Mucinous and non-mucinous colorectal cancers show differential expression of chemotherapy metabolism and resistance genes.

Previous research has identified differences in mutation frequency in genes implicated in chemotherapy resistance between mucinous and non-mucinous colorectal cancers (CRC). We hypothesized that outcomes in mucinous and non-mucinous CRC may be influenced by expression of genes responsible for chemotherapy resistance. Gene expression data from primary tumor samples were extracted from The Cancer Genome Atlas PanCancer Atlas. The distribution of clinical, pathological, and gene expression variables was compared between 74 mucinous and 521 non-mucinous CRCs. Predictors of overall survival (OS) were assessed in a multivariate analysis. Kaplan-Meier curves were constructed to compare survival according to gene expression using the log rank test. The median expression of 5-FU-related genes TYMS, TYMP, and DYPD was significantly higher in mucinous CRC compared to non-mucinous CRC (p < 0.001, p = 0.003, p < 0.001, respectively). The median expression of oxaliplatin-related genes ATP7B and SRPK1 was significantly reduced in mucinous versus non-mucinous CRC (p = 0.004, p = 0.007, respectively). At multivariate analysis, age (odds ratio (OR) = 0.96, p < 0.001), node positive disease (OR = 0.49, p = 0.005), and metastatic disease (OR = 0.32, p < 0.001) remained significant negative predictors of OS, while high SRPK1 remained a significant positive predictor of OS (OR = 1.59, p = 0.037). Subgroup analysis of rectal cancers demonstrated high SRPK1 expression was associated with significantly longer OS compared to low SRPK1 expression (p = 0.011). This study highlights that the molecular differences in mucinous CRC and non-mucinous CRC extend to chemotherapy resistance gene expression. SRPK1 gene expression was associated with OS, with a prognostic role identified in rectal cancers.

Risk of colorectal cancer associated with BRCA1 and/or BRCA2 mutation carriers: systematic review and meta-analysis.

BACKGROUND: Carriers of the BRCA1 and/or BRCA2 mutation incur a lifetime risk of up to 85 per cent for breast cancer, and between 20 and 40 per cent for ovarian cancer. Efforts to estimate the lifetime risk of developing colorectal cancer for BRCA mutation carriers have produced conflicting results. Consequently, there are no formal guidelines regarding the need for bowel screening for individuals with BRCA1 and/or BRCA2 mutations. This systematic review and meta-analysis determined the risk of colorectal cancer associated with BRCA carrier mutations. METHODS: The primary outcome was incidence of colorectal cancer in BRCA mutation carriers. Secondary outcomes were the incidence in BRCA1 and BRCA2 carriers, Ashkenazi Jews, and age- and sex-matched cohorts. RESULTS: Eleven studies were included in the review, with an overall population of 14 252 and 4831 colorectal cancers identified. Nine studies were included in the meta-analysis. There was no increase in colorectal cancer among patients carrying a BRCA mutation (odds ratio 1·03, 95 per cent c.i. 0·80 to 1·32; P = 0·82). After adjustment for Ashkenazi heritage, and age and sex estimates, there was no increased odds of developing colorectal cancer (with no heterogeneity, I2  = 0 per cent). CONCLUSION: BRCA1 and/or BRCA2 mutation carriers are not at a higher risk of colorectal cancer.

