To the Editor:

Protothecosis infections are caused by an achlorophyllic algae of the species Prototheca. Prototheca organisms are found mostly in soil and water.¹ Human infections are rare and involve 2 species, Prototheca wickerhamii and Prototheca zopfii. The former most commonly is responsible for human infections, though P zopfii results in more serious systemic infections with a poor prognosis. There are various types of Prototheca infection presentations, with a 2007 review of 117 cases reporting that cutaneous infections are most common (66%), followed by systemic infections (19%), and olecranon bursitis (15%).² Skin lesions most commonly occur on the extremities and face, and they present as vesiculobullous and ulcerative lesions with purulent drainage. The skin lesions also may appear as erythematous plaques or nodules, subcutaneous papules, verrucous or herpetiformis lesions, or pyogenic granuloma–like lesions.³ Protothecosis typically affects immunocompromised individuals, especially those with a history of chronic corticosteroid use, malignancy, diabetes mellitus, AIDS, and/or organ transplant.¹ We present a case of cutaneous protothecosis on the dorsal distal extremity of a 94-year-old woman. History of exposure to soil while gardening was elicited from the patient, and no immunosuppressive history was present aside from the patient’s age. This case may prompt workup for malignancy or immunosuppression in this patient subset.

A 94-year-old woman with a medical history of cutaneous squamous cell carcinoma (SCC) presented with a growing lesion on the dorsal surface of the left fourth digit of 2 months’ duration. The patient reported the lesion was painful, and she noted preceding trauma to the area that was suspected to have occurred while gardening. Physical examination revealed an ulcerated, hypertrophic, erythematous nodule on the dorsal surface of the left fourth metacarpophalangeal joint. The differential diagnosis included SCC, inflamed cyst, verruca vulgaris, and orf virus due to the clinical presentation. A shave biopsy was performed, and the lesion subsequently was treated with electrodesiccation and curettage.

Histopathologic evaluation revealed pseudoepitheliomatous hyperplasia with a mixed inflammatory infiltrate including lymphocytes and histiocytes. A morula within the dermis was characteristic of a protothecosis infection (Figure 1). On follow-up visit 6 weeks later, the lesion had grown back to its original size and morphology (Figure 2). At this time, the lesion was again treated with shave removal, followed by electrodesiccation and curettage, and the patient was placed on oral fluconazole 200 mg daily for 1 month. When the lesion did not resolve with fluconazole, she was referred to infectious disease as well as general surgery for surgical removal and debridement of the lesion. Unfortunately, the patient was lost to follow-up.

Protothecosis is an infectious disease comprised of achlorophyllic algae found in soil and water that rarely affects humans. When it does affect humans, cutaneous infections are most common. All human cases in which organisms were identified to species level have been caused by P wickerhamii or P zopfii species.² Inoculation is suspected to occur through trauma to affected skin, especially when in the context of contaminated water. Our patient reported history of trauma to the hand, with soil from gardening as the potential aquagenic source of the infection.

The clinical presentation of protothecosis ranges from localized cutaneous to disseminated systemic infections, with most reported cases of systemic disease occurring in immunocompromised individuals. The cutaneous lesions of protothecosis vary greatly in clinical appearance including ulcerative nodules (as in our case), papules, plaques, pustules, and vesicles with erosion or crusting.⁴

Cutaneous protothecosis has the potential to mimic many other skin diseases and lesions, and, given its rarity, it may not be on the radar of dermatologists. Our patient’s lesion was presumed to be a skin cancer and was treated as such because of the history of SCC and clinical presentation. Although excision of individual lesions of protothecosis can be curative, electrodesiccation and curettage does not appear to be an adequate treatment, as the lesion subsequently recurred. It also is possible that this case represents P zopfii infection, as it did not respond to treatment with oral fluconazole, though in vitro studies with fluconazole to both P zopfii and P wickerhamii had variable treatment success.² Also, the histopathologic findings were most consistent with P wickerhamii, revealing small, round, symmetrical morula, compared to P zopfii, which typically will display oval or cylindrical, asymmetrical, random internal segmentation.⁵ This case may warrant determination of species, which can be accomplished by a culture on Sabouraud dextrose agar, carbohydrate and alcohol assimilation test, yeast biochemical card, serological typing by immunoblotting, immunofluorescence study using species-specific antibodies, or amplification by polymerase chain reaction for small subunit ribosomal DNA sequences.^2,6-8

The natural history of isolated skin disease is an indolent progressive course; however, reports do exist noting spontaneous resolution.^4,9 Treatment options for Prototheca infections can be disappointing and consist of both surgical and medical management, or a combination of the 2 approaches. Reports in the literature support the use of antifungals including ketoconazole, voriconazole, itraconazole, fluconazole, and amphotericin B, with the latter displaying the best activity against Prototheca species.² Tetracycline has been used in combination with oral or topical amphotericin B and was found to be synergistic in vitro and in case reports at successfully treating cutaneous protothecosis infections. It is possible that our patient was not treated with fluconazole long enough for it to become therapeutic, as most reported treatment regimens are weeks to months in length. Conversely, it may have been of benefit to transition the patient to topical amphotericin B and tetracycline, as fluconazole failed in this patient. However, treatment successes and failures are limited to case reports/case series and in vitro studies, with prospective studies lacking. Due to the variability with in vitro susceptibility profiles for Prototheca species, it generally is not recommended to pursue in vitro susceptibility testing in the management of Prototheca skin infections due to the inconsistency demonstrated between in vitro activity and clinical response to therapy.²

To the Editor:

Protothecosis infections are caused by an achlorophyllic algae of the species Prototheca. Prototheca organisms are found mostly in soil and water.¹ Human infections are rare and involve 2 species, Prototheca wickerhamii and Prototheca zopfii. The former most commonly is responsible for human infections, though P zopfii results in more serious systemic infections with a poor prognosis. There are various types of Prototheca infection presentations, with a 2007 review of 117 cases reporting that cutaneous infections are most common (66%), followed by systemic infections (19%), and olecranon bursitis (15%).² Skin lesions most commonly occur on the extremities and face, and they present as vesiculobullous and ulcerative lesions with purulent drainage. The skin lesions also may appear as erythematous plaques or nodules, subcutaneous papules, verrucous or herpetiformis lesions, or pyogenic granuloma–like lesions.³ Protothecosis typically affects immunocompromised individuals, especially those with a history of chronic corticosteroid use, malignancy, diabetes mellitus, AIDS, and/or organ transplant.¹ We present a case of cutaneous protothecosis on the dorsal distal extremity of a 94-year-old woman. History of exposure to soil while gardening was elicited from the patient, and no immunosuppressive history was present aside from the patient’s age. This case may prompt workup for malignancy or immunosuppression in this patient subset.

A 94-year-old woman with a medical history of cutaneous squamous cell carcinoma (SCC) presented with a growing lesion on the dorsal surface of the left fourth digit of 2 months’ duration. The patient reported the lesion was painful, and she noted preceding trauma to the area that was suspected to have occurred while gardening. Physical examination revealed an ulcerated, hypertrophic, erythematous nodule on the dorsal surface of the left fourth metacarpophalangeal joint. The differential diagnosis included SCC, inflamed cyst, verruca vulgaris, and orf virus due to the clinical presentation. A shave biopsy was performed, and the lesion subsequently was treated with electrodesiccation and curettage.

Histopathologic evaluation revealed pseudoepitheliomatous hyperplasia with a mixed inflammatory infiltrate including lymphocytes and histiocytes. A morula within the dermis was characteristic of a protothecosis infection (Figure 1). On follow-up visit 6 weeks later, the lesion had grown back to its original size and morphology (Figure 2). At this time, the lesion was again treated with shave removal, followed by electrodesiccation and curettage, and the patient was placed on oral fluconazole 200 mg daily for 1 month. When the lesion did not resolve with fluconazole, she was referred to infectious disease as well as general surgery for surgical removal and debridement of the lesion. Unfortunately, the patient was lost to follow-up.

Protothecosis is an infectious disease comprised of achlorophyllic algae found in soil and water that rarely affects humans. When it does affect humans, cutaneous infections are most common. All human cases in which organisms were identified to species level have been caused by P wickerhamii or P zopfii species.² Inoculation is suspected to occur through trauma to affected skin, especially when in the context of contaminated water. Our patient reported history of trauma to the hand, with soil from gardening as the potential aquagenic source of the infection.

The clinical presentation of protothecosis ranges from localized cutaneous to disseminated systemic infections, with most reported cases of systemic disease occurring in immunocompromised individuals. The cutaneous lesions of protothecosis vary greatly in clinical appearance including ulcerative nodules (as in our case), papules, plaques, pustules, and vesicles with erosion or crusting.⁴

Cutaneous protothecosis has the potential to mimic many other skin diseases and lesions, and, given its rarity, it may not be on the radar of dermatologists. Our patient’s lesion was presumed to be a skin cancer and was treated as such because of the history of SCC and clinical presentation. Although excision of individual lesions of protothecosis can be curative, electrodesiccation and curettage does not appear to be an adequate treatment, as the lesion subsequently recurred. It also is possible that this case represents P zopfii infection, as it did not respond to treatment with oral fluconazole, though in vitro studies with fluconazole to both P zopfii and P wickerhamii had variable treatment success.² Also, the histopathologic findings were most consistent with P wickerhamii, revealing small, round, symmetrical morula, compared to P zopfii, which typically will display oval or cylindrical, asymmetrical, random internal segmentation.⁵ This case may warrant determination of species, which can be accomplished by a culture on Sabouraud dextrose agar, carbohydrate and alcohol assimilation test, yeast biochemical card, serological typing by immunoblotting, immunofluorescence study using species-specific antibodies, or amplification by polymerase chain reaction for small subunit ribosomal DNA sequences.^2,6-8

The natural history of isolated skin disease is an indolent progressive course; however, reports do exist noting spontaneous resolution.^4,9 Treatment options for Prototheca infections can be disappointing and consist of both surgical and medical management, or a combination of the 2 approaches. Reports in the literature support the use of antifungals including ketoconazole, voriconazole, itraconazole, fluconazole, and amphotericin B, with the latter displaying the best activity against Prototheca species.² Tetracycline has been used in combination with oral or topical amphotericin B and was found to be synergistic in vitro and in case reports at successfully treating cutaneous protothecosis infections. It is possible that our patient was not treated with fluconazole long enough for it to become therapeutic, as most reported treatment regimens are weeks to months in length. Conversely, it may have been of benefit to transition the patient to topical amphotericin B and tetracycline, as fluconazole failed in this patient. However, treatment successes and failures are limited to case reports/case series and in vitro studies, with prospective studies lacking. Due to the variability with in vitro susceptibility profiles for Prototheca species, it generally is not recommended to pursue in vitro susceptibility testing in the management of Prototheca skin infections due to the inconsistency demonstrated between in vitro activity and clinical response to therapy.²

To the Editor:

Protothecosis infections are caused by an achlorophyllic algae of the species Prototheca. Prototheca organisms are found mostly in soil and water.¹ Human infections are rare and involve 2 species, Prototheca wickerhamii and Prototheca zopfii. The former most commonly is responsible for human infections, though P zopfii results in more serious systemic infections with a poor prognosis. There are various types of Prototheca infection presentations, with a 2007 review of 117 cases reporting that cutaneous infections are most common (66%), followed by systemic infections (19%), and olecranon bursitis (15%).² Skin lesions most commonly occur on the extremities and face, and they present as vesiculobullous and ulcerative lesions with purulent drainage. The skin lesions also may appear as erythematous plaques or nodules, subcutaneous papules, verrucous or herpetiformis lesions, or pyogenic granuloma–like lesions.³ Protothecosis typically affects immunocompromised individuals, especially those with a history of chronic corticosteroid use, malignancy, diabetes mellitus, AIDS, and/or organ transplant.¹ We present a case of cutaneous protothecosis on the dorsal distal extremity of a 94-year-old woman. History of exposure to soil while gardening was elicited from the patient, and no immunosuppressive history was present aside from the patient’s age. This case may prompt workup for malignancy or immunosuppression in this patient subset.

