Search

O subprojeto Repercussão de um movimento formativo: em foco professores que atuam junto a alunos com doenças crônicas (DC) propõe ações a serem desenvolvidas durante a elaboração e execução de um curso de formação continuada, no sentido de analisar e compreender a repercussão dessa formação a respeito da DC, verificando se esse processo formativo reverbera na prática docente, na direção de efetivar e/ou melhorar a inclusão e permanência de alunos com doença crônica na ambiência escolar. Assim

PurposePalliative care requires integration between services, organisations and the community. A series of community engagement programmes, named “Listening Events”, were conducted across the Isle of Man. The aim was to involve the community in the development of Hospice strategy by sharing their views on the future of palliative and end of life care.Design/methodology/approachThree Listening Event programmes were conducted in community settings, secondary schools and the Isle of Man’s University College. The investigators facilitated discussions on current knowledge of Hospice services, what would matter to people should they need to use these, and how Hospice could best serve the community in the future. Participants and investigators noted thoughts and comments. Data were analysed using thematic analysis.FindingsIn total, 899 people participated from across the community. Main themes surrounded effective care, person-centred care and integrated care. Most themes agreed across the three programmes, despite some nuances.Originality/valueThe results were used as an evidence base from which Hospice Isle of Man’s new strategy was derived in order to ensure that it aligned with the community’s needs. By initiating conversations and discussions in the community, the Listening Events may have also increased understanding about hospice care.

PurposeThis case study aims to understand the experience of care from a patient/carer perspective and to describe how the method can be replicated to address gaps in evidence relating to integrated person-centred care.Design/methodology/approachThe case study was constructed using data extracted from personal diaries and medical records kept by a person with a complex condition, correspondence with family from the last 18 months of life and interviews with the carer and long-term conditions coordinator. The number of professionals or teams involved in providing care from statutory services, the third sector, and private providers were counted to understand the ecosystem of care. The number of contacts was plotted by provider and purpose of care. The type of care and hours of respite were estimated. A protocol was developed to assess the feasibility of replicating the data and analyses used.FindingsThere were 35 care providers from the public, private and the third sector, demonstrating that only the patient or carer can identify the ecosystem of care. The majority of care was for respite and on average, the carer provided four hours of care per every respite care hour. The method was replicated successfully.Research limitations/implicationsThe case study formed the basis of a workshop that brought together health care professionals from the public services and the third sector. The discussion led to the identification of gaps and areas where greater coordination between providers would benefit patients.Originality/valueThe case study method combines contemporaneous patient and carer sources of data and health service activity to create a detailed account of care at the end of life. The approach addresses gaps in person-centred evidence for the development and evaluation of integrated palliative and end-of-life care.

IntroductionInformal carers play a vital role in caring for palliative and end of life care patients and as such need to be adequately supported. Hospice Isle of Man sought to understand the experience of carers to ensure services meet their needs. The aims of the study were to identify the support carers access and value; the factors that assist or hinder accessing support; and to understand carer wellbeing.MethodsUsing a mixed methods study design, a survey was developed based on carer reported outcome measures (Michels et al., 2016). Data were collected on demographics and domains of the carer experience using multiple choice questions with an option to comment on the answer. Physical and emotional well-being were measured using a Likert scale of 0 to 10 (excellent). Surveys were distributed by clinical staff to carers of patients on their caseloads between November 2017 and February 2018. Descriptive statistics were conducted. Statistical significance was set at α=0.05 and tested using a Student’s t-test when comparing two group means and the Pearson’s Chi-squared test for proportions. Thematic analysis of the comments was carried out according to the phases outlined in Braun and Clarke, 2006.ResultsA total of 44 carers returned the survey. The average age of carers was 58.0 ± 17.1 years, ranging between 7 to 84 years, 66% were female, 50% were retired and 20% were in paid work. Carers were a spouse or partner (68%) or children (23%) and 89% were living with the person. Fewer carers rated their physical health below 5 compared to emotional health (25% and 39%, respectively). The majority (68%) sometimes felt “out of control” since their loved one’s illness (32% said never or rarely). The median number of years caring was 2, range

IntroductionIsle of Man (IOM) is a British crown dependency with 83,000 residents. To provide an evidence-base for the Island strategy on integrated palliative and end of life care, Hospice Isle of Man carried out a needs assessment, which involves the collection and analysis of data describing services and identifying gaps. Many data sources normally used for this purpose are not available in the IOM so we compensated by extensive engagement with those working in relevant services and organisations as well as the public. This paper focuses on what we learned about carers.MethodsInterviews were carried out with over 60 professionals who work with people with life-limiting illness and twelve patients/carers. The questions were: “What works well?” What does not work well” and “What are the gaps” from your perspective in integrated palliative and end of life care.ResultsWe found that some people at end of life have no carers but, even for those that do, some don’t ask for help because they don’t recognise that they are carers, that they need help or that they don’t ask because they are afraid of being separated from their loved one. Carers’ needs are often overlooked and can be emotional, physical or financial and can cause problems even long after bereavement. There was a perception that carers with links to Hospice were well supported. A need for better communication between the professionals and with patients and families was highlighted as well as a need for better involvement of patients and their families in decisions. Carers provide and coordinate care but they are not recognised by the system. Having a professional to help navigate the system is invaluable as is better information about the support services available. In the particular case of the IOM, off-Island care is a substantial burden for patients and carers. Many patients and carers feel alone and not understood and both patients and carers are at risk of mental health problems when facing end of life.Discussion/ConclusionsThe problems faced by carers in the IOM are similar to those in other communities. However, there are additional challenges due to being on a small island. An effective resolution of these problems is essential if we are to achieve integrated care in an appropriate setting at the end of life. Some initiatives already in place should help but new approaches are needed. The data already collected will be a useful basis for future evaluation.

