Local Sn Dipolar-Character Displacements behind the Low Thermal Conductivity in SnSe Thermoelectric.

The local atomic structure of SnSe was characterized across its orthorhombic-to-orthorhombic structural phase transition using x-ray pair distribution function analysis. Substantial Sn displacements with a dipolar character persist in the high-symmetry high-temperature phase, albeit with a symmetry different from that of the ordered displacements below the transition. The analysis implies that the transition is neither order-disorder nor displacive but rather a complex crossover. Robust ferrocoupled SnSe intralayer distortions suggest a ferroelectriclike instability as the driving force. These local symmetry-lowering Sn displacements are likely integral to the ultralow lattice thermal conductivity mechanism in SnSe.

Costs and quality of life associated with acute upper gastrointestinal bleeding in the UK: cohort analysis of patients in a cluster randomised trial.

OBJECTIVES: Data on costs associated with acute upper gastrointestinal bleeding (AUGIB) are scarce. We provide estimates of UK healthcare costs, indirect costs and health-related quality of life (HRQoL) for patients presenting to hospital with AUGIB. SETTING: Six UK university hospitals with >20 AUGIB admissions per month, >400 adult beds, 24 h endoscopy, and on-site access to intensive care and surgery. PARTICIPANTS: 936 patients aged ≥18 years, admitted with AUGIB, and enrolled between August 2012 and March 2013 in the TRIGGER trial of AUGIB comparing restrictive versus liberal red blood cell (RBC) transfusion thresholds. PRIMARY AND SECONDARY OUTCOME MEASURES: Healthcare resource use during hospitalisation and postdischarge up to 28  days, unpaid informal care, time away from paid employment and HRQoL using the EuroQol EQ-5D at 28  days were measured prospectively. National unit costs were used to value resource use. Initial in-hospital treatment costs were upscaled to a UK level. RESULTS: Mean initial in-hospital costs were £2458 (SE=£216) per patient. Inpatient bed days, endoscopy and RBC transfusions were key cost drivers. Postdischarge healthcare costs were £391 (£44) per patient. One-third of patients received unpaid informal care and the quarter in paid employment required time away from work. Mean HRQoL for survivors was 0.74. Annual initial inhospital treatment cost for all AUGIB cases in the UK was estimated to be £155.5 million, with exploratory analyses of the incremental costs of treating hospitalised patients developing AUGIB generating figures of between £143 million and £168 million. CONCLUSIONS: AUGIB is a large burden for UK hospitals with inpatient stay, endoscopy and RBC transfusions as the main cost drivers. It is anticipated that this work will enable quantification of the impact of cost reduction strategies in AUGIB and will inform economic analyses of novel or existing interventions for AUGIB. TRIAL REGISTRATION NUMBER: ISRCTN85757829 and NCT02105532.

Factors influencing dyspepsia-related consultation: differences between a rural and an urban population.

BACKGROUND: Dyspepsia is a common, chronic condition but medical consultation rates for symptoms remain variable. We aimed to examine two populations with varied health-care provision to determine predictive factors for dyspepsia-related consultation. METHODS: A cross-sectional, population-based study in both an urban and a rural community within a single Asian country was conducted. Details on dyspepsia-related consultation rates over a fixed period and independent factors influencing them were identified. KEY RESULTS: A total of 4039/5370 (75.2%) adults from representative rural and urban areas in this country agreed to participate in the study. Although mean ages of respondents were similar (40.4years), the demographics of both populations varied in terms of gender (62.7% female, rural vs 55.7% female, urban, P<0.0001), marital status (75.4% rural vs 70.5% urban, P=0.002), ethnicity, (79% Malay rural vs 45.3% Malays urban, P<0.0001) and socio-economic status (professional occupation 7.1% rural vs 47.3% urban, P<0.0001). Dyspepsia-related consultation rates were found to be higher among rural compared to urban adults (41.4%vs 28.7%, P<0.0001). Over-the-counter medication consumption was higher among urban compared to rural dyspepsia sufferers (n=157 vs n=35, P<0.0001). Following logistic regression, rural population (OR 3.14, 95% CI=1.65-6.0), low quality of life (OR 1.90, 95% CI=1.17-3.10), and self-medication (OR 0.40, 95% CI=0.25-0.62) were found to independently predict dyspepsia-related consultation. CONCLUSIONS & INFERENCES: Dyspepsia-related consultation varied significantly between urban and rural communities. Factors within the rural population, self-medication practices, and a low quality of life independently influenced dyspepsia-related consultation.

