Rural families that live far from their child’s cancer center face unique challenges, particularly lost work and missed family activities, because of long drives and inadequate emergency care at local hospitals, a small study has found.

Lead author Emily B. Walling, MD, of the University of Michigan, Ann Arbor, and her colleagues interviewed 18 caregivers with children who received treatment at St. Louis (Mo.) Children’s Hospital, an urban pediatric hospital. The caregivers lived in a rural area 2 or more hours’ driving distance from the hospital, and their children had received six or more treatments of chemotherapy and/or radiation at the cancer center. To be eligible, families had to have sought emergency care related to their child’s cancer diagnosis at least once in their local community. A total of 18 caregivers (12 mothers and 6 fathers) from 16 families were identified. The families answered questions focused on how the distance between home and hospital affected their child’s cancer treatment.

From the 18 interviews, investigators determined that top problems encountered by the rural families included poor emergent care at local hospitals, strain on family members because of extended travel time, and challenges in managing and coping with a pediatric diagnosis, according to the study published in the Journal of Oncology Practice.

In regards to emergency care, the families reported frustration with local emergency care providers who they felt did not take their concerns seriously. Parents also noted a lack of resources and training related to specialized care at local hospitals. Because of inadequacies at local hospitals, the caregivers reported delays in care, poor symptom management, incorrect procedures, inability to access central lines, and underappreciation of the child’s immunocompromised state, according to the study. The parents also reported that local hospital providers sometimes failed to follow the recommendations of oncology specialists at St. Louis Children’s Hospital and that other times there was redundant care between both health care centers.

Interviewees also described disruption to family members and guilt about missing important activities of other children because of long drives to the urban cancer center. Caregivers worried about missed school for children and separation from siblings. Families also reported financial burdens from missed work and increased costs associated with food, gas, and housing while away from home. In addition, inclement weather increased travel stress, as did treatment-related problems during the drive not easily managed in a vehicle.

Based on the interviews, investigators recommended steps to improve the care of rural pediatric cancer patients, including improved guidance to caregivers about unexpected trips to local hospitals, more outreach to local hospitals, and better medical visit coordination. If local hospitals are identified at diagnosis, communication between the local hospital and cancer center could be established early, study authors wrote. If deficiencies in care are discovered, local hospitals may be prompted to “stock materials or parents could be redirected to other hospitals at which they are routinely available,” authors suggested.

“This would foster collaboration between local physicians and specialists at the cancer-treating hospital, and thereby lower levels of frustration and increase parent’s trust of local providers,” authors wrote.

[email protected]

SOURCE: Walling EB et al. J Oncol Pract. 2019 Jan 31. doi: 10.1200/JOP.18.00115.

Rural families that live far from their child’s cancer center face unique challenges, particularly lost work and missed family activities, because of long drives and inadequate emergency care at local hospitals, a small study has found.

Lead author Emily B. Walling, MD, of the University of Michigan, Ann Arbor, and her colleagues interviewed 18 caregivers with children who received treatment at St. Louis (Mo.) Children’s Hospital, an urban pediatric hospital. The caregivers lived in a rural area 2 or more hours’ driving distance from the hospital, and their children had received six or more treatments of chemotherapy and/or radiation at the cancer center. To be eligible, families had to have sought emergency care related to their child’s cancer diagnosis at least once in their local community. A total of 18 caregivers (12 mothers and 6 fathers) from 16 families were identified. The families answered questions focused on how the distance between home and hospital affected their child’s cancer treatment.

From the 18 interviews, investigators determined that top problems encountered by the rural families included poor emergent care at local hospitals, strain on family members because of extended travel time, and challenges in managing and coping with a pediatric diagnosis, according to the study published in the Journal of Oncology Practice.

In regards to emergency care, the families reported frustration with local emergency care providers who they felt did not take their concerns seriously. Parents also noted a lack of resources and training related to specialized care at local hospitals. Because of inadequacies at local hospitals, the caregivers reported delays in care, poor symptom management, incorrect procedures, inability to access central lines, and underappreciation of the child’s immunocompromised state, according to the study. The parents also reported that local hospital providers sometimes failed to follow the recommendations of oncology specialists at St. Louis Children’s Hospital and that other times there was redundant care between both health care centers.

Interviewees also described disruption to family members and guilt about missing important activities of other children because of long drives to the urban cancer center. Caregivers worried about missed school for children and separation from siblings. Families also reported financial burdens from missed work and increased costs associated with food, gas, and housing while away from home. In addition, inclement weather increased travel stress, as did treatment-related problems during the drive not easily managed in a vehicle.

Based on the interviews, investigators recommended steps to improve the care of rural pediatric cancer patients, including improved guidance to caregivers about unexpected trips to local hospitals, more outreach to local hospitals, and better medical visit coordination. If local hospitals are identified at diagnosis, communication between the local hospital and cancer center could be established early, study authors wrote. If deficiencies in care are discovered, local hospitals may be prompted to “stock materials or parents could be redirected to other hospitals at which they are routinely available,” authors suggested.

“This would foster collaboration between local physicians and specialists at the cancer-treating hospital, and thereby lower levels of frustration and increase parent’s trust of local providers,” authors wrote.

[email protected]

SOURCE: Walling EB et al. J Oncol Pract. 2019 Jan 31. doi: 10.1200/JOP.18.00115.

Rural families that live far from their child’s cancer center face unique challenges, particularly lost work and missed family activities, because of long drives and inadequate emergency care at local hospitals, a small study has found.

Lead author Emily B. Walling, MD, of the University of Michigan, Ann Arbor, and her colleagues interviewed 18 caregivers with children who received treatment at St. Louis (Mo.) Children’s Hospital, an urban pediatric hospital. The caregivers lived in a rural area 2 or more hours’ driving distance from the hospital, and their children had received six or more treatments of chemotherapy and/or radiation at the cancer center. To be eligible, families had to have sought emergency care related to their child’s cancer diagnosis at least once in their local community. A total of 18 caregivers (12 mothers and 6 fathers) from 16 families were identified. The families answered questions focused on how the distance between home and hospital affected their child’s cancer treatment.

From the 18 interviews, investigators determined that top problems encountered by the rural families included poor emergent care at local hospitals, strain on family members because of extended travel time, and challenges in managing and coping with a pediatric diagnosis, according to the study published in the Journal of Oncology Practice.

In regards to emergency care, the families reported frustration with local emergency care providers who they felt did not take their concerns seriously. Parents also noted a lack of resources and training related to specialized care at local hospitals. Because of inadequacies at local hospitals, the caregivers reported delays in care, poor symptom management, incorrect procedures, inability to access central lines, and underappreciation of the child’s immunocompromised state, according to the study. The parents also reported that local hospital providers sometimes failed to follow the recommendations of oncology specialists at St. Louis Children’s Hospital and that other times there was redundant care between both health care centers.

Interviewees also described disruption to family members and guilt about missing important activities of other children because of long drives to the urban cancer center. Caregivers worried about missed school for children and separation from siblings. Families also reported financial burdens from missed work and increased costs associated with food, gas, and housing while away from home. In addition, inclement weather increased travel stress, as did treatment-related problems during the drive not easily managed in a vehicle.

Based on the interviews, investigators recommended steps to improve the care of rural pediatric cancer patients, including improved guidance to caregivers about unexpected trips to local hospitals, more outreach to local hospitals, and better medical visit coordination. If local hospitals are identified at diagnosis, communication between the local hospital and cancer center could be established early, study authors wrote. If deficiencies in care are discovered, local hospitals may be prompted to “stock materials or parents could be redirected to other hospitals at which they are routinely available,” authors suggested.

“This would foster collaboration between local physicians and specialists at the cancer-treating hospital, and thereby lower levels of frustration and increase parent’s trust of local providers,” authors wrote.

[email protected]

SOURCE: Walling EB et al. J Oncol Pract. 2019 Jan 31. doi: 10.1200/JOP.18.00115.

EXPERT COMMENTARY

Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2019;364:k4810.

The Women’s Health Initiative trials, in which menopausal women were randomly assigned to treatment with oral CEE or placebo, found that statistically the largest risk associated with menopausal hormone therapy (HT) was increased VTE.¹ Recently, investigators in the United Kingdom (UK) published results of their research aimed at determining the association between the risk of VTE and the use of different types of HT.²

Details of the study

Vinogradova and colleagues used 2 UK primary care research databases, QResearch and Clinical Practice Research Datalink, to identify cases of incident VTE in general practice records, hospital admissions, and mortality records. They identified 80,396 women (aged 40 to 79 years) diagnosed with VTE between 1998 and 2017 and 391,494 control women matched by age and general practice. The mean age of the case and control women was approximately 64 years; the great majority of women were white. Analyses were adjusted for smoking, body mass index (BMI), family history of VTE, and comorbidities associated with VTE.

Types of HT used. The investigators found that 5,795 (7.2%) women with VTE and 21,670 (5.5%) controls were exposed to HT in the 90 days before the index date (the first date of VTE diagnosis for cases became the index date for matched controls). In those exposed to HT:

• 4,915 (85%) cases and 16,938 (78%) controls used oral preparations (including 102 [1.8%] cases and 312 [1.4%] controls who also had transdermal preparations)
• 880 (14%) cases and 4,731 (19%) controls used transdermal HT only.

Association of VTE with HT. Risk of VTE was increased with all oral HT formulations, including combined (estrogen plus progestogen) and estrogen-only preparations. Use of oral CEE (odds ratio [OR], 1.49) and estradiol (OR, 1.27) were both associated with an elevated risk of VTE (P<.05 for both comparisons). In contrast, use of transdermal estradiol (the great majority of which was administered by patch) was not associated with an elevated risk of VTE (OR, 0.96).

Direct comparison of oral estradiol and CEE found that the lower VTE risk with oral estradiol achieved statistical significance (P = .005). Direct comparison of oral and transdermal estrogen revealed an OR of 1.7 for the oral route of administration (P<.001)

Continue to: Study strengths and weaknesses

Study strengths and weaknesses

This study used data from the 2 largest primary care databases in the United Kingdom. Analyses were adjusted for numerous confounding factors, including acute and chronic conditions, lifestyle factors, and social deprivation. Additional sensitivity analyses were conducted and yielded results similar to those of the main analysis.

Several limitations could have resulted in some residual confounding bias. For example, drug exposure information was based on HT prescriptions and not actual use; data on some factors were not available, such as indications for HT, age at menopause, and education level; and for a small proportion of women, some data (smoking status, alcohol consumption, BMI) were missing and had to be imputed for analysis.

EXPERT COMMENTARY

Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2019;364:k4810.