ObjectiveTo investigate whether a child’s genotype affects a mother’s risk of rheumatoid arthritis (RA) beyond the risk associated with her genotype and to test whether exposure to fetal alleles inherited from the father increases risk of RA among mothers without risk alleles.MethodsA case–control study was conducted among 1165 mothers (170 cases/995 controls) and their respective 1482 children. We tested the association between having any child with alleles encoding amino acids (AAs) associated with RA including the ‘shared epitope’ (SE) and DERAA AA sequences at positions 70–74; AA valine, lysine and alanine at positions 11, 71 and 74 of HLA-DRB1; aspartic acid at position 9 of HLA-B and phenylalanine at position 9 of DPB1. We used logistic regression models to estimate OR and 95% CI for each group of alleles, adjusting for maternal genotype and number of live births.ResultsWe found increased risk of RA among mothers who had any child with SE (OR 3.0; 95% CI 2.0 to 4.6); DERAA (OR 1.7; 95% CI 1.1 to 2.6); or valine (OR 2.3; 95% CI 1.6 to 3.5), lysine (OR 2.3; 95% CI 1.5 to 3.4) and alanine (OR 2.8; 95% CI 1.2 to 6.4) at DRB1 positions 11, 71 and 74, respectively. Among non-carrier mothers, increased risk of RA was associated with having children who carried DERAA (OR 1.7; 95% CI 1.0 to 2.7) and alleles encoding lysine at DRB1 position 71 (OR 2.3; 95% CI 1.5 to 4.8).ConclusionFindings support the hypothesis that a child’s genotype can contribute independently to risk of RA among mothers.

Background Hospice Isle of Man’s aim is to provide access to those who could benefit regardless of diagnosis. The hospice began offering services to non-cancer patients in 2016. Little is known about how many could benefit or the extent of the hospice’s involvement by disease category. The Isle of Man is not included in Hospice UK’s PopNAT. Aims To estimate the number of persons who could have potentially benefited from palliative and end-of-life care. To understand differences in hospice involvement by disease category. Methods The Isle of Man Registry maintains weekly Excel sheets with death certificate data. We extracted variables of interest for the period between 1 January 2013 to 31 December 2018. We created a variable for palliative need based on cause of death where there was any mention of cancer, Alzheimer’s/dementia, organ failure or a neurodegenerative condition. Using hospice records, we identified persons who received hospice care for the years 2016–2018. We estimated unmet need by comparing hospice involvement and presence of a condition likely to benefit from palliative care and compared hospice involvement by palliative disease category. Results There were 5,005 deaths between 2013 and 2018, representing 1% of the population per year. Prior to 2016, the hospice cared for 30% of persons who died. By 2018, 39% had hospice care representing a 21% increase from 2016. Of all deaths between 2013 and 2018, 30% had a palliative condition and hospice care. An additional 34% had a palliative condition but no hospice care. The hospice was involved in 88% of all cancer cases but only in a quarter or less of cases with organ failure (28%), neurodegenerative conditions (26%), or Alzheimer’s/dementia (16%). Conclusions Since 2016, more persons received hospice care. However, persons with non-cancer conditions who could benefit remained under-represented compared to those with cancer. Future studies are needed to understand the factors contributing to this difference.

Background Hospice UK is promoting ECHO™ (Extension of Community Healthcare Outcomes) to democratise specialist skills and increase confidence of staff in palliative and end-of-life care. Hospice Isle of Man is reaching the end of the first year of Project ECHO™ with local nursing homes. Aim To carry out a formative evaluation of project ECHO™ at the end of its first year of operation and prepare for a summative evaluation at the end of five years. Methods The logic model identifies resources and inputs, activities, outputs, short and longer-term outcomes. Inputs, activities and outputs come from routinely collected data and short-term outcomes from a mix of ad-hoc quantitative data from surveys and qualitative data from interviews. For longer-term outcomes we have 1) set up a data collection exercise to obtain feedback from all of those experiencing bereavement, 2) identified sources of data on place of care at the end-of-life with the aim of determining whether experiences change over the period of Project ECHO™’s operation. Results We are currently conducting the formative evaluation with nursing homes using the quantitative data described in the first three categories of the logic model. We are also carrying out qualitative interviews with those who participated in the first year of Project ECHO™. We trialled a validated questionnaire (Grande et al. End-of-life skills survey) on end-of life skills and confidence which will be a required part of enrolment for those who join further ECHO™s and will map to our Island skills framework. Feedback is positive and Project ECHO™ will continue in nursing homes with further ECHO™s including residential homes and other community providers. Conclusion With the formative evaluation we are learning lessons about how best to deliver Project ECHO™ in nursing homes and extend it to other sites. We have set up measures which we hope will shed light on longer-term outcomes.

