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Lou F.,SUNY Downstate Medical Center | Sarkaria I.,Sloan Kettering Cancer Center | Pietanza C.,Sloan Kettering Cancer Center | Travis W.,Sloan Kettering Cancer Center | And 5 more authors.
Annals of Thoracic Surgery | Year: 2013

Background: The current guidelines for follow-up care after treatment of non-small cell lung cancer recommend continued surveillance for detection of recurrent or metachronous disease. However, carcinoid tumors, especially those with a typical histologic profile, tend to be less aggressive. Our goal was to determine the patterns of relapse and the manner of detection of recurrences, to guide follow-up care after resection. Methods: Patients who underwent operations for pulmonary carcinoids at our institution were identified from a prospectively maintained database, and their medical records were reviewed for relapse patterns, detection methods, and outcomes. Results: A total of 337 patients who underwent resection between 1993 and 2010 were included, with a median follow-up time of 3.5 years. Typical and atypical carcinoids were present in 291 (86%) and 46 (14%) patients, respectively. Recurrences occurred in 21 patients (6%), with distant metastases in 20 patients (95%) and locoregional recurrence in only 1 patient. Most recurrences (15 [76%]) were not detected through scheduled surveillance imaging but after the presentation of symptoms (7 [33%]) or incidentally by studies performed for unrelated reasons (8 [38%]). The risk of recurrence increased with positive lymph nodes and atypical histologic type. Only 9 of 291 patients (3%) with typical carcinoids experienced recurrences, with a median time to recurrence of 4 years (range, 0.8-12 years). Conversely, 12 of 46 patients (26%) with atypical carcinoids experienced recurrences, with a median time to recurrence of 1.8 years (range, 0.2-7 years). Conclusions: After complete resection, scheduled surveillance imaging failed to detect most recurrences. Recurrence was rare in patients with node-negative typical carcinoids. Given the low risk of recurrence and the unclear efficacy of surveillance imaging, routine surveillance imaging may not be warranted in this cohort. © 2013 The Society of Thoracic Surgeons.


Kita M.,Virginia Mason Medical Center | Fox R.J.,Cleveland Clinic | Phillips J.T.,Baylor Research Institute | Hutchinson M.,St Vincents University Hospital Dublin | And 9 more authors.
Multiple Sclerosis | Year: 2014

Multiple sclerosis (MS) has a significant impact on health-related quality of life (HRQoL) with symptoms adversely affecting many aspects of everyday living. BG-12 (dimethyl fumarate) demonstrated significant efficacy in the phase III studies DEFINE and CONFIRM in patients with relapsing-remitting MS. In CONFIRM, HRQoL was worse in patients with greater disability at baseline, and who relapsed during the study, and improved with BG-12 treatment. Mean Short Form-36 Physical Component Summary scores for BG-12 increased over 2 years and scores for placebo decreased. Coupled with clinical and neuroradiological benefits, these HRQoL results further support BG-12 as an effective oral treatment for relapsing MS. © 2013 The Author(s).


Havrdova E.,Charles University | Hutchinson M.,St Vincents University Hospital Dublin | Kurukulasuriya N.C.,Biogen Idec | Raghupathi K.,Biogen Idec | And 3 more authors.
Expert Opinion on Pharmacotherapy | Year: 2013

Introduction: Multiple sclerosis (MS) is an autoimmune neurodegenerative disease of the central nervous system involving inflammation, chronic demyelination and axonal loss. MS affects more than 2 million people worldwide. Areas covered: This article aims to summarize the findings from two pivotal 2-year, randomized, double-blind, placebo-controlled, Phase III studies of BG-12 (dimethyl fumarate) for relapsing-remitting MS (RRMS): DEFINE (Determination of the Efficacy and Safety of Oral Fumarate in RRMS) and CONFIRM (Comparator and an Oral Fumarate in RRMS). Results from both studies demonstrated that BG-12 provides clinical and radiological efficacy over 2 years across a range of outcomes. These results were apparent as early as 12 weeks and sustained over the course of both studies. BG-12 was found to have an acceptable safety profile, with a similar overall incidence of adverse events across all treatment groups. Expert opinion: The combination of robust efficacy, ease of administration and established safety profile is unique to a new therapy in MS. Findings from the pivotal Phase III studies support BG-12 as a potential initial oral treatment for patients with RRMS or as an alternative to other currently available therapies. © Informa UK, Ltd.


