ESMO Expert Consensus Statements on Cancer Survivorship: promoting high-quality survivorship care and research in Europe.

BACKGROUND: The increased number of cancer survivors and the recognition of physical and psychosocial challenges, present from cancer diagnosis through active treatment and beyond, led to the discipline of cancer survivorship. DESIGN AND METHODS: Herein, we reflected on the different components of survivorship care, existing models and priorities, in order to facilitate the promotion of high-quality European survivorship care and research. RESULTS: We identified five main components of survivorship care: (i) physical effects of cancer and chronic medical conditions; (ii) psychological effects of cancer; (iii) social, work and financial effects of cancer; (iv) surveillance for recurrences and second cancers; and (v) cancer prevention and overall health and well-being promotion. Survivorship care can be delivered by structured care models including but not limited to shared models integrating primary care and oncology services. The choice of the care model to be implemented has to be adapted to local realities. High-quality care should be expedited by the generation of: (i) focused and shared European recommendations, (ii) creation of tools to facilitate implementation of coordinated care and (iii) survivorship educational programs for health care teams and patients. The research agenda should be defined with the participation of health care providers, researchers, policy makers, patients and caregivers. The following patient-centered survivorship research areas were highlighted: (i) generation of a big data platform to collect long-term real-world data in survivors and healthy controls to (a) understand the resources, needs and preferences of patients with cancer, and (b) understand biological determinants of survivorship issues, and (ii) develop innovative effective interventions focused on the main components of survivorship care. CONCLUSIONS: The European Society for Medical Oncology (ESMO) can actively contribute in the efforts of the oncology community toward (a) promoting the development of high-quality survivorship care programs, (b) providing educational material and (c) aiding groundbreaking research by reflecting on priorities and by supporting research networking.

'They don't actually join the dots': An exploration of organizational change in Irish opiate community treatment services.

BACKGROUND: People who use community-based drug treatment services spend a considerable amount of their time in treatment in direct contact with frontline staff. These staff are also fundamental to supporting the implementation of change to meet service user needs. Yet, very little is known about staff perspectives on the process and internal dynamics of drug treatment services, their views about what makes services work effectively, and how services can more effectively adopt to changes in practice. AIM AND METHOD: Conducted across Irish community opiate prescribing services and drawing on data from 12 in-depth qualitative interviews with frontline staff. This paper examines the narratives of staff about the factors which influence the dynamics and process of treatment services, particularly in relation to the implantation of change. FINDINGS: Change itself was described both in respect of how a service responded to immediate service user needs or supported planned change. Little distinction was made in respect of service attributes which facilitated a response in either context. Overwhelmingly, staff contextualised current service effectiveness, historical change, and desired change in how effectively their services met service user needs, which was also viewed as a significant motivation for change. Differences in operational standards across services in terms of practices, policy implementation, job roles, divisions between professional groups, and recruitment and retention of staff inhibited change adoption. Factors which were identified in terms of inhibiting or facilitating planned change were consistent with the wider literature on change implementation but provided unique insights in the context of substance misuse services. CONCLUSIONS: A range of interdependent factors which influence an 'eco-system' of service delivery were identified. Effective policy implementation in Ireland remains aspirational, but findings reported in this paper have important implications for future planning and design of services for people who use drugs, and provide a good basis for further investigation.

Cancer and breast cancer awareness interventions in an intellectual disability context: A review of the literature.

BACKGROUND: Women with an intellectual disability (ID) have a similar risk of developing breast cancer as women in the general population yet present with later stage breast cancers, which have poorer outcomes. AIM: To identify whether there is a need to develop a breast cancer awareness intervention for women with an ID. METHODS: Interventions aimed at increasing cancer awareness and breast cancer awareness for people with an ID were identified and critically appraised. RESULTS: Five interventions to increase cancer awareness or breast cancer awareness in people with an ID were identified. CONCLUSION: The review highlighted the paucity of theoretically underpinned breast cancer awareness interventions specifically aimed at women with an ID. Facilitating breast cancer awareness for women with an ID could potentially lead to earlier presentation of potential symptoms of breast cancer, earlier treatment, better prognosis and ultimately, improved survival. This article establishes that there is a need for an intervention underpinned by theory to increase breast cancer awareness in women with an ID.

