacting with “patients” in simulated clinical environments.

For example, a trans individual acting as a patient will simulate acid reflux by pretending to have pain in their stomach and chest. Then, over the course of the examination, they will reveal that they are transgender.

In the early years of this program, some students’ bedside manner would change once the patient’s gender identity was revealed, said Elaine Stephens, a trans woman who participates in UAB’s standardized patient program. “Sometimes they would immediately start asking about sexual activity,” Stephens said.

Since UAB launched its program, students’ reactions have improved significantly, she said.

This progress is being replicated by other medical schools, said Ms. Moehlig. “But it’s a slow start, and these are large institutions that take a long time to move forward.”

Advocates also are working outside medical schools to improve care in rural areas. In Colorado, the nonprofit Extension for Community Health Outcomes, or ECHO Colorado, has been offering monthly virtual classes on gender-affirming care to rural providers since 2020. The classes became so popular that the organization created a 4-week boot camp in 2021 for providers to learn about hormone therapy management, proper terminologies, surgical options, and supporting patients’ mental health.

For many years, doctors failed to recognize the need to learn about gender-affirming care, said Caroline Kirsch, DO, director of osteopathic education at the University of Wyoming Family Medicine Residency Program–Casper. In Casper, this led to “a number of patients traveling to Colorado to access care, which is a large burden for them financially,” said Dr. Kirsch, who has participated in the ECHO Colorado program.

“Things that haven’t been as well taught historically in medical school are things that I think many physicians feel anxious about initially,” she said. “The earlier you learn about this type of care in your career, the more likely you are to see its potential and be less anxious about it.”

Educating more providers about trans-related care has become increasingly vital in recent years as gender-affirming clinics nationwide experience a rise in harassment and threats. For instance, Vanderbilt University Medical Center’s Clinic for Transgender Health became the target of far-right hate on social media last year. After growing pressure from Tennessee’s Republican lawmakers, the clinic paused gender-affirmation surgeries on patients younger than 18, potentially leaving many trans individuals without necessary care.

Stephens hopes to see more medical schools include coursework on trans health care. She also wishes for doctors to treat trans people as they would any other patient.

“Just provide quality health care,” she tells the medical students at UAB. “We need health care like everyone else does.”
 

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

For Tammy Rainey, finding a health care provider who knows about gender-affirming care has been a challenge in the rural northern Mississippi town where she lives.

As a transgender woman, Ms. Rainey needs the hormone estrogen, which allows her to physically transition by developing more feminine features. But when she asked her doctor for an estrogen prescription, he said he couldn’t provide that type of care.

“He’s generally a good guy and doesn’t act prejudiced. He gets my name and pronouns right,” said Ms. Rainey. “But when I asked him about hormones, he said, ‘I just don’t feel like I know enough about that. I don’t want to get involved in that.’ ”

So Ms. Rainey drives around 170 miles round trip every 6 months to get a supply of estrogen from a clinic in Memphis, Tenn., to take home with her.

The obstacles Ms. Rainey overcomes to access care illustrate a type of medical inequity that transgender people who live in the rural United States often face: A general lack of education about trans-related care among small-town health professionals who might also be reluctant to learn.

“Medical communities across the country are seeing clearly that there is a knowledge gap in the provision of gender-affirming care,” said Morissa Ladinsky, MD, a pediatrician who co-leads the Youth Multidisciplinary Gender Team at the University of Alabama–Birmingham (UAB).

Accurately counting the number of transgender people in rural America is hindered by a lack of U.S. census data and uniform state data. However, the Movement Advancement Project, a nonprofit organization that advocates for LGBTQ+ issues, used 2014-17 Centers for Disease Control and Prevention data from selected ZIP codes in 35 states to estimate that roughly one in six transgender adults in the United States live in a rural area. When that report was released in 2019, there were an estimated 1.4 million transgender people 13 and older nationwide. That number is now at least 1.6 million, according to the Williams Institute, a nonprofit think tank at the UCLA School of Law.