The Women’s Health Initiative trials, in which menopausal women were randomly assigned to treatment with oral CEE or placebo, found that statistically the largest risk associated with menopausal hormone therapy (HT) was increased VTE.¹ Recently, investigators in the United Kingdom (UK) published results of their research aimed at determining the association between the risk of VTE and the use of different types of HT.²

Details of the study

Vinogradova and colleagues used 2 UK primary care research databases, QResearch and Clinical Practice Research Datalink, to identify cases of incident VTE in general practice records, hospital admissions, and mortality records. They identified 80,396 women (aged 40 to 79 years) diagnosed with VTE between 1998 and 2017 and 391,494 control women matched by age and general practice. The mean age of the case and control women was approximately 64 years; the great majority of women were white. Analyses were adjusted for smoking, body mass index (BMI), family history of VTE, and comorbidities associated with VTE.

Types of HT used. The investigators found that 5,795 (7.2%) women with VTE and 21,670 (5.5%) controls were exposed to HT in the 90 days before the index date (the first date of VTE diagnosis for cases became the index date for matched controls). In those exposed to HT:

• 4,915 (85%) cases and 16,938 (78%) controls used oral preparations (including 102 [1.8%] cases and 312 [1.4%] controls who also had transdermal preparations)
• 880 (14%) cases and 4,731 (19%) controls used transdermal HT only.

Association of VTE with HT. Risk of VTE was increased with all oral HT formulations, including combined (estrogen plus progestogen) and estrogen-only preparations. Use of oral CEE (odds ratio [OR], 1.49) and estradiol (OR, 1.27) were both associated with an elevated risk of VTE (P<.05 for both comparisons). In contrast, use of transdermal estradiol (the great majority of which was administered by patch) was not associated with an elevated risk of VTE (OR, 0.96).

Direct comparison of oral estradiol and CEE found that the lower VTE risk with oral estradiol achieved statistical significance (P = .005). Direct comparison of oral and transdermal estrogen revealed an OR of 1.7 for the oral route of administration (P<.001)

Continue to: Study strengths and weaknesses

Study strengths and weaknesses

This study used data from the 2 largest primary care databases in the United Kingdom. Analyses were adjusted for numerous confounding factors, including acute and chronic conditions, lifestyle factors, and social deprivation. Additional sensitivity analyses were conducted and yielded results similar to those of the main analysis.

Several limitations could have resulted in some residual confounding bias. For example, drug exposure information was based on HT prescriptions and not actual use; data on some factors were not available, such as indications for HT, age at menopause, and education level; and for a small proportion of women, some data (smoking status, alcohol consumption, BMI) were missing and had to be imputed for analysis.

EXPERT COMMENTARY

Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2019;364:k4810.

The Women’s Health Initiative trials, in which menopausal women were randomly assigned to treatment with oral CEE or placebo, found that statistically the largest risk associated with menopausal hormone therapy (HT) was increased VTE.¹ Recently, investigators in the United Kingdom (UK) published results of their research aimed at determining the association between the risk of VTE and the use of different types of HT.²

Details of the study

Vinogradova and colleagues used 2 UK primary care research databases, QResearch and Clinical Practice Research Datalink, to identify cases of incident VTE in general practice records, hospital admissions, and mortality records. They identified 80,396 women (aged 40 to 79 years) diagnosed with VTE between 1998 and 2017 and 391,494 control women matched by age and general practice. The mean age of the case and control women was approximately 64 years; the great majority of women were white. Analyses were adjusted for smoking, body mass index (BMI), family history of VTE, and comorbidities associated with VTE.

Types of HT used. The investigators found that 5,795 (7.2%) women with VTE and 21,670 (5.5%) controls were exposed to HT in the 90 days before the index date (the first date of VTE diagnosis for cases became the index date for matched controls). In those exposed to HT:

• 4,915 (85%) cases and 16,938 (78%) controls used oral preparations (including 102 [1.8%] cases and 312 [1.4%] controls who also had transdermal preparations)
• 880 (14%) cases and 4,731 (19%) controls used transdermal HT only.

Association of VTE with HT. Risk of VTE was increased with all oral HT formulations, including combined (estrogen plus progestogen) and estrogen-only preparations. Use of oral CEE (odds ratio [OR], 1.49) and estradiol (OR, 1.27) were both associated with an elevated risk of VTE (P<.05 for both comparisons). In contrast, use of transdermal estradiol (the great majority of which was administered by patch) was not associated with an elevated risk of VTE (OR, 0.96).

Direct comparison of oral estradiol and CEE found that the lower VTE risk with oral estradiol achieved statistical significance (P = .005). Direct comparison of oral and transdermal estrogen revealed an OR of 1.7 for the oral route of administration (P<.001)

Continue to: Study strengths and weaknesses

Study strengths and weaknesses

This study used data from the 2 largest primary care databases in the United Kingdom. Analyses were adjusted for numerous confounding factors, including acute and chronic conditions, lifestyle factors, and social deprivation. Additional sensitivity analyses were conducted and yielded results similar to those of the main analysis.

Several limitations could have resulted in some residual confounding bias. For example, drug exposure information was based on HT prescriptions and not actual use; data on some factors were not available, such as indications for HT, age at menopause, and education level; and for a small proportion of women, some data (smoking status, alcohol consumption, BMI) were missing and had to be imputed for analysis.

Patients with RA in clinical remission who received an MRI-based treat-to-target strategy did not achieve superior disease activity remission rates (85% vs. 88%) or reduced radiographic progression (66% vs. 62%), compared with a conventional treat-to-target strategy, according to results of the Danish, 2-year, investigator-initiated, randomized, multicenter IMAGINE-RA trial published in JAMA (2019 Feb 5. doi: 10.1001/jama.2018.21362).

We covered this study at the 2018 European Congress of Rheumatology before it was published in the journal. Read the story at the link above.

[email protected]

Patients with RA in clinical remission who received an MRI-based treat-to-target strategy did not achieve superior disease activity remission rates (85% vs. 88%) or reduced radiographic progression (66% vs. 62%), compared with a conventional treat-to-target strategy, according to results of the Danish, 2-year, investigator-initiated, randomized, multicenter IMAGINE-RA trial published in JAMA (2019 Feb 5. doi: 10.1001/jama.2018.21362).

We covered this study at the 2018 European Congress of Rheumatology before it was published in the journal. Read the story at the link above.

[email protected]

Patients with RA in clinical remission who received an MRI-based treat-to-target strategy did not achieve superior disease activity remission rates (85% vs. 88%) or reduced radiographic progression (66% vs. 62%), compared with a conventional treat-to-target strategy, according to results of the Danish, 2-year, investigator-initiated, randomized, multicenter IMAGINE-RA trial published in JAMA (2019 Feb 5. doi: 10.1001/jama.2018.21362).

We covered this study at the 2018 European Congress of Rheumatology before it was published in the journal. Read the story at the link above.

[email protected]

To the Editor:

A 60-year-old woman with a history of lymphoma presented to the emergency department for evaluation of intermittent diarrhea and vomiting of 2 weeks’ duration. On presentation, a rather large dressing covering the entire right half of the face was noted. Removal of the bandage revealed a necrotic, extensively destructive, right-sided facial lesion with a fully exposed ocular globe (Figure 1). The patient lived alone and was accompanied by a neighbor, who disclosed that the lesion had been neglected and enlarged over the last 15 years. Moreover, the neighbor reported that the patient had recently experienced several episodes of vertigo and frequent falls.

On admission to the hospital, dermatology was consulted and initial workup included computed tomography (CT) scan of the head and maxillofacial region, which showed a destructive process involving the right frontotemporal bone, maxillofacial region, sphenoid, and skull base with exposure of intracranial contents (Figure 2). An aggressive wound care regimen was instituted. Biopsy of the wound margin revealed nodular and focally infiltrative basal cell carcinoma (BCC) (Figure 3). Culture of the necrotic bone grew Rhizopus, a causative organism of mucormycosis, and the patient was treated with posaconazole. A CT scan of the chest and abdomen showed multiple bilateral pulmonary nodules and necrotic lymph nodes in the left hilum and left axilla. The patient refused bronchoscopy to further evaluate the pulmonary nodules. Ultrasound-guided biopsy of the left axillarylymph node revealed metastatic disease (Figure 4).

Several days into her hospitalization, the patient developed radicular pain in both arms and weakness in all 4 extremities. A CT scan of the neck revealed a pathologic fracture of the C7 vertebrae. Several medical and surgical services as well as psychiatry were consulted. Given the extensive nature of the disease involvement with limited treatment options, the patient sought to forego further interventions and was discharged to hospice care.

Basal cell carcinomas rarely metastasize, with a reported incidence of 0.0028% to 0.5%.¹ The likelihood of metastasis is most closely related to tumor size and depth of invasion. Tumors greater than 3 cm in diameter have a 2% incidence of metastatic spread and/or death. The incidence of metastatic spread and/or death is estimated to be 25% for tumors with a diameter of 5 cm and 50% for tumors with a diameter of 10 cm or greater.² Other risk factors for metastatic spread include long duration of disease, failure to respond to conventional treatment, and prior radiation treatment in the affected area.¹ In one review, the median interval between onset of BCC and metastasis was 9 years.³ In our case, 15 years of neglect most likely led to the aggressiveness of the tumor. Although the workup in our patient was limited per her request, there was no evidence that her lymphoma had recurred or that she was in any other way immunocompromised. Unfortunately, in this patient’s case, the local destructiveness of the carcinoma with subsequent bony invasion and necrosis was complicated with secondary Rhizopus infection. A PubMed search of articles indexed for MEDLINE using the terms basal cell carcinoma and mucormycosis revealed no other reported cases of BCC associated with mucormycosis; therefore, our case represents a rare presentation of this association. Rhinocerebral mucormycosis is the most common manifestation of mucormycosis and more commonly occurs in diabetics with ketoacidosis and in severely debilitated or immunosuppressed individuals.⁴ The extensive bony destruction, especially of the nasal region, of our patient’s tumor likely led to secondary infection with Rhizopus.

