The Development of a Multi-Modal Cancer Rehabilitation (Including Prehabilitation) Service in Sheffield, UK: Designing the Active Together Service.

Cancer patients undergoing major interventions face numerous challenges, including the adverse effects of cancer and the side effects of treatment. Cancer rehabilitation is vital in ensuring cancer patients have the support they need to maximise treatment outcomes and minimise treatment-related side effects and symptoms. The Active Together service is a multi-modal rehabilitation service designed to address critical support gaps for cancer patients. The service is located and provided in Sheffield, UK, an area with higher cancer incidence and mortality rates than the national average. The service aligns with local and regional cancer care objectives and aims to improve the clinical and quality-of-life outcomes of cancer patients by using lifestyle behaviour-change techniques to address their physical, nutritional, and psychological needs. This paper describes the design and initial implementation of the Active Together service, highlighting its potential to support and benefit cancer patients.

PD-1-expressing macrophages and CD8 T cells are independent predictors of clinical benefit from PD-1 inhibition in advanced mesothelioma.

BACKGROUND: Few tissue biomarkers exist to date that could enrich patient with cancer populations to benefit from immune checkpoint blockade by programmed cell death protein 1/ligand-1 (PD-/L-1) inhibitors. PD-L1 expression has value in this context in some tumor types but is an imperfect predictor of clinical benefit. In malignant pleural mesothelioma, PD-L1 expression is not predictive of the benefit from PD-1 blockade. We aimed to identify novel markers in malignant pleural mesothelioma to select patients better. METHODS: We performed a multiplex-immune histochemistry analysis of tumor samples from the phase III PROMISE-meso study, which randomized 144 pretreated patients to receive either pembrolizumab or standard second-line chemotherapy. Our panel focused on CD8+T cell, CD68+macrophages, and the expression of PD-1 and PD-L1 on these and cancer cells. We analyzed single and double positive cells within cancer tissues (infiltrating immune cells) and in the stroma. In addition, we performed cell neighborhood analysis. The cell counts were compared with clinical outcomes, including responses, progression-free and overall survivals. RESULTS: We confirmed the absence of predictive value for PD-L1 in this cohort of patients. Furthermore, total CD8 T cells, CD68+macrophages, or inflammatory subtypes (desert, excluded, inflamed) did not predict outcomes. In contrast, PD-1-expressing CD8+T cells (exhausted T cells) and PD-1-expressing CD68+macrophages were both independent predictors of progression-free survival benefit from pembrolizumab. Patients with tumors simultaneously harboring PD1+T cells and PD-1+macrophages benefited the most from immune therapy. CONCLUSION: We analyzed a large cohort of patients within a phase III study and found that not only PD-1+CD8 T cells but also PD-1+CD68+ macrophages are predictive. This data provides evidence for the first time for the existence of PD-1+macrophages in mesothelioma and their clinical relevance for immune checkpoint blockade.

Principles for secondary traumatic stress-responsive practice: An expert consensus approach.

OBJECTIVE: Though research on secondary traumatic stress (STS) has greatly increased in the past decade, to date the field lacks a coherent set of guiding principles for practice that behavioral health providers and organizations can use to mitigate the occurrence and impact of STS. As such it is important to identify effective strategies, grounded in research and professional experience, to reduce the occurrence and impact of STS among behavioral health professionals and organizations. METHOD: We conducted a four-stage modified Delphi survey. Thirty-one international STS experts were invited to participate, with a minimum of 19 responding in each round. Thematic analysis was conducted on qualitative data, which was incorporated into revisions of the principles. RESULTS: Consensus was achieved on 14 principles, seven targeted at individual professionals, and seven targeted at organizations. CONCLUSIONS: This is the first effort to delineate principles for practice intended to reduce the occurrence and impact of STS in individual and organizational practice in behavioral health services. The principles are intended to inform best practices for individuals and organizations providing services to persons and communities who have experienced trauma and thereby improve the quality and effectiveness of services to traumatized populations. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Time to embed physical activity within usual care in cancer services: A qualitative study of cancer healthcare professionals' views at a single centre in England.

