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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.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.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.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.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.

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. Mol Cancer Res; 12(3); 408–20. ©2013 AACR.

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PDF file - 669K, Figure S1. FACS sorting of HER2-enriched fraction of SKBR3 and analysis of same by FACS in parental derivatives. Figure S2. Inhibition of HER2 signaling by Lapatinib in SKR6 and SKR6LR cells. Figure S3. Xenograft histopathology. Figure S4. NF-κB DNA binding activity by electrophoretic mobility shift assay (EMSA). Figure S5. Geno Ontology (GO) terms for genes found in clusters II, III and IV from Figure 5B. Figure S6. Hypothesis: Constitutive activation of NF-kB accelerates tumor growth by evading drug sensitivity resulting in poor clinical outcome.

A growing number of nonmedical caregivers seek to improve dying in the United States. They call themselves end-of-life doulas, death midwives, soul guides, compassionate companions, and vigilers, among other names. These new faces at the bedside share a common goal of comforting the dying and their loved ones. Their work is both humanitarian and spiritual as they bring compassionate presence into the sacred space of dying. Thousands of individuals provide end-of-life caregiving through volunteer programs in hospitals, hospices, and community non-profits; hundreds more provide their services to clients for a fee. Using in-depth interviews and analysis of print and online materials, this article traces the development of nonmedical end-of-life caregiving from volunteer vigiling and companioning programs to the professionalization of end-of-life doulaing. Though professional doulas are in the media spotlight, this work began with volunteers who continue to provide most of the nonmedical end-of-life care support for the dying in the United States.

This special issue is a tribute to our mentor, colleague and friend, Gavril W. Pasternak, MD, PhD. Homage to the breadth and depth of his work (~ 450 publications) over a 40 career in pharmacology and medicine cannot be captured fully in one special issue, but the 22 papers collected herein represent seven of the topics near and dear to Gav’s heart, and the colleagues, friends and mentees who held him near to theirs. The seven themes include: (1) sites and mechanisms of opioid actions in vivo; (2) development of novel analgesic agents; (3) opioid tolerance, withdrawal and addiction: mechanisms and treatment; (4) opioid receptor splice variants; (5) novel research tools and approaches; (6) receptor signaling and crosstalk in vitro; and (7) mentorship. This introduction to the issue summarizes contributions and includes formal and personal remembrances of Gav that illustrate his personality, warmth, and dedication to making a difference in patient care and people’s lives.

Phenomenon: Physicians are under intense pressure to improve clinical productivity. High clinical load, limited availability, and decreased clinical efficiency are well-documented barriers to precepting medical students and threaten clinical productivity. In an era of increasing medical student enrollment, these barriers have already led to a decreased availability of clinical teachers and training sites across the United States. Improved preceptor satisfaction could have a great impact on recruitment and retention of medical student preceptors and is likely linked to changes in productivity. Curriculum structure could impact both preceptor productivity and satisfaction. Comparing productivity and satisfaction of physician preceptors teaching in longitudinal integrated clerkships (LICs) to those teaching in traditional block rotations (TBRs), or in both settings (LIC-TBR), could lead to a better understanding of the impact of curriculum structure on preceptor productivity and satisfaction. Approach: Data were collected through a quantitative cross-sectional survey of outpatient physician preceptors in North Carolina in 2017. Preceptor satisfaction and student influence on productivity-related aspects of practice were analyzed with bivariate chi-square statistics and multivariate logistic regression. Findings: Analyses included 338 physician preceptors: 79 LIC (23%), 50 LIC-TBR (15%), and 209 TBR preceptors (62%). LIC preceptors were more likely to indicate being "very satisfied" with precepting than either their LIC-TBR or TBR counterparts. There were no differences in perceived productivity-related aspects of practice across the different curricula, such as patient flow, income, or physician working hours. Logistic regressions controlling for potential confounding variables suggested that those teaching in LICs were almost 3 times more likely to be "very satisfied" relative to those teaching in LIC-TBR and TBR settings and that the negative influence of students on patient flow and physician working hours had an adverse effect on preceptor satisfaction. Insights: Preceptor satisfaction was high overall, though satisfaction was significantly higher among preceptors who teach in LICs. The perceived impact of students on clinical productivity was stable across the different curricula. In an era of increasing need for physician preceptors, the higher satisfaction of those who teach in LICs should be considered in curricular design and for preceptor recruitment and retention.