ANTECEDENTES: Las portadoras de la mutación BRCA1 y/o BRCA2 presentan un riesgo a lo largo de la vida de hasta un 85% para presentar un cáncer de mama y entre 20-40% para el cáncer de ovario. Los esfuerzos para estimar el riesgo de desarrollar cáncer colorrectal (colorectal cancer, CCR) a lo largo de la vida en portadoras de mutaciones BRCA han dado resultados contradictorios. En consecuencia, no existen pautas formales con respecto a la necesidad de realizar el cribado de CRC en personas portadoras de mutaciones BRCA1 y/o BRCA2. Esta revisión sistemática y metaanálisis analiza el riesgo de CRC asociado en pacientes portadoras de mutaciones BRCA. MÉTODOS: Se incluyeron nueve estudios en el metaanálisis. La población general del estudio fue de 18.839 pacientes, con 4.978 con CRC identificado. La variable principal fue la incidencia de cáncer colorrectal en portadoras de mutaciones BRCA. Las variables secundarias incluyeron el análisis de la incidencia de subgrupos en BRCA 1, BRCA 2, etnia judía Ashkenazi y cohortes emparejadas por edad y sexo. RESULTADOS: No hubo un aumento de CRC en pacientes con una mutación BRCA (razón de oportunidades, odds ratio, OR 1,03; i.c. del 95% 0,80-1,32; P = 0,82). Cuando se ajustó de acuerdo con la ascendencia Ashkenazi y las estimaciones de edad y sexo, no hubo mayores probabilidades de desarrollar cáncer colorrectal (sin heterogeneidad en los estudios (I2 = 0)). CONCLUSIÓN: Este metaanálisis concluye que el riesgo de cáncer colorrectal no fue significativamente mayor en las portadoras de mutaciones BRCA1 y/o BRCA2. Sin embargo, se requiere más evidencia antes de no recomendar la colonoscopia de cribado a las portadoras de la mutación BRCA1/2. Las pruebas de inmunoquímica fecal pueden ser una alternativa apropiada en esta población.

Diversity and bioactivity of fungi associated with the marine sea cucumber Holothuria poli: disclosing the strains potential for biomedical applications.

AIMS: Identification of the mycobiota associated to the marine echinoderm Holothuria poli and investigation of cytotoxic and pro-osteogenic potential of isolated strains. METHODS AND RESULTS: Fungal strains were isolated from the animal's body-wall, intestine and faeces. The species identification was based on DNA barcoding and morphophysiological observations. Forty-seven species were identified, all are Ascomycota and mainly belonging to Aspergillus and Penicillium genera. Sixteen strains were grown on three media for chemical extraction. Cytotoxic activity was tested on a hepatic cancer cell line (HepG2), the cells viability was evaluated after treatment using a resazurin based assay (AlamarBlue). Pro-osteogenic activity was tested on human Mesenchymal stem cell, differentiation was measured as the alkaline phosphatase production through reaction with p-nitrophenylphosphate or as the cells ability to mineralize calcium using a colorimetric kit (StanBio). Cytotoxic activity was recorded for four fungal species while five of 48 extracts highlighted bioactivity towards human mesenchymal stem cells. CONCLUSIONS: The presence of relevant animal-associated mycobiota was observed in H. poli and selected strains showed cytotoxic potential and pro-osteogenic activity. SIGNIFICANCE AND IMPACT OF THE STUDY: Our work represents the first report of a Mediterranean Sea cucumber mycobiota and highlights the isolates potential to synthetize compounds of pharmaceutical interest for regenerative medicine.

The utility of preoperative radiological evaluation of early rectal neoplasia: a systematic review and meta-analysis.

AIM: The diagnostic role for preoperative imaging of clinically benign rectal adenomas is unclear. The objective of this systematic review and meta-analysis was to examine the diagnostic accuracy of preoperative imaging in distinguishing benign adenomas from rectal cancer. METHOD: A systematic search was performed for all studies published that correlated staging of clinically benign rectal adenomas with endorectal ultrasound (ERUS) or MRI and histology. Imaging was compared with postoperative histology and data on the numbers of true positives, false positives, true negatives and false negatives were extracted. Summary estimates of sensitivity and specificity with 95% CIs were calculated using a bivariate random effects model. The QUADAS2 tool was used to determine the methodological quality of included studies. RESULTS: Eleven studies describing 1511 patients were retrieved. A total of 1134 patients underwent local excision and 377 had a formal proctectomy. A benign rectal adenoma was diagnosed in 840 and 214 had a T1 rectal cancer. For confirming benign adenomas, the pooled sensitivity of ERUS was 0.81 (95% CI 0.69-0.89) and specificity was 0.85 (95% CI 0.68-0.93). For detecting occult T1 tumours, the pooled sensitivity of ERUS was 0.50 (95% CI 0.33-0.66) and specificity was 0.89 (95% CI 0.82-0.94). Quantitative analysis of MRI could not be performed due to insufficient studies. CONCLUSION: This study demonstrates the limited accuracy of preoperative ERUS in distinguishing benign adenomas from T1 rectal cancer. Preoperative imaging must be interpreted with caution to prevent over-staging and unnecessary proctectomy. We propose that clinically benign lesions may undergo local excision, with subsequent management based on final histology.