PURPOSE: An increasing number of people affected by cancer (PABC) are living longer lives as treatment continues to advance. There is growing evidence for physical activity (PA) supporting health in this population before, during and after cancer treatment, but PA advice is not part of usual care. This study investigates views of frontline oncology healthcare professionals (HCPs) in one NHS teaching hospital in England to understand the role of PA advice across cancer services. MATERIALS AND METHODS: This was a qualitative study interviewing HCPs and using thematic analysis. RESULTS: Four main themes were identified: 1. Awareness of the roles of PA in cancer; 2. Patient-specific factors in rehabilitation; 3. Cancer-specific factors in rehabilitation; 4. Barriers and opportunities to integrating PA within usual care. HCPs' awareness of the role of PA in cancer rehabilitation was low overall and PA was found not to be embedded within rehabilitation. Contrastingly, there was awareness of PA's potential to impact disease and treatment-related outcomes positively. Ideas for PA integration included training for staff and giving PA advice within consultations. CONCLUSIONS: Low awareness of benefits of PA-based rehabilitation and lack of integration in usual care contrasted with HCPs' interest in this area's potential. Training HCPs to begin the conversation with patients affected by cancer in teachable moments may increase patient access.Implications for rehabilitationIntegrating physical activity education and training for trainees and existing healthcare professionals workforce would help embed physical activity into routine clinical practice.Brief advice intervention training during every consultation, such as providing relevant individualised information and signposting, can be impactful.Physical activity within a broader cancer rehabilitation programme should be integrated as standard for every cancer patient.Individualised plans may include prehabilitation, restorative rehabilitation and palliative rehabilitation.Patient preferences and the patient experience should continue to shape service design.There is a need to ensure physical activity advice is consistent throughout healthcare settings and not fragmented between primary, secondary and tertiary care.

Allied health professional's self-reported competences and confidence to deliver physical activity advice to cancer patients at a single Centre in England.

PURPOSE: Allied Health Professionals (AHPs) are well placed to deliver physical activity advice but this is currently not routine clinical practice. Increasing evidence demonstrates physical activity can improve quality-of-life for people affected by cancer, enable behaviour change, improve survival and reduce long-term treatment effects. We aimed to understand AHPs' current knowledge and practice in advising about physical activity. MATERIALS AND METHODS: AHPs' self-reported knowledge, competency and training needs in managing physical effects of cancer, and the merits of physical activity data were collected via an online survey. The survey link was cascaded electronically to all NHS and NHS-affiliated AHPs working across several generic and non-cancer-specific healthcare interfaces across one city in England. RESULTS: Eighty AHPs responded. Forty-one percent of AHPs had patients with current or past diagnoses of cancer. Overall, AHPs reported low confidence in giving physical activity advice, with physiotherapists the most confident. 60% of respondents identified training needs concerning the impact of cancer. CONCLUSIONS: Although the merits of physical activity for people affected by cancer is clearly evidenced, low levels of AHP confidence and competence in discussing this topic limit patients' awareness and access to services. Addressing this confidence and competence has potential to improve patient outcome.

People affected by cancer frequently experience disease and treatment-related impacts which can be detrimental to physical health and well-beingPhysical activity, can restore aspects of physical health and quality of life before, during and after cancer treatmentPeople affected by cancer have frequent points of contact with Allied Health Professionals throughout the cancer pathway and beyond via a variety of rehabilitation servicesWith increased confidence, Allied Health Professionals have the potential to "make every contact count" by providing physical activity advice and information to people affected by cancer across a variety of rehabilitation settingsTraining opportunities and bespoke learning and development offers may provide the platform for improving Allied Health Professional competences and confidence to deliver physical activity advice to people affected by cancerImproving Allied Health Professional skills, knowledge and confidence for people affected by cancer has the potential to influence patient outcomes.

A prognostic score for patients with malignant pleural mesothelioma (MPM) receiving second-line immunotherapy or chemotherapy in the ETOP 9-15 PROMISE-meso phase III trial.

