A 25-year-old man presented with multiple sternal cysts that he first noticed when he was aged 18 years and had persisted despite treatment with topical anti-acne agents, including tretinoin. No other medications were used. The patient was unable to express purulent material from the lesions and reported no infection or additional trauma to the affected area. He had no other significant past medical history and no family history of similar skin lesions.

A physical examination revealed an otherwise healthy-appearing male with multiple uniform painless cystic papules scattered across his central chest that were smooth and flesh-colored to slightly yellow-colored, measuring 2 mm to 6 mm in diameter (Figure).  A ring of erythema surrounded the lesions that had been recently manipulated by the patient. There were no overlying central puncta, and the remainder of his body was spared.

Related: Mohs Micrographic Surgery in the VHA

• What is your diagnosis?
• How would you treat this patient?

Diagnosis

The patient was diagnosed with steatocystoma multiplex based on his poor response to topical anti-acne agents, the location of his lesions, and histopathology of a biopsy specimen. Steatocystoma multiplex, sometimes termed sebocystomatosis, typically presents between puberty and the third decade of life. Lesions are usually < 2 cm in diameter and occur as multiple smooth skin-colored or yellow-colored painless papules on areas with high concentrations of hormonally sensitive sebaceous glands, especially the chest. Lesions also can be found in the axillae and on the neck.^1-3 Solitary lesions can occur and are termed steatocystoma simplex.

The timing and location of presentation can easily be mistaken for acne vulgaris, but steatocystoma lesions are true sebaceous cysts, which are rare, and spontaneous resolution with increasing age does not typically occur. The diagnosis of steatocystoma often goes unreported because the disease is usually asymptomatic and mimics more common benign skin conditions, so an accurate prevalence and incidence are both unknown.

First on the differential diagnosis is acne vulgaris, which also presents at puberty and affects nearly 85% of adolescents. However, acne is less common in people of Asian or African descent and may progress along a continuum of increasingly severe and larger lesions, including the primary comedones and papules followed by pustules, nodules, and pseudocysts. Painful lesions develop from inflammation of pilosebaceous units concentrated on the face, neck, trunk, upper arms, or buttocks and are typically worse in males. Resolution often occurs spontaneously by the third decade of life, but scarring can persist.⁴

Related: Using Dermoscopy to Identify Melanoma and Improve Diagnostic Discrimination

Eruptive vellus hair cysts present as dozens of skin-colored small (1-4 mm) painless dome-shaped papules, sometimes with erythema and crusting. Typically these appear on the head, trunk, or flexor surfaces of infants (familial cases) or adolescents (sporadic cases) without bias for gender or ethnicity. Although benign and potential mimickers of steatocystoma and acne, these lesions can also be associated with more serious syndromes, like ectodermal dysplasias and pachyonychia congenita.^2,3

Epidermoid cysts are common benign solitary skin-colored subcutaneous dome-shaped nodules that contain a central punctum through which cheeselike keratinaceous material can be expressed.⁴ These benign lesions arising from the dermis can enlarge to several centimeters, and adults of both genders and most ethnicities tend to develop the lesions on the trunk or face, with small cysts on the face termed milia. Ruptured cysts can incite intense inflammation, and multiple epidermoid cysts should raise concern for Gardner syndrome.^2,3

About This Condition

Steatocystoma lesions are benign and thought to arise from a mutation in keratin 17. The mutation can be inherited in an autosomal dominant pattern, but sporadic nonheritable cases are more common.⁵ There are no distinct associations with gender or ethnicity. The dermal cysts arise from the sebaceous ducts of the pilosebaceous unit, and histopathology typically shows numerous mature sebaceous cells encased by a thin wall of stratified squamous epithelium.² Immunohistochemical staining for the defective keratin can help diagnose biopsy specimens, and histopathology confirmed the diagnosis in this case.

Related: Recurring Bilateral Rash Concomitant With Upper Respiratory Tract Infection in a Healthy Adult Male

Treatment

Steatocystoma is usually asymptomatic, so patients mainly present to physicians for cosmetic reasons. Puncturing the cyst wall within the dermis produces translucent sebum-containing fluid, and ruptured cysts can incite inflammation, pain, and scarring.² However, prognosis is good, and treatment consists of excision, aspiration and curettage of the cyst wall, oral isotretinoin, or laser therapy. Our patient elected to forego treatment and will consider definitive removal in the future, since the lesions will persist and potentially enlarge. Accurate diagnosis of this rare cause of chest papules improves the timeliness and efficacy of appropriate treatment, favoring good cosmesis.

A 25-year-old man presented with multiple sternal cysts that he first noticed when he was aged 18 years and had persisted despite treatment with topical anti-acne agents, including tretinoin. No other medications were used. The patient was unable to express purulent material from the lesions and reported no infection or additional trauma to the affected area. He had no other significant past medical history and no family history of similar skin lesions.

A physical examination revealed an otherwise healthy-appearing male with multiple uniform painless cystic papules scattered across his central chest that were smooth and flesh-colored to slightly yellow-colored, measuring 2 mm to 6 mm in diameter (Figure).  A ring of erythema surrounded the lesions that had been recently manipulated by the patient. There were no overlying central puncta, and the remainder of his body was spared.

Related: Mohs Micrographic Surgery in the VHA

• What is your diagnosis?
• How would you treat this patient?

Diagnosis

The patient was diagnosed with steatocystoma multiplex based on his poor response to topical anti-acne agents, the location of his lesions, and histopathology of a biopsy specimen. Steatocystoma multiplex, sometimes termed sebocystomatosis, typically presents between puberty and the third decade of life. Lesions are usually < 2 cm in diameter and occur as multiple smooth skin-colored or yellow-colored painless papules on areas with high concentrations of hormonally sensitive sebaceous glands, especially the chest. Lesions also can be found in the axillae and on the neck.^1-3 Solitary lesions can occur and are termed steatocystoma simplex.

The timing and location of presentation can easily be mistaken for acne vulgaris, but steatocystoma lesions are true sebaceous cysts, which are rare, and spontaneous resolution with increasing age does not typically occur. The diagnosis of steatocystoma often goes unreported because the disease is usually asymptomatic and mimics more common benign skin conditions, so an accurate prevalence and incidence are both unknown.

First on the differential diagnosis is acne vulgaris, which also presents at puberty and affects nearly 85% of adolescents. However, acne is less common in people of Asian or African descent and may progress along a continuum of increasingly severe and larger lesions, including the primary comedones and papules followed by pustules, nodules, and pseudocysts. Painful lesions develop from inflammation of pilosebaceous units concentrated on the face, neck, trunk, upper arms, or buttocks and are typically worse in males. Resolution often occurs spontaneously by the third decade of life, but scarring can persist.⁴

Related: Using Dermoscopy to Identify Melanoma and Improve Diagnostic Discrimination

Eruptive vellus hair cysts present as dozens of skin-colored small (1-4 mm) painless dome-shaped papules, sometimes with erythema and crusting. Typically these appear on the head, trunk, or flexor surfaces of infants (familial cases) or adolescents (sporadic cases) without bias for gender or ethnicity. Although benign and potential mimickers of steatocystoma and acne, these lesions can also be associated with more serious syndromes, like ectodermal dysplasias and pachyonychia congenita.^2,3

Epidermoid cysts are common benign solitary skin-colored subcutaneous dome-shaped nodules that contain a central punctum through which cheeselike keratinaceous material can be expressed.⁴ These benign lesions arising from the dermis can enlarge to several centimeters, and adults of both genders and most ethnicities tend to develop the lesions on the trunk or face, with small cysts on the face termed milia. Ruptured cysts can incite intense inflammation, and multiple epidermoid cysts should raise concern for Gardner syndrome.^2,3

About This Condition

Steatocystoma lesions are benign and thought to arise from a mutation in keratin 17. The mutation can be inherited in an autosomal dominant pattern, but sporadic nonheritable cases are more common.⁵ There are no distinct associations with gender or ethnicity. The dermal cysts arise from the sebaceous ducts of the pilosebaceous unit, and histopathology typically shows numerous mature sebaceous cells encased by a thin wall of stratified squamous epithelium.² Immunohistochemical staining for the defective keratin can help diagnose biopsy specimens, and histopathology confirmed the diagnosis in this case.

Related: Recurring Bilateral Rash Concomitant With Upper Respiratory Tract Infection in a Healthy Adult Male

Treatment

Steatocystoma is usually asymptomatic, so patients mainly present to physicians for cosmetic reasons. Puncturing the cyst wall within the dermis produces translucent sebum-containing fluid, and ruptured cysts can incite inflammation, pain, and scarring.² However, prognosis is good, and treatment consists of excision, aspiration and curettage of the cyst wall, oral isotretinoin, or laser therapy. Our patient elected to forego treatment and will consider definitive removal in the future, since the lesions will persist and potentially enlarge. Accurate diagnosis of this rare cause of chest papules improves the timeliness and efficacy of appropriate treatment, favoring good cosmesis.

A 25-year-old man presented with multiple sternal cysts that he first noticed when he was aged 18 years and had persisted despite treatment with topical anti-acne agents, including tretinoin. No other medications were used. The patient was unable to express purulent material from the lesions and reported no infection or additional trauma to the affected area. He had no other significant past medical history and no family history of similar skin lesions.

A physical examination revealed an otherwise healthy-appearing male with multiple uniform painless cystic papules scattered across his central chest that were smooth and flesh-colored to slightly yellow-colored, measuring 2 mm to 6 mm in diameter (Figure).  A ring of erythema surrounded the lesions that had been recently manipulated by the patient. There were no overlying central puncta, and the remainder of his body was spared.

Related: Mohs Micrographic Surgery in the VHA

• What is your diagnosis?
• How would you treat this patient?

Diagnosis

The patient was diagnosed with steatocystoma multiplex based on his poor response to topical anti-acne agents, the location of his lesions, and histopathology of a biopsy specimen. Steatocystoma multiplex, sometimes termed sebocystomatosis, typically presents between puberty and the third decade of life. Lesions are usually < 2 cm in diameter and occur as multiple smooth skin-colored or yellow-colored painless papules on areas with high concentrations of hormonally sensitive sebaceous glands, especially the chest. Lesions also can be found in the axillae and on the neck.^1-3 Solitary lesions can occur and are termed steatocystoma simplex.

The timing and location of presentation can easily be mistaken for acne vulgaris, but steatocystoma lesions are true sebaceous cysts, which are rare, and spontaneous resolution with increasing age does not typically occur. The diagnosis of steatocystoma often goes unreported because the disease is usually asymptomatic and mimics more common benign skin conditions, so an accurate prevalence and incidence are both unknown.

First on the differential diagnosis is acne vulgaris, which also presents at puberty and affects nearly 85% of adolescents. However, acne is less common in people of Asian or African descent and may progress along a continuum of increasingly severe and larger lesions, including the primary comedones and papules followed by pustules, nodules, and pseudocysts. Painful lesions develop from inflammation of pilosebaceous units concentrated on the face, neck, trunk, upper arms, or buttocks and are typically worse in males. Resolution often occurs spontaneously by the third decade of life, but scarring can persist.⁴

Related: Using Dermoscopy to Identify Melanoma and Improve Diagnostic Discrimination

Eruptive vellus hair cysts present as dozens of skin-colored small (1-4 mm) painless dome-shaped papules, sometimes with erythema and crusting. Typically these appear on the head, trunk, or flexor surfaces of infants (familial cases) or adolescents (sporadic cases) without bias for gender or ethnicity. Although benign and potential mimickers of steatocystoma and acne, these lesions can also be associated with more serious syndromes, like ectodermal dysplasias and pachyonychia congenita.^2,3

Epidermoid cysts are common benign solitary skin-colored subcutaneous dome-shaped nodules that contain a central punctum through which cheeselike keratinaceous material can be expressed.⁴ These benign lesions arising from the dermis can enlarge to several centimeters, and adults of both genders and most ethnicities tend to develop the lesions on the trunk or face, with small cysts on the face termed milia. Ruptured cysts can incite intense inflammation, and multiple epidermoid cysts should raise concern for Gardner syndrome.^2,3

About This Condition

Steatocystoma lesions are benign and thought to arise from a mutation in keratin 17. The mutation can be inherited in an autosomal dominant pattern, but sporadic nonheritable cases are more common.⁵ There are no distinct associations with gender or ethnicity. The dermal cysts arise from the sebaceous ducts of the pilosebaceous unit, and histopathology typically shows numerous mature sebaceous cells encased by a thin wall of stratified squamous epithelium.² Immunohistochemical staining for the defective keratin can help diagnose biopsy specimens, and histopathology confirmed the diagnosis in this case.

Related: Recurring Bilateral Rash Concomitant With Upper Respiratory Tract Infection in a Healthy Adult Male

Treatment

Steatocystoma is usually asymptomatic, so patients mainly present to physicians for cosmetic reasons. Puncturing the cyst wall within the dermis produces translucent sebum-containing fluid, and ruptured cysts can incite inflammation, pain, and scarring.² However, prognosis is good, and treatment consists of excision, aspiration and curettage of the cyst wall, oral isotretinoin, or laser therapy. Our patient elected to forego treatment and will consider definitive removal in the future, since the lesions will persist and potentially enlarge. Accurate diagnosis of this rare cause of chest papules improves the timeliness and efficacy of appropriate treatment, favoring good cosmesis.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and has an associated treatment cost of $9,800 per patient per year in the US.^1-3 Within 5 years of hospital discharge for a COPD exacerbation, the rehospitalization risk is 44%, and the mortality rate is 55%.⁴ COPD affects more than 11 million Americans, and the disease prevalence among US veterans is 3-fold higher.^5,6

Patients hospitalized for COPD have a 30-day readmission rate of 22.6%.⁷ Given the high patient burden, COPD was added to the Medicare Hospital Readmission Reductions Program in 2015, resulting in financial penalties for COPD readmissions within 30 days of hospital discharge.⁸ Ensuring timely access to follow-up care has been shown to significantly reduce risk for hospital readmissions.⁹ However, in a national review of Medicare claims, only 50% of patients readmitted to the hospital had a primary care provider (PCP) follow-up visit within 30 days of their hospital discharge.¹⁰ Despite the need to provide prompt patient follow-up during the transition from hospital to home, gaps within the health care system create barriers to providing timely postdischarge care.^10-12 These gaps include breakdowns in practitioner and patient communication, lengthy time to follow-up, and incomplete medication reconciliation.¹³ To address this unmet need, clinics and hospitals require solutions that can be implemented quickly, using the resources of their current clinical models.

Pharmacists and registered nurses (RNs) within the US federal health care system are well positioned for involvement in the postdischarge care of high-risk patients with COPD. Ambulatory care practitioners within the US Department of Veterans Affairs (VA) health care system are integrated into patient aligned care teams (PACT). Each team consists of a PCP, pharmacist, RN, social worker, dietitian, licensed practical nurse, and medical scheduling support assistant.¹⁴ Each PACT team works together to provide patient education, chronic disease management, and medication optimization, and each team member contributes their unique training and expertise.

Interprofessional care is considered an integral method to improve health outcomes through effective teamwork and communication.¹⁵ Although interprofessional interventions are cited extensively in the literature highlighting medicine and nursing, a gap exists in the exploration of pharmacist contributions within interprofessional teams.¹⁶ The incorporation of clinical pharmacists in the literature is especially limited when considering transitions of care and the patient medical home.¹⁷ Given the critical and collaborative role pharmacists play within the PACT medical home, the COPD CARE (Chronic Obstructive Pulmonary Disease Coordinated Access to Reduce Exacerbations) service provides an opportunity to leverage pharmacists as prescribers with a scope of practice who coordinate transitions of care for patients with COPD.¹⁸ The service was designed to be collaborative within the PACT model and with the intent of reducing 30-day readmissions to the hospital or emergency department (ED) due to a COPD exacerbation.

This evaluation involved the identifying patients recently hospitalized for COPD; clinic follow-up, coordinated by a clinical pharmacist and nurse, within 30 days of hospital or ED discharge; the use of a COPD action plan; and timely triage of patients at high risk for COPD reexacerbation or with comorbid symptoms to PCPs. The COPD CARE service, leveraged the patient-centered medical home (PCMH) model for transitions of care after COPD exacerbations. The PCMH is a primary care model focused on the following functions: (1) comprehensive care; (2) patient-centered care; (3) coordinated care; (4) accessible service; and (5) quality and safety.¹⁹

Methods

The COPD CARE service was implemented on October 1, 2015, and evaluated through March 1, 2016 (Figure 1). All veterans receiving primary care through the pilot clinic site with a hospital admission or ED visit for COPD exacerbation were offered this intervention. 

