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BACKGROUND Palliative care remains suboptimal in end-stage liver disease. AIM To inform a definitive study, we assessed palliative long-term abdominal drains in end-stage liver disease to determine recruitment, attrition, safety/potential effectiveness, questionnaires/interview uptake/completion and make a preliminary cost comparison. METHODS A 12-week feasibility nonblinded randomised controlled trial comparing large-volume paracentesis vs long-term abdominal drains in refractory ascites due to end-stage liver disease with fortnightly home visits for clinical/questionnaire-based assessments. Study success criteria were attrition not >50%

Introduction The REDUCe study is a multicentre feasibility randomised controlled trial (RCT) comparing palliative long term abdominal drains (LTAD) with standard care, recurrent large volume paracentesis (LVP), in advanced cirrhosis and refractory ascites (RA), where ineligible for liver transplant (LT). Limited data exist on symptom burden in this group. Clinical, patient/carer reported, qualitative and health economic (HE) assessments were performed to resolve uncertainties and inform the design of a definitive RCT of LTAD as a palliative strategy in RA. Here we report on patient/carer reported outcomes. Methods Patients randomised 1:1 (LVP or LTAD). The LTAD group had community nurse home visits for ascites drainage. The LVP arm received standard care attending hospital. Follow up was 12 weeks with home visits every two weeks for clinical and questionnaire-based assessments: palliative care needs/symptom burden (IPOS); quality of life (QoL) (SF-LDQOL) and EQ-5D-5L; carer burden (ZBI-12) and service use. Results Thirty-six patients were randomised; 19 LVP and 17 LTAD. Uptake of questionnaires was high (>85%). Only 47% of the participants had carers who could complete ZBI-12 (9 LTAD vs 8 LVP). Symptom burden score (IPOS) was comparable in both groups at baseline and 12 weeks follow up. Compared to baseline, the EQ-5D-5L Health index worsened in LTAD but remained stable in LVP group, the reverse being true for the EQ-5D-5L visual analogue scale. SF-LDQoL: baseline domains were higher in the LTAD group, during follow up scores became similar in both groups (data not shown) except in the following domains where LTAD group had lower scores: memory, distress, loneliness and hopelessness. Baseline carer burden (ZBI-12) in LTAD was higher, but remained stable; however, in LVP carer burden was higher at 12 week follow up (table 1). Conclusions Preliminary data from REDUCe confirms and extends findings of significant symptom and carer burden in advanced cirrhosis and RA. LTAD may help mitigate carer burden, which was higher in the LVP group. Results of other PROM (SF-LDQOL and EQ-5D-5L) were variable. This may reflect the timing of questionnaire completion in relation to ascites drainage and large sampling variability. Finally the presence of the LTAD may have been a constant reminder of the palliative nature of the illness. Our results need further validation. Results will inform appropriate QoL assessment tools for definitive RCT design.

Introduction Ascites develops in about 90% with advanced cirrhosis; when refractory to medical therapy, standard of care is repeated large volume paracentesis (LVP) with albumin support. Refractory ascites (RA) confers a median life expectancy of six months without liver transplantation (LT). LVP is not an optimal palliative strategy. One alternative is long-term abdominal drains (LTAD), used in advanced malignant ascites, also enabling community management. Our ultimate aim is to improve end of life care (EoLC) in advanced cirrhosis and RA. This feasibility randomised controlled trial (RCT) aimed to resolve uncertainties in designing a definitive RCT. Methods Multicentre feasibility RCT with 1:1 randomisation between standard of care (LVP) vs. LTAD (Rocket Medical) in adults with RA, ineligible for LT. Both arms received prophylactic antibiotics. LTAD were inserted under ultrasound guidance. Community nurses undertook home visits to drain ascites dependent on symptoms; (maximum 6L/week), without albumin support. Follow up was 12 weeks with home visits every two weeks for the following assessments: clinical, questionnaire based to include quality of life, palliative care needs, carer burden and health economics (HE). Here we report clinical and HE outcomes. Results Thirty six patients were randomised; 19 LVP (two withdrew, wanting LTAD) and 17 LTAD (one withdrew - insufficient ascites). Mean age (years) LTAD vs. LVP 66 ± 10.4 vs. 68 ± 12; predominately male (76% vs. 74%). Participants were well matched at baseline in liver tests and prognostic scores: LTAD vs. LVP (serum bilirubin (μmol/L) 26 ± 15.8 vs. 16 ±10, serum albumin (g/L) 33 ± 4.2 vs. 31 ± 3.3, serum creatinine (mmol/L) 113 ± 46.7 vs.118 ± 53.1; MELD 14 ± 4.6 vs. 16 ± 7.2). One LTAD participant required hospitalisation for repeated LVP. Serum albumin (g/L) in the LTAD arm declined to 29 ± 3.3 at week two, subsequently remaining stable LTAD vs. LVP (29 ± 5.6 vs. 31 ± 5.5). Serum creatinine remained stable in both arms. There were no LTAD related serious adverse reactions. LTAD related adverse reactions included mild cellulitis (n=4) and small volume leakage around LTAD insertion site (n=3), all resolving rapidly. Peritonitis was rare, LTAD (possible) n=1 and LVP n=2. Overall mortality was 36% (12/33). Mortality and median survival (days in those who died) were 7/16 (44%) vs. 5/17 (29%), 53 days (IQR 43) vs. 61 days (IQR 35) in LTAD vs. LVP respectively. All but one death was liver related. Those in LTAD arm spent ≈20% less time in hospital. All nine alive in the LTAD arm at end of study elected to keep LTAD in. Detailed clinical and HE analysis is underway. Conclusions Preliminary data from the REDUCe study supports the safety and efficacy of palliative LTAD in RA due to advanced cirrhosis. LTAD allows successful management in the community with reduction in health resource utilisation. Proceeding to a definitive RCT is justified.