Background Isle of Man (IOM) is a crown dependency with 83,000 residents. To provide an evidence-base for the strategy on person-centred, palliative and end of life care, Hospice Isle of Man carried out a needs assessment. Typically this involves quantitative and qualitative data describing services and identifying gaps. Many data sources used for this purpose in the UK (e.g. Hospice UK’s PopNAT) are not available in the IOM so we compensated by extensive engagement with those working in relevant services and organisations as well as the public. Aim To carry out a needs assessment on palliative and end of life care. Methods Population demographics and weekly death data were processed to enable predictions of need for palliative and end of life care. Interviews were carried out with over 60 representatives of services and organisations involved in care for those with life limiting conditions, in elderly care, end of life or bereavement support. The questions were: ‘What works well?’, ‘What does not work well?’, ‘What are the gaps?’ and ‘What might be solutions?’ in palliative and end of life care. Adult members of the public, schoolchildren and college students were asked what would matter to them if using Hospice services to ensure a focus on person-centred care. Results We discovered that the hospice was probably reaching around half of those who could benefit but users were very positive about it. Passion for Island services, but frustration with aspects of the system, was identified among professionals and some disjointedness among third sector groups. The majority of the data are currently being analysed and will be presented at Hospice UK’s 2019 conference. Conclusion Expert views of those working in the services and charities, supplemented by person-centred perceptions of the public and available data are shedding necessary light on the Island’s needs for palliative and end of life care. (Support provided by Manx Lottery Trust)

Background Co-design of services is increasingly recognised as an important means of ensuring development of people-centred services. Young people and adolescents are not often consulted when designing adult services but Hospice Isle of Man (IoM) aimed to change that. Aims To engage with young people. To explore their attitudes towards death, dying, bereavement and Hospice. Methods Hospice IoM’s public engagement strategy started with ‘Listening Events’ in seven community settings which obtained views towards Hospice. Males and young people were under-represented so events were offered in secondary schools. A short session on end-of-life and palliative care was incorporated with activities to ascertain understanding of Hospice, uncover what was most valued and obtain recommendations for Hospice’s future. Students were asked ‘What do you know about Hospice’? ‘If you or a family member became seriously unwell and needed Hospice services, what would be most important to you?’ and ‘How could we make Hospice a better service?’ Responses were made on post-it notes and analysed using NVivo. Themes and sub-themes within responses were identified. Results 203 students (105 males, 98 female) aged 11 to 16, participated. For the first question, the themes were purpose (sub-themes helping and caring), services (sick or illness) and users. It was clear that many young people knew nothing about Hospice. For the second questions on what matters themes ‘were how you feel’, ‘support services’, ‘staff qualities’, ‘environment’, ‘loved ones’ and ‘entertainment/activities’. For the third question, community activities and age-appropriate care feature with suggestions that Hospice should feature more prominently within the local community and online. Conclusion Young people provided a wealth of information from their own perspective and appreciated being involved at this level. These findings will inform future Hospice strategies, and the engagement with youth may empower new relationships between Hospice and the Island’s next generation.

Systemic lupus erythematosus (SLE) disproportionately affects women of reproductive age. During pregnancy, women are exposed to various sources of fetal material possibly constituting a significant immunologic exposure relevant to the development of SLE. The objective of this study was to investigate whether having any children who carry DRB1 alleles associated with SLE increase the risk of maternal SLE. This case-control study is based on the University of California, San Francisco Mother-Child Immunogenetic Study and from studies at the Inova Translational Medicine Institute. Analyses were conducted using data for 1304 mothers (219 cases/1085 controls) and their respective 1664 children. We selected alleles based on their known association with risk of SLE (DRB1*03:01, *15:01, or *08:01) or Epstein-Barr virus (EBV) glycoproteins (*04:01) due to the established EBV association with SLE risk. We used logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (CI) for each allele of interest, taking into account maternal genotype and number of live births. We found an increase in risk of maternal SLE associated with exposure to children who inherited DRB1*04:01 from their father (OR 1.9; 95% CI, 1.1-3.2), among *04:01 allele-negative mothers. Increased risk was only present among mothers who were positive for one or more SLE risk-associated alleles (*03:01, *15:01 and/or *08:01). We did not find increased risk of maternal SLE associated with any other tested allele. These findings support the hypothesis that a child's alleles inherited from the father influence a mother's subsequent risk of SLE.

Background Informal carers are vital in caring for palliative and end of life care (EoLC) patients and need to be adequately supported. Hospice Isle of Man sought to understand the unique carer experience and identify areas for service development. Aims To identify the support carers access and value; the factors that assist or hinder accessing support; and to understand carer wellbeing. Methods Using a mixed methods study design, a survey was developed based on carer reported outcome measures (Michekls et al., 2016). Data were collected on demographics and domains of the carer experience. Surveys were distributed by clinical staff to carers of patients on their case-loads between November 2017 and February 2018. We calculated frequencies for multiple-choice questions and conducted thematic analyses on qualitative responses. Results A total of 44 carers returned the survey. The average age of carers was 58.0±17.1 years, ranging between 7 to 84 years and 66% were female. A large proportion (68%) felt ‘out of control’ since their loved one’s illness. Qualitative analyses highlighted themes of feeling ‘dictated to by the illness’ and having ‘no free time’. Half of carers received ‘some’ or ‘little’ support from their family and friends. Services provided ‘some’ assistance to 61% of the sample, ‘a lot’ to 32% and ‘a little’ to 7%. Carers valued responsiveness, access to out of hours, information and reassurance. Analyses revealed difficulties in asking family for support and found practical support from external agencies to be vital. Despite these challenges, 57% of carers described the role as fulfilling. Conclusion Carers primarily rely on services, and not families, for support. Service strategies need to recognise that although carers face challenges, they also find fulfilment and they need to support carers in ways to mitigate the feelings of loss of control.