INTRODUCTION: Clinical and laboratory parameters associated with response for patients with advanced pre-treated malignant pleural mesothelioma (MPM) are lacking. We aimed to identify prognostic and predictive markers among patients with relapsed MPM who were randomised into the ETOP 9-15 PROMISE-meso phase III trial, evaluating pembrolizumab and chemotherapy. METHODS: Baseline clinical and laboratory parameters were investigated for prognostic or predictive value on progression-free survival (PFS) and overall survival (OS) in a retrospective analysis, based on the full cohort of 144 MPM patients. These consisted of immune-inflammatory indexes (neutrophil-lymphocyte ratio [NLR], systemic immune-inflammatory index [SII], lactate dehydrogenase [LDH]) along with other already known prognostic baseline characteristics and laboratory values. Cut-offs were chosen independently of outcome. Based on Cox multivariable analysis for PFS in the whole cohort, a risk factor model was built to illustrate the prognostic stratification of patients by the combination of the derived independent prognostic factors, taking into account the EORTC score, a validated prognostic score in MPM. All models were stratified by histology and adjusted by treatment. RESULTS: In the stratified multivariable analysis in the whole cohort, high SII (hazard ratio (HR) 2.06; 95%CI 1.39-3.05) and low haemoglobin (HR 1.62; 95%CI 1.06-2.50) were associated with worse PFS. Based on these two prognostic factors, a mesothelioma risk score (MRS) was constructed with three PFS risk prognosis categories: favourable, intermediate and poor with 0, 1 and 2 risk factors, respectively (corresponding percent of cohort: 24%, 34% and 42% and median PFS: 5.8, 4.2 and 2.1 months). The derived MRS stratified the prognosis for PFS and OS, overall and within each of the EORTC groups. No significant predictors of treatment benefit were identified. CONCLUSIONS: The proposed MRS is prognostic of patient outcome and it fine-tunes the prognosis of patients with pre-treated MPM alone or when used with the already established EORTC score.

Oncolytic herpesvirus therapy for mesothelioma - A phase I/IIa trial of intrapleural administration of HSV1716.

OBJECTIVES: Malignant Pleural Mesothelioma (MPM) remains a major oncological challenge with limited therapeutic options. HSV1716 is a replication restricted oncolytic herpes simplex virus with anti-tumor effects in multiple cell lines including MPM. Intrapleural treatment appeals because MPM is typically multifocal but confined to the pleura, and distant metastases are uncommon. We assessed the safety and possible efficacy of intrapleural HSV1716 for inoperable MPM. MATERIALS AND METHODS: Patients with MPM received 1 × 107iu HSV1716 injected via an indwelling intrapleural catheter (IPC) on one, two or four occasions a week apart. The primary endpoint was the safety and tolerability of HSV1716. Secondary endpoints were assessment of HSV1716 replication, detection of immune response and evaluation of tumor response. RESULTS: Of thirteen patients enrolled, five had received previous pemetrexed-cisplatin chemotherapy, and eight were chemotherapy naïve. Three patients were enrolled to receive one dose, three patients to two doses and seven patients to four doses. The treatment was well-tolerated with few virus-related adverse events and no dose limiting toxicities. Twelve patients were evaluable for response, as one patient withdrew early after a catheter fracture. There was evidence of viral replication/persistence in pleural fluid in seven of the twelve patients. Induction of Th1 cytokine responses to HSV1716 treatment occurred in eight patients and four patients developed novel anti-tumor IgG. No objective responses were observed but disease stabilization was reported in 50 % of patients at 8 weeks. CONCLUSIONS: Intrapleural HSV1716 was well-tolerated and demonstrated an anti-tumor immune response in MPM patients. These results provide a rationale for further studies with this agent in MPM and in combination with other therapies.

Radical accelerated radiotherapy for non-small cell lung cancer (NSCLC): A 5-year retrospective review of two dose fractionation schedules.

BACKGROUND AND PURPOSE: Numerous fractionation regimes are used for inoperable NSCLC patients not suitable for stereotactic ablative radiotherapy. Continuous hyperfractionated accelerated radiotherapy (CHART, 54 Gy, 36 fractions over 12 days) and hypofractionated accelerated radiotherapy (55 Gy, 20 fractions over 4 weeks) are recommended UK schedules. In this single-centre retrospective analysis, we compare both fractionation schemes for patients treated at our institution from 2010 to 15. MATERIALS AND METHODS: Clinical demographic, tumour and survival data were collected alongside radiotherapy dosimetric data from the Varian Eclipse Scripting application programming interface. Differences were assessed using independent samples t-tests. Multivariate survival analysis was performed using Cox regression. RESULTS: We identified 563 eligible patients; 43% received CHART and 57% hypofractionated radiotherapy. Median age was 71 years, 56% were male, 95% PET staged with 53% WHO performance status 0-1. 30%, 14%, 50% and 6% were stage I, II, III and IV, respectively. 38% of patients underwent induction chemotherapy. 99% completed their prescribed radiotherapy treatment. Overall response rate was 50% with a 6.5% 90-day mortality rate. Median disease-free survival was 19 months, 50% recurred locally. Median overall survival was 22.5 months with 48% alive at 2 years. Multivariate analysis identified histology, stage, performance status, chemotherapy and radiotherapy response as independent predictors of survival; no significant differences between radiotherapy regimes were observed. CONCLUSION: In our centre, CHART and hypofractionated accelerated radiotherapy produce similar outcomes. Dose escalation studies are in progress to develop these schedules to match outcomes reported in concurrent chemo-radiation studies.

