Six Key Approaches in Open Society Foundations' Support for Global Palliative Care Development.

CONTEXT: Between 1998 and 2021, the Open Society Foundations (OSF) network invested around US$50 million in supporting the emerging field of palliative care worldwide, funding different approaches and interventions to advance its objective of putting palliative care on the global public health agenda. OBJECTIVE: To describe six approaches that were instrumental to the successes of Open Society Foundations' support in building the global field of palliative care. A robust discussion of lessons learnt is unfortunately not possible because Open Society Foundations did not commission a rigorous evaluation of the impacts of its investments. METHODS: This article describes these six approaches: Investing in versatile palliative care leaders at national and regional level; investing in palliative care champions within the OSF network; proactively engaging the World Health Organization (WHO) in efforts to promote palliative care; developing tools and skills to improve palliative care financing; using a human rights-based approach; and supporting self-advocacy by people with palliative care needs. RESULTS: Deep, long-term investments in national and regional champions from the palliative care community and OSF's own network built palliative care leaders with well-rounded skills, knowledge and opportunities to develop their own networks. The active engagement and involvement of the WHO in efforts to advance palliative care enhanced the credibility of palliative care as a discipline as well its champions, whereas the human rights approach resulted in more diverse strategies to overcome barriers to palliative care. The focus on palliative care financing and self-advocacy showed significant promise for impact. DISCUSSION: The approaches and strategies described helped a nascent palliative care field develop into a health service that is increasingly integrated into public health systems. Other funders and national governments can build on OSF's long term support for the palliative care field and support further integration of palliative care within public health to increase access.

Redefining Palliative Care-A New Consensus-Based Definition.

CONTEXT: The International Association for Hospice and Palliative Care developed a consensus-based definition of palliative care (PC) that focuses on the relief of serious health-related suffering, a concept put forward by the Lancet Commission Global Access to Palliative Care and Pain Relief. OBJECTIVE: The main objective of this article is to present the research behind the new definition. METHODS: The three-phased consensus process involved health care workers from countries in all income levels. In Phase 1, 38 PC experts evaluated the components of the World Health Organization definition and suggested new/revised ones. In Phase 2, 412 International Association for Hospice and Palliative Care members in 88 countries expressed their level of agreement with the suggested components. In Phase 3, using results from Phase 2, the expert panel developed the definition. RESULTS: The consensus-based definition is as follows: Palliative care is the active holistic care of individuals across all ages with serious health-related suffering due to severe illness and especially of those near the end of life. It aims to improve the quality of life of patients, their families and their caregivers. The definition includes a number of bullet points with additional details as well as recommendations for governments to reduce barriers to PC. CONCLUSION: Participants had significantly different perceptions and interpretations of PC. The greatest challenge faced by the core group was trying to find a middle ground between those who think that PC is the relief of all suffering and those who believe that PC describes the care of those with a very limited remaining life span.

End of life: Expert care and support, not physician-hastened death.

In legal physician-hastened death, a physician prescribes medication with the primary intent of causing the death of a willing terminally ill patient. This practice differs radically from palliative sedation, intended to relieve a patient's suffering rather than cause a patient's death. In this position paper, we argue that the practice of physician-hastened death is contrary to the interests of patients, their families, and the sound ethical practice of medicine. Therefore, the American Academy of Neurology should advise its members against this practice, as it had done until 2018.

Primary Care Women's Health Screening: A Case Study of a Community Engaged Human Centered Design Approach to Enhancing the Screening Process.