Background The integrated care concept is being implemented world-wide but is often considered setting-specific. Small islands are one of these settings which face particular issues. Hospice Isle of Man is taking a measured approach, from which we hope that others might be able to benefit. Aim To develop a strategy for integrated palliative and end of life care on a small island. Methods Create connections and networks to support the planning, implementation and evaluation stages of the work Identify, via a needs assessment, what works, what gaps need filled and what matters to the population and professionals Identify particular issues facing small islands and ensure that any recommendations for change lead to solutions which are sustainable in the longer term. Results to date Hospice Isle of Man formed relationships with the International Foundation for Integrated Care (IFIC) and IFIC Scotland who facilitated two face-to-face stakeholder meetings in 2017 and 2018. Using an example of a patient journey, areas that could be improved were identified. As a result, Hospice Isle of Man, public health care providers and charities meet bi-monthly to discuss the progress of the needs assessment and consider how to work more closely together. Engagement activities for the needs assessment have included members of the public, patients and carers, schoolchildren, community groups, public and private health care providers, nursing home staff and residents with their families. Conclusions Many of the issues encountered are similar to those in other settings and proximity does not always lead to closeness although personal connections are an advantage. There is some consistency so far in the views of participants that we aim for the right care, in the right place at the right time, although the small island setting presents some unique challenges.

Background To deliver person-centred integrated end of life care, providers need to understand the experience of patients and carers. Real-time experience may differ from retrospective accounts of experience which may have implications for initiatives to improve care. Aims To explore the benefits of using a combination of prospective and retrospective data collection methods from multiple sources to understand the experience of care of a patient and carer. Methods The carer of a patient with progressive supranuclear palsy was approached six months after death for an interview. Using personal diaries, we extracted data on face-to-face contacts with Department of Health and Social Care (DHSC), charities and private care providers for the last 18 months of life. Numbers of contacts were plotted by month and sector. A timeline from pre-diagnosis to after death was created using details provided by the carer and verified by correspondence generated at the time of care. Results In the last 18 months of life, the patient received care from 25 DHSC providers, four charities, six private providers, plus family and friends. The patient had an average of 24±8 encounters per month. DHSC activity declined in April, September and December (1st 12 months). The main providers of care in the last months of life were from the voluntary and private sector. The carer developed a system for organising documentation, appointments, medications and outside services. The carer reported that the long-term conditions coordinator was invaluable for coordinating DHSC care. However, the carer remained the overall coordinator. Correspondence was critical in constructing an accurate and unbiased timeline. The results surprised the carer when compared to their recollection of events. Conclusions A combined approach to data collection is a promising method to capture user experience to inform service design and delivery. Further cases studies in different conditions are planned.

Background Hospice Isle of Man (IoM) is celebrating its 35th anniversary. To thank the community and to inform the next five-year strategy, the hospice conducted a series of community listening events with the theme of ‘What matters to you, matters to us’. Aims To understand what the public knew about Hospice and learn about their experience; to find out what matters most when confronted with end of life; and to ask how the hospice can best serve the IoM. Methods Hospice staff approached members of the public at supermarkets and community events at seven locations. Events took place between January and February 2018 during business hours. Demographic data were collected on age and sex. Interviewers recorded responses that were analysed using thematic analysis according to the aims. Results A total of 278 persons from a population of 83 000 provided comments. The majority were female (63%) and over 55 (68%), 32% had used services, and 74% had general awareness of hospice. Respondents were aware of specialist skills and services and/or were supporters. However, only 5% knew about the range of services and there were misconceptions about who the hospice serves. Others preferred ‘not to think about it’ or felt there was ‘one way out’. Overall, experience with Hospice was positive and many felt it was ‘for families’. What mattered to people included: kind, compassionate and effective care, emotional support, person-centred care, equity, the environment, open access, good communication, honesty and helping others talk about death. Hospice can best serve by making services available ‘to all who need it’, ensure sustainability, by supporting families, friends/co-workers, schools and by improving transparency of its accounts. Conclusions Hospice needs to raise awareness of its services. Hospice care is valued and needs to be provided at the right time and place for all who need it.

Background There is a welcome and appropriate movement, encouraged by Hospice UK, towards increasing the role of research in palliative and end of life care. Aim To enable Hospice Isle of Man to reposition as a Research Active Hospice. Methods A survey was undertaken to ascertain the current level of research interest and awareness in Hospice Isle of Man. Results to date The survey was completed by 25 staff and 45 volunteers. The majority (88%) of clinical staff had some research training but most had no recent opportunity to engage in research; over 70% agreed that research added value to their daily work but only 40% were confident in their critical appraisal skills. As a result further training e.g. in critical appraisal skills within journal clubs is being initiated. Amongst the volunteers 22% were identified to have research skills but very few were actively engaged in research. These volunteers will be invited to participate in future projects. Funding from the Scholl Foundation and the Manx Lottery Trust has enabled research staff to be recruited and has facilitated protected time for some clinical staff to participate in research with peer support and skill sharing in, for example, developing outcome measurements, appropriate analyses and interpretation of data and considering how the value of routine data can be improved. Initial uncertainty about the role of research and researchers is gradually being replaced with appreciation of their support in enhancing research awareness and activity among staff. Conclusion Hospice Isle of Man had a low level of research activity however a step-change has been achieved by utilising existing skills and interests of the clinical staff. Key drivers were obtaining funding for protected research time for key clinical staff and employing experienced researchers to support and complement the clinical staff to develop an active research culture.

