Palliative care is specialized medical care focused on providing relief from the symptoms, pain, and stress of a serious illness. The goal is to improve the quality of life for both the patient and the family. In all settings, palliative care has been found to improve patients’ quality of life,^1,2 improve family satisfaction and well-being,³ reduce resource utilization and costs,⁴ and, in some studies, increase the length of life for seriously ill patients.⁵

Given the frequency with which seriously ill patients are hospitalized, hospitalists are well positioned to identify those who could benefit from palliative care interventions.⁶ Hospitalists routinely use primary palliative care skills, including pain and symptom management and skilled care planning conversations. For complex cases, such as patients with intractable symptoms or major family conflict, hospitalists may refer to specialist palliative care teams for consultation.

The Society of Hospital Medicine (SHM) defines the key primary palliative care responsibilities for hospitalists as (1) leading discussions on the goals of care and advance care planning with patients and families, (2) screening and treating common physical symptoms, and (3) referring patients to community services to provide support postdischarge.⁷ According to data in the National Palliative Care Registry,⁸ 48% of all palliative care referrals in 2015 came from hospitalists, which is more than double the percentage of referrals from any other specialty.⁹

In a recent survey conducted by SHM about serious illness communication, 53% of hospitalists reported concerns about a patient or family’s understanding of their prognosis, and 50% indicated that they do not feel confident managing family conflict.¹⁰

Context

Patients with multiple serious chronic conditions are often forced to rely on emergency services when crises, such as uncontrolled pain or dyspnea exacerbation, occur after hours, resulting in the revolving-door hospitalizations that typically characterize their care.¹¹ As the prevalence of serious illness rises and the shift to value-based payment accelerates, hospitals are under increasing pressure to deliver efficient and high-quality services that meet the needs of seriously ill patients. The integration of standardized palliative care screening and assessment enables hospitalists and other providers to identify high-need individuals and match services and delivery models to needs, whether it be respite care for an exhausted and overwhelmed family caregiver or a home protocol for managing recurrent dyspnea crises for a patient with chronic obstructive pulmonary disease (COPD). This process improves the quality of care and quality of life, and in doing so, prevents the need for costly crisis care.

Reducing Readmissions

By identifying patients in need of extra symptom management support, or those at a turning point requiring discussion about achievable priorities for care, hospitalists can avert crises for patients earlier in the disease trajectory either by managing the patient’s palliative needs themselves or by connecting patients with specialty palliative care services as needed. This leads to a better quality of life (and survival in some studies) for both patients and their families^1,3,5 and reduces unnecessary emergency department (ED) and hospital use.¹² Hospitalists providing palliative care can also reduce readmissions by improving care coordination, including clinical communication and medication reconciliation after discharge.¹³

A 2015 Harvard Business Review study found that the quality of communication in the hospital is the strongest independent predictor of readmissions when combined with process-of-care improvements, such as standardized patient screening and assessment of family caregiver capacity.¹⁴ While medical education prepares physicians to deliver evidence-based medical care, it currently offers little to no training in communication skills, despite mounting evidence that this is a critical component of quality healthcare.

Cost Savings

Hospital palliative care teams are associated with significant hospital cost savings that result from aligning care with patient priorities, leading, in turn, to reduced nonbeneficial hospital imaging, medications, procedures, and length of stay.¹⁵ See the table^16,17 for examples of cost and quality outcomes of specialist palliative care provision and evidence supporting each outcome.^18-25

Multiple studies consistently demonstrate that inpatient palliative care teams reduce hospital costs.²⁶ One randomized controlled trial investigating the impact of an inpatient palliative care service found that patients who received care from the palliative care team reported greater satisfaction with their care, had fewer intensive care unit admissions, had more advanced directives at hospital discharge, longer hospice length of stay, and lower total healthcare costs (a net difference of $6766 per patient).²³

Research shows that the earlier palliative care is provided, the greater the impact on the subsequent course of care,²⁷ suggesting that hospitalists who provide frontline palliative care interventions as early as possible in a seriously ill patient’s stay will be able to provide higher quality care with lower overall costs. Notably, the majority of research on cost savings associated with palliative care has focused on the impact of specialist palliative care teams, and further research is needed to understand the economic impact of primary palliative care provision.

Improving Satisfaction

Shifting to value-based payment means that the patient and family experience determine an increasingly large percentage of hospital and provider reimbursement. Palliative care approaches, such as family caregiver assessment and support, access to 24/7 assistance after discharge, and person-centered care by an interdisciplinary team, improve performance in all of these measures. Communication skills training improves patient satisfaction scores, and skilled discussions about achievable priorities for care are associated with better quality of life, reduced nonbeneficial and burdensome treatments, and an increase in goal-concordant care.¹⁹ Communication skills training has also been shown to reduce burnout and improve empathy among physicians.^28,29

Though more evidence is needed to understand the impact of primary palliative care provision by hospitalists, the strong evidence on the benefits of specialty palliative care suggests that the skilled provision of primary palliative care by hospitalists will result in higher quality, higher value care. A number of training options exist for midcareer hospital medicine clinicians, including both in-person and online training in communication and other palliative care skills.

• The Center to Advance Palliative Care (CAPC) is a membership organization that offers online continuing education unit and continuing medical education courses on communication skills, pain and symptom management, caregiver support, and care coordination. CAPC also offers courses on palliative interventions for patients with dementia, COPD, and heart failure.
• SHM is actively invested in engaging hospitalists in palliative care skills training. SHM provides free toolkits on a variety of topics within the palliative care domain, including pain management, postacute care transitions, and opioid safety. The recently released Serious Illness Communication toolkit offers background on the role of hospitalists in palliative care provision, a pathway for fitting goals-of-care conversations into hospitalist workflow and recommended metrics and training resources. SHM also uses a mentored implementation model in which expert physicians mentor hospital team members on best practices in palliative care. SHM’s Palliative Care Task Force seeks to identify educational activities for hospitalists and create opportunities to integrate palliative care in hospital medicine.³⁰
• The Serious Illness Care Program at Ariadne Labs in Boston aims to facilitate conversations between clinicians and seriously ill patients through its Serious Illness Conversation Guide, combined with technical assistance on workflow redesign to help clinicians conduct and document serious illness conversations.
• VitalTalk specializes in clinical communication education. Through online and in-person train-the-trainer programs, VitalTalk equips clinicians to lead communication training programs at their home institutions.
• The Education in Palliative and End-of-Life Care Program and End-of-Life Nursing Education Consortium (ELNEC) uses a train-the-trainer approach to educate providers in palliative care clinical competencies and increase the reach of primary palliative care provision. ELNEC workshops are complemented by a curriculum of online clinical training modules.

Though palliative care skills training is a necessary first step, hospitalists also cite lack of time, difficulty finding records of previous patient discussions, and frequent handoffs as among the barriers to integrating palliative care into their practice.¹⁰ Studies examining the process of palliative care and hospital culture change have found that barriers to palliative care integration include a culture of aggressive care in EDs, lack of standardized patient identification criteria, and limited knowledge about and staffing for palliative care.³¹ These data indicate the need for system changes that enable hospitalists to operationalize palliative care principles.

Health systems must implement systems and processes that routinize palliative care, making it part of the mainstream course of care for seriously ill patients and their caregivers. This includes developing systems for the identification of patients with palliative care needs, embedding palliative care assessment and referral into clinical workflows, and enabling standardized palliative care documentation in electronic medical records. While palliative care skills training is essential, investment in systems change is no less critical to embedding palliative care practices in clinical norms across specialties.

Hospitalists can use a palliative approach to improve care quality and quality of life for seriously ill patients while helping to avoid preventable and unnecessary 911 calls, ED visits, and hospitalizations. The shift towards value-based payment is a strong incentive for hospitals and hospitalists to direct resources toward practices that improve the quality of life and care for the highest-need patients and their families. When equipped with the tools they need to provide palliative care, either themselves or in collaboration with palliative care teams, hospitalists have the opportunity to profoundly redirect the experience of care for seriously ill patients and their families.

Disclosure

The authors declared no conflicts of interest.

Palliative care is specialized medical care focused on providing relief from the symptoms, pain, and stress of a serious illness. The goal is to improve the quality of life for both the patient and the family. In all settings, palliative care has been found to improve patients’ quality of life,^1,2 improve family satisfaction and well-being,³ reduce resource utilization and costs,⁴ and, in some studies, increase the length of life for seriously ill patients.⁵

Given the frequency with which seriously ill patients are hospitalized, hospitalists are well positioned to identify those who could benefit from palliative care interventions.⁶ Hospitalists routinely use primary palliative care skills, including pain and symptom management and skilled care planning conversations. For complex cases, such as patients with intractable symptoms or major family conflict, hospitalists may refer to specialist palliative care teams for consultation.