To apply a Human Centered Design (HCD) approach to co-designing a comprehensive women’s health screening tool with community partners. 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. 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. 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.

Purpose Closures of rural labor and delivery (L/D) units have prompted national and state-based efforts to assess the impact on birth outcomes. This study explores local effects of L/D closures in rural areas of North Carolina (NC). Methods This is a retrospective cohort study of birth outcomes of 4,065 women in 5 rural areas of NC with L/D unit closures between 2013 and 2017. Outcomes were abstracted from birth certificate data from the NC Vital Statistics Reporting System. Localized outcomes 1 year prior to L/D unit closure were compared with outcomes 1 and 2 years post closure, including: (1) birth location and demographics, (2) change in travel patterns for birth, and (3) birth outcomes, including rates of labor induction, cesarean deliveries, maternal morbidity, and neonatal outcomes. Findings Before closures, 25%-56% of deliveries occurred outside county of residence. Commercially insured and college-educated women were more likely to deliver out-of-area. Closures increased travel distance to delivery hospital an average of 7-27 miles. In 2 areas, cesarean delivery rates decreased despite an increase in labor inductions. There was also variability between areas in prenatal care adequacy and breastfeeding. Conclusions We found that L/D unit closures in rural NC disproportionately affected women on Medicaid. The impact showed area-specific variability, highlighting effects potentially masked by statewide or national analyses. Implications for future L/D closures would be eased by regional coordination and planning to mitigate negative effects, and state and national policies should address the excess burden placed on vulnerable populations.

Background: The International Association for Hospice and Palliative Care (IAHPC) 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. Aim: The objective of this paper 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 one, 38 PC experts evaluated the components of the World Health Organization (WHO) definition and suggested new/revised ones. In phase two, 412 IAHPC members in 88 countries expressed their level of agreement with the suggested components. In phase three, using results from phase two, the expert panel developed the definition. Results: The consensus-based definition is “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 palliative care. Conclusions: 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.

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 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.

Pain has always been an important part of human immunodeficiency virus (HIV) disease and its experience for patients. In this guideline, we review the types of chronic pain commonly seen among persons living with HIV (PLWH) and review the limited evidence base for treatment of chronic noncancer pain in this population. We also review the management of chronic pain in special populations of PLWH, including persons with substance use and mental health disorders. Finally, a general review of possible pharmacokinetic interactions is included to assist the HIV clinician in the treatment of chronic pain in this population. It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. The Infectious Diseases Society of American considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient’s individual circumstances.

Pain has always been an important part of human immunodeficiency virus (HIV) disease and its experience for patients. In this guideline, we review the types of chronic pain commonly seen among persons living with HIV (PLWH) and review the limited evidence base for treatment of chronic noncancer pain in this population. We also review the management of chronic pain in special populations of PLWH, including persons with substance use and mental health disorders. Finally, a general review of possible pharmacokinetic interactions is included to assist the HIV clinician in the treatment of chronic pain in this population.It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. The Infectious Diseases Society of American considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

Introduction: Despite evidence demonstrating that medications for opioid use disorder (OUD) reduce morbidity and mortality, the majority of patients do not receive treatment. The National Academies of Science call for more research exploring the patient9s perspective of treatment modalities to increase access to individualized, patient-centered care. We aim to build on existing literature by describing patient experiences treated for OUD in a rural family medicine setting. Methods: We employed a convenience sampling methodology to complete brief, structured interviews with thematic data analysis for 30 of 57 eligible patients receiving office-based opioid treatment (OBOT) in the primary care setting. Results: Participants9 experiences with OBOT were generally positive and shaped by societal structures and institutions, their life before treatment, their treatment history, and the kind of care they received in OBOT. Patients identified accessibility and privacy as advantages to receiving OBOT in primary care. Discussion: This research identifies ways providers can provide individualized and effective OUD treatment within the family medicine setting.

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.