A public health needs assessment for domestic indoor overheating.

OBJECTIVES: Indoor overheating is a potentially fatal health hazard that was identified as an issue requiring urgent action in the 2017 UK Climate Change Risk Assessment. We aimed to make research on this issue more accessible to local public health teams to encourage its inclusion in local strategic needs assessments. STUDY DESIGN: Epidemiological health needs assessment. METHODS: We adapted established health needs assessment methods, focussing on the epidemiological component, drawing evidence from a non-systematic literature review that was complemented by discussion with experts. RESULTS: Indoor overheating arises from an interaction between occupants' susceptibility to heat, their behaviour and the building's location and its characteristics. Many of these factors are interrelated and, at a national level, are expected to vary over time with demographic and climate change. Understanding these factors, ways to mitigate them and a long-term view are all essential for managing overheating risk. CONCLUSIONS: There is a need for services to be provided at the local level that consider the home environment and its impact on health in all seasons. A population-level approach to risk management across a local area is also useful to inform collaborative efforts to reduce future incidence of overheating and better understand how it varies with socio-economic deprivation.

Late cardiac effects of chemotherapy in breast cancer survivors treated with adjuvant doxorubicin: 10-year follow-up.

Doxorubicin (Dox), a mainstay of adjuvant breast cancer treatment, is associated with cardiac toxicity in the form of left ventricular dysfunction (LVD), LV diastolic dysfunction, or LV systolic dysfunction. Study objectives were to evaluate the prevalence of LVD in long-term breast cancer survivors treated with Dox and determine if brain-type natriuretic peptide (BNP) may help identify patients at risk for LVD. Patients who participated in prospective clinical trials of adjuvant Dox-based chemotherapy for breast cancer with a baseline left ventricular (LV) ejection fraction evaluation from 1999 to 2006 were retrospectively identified from the St Vincent's University Hospital database. Patients were invited to undergo transthoracic echocardiography, BNP analysis, and cardiovascular (CV) risk factor assessment. LVDD was defined as left atrial volume index >34 mL/m(2) and/or lateral wall E prime <10 m/s, and LVSD as LVEF <50 %. Of 212 patients identified, 154 participated, 19 patients had died (no cardiac deaths), and 39 declined. Mean age was 60.7 [55:67] years. A majority of the patients (128, 83 %) had low CV risk (0/1 risk factors), 21 (13.6 %) had 2 RFs, and 5 (3.2 %) ≥3 RFs. BMI was 27.2 ± 4.9 kg/m(2). Median Dox dose was 240 mg/m(2) [225-298]; 92 patients (59.7 %) received ≤240 mg/m(2) and 62 (40.3 %) > 240 mg/m(2). Baseline LVEF was 68.2 ± 8 %. At follow-up of 10.8 ± 2.2 years, LVEF was 64.4 ± 6 %. Three (1.9 %) subjects had LVEF <50 % and one (0.7 %) had LVDD. Dox >240 mg/m2 was associated with any LVEF drop. BNP levels at follow-up were 20.3 pg/ml [9.9-36.5] and 21.1 pg/ml [9.8-37.7] in those without LVD and 61.5 pg/ml [50-68.4] in those with LVD (p = 0.04). Long-term prospective data describing the impact of Dox on cardiotoxicity are sparse. At over 10 years of follow-up, decreases in LVEF are common, and dose related, but LVD as defined is infrequent (2.6 %). Monitoring with BNP for subclinical LVD needs further evaluation.

Conservative management of neurocysticercosis in a patient with hematopoietic stem cell transplantation: a case report and review.