PURPOSE: To apply a Human Centered Design (HCD) approach to co-designing a comprehensive women's health screening tool with community partners. DESCRIPTION: Evidenced-based health screenings for behaviors and risks are important tools in primary health care and disease prevention, especially for women. However, numerous barriers limit the effective implementation of comprehensive health screenings, and often lead to excluding important risks such as intimate partner violence (IPV). Utilizing a human centered design approach (HCD), Mountain Area Health Education Center (MAHEC, NC USA) developed a community co-designed 9-topic health screening for women. Key end-users were recruited to participate in the design process, including women who identified IPV as a health issue in their community, Spanish speaking women, domestic violence program organizers, and MAHEC staff. ASSESSMENT: A total of 21 participants collaborated during three design sessions on two specific goals: 1) creating a comprehensive women's health screening tool from the existing tools that were in use in our clinics at the time, and 2) incorporating IPV screening. Through the HCD sessions, participants highlighted the impact of what they termed "Triple T: time, trust and talk" on the effectiveness of women's health screening. CONCLUSION: Our co-designed women's health screening tool is a first step towards addressing screening barriers from both primary care provider's and community women's perspectives. Future research will explore the facilitators of and barriers to implementing the tools in different primary care settings. Future work should also more systematically examine whether and how screening processes may reinforce or contribute to women's feelings of being stereotyped, and how screening processes can be designed to avoid stereotype threat, which has the potential to reduce the effectiveness of screenings intended to promote women's health.

White Paper for Global Palliative Care Advocacy: Recommendations from a PAL-LIFE Expert Advisory Group of the Pontifical Academy for Life, Vatican City.

BACKGROUND: The Pontifical Academy for Life (PAV) is an academic institution of the Holy See (Vatican), which aims to develop and promote Catholic teachings on questions of biomedical ethics. Palliative care (PC) experts from around the world professing different faiths were invited by the PAV to develop strategic recommendations for the global development of PC ("PAL-LIFE group"). DESIGN: Thirteen experts in PC advocacy participated in an online Delphi process. In four iterative rounds, participants were asked to identify the most significant stakeholder groups and then propose for each, strategic recommendations to advance PC. Each round incorporated the feedback from previous rounds until consensus was achieved on the most important recommendations. In a last step, the ad hoc group was asked to rank the stakeholders' groups by order of importance on a 13-point scale and to propose suggestions for implementation. A cluster analysis provided a classification of the stakeholders in different levels of importance for PC development. RESULTS: Thirteen stakeholder groups and 43 recommendations resulted from the first round, and, of those, 13 recommendations were chosen as the most important (1 for each stakeholder group). Five groups had higher scores. The recommendation chosen for these top 5 groups were as follows: (1) Policy makers: Ensure universal access to PC; (2) Academia: Offer mandatory PC courses to undergraduates; (3) Healthcare workers: PC professionals should receive adequate certification; (4) Hospitals and healthcare centers: Every healthcare center should ensure access to PC medicines; and (5) PC associations: National Associations should be effective advocates and work with their governments in the process of implementing international policy framework. A recommendation for each of the remaining eight groups is also presented. DISCUSSION: This white paper represents a position statement of the PAV developed through a consensus process in regard to advocacy strategies for the advancement of PC in the world.

World Health Organization Public Health Model: A Roadmap for Palliative Care Development.

The Open Society Foundation's International Palliative Care Initiative (IPCI) began to support palliative care development in Central and Eastern Europe and the Former Soviet Union in 1999. Twenty-five country representatives were invited to discuss the need for palliative care in their countries and to identify key areas that should be addressed to improve the care of adults and children with life-limiting illnesses. As a public health concern, progress in palliative care requires integration into health policy, education and training of health care professionals, availability of essential pain relieving medications, and health care services. IPCI created the Palliative Care Roadmap to serve as a model for government and/or nongovernment organizations to use to frame the necessary elements and steps for palliative care integration. The roadmap includes the creation of multiple Ministry of Health-approved working groups to address: palliative care inclusion in national health policy, legislation, and finance; availability of essential palliative care medications, especially oral opioids; education and training of health care professionals; and the implementation of palliative care services at home or in inpatient settings for adults and children. Each working group is tasked with developing a pathway with multiple signposts as indicators of progress made. The roadmap may be entered at different signposts depending upon the state of palliative care development in the country. The progress of the working groups often takes place simultaneously but at variable rates. Based on our experience, the IPCI Roadmap is one possible framework for palliative care development in resource constrained countries but requires both health care professional engagement and political will for progress to be made.

Leadership Development Initiative: Growing Global Leaders Advancing Palliative Care.

The International Palliative Care Leadership Development Initiative (LDI) was a model demonstration project that aimed to expand the global network of palliative care leaders in low- and moderate-resource countries who are well positioned to apply their new leadership skills. Thirty-nine palliative medicine physicians from 25 countries successfully completed the two-year curriculum that included three thematic residential courses, mentorship, and site visits by senior global palliative care leaders and personal projects to apply their new leadership skills. The focus on self-reflection, leadership behaviors and practices, strategic planning, high-level communication, and teaching skills led to significant personal and professional transformation among the participants, mentors, and the LDI team. The resulting residential course curriculum and the personal leadership stories and biosketches of the leaders are now available open access at IPCRC.net. Already, within their first-year postgraduation, the leaders are using their new leadership skills to grow palliative care capacity through significant changes in policy, improved opioid/other medication availability, new and enhanced educational curricula and continuing education activities, and development/expansion of palliative care programs in their organizations and regions. We are not aware of another palliative care initiative that achieves the global reach and ripple effect that LDI has produced.

The International Palliative Care Initiative.

This journal series describes the Open Society Foundation's International Palliative Care Initiative (IPCI) and the work of its national, regional, and international foundations and grantees to advance and develop palliative care globally. It provides examples of funding initiatives of IPCI honoring both grass roots and elite strategies of IPCI to integrate palliative care into national and international health policy based on a human rights approach.

Development and Validation of an Algorithm to Identify Patients with Multiple Myeloma Using Administrative Claims Data.

PURPOSE: The objective was to expand on prior work by developing and validating a new algorithm to identify multiple myeloma (MM) patients in administrative claims. METHODS: Two files were constructed to select MM cases from MarketScan Oncology Electronic Medical Records (EMR) and controls from the MarketScan Primary Care EMR during January 1, 2000-March 31, 2014. Patients were linked to MarketScan claims databases, and files were merged. Eligible cases were age ≥18, had a diagnosis and visit for MM in the Oncology EMR, and were continuously enrolled in claims for ≥90 days preceding and ≥30 days after diagnosis. Controls were age ≥18, had ≥12 months of overlap in claims enrollment (observation period) in the Primary Care EMR and ≥1 claim with an ICD-9-CM diagnosis code of MM (203.0×) during that time. Controls were excluded if they had chemotherapy; stem cell transplant; or text documentation of MM in the EMR during the observation period. A split sample was used to develop and validate algorithms. A maximum of 180 days prior to and following each MM diagnosis was used to identify events in the diagnostic process. Of 20 algorithms explored, the baseline algorithm of 2 MM diagnoses and the 3 best performing were validated. Values for sensitivity, specificity, and positive predictive value (PPV) were calculated. CONCLUSION: Three claims-based algorithms were validated with ~10% improvement in PPV (87-94%) over prior work (81%) and the baseline algorithm (76%) and can be considered for future research. Consistent with prior work, it was found that MM diagnoses before and after tests were needed.

Prescribing Patterns of Oral Antineoplastic Therapies Observed in the Treatment of Patients With Advanced Prostate Cancer Between 2012 and 2014: Results of an Oncology EMR Analysis.

PURPOSE: The purpose of this study was to examine, using a US electronic medical records (EMR) database, the clinical characteristics and real-world treatment sequences in men with advanced prostate cancer who initiated treatment with abiraterone acetate or enzalutamide. METHODS: This retrospective, observational study evaluated adult male patients with a diagnosis of prostate cancer (International Classification of Diseases, Ninth Revision, Clinical Modification code 185) in the EMR database between July 1, 2011, and March 31, 2014, who had initiated first-line treatment with abiraterone acetate or enzalutamide between September 1, 2012, and March 31, 2014. The first record for a patient initiating abiraterone acetate or enzalutamide was the index date. Patients had 6 months of pre-index medical record history and a variable length follow-up period, extending from the index date to the end of medical record data availability or date of the end of the study (March 31, 2014). The sequence of first- and second-line therapies for advanced prostate cancer therapy was reported. FINDINGS: A total of 809 patients met study inclusion and exclusion criteria. This study found that the majority of patients who initiated treatment with either abiraterone acetate or enzalutamide between September 1, 2012, and March 31, 2014, received a single line of therapy (72%); abiraterone acetate was the most common first-line treatment (74% of first-line patients). A subset of patients treated first-line with either abiraterone acetate or enzalutamide were transitioned to an oral second-line agent (17% of first-line abiraterone acetate-treated patients transitioned to second-line enzalutamide, and 16% of first-line enzalutamide-treated patients transitioned to second-line abiraterone acetate). Chemotherapy with docetaxel was also a commonly observed second-line treatment selection, occurring in 8% of first-line abiraterone acetate-treated patients and in 7% of first-line enzalutamide-treated patients. IMPLICATIONS: This EMR study is among the first to present evidence of US physician practice prescribing patterns regarding initiation of oral antineoplastic agents and use of subsequent therapies in patients with advanced prostate cancer.

The interprofessional clinical experience: interprofessional education in the nursing home.

The interprofessional clinical experience (ICE) was designed to introduce trainees to the roles of different healthcare professionals, provide an opportunity to participate in an interprofessional team, and familiarize trainees with caring for older adults in the nursing home setting. Healthcare trainees from seven professions (dentistry, medicine, nursing, nutrition, occupational therapy, optometry and social work) participated in ICE. This program consisted of individual patient interviews followed by a team meeting to develop a comprehensive care plan. To evaluate the impact of ICE on attitudinal change, the UCLA Geriatric Attitudes Scale and a post-experience assessment were used. The post-experience assessment evaluated the trainees' perception of potential team members' roles and attitudes about interprofessional team care of the older adult. Attitudes toward interprofessional teamwork and the older adult were generally positive. ICE is a novel program that allows trainees across healthcare professions to experience interprofessional teamwork in the nursing home setting.

Current challenges in health economic modeling of cancer therapies: a research inquiry.

BACKGROUND: The demand for economic models that evaluate cancer treatments is increasing, as healthcare decision makers struggle for ways to manage their budgets while providing the best care possible to patients with cancer. Yet, after nearly 2 decades of cultivating and refining techniques for modeling the cost-effectiveness and budget impact of cancer therapies, serious methodologic and policy challenges have emerged that question the adequacy of economic modeling as a sound decision-making tool in oncology. OBJECTIVES: We sought to explore some of the contentious issues associated with the development and use of oncology economic models as informative tools in current healthcare decision-making. Our objective was to draw attention to these complex pharmacoeconomic concerns and to promote discussion within the oncology and health economics research communities. METHODS: Using our combined expertise in health economics research and economic modeling, we structured our inquiry around the following 4 questions: (1) Are economic models adequately addressing questions relevant to oncology decision makers; (2) What are the methodologic limitations of oncology economic models; (3) What guidelines are followed for developing oncology economic models; and (4) Is the evolution of oncology economic modeling keeping pace with treatment innovation? Within the context of each of these questions, we discuss issues related to the technical limitations of oncology modeling, the availability of adequate data for developing models, and the problems with how modeling analyses and results are presented and interpreted. DISCUSSION: There is general acceptance that economic models are good, essential tools for decision-making, but the practice of oncology and its rapidly evolving technologies present unique challenges that make assessing and demonstrating value especially complex. There is wide latitude for improvement in oncology modeling methodologies and how model results are presented and interpreted. CONCLUSION: Complex technical and data availability issues with oncology economic modeling pose serious concerns that need to be addressed. It is our hope that this article will provide a framework to guide future discourse on this important topic.

NF-κB activation-induced anti-apoptosis renders HER2-positive cells drug resistant and accelerates tumor growth.

UNLABELLED: Breast cancers with HER2 overexpression are sensitive to drugs targeting the receptor or its kinase activity. HER2-targeting drugs are initially effective against HER2-positive breast cancer, but resistance inevitably occurs. We previously found that NF-κB is hyperactivated in a subset of HER2-positive breast cancer cells and tissue specimens. In this study, we report that constitutively active NF-κB rendered HER2-positive cancer cells resistant to anti-HER2 drugs and cells selected for lapatinib resistance upregulated NF-κB. In both circumstances, cells were antiapoptotic and grew rapidly as xenografts. Lapatinib-resistant cells were refractory to HER2 and NF-κB inhibitors alone but were sensitive to their combination, suggesting a novel therapeutic strategy. A subset of NF-κB-responsive genes was overexpressed in HER2-positive and triple-negative breast cancers, and patients with this NF-κB signature had poor clinical outcome. Anti-HER2 drug resistance may be a consequence of NF-κB activation, and selection for resistance results in NF-κB activation, suggesting that this transcription factor is central to oncogenesis and drug resistance. Clinically, the combined targeting of HER2 and NF-κB suggests a potential treatment paradigm for patients who relapse after anti-HER2 therapy. Patients with these cancers may be treated by simultaneously suppressing HER2 signaling and NF-κB activation. IMPLICATIONS: The combination of an inhibitor of IκB kinase (IKK) inhibitor and anti-HER2 drugs may be a novel treatment strategy for drug-resistant human breast cancers.

A checklist for ascertaining study cohorts in oncology health services research using secondary data: report of the ISPOR oncology good outcomes research practices working group.

OBJECTIVES: The ISPOR Oncology Special Interest Group formed a working group at the end of 2010 to develop standards for conducting oncology health services research using secondary data. The first mission of the group was to develop a checklist focused on issues specific to selection of a sample of oncology patients using a secondary data source. METHODS: A systematic review of the published literature from 2006 to 2010 was conducted to characterize the use of secondary data sources in oncology and inform the leadership of the working group prior to the construction of the checklist. A draft checklist was subsequently presented to the ISPOR membership in 2011 with subsequent feedback from the larger Oncology Special Interest Group also incorporated into the final checklist. RESULTS: The checklist includes six elements: identification of the cancer to be studied, selection of an appropriate data source, evaluation of the applicability of published algorithms, development of custom algorithms (if needed), validation of the custom algorithm, and reporting and discussions of the ascertainment criteria. The checklist was intended to be applicable to various types of secondary data sources, including cancer registries, claims databases, electronic medical records, and others. CONCLUSIONS: This checklist makes two important contributions to oncology health services research. First, it can assist decision makers and reviewers in evaluating the quality of studies using secondary data. Second, it highlights methodological issues to be considered when researchers are constructing a study cohort from a secondary data source.

Prevalence of germline TP53 mutations in HER2+ breast cancer patients.

Breast cancer is the most frequent tumor in Li-Fraumeni syndrome (LFS), a rare inherited cancer syndrome associated with germline mutations in the TP53 gene. Recent data show that breast cancer in germline TP53 mutation carriers is commonly HER2+ (63-83 %). We assessed the prevalence of germline TP53 mutations in a cohort of women with HER2+ breast cancer diagnosed age ≤50 years. We identified blood specimens from 213 women with primary invasive HER2+ breast cancer age ≤50 years from a single center. Exon grouping analysis sequencing and multiplex ligation-dependent probe amplification techniques were used to screen for germline TP53 mutations. Among 213 women with HER2+ breast cancer age ≤50 years, 3 (ages at diagnosis 23, 32, 44 years) were found to carry a TP53 mutation (1.4 %, 95 % CI 0.3-4.1 %). ER/PR status was not uniform. Two TP53 carriers met Chompret criteria for LFS; none met classic LFS criteria. Although two-thirds of breast cancers in women with TP53 mutations are HER2+, we observed a low prevalence of germline TP53 mutations among unselected young women with HER2+ breast cancer. Given the potential clinical impact, consideration of germline TP53 testing should be given to young women with HER2+ breast cancer, especially if family cancer history is notable.

Palliative and end-of-life care in the global response to multidrug-resistant tuberculosis.

Multidrug-resistant (MDR) tuberculosis is costly, difficult to treat, and poses a global threat to tuberculosis control. The high burden of disease and treatment for patients, poor cure rates, and high mortality bring distress to patients, families, and caregivers. Despite guidance to improve treatment outcomes, little attention has been paid to palliative care of patients and families, such as for physical, psychosocial, social, and spiritual difficulties. An international expert symposium was convened to articulate an appropriate palliative care response for people with MDR tuberculosis. Several policies should be updated to ensure that palliative and end-of-life care is in place alongside treatment should cure be achieved, and to the end of life if not. Many services have been developed that exemplify integrated palliative care (ie, provided from within existing tuberculosis care). We recommend that existing expertise within palliative care can be used, which will improve management of problems such as dyspnoea, cachexia, and haemoptysis for patients across care settings, including at home, and enhance performance of control programmes.

Relationship between potential opioid-related adverse effects and hospital length of stay in patients receiving opioids after orthopedic surgery.

STUDY OBJECTIVE: To determine whether there is an association between opioid-related adverse effects and postoperative hospital length of stay (p-LOS). DESIGN: Retrospective medical record review. SETTING: Large academic medical center. PATIENTS: Random sample of 402 patients (mean age 60.2 yrs, 50.3% female) who underwent orthopedic spine, hip, knee, or shoulder surgery during 2007 and received opioids during or after the procedure. MEASUREMENTS AND MAIN RESULTS: Potential opioid-related adverse effects were identified by using established criteria. Bivariate and multivariate analyses (generalized linear regression model, log transformed) were used to identify predictors of p-LOS. The model also estimated the effect of specific types of adverse effects and adverse-effect combinations on p-LOS. Mean ± SD p-LOS was 3.0 ± 2.1 days; median oral morphine equivalent postoperative dose was 60 mg/day. More than half of the patients (54.2%) experienced one or more adverse effects, 25.6% experienced two or more adverse effects, and 7.2% experienced three or more adverse effects. The composite of nausea and vomiting was experienced by 36.1% of study patients, and 12.6% had at least one emesis episode. Constipation and confusion were documented in 6.5% and 3.7% of patients, respectively. Constipation (p<0.0001), emesis (p<0.001), and confusion (p<0.01) were associated with increased p-LOS after adjusting for other significant variables. Patients with constipation had an adjusted 49% (95% confidence interval [CI] 25-77%) longer p-LOS (additional 1.4 days) compared with patients without constipation. Emesis and confusion significantly increased p-LOS by 25% (95% CI 10-42%) and 38% (95% CI 11-72%), respectively. Incremental increases in p-LOS for patients with two adverse effects (p=0.02), three adverse effects (p<0.001), and four adverse effects (p<0.001) versus patients with no adverse effects were 15%, 40%, and 82%, respectively. CONCLUSION: Constipation, emesis, and confusion were associated with increased p-LOS in patients receiving opioids after orthopedic surgery. In addition, there was a significant linear relationship between the number of adverse effects/patient and increased p-LOS, and the strength of the association increased as the number of adverse effects increased. Although the opioid dosages and adverse-effect rates were typical, these findings reinforce the need to balance pain management with risk of events.