Patient Eligibility and Recruitment

Patients were excluded from the service if COPD or COPD-related diagnoses were not listed in their electronic health record (EHR) problem list. Patients who had previously received components of the intervention through consultation with specialty services were excluded. If a patient declined the service, they received the standard of care. This project was undertaken for programmatic evaluation and qualified for quality improvement (QI) exemption; as such an internal review board approval was not required.

Intervention

Participants enrolled in the COPD CARE service were scheduled for an interprofessional postdischarge follow-up visit with a pharmacist and nurse at the pilot outpatient clinic site, and this visit was termed the COPD CARE health visit. Participants ideally were seen within 30 days of discharge. The goal was to improve access to care while preventing a 30-day readmission. Within this 30-day window, the target follow-up period was 2 to 3 weeks postdischarge for the face-to-face visit. Patients who required postdischarge care for additional medical conditions received a clinic appointment with their PCP on the same day as their COPD CARE health visit. The COPD CARE health visit focused on 3 objectives: (1) COPD disease management and referrals; (2) COPD plan development; and (3) inhaler technique review and teaching.^20,21

COPD Monitoring

During the 45-minute COPD CARE health visit, the pharmacist provided extensive disease management based on the GOLD guideline recommendation.²² In addition, the pharmacist administered the COPD Assessment Test (CAT) and reviewed patient COPD exacerbation history to guide prescribing.²² The patient and pharmacist also reviewed previous spirometry results if obtained within the past 2 years. COPD triggers and symptoms were assessed along with opportunities for therapeutic and lifestyle modifications.

Plan Development

Patients in the COPD CARE service also were given a COPD plan to improve health outcomes. (Figure 2). The plan included patient instructions to initiate steroid and antibiotic therapy if the patient experienced symptoms of increased cough, mucus production, and purulence, thereby reaching the high-yellow zone. 

Patient Referrals

Patient referrals also were a critical component of the COPD CARE service. Pharmacists placed referrals for tobacco treatment services, pulmonary rehabilitation, a COPD group education class, and referral to specialty care if needed.

Inhaler Technique Review

Either the pharmacist or RN review the inhaler technique, and corrections and teachback methods used to ensure patient understanding.²³ Patients were encouraged to bring home inhalers into clinic for technique assessment. Demonstration inhalers also were available and used by pharmacists and nurses for inhaler teaching as needed. The pharmacist indicated through chart documentation whether the patient’s inhaler technique was correct or whether modifications were made to improve medication delivery. Medication reconciliation also was performed for inhaled devices to insure patients were using medications as prescribed.

Outcomes

The primary outcome of this evaluation was an assessment of interventions made by the interprofessional care team during the COPD CARE health visit. Secondary outcomes included assessment of 30-day readmission rates as well as patient access to the primary care team using this interprofessional care model.

Data were collected after study completion through review of the EHR at baseline and at the end of the evaluation period. Baseline demographic information was collected through a retrospective chart review. Readmission rates were calculated as a composite of ED visits and rehospitalization within 30 days of discharge due to a COPD exacerbation.

Patients’ spirometry results were used in composite with clinical symptoms and risk of exacerbations to calculate GOLD staging.²⁴

Results

A total of 19 patients admitted to the hospital or ED received follow-up through the COPD CARE service. Patients included in this analysis were primarily older adult white males.

Referrals were placed for 53% of patients in the COPD CARE service, with 21% of patients accepting referral to tobacco treatment clinic, and 32% of patients accepting referral to pulmonary rehabilitation. COPD plans were issued to all of patients in this service. Pharmacists modified therapy 58% of the time, with a review of medications prescribed by the clinical pharmacist (eApendixes 1 and 2, available at mdedge.com/fedprac).

Patients had a 0% composite readmission rate to the ED or hospital for a COPD exacerbation within 30-days of discharge. Access to care, defined as a visit with the primary care PACT team within 30 days of discharge, was achieved in 14 of the 19 patients (73.7%). Additionally, 12 of 19 patients (63.2%) in the COPD CARE service no longer needed to see their PCP following discharge, saving their provider a visit.

The pharmacist corrected patient inhaler technique in 52.6% of the patients participating in the service.

Discussion

The intent of this QI initiative was to assess a novel clinic intervention for a high-risk patient population during COPD care transitions. The strengths of this intervention involved a rapid cycle implementation using the existing medical home model and its multiprong approach to coordinating care. This approach involved coordinating self-direction COPD plans, timely hospital follow-up, and the innovative use of the interprofessional primary care team.

The COPD CARE service improved patient access to follow-up with no COPD readmissions in the intervention group. The COPD CARE service also validated the use of a coordinated medical home consisting of clinical pharmacists and nurses who provided the initial COPD disease monitoring and plan development. This intervention also resulted in patients receiving greater access to their PACT teams within 30 days of discharge and a higher rate of referrals to tobacco cessation clinics within the COPD CARE group. In addition, use of tools that enabled patients to self-manage their care, such as the COPD plan, was greater in the COPD CARE group.

The interventions made in-clinic likely contributed to service results (eAppendix 3). 

In addition, the COPD CARE service provided necessary referrals to pulmonary rehabilitation, nutrition, and tobacco treatment clinics at a higher rate than those patients in the standard of care group. The high percentage of referrals placed to tobacco treatment clinic and pulmonary rehabilitation contributes to improvements in COPD disease control long-term.²⁵ 

The COPD CARE service may best be described as a model for application of the interprofessional team in clinical practice, with the clinical pharmacist uniquely positioned for chronic disease management in the postacute care setting.²⁶ Previously, literature has documented pharmacists as integral members of the team during patient care transitions. Pharmacist completion of medication reconciliation compared with usual care has shown a 28% relative risk (RR) reduction in ED visits and a 67% RR reduction in adverse drug event-related hospital revisits.²⁷ Findings of the COPD CARE service are consistent with the literature and advance the role of pharmacists within the medical home model as prescribers for disease management.²⁷

The interprofessional, team-based design of the COPD CARE service also is supported by recent recommendations from the COPD Foundation, as detailed in the 2nd National COPD Readmission Summit.²⁸ Use of a proactive, team-based care model is emphasized as a central element to coordinating care transitions, with an expectation of 360 degree accountability by all team members for the patients care both during and after hospitalization. The clearly defined roles of each team member within the COPD CARE service, coupled with the expectation that each team member practices with autonomy and accountability, exemplifies the COPD Foundation vision for enhancing COPD care. In addition, the COPD CARE service uses many of the best practices detailed by the COPD Foundation, including the use of spirometry, referrals to pulmonary rehabilitation, and use of motivational interviewing for tobacco treatment clinic referral.

Limitations

This QI initiative has several limitations. By virtue of the study being designed as a practice improvement intervention with rapid implementation, the existing clinic referral structures were used to offer the service to eligible patients. This standard of care included routine telephone contact by a nurse case manager following hospital discharge. Although all patients in the COPD CARE service received the intervention, 5 patients were not seen within the 30-day window, resulting in an implementation rate of 73%. Of the 5 patients that were not seen, 4 were discharged from the ED. Timely follow-up in primary care clinic from the ED required the use of a time-intensive chart review for referral and subsequent delay in intervention delivery.A streamlined clinic referral process from the ED likely would further improve patient scheduling and result in a greater number of patients who would receive the intervention within 30 days of discharge. Despite this limitation, the COPD CARE service was able to see a large percentage of patients within the 30-day time frame postdischarge.

Future Directions

Although a major objective of this service was to reduce readmissions 30 days postdischarge, it is possible interventions made in clinic may have long-term beneficial effects.^25,29 Future research should evaluate the impact of this interprofessional service on long-term disease outcomes, thereby determining whether the promising readmission results are sustained beyond 30 days postdischarge.³⁰ In addition, incorporation of respiratory therapy and inpatient pharmacists during hospital discharge could provide a more effective and sustainable transition from hospital to home before the COPD CARE clinic visit.

Future implementations and evaluations of this COPD CARE service will in turn benefit from a key component of our intervention, which includes the collection of timely CAT scores, spirometry data, and adherence rates for COPD patients.³¹ Furthermore, the intervention was successfully delivered to a population recently hospitalized or seen in the ED, and therefore, at high risk for future COPD exacerbations. This initiative provides positive proof of a concept QI project using the existing PACT team model to reduce 30-day readmission rates in patients with COPD at high risk for exacerbation. Future efforts will focus on delivering this intervention to patients with mild, moderate, and severe COPD within a wide range of primary clinics.

Conslusion

The COPD CARE service involved the coordinated postdischarge care facilitated by an interprofessional team of clinical pharmacists, nurses and PCPs. The COPD CARE service leveraged an interprofessional team, centered on the PACT medical home, to make clinic interventions resulting in a 0% readmission rate and 63.2% increase in PCP access. The COPD CARE service further demonstrated the impact of coordinated efforts by interprofessional teams to optimize care for COPD management.

Acknowledgments
The authors thank Stephanie Gruber, PharmD; Lieneke Hafeman, RN; Molly Obermark, PharmD; Julia Peek, RT; Mark Regan, MD; Chris Roelke, RN; Steve Shoyer, PharmD; John Thielemann, RN; Sandy Tompkins, BS; and Wendi Wenger, RN, for their integral roles in the COPD CARE service.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and has an associated treatment cost of $9,800 per patient per year in the US.^1-3 Within 5 years of hospital discharge for a COPD exacerbation, the rehospitalization risk is 44%, and the mortality rate is 55%.⁴ COPD affects more than 11 million Americans, and the disease prevalence among US veterans is 3-fold higher.^5,6

Patients hospitalized for COPD have a 30-day readmission rate of 22.6%.⁷ Given the high patient burden, COPD was added to the Medicare Hospital Readmission Reductions Program in 2015, resulting in financial penalties for COPD readmissions within 30 days of hospital discharge.⁸ Ensuring timely access to follow-up care has been shown to significantly reduce risk for hospital readmissions.⁹ However, in a national review of Medicare claims, only 50% of patients readmitted to the hospital had a primary care provider (PCP) follow-up visit within 30 days of their hospital discharge.¹⁰ Despite the need to provide prompt patient follow-up during the transition from hospital to home, gaps within the health care system create barriers to providing timely postdischarge care.^10-12 These gaps include breakdowns in practitioner and patient communication, lengthy time to follow-up, and incomplete medication reconciliation.¹³ To address this unmet need, clinics and hospitals require solutions that can be implemented quickly, using the resources of their current clinical models.

Pharmacists and registered nurses (RNs) within the US federal health care system are well positioned for involvement in the postdischarge care of high-risk patients with COPD. Ambulatory care practitioners within the US Department of Veterans Affairs (VA) health care system are integrated into patient aligned care teams (PACT). Each team consists of a PCP, pharmacist, RN, social worker, dietitian, licensed practical nurse, and medical scheduling support assistant.¹⁴ Each PACT team works together to provide patient education, chronic disease management, and medication optimization, and each team member contributes their unique training and expertise.

Interprofessional care is considered an integral method to improve health outcomes through effective teamwork and communication.¹⁵ Although interprofessional interventions are cited extensively in the literature highlighting medicine and nursing, a gap exists in the exploration of pharmacist contributions within interprofessional teams.¹⁶ The incorporation of clinical pharmacists in the literature is especially limited when considering transitions of care and the patient medical home.¹⁷ Given the critical and collaborative role pharmacists play within the PACT medical home, the COPD CARE (Chronic Obstructive Pulmonary Disease Coordinated Access to Reduce Exacerbations) service provides an opportunity to leverage pharmacists as prescribers with a scope of practice who coordinate transitions of care for patients with COPD.¹⁸ The service was designed to be collaborative within the PACT model and with the intent of reducing 30-day readmissions to the hospital or emergency department (ED) due to a COPD exacerbation.

This evaluation involved the identifying patients recently hospitalized for COPD; clinic follow-up, coordinated by a clinical pharmacist and nurse, within 30 days of hospital or ED discharge; the use of a COPD action plan; and timely triage of patients at high risk for COPD reexacerbation or with comorbid symptoms to PCPs. The COPD CARE service, leveraged the patient-centered medical home (PCMH) model for transitions of care after COPD exacerbations. The PCMH is a primary care model focused on the following functions: (1) comprehensive care; (2) patient-centered care; (3) coordinated care; (4) accessible service; and (5) quality and safety.¹⁹

Methods

The COPD CARE service was implemented on October 1, 2015, and evaluated through March 1, 2016 (Figure 1). All veterans receiving primary care through the pilot clinic site with a hospital admission or ED visit for COPD exacerbation were offered this intervention. 

Patient Eligibility and Recruitment

Patients were excluded from the service if COPD or COPD-related diagnoses were not listed in their electronic health record (EHR) problem list. Patients who had previously received components of the intervention through consultation with specialty services were excluded. If a patient declined the service, they received the standard of care. This project was undertaken for programmatic evaluation and qualified for quality improvement (QI) exemption; as such an internal review board approval was not required.

Intervention

Participants enrolled in the COPD CARE service were scheduled for an interprofessional postdischarge follow-up visit with a pharmacist and nurse at the pilot outpatient clinic site, and this visit was termed the COPD CARE health visit. Participants ideally were seen within 30 days of discharge. The goal was to improve access to care while preventing a 30-day readmission. Within this 30-day window, the target follow-up period was 2 to 3 weeks postdischarge for the face-to-face visit. Patients who required postdischarge care for additional medical conditions received a clinic appointment with their PCP on the same day as their COPD CARE health visit. The COPD CARE health visit focused on 3 objectives: (1) COPD disease management and referrals; (2) COPD plan development; and (3) inhaler technique review and teaching.^20,21

COPD Monitoring

During the 45-minute COPD CARE health visit, the pharmacist provided extensive disease management based on the GOLD guideline recommendation.²² In addition, the pharmacist administered the COPD Assessment Test (CAT) and reviewed patient COPD exacerbation history to guide prescribing.²² The patient and pharmacist also reviewed previous spirometry results if obtained within the past 2 years. COPD triggers and symptoms were assessed along with opportunities for therapeutic and lifestyle modifications.

Plan Development

Patients in the COPD CARE service also were given a COPD plan to improve health outcomes. (Figure 2). The plan included patient instructions to initiate steroid and antibiotic therapy if the patient experienced symptoms of increased cough, mucus production, and purulence, thereby reaching the high-yellow zone. 

Patient Referrals

Patient referrals also were a critical component of the COPD CARE service. Pharmacists placed referrals for tobacco treatment services, pulmonary rehabilitation, a COPD group education class, and referral to specialty care if needed.

Inhaler Technique Review

Either the pharmacist or RN review the inhaler technique, and corrections and teachback methods used to ensure patient understanding.²³ Patients were encouraged to bring home inhalers into clinic for technique assessment. Demonstration inhalers also were available and used by pharmacists and nurses for inhaler teaching as needed. The pharmacist indicated through chart documentation whether the patient’s inhaler technique was correct or whether modifications were made to improve medication delivery. Medication reconciliation also was performed for inhaled devices to insure patients were using medications as prescribed.

Outcomes

The primary outcome of this evaluation was an assessment of interventions made by the interprofessional care team during the COPD CARE health visit. Secondary outcomes included assessment of 30-day readmission rates as well as patient access to the primary care team using this interprofessional care model.

Data were collected after study completion through review of the EHR at baseline and at the end of the evaluation period. Baseline demographic information was collected through a retrospective chart review. Readmission rates were calculated as a composite of ED visits and rehospitalization within 30 days of discharge due to a COPD exacerbation.

Patients’ spirometry results were used in composite with clinical symptoms and risk of exacerbations to calculate GOLD staging.²⁴

Results

A total of 19 patients admitted to the hospital or ED received follow-up through the COPD CARE service. Patients included in this analysis were primarily older adult white males.

Referrals were placed for 53% of patients in the COPD CARE service, with 21% of patients accepting referral to tobacco treatment clinic, and 32% of patients accepting referral to pulmonary rehabilitation. COPD plans were issued to all of patients in this service. Pharmacists modified therapy 58% of the time, with a review of medications prescribed by the clinical pharmacist (eApendixes 1 and 2, available at mdedge.com/fedprac).

Patients had a 0% composite readmission rate to the ED or hospital for a COPD exacerbation within 30-days of discharge. Access to care, defined as a visit with the primary care PACT team within 30 days of discharge, was achieved in 14 of the 19 patients (73.7%). Additionally, 12 of 19 patients (63.2%) in the COPD CARE service no longer needed to see their PCP following discharge, saving their provider a visit.