Approximately 85% of all metastatic BCCs originate in the head and neck region, with lymph nodes being the first site of metastasis and involved in approximately half of all cases.^1,4 Metastases to the lungs, bone, liver, and other viscera can occur with advanced disease. Metastasis generally portends a poor prognosis, with survival rarely exceeding 1.5 years. Until recently, therapeutic options for metastatic disease were limited, with marginal response to chemotherapy with methotrexate, fluorouracil, bleomycin, and cisplatin.⁴ Vismodegib, a novel smoothened receptor inhibitor that blocks the sonic hedgehog pathway implicated in BCC carcinogenesis, offers a new promising treatment for management and control of advanced disease.⁵

To the Editor:

A 60-year-old woman with a history of lymphoma presented to the emergency department for evaluation of intermittent diarrhea and vomiting of 2 weeks’ duration. On presentation, a rather large dressing covering the entire right half of the face was noted. Removal of the bandage revealed a necrotic, extensively destructive, right-sided facial lesion with a fully exposed ocular globe (Figure 1). The patient lived alone and was accompanied by a neighbor, who disclosed that the lesion had been neglected and enlarged over the last 15 years. Moreover, the neighbor reported that the patient had recently experienced several episodes of vertigo and frequent falls.

On admission to the hospital, dermatology was consulted and initial workup included computed tomography (CT) scan of the head and maxillofacial region, which showed a destructive process involving the right frontotemporal bone, maxillofacial region, sphenoid, and skull base with exposure of intracranial contents (Figure 2). An aggressive wound care regimen was instituted. Biopsy of the wound margin revealed nodular and focally infiltrative basal cell carcinoma (BCC) (Figure 3). Culture of the necrotic bone grew Rhizopus, a causative organism of mucormycosis, and the patient was treated with posaconazole. A CT scan of the chest and abdomen showed multiple bilateral pulmonary nodules and necrotic lymph nodes in the left hilum and left axilla. The patient refused bronchoscopy to further evaluate the pulmonary nodules. Ultrasound-guided biopsy of the left axillarylymph node revealed metastatic disease (Figure 4).

Several days into her hospitalization, the patient developed radicular pain in both arms and weakness in all 4 extremities. A CT scan of the neck revealed a pathologic fracture of the C7 vertebrae. Several medical and surgical services as well as psychiatry were consulted. Given the extensive nature of the disease involvement with limited treatment options, the patient sought to forego further interventions and was discharged to hospice care.

Basal cell carcinomas rarely metastasize, with a reported incidence of 0.0028% to 0.5%.¹ The likelihood of metastasis is most closely related to tumor size and depth of invasion. Tumors greater than 3 cm in diameter have a 2% incidence of metastatic spread and/or death. The incidence of metastatic spread and/or death is estimated to be 25% for tumors with a diameter of 5 cm and 50% for tumors with a diameter of 10 cm or greater.² Other risk factors for metastatic spread include long duration of disease, failure to respond to conventional treatment, and prior radiation treatment in the affected area.¹ In one review, the median interval between onset of BCC and metastasis was 9 years.³ In our case, 15 years of neglect most likely led to the aggressiveness of the tumor. Although the workup in our patient was limited per her request, there was no evidence that her lymphoma had recurred or that she was in any other way immunocompromised. Unfortunately, in this patient’s case, the local destructiveness of the carcinoma with subsequent bony invasion and necrosis was complicated with secondary Rhizopus infection. A PubMed search of articles indexed for MEDLINE using the terms basal cell carcinoma and mucormycosis revealed no other reported cases of BCC associated with mucormycosis; therefore, our case represents a rare presentation of this association. Rhinocerebral mucormycosis is the most common manifestation of mucormycosis and more commonly occurs in diabetics with ketoacidosis and in severely debilitated or immunosuppressed individuals.⁴ The extensive bony destruction, especially of the nasal region, of our patient’s tumor likely led to secondary infection with Rhizopus.

Approximately 85% of all metastatic BCCs originate in the head and neck region, with lymph nodes being the first site of metastasis and involved in approximately half of all cases.^1,4 Metastases to the lungs, bone, liver, and other viscera can occur with advanced disease. Metastasis generally portends a poor prognosis, with survival rarely exceeding 1.5 years. Until recently, therapeutic options for metastatic disease were limited, with marginal response to chemotherapy with methotrexate, fluorouracil, bleomycin, and cisplatin.⁴ Vismodegib, a novel smoothened receptor inhibitor that blocks the sonic hedgehog pathway implicated in BCC carcinogenesis, offers a new promising treatment for management and control of advanced disease.⁵

To the Editor:

A 60-year-old woman with a history of lymphoma presented to the emergency department for evaluation of intermittent diarrhea and vomiting of 2 weeks’ duration. On presentation, a rather large dressing covering the entire right half of the face was noted. Removal of the bandage revealed a necrotic, extensively destructive, right-sided facial lesion with a fully exposed ocular globe (Figure 1). The patient lived alone and was accompanied by a neighbor, who disclosed that the lesion had been neglected and enlarged over the last 15 years. Moreover, the neighbor reported that the patient had recently experienced several episodes of vertigo and frequent falls.

On admission to the hospital, dermatology was consulted and initial workup included computed tomography (CT) scan of the head and maxillofacial region, which showed a destructive process involving the right frontotemporal bone, maxillofacial region, sphenoid, and skull base with exposure of intracranial contents (Figure 2). An aggressive wound care regimen was instituted. Biopsy of the wound margin revealed nodular and focally infiltrative basal cell carcinoma (BCC) (Figure 3). Culture of the necrotic bone grew Rhizopus, a causative organism of mucormycosis, and the patient was treated with posaconazole. A CT scan of the chest and abdomen showed multiple bilateral pulmonary nodules and necrotic lymph nodes in the left hilum and left axilla. The patient refused bronchoscopy to further evaluate the pulmonary nodules. Ultrasound-guided biopsy of the left axillarylymph node revealed metastatic disease (Figure 4).

Several days into her hospitalization, the patient developed radicular pain in both arms and weakness in all 4 extremities. A CT scan of the neck revealed a pathologic fracture of the C7 vertebrae. Several medical and surgical services as well as psychiatry were consulted. Given the extensive nature of the disease involvement with limited treatment options, the patient sought to forego further interventions and was discharged to hospice care.

Basal cell carcinomas rarely metastasize, with a reported incidence of 0.0028% to 0.5%.¹ The likelihood of metastasis is most closely related to tumor size and depth of invasion. Tumors greater than 3 cm in diameter have a 2% incidence of metastatic spread and/or death. The incidence of metastatic spread and/or death is estimated to be 25% for tumors with a diameter of 5 cm and 50% for tumors with a diameter of 10 cm or greater.² Other risk factors for metastatic spread include long duration of disease, failure to respond to conventional treatment, and prior radiation treatment in the affected area.¹ In one review, the median interval between onset of BCC and metastasis was 9 years.³ In our case, 15 years of neglect most likely led to the aggressiveness of the tumor. Although the workup in our patient was limited per her request, there was no evidence that her lymphoma had recurred or that she was in any other way immunocompromised. Unfortunately, in this patient’s case, the local destructiveness of the carcinoma with subsequent bony invasion and necrosis was complicated with secondary Rhizopus infection. A PubMed search of articles indexed for MEDLINE using the terms basal cell carcinoma and mucormycosis revealed no other reported cases of BCC associated with mucormycosis; therefore, our case represents a rare presentation of this association. Rhinocerebral mucormycosis is the most common manifestation of mucormycosis and more commonly occurs in diabetics with ketoacidosis and in severely debilitated or immunosuppressed individuals.⁴ The extensive bony destruction, especially of the nasal region, of our patient’s tumor likely led to secondary infection with Rhizopus.

Approximately 85% of all metastatic BCCs originate in the head and neck region, with lymph nodes being the first site of metastasis and involved in approximately half of all cases.^1,4 Metastases to the lungs, bone, liver, and other viscera can occur with advanced disease. Metastasis generally portends a poor prognosis, with survival rarely exceeding 1.5 years. Until recently, therapeutic options for metastatic disease were limited, with marginal response to chemotherapy with methotrexate, fluorouracil, bleomycin, and cisplatin.⁴ Vismodegib, a novel smoothened receptor inhibitor that blocks the sonic hedgehog pathway implicated in BCC carcinogenesis, offers a new promising treatment for management and control of advanced disease.⁵

BROOKLYN, N.Y. – The legalization of marijuana almost certainly will complicate the treatment of substance use disorder in adolescents, particularly when SUD occurs as a comorbidity of bipolar disorder or other psychiatric diseases, according to an expert review at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

The full effects of marijuana legalization on SUD have not yet been comprehensively studied in children or adults, but the consequences of easier access, diminished stigma, and potential for a diminished sense of harm are widely considered to be an important obstacle to successful therapy in children, said Timothy E. Wilens, MD, chief of the division of child and adolescent psychiatry at Massachusetts General Hospital, Boston.

Comorbid substance use in children with mood disorders or ADHD has long been understood as a form of self-medication. However, use of marijuana, alcohol, or other mood-altering drugs also are known to interfere with treatment, Dr. Wilens said.

The problem is common among adults as well, but adolescents pose a greater challenge.

“Youths are more vulnerable to developing a substance use disorder because reward pathways develop before control pathways,” Dr. Wilens said. He cited data showing that about half of individuals who develop SUD, many of whom have other psychiatric diagnoses, do so by age 18 years, and 80% do so by age 26 years.

“Substance use disorder is a pediatric issue,” he emphasized.

The problem with legalization of marijuana is that adolescents are likely to conclude that what is safe for adults is safe for children. Citing a study that associated increased use of marijuana with reduced perception of harm (and the opposite), Dr. Wilens predicted that adolescents with comorbid SUD would resist treatment.

Because of those concerns, Massachusetts General Hospital, which is based in a state where recreational marijuana use is permitted, has issued a position statement. The statement endorses the study of marijuana for benefit and for harm but expresses specific concern about “the recreational use of marijuana at any age because of the potential downstream effects on children.”

Dr. Wilens expressed particular concern about parental use of marijuana in front of children because of the implication that it is safe and acceptable. For children at risk of comorbid substance use because of a mood disorder, he cautioned parents against even concealed use of marijuana because of the low likelihood that it will go unnoticed.

“Substance use disorders are associated with a more pernicious and longer course in adolescents than children,” said Dr. Wilens, paraphrasing one of the bullet points from the Massachusetts General position statement, which outlines the potential harms for children. Another of the bullet points maintains, “there are known structural and functional brain changes” that have been documented when marijuana use begins in childhood.

Citing a correlation between parental and adolescent marijuana use, Dr. Wilens said the legalization of marijuana appears destined to exacerbate the already considerable challenge of substance use in children. He noted that a very high proportion of adolescents with or without mood disorders experiment with marijuana at some point in high school, so there already is resistance to a characterization that it is harmful.

A realistic approach is therefore required in helping adolescents with comorbid substance use to curb this form of self-medication. It is essential to set priorities, he said, when treating adolescents with SUD and comorbid psychiatric disorders. “Don’t even think about treating substance use disorder until you treat the bipolar disease,” he said.