Embolization for non-variceal upper gastrointestinal tract haemorrhage: a systematic review.

AIM: To assess the published evidence on the endovascular treatment of non-variceal upper gastrointestinal haemorrhage. MATERIALS AND METHODS: An Ovid Medline search of published literature was performed (1966-2009). Non-English literature, experimental studies, variceal haemorrhage and case series with fewer than five patients were excluded. The search yielded 1888 abstracts. Thirty-five articles were selected for final analysis. RESULTS: The total number of pooled patients was 927. The technical and clinical success of embolization ranged from 52-100% and 44-100%, respectively. The pooled mean technical/clinical success rate in primary upper gastrointestinal tract haemorrhage (PUGITH) only, trans-papillary haemorrhage (TPH) only, and mixed studies were 84%/67%, 93%/89%, and 93%/64%, respectively. Clinical outcome was adversely affected by multi-organ failure, shock, corticosteroids, transfusion, and coagulopathy. The anatomical source of haemorrhage and procedural variables did not affect the outcome. A successful embolization improved survival by 13.3 times. Retrospective comparison with surgery demonstrated equivalent mortality and clinical success, despite embolization being applied to a more elderly population with a higher prevalence of co-morbidities. CONCLUSIONS: Embolization is effective in this very difficult cohort of patients with outcomes similar to surgery.

Review article: methods of measuring gastric acid secretion.

BACKGROUND: Gastric acid has an important pathophysiological role in human beings. Numerous methods have been evaluated over the years in an attempt to measure gastric acid and stomach acidity, to study the role of gastric acid in gastrointestinal diseases in humans and to evaluate the effects of acid suppressing drugs. AIM: To review methods that have been used to measure gastric acid and gastric acidity. METHODS: Searches of the electronic databases PUBMED, MEDLINE and EMBASE, were performed with articles restricted to English language and human subjects. References were also identified from the bibliographies of selected articles. RESULTS: Methods for measuring gastric acid include both invasive and non-invasive techniques. Invasive tests include the conventional gastric acid aspiration tests, gastric pH measurement techniques and endoscopic methods. Non-invasive methods use urinary analysis, breath analysis, serum pepsinogens assay, scintigraphic techniques, impedence tomography and alkaline tide for measurement of gastric acid. CONCLUSIONS: Several methods of measuring gastric acid exist. Invasive tube tests are uncomfortable and time consuming, whereas most of the non-invasive methods are at best semiquantitative and useful in detecting low or absent acid secretion. Further attempts to explore new methods for measuring gastric acid are therefore warranted.

Establishing a biologics service for patients with inflammatory bowel disease.

The use of anti-TNF therapy in the management of Crohn's disease and, to a lesser extent ulcerative colitis, is increasing. This article aims to discuss the practicalities of establishing a biologics service for patients with inflammatory bowel disease. Current guidelines on the use of these drugs are reviewed followed by a discussion on the choice of which anti-TNF agent to use based on costs and patient choice. A model for the initiation, administration, monitoring and assessment of patients receiving anti-TNF therapy is proposed. The need for a national biologics registry is highlighted in the summary.

Evidence-based use of anti-TNFα therapy in Crohn's disease; where are we in 2011?