A 94-year-old woman with a medical history of cutaneous squamous cell carcinoma (SCC) presented with a growing lesion on the dorsal surface of the left fourth digit of 2 months’ duration. The patient reported the lesion was painful, and she noted preceding trauma to the area that was suspected to have occurred while gardening. Physical examination revealed an ulcerated, hypertrophic, erythematous nodule on the dorsal surface of the left fourth metacarpophalangeal joint. The differential diagnosis included SCC, inflamed cyst, verruca vulgaris, and orf virus due to the clinical presentation. A shave biopsy was performed, and the lesion subsequently was treated with electrodesiccation and curettage.

Histopathologic evaluation revealed pseudoepitheliomatous hyperplasia with a mixed inflammatory infiltrate including lymphocytes and histiocytes. A morula within the dermis was characteristic of a protothecosis infection (Figure 1). On follow-up visit 6 weeks later, the lesion had grown back to its original size and morphology (Figure 2). At this time, the lesion was again treated with shave removal, followed by electrodesiccation and curettage, and the patient was placed on oral fluconazole 200 mg daily for 1 month. When the lesion did not resolve with fluconazole, she was referred to infectious disease as well as general surgery for surgical removal and debridement of the lesion. Unfortunately, the patient was lost to follow-up.

Protothecosis is an infectious disease comprised of achlorophyllic algae found in soil and water that rarely affects humans. When it does affect humans, cutaneous infections are most common. All human cases in which organisms were identified to species level have been caused by P wickerhamii or P zopfii species.² Inoculation is suspected to occur through trauma to affected skin, especially when in the context of contaminated water. Our patient reported history of trauma to the hand, with soil from gardening as the potential aquagenic source of the infection.

The clinical presentation of protothecosis ranges from localized cutaneous to disseminated systemic infections, with most reported cases of systemic disease occurring in immunocompromised individuals. The cutaneous lesions of protothecosis vary greatly in clinical appearance including ulcerative nodules (as in our case), papules, plaques, pustules, and vesicles with erosion or crusting.⁴

Cutaneous protothecosis has the potential to mimic many other skin diseases and lesions, and, given its rarity, it may not be on the radar of dermatologists. Our patient’s lesion was presumed to be a skin cancer and was treated as such because of the history of SCC and clinical presentation. Although excision of individual lesions of protothecosis can be curative, electrodesiccation and curettage does not appear to be an adequate treatment, as the lesion subsequently recurred. It also is possible that this case represents P zopfii infection, as it did not respond to treatment with oral fluconazole, though in vitro studies with fluconazole to both P zopfii and P wickerhamii had variable treatment success.² Also, the histopathologic findings were most consistent with P wickerhamii, revealing small, round, symmetrical morula, compared to P zopfii, which typically will display oval or cylindrical, asymmetrical, random internal segmentation.⁵ This case may warrant determination of species, which can be accomplished by a culture on Sabouraud dextrose agar, carbohydrate and alcohol assimilation test, yeast biochemical card, serological typing by immunoblotting, immunofluorescence study using species-specific antibodies, or amplification by polymerase chain reaction for small subunit ribosomal DNA sequences.^2,6-8

The natural history of isolated skin disease is an indolent progressive course; however, reports do exist noting spontaneous resolution.^4,9 Treatment options for Prototheca infections can be disappointing and consist of both surgical and medical management, or a combination of the 2 approaches. Reports in the literature support the use of antifungals including ketoconazole, voriconazole, itraconazole, fluconazole, and amphotericin B, with the latter displaying the best activity against Prototheca species.² Tetracycline has been used in combination with oral or topical amphotericin B and was found to be synergistic in vitro and in case reports at successfully treating cutaneous protothecosis infections. It is possible that our patient was not treated with fluconazole long enough for it to become therapeutic, as most reported treatment regimens are weeks to months in length. Conversely, it may have been of benefit to transition the patient to topical amphotericin B and tetracycline, as fluconazole failed in this patient. However, treatment successes and failures are limited to case reports/case series and in vitro studies, with prospective studies lacking. Due to the variability with in vitro susceptibility profiles for Prototheca species, it generally is not recommended to pursue in vitro susceptibility testing in the management of Prototheca skin infections due to the inconsistency demonstrated between in vitro activity and clinical response to therapy.²

Bimekizumab has been approved by the European Commission for the treatment of moderate to severe plaque psoriasis in adults, according to a statement from the manufacturer.

Bimekizumab (Bimzelx), a humanized IgG1 monoclonal antibody, is the first approved treatment for moderate to severe plaque psoriasis that selectively inhibits interleukin (IL)–17A and IL-17F, the statement from UCB said.

In the United States, the Food and Drug Administration is expected to make a decision on approval of bimekizumab for treating psoriasis on Oct. 15.

Approval in the EU was based on data from three phase 3 trials including a total of 1,480 adult patients with moderate to severe psoriasis, which found that those treated with bimekizumab experienced significantly greater skin clearance, compared with placebo, ustekinumab, and adalimumab, with a favorable safety profile, according to the company.

In all three studies (BE VIVID, BE READY, and BE SURE), more than 80% of patients treated with bimekizumab showed improved skin clearance after 16 weeks, significantly more than those treated with ustekinumab, placebo, or adalimumab, based on an improvement of at least 90% in the Psoriasis Area & Severity Index (PASI 90) and an Investigator’s Global Assessment (IGA) response of clear or almost clear skin (IGA 0/1). In all three studies, these clinical responses persisted after 1 year.

The recommended dose of bimekizumab is 320 mg, given in two subcutaneous injections every 4 weeks to week 16, then every 8 weeks. However, for “some patients” weighing 120 kg or more who have not achieved complete skin clearance at 16 weeks, 320 mg every 4 weeks after that time may improve response to treatment, according to the company statement.

The most common treatment-related adverse events in the studies were upper respiratory tract infections (a majority of which were nasopharyngitis), reported by 14.5% of patients, followed by oral candidiasis, reported by 7.3%.

Results of BE READY and BE VIVID were published in The Lancet. Results of the BE SURE study were published in The New England Journal of Medicine.

Bimekizumab is contraindicated for individuals with clinically important active infections such as tuberculosis, and for individuals with any hypersensitivity to the active substance. More details on bimekizumab are available on the website of the European Medicines Agency.

Bimekizumab has been approved by the European Commission for the treatment of moderate to severe plaque psoriasis in adults, according to a statement from the manufacturer.

Bimekizumab (Bimzelx), a humanized IgG1 monoclonal antibody, is the first approved treatment for moderate to severe plaque psoriasis that selectively inhibits interleukin (IL)–17A and IL-17F, the statement from UCB said.

In the United States, the Food and Drug Administration is expected to make a decision on approval of bimekizumab for treating psoriasis on Oct. 15.

Approval in the EU was based on data from three phase 3 trials including a total of 1,480 adult patients with moderate to severe psoriasis, which found that those treated with bimekizumab experienced significantly greater skin clearance, compared with placebo, ustekinumab, and adalimumab, with a favorable safety profile, according to the company.

In all three studies (BE VIVID, BE READY, and BE SURE), more than 80% of patients treated with bimekizumab showed improved skin clearance after 16 weeks, significantly more than those treated with ustekinumab, placebo, or adalimumab, based on an improvement of at least 90% in the Psoriasis Area & Severity Index (PASI 90) and an Investigator’s Global Assessment (IGA) response of clear or almost clear skin (IGA 0/1). In all three studies, these clinical responses persisted after 1 year.

The recommended dose of bimekizumab is 320 mg, given in two subcutaneous injections every 4 weeks to week 16, then every 8 weeks. However, for “some patients” weighing 120 kg or more who have not achieved complete skin clearance at 16 weeks, 320 mg every 4 weeks after that time may improve response to treatment, according to the company statement.

The most common treatment-related adverse events in the studies were upper respiratory tract infections (a majority of which were nasopharyngitis), reported by 14.5% of patients, followed by oral candidiasis, reported by 7.3%.

Results of BE READY and BE VIVID were published in The Lancet. Results of the BE SURE study were published in The New England Journal of Medicine.

Bimekizumab is contraindicated for individuals with clinically important active infections such as tuberculosis, and for individuals with any hypersensitivity to the active substance. More details on bimekizumab are available on the website of the European Medicines Agency.

Bimekizumab has been approved by the European Commission for the treatment of moderate to severe plaque psoriasis in adults, according to a statement from the manufacturer.

Bimekizumab (Bimzelx), a humanized IgG1 monoclonal antibody, is the first approved treatment for moderate to severe plaque psoriasis that selectively inhibits interleukin (IL)–17A and IL-17F, the statement from UCB said.

In the United States, the Food and Drug Administration is expected to make a decision on approval of bimekizumab for treating psoriasis on Oct. 15.

Approval in the EU was based on data from three phase 3 trials including a total of 1,480 adult patients with moderate to severe psoriasis, which found that those treated with bimekizumab experienced significantly greater skin clearance, compared with placebo, ustekinumab, and adalimumab, with a favorable safety profile, according to the company.

In all three studies (BE VIVID, BE READY, and BE SURE), more than 80% of patients treated with bimekizumab showed improved skin clearance after 16 weeks, significantly more than those treated with ustekinumab, placebo, or adalimumab, based on an improvement of at least 90% in the Psoriasis Area & Severity Index (PASI 90) and an Investigator’s Global Assessment (IGA) response of clear or almost clear skin (IGA 0/1). In all three studies, these clinical responses persisted after 1 year.

The recommended dose of bimekizumab is 320 mg, given in two subcutaneous injections every 4 weeks to week 16, then every 8 weeks. However, for “some patients” weighing 120 kg or more who have not achieved complete skin clearance at 16 weeks, 320 mg every 4 weeks after that time may improve response to treatment, according to the company statement.

The most common treatment-related adverse events in the studies were upper respiratory tract infections (a majority of which were nasopharyngitis), reported by 14.5% of patients, followed by oral candidiasis, reported by 7.3%.

Results of BE READY and BE VIVID were published in The Lancet. Results of the BE SURE study were published in The New England Journal of Medicine.

Bimekizumab is contraindicated for individuals with clinically important active infections such as tuberculosis, and for individuals with any hypersensitivity to the active substance. More details on bimekizumab are available on the website of the European Medicines Agency.

Parkinson’s disease patients who develop anxiety early in their disease are at risk for reduced physical activity, which promotes further anxiety and cognitive decline, data from nearly 500 individuals show.

Anxiety occurs in 20%-60% of Parkinson’s disease (PD) patients but often goes undiagnosed, wrote Jacob D. Jones, PhD, of California State University, San Bernardino, and colleagues.

“Anxiety can attenuate motivation to engage in physical activity leading to more anxiety and other negative cognitive outcomes,” although physical activity has been shown to improve cognitive function in PD patients, they said. However, physical activity as a mediator between anxiety and cognitive function in PD has not been well studied, they noted.

In a study published in Mental Health and Physical Activity the researchers identified 487 adults with newly diagnosed PD within the past 2 years who were enrolled in the Parkinson’s Progression Markers Initiative. Participants were followed for up to 5 years and completed neuropsychological tests, tests of motor severity, and self-reports on anxiety and physical activity. Anxiety was assessed using the State-Trait Anxiety Inventory-Trait (STAI-T) subscale. Physical activity was assessed using the Physical Activity Scale for the Elderly (PASE). Motor severity was assessed using the Unified Parkinson’s Disease Rating Scale-Part III (UPDRS). The average age of the participants was 61 years, 65% were men, and 96% were White.

Using a direct-effect model, the researchers found that individuals whose anxiety increased during the study period also showed signs of cognitive decline. A significant between-person effect showed that individuals who were generally more anxious also scored lower on cognitive tests over the 5-year study period.

In a mediation model computed with structural equation modeling, physical activity mediated the link between anxiety and cognition, most notably household activity.

“There was a significant within-person association between anxiety and household activities, meaning that individuals who became more anxious over the 5-year study also became less active in the home,” reported Dr. Jones and colleagues.

However, no significant indirect effect was noted regarding the between-person findings of the impact of physical activity on anxiety and cognitive decline. Although more severe anxiety was associated with less activity, cognitive performance was not associated with either type of physical activity.