As the symptoms are relieved, the need for self-medication is likely to diminish, but Dr. Wilens cautioned against being too rigid when helping adolescents move away from marijuana and alcohol. He believes a zero tolerance approach can be counterproductive. Rather, he advocates a “harm reduction” approach in which adolescents agree to reasonable reductions, like avoiding marijuana during the week, while they eliminate dependence.

In an overview of pharmacotherapy to reduce cravings for drugs, he cited evidence, as well as personal experience, that over-the-counter N-acetylcysteine can be a useful tool. However, adolescents in particular should be warned about the pungent smell, which has been a barrier to adherence. He also suggested that psychotherapy, with or without pharmacotherapy, is helpful.

Treatment of comorbid SUD is a critical part of achieving control of accompanying psychiatric diseases, but this task might be complicated by legalized recreational marijuana, Dr. Wilens concluded. He encouraged clinicians to recognize that challenge.

Dr. Wilens reported financial relationships with Ironshore Pharmaceuticals, Janssen, KemPharm, and Otsuka Pharmaceutical.
 

BROOKLYN, N.Y. – The legalization of marijuana almost certainly will complicate the treatment of substance use disorder in adolescents, particularly when SUD occurs as a comorbidity of bipolar disorder or other psychiatric diseases, according to an expert review at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

The full effects of marijuana legalization on SUD have not yet been comprehensively studied in children or adults, but the consequences of easier access, diminished stigma, and potential for a diminished sense of harm are widely considered to be an important obstacle to successful therapy in children, said Timothy E. Wilens, MD, chief of the division of child and adolescent psychiatry at Massachusetts General Hospital, Boston.

Comorbid substance use in children with mood disorders or ADHD has long been understood as a form of self-medication. However, use of marijuana, alcohol, or other mood-altering drugs also are known to interfere with treatment, Dr. Wilens said.

The problem is common among adults as well, but adolescents pose a greater challenge.

“Youths are more vulnerable to developing a substance use disorder because reward pathways develop before control pathways,” Dr. Wilens said. He cited data showing that about half of individuals who develop SUD, many of whom have other psychiatric diagnoses, do so by age 18 years, and 80% do so by age 26 years.

“Substance use disorder is a pediatric issue,” he emphasized.

The problem with legalization of marijuana is that adolescents are likely to conclude that what is safe for adults is safe for children. Citing a study that associated increased use of marijuana with reduced perception of harm (and the opposite), Dr. Wilens predicted that adolescents with comorbid SUD would resist treatment.

Because of those concerns, Massachusetts General Hospital, which is based in a state where recreational marijuana use is permitted, has issued a position statement. The statement endorses the study of marijuana for benefit and for harm but expresses specific concern about “the recreational use of marijuana at any age because of the potential downstream effects on children.”

Dr. Wilens expressed particular concern about parental use of marijuana in front of children because of the implication that it is safe and acceptable. For children at risk of comorbid substance use because of a mood disorder, he cautioned parents against even concealed use of marijuana because of the low likelihood that it will go unnoticed.

“Substance use disorders are associated with a more pernicious and longer course in adolescents than children,” said Dr. Wilens, paraphrasing one of the bullet points from the Massachusetts General position statement, which outlines the potential harms for children. Another of the bullet points maintains, “there are known structural and functional brain changes” that have been documented when marijuana use begins in childhood.

Citing a correlation between parental and adolescent marijuana use, Dr. Wilens said the legalization of marijuana appears destined to exacerbate the already considerable challenge of substance use in children. He noted that a very high proportion of adolescents with or without mood disorders experiment with marijuana at some point in high school, so there already is resistance to a characterization that it is harmful.

A realistic approach is therefore required in helping adolescents with comorbid substance use to curb this form of self-medication. It is essential to set priorities, he said, when treating adolescents with SUD and comorbid psychiatric disorders. “Don’t even think about treating substance use disorder until you treat the bipolar disease,” he said.

As the symptoms are relieved, the need for self-medication is likely to diminish, but Dr. Wilens cautioned against being too rigid when helping adolescents move away from marijuana and alcohol. He believes a zero tolerance approach can be counterproductive. Rather, he advocates a “harm reduction” approach in which adolescents agree to reasonable reductions, like avoiding marijuana during the week, while they eliminate dependence.

In an overview of pharmacotherapy to reduce cravings for drugs, he cited evidence, as well as personal experience, that over-the-counter N-acetylcysteine can be a useful tool. However, adolescents in particular should be warned about the pungent smell, which has been a barrier to adherence. He also suggested that psychotherapy, with or without pharmacotherapy, is helpful.

Treatment of comorbid SUD is a critical part of achieving control of accompanying psychiatric diseases, but this task might be complicated by legalized recreational marijuana, Dr. Wilens concluded. He encouraged clinicians to recognize that challenge.

Dr. Wilens reported financial relationships with Ironshore Pharmaceuticals, Janssen, KemPharm, and Otsuka Pharmaceutical.
 

BROOKLYN, N.Y. – The legalization of marijuana almost certainly will complicate the treatment of substance use disorder in adolescents, particularly when SUD occurs as a comorbidity of bipolar disorder or other psychiatric diseases, according to an expert review at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

The full effects of marijuana legalization on SUD have not yet been comprehensively studied in children or adults, but the consequences of easier access, diminished stigma, and potential for a diminished sense of harm are widely considered to be an important obstacle to successful therapy in children, said Timothy E. Wilens, MD, chief of the division of child and adolescent psychiatry at Massachusetts General Hospital, Boston.

Comorbid substance use in children with mood disorders or ADHD has long been understood as a form of self-medication. However, use of marijuana, alcohol, or other mood-altering drugs also are known to interfere with treatment, Dr. Wilens said.

The problem is common among adults as well, but adolescents pose a greater challenge.

“Youths are more vulnerable to developing a substance use disorder because reward pathways develop before control pathways,” Dr. Wilens said. He cited data showing that about half of individuals who develop SUD, many of whom have other psychiatric diagnoses, do so by age 18 years, and 80% do so by age 26 years.

“Substance use disorder is a pediatric issue,” he emphasized.

The problem with legalization of marijuana is that adolescents are likely to conclude that what is safe for adults is safe for children. Citing a study that associated increased use of marijuana with reduced perception of harm (and the opposite), Dr. Wilens predicted that adolescents with comorbid SUD would resist treatment.

Because of those concerns, Massachusetts General Hospital, which is based in a state where recreational marijuana use is permitted, has issued a position statement. The statement endorses the study of marijuana for benefit and for harm but expresses specific concern about “the recreational use of marijuana at any age because of the potential downstream effects on children.”

Dr. Wilens expressed particular concern about parental use of marijuana in front of children because of the implication that it is safe and acceptable. For children at risk of comorbid substance use because of a mood disorder, he cautioned parents against even concealed use of marijuana because of the low likelihood that it will go unnoticed.

“Substance use disorders are associated with a more pernicious and longer course in adolescents than children,” said Dr. Wilens, paraphrasing one of the bullet points from the Massachusetts General position statement, which outlines the potential harms for children. Another of the bullet points maintains, “there are known structural and functional brain changes” that have been documented when marijuana use begins in childhood.

Citing a correlation between parental and adolescent marijuana use, Dr. Wilens said the legalization of marijuana appears destined to exacerbate the already considerable challenge of substance use in children. He noted that a very high proportion of adolescents with or without mood disorders experiment with marijuana at some point in high school, so there already is resistance to a characterization that it is harmful.

A realistic approach is therefore required in helping adolescents with comorbid substance use to curb this form of self-medication. It is essential to set priorities, he said, when treating adolescents with SUD and comorbid psychiatric disorders. “Don’t even think about treating substance use disorder until you treat the bipolar disease,” he said.

As the symptoms are relieved, the need for self-medication is likely to diminish, but Dr. Wilens cautioned against being too rigid when helping adolescents move away from marijuana and alcohol. He believes a zero tolerance approach can be counterproductive. Rather, he advocates a “harm reduction” approach in which adolescents agree to reasonable reductions, like avoiding marijuana during the week, while they eliminate dependence.

In an overview of pharmacotherapy to reduce cravings for drugs, he cited evidence, as well as personal experience, that over-the-counter N-acetylcysteine can be a useful tool. However, adolescents in particular should be warned about the pungent smell, which has been a barrier to adherence. He also suggested that psychotherapy, with or without pharmacotherapy, is helpful.

Treatment of comorbid SUD is a critical part of achieving control of accompanying psychiatric diseases, but this task might be complicated by legalized recreational marijuana, Dr. Wilens concluded. He encouraged clinicians to recognize that challenge.

Dr. Wilens reported financial relationships with Ironshore Pharmaceuticals, Janssen, KemPharm, and Otsuka Pharmaceutical.
 

In an era when we have access to a dizzying array of biologics for psoriasis treatment, it is easy to forget that topical therapies are still the bread and butter of treatment. For the majority of patients living with psoriasis, topical treatment is the only therapy they receive; indeed, a recent study examining a large national payer database found that 86% of psoriasis patients were managed with topical medications only.¹ Thus, it is extremely important to understand how to optimize topical treatments, recognize pitfalls in management, and utilize newer agents that can been added to our treatment armamentarium for psoriasis.

In general, steroids have been the mainstay of topical treatment of psoriasis. Their broad anti-inflammatory activity works well against both the visible signs and symptoms of psoriasis as well as the underlying inflammatory milieu of the disease; however, these treatments are not without their downsides. Hypothalamic-pituitary-adrenal (HPA) axis suppression, especially in higher-potency topical steroids, is a serious concern that limits their use. In one study comparing lotion and cream formulations of clobetasol propionate, HPA axis suppression was seen in 80% (8/10) of adults in the lotion group and 30% (3/10) in the cream group after 4 weeks of treatment.² These findings are not new; a 1987 study found that patients using less than 50 g of topical clobetasol per week, which is considered a low dose, could still exhibit HPA axis suppression.³ Severe HPA axis suppression may occur; one study of various topical steroids found some degree of HPA axis suppression in 38% (19/50) of patients, with a direct correlation with topical steroid potency.⁴ Additionally, cutaneous side effects such as striae formation, atrophy, and the possibility of tachyphylaxis must be considered. Various treatment regimens have been developed to limit topical steroid use, including steroid-sparing medications (eg, calcipotriene) used in conjunction with topical steroids, systemic treatments (eg, phototherapy) added on, or higher-potency topical steroids rotated with lower-potency steroids. Implementing other agents, such as topical retinoids or keratolytics, into the treatment regimen also is an important consideration in the overall approach to topical psoriasis therapy.

