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    ABSTRACT: Limited evidence is available on the economic burden of ulcerative colitis (UC) in the UK, particularly relating to the impact of relapse frequency on direct medical costs. This study identifies and assesses medical resource utilization (MRU) and associated direct costs in mild and moderate UC patients in the UK. A retrospective chart review of patients with mild-to-moderate UC diagnosed at least 1 year before the study was performed. From 33 general practitioner (GP) and 34 gastroenterologist sites, charts of the last three UC patients fulfilling the inclusion criteria were reviewed. Descriptive statistics were calculated for MRU and 2011 costs (GB£) by number of relapses. The study population included 201 patients with a mean age of 39.9 years; 44% were women and the mean disease duration was 7.4 years. UC-related costs of each MRU category increased with the number of relapses. Comparing patients without relapse with those with more than two relapses, the mean annual UC-related costs were £14 versus £2556 for hospitalizations; £218 versus £988 for visits (including nurse, GP, specialist, and other visits); £21 versus £1303 for procedures; £17 versus £188 for diagnostics; and £1168 versus £6660 for all-cause total costs. Age, sex, and site of data reporting (GP vs. gastroenterologist) were not associated with MRU or costs. Patients with mild-to-moderate UC incurred considerable costs that increased markedly with the number of relapses. These findings support the importance of maintenance therapies in UC that reduce or prevent relapses. Quantifying the relationship between relapse rate and costs will inform future health economic studies.
    European journal of gastroenterology & hepatology 10/2013;
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    ABSTRACT: Transcatheter hepatic therapy with irinotecan-eluting beads (DEBIRI(®)) allows targeted delivery of irinotecan direct to liver tissue and colorectal liver metastases (CRLM). Accurate assessment of tumour response to therapy is vital to guide optimal treatment. Preliminary work has suggested existing criteria for radiological response may not reflect pathological response after neoadjuvant DEBIRI. This study assessed the relationship between existing and novel radiological response criteria and pathological tumour response as well as long-term outcome. Patients with easily resectable CRLM were treated with DEBIRI 4 weeks prior to resection and pathological tumour response graded using a validated system. Radiological response was assessed using RECIST and novel morphological response criteria. Twenty-two patients with 37 lesions were treated with DEBIRI. Median residual tumour was 20% (range 0-80), median necrosis 45% (10-100) and median fibrosis 10% (10-70). Twenty patients (91%) demonstrated stable disease by RECIST, with 11 (50%) demonstrating partial morphological response. Neither radiological response criteria correlated with pathological response. Overall median disease free survival (DFS) was 13.6 months (95% CI 4.7-22.5). Radiological response was not associated with DFS. Existing criteria reporting short-term radiological response to DEBIRI do not accurately predict pathological tumour response or long-term outcome. Further work is necessary to define the optimum timing and method of assessing response to DEBIRI.
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 08/2013;
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    ABSTRACT: We have recently shown that kidney-derived stem cells (KSCs) isolated from the mouse newborn kidney differentiate into a range of kidney-specific cell types. However, the functionality and integration capacity of these mouse KSCs remain unknown. Therefore, the main objectives of this study were (1) to determine if proximal tubule-like cells, generated in vitro from KSCs, displayed absorptive function typical of proximal tubule cells in vivo, and (2) to establish whether the ability of KSCs to integrate into developing nephrons was comparable with that of metanephric mesenchyme (MM), a transient population of progenitor cells that gives rise to the nephrons during kidney organogenesis. We found that proximal tubule-like cells generated in vitro from mouse KSCs displayed megalin-dependent absorptive function. Subsequently, we used a chimeric kidney rudiment culture system to show that the KSCs could generate proximal tubule cells and podocytes that were appropriately located within the developing nephrons. Finally, we compared the ability of KSCs to integrate into developing kidneys ex vivo with that of metanephric mesenchyme cells. We found that KSCs integrated into nascent nephrons to a similar extent as metanephric mesenchyme cells while both were excluded from ureteric bud branches. Our analysis of the behavior of the two cell types shows that some, but not all KSC characteristics are similar to those of the MM.
    PLoS ONE 06/2013; 8(5):e62953.