The presence of a within-person effect “suggests that reductions in physical activity, specifically within the first 5 years of disease onset, may be detrimental to mental health,” the researchers emphasized. Given that the study population was newly diagnosed with PD “it is likely the within-person terms are more sensitive to changes in anxiety, physical activity, and cognition that are more directly the result of the PD process, as opposed to lifestyle/preexisting traits,” they said.

The study findings were limited by several factors, including the use of self-reports to measure physical activity, and the lack of granular information about the details of physical activity, the researchers noted. Another limitation was the inclusion of only newly diagnosed PD patients, which might limit generalizability.

“Future research is warranted to understand if other modes, intensities, or complexities of physical activity impact individuals with PD in a different manner in relation to cognition,” they said.

Dr. Jones and colleagues had no disclosures. The PPMI is supported by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including numerous pharmaceutical companies.

Parkinson’s disease patients who develop anxiety early in their disease are at risk for reduced physical activity, which promotes further anxiety and cognitive decline, data from nearly 500 individuals show.

Anxiety occurs in 20%-60% of Parkinson’s disease (PD) patients but often goes undiagnosed, wrote Jacob D. Jones, PhD, of California State University, San Bernardino, and colleagues.

“Anxiety can attenuate motivation to engage in physical activity leading to more anxiety and other negative cognitive outcomes,” although physical activity has been shown to improve cognitive function in PD patients, they said. However, physical activity as a mediator between anxiety and cognitive function in PD has not been well studied, they noted.

In a study published in Mental Health and Physical Activity the researchers identified 487 adults with newly diagnosed PD within the past 2 years who were enrolled in the Parkinson’s Progression Markers Initiative. Participants were followed for up to 5 years and completed neuropsychological tests, tests of motor severity, and self-reports on anxiety and physical activity. Anxiety was assessed using the State-Trait Anxiety Inventory-Trait (STAI-T) subscale. Physical activity was assessed using the Physical Activity Scale for the Elderly (PASE). Motor severity was assessed using the Unified Parkinson’s Disease Rating Scale-Part III (UPDRS). The average age of the participants was 61 years, 65% were men, and 96% were White.

Using a direct-effect model, the researchers found that individuals whose anxiety increased during the study period also showed signs of cognitive decline. A significant between-person effect showed that individuals who were generally more anxious also scored lower on cognitive tests over the 5-year study period.

In a mediation model computed with structural equation modeling, physical activity mediated the link between anxiety and cognition, most notably household activity.

“There was a significant within-person association between anxiety and household activities, meaning that individuals who became more anxious over the 5-year study also became less active in the home,” reported Dr. Jones and colleagues.

However, no significant indirect effect was noted regarding the between-person findings of the impact of physical activity on anxiety and cognitive decline. Although more severe anxiety was associated with less activity, cognitive performance was not associated with either type of physical activity.

The presence of a within-person effect “suggests that reductions in physical activity, specifically within the first 5 years of disease onset, may be detrimental to mental health,” the researchers emphasized. Given that the study population was newly diagnosed with PD “it is likely the within-person terms are more sensitive to changes in anxiety, physical activity, and cognition that are more directly the result of the PD process, as opposed to lifestyle/preexisting traits,” they said.

The study findings were limited by several factors, including the use of self-reports to measure physical activity, and the lack of granular information about the details of physical activity, the researchers noted. Another limitation was the inclusion of only newly diagnosed PD patients, which might limit generalizability.

“Future research is warranted to understand if other modes, intensities, or complexities of physical activity impact individuals with PD in a different manner in relation to cognition,” they said.

Dr. Jones and colleagues had no disclosures. The PPMI is supported by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including numerous pharmaceutical companies.

Parkinson’s disease patients who develop anxiety early in their disease are at risk for reduced physical activity, which promotes further anxiety and cognitive decline, data from nearly 500 individuals show.

Anxiety occurs in 20%-60% of Parkinson’s disease (PD) patients but often goes undiagnosed, wrote Jacob D. Jones, PhD, of California State University, San Bernardino, and colleagues.

“Anxiety can attenuate motivation to engage in physical activity leading to more anxiety and other negative cognitive outcomes,” although physical activity has been shown to improve cognitive function in PD patients, they said. However, physical activity as a mediator between anxiety and cognitive function in PD has not been well studied, they noted.

In a study published in Mental Health and Physical Activity the researchers identified 487 adults with newly diagnosed PD within the past 2 years who were enrolled in the Parkinson’s Progression Markers Initiative. Participants were followed for up to 5 years and completed neuropsychological tests, tests of motor severity, and self-reports on anxiety and physical activity. Anxiety was assessed using the State-Trait Anxiety Inventory-Trait (STAI-T) subscale. Physical activity was assessed using the Physical Activity Scale for the Elderly (PASE). Motor severity was assessed using the Unified Parkinson’s Disease Rating Scale-Part III (UPDRS). The average age of the participants was 61 years, 65% were men, and 96% were White.

Using a direct-effect model, the researchers found that individuals whose anxiety increased during the study period also showed signs of cognitive decline. A significant between-person effect showed that individuals who were generally more anxious also scored lower on cognitive tests over the 5-year study period.

In a mediation model computed with structural equation modeling, physical activity mediated the link between anxiety and cognition, most notably household activity.

“There was a significant within-person association between anxiety and household activities, meaning that individuals who became more anxious over the 5-year study also became less active in the home,” reported Dr. Jones and colleagues.

However, no significant indirect effect was noted regarding the between-person findings of the impact of physical activity on anxiety and cognitive decline. Although more severe anxiety was associated with less activity, cognitive performance was not associated with either type of physical activity.

The presence of a within-person effect “suggests that reductions in physical activity, specifically within the first 5 years of disease onset, may be detrimental to mental health,” the researchers emphasized. Given that the study population was newly diagnosed with PD “it is likely the within-person terms are more sensitive to changes in anxiety, physical activity, and cognition that are more directly the result of the PD process, as opposed to lifestyle/preexisting traits,” they said.

The study findings were limited by several factors, including the use of self-reports to measure physical activity, and the lack of granular information about the details of physical activity, the researchers noted. Another limitation was the inclusion of only newly diagnosed PD patients, which might limit generalizability.

“Future research is warranted to understand if other modes, intensities, or complexities of physical activity impact individuals with PD in a different manner in relation to cognition,” they said.

Dr. Jones and colleagues had no disclosures. The PPMI is supported by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including numerous pharmaceutical companies.

In this month’s column we continue to discuss recommendations from the gynecologic oncologist to the general gynecologist.

Don’t screen average-risk women for ovarian cancer.

Ovarian cancer is most often diagnosed at an advanced stage, which limits the curability of the disease. Consequently, there is a strong focus on attempting to diagnose the disease at earlier, more curable stages. This leads to the impulse by some well-intentioned providers to implement screening tests, such as ultrasounds and tumor markers, for all women. Unfortunately, the screening of “average risk” women for ovarian cancer is not recommended. Randomized controlled trials of tens of thousands of women have not observed a clinically significant decrease in ovarian cancer mortality with the addition of screening with tumor markers and ultrasound.¹ These studies did observe a false-positive rate of 5%. While that may seem like a low rate of false-positive testing, the definitive diagnostic test which follows is a major abdominal surgery (oophorectomy) and serious complications are encountered in 15% of patients undergoing surgery for false-positive ovarian cancer screening.¹ Therefore, quite simply, the harms are not balanced by benefits.

The key to offering patients appropriate and effective screening is case selection. It is important to identify which patients are at higher risk for ovarian cancer and offer those women testing for germline mutations and screening strategies. An important component of a well-woman visit is to take a thorough family history of cancer. Women are considered at high risk for having hereditary predisposition to ovarian cancer if they have a first- or second-degree relative with breast cancer younger than 45-50 years, or any age if Ashkenazi Jewish, triple-negative breast cancer younger than 60 years of age, two or more primary breast cancers with the first diagnosed at less than 50 years of age, male breast cancer, ovarian cancer, pancreatic cancer, a known BRCA 1/2 mutation, or a personal history of those same conditions. These women should be recommended to undergo genetic testing for BRCA 1, 2, and Lynch syndrome. They should not automatically be offered ovarian cancer screening. If a patient has a more remote family history for ovarian cancer, their personal risk may be somewhat elevated above the baseline population risk, however, not substantially enough to justify implementing screening in the absence of a confirmed genetic mutation.

While screening tests may not be appropriate for all patients, all patients should be asked about the early symptoms of ovarian cancer because these are consistently present, and frequently overlooked, prior to the eventual diagnosis of advanced disease. Those symptoms include abdominal discomfort, abdominal swelling and bloating, and urinary urgency.² Consider offering all patients a dedicated ovarian cancer specific review of systems that includes inquiries about these symptoms at their annual wellness visits.
 

Opt for vertical midline incisions when surgery is anticipated to be complex

What is the first thing gynecologic oncologists do when called in to assist in a difficult gynecologic procedure? Get better exposure. Exposure is the cornerstone of safe, effective surgery. Sometimes this simply means placing a more effective retractor. In other cases, it might mean extending the incision. However, if the incision is a low transverse incision (the go-to for many gynecologists because of its favorable cosmetic and pain-producing profile) this proves to be difficult. Attempting to assist in a complicated case, such as a frozen pelvis, severed ureter or rectal injury, through a pfannensteil incision can be extraordinarily difficult, and while these incisions can be extended by incising the rectus muscle bellies, upper abdominal visualization remains elusive in most patients. This is particularly problematic if the ureter or splenic flexure need to be mobilized, or if extensive lysis of adhesions is necessary to ensure there is no occult enterotomy. As my mentor Dr. John Soper once described to me: “It’s like trying to scratch your armpit by reaching through your fly.”

While pfannensteil incisions come naturally, and comfortably, to most gynecologists, likely because of their frequent application during cesarean section, all gynecologists should be confident in the steps and anatomy for vertical midline, or paramedian incisions. This is not only beneficial for complex gynecologic cases, but also in the event of vascular emergency. In the hands of an experienced abdominal/pelvic surgeon, the vertical midline incision is the quickest way to safely enter the abdomen, and provides the kind of exposure that may be critical in safely repairing or controlling hemorrhage from a major vessel.

While low transverse incisions may be more cosmetic, less painful, and associated with fewer wound complications, our first concern as surgeons should be mitigating complications. In situations where risks of complications are high, it is best to not handicap ourselves with the incision location. And always remember, wound complications are highest when a transverse incision needs to be converted to a vertical one with a “T.”
 

It’s not just about diagnosis of cancer, it’s also prevention

Detection of cancer is an important role of the obstetrician gynecologist. However, equally important is being able to seize opportunities for cancer prevention. Cervical, vulvar, endometrial and ovarian cancer are all known to have preventative strategies.

All patients up to the age of 45 should be offered vaccination against HPV. Initial indications for HPV vaccination were for women up to age 26; however, recent data support the safety and efficacy of the vaccine in older women.³ HPV vaccination is most effective at preventing cancer when administered prior to exposure (ideally age 9-11), leaving this in the hands of our pediatrician colleagues. However, we must be vigilant to inquire about vaccination status for all our patients and encourage vaccines for those who were missed earlier in their life.

Patients should be counseled regarding the significant risk reduction for cancer that is gained from use of oral hormonal contraceptives and progestin-releasing IUDs (especially for endometrial and ovarian cancers). Providing them with knowledge of this information when considering options for contraception or menstrual cycle management is important in their decision-making process.

Endometrial cancer incidence is sadly on the rise in the United States, likely secondary to increasing rates of obesity. Pregnancy is a time when many women begin to gain, and accumulate, weight and therefore obstetric providers have a unique opportunity to assist patients in strategies to normalize their weight after pregnancy. Many of my patients with endometrial cancer state that they have never heard that it is associated with obesity. This suggests that more can be done to educate patients on the carcinogenic effect of obesity (for both endometrial and breast cancer), which may aid in motivating change of modifiable behaviors.