Economics of Early Warning Scores for identifying clinical deterioration-a systematic review.

AIM: In 2013, a National Early Warning System (EWS) was implemented in Ireland. Whilst evidence exists to support the clinical effectiveness of EWS in the acute health care setting, there is a paucity of information on their cost and cost effectiveness. The objective of this systematic literature review was to critically evaluate the economic literature on the use of EWS in adult patients in acute health care settings for the timely detection of physiological deterioration. METHODS: A systematic literature review was conducted to accumulate the economic evidence on the use of EWS in adult patients in acute health care settings. RESULTS: The search yielded one health technology assessment, two budget impact analyses and two cost descriptions. Three of the studies were Irish, and considered the national EWS system. A Dutch study reported financial consequences of a single parameter EWS, as part of a rapid response system, in a surgical ward. The fifth study examined an advanced triage system in a medical emergency admission unit in Wales. CONCLUSIONS: The economic evidence on the use of EWS amongst adult patients in acute health care settings for the timely detection of physiological deterioration is limited. Further research is required to investigate the cost effectiveness of EWS, and the appropriateness of using standard methods to do so. The recent implementation of a national EWS in Ireland offers a unique opportunity to bridge this gap in the literature to examine the costs and cost effectiveness of a nationally implemented EWS system.

Lack of Heterogeneity in Bacteriocin Production Across a Selection of Commercial Probiotic Products.

Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit to the host. Bacteriocin production has often been mooted as a desirable probiotic trait and, in specific cases, has been shown to promote probiotic survival within the gastrointestinal tract, contribute to the control of pathogens and even influence host gene expression in the gut. However, it is not clear what proportion of probiotic strains routinely found in commercial products produces bacteriocins, and additionally, it is not known which bacteriocins are produced most frequently. To address this, we conducted a culture-based assessment of the bacteriocinogenic ability of bacterial strains found in a variety of commercially available probiotic products. We detected eight bacteriocin-producing isolates from 16 tested products. Interestingly, in all cases, the isolates were Lactobacillus acidophilus, and the bacteriocin produced was identified as the narrow spectrum class II bacteriocin, lactacin B. The apparent absence of other bacteriocin-producing strains from across these products suggests a lack of heterogeneity in bacteriocin production within probiotic products and suggests that bacteriocin production is not being optimally harnessed as a probiotic trait.

Is psychosocial and cognitive dysfunction misattributed to the virus in hepatitis C infection? Select psychosocial contributors identified.

Chronic hepatitis C is associated with health-related quality of life and cognitive impairments, even in mild disease. Recent evidence demonstrating hepatitis C virus (HCV) neurotropism has strengthened a neuropathophysiological hypothesis. However, sample heterogeneity confounds study outcomes. A uniquely homogeneous cohort of Irish women, following an iatrogenic HCV outbreak, offers a rare opportunity to control for HCV chronicity and the virus' purported impact on quality of life and cognition. A multi site, three-group, cross-sectional design was employed. Noncirrhotic, iatrogenically infected women, developing either acute or chronic infection, were recruited from prospective tertiary-care liver clinics and the community. Well-matched healthy controls were also recruited. All participants completed a psychosocial survey and were invited to undergo a comprehensive neuropsychological test battery. Significantly distressed psychosocial symptom profiles were observed in those with an iatrogenic HCV exposure history, which was independent of viral chronicity. Chronic and cleared HCV cohorts were not differentiated from each other. Two distinct subgroups, demarcated along 'impaired' vs 'nonimpaired' quality-of-life reports, were clearly identified and logistic regression analysis identified depressed mood and cognitive fatigue, rather than viral status, as statistically significant predictors of group membership. Compared with matched controls, significant cognitive impairments were not observed in either HCV cohort. Our findings provide strong evidence of nonviral factors accounting for quality of life impairment in chronic HCV and they also appear to question existing reports of cognitive dysfunction in mild disease. Depressed mood and cognitive fatigue appear to be critical psychosocial mediators of reduced quality-of-life and we hypothesize that metabolite abnormalities reported in HCV samples may also be confounded by these factors, given the associated literature.