Neurocysticercosis, an infection of the central nervous system with the larval stage of the cestode Taenia solium, is common in developing countries but its occurrence and management in allogeneic hematopoietic stem cell transplantation (HSCT) has not been reported previously, to our knowledge. We report the case of an immigrant female patient who underwent a matched-related allogeneic HSCT for acute lymphoblastic leukemia and was incidentally found to have a solitary viable neurocysticercosis lesion. However, despite severe immunosuppression, the size of the cyst did not increase. More importantly, restoration of the immune system did not induce significant inflammation or seizures. Subsequent follow-up demonstrated complete resolution of the neurocysticercosis lesion. Thus, in the setting of HSCT, an asymptomatic patient with a single neurocysticercosis lesion was successfully managed without the use of anthelmintics, steroids, or anti-epileptics.

Post-traumatic immunosuppression is reversed by anti-coagulated salvaged blood transfusion: deductions from studying immune status after knee arthroplasty.

Major trauma increases vulnerability to systemic infections due to poorly defined immunosuppressive mechanisms. It confers no evolutionary advantage. Our objective was to develop better biomarkers of post-traumatic immunosuppression (PTI) and to extend our observation that PTI was reversed by anti-coagulated salvaged blood transfusion, in the knowledge that others have shown that non-anti-coagulated (fibrinolysed) salvaged blood was immunosuppressive. A prospective non-randomized cohort study of patients undergoing primary total knee arthroplasty included 25 who received salvaged blood transfusions collected post-operatively into acid-citrate-dextrose anti-coagulant (ASBT cohort), and 18 non-transfused patients (NSBT cohort). Biomarkers of sterile trauma included haematological values, damage-associated molecular patterns (DAMPs), cytokines and chemokines. Salvaged blood was analysed within 1 and 6 h after commencing collection. Biomarkers were expressed as fold-changes over preoperative values. Certain biomarkers of sterile trauma were common to all 43 patients, including supranormal levels of: interleukin (IL)-6, IL-1-receptor-antagonist, IL-8, heat shock protein-70 and calgranulin-S100-A8/9. Other proinflammatory biomarkers which were subnormal in NSBT became supranormal in ASBT patients, including IL-1ß, IL-2, IL-17A, interferon (IFN)-γ, tumour necrosis factor (TNF)-α and annexin-A2. Furthermore, ASBT exhibited subnormal levels of anti-inflammatory biomarkers: IL-4, IL-5, IL-10 and IL-13. Salvaged blood analyses revealed sustained high levels of IL-9, IL-10 and certain DAMPs, including calgranulin-S100-A8/9, alpha-defensin and heat shock proteins 27, 60 and 70. Active synthesis during salvaged blood collection yielded increasingly elevated levels of annexin-A2, IL-1ß, Il-1-receptor-antagonist, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IFN-γ, TNF-α, transforming growth factor (TGF)-ß1, monocyte chemotactic protein-1 and macrophage inflammatory protein-1α. Elevated levels of high-mobility group-box protein-1 decreased. In conclusion, we demonstrated that anti-coagulated salvaged blood reversed PTI, and was attributed to immune stimulants generated during salvaged blood collection.

The novel toluidine sulphonamide EL102 shows pre-clinical in vitro and in vivo activity against prostate cancer and circumvents MDR1 resistance.

BACKGROUND: Taxanes are routinely used for the treatment of prostate cancer, however the majority of patients eventually develop resistance. We investigated the potential efficacy of EL102, a novel toluidine sulphonamide, in pre-clinical models of prostate cancer. METHODS: The effect of EL102 and/or docetaxel on PC-3, DU145, 22Rv1 and CWR22 prostate cancer cells was assessed using cell viability, cell cycle analysis and PARP cleavage assays. Tubulin polymerisation and immunofluorescence assays were used to assess tubulin dynamics. CWR22 xenograft murine model was used to assess effects on tumour proliferation. Multidrug-resistant lung cancer DLKPA was used to assess EL102 in a MDR1-mediated drug resistance background. RESULTS: EL102 has in vitro activity against prostate cancer, characterised by accumulation in G2/M, induction of apoptosis, inhibition of Hif1α, and inhibition of tubulin polymerisation and decreased microtubule stability. In vivo, a combination of EL102 and docetaxel exhibits superior tumour inhibition. The DLKP cell line and multidrug-resistant DLKPA variant (which exhibits 205 to 691-fold greater resistance to docetaxel, paclitaxel, vincristine and doxorubicin) are equally sensitive to EL102. CONCLUSION: EL102 shows potential as both a single agent and within combination regimens for the treatment of prostate cancer, particularly in the chemoresistance setting.