The fallopian tubes are the source of many ovarian cancers and knowledge of this has led to the recommendation to perform opportunistic salpingectomy as a cancer risk-reducing strategy. Hysterectomy and sterilization procedures are most apropos for this modification. While prospective data to confirm a reduced risk of ovarian cancer with opportunistic salpingectomy are lacking, a reduced incidence of cancer has been observed when the tubes have been removed for indicated surgeries; there appear to be no significant deleterious sequelae.^4,5 A focus should be made on removal of the entire distal third of the tube, particularly the fimbriated ends, as this is the portion most implicated in malignancy.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no relevant disclosures. Contact her at [email protected].
 

References

1. Buys SS et al. JAMA. 2011;305(22):2295.

2. Goff BA et al. JAMA. 2004;291(22):2705.

3. Castellsagué X et al. Br J Cancer. 2011;105(1):28.

4. Yoon SH et al. Eur J Cancer. 2016 Mar;55:38-46.

5. Hanley GE et al. Am J Obstet Gynecol. 2018;219(2):172.

In this month’s column we continue to discuss recommendations from the gynecologic oncologist to the general gynecologist.

Don’t screen average-risk women for ovarian cancer.

Ovarian cancer is most often diagnosed at an advanced stage, which limits the curability of the disease. Consequently, there is a strong focus on attempting to diagnose the disease at earlier, more curable stages. This leads to the impulse by some well-intentioned providers to implement screening tests, such as ultrasounds and tumor markers, for all women. Unfortunately, the screening of “average risk” women for ovarian cancer is not recommended. Randomized controlled trials of tens of thousands of women have not observed a clinically significant decrease in ovarian cancer mortality with the addition of screening with tumor markers and ultrasound.¹ These studies did observe a false-positive rate of 5%. While that may seem like a low rate of false-positive testing, the definitive diagnostic test which follows is a major abdominal surgery (oophorectomy) and serious complications are encountered in 15% of patients undergoing surgery for false-positive ovarian cancer screening.¹ Therefore, quite simply, the harms are not balanced by benefits.

The key to offering patients appropriate and effective screening is case selection. It is important to identify which patients are at higher risk for ovarian cancer and offer those women testing for germline mutations and screening strategies. An important component of a well-woman visit is to take a thorough family history of cancer. Women are considered at high risk for having hereditary predisposition to ovarian cancer if they have a first- or second-degree relative with breast cancer younger than 45-50 years, or any age if Ashkenazi Jewish, triple-negative breast cancer younger than 60 years of age, two or more primary breast cancers with the first diagnosed at less than 50 years of age, male breast cancer, ovarian cancer, pancreatic cancer, a known BRCA 1/2 mutation, or a personal history of those same conditions. These women should be recommended to undergo genetic testing for BRCA 1, 2, and Lynch syndrome. They should not automatically be offered ovarian cancer screening. If a patient has a more remote family history for ovarian cancer, their personal risk may be somewhat elevated above the baseline population risk, however, not substantially enough to justify implementing screening in the absence of a confirmed genetic mutation.

While screening tests may not be appropriate for all patients, all patients should be asked about the early symptoms of ovarian cancer because these are consistently present, and frequently overlooked, prior to the eventual diagnosis of advanced disease. Those symptoms include abdominal discomfort, abdominal swelling and bloating, and urinary urgency.² Consider offering all patients a dedicated ovarian cancer specific review of systems that includes inquiries about these symptoms at their annual wellness visits.
 

Opt for vertical midline incisions when surgery is anticipated to be complex

What is the first thing gynecologic oncologists do when called in to assist in a difficult gynecologic procedure? Get better exposure. Exposure is the cornerstone of safe, effective surgery. Sometimes this simply means placing a more effective retractor. In other cases, it might mean extending the incision. However, if the incision is a low transverse incision (the go-to for many gynecologists because of its favorable cosmetic and pain-producing profile) this proves to be difficult. Attempting to assist in a complicated case, such as a frozen pelvis, severed ureter or rectal injury, through a pfannensteil incision can be extraordinarily difficult, and while these incisions can be extended by incising the rectus muscle bellies, upper abdominal visualization remains elusive in most patients. This is particularly problematic if the ureter or splenic flexure need to be mobilized, or if extensive lysis of adhesions is necessary to ensure there is no occult enterotomy. As my mentor Dr. John Soper once described to me: “It’s like trying to scratch your armpit by reaching through your fly.”

While pfannensteil incisions come naturally, and comfortably, to most gynecologists, likely because of their frequent application during cesarean section, all gynecologists should be confident in the steps and anatomy for vertical midline, or paramedian incisions. This is not only beneficial for complex gynecologic cases, but also in the event of vascular emergency. In the hands of an experienced abdominal/pelvic surgeon, the vertical midline incision is the quickest way to safely enter the abdomen, and provides the kind of exposure that may be critical in safely repairing or controlling hemorrhage from a major vessel.

While low transverse incisions may be more cosmetic, less painful, and associated with fewer wound complications, our first concern as surgeons should be mitigating complications. In situations where risks of complications are high, it is best to not handicap ourselves with the incision location. And always remember, wound complications are highest when a transverse incision needs to be converted to a vertical one with a “T.”
 

It’s not just about diagnosis of cancer, it’s also prevention

Detection of cancer is an important role of the obstetrician gynecologist. However, equally important is being able to seize opportunities for cancer prevention. Cervical, vulvar, endometrial and ovarian cancer are all known to have preventative strategies.

All patients up to the age of 45 should be offered vaccination against HPV. Initial indications for HPV vaccination were for women up to age 26; however, recent data support the safety and efficacy of the vaccine in older women.³ HPV vaccination is most effective at preventing cancer when administered prior to exposure (ideally age 9-11), leaving this in the hands of our pediatrician colleagues. However, we must be vigilant to inquire about vaccination status for all our patients and encourage vaccines for those who were missed earlier in their life.

Patients should be counseled regarding the significant risk reduction for cancer that is gained from use of oral hormonal contraceptives and progestin-releasing IUDs (especially for endometrial and ovarian cancers). Providing them with knowledge of this information when considering options for contraception or menstrual cycle management is important in their decision-making process.

Endometrial cancer incidence is sadly on the rise in the United States, likely secondary to increasing rates of obesity. Pregnancy is a time when many women begin to gain, and accumulate, weight and therefore obstetric providers have a unique opportunity to assist patients in strategies to normalize their weight after pregnancy. Many of my patients with endometrial cancer state that they have never heard that it is associated with obesity. This suggests that more can be done to educate patients on the carcinogenic effect of obesity (for both endometrial and breast cancer), which may aid in motivating change of modifiable behaviors.

The fallopian tubes are the source of many ovarian cancers and knowledge of this has led to the recommendation to perform opportunistic salpingectomy as a cancer risk-reducing strategy. Hysterectomy and sterilization procedures are most apropos for this modification. While prospective data to confirm a reduced risk of ovarian cancer with opportunistic salpingectomy are lacking, a reduced incidence of cancer has been observed when the tubes have been removed for indicated surgeries; there appear to be no significant deleterious sequelae.^4,5 A focus should be made on removal of the entire distal third of the tube, particularly the fimbriated ends, as this is the portion most implicated in malignancy.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no relevant disclosures. Contact her at [email protected].
 

References

1. Buys SS et al. JAMA. 2011;305(22):2295.

2. Goff BA et al. JAMA. 2004;291(22):2705.

3. Castellsagué X et al. Br J Cancer. 2011;105(1):28.

4. Yoon SH et al. Eur J Cancer. 2016 Mar;55:38-46.

5. Hanley GE et al. Am J Obstet Gynecol. 2018;219(2):172.

In this month’s column we continue to discuss recommendations from the gynecologic oncologist to the general gynecologist.

Don’t screen average-risk women for ovarian cancer.

Ovarian cancer is most often diagnosed at an advanced stage, which limits the curability of the disease. Consequently, there is a strong focus on attempting to diagnose the disease at earlier, more curable stages. This leads to the impulse by some well-intentioned providers to implement screening tests, such as ultrasounds and tumor markers, for all women. Unfortunately, the screening of “average risk” women for ovarian cancer is not recommended. Randomized controlled trials of tens of thousands of women have not observed a clinically significant decrease in ovarian cancer mortality with the addition of screening with tumor markers and ultrasound.¹ These studies did observe a false-positive rate of 5%. While that may seem like a low rate of false-positive testing, the definitive diagnostic test which follows is a major abdominal surgery (oophorectomy) and serious complications are encountered in 15% of patients undergoing surgery for false-positive ovarian cancer screening.¹ Therefore, quite simply, the harms are not balanced by benefits.

The key to offering patients appropriate and effective screening is case selection. It is important to identify which patients are at higher risk for ovarian cancer and offer those women testing for germline mutations and screening strategies. An important component of a well-woman visit is to take a thorough family history of cancer. Women are considered at high risk for having hereditary predisposition to ovarian cancer if they have a first- or second-degree relative with breast cancer younger than 45-50 years, or any age if Ashkenazi Jewish, triple-negative breast cancer younger than 60 years of age, two or more primary breast cancers with the first diagnosed at less than 50 years of age, male breast cancer, ovarian cancer, pancreatic cancer, a known BRCA 1/2 mutation, or a personal history of those same conditions. These women should be recommended to undergo genetic testing for BRCA 1, 2, and Lynch syndrome. They should not automatically be offered ovarian cancer screening. If a patient has a more remote family history for ovarian cancer, their personal risk may be somewhat elevated above the baseline population risk, however, not substantially enough to justify implementing screening in the absence of a confirmed genetic mutation.

While screening tests may not be appropriate for all patients, all patients should be asked about the early symptoms of ovarian cancer because these are consistently present, and frequently overlooked, prior to the eventual diagnosis of advanced disease. Those symptoms include abdominal discomfort, abdominal swelling and bloating, and urinary urgency.² Consider offering all patients a dedicated ovarian cancer specific review of systems that includes inquiries about these symptoms at their annual wellness visits.
 

Opt for vertical midline incisions when surgery is anticipated to be complex

What is the first thing gynecologic oncologists do when called in to assist in a difficult gynecologic procedure? Get better exposure. Exposure is the cornerstone of safe, effective surgery. Sometimes this simply means placing a more effective retractor. In other cases, it might mean extending the incision. However, if the incision is a low transverse incision (the go-to for many gynecologists because of its favorable cosmetic and pain-producing profile) this proves to be difficult. Attempting to assist in a complicated case, such as a frozen pelvis, severed ureter or rectal injury, through a pfannensteil incision can be extraordinarily difficult, and while these incisions can be extended by incising the rectus muscle bellies, upper abdominal visualization remains elusive in most patients. This is particularly problematic if the ureter or splenic flexure need to be mobilized, or if extensive lysis of adhesions is necessary to ensure there is no occult enterotomy. As my mentor Dr. John Soper once described to me: “It’s like trying to scratch your armpit by reaching through your fly.”

While pfannensteil incisions come naturally, and comfortably, to most gynecologists, likely because of their frequent application during cesarean section, all gynecologists should be confident in the steps and anatomy for vertical midline, or paramedian incisions. This is not only beneficial for complex gynecologic cases, but also in the event of vascular emergency. In the hands of an experienced abdominal/pelvic surgeon, the vertical midline incision is the quickest way to safely enter the abdomen, and provides the kind of exposure that may be critical in safely repairing or controlling hemorrhage from a major vessel.

While low transverse incisions may be more cosmetic, less painful, and associated with fewer wound complications, our first concern as surgeons should be mitigating complications. In situations where risks of complications are high, it is best to not handicap ourselves with the incision location. And always remember, wound complications are highest when a transverse incision needs to be converted to a vertical one with a “T.”
 

It’s not just about diagnosis of cancer, it’s also prevention

Detection of cancer is an important role of the obstetrician gynecologist. However, equally important is being able to seize opportunities for cancer prevention. Cervical, vulvar, endometrial and ovarian cancer are all known to have preventative strategies.

All patients up to the age of 45 should be offered vaccination against HPV. Initial indications for HPV vaccination were for women up to age 26; however, recent data support the safety and efficacy of the vaccine in older women.³ HPV vaccination is most effective at preventing cancer when administered prior to exposure (ideally age 9-11), leaving this in the hands of our pediatrician colleagues. However, we must be vigilant to inquire about vaccination status for all our patients and encourage vaccines for those who were missed earlier in their life.