The Society of Hospital Medicine (SHM) defines the key primary palliative care responsibilities for hospitalists as (1) leading discussions on the goals of care and advance care planning with patients and families, (2) screening and treating common physical symptoms, and (3) referring patients to community services to provide support postdischarge.⁷ According to data in the National Palliative Care Registry,⁸ 48% of all palliative care referrals in 2015 came from hospitalists, which is more than double the percentage of referrals from any other specialty.⁹

In a recent survey conducted by SHM about serious illness communication, 53% of hospitalists reported concerns about a patient or family’s understanding of their prognosis, and 50% indicated that they do not feel confident managing family conflict.¹⁰

Context

Patients with multiple serious chronic conditions are often forced to rely on emergency services when crises, such as uncontrolled pain or dyspnea exacerbation, occur after hours, resulting in the revolving-door hospitalizations that typically characterize their care.¹¹ As the prevalence of serious illness rises and the shift to value-based payment accelerates, hospitals are under increasing pressure to deliver efficient and high-quality services that meet the needs of seriously ill patients. The integration of standardized palliative care screening and assessment enables hospitalists and other providers to identify high-need individuals and match services and delivery models to needs, whether it be respite care for an exhausted and overwhelmed family caregiver or a home protocol for managing recurrent dyspnea crises for a patient with chronic obstructive pulmonary disease (COPD). This process improves the quality of care and quality of life, and in doing so, prevents the need for costly crisis care.

Reducing Readmissions

By identifying patients in need of extra symptom management support, or those at a turning point requiring discussion about achievable priorities for care, hospitalists can avert crises for patients earlier in the disease trajectory either by managing the patient’s palliative needs themselves or by connecting patients with specialty palliative care services as needed. This leads to a better quality of life (and survival in some studies) for both patients and their families^1,3,5 and reduces unnecessary emergency department (ED) and hospital use.¹² Hospitalists providing palliative care can also reduce readmissions by improving care coordination, including clinical communication and medication reconciliation after discharge.¹³

A 2015 Harvard Business Review study found that the quality of communication in the hospital is the strongest independent predictor of readmissions when combined with process-of-care improvements, such as standardized patient screening and assessment of family caregiver capacity.¹⁴ While medical education prepares physicians to deliver evidence-based medical care, it currently offers little to no training in communication skills, despite mounting evidence that this is a critical component of quality healthcare.

Cost Savings

Hospital palliative care teams are associated with significant hospital cost savings that result from aligning care with patient priorities, leading, in turn, to reduced nonbeneficial hospital imaging, medications, procedures, and length of stay.¹⁵ See the table^16,17 for examples of cost and quality outcomes of specialist palliative care provision and evidence supporting each outcome.^18-25

Multiple studies consistently demonstrate that inpatient palliative care teams reduce hospital costs.²⁶ One randomized controlled trial investigating the impact of an inpatient palliative care service found that patients who received care from the palliative care team reported greater satisfaction with their care, had fewer intensive care unit admissions, had more advanced directives at hospital discharge, longer hospice length of stay, and lower total healthcare costs (a net difference of $6766 per patient).²³

Research shows that the earlier palliative care is provided, the greater the impact on the subsequent course of care,²⁷ suggesting that hospitalists who provide frontline palliative care interventions as early as possible in a seriously ill patient’s stay will be able to provide higher quality care with lower overall costs. Notably, the majority of research on cost savings associated with palliative care has focused on the impact of specialist palliative care teams, and further research is needed to understand the economic impact of primary palliative care provision.

Improving Satisfaction

Shifting to value-based payment means that the patient and family experience determine an increasingly large percentage of hospital and provider reimbursement. Palliative care approaches, such as family caregiver assessment and support, access to 24/7 assistance after discharge, and person-centered care by an interdisciplinary team, improve performance in all of these measures. Communication skills training improves patient satisfaction scores, and skilled discussions about achievable priorities for care are associated with better quality of life, reduced nonbeneficial and burdensome treatments, and an increase in goal-concordant care.¹⁹ Communication skills training has also been shown to reduce burnout and improve empathy among physicians.^28,29

Though more evidence is needed to understand the impact of primary palliative care provision by hospitalists, the strong evidence on the benefits of specialty palliative care suggests that the skilled provision of primary palliative care by hospitalists will result in higher quality, higher value care. A number of training options exist for midcareer hospital medicine clinicians, including both in-person and online training in communication and other palliative care skills.

• The Center to Advance Palliative Care (CAPC) is a membership organization that offers online continuing education unit and continuing medical education courses on communication skills, pain and symptom management, caregiver support, and care coordination. CAPC also offers courses on palliative interventions for patients with dementia, COPD, and heart failure.
• SHM is actively invested in engaging hospitalists in palliative care skills training. SHM provides free toolkits on a variety of topics within the palliative care domain, including pain management, postacute care transitions, and opioid safety. The recently released Serious Illness Communication toolkit offers background on the role of hospitalists in palliative care provision, a pathway for fitting goals-of-care conversations into hospitalist workflow and recommended metrics and training resources. SHM also uses a mentored implementation model in which expert physicians mentor hospital team members on best practices in palliative care. SHM’s Palliative Care Task Force seeks to identify educational activities for hospitalists and create opportunities to integrate palliative care in hospital medicine.³⁰
• The Serious Illness Care Program at Ariadne Labs in Boston aims to facilitate conversations between clinicians and seriously ill patients through its Serious Illness Conversation Guide, combined with technical assistance on workflow redesign to help clinicians conduct and document serious illness conversations.
• VitalTalk specializes in clinical communication education. Through online and in-person train-the-trainer programs, VitalTalk equips clinicians to lead communication training programs at their home institutions.
• The Education in Palliative and End-of-Life Care Program and End-of-Life Nursing Education Consortium (ELNEC) uses a train-the-trainer approach to educate providers in palliative care clinical competencies and increase the reach of primary palliative care provision. ELNEC workshops are complemented by a curriculum of online clinical training modules.

Though palliative care skills training is a necessary first step, hospitalists also cite lack of time, difficulty finding records of previous patient discussions, and frequent handoffs as among the barriers to integrating palliative care into their practice.¹⁰ Studies examining the process of palliative care and hospital culture change have found that barriers to palliative care integration include a culture of aggressive care in EDs, lack of standardized patient identification criteria, and limited knowledge about and staffing for palliative care.³¹ These data indicate the need for system changes that enable hospitalists to operationalize palliative care principles.

Health systems must implement systems and processes that routinize palliative care, making it part of the mainstream course of care for seriously ill patients and their caregivers. This includes developing systems for the identification of patients with palliative care needs, embedding palliative care assessment and referral into clinical workflows, and enabling standardized palliative care documentation in electronic medical records. While palliative care skills training is essential, investment in systems change is no less critical to embedding palliative care practices in clinical norms across specialties.

Hospitalists can use a palliative approach to improve care quality and quality of life for seriously ill patients while helping to avoid preventable and unnecessary 911 calls, ED visits, and hospitalizations. The shift towards value-based payment is a strong incentive for hospitals and hospitalists to direct resources toward practices that improve the quality of life and care for the highest-need patients and their families. When equipped with the tools they need to provide palliative care, either themselves or in collaboration with palliative care teams, hospitalists have the opportunity to profoundly redirect the experience of care for seriously ill patients and their families.

Disclosure

The authors declared no conflicts of interest.

Palliative care is specialized medical care focused on providing relief from the symptoms, pain, and stress of a serious illness. The goal is to improve the quality of life for both the patient and the family. In all settings, palliative care has been found to improve patients’ quality of life,^1,2 improve family satisfaction and well-being,³ reduce resource utilization and costs,⁴ and, in some studies, increase the length of life for seriously ill patients.⁵

Given the frequency with which seriously ill patients are hospitalized, hospitalists are well positioned to identify those who could benefit from palliative care interventions.⁶ Hospitalists routinely use primary palliative care skills, including pain and symptom management and skilled care planning conversations. For complex cases, such as patients with intractable symptoms or major family conflict, hospitalists may refer to specialist palliative care teams for consultation.

The Society of Hospital Medicine (SHM) defines the key primary palliative care responsibilities for hospitalists as (1) leading discussions on the goals of care and advance care planning with patients and families, (2) screening and treating common physical symptoms, and (3) referring patients to community services to provide support postdischarge.⁷ According to data in the National Palliative Care Registry,⁸ 48% of all palliative care referrals in 2015 came from hospitalists, which is more than double the percentage of referrals from any other specialty.⁹

In a recent survey conducted by SHM about serious illness communication, 53% of hospitalists reported concerns about a patient or family’s understanding of their prognosis, and 50% indicated that they do not feel confident managing family conflict.¹⁰

Context

Patients with multiple serious chronic conditions are often forced to rely on emergency services when crises, such as uncontrolled pain or dyspnea exacerbation, occur after hours, resulting in the revolving-door hospitalizations that typically characterize their care.¹¹ As the prevalence of serious illness rises and the shift to value-based payment accelerates, hospitals are under increasing pressure to deliver efficient and high-quality services that meet the needs of seriously ill patients. The integration of standardized palliative care screening and assessment enables hospitalists and other providers to identify high-need individuals and match services and delivery models to needs, whether it be respite care for an exhausted and overwhelmed family caregiver or a home protocol for managing recurrent dyspnea crises for a patient with chronic obstructive pulmonary disease (COPD). This process improves the quality of care and quality of life, and in doing so, prevents the need for costly crisis care.