The pharmacist corrected patient inhaler technique in 52.6% of the patients participating in the service.

Discussion

The intent of this QI initiative was to assess a novel clinic intervention for a high-risk patient population during COPD care transitions. The strengths of this intervention involved a rapid cycle implementation using the existing medical home model and its multiprong approach to coordinating care. This approach involved coordinating self-direction COPD plans, timely hospital follow-up, and the innovative use of the interprofessional primary care team.

The COPD CARE service improved patient access to follow-up with no COPD readmissions in the intervention group. The COPD CARE service also validated the use of a coordinated medical home consisting of clinical pharmacists and nurses who provided the initial COPD disease monitoring and plan development. This intervention also resulted in patients receiving greater access to their PACT teams within 30 days of discharge and a higher rate of referrals to tobacco cessation clinics within the COPD CARE group. In addition, use of tools that enabled patients to self-manage their care, such as the COPD plan, was greater in the COPD CARE group.

The interventions made in-clinic likely contributed to service results (eAppendix 3). 

In addition, the COPD CARE service provided necessary referrals to pulmonary rehabilitation, nutrition, and tobacco treatment clinics at a higher rate than those patients in the standard of care group. The high percentage of referrals placed to tobacco treatment clinic and pulmonary rehabilitation contributes to improvements in COPD disease control long-term.²⁵ 

The COPD CARE service may best be described as a model for application of the interprofessional team in clinical practice, with the clinical pharmacist uniquely positioned for chronic disease management in the postacute care setting.²⁶ Previously, literature has documented pharmacists as integral members of the team during patient care transitions. Pharmacist completion of medication reconciliation compared with usual care has shown a 28% relative risk (RR) reduction in ED visits and a 67% RR reduction in adverse drug event-related hospital revisits.²⁷ Findings of the COPD CARE service are consistent with the literature and advance the role of pharmacists within the medical home model as prescribers for disease management.²⁷

The interprofessional, team-based design of the COPD CARE service also is supported by recent recommendations from the COPD Foundation, as detailed in the 2nd National COPD Readmission Summit.²⁸ Use of a proactive, team-based care model is emphasized as a central element to coordinating care transitions, with an expectation of 360 degree accountability by all team members for the patients care both during and after hospitalization. The clearly defined roles of each team member within the COPD CARE service, coupled with the expectation that each team member practices with autonomy and accountability, exemplifies the COPD Foundation vision for enhancing COPD care. In addition, the COPD CARE service uses many of the best practices detailed by the COPD Foundation, including the use of spirometry, referrals to pulmonary rehabilitation, and use of motivational interviewing for tobacco treatment clinic referral.

Limitations

This QI initiative has several limitations. By virtue of the study being designed as a practice improvement intervention with rapid implementation, the existing clinic referral structures were used to offer the service to eligible patients. This standard of care included routine telephone contact by a nurse case manager following hospital discharge. Although all patients in the COPD CARE service received the intervention, 5 patients were not seen within the 30-day window, resulting in an implementation rate of 73%. Of the 5 patients that were not seen, 4 were discharged from the ED. Timely follow-up in primary care clinic from the ED required the use of a time-intensive chart review for referral and subsequent delay in intervention delivery.A streamlined clinic referral process from the ED likely would further improve patient scheduling and result in a greater number of patients who would receive the intervention within 30 days of discharge. Despite this limitation, the COPD CARE service was able to see a large percentage of patients within the 30-day time frame postdischarge.

Future Directions

Although a major objective of this service was to reduce readmissions 30 days postdischarge, it is possible interventions made in clinic may have long-term beneficial effects.^25,29 Future research should evaluate the impact of this interprofessional service on long-term disease outcomes, thereby determining whether the promising readmission results are sustained beyond 30 days postdischarge.³⁰ In addition, incorporation of respiratory therapy and inpatient pharmacists during hospital discharge could provide a more effective and sustainable transition from hospital to home before the COPD CARE clinic visit.

Future implementations and evaluations of this COPD CARE service will in turn benefit from a key component of our intervention, which includes the collection of timely CAT scores, spirometry data, and adherence rates for COPD patients.³¹ Furthermore, the intervention was successfully delivered to a population recently hospitalized or seen in the ED, and therefore, at high risk for future COPD exacerbations. This initiative provides positive proof of a concept QI project using the existing PACT team model to reduce 30-day readmission rates in patients with COPD at high risk for exacerbation. Future efforts will focus on delivering this intervention to patients with mild, moderate, and severe COPD within a wide range of primary clinics.

Conslusion

The COPD CARE service involved the coordinated postdischarge care facilitated by an interprofessional team of clinical pharmacists, nurses and PCPs. The COPD CARE service leveraged an interprofessional team, centered on the PACT medical home, to make clinic interventions resulting in a 0% readmission rate and 63.2% increase in PCP access. The COPD CARE service further demonstrated the impact of coordinated efforts by interprofessional teams to optimize care for COPD management.

Acknowledgments
The authors thank Stephanie Gruber, PharmD; Lieneke Hafeman, RN; Molly Obermark, PharmD; Julia Peek, RT; Mark Regan, MD; Chris Roelke, RN; Steve Shoyer, PharmD; John Thielemann, RN; Sandy Tompkins, BS; and Wendi Wenger, RN, for their integral roles in the COPD CARE service.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and has an associated treatment cost of $9,800 per patient per year in the US.^1-3 Within 5 years of hospital discharge for a COPD exacerbation, the rehospitalization risk is 44%, and the mortality rate is 55%.⁴ COPD affects more than 11 million Americans, and the disease prevalence among US veterans is 3-fold higher.^5,6

Patients hospitalized for COPD have a 30-day readmission rate of 22.6%.⁷ Given the high patient burden, COPD was added to the Medicare Hospital Readmission Reductions Program in 2015, resulting in financial penalties for COPD readmissions within 30 days of hospital discharge.⁸ Ensuring timely access to follow-up care has been shown to significantly reduce risk for hospital readmissions.⁹ However, in a national review of Medicare claims, only 50% of patients readmitted to the hospital had a primary care provider (PCP) follow-up visit within 30 days of their hospital discharge.¹⁰ Despite the need to provide prompt patient follow-up during the transition from hospital to home, gaps within the health care system create barriers to providing timely postdischarge care.^10-12 These gaps include breakdowns in practitioner and patient communication, lengthy time to follow-up, and incomplete medication reconciliation.¹³ To address this unmet need, clinics and hospitals require solutions that can be implemented quickly, using the resources of their current clinical models.

Pharmacists and registered nurses (RNs) within the US federal health care system are well positioned for involvement in the postdischarge care of high-risk patients with COPD. Ambulatory care practitioners within the US Department of Veterans Affairs (VA) health care system are integrated into patient aligned care teams (PACT). Each team consists of a PCP, pharmacist, RN, social worker, dietitian, licensed practical nurse, and medical scheduling support assistant.¹⁴ Each PACT team works together to provide patient education, chronic disease management, and medication optimization, and each team member contributes their unique training and expertise.

Interprofessional care is considered an integral method to improve health outcomes through effective teamwork and communication.¹⁵ Although interprofessional interventions are cited extensively in the literature highlighting medicine and nursing, a gap exists in the exploration of pharmacist contributions within interprofessional teams.¹⁶ The incorporation of clinical pharmacists in the literature is especially limited when considering transitions of care and the patient medical home.¹⁷ Given the critical and collaborative role pharmacists play within the PACT medical home, the COPD CARE (Chronic Obstructive Pulmonary Disease Coordinated Access to Reduce Exacerbations) service provides an opportunity to leverage pharmacists as prescribers with a scope of practice who coordinate transitions of care for patients with COPD.¹⁸ The service was designed to be collaborative within the PACT model and with the intent of reducing 30-day readmissions to the hospital or emergency department (ED) due to a COPD exacerbation.

This evaluation involved the identifying patients recently hospitalized for COPD; clinic follow-up, coordinated by a clinical pharmacist and nurse, within 30 days of hospital or ED discharge; the use of a COPD action plan; and timely triage of patients at high risk for COPD reexacerbation or with comorbid symptoms to PCPs. The COPD CARE service, leveraged the patient-centered medical home (PCMH) model for transitions of care after COPD exacerbations. The PCMH is a primary care model focused on the following functions: (1) comprehensive care; (2) patient-centered care; (3) coordinated care; (4) accessible service; and (5) quality and safety.¹⁹

Methods

The COPD CARE service was implemented on October 1, 2015, and evaluated through March 1, 2016 (Figure 1). All veterans receiving primary care through the pilot clinic site with a hospital admission or ED visit for COPD exacerbation were offered this intervention. 

Patient Eligibility and Recruitment

Patients were excluded from the service if COPD or COPD-related diagnoses were not listed in their electronic health record (EHR) problem list. Patients who had previously received components of the intervention through consultation with specialty services were excluded. If a patient declined the service, they received the standard of care. This project was undertaken for programmatic evaluation and qualified for quality improvement (QI) exemption; as such an internal review board approval was not required.

Intervention

Participants enrolled in the COPD CARE service were scheduled for an interprofessional postdischarge follow-up visit with a pharmacist and nurse at the pilot outpatient clinic site, and this visit was termed the COPD CARE health visit. Participants ideally were seen within 30 days of discharge. The goal was to improve access to care while preventing a 30-day readmission. Within this 30-day window, the target follow-up period was 2 to 3 weeks postdischarge for the face-to-face visit. Patients who required postdischarge care for additional medical conditions received a clinic appointment with their PCP on the same day as their COPD CARE health visit. The COPD CARE health visit focused on 3 objectives: (1) COPD disease management and referrals; (2) COPD plan development; and (3) inhaler technique review and teaching.^20,21

COPD Monitoring

During the 45-minute COPD CARE health visit, the pharmacist provided extensive disease management based on the GOLD guideline recommendation.²² In addition, the pharmacist administered the COPD Assessment Test (CAT) and reviewed patient COPD exacerbation history to guide prescribing.²² The patient and pharmacist also reviewed previous spirometry results if obtained within the past 2 years. COPD triggers and symptoms were assessed along with opportunities for therapeutic and lifestyle modifications.

Plan Development

Patients in the COPD CARE service also were given a COPD plan to improve health outcomes. (Figure 2). The plan included patient instructions to initiate steroid and antibiotic therapy if the patient experienced symptoms of increased cough, mucus production, and purulence, thereby reaching the high-yellow zone. 

Patient Referrals

Patient referrals also were a critical component of the COPD CARE service. Pharmacists placed referrals for tobacco treatment services, pulmonary rehabilitation, a COPD group education class, and referral to specialty care if needed.

Inhaler Technique Review

Either the pharmacist or RN review the inhaler technique, and corrections and teachback methods used to ensure patient understanding.²³ Patients were encouraged to bring home inhalers into clinic for technique assessment. Demonstration inhalers also were available and used by pharmacists and nurses for inhaler teaching as needed. The pharmacist indicated through chart documentation whether the patient’s inhaler technique was correct or whether modifications were made to improve medication delivery. Medication reconciliation also was performed for inhaled devices to insure patients were using medications as prescribed.

Outcomes

The primary outcome of this evaluation was an assessment of interventions made by the interprofessional care team during the COPD CARE health visit. Secondary outcomes included assessment of 30-day readmission rates as well as patient access to the primary care team using this interprofessional care model.

Data were collected after study completion through review of the EHR at baseline and at the end of the evaluation period. Baseline demographic information was collected through a retrospective chart review. Readmission rates were calculated as a composite of ED visits and rehospitalization within 30 days of discharge due to a COPD exacerbation.

Patients’ spirometry results were used in composite with clinical symptoms and risk of exacerbations to calculate GOLD staging.²⁴

Results

A total of 19 patients admitted to the hospital or ED received follow-up through the COPD CARE service. Patients included in this analysis were primarily older adult white males.

Referrals were placed for 53% of patients in the COPD CARE service, with 21% of patients accepting referral to tobacco treatment clinic, and 32% of patients accepting referral to pulmonary rehabilitation. COPD plans were issued to all of patients in this service. Pharmacists modified therapy 58% of the time, with a review of medications prescribed by the clinical pharmacist (eApendixes 1 and 2, available at mdedge.com/fedprac).

Patients had a 0% composite readmission rate to the ED or hospital for a COPD exacerbation within 30-days of discharge. Access to care, defined as a visit with the primary care PACT team within 30 days of discharge, was achieved in 14 of the 19 patients (73.7%). Additionally, 12 of 19 patients (63.2%) in the COPD CARE service no longer needed to see their PCP following discharge, saving their provider a visit.

The pharmacist corrected patient inhaler technique in 52.6% of the patients participating in the service.

Discussion

The intent of this QI initiative was to assess a novel clinic intervention for a high-risk patient population during COPD care transitions. The strengths of this intervention involved a rapid cycle implementation using the existing medical home model and its multiprong approach to coordinating care. This approach involved coordinating self-direction COPD plans, timely hospital follow-up, and the innovative use of the interprofessional primary care team.

The COPD CARE service improved patient access to follow-up with no COPD readmissions in the intervention group. The COPD CARE service also validated the use of a coordinated medical home consisting of clinical pharmacists and nurses who provided the initial COPD disease monitoring and plan development. This intervention also resulted in patients receiving greater access to their PACT teams within 30 days of discharge and a higher rate of referrals to tobacco cessation clinics within the COPD CARE group. In addition, use of tools that enabled patients to self-manage their care, such as the COPD plan, was greater in the COPD CARE group.

The interventions made in-clinic likely contributed to service results (eAppendix 3). 

In addition, the COPD CARE service provided necessary referrals to pulmonary rehabilitation, nutrition, and tobacco treatment clinics at a higher rate than those patients in the standard of care group. The high percentage of referrals placed to tobacco treatment clinic and pulmonary rehabilitation contributes to improvements in COPD disease control long-term.²⁵ 

The COPD CARE service may best be described as a model for application of the interprofessional team in clinical practice, with the clinical pharmacist uniquely positioned for chronic disease management in the postacute care setting.²⁶ Previously, literature has documented pharmacists as integral members of the team during patient care transitions. Pharmacist completion of medication reconciliation compared with usual care has shown a 28% relative risk (RR) reduction in ED visits and a 67% RR reduction in adverse drug event-related hospital revisits.²⁷ Findings of the COPD CARE service are consistent with the literature and advance the role of pharmacists within the medical home model as prescribers for disease management.²⁷

The interprofessional, team-based design of the COPD CARE service also is supported by recent recommendations from the COPD Foundation, as detailed in the 2nd National COPD Readmission Summit.²⁸ Use of a proactive, team-based care model is emphasized as a central element to coordinating care transitions, with an expectation of 360 degree accountability by all team members for the patients care both during and after hospitalization. The clearly defined roles of each team member within the COPD CARE service, coupled with the expectation that each team member practices with autonomy and accountability, exemplifies the COPD Foundation vision for enhancing COPD care. In addition, the COPD CARE service uses many of the best practices detailed by the COPD Foundation, including the use of spirometry, referrals to pulmonary rehabilitation, and use of motivational interviewing for tobacco treatment clinic referral.

Limitations

This QI initiative has several limitations. By virtue of the study being designed as a practice improvement intervention with rapid implementation, the existing clinic referral structures were used to offer the service to eligible patients. This standard of care included routine telephone contact by a nurse case manager following hospital discharge. Although all patients in the COPD CARE service received the intervention, 5 patients were not seen within the 30-day window, resulting in an implementation rate of 73%. Of the 5 patients that were not seen, 4 were discharged from the ED. Timely follow-up in primary care clinic from the ED required the use of a time-intensive chart review for referral and subsequent delay in intervention delivery.A streamlined clinic referral process from the ED likely would further improve patient scheduling and result in a greater number of patients who would receive the intervention within 30 days of discharge. Despite this limitation, the COPD CARE service was able to see a large percentage of patients within the 30-day time frame postdischarge.

Future Directions

Although a major objective of this service was to reduce readmissions 30 days postdischarge, it is possible interventions made in clinic may have long-term beneficial effects.^25,29 Future research should evaluate the impact of this interprofessional service on long-term disease outcomes, thereby determining whether the promising readmission results are sustained beyond 30 days postdischarge.³⁰ In addition, incorporation of respiratory therapy and inpatient pharmacists during hospital discharge could provide a more effective and sustainable transition from hospital to home before the COPD CARE clinic visit.