The study objective was to test the hypothesis that having histocompatible children increases the risk of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), possibly by contributing to the persistence of fetal cells acquired during pregnancy. We conducted a case control study using data from the UC San Francisco Mother Child Immunogenetic Study and studies at the Inova Translational Medicine Institute. We imputed human leukocyte antigen (HLA) alleles and minor histocompatibility antigens (mHags). We created a variable of exposure to histocompatible children. We estimated an average sequence similarity matching (SSM) score for each mother based on discordant mother-child alleles as a measure of histocompatibility. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals. A total of 138 RA, 117 SLE, and 913 control mothers were analyzed. Increased risk of RA was associated with having any child compatible at HLA-B (OR 1.9; 1.2-3.1), DPB1 (OR 1.8; 1.2-2.6) or DQB1 (OR 1.8; 1.2-2.7). Compatibility at mHag ZAPHIR was associated with reduced risk of SLE among mothers carrying the HLA-restriction allele B*07:02 (n = 262; OR 0.4; 0.2-0.8). Our findings support the hypothesis that mother-child histocompatibility is associated with risk of RA and SLE.

ObjectivesRheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) disproportionately affect women during and following childbearing years. Antihuman leucocyte antigen (HLA) alloantibody responses are common in healthy parous women, and as these diseases are both linked with HLA and immune dysregulation, we sought to evaluate anti-HLA antibodies in RA and SLE.MethodsAnti-HLA antibodies were measured among parous SLE cases (n=224), parous RA cases (n=202) and healthy parous controls (n=239) and compared with each other as well as with nulliparous female and male controls. Antibody specificities were identified and compared against subject HLA types to determine autoreactivity versus alloreactivity. The association of anti-HLA antibodies with clinical outcomes was evaluated.ResultsLevels and frequencies of anti-HLA antibodies were significantly higher among parous females with SLE (52%) or RA (46%) compared with controls (26%), and anti-HLA antibodies were also found among nulliparous females and males with SLE and RA. Autoreactive anti-HLA antibodies were observed among SLE and RA antibody-positive subjects, but not healthy controls, with the highest frequency of autoreactive anti-HLA antibodies found in the SLE subjects. Higher levels of anti-HLA antibodies were associated with nephritis among the nulliparous SLE cases (pConclusionsBoth autoreactive and alloreactive anti-HLA antibodies were found at high levels in RA and SLE subjects. These occurred even in the absence of alloexposure, particularly among SLE subjects and may be linked with disease severity.

Healthy pregnancy is the most successful form of graft tolerance, whereas preterm labor (PTL) may represent a breakdown in maternal-fetal tolerance. Although maternal immune responses have been implicated in pregnancy complications, fetal immune responses against maternal antigens are often not considered. To examine the fetal immune system in the relevant clinical setting, we analyzed maternal and cord blood in patients with PTL and healthy term controls. We report here that the cord blood of preterm infants has higher amounts of inflammatory cytokines and a greater activation of dendritic cells. Moreover, preterm cord blood is characterized by the presence of a population of central memory cells with a type 1 T helper phenotype, which is absent in term infants, and an increase in maternal microchimerism. T cells from preterm infants mount a robust proliferative, proinflammatory response to maternal antigens compared to term infants yet fail to respond to third-party antigens. Furthermore, we show that T cells from preterm infants stimulate uterine myometrial contractility through interferon-γ and tumor necrosis factor–α. In parallel, we found that adoptive transfer of activated T cells directly into mouse fetuses resulted in pregnancy loss. Our findings indicate that fetal inflammation and rejection of maternal antigens can contribute to the signaling cascade that promotes uterine contractility and that aberrant fetal immune responses should be considered in the pathogenesis of PTL.

Breast cancer incidence rates have declined among older but not younger women; the latter are more likely to be diagnosed with breast cancers carrying a poor prognosis. Epidemiological evidence supports an increase in breast cancer incidence following pregnancy with risk elevated as much as 10 years post-partum. We investigated the association between years since last full-term pregnancy at the time of diagnosis (10 years) and breast tumor subtype in a case series of premenopausal Hispanic women (n = 627). Participants were recruited in the United States, Mexico, and Spain. Cases with known estrogen receptor (ER), progesterone receptor (PR), and HER2 status, with one or more full-term pregnancies >/=1 year prior to diagnosis were eligible for this analysis. Cases were classified into three tumor subtypes according to hormone receptor (HR+ = ER+ and/or PR+; HR- = ER- and PR-) expression and HER2 status: HR+/HER2-, HER2+ (regardless of HR), and triple negative breast cancer. Case-only odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for HER2+ tumors in reference to HR+/HER2- tumors. Participants were pooled in a mixed-effects logistic regression model with years since pregnancy as a fixed effect and study site as a random effect. When compared to HR+/HER2- cases, women with HER2+ tumors were more likely be diagnosed in the post-partum period of 45 years) did not materially alter our results (OR = 1.78; 95 % CI, 1.08-2.93). These findings support the novel hypothesis that factors associated with the post-partum breast, possibly hormonal, are involved in the development of HER2+ tumors.