X-ray image enhancement via determinant based feature selection.

Previous work has investigated the feasibility of using Eigenimage-based enhancement tools to highlight abnormalities on chest X-rays (Butler et al in J Med Imaging Radiat Oncol 52:244-253, 2008). While promising, this approach has been limited by computational restrictions of standard clinical workstations, and uncertainty regarding what constitutes an adequate sample size. This paper suggests an alternative mathematical model to the above referenced singular value decomposition method, which can significantly reduce both the required sample size and the time needed to perform analysis. Using this approach images can be efficiently separated into normal and abnormal parts, with the potential for rapid highlighting of pathology.

Low incidence of Pneumocystis jirovecii pneumonia in an unprophylaxed liver transplant cohort.

BACKGROUND: Liver transplant recipients are managed with a range of immunosuppressive regimens that place them at heightened risk of life-threatening opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP). No routine PJP prophylaxis is used at out institution. We reviewed the incidence of PJP in this cohort of unprophylaxed liver transplant recipients. METHODS: We examined all liver transplants performed between January 2000 and January 2012 in Ireland's National Liver Transplant Centre, St. Vincent's University Hospital, Dublin. Cases were identified through a computerized database and through the histopathology and microbiology registration system. The diagnosis of PJP was confirmed by identification of Pneumocystis cysts in bronchoalveolar lavage (BAL) fluid or on autopsy specimens using Grocott-Gomori methenamine-silver nitrate or modified Wright-Giemsa staining methods. RESULTS: During the study period, 687 liver transplants were performed. We found 7 cases of PJP with an incidence rate of 0.84 per 1000 person transplant years. Five cases occurred within 12 months of transplant with 2 cases occurring at 56 and 60 months, respectively. Two cases were diagnosed at postmortem; 1 previously had negative cytology from BAL, while the other could not be bronchoscoped because of rapid deterioration in the clinical condition. Three of the 5 treated patients died. CONCLUSIONS: The incidence of PJP in this cohort was very low, but the case fatality rate was high. Two cases occurred well after the usual recommended period of prophylaxis. In institutions with a very low risk of infection, targeted rather than universal prophylaxis may be reasonable.

The advent of successful organ transplantation in the Irish HIV positive cohort.

BACKGROUND: Liver disease is an increasing cause of morbidity and mortality in Human immunodeficiency virus (HIV) positive patients. AIM: To describe the first cases of organ transplantation in HIV positive patients in Ireland. METHOD: We report the Irish patients with HIV who received liver transplantation and performed a chart review. RESULT: Two patients received liver transplantation for end stage liver disease caused by Hepatitis C, with survival at 2 years of 100%. CONCLUSION: Liver transplantation is a feasible treatment for patients with HIV and end stage liver disease. The success of transplantation in the HIV positive population should encourage the provision of other medical and surgical interventions previously not offered to patients with HIV.

Rapid, early and sustained virological responses in a cohort of Irish patients treated with pegylated interferon and ribavirin for chronic hepatitis C virus infection.

BACKGROUND: The response to the treatment with pegylated interferon (PEG IFN)-α combined with ribavirin in chronic hepatitis C virus (HCV) infection varies with some patients having a rapid or early response which is not sustained. AIMS: To investigate the rates of rapid virological response (RVR), early virological response (EVR) and sustained virological response (SVR) in an Irish cohort of HCV infected patients receiving IFN-α/ribavirin. METHODS: Rates of RVR, EVR and SVR were examined in 123 patients undergoing standard treatment for chronic HCV infection between 2001 and 2007 at a Dublin Teaching Hospital. RESULTS: The rates of RVR, EVR and SVR in genotype 1 patients were 48, 68 and 50%, while in genotype 2/3 patients they were 87, 93 and 87%, respectively. The positive predictive values (PPV) of RVR for SVR in genotype 1 and genotype 2/3 patients were 90 and 92.4%, respectively. CONCLUSION: The rates of response to PEG IFN-α/ribavirin in Irish patients are consistent with other international reports. We support the regular monitoring of rapid and early virological response as a standard of care in treating chronic hepatitis C patients.

Chronic hepatitis C infection blocks the ability of dendritic cells to secrete IFN-α and stimulate T-cell proliferation.