Reducing Readmissions

By identifying patients in need of extra symptom management support, or those at a turning point requiring discussion about achievable priorities for care, hospitalists can avert crises for patients earlier in the disease trajectory either by managing the patient’s palliative needs themselves or by connecting patients with specialty palliative care services as needed. This leads to a better quality of life (and survival in some studies) for both patients and their families^1,3,5 and reduces unnecessary emergency department (ED) and hospital use.¹² Hospitalists providing palliative care can also reduce readmissions by improving care coordination, including clinical communication and medication reconciliation after discharge.¹³

A 2015 Harvard Business Review study found that the quality of communication in the hospital is the strongest independent predictor of readmissions when combined with process-of-care improvements, such as standardized patient screening and assessment of family caregiver capacity.¹⁴ While medical education prepares physicians to deliver evidence-based medical care, it currently offers little to no training in communication skills, despite mounting evidence that this is a critical component of quality healthcare.

Cost Savings

Hospital palliative care teams are associated with significant hospital cost savings that result from aligning care with patient priorities, leading, in turn, to reduced nonbeneficial hospital imaging, medications, procedures, and length of stay.¹⁵ See the table^16,17 for examples of cost and quality outcomes of specialist palliative care provision and evidence supporting each outcome.^18-25

Multiple studies consistently demonstrate that inpatient palliative care teams reduce hospital costs.²⁶ One randomized controlled trial investigating the impact of an inpatient palliative care service found that patients who received care from the palliative care team reported greater satisfaction with their care, had fewer intensive care unit admissions, had more advanced directives at hospital discharge, longer hospice length of stay, and lower total healthcare costs (a net difference of $6766 per patient).²³

Research shows that the earlier palliative care is provided, the greater the impact on the subsequent course of care,²⁷ suggesting that hospitalists who provide frontline palliative care interventions as early as possible in a seriously ill patient’s stay will be able to provide higher quality care with lower overall costs. Notably, the majority of research on cost savings associated with palliative care has focused on the impact of specialist palliative care teams, and further research is needed to understand the economic impact of primary palliative care provision.

Improving Satisfaction

Shifting to value-based payment means that the patient and family experience determine an increasingly large percentage of hospital and provider reimbursement. Palliative care approaches, such as family caregiver assessment and support, access to 24/7 assistance after discharge, and person-centered care by an interdisciplinary team, improve performance in all of these measures. Communication skills training improves patient satisfaction scores, and skilled discussions about achievable priorities for care are associated with better quality of life, reduced nonbeneficial and burdensome treatments, and an increase in goal-concordant care.¹⁹ Communication skills training has also been shown to reduce burnout and improve empathy among physicians.^28,29

Though more evidence is needed to understand the impact of primary palliative care provision by hospitalists, the strong evidence on the benefits of specialty palliative care suggests that the skilled provision of primary palliative care by hospitalists will result in higher quality, higher value care. A number of training options exist for midcareer hospital medicine clinicians, including both in-person and online training in communication and other palliative care skills.

• The Center to Advance Palliative Care (CAPC) is a membership organization that offers online continuing education unit and continuing medical education courses on communication skills, pain and symptom management, caregiver support, and care coordination. CAPC also offers courses on palliative interventions for patients with dementia, COPD, and heart failure.
• SHM is actively invested in engaging hospitalists in palliative care skills training. SHM provides free toolkits on a variety of topics within the palliative care domain, including pain management, postacute care transitions, and opioid safety. The recently released Serious Illness Communication toolkit offers background on the role of hospitalists in palliative care provision, a pathway for fitting goals-of-care conversations into hospitalist workflow and recommended metrics and training resources. SHM also uses a mentored implementation model in which expert physicians mentor hospital team members on best practices in palliative care. SHM’s Palliative Care Task Force seeks to identify educational activities for hospitalists and create opportunities to integrate palliative care in hospital medicine.³⁰
• The Serious Illness Care Program at Ariadne Labs in Boston aims to facilitate conversations between clinicians and seriously ill patients through its Serious Illness Conversation Guide, combined with technical assistance on workflow redesign to help clinicians conduct and document serious illness conversations.
• VitalTalk specializes in clinical communication education. Through online and in-person train-the-trainer programs, VitalTalk equips clinicians to lead communication training programs at their home institutions.
• The Education in Palliative and End-of-Life Care Program and End-of-Life Nursing Education Consortium (ELNEC) uses a train-the-trainer approach to educate providers in palliative care clinical competencies and increase the reach of primary palliative care provision. ELNEC workshops are complemented by a curriculum of online clinical training modules.

Though palliative care skills training is a necessary first step, hospitalists also cite lack of time, difficulty finding records of previous patient discussions, and frequent handoffs as among the barriers to integrating palliative care into their practice.¹⁰ Studies examining the process of palliative care and hospital culture change have found that barriers to palliative care integration include a culture of aggressive care in EDs, lack of standardized patient identification criteria, and limited knowledge about and staffing for palliative care.³¹ These data indicate the need for system changes that enable hospitalists to operationalize palliative care principles.

Health systems must implement systems and processes that routinize palliative care, making it part of the mainstream course of care for seriously ill patients and their caregivers. This includes developing systems for the identification of patients with palliative care needs, embedding palliative care assessment and referral into clinical workflows, and enabling standardized palliative care documentation in electronic medical records. While palliative care skills training is essential, investment in systems change is no less critical to embedding palliative care practices in clinical norms across specialties.

Hospitalists can use a palliative approach to improve care quality and quality of life for seriously ill patients while helping to avoid preventable and unnecessary 911 calls, ED visits, and hospitalizations. The shift towards value-based payment is a strong incentive for hospitals and hospitalists to direct resources toward practices that improve the quality of life and care for the highest-need patients and their families. When equipped with the tools they need to provide palliative care, either themselves or in collaboration with palliative care teams, hospitalists have the opportunity to profoundly redirect the experience of care for seriously ill patients and their families.

Disclosure

The authors declared no conflicts of interest.

Image by Difu Wu

The US Food and Drug Administration (FDA) has expanded the approved indication for bosutinib (BOSULIF®).

The tyrosine kinase inhibitor (TKI) is now approved to treat adults with newly diagnosed, chronic phase, Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML).

Bosutinib has accelerated approval for this indication. The approval was based on molecular and cytogenetic response rates.

Continued approval may be contingent upon verification and confirmation of clinical benefit in an ongoing, long-term follow-up trial.

Bosutinib was first approved by the FDA in September 2012. At that time, the TKI was approved to treat adults with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy.

A 400 mg tablet of bosutinib was recently approved by the FDA, adding to the previously approved 100 mg and 500 mg strengths.

The recommended dose of bosutinib for newly diagnosed patients is 400 mg orally once daily with food.

For patients who are resistant or intolerant to prior TKI therapy, the recommended dose is 500 mg orally once daily with food.

BFORE trial

The approval of bosutinib in adults with newly diagnosed, chronic phase, Ph+ CML was based on the phase 3 BFORE trial. Results from the trial were presented at the 2017 ASCO Annual Meeting.

In this ongoing study, researchers are comparing bosutinib and imatinib as first-line treatment of chronic phase CML.

As of the ASCO presentation, the trial had enrolled 536 patients who were randomized 1:1 to receive bosutinib (n=268) or imatinib (n=268).

The presentation included results in a modified intent-to-treat population of Ph+ patients with e13a2/e14a2 transcripts who had at least 12 months of follow-up. In this group, there were 246 patients in the bosutinib arm and 241 in the imatinib arm.

Most of the patients were still on therapy at the 12-month mark or beyond—78% in the bosutinib arm and 73.2% in the imatinib arm. The median treatment duration was 14.1 months and 13.8 months, respectively.

At 12 months, the rate of major molecular response was 47.2% in the bosutinib arm and 36.9% in the imatinib arm (P=0.02). The rate of complete cytogenetic response was 77.2% and 66.4%, respectively (P<0.008).

One patient in the bosutinib arm and 4 in the imatinib arm discontinued treatment due to disease progression, while 12.7% and 8.7%, respectively, discontinued treatment due to drug-related toxicity.

Adverse events that were more common in the bosutinib arm than the imatinib arm included grade 3 or higher diarrhea (7.8% vs 0.8%), increased alanine levels (19% vs 1.5%), increased aspartate levels (9.7% vs 1.9%), cardiovascular events (3% vs 0.4%), and peripheral vascular events (1.5% vs 1.1%).

Cerebrovascular events were more common with imatinib than bosutinib (0.4% and 0%, respectively).

Pfizer and Avillion entered into an exclusive collaborative development agreement in 2014 to conduct the BFORE trial.

Under the terms of the agreement, Avillion provided funding and conducted the trial to generate the clinical data used to support regulatory filings for marketing authorization for bosutinib as first-line treatment for patients with chronic phase, Ph+ CML.

With this approval, Avillion is eligible to receive milestone payments from Pfizer. Pfizer retains all rights to commercialize bosutinib globally.

Image by Difu Wu

The US Food and Drug Administration (FDA) has expanded the approved indication for bosutinib (BOSULIF®).

The tyrosine kinase inhibitor (TKI) is now approved to treat adults with newly diagnosed, chronic phase, Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML).

Bosutinib has accelerated approval for this indication. The approval was based on molecular and cytogenetic response rates.

Continued approval may be contingent upon verification and confirmation of clinical benefit in an ongoing, long-term follow-up trial.