In this commentary, we discuss the challenges and opportunities for epidemiologic studies in evaluating breast cancer as a set of discrete diseases. We show examples of the strengths of the case-only design in assessing the relative correlation of established risk factors and the different cancer

The Isle of Man is a small island of 83,000 residents situated in the Irish Sea. The Island is a self-governing Crown Dependency of the United Kingdom. Due to its geographic isolation, the Island provides a unique opportunity to re-design and co-create a model of care that incorporates private, public, third sector and community elements. Financially strained health services recognise that sustainability depends on integration across sectors in the community. Hospice Isle of Man, the only specialist provider of end of life care on the Island, is working with the Department of Health and Social Care and the Council of Voluntary Organisations to develop the Isle of Man’s Integrated Palliative and End of Life Care Strategy. The World Health Organization and the Worldwide Palliative Care Alliance have underscored the need for palliative care to be based on individual needs rather than on disease-specific diagnoses or prognosis Connor and Sepulveda, 2014. In order to provide the right care, at the right time, in the right place, the Island-wide strategy requires a population-based approach and methods to match patients and services based on needs. Early stakeholder engagement facilitated through a workshop held on December 7th, 2017 with members of the health services including primary care, mental health, social health, third sector and carers identified the need for earlier identification of patients at the end of life in order to provide the most appropriate services. It was recognised that patient networks and resources must be taken into account in order for gaps to be adequately identified and to meet patient needs. Patient journey case studies with different diagnoses identified needs across the spectrum of care – including the third sector and patient networks. Age-based segmentation fails to recognize the contribution and potential capacity of those who would otherwise be considered “dependent” in traditional demographic analyses. Cross-sector integration of care raises additional questions and challenges. Who leads the process? What does person-centred care look like with cross-sector involvement? Who can function as a “key worker”? How will fragmented services organise? How do charitable organisations balance mission and goals with the requirements of an integrated network? What trade-offs are stakeholders willing to make? By combining findings obtained through focus groups, patient and carer journeys and cross-sector workshops we identify the non-medical determinants of need for community end of life support and propose strategies to meet them. These findings will form the basis for initiatives that will be piloted and evaluated prior to Island-wide implementation.

Breast cancer is the number one cause of cancer deaths among Hispanic women in the United States, and in Mexico, it recently became the primary cause of cancer deaths. This malignnancy represents a poorly understood and understudied disease in Hispanic women. The ELLA Binational Breast Cancer Study was established in 2006 as a multi-center study to assess patterns of breast tumor markers, clinical characteristics, and their risk factors in women of Mexican descent. We describe the design and implementation of the ELLA Study and provide a risk factor comparison between women in the U.S. and those in Mexico based on a sample of 765 patients (364 in the U.S. and 401 in Mexico). Compared to women in Mexico, U.S. women had significantly (p < 0.05) lower parity (3.2 vs. 3.9 mean live births) and breastfeeding rates (57.5% vs. 80.5%), higher use of oral contraceptives (60.7% vs. 50.1%) and hormone replacement therapy (23.3% vs. 7.6%), and higher family history of breast cancer (15.7% vs. 9.0%). Results show that differences in breast cancer risk factor patterns exist between Mexico and U.S. women. We provide lessons learned from the conduct of our study. Binational studies are an important step in understanding disease patterns and etiology for women in both countries.

OBJECTIVE: This study examined factors that influence mammography use and breast cancer detection, including education, health insurance, and acculturation, among Mexican-American (MA) and African-American (AA) women. METHODS: The study included 670 breast cancer cases (388 MAs and 282 AAs), aged 40–86 years at diagnosis. Data on mammography use, detection, and delay in seeking care were collected via questionnaires and medical records. Using a language-based bidimensional acculturation measure, MAs were classified as English-dominant (n = 67), bilingual (n = 173), and Spanish-dominant (n = 148). Mammography prior to diagnosis was assessed by racial/ethnic acculturation subgroup using logistic regression. RESULTS: In age-adjusted models, mammography use was non-significantly lower among English-dominant (OR = 0.84; 95% CI: 0.45–1.59) and bilingual (OR = 0.86; 95% CI: 0.55–1.35) MAs and significantly lower among Spanish-dominant MAs (OR = 0.53; 95% CI: 0.34–0.83) than among AA women. After adjustment for education or insurance, there was no difference in mammography use by race/ethnicity and acculturation subgroup. Despite high self-reported mammography use (75%), a large proportion of cases reported self-detection (59%) and delay in seeking care >90 days (17%). CONCLUSIONS: These findings favor promoting culturally appropriate messaging about the benefits and limitations of mammography, education about breast awareness, and prompt reporting of findings to a health professional.

Background: Women of Mexican and African-American descent have a higher mortality and a higher proportion of triple negative or basal-like breast cancer with BRCA like features. Basal-like breast cancer subtype is associated with an elevated Ki67 index and extensive genomic instability. This increase in the Ki67 index indicates cell proliferation and perhaps greater DNA damage; double strand breaks are the most consequential DNA lesions. Knockdown of RING-finger 8 (RNF8), an E3 ubiquitin-protein ligase, by siRNA inhibit focus formation at double strand breaks sites suggesting that RNF8 is an important regulator of the DNA repair system. We are investigating the hypothesis that RNF8 is a modulator of genomic integrity by acting as a regulator of BRCA1 and 53BP1 proteins in human breast cancers. Methods: We compared RNF8, p53 binding protein 1 (53BP1), cyclin B1 (CB1) and Ki67 mRNA expression in 57 formalin fixed paraffin embedded human breast cancer taken from a population of Mexican women enriched for basal-like tumors. Further we investigated copy number alterations in the 6p21.2 chromosomal region that contains RNF8 in a subset of 971 early stage breast cancers categorized by tumor subtype considering race/ethnicity. Results: RNF8 and 53BP1 were found to exhibit variable expression at the mRNA level by Ki67 and CB1 expression levels. The combined effect RNF8 high/53BP1 low was associated with high expression of Ki67 (p=0.028). Conversely, RNF8 low expression was associated with low expression of Ki67 (p = 0.017), low CB1 (p = 0.035) and was independent of the 53BP1 expression. In a sample set of 971 stage I/II breast cancers, copy number gain at 6p21.3 (RNF8 locus) was positively associated with triple negative breast cancer (p< 0.0001), high grade tumors (p=0.0017) and large size tumors (p=0.051). Gain in the genomic regions containing the RNF8 locus was significantly associated with greater genomic instability (fdr=0.01). Additionally, though not significant given small sample size, African-Americans were ∼2-fold more likely than Non-Hispanic Whites or Hispanics to be diagnosed with tumors showing gain at the RNF8 locus (p=0.11). Different groups have established that RNF8 is recruited to DNA damaged sites and subsequently mediates DNA repair by accumulation of BRCA1 and 53BP1 at DNA lesions. Recently, two groups have independently determined, in a BRCA deficient environment, that chromosomal instability is promoted in the presence of 53BP1. Additionally, it was shown that 53BP1 depletion can restore the DNA repair functions. In this report, we demonstrate differential expression of RNF8 and 53BP1 in a series of human breast cancers and an association between RNF8/53BP1 levels, proliferation, and tumor subtype. Our findings suggest that some breast tumors present an altered DNA repair pathway resulting in activation of RNF8 and de-regulation of 53BP1, which we hypothesize, may contribute to genomic instability and more proliferative tumors. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A65.