Patients should be counseled regarding the significant risk reduction for cancer that is gained from use of oral hormonal contraceptives and progestin-releasing IUDs (especially for endometrial and ovarian cancers). Providing them with knowledge of this information when considering options for contraception or menstrual cycle management is important in their decision-making process.

Endometrial cancer incidence is sadly on the rise in the United States, likely secondary to increasing rates of obesity. Pregnancy is a time when many women begin to gain, and accumulate, weight and therefore obstetric providers have a unique opportunity to assist patients in strategies to normalize their weight after pregnancy. Many of my patients with endometrial cancer state that they have never heard that it is associated with obesity. This suggests that more can be done to educate patients on the carcinogenic effect of obesity (for both endometrial and breast cancer), which may aid in motivating change of modifiable behaviors.

The fallopian tubes are the source of many ovarian cancers and knowledge of this has led to the recommendation to perform opportunistic salpingectomy as a cancer risk-reducing strategy. Hysterectomy and sterilization procedures are most apropos for this modification. While prospective data to confirm a reduced risk of ovarian cancer with opportunistic salpingectomy are lacking, a reduced incidence of cancer has been observed when the tubes have been removed for indicated surgeries; there appear to be no significant deleterious sequelae.^4,5 A focus should be made on removal of the entire distal third of the tube, particularly the fimbriated ends, as this is the portion most implicated in malignancy.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no relevant disclosures. Contact her at [email protected].
 

References

1. Buys SS et al. JAMA. 2011;305(22):2295.

2. Goff BA et al. JAMA. 2004;291(22):2705.

3. Castellsagué X et al. Br J Cancer. 2011;105(1):28.

4. Yoon SH et al. Eur J Cancer. 2016 Mar;55:38-46.

5. Hanley GE et al. Am J Obstet Gynecol. 2018;219(2):172.

Obstructive sleep apnea is becoming more common in children and adolescents as the prevalence of obesity increases, but it may also be a preventable risk factor for cardiovascular disease, according to a new scientific statement from the American Heart Association.

The statement focuses on the links between OSA and CVD risk factors in children and adolescents, and reviews diagnostic strategies and treatments. The writing committee reported that 1%-6% of children and adolescents have OSA, as do up to 60% of adolescents considered obese.

The statement was created by the AHA’s Atherosclerosis, Hypertension, and Obesity in the Young subcommittee of the Council on Cardiovascular Disease in the Young and was published online in the Journal of the American Heart Association.

Carissa M. Baker-Smith, MD, chair of the writing group chair and director of pediatric preventive cardiology at Nemours Cardiac Center, Alfred I. duPont Hospital for Children, Wilmington, Del., explained the rationale for issuing the statement at this time, noting that the relationship between OSA and CVD in adults is well documented.

“There has been less focus on the importance of recognizing and treating sleep apnea in youth,” she said in an interview. “Thus, we felt that it was vitally important to get the word out to parents and to providers that paying attention to the quality and duration of your child’s sleep is vitally important to a child’s long-term heart health. Risk factors for heart disease, when present in childhood, can persist into adulthood.”
 

Clarity on polysomnography

For making the diagnosis of OSA in children, the statement provides clarity on the use of polysomnography and the role of the apnea-hypopnea index, which is lower in children with OSA than in adults. “One controversy, or at least as I saw it, was whether or not polysomnography testing is always required to make the diagnosis of OSA and before proceeding with tonsil and adenoid removal among children for whom enlarged tonsils and adenoids are present,” Dr. Baker-Smith said. “Polysomnography testing is not always needed before an ear, nose, and throat surgeon may recommend surgery.”

The statement also noted that history and physical examination may not yield enough reliable information to distinguish OSA from snoring.

In areas where sleep laboratories that work with children aren’t available, alternative tests such as daytime nap polysomnography, nocturnal oximetry, and nocturnal video recording may be used – with a caveat. “These alternative tests have weaker positive and negative predictive values when compared with polysomnography,” the writing committee noted. Home sleep apnea tests aren’t recommended in children. Questionnaires “are useful as screening, but not as diagnostic tools.”

Pediatric patients being evaluated for OSA should also be screened for hypertension and metabolic syndrome, as well as central nervous system and behavioral disorders. Diagnosing OSA in children and adolescents requires “a high index of suspicion,” the committee wrote.

Pediatricians and pediatric cardiologists should exercise that high index of suspicion when receiving referrals for cardiac evaluations for attention deficit hyperactivity disorder medication, Dr. Baker-Smith said. “Take the time to ask about a child’s sleep – snoring, apnea, etc. – especially if the child has obesity, difficulty focusing during the day, and if there is evidence of systemic hypertension or other signs of metabolic syndrome,” she said.

Risk factors for OSA in children

The statement also reviewed risk factors for OSA, among them obesity, particularly among children younger than 6 years. Other risk factors include upper and lower airway disease, hypotonia, parental history of hyperplasia of the adenoids and tonsils, craniofacial malformations, and neuromuscular disorders. However, the committee cited “limited data” to support that children with congenital heart disease may be at greater risk for OSA and sleep-disordered breathing (SDB).

Black children are at significantly greater risk, and socioeconomic factors “may be potential confounders,” the committee stated. Other risk factors include allergic rhinitis and sickle cell disease.

But the statement underscores that “obesity is the main risk factor” for OSA in children and adolescents, and that the presence of increased inflammation may explain this relationship. Steroids may alleviate these symptoms, even in nonobese children, and removal of the adenoids or tonsils is an option to reduce inflammation in children with OSA.

“Obesity is a significant risk factor for sleep disturbances and obstructive sleep apnea, and the severity of sleep apnea may be improved by weight-loss interventions, which then improves metabolic syndrome factors such as insulin sensitivity,” Dr. Baker-Smith said. “We need to increase awareness about how the rising prevalence of obesity may be impacting sleep quality in kids and recognize sleep-disordered breathing as something that could contribute to risks for hypertension and later cardiovascular disease.”

Children in whom OSA is suspected should also undergo screening for metabolic syndrome, and central nervous system and behavioral disorders.
 

Cardiovascular risks

The statement explores the connection between cardiovascular complications and SDB and OSA in depth.

“Inadequate sleep duration of < 5 hours per night in children and adolescents has been linked to an increased risk of hypertension and is also associated with an increased prevalence of obesity,” the committee wrote.

However, the statement left one question hanging: whether OSA alone or obesity cause higher BP in younger patients with OSA. But the committee concluded that BP levels increase with the severity of OSA, although the effects can vary with age. OSA in children peaks between ages 2 and 8, corresponding to the peak prevalence of hypertrophy of the tonsils and adenoids. Children aged 10-11 with more severe OSA may have BP dysregulation, while older adolescents develop higher sustained BP. Obesity may be a confounder for daytime BP elevations, while nighttime hypertension depends less on obesity and more on OSA severity.

“OSA is associated with abnormal BP in youth and, in particular, higher nighttime blood pressures and loss of the normal decline in BP that should occur during sleep,” Dr. Baker-Smith said. “Children with OSA appear to have higher BP than controls during both sleep and wake times, and BP levels increase with increasing severity of OSA.”

Nonetheless, children with OSA are at greater risk for other cardiovascular problems. Left ventricular hypertrophy may be a secondary outcome. “The presence of obstructive sleep apnea in children is associated with an 11-fold increased risk for LVH in children, a relationship not seen in the presence of primary snoring alone,” Dr. Baker-Smith said.

Dr. Baker-Smith had no relevant disclosures. Coauthor Amal Isaiah, MD, is coinventor of an imaging system for sleep apnea and receives royalties from the University of Maryland. The other coauthors have no relevant financial relationships to disclose.

[email protected]

Obstructive sleep apnea is becoming more common in children and adolescents as the prevalence of obesity increases, but it may also be a preventable risk factor for cardiovascular disease, according to a new scientific statement from the American Heart Association.

The statement focuses on the links between OSA and CVD risk factors in children and adolescents, and reviews diagnostic strategies and treatments. The writing committee reported that 1%-6% of children and adolescents have OSA, as do up to 60% of adolescents considered obese.

The statement was created by the AHA’s Atherosclerosis, Hypertension, and Obesity in the Young subcommittee of the Council on Cardiovascular Disease in the Young and was published online in the Journal of the American Heart Association.

Carissa M. Baker-Smith, MD, chair of the writing group chair and director of pediatric preventive cardiology at Nemours Cardiac Center, Alfred I. duPont Hospital for Children, Wilmington, Del., explained the rationale for issuing the statement at this time, noting that the relationship between OSA and CVD in adults is well documented.

“There has been less focus on the importance of recognizing and treating sleep apnea in youth,” she said in an interview. “Thus, we felt that it was vitally important to get the word out to parents and to providers that paying attention to the quality and duration of your child’s sleep is vitally important to a child’s long-term heart health. Risk factors for heart disease, when present in childhood, can persist into adulthood.”
 

Clarity on polysomnography

For making the diagnosis of OSA in children, the statement provides clarity on the use of polysomnography and the role of the apnea-hypopnea index, which is lower in children with OSA than in adults. “One controversy, or at least as I saw it, was whether or not polysomnography testing is always required to make the diagnosis of OSA and before proceeding with tonsil and adenoid removal among children for whom enlarged tonsils and adenoids are present,” Dr. Baker-Smith said. “Polysomnography testing is not always needed before an ear, nose, and throat surgeon may recommend surgery.”

The statement also noted that history and physical examination may not yield enough reliable information to distinguish OSA from snoring.

In areas where sleep laboratories that work with children aren’t available, alternative tests such as daytime nap polysomnography, nocturnal oximetry, and nocturnal video recording may be used – with a caveat. “These alternative tests have weaker positive and negative predictive values when compared with polysomnography,” the writing committee noted. Home sleep apnea tests aren’t recommended in children. Questionnaires “are useful as screening, but not as diagnostic tools.”

Pediatric patients being evaluated for OSA should also be screened for hypertension and metabolic syndrome, as well as central nervous system and behavioral disorders. Diagnosing OSA in children and adolescents requires “a high index of suspicion,” the committee wrote.

Pediatricians and pediatric cardiologists should exercise that high index of suspicion when receiving referrals for cardiac evaluations for attention deficit hyperactivity disorder medication, Dr. Baker-Smith said. “Take the time to ask about a child’s sleep – snoring, apnea, etc. – especially if the child has obesity, difficulty focusing during the day, and if there is evidence of systemic hypertension or other signs of metabolic syndrome,” she said.

Risk factors for OSA in children

The statement also reviewed risk factors for OSA, among them obesity, particularly among children younger than 6 years. Other risk factors include upper and lower airway disease, hypotonia, parental history of hyperplasia of the adenoids and tonsils, craniofacial malformations, and neuromuscular disorders. However, the committee cited “limited data” to support that children with congenital heart disease may be at greater risk for OSA and sleep-disordered breathing (SDB).

Black children are at significantly greater risk, and socioeconomic factors “may be potential confounders,” the committee stated. Other risk factors include allergic rhinitis and sickle cell disease.

But the statement underscores that “obesity is the main risk factor” for OSA in children and adolescents, and that the presence of increased inflammation may explain this relationship. Steroids may alleviate these symptoms, even in nonobese children, and removal of the adenoids or tonsils is an option to reduce inflammation in children with OSA.

“Obesity is a significant risk factor for sleep disturbances and obstructive sleep apnea, and the severity of sleep apnea may be improved by weight-loss interventions, which then improves metabolic syndrome factors such as insulin sensitivity,” Dr. Baker-Smith said. “We need to increase awareness about how the rising prevalence of obesity may be impacting sleep quality in kids and recognize sleep-disordered breathing as something that could contribute to risks for hypertension and later cardiovascular disease.”

Children in whom OSA is suspected should also undergo screening for metabolic syndrome, and central nervous system and behavioral disorders.
 

Cardiovascular risks

The statement explores the connection between cardiovascular complications and SDB and OSA in depth.

“Inadequate sleep duration of < 5 hours per night in children and adolescents has been linked to an increased risk of hypertension and is also associated with an increased prevalence of obesity,” the committee wrote.