Bosutinib was first approved by the FDA in September 2012. At that time, the TKI was approved to treat adults with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy.

A 400 mg tablet of bosutinib was recently approved by the FDA, adding to the previously approved 100 mg and 500 mg strengths.

The recommended dose of bosutinib for newly diagnosed patients is 400 mg orally once daily with food.

For patients who are resistant or intolerant to prior TKI therapy, the recommended dose is 500 mg orally once daily with food.

BFORE trial

The approval of bosutinib in adults with newly diagnosed, chronic phase, Ph+ CML was based on the phase 3 BFORE trial. Results from the trial were presented at the 2017 ASCO Annual Meeting.

In this ongoing study, researchers are comparing bosutinib and imatinib as first-line treatment of chronic phase CML.

As of the ASCO presentation, the trial had enrolled 536 patients who were randomized 1:1 to receive bosutinib (n=268) or imatinib (n=268).

The presentation included results in a modified intent-to-treat population of Ph+ patients with e13a2/e14a2 transcripts who had at least 12 months of follow-up. In this group, there were 246 patients in the bosutinib arm and 241 in the imatinib arm.

Most of the patients were still on therapy at the 12-month mark or beyond—78% in the bosutinib arm and 73.2% in the imatinib arm. The median treatment duration was 14.1 months and 13.8 months, respectively.

At 12 months, the rate of major molecular response was 47.2% in the bosutinib arm and 36.9% in the imatinib arm (P=0.02). The rate of complete cytogenetic response was 77.2% and 66.4%, respectively (P<0.008).

One patient in the bosutinib arm and 4 in the imatinib arm discontinued treatment due to disease progression, while 12.7% and 8.7%, respectively, discontinued treatment due to drug-related toxicity.

Adverse events that were more common in the bosutinib arm than the imatinib arm included grade 3 or higher diarrhea (7.8% vs 0.8%), increased alanine levels (19% vs 1.5%), increased aspartate levels (9.7% vs 1.9%), cardiovascular events (3% vs 0.4%), and peripheral vascular events (1.5% vs 1.1%).

Cerebrovascular events were more common with imatinib than bosutinib (0.4% and 0%, respectively).

Pfizer and Avillion entered into an exclusive collaborative development agreement in 2014 to conduct the BFORE trial.

Under the terms of the agreement, Avillion provided funding and conducted the trial to generate the clinical data used to support regulatory filings for marketing authorization for bosutinib as first-line treatment for patients with chronic phase, Ph+ CML.

With this approval, Avillion is eligible to receive milestone payments from Pfizer. Pfizer retains all rights to commercialize bosutinib globally.

Image by Difu Wu

The US Food and Drug Administration (FDA) has expanded the approved indication for bosutinib (BOSULIF®).

The tyrosine kinase inhibitor (TKI) is now approved to treat adults with newly diagnosed, chronic phase, Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML).

Bosutinib has accelerated approval for this indication. The approval was based on molecular and cytogenetic response rates.

Continued approval may be contingent upon verification and confirmation of clinical benefit in an ongoing, long-term follow-up trial.

Bosutinib was first approved by the FDA in September 2012. At that time, the TKI was approved to treat adults with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy.

A 400 mg tablet of bosutinib was recently approved by the FDA, adding to the previously approved 100 mg and 500 mg strengths.

The recommended dose of bosutinib for newly diagnosed patients is 400 mg orally once daily with food.

For patients who are resistant or intolerant to prior TKI therapy, the recommended dose is 500 mg orally once daily with food.

BFORE trial

The approval of bosutinib in adults with newly diagnosed, chronic phase, Ph+ CML was based on the phase 3 BFORE trial. Results from the trial were presented at the 2017 ASCO Annual Meeting.

In this ongoing study, researchers are comparing bosutinib and imatinib as first-line treatment of chronic phase CML.

As of the ASCO presentation, the trial had enrolled 536 patients who were randomized 1:1 to receive bosutinib (n=268) or imatinib (n=268).

The presentation included results in a modified intent-to-treat population of Ph+ patients with e13a2/e14a2 transcripts who had at least 12 months of follow-up. In this group, there were 246 patients in the bosutinib arm and 241 in the imatinib arm.

Most of the patients were still on therapy at the 12-month mark or beyond—78% in the bosutinib arm and 73.2% in the imatinib arm. The median treatment duration was 14.1 months and 13.8 months, respectively.

At 12 months, the rate of major molecular response was 47.2% in the bosutinib arm and 36.9% in the imatinib arm (P=0.02). The rate of complete cytogenetic response was 77.2% and 66.4%, respectively (P<0.008).

One patient in the bosutinib arm and 4 in the imatinib arm discontinued treatment due to disease progression, while 12.7% and 8.7%, respectively, discontinued treatment due to drug-related toxicity.

Adverse events that were more common in the bosutinib arm than the imatinib arm included grade 3 or higher diarrhea (7.8% vs 0.8%), increased alanine levels (19% vs 1.5%), increased aspartate levels (9.7% vs 1.9%), cardiovascular events (3% vs 0.4%), and peripheral vascular events (1.5% vs 1.1%).

Cerebrovascular events were more common with imatinib than bosutinib (0.4% and 0%, respectively).

Pfizer and Avillion entered into an exclusive collaborative development agreement in 2014 to conduct the BFORE trial.

Under the terms of the agreement, Avillion provided funding and conducted the trial to generate the clinical data used to support regulatory filings for marketing authorization for bosutinib as first-line treatment for patients with chronic phase, Ph+ CML.

With this approval, Avillion is eligible to receive milestone payments from Pfizer. Pfizer retains all rights to commercialize bosutinib globally.

© Todd Buchanan 2017

ATLANTA—One of the largest single-center studies of fludarabine/melphalan-based allogeneic hematopoietic stem cell transplant (allo-HSCT) for patients with myelofibrosis (MF) shows excellent overall survival (OS) with a low risk of relapse, according to investigators.

Allo-HSCT is the only potential curative treatment modality for MF.

However, it is associated with risks of transplant-related morbidity and mortality from graft-versus-host disease (GVHD), infection, graft rejection, and regimen-related toxicities.

This necessitates careful patient selection and intense peri-transplant management, said study investigator Haris Ali, MD, of the City of Hope Medical Center in Duarte, California.

He noted that there has been a 5-fold increase in allo-HSCT in the last 2 decades, mainly among older patients, due to the increase in reduced-intensity conditioning.

At the 2017 ASH Annual Meeting (in abstract 199), Dr Ali reported on a cohort of 110 MF patients who underwent allo-HSCT with fludarabine/melphalan conditioning at City of Hope between 2004 and 2017.

The patients, 58 with primary MF and 52 with secondary MF, were without prior acute leukemic transformation. They were a median age of 58.5 at the time of transplant, with a median interval of 15.2 months from MF diagnosis.

Virtually all (n=107) received peripheral blood stem cells, and 3 were transplanted with bone marrow as the stem cell source. Forty-nine allo-HSCT donors were matched related, 32 were matched unrelated, 27 were mismatched unrelated, 1 was mismatched relative, and 1 was haploidentical family.

Three-quarters of the patients had intermediate-2 or high-risk disease. Of the 110 patients, 16 had splenectomy prior to allo-HSCT. All but 2 patients engrafted.

After a median follow-up of 56.8 months, the 2-year OS rate was 74%, and the 5-year OS rate was 65%.

Non-relapse mortality at 2 years was 12%. At 5 years, it was 24%.

“The risk of non-relapse mortality was acceptable, considering the relatively older age of a large subset of patients; nearly half were over age 60 at allo-HSCT,” Dr Ali said.

In a univariate analysis, mismatched donors and matched unrelated donors were significantly associated with worse OS compared with matched related donors.

The cumulative incidence of relapse was 17% at 2 years and 5 years.

Splenectomy prior to transplant was associated with higher relapse risk, Dr Ali noted.

“Cytogenetic abnormalities were not associated with transplant relapse or other outcomes in our cohort,” he added.

Mutational changes are being tested in pre-transplant samples and will be reported at a later date.

The incidence of grade 2-4 and 3-4 acute GVHD at 100 days was 45% and 17%, respectively.

At 36 months, the cumulative incidence of all chronic GVHD was 66%. For extensive chronic GVHD, it was 59%.

“Interestingly, prior use of ruxolitinib increased the risk of grade 3-4 acute GVHD, possibly due to known inflammatory cytokine rebound,” Dr Ali said.

Extended use of ruxolitinib until day 30 or longer is currently being evaluated in a prospective trial at City of Hope (NCT02917096).

Dr Ali disclosed consulting fees from Incyte.

© Todd Buchanan 2017

ATLANTA—One of the largest single-center studies of fludarabine/melphalan-based allogeneic hematopoietic stem cell transplant (allo-HSCT) for patients with myelofibrosis (MF) shows excellent overall survival (OS) with a low risk of relapse, according to investigators.

Allo-HSCT is the only potential curative treatment modality for MF.

However, it is associated with risks of transplant-related morbidity and mortality from graft-versus-host disease (GVHD), infection, graft rejection, and regimen-related toxicities.