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    ABSTRACT: The intestinal hormone cholecystokinin (CCK) delays gastric emptying and inhibits food intake by actions on vagal afferent neurons. Recent studies suggest plasminogen activator inhibitor (PAI)-1 suppresses the effect of CCK on food intake. In this study we asked whether PAI-1 also modulated CCK effects on gastric emptying. Five minute gastric emptying of liquid test meals was studied in conscious wild type mice (C57BL/6) and in transgenic mice over-expressing PAI-1 in gastric parietal cells (PAI-1H/Kβ mice), or null for PAI-1. The effects of exogenous PAI-1 and CCK8s on gastric emptying were studied after ip administration. Intragastric peptone delayed gastric emptying in C57BL/6 mice by a mechanism sensitive to the CCK-1 receptor antagonist lorglumide. Peptone did not delay gastric emptying in PAI-1-H/Kβ mice. Exogenous CCK delayed gastric emptying of a control test meal in C57BL/6 mice and this was attenuated by administration of PAI-1; exogenous CCK had no effect on emptying in PAI-1-H/Kβ mice. Prior administration of gastrin to increase gastric PAI-1 inhibited CCK-dependent effects on gastric emptying in C57BL/6 mice but not in PAI-1 null mice. Thus, both endogenous and exogenous PAI-1 inhibit the effects of CCK (whether exogenous or endogenous) on gastric emptying. The data are compatible with emerging evidence that gastric PAI-1 modulates vagal effects of CCK.
    Regulatory Peptides 06/2013;
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    ABSTRACT: PURPOSE: The response of colorectal liver metastases to the cytotoxic agent irinotecan varies widely. Attempts to correlate tumour metabolism with response have been mixed. This study investigated the hepatic metabolism of irinotecan as a potential predictor of tumour response to irinotecan-eluting beads (DEBIRI). METHODS: Ten patients with colorectal liver metastases were treated with 200 mg irinotecan (as DEBIRI) as part of the PARAGON II study. Hepatic expression of key metabolising enzymes was measured using mass spectrometry-based proteomics. Serum drug concentrations and hepatic irinotecan metabolism were characterised and correlated with tumour response. RESULTS: Serum concentrations of irinotecan metabolites did not correlate with hepatic metabolism or pathological response. There was a strong correlation between hepatic CES-2 expression and activation of irinotecan (r (2) = 0.96, p < 0.001). Patients with a UGT1A1*28 6/7 SNP showed no difference in drug metabolism or pathological response. Hepatic CES-2 mediated activation of irinotecan clearly correlated with tumour replacement by fibrosis (r (2) = 0.54, p = 0.01). CONCLUSION: This study provides the first evidence that hepatic activation of irinotecan predicts tumour response. Delivery of liver-targeted irinotecan to normal liver tissue rather than tumour may be a more rational approach to maximise response.
    Cancer Chemotherapy and Pharmacology 06/2013;
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    ABSTRACT: Following the publication of the EORTC trial (40983), perioperative chemotherapy has become the standard of care for all patients with resectable colorectal cancer liver metastases (CRLM). However recently presented data suggest that the earlier advantage seen in progression free survival (PFS) may not translate over into a meaningful overall survival (OS) advantage. At the other end of the spectrum, patients with irresectable but liver limited CRLM continue to be offered treatment based on improving PFS, at the expense of regimens with greater response rates (but maybe poorer PFS rates) that could bring them to potentially curative liver resection. We therefore argue that patients with liver limited CRLM should be managed in three separate groups:
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 05/2013;
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    ABSTRACT: AIMS: Staging laparoscopy has been recommended in the management of patients with colorectal liver metastases prior to hepatectomy in order to reduce the incidence and associated morbidity of futile laparotomies. The utility of staging laparoscopy has not been assessed in patients undergoing CT, PET-CT and MRI as standard preoperative staging. METHODS: All patients undergoing attempted open hepatectomy for colorectal liver metastases between 1/4/2008 and 31/3/2012 were identified from a prospectively maintained research database. All patients who underwent futile laparotomy were identified, with demographics and operative notes subsequently analysed. RESULTS: A total of 274 patients underwent attempted open hepatectomy during the study period. At laparotomy 12 (4.4%) patients were found to have irresectable disease. There were no unifying demographic factors within the patients undergoing futile laparotomy. CONCLUSIONS: With modern imaging, the potential yield of staging laparoscopy is low. Staging laparoscopy should not be used routinely, but may have a role in the case of specific clinical concerns.