Notably, a number of newly approved topical treatments for psoriasis have emerged, and more are in the pipeline. When evaluating these agents, important considerations include safety, length of treatment course, and efficacy. Several of these agents hold promise for patients with psoriasis.

The newest agent, halobetasol propionate lotion 0.01%, was approved for treatment of psoriasis in October 2018. Compared to halobetasol 0.05% cream or ointment, halobetasol propionate lotion 0.01% has one-fifth the concentration of the active ingredient with the same degree of success in efficacy scores.⁹ This reduction in drug concentration is possible because the proprietary lotion base allows for better drug delivery of the active ingredient. Importantly, HPA axis suppression was assessed over an 8-week period of use and no suppression was noted.⁹ Generic class I steroids should only be used for 2 weeks, which is the standard treatment period used in comparator trials; however, many patients will still have active lesions on their body after 2 weeks of treatment, and if using generic clobetasol or betamethasone dipropionate, the choice becomes whether to keep applying the medication and risk HPA axis suppression and cutaneous side effects or switch to a less effective treatment. However, some of the newer agents are indicated for 4 to 8 weeks of treatment.

Utilizing other classes of agents such as retinoids and keratolytics in our treatment armamentarium for psoriasis often is helpful. It has long been known that tazarotene can be combined with topical steroids for increased efficacy and limitation of the irritating effects of the retinoid.¹⁰ Similarly, keratolytics play a role in allowing a topically applied medication to penetrate deep enough to affect the underlying inflammation of psoriasis. Medications that include salicylic acid or urea may help to remove ostraceous scales from thick psoriasis lesions that would otherwise prevent delivery of topical steroids to achieve clinically meaningful results. For scalp psoriasis, there are salicylic acid solutions as well as newer agents such as a dimethicone-based topical product.¹¹

Nonsteroidal topical anti-inflammatories also have been used off label for psoriasis treatment. These agents are especially useful in patients who were not successfully treated with calcipotriene or need adjunctive therapy. Although not extremely effective against plaque psoriasis, topical tacrolimus in particular seems to have a place in the treatment of inverse psoriasis where it can be utilized without concern for long-term side effects.¹² Crisaborole ointment, a topical medication approved for treatment of atopic dermatitis, was studied in phase 2 trials, but development has not progressed for a psoriasis indication.¹³ It is reasonable to consider this medication in the same way that tacrolimus has been used, however, considering that the mechanism of action—phosphodiesterase type 4 inhibition—has successfully been implemented in an oral medication to treat psoriasis, apremilast.

There are numerous topical medications in the pipeline that are being developed to treat psoriasis. Of them, the most relevant is a fixed-dose combination of halobetasol propionate 0.01% and tazarotene 0.045% in a proprietary lotion vehicle. A decision from the US Food and Drug Administration is expected in the first quarter of 2019. This medication capitalizes on the aforementioned synergistic effects of tazarotene and a superpotent topical steroid to achieve improved efficacy. Similar to halobetasol lotion 0.01%, this product was evaluated over an 8-week period, and no HPA axis suppression was observed. Efficacy was significantly improved versus both placebo and either halobetasol or tazarotene alone.¹⁴

Overall, it is promising that after a long period of relative stagnancy, we have numerous new agents available and upcoming for the topical treatment of psoriasis. For the vast majority of patients, topical medications still represent the mainstay of treatment, and it is important that we have access to better, safer medications in this category.

In an era when we have access to a dizzying array of biologics for psoriasis treatment, it is easy to forget that topical therapies are still the bread and butter of treatment. For the majority of patients living with psoriasis, topical treatment is the only therapy they receive; indeed, a recent study examining a large national payer database found that 86% of psoriasis patients were managed with topical medications only.¹ Thus, it is extremely important to understand how to optimize topical treatments, recognize pitfalls in management, and utilize newer agents that can been added to our treatment armamentarium for psoriasis.

In general, steroids have been the mainstay of topical treatment of psoriasis. Their broad anti-inflammatory activity works well against both the visible signs and symptoms of psoriasis as well as the underlying inflammatory milieu of the disease; however, these treatments are not without their downsides. Hypothalamic-pituitary-adrenal (HPA) axis suppression, especially in higher-potency topical steroids, is a serious concern that limits their use. In one study comparing lotion and cream formulations of clobetasol propionate, HPA axis suppression was seen in 80% (8/10) of adults in the lotion group and 30% (3/10) in the cream group after 4 weeks of treatment.² These findings are not new; a 1987 study found that patients using less than 50 g of topical clobetasol per week, which is considered a low dose, could still exhibit HPA axis suppression.³ Severe HPA axis suppression may occur; one study of various topical steroids found some degree of HPA axis suppression in 38% (19/50) of patients, with a direct correlation with topical steroid potency.⁴ Additionally, cutaneous side effects such as striae formation, atrophy, and the possibility of tachyphylaxis must be considered. Various treatment regimens have been developed to limit topical steroid use, including steroid-sparing medications (eg, calcipotriene) used in conjunction with topical steroids, systemic treatments (eg, phototherapy) added on, or higher-potency topical steroids rotated with lower-potency steroids. Implementing other agents, such as topical retinoids or keratolytics, into the treatment regimen also is an important consideration in the overall approach to topical psoriasis therapy.

Notably, a number of newly approved topical treatments for psoriasis have emerged, and more are in the pipeline. When evaluating these agents, important considerations include safety, length of treatment course, and efficacy. Several of these agents hold promise for patients with psoriasis.

The newest agent, halobetasol propionate lotion 0.01%, was approved for treatment of psoriasis in October 2018. Compared to halobetasol 0.05% cream or ointment, halobetasol propionate lotion 0.01% has one-fifth the concentration of the active ingredient with the same degree of success in efficacy scores.⁹ This reduction in drug concentration is possible because the proprietary lotion base allows for better drug delivery of the active ingredient. Importantly, HPA axis suppression was assessed over an 8-week period of use and no suppression was noted.⁹ Generic class I steroids should only be used for 2 weeks, which is the standard treatment period used in comparator trials; however, many patients will still have active lesions on their body after 2 weeks of treatment, and if using generic clobetasol or betamethasone dipropionate, the choice becomes whether to keep applying the medication and risk HPA axis suppression and cutaneous side effects or switch to a less effective treatment. However, some of the newer agents are indicated for 4 to 8 weeks of treatment.

Utilizing other classes of agents such as retinoids and keratolytics in our treatment armamentarium for psoriasis often is helpful. It has long been known that tazarotene can be combined with topical steroids for increased efficacy and limitation of the irritating effects of the retinoid.¹⁰ Similarly, keratolytics play a role in allowing a topically applied medication to penetrate deep enough to affect the underlying inflammation of psoriasis. Medications that include salicylic acid or urea may help to remove ostraceous scales from thick psoriasis lesions that would otherwise prevent delivery of topical steroids to achieve clinically meaningful results. For scalp psoriasis, there are salicylic acid solutions as well as newer agents such as a dimethicone-based topical product.¹¹

Nonsteroidal topical anti-inflammatories also have been used off label for psoriasis treatment. These agents are especially useful in patients who were not successfully treated with calcipotriene or need adjunctive therapy. Although not extremely effective against plaque psoriasis, topical tacrolimus in particular seems to have a place in the treatment of inverse psoriasis where it can be utilized without concern for long-term side effects.¹² Crisaborole ointment, a topical medication approved for treatment of atopic dermatitis, was studied in phase 2 trials, but development has not progressed for a psoriasis indication.¹³ It is reasonable to consider this medication in the same way that tacrolimus has been used, however, considering that the mechanism of action—phosphodiesterase type 4 inhibition—has successfully been implemented in an oral medication to treat psoriasis, apremilast.

There are numerous topical medications in the pipeline that are being developed to treat psoriasis. Of them, the most relevant is a fixed-dose combination of halobetasol propionate 0.01% and tazarotene 0.045% in a proprietary lotion vehicle. A decision from the US Food and Drug Administration is expected in the first quarter of 2019. This medication capitalizes on the aforementioned synergistic effects of tazarotene and a superpotent topical steroid to achieve improved efficacy. Similar to halobetasol lotion 0.01%, this product was evaluated over an 8-week period, and no HPA axis suppression was observed. Efficacy was significantly improved versus both placebo and either halobetasol or tazarotene alone.¹⁴

Overall, it is promising that after a long period of relative stagnancy, we have numerous new agents available and upcoming for the topical treatment of psoriasis. For the vast majority of patients, topical medications still represent the mainstay of treatment, and it is important that we have access to better, safer medications in this category.

In an era when we have access to a dizzying array of biologics for psoriasis treatment, it is easy to forget that topical therapies are still the bread and butter of treatment. For the majority of patients living with psoriasis, topical treatment is the only therapy they receive; indeed, a recent study examining a large national payer database found that 86% of psoriasis patients were managed with topical medications only.¹ Thus, it is extremely important to understand how to optimize topical treatments, recognize pitfalls in management, and utilize newer agents that can been added to our treatment armamentarium for psoriasis.

In general, steroids have been the mainstay of topical treatment of psoriasis. Their broad anti-inflammatory activity works well against both the visible signs and symptoms of psoriasis as well as the underlying inflammatory milieu of the disease; however, these treatments are not without their downsides. Hypothalamic-pituitary-adrenal (HPA) axis suppression, especially in higher-potency topical steroids, is a serious concern that limits their use. In one study comparing lotion and cream formulations of clobetasol propionate, HPA axis suppression was seen in 80% (8/10) of adults in the lotion group and 30% (3/10) in the cream group after 4 weeks of treatment.² These findings are not new; a 1987 study found that patients using less than 50 g of topical clobetasol per week, which is considered a low dose, could still exhibit HPA axis suppression.³ Severe HPA axis suppression may occur; one study of various topical steroids found some degree of HPA axis suppression in 38% (19/50) of patients, with a direct correlation with topical steroid potency.⁴ Additionally, cutaneous side effects such as striae formation, atrophy, and the possibility of tachyphylaxis must be considered. Various treatment regimens have been developed to limit topical steroid use, including steroid-sparing medications (eg, calcipotriene) used in conjunction with topical steroids, systemic treatments (eg, phototherapy) added on, or higher-potency topical steroids rotated with lower-potency steroids. Implementing other agents, such as topical retinoids or keratolytics, into the treatment regimen also is an important consideration in the overall approach to topical psoriasis therapy.

Notably, a number of newly approved topical treatments for psoriasis have emerged, and more are in the pipeline. When evaluating these agents, important considerations include safety, length of treatment course, and efficacy. Several of these agents hold promise for patients with psoriasis.