This necessitates careful patient selection and intense peri-transplant management, said study investigator Haris Ali, MD, of the City of Hope Medical Center in Duarte, California.

He noted that there has been a 5-fold increase in allo-HSCT in the last 2 decades, mainly among older patients, due to the increase in reduced-intensity conditioning.

At the 2017 ASH Annual Meeting (in abstract 199), Dr Ali reported on a cohort of 110 MF patients who underwent allo-HSCT with fludarabine/melphalan conditioning at City of Hope between 2004 and 2017.

The patients, 58 with primary MF and 52 with secondary MF, were without prior acute leukemic transformation. They were a median age of 58.5 at the time of transplant, with a median interval of 15.2 months from MF diagnosis.

Virtually all (n=107) received peripheral blood stem cells, and 3 were transplanted with bone marrow as the stem cell source. Forty-nine allo-HSCT donors were matched related, 32 were matched unrelated, 27 were mismatched unrelated, 1 was mismatched relative, and 1 was haploidentical family.

Three-quarters of the patients had intermediate-2 or high-risk disease. Of the 110 patients, 16 had splenectomy prior to allo-HSCT. All but 2 patients engrafted.

After a median follow-up of 56.8 months, the 2-year OS rate was 74%, and the 5-year OS rate was 65%.

Non-relapse mortality at 2 years was 12%. At 5 years, it was 24%.

“The risk of non-relapse mortality was acceptable, considering the relatively older age of a large subset of patients; nearly half were over age 60 at allo-HSCT,” Dr Ali said.

In a univariate analysis, mismatched donors and matched unrelated donors were significantly associated with worse OS compared with matched related donors.

The cumulative incidence of relapse was 17% at 2 years and 5 years.

Splenectomy prior to transplant was associated with higher relapse risk, Dr Ali noted.

“Cytogenetic abnormalities were not associated with transplant relapse or other outcomes in our cohort,” he added.

Mutational changes are being tested in pre-transplant samples and will be reported at a later date.

The incidence of grade 2-4 and 3-4 acute GVHD at 100 days was 45% and 17%, respectively.

At 36 months, the cumulative incidence of all chronic GVHD was 66%. For extensive chronic GVHD, it was 59%.

“Interestingly, prior use of ruxolitinib increased the risk of grade 3-4 acute GVHD, possibly due to known inflammatory cytokine rebound,” Dr Ali said.

Extended use of ruxolitinib until day 30 or longer is currently being evaluated in a prospective trial at City of Hope (NCT02917096).

Dr Ali disclosed consulting fees from Incyte.

© Todd Buchanan 2017

ATLANTA—One of the largest single-center studies of fludarabine/melphalan-based allogeneic hematopoietic stem cell transplant (allo-HSCT) for patients with myelofibrosis (MF) shows excellent overall survival (OS) with a low risk of relapse, according to investigators.

Allo-HSCT is the only potential curative treatment modality for MF.

However, it is associated with risks of transplant-related morbidity and mortality from graft-versus-host disease (GVHD), infection, graft rejection, and regimen-related toxicities.

This necessitates careful patient selection and intense peri-transplant management, said study investigator Haris Ali, MD, of the City of Hope Medical Center in Duarte, California.

He noted that there has been a 5-fold increase in allo-HSCT in the last 2 decades, mainly among older patients, due to the increase in reduced-intensity conditioning.

At the 2017 ASH Annual Meeting (in abstract 199), Dr Ali reported on a cohort of 110 MF patients who underwent allo-HSCT with fludarabine/melphalan conditioning at City of Hope between 2004 and 2017.

The patients, 58 with primary MF and 52 with secondary MF, were without prior acute leukemic transformation. They were a median age of 58.5 at the time of transplant, with a median interval of 15.2 months from MF diagnosis.

Virtually all (n=107) received peripheral blood stem cells, and 3 were transplanted with bone marrow as the stem cell source. Forty-nine allo-HSCT donors were matched related, 32 were matched unrelated, 27 were mismatched unrelated, 1 was mismatched relative, and 1 was haploidentical family.

Three-quarters of the patients had intermediate-2 or high-risk disease. Of the 110 patients, 16 had splenectomy prior to allo-HSCT. All but 2 patients engrafted.

After a median follow-up of 56.8 months, the 2-year OS rate was 74%, and the 5-year OS rate was 65%.

Non-relapse mortality at 2 years was 12%. At 5 years, it was 24%.

“The risk of non-relapse mortality was acceptable, considering the relatively older age of a large subset of patients; nearly half were over age 60 at allo-HSCT,” Dr Ali said.

In a univariate analysis, mismatched donors and matched unrelated donors were significantly associated with worse OS compared with matched related donors.

The cumulative incidence of relapse was 17% at 2 years and 5 years.

Splenectomy prior to transplant was associated with higher relapse risk, Dr Ali noted.

“Cytogenetic abnormalities were not associated with transplant relapse or other outcomes in our cohort,” he added.

Mutational changes are being tested in pre-transplant samples and will be reported at a later date.

The incidence of grade 2-4 and 3-4 acute GVHD at 100 days was 45% and 17%, respectively.

At 36 months, the cumulative incidence of all chronic GVHD was 66%. For extensive chronic GVHD, it was 59%.

“Interestingly, prior use of ruxolitinib increased the risk of grade 3-4 acute GVHD, possibly due to known inflammatory cytokine rebound,” Dr Ali said.

Extended use of ruxolitinib until day 30 or longer is currently being evaluated in a prospective trial at City of Hope (NCT02917096).

Dr Ali disclosed consulting fees from Incyte.

MRI scanner

The US Food and Drug Administration (FDA) has issued new safety-related requirements pertaining to gadolinium-based contrast agents (GBCAs) used for magnetic resonance imaging (MRI).

The agency’s action is due to the fact that gadolinium can be retained in patients’ brains and other body tissues for months to years after they receive GBCAs.

The only known adverse event related to gadolinium retention is nephrogenic systemic fibrosis, which occurs in a small subgroup of patients with pre-existing kidney failure.

Patients with normal kidney function and gadolinium retention have experienced adverse events involving multiple organ systems. However, the FDA has found no evidence confirming that gadolinium retention is causing these events.

Therefore, the agency concluded that the benefit of all approved GBCAs continues to outweigh any potential risks.

Still, the FDA has issued the following safety requirements related to GBCAs:

• Patients receiving GBCAs must read a new medication guide explaining about gadolinium retention
• Manufacturers of GBCAs must conduct human and animal studies to assess the safety of GBCAs
• Labels of GBCAs must be updated with a “Warning and Precaution” about gadolinium retention
• Labels must be changed to include mention of gadolinium retention in the Adverse Reactions, Pregnancy, Clinical Pharmacology, and Patient Instructions sections.

The FDA is also recommending that healthcare professionals consider the retention characteristics of each agent when choosing a GBCA for patients who may be at higher risk for gadolinium retention. This includes patients requiring multiple lifetime doses, pregnant women, children, and patients with inflammatory conditions.

In its latest safety communication on gadolinium retention, the FDA noted that linear GBCAs result in more and longer retention than macrocyclic GBCAs.

Specifically, gadolinium retention is higher with Omniscan (gadodiamide) or OptiMARK (gadoversetamide) than with Eovist (gadoxetate disodium), Magnevist (gadopentetate dimeglumine), or MultiHance (gadobenate dimeglumine).

Gadolinium retention is lowest with Dotarem (gadoterate meglumine), Gadavist (gadobutrol), and ProHance (gadoteridol), which all have similar levels of gadolinium retention.

Finally, the FDA is recommending that healthcare professionals minimize repeated GBCA imaging studies when possible, particularly closely spaced MRI studies. However, necessary GBCA MRI scans should not be deferred or avoided.

The FDA said it is still assessing the health effects of gadolinium retention and will update the public when new information becomes available. In the meantime, patients and healthcare professionals can report adverse events involving GBCAs to the agency’s MedWatch program.

MRI scanner

The US Food and Drug Administration (FDA) has issued new safety-related requirements pertaining to gadolinium-based contrast agents (GBCAs) used for magnetic resonance imaging (MRI).

The agency’s action is due to the fact that gadolinium can be retained in patients’ brains and other body tissues for months to years after they receive GBCAs.

The only known adverse event related to gadolinium retention is nephrogenic systemic fibrosis, which occurs in a small subgroup of patients with pre-existing kidney failure.

Patients with normal kidney function and gadolinium retention have experienced adverse events involving multiple organ systems. However, the FDA has found no evidence confirming that gadolinium retention is causing these events.

Therefore, the agency concluded that the benefit of all approved GBCAs continues to outweigh any potential risks.

Still, the FDA has issued the following safety requirements related to GBCAs:

• Patients receiving GBCAs must read a new medication guide explaining about gadolinium retention
• Manufacturers of GBCAs must conduct human and animal studies to assess the safety of GBCAs
• Labels of GBCAs must be updated with a “Warning and Precaution” about gadolinium retention
• Labels must be changed to include mention of gadolinium retention in the Adverse Reactions, Pregnancy, Clinical Pharmacology, and Patient Instructions sections.

The FDA is also recommending that healthcare professionals consider the retention characteristics of each agent when choosing a GBCA for patients who may be at higher risk for gadolinium retention. This includes patients requiring multiple lifetime doses, pregnant women, children, and patients with inflammatory conditions.