Comparing the Tonojet disposable tonometer with the traditional Goldmann tonometer in glaucomatous and non-glaucomatous eyes.

Applanation tonometry is widely performed as the most accurate method of measuring intraocular pressure in the clinical setting. Disposable tonometer heads reduce the risk of transmitting infection during applanation and eliminate tonometer head cleaning, which is time-consuming. We performed a study to investigate whether the Tonojet disposable tonometer (Luneau, France) gave comparable intraocular pressure measurements to the standard Goldmann tonometer produced by Haag Streit (Switzerland). The study was performed in a busy general secondary referral ophthalmology clinic in Beaumont Hospital over a 15-day period. We measured intraocular pressure with the Goldmann and Tonojet tonometers in 293 eyes. Patients were randomised as to which tonometer was used first. A diagnosis of glaucoma or ocular hypertension was noted. Central corneal thickness (CCT) was measured. The measurements taken with the Tonojet were on average 2.2 mmHg lower than corresponding measurements taken with the Goldmann applanation tonometer head. The bias was present over the entire range of pressures. The 95 % limits of agreement between the two tonometers ranged from -5.9 to +1.4 mmHg. In the cohort of eyes with ocular hypertension/glaucoma the difference was significantly higher (2.8 vs. 2.1 mmHg). The bias was independent of CCT. We found that the Tonojet disposable tonometer tends to underestimate intraocular pressure compared with the Goldmann. The bias is non-systematic, present over the entire range of pressures and independent of corneal thickness. We conclude that the Tonojet is not sufficiently accurate to constitute a suitable alternative to the Goldmann.

Centralisation of rectal cancer care has improved patient survival in the republic of Ireland.

BACKGROUND: Centralisation of rectal cancer surgery to designated centres was a key objective of the Irish national cancer control program. A national audit of rectal cancer surgery indicated centralisation was associated with improved early surgical outcomes. This study aimed to determine the impact of implementation of the national cancer strategy on survival from rectal cancer. MATERIALS AND METHODS: Data were collected from the National Cancer Registry of Ireland to include all patients with Stage I-III rectal cancer undergoing rectal cancer surgery with curative intent between 2003 and 2012. Five-year overall survival and cancer-specific survival was compared between patients in the pre-centralisation (2003-2007) and post-centralisation period (2008-2012) and between patients receiving surgery in designated cancer centres and non-cancer centres. RESULTS: The proportion of rectal cancer surgery performed in a designated cancer centre increased from 42% during 2003-2007 to 58% during 2008-2012. Five-year overall survival increased from 66.1% in 2003-2007 to 73.5% in 2008-2012 (p < 0.001). Five-year cancer-specific survival increased from 75.3% in 2003-2007 to 81.9% in 2008-2012 (p < 0.001). Surgery in a cancer centre and surgery post-centralisation were significantly associated with overall and cancer specific survival using Cox proportional hazards regression. CONCLUSION: Survival following resection of rectal cancer was significantly improved following implementation of a national cancer strategy incorporating centralisation of rectal cancer surgery.

Microsatellite instability and response to neoadjuvant chemoradiotherapy in rectal cancer: A systematic review and meta-analysis.