The newest agent, halobetasol propionate lotion 0.01%, was approved for treatment of psoriasis in October 2018. Compared to halobetasol 0.05% cream or ointment, halobetasol propionate lotion 0.01% has one-fifth the concentration of the active ingredient with the same degree of success in efficacy scores.⁹ This reduction in drug concentration is possible because the proprietary lotion base allows for better drug delivery of the active ingredient. Importantly, HPA axis suppression was assessed over an 8-week period of use and no suppression was noted.⁹ Generic class I steroids should only be used for 2 weeks, which is the standard treatment period used in comparator trials; however, many patients will still have active lesions on their body after 2 weeks of treatment, and if using generic clobetasol or betamethasone dipropionate, the choice becomes whether to keep applying the medication and risk HPA axis suppression and cutaneous side effects or switch to a less effective treatment. However, some of the newer agents are indicated for 4 to 8 weeks of treatment.

Utilizing other classes of agents such as retinoids and keratolytics in our treatment armamentarium for psoriasis often is helpful. It has long been known that tazarotene can be combined with topical steroids for increased efficacy and limitation of the irritating effects of the retinoid.¹⁰ Similarly, keratolytics play a role in allowing a topically applied medication to penetrate deep enough to affect the underlying inflammation of psoriasis. Medications that include salicylic acid or urea may help to remove ostraceous scales from thick psoriasis lesions that would otherwise prevent delivery of topical steroids to achieve clinically meaningful results. For scalp psoriasis, there are salicylic acid solutions as well as newer agents such as a dimethicone-based topical product.¹¹

Nonsteroidal topical anti-inflammatories also have been used off label for psoriasis treatment. These agents are especially useful in patients who were not successfully treated with calcipotriene or need adjunctive therapy. Although not extremely effective against plaque psoriasis, topical tacrolimus in particular seems to have a place in the treatment of inverse psoriasis where it can be utilized without concern for long-term side effects.¹² Crisaborole ointment, a topical medication approved for treatment of atopic dermatitis, was studied in phase 2 trials, but development has not progressed for a psoriasis indication.¹³ It is reasonable to consider this medication in the same way that tacrolimus has been used, however, considering that the mechanism of action—phosphodiesterase type 4 inhibition—has successfully been implemented in an oral medication to treat psoriasis, apremilast.

There are numerous topical medications in the pipeline that are being developed to treat psoriasis. Of them, the most relevant is a fixed-dose combination of halobetasol propionate 0.01% and tazarotene 0.045% in a proprietary lotion vehicle. A decision from the US Food and Drug Administration is expected in the first quarter of 2019. This medication capitalizes on the aforementioned synergistic effects of tazarotene and a superpotent topical steroid to achieve improved efficacy. Similar to halobetasol lotion 0.01%, this product was evaluated over an 8-week period, and no HPA axis suppression was observed. Efficacy was significantly improved versus both placebo and either halobetasol or tazarotene alone.¹⁴

Overall, it is promising that after a long period of relative stagnancy, we have numerous new agents available and upcoming for the topical treatment of psoriasis. For the vast majority of patients, topical medications still represent the mainstay of treatment, and it is important that we have access to better, safer medications in this category.

Nonalcoholic steatohepatitis may soon supplant chronic hepatitis C as the leading cause of hepatocellular carcinoma among patients awaiting liver transplantation, according to the findings of a national longitudinal registry study.

The proportion of affected patients with nonalcoholic steatohepatitis (NASH) rose nearly 700% between 2002 and 2017 (P less than .0001), making NASH the only etiology to significantly rise in prevalence, reported Zobair Younossi, MD, MPH, of Inova Health System in Falls Church, Va., and his associates. Chronic hepatitis C remained the most common cause of liver cancer during the study period, but its prevalence fell by more than 10% in the last 3 years (2014-2017). These trends reflect the advent of “new, highly effective antiviral regimens” for hepatitis C, the global epidemic of obesity and metabolic syndrome, and the urgent need for effective, safe treatments for NASH, they wrote in Clinical Gastroenterology and Hepatology.

Historically, hepatocellular carcinoma is usually caused by chronic hepatitis C or B infection, but the global rise of obesity and type 2 diabetes mellitus has led to epidemic levels of NASH, a progressive form of nonalcoholic fatty liver disease that lacks useful predictive noninvasive biomarkers or safe treatments. This phenomenon, coupled with the advent of new, often-curative treatments for viral hepatitis, is making NASH a leading driver of both fibrosis and liver transplantation in the United States. To compare trends in liver cancer etiologies among transplant candidates, Dr. Younossi and his associates analyzed data on 158,347 adults who were wait-listed between 2002 and 2017 and captured by the national Scientific Registry of Transplant Recipients.

A total of 26,121 (16.5%) patients awaiting liver transplant had hepatocellular carcinoma. This proportion nearly quadrupled over the study period, from 6% to 23% (P less than .0001) and rose significantly (P less than .0001) for all liver cancer etiologies (hepatitis C and B, alcoholic liver disease, and NASH). However, the absolute rise in prevalence was far greater for NASH (1050%) than for chronic hepatitis C (more than 500%) or any other etiology.

Furthermore, while most (65%) liver cancer cases involved chronic hepatitis C, the proportion of cases involving NASH rose from 2% in 2002 to 18% in 2017 (P less than .0001). By 2017, NASH topped alcoholic liver disease, comorbid hepatitis C with alcoholic liver disease, and chronic hepatitis B as an etiology of hepatocellular carcinoma among patients listed for transplant. Conversely, by 2017, less than 50% of liver cancers were caused by hepatitis C – a more than 10% drop from 2014. Over the study period, NASH was the only etiology whose prevalence significantly increased among transplant-listed patients with hepatocellular carcinoma.

In this study, etiology of liver cancer did not seem to affect the likelihood of either death or transplantation. However, serious cardiovascular disease or late-stage cancer diagnosis might exclude many NASH patients from transplantation, the researchers wrote. “Thus, the population reported here actually may underestimate the true proportion of hepatocellular carcinoma cases related to nonalcoholic fatty liver disease and NASH in the United States. Because NASH is on a trajectory to become the most common cause of hepatocellular carcinoma in the United States, effective prevention strategies and treatment options are urgently needed for this currently underserved patient population.”

Minneapolis Medical Research Foundation is the contractor for the registry and supplied the data. Dr. Younossi reported ties to Bristol-Myers Squibb, Gilead Sciences, AbbVie, Intercept Pharmaceuticals, and GlaxoSmithKline.

SOURCE: Younossi Z et al. Clin Gastroenterol Hepatol. 2018 Jun 14. doi: 10.1016/j.cgh.2018.05.057.

Nonalcoholic steatohepatitis may soon supplant chronic hepatitis C as the leading cause of hepatocellular carcinoma among patients awaiting liver transplantation, according to the findings of a national longitudinal registry study.

The proportion of affected patients with nonalcoholic steatohepatitis (NASH) rose nearly 700% between 2002 and 2017 (P less than .0001), making NASH the only etiology to significantly rise in prevalence, reported Zobair Younossi, MD, MPH, of Inova Health System in Falls Church, Va., and his associates. Chronic hepatitis C remained the most common cause of liver cancer during the study period, but its prevalence fell by more than 10% in the last 3 years (2014-2017). These trends reflect the advent of “new, highly effective antiviral regimens” for hepatitis C, the global epidemic of obesity and metabolic syndrome, and the urgent need for effective, safe treatments for NASH, they wrote in Clinical Gastroenterology and Hepatology.

Historically, hepatocellular carcinoma is usually caused by chronic hepatitis C or B infection, but the global rise of obesity and type 2 diabetes mellitus has led to epidemic levels of NASH, a progressive form of nonalcoholic fatty liver disease that lacks useful predictive noninvasive biomarkers or safe treatments. This phenomenon, coupled with the advent of new, often-curative treatments for viral hepatitis, is making NASH a leading driver of both fibrosis and liver transplantation in the United States. To compare trends in liver cancer etiologies among transplant candidates, Dr. Younossi and his associates analyzed data on 158,347 adults who were wait-listed between 2002 and 2017 and captured by the national Scientific Registry of Transplant Recipients.

A total of 26,121 (16.5%) patients awaiting liver transplant had hepatocellular carcinoma. This proportion nearly quadrupled over the study period, from 6% to 23% (P less than .0001) and rose significantly (P less than .0001) for all liver cancer etiologies (hepatitis C and B, alcoholic liver disease, and NASH). However, the absolute rise in prevalence was far greater for NASH (1050%) than for chronic hepatitis C (more than 500%) or any other etiology.

Furthermore, while most (65%) liver cancer cases involved chronic hepatitis C, the proportion of cases involving NASH rose from 2% in 2002 to 18% in 2017 (P less than .0001). By 2017, NASH topped alcoholic liver disease, comorbid hepatitis C with alcoholic liver disease, and chronic hepatitis B as an etiology of hepatocellular carcinoma among patients listed for transplant. Conversely, by 2017, less than 50% of liver cancers were caused by hepatitis C – a more than 10% drop from 2014. Over the study period, NASH was the only etiology whose prevalence significantly increased among transplant-listed patients with hepatocellular carcinoma.

In this study, etiology of liver cancer did not seem to affect the likelihood of either death or transplantation. However, serious cardiovascular disease or late-stage cancer diagnosis might exclude many NASH patients from transplantation, the researchers wrote. “Thus, the population reported here actually may underestimate the true proportion of hepatocellular carcinoma cases related to nonalcoholic fatty liver disease and NASH in the United States. Because NASH is on a trajectory to become the most common cause of hepatocellular carcinoma in the United States, effective prevention strategies and treatment options are urgently needed for this currently underserved patient population.”

Minneapolis Medical Research Foundation is the contractor for the registry and supplied the data. Dr. Younossi reported ties to Bristol-Myers Squibb, Gilead Sciences, AbbVie, Intercept Pharmaceuticals, and GlaxoSmithKline.

SOURCE: Younossi Z et al. Clin Gastroenterol Hepatol. 2018 Jun 14. doi: 10.1016/j.cgh.2018.05.057.

Nonalcoholic steatohepatitis may soon supplant chronic hepatitis C as the leading cause of hepatocellular carcinoma among patients awaiting liver transplantation, according to the findings of a national longitudinal registry study.