In its latest safety communication on gadolinium retention, the FDA noted that linear GBCAs result in more and longer retention than macrocyclic GBCAs.

Specifically, gadolinium retention is higher with Omniscan (gadodiamide) or OptiMARK (gadoversetamide) than with Eovist (gadoxetate disodium), Magnevist (gadopentetate dimeglumine), or MultiHance (gadobenate dimeglumine).

Gadolinium retention is lowest with Dotarem (gadoterate meglumine), Gadavist (gadobutrol), and ProHance (gadoteridol), which all have similar levels of gadolinium retention.

Finally, the FDA is recommending that healthcare professionals minimize repeated GBCA imaging studies when possible, particularly closely spaced MRI studies. However, necessary GBCA MRI scans should not be deferred or avoided.

The FDA said it is still assessing the health effects of gadolinium retention and will update the public when new information becomes available. In the meantime, patients and healthcare professionals can report adverse events involving GBCAs to the agency’s MedWatch program.

MRI scanner

The US Food and Drug Administration (FDA) has issued new safety-related requirements pertaining to gadolinium-based contrast agents (GBCAs) used for magnetic resonance imaging (MRI).

The agency’s action is due to the fact that gadolinium can be retained in patients’ brains and other body tissues for months to years after they receive GBCAs.

The only known adverse event related to gadolinium retention is nephrogenic systemic fibrosis, which occurs in a small subgroup of patients with pre-existing kidney failure.

Patients with normal kidney function and gadolinium retention have experienced adverse events involving multiple organ systems. However, the FDA has found no evidence confirming that gadolinium retention is causing these events.

Therefore, the agency concluded that the benefit of all approved GBCAs continues to outweigh any potential risks.

Still, the FDA has issued the following safety requirements related to GBCAs:

• Patients receiving GBCAs must read a new medication guide explaining about gadolinium retention
• Manufacturers of GBCAs must conduct human and animal studies to assess the safety of GBCAs
• Labels of GBCAs must be updated with a “Warning and Precaution” about gadolinium retention
• Labels must be changed to include mention of gadolinium retention in the Adverse Reactions, Pregnancy, Clinical Pharmacology, and Patient Instructions sections.

The FDA is also recommending that healthcare professionals consider the retention characteristics of each agent when choosing a GBCA for patients who may be at higher risk for gadolinium retention. This includes patients requiring multiple lifetime doses, pregnant women, children, and patients with inflammatory conditions.

In its latest safety communication on gadolinium retention, the FDA noted that linear GBCAs result in more and longer retention than macrocyclic GBCAs.

Specifically, gadolinium retention is higher with Omniscan (gadodiamide) or OptiMARK (gadoversetamide) than with Eovist (gadoxetate disodium), Magnevist (gadopentetate dimeglumine), or MultiHance (gadobenate dimeglumine).

Gadolinium retention is lowest with Dotarem (gadoterate meglumine), Gadavist (gadobutrol), and ProHance (gadoteridol), which all have similar levels of gadolinium retention.

Finally, the FDA is recommending that healthcare professionals minimize repeated GBCA imaging studies when possible, particularly closely spaced MRI studies. However, necessary GBCA MRI scans should not be deferred or avoided.

The FDA said it is still assessing the health effects of gadolinium retention and will update the public when new information becomes available. In the meantime, patients and healthcare professionals can report adverse events involving GBCAs to the agency’s MedWatch program.

SAN DIEGO – Zika virus can persist in blood components for several months, long after it is no longer detectable in plasma and other body fluids, based on data reported at the annual meeting of the American Association of Blood Banks.

The presence of Zika virus in plasma declined rapidly following donation, but could be detected in red blood cells (RBCs) and whole blood for up to 3 months. In addition, the virus was also detected intermittently in peripheral blood mononuclear cells (PBMCs) at low levels after clearance from plasma.

“There was longer persistence of Zika RNA in whole blood and RBC blood components than in plasma and other body fluids. It was detected at high levels and persists for about 6 weeks,” Mars Stone, PhD said in presenting the findings.

The findings were based on 2016 data collected in Puerto Rico, which began screening blood donations for Zika virus RNA under an investigational protocol by using a nucleic acid test; they began doing so as a result of guidance from the U.S. Food and Drug Administration. Approximately 350 confirmed infected – that is, nucleic acid test positive (NAT+) – donations were detected through December 2016.

The FDA approved the cobas Zika test used in the study on October 5. Intended for use by blood collection establishments to detect Zika virus in blood donations, the test is manufactured by Roche Molecular Systems. Dr. Stone is an employee of Blood Systems Research Institute, a confirmatory laboratory for Roche.

Of the 52,942 donations collected between April 3 and Dec. 31, 352 were reactive for ZIKV RNA. Plasma from blood donors was screened by individual donation NAT for the presence of ZIKV RNA with the cobas Zika test. At an interval of between 57 and 120 days, no Zika RNA was found in 350 samples of plasma, but it was found in 38.2% (34 samples) of RBCs and 40.0% (35 samples) of whole blood.

In urine and saliva, the virus was detected in high levels at 1-2 weeks, but then rapidly waned. In semen, it was detected at high levels and persisted for about 6 weeks.

“But despite the huge epidemics in Latin America, Puerto Rico, and the other Caribbean islands, there have been no cases of transfusion-related infections linked to RBC transfusions when plasma NAT screening was negative,” said Dr. Stone. “So we are tentatively confirming that red cell–associated virus is not infectious and that plasma NAT screening is likely sufficient.”

The authors point out that RNA persistence has been reported in whole blood long after the virus cleared from plasma and therefore have raised concerns about the risk of transfusion-related viral transmission. The goal of the current study was to characterize the dynamics of infection using donors who were infected with Zika virus.

To date there are 56 donors enrolled in the study, primarily male and from Puerto Rico. Most of them are also positive for dengue fever, Dr. Stone pointed out. “The epidemic in Puerto Rico reached peak in June 2016 but has very little activity this year.”

Plasma and RBCs were collected from index donations, while blood, urine, saliva, and semen samples were collected prospectively at weeks 1, 3, 6, 12, and 24 following index donations. Blood compartments and body fluids were tested for Zika RNA by real time reverse transcription polymerase chain reaction testing, and plasma samples were tested for Zika-specific immunoglobulin M and immunoglobulin G antibodies.

In plasma, Zika virus RNA rapidly decreased after index donations but persisted for up to 3 months in RBCs and whole blood. In peripheral blood mononuclear cells, Zika virus was detected intermittently at low levels but waned by 3 months. In peripheral blood mononuclear cells, Zika RNA was detected in 5.9% (17 samples) at 121-196 days.

Among donors who entered the study while in the acute preseroconversion stage of infection, 65% developed Zika virus symptoms at 1 week post index donation, compared with 30% of donors detected after seroconversion.

The study was funded by the U.S. Department of Health & Human Services.

SOURCE: Stone M et al. AABB 2017 Abstract C9-A01AC.

SAN DIEGO – Zika virus can persist in blood components for several months, long after it is no longer detectable in plasma and other body fluids, based on data reported at the annual meeting of the American Association of Blood Banks.

The presence of Zika virus in plasma declined rapidly following donation, but could be detected in red blood cells (RBCs) and whole blood for up to 3 months. In addition, the virus was also detected intermittently in peripheral blood mononuclear cells (PBMCs) at low levels after clearance from plasma.

“There was longer persistence of Zika RNA in whole blood and RBC blood components than in plasma and other body fluids. It was detected at high levels and persists for about 6 weeks,” Mars Stone, PhD said in presenting the findings.

The findings were based on 2016 data collected in Puerto Rico, which began screening blood donations for Zika virus RNA under an investigational protocol by using a nucleic acid test; they began doing so as a result of guidance from the U.S. Food and Drug Administration. Approximately 350 confirmed infected – that is, nucleic acid test positive (NAT+) – donations were detected through December 2016.

The FDA approved the cobas Zika test used in the study on October 5. Intended for use by blood collection establishments to detect Zika virus in blood donations, the test is manufactured by Roche Molecular Systems. Dr. Stone is an employee of Blood Systems Research Institute, a confirmatory laboratory for Roche.

Of the 52,942 donations collected between April 3 and Dec. 31, 352 were reactive for ZIKV RNA. Plasma from blood donors was screened by individual donation NAT for the presence of ZIKV RNA with the cobas Zika test. At an interval of between 57 and 120 days, no Zika RNA was found in 350 samples of plasma, but it was found in 38.2% (34 samples) of RBCs and 40.0% (35 samples) of whole blood.

In urine and saliva, the virus was detected in high levels at 1-2 weeks, but then rapidly waned. In semen, it was detected at high levels and persisted for about 6 weeks.

“But despite the huge epidemics in Latin America, Puerto Rico, and the other Caribbean islands, there have been no cases of transfusion-related infections linked to RBC transfusions when plasma NAT screening was negative,” said Dr. Stone. “So we are tentatively confirming that red cell–associated virus is not infectious and that plasma NAT screening is likely sufficient.”