Dendritic cells (DCs) are likely to play a key role in the compromised T-cell function associated with hepatitis C Virus (HCV) infection. However, studies of DC function in HCV-infected patients to date have yielded conflicting findings possibly because of patient and virus heterogeneity. Here, we report the characterization of monocyte-derived DCs obtained from a homogenous cohort of women who were infected with HCV genotype 1b following exposure to contaminated anti-D immunoglobulin from a single donor source. Patients included in the study had not received anti-viral therapy and all had mild liver disease. We show that phenotypically normal monocyte-derived dendritic cells (MDDCs) (CD11c(+) HLA(-) DR(+) CD1a(+) CD14(lo) ) can be obtained from these patients. These cells respond to both Poly(I:C) and LPS, by up-regulating expression of CD86. They secrete high levels of IL-8 and CCL5 in response to LPS, an indication that the MyD88-dependent and MyD88-independent signalling pathways downstream of TLR4 ligation are functioning normally. However, these cells are poor stimulators of T-cell proliferation in allogeneic mixed lymphocyte reactions. Furthermore, patient MDDCs fail to secrete IFN-α in response to poly(I:C) or IFN-ß stimulation. Altered DC function may contribute to impaired cellular immune responses and chronicity of disease following HCV infection in this cohort. An effective therapeutic vaccine for chronic HCV infection will most likely need to target DCs to elicit an appropriate cellular response; therefore, it is important to resolve how the DCs of different patient cohorts respond to stimulation via TLRs.

Identification of disease-associated DNA methylation in intestinal tissues from patients with inflammatory bowel disease.

Overwhelming evidence supports the theory that inflammatory bowel disease (IBD) is caused by a complex interplay between genetic predispositions of multiple genes, combined with an abnormal interaction with environmental factors. It is becoming apparent that epigenetic factors can have a significant contribution in the pathogenesis of disease. Changes in the methylation state of IBD-associated genes could significantly alter levels of gene expression, potentially contributing to disease onset and progression. We have explored the role of DNA methylation in IBD pathogenesis. DNA methylation profiles (1505 CpG sites of 807 genes) of matched diseased (n = 26) and non-diseased (n = 26) intestinal tissues from 26 patients with IBD [Crohn's disease (CD) n = 9, ulcerative colitis (UC) n = 17] were profiled using the GoldenGate™ methylation assay. After an initial identification of a panel of 50 differentially methylated CpG sites from a training set (14 non-diseased and 14 diseased tissues) and subsequent validation with a testing set (12 non-diseased and 12 diseased tissues), we identified seven CpG sites that are differentially methylated in intestinal tissues of IBD patients. We have also identified changes in DNA methylation associated with the two major IBD subtypes, CD and UC. This study reports IBD-associated changes in DNA methylation in intestinal tissue, which may be disease subtype-specific.

PhD Away Days: a component of PhD supervision.

AIM: This paper describes a peer-to-peer and supervisor support and mentoring process that was implemented in one PhD programme in nursing in the Republic of Ireland. BACKGROUND: PhD Away Days are held once per year and attended by all enrolled PhD students and their academic supervisors. Positive evaluations were obtained both from students and supervisors as collective learning occurred and group cohesiveness developed. All participants expressed interest in continuing the PhD Away Days as they learned from others' experiences. In addition, the range of topics provided learning on topics of concern across content areas, e.g. conceptual and theoretical developments, research design, challenges in data collection, and analysis and publication plans. Most importantly, there was a feeling of togetherness among students, thus decreasing the feeling of being alone with the challenges of PhD work. CONCLUSIONS: Plans for the future include the need to have the PhD Away Days continued structured around key topics of concern to both students and supervisors, and to implement content-specific modules in the PhD programme.

Ochroconis gallopava peritonitis in a cardiac transplant patient on continuous ambulatory peritoneal dialysis.

Ochroconis gallopava has rarely been isolated in immunosuppressed patients. We report the first case to our knowledge of O. gallopava peritonitis in a cardiac transplant patient on continuous ambulatory peritoneal dialysis. A 58-year-old man who had undergone cardiac transplant 8 years earlier alerted his dialysis nurses to the presence of black material in his catheter lumen. Fungal hyphae were seen on direct microscopy of the black material and from the dialysate effluent, and O. gallopava was cultured from both after 1 day. He was treated successfully with a single dose of intravenous voriconazole, followed by 2 weeks of oral voriconazole.