BACKGROUND: Oesophageal adenocarcinoma is the sixth most common cause of cancer death worldwide and Barrett's oesophagus is the biggest risk factor. We aimed to evaluate the efficacy of high-dose esomeprazole proton-pump inhibitor (PPI) and aspirin for improving outcomes in patients with Barrett's oesophagus.METHODS: The Aspirin and Esomeprazole Chemoprevention in Barrett's metaplasia Trial had a 2 × 2 factorial design and was done at 84 centres in the UK and one in Canada. Patients with Barrett's oesophagus of 1 cm or more were randomised 1:1:1:1 using a computer-generated schedule held in a central trials unit to receive high-dose (40 mg twice-daily) or low-dose (20 mg once-daily) PPI, with or without aspirin (300 mg per day in the UK, 325 mg per day in Canada) for at least 8 years, in an unblinded manner. Reporting pathologists were masked to treatment allocation. The primary composite endpoint was time to all-cause mortality, oesophageal adenocarcinoma, or high-grade dysplasia, which was analysed with accelerated failure time modelling adjusted for minimisation factors (age, Barrett's oesophagus length, intestinal metaplasia) in all patients in the intention-to-treat population. This trial is registered with EudraCT, number 2004-003836-77.FINDINGS: Between March 10, 2005, and March 1, 2009, 2557 patients were recruited. 705 patients were assigned to low-dose PPI and no aspirin, 704 to high-dose PPI and no aspirin, 571 to low-dose PPI and aspirin, and 577 to high-dose PPI and aspirin. Median follow-up and treatment duration was 8·9 years (IQR 8·2-9·8), and we collected 20 095 follow-up years and 99·9% of planned data. 313 primary events occurred. High-dose PPI (139 events in 1270 patients) was superior to low-dose PPI (174 events in 1265 patients; time ratio [TR] 1·27, 95% CI 1·01-1·58, p=0·038). Aspirin (127 events in 1138 patients) was not significantly better than no aspirin (154 events in 1142 patients; TR 1·24, 0·98-1·57, p=0·068). If patients using non-steroidal anti-inflammatory drugs were censored at the time of first use, aspirin was significantly better than no aspirin (TR 1·29, 1·01-1·66, p=0·043; n=2236). Combining high-dose PPI with aspirin had the strongest effect compared with low-dose PPI without aspirin (TR 1·59, 1·14-2·23, p=0·0068). The numbers needed to treat were 34 for PPI and 43 for aspirin. Only 28 (1%) participants reported study-treatment-related serious adverse events.INTERPRETATION: High-dose PPI and aspirin chemoprevention therapy, especially in combination, significantly and safely improved outcomes in patients with Barrett's oesophagus.FUNDING: Cancer Research UK, AstraZeneca, Wellcome Trust, and Health Technology Assessment.