In vitro fertilization of ovine oocytes vitrified by solid surface vitrification at germinal vesicle stage.

Cryopreservation of immature oocytes at germinal vesicle (GV) stage would provide a readily available source of oocytes for use in research and allow experiments to be performed irrespective of seasonality or other constraints. This study was designed to evaluate the recovery, viability, maturation status, fertilization events and subsequent development of ovine oocytes vitrified at GV stage using solid surface vitrification (SSV). Cumulus oocyte complexes (COCs) obtained from mature ewes were randomly divided into three groups (1) SSV (oocytes were vitrified using SSV), (2) EXP (oocytes were exposed to vitrification and warming solutions without vitrification) or (3) Untreated (control). Following vitrification and warming, viable oocytes were matured in vitro for 24h. After that, nuclear maturation was evaluated using orcein staining. Matured oocytes were fertilized and cultured in vitro for 7days. Following SSV, 75.7% 143/189 oocytes were recovered. Of those oocytes recovered 74.8%, 107/143 were morphologically normal (viable). Frequencies of in vitro maturation were significantly (P<0.01) decreased in SSV and EXP groups as compared to control. In vitro fertilization rates were significantly (P<0.01) decreased in SSV (39.3%) group as compared to EXP (56.4%) and control (64.7%) groups. Cleavage at 48h post insemination (pi) and development to the blastocyst stage on day 7 pi were significantly (P<0.001) decreased in SSV oocytes as compared to EXP and control groups. In conclusion, immature ovine oocytes vitrified using SSV as a simple and rapid procedure can survive and subsequently be matured, fertilized and cultured in vitro up to the blastocyst stage, although the frequency of development is low.

Evaluation of a fibrillin 2 gene haplotype associated with hip dysplasia and incipient osteoarthritis in dogs.

OBJECTIVE: To determine whether a mutation in the fibrillin 2 gene (FBN2) is associated with canine hip dysplasia (CHD) and osteoarthritis in dogs. ANIMALS: 1,551 dogs. Procedures-Hip conformation was measured radiographically. The FBN2 was sequenced from genomic DNA of 21 Labrador Retrievers and 2 Greyhounds, and a haplotype in intron 30 of FBN2 was sequenced in 90 additional Labrador Retrievers and 143 dogs of 6 other breeds. Steady-state values of FBN2 mRNA and control genes were measured in hip joint tissues of fourteen 8-month-old Labrador Retriever-Greyhound crossbreeds. RESULTS: The Labrador Retrievers homozygous for a 10-bp deletion haplotype in intron 30 of FBN2 had significantly worse CHD as measured via higher distraction index and extended-hip joint radiograph score and a lower Norberg angle and dorsolateral subluxation score. Among 143 dogs of 6 other breeds, those homozygous for the same deletion haplotype also had significantly worse radiographic CHD. Among the 14 crossbred dogs, as the dorsolateral subluxation score decreased, the capsular FBN2 mRNA increased significantly. Those dogs with incipient hip joint osteoarthritis had significantly increased capsular FBN2 mRNA, compared with those dogs without osteoarthritis. Dogs homozygous for the FBN2 deletion haplotype had significantly less FBN2 mRNA in their femoral head articular cartilage. CONCLUSIONS AND CLINICAL RELEVANCE: The FBN2 deletion haplotype was associated with CHD. Capsular gene expression of FBN2 was confounded by incipient secondary osteoarthritis in dysplastic hip joints. Genes influencing complex traits in dogs can be identified by genome-wide screening, fine mapping, and candidate gene screening.

Oral presentation of malignant mesothelioma.

We report a case of metastatic mesothelioma presenting as an oral metastasis in a 46-year-old patient. The patient presented with 2 polypoid lesions that appeared to be benign on the dorsum of the tongue. Excisional biopsy showed the presence of metastatic carcinoma that on further investigation proved to be mesothelioma. The initial presentation of mesothelioma as an oral metastasis is not previously reported. This article highlights the importance of biopsy and histopathological diagnosis in presumed benign lesions and the role of the general dental practitioner in screening for oral neoplasms.

Reprogramming of ovine somatic cells with Xenopus laevis oocyte extract prior to SCNT improves live birth rate.