Duggan S.N.,Trinity College Dublin | Purcell C.,Trinity College Dublin | Kilbane M.,St Vincents University Hospital | O'Keane M.,St Vincents University Hospital | And 5 more authors.
American Journal of Gastroenterology | Year: 2015

INTRODUCTION:Because of deteriorating exocrine function, malabsorption renders chronic pancreatitis (CP) patients at risk of osteoporosis and fracture. However, the pathogenesis of low bone mineral density (BMD) has not been characterized. We hypothesized that bone turnover is elevated in CP, and we sought to investigate an association between bone metabolism and systemic inflammation. METHODS: Twenty-nine CP patients and twenty-nine matched controls were recruited. Bone-turnover markers procollagen 1 amino-terminal propeptide (P1NP), OC (osteocalcin; bone formation markers), and carboxy-terminal telopeptide of type I collagen (CTX-I; bone resorption marker) were measured along with vitamin D (25-hydroxyvitamin D, 25OHD), parathyroid hormone (PTH), interleukin 6 (IL-6), high-sensitivity (hs) C-reactive protein (CRP), and sex/thyroid hormones. BMD was measured by dual-energy X-ray absorptiometry. Smoking status was noted. RESULTS: Of the CP patients, 31% had osteoporosis and 44.8% osteopenia (controls: 6.9 and 51.7%, respectively; P=0.019). BMD was lower for patients at the lumbar spine (P=0.014) and femoral neck (P=0.029). Patients had elevated bone formation (P1NP (P=0.0068), OC (P=0.033)) and bone resportion (CTX-I (P=0.016)) compared with controls. Patients had lower 25OHD compared with controls (P=0.0126) and higher inflammatory markers (hsCRP, P=0.0013). Sex and thyroid hormone levels were similar. Patients with lowest 25OHD levels had highest P1NP. In a multivariable model, age, PTH, and smoking were predictive of 25OHD. Patients with osteoporosis had higher P1NP, PTH, and IL-6 and lower 25OHD. Using analysis of variance, inflammation (hsCRP) was highest in those with lowest 25OHD and lowest BMD. CONCLUSIONS: For the first time, bone turnover was shown to be abnormal in CP, and importantly, an association between low 25-OHD, smoking, and systematic inflammation was identified. Moreover, those with osteoporosis had the highest systemic inflammation. Together these factors provide an avenue for potential modification of risk factors, which may ultimately reduce bone loss and avert fractures in this group. © 2015 by the American College of Gastroenterology.


Ademowo O.S.,University College Dublin | Hernandez B.,University College Dublin | Collins E.,University College Dublin | Collins E.,St Vincents University Hospital Dublin | And 9 more authors.
Annals of the Rheumatic Diseases | Year: 2016

Objective Biological therapies, which include antitumour necrosis factor-α and T-cell inhibitors, are potentially effective treatments for psoriatic arthritis (PsA) but are costly and may induce a number of side effects. Response to treatment in PsA is variable and difficult to predict. Here, we sought to identify a panel of protein biomarkers that could be used to predict which patients diagnosed with PsA will respond to biologic treatment. Methods An integrated discovery to targeted proteomics approach was used to investigate the protein profiles of good and non-responders to biological treatments in patients with PsA. Reverse-phase liquid chromatography coupled to tandem mass spectrometry was used to generate protein profiles of synovial tissue obtained at baseline from 10 patients with PsA. Targeted proteomics using multiple reaction monitoring (MRM) was used to confirm and prevalidate a potential protein biomarker panel in 18 and 7 PsA patient samples, respectively. Results A panel of 107 proteins was selected, and targeted mass spectrometry MRM assays were successfully developed for 57 of the proteins. The 57 proteins include S100-A8, S100-A10, Ig kappa chain C fibrinogen-α and γ, haptoglobin, annexin A1 and A2, collagen alpha-2, vitronectin, and alpha-1 acid glycoprotein. The proteins were measured simultaneously and confirmed to be predictive of response to treatment with an area under the curve of 0.76. In a blinded study using a separate cohort of patients, the panel was able to predict response to treatment. Conclusions The approach reported here and the initial data provide evidence that a multiplexed protein assay of a panel of biomarkers that predict response to treatment could be developed.