Background: Obesity rates are increasing rapidly around the globe. Obesity is associated with negative health consequences including increased risk of all-cause mortality and increased breast cancer morbidity. In the U.S., some of the highest rates of obesity are found among Hispanic women. Additionally, factors associated with low socioeconomic status have also been shown to be positively associated with obesity in the U.S., independent of race or ethnicity; higher parity (i.e., three or more full-term births) has also been implicated as a contributing factor. The aim of this study was to evaluate the independent contribution of parity on obesity in a highly parous population of Mexican and Mexican-American women diagnosed with breast cancer. Methods: Participants are from the Ella Binational Breast Cancer Study, a study of women of Mexican descent who were 18 years of age and older at time of enrollment and who were diagnosed with invasive breast cancer within 24 months of recruitment. Each participant completed an interviewer-administered risk factor questionnaire, provided a blood or saliva sample, and consented to provide tumor tissue and access to medical record data. Obesity was defined as having a body mass index (BMI) ≥30 kg/m2, which was calculated from self-reported height and weight. Parity was defined as the number of full-term live births. Age at interview, age at first full-term pregnancy, level of education, employment, smoking status, menopausal status, age at menarche, and breastfeeding were assessed as potential confounding factors. Among U.S. participants, level of acculturation, interview language and nativity were also evaluated as confounders. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multinomial logistic regression. Results: Mean age was higher for U.S. compared to Mexican participants (54.4 ± 12.6 vs. 50.1 ± 12.0). Approximately 51% (n=608) of participants resided in Mexico and 49% (n=579) in the U.S. Among U.S. participants, 54% were born in Mexico and of these, 42% have lived in the U.S. < 10 years. A higher proportion of the U.S. than Mexican women were classified as obese (40.8% vs. 34.5%). Parity was slightly higher among Mexican compared to U.S. women (3.9 ± 2.4 vs. 3.1 ± 1.7 births). We observed a positive association between parity and obesity. In the age-adjusted model, using women with 1–2 live births as the referent group, the OR (95% CI) for women with three full-term births was 1.49 (95% CI, 1.09–2.06). For women with four or more births, the OR (95% CI) was 1.40 (1.02–1.91); Ptrend=0.04. The association was attenuated with the inclusion of education in the model (Ptrend=0.15). When stratified by country of residence at the time of interview, the positive association persisted. Conclusions: Our results show a significant, positive association between parity and obesity that was not independent of education. Results of our work suggest that both pre and postnatal periods are important adult life periods for health care providers to implement obesity prevention strategies and interventions. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A80.

Background: Risk of dying from breast cancer is higher among Hispanic women compared to non-Hispanic whites (NHW) despite lower overall incidence rates and a more favorable risk factor profile. Part of the observed disparity can be explained by aggressive tumor biology although unequal access to care is also a key factor. A recent pooled case-only study suggests Hispanic women are more likely to be diagnosed with HER2-positive tumors compared to NHWs. Given the high parity rates among Hispanics and recent interest in the differential effect of reproductive factors on breast tumor subtypes, we investigated the relative correlation between reproductive factors and tumor phenotype stratified on HER2 status. Methods: A total of 459 women of Mexican origin from the case-only ELLA Binational Breast Cancer Study were classified into hormone receptor (HR) positive cases (estrogen or progesterone-receptor positive, HER2-negative) and HER2-overexpressing cases (HER2+, HR-). Women negative for all three markers (triple negative) were not considered in these analyses. Reproductive factors considered in the analysis include age at first full-term pregnancy, total number of full-term pregnancies, ever breastfeeding, breastfeeding after last pregnancy, and time since last pregnancy. Time to diagnosis since last pregnancy was classified as either ≤10 years or >10 years. We conducted separate analyses for women diagnosed at ≤ 40 years (n=72) and at >40 years of age (n=386). Differences were tested using a Pearson chi-square test or Student's t-test. We calculated case-case odds ratios (OR) and 95% confidence intervals (CI) using logistic regression to estimate the relative correlation between time since last pregnancy and HER2+ tumors in reference to HR+ tumors. Models included age at diagnosis, recruitment site, age at first pregnancy, number of pregnancies and breastfeeding. Results: Out of 459 women, 338 (74%) were HR+ and 121 (26%) HER2+. No significant differences were observed in the proportion of HR+ tumors among women ≤ 40 and those > 40 (79% vs. 73%, respectively; p=0.22). HER2+ cases were younger at diagnosis compared to HR+ cases (mean age 51.8 vs. 53.1, respectively; p= 0.30). HER2+ cases were more likely to be diagnosed after the age of 40 compared to HR+ cases (OR 4.37; 95% CI: 1.84,10.40) and were more likely to occur within the 10-year period following the last pregnancy (OR=3.99; 95% CI: 1.95,8.16). No difference was observed for age at first full-term pregnancy (OR 0.99; 95% CI: 0.95,1.03), number of full-term pregnancies (OR 0.95; 95% CI: 0.84,1.07) or ever breastfeeding (OR 0.98; 95% CI: 0.59,1.62). A significant interaction was observed between time since last pregnancy and age at diagnosis (p=0.03). Stratified results suggest the relationship between time since last pregnancy and tumor phenotype is stronger in the >40 age group (OR 3.68; 95% CI: 1.60,8.44) compared to those ≤40 (OR 2.68; 95% CI: 0.19,37.16). Conclusions: HER2+ tumors were more likely to be diagnosed in the 10-year period after the last pregnancy compared to HR+ tumors, independent of age. These findings suggest a relationship between HER2+ breast cancer and pregnancy history that differs from that with HR+ tumors, supporting the presence of etiologic heterogeneity in these subtypes. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A89.