The proportion of affected patients with nonalcoholic steatohepatitis (NASH) rose nearly 700% between 2002 and 2017 (P less than .0001), making NASH the only etiology to significantly rise in prevalence, reported Zobair Younossi, MD, MPH, of Inova Health System in Falls Church, Va., and his associates. Chronic hepatitis C remained the most common cause of liver cancer during the study period, but its prevalence fell by more than 10% in the last 3 years (2014-2017). These trends reflect the advent of “new, highly effective antiviral regimens” for hepatitis C, the global epidemic of obesity and metabolic syndrome, and the urgent need for effective, safe treatments for NASH, they wrote in Clinical Gastroenterology and Hepatology.

Historically, hepatocellular carcinoma is usually caused by chronic hepatitis C or B infection, but the global rise of obesity and type 2 diabetes mellitus has led to epidemic levels of NASH, a progressive form of nonalcoholic fatty liver disease that lacks useful predictive noninvasive biomarkers or safe treatments. This phenomenon, coupled with the advent of new, often-curative treatments for viral hepatitis, is making NASH a leading driver of both fibrosis and liver transplantation in the United States. To compare trends in liver cancer etiologies among transplant candidates, Dr. Younossi and his associates analyzed data on 158,347 adults who were wait-listed between 2002 and 2017 and captured by the national Scientific Registry of Transplant Recipients.

A total of 26,121 (16.5%) patients awaiting liver transplant had hepatocellular carcinoma. This proportion nearly quadrupled over the study period, from 6% to 23% (P less than .0001) and rose significantly (P less than .0001) for all liver cancer etiologies (hepatitis C and B, alcoholic liver disease, and NASH). However, the absolute rise in prevalence was far greater for NASH (1050%) than for chronic hepatitis C (more than 500%) or any other etiology.

Furthermore, while most (65%) liver cancer cases involved chronic hepatitis C, the proportion of cases involving NASH rose from 2% in 2002 to 18% in 2017 (P less than .0001). By 2017, NASH topped alcoholic liver disease, comorbid hepatitis C with alcoholic liver disease, and chronic hepatitis B as an etiology of hepatocellular carcinoma among patients listed for transplant. Conversely, by 2017, less than 50% of liver cancers were caused by hepatitis C – a more than 10% drop from 2014. Over the study period, NASH was the only etiology whose prevalence significantly increased among transplant-listed patients with hepatocellular carcinoma.

In this study, etiology of liver cancer did not seem to affect the likelihood of either death or transplantation. However, serious cardiovascular disease or late-stage cancer diagnosis might exclude many NASH patients from transplantation, the researchers wrote. “Thus, the population reported here actually may underestimate the true proportion of hepatocellular carcinoma cases related to nonalcoholic fatty liver disease and NASH in the United States. Because NASH is on a trajectory to become the most common cause of hepatocellular carcinoma in the United States, effective prevention strategies and treatment options are urgently needed for this currently underserved patient population.”

Minneapolis Medical Research Foundation is the contractor for the registry and supplied the data. Dr. Younossi reported ties to Bristol-Myers Squibb, Gilead Sciences, AbbVie, Intercept Pharmaceuticals, and GlaxoSmithKline.

SOURCE: Younossi Z et al. Clin Gastroenterol Hepatol. 2018 Jun 14. doi: 10.1016/j.cgh.2018.05.057.

All across the nation, community by community, states are doing better at making sure veterans have homes. According to the latest VA tally, 3 states (Connecticut, Delaware, and Virginia) and 66 communities have “effectively ended” veteran homelessness. The latest to join the list is Little Rock, Arkansas.

Since 2010, homelessness has been nearly halved; between years 2017 and 2018, it declined by 5%. The progress is due in large part to Home, Together, a program run by the VA with the Department of Housing and Urban Development, and other federal, state and local partners. Using HUD’s “targeted” housing vouchers and the VA’s homelessness programs (www.va.gov/homeless/for_homeless_veterans.asp), nearly 700,000 veterans and their family members have been permanently housed, rapidly rehoused, or prevented from falling into homelessness.

VA medical centers are key to helping drive down the homeless numbers, the VA says. For instance, the Central Arkansas Veterans Healthcare System collaborates with state and local government, nonprofits, corporate partners, and community members to find homes, jobs, transportation, and services for veterans. The VA health care resources form a “band of care,” the VA says, which provides a holistic support system, including for those experiencing homelessness.

 “No American veteran should be without a safe and stable place to call home,” said VA Secretary Robert Wilkie. “We will continue this important work until we achieve a day when homelessness among veterans is rare and brief in every community across our country.”

All across the nation, community by community, states are doing better at making sure veterans have homes. According to the latest VA tally, 3 states (Connecticut, Delaware, and Virginia) and 66 communities have “effectively ended” veteran homelessness. The latest to join the list is Little Rock, Arkansas.

Since 2010, homelessness has been nearly halved; between years 2017 and 2018, it declined by 5%. The progress is due in large part to Home, Together, a program run by the VA with the Department of Housing and Urban Development, and other federal, state and local partners. Using HUD’s “targeted” housing vouchers and the VA’s homelessness programs (www.va.gov/homeless/for_homeless_veterans.asp), nearly 700,000 veterans and their family members have been permanently housed, rapidly rehoused, or prevented from falling into homelessness.

VA medical centers are key to helping drive down the homeless numbers, the VA says. For instance, the Central Arkansas Veterans Healthcare System collaborates with state and local government, nonprofits, corporate partners, and community members to find homes, jobs, transportation, and services for veterans. The VA health care resources form a “band of care,” the VA says, which provides a holistic support system, including for those experiencing homelessness.

 “No American veteran should be without a safe and stable place to call home,” said VA Secretary Robert Wilkie. “We will continue this important work until we achieve a day when homelessness among veterans is rare and brief in every community across our country.”

All across the nation, community by community, states are doing better at making sure veterans have homes. According to the latest VA tally, 3 states (Connecticut, Delaware, and Virginia) and 66 communities have “effectively ended” veteran homelessness. The latest to join the list is Little Rock, Arkansas.

Since 2010, homelessness has been nearly halved; between years 2017 and 2018, it declined by 5%. The progress is due in large part to Home, Together, a program run by the VA with the Department of Housing and Urban Development, and other federal, state and local partners. Using HUD’s “targeted” housing vouchers and the VA’s homelessness programs (www.va.gov/homeless/for_homeless_veterans.asp), nearly 700,000 veterans and their family members have been permanently housed, rapidly rehoused, or prevented from falling into homelessness.

VA medical centers are key to helping drive down the homeless numbers, the VA says. For instance, the Central Arkansas Veterans Healthcare System collaborates with state and local government, nonprofits, corporate partners, and community members to find homes, jobs, transportation, and services for veterans. The VA health care resources form a “band of care,” the VA says, which provides a holistic support system, including for those experiencing homelessness.

 “No American veteran should be without a safe and stable place to call home,” said VA Secretary Robert Wilkie. “We will continue this important work until we achieve a day when homelessness among veterans is rare and brief in every community across our country.”

A shift in Medicare drug coverage from Part B to Part D might save the government money, but might cost patients. Also today, there’s no single treatment for fibromyalgia, obesity-related cancers are increasing in younger adults, and pregnancy problems predict cardiovascular future.

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A shift in Medicare drug coverage from Part B to Part D might save the government money, but might cost patients. Also today, there’s no single treatment for fibromyalgia, obesity-related cancers are increasing in younger adults, and pregnancy problems predict cardiovascular future.

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Spotify

A shift in Medicare drug coverage from Part B to Part D might save the government money, but might cost patients. Also today, there’s no single treatment for fibromyalgia, obesity-related cancers are increasing in younger adults, and pregnancy problems predict cardiovascular future.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify

CHICAGO – The Global Registry for Endovascular Aortic Treatment is a unique resource that, although still early in its planned 10-year follow-up period, has already yielded important insights into one of the hottest topics in endovascular repair of abdominal aortic aneurysms: that is, the impact of the proximal aortic neck, Clayton J. Brinster, MD, said at a symposium on vascular surgery sponsored by Northwestern University.

The Global Registry for Endovascular Aortic Treatment (GREAT) is a prospective, observational, real-world registry that enrolled more than 5,000 consecutive patients undergoing endovascular aortic repair (EVAR) in the United States, Europe, Australia, New Zealand, and Brazil before enrollment closed in October 2016.

GREAT is the largest stent graft registry in the world. One of its special features is that it has essentially no exclusion criteria. This enables researchers to compare outcomes in patients undergoing on-label EVAR using devices deployed within the official instructions for use (IFU) to results in real-world practice, which not infrequently entails treatment for nonstandard indications using devices outside the narrowly defined IFU generated via pivotal clinical trials, explained Dr. Brinster, a vascular surgeon at the Ochsner Clinic Foundation in New Orleans.

The biggest limitation of GREAT is that it’s sponsored by Gore and restricted to recipients of GORE thoracic and abdominal stent grafts. However, the registry has an oversight and safety monitoring board that is independent of the company, Dr. Brinster continued.

He highlighted three recently published studies that have utilized early GREAT data to examine the impact on EVAR outcomes of various features of the proximal aortic neck.

An international team of investigators analyzed the incidence and impact of noncylindrical neck anatomy, defined as a 2-mm or greater change in diameter over the first 15 mm of proximal aortic neck length. Of 3,077 GREAT participants treated with the Gore Excluder endograft, 1,312, or 43%, had an hourglass, tapered, or conical neck shape that qualified as noncylindrical. Noncylindrical necks were more common in women. Fifteen percent of patients with a noncylindrical neck received the device outside the Excluder IFU, as did 11% with a cylindrical neck.

After an average follow-up of about 20 months, the noncylindrical neck group had a 3.1% rate of device-related intervention, significantly better than the 4.9% rate in patients with a cylindrical neck. In a multivariate regression analysis, female gender and maximum abdominal aortic aneurysm diameter were significant risk factors for device-related or endoleak-specific reintervention; noncylindrical neck morphology was not. Indeed, women were 2.2-fold more likely to require device-related reintervention than men (J Vasc Surg. 2018; 68[6]:1714-24).
 

Large proximal aortic neck

Of 3,166 consecutive patients in GREAT, 37.6% had a large aortic neck diameter, defined as 25 mm or wider. The rate of 5-year freedom from type Ia endoleak was 96.8% in the large-neck group, significantly less than the 98.6% rate in patients with a normal aortic neck diameter. Of note, rates didn’t diverge until after 2 years of follow-up, emphasizing the need for careful long-term surveillance despite initial technical success.