Frohlich S.,St Vincents University Hospital Dublin | Frohlich S.,University College Dublin | Murphy N.,St Vincents University Hospital Dublin | Murphy N.,University College Dublin | And 5 more authors.
Journal of Critical Care | Year: 2014

Background: An increasing number of patients with alcoholic liver disease (ALD) are being referred for critical care support, but limited information is available on their short- and medium-term outcomes. This study aimed to determine mortality rates, identify optimal predictors of prognosis, and determine the appropriate time to apply these predictors in patients with ALD admitted to intensive care unit (ICU). Methods: In this retrospective study, patients admitted to ICU between 2009 and 2012 with a primary diagnosis of ALD were included. Survival was calculated using the Kaplan-Meier method, risk factors for death determined by logistic regression analysis, and discriminative capacity of models using receiver operating characteristic curves. Results: Of 170 patients admitted with liver disease, 62 met the inclusion criteria. Survival rates in the ICU, in hospital, and at 6 months were 40.3% (95% confidence interval [CI], 30.7%-49.9%), 35.5% (95% CI, 25.35%-45.65%), and 29% (95% CI, 19.4%-38.6%), respectively. Multiple linear regression analysis of day 1 variables produced an equation with Sequential Organ Failure Assessment score and lactate as significant predictors of mortality; this model had an area under the receiver operating characteristic curve of 0.93. A score greater than 12 in this model correlated with a mortality of more than 80% at all time points and was more accurate than any other score examined. Conclusion: Patients admitted to ICU with ALD have a very high inhospital mortality. A combination of the established Sequential Organ Failure Assessment score and lactate provided the most accurate predictor of outcome on day of admission and at all subsequent time points. © 2014.


Mcnamara M.S.,University College Dublin | Fealy G.M.,University College Dublin | Casey M.,University College Dublin | O'Connor T.,University College Dublin | And 3 more authors.
Journal of Clinical Nursing | Year: 2014

Aims and objectives: To evaluate mentoring, coaching and action learning interventions used to develop nurses' and midwives' clinical leadership competencies and to describe the programme participants' experiences of the interventions. Background: Mentoring, coaching and action learning are effective interventions in clinical leadership development and were used in a new national clinical leadership development programme, introduced in Ireland in 2011. An evaluation of the programme focused on how participants experienced the interventions. Design: A qualitative design, using multiple data sources and multiple data collection methods. Methods: Methods used to generate data on participant experiences of individual interventions included focus groups, individual interviews and nonparticipant observation. Seventy participants, including 50 programme participants and those providing the interventions, contributed to the data collection. Results: Mentoring, coaching and action learning were positively experienced by participants and contributed to the development of clinical leadership competencies, as attested to by the programme participants and intervention facilitators. Conclusions: The use of interventions that are action-oriented and focused on service development, such as mentoring, coaching and action learning, should be supported in clinical leadership development programmes. Being quite different to short attendance courses, these interventions require longer-term commitment on the part of both individuals and their organisations. Relevance to clinical practice: In using mentoring, coaching and action learning interventions, the focus should be on each participant's current role and everyday practice and on helping the participant to develop and demonstrate clinical leadership skills in these contexts. © 2014 John Wiley & Sons Ltd.


PubMed | Medical University of Lódz, Montreal Neurological Institute, Ruhr University Bochum, Cleveland Clinic and 5 more.
Type: Journal Article | Journal: Annals of clinical and translational neurology | Year: 2015