Relying on in-depth interviews and the National Study of American Twentysomethings, this chapter describes the heterogeneous young adults who are religious unaffiliated. Known in the popular press as the Nones, most of these young adults were raised in a Christian religious tradition, which they now reject, but that does not mean they have no interest in religion. Some are anti-religious and many are disinterested, but others hold traditional beliefs in a personal God and in an afterlife while rejecting religious institutions. Still others create an eclectic spirituality that draws from many religious traditions. The chapter provides estimated proportions of Nones who are philosophical secularists, indifferent secularists, spiritual eclectics, and unaffiliated believers. This chapter examines the role of context in the fluid religious, spiritual, and secular identities of twentysomething Nones and reports on the values, behaviors, and confidence in social institutions of this growing population.

The story of Ted, a World War II sailor for the U.S. Navy, and his teenage bride, Dottie, opens the chapter, setting up the contrast with emerging adulthood today. Their early marriage, five children, and Ted’s living wage from work for the electric company represent an era long gone. Financial independence today requires dual incomes and years of preparation, pushing back marriage and parenthood nearly a decade. Despite these changes, the religious lives of American twentysomethings demonstrate stability more than change. Survey analysis of the project’s National Study of American Twentysomethings (2013) and the National Science Foundation’s General Social Survey (1972–2016) demonstrate a stable proportion of religious committed young adults—about 1 in 4, and a rise in religiously unaffiliated young adults —from the ranks of the semi-religious. Widespread prayer, participation in worship, favorable attitudes toward congregations, and frustration with angry “religious people” are among the chapter’s notable findings.

Chapter 5 explores the religious, spiritual, and secular lives of Evangelical twentysomethings, who account for 30% of all twentysomethings. Using congregational ethnographies of two Evangelical churches, this chapter describes why and how religiously active Evangelicals, which includes most Evangelicals, select a church to join. Relying on in-depth interviews, this chapter identifies what draws Evangelicals to church and what kinds of churches appeal to them. This chapter also describes the distinctive strategies deployed by Black and multiracial churches to attract young adults. Using the National Study of American Twentysomething findings, the chapter examines what distinguishes Active, Nominal, and Estranged Evangelical twentysomethings. In conclusion, this chapter closes with analysis of the similarities and differences among Evangelical, Mainline Protestant, and Catholic twentysomethings.

Four young adults with thoughtful religious, spiritual, and secular views are profiled. Maria, a devout Catholic Latina who is a graduate student in speech pathology; Jeremy, an enthusiastic Mainline Protestant whose gay and biracial identity left him wary of religion; Lee, an Evangelical convert who switched from a Chinese to a multiracial congregation; and Abby, who rejected the White middle-class Evangelicalism of her childhood for atheism and then adopted an eclectic spirituality. Emerging adulthood is then described, as is the book’s qualitative and survey methodology and its focus on 91% of American twentysomethings who identify as Catholic, Mainline Protestant, Evangelical, or religiously unaffiliated (i.e., Nones). The book’s seven scholarly contributions are stated and the next six chapters are introduced.

One out of 7 American twentysomethings affiliate with a Mainline denomination, and 33% of Mainline Protestant twentysomethings attend worship a couple of times monthly or more. Drawing from ethnographies of an arts-focused multiracial church, a small emerging church, and a Midwestern family church, this chapter describes why and how religiously active “Mainliners” seek out these church communities. Through analysis of in-depth interviews, it identifies what draws them to church when so many of their peers are wary of churches and what kinds of churches appeal to religiously active Mainliners. This chapter also describes the distinctive strategies deployed by Mainline congregations to attract young adults and how these differ in urban and Midwestern contexts. Then the chapter turns to results from our national survey of twentysomethings and applies the Active, Nominal, and Estranged typology to examine the religious, spiritual, and secular lives of Mainliner twentysomethings.