One in three trans people in rural areas experienced discrimination by a health care provider in the year leading up to the 2015 U.S. Transgender Survey Report, according to an analysis by MAP. A third of all trans individuals report having to teach their doctors about their health care needs to receive appropriate care, and 62% worry about being negatively judged by a health care provider because of their sexual orientation or gender identity, according to data collected by the Williams Institute and other organizations.

A lack of local rural providers knowledgeable in trans care can mean long drives to gender-affirming clinics in metropolitan areas. Rural trans people are three times as likely as are all transgender adults to travel 25-49 miles for routine care.

In Colorado, for example, many trans people outside Denver struggle to find proper care. Those who do have a trans-inclusive provider are more likely to receive wellness exams, less likely to delay care due to discrimination, and less likely to attempt suicide, according to results from the Colorado Transgender Health Survey published in 2018.

Much of the lack of care experienced by trans people is linked to insufficient education on LGBTQ+ health in medical schools across the country. In 2014, the Association of American Medical Colleges, which represents 170 accredited medical schools in the United States and Canada, released its first curriculum guidelines on caring for LGBTQ+ patients. As of 2018, 76% of medical schools included LGBTQ health themes in their curriculum, with half providing three or fewer classes on this topic.

Perhaps because of this, almost 77% of students from 10 medical schools in New England felt “not competent” or “somewhat not competent” in treating gender minority patients, according to a 2018 pilot study. Another paper, published last year, found that even clinicians who work in trans-friendly clinics lack knowledge about hormones, gender-affirming surgical options, and how to use appropriate pronouns and trans-inclusive language.

Throughout medical school, trans care was only briefly mentioned in endocrinology class, said Justin Bailey, MD, who received his medical degree from UAB in 2021 and is now a resident there. “I don’t want to say the wrong thing or use the wrong pronouns, so I was hesitant and a little bit tepid in my approach to interviewing and treating this population of patients,” he said.

On top of insufficient medical school education, some practicing doctors don’t take the time to teach themselves about trans people, said Kathie Moehlig, founder of TransFamily Support Services, a nonprofit organization that offers a range of services to transgender people and their families. They are very well intentioned yet uneducated when it comes to transgender care, she said.

Some medical schools, like the one at UAB, have pushed for change. Since 2017, Dr. Ladinsky and her colleagues have worked to include trans people in their standardized patient program, which gives medical students hands-on experience and feedback by interacting with “patients” in simulated clinical environments.

For example, a trans individual acting as a patient will simulate acid reflux by pretending to have pain in their stomach and chest. Then, over the course of the examination, they will reveal that they are transgender.

In the early years of this program, some students’ bedside manner would change once the patient’s gender identity was revealed, said Elaine Stephens, a trans woman who participates in UAB’s standardized patient program. “Sometimes they would immediately start asking about sexual activity,” Stephens said.

Since UAB launched its program, students’ reactions have improved significantly, she said.

This progress is being replicated by other medical schools, said Ms. Moehlig. “But it’s a slow start, and these are large institutions that take a long time to move forward.”

Advocates also are working outside medical schools to improve care in rural areas. In Colorado, the nonprofit Extension for Community Health Outcomes, or ECHO Colorado, has been offering monthly virtual classes on gender-affirming care to rural providers since 2020. The classes became so popular that the organization created a 4-week boot camp in 2021 for providers to learn about hormone therapy management, proper terminologies, surgical options, and supporting patients’ mental health.

For many years, doctors failed to recognize the need to learn about gender-affirming care, said Caroline Kirsch, DO, director of osteopathic education at the University of Wyoming Family Medicine Residency Program–Casper. In Casper, this led to “a number of patients traveling to Colorado to access care, which is a large burden for them financially,” said Dr. Kirsch, who has participated in the ECHO Colorado program.

“Things that haven’t been as well taught historically in medical school are things that I think many physicians feel anxious about initially,” she said. “The earlier you learn about this type of care in your career, the more likely you are to see its potential and be less anxious about it.”