Future implementations and evaluations of this COPD CARE service will in turn benefit from a key component of our intervention, which includes the collection of timely CAT scores, spirometry data, and adherence rates for COPD patients.³¹ Furthermore, the intervention was successfully delivered to a population recently hospitalized or seen in the ED, and therefore, at high risk for future COPD exacerbations. This initiative provides positive proof of a concept QI project using the existing PACT team model to reduce 30-day readmission rates in patients with COPD at high risk for exacerbation. Future efforts will focus on delivering this intervention to patients with mild, moderate, and severe COPD within a wide range of primary clinics.

Conslusion

The COPD CARE service involved the coordinated postdischarge care facilitated by an interprofessional team of clinical pharmacists, nurses and PCPs. The COPD CARE service leveraged an interprofessional team, centered on the PACT medical home, to make clinic interventions resulting in a 0% readmission rate and 63.2% increase in PCP access. The COPD CARE service further demonstrated the impact of coordinated efforts by interprofessional teams to optimize care for COPD management.

Acknowledgments
The authors thank Stephanie Gruber, PharmD; Lieneke Hafeman, RN; Molly Obermark, PharmD; Julia Peek, RT; Mark Regan, MD; Chris Roelke, RN; Steve Shoyer, PharmD; John Thielemann, RN; Sandy Tompkins, BS; and Wendi Wenger, RN, for their integral roles in the COPD CARE service.

The weather grows colder, the leaves are changing colors then falling, and it is time to gather close all we hold dear and to remember those who have gone before and those who have given for us—it is November. Across the world nations set aside a day to honor fallen heroes and wounded warriors. In Canada and Australia, it is Remembrance Day, in the US, it is Veterans Day, November 11.

War is older than recorded history, and every culture has experiences of violent conflict. Thus, every society has those men and women who have been harmed in body and mind and soul in mortal combat and yet survived and those who have perished on the battlefield or in its aftermath or wished they had.

The bloody, brutal human toll of organized strife has led many a society to recognize a moral obligation to develop a dedicated means of delivering medical care and social support to not just those who are serving actively but to those whose days in action are past. The utilitarian rationale for military medicine is clearly stated in the United States Army Medical Command mission, “Army Medicine provides sustained health services and research in support of the Total Force to enable readiness and conserve the fighting strength while caring for our Soldiers for Life and Families.”¹ It is a measure of the self-sacrifice of those who have sworn to defend their homeland and their healing brothers and sisters in arms that they deliberately make this commitment to each other and their fellow citizens. Yet we cannot easily extend this logic to the care of veterans. Why have diverse countries across millennia seen fit to carve out a special space for veteran health care? In this column, we will seek an answer in culture and history.

Related: Why VA Health Care Is Different

The Roman Empire, which relied heavily on its soldiers for the peace and prosperity of the empire was among the first political entities to recognize the need for military health care and to dedicate human and financial capital to subsidize care for veterans. Among the first hospitals in the world were built to care for Roman legions and the ancient medics like their modern counterparts advanced medical and especially surgical progress that benefited the public.²Today it is not only the US that has special systems of health care for veterans. The Australia Department of Veterans’ Affairs provides many of the same health and social service benefits as those of the US Department of Veterans Affairs (VA). Likewise, Veterans Affairs Canada (VAC) offers those who served and are eligible a variety of resources, including health care. Why does VAC provide health care for veterans?

Veterans Affairs Canada deeply values the contribution that Veterans have made to the development of our nation and we honour the sacrifices they have made.... In expressing Canada’s gratitude to them, we strive to exemplify many of the same principles which they represent–integrity, respect, service and commitment, accountability, and teamwork. ³

Many of these same motifs are repeated in the legislation that officially changed the November 11th commemoration from Armistice Day to Veterans Day. The holiday originated to mark the ending of the terrible First World War in which so many young men’s futures ended in the stench and mud of European trenches. Where Armistice Day celebrated the peace of the Treaty of Versailles and Memorial Day commemorates those in uniform who made the ultimate sacrifice; Veterans Day honors all veterans those still with us and those who have gone before. At the urging of veterans service organizations, as President, the great Army general Dwight D. Eisenhower declared in 1954 November 11 to be Veterans Day with these words:

On that day let us solemnly remember the sacrifices of all those who fought so valiantly, on the seas, in the air, and on foreign shores, to preserve our heritage of freedom, and let us reconsecrate ourselves to the task of promoting an enduring peace so that their efforts shall not have been in vain. ⁴

From these and other political proclamations, we can discern 4 ethical purposes that have motivated so many eras and states to maintain institutions to protect the health and promote the well-being of veterans. The first is gratitude, for those who lost something precious—be it health, function, soundness of mind, wholeness of limb, even life itself. The soldiers, airmen, sailors, marines, and others deserve not only our thanks, but also giving of our substance through taxes and the discharge of our democratic duties to support them through health care and housing, benefits, and burial.

Related: Am I My Brother’s/Sister’s Keeper?

The second purpose is that we owe all veterans a debt, a debt we can never fully repay, because no price can be placed on mental health, on freedom from pain and suffering, from being without a husband or a mother, and yet that is the price that many veterans paid. The least we can do is ensure that they have a health care system that understands the nature of their narratives and invests in the development of expertise particularity in psychophysical sequelae of war like traumatic brain injuries, amputations, posttraumatic stress disorder, and substance use.

The third purpose is that those who carried weapons, who were shot at, and who suffered so many other assaults outside the range of expected human experience fought to secure for all generations the 2 most precious qualities of civilization: freedom and peace. Once their work was done and the uniform hung in the closet and the medals put in a drawer, service men and women passed on to all of us—especially those who are committed to provide their medical care—that cause.

The fourth purpose is the simplest yet perhaps the most morally compelling—to remember the history of sacrifice. In my VA and in many others, unlike any private hospital on the planet, the walls are filled with military memorabilia. There is a memorial statute of a Medal of Honor winner for whom the facility is named in front of the main hospital with a giant American flag waiving proudly. All these symbols tell the veteran walking through the halls that this he or she is the primary ethical justification for this health care organization.

Related: The VA Cannot Be Privatized

These are the most powerful arguments to refute the many recent articles that question the very existence of the VA. Many of those authors, including one of my mentors, have ethical grounds for their calls for an end to a separate health care system for veterans.⁵ Believe me, after nearly 2 decades in the VA, I know firsthand we have much to improve in efficiency, responsiveness, and accountability. But is it really an ethical or even a scientific truth that veteran health care can be delivered more successfully by the private sector? That depends on the terms in which success is defined. Many of those who so blithely and at times irresponsibly proclaim that “we do not need a VA” display in the words of my own admired commander, “the reckless courage of noncombatants.” Solid health care research from independent sources suggests that the VA offers most community health care organizations a run for their money in terms of economies of scale and quality of outcomes in many areas.⁶ Yet this column contends that the measure of success for veteran health care is that the majority of VA and US Department of Defense health care professionals and administrators remain dedicated to these 4 core purposes. Success for these institutions is to seek and to strive through research, teaching, and clinical care to discover and deliver those therapies and medicaments with the most potential to preserve and enhance freedom of body and peace of mind that veterans deserve every day, not only on November 11.

The weather grows colder, the leaves are changing colors then falling, and it is time to gather close all we hold dear and to remember those who have gone before and those who have given for us—it is November. Across the world nations set aside a day to honor fallen heroes and wounded warriors. In Canada and Australia, it is Remembrance Day, in the US, it is Veterans Day, November 11.

War is older than recorded history, and every culture has experiences of violent conflict. Thus, every society has those men and women who have been harmed in body and mind and soul in mortal combat and yet survived and those who have perished on the battlefield or in its aftermath or wished they had.

The bloody, brutal human toll of organized strife has led many a society to recognize a moral obligation to develop a dedicated means of delivering medical care and social support to not just those who are serving actively but to those whose days in action are past. The utilitarian rationale for military medicine is clearly stated in the United States Army Medical Command mission, “Army Medicine provides sustained health services and research in support of the Total Force to enable readiness and conserve the fighting strength while caring for our Soldiers for Life and Families.”¹ It is a measure of the self-sacrifice of those who have sworn to defend their homeland and their healing brothers and sisters in arms that they deliberately make this commitment to each other and their fellow citizens. Yet we cannot easily extend this logic to the care of veterans. Why have diverse countries across millennia seen fit to carve out a special space for veteran health care? In this column, we will seek an answer in culture and history.

Related: Why VA Health Care Is Different

The Roman Empire, which relied heavily on its soldiers for the peace and prosperity of the empire was among the first political entities to recognize the need for military health care and to dedicate human and financial capital to subsidize care for veterans. Among the first hospitals in the world were built to care for Roman legions and the ancient medics like their modern counterparts advanced medical and especially surgical progress that benefited the public.²Today it is not only the US that has special systems of health care for veterans. The Australia Department of Veterans’ Affairs provides many of the same health and social service benefits as those of the US Department of Veterans Affairs (VA). Likewise, Veterans Affairs Canada (VAC) offers those who served and are eligible a variety of resources, including health care. Why does VAC provide health care for veterans?

Veterans Affairs Canada deeply values the contribution that Veterans have made to the development of our nation and we honour the sacrifices they have made.... In expressing Canada’s gratitude to them, we strive to exemplify many of the same principles which they represent–integrity, respect, service and commitment, accountability, and teamwork. ³

Many of these same motifs are repeated in the legislation that officially changed the November 11th commemoration from Armistice Day to Veterans Day. The holiday originated to mark the ending of the terrible First World War in which so many young men’s futures ended in the stench and mud of European trenches. Where Armistice Day celebrated the peace of the Treaty of Versailles and Memorial Day commemorates those in uniform who made the ultimate sacrifice; Veterans Day honors all veterans those still with us and those who have gone before. At the urging of veterans service organizations, as President, the great Army general Dwight D. Eisenhower declared in 1954 November 11 to be Veterans Day with these words:

On that day let us solemnly remember the sacrifices of all those who fought so valiantly, on the seas, in the air, and on foreign shores, to preserve our heritage of freedom, and let us reconsecrate ourselves to the task of promoting an enduring peace so that their efforts shall not have been in vain. ⁴

From these and other political proclamations, we can discern 4 ethical purposes that have motivated so many eras and states to maintain institutions to protect the health and promote the well-being of veterans. The first is gratitude, for those who lost something precious—be it health, function, soundness of mind, wholeness of limb, even life itself. The soldiers, airmen, sailors, marines, and others deserve not only our thanks, but also giving of our substance through taxes and the discharge of our democratic duties to support them through health care and housing, benefits, and burial.

Related: Am I My Brother’s/Sister’s Keeper?

The second purpose is that we owe all veterans a debt, a debt we can never fully repay, because no price can be placed on mental health, on freedom from pain and suffering, from being without a husband or a mother, and yet that is the price that many veterans paid. The least we can do is ensure that they have a health care system that understands the nature of their narratives and invests in the development of expertise particularity in psychophysical sequelae of war like traumatic brain injuries, amputations, posttraumatic stress disorder, and substance use.

The third purpose is that those who carried weapons, who were shot at, and who suffered so many other assaults outside the range of expected human experience fought to secure for all generations the 2 most precious qualities of civilization: freedom and peace. Once their work was done and the uniform hung in the closet and the medals put in a drawer, service men and women passed on to all of us—especially those who are committed to provide their medical care—that cause.

The fourth purpose is the simplest yet perhaps the most morally compelling—to remember the history of sacrifice. In my VA and in many others, unlike any private hospital on the planet, the walls are filled with military memorabilia. There is a memorial statute of a Medal of Honor winner for whom the facility is named in front of the main hospital with a giant American flag waiving proudly. All these symbols tell the veteran walking through the halls that this he or she is the primary ethical justification for this health care organization.

Related: The VA Cannot Be Privatized

These are the most powerful arguments to refute the many recent articles that question the very existence of the VA. Many of those authors, including one of my mentors, have ethical grounds for their calls for an end to a separate health care system for veterans.⁵ Believe me, after nearly 2 decades in the VA, I know firsthand we have much to improve in efficiency, responsiveness, and accountability. But is it really an ethical or even a scientific truth that veteran health care can be delivered more successfully by the private sector? That depends on the terms in which success is defined. Many of those who so blithely and at times irresponsibly proclaim that “we do not need a VA” display in the words of my own admired commander, “the reckless courage of noncombatants.” Solid health care research from independent sources suggests that the VA offers most community health care organizations a run for their money in terms of economies of scale and quality of outcomes in many areas.⁶ Yet this column contends that the measure of success for veteran health care is that the majority of VA and US Department of Defense health care professionals and administrators remain dedicated to these 4 core purposes. Success for these institutions is to seek and to strive through research, teaching, and clinical care to discover and deliver those therapies and medicaments with the most potential to preserve and enhance freedom of body and peace of mind that veterans deserve every day, not only on November 11.

The weather grows colder, the leaves are changing colors then falling, and it is time to gather close all we hold dear and to remember those who have gone before and those who have given for us—it is November. Across the world nations set aside a day to honor fallen heroes and wounded warriors. In Canada and Australia, it is Remembrance Day, in the US, it is Veterans Day, November 11.

War is older than recorded history, and every culture has experiences of violent conflict. Thus, every society has those men and women who have been harmed in body and mind and soul in mortal combat and yet survived and those who have perished on the battlefield or in its aftermath or wished they had.

The bloody, brutal human toll of organized strife has led many a society to recognize a moral obligation to develop a dedicated means of delivering medical care and social support to not just those who are serving actively but to those whose days in action are past. The utilitarian rationale for military medicine is clearly stated in the United States Army Medical Command mission, “Army Medicine provides sustained health services and research in support of the Total Force to enable readiness and conserve the fighting strength while caring for our Soldiers for Life and Families.”¹ It is a measure of the self-sacrifice of those who have sworn to defend their homeland and their healing brothers and sisters in arms that they deliberately make this commitment to each other and their fellow citizens. Yet we cannot easily extend this logic to the care of veterans. Why have diverse countries across millennia seen fit to carve out a special space for veteran health care? In this column, we will seek an answer in culture and history.

Related: Why VA Health Care Is Different

The Roman Empire, which relied heavily on its soldiers for the peace and prosperity of the empire was among the first political entities to recognize the need for military health care and to dedicate human and financial capital to subsidize care for veterans. Among the first hospitals in the world were built to care for Roman legions and the ancient medics like their modern counterparts advanced medical and especially surgical progress that benefited the public.²Today it is not only the US that has special systems of health care for veterans. The Australia Department of Veterans’ Affairs provides many of the same health and social service benefits as those of the US Department of Veterans Affairs (VA). Likewise, Veterans Affairs Canada (VAC) offers those who served and are eligible a variety of resources, including health care. Why does VAC provide health care for veterans?

Veterans Affairs Canada deeply values the contribution that Veterans have made to the development of our nation and we honour the sacrifices they have made.... In expressing Canada’s gratitude to them, we strive to exemplify many of the same principles which they represent–integrity, respect, service and commitment, accountability, and teamwork. ³

Many of these same motifs are repeated in the legislation that officially changed the November 11th commemoration from Armistice Day to Veterans Day. The holiday originated to mark the ending of the terrible First World War in which so many young men’s futures ended in the stench and mud of European trenches. Where Armistice Day celebrated the peace of the Treaty of Versailles and Memorial Day commemorates those in uniform who made the ultimate sacrifice; Veterans Day honors all veterans those still with us and those who have gone before. At the urging of veterans service organizations, as President, the great Army general Dwight D. Eisenhower declared in 1954 November 11 to be Veterans Day with these words:

On that day let us solemnly remember the sacrifices of all those who fought so valiantly, on the seas, in the air, and on foreign shores, to preserve our heritage of freedom, and let us reconsecrate ourselves to the task of promoting an enduring peace so that their efforts shall not have been in vain. ⁴

From these and other political proclamations, we can discern 4 ethical purposes that have motivated so many eras and states to maintain institutions to protect the health and promote the well-being of veterans. The first is gratitude, for those who lost something precious—be it health, function, soundness of mind, wholeness of limb, even life itself. The soldiers, airmen, sailors, marines, and others deserve not only our thanks, but also giving of our substance through taxes and the discharge of our democratic duties to support them through health care and housing, benefits, and burial.

Related: Am I My Brother’s/Sister’s Keeper?

The second purpose is that we owe all veterans a debt, a debt we can never fully repay, because no price can be placed on mental health, on freedom from pain and suffering, from being without a husband or a mother, and yet that is the price that many veterans paid. The least we can do is ensure that they have a health care system that understands the nature of their narratives and invests in the development of expertise particularity in psychophysical sequelae of war like traumatic brain injuries, amputations, posttraumatic stress disorder, and substance use.