BACKGROUND: Response to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer is variable. Identification of biomarkers to predict response is desirable in order to provide prognostic information and targeted therapy. Several studies have investigated microsatellite instability (MSI) as a predictor of response to CRT with contradictory results. This study aims to clarify the effect of MSI status on response to CRT in locally advanced rectal cancer through systematic review and meta-analysis. METHODS: A systematic search of PubMed, Embase and Cochrane databases was performed for all studies relating to MSI and response to CRT in rectal cancer using the search algorithm (Microsatellite Instability) AND (Chemoradiotherapy) AND (Rectal Cancer). From each included study the number of patients with MSI tumors and Microsatellite Stable (MSS) tumors and the numbers achieving pathological complete response (pCR) were recorded. Pooled outcome measures were determined using a random effects model and the odds ratio estimated with variance and 95% confidence interval. RESULTS: Nine published studies were identified reporting data on MSI and its effect on outcome after CRT for locally advanced rectal cancer. Five studies describing 5,877 patients included data on MSI and the number of patients achieving pCR. There was no significant association between MSI and pCR (MSI Vs MSS: 10.1% Vs 6.6%, OR 1.38, 95% CI: 0.7-2.72, p = 0.35). CONCLUSION: This meta-analysis concludes that there appears to be no significant difference in pCR rate following CRT in patients with MSI versus MSS rectal tumors.

A review of the strengths and weaknesses of quantitative methods used in health impact assessment.

OBJECTIVES: To explore some of the strengths and weaknesses of purely quantitative approaches used in health impact assessment (HIA) and the implication of this for policy making. STUDY DESIGN: The studies presented generally used a variety of quantitative risk assessment (QRA) methodologies. METHODS: For each population, concentration-response (CR) or exposure-response (ER) functions, typically expressed as percentage change in health effect per unit change in concentration or exposure, were applied to estimates of population exposure and background rates of morbidity and mortality in order to calculate the attributable health impact or burden. In some cases, this burden was then costed according to standard economic models. RESULTS: In most of the studies discussed, where a reliable CR or ER relationship was available, it was possible to quantify the impact(s) of the relevant environmental stressors on health, and to estimate the associated uncertainties. CONCLUSIONS: QRA has an important role in producing estimates for the health impacts of those risk factors where there is a sufficient base of research to quantify relationships between population exposure and health, and to predict the effects of policies on population exposure. However, quantified HIA is not an infallible process and can give an illusion of certainty that belies the complexity of the interactions involved, particularly where multiple determinants of health are likely to be affected. It is important that any uncertainties associated with that which has been quantified, as well as the likely impacts of that which cannot be quantified, are assessed and represented comprehensively. A simplistic application of QRA estimates is an inadequate HIA, as it may encourage policy makers and others to attach more importance to those impacts that are easier to quantify but which do not necessarily have the greatest associated burden.

Adherence to clinical guidelines and the potential economic benefits of admission avoidance for acute uncomplicated diverticulitis.

BACKGROUND: The treatment paradigm for acute diverticulitis is changing. There is an increasing trend towards managing patients with uncomplicated diverticulitis in the community. AIMS: The aim of this study was to analyse how acute diverticulitis is managed in our institution and also to analyse national data pertaining to treatment of acute diverticulitis. METHODS: A prospective database of all patients admitted to our institution over a 2-year period (2014-2016) with acute diverticulitis was maintained. Severity of disease, treatment received and average length of stay (LOS) were analysed for all patients. Contemporaneous hospital inpatient enquiry (HIPE) data was interrogated to analyse current management for acute diverticulitis at a national level. RESULTS: One hundred twenty-six patients were admitted to our institution with acute diverticulitis during the study period (inpatient stay = €1277/night). Of patients, 59.5% had uncomplicated diverticulitis while 40.5% had complicated disease. The median LOS was 4 (range 1-34) days and 8 (range 2-51) days in the uncomplicated and complicated group, respectively. Based on HIPE data, there were 11,357 patients with uncomplicated diverticulitis and 526 patients with complicated diverticulitis admitted to Irish hospitals in the year 2015. Nationally, the median LOS for those with uncomplicated diverticulitis was 3 (range 1-142) days and for those with complicated diverticulitis the median LOS was 7 (range 1-308) days. Projected total cost for hospital stay nationally for uncomplicated diverticulitis amounted to €43.5 million for the year 2015. CONCLUSIONS: At present, uncomplicated diverticulitis in Ireland is not being managed as per evidence-based guidelines. Changing practice could result in significant cost savings for surgical departments.