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 04/2013;
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    ABSTRACT: BACKGROUND: Published data on the outcome of Copeland shoulder resurfacing arthroplasty (CSRA) are limited. This observational case series study reports the functional and radiological outcome of CSRA during a mean follow-up of 4 years and highlights the correlation between key outcome measures. METHODS: One-hundred two consecutive patients with osteoarthritis (OA-47.1%), rheumatoid arthritis (RA-40.2%), rotator cuff arthropathy (RCA-8.8%), and avascular necrosis (AVN-3.9%) underwent CSRA. The outcome assessment included pain and satisfaction, physical limitation, Oxford Shoulder score (OSS), Constant score (CS), and SF-12. Imaging was reviewed for glenoid morphology (Walch classification) and humeral head (HH) migration. RESULTS: Highest patient satisfaction and lowest pain levels were related to the primary pathology with AVN best followed by OA, RA, and with RCA having the poorest outcome. Comparing the two largest groups the CS was significantly higher in OA (61 ± 21.3) than RA (44 ± 20.5). OSS showed a significant correlation with CS and physical subscale of SF-12. Walch type A (67.6%) and HH migration (47%) were the commonest radiographic observations. OSS, CS, pain, and satisfaction were significantly different between migration and nonmigration groups. CONCLUSION: The CSRA resulted in satisfactory outcome in many patients. AVN and OA were associated with the best and RCA with the poorest results. The CSRA was associated with glenoid erosion and HH migration particularly in RCA. CSRA remains an option in the treatment of arthritic conditions of the shoulder but its future use may be limited to younger patients where implanting a glenoid may be regarded as problematic.
    Journal of shoulder and elbow surgery / American Shoulder and Elbow Surgeons ... [et al.] 04/2013;
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    ABSTRACT: OBJECTIVE: To determine whether variation in gastroscopy rates in English general practice populations is associated with inequality in oesophagogastric (OG) cancer outcome. DESIGN: Retrospective observational study of the Hospital Episode Statistics (HES) dataset for England (2006-2008) linked to death registration. METHODS: were validated using independent local and national data. General practices with new cases of OG cancer were included. Practices were grouped into tertiles according to standardised elective gastroscopy rate per capita (low, medium or high). Outcome measures for cancer cases were: emergency admission during diagnostic pathway, major surgical resection and mortality at 1 year. Covariates were: age group, gender, comorbidity, general practice average deprivation and patient deprivation. RESULTS: 22 488 incident cases of OG cancer from 6513 general practices were identified. Patients registered with the low tertile group of practices had the lowest rate of major surgery, highest rate of emergency admission and highest mortality. The inequality was widest for the most socioeconomically deprived cases. After adjustment for covariates in logistic regression, the gastroscopy rate (low, medium or high) at the patient's general practice was an independent predictor of emergency admission, major surgery and mortality. CONCLUSIONS: There is wide variation in the rate of gastroscopy among general practice populations in England. On average, OG cancer patients belonging to practices with the lowest rates of gastroscopy are at greater risk of poor outcome. These findings suggest that initiatives or current guidelines aimed at limiting the use of gastroscopy may adversely affect cancer outcomes.
    Gut 02/2013;
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    ABSTRACT: The bacterial load and degree of antibiotic resistance present in untreated and antibiotic-treated semen samples were investigated in five bulls standing at a cattle-breeding centre. Bacterial load was determined by colony counts from semen samples cultured on brain heart infusion and nutrient agar plates. Antibiotic resistance in these bacteria was assessed by measuring the diameter of bacterial growth inhibition zones around discs containing different concentrations of antibiotics. Representative antibiotic-resistant bacterial isolates were selected for identification. Untreated semen contained few culturable bacteria, and all were completely sensitive to gentamycin, spectinomycin and lincomycin: six of the isolates showed some resistance to tylosin. In semen to which antibiotics had been added as part of the routine production process, two isolates were sensitive to all of the antibiotics tested, and the remainder were resistant to all. Resistant Gram-negative isolates that were identified included Pseudomonas and Stenotrophomonas spp. both in the class Gammaproteobacteria and a Sphingomonas sp. which is in the class Alphaproteobacteria.
    Reproduction in Domestic Animals 01/2013;
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