Hepatic transplantation outcomes for carefully selected cirrhotic patients with hepatocellular carcinoma: experience at a small- to medium-volume centre.

BACKGROUND: Hepatic transplantation outcomes for cirrhotic patients with hepatocellular carcinoma (HCC) at a small- to medium-volume centre are not fully known due to relative novelty of patient selection criteria. AIM: To determine hepatic transplantation outcomes for HCC at a small- to medium-volume centre. Patients and methods Hepatocellular carcinoma patients were listed for transplantation according to the International Guideline and further categorized as those fulfilling or exceeding Milan or University of San Francisco (UCSF) criteria on explanted liver morphology. Outcomes including mortality, retransplantation, and tumour recurrence rate were analysed. RESULTS: Twenty-six patients had HCC and on explanted liver morphology, Milan and UCSF criteria met 15 and 18 patients, respectively. Patients and graft survival at 3 months, 1 and 5 years were 100, 96, 84, and 88, 84, 77%, respectively. Outcomes favoured Milan criteria but did not reach statistical significance. CONCLUSIONS: Hepatic transplantation for HCC at a small-to medium-volume transplant centre had comparable survival outcomes to high-volume centres.

Significant influence of the primary liver disease on the outcomes of hepatic retransplantation.

BACKGROUND: There are many indications for hepatic retransplantation. AIM: To identify factors influencing retransplantation needs and outcomes. PATIENTS AND METHODS: Retransplantation records from January 1993 to March 2005 were analysed. Patient and disease characteristics and survival outcomes for retransplantation were compared between various groups. RESULTS: Totally, 286 primary and 42 hepatic retransplantations were performed. Retransplantation indications included primary sclerosing cholangitis (PSC), primary biliary cirrhosis, chronic hepatitis C (HCV), chronic active hepatitis (CAH), and alcohol-related disease. Mean follow-up post-retransplantation was 31 +/- 9 months. Actuarial patient survival at 3 months, 1 year, 3 years, 5 years, and at the end of study was 71.4, 69, 59.5, 54.7, and 50%, respectively. Early and late retransplantation had 1-year survival of 73 and 68.5%, respectively. Retransplantation need was significantly higher for PSC, HCV, and CAH. CONCLUSIONS: Hepatic retransplantation remains a successful salvage option for transplant complications; however, its need is significantly influenced by the primary liver disease.

The high prevalence of unrecognized anaemia in patients with diabetes and chronic kidney disease: a population-based study.

BACKGROUND: Anaemia occurs early in the course of diabetes-related chronic kidney disease (CKD). There is little evidence about the prevalence of anaemia in people with diabetes. The aim of this study was to assess the prevalence of anaemia, by stage of CKD, in the general diabetic population. METHODS: Haemoglobin (Hb) was measured on all glycated haemoglobin (HbA1c) samples and the most recent (< 4 months) estimated glomerular filtration rate (eGFR) was obtained. Anaemia (at treatment level) was defined as Hb < 110 g/l or the use of erythropoetic stimulating agents (ESA). RESULTS: Twelve per cent (10-14%) of people had Hb < 110 g/l. The prevalence of anaemia increased progressively with worsening CKD. People with CKD stage 3 accounted for the largest number of people with anaemia; 18% (95% CI 13-24%) had Hb < 110 g/l. Those with eGFR < 60 ml/min/1.73 m2 and not on ESA or dialysis were four (2-7) times more likely than patients with better renal function to have Hb < 110 g/l. The relation between Hb and eGFR became approximately linear below an eGFR of 83 ml/min/1.73 m2, where, for every 1 ml/min/1.73 m2 fall in eGFR, there was a 0.4 (0.3-0.5) g/l fall in haemoglobin. CONCLUSIONS: This study demonstrates that anaemia, at levels where treatment is indicated, occurs commonly in people with diabetes and CKD stage 3 or worse. The screening for anaemia in current diabetes management should be extended.