The efficacy of anti-tumour necrosis factor (anti-TNFα) therapy with infliximab and adalimumab in moderate to severe Crohn's disease has now been proved. This article reviews the evidence supporting best practice with these agents in the light of recent National Institute for Health and Clinical Excellence guidance. Recent studies point to greater efficacy when these drugs are used early in the disease, particularly when mucosal healing can be achieved. For infliximab, the combination with immunomodulator drugs appears to afford greater efficacy, but possibly at the expense of the risk of rare but serious side effects. Patients should be selected carefully for treatment based on prognostic factors predicting aggressive disease, on the one hand, and comorbid factors that might predict side effects, on the other. Multiple drug combinations should be avoided where possible. Finally, a minority of patients in stable remission with complete mucosal healing may be selected for anti-TNFα drug withdrawal.

Costs of care for Crohn's disease following the introduction of infliximab: a single-centre UK experience.

BACKGROUND: Infliximab is effective for induction and maintenance of remission in patients with Crohn's disease. There are few data, however, examining effect of infliximab therapy on management costs of Crohn's disease. AIM: To assess Crohn's disease-related costs of care and resource use in a single-centre cohort of patients with Crohn's disease 12 months pre- and post-infliximab therapy. METHODS: Data on 100 consecutive patients receiving infliximab were collected. Crohn's disease-related resource use was collected 12 months pre- and post-infliximab. National Health Service reference costs were applied to these data and the total Crohn's disease-related health service costs per patient were calculated (£UK). The cost of infliximab therapy was not included in our analysis. RESULTS: Cost savings were demonstrated in all areas of Crohn's disease-related resource use following infliximab therapy. Mean total Crohn's disease-related cost reduction, 12 months following commencement of infliximab therapy, was £2750 per patient. Mean costs at 12 months post-infliximab in responders were lower than in nonresponders (£1656 vs. £3608, P = 0.02). The number of hospitalizations was reduced. Requirements for examination under anaesthesia were also significantly decreased. CONCLUSION: Infliximab use resulted in Crohn's disease-related cost savings and hospital resource use, although this was not sufficient to cover the cost of therapy.

Ethnic variation, epidemiological factors and quality of life impairment associated with dyspepsia in urban Malaysia.

BACKGROUND: The role of ethnicity in the development of dyspepsia remains uncertain. AIMS: To examine the epidemiology of dyspepsia in a multi-ethnic Asian population and its impact on health-related quality of life (HRQOL). METHODS: A cross-sectional survey was conducted in a representative urban population in Kuala Lumpur, Malaysia. RESULTS: A total of 2039 adults (mean +/- s.d. age: 40.5 +/- 11.8 years, males 44.2%, ethnicity: Malays 45.3%, Chinese 38.0% and Indians 13.1%, tertiary education level 62%, professional employment 47.7% and median monthly income USD 850.00) were interviewed. Dyspepsia was prevalent in 496 (24.3%) adults. Independent predictors for dyspepsia, explored by logistic regression, were identified as: Malay (OR 2.17, 95% CI = 1.57-2.99) and Indian (OR 1.59, 95% CI = 1.03-2.45) ethnicity, heavy chilli intake (OR 2.35, 95% CI = 1.15-4.80), use of regular analgesia (OR 3.51, 95% CI = 2.54-4.87) and chronic illness (OR 1.67, 95% CI = 1.22-2.28). HRQOL was assessed with the EQ-5D and significantly lower scores were noted in dyspeptics compared with healthy controls (0.85 +/- 0.17 vs. 0.95 +/- 0.12, P < 0.0001). CONCLUSION: Ethnicity, in addition to recognized epidemiological factors, is a risk factor for dyspepsia in an urban multi-racial Asian population.

Evaluation of the need for endoscopy to identify low-risk patients presenting with an acute upper gastrointestinal bleed suitable for early discharge.

AIMS: To audit the safety of differing protocol-driven early-discharge policies, from two sites, for low-risk acute upper gastrointestinal (GI) bleeding and determine if default early (<24 h) in-patient endoscopy is necessary. METHODS: All patients with low-risk acute upper GI bleeding presenting to two separate hospital sites in Leeds from August 2002 to March 2005 were identified. Both hospitals operate nurse-led process-driven protocols for discharge within 24 h, but only one includes default endoscopy. Relevant information was obtained from patients' notes, patient administration systems, discharge letters and endoscopy records. RESULTS: 120 patients were admitted to site A