The 5-year rate of freedom from the primary composite endpoint of type Ia endoleak, reintervention, aortic rupture, or isolated aortic-related mortality was also significantly worse in the large-neck group: 81.3% versus 87%. Moreover, the 5-year survival rate was only 64.6% in the large–aortic neck group, compared with 76.5% in the comparator arm, even though aortic-related mortality didn’t differ between the two groups. “The findings raise the question of whether young patients, with predicted life expectancies exceeding 10 years, should receive standard endovascular intervention if they have large aortic neck diameters at baseline (Eur J Vasc Endovasc Surg. 2018;56[2]:189-99).

Severe neck angulation

Australian investigators wondered if the IFU for the Gore C3 Excluder was overly restrictive in defining abdominal aortic aneurysms with necks greater than 60 degrees as off-label for the device. In the first 1,394 patients enrolled in GREAT, the researchers identified 127 (9.2%) who exhibited more than 60 and less than 140 degrees of neck angulation and didn’t require endoanchors for proximal fixation. Their mean neck angle was 78 degrees, with a mean neck length of 29 mm. Mean graft oversizing was 23.5%, which was also outside the Excluder IFU.

During a median follow-up of 236 days there were 7 type Ia endoleaks, for an incidence of 5.6%. The degree of neck angulation, neck length, and the amount of oversizing were not associated with endoleak (Ann Vasc Surg. 2018;49:152-57). However, Dr. Brinster wants to see longer follow-up data before he is prepared to accept that a mean 23.5% graft oversizing is a benign intervention.

“One must remember that, with that percentage of oversizing in an already abnormal neck, aortic neck dilation could be a significant problem longer term,” the vascular surgeon said.

Dr. Brinster reported having no conflicts regarding his presentation.

[email protected]

CHICAGO – The Global Registry for Endovascular Aortic Treatment is a unique resource that, although still early in its planned 10-year follow-up period, has already yielded important insights into one of the hottest topics in endovascular repair of abdominal aortic aneurysms: that is, the impact of the proximal aortic neck, Clayton J. Brinster, MD, said at a symposium on vascular surgery sponsored by Northwestern University.

The Global Registry for Endovascular Aortic Treatment (GREAT) is a prospective, observational, real-world registry that enrolled more than 5,000 consecutive patients undergoing endovascular aortic repair (EVAR) in the United States, Europe, Australia, New Zealand, and Brazil before enrollment closed in October 2016.

GREAT is the largest stent graft registry in the world. One of its special features is that it has essentially no exclusion criteria. This enables researchers to compare outcomes in patients undergoing on-label EVAR using devices deployed within the official instructions for use (IFU) to results in real-world practice, which not infrequently entails treatment for nonstandard indications using devices outside the narrowly defined IFU generated via pivotal clinical trials, explained Dr. Brinster, a vascular surgeon at the Ochsner Clinic Foundation in New Orleans.

The biggest limitation of GREAT is that it’s sponsored by Gore and restricted to recipients of GORE thoracic and abdominal stent grafts. However, the registry has an oversight and safety monitoring board that is independent of the company, Dr. Brinster continued.

He highlighted three recently published studies that have utilized early GREAT data to examine the impact on EVAR outcomes of various features of the proximal aortic neck.

An international team of investigators analyzed the incidence and impact of noncylindrical neck anatomy, defined as a 2-mm or greater change in diameter over the first 15 mm of proximal aortic neck length. Of 3,077 GREAT participants treated with the Gore Excluder endograft, 1,312, or 43%, had an hourglass, tapered, or conical neck shape that qualified as noncylindrical. Noncylindrical necks were more common in women. Fifteen percent of patients with a noncylindrical neck received the device outside the Excluder IFU, as did 11% with a cylindrical neck.

After an average follow-up of about 20 months, the noncylindrical neck group had a 3.1% rate of device-related intervention, significantly better than the 4.9% rate in patients with a cylindrical neck. In a multivariate regression analysis, female gender and maximum abdominal aortic aneurysm diameter were significant risk factors for device-related or endoleak-specific reintervention; noncylindrical neck morphology was not. Indeed, women were 2.2-fold more likely to require device-related reintervention than men (J Vasc Surg. 2018; 68[6]:1714-24).
 

Large proximal aortic neck

Of 3,166 consecutive patients in GREAT, 37.6% had a large aortic neck diameter, defined as 25 mm or wider. The rate of 5-year freedom from type Ia endoleak was 96.8% in the large-neck group, significantly less than the 98.6% rate in patients with a normal aortic neck diameter. Of note, rates didn’t diverge until after 2 years of follow-up, emphasizing the need for careful long-term surveillance despite initial technical success.

The 5-year rate of freedom from the primary composite endpoint of type Ia endoleak, reintervention, aortic rupture, or isolated aortic-related mortality was also significantly worse in the large-neck group: 81.3% versus 87%. Moreover, the 5-year survival rate was only 64.6% in the large–aortic neck group, compared with 76.5% in the comparator arm, even though aortic-related mortality didn’t differ between the two groups. “The findings raise the question of whether young patients, with predicted life expectancies exceeding 10 years, should receive standard endovascular intervention if they have large aortic neck diameters at baseline (Eur J Vasc Endovasc Surg. 2018;56[2]:189-99).

Severe neck angulation

Australian investigators wondered if the IFU for the Gore C3 Excluder was overly restrictive in defining abdominal aortic aneurysms with necks greater than 60 degrees as off-label for the device. In the first 1,394 patients enrolled in GREAT, the researchers identified 127 (9.2%) who exhibited more than 60 and less than 140 degrees of neck angulation and didn’t require endoanchors for proximal fixation. Their mean neck angle was 78 degrees, with a mean neck length of 29 mm. Mean graft oversizing was 23.5%, which was also outside the Excluder IFU.

During a median follow-up of 236 days there were 7 type Ia endoleaks, for an incidence of 5.6%. The degree of neck angulation, neck length, and the amount of oversizing were not associated with endoleak (Ann Vasc Surg. 2018;49:152-57). However, Dr. Brinster wants to see longer follow-up data before he is prepared to accept that a mean 23.5% graft oversizing is a benign intervention.

“One must remember that, with that percentage of oversizing in an already abnormal neck, aortic neck dilation could be a significant problem longer term,” the vascular surgeon said.

Dr. Brinster reported having no conflicts regarding his presentation.

[email protected]

CHICAGO – The Global Registry for Endovascular Aortic Treatment is a unique resource that, although still early in its planned 10-year follow-up period, has already yielded important insights into one of the hottest topics in endovascular repair of abdominal aortic aneurysms: that is, the impact of the proximal aortic neck, Clayton J. Brinster, MD, said at a symposium on vascular surgery sponsored by Northwestern University.

The Global Registry for Endovascular Aortic Treatment (GREAT) is a prospective, observational, real-world registry that enrolled more than 5,000 consecutive patients undergoing endovascular aortic repair (EVAR) in the United States, Europe, Australia, New Zealand, and Brazil before enrollment closed in October 2016.

GREAT is the largest stent graft registry in the world. One of its special features is that it has essentially no exclusion criteria. This enables researchers to compare outcomes in patients undergoing on-label EVAR using devices deployed within the official instructions for use (IFU) to results in real-world practice, which not infrequently entails treatment for nonstandard indications using devices outside the narrowly defined IFU generated via pivotal clinical trials, explained Dr. Brinster, a vascular surgeon at the Ochsner Clinic Foundation in New Orleans.

The biggest limitation of GREAT is that it’s sponsored by Gore and restricted to recipients of GORE thoracic and abdominal stent grafts. However, the registry has an oversight and safety monitoring board that is independent of the company, Dr. Brinster continued.

He highlighted three recently published studies that have utilized early GREAT data to examine the impact on EVAR outcomes of various features of the proximal aortic neck.

An international team of investigators analyzed the incidence and impact of noncylindrical neck anatomy, defined as a 2-mm or greater change in diameter over the first 15 mm of proximal aortic neck length. Of 3,077 GREAT participants treated with the Gore Excluder endograft, 1,312, or 43%, had an hourglass, tapered, or conical neck shape that qualified as noncylindrical. Noncylindrical necks were more common in women. Fifteen percent of patients with a noncylindrical neck received the device outside the Excluder IFU, as did 11% with a cylindrical neck.

After an average follow-up of about 20 months, the noncylindrical neck group had a 3.1% rate of device-related intervention, significantly better than the 4.9% rate in patients with a cylindrical neck. In a multivariate regression analysis, female gender and maximum abdominal aortic aneurysm diameter were significant risk factors for device-related or endoleak-specific reintervention; noncylindrical neck morphology was not. Indeed, women were 2.2-fold more likely to require device-related reintervention than men (J Vasc Surg. 2018; 68[6]:1714-24).
 

Large proximal aortic neck

Of 3,166 consecutive patients in GREAT, 37.6% had a large aortic neck diameter, defined as 25 mm or wider. The rate of 5-year freedom from type Ia endoleak was 96.8% in the large-neck group, significantly less than the 98.6% rate in patients with a normal aortic neck diameter. Of note, rates didn’t diverge until after 2 years of follow-up, emphasizing the need for careful long-term surveillance despite initial technical success.

The 5-year rate of freedom from the primary composite endpoint of type Ia endoleak, reintervention, aortic rupture, or isolated aortic-related mortality was also significantly worse in the large-neck group: 81.3% versus 87%. Moreover, the 5-year survival rate was only 64.6% in the large–aortic neck group, compared with 76.5% in the comparator arm, even though aortic-related mortality didn’t differ between the two groups. “The findings raise the question of whether young patients, with predicted life expectancies exceeding 10 years, should receive standard endovascular intervention if they have large aortic neck diameters at baseline (Eur J Vasc Endovasc Surg. 2018;56[2]:189-99).

Severe neck angulation

Australian investigators wondered if the IFU for the Gore C3 Excluder was overly restrictive in defining abdominal aortic aneurysms with necks greater than 60 degrees as off-label for the device. In the first 1,394 patients enrolled in GREAT, the researchers identified 127 (9.2%) who exhibited more than 60 and less than 140 degrees of neck angulation and didn’t require endoanchors for proximal fixation. Their mean neck angle was 78 degrees, with a mean neck length of 29 mm. Mean graft oversizing was 23.5%, which was also outside the Excluder IFU.

During a median follow-up of 236 days there were 7 type Ia endoleaks, for an incidence of 5.6%. The degree of neck angulation, neck length, and the amount of oversizing were not associated with endoleak (Ann Vasc Surg. 2018;49:152-57). However, Dr. Brinster wants to see longer follow-up data before he is prepared to accept that a mean 23.5% graft oversizing is a benign intervention.

“One must remember that, with that percentage of oversizing in an already abnormal neck, aortic neck dilation could be a significant problem longer term,” the vascular surgeon said.

Dr. Brinster reported having no conflicts regarding his presentation.

[email protected]