A comparison of HFrEF vs HFpEF's clinical workload and cost in the first year following hospitalization and enrollment in a disease management program.

BACKGROUND: Admission with heart failure (HF) is a milestone in the progression of the disease, often resulting in higher intensity medical care and ensuing readmissions. Whilst there is evidence supporting enrolling patients in a heart failure disease management program (HF-DMP), not all reported HF-DMPs have systematically enrolled patients with HF with preserved ejection fraction (HFpEF) and there is a scarcity of literature differentiating costs based on HF-phenotype. METHODS: 1292 consenting, consecutive patients admitted with a primary diagnosis of HF were enrolled in a hospital based HF-DMP and categorized as HFpEF (EF≥45%) or HFrEF (EF<45%). Hospitalizations, primary care, medications, and DMP workload with associated costs were evaluated assessing DMP clinic-visits, telephonic contact, medication changes over 1year using a mixture of casemix and micro-costing techniques. RESULTS: The total average annual cost per patient was marginally higher in patients with HFrEF €13,011 (12,011, 14,078) than HFpEF, €12,206 (11,009, 13,518). However, emergency non-cardiovascular admission rates and average cost per patient were higher in the HFpEF vs HFrEF group (0.46 vs 0.31 per patient/12months) & €655 (318, 1073) vs €584 (396, 812). In the first 3months of the outpatient HF-DMP the HFrEF population cost more on average €791 (764, 819) vs €693 (660, 728). CONCLUSION: There are greater short-term (3-month) costs of HFrEF versus HFpEF as part of a HF-DMP following an admission. However, long-term (3-12month) costs of HFpEF are greater because of higher non-cardiovascular rehospitalisations. As HFpEF becomes the dominant form of HF, more work is required in HF-DMPs to address prevention of non-cardiovascular rehospitalisations and to integrate hospital based HF-DMPs into primary healthcare structures.

Ion-beam modification of 2-D materials - single implant atom analysis via annular dark-field electron microscopy.

Functionalisation of two-dimensional (2-D) materials via low energy ion implantation could open possibilities for fabrication of devices based on such materials. Nanoscale patterning and/or electronically doping can thus be achieved, compatible with large scale integrated semiconductor technologies. Using atomic resolution High Angle Annular Dark Field (HAADF) scanning transmission electron microscopy supported by image simulation, we show that sites and chemical nature of individual implants/ dopants in graphene, as well as impurities in hBN, can uniquely and directly be identified on grounds of their position and their image intensity in accordance with predictions from Z-contrast theories. Dopants in graphene (e.g., N) are predominantly substitutional. In other 2-Ds, e.g. dichalcogenides, the situation is more complicated since implants can be embedded in different layers and substitute for different elements. Possible configurations of Se-implants in MoS2 are discussed and image contrast calculations performed. Implants substituting for S in the top or bottom layer can undoubtedly be identified. We show, for the first time, using HAADF contrast measurement that successful Se-integration into MoS2 can be achieved via ion implantation, and we demonstrate the possibility of HAADF image contrast measurements for identifying impurities and dopants introduced into in 2-Ds.

Concussion in rugby: knowledge and attitudes of players.

BACKGROUND: Concussion is a traumatic brain injury, resulting in the alteration of mental status with or without loss of consciousness. There is increasing awareness that recurrent concussion may contribute to long-term neurological complication. AIMS: To determine player knowledge and attitudes regarding concussion. To identify sources of information and medical care, and to estimate the incidence of concussion in this group. To determine if player gender and grade of competition are associated with differences in knowledge, attitudes, medical care, and incidence. METHODS: Five rugby teams were recruited and players invited to complete a paper-based questionnaire. The questionnaire sought information on player demographics, knowledge level, attitudes and concussion experience. RESULTS: 90.8 % of players knew they should not continue playing when concussed. 75 % of players would continue an important game even if concussed. Of those concussed, 39.1 % have tried to influence medical assessment with 78.2 % stating it is possible or quite easy to do so. Males are less likely to worry about long-term effects of concussion (χ (2) = 9.23, p = 0.026). Club players are less likely to have medical care at training (χ (2) = 28.2, p < 0.001) or matches (χ (2) = 19.47 p < 0.001). CONCLUSION: Despite good knowledge of concussion complications, management players engage in unsafe behaviour with little difference between gender and competition grades. Information regarding symptoms and management should be available to all players, coaches, and parents. Provision of medical care should be mandatory at every level of competition.