The third purpose is that those who carried weapons, who were shot at, and who suffered so many other assaults outside the range of expected human experience fought to secure for all generations the 2 most precious qualities of civilization: freedom and peace. Once their work was done and the uniform hung in the closet and the medals put in a drawer, service men and women passed on to all of us—especially those who are committed to provide their medical care—that cause.

The fourth purpose is the simplest yet perhaps the most morally compelling—to remember the history of sacrifice. In my VA and in many others, unlike any private hospital on the planet, the walls are filled with military memorabilia. There is a memorial statute of a Medal of Honor winner for whom the facility is named in front of the main hospital with a giant American flag waiving proudly. All these symbols tell the veteran walking through the halls that this he or she is the primary ethical justification for this health care organization.

Related: The VA Cannot Be Privatized

These are the most powerful arguments to refute the many recent articles that question the very existence of the VA. Many of those authors, including one of my mentors, have ethical grounds for their calls for an end to a separate health care system for veterans.⁵ Believe me, after nearly 2 decades in the VA, I know firsthand we have much to improve in efficiency, responsiveness, and accountability. But is it really an ethical or even a scientific truth that veteran health care can be delivered more successfully by the private sector? That depends on the terms in which success is defined. Many of those who so blithely and at times irresponsibly proclaim that “we do not need a VA” display in the words of my own admired commander, “the reckless courage of noncombatants.” Solid health care research from independent sources suggests that the VA offers most community health care organizations a run for their money in terms of economies of scale and quality of outcomes in many areas.⁶ Yet this column contends that the measure of success for veteran health care is that the majority of VA and US Department of Defense health care professionals and administrators remain dedicated to these 4 core purposes. Success for these institutions is to seek and to strive through research, teaching, and clinical care to discover and deliver those therapies and medicaments with the most potential to preserve and enhance freedom of body and peace of mind that veterans deserve every day, not only on November 11.

CHICAGO – Etanercept monotherapy showed greater efficacy, compared with methotrexate monotherapy for the treatment of psoriatic arthritis, and combining the two agents provided no benefit over etanercept alone for most outcomes in the randomized, controlled, international, phase 3 SEAM-PsA study.

A 20% improvement in American College of Rheumatology criteria at week 24 – the primary endpoint of the study – was significantly greater in 284 patients treated with etanercept monotherapy and in 283 patients treated with combination etanercept and methotrexate than in 284 patients treated with methotrexate monotherapy (60.9% and 65.0% vs. 50.7%, respectively), Philip J. Mease, MD, of the Swedish Medical Center and the University of Washington, Seattle, and his colleagues reported in a late-breaking poster on the SEAM-PsA (Etanercept and Methotrexate in Subjects with Psoriatic Arthritis) study at the annual meeting of the American College of Rheumatology.

The key secondary endpoint of minimal disease activity response at week 24 also was significantly greater in the etanercept monotherapy and combination groups than in the methotrexate monotherapy group (35.9% and 35.7% vs. 22.9%, respectively), the investigators noted.

Additionally, at week 48, the etanercept monotherapy group and combination group both showed less radiographic progression than did the methotrexate monotherapy arm (mean change in modified total Sharp score from baseline, –0.04 and –0.01 vs. 0.08).


Overall, the etanercept monotherapy group and combination therapy group had similar results, with some differences in skin outcomes. Treatment was well tolerated, and except for more nausea occurring with methotrexate, adverse event rates were similar in the three study arms. No new safety signals were observed.

“The most common serious adverse events were infections and infestations, which occurred in 1.1% of patients in the methotrexate monotherapy arm, 2.8% of patients in the etanercept monotherapy arm, and 2.5% of patients in the combination therapy arm,” they wrote.

Study participants were biologic-naive adults with active PsA and no prior methotrexate treatment for their disease. They had a mean age of 48.4 years, most were white, and median disease duration was 0.6 years.

They were randomized to receive either 50 mg subcutaneous injections of etanercept plus oral placebo weekly, 50 mg subcutaneous etanercept plus 20 mg oral methotrexate weekly, or 20 mg oral methotrexate plus placebo injections weekly; the groups were well balanced with respect to baseline characteristics, the investigators said.

Rescue therapy of etanercept plus methotrexate was given after 24 weeks in patients with less than 20% improvement in tender joint counts and swollen joint counts from baseline.

“Agents used to treat PsA include disease-modifying antirheumatic drugs such as methotrexate and tumor necrosis factor inhibitors, but how to optimally use these agents to treat PsA is unknown,” they wrote, explaining that while methotrexate is widely used in this setting, little clinical evidence exists to guide its use, and that while tumor necrosis factor inhibitors have shown efficacy in PsA, the benefit of adding methotrexate remains unclear.

The current findings, however, demonstrate that adding methotrexate does not appear to increase the efficacy of etanercept monotherapy for most outcomes.

An exception was with combination therapy for some skin-related outcomes, including percent improvement in psoriasis-affected body surface area and percentage of patients with “status clear or almost clear,” they said.

Further, methotrexate monotherapy in this study appeared to have some “meaningful efficacy for both articular and nonarticular PsA symptoms,” the investigators noted.

“These results provide information of practical value for clinical practice when considering treatment option for PsA,” they concluded.

The study was supported by Amgen. Dr. Mease reported receiving research grants, speaker fees, and/or consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Galapagos, Genentech, Janssen Pharmaceuticals, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, and UCB.

sworcester@mdedge.com

SOURCE: Mease PJ et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract L11.

CHICAGO – Etanercept monotherapy showed greater efficacy, compared with methotrexate monotherapy for the treatment of psoriatic arthritis, and combining the two agents provided no benefit over etanercept alone for most outcomes in the randomized, controlled, international, phase 3 SEAM-PsA study.

A 20% improvement in American College of Rheumatology criteria at week 24 – the primary endpoint of the study – was significantly greater in 284 patients treated with etanercept monotherapy and in 283 patients treated with combination etanercept and methotrexate than in 284 patients treated with methotrexate monotherapy (60.9% and 65.0% vs. 50.7%, respectively), Philip J. Mease, MD, of the Swedish Medical Center and the University of Washington, Seattle, and his colleagues reported in a late-breaking poster on the SEAM-PsA (Etanercept and Methotrexate in Subjects with Psoriatic Arthritis) study at the annual meeting of the American College of Rheumatology.

The key secondary endpoint of minimal disease activity response at week 24 also was significantly greater in the etanercept monotherapy and combination groups than in the methotrexate monotherapy group (35.9% and 35.7% vs. 22.9%, respectively), the investigators noted.

Additionally, at week 48, the etanercept monotherapy group and combination group both showed less radiographic progression than did the methotrexate monotherapy arm (mean change in modified total Sharp score from baseline, –0.04 and –0.01 vs. 0.08).


Overall, the etanercept monotherapy group and combination therapy group had similar results, with some differences in skin outcomes. Treatment was well tolerated, and except for more nausea occurring with methotrexate, adverse event rates were similar in the three study arms. No new safety signals were observed.

“The most common serious adverse events were infections and infestations, which occurred in 1.1% of patients in the methotrexate monotherapy arm, 2.8% of patients in the etanercept monotherapy arm, and 2.5% of patients in the combination therapy arm,” they wrote.

Study participants were biologic-naive adults with active PsA and no prior methotrexate treatment for their disease. They had a mean age of 48.4 years, most were white, and median disease duration was 0.6 years.

They were randomized to receive either 50 mg subcutaneous injections of etanercept plus oral placebo weekly, 50 mg subcutaneous etanercept plus 20 mg oral methotrexate weekly, or 20 mg oral methotrexate plus placebo injections weekly; the groups were well balanced with respect to baseline characteristics, the investigators said.

Rescue therapy of etanercept plus methotrexate was given after 24 weeks in patients with less than 20% improvement in tender joint counts and swollen joint counts from baseline.

“Agents used to treat PsA include disease-modifying antirheumatic drugs such as methotrexate and tumor necrosis factor inhibitors, but how to optimally use these agents to treat PsA is unknown,” they wrote, explaining that while methotrexate is widely used in this setting, little clinical evidence exists to guide its use, and that while tumor necrosis factor inhibitors have shown efficacy in PsA, the benefit of adding methotrexate remains unclear.

The current findings, however, demonstrate that adding methotrexate does not appear to increase the efficacy of etanercept monotherapy for most outcomes.

An exception was with combination therapy for some skin-related outcomes, including percent improvement in psoriasis-affected body surface area and percentage of patients with “status clear or almost clear,” they said.

Further, methotrexate monotherapy in this study appeared to have some “meaningful efficacy for both articular and nonarticular PsA symptoms,” the investigators noted.

“These results provide information of practical value for clinical practice when considering treatment option for PsA,” they concluded.

The study was supported by Amgen. Dr. Mease reported receiving research grants, speaker fees, and/or consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Galapagos, Genentech, Janssen Pharmaceuticals, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, and UCB.

sworcester@mdedge.com

SOURCE: Mease PJ et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract L11.

CHICAGO – Etanercept monotherapy showed greater efficacy, compared with methotrexate monotherapy for the treatment of psoriatic arthritis, and combining the two agents provided no benefit over etanercept alone for most outcomes in the randomized, controlled, international, phase 3 SEAM-PsA study.

A 20% improvement in American College of Rheumatology criteria at week 24 – the primary endpoint of the study – was significantly greater in 284 patients treated with etanercept monotherapy and in 283 patients treated with combination etanercept and methotrexate than in 284 patients treated with methotrexate monotherapy (60.9% and 65.0% vs. 50.7%, respectively), Philip J. Mease, MD, of the Swedish Medical Center and the University of Washington, Seattle, and his colleagues reported in a late-breaking poster on the SEAM-PsA (Etanercept and Methotrexate in Subjects with Psoriatic Arthritis) study at the annual meeting of the American College of Rheumatology.

The key secondary endpoint of minimal disease activity response at week 24 also was significantly greater in the etanercept monotherapy and combination groups than in the methotrexate monotherapy group (35.9% and 35.7% vs. 22.9%, respectively), the investigators noted.

Additionally, at week 48, the etanercept monotherapy group and combination group both showed less radiographic progression than did the methotrexate monotherapy arm (mean change in modified total Sharp score from baseline, –0.04 and –0.01 vs. 0.08).


Overall, the etanercept monotherapy group and combination therapy group had similar results, with some differences in skin outcomes. Treatment was well tolerated, and except for more nausea occurring with methotrexate, adverse event rates were similar in the three study arms. No new safety signals were observed.

“The most common serious adverse events were infections and infestations, which occurred in 1.1% of patients in the methotrexate monotherapy arm, 2.8% of patients in the etanercept monotherapy arm, and 2.5% of patients in the combination therapy arm,” they wrote.

Study participants were biologic-naive adults with active PsA and no prior methotrexate treatment for their disease. They had a mean age of 48.4 years, most were white, and median disease duration was 0.6 years.

They were randomized to receive either 50 mg subcutaneous injections of etanercept plus oral placebo weekly, 50 mg subcutaneous etanercept plus 20 mg oral methotrexate weekly, or 20 mg oral methotrexate plus placebo injections weekly; the groups were well balanced with respect to baseline characteristics, the investigators said.

Rescue therapy of etanercept plus methotrexate was given after 24 weeks in patients with less than 20% improvement in tender joint counts and swollen joint counts from baseline.

“Agents used to treat PsA include disease-modifying antirheumatic drugs such as methotrexate and tumor necrosis factor inhibitors, but how to optimally use these agents to treat PsA is unknown,” they wrote, explaining that while methotrexate is widely used in this setting, little clinical evidence exists to guide its use, and that while tumor necrosis factor inhibitors have shown efficacy in PsA, the benefit of adding methotrexate remains unclear.

The current findings, however, demonstrate that adding methotrexate does not appear to increase the efficacy of etanercept monotherapy for most outcomes.

An exception was with combination therapy for some skin-related outcomes, including percent improvement in psoriasis-affected body surface area and percentage of patients with “status clear or almost clear,” they said.

Further, methotrexate monotherapy in this study appeared to have some “meaningful efficacy for both articular and nonarticular PsA symptoms,” the investigators noted.

“These results provide information of practical value for clinical practice when considering treatment option for PsA,” they concluded.

The study was supported by Amgen. Dr. Mease reported receiving research grants, speaker fees, and/or consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Galapagos, Genentech, Janssen Pharmaceuticals, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, and UCB.

sworcester@mdedge.com

SOURCE: Mease PJ et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract L11.

In 1992, then-governor of Massachusetts William F. Weld signed a bill into law legalizing the use of marijuana for glaucoma, cancer therapy, and certain asthmatic disorders under a limited Department of Public Health (DPH) research program. In 1996, the legislature gave DPH the power to approve any Massachusetts patient to “possess and use pot” legally for relief of symptoms.¹ In my position as Health Policy Coordinator with DPH, those two acts were my introduction to the controversy of medical marijuana.

Since then, the popularity of—or rather, the shift in public sentiment regarding—marijuana (cannabis/cannabinoid) use has changed. There has been significant interest in the use of marijuana as an adjunct to treating chronic and/or debilitating medical conditions. There is also increasing interest in the potential therapeutic uses of marijuana and other cannabinoid compounds.

In recent years, we’ve seen significant momentum on this front. Point in fact, in fiscal year 2017, the National Institutes of Health supported projects on cannabinoid research totaling almost $140 million.² More than 30 US jurisdictions have passed legislation to legalize marijuana for medical use (while a few have legalized its use, period).³ All of which has prompted quite the debate not only among the public but also among health care providers.

A review of the history of cannabis use is very interesting—specifically, that the use of cannabis as a therapeutic modality predates recorded history. Cannabis was very popular in ancient China, India, and Greece as a medicine to alleviate pain or cure a variety of ailments.^4,5 In the early 1900s, cannabis was available OTC and commonly used for a variety of illnesses in the US. The first law regarding marijuana was enacted in 1619 at Jamestown Colony, Virginia; it “ordered” all farmers to grow Indian hempseed.⁶

But by 1906, cannabis was labeled as a poison in many states, and by the 1920s absolute prohibitions began. The Controlled Substances Act of 1970 outlawed cannabis for any use. Despite that ban, marijuana is the most common illegal drug used in the US today.⁷

Marijuana, not a completely benign substance, occupies a unique position in our society. On the one hand, it is a recreational compound, used to attain pleasant euphoria and a sense of relaxation. On the other, it has been used as a therapeutic compound, relieving nausea and anorexia from chemotherapy. In the former, it is viewed by many as a dangerous drug that can lead to madness (as depicted in the film Reefer Madness).⁸ In the latter, its use as an effective analgesic and appetite stimulant has been supported by people who have realized a therapeutic benefit.

The potential medicinal benefits of marijuana and its components have been the subject of research and ongoing heated debates. Decades of anecdotal evidence regarding the effectiveness of marijuana on the aforementioned symptoms have been documented. There are also numerous studies on marijuana as a therapeutic agent for multiple conditions, using the plant itself or extracts derived from it.^9-11

Continue to: Perhaps most interesting...

Perhaps most interesting, emerging data suggest that use and abuse of prescription drugs may be decreasing in states where medical cannabis is legal.¹² Two recent studies examining cannabis laws and prescription of opioids found that “medical cannabis laws are associated with significant reductions in opioid prescribing in the Medicare Part D population,” concluding that the potential for marijuana to decrease opioid use in the Medicaid population deserves consideration during policy discussions about marijuana reform and the opioid epidemic.^{13, 14}

The support for policy changes in states that have legalized marijuana for medical use suggests it is gaining greater acceptance in our society. The increase in jurisdictions that have approved marijuana for medical use requires that we, as health care providers, understand the implications for our practice and educate ourselves on the laws and regulations in our respective states.

Recent guidelines from the National Council of State Boards of Nursing (NCSBN) identify six principles of essential knowledge for NPs (that could apply to PAs, as well) who care for patients who qualify to participate in a Medical Marijuana Program (MMP). These include principles of safe and knowledgeable practice for clinicians when qualifying a patient for an MMP.³ Note that I said qualifying a patient and not prescribing marijuana. Federal law still classifies cannabis as a Schedule I controlled substance, thus prohibiting the actual prescription of marijuana, and prohibits pharmacies from dispensing cannabis. Quite a contradiction!

All of that said, it is incumbent upon each of us to understand the complexities of the MMP in our state. Each has its own specifications as to the qualifying conditions or symptoms, as well as the requirements to become an approved provider. And each is as diverse as the opinions on marijuana use.

Without doubt, the debate and dichotomy about medical marijuana will ensue for years. What we as health care providers must do is keep current on the laws and regulations not only in our state, but also at the federal level. As a primer on the status of MMPs and provider approval, I encourage all to review the NCSBN document.³

As always, you can share your thoughts with me via NPeditor@mdedge.com.