The birth of live animals following somatic cell nuclear transfer (SCNT) has demonstrated that oocytes can reprogram the genome of differentiated cells. However, in all species the frequency of development of healthy offspring is low; for example, in sheep, approximately only 5% of blastocysts transferred develop to term, and less than 3% develop to adulthood. Such low efficiencies, coupled with the occurrence of developmental abnormalities, have been attributed to incomplete or incorrect reprogramming. Cytoplasmic extracts from both mammalian and amphibian oocytes can alter the epigenetic state of mammalian somatic nuclei and reprogram gene expression to more resemble that of pluripotent cells. Therefore, it may be possible to increase the frequency or success of normal development by pretreating somatic cells to be used as nuclear donors prior to SCNT. In the present study, permeabilized ovine fetal fibroblasts were pretreated with a cytoplasmic extract produced from germinal vesicle (GV) stage Xenopus laevis oocytes. No increase in the frequency of development to blastocyst stage or pregnancy rate was observed; however, live birth and survival rates were significantly improved. Development to term of blastocysts transferred increased from 3.1% in the control group, to 14.7% in the treated group (a 4.7-fold increase), and even though the subsequent survival of lambs produced from treated cells was reduced by 60%, the percentage of lambs surviving to adulthood of blastocysts transferred (5.9%) increased 1.9-fold compared to controls. This study is the first to report the birth of live offspring and an increase in cloning efficiency, after crossspecies pre-reprogramming using Xenopus GV stage oocyte extract.

ERK signaling in the pituitary is required for female but not male fertility.

Males and females require different patterns of pituitary gonadotropin secretion for fertility. The mechanisms underlying these gender-specific profiles of pituitary hormone production are unknown; however, they are fundamental to understanding the sexually dimorphic control of reproductive function at the molecular level. Several studies suggest that ERK1 and -2 are essential modulators of hypothalamic GnRH-mediated regulation of pituitary gonadotropin production and fertility. To test this hypothesis, we generated mice with a pituitary-specific depletion of ERK1 and 2 and examined a range of physiological parameters including fertility. We find that ERK signaling is required in females for ovulation and fertility, whereas male reproductive function is unaffected by this signaling deficiency. The effects of ERK pathway ablation on LH biosynthesis underlie this gender-specific phenotype, and the molecular mechanism involves a requirement for ERK-dependent up-regulation of the transcription factor Egr1, which is necessary for LHbeta expression. Together, these findings represent a significant advance in elucidating the molecular basis of gender-specific regulation of the hypothalamic-pituitary-gonadal axis and sexually dimorphic control of fertility.

c-kit expression identifies cardiovascular precursors in the neonatal heart.

Directed differentiation of embryonic stem cells indicates that mesodermal lineages in the mammalian heart (cardiac, endothelial, and smooth muscle cells) develop from a common, multipotent cardiovascular precursor. To isolate and characterize the lineage potential of a resident pool of cardiovascular progenitor cells (CPcs), we developed BAC transgenic mice in which enhanced green fluorescent protein (EGFP) is placed under control of the c-kit locus (c-kit(BAC)-EGFP mice). Discrete c-kit-EGFP(+) cells were observed at different stages of differentiation in embryonic hearts, increasing in number to a maximum at about postnatal day (PN) 2; thereafter, EGFP(+) cells declined and were rarely observed in the adult heart. EGFP(+) cells purified from PN 0-5 hearts were nestin(+) and expanded in culture; 67% of cells were fluorescent after 9 days. Purified cells differentiated into endothelial, cardiac, and smooth muscle cells, and differentiation could be directed by specific growth factors. CPc-derived cardiac myocytes displayed rhythmic beating and action potentials characteristic of multiple cardiac cell types, similar to ES cell-derived cardiomyocytes. Single-cell dilution studies confirmed the potential of individual CPcs to form all 3 cardiovascular lineages. In adult hearts, cryoablation resulted in c-kit-EGFP(+) expression, peaking 7 days postcryolesion. Expression occurred in endothelial and smooth muscle cells in the revascularizing infarct, and in terminally differentiated cardiomyocytes in the border zone surrounding the infarct. Thus, c-kit expression marks CPc in the neonatal heart that are capable of directed differentiation in vitro; however, c-kit expression in cardiomyocytes in the adult heart after injury does not identify cardiac myogenesis.

mCLCA4 ER processing and secretion requires luminal sorting motifs.