The authors point out that RNA persistence has been reported in whole blood long after the virus cleared from plasma and therefore have raised concerns about the risk of transfusion-related viral transmission. The goal of the current study was to characterize the dynamics of infection using donors who were infected with Zika virus.

To date there are 56 donors enrolled in the study, primarily male and from Puerto Rico. Most of them are also positive for dengue fever, Dr. Stone pointed out. “The epidemic in Puerto Rico reached peak in June 2016 but has very little activity this year.”

Plasma and RBCs were collected from index donations, while blood, urine, saliva, and semen samples were collected prospectively at weeks 1, 3, 6, 12, and 24 following index donations. Blood compartments and body fluids were tested for Zika RNA by real time reverse transcription polymerase chain reaction testing, and plasma samples were tested for Zika-specific immunoglobulin M and immunoglobulin G antibodies.

In plasma, Zika virus RNA rapidly decreased after index donations but persisted for up to 3 months in RBCs and whole blood. In peripheral blood mononuclear cells, Zika virus was detected intermittently at low levels but waned by 3 months. In peripheral blood mononuclear cells, Zika RNA was detected in 5.9% (17 samples) at 121-196 days.

Among donors who entered the study while in the acute preseroconversion stage of infection, 65% developed Zika virus symptoms at 1 week post index donation, compared with 30% of donors detected after seroconversion.

The study was funded by the U.S. Department of Health & Human Services.

SOURCE: Stone M et al. AABB 2017 Abstract C9-A01AC.

SAN DIEGO – Zika virus can persist in blood components for several months, long after it is no longer detectable in plasma and other body fluids, based on data reported at the annual meeting of the American Association of Blood Banks.

The presence of Zika virus in plasma declined rapidly following donation, but could be detected in red blood cells (RBCs) and whole blood for up to 3 months. In addition, the virus was also detected intermittently in peripheral blood mononuclear cells (PBMCs) at low levels after clearance from plasma.

“There was longer persistence of Zika RNA in whole blood and RBC blood components than in plasma and other body fluids. It was detected at high levels and persists for about 6 weeks,” Mars Stone, PhD said in presenting the findings.

The findings were based on 2016 data collected in Puerto Rico, which began screening blood donations for Zika virus RNA under an investigational protocol by using a nucleic acid test; they began doing so as a result of guidance from the U.S. Food and Drug Administration. Approximately 350 confirmed infected – that is, nucleic acid test positive (NAT+) – donations were detected through December 2016.

The FDA approved the cobas Zika test used in the study on October 5. Intended for use by blood collection establishments to detect Zika virus in blood donations, the test is manufactured by Roche Molecular Systems. Dr. Stone is an employee of Blood Systems Research Institute, a confirmatory laboratory for Roche.

Of the 52,942 donations collected between April 3 and Dec. 31, 352 were reactive for ZIKV RNA. Plasma from blood donors was screened by individual donation NAT for the presence of ZIKV RNA with the cobas Zika test. At an interval of between 57 and 120 days, no Zika RNA was found in 350 samples of plasma, but it was found in 38.2% (34 samples) of RBCs and 40.0% (35 samples) of whole blood.

In urine and saliva, the virus was detected in high levels at 1-2 weeks, but then rapidly waned. In semen, it was detected at high levels and persisted for about 6 weeks.

“But despite the huge epidemics in Latin America, Puerto Rico, and the other Caribbean islands, there have been no cases of transfusion-related infections linked to RBC transfusions when plasma NAT screening was negative,” said Dr. Stone. “So we are tentatively confirming that red cell–associated virus is not infectious and that plasma NAT screening is likely sufficient.”

The authors point out that RNA persistence has been reported in whole blood long after the virus cleared from plasma and therefore have raised concerns about the risk of transfusion-related viral transmission. The goal of the current study was to characterize the dynamics of infection using donors who were infected with Zika virus.

To date there are 56 donors enrolled in the study, primarily male and from Puerto Rico. Most of them are also positive for dengue fever, Dr. Stone pointed out. “The epidemic in Puerto Rico reached peak in June 2016 but has very little activity this year.”

Plasma and RBCs were collected from index donations, while blood, urine, saliva, and semen samples were collected prospectively at weeks 1, 3, 6, 12, and 24 following index donations. Blood compartments and body fluids were tested for Zika RNA by real time reverse transcription polymerase chain reaction testing, and plasma samples were tested for Zika-specific immunoglobulin M and immunoglobulin G antibodies.

In plasma, Zika virus RNA rapidly decreased after index donations but persisted for up to 3 months in RBCs and whole blood. In peripheral blood mononuclear cells, Zika virus was detected intermittently at low levels but waned by 3 months. In peripheral blood mononuclear cells, Zika RNA was detected in 5.9% (17 samples) at 121-196 days.

Among donors who entered the study while in the acute preseroconversion stage of infection, 65% developed Zika virus symptoms at 1 week post index donation, compared with 30% of donors detected after seroconversion.

The study was funded by the U.S. Department of Health & Human Services.

SOURCE: Stone M et al. AABB 2017 Abstract C9-A01AC.

Clinical question: Is alcohol septal ablation (ASA) safe in younger patients with obstructive hypertrophic cardiomyopathy (HCM)?

Background: ASA is a class III recommendation for younger patients when myectomy is a viable option. This recommendation was based on the lack of evidence for younger patients whereas myectomy already was proven to be safe and effective.

Dr. Setji is a hospitalist and medical director, Duke University Hospital.

Clinical question: Is alcohol septal ablation (ASA) safe in younger patients with obstructive hypertrophic cardiomyopathy (HCM)?

Background: ASA is a class III recommendation for younger patients when myectomy is a viable option. This recommendation was based on the lack of evidence for younger patients whereas myectomy already was proven to be safe and effective.

Dr. Setji is a hospitalist and medical director, Duke University Hospital.

Clinical question: Is alcohol septal ablation (ASA) safe in younger patients with obstructive hypertrophic cardiomyopathy (HCM)?

Background: ASA is a class III recommendation for younger patients when myectomy is a viable option. This recommendation was based on the lack of evidence for younger patients whereas myectomy already was proven to be safe and effective.

Dr. Setji is a hospitalist and medical director, Duke University Hospital.

Starting in 2018, skilled nursing facilities (SNFs), like acute care hospitals before them, will be subject to a penalty of up to 2% of their Medicare reimbursement for posting higher-than-average rates of hospital readmissions.

The Protecting Access to Medicare Act of 2014 established a value-based purchasing component for SNFs, including incentives for high-performing facilities and a measure for all-cause, all-condition readmissions to any hospital from the SNF within 30 days following hospital discharge – designed to recognize and reward, or punish, facilities’ performance on preventing unnecessary readmissions. Public reporting of SNF quality data, including readmission rates, started in October 2017. Penalties follow a year later. Some patients’ readmissions could trigger penalties for both the hospital and the SNF.

According to 2010 data, 23.5% of patients discharged from acute care hospitals to SNFs were readmitted to the hospital within 30 days, at a financial cost of $10,362 per readmission or $4.34 billion per year.¹ Seventy eight percent of these readmissions were labeled avoidable. More recent evidence suggests that hospitalization rates for dual-eligible patients living in long-term care facilities decreased by 31% between 2010 and 2015.²As increasing numbers of hospitalists spend some or all of their work week in post-acute care settings, how will the SNF readmission penalty affect their relationships with post-acute facilities?

The hospitalist’s role in post-acute care

Hospitalists who work in post-acute care typically make scheduled, billable medical visits to patients in long-term care facilities, and may also take on roles such as facility medical director or contribute to quality improvement. Relationships may be initiated by a facility seeking more medical coverage, by a hospitalist group seeking additional work or an ability to impact on the post-acute care delivered to hospital patients discharged to the facility, or by health systems, health plans, or accountable care organizations seeking to better manage the quality of care transitions for their beneficiaries.

What happens in post-acute care

Cari Levy, MD, PhD, who does hospital coverage and post-acute care for a number of facilities and home health agencies in the Denver area, calls the changes coming to SNFs a thrilling time for post-acute care.

“Suddenly medical professionals care about what happens in the post-acute world,” she said. “Everyone is now looking at the same measures. If this works the way it should, there would be a lot more mutual respect between providers.”

SNFs that are concerned about their readmissions rates will want to do root cause analysis to figure out what’s going on, Dr. Levy said. “Maybe the doctor didn’t do a good assessment. Maybe it was just a tough case. Once you start talking, you’ll develop systems to help everyone responsible. Hospitalists can be part of that conversation,” she said.

Opportunities from reforms

Robert Burke, MD, FHM, assistant chief of Hospital Medicine at the Denver VA Medical Center, is lead author of a study in the Journal of Hospital Medicine highlighting implications and opportunities from reforms in post-acute care.³ Hospitalists may not appreciate that post-acute care is poised to undergo transformative change from the recently legislated reforms, opening opportunities for hospitalists to improve health care value by improving transitions of care, he noted.

References

1. Mor V et al. The revolving door of rehospitalization from skilled nursing facilities. Health Aff (Millwood). 2010 Jan-Feb;29(1):57-64.

2. Brennan N et al. Data Brief: Sharp reduction in avoidable hospitalizations among long-term care facility residents. The CMS Blog, 2017 Jan 17.