Background and aims: Ascites develops in about 90% with advanced cirrhosis; when refractory to medical therapy, standard of care is repeated large volume paracentesis (LVP) with albumin support. Refractory ascites (RA) confers a median life expectancy of six months without liver transplantation (LT). LVP is not an optimal palliative strategy. One alternative is long-term abdominal drains (LTAD), used in advanced malignant ascites, also enabling community management. Our ultimate aim is to improve end of life care (EoLC) in advanced cirrhosis and RA. This feasibility randomised controlled trial (RCT) aimed to resolve uncertainties in designing a definitive RCT. Method: Multicentre feasibility RCT with 1:1 randomisation between standard of care (LVP) vs. LTAD (Rocket Medical) in adults with RA, ineligible for LT. Both arms received prophylactic antibiotics. LTAD were inserted under ultrasound guidance. Community nurses undertook home visits to drain ascites dependent on symptoms; (maximum 6L/week), without albumin support. Follow-up was 12 weeks with home visits every two weeks for the following assessments: clinical, questionnaire based to include quality of life, palliative care needs, carer burden and health economics (HE). Here we report clinical and HE outcomes. Results: Thirty six patients were randomised; 19 LVP (two withdrew, wanting LTAD) and 17 LTAD (one withdrew-insufficient ascites). Mean age (years) LTAD vs. LVP 66 + 10.4 vs. 68 ± 12; predominately male (76% vs. 74%). Participants were well matched at baseline in liver tests and prognostic scores: LTAD vs. LVP (serum bilirubin (μmol/L) 26 ± 15.8 vs. 16 ±10, serum albumin (g/L) 33 ± 4.2 vs. 31 ± 3.3, serum creatinine (mmol/L) 113 ± 46.7 vs.118 ± 53.1; MELD 14 ± 4.6 vs. 16 ± 7.2). One LTAD participant required hospitalisation for repeated LVP. Serum albumin (g/L) in the LTAD arm declined to 29 ± 3.3 at week two, subsequently remaining stable LTAD vs. LVP (29 ± 5.6 vs. 31 ± 5.5). Serum creatinine remained stable in both arms. There were no LTAD related serious adverse reactions. LTAD related adverse reactions included mild cellulitis (n = 4) and small volume leakage around LTAD insertion site (n = 3), all resolving rapidly. Peritonitis was rare, LTAD (possible) n = 1 and LVP n = 2. Overall mortality was 36% (12/33). Mortality and median survival (days in those who died) were 7/16 (44%) vs. 5/17 (29%), 53 days (IQR 43) vs. 61 days (IQR 35) in LTAD vs. LVP respectively. All but one death was liver related. Those in LTAD arm spent ≈20% less time in hospital. All nine alive in the LTAD arm at end of study elected to keep LTAD in. Detailed clinical and HE analysis is underway. Conclusion: Preliminary data from the REDUCe study supports the safety and efficacy of palliative LTAD in RA due to advanced cirrhosis. LTAD allows successful management in the community with reduction in health resource utilisation. Proceeding to a definitive RCT is justified.

We report a case of HIV-associated Cytomegalovirus colitis complicated by large bowel perforation. A 62-year-old man of same-sex relationship was not known to have HIV, but a diagnosis of inflammatory bowel disease was made early in his admission, with steroid treatment initiated. He was later confirmed to be HIV positive, and found to have multiple microperforations of the bowel necessitating ileocecectomy and Hartmann's procedures.

In this paper we explore whether power issues enhance and/or inhibit retention of foundation‐learners in vocational education in Aotearoa New Zealand. After surveying reasons given for early departure in the retention literature, the paper offers Foucault’s notion of governmentality as another possible factor in early departure. The paper explores three aspects of governmentality through the data: whether student resistance to the exercise of power creates conditions for early departure; whether the process of group formation, identity building and behaviour creates power dynamics within groups that inhibit or enhance retention; whether self‐disciplining, using power on oneself to conform to others’ expectations, norms or rules, influences learners’ decisions about staying or leaving early. Our conclusions are tentative but we suggest that power issues do play a part in helping learners decide whether or not to complete their courses of study.