However, the statement left one question hanging: whether OSA alone or obesity cause higher BP in younger patients with OSA. But the committee concluded that BP levels increase with the severity of OSA, although the effects can vary with age. OSA in children peaks between ages 2 and 8, corresponding to the peak prevalence of hypertrophy of the tonsils and adenoids. Children aged 10-11 with more severe OSA may have BP dysregulation, while older adolescents develop higher sustained BP. Obesity may be a confounder for daytime BP elevations, while nighttime hypertension depends less on obesity and more on OSA severity.

“OSA is associated with abnormal BP in youth and, in particular, higher nighttime blood pressures and loss of the normal decline in BP that should occur during sleep,” Dr. Baker-Smith said. “Children with OSA appear to have higher BP than controls during both sleep and wake times, and BP levels increase with increasing severity of OSA.”

Nonetheless, children with OSA are at greater risk for other cardiovascular problems. Left ventricular hypertrophy may be a secondary outcome. “The presence of obstructive sleep apnea in children is associated with an 11-fold increased risk for LVH in children, a relationship not seen in the presence of primary snoring alone,” Dr. Baker-Smith said.

Dr. Baker-Smith had no relevant disclosures. Coauthor Amal Isaiah, MD, is coinventor of an imaging system for sleep apnea and receives royalties from the University of Maryland. The other coauthors have no relevant financial relationships to disclose.

[email protected]

Obstructive sleep apnea is becoming more common in children and adolescents as the prevalence of obesity increases, but it may also be a preventable risk factor for cardiovascular disease, according to a new scientific statement from the American Heart Association.

The statement focuses on the links between OSA and CVD risk factors in children and adolescents, and reviews diagnostic strategies and treatments. The writing committee reported that 1%-6% of children and adolescents have OSA, as do up to 60% of adolescents considered obese.

The statement was created by the AHA’s Atherosclerosis, Hypertension, and Obesity in the Young subcommittee of the Council on Cardiovascular Disease in the Young and was published online in the Journal of the American Heart Association.

Carissa M. Baker-Smith, MD, chair of the writing group chair and director of pediatric preventive cardiology at Nemours Cardiac Center, Alfred I. duPont Hospital for Children, Wilmington, Del., explained the rationale for issuing the statement at this time, noting that the relationship between OSA and CVD in adults is well documented.

“There has been less focus on the importance of recognizing and treating sleep apnea in youth,” she said in an interview. “Thus, we felt that it was vitally important to get the word out to parents and to providers that paying attention to the quality and duration of your child’s sleep is vitally important to a child’s long-term heart health. Risk factors for heart disease, when present in childhood, can persist into adulthood.”
 

Clarity on polysomnography

For making the diagnosis of OSA in children, the statement provides clarity on the use of polysomnography and the role of the apnea-hypopnea index, which is lower in children with OSA than in adults. “One controversy, or at least as I saw it, was whether or not polysomnography testing is always required to make the diagnosis of OSA and before proceeding with tonsil and adenoid removal among children for whom enlarged tonsils and adenoids are present,” Dr. Baker-Smith said. “Polysomnography testing is not always needed before an ear, nose, and throat surgeon may recommend surgery.”

The statement also noted that history and physical examination may not yield enough reliable information to distinguish OSA from snoring.

In areas where sleep laboratories that work with children aren’t available, alternative tests such as daytime nap polysomnography, nocturnal oximetry, and nocturnal video recording may be used – with a caveat. “These alternative tests have weaker positive and negative predictive values when compared with polysomnography,” the writing committee noted. Home sleep apnea tests aren’t recommended in children. Questionnaires “are useful as screening, but not as diagnostic tools.”

Pediatric patients being evaluated for OSA should also be screened for hypertension and metabolic syndrome, as well as central nervous system and behavioral disorders. Diagnosing OSA in children and adolescents requires “a high index of suspicion,” the committee wrote.

Pediatricians and pediatric cardiologists should exercise that high index of suspicion when receiving referrals for cardiac evaluations for attention deficit hyperactivity disorder medication, Dr. Baker-Smith said. “Take the time to ask about a child’s sleep – snoring, apnea, etc. – especially if the child has obesity, difficulty focusing during the day, and if there is evidence of systemic hypertension or other signs of metabolic syndrome,” she said.

Risk factors for OSA in children

The statement also reviewed risk factors for OSA, among them obesity, particularly among children younger than 6 years. Other risk factors include upper and lower airway disease, hypotonia, parental history of hyperplasia of the adenoids and tonsils, craniofacial malformations, and neuromuscular disorders. However, the committee cited “limited data” to support that children with congenital heart disease may be at greater risk for OSA and sleep-disordered breathing (SDB).

Black children are at significantly greater risk, and socioeconomic factors “may be potential confounders,” the committee stated. Other risk factors include allergic rhinitis and sickle cell disease.

But the statement underscores that “obesity is the main risk factor” for OSA in children and adolescents, and that the presence of increased inflammation may explain this relationship. Steroids may alleviate these symptoms, even in nonobese children, and removal of the adenoids or tonsils is an option to reduce inflammation in children with OSA.

“Obesity is a significant risk factor for sleep disturbances and obstructive sleep apnea, and the severity of sleep apnea may be improved by weight-loss interventions, which then improves metabolic syndrome factors such as insulin sensitivity,” Dr. Baker-Smith said. “We need to increase awareness about how the rising prevalence of obesity may be impacting sleep quality in kids and recognize sleep-disordered breathing as something that could contribute to risks for hypertension and later cardiovascular disease.”

Children in whom OSA is suspected should also undergo screening for metabolic syndrome, and central nervous system and behavioral disorders.
 

Cardiovascular risks

The statement explores the connection between cardiovascular complications and SDB and OSA in depth.

“Inadequate sleep duration of < 5 hours per night in children and adolescents has been linked to an increased risk of hypertension and is also associated with an increased prevalence of obesity,” the committee wrote.

However, the statement left one question hanging: whether OSA alone or obesity cause higher BP in younger patients with OSA. But the committee concluded that BP levels increase with the severity of OSA, although the effects can vary with age. OSA in children peaks between ages 2 and 8, corresponding to the peak prevalence of hypertrophy of the tonsils and adenoids. Children aged 10-11 with more severe OSA may have BP dysregulation, while older adolescents develop higher sustained BP. Obesity may be a confounder for daytime BP elevations, while nighttime hypertension depends less on obesity and more on OSA severity.

“OSA is associated with abnormal BP in youth and, in particular, higher nighttime blood pressures and loss of the normal decline in BP that should occur during sleep,” Dr. Baker-Smith said. “Children with OSA appear to have higher BP than controls during both sleep and wake times, and BP levels increase with increasing severity of OSA.”

Nonetheless, children with OSA are at greater risk for other cardiovascular problems. Left ventricular hypertrophy may be a secondary outcome. “The presence of obstructive sleep apnea in children is associated with an 11-fold increased risk for LVH in children, a relationship not seen in the presence of primary snoring alone,” Dr. Baker-Smith said.

Dr. Baker-Smith had no relevant disclosures. Coauthor Amal Isaiah, MD, is coinventor of an imaging system for sleep apnea and receives royalties from the University of Maryland. The other coauthors have no relevant financial relationships to disclose.

[email protected]

A COVID-19 booster shot may be beneficial for patients with cancer who are undergoing treatment, according to new findings from an Israeli case-control study.

The seropositivity rate among the patients with cancer remained high (87%) about 4 months after the patients had received the second BNT162b2 (Pfizer/BioNTech) vaccination. However, the median IgG titer in the patients and the control persons who were without cancer decreased over time. Notably, in a previous analysis that the authors conducted and in the current one, the IgG titers were statistically significantly lower in the patients with cancer as compared to control persons.

The correlation between antibody levels following vaccination and clinical protection has yet to be proven, but the accumulating evidence supports antibody response as a possible correlate of disease protection.

“Our data can’t predict if a third booster dose is necessary,” said study author Salomon M. Stemmer, MD, professor at the Institute of Oncology of Rabin Medical Center, Petah Tikva, Israel. “It does seem quite logical that a booster dose will cause an increase in IgG levels.”

The findings were published Aug. 11, 2021, in a research letter in JAMA Oncology.

In their previous study, Dr. Stemmer and colleagues compared the rates of anti–spike antibody response to the initial shot of the BNT162b2 vaccine among 102 adults with solid-tumor cancers who were undergoing treatment with that of 78 healthy control persons. They found that a high percentage of patients undergoing treatment for cancer (90%) achieved a sufficient antibody response to the BNT162b2 vaccine.
 

Booster endorsed

Responses to COVID-19 vaccination have varied among patients with cancer. For patients with solid tumors, responses have been good even while the patients were receiving systemic therapy. However, among patients with blood cancers, particularly those receiving immunosuppressive therapies, responses have been poor. Studies have identified factors associated with a poor response, but it has been unclear whether to recommend booster shots.

In August the Food and Drug Administration authorized a third dose of either the Pfizer or the Moderna COVID-19 vaccine for all individuals with compromised immune systems. Those eligible for a third dose include solid-organ transplant recipients, those undergoing cancer treatments, and people with autoimmune diseases that suppress their immune systems.
 

IgG titers lower in cancer patients

In the current analysis, the authors evaluated the anti-S response in the patients with cancer approximately 4 months after they had received the second vaccine dose. They compared the responses in those patients with the responses in a control group.

The cohort included 95 patients from the prior study and 66 control persons. The most common malignancies were gastrointestinal (26%), lung (25%), and breast (18%).

All patients were receiving systemic therapy. Chemotherapy was the most common (28%), followed by immunotherapy (21%) and combination chemotherapy/biological therapy (20%).

At a median of 123 days after the second vaccination, 83 patients with cancer (87%) and all of the control patients (100%) were seropositive for anti-S IgG antibodies. The median titer levels were significantly lower among case patients as compared with control patients (417 AU/mL [interquartile range, 136-895] vs. 1,220 AU/mL [IQR, 588-1,987]; P < .001)

There was a 3.6-fold range in median titer values across tumor types and an even wider range (8.8-fold) across the different types of treatment. The lowest titers were observed among patients who had received immunotherapy plus chemotherapy/biological therapy (median [IQR], 94.4 [49.4-191] AU/mL vs. 147 [62.8-339] AU/mL).

In an exploratory multivariable analysis, treatments with chemotherapy plus immunotherapy and immunotherapy plus biological therapy were significantly associated with lower IgG titers.
 

No downside for cancer patients

The Biden administration announced a plan to begin booster COVID-19 vaccinations for all American adults in September, with recommendations that the third vaccine be given at least 8 months after the second mRNA vaccine dose.

Jeremy M. Levin, DPhil, the chairman and CEO of Ovid Therapeutics, explained that, concerning boosters, “it is inconceivable that we will have all data at this stage.

“Knowledge about how boosters work and don’t work and when you should ideally have them is imperfect,” he told this news organization. “However, we can have a lot of confidence in the fact that hundreds of millions of people have received the vaccine, so we know a lot about the safety and efficacy.”

Immunocompromised adults represent less than 5% of the total population, and most of the available data on vaccination are from patients who have undergone solid-organ transplant, Dr. Levin explained. Studies have shown that their response is less robust to vaccination in comparison with adults in the general population.

“Although it is still preliminary, the strongest data come from Israel,” he said, “where they found that the booster was highly effective and doubled the number of transplant patients who developed antibodies.”

But data are not yet available in the setting of cancer. “But even though we don’t have the data yet, the answer is that no matter, the booster process is essential,” he said. “The evidence we have is that boosters raise the immune response, and it is the best data we have now.”

Martin J. Edelman, MD, chair, department of hematology/oncology, Fox Chase Cancer Center, Philadelphia, noted that the current recommendation is that patients who are immunocompromised receive a booster immediately.

At his health system, this is interpreted to include patients who have undergone the following treatments: Transplant (solid-organ and bone marrow transplant), hemodialysis, hematologic malignancy treatment, active immunosuppressive (chemotherapy, chemoimmunotherapy, and nonhormonal or single-agent immunotherapy) treatment, rheumatology treatments, and high-dose steroids.

“As for cancer patients, we are making arrangements to vaccinate patients who meet the above criteria now,” he said. “There is no known downside to receiving booster immediately. While there may be less of a response than waiting for completion of treatment, we know that patients on active therapy are frequently able to mount a response, and any response is better than none.”