PATI: Patient accessed tailored information: A pilot study to evaluate the effect on preoperative breast cancer patients of information delivered via a mobile application.

OBJECTIVES: The information needs of cancer patients are highly variable. Literature suggests an improved ability to modulate personalised stress, increased patient involvement with decision making, greater satisfaction with treatment choices and reduced anxiety levels in cancer patients who have access to information. The aim of this project was to evaluate the effects of a mobile information application on anxiety levels of patients undergoing surgery for breast cancer. MATERIALS AND METHODS: An application was developed for use with Apple iPad containing information on basic breast cancer biology, different treatments used and surgical techniques. Content and face validity studies were performed. A randomized control trial was designed, with a 1:2 allocation. Data collected include basic demographics and type of surgery. Questionnaires used included: the HADS, Mini-MAC, information technology familiarity and information satisfaction. RESULTS: A total of 39 women participated. 13 women had access to an iPad containing additional information and 26 women acted as controls. The mean age was 54 and technology familiarity was similar among both groups. Anxiety and depression scores at seven days were significantly lower in control patients without access to the additional information provided by the mobile application (p = 0.022 and 0.029 respectively). CONCLUSION: Anxiety and depression in breast cancer patients is both multifactorial and significant, with anxiety levels directly correlating with reduced quality of life. Intuitively, information should improve anxiety levels, however, we have demonstrated that surgical patients with less information reported significantly lower anxiety. We advise the thorough testing and auditing of information initiatives before deployment.

Measuring the Effect of Carers on Patients' Risk of Adverse Healthcare Outcomes Using the Caregiver Network Score.

BACKGROUND: Although caregivers are important in the management of frail, community-dwelling older adults, the influence of different caregiver network types on the risk of adverse healthcare outcomes is unknown. OBJECTIVE: To examine the association between caregiver type and the caregiver network subtest of The Risk Instrument for Screening in the Community (RISC), a five point Likert scale scored from one ("can manage") to five ("absent/liability"). To measure the association between caregiver network scores and the one-year incidence of institutionalisation, hospitalisation and death. DESIGN: Observational cohort study. SETTING AND PARTICIPANTS: Community-dwelling adults, aged >65, attending health centres in Ireland, (n=779). PROCEDURE AND MEASUREMENTS: The caregiver network subtest of the RISC was scored by public health nurses. Caregivers were grouped dichotomously into low-risk (score of one) or high-risk (scores two-five). RESULTS: The majority of patients had a primary caregiver (582/779; 75%), most often their child (200/582; 34%). Caregiver network scores were highest, indicating greatest risk, when patients had no recognised primary caregiver and lowest when only a spouse or child was available. Despite this, patients with a caregiver were significantly more likely to be institutionalised than those where none was required or identified (11.5% versus 6.5%, p=0.047). The highest one-year incidence of adverse outcomes occurred when state provided care was the sole support; the lowest when private care was the sole support. Significantly more patients whose caregiver networks were scored high-risk required institutionalisation than low-risk networks; this association was strongest for perceived difficulty managing medical domain issues, odds ratio (OR) 3.87:(2.22-6.76). Only perceived difficulty managing ADL was significantly associated with death, OR 1.72:(1.06-2.79). There was no association between caregiver network scores and risk of hospitalisation. CONCLUSION: This study operationalizes a simple method to evaluate caregiver networks. Networks consisting of close family (spouse/children) and those reflecting greater socioeconomic privilege (private supports) were associated with lower incidence of adverse outcomes. Caregiver network scores better predicted institutionalisation than hospitalisation or death.