3. Burke RE et al. Post-acute care reform: Implications and opportunities for hospitalists. J Hosp Med. 2017 Jan;12(1);46-51.

Starting in 2018, skilled nursing facilities (SNFs), like acute care hospitals before them, will be subject to a penalty of up to 2% of their Medicare reimbursement for posting higher-than-average rates of hospital readmissions.

The Protecting Access to Medicare Act of 2014 established a value-based purchasing component for SNFs, including incentives for high-performing facilities and a measure for all-cause, all-condition readmissions to any hospital from the SNF within 30 days following hospital discharge – designed to recognize and reward, or punish, facilities’ performance on preventing unnecessary readmissions. Public reporting of SNF quality data, including readmission rates, started in October 2017. Penalties follow a year later. Some patients’ readmissions could trigger penalties for both the hospital and the SNF.

According to 2010 data, 23.5% of patients discharged from acute care hospitals to SNFs were readmitted to the hospital within 30 days, at a financial cost of $10,362 per readmission or $4.34 billion per year.¹ Seventy eight percent of these readmissions were labeled avoidable. More recent evidence suggests that hospitalization rates for dual-eligible patients living in long-term care facilities decreased by 31% between 2010 and 2015.²As increasing numbers of hospitalists spend some or all of their work week in post-acute care settings, how will the SNF readmission penalty affect their relationships with post-acute facilities?

The hospitalist’s role in post-acute care

Hospitalists who work in post-acute care typically make scheduled, billable medical visits to patients in long-term care facilities, and may also take on roles such as facility medical director or contribute to quality improvement. Relationships may be initiated by a facility seeking more medical coverage, by a hospitalist group seeking additional work or an ability to impact on the post-acute care delivered to hospital patients discharged to the facility, or by health systems, health plans, or accountable care organizations seeking to better manage the quality of care transitions for their beneficiaries.

What happens in post-acute care

Cari Levy, MD, PhD, who does hospital coverage and post-acute care for a number of facilities and home health agencies in the Denver area, calls the changes coming to SNFs a thrilling time for post-acute care.

“Suddenly medical professionals care about what happens in the post-acute world,” she said. “Everyone is now looking at the same measures. If this works the way it should, there would be a lot more mutual respect between providers.”

SNFs that are concerned about their readmissions rates will want to do root cause analysis to figure out what’s going on, Dr. Levy said. “Maybe the doctor didn’t do a good assessment. Maybe it was just a tough case. Once you start talking, you’ll develop systems to help everyone responsible. Hospitalists can be part of that conversation,” she said.

Opportunities from reforms

Robert Burke, MD, FHM, assistant chief of Hospital Medicine at the Denver VA Medical Center, is lead author of a study in the Journal of Hospital Medicine highlighting implications and opportunities from reforms in post-acute care.³ Hospitalists may not appreciate that post-acute care is poised to undergo transformative change from the recently legislated reforms, opening opportunities for hospitalists to improve health care value by improving transitions of care, he noted.

References

1. Mor V et al. The revolving door of rehospitalization from skilled nursing facilities. Health Aff (Millwood). 2010 Jan-Feb;29(1):57-64.

2. Brennan N et al. Data Brief: Sharp reduction in avoidable hospitalizations among long-term care facility residents. The CMS Blog, 2017 Jan 17.

3. Burke RE et al. Post-acute care reform: Implications and opportunities for hospitalists. J Hosp Med. 2017 Jan;12(1);46-51.

Starting in 2018, skilled nursing facilities (SNFs), like acute care hospitals before them, will be subject to a penalty of up to 2% of their Medicare reimbursement for posting higher-than-average rates of hospital readmissions.

The Protecting Access to Medicare Act of 2014 established a value-based purchasing component for SNFs, including incentives for high-performing facilities and a measure for all-cause, all-condition readmissions to any hospital from the SNF within 30 days following hospital discharge – designed to recognize and reward, or punish, facilities’ performance on preventing unnecessary readmissions. Public reporting of SNF quality data, including readmission rates, started in October 2017. Penalties follow a year later. Some patients’ readmissions could trigger penalties for both the hospital and the SNF.

According to 2010 data, 23.5% of patients discharged from acute care hospitals to SNFs were readmitted to the hospital within 30 days, at a financial cost of $10,362 per readmission or $4.34 billion per year.¹ Seventy eight percent of these readmissions were labeled avoidable. More recent evidence suggests that hospitalization rates for dual-eligible patients living in long-term care facilities decreased by 31% between 2010 and 2015.²As increasing numbers of hospitalists spend some or all of their work week in post-acute care settings, how will the SNF readmission penalty affect their relationships with post-acute facilities?

The hospitalist’s role in post-acute care

Hospitalists who work in post-acute care typically make scheduled, billable medical visits to patients in long-term care facilities, and may also take on roles such as facility medical director or contribute to quality improvement. Relationships may be initiated by a facility seeking more medical coverage, by a hospitalist group seeking additional work or an ability to impact on the post-acute care delivered to hospital patients discharged to the facility, or by health systems, health plans, or accountable care organizations seeking to better manage the quality of care transitions for their beneficiaries.

What happens in post-acute care

Cari Levy, MD, PhD, who does hospital coverage and post-acute care for a number of facilities and home health agencies in the Denver area, calls the changes coming to SNFs a thrilling time for post-acute care.

“Suddenly medical professionals care about what happens in the post-acute world,” she said. “Everyone is now looking at the same measures. If this works the way it should, there would be a lot more mutual respect between providers.”

SNFs that are concerned about their readmissions rates will want to do root cause analysis to figure out what’s going on, Dr. Levy said. “Maybe the doctor didn’t do a good assessment. Maybe it was just a tough case. Once you start talking, you’ll develop systems to help everyone responsible. Hospitalists can be part of that conversation,” she said.

Opportunities from reforms

Robert Burke, MD, FHM, assistant chief of Hospital Medicine at the Denver VA Medical Center, is lead author of a study in the Journal of Hospital Medicine highlighting implications and opportunities from reforms in post-acute care.³ Hospitalists may not appreciate that post-acute care is poised to undergo transformative change from the recently legislated reforms, opening opportunities for hospitalists to improve health care value by improving transitions of care, he noted.

References

1. Mor V et al. The revolving door of rehospitalization from skilled nursing facilities. Health Aff (Millwood). 2010 Jan-Feb;29(1):57-64.

2. Brennan N et al. Data Brief: Sharp reduction in avoidable hospitalizations among long-term care facility residents. The CMS Blog, 2017 Jan 17.

3. Burke RE et al. Post-acute care reform: Implications and opportunities for hospitalists. J Hosp Med. 2017 Jan;12(1);46-51.

SAN DIEGO – The presence of Corynebacterium in the gut microbiome of people with two G alleles at the rs356219 single nucleotide polymorphism locus of the alpha-synuclein gene was associated with 100% probability of having Parkinson’s disease in a study conducted by the NeuroGenetics Research Consortium.

If the finding is replicated, it means that Corynebacterium is the trigger for Parkinson’s disease (PD) in people with the GG genotype. The GG signature at rs356219 is the strongest genetic risk factor for PD identified to date, but it’s not necessarily strong enough to cause the disease on its own. “It definitely needs a trigger,” and there’s a good chance that Corynebacterium is it, said senior investigator Haydeh Payami, PhD, professor of neurology and genomics at the University of Alabama, Birmingham.

Kuo Chun Hung/Thinkstock

[email protected]

SOURCE: Wallen Z et al. ANA 2017 abstract number S268

SAN DIEGO – The presence of Corynebacterium in the gut microbiome of people with two G alleles at the rs356219 single nucleotide polymorphism locus of the alpha-synuclein gene was associated with 100% probability of having Parkinson’s disease in a study conducted by the NeuroGenetics Research Consortium.

If the finding is replicated, it means that Corynebacterium is the trigger for Parkinson’s disease (PD) in people with the GG genotype. The GG signature at rs356219 is the strongest genetic risk factor for PD identified to date, but it’s not necessarily strong enough to cause the disease on its own. “It definitely needs a trigger,” and there’s a good chance that Corynebacterium is it, said senior investigator Haydeh Payami, PhD, professor of neurology and genomics at the University of Alabama, Birmingham.

Kuo Chun Hung/Thinkstock

[email protected]

SOURCE: Wallen Z et al. ANA 2017 abstract number S268

SAN DIEGO – The presence of Corynebacterium in the gut microbiome of people with two G alleles at the rs356219 single nucleotide polymorphism locus of the alpha-synuclein gene was associated with 100% probability of having Parkinson’s disease in a study conducted by the NeuroGenetics Research Consortium.

If the finding is replicated, it means that Corynebacterium is the trigger for Parkinson’s disease (PD) in people with the GG genotype. The GG signature at rs356219 is the strongest genetic risk factor for PD identified to date, but it’s not necessarily strong enough to cause the disease on its own. “It definitely needs a trigger,” and there’s a good chance that Corynebacterium is it, said senior investigator Haydeh Payami, PhD, professor of neurology and genomics at the University of Alabama, Birmingham.

Kuo Chun Hung/Thinkstock

[email protected]

SOURCE: Wallen Z et al. ANA 2017 abstract number S268