In 1992, then-governor of Massachusetts William F. Weld signed a bill into law legalizing the use of marijuana for glaucoma, cancer therapy, and certain asthmatic disorders under a limited Department of Public Health (DPH) research program. In 1996, the legislature gave DPH the power to approve any Massachusetts patient to “possess and use pot” legally for relief of symptoms.¹ In my position as Health Policy Coordinator with DPH, those two acts were my introduction to the controversy of medical marijuana.

Since then, the popularity of—or rather, the shift in public sentiment regarding—marijuana (cannabis/cannabinoid) use has changed. There has been significant interest in the use of marijuana as an adjunct to treating chronic and/or debilitating medical conditions. There is also increasing interest in the potential therapeutic uses of marijuana and other cannabinoid compounds.

In recent years, we’ve seen significant momentum on this front. Point in fact, in fiscal year 2017, the National Institutes of Health supported projects on cannabinoid research totaling almost $140 million.² More than 30 US jurisdictions have passed legislation to legalize marijuana for medical use (while a few have legalized its use, period).³ All of which has prompted quite the debate not only among the public but also among health care providers.

A review of the history of cannabis use is very interesting—specifically, that the use of cannabis as a therapeutic modality predates recorded history. Cannabis was very popular in ancient China, India, and Greece as a medicine to alleviate pain or cure a variety of ailments.^4,5 In the early 1900s, cannabis was available OTC and commonly used for a variety of illnesses in the US. The first law regarding marijuana was enacted in 1619 at Jamestown Colony, Virginia; it “ordered” all farmers to grow Indian hempseed.⁶

But by 1906, cannabis was labeled as a poison in many states, and by the 1920s absolute prohibitions began. The Controlled Substances Act of 1970 outlawed cannabis for any use. Despite that ban, marijuana is the most common illegal drug used in the US today.⁷

Marijuana, not a completely benign substance, occupies a unique position in our society. On the one hand, it is a recreational compound, used to attain pleasant euphoria and a sense of relaxation. On the other, it has been used as a therapeutic compound, relieving nausea and anorexia from chemotherapy. In the former, it is viewed by many as a dangerous drug that can lead to madness (as depicted in the film Reefer Madness).⁸ In the latter, its use as an effective analgesic and appetite stimulant has been supported by people who have realized a therapeutic benefit.

The potential medicinal benefits of marijuana and its components have been the subject of research and ongoing heated debates. Decades of anecdotal evidence regarding the effectiveness of marijuana on the aforementioned symptoms have been documented. There are also numerous studies on marijuana as a therapeutic agent for multiple conditions, using the plant itself or extracts derived from it.^9-11

Continue to: Perhaps most interesting...

Perhaps most interesting, emerging data suggest that use and abuse of prescription drugs may be decreasing in states where medical cannabis is legal.¹² Two recent studies examining cannabis laws and prescription of opioids found that “medical cannabis laws are associated with significant reductions in opioid prescribing in the Medicare Part D population,” concluding that the potential for marijuana to decrease opioid use in the Medicaid population deserves consideration during policy discussions about marijuana reform and the opioid epidemic.^{13, 14}

The support for policy changes in states that have legalized marijuana for medical use suggests it is gaining greater acceptance in our society. The increase in jurisdictions that have approved marijuana for medical use requires that we, as health care providers, understand the implications for our practice and educate ourselves on the laws and regulations in our respective states.

Recent guidelines from the National Council of State Boards of Nursing (NCSBN) identify six principles of essential knowledge for NPs (that could apply to PAs, as well) who care for patients who qualify to participate in a Medical Marijuana Program (MMP). These include principles of safe and knowledgeable practice for clinicians when qualifying a patient for an MMP.³ Note that I said qualifying a patient and not prescribing marijuana. Federal law still classifies cannabis as a Schedule I controlled substance, thus prohibiting the actual prescription of marijuana, and prohibits pharmacies from dispensing cannabis. Quite a contradiction!

All of that said, it is incumbent upon each of us to understand the complexities of the MMP in our state. Each has its own specifications as to the qualifying conditions or symptoms, as well as the requirements to become an approved provider. And each is as diverse as the opinions on marijuana use.

Without doubt, the debate and dichotomy about medical marijuana will ensue for years. What we as health care providers must do is keep current on the laws and regulations not only in our state, but also at the federal level. As a primer on the status of MMPs and provider approval, I encourage all to review the NCSBN document.³

As always, you can share your thoughts with me via NPeditor@mdedge.com.

In 1992, then-governor of Massachusetts William F. Weld signed a bill into law legalizing the use of marijuana for glaucoma, cancer therapy, and certain asthmatic disorders under a limited Department of Public Health (DPH) research program. In 1996, the legislature gave DPH the power to approve any Massachusetts patient to “possess and use pot” legally for relief of symptoms.¹ In my position as Health Policy Coordinator with DPH, those two acts were my introduction to the controversy of medical marijuana.

Since then, the popularity of—or rather, the shift in public sentiment regarding—marijuana (cannabis/cannabinoid) use has changed. There has been significant interest in the use of marijuana as an adjunct to treating chronic and/or debilitating medical conditions. There is also increasing interest in the potential therapeutic uses of marijuana and other cannabinoid compounds.

In recent years, we’ve seen significant momentum on this front. Point in fact, in fiscal year 2017, the National Institutes of Health supported projects on cannabinoid research totaling almost $140 million.² More than 30 US jurisdictions have passed legislation to legalize marijuana for medical use (while a few have legalized its use, period).³ All of which has prompted quite the debate not only among the public but also among health care providers.

A review of the history of cannabis use is very interesting—specifically, that the use of cannabis as a therapeutic modality predates recorded history. Cannabis was very popular in ancient China, India, and Greece as a medicine to alleviate pain or cure a variety of ailments.^4,5 In the early 1900s, cannabis was available OTC and commonly used for a variety of illnesses in the US. The first law regarding marijuana was enacted in 1619 at Jamestown Colony, Virginia; it “ordered” all farmers to grow Indian hempseed.⁶

But by 1906, cannabis was labeled as a poison in many states, and by the 1920s absolute prohibitions began. The Controlled Substances Act of 1970 outlawed cannabis for any use. Despite that ban, marijuana is the most common illegal drug used in the US today.⁷

Marijuana, not a completely benign substance, occupies a unique position in our society. On the one hand, it is a recreational compound, used to attain pleasant euphoria and a sense of relaxation. On the other, it has been used as a therapeutic compound, relieving nausea and anorexia from chemotherapy. In the former, it is viewed by many as a dangerous drug that can lead to madness (as depicted in the film Reefer Madness).⁸ In the latter, its use as an effective analgesic and appetite stimulant has been supported by people who have realized a therapeutic benefit.

The potential medicinal benefits of marijuana and its components have been the subject of research and ongoing heated debates. Decades of anecdotal evidence regarding the effectiveness of marijuana on the aforementioned symptoms have been documented. There are also numerous studies on marijuana as a therapeutic agent for multiple conditions, using the plant itself or extracts derived from it.^9-11

Continue to: Perhaps most interesting...

Perhaps most interesting, emerging data suggest that use and abuse of prescription drugs may be decreasing in states where medical cannabis is legal.¹² Two recent studies examining cannabis laws and prescription of opioids found that “medical cannabis laws are associated with significant reductions in opioid prescribing in the Medicare Part D population,” concluding that the potential for marijuana to decrease opioid use in the Medicaid population deserves consideration during policy discussions about marijuana reform and the opioid epidemic.^{13, 14}

The support for policy changes in states that have legalized marijuana for medical use suggests it is gaining greater acceptance in our society. The increase in jurisdictions that have approved marijuana for medical use requires that we, as health care providers, understand the implications for our practice and educate ourselves on the laws and regulations in our respective states.

Recent guidelines from the National Council of State Boards of Nursing (NCSBN) identify six principles of essential knowledge for NPs (that could apply to PAs, as well) who care for patients who qualify to participate in a Medical Marijuana Program (MMP). These include principles of safe and knowledgeable practice for clinicians when qualifying a patient for an MMP.³ Note that I said qualifying a patient and not prescribing marijuana. Federal law still classifies cannabis as a Schedule I controlled substance, thus prohibiting the actual prescription of marijuana, and prohibits pharmacies from dispensing cannabis. Quite a contradiction!

All of that said, it is incumbent upon each of us to understand the complexities of the MMP in our state. Each has its own specifications as to the qualifying conditions or symptoms, as well as the requirements to become an approved provider. And each is as diverse as the opinions on marijuana use.

Without doubt, the debate and dichotomy about medical marijuana will ensue for years. What we as health care providers must do is keep current on the laws and regulations not only in our state, but also at the federal level. As a primer on the status of MMPs and provider approval, I encourage all to review the NCSBN document.³

As always, you can share your thoughts with me via NPeditor@mdedge.com.

The FDA approves sufentanil for managing pain in patients who are in certified medical health care settings. Also today, Crohn’s disease is tied to anal canal high-risk HPV vaccination. Also today, ultrasound denervation tops radiofrequecy ablation for resistant hypertension, and primary care needs pile up for patients with sickle cell disease.

Amazon Alexa
Apple Podcasts
Spotify

The FDA approves sufentanil for managing pain in patients who are in certified medical health care settings. Also today, Crohn’s disease is tied to anal canal high-risk HPV vaccination. Also today, ultrasound denervation tops radiofrequecy ablation for resistant hypertension, and primary care needs pile up for patients with sickle cell disease.

Amazon Alexa
Apple Podcasts
Spotify

The FDA approves sufentanil for managing pain in patients who are in certified medical health care settings. Also today, Crohn’s disease is tied to anal canal high-risk HPV vaccination. Also today, ultrasound denervation tops radiofrequecy ablation for resistant hypertension, and primary care needs pile up for patients with sickle cell disease.

Amazon Alexa
Apple Podcasts
Spotify

BERLIN—The risk of cancer, and breast cancer in particular, was not elevated above background levels in a large cohort of patients with multiple sclerosis (MS) taking disease-modifying therapies, according to research presented at ECTRIMS 2018.

Those findings from the Nordic cohort study COMBAT-MS stand in contrast to previous work showing an elevated cancer risk for some monoclonal antibodies.

After statistical adjustment and use of rituximab as the standard, the hazard ratio (HR) for any malignancy with fingolimod was 1.74 (95% confidence interval [CI], 0.92–3.28). For natalizumab, the malignancy HR was 1.06 (95% CI, 0.53–2.10), said Peter Alping, a PhD student in the Department of Clinical Neuroscience at the Karolinska Institute in Stockholm.

Surveillance for Risk of Malignancy

Limited data exist for real-world MS cohorts exposed to novel disease-modifying therapies, said Mr. Alping. Rituximab has been studied in patients with rheumatoid arthritis, but the treatment regimens and patient characteristics differ in patients with MS, he noted. However, surveillance for risk of malignancy is important “since modern disease-modifying therapies exert a more profound effect on the immune system, and we know that the immune system is vital in fighting and preventing cancers,” he said.

The anti-CD20 monoclonal antibody ocrelizumab was studied in the ORATORIO trial. “There, they saw an imbalance in the numbers of breast cancers between the ocrelizumab and placebo groups,” said Mr. Alping. There were four breast cancers in the ocrelizumab population, which would translate to 26.1 cancers per 10,000 person-years, as opposed to the zero breast cancers in the placebo group. “To what degree is cancer risk a concern with novel [disease-modifying therapy] use in MS?” Mr. Alping asked.

To answer the question, he and his colleagues at the Karolinska Institute sought to compare the risk of cancer in patients with MS who were treated with rituximab, fingolimod, and natalizumab.

They conducted a nationwide cohort study using the Swedish MS registry. The researchers examined treatment episodes between 2011 and 2016. In Sweden, the MS registry is linked to the overall patient registry, as well as to registries for cancer and prescription drug use. In addition, patient data are linked to national census data.

Mr. Alping and his colleagues identified the first instance of use for an MS patient of rituximab, natalizumab, or fingolimod between 2011 and 2016. Then they matched patient records from the general population by age, sex, and geographic location to enroll matched controls at the same time point as the MS match entered the study.

Patients treated with mitoxantrone, those who emigrated, and those who died during the study period were excluded from the study.

The statistical analysis used an ever-treated approach and did not attempt to weight exposure duration or dose. However, statistical adjustments were made for patient and control demographics and medical history, history of cancer, and MS disease characteristics.

Comparing Incidence Rates

At baseline, 1,558 patients had been treated with fingolimod, 1,761 with natalizumab, and 3,012 with rituximab. Less than one-third of the patients (26.3%–31.6%) were male, and the mean age was 35–43. Most patients (66%–86%) had received one or two previous therapies. The mean Expanded Disability Status Scale (EDSS) score was 2.20–2.88. Less than 2% of patients (0.9%–1.7%) had a history of cancer.

Overall, the incidence of cancer in the MS cohort ranged from 23.09 per 10,000 person-years for rituximab ever-takers to 46.28 for those who had ever taken fingolimod. Among the general population, rates of any malignancy were 29.62 per 10,000 person-years.

Breast cancer rates in the MS cohort ranged from 2.19 to 2.92/10,000 person-years. For the general population, the rate was 12.07/10,000 person-years.

Using a Cox regression analysis employing MS-specific covariates and using rituximab as the reference, Mr. Alping and his colleagues calculated an inverse proportion-weighted HR for any malignancy under the various treatment conditions.

Among women taking rituximab, 2,274 therapy starts occurred, and one breast cancer was seen in 4,050 person-years. This yielded an incidence of 2.32 cancers per 10,000 person-years (95% CI, 0.06–12.9). This contrasts with the adjusted incidence rate in the general female population of 11.06 breast cancers per 10,000 person-years.

Looking at all the therapy episodes captured in the cohort study, there were 6,660 incidences of therapy initiation, and 52 malignancies were seen over 17,283 person-years, Mr. Alping said.

No Increased Risk When Compared With the General Population

“For malignant cancer of any type, we found no increased risk for rituximab, compared with fingolimod and natalizumab,” Mr. Alping said, noting the wide confidence intervals in the adjusted data. The incidence of breast cancer in women who have taken rituximab is “comparable to, or possibly lower than, that of the general female population, and lower than the incidence rate reported in the ORATORIO trial for ocrelizumab,” he said. “The overall cancer risk and risk of breast cancer might not be major concerns in the short term when treating MS patients with rituximab, relative to other disease-modifying therapies,” Mr. Alping concluded.

The study was partially funded by the Patient-Centered Outcomes Research Institute.

—Kari Oakes

BERLIN—The risk of cancer, and breast cancer in particular, was not elevated above background levels in a large cohort of patients with multiple sclerosis (MS) taking disease-modifying therapies, according to research presented at ECTRIMS 2018.

Those findings from the Nordic cohort study COMBAT-MS stand in contrast to previous work showing an elevated cancer risk for some monoclonal antibodies.

After statistical adjustment and use of rituximab as the standard, the hazard ratio (HR) for any malignancy with fingolimod was 1.74 (95% confidence interval [CI], 0.92–3.28). For natalizumab, the malignancy HR was 1.06 (95% CI, 0.53–2.10), said Peter Alping, a PhD student in the Department of Clinical Neuroscience at the Karolinska Institute in Stockholm.

Surveillance for Risk of Malignancy

Limited data exist for real-world MS cohorts exposed to novel disease-modifying therapies, said Mr. Alping. Rituximab has been studied in patients with rheumatoid arthritis, but the treatment regimens and patient characteristics differ in patients with MS, he noted. However, surveillance for risk of malignancy is important “since modern disease-modifying therapies exert a more profound effect on the immune system, and we know that the immune system is vital in fighting and preventing cancers,” he said.

The anti-CD20 monoclonal antibody ocrelizumab was studied in the ORATORIO trial. “There, they saw an imbalance in the numbers of breast cancers between the ocrelizumab and placebo groups,” said Mr. Alping. There were four breast cancers in the ocrelizumab population, which would translate to 26.1 cancers per 10,000 person-years, as opposed to the zero breast cancers in the placebo group. “To what degree is cancer risk a concern with novel [disease-modifying therapy] use in MS?” Mr. Alping asked.

To answer the question, he and his colleagues at the Karolinska Institute sought to compare the risk of cancer in patients with MS who were treated with rituximab, fingolimod, and natalizumab.

They conducted a nationwide cohort study using the Swedish MS registry. The researchers examined treatment episodes between 2011 and 2016. In Sweden, the MS registry is linked to the overall patient registry, as well as to registries for cancer and prescription drug use. In addition, patient data are linked to national census data.