Dr. Edelman added that this area is changing very rapidly. “We will modify our approach as information and guidance from appropriate organizations, such as the FDA and CDC, become available.”

Dr. Stemmer has received institutional research grants from CAN-FITE, AstraZeneca, Bioline RX, BMS, Halozyme, Clovis Oncology, CTG Pharma, Exelixis, Geicam, Incyte, Lilly, Moderna, Teva Pharmaceuticals, and Roche, and owns stocks and options in CTG Pharma, DocBoxMD, Tyrnovo, VYPE, Cytora, and CAN-FITE. Dr. Edelman has received personal fees and other compensation from Windmil, Biomarker Strategies, AstraZeneca, Takeda, GlaxoSmithKline, Apexigen, Nektar, Bristol-Myers Squibb, Armo, Bergen Bio, and Apexigen outside the submitted work. He has submitted a patent for epigenetic modifications to increase susceptibility to radiopharmaceuticals and is a paid adviser for Kanaph and Flame. Dr. Levin is chairman and CEO of Ovid Therapeutics.

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

A COVID-19 booster shot may be beneficial for patients with cancer who are undergoing treatment, according to new findings from an Israeli case-control study.

The seropositivity rate among the patients with cancer remained high (87%) about 4 months after the patients had received the second BNT162b2 (Pfizer/BioNTech) vaccination. However, the median IgG titer in the patients and the control persons who were without cancer decreased over time. Notably, in a previous analysis that the authors conducted and in the current one, the IgG titers were statistically significantly lower in the patients with cancer as compared to control persons.

The correlation between antibody levels following vaccination and clinical protection has yet to be proven, but the accumulating evidence supports antibody response as a possible correlate of disease protection.

“Our data can’t predict if a third booster dose is necessary,” said study author Salomon M. Stemmer, MD, professor at the Institute of Oncology of Rabin Medical Center, Petah Tikva, Israel. “It does seem quite logical that a booster dose will cause an increase in IgG levels.”

The findings were published Aug. 11, 2021, in a research letter in JAMA Oncology.

In their previous study, Dr. Stemmer and colleagues compared the rates of anti–spike antibody response to the initial shot of the BNT162b2 vaccine among 102 adults with solid-tumor cancers who were undergoing treatment with that of 78 healthy control persons. They found that a high percentage of patients undergoing treatment for cancer (90%) achieved a sufficient antibody response to the BNT162b2 vaccine.
 

Booster endorsed

Responses to COVID-19 vaccination have varied among patients with cancer. For patients with solid tumors, responses have been good even while the patients were receiving systemic therapy. However, among patients with blood cancers, particularly those receiving immunosuppressive therapies, responses have been poor. Studies have identified factors associated with a poor response, but it has been unclear whether to recommend booster shots.

In August the Food and Drug Administration authorized a third dose of either the Pfizer or the Moderna COVID-19 vaccine for all individuals with compromised immune systems. Those eligible for a third dose include solid-organ transplant recipients, those undergoing cancer treatments, and people with autoimmune diseases that suppress their immune systems.
 

IgG titers lower in cancer patients

In the current analysis, the authors evaluated the anti-S response in the patients with cancer approximately 4 months after they had received the second vaccine dose. They compared the responses in those patients with the responses in a control group.

The cohort included 95 patients from the prior study and 66 control persons. The most common malignancies were gastrointestinal (26%), lung (25%), and breast (18%).

All patients were receiving systemic therapy. Chemotherapy was the most common (28%), followed by immunotherapy (21%) and combination chemotherapy/biological therapy (20%).

At a median of 123 days after the second vaccination, 83 patients with cancer (87%) and all of the control patients (100%) were seropositive for anti-S IgG antibodies. The median titer levels were significantly lower among case patients as compared with control patients (417 AU/mL [interquartile range, 136-895] vs. 1,220 AU/mL [IQR, 588-1,987]; P < .001)

There was a 3.6-fold range in median titer values across tumor types and an even wider range (8.8-fold) across the different types of treatment. The lowest titers were observed among patients who had received immunotherapy plus chemotherapy/biological therapy (median [IQR], 94.4 [49.4-191] AU/mL vs. 147 [62.8-339] AU/mL).

In an exploratory multivariable analysis, treatments with chemotherapy plus immunotherapy and immunotherapy plus biological therapy were significantly associated with lower IgG titers.
 

No downside for cancer patients

The Biden administration announced a plan to begin booster COVID-19 vaccinations for all American adults in September, with recommendations that the third vaccine be given at least 8 months after the second mRNA vaccine dose.

Jeremy M. Levin, DPhil, the chairman and CEO of Ovid Therapeutics, explained that, concerning boosters, “it is inconceivable that we will have all data at this stage.

“Knowledge about how boosters work and don’t work and when you should ideally have them is imperfect,” he told this news organization. “However, we can have a lot of confidence in the fact that hundreds of millions of people have received the vaccine, so we know a lot about the safety and efficacy.”

Immunocompromised adults represent less than 5% of the total population, and most of the available data on vaccination are from patients who have undergone solid-organ transplant, Dr. Levin explained. Studies have shown that their response is less robust to vaccination in comparison with adults in the general population.

“Although it is still preliminary, the strongest data come from Israel,” he said, “where they found that the booster was highly effective and doubled the number of transplant patients who developed antibodies.”

But data are not yet available in the setting of cancer. “But even though we don’t have the data yet, the answer is that no matter, the booster process is essential,” he said. “The evidence we have is that boosters raise the immune response, and it is the best data we have now.”

Martin J. Edelman, MD, chair, department of hematology/oncology, Fox Chase Cancer Center, Philadelphia, noted that the current recommendation is that patients who are immunocompromised receive a booster immediately.

At his health system, this is interpreted to include patients who have undergone the following treatments: Transplant (solid-organ and bone marrow transplant), hemodialysis, hematologic malignancy treatment, active immunosuppressive (chemotherapy, chemoimmunotherapy, and nonhormonal or single-agent immunotherapy) treatment, rheumatology treatments, and high-dose steroids.

“As for cancer patients, we are making arrangements to vaccinate patients who meet the above criteria now,” he said. “There is no known downside to receiving booster immediately. While there may be less of a response than waiting for completion of treatment, we know that patients on active therapy are frequently able to mount a response, and any response is better than none.”

Dr. Edelman added that this area is changing very rapidly. “We will modify our approach as information and guidance from appropriate organizations, such as the FDA and CDC, become available.”

Dr. Stemmer has received institutional research grants from CAN-FITE, AstraZeneca, Bioline RX, BMS, Halozyme, Clovis Oncology, CTG Pharma, Exelixis, Geicam, Incyte, Lilly, Moderna, Teva Pharmaceuticals, and Roche, and owns stocks and options in CTG Pharma, DocBoxMD, Tyrnovo, VYPE, Cytora, and CAN-FITE. Dr. Edelman has received personal fees and other compensation from Windmil, Biomarker Strategies, AstraZeneca, Takeda, GlaxoSmithKline, Apexigen, Nektar, Bristol-Myers Squibb, Armo, Bergen Bio, and Apexigen outside the submitted work. He has submitted a patent for epigenetic modifications to increase susceptibility to radiopharmaceuticals and is a paid adviser for Kanaph and Flame. Dr. Levin is chairman and CEO of Ovid Therapeutics.

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

A COVID-19 booster shot may be beneficial for patients with cancer who are undergoing treatment, according to new findings from an Israeli case-control study.

The seropositivity rate among the patients with cancer remained high (87%) about 4 months after the patients had received the second BNT162b2 (Pfizer/BioNTech) vaccination. However, the median IgG titer in the patients and the control persons who were without cancer decreased over time. Notably, in a previous analysis that the authors conducted and in the current one, the IgG titers were statistically significantly lower in the patients with cancer as compared to control persons.

The correlation between antibody levels following vaccination and clinical protection has yet to be proven, but the accumulating evidence supports antibody response as a possible correlate of disease protection.

“Our data can’t predict if a third booster dose is necessary,” said study author Salomon M. Stemmer, MD, professor at the Institute of Oncology of Rabin Medical Center, Petah Tikva, Israel. “It does seem quite logical that a booster dose will cause an increase in IgG levels.”

The findings were published Aug. 11, 2021, in a research letter in JAMA Oncology.

In their previous study, Dr. Stemmer and colleagues compared the rates of anti–spike antibody response to the initial shot of the BNT162b2 vaccine among 102 adults with solid-tumor cancers who were undergoing treatment with that of 78 healthy control persons. They found that a high percentage of patients undergoing treatment for cancer (90%) achieved a sufficient antibody response to the BNT162b2 vaccine.
 

Booster endorsed

Responses to COVID-19 vaccination have varied among patients with cancer. For patients with solid tumors, responses have been good even while the patients were receiving systemic therapy. However, among patients with blood cancers, particularly those receiving immunosuppressive therapies, responses have been poor. Studies have identified factors associated with a poor response, but it has been unclear whether to recommend booster shots.

In August the Food and Drug Administration authorized a third dose of either the Pfizer or the Moderna COVID-19 vaccine for all individuals with compromised immune systems. Those eligible for a third dose include solid-organ transplant recipients, those undergoing cancer treatments, and people with autoimmune diseases that suppress their immune systems.
 

IgG titers lower in cancer patients

In the current analysis, the authors evaluated the anti-S response in the patients with cancer approximately 4 months after they had received the second vaccine dose. They compared the responses in those patients with the responses in a control group.

The cohort included 95 patients from the prior study and 66 control persons. The most common malignancies were gastrointestinal (26%), lung (25%), and breast (18%).

All patients were receiving systemic therapy. Chemotherapy was the most common (28%), followed by immunotherapy (21%) and combination chemotherapy/biological therapy (20%).

At a median of 123 days after the second vaccination, 83 patients with cancer (87%) and all of the control patients (100%) were seropositive for anti-S IgG antibodies. The median titer levels were significantly lower among case patients as compared with control patients (417 AU/mL [interquartile range, 136-895] vs. 1,220 AU/mL [IQR, 588-1,987]; P < .001)

There was a 3.6-fold range in median titer values across tumor types and an even wider range (8.8-fold) across the different types of treatment. The lowest titers were observed among patients who had received immunotherapy plus chemotherapy/biological therapy (median [IQR], 94.4 [49.4-191] AU/mL vs. 147 [62.8-339] AU/mL).

In an exploratory multivariable analysis, treatments with chemotherapy plus immunotherapy and immunotherapy plus biological therapy were significantly associated with lower IgG titers.
 

No downside for cancer patients

The Biden administration announced a plan to begin booster COVID-19 vaccinations for all American adults in September, with recommendations that the third vaccine be given at least 8 months after the second mRNA vaccine dose.

Jeremy M. Levin, DPhil, the chairman and CEO of Ovid Therapeutics, explained that, concerning boosters, “it is inconceivable that we will have all data at this stage.

“Knowledge about how boosters work and don’t work and when you should ideally have them is imperfect,” he told this news organization. “However, we can have a lot of confidence in the fact that hundreds of millions of people have received the vaccine, so we know a lot about the safety and efficacy.”

Immunocompromised adults represent less than 5% of the total population, and most of the available data on vaccination are from patients who have undergone solid-organ transplant, Dr. Levin explained. Studies have shown that their response is less robust to vaccination in comparison with adults in the general population.

“Although it is still preliminary, the strongest data come from Israel,” he said, “where they found that the booster was highly effective and doubled the number of transplant patients who developed antibodies.”

But data are not yet available in the setting of cancer. “But even though we don’t have the data yet, the answer is that no matter, the booster process is essential,” he said. “The evidence we have is that boosters raise the immune response, and it is the best data we have now.”

Martin J. Edelman, MD, chair, department of hematology/oncology, Fox Chase Cancer Center, Philadelphia, noted that the current recommendation is that patients who are immunocompromised receive a booster immediately.

At his health system, this is interpreted to include patients who have undergone the following treatments: Transplant (solid-organ and bone marrow transplant), hemodialysis, hematologic malignancy treatment, active immunosuppressive (chemotherapy, chemoimmunotherapy, and nonhormonal or single-agent immunotherapy) treatment, rheumatology treatments, and high-dose steroids.