Educating more providers about trans-related care has become increasingly vital in recent years as gender-affirming clinics nationwide experience a rise in harassment and threats. For instance, Vanderbilt University Medical Center’s Clinic for Transgender Health became the target of far-right hate on social media last year. After growing pressure from Tennessee’s Republican lawmakers, the clinic paused gender-affirmation surgeries on patients younger than 18, potentially leaving many trans individuals without necessary care.

Stephens hopes to see more medical schools include coursework on trans health care. She also wishes for doctors to treat trans people as they would any other patient.

“Just provide quality health care,” she tells the medical students at UAB. “We need health care like everyone else does.”
 

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Watching a screen more than an hour a day as a toddler is directly linked with poorer communication and daily living skills at age 4, but outdoor play may lessen some of the effects, new research suggests.

The results point to outdoor play as a potential targeted intervention to counter suboptimal brain development in young children who are watching screens at increasingly younger ages.

The findings were published online in JAMA Pediatrics.

The researchers first investigated whether higher screen time (more than 1 hour a day on a device or watching television) at age 2 years is associated with neurodevelopmental outcomes at age 4.

They found the 885 children in the sample from the Japanese Hamamatsu Birth Cohort Study for Mothers and Children who had more screen time had lower scores on communication and daily living skills than children who watched less than an hour a day.

Scores were based on the Vineland Adaptive Behavior Scale according to parent responses to questions. The children included were born between December 2007 and March 2012 and were followed from 18 months to 4 years.

After finding the connection between screen time and lower scores, the researchers investigated whether outdoor play (at least 30 minutes a day) introduced at a 2 years and 8 months made a difference. They considered 6 or 7 days per week frequent outdoor play.
 

Outdoor play mitigated poorer daily living scores

The researchers found that the outdoor play intervention mitigated 18% of the association between high screen time and lower daily living scores but did not mitigate the lower communication scores.

They also found that more screen time at age 2 was significantly linked with infrequent outdoor play at age 32 months (odds ratio, 2.03; 95% confidence interval, 1.48-2.76).

The associations were consistent after taking into account factors including a child’s sex, parental education, and any autism spectrum disorder symptoms at age 18 months.

The authors noted that neurodevelopment concerns with screen use are particularly troubling as the age for use is getting younger.

A recent meta-analysis found that 75% of children younger than 2 use or watch screens, even though guidelines recommend against any screen time before 2.

In addition, the “COVID-19 pandemic led to children having more screen time, less outdoor play, and less physical activity, putting them at potentially greater risk for neurodevelopmental problems,” the authors noted.

“What is concerning is that data show screen time has not decreased after seclusion measures were lifted,” they added.
 

Proven benefits for outdoor play

Jennifer Cross, MD,* assistant professor and section chief for developmental pediatrics at Weill Cornell Medicine, New York, who was not part of the study, said the mitigation properties of outdoor play were something she hadn’t seen before but the concept makes sense.

“The overwhelming evidence is that screen time is not helpful for young children under the age of 2,” she said.

Outdoor play, on the other hand, has proven benefits.

“Physical activity has been shown to be good for physical and mental health so there’s no reason to believe it wouldn’t be good for 2-and-a-half-year olds,” Dr. Cross said. “It’s also good for developmental health. You want them to be engaged in imaginative play and be interactive.”

“[Outdoor play] gets them away from screens and gives them an opportunity to experience another environment and work on their motor skills and motor planning,” she added. “Exercise will change, briefly, the way our brains process information.”

Dr. Cross added that a lot of motor skills are involved in daily living skills, such as feeding, dressing, and toileting.

Screen time is increasing

The authors acknowledged that screen time may be underestimated by parents. They also noted that they did not have access to what children were watching on the screens.

“This should have been collected because the effect of high screen time differs depending on the type of program,” the authors wrote.

They added that children born in the 2020s may have been exposed to more screen time than the children reared in the early 2010s in this study.

Dr. Cross said screen use in the 2020s may be higher than estimated here and higher in certain populations globally, so it’s not easy to tell if the intervention in this study would have the same mitigating effect on a real-world population.