Few realize how much Americans’ journey through their twenties has changed during the past half-century or understand how incorrect popular assumptions about young adults’ religious, spiritual, and secular lives are. Today’s twentysomethings have been labelled the “lost generation”—for their presumed inability to identify and lead fulfilling lives, “kidults”—for their alleged refusal to “grow up” and accept adult responsibilities, and the “least religious generation”—for their purported disinterest in religion and spirituality. These characterizations are not only unflattering, they are deeply flawed. The Twentysomething Soul tells an optimistic story about American twentysomethings. Drawing on hundreds of interviews and a survey of thousands across America, it introduces readers to the full spectrum of American young adults, many of whom live purposefully, responsibly, and reflectively. Some prioritize faith and spirituality. Others reject their childhood religion to explore alternatives and practice a personal spirituality. Still others sideline religion and spirituality until their lives get settled or reject organized religion completely. There is change occurring in the religious and spiritual lives of young adults, but little of it is among the 1 in 4 American twentysomethings who have consistently prioritized religious commitment during the past half-century. The change is rather among the now 3 in 10 young adults who, though intentionally unaffiliated with religion, affirm a variety of religious, spiritual, and secular beliefs. The Twentysomething Soul will change the way readers view contemporary young adults, giving an accurate—and refreshing—understanding of their religious, spiritual, and secular lives.

Two out of 5 Catholic twentysomethings, or 3.2 million American young adults, attend worship a couple of times monthly or more. If all 3.2 million were to gather in the same place, they would become America’s third-largest city. This chapter focuses on these religiously Active Catholics, drawing from ethnographies of a multigenerational mega-parish, a Catholic student center at a non-Catholic university, and two diocesan young adult ministries. This chapter describes how religiously active twentysomethings find these congregations and ministries, and what participation means to these young adult Catholics. This chapter also describes what characteristics these congregations and ministries have that most engages young adults, and how these engagements differ between college and post-college twentysomethings. The chapter closes with results from its National Study of American Twentysomethings, applying an active, nominal, and estranged typology to understand Catholic young adults, and offering a prediction about Catholic affiliation in the United States.

The concluding chapter summarizes the book’s findings on the religious, spiritual, and secular lives of American twentysomethings. It compares the findings from the National Study of American Twentysomethings with research on adolescent religiosity and analyses the role of spirituality in the lives of Christian and religiously unaffiliated Twentysomethings. Chapter 7 also includes multivariate analyses of the strength of association between religion, spirituality, and eight life statuses. Lastly, this chapter discusses the importance of the 20s to understanding the life course as well as thinking about what the future holds for America’s Christian traditions and the growing number of adults with no religious affiliation.

Drawn from ethnographic observation in the Washington, D.C., area, this chapter explores how racially diverse, highly educated, and highly involved young adult Catholics in the region of Washington, D.C., relate to parishes. The Catholic scene, for young adults in this locale, is constructed through the efforts of parish-based young adult groups, diocesan offices for Young Adult Ministry, and parachurch organizations. Consequently, this group relates to parishes in three distinct but overlapping ways: parish as home, parish as hub, and parish as sacrament-station. This chapter suggests that scholars rethink the centrality and functions of the parish in American Catholicism. Using the D.C. region in this study, it would be a mistake to assume that young adults who are “loosely tethered” to D.C. parishes are disengaged from the church.

To measure community-based preceptors' overall satisfaction and motivations, the influence of students on preceptors' practices, and compare with 2005 and 2011 studies.North Carolina primary care preceptors across disciplines (physicians, pharmacists, advanced practice nurses, physician assistants) received survey invitations via e-mail, fax, postcard, and/or full paper survey. Most questions in 2017 were the same as questions used in prior years, including satisfaction with precepting, likelihood to continue precepting, perceived influence of teaching students in their practice, and incentives for precepting. A brief survey or phone interview was conducted with 62 nonresponders. Chi-square tests were used to examine differences across discipline groups and to compare group responses over time.Of the 2,786 preceptors contacted, 893 (32.1%) completed questionnaires. Satisfaction (816/890; 91.7%) and likelihood of continuing to precept (778/890; 87.4%) remained unchanged from 2005 and 2011. However, more preceptors reported a negative influence for patient flow (422/888; 47.5%) in 2017 than in 2011 (452/1,266; 35.7%) and 2005 (496/1,379; 36.0%) (P.0001), and work hours (392/889; 44.1%) in 2017 than in 2011 (416/1,268; 32.8%) and 2005 (463/1,392; 33.3%) (P.0001). Importance of receiving payment for teaching increased from 32.2% (371/1,152) in 2011 to 46.4% (366/789) in 2017 (P.0001).This 2017 survey suggests preceptor satisfaction and likelihood to continue precepting have remained unchanged from prior years. However, increased reporting of negative influence of students on practice and growing value of receiving payment highlight growing concerns about preceptors' time and finances and present a call to action.