Obtain a more precise estimate of the efficacy of delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) in relapsing multiple sclerosis (MS) and examine the consistency of DMFs effects across patient subgroups stratified by baseline demographic and disease characteristics.A prespecified integrated analysis of the randomized, double-blind, placebo-controlled, Phase 3 DEFINE and CONFIRM trials was conducted.The intent-to-treat population comprised 2301 patients randomized to receive placebo (n=771) or DMF 240mg twice daily (BID; n=769) or three times daily (TID; n=761). At 2years, DMF BID and TID reduced the annualized relapse rate by 49% and 49% (both P<0.0001), risk of relapse by 43% and 47% (both P<0.0001), risk of 12-week confirmed disability progression by 32% (P=0.0034) and 30% (P=0.0059), and risk of 24-week confirmed disability progression by 29% (P=0.0278) and 32% (P=0.0177), respectively, compared with placebo. In a subset of patients (MRI cohort), DMF BID and TID reduced the mean number of new/enlarging T2-hyperintense lesions by 78% and 73%, gadolinium-enhancing lesion activity by 83% and 70%, and mean number of new nonenhancing T1-hypointense lesions by 65% and 64% (all P<0.0001 vs. placebo). Effects were generally consistent across patient subgroups.The integrated analysis provides a more precise estimate of DMFs efficacy. DMF demonstrated a robust reduction in disease activity and a consistent therapeutic effect across patient subgroups.


Mohan H.M.,St Vincents University Hospital Dublin | Evans M.D.,Singleton Hospital | Larkin J.O.,St Vincents University Hospital Dublin | Beynon J.,Singleton Hospital | Winter D.C.,St Vincents University Hospital Dublin
Annals of Surgical Oncology | Year: 2013

Background: The objective of this study was to critically evaluate current literature on outcomes following multivisceral resection (MVR) in colorectal cancer (CRC). Adequate surgical resection with clear margins is imperative in achieving long-term survival in colorectal cancer. Where there is adherence to or invasion of adjacent organs, (MVR) may be needed to achieve complete disease clearance. Methods: A systematic review of MVR in CRC was performed. Pubmed/Medline and Cochrane databases were searched for English language articles from 1995 to 2012 using a predefined strategy. Retrieved abstracts were independently screened for relevance and data extracted from selected studies by 2 researchers. Results are reported as weighted means. Results: Included were 22 studies comprising 1575 patients (87.0 % primary colorectal cancer; 13.0 % recurrent, 63.8 % rectal; 36.2 % colon). The most common organs resected were the bladder and reproductive organs. The perioperative mortality was 4.2 % with morbidity of 41.5 % (95 % CI, 40.8-42.2 %). The overall 5-year survival rate was 50.3 % (95 % CI, 49.9-50.8 %). Surgery for recurrence was associated with worse outcomes than primary tumors with 5-year survival 19.5 % (95 % CI, 17.8-21.1 %) for recurrent rectal cancer and primary rectal tumors 5-year overall survival 52.8 % (95 % CI, 52.0-53.8 %). R0 resection was the strongest factor associated with long-term survival. Conclusions: Multivisceral resection provides the best possibility of long-term survival in locally advanced primary colorectal cancer in which a clear margin has been achieved. © 2013 Society of Surgical Oncology.


PubMed | St Vincents University Hospital Dublin
Type: | Journal: Frontiers in molecular neuroscience | Year: 2015

Epidemiological studies suggest that vitamin D insufficiency may be prevalent in young as well as older populations. The pleiotropic effects of vitamin D are now beyond dispute and a growing number of studies provide accumulating evidence of a role for vitamin D in brain development and function. A number of studies to date have investigated the effects of early-life vitamin D deprivation on adult hippocampus in animals and humans, and there is a growing body of evidence to suggest a role for this hormone in the development of selected hippocampal functions such as latent inhibition and hole board habituation in rats. There are few studies to date of vitamin D deprivation or supplementation on early hippocampal development in vivo. However, a small number of studies, mostly in vitro, point to a role for vitamin D in differentiation and development of hippocampal neurons. There is also limited evidence that supplementation with vitamin D following a period of deprivation is capable of restoring cellular activity and later function. Further avenues of future research are outlined including animal studies on the effects of vitamin D deprivation and inadequacy on early hippocampal biochemistry and function, e.g., measurement of BDNF levels, GABAergic activity, long-term potentiation (LTP) and spatial navigation. It also remains to be established if there are critical developmental windows during which vitamin D is required. In light of the importance of the hippocampus in LTP and spatial learning, further investigations on the early effects of vitamin D deprivation on hippocampal development are warranted.

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