Mr. Alping and his colleagues identified the first instance of use for an MS patient of rituximab, natalizumab, or fingolimod between 2011 and 2016. Then they matched patient records from the general population by age, sex, and geographic location to enroll matched controls at the same time point as the MS match entered the study.

Patients treated with mitoxantrone, those who emigrated, and those who died during the study period were excluded from the study.

The statistical analysis used an ever-treated approach and did not attempt to weight exposure duration or dose. However, statistical adjustments were made for patient and control demographics and medical history, history of cancer, and MS disease characteristics.

Comparing Incidence Rates

At baseline, 1,558 patients had been treated with fingolimod, 1,761 with natalizumab, and 3,012 with rituximab. Less than one-third of the patients (26.3%–31.6%) were male, and the mean age was 35–43. Most patients (66%–86%) had received one or two previous therapies. The mean Expanded Disability Status Scale (EDSS) score was 2.20–2.88. Less than 2% of patients (0.9%–1.7%) had a history of cancer.

Overall, the incidence of cancer in the MS cohort ranged from 23.09 per 10,000 person-years for rituximab ever-takers to 46.28 for those who had ever taken fingolimod. Among the general population, rates of any malignancy were 29.62 per 10,000 person-years.

Breast cancer rates in the MS cohort ranged from 2.19 to 2.92/10,000 person-years. For the general population, the rate was 12.07/10,000 person-years.

Using a Cox regression analysis employing MS-specific covariates and using rituximab as the reference, Mr. Alping and his colleagues calculated an inverse proportion-weighted HR for any malignancy under the various treatment conditions.

Among women taking rituximab, 2,274 therapy starts occurred, and one breast cancer was seen in 4,050 person-years. This yielded an incidence of 2.32 cancers per 10,000 person-years (95% CI, 0.06–12.9). This contrasts with the adjusted incidence rate in the general female population of 11.06 breast cancers per 10,000 person-years.

Looking at all the therapy episodes captured in the cohort study, there were 6,660 incidences of therapy initiation, and 52 malignancies were seen over 17,283 person-years, Mr. Alping said.

No Increased Risk When Compared With the General Population

“For malignant cancer of any type, we found no increased risk for rituximab, compared with fingolimod and natalizumab,” Mr. Alping said, noting the wide confidence intervals in the adjusted data. The incidence of breast cancer in women who have taken rituximab is “comparable to, or possibly lower than, that of the general female population, and lower than the incidence rate reported in the ORATORIO trial for ocrelizumab,” he said. “The overall cancer risk and risk of breast cancer might not be major concerns in the short term when treating MS patients with rituximab, relative to other disease-modifying therapies,” Mr. Alping concluded.

The study was partially funded by the Patient-Centered Outcomes Research Institute.

—Kari Oakes

BERLIN—The risk of cancer, and breast cancer in particular, was not elevated above background levels in a large cohort of patients with multiple sclerosis (MS) taking disease-modifying therapies, according to research presented at ECTRIMS 2018.

Those findings from the Nordic cohort study COMBAT-MS stand in contrast to previous work showing an elevated cancer risk for some monoclonal antibodies.

After statistical adjustment and use of rituximab as the standard, the hazard ratio (HR) for any malignancy with fingolimod was 1.74 (95% confidence interval [CI], 0.92–3.28). For natalizumab, the malignancy HR was 1.06 (95% CI, 0.53–2.10), said Peter Alping, a PhD student in the Department of Clinical Neuroscience at the Karolinska Institute in Stockholm.

Surveillance for Risk of Malignancy

Limited data exist for real-world MS cohorts exposed to novel disease-modifying therapies, said Mr. Alping. Rituximab has been studied in patients with rheumatoid arthritis, but the treatment regimens and patient characteristics differ in patients with MS, he noted. However, surveillance for risk of malignancy is important “since modern disease-modifying therapies exert a more profound effect on the immune system, and we know that the immune system is vital in fighting and preventing cancers,” he said.

The anti-CD20 monoclonal antibody ocrelizumab was studied in the ORATORIO trial. “There, they saw an imbalance in the numbers of breast cancers between the ocrelizumab and placebo groups,” said Mr. Alping. There were four breast cancers in the ocrelizumab population, which would translate to 26.1 cancers per 10,000 person-years, as opposed to the zero breast cancers in the placebo group. “To what degree is cancer risk a concern with novel [disease-modifying therapy] use in MS?” Mr. Alping asked.

To answer the question, he and his colleagues at the Karolinska Institute sought to compare the risk of cancer in patients with MS who were treated with rituximab, fingolimod, and natalizumab.

They conducted a nationwide cohort study using the Swedish MS registry. The researchers examined treatment episodes between 2011 and 2016. In Sweden, the MS registry is linked to the overall patient registry, as well as to registries for cancer and prescription drug use. In addition, patient data are linked to national census data.

Mr. Alping and his colleagues identified the first instance of use for an MS patient of rituximab, natalizumab, or fingolimod between 2011 and 2016. Then they matched patient records from the general population by age, sex, and geographic location to enroll matched controls at the same time point as the MS match entered the study.

Patients treated with mitoxantrone, those who emigrated, and those who died during the study period were excluded from the study.

The statistical analysis used an ever-treated approach and did not attempt to weight exposure duration or dose. However, statistical adjustments were made for patient and control demographics and medical history, history of cancer, and MS disease characteristics.

Comparing Incidence Rates

At baseline, 1,558 patients had been treated with fingolimod, 1,761 with natalizumab, and 3,012 with rituximab. Less than one-third of the patients (26.3%–31.6%) were male, and the mean age was 35–43. Most patients (66%–86%) had received one or two previous therapies. The mean Expanded Disability Status Scale (EDSS) score was 2.20–2.88. Less than 2% of patients (0.9%–1.7%) had a history of cancer.

Overall, the incidence of cancer in the MS cohort ranged from 23.09 per 10,000 person-years for rituximab ever-takers to 46.28 for those who had ever taken fingolimod. Among the general population, rates of any malignancy were 29.62 per 10,000 person-years.

Breast cancer rates in the MS cohort ranged from 2.19 to 2.92/10,000 person-years. For the general population, the rate was 12.07/10,000 person-years.

Using a Cox regression analysis employing MS-specific covariates and using rituximab as the reference, Mr. Alping and his colleagues calculated an inverse proportion-weighted HR for any malignancy under the various treatment conditions.

Among women taking rituximab, 2,274 therapy starts occurred, and one breast cancer was seen in 4,050 person-years. This yielded an incidence of 2.32 cancers per 10,000 person-years (95% CI, 0.06–12.9). This contrasts with the adjusted incidence rate in the general female population of 11.06 breast cancers per 10,000 person-years.

Looking at all the therapy episodes captured in the cohort study, there were 6,660 incidences of therapy initiation, and 52 malignancies were seen over 17,283 person-years, Mr. Alping said.

No Increased Risk When Compared With the General Population

“For malignant cancer of any type, we found no increased risk for rituximab, compared with fingolimod and natalizumab,” Mr. Alping said, noting the wide confidence intervals in the adjusted data. The incidence of breast cancer in women who have taken rituximab is “comparable to, or possibly lower than, that of the general female population, and lower than the incidence rate reported in the ORATORIO trial for ocrelizumab,” he said. “The overall cancer risk and risk of breast cancer might not be major concerns in the short term when treating MS patients with rituximab, relative to other disease-modifying therapies,” Mr. Alping concluded.

The study was partially funded by the Patient-Centered Outcomes Research Institute.

—Kari Oakes

Photo by Bill Branson

Denosumab can be effective against osteoporosis caused by transfusion-dependent thalassemia (TDT), according to research published in Blood Advances.

Researchers found that patients who received twice-yearly injections of denosumab experienced a significant increase in bone density and reduction in bone pain.

“Not only is denosumab associated with improved bone health and reduced pain, but its ease of administration may very well make this drug superior to bisphosphonates for the treatment of osteoporosis in patients with TDT and osteoporosis,” said study author Evangelos Terpos, MD, of the National and Kapodistrian University of Athens in Greece.

For this phase 2b study, Dr. Terpos and his colleagues evaluated 63 patients with TDT and osteoporosis.

They were randomized (in a double-blinded fashion) to receive 60 mg of denosumab (n=32) or placebo (n=31) on days 0 and 180 of a 12-month period. Patients in both arms also received daily supplements of calcium and vitamin D.

Baseline characteristics were largely similar between the treatment arms.

However, the mean value of bone-specific alkaline phosphatase (bALP) was significantly lower in the placebo arm than the denosumab arm—68.48 IU/L and 85.45 IU/L, respectively (P=0.013).

And the mean value of the tartrate-resistant acid phosphatase isoform-5b (TRACP-5b) marker was significantly higher in the denosumab arm than in the placebo arm—0.42 IU/L and 0.16 IU/L, respectively (P=0.026).

Results

The researchers measured bone mineral density in the L1-L4 lumbar spine, the wrist, and the femoral neck.

At 12 months, the mean increase in L1-L4 bone mineral density was 5.92% in the denosumab arm and 2.92% in the placebo arm (P=0.043).

The mean decrease in wrist bone mineral density was -0.26% and -3.92%, respectively (P=0.035).

And the mean increase in femoral neck bone mineral density was 4.08% and 1.96%, respectively (P=0.870).

Patients in the denosumab arm had a significant reduction in bone pain at 12 months, according to the McGill-Melzack scoring system and Huskisson’s visual analog scale (P<0.001 for both).

However, there was no significant change in pain for patients in the placebo arm (P=0.356 with Huskisson’s and P=0.768 with McGill-Melzack).

At 12 months, patients in the denosumab arm had experienced a significant reduction from baseline (P<0.001 for all) in several markers of bone remodeling, including:

• Soluble receptor activator of nuclear factor kappa-B ligand (sRANKL)
• Osteoprotegerin (OPG)
• sRANKL/OPG ratio
• C-terminal crosslinking telopeptide of type I collagen (CTX)
• TRACP-5b
• bALP.

There were no significant changes in dickkopf-1 (Dkk-1), sclerostin, or osteocalcin (OC) in the denosumab arm.

In the placebo arm, patients had a significant increase from baseline in several markers of bone remodeling, including sRANKL, OPG, Dkk-1, sclerostin, CTX, TRACP-5b, and bALP (P<0.001 for all). There was no significant change from baseline in the sRANKL/OPG ratio or OC.

In all, there were 17 adverse events (AEs) in 14 patients.

There were three grade 1 AEs in the placebo arm and 11 in the denosumab arm. Most grade 1 AEs in the denosumab arm were test abnormalities, although three were not—headache, diarrhea, and fever.

There were three serious AEs in the denosumab arm as well—pleural effusion (grade 3), atrial fibrillation (grade 3), and supraventricular tachycardia (grade 4). All three of these AEs were considered unrelated to denosumab.

This study was funded by Amgen, which markets denosumab as Xgeva. The authors said they had no competing financial interests.

Photo by Bill Branson

Denosumab can be effective against osteoporosis caused by transfusion-dependent thalassemia (TDT), according to research published in Blood Advances.

Researchers found that patients who received twice-yearly injections of denosumab experienced a significant increase in bone density and reduction in bone pain.

“Not only is denosumab associated with improved bone health and reduced pain, but its ease of administration may very well make this drug superior to bisphosphonates for the treatment of osteoporosis in patients with TDT and osteoporosis,” said study author Evangelos Terpos, MD, of the National and Kapodistrian University of Athens in Greece.

For this phase 2b study, Dr. Terpos and his colleagues evaluated 63 patients with TDT and osteoporosis.

They were randomized (in a double-blinded fashion) to receive 60 mg of denosumab (n=32) or placebo (n=31) on days 0 and 180 of a 12-month period. Patients in both arms also received daily supplements of calcium and vitamin D.

Baseline characteristics were largely similar between the treatment arms.

However, the mean value of bone-specific alkaline phosphatase (bALP) was significantly lower in the placebo arm than the denosumab arm—68.48 IU/L and 85.45 IU/L, respectively (P=0.013).

And the mean value of the tartrate-resistant acid phosphatase isoform-5b (TRACP-5b) marker was significantly higher in the denosumab arm than in the placebo arm—0.42 IU/L and 0.16 IU/L, respectively (P=0.026).

Results

The researchers measured bone mineral density in the L1-L4 lumbar spine, the wrist, and the femoral neck.

At 12 months, the mean increase in L1-L4 bone mineral density was 5.92% in the denosumab arm and 2.92% in the placebo arm (P=0.043).

The mean decrease in wrist bone mineral density was -0.26% and -3.92%, respectively (P=0.035).

And the mean increase in femoral neck bone mineral density was 4.08% and 1.96%, respectively (P=0.870).

Patients in the denosumab arm had a significant reduction in bone pain at 12 months, according to the McGill-Melzack scoring system and Huskisson’s visual analog scale (P<0.001 for both).

However, there was no significant change in pain for patients in the placebo arm (P=0.356 with Huskisson’s and P=0.768 with McGill-Melzack).

At 12 months, patients in the denosumab arm had experienced a significant reduction from baseline (P<0.001 for all) in several markers of bone remodeling, including:

• Soluble receptor activator of nuclear factor kappa-B ligand (sRANKL)
• Osteoprotegerin (OPG)
• sRANKL/OPG ratio
• C-terminal crosslinking telopeptide of type I collagen (CTX)
• TRACP-5b
• bALP.

There were no significant changes in dickkopf-1 (Dkk-1), sclerostin, or osteocalcin (OC) in the denosumab arm.

In the placebo arm, patients had a significant increase from baseline in several markers of bone remodeling, including sRANKL, OPG, Dkk-1, sclerostin, CTX, TRACP-5b, and bALP (P<0.001 for all). There was no significant change from baseline in the sRANKL/OPG ratio or OC.

In all, there were 17 adverse events (AEs) in 14 patients.

There were three grade 1 AEs in the placebo arm and 11 in the denosumab arm. Most grade 1 AEs in the denosumab arm were test abnormalities, although three were not—headache, diarrhea, and fever.

There were three serious AEs in the denosumab arm as well—pleural effusion (grade 3), atrial fibrillation (grade 3), and supraventricular tachycardia (grade 4). All three of these AEs were considered unrelated to denosumab.

This study was funded by Amgen, which markets denosumab as Xgeva. The authors said they had no competing financial interests.

Photo by Bill Branson

Denosumab can be effective against osteoporosis caused by transfusion-dependent thalassemia (TDT), according to research published in Blood Advances.

Researchers found that patients who received twice-yearly injections of denosumab experienced a significant increase in bone density and reduction in bone pain.

“Not only is denosumab associated with improved bone health and reduced pain, but its ease of administration may very well make this drug superior to bisphosphonates for the treatment of osteoporosis in patients with TDT and osteoporosis,” said study author Evangelos Terpos, MD, of the National and Kapodistrian University of Athens in Greece.

For this phase 2b study, Dr. Terpos and his colleagues evaluated 63 patients with TDT and osteoporosis.

They were randomized (in a double-blinded fashion) to receive 60 mg of denosumab (n=32) or placebo (n=31) on days 0 and 180 of a 12-month period. Patients in both arms also received daily supplements of calcium and vitamin D.

Baseline characteristics were largely similar between the treatment arms.

However, the mean value of bone-specific alkaline phosphatase (bALP) was significantly lower in the placebo arm than the denosumab arm—68.48 IU/L and 85.45 IU/L, respectively (P=0.013).

And the mean value of the tartrate-resistant acid phosphatase isoform-5b (TRACP-5b) marker was significantly higher in the denosumab arm than in the placebo arm—0.42 IU/L and 0.16 IU/L, respectively (P=0.026).

Results

The researchers measured bone mineral density in the L1-L4 lumbar spine, the wrist, and the femoral neck.

At 12 months, the mean increase in L1-L4 bone mineral density was 5.92% in the denosumab arm and 2.92% in the placebo arm (P=0.043).

The mean decrease in wrist bone mineral density was -0.26% and -3.92%, respectively (P=0.035).

And the mean increase in femoral neck bone mineral density was 4.08% and 1.96%, respectively (P=0.870).

Patients in the denosumab arm had a significant reduction in bone pain at 12 months, according to the McGill-Melzack scoring system and Huskisson’s visual analog scale (P<0.001 for both).

However, there was no significant change in pain for patients in the placebo arm (P=0.356 with Huskisson’s and P=0.768 with McGill-Melzack).

