Existential suffering in the day to day lives of those living with palliative care needs arising from chronic obstructive pulmonary disease (COPD): A systematic integrative literature review.

BACKGROUND: The impact of living with palliative care needs arising from COPD disrupts an individual's existential situation. However, no comprehensive synthesis of existing research has been published to determine the presentation and impact of existential suffering. AIM: To provide a synthesis of existing evidence on existential suffering for those living with palliative care needs arising from COPD. DESIGN: This is an integrative review paper, undertaken using the methodological approach developed by Soares and reported in accordance with PRISMA guidelines. Data analysis was undertaking using an integrated convergent synthesis approach. DATA SOURCES: Nine electronic databases were searched from April 2019 to December 2019. A second search was undertaken in January 2021 to identify recently published papers meeting the inclusion and exclusion criteria. No date restrictions were imposed. Only papers published in the English Language were considered for inclusion. Empirical research papers employing qualitative and/or quantitative methodologies and systematic literature reviews were included. Articles were accepted for inclusion if they discussed any component of existential suffering when living with COPD and palliative care needs. RESULTS: Thirty-five papers were included within this review comprising of seven systematic reviews, 10 quantitative studies and 18 qualitative studies. The following themes relating to existential suffering were found: Liminality, Lamented Life, Loss of Personal Liberty, Life meaning and Existential isolation. The absence of life meaning, and purpose was of most importance to participants. CONCLUSIONS: This review suggests existential suffering is present and of significant impact within the daily lives of those living with palliative care needs arising from COPD. The absence of life meaning has the most significant impact. Further research is required to understand the essential components of an intervention to address existential suffering for this patient group, to ensure holistic palliative care delivery.

Role and support needs of nurses in delivering palliative and end of life care.

The coronavirus disease 2019 (COVID-19) pandemic has led to a significant increase in the demand for palliative and end of life care, particularly in the community. Furthermore, palliative and end of life care services face growing pressures due to the increasing number of older people and increasing prevalence of chronic illness. Palliative and end of life care cannot be provided solely by specialists but needs to be integrated into mainstream healthcare. All nurses have a role in supporting patients with life-limiting conditions, and their families, by providing what is termed 'generalist palliative care'. However, some nurses may feel unprepared, unsupported or lacking the confidence and skills for that role. This article explores the definitions of palliative and end of life care, as well as the changes and challenges in service provision brought about by the COVID-19 pandemic. It also considers how nurses who have not specialised in this area of practice can be supported to care effectively for patients with life-limiting conditions, and their families, notably through workforce development initiatives such as training programmes and clinical supervision. This could not only increase the skills of the nursing workforce but also improve patient care.

KRAS mutation analysis by PCR: a comparison of two methods.

BACKGROUND: KRAS mutation assays are important companion diagnostic tests to guide anti-EGFR antibody treatment of metastatic colorectal cancer. Direct comparison of newer diagnostic methods with existing methods is an important part of validation of any new technique. In this this study, we have compared the Therascreen (Qiagen) ARMS assay with Competitive Allele-Specific TaqMan PCR (castPCR, Life Technologies) to determine equivalence for KRAS mutation analysis. METHODS: DNA was extracted by Maxwell (Promega) from 99 colorectal cancers. The ARMS-based Therascreen and a customized castPCR assay were performed according to the manufacturer's instructions. All assays were performed on either an Applied Biosystems 7500 Fast Dx or a ViiA7 real-time PCR machine (both from Life Technologies). The data were collected and discrepant results re-tested with newly extracted DNA from the same blocks in both assay types. RESULTS: Of the 99 tumors included, Therascreen showed 62 tumors to be wild-type (WT) for KRAS, while 37 had KRAS mutations on initial testing. CastPCR showed 61 tumors to be wild-type (WT) for KRAS, while 38 had KRAS mutations. Thirteen tumors showed BRAF mutation in castPCR and in one of these there was also a KRAS mutation. The custom castPCR plate included several other KRAS mutations and BRAF V600E, not included in Therascreen, explaining the higher number of mutations detected by castPCR. Re-testing of discrepant results was required in three tumors, all of which then achieved concordance for KRAS. CastPCR assay Ct values were on average 2 cycles lower than Therascreen. CONCLUSION: There was excellent correlation between the two methods. Although castPCR assay shows lower Ct values than Therascreen, this is unlikely to be clinically significant.

Activity of EGFR, mTOR and PI3K inhibitors in an isogenic breast cell line model.

BACKGROUND: The epidermal growth factor receptor family is expressed in breast cancer, and agents targeting this pathway have single agent effects (e.g. traztuzumab). Development of resistance may be due to the presence of alternative pathways, particularly activation of the PI3K/Akt/MTOR pathway. We have therefore examined the effect of inhibitors of this pathway (ZSTK474 and sirolimus) in combination with the epidermal growth factor (EGFR) inhibitors erlotinib and gefitinib in breast MCF10a isogenic cell lines with EGFR, BRAF, AKT, and PI3K mutations. RESULTS: PI3K mutation conferred increased activity of EGFR inhibitors against MCF10a cells in comparison with the parental cell line and other mutations studied. Combination of EGFR inhibitors with either the PI3K inhibitor ZSTK474 or the MTOR inhibitor sirolimus showed increased activity. CONCLUSIONS: These results are encouraging for the use of combinations targeting the PI3K and EGFR pathway simultaneously.

Breast cancer is a promising target for vaccination using cancer-testis antigens known to elicit immune responses.

INTRODUCTION: Cancer-testis antigens (CTAGs) are expressed solely in germ cells and in malignant tissues. They are targets of immune responses mediated by cytotoxic T cells in some cancers, and there is much interest in developing vaccines that induce these responses. The purpose of the present study was to ascertain the frequency of expression of CTAGs in breast cancer. METHODS: Breast tumours were collected sequentially in the Southampton Tumour Bank from donors who had given written informed consent. Stored samples where there was sufficient material were sampled in sequence. An initial series of 42 tumours was screened for expression of 17 different CTAGs. A second panel of 40 tumours was screened for the expression of those antigens present in the first panel. RESULTS: Ninety-three per cent of tumours in the first series expressed at least one CTAG, and 62% expressed the single antigen CTAG1. Eighty per cent of tumours in the second series expressed at least one CTAG, 50% expressing CTAG1. Tumours exhibiting higher risk features tended to express more CTAGs. CONCLUSION: More than two-thirds of breast cancers would be covered by a vaccine directed against just three CTAGs - CTAG1, BAGE1, and MAGEA10 - all of which are known to be targets of cytotoxic-T-lymphocyte responses.