Purpose of Study: Studies have shown that breast cancer (BC) risk is higher in U.S.-born Hispanics than foreign-born Hispanics and is modified by age at migration, duration of residence in the U.S., and level of acculturation. Furthermore, epidemiological data support the notion of distinct reproductive factor associations for specific BC tumor subtypes. The aim of this study is to assess the association between established BC risk factors and level of acculturation and country of residence among Mexican American (MA) and Mexican BC cases. Experimental Procedures: This case-only study examined the risk factor profile in 606 Mexican and 488 MA (20% US-born and 80% foreign-born) women, with a confirmed diagnosis of invasive BC, who were recruited into the ELLA Binational Breast Cancer Study between March 1,2007, and May 31,2010. Participants completed an interviewer-administered risk factor questionnaire, consented to a medical record review, and provided tissue and saliva or blood specimens. An eight-item language-based Bidimensional Acculturation Scale (BAS) was used to classify MA women as English-dominant (n=88), bilingual (n=221), or Spanish-dominant (n=179). The BAS is highly correlated with nativity and time in the US, however language use/exposure was focal for this study since it is the single strongest predictor of acculturation. Chi-square tests, ANOVA, and regression models to test for trend were used to assess variation in the risk factor profile by level of acculturation. Summary of Results: Age at diagnosis was generally low; the lowest was among MA-bilingual women (48.9 = 12.0 years) and highest among Mexican women (53.7 = 12.7 years). Considering a gradient of increasing acculturation from Mexican (lowest) to MA-English dominant (highest) women, there were clear trends for decreasing rates of breastfeeding (80.2 to 35.2%; p-trend Conclusion: Our results show that heterogeneity in BC risk factor patterns by level of acculturation is present. Given the recent data supporting distinct correlations between specific risk factors and BC subtypes, it will be essential to consider level of acculturation and country of residence when assessing the prevalence of these subtypes. The trends observed in risk factor profiles by level of acculturation in the ELLA Study could provide important explanations for differences in disease patterns between groups. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):PR-5.

Screening mammography is associated with early detection of breast cancer (BC) and reduced BC mortality. To understand factors that influence screening mammography receipt in minority women with unrecognized risk factors for BC, this study examined BC screening behaviors among women with BC. Due to the BC survival disparities observed in African American (AA) and Mexican American (MA) women compared to whites, AA and MA women living in Texas and Arizona who were participants of the ELLA Binational Breast Cancer Study were selected for this study based on a diagnosis of BC. Data on socioeconomic status (SES), reproductive history, family history, insurance status, acculturation, and breast health history were collected via questionnaires and medical record abstraction. 601 women aged 40 years or older at time of BC diagnosis were included in this study, including 270 AA, 151 MA women classified as high-acculturation (MA-HA) and 180 MA women classified as low-acculturation (MA-LA). Logistic regression analysis was used to assess differences in mammography receipt in the last five years prior to BC diagnosis stratified by race/ethnicity and acculturation and for all groups combined. MA women in this study suffer a larger disparity than AA women with regards to screening mammography. Despite high rates of screening mammography among AA and MA women, 62% of BC was self-detected in the study population. AA women (OR=1.0) and MA-HA (OR=0.91; 95% CI: 0.57-1.48) women were more than twice as likely to receive screening mammography compared to MA-LA (OR=0.38; 95% CI: 0.25-0.59), adjusted for age. After adjusting for age, education, and insurance, there was no significant difference in screening mammography receipt between these three groups. Women who had a known family history of BC were more than twice as likely to receive screening mammography than women who had unknown or no family history (OR=2.02; 95% CI: 1.19-3.55). However, although AA and MA-HA women were twice as likely as MA-LA to report a family history of BC (20% vs. 23% vs. 12%, respectively), recognized family history did not account for the differences in screening mammography use between these groups. Thus, the differences observed in screening mammography receipt by race/ethnicity and acculturation among AA, MA-HA, and MA-LA are likely explained by SES variables, including education and insurance. Due to the large proportion of AA and MA women who reported self-detecting their BC, women must be educated about the importance of breast awareness and prompt reporting of findings to a health professional after noticing breast changes. In addition, cancer screening programs targeting underserved women should provide culturally appropriate messages about the importance of knowing their family history and the benefits of screening mammography. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2806.