At 12 months, patients in the denosumab arm had experienced a significant reduction from baseline (P<0.001 for all) in several markers of bone remodeling, including:

• Soluble receptor activator of nuclear factor kappa-B ligand (sRANKL)
• Osteoprotegerin (OPG)
• sRANKL/OPG ratio
• C-terminal crosslinking telopeptide of type I collagen (CTX)
• TRACP-5b
• bALP.

There were no significant changes in dickkopf-1 (Dkk-1), sclerostin, or osteocalcin (OC) in the denosumab arm.

In the placebo arm, patients had a significant increase from baseline in several markers of bone remodeling, including sRANKL, OPG, Dkk-1, sclerostin, CTX, TRACP-5b, and bALP (P<0.001 for all). There was no significant change from baseline in the sRANKL/OPG ratio or OC.

In all, there were 17 adverse events (AEs) in 14 patients.

There were three grade 1 AEs in the placebo arm and 11 in the denosumab arm. Most grade 1 AEs in the denosumab arm were test abnormalities, although three were not—headache, diarrhea, and fever.

There were three serious AEs in the denosumab arm as well—pleural effusion (grade 3), atrial fibrillation (grade 3), and supraventricular tachycardia (grade 4). All three of these AEs were considered unrelated to denosumab.

This study was funded by Amgen, which markets denosumab as Xgeva. The authors said they had no competing financial interests.

Photo by Rhoda Baer

The U.S. Food and Drug Administration (FDA) and European Commission (EC) have approved Coherus BioSciences, Inc.’s pegfilgrastim-cbqv (Udenyca™), a biosimilar of Amgen’s pegfilgrastim product (Neulasta).

Both agencies approved pegfilgrastim-cbqv (formerly CHS-1701) for cancer patients receiving myelosuppressive chemotherapy.

Pegfilgrastim-cbqv is FDA-approved “to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.”

The product is EC-approved to reduce “the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).”

The U.S. prescribing information for pegfilgrastim-cbqv is available at www.UDENYCA.com, and the European summary of product characteristics is available on the European Medicines Agency’s website.

The FDA and EC approvals of pegfilgrastim-cbqv were supported by analyses establishing biosimilarity as well as pharmacokinetic, pharmacodynamic, and immunogenicity studies of healthy subjects (NCT02650973, NCT02385851, and NCT02418104).

Results from one of these studies (NCT02650973) were presented at the 2017 ASCO Annual Meeting.

“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” said Barbara Finck, MD, chief medical officer of Coherus BioSciences.

“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”

Photo by Rhoda Baer

The U.S. Food and Drug Administration (FDA) and European Commission (EC) have approved Coherus BioSciences, Inc.’s pegfilgrastim-cbqv (Udenyca™), a biosimilar of Amgen’s pegfilgrastim product (Neulasta).

Both agencies approved pegfilgrastim-cbqv (formerly CHS-1701) for cancer patients receiving myelosuppressive chemotherapy.

Pegfilgrastim-cbqv is FDA-approved “to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.”

The product is EC-approved to reduce “the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).”

The U.S. prescribing information for pegfilgrastim-cbqv is available at www.UDENYCA.com, and the European summary of product characteristics is available on the European Medicines Agency’s website.

The FDA and EC approvals of pegfilgrastim-cbqv were supported by analyses establishing biosimilarity as well as pharmacokinetic, pharmacodynamic, and immunogenicity studies of healthy subjects (NCT02650973, NCT02385851, and NCT02418104).

Results from one of these studies (NCT02650973) were presented at the 2017 ASCO Annual Meeting.

“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” said Barbara Finck, MD, chief medical officer of Coherus BioSciences.

“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”

Photo by Rhoda Baer

The U.S. Food and Drug Administration (FDA) and European Commission (EC) have approved Coherus BioSciences, Inc.’s pegfilgrastim-cbqv (Udenyca™), a biosimilar of Amgen’s pegfilgrastim product (Neulasta).

Both agencies approved pegfilgrastim-cbqv (formerly CHS-1701) for cancer patients receiving myelosuppressive chemotherapy.

Pegfilgrastim-cbqv is FDA-approved “to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.”

The product is EC-approved to reduce “the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).”

The U.S. prescribing information for pegfilgrastim-cbqv is available at www.UDENYCA.com, and the European summary of product characteristics is available on the European Medicines Agency’s website.

The FDA and EC approvals of pegfilgrastim-cbqv were supported by analyses establishing biosimilarity as well as pharmacokinetic, pharmacodynamic, and immunogenicity studies of healthy subjects (NCT02650973, NCT02385851, and NCT02418104).

Results from one of these studies (NCT02650973) were presented at the 2017 ASCO Annual Meeting.

“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” said Barbara Finck, MD, chief medical officer of Coherus BioSciences.

“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”

MUNICH – Getting less than 6 hours of sleep nightly on a regular basis or waking up multiple times was independently associated with increased risk of subclinical atherosclerosis in the Spanish PESA study, Fernando Dominguez, MD, reported at the annual congress of the European Society of Cardiology.

Moreover, a graded response was evident in PESA (Progression of Early Subclinical Atherosclerosis): The more times an individual typically awoke per night, the greater the number of atherosclerotic carotid or femoral artery territories documented on three-dimensional vascular ultrasound, added Dr. Dominguez of the Spanish National Center for Cardiovascular Research in Madrid.

“These findings show that sleep is associated with cardiovascular health and suggest that the modification of abnormal sleep patterns may contribute to the reduction of burden of cardiovascular diseases,” the cardiologist said.

The cross-sectional PESA study, whose principal investigator was Valentin Fuster, MD, PhD, included 3,974 middle-aged Madrid bank employees free of known heart disease or history of stroke who wore a waistband activity monitor for a week to record sleep quantity and quality. They also underwent three-dimensional vascular ultrasound and measurement of coronary artery calcium.

PESA was one of several large studies presented at the meeting that focused on deviations from normal sleep as a marker for increased risk of cardiovascular disease and/or mortality. Of note, however, PESA was the only one to use activity monitoring technology to track sleep.

“It was essential to use objectively measured sleep variables, because they showed huge disparity with patients’ self-reports on sleep questionnaires,” Dr. Dominguez explained.

Indeed, while 10.7% of PESA participants self-reported sleeping less than 6 hours per night on the Sleep Habits Questionnaire, actigraphy showed the true rate was 27.1%.

Based on actigraphic findings, subjects were divided into tertiles based upon average hours of sleep per night, ranging from less than 6 to more than 8. They were also grouped in quintiles based upon their extent of fragmented sleep.

Subjects with short sleep were significantly older and more likely to have high blood pressure, a higher body mass index, and metabolic syndrome than those who averaged 7-8 hours of sleep. Individuals in the top quintile for sleep awakening were older and had higher prevalences of smoking and hypertension than those in the lowest quintile.

In multivariate analyses adjusted for these differences as well as for physical activity, depression, obstructive sleep apnea, daily calorie consumption, alcohol intake, and other potential confounders, subjects who slept less than 6 hours per night had a 27% greater volume of noncoronary plaque than those who slept 7-8 hours. They also had 21% more vascular territories laden with subclinical atherosclerosis. The risk of subclinical noncoronary atherosclerosis was greater among women who averaged less than 6 hours of sleep per night, representing a 48% relative risk increase in plaque volume, versus 21% in men.

At the other extreme, women who slept more than 8 hours per night had an 83% increased plaque volume, while men who slept that much had no increase in risk, compared with men who slept for 7-8 hours.

Subjects in the top quintile for sleep fragmentation had 34% more vascular territories affected by atherosclerosis than those in the lowest quintile. Their noncoronary plaque burden was 23% greater as well.
 

An 11-study meta-analysis

Epameinondas Fountas, MD, of the Onassis Cardiac Surgery Center in Athens, presented a meta-analysis of 11 prospective studies of the relationship between daily sleep duration and cardiovascular disease morbidity and mortality published within the past 5 years, reflecting burgeoning interest in this hot-button topic. Collectively, the meta-analysis totaled 1,000,541 adults without baseline cardiovascular disease who were followed for an average of 9.3 years.

Swedes weigh in

Moa Bengtsson, a combined medical/PhD student at the University of Gothenburg (Sweden), presented a prospective study of 798 men who were 50 years old in 1993, when they underwent a physical examination and completed extensive lifestyle questionnaires that included average self-reported sleep duration. Among the 759 men still available for evaluation after 21 years, or nearly 15,000 person-years of followup, those who reported sleeping an average of 5 hours or less per night back at age 50 were 93% more likely to have experienced a major cardiovascular event by age 71 -- acute MI, stroke, coronary revascularization, heart failure hospitalization, or cardiovascular death -- compared with those who averaged 7-8 hours of shut eye.

bjancin@mdedge.com

MUNICH – Getting less than 6 hours of sleep nightly on a regular basis or waking up multiple times was independently associated with increased risk of subclinical atherosclerosis in the Spanish PESA study, Fernando Dominguez, MD, reported at the annual congress of the European Society of Cardiology.

Moreover, a graded response was evident in PESA (Progression of Early Subclinical Atherosclerosis): The more times an individual typically awoke per night, the greater the number of atherosclerotic carotid or femoral artery territories documented on three-dimensional vascular ultrasound, added Dr. Dominguez of the Spanish National Center for Cardiovascular Research in Madrid.

“These findings show that sleep is associated with cardiovascular health and suggest that the modification of abnormal sleep patterns may contribute to the reduction of burden of cardiovascular diseases,” the cardiologist said.

The cross-sectional PESA study, whose principal investigator was Valentin Fuster, MD, PhD, included 3,974 middle-aged Madrid bank employees free of known heart disease or history of stroke who wore a waistband activity monitor for a week to record sleep quantity and quality. They also underwent three-dimensional vascular ultrasound and measurement of coronary artery calcium.

PESA was one of several large studies presented at the meeting that focused on deviations from normal sleep as a marker for increased risk of cardiovascular disease and/or mortality. Of note, however, PESA was the only one to use activity monitoring technology to track sleep.

“It was essential to use objectively measured sleep variables, because they showed huge disparity with patients’ self-reports on sleep questionnaires,” Dr. Dominguez explained.

Indeed, while 10.7% of PESA participants self-reported sleeping less than 6 hours per night on the Sleep Habits Questionnaire, actigraphy showed the true rate was 27.1%.

Based on actigraphic findings, subjects were divided into tertiles based upon average hours of sleep per night, ranging from less than 6 to more than 8. They were also grouped in quintiles based upon their extent of fragmented sleep.

Subjects with short sleep were significantly older and more likely to have high blood pressure, a higher body mass index, and metabolic syndrome than those who averaged 7-8 hours of sleep. Individuals in the top quintile for sleep awakening were older and had higher prevalences of smoking and hypertension than those in the lowest quintile.

In multivariate analyses adjusted for these differences as well as for physical activity, depression, obstructive sleep apnea, daily calorie consumption, alcohol intake, and other potential confounders, subjects who slept less than 6 hours per night had a 27% greater volume of noncoronary plaque than those who slept 7-8 hours. They also had 21% more vascular territories laden with subclinical atherosclerosis. The risk of subclinical noncoronary atherosclerosis was greater among women who averaged less than 6 hours of sleep per night, representing a 48% relative risk increase in plaque volume, versus 21% in men.

At the other extreme, women who slept more than 8 hours per night had an 83% increased plaque volume, while men who slept that much had no increase in risk, compared with men who slept for 7-8 hours.

Subjects in the top quintile for sleep fragmentation had 34% more vascular territories affected by atherosclerosis than those in the lowest quintile. Their noncoronary plaque burden was 23% greater as well.
 

An 11-study meta-analysis

Epameinondas Fountas, MD, of the Onassis Cardiac Surgery Center in Athens, presented a meta-analysis of 11 prospective studies of the relationship between daily sleep duration and cardiovascular disease morbidity and mortality published within the past 5 years, reflecting burgeoning interest in this hot-button topic. Collectively, the meta-analysis totaled 1,000,541 adults without baseline cardiovascular disease who were followed for an average of 9.3 years.

Swedes weigh in

Moa Bengtsson, a combined medical/PhD student at the University of Gothenburg (Sweden), presented a prospective study of 798 men who were 50 years old in 1993, when they underwent a physical examination and completed extensive lifestyle questionnaires that included average self-reported sleep duration. Among the 759 men still available for evaluation after 21 years, or nearly 15,000 person-years of followup, those who reported sleeping an average of 5 hours or less per night back at age 50 were 93% more likely to have experienced a major cardiovascular event by age 71 -- acute MI, stroke, coronary revascularization, heart failure hospitalization, or cardiovascular death -- compared with those who averaged 7-8 hours of shut eye.

bjancin@mdedge.com

MUNICH – Getting less than 6 hours of sleep nightly on a regular basis or waking up multiple times was independently associated with increased risk of subclinical atherosclerosis in the Spanish PESA study, Fernando Dominguez, MD, reported at the annual congress of the European Society of Cardiology.

Moreover, a graded response was evident in PESA (Progression of Early Subclinical Atherosclerosis): The more times an individual typically awoke per night, the greater the number of atherosclerotic carotid or femoral artery territories documented on three-dimensional vascular ultrasound, added Dr. Dominguez of the Spanish National Center for Cardiovascular Research in Madrid.

“These findings show that sleep is associated with cardiovascular health and suggest that the modification of abnormal sleep patterns may contribute to the reduction of burden of cardiovascular diseases,” the cardiologist said.

The cross-sectional PESA study, whose principal investigator was Valentin Fuster, MD, PhD, included 3,974 middle-aged Madrid bank employees free of known heart disease or history of stroke who wore a waistband activity monitor for a week to record sleep quantity and quality. They also underwent three-dimensional vascular ultrasound and measurement of coronary artery calcium.

PESA was one of several large studies presented at the meeting that focused on deviations from normal sleep as a marker for increased risk of cardiovascular disease and/or mortality. Of note, however, PESA was the only one to use activity monitoring technology to track sleep.

“It was essential to use objectively measured sleep variables, because they showed huge disparity with patients’ self-reports on sleep questionnaires,” Dr. Dominguez explained.

Indeed, while 10.7% of PESA participants self-reported sleeping less than 6 hours per night on the Sleep Habits Questionnaire, actigraphy showed the true rate was 27.1%.

Based on actigraphic findings, subjects were divided into tertiles based upon average hours of sleep per night, ranging from less than 6 to more than 8. They were also grouped in quintiles based upon their extent of fragmented sleep.

Subjects with short sleep were significantly older and more likely to have high blood pressure, a higher body mass index, and metabolic syndrome than those who averaged 7-8 hours of sleep. Individuals in the top quintile for sleep awakening were older and had higher prevalences of smoking and hypertension than those in the lowest quintile.

In multivariate analyses adjusted for these differences as well as for physical activity, depression, obstructive sleep apnea, daily calorie consumption, alcohol intake, and other potential confounders, subjects who slept less than 6 hours per night had a 27% greater volume of noncoronary plaque than those who slept 7-8 hours. They also had 21% more vascular territories laden with subclinical atherosclerosis. The risk of subclinical noncoronary atherosclerosis was greater among women who averaged less than 6 hours of sleep per night, representing a 48% relative risk increase in plaque volume, versus 21% in men.

At the other extreme, women who slept more than 8 hours per night had an 83% increased plaque volume, while men who slept that much had no increase in risk, compared with men who slept for 7-8 hours.

Subjects in the top quintile for sleep fragmentation had 34% more vascular territories affected by atherosclerosis than those in the lowest quintile. Their noncoronary plaque burden was 23% greater as well.
 

An 11-study meta-analysis

Epameinondas Fountas, MD, of the Onassis Cardiac Surgery Center in Athens, presented a meta-analysis of 11 prospective studies of the relationship between daily sleep duration and cardiovascular disease morbidity and mortality published within the past 5 years, reflecting burgeoning interest in this hot-button topic. Collectively, the meta-analysis totaled 1,000,541 adults without baseline cardiovascular disease who were followed for an average of 9.3 years.

Swedes weigh in

Moa Bengtsson, a combined medical/PhD student at the University of Gothenburg (Sweden), presented a prospective study of 798 men who were 50 years old in 1993, when they underwent a physical examination and completed extensive lifestyle questionnaires that included average self-reported sleep duration. Among the 759 men still available for evaluation after 21 years, or nearly 15,000 person-years of followup, those who reported sleeping an average of 5 hours or less per night back at age 50 were 93% more likely to have experienced a major cardiovascular event by age 71 -- acute MI, stroke, coronary revascularization, heart failure hospitalization, or cardiovascular death -- compared with those who averaged 7-8 hours of shut eye.

bjancin@mdedge.com