Summary Background : Non-steroidal anti-inflammatory drugs use may protect against development of oesophageal adenocarcinoma. Aim : To define the consequences of non-steroidal anti-inflammatory drugs use in patients with Barrett's oesophagus. Methods : Records of all Barrett's oesophagus/oesophageal adenocarcinoma patients examined in Blackpool-Wyre-Fylde area were reviewed. All surviving patients completed validated questionnaires. Results : Use of non-steroidal anti-inflammatory drugs of any type and at any frequency was more prevalent in Barrett's oesophagus patients [147 (38%) Barrett's oesophagus vs. 30 (26%) oesophageal adenocarcinoma, P = 0.02]. Daily use of non-steroidal anti-inflammatory drugs was more prevalent in Barrett's oesophagus patients [88 (23%) Barrett's oesophagus vs. 14 (12%) oesophageal adenocarcinoma, P = 0.02], due to more prevalent consumption of non-aspirin non-steroidal anti-inflammatory drugs [48 (13%) Barrett's oesophagus vs. four (4%) oesophageal adenocarcinoma, P =0.009]. There was no difference between the two groups in usage of either daily low-dose aspirin or of occasional non-steroidal anti-inflammatory drugs. In logistic regression analysis any use of non-steroidal anti-inflammatory drugs [odds ratio (OR) = 0571 (95% CI: 0.359–0.909), P = 0.018] and daily use of non-aspirin non-steroidal anti-inflammatory drugs [OR = 0.297 (95% CI: 0.097–0.911), P = 0.034] were significant protective factors. Non-steroidal anti-inflammatory drugs use did not affect the survival of oesophageal adenocarcinoma patients. Oesophageal adenocarcinoma and Barrett's oesophagus consuming non-steroidal anti-inflammatory drugs did not differ in upper gastrointestinal bleeding [26 (15%) non-steroidal anti-inflammatory drugs consumers vs. 29 (9%) non-consumers, P = 0.08], oesophageal ulcers [31 (18%) non-steroidal anti-inflammatory drug consumers vs. 49 (15%) non-consumers, P = 0.43] or stricturing [19 (11%) non-steroidal anti-inflammatory drug consumers vs. 41 (13%) non-consumers, P = 0.58]. Conclusions : (i) Daily use of non-steroidal anti-inflammatory drugs is more prevalent in Barrett's oesophagus than oesophageal adenocarcinoma patients, because of a more prevalent use of non-aspirin non-steroidal anti-inflammatory drugs. (ii) Use of non-steroidal anti-inflammatory drugs in Barrett's oesophagus patients is safe if acid suppression is adequate.

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (P combined = 4.09 × 10-9; odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (P combined = 2.74 × 10-10; OR = 1.14, 95% CI = 1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus. © 2012 Nature America, Inc. All rights reserved.

An aymptomatic 56-year-old man presented with a self-referred non-contrast computed tomography (CT) scan that showed an abnormality in the mesentery. There was no clinical indication for the CT scan. Three years previously he had undergone radiotherapy and hormonal therapy for prostate cancer. His prostate specific antigen levels had remained normal and he was in good health. There was no clinical or biochemical abnormality. A repeat abdominal CT scan with contrast showed a 36 mm mass in the …

The clinical features of 27 patients identified in an outbreak of botulism in Lancashire, England, and North Wales are reviewed. All but 1 of the patients (age range 14 months to 74 years) were admitted to hospital: 12 were treated in intensive care units, and 8 received positive pressure ventilation. 1 patient died with an aspiration pneumonia. The clinical presentations contained several unusual features, with evidence of segmental demyelination in some patients and drowsiness, sore throats, and fever in others. The widely dispersed source of intoxication with patients presenting singly to several hospitals added to the difficulties of diagnosis. Successful clinical management depends on full and early recognition both of the dangers of impaired oropharyngeal function and of the rapid neurological changes in botulism.

Differences in heart stability of human pancreatic ribonuclease (cRNase) and serum ribonuclease were abolished by aprotinin, suggesting that the pancreatic enzyme was similar to the serum enzyme, but was being destroyed by proteases. Serum ribonuclease levels in normal subjects correlated with age but were unaffected by meal ingestion. Serum ribonuclease was not found to be useful in the detection of pancreatic cancer and was more frequently abnormal in patients with other solid tumours or renal failure.

Introduction Hereditary causes of visceral thrombosis or thrombosis should be sought among young patients. We present a case of a young man presenting with multiple hepatic infarctions resulting in portal hypertension due to homozygosity of the prothrombin gene mutation not previously described in literature. Case presentation A 42-year-old Caucasian man with a previous history of idiopathic deep vein thrombosis 11 years earlier presented with vague abdominal pains and mildly abnormal liver function tests. An ultrasound and computed tomography scan showed evidence of hepatic infarction and portal hypertension (splenic varices). A thrombophilia screen confirmed a homozygous mutation for the prothrombin gene mutation, with mildly reduced levels of anti-thrombin III (AT III). Subsequent testing of his father and brother revealed heterozygosity for the same gene mutation. Conclusion Hepatic infarction is unusual due to the rich dual arterial and venous blood supply to the liver. In the absence of an arterial or haemodynamic insult causing hepatic infarction, a thrombophilia should be considered. To our knowledge, this is the first reported case of a hepatic infarction due to homozygosity of the prothrombin gene mutation. It is unclear whether homozygotes have a higher risk of thrombosis than heterozygotes. In someone presenting with a first thrombosis with this mutation, the case for life-long anticoagulation is unclear, but it may be necessary to prevent a second and more severe second thrombotic event, as occurred in this case.