Ca(+)-activated Cl(-) channel (CLCA) proteins are encoded by a family of highly related and clustered genes in mammals that are markedly upregulated in inflammation and have been shown to affect chloride transport. Here we describe the cellular processing and regulatory sequences underlying murine (m) CLCA4 proteins. The 125-kDa mCLCA4 gene product is cleaved to 90- and 40-kDa fragments, and the NH(2)- and COOH-terminal fragments are secreted, where they are found in cell media and associated with the plasma membrane. The 125-kDa full-length protein is only found in the endoplasmic reticulum (ER), and specific luminal diarginine retention and dileucine forward trafficking signals contained within the CLCA4 sequence regulate export from the ER and proteolytic processing. Mutation of the dileucine luminal sequences resulted in ER trapping of the immaturely glycosylated 125-kDa peptide, indicating that proteolytic cleavage occurs following recognition of the trafficking motifs. Moreover, the mutated dileucine and diarginine signal sequences directed processing of a secreted form of enhanced green fluorescent protein in a manner consistent with the effects on mCLCA4.

Active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): a multicentre randomised trial.

BACKGROUND: Malignant pleural mesothelioma is almost always fatal, and few treatment options are available. Although active symptom control (ASC) has been recommended for the management of this disease, no consensus exists for the role of chemotherapy. We investigated whether the addition of chemotherapy to ASC improved survival and quality of life. METHODS: 409 patients with malignant pleural mesothelioma, from 76 centres in the UK and two in Australia, were randomly assigned to ASC alone (treatment could include steroids, analgesic drugs, bronchodilators, palliative radiotherapy [n=136]); to ASC plus MVP (four cycles of mitomycin 6 mg/m2, vinblastine 6 mg/m2, and cisplatin 50 mg/m2 every 3 weeks [n=137]); or to ASC plus vinorelbine (one injection of vinorelbine 30 mg/m2 every week for 12 weeks [n=136]). Randomisation was done by minimisation, with stratification for WHO performance status, histology, and centre. Follow-up was every 3 weeks to 21 weeks after randomisation, and every 8 weeks thereafter. Because of slow accrual, the two chemotherapy groups were combined and compared with ASC alone for the primary outcome of overall survival. Analysis was by intention to treat. This study is registered, number ISRCTN54469112. FINDINGS: At the time of analysis, 393 (96%) patients had died (ASC 132 [97%], ASC plus MVP 132 [96%], ASC plus vinorelbine 129 [95%]). Compared with ASC alone, we noted a small, non-significant survival benefit for ASC plus chemotherapy (hazard ratio [HR] 0.89 [95% CI 0.72-1.10]; p=0.29). Median survival was 7.6 months in the ASC alone group and 8.5 months in the ASC plus chemotherapy group. Exploratory analyses suggested a survival advantage for ASC plus vinorelbine compared with ASC alone (HR 0.80 [0.63-1.02]; p=0.08), with a median survival of 9.5 months. There was no evidence of a survival benefit with ASC plus MVP (HR 0.99 [0.78-1.27]; p=0.95). We observed no between-group differences in four predefined quality-of-life subscales (physical functioning, pain, dyspnoea, and global health status) at any of the assessments in the first 6 months. INTERPRETATION: The addition of chemotherapy to ASC offers no significant benefits in terms of overall survival or quality of life. However, exploratory analyses suggested that vinorelbine merits further investigation.

'Transforming' self and world: a phenomenological study of a changing lifeworld following a cochlear implant.

After 50 years of being profoundly deaf, Patricia (Pat) finds her world 'transformed'-literally and metaphorically-when she receives a cochlear implant. Her sense of self and the taken-for-granted, comfortable world she knew before surgery disappear and she is thrown into an alien, surreal existence full of hyper-noise. Entry into this new world of sounds proves a mixed blessing as Pat struggles to come to terms with her changing relationships, not only with others (who now feel somehow 'different' to her) but also with herself. On good days, she is exhilarated by all her sensory gains and her feeling of being more connected with and to the world. On bad days she is distracted and overwhelmed by the intrusive noise and she is forcibly confronted with the painful reality of her own disability (past and present). The challenge she confronts is not simply the cognitive-perceptual one of learning to discriminate between sounds. Pat must also re-orientate herself and learn to cope with her transformed self and world. She must undertake a journey to come to terms with her past, present and future being. Pat shared her story with me and together we undertook collaborative existential phenomenological research, co-creating a narrative of her journey over the year and a half following her implant. This paper presents this narrative followed by an existential analysis of Pat's disrupted, changing lifeworld.