“As for cancer patients, we are making arrangements to vaccinate patients who meet the above criteria now,” he said. “There is no known downside to receiving booster immediately. While there may be less of a response than waiting for completion of treatment, we know that patients on active therapy are frequently able to mount a response, and any response is better than none.”

Dr. Edelman added that this area is changing very rapidly. “We will modify our approach as information and guidance from appropriate organizations, such as the FDA and CDC, become available.”

Dr. Stemmer has received institutional research grants from CAN-FITE, AstraZeneca, Bioline RX, BMS, Halozyme, Clovis Oncology, CTG Pharma, Exelixis, Geicam, Incyte, Lilly, Moderna, Teva Pharmaceuticals, and Roche, and owns stocks and options in CTG Pharma, DocBoxMD, Tyrnovo, VYPE, Cytora, and CAN-FITE. Dr. Edelman has received personal fees and other compensation from Windmil, Biomarker Strategies, AstraZeneca, Takeda, GlaxoSmithKline, Apexigen, Nektar, Bristol-Myers Squibb, Armo, Bergen Bio, and Apexigen outside the submitted work. He has submitted a patent for epigenetic modifications to increase susceptibility to radiopharmaceuticals and is a paid adviser for Kanaph and Flame. Dr. Levin is chairman and CEO of Ovid Therapeutics.

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

Annual health care costs for patients with psoriatic arthritis rose over recent 5-year periods across all categories of resource use to a significantly greater extent than among patients with psoriasis only or those without any psoriatic disease diagnoses, according to commercial insurance claims data.

Thinkstock Photos

Using an IBM MarketScan Commercial Database, researchers examined claims data for 208,434 patients with psoriasis, 47,274 with PsA, and 255,708 controls who had neither psoriasis nor PsA. Controls were matched for age and sex. Those with RA, ankylosing spondylitis, Crohn’s disease, or ulcerative colitis were excluded.

The investigators examined data for 2009-2020, following patients for 5 years within that period. They looked at hospitalizations, outpatient and pharmacy services, lab services, and office visits, Steven Peterson, director of market access for rheumatology at Janssen Pharmaceuticals, said in his presentation of the data at the Pan American League of Associations for Rheumatology 2021 annual meeting, held recently as a virtual event.

The research was also published online May 2, 2021, in Clinical Rheumatology.

Big differences between the groups were seen in the first year, when the average health care costs for the PsA group were $28,322, about half of which was outpatient drug costs. That compared with $12,039 for the psoriasis group and $6,672 for the control group.

The differences tended to widen over time. By the fifth year, average costs for the PsA group were $34,290, nearly 60% of which were drug costs. That compared with $12,877 for the psoriasis group and $8,569 for the control group. In each year examined, outpatient drug costs accounted for less than half of the expenses for the psoriasis group and about a quarter for the control group.

Researchers found that the PsA group needed 28.7 prescriptions per person per year, compared with 17.0 and 12.7 in the psoriasis and control groups, respectively, Mr. Peterson said. He also noted that patients with PsA and psoriasis tended to have higher rates of hypertension, depression, and anxiety.

“The cost and resource utilization disparity between these patient groups demonstrates the high remaining unmet medical need for patients with psoriasis and psoriatic arthritis,” Mr. Peterson said during the virtual proceedings.

Do findings reflect treatment advances?

Elaine Husni, MD, MPH, director of the Arthritis and Musculoskeletal Center at the Cleveland Clinic, where she studies health outcomes in PsA, said the findings are helpful in pointing to a trend across a large sample. But she added it’s important to remember that the increasing costs could reflect recent advances in PsA treatment, which include costly biologic drugs.

“There’s a ton more treatments for psoriasis and psoriatic arthritis than there were even just 5 years ago,” she said in an interview. She was not involved in the research.

Dr. Husni would like to see a more detailed look at the costs, from the categories of expenses to the patients who are incurring the highest costs.  

“Is it just a couple of percent of really sick patients that are driving the psoriatic arthritis group?” she wondered.

She also pointed out that PsA is going to be more expensive by its very nature. PsA tends to develop 3-10 years after psoriasis, adding to the costs for someone who already has psoriasis and at a time when they are older and likely have higher health care costs because of comorbidities that develop with age.

Dr. Husni said she does think about treatment costs, in that a less expensive first-line drug might be more appropriate than going straight to a more expensive biologic, especially because they also tend to be safer. She said it’s not just a simple question of curbing costs.

“Is there a way that we can personalize medicine?” she asked. “Is there a way that we can be more accurate about which people may need the more expensive drugs, and which patients may need the less expensive drugs? Are we getting better at monitoring so we can avoid high-cost events?”

Mr. Peterson is an employee of Janssen Pharmaceuticals. Dr. Husni reported serving as a consultant to AbbVie, Amgen, Bristol-Myers Squibb, UCB, Novartis, Lilly, and Pfizer.

* Update, 9/28/21: The headline and parts of this story were updated to better reflect the study on which it reports.

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

Annual health care costs for patients with psoriatic arthritis rose over recent 5-year periods across all categories of resource use to a significantly greater extent than among patients with psoriasis only or those without any psoriatic disease diagnoses, according to commercial insurance claims data.

Thinkstock Photos

Using an IBM MarketScan Commercial Database, researchers examined claims data for 208,434 patients with psoriasis, 47,274 with PsA, and 255,708 controls who had neither psoriasis nor PsA. Controls were matched for age and sex. Those with RA, ankylosing spondylitis, Crohn’s disease, or ulcerative colitis were excluded.

The investigators examined data for 2009-2020, following patients for 5 years within that period. They looked at hospitalizations, outpatient and pharmacy services, lab services, and office visits, Steven Peterson, director of market access for rheumatology at Janssen Pharmaceuticals, said in his presentation of the data at the Pan American League of Associations for Rheumatology 2021 annual meeting, held recently as a virtual event.

The research was also published online May 2, 2021, in Clinical Rheumatology.

Big differences between the groups were seen in the first year, when the average health care costs for the PsA group were $28,322, about half of which was outpatient drug costs. That compared with $12,039 for the psoriasis group and $6,672 for the control group.

The differences tended to widen over time. By the fifth year, average costs for the PsA group were $34,290, nearly 60% of which were drug costs. That compared with $12,877 for the psoriasis group and $8,569 for the control group. In each year examined, outpatient drug costs accounted for less than half of the expenses for the psoriasis group and about a quarter for the control group.

Researchers found that the PsA group needed 28.7 prescriptions per person per year, compared with 17.0 and 12.7 in the psoriasis and control groups, respectively, Mr. Peterson said. He also noted that patients with PsA and psoriasis tended to have higher rates of hypertension, depression, and anxiety.

“The cost and resource utilization disparity between these patient groups demonstrates the high remaining unmet medical need for patients with psoriasis and psoriatic arthritis,” Mr. Peterson said during the virtual proceedings.

Do findings reflect treatment advances?

Elaine Husni, MD, MPH, director of the Arthritis and Musculoskeletal Center at the Cleveland Clinic, where she studies health outcomes in PsA, said the findings are helpful in pointing to a trend across a large sample. But she added it’s important to remember that the increasing costs could reflect recent advances in PsA treatment, which include costly biologic drugs.

“There’s a ton more treatments for psoriasis and psoriatic arthritis than there were even just 5 years ago,” she said in an interview. She was not involved in the research.

Dr. Husni would like to see a more detailed look at the costs, from the categories of expenses to the patients who are incurring the highest costs.  

“Is it just a couple of percent of really sick patients that are driving the psoriatic arthritis group?” she wondered.

She also pointed out that PsA is going to be more expensive by its very nature. PsA tends to develop 3-10 years after psoriasis, adding to the costs for someone who already has psoriasis and at a time when they are older and likely have higher health care costs because of comorbidities that develop with age.

Dr. Husni said she does think about treatment costs, in that a less expensive first-line drug might be more appropriate than going straight to a more expensive biologic, especially because they also tend to be safer. She said it’s not just a simple question of curbing costs.

“Is there a way that we can personalize medicine?” she asked. “Is there a way that we can be more accurate about which people may need the more expensive drugs, and which patients may need the less expensive drugs? Are we getting better at monitoring so we can avoid high-cost events?”

Mr. Peterson is an employee of Janssen Pharmaceuticals. Dr. Husni reported serving as a consultant to AbbVie, Amgen, Bristol-Myers Squibb, UCB, Novartis, Lilly, and Pfizer.

* Update, 9/28/21: The headline and parts of this story were updated to better reflect the study on which it reports.

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

Annual health care costs for patients with psoriatic arthritis rose over recent 5-year periods across all categories of resource use to a significantly greater extent than among patients with psoriasis only or those without any psoriatic disease diagnoses, according to commercial insurance claims data.

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Using an IBM MarketScan Commercial Database, researchers examined claims data for 208,434 patients with psoriasis, 47,274 with PsA, and 255,708 controls who had neither psoriasis nor PsA. Controls were matched for age and sex. Those with RA, ankylosing spondylitis, Crohn’s disease, or ulcerative colitis were excluded.

The investigators examined data for 2009-2020, following patients for 5 years within that period. They looked at hospitalizations, outpatient and pharmacy services, lab services, and office visits, Steven Peterson, director of market access for rheumatology at Janssen Pharmaceuticals, said in his presentation of the data at the Pan American League of Associations for Rheumatology 2021 annual meeting, held recently as a virtual event.

The research was also published online May 2, 2021, in Clinical Rheumatology.

Big differences between the groups were seen in the first year, when the average health care costs for the PsA group were $28,322, about half of which was outpatient drug costs. That compared with $12,039 for the psoriasis group and $6,672 for the control group.

The differences tended to widen over time. By the fifth year, average costs for the PsA group were $34,290, nearly 60% of which were drug costs. That compared with $12,877 for the psoriasis group and $8,569 for the control group. In each year examined, outpatient drug costs accounted for less than half of the expenses for the psoriasis group and about a quarter for the control group.

Researchers found that the PsA group needed 28.7 prescriptions per person per year, compared with 17.0 and 12.7 in the psoriasis and control groups, respectively, Mr. Peterson said. He also noted that patients with PsA and psoriasis tended to have higher rates of hypertension, depression, and anxiety.

“The cost and resource utilization disparity between these patient groups demonstrates the high remaining unmet medical need for patients with psoriasis and psoriatic arthritis,” Mr. Peterson said during the virtual proceedings.

Do findings reflect treatment advances?

Elaine Husni, MD, MPH, director of the Arthritis and Musculoskeletal Center at the Cleveland Clinic, where she studies health outcomes in PsA, said the findings are helpful in pointing to a trend across a large sample. But she added it’s important to remember that the increasing costs could reflect recent advances in PsA treatment, which include costly biologic drugs.

“There’s a ton more treatments for psoriasis and psoriatic arthritis than there were even just 5 years ago,” she said in an interview. She was not involved in the research.

Dr. Husni would like to see a more detailed look at the costs, from the categories of expenses to the patients who are incurring the highest costs.  

“Is it just a couple of percent of really sick patients that are driving the psoriatic arthritis group?” she wondered.

She also pointed out that PsA is going to be more expensive by its very nature. PsA tends to develop 3-10 years after psoriasis, adding to the costs for someone who already has psoriasis and at a time when they are older and likely have higher health care costs because of comorbidities that develop with age.

Dr. Husni said she does think about treatment costs, in that a less expensive first-line drug might be more appropriate than going straight to a more expensive biologic, especially because they also tend to be safer. She said it’s not just a simple question of curbing costs.

“Is there a way that we can personalize medicine?” she asked. “Is there a way that we can be more accurate about which people may need the more expensive drugs, and which patients may need the less expensive drugs? Are we getting better at monitoring so we can avoid high-cost events?”

Mr. Peterson is an employee of Janssen Pharmaceuticals. Dr. Husni reported serving as a consultant to AbbVie, Amgen, Bristol-Myers Squibb, UCB, Novartis, Lilly, and Pfizer.

* Update, 9/28/21: The headline and parts of this story were updated to better reflect the study on which it reports.

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