However, she said, the effect of outdoor play is always going to be helpful for brain development and there’s no downside.

“Exercise is just as important for little kids as it is for grown-ups,” she said.

The authors reported no relevant financial disclosures. Dr. Cross reported no relevant financial disclosures.

*Dr. Jennifer Cross is the correct name, not Dr. Jennifer Frost. The correction was made on Jan. 27, 2023.

Watching a screen more than an hour a day as a toddler is directly linked with poorer communication and daily living skills at age 4, but outdoor play may lessen some of the effects, new research suggests.

The results point to outdoor play as a potential targeted intervention to counter suboptimal brain development in young children who are watching screens at increasingly younger ages.

The findings were published online in JAMA Pediatrics.

The researchers first investigated whether higher screen time (more than 1 hour a day on a device or watching television) at age 2 years is associated with neurodevelopmental outcomes at age 4.

They found the 885 children in the sample from the Japanese Hamamatsu Birth Cohort Study for Mothers and Children who had more screen time had lower scores on communication and daily living skills than children who watched less than an hour a day.

Scores were based on the Vineland Adaptive Behavior Scale according to parent responses to questions. The children included were born between December 2007 and March 2012 and were followed from 18 months to 4 years.

After finding the connection between screen time and lower scores, the researchers investigated whether outdoor play (at least 30 minutes a day) introduced at a 2 years and 8 months made a difference. They considered 6 or 7 days per week frequent outdoor play.
 

Outdoor play mitigated poorer daily living scores

The researchers found that the outdoor play intervention mitigated 18% of the association between high screen time and lower daily living scores but did not mitigate the lower communication scores.

They also found that more screen time at age 2 was significantly linked with infrequent outdoor play at age 32 months (odds ratio, 2.03; 95% confidence interval, 1.48-2.76).

The associations were consistent after taking into account factors including a child’s sex, parental education, and any autism spectrum disorder symptoms at age 18 months.

The authors noted that neurodevelopment concerns with screen use are particularly troubling as the age for use is getting younger.

A recent meta-analysis found that 75% of children younger than 2 use or watch screens, even though guidelines recommend against any screen time before 2.

In addition, the “COVID-19 pandemic led to children having more screen time, less outdoor play, and less physical activity, putting them at potentially greater risk for neurodevelopmental problems,” the authors noted.

“What is concerning is that data show screen time has not decreased after seclusion measures were lifted,” they added.
 

Proven benefits for outdoor play

Jennifer Cross, MD,* assistant professor and section chief for developmental pediatrics at Weill Cornell Medicine, New York, who was not part of the study, said the mitigation properties of outdoor play were something she hadn’t seen before but the concept makes sense.

“The overwhelming evidence is that screen time is not helpful for young children under the age of 2,” she said.

Outdoor play, on the other hand, has proven benefits.

“Physical activity has been shown to be good for physical and mental health so there’s no reason to believe it wouldn’t be good for 2-and-a-half-year olds,” Dr. Cross said. “It’s also good for developmental health. You want them to be engaged in imaginative play and be interactive.”

“[Outdoor play] gets them away from screens and gives them an opportunity to experience another environment and work on their motor skills and motor planning,” she added. “Exercise will change, briefly, the way our brains process information.”

Dr. Cross added that a lot of motor skills are involved in daily living skills, such as feeding, dressing, and toileting.

Screen time is increasing

The authors acknowledged that screen time may be underestimated by parents. They also noted that they did not have access to what children were watching on the screens.

“This should have been collected because the effect of high screen time differs depending on the type of program,” the authors wrote.

They added that children born in the 2020s may have been exposed to more screen time than the children reared in the early 2010s in this study.

Dr. Cross said screen use in the 2020s may be higher than estimated here and higher in certain populations globally, so it’s not easy to tell if the intervention in this study would have the same mitigating effect on a real-world population.

However, she said, the effect of outdoor play is always going to be helpful for brain development and there’s no downside.

“Exercise is just as important for little kids as it is for grown-ups,” she said.

The authors reported no relevant financial disclosures. Dr. Cross reported no relevant financial disclosures.

*Dr. Jennifer Cross is the correct name, not Dr. Jennifer Frost. The correction was made on Jan. 27, 2023.

Watching a screen more than an hour a day as a toddler is directly linked with poorer communication and daily living skills at age 4, but outdoor play may lessen some of the effects, new research suggests.

The results point to outdoor play as a potential targeted intervention to counter suboptimal brain development in young children who are watching screens at increasingly younger ages.

The findings were published online in JAMA Pediatrics.

The researchers first investigated whether higher screen time (more than 1 hour a day on a device or watching television) at age 2 years is associated with neurodevelopmental outcomes at age 4.

They found the 885 children in the sample from the Japanese Hamamatsu Birth Cohort Study for Mothers and Children who had more screen time had lower scores on communication and daily living skills than children who watched less than an hour a day.

Scores were based on the Vineland Adaptive Behavior Scale according to parent responses to questions. The children included were born between December 2007 and March 2012 and were followed from 18 months to 4 years.

After finding the connection between screen time and lower scores, the researchers investigated whether outdoor play (at least 30 minutes a day) introduced at a 2 years and 8 months made a difference. They considered 6 or 7 days per week frequent outdoor play.
 

Outdoor play mitigated poorer daily living scores

The researchers found that the outdoor play intervention mitigated 18% of the association between high screen time and lower daily living scores but did not mitigate the lower communication scores.

They also found that more screen time at age 2 was significantly linked with infrequent outdoor play at age 32 months (odds ratio, 2.03; 95% confidence interval, 1.48-2.76).

The associations were consistent after taking into account factors including a child’s sex, parental education, and any autism spectrum disorder symptoms at age 18 months.

The authors noted that neurodevelopment concerns with screen use are particularly troubling as the age for use is getting younger.

A recent meta-analysis found that 75% of children younger than 2 use or watch screens, even though guidelines recommend against any screen time before 2.

In addition, the “COVID-19 pandemic led to children having more screen time, less outdoor play, and less physical activity, putting them at potentially greater risk for neurodevelopmental problems,” the authors noted.

“What is concerning is that data show screen time has not decreased after seclusion measures were lifted,” they added.
 

Proven benefits for outdoor play

Jennifer Cross, MD,* assistant professor and section chief for developmental pediatrics at Weill Cornell Medicine, New York, who was not part of the study, said the mitigation properties of outdoor play were something she hadn’t seen before but the concept makes sense.

“The overwhelming evidence is that screen time is not helpful for young children under the age of 2,” she said.

Outdoor play, on the other hand, has proven benefits.

“Physical activity has been shown to be good for physical and mental health so there’s no reason to believe it wouldn’t be good for 2-and-a-half-year olds,” Dr. Cross said. “It’s also good for developmental health. You want them to be engaged in imaginative play and be interactive.”

“[Outdoor play] gets them away from screens and gives them an opportunity to experience another environment and work on their motor skills and motor planning,” she added. “Exercise will change, briefly, the way our brains process information.”

Dr. Cross added that a lot of motor skills are involved in daily living skills, such as feeding, dressing, and toileting.

Screen time is increasing

The authors acknowledged that screen time may be underestimated by parents. They also noted that they did not have access to what children were watching on the screens.

“This should have been collected because the effect of high screen time differs depending on the type of program,” the authors wrote.

They added that children born in the 2020s may have been exposed to more screen time than the children reared in the early 2010s in this study.

Dr. Cross said screen use in the 2020s may be higher than estimated here and higher in certain populations globally, so it’s not easy to tell if the intervention in this study would have the same mitigating effect on a real-world population.

However, she said, the effect of outdoor play is always going to be helpful for brain development and there’s no downside.

“Exercise is just as important for little kids as it is for grown-ups,” she said.

The authors reported no relevant financial disclosures. Dr. Cross reported no relevant financial disclosures.

*Dr. Jennifer Cross is the correct name, not Dr. Jennifer Frost. The correction was made on Jan. 27, 2023.