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.

It has been proposed that medical organizations adopt neutrality with respect to physician-assisted suicide (PAS), given that the practice is legal in some jurisdictions and that membership is divided. We review developments in end-of-life care and the role of medical organizations with respect to the legalization of PAS since the 1990s. We argue that moving from opposition to neutrality is not ethically neutral, but a substantive shift from prohibited to optional. We argue that medical organizations already oppose many practices that are legal in many jurisdictions, and that unanimity among membership has not been required for any other clinical or ethical policy positions. Moreover, on an issue so central to the meaning of medical professionalism, it seems important for organized medicine to take a stand. We subsequently review the arguments in favor of PAS (arguments from autonomy and mercy, and against the distinction between killing and allowing to die (K/ATD)) and the arguments against legalization (the limits of autonomy, effects on the patient-physician relationship, the meaning of healing, the validity of the K/ATD distinction, the social nature of suicide, the availability of alternatives, the propensity for incremental extension, and the meaning of control). We conclude that organized medicine should continue its opposition to PAS.

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.

Background National vaccine adoption decisions may be better understood by linking multiple data sources. When examining countries’ decisions to adopt the hepatitis A vaccine, applying multiple research methods can facilitate assessments of gaps between evidence and policy. We conducted a literature review on hepatitis A and stakeholder interviews about decisions to adopt the vaccine in six countries (Chile, India, South Korea, Mexico, Russia, and Taiwan). Methods A systematic literature review was conducted across five literature databases. The review identified and abstracted 340 articles, supplemented by internet search. In addition, we interviewed 62 experts and opinion leaders on hepatitis A and/or vaccines. Data from the two sources were analyzed to identify gaps around epidemiologic data, economic data, and barriers/facilitators of hepatitis A vaccine adoption. Results Epidemiologic data gaps were found in Chile and Russia, where stakeholders believed data to be more solid than the literature documented. Economic data on hepatitis A was found to be weak across all countries despite stakeholders’ agreement on its importance. Barriers and facilitators of vaccine adoption such as political will, prioritization among vaccines, and global or local recommendations were discussed more by stakeholders than the literature. Stakeholders in India and Mexico were not concerned with the lack of data, despite growing recognition in the literature of the epidemiological transition and threat of outbreaks. Conclusions Triangulation of results from two methods captured a richer story behind vaccine adoption decisions for hepatitis A. The discrepancy between policymakers’ beliefs and existing data suggest a decline in priority of hepatitis A or weak investment in data collection. Filling the confirmed data gaps in seroprevalence or economic data is important to help guide policy decisions. Greater communication of the risk of hepatitis A and the benefits of the vaccine may help countries undergoing the epidemiologic transition.

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. Mol Cancer Res; 12(3); 408–20. ©2013 AACR.

Date Presented 04/04/19 Deficits in ADL have been linked to the older adults’ ability to remain at home; little research has focused on the environmental modifications, equipment, and other strategies needed. This study used a technology survey and interviews to explore the ADL strategies used by community-dwelling older adults and their perspectives on factors impacting their ability to stay at home. Results will inform the development of effective ADL interventions using technology and environmental supports. Primary Author and Speaker: Kathleen Foley Additional Authors and Speakers: Jamie Gentry, Tralisa Myers, Lindsay Rankin, Kristin Shepard

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.

Successful interprofessional teams are essential when caring for older adults with multiple complex medical conditions that require ongoing management from a variety of disciplines across healthcare settings. To successfully integrate interprofessional education into the healthcare professions curriculum, the most effective learning experiences should utilize adult learning principles, reflect real-life practice, and allow for interaction among trainees representing a variety of health professions. Interprofessional clinical experiences are essential to prepare future healthcare professionals to provide quality patient care and understand the best methods for utilizing members of the healthcare team to provide that care. To meet this need, the University of Alabama at Birmingham Geriatric Education Center has developed an Interprofessional Clinical Experience (ICE) to expose future healthcare providers to an applied training experience with older adults in the nursing home setting. This paper outlines how this program was developed, methods used for program evaluation, and how the outcome data influenced program revisions.

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.

To determine the prevalence and nature of pain in multiple sclerosis, we evaluated by questionnaire, interview, and chart review 159 patients residing in Middlesex County and followed in the MS Clinic at University Hospital, London, Ontario, Canada. Eighty-eight patients (55%) had either an acute or chronic pain syndrome at some time during their disease. Fifteen patients (9%) with acute pain syndromes had episodes of paroxysmal tic-like pain diagnosed in seven as trigeminal neuralgia. Chronic pain syndromes, present for a mean duration of 4.9 years, occurred in 76 patients (48%) and included dysesthetic extremity pain (29%), back pain (14%), painful leg spasms (13%), and abdominal pain (2%). MS patients with pain were similar to the pain-free group in mean age of onset (34.0 versus 31.9 years), average duration of disease (13.3 versus 12.1 years), spinal cord involvement (97% for each group), and mean rating on Kurtzke Disability Status Scale (4.2 versus 3.5). They differed in sex ratio with a higher female-to-male ratio in the pain group (3:1 versus 1.4:1). Chronic pain is a common feature of well-established MS and is usually associated with a myelopathy. Therapy must be individualized for each specific pain syndrome.

Importance Low mobility is common during hospitalization and associated with loss or declines in ability to perform activities of daily living (ADL) and limitations in community mobility. Objective To examine the effect of an in-hospital mobility program (MP) on posthospitalization function and community mobility. Design, Setting, and Participants This single-blind randomized clinical trial used masked assessors to compare a MP with usual care (UC). Patients admitted to the medical wards of the Birmingham Veterans Affairs Medical Center from January 12, 2010, through June 29, 2011, were followed up throughout hospitalization with 1-month posthospitalization telephone follow-up. One hundred hospitalized patients 65 years or older were randomly assigned to the MP or UC groups. Patients were cognitively intact and able to walk 2 weeks before hospitalization. Data analysis was performed from November 21, 2012, to March 14, 2016. Interventions Patients in the MP group were assisted with ambulation up to twice daily, and a behavioral strategy was used to encourage mobility. Patients in the UC group received twice-daily visits. Main Outcomes and Measures Changes in self-reported ADL and community mobility were assessed using the Katz ADL scale and the University of Alabama at Birmingham Study of Aging Life-Space Assessment (LSA), respectively. The LSA measures community mobility based on the distance through which a person reports moving during the preceding 4 weeks. Results Of 100 patients, 8 did not complete the study (6 in the MP group and 2 in the UC group). Patients (mean age, 73.9 years; 97 male [97.0%]; and 19 black [19.0%]) had a median length of stay of 3 days. No significant differences were found between groups at baseline. For all periods, groups were similar in ability to perform ADL; however, at 1-month after hospitalization, the LSA score was significantly higher in the MP (LSA score, 52.5) compared with the UC group (LSA score, 41.6) ( P = .02). For the MP group, the 1-month posthospitalization LSA score was similar to the LSA score measured at admission. For the UC group, the LSA score decreased by approximately 10 points. Conclusions and Relevance A simple MP intervention had no effect on ADL function. However, the MP intervention enabled patients to maintain their prehospitalization community mobility, whereas those in the UC group experienced clinically significant declines. Lower life-space mobility is associated with increased risk of death, nursing home admission, and functional decline, suggesting that declines such as those observed in the UC group would be of great clinical importance. Trial Registration clinicaltrials.gov Identifier:NCT00715962

Screening for medical referral is essential to physical therapist practice; however, no studies have examined medical screening across physical therapy practice settings. The purpose of this study was to determine if physical therapists in a variety of practice settings, given brief clinical vignettes, would screen for medical referral in a similar manner. The Delphi Technique was implemented to establish content validity, although only 2 vignettes reached 100% consensus by the expert panel. After reviewing the vignettes, physical therapist subjects determined if they would provide intervention, provide intervention and refer, or refer before intervention. To determine which variables were associated with identified appropriate decisions in each category, 4 sets of logistic regressions were performed. A random sample of APTA members in targeted sections (n=214) completed the survey. Physical therapists with more than 23 years experience were 7 times more likely to make similar management decisions in noncritical vignettes then those with 11 years or less. Half of the participants practiced in outpatient practice settings. In critical medical vignettes, 86% of physical therapists made similar decisions. Physical therapists in this study made identified appropriate management decisions for 90% of the vignettes. Board certification, practice setting and highest earned degree were not found to be statistically significant. It is imperative not only to ensure that the client is appropriate for physical therapy intervention, but it is also vital to recognize and identify signs and symptoms that warrant evaluation by other health care providers.

Summary 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.

tudy 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

A series of tridentate pincer ligands, each possessing two sulfur- and one nitrogen-donor functionalities (SNS), based on bis-imidazole or bis-triazole salts were metallated with ZnCl 2 to give new tridentate SNS pincer zinc(II) complexes [(SNS)ZnCl] + . The zinc complexes serve as models for the zinc active site in liver alcohol dehydrogenase (LADH) and were characterized with single crystal X-ray diffraction, 1 H, 13 C, and HSQC NMR spectroscopies, electrospray mass spectrometry, and elemental analysis. The zinc complexes feature SNS donor atoms and pseudotetrahedral geometry about the zinc center, as is seen for liver alcohol dehydrogenase. The bond lengths and bond angles of the zinc complexes correlate well to those in horse LADH. The SNS ligand precursors were characterized with 1 H, 13 C, and HSQC NMR spectroscopies, elemental analysis, and cyclic voltammetry, and were found to be redox active. Gaussian calculations were performed and agree with the experimentally observed oxidation potentials for the pincer ligand precursors. The zinc complexes were screened for the reduction of electron-poor aldehydes in the presence of a hydrogen donor, 1-benzyl-1,4-dihydronicotinamide (BNAH), and it was determined that they enhance the reduction of electron-poor aldehydes. The SNS zinc pincer complexes with bis-triazole ligand precursors exhibit higher activity for the reduction of 4-nitrobenzaldehyde than do SNS zinc pincer complexes with bis-imidazole ligand precursors. Quantitative stoichiometric conversion was seen for the reduction of pyridine-2-carboxaldehyde via SNS zinc pincer complexes with either bis-imidazole or bis-triazole ligand precursors.

Background This analysis was carried out to evaluate the cost-effectiveness of adjuvant radiation therapy (ART) versus observation, using a decision analysis model based primarily upon the published results of the Southwest Oncology Group prospective trial (SWOG 8794). Patients and methods A decision analysis model was designed to compare ART versus observation over a 10-year time horizon. Probabilities of treatment success, utilization of salvage treatments, and rates of adverse events were taken from published results of SWOG 8794. Cost inputs were based on 2010 Medicare reimbursement rates. Primary outcome measure was incremental cost per prostate-specific antigen (PSA) success (i.e. serum PSA level Results ART results in a higher PSA success rate than observation with probability of 0.43 versus 0.22. The mean incremental cost per patient for ART versus observation was $6023. The mean incremental cost-effectiveness ratio was $26 983 over the 10-year period. Conclusions ART appears cost effective compared with observation based upon this decision analysis model. Future research should consider more costly radiation therapy (RT) approaches, such as intensity-modulated RT, and should evaluate the cost-effectiveness of ART versus early salvage RT.

Purpose: Despite results of randomized trials that support adjuvant radiation therapy (RT) after radical prostatectomy (RP) for prostate cancer with adverse pathologic features (APF), many clinicians favor selective use of salvage RT. This survey was conducted to evaluate the beliefs and practices of radiation oncologists (RO) and urologists (U) regarding RT after RP. Methods and Materials: We designed a Web-based survey of post-RP RT beliefs and policies. Survey invitations were e-mailed to a list of 926 RO and 591 U. APF were defined as extracapsular extension, seminal vesicle invasion, or positive surgical margin. Differences between U and RO in adjuvant RT recommendations were evaluated by comparative statistics. Multivariate analyses were performed to evaluate factors predictive of adjuvant RT recommendation. Results: Analyzable surveys were completed by 218 RO and 92 U (overallresponse rate, 20%). Adjuvant RT was recommended based on APF by 68% of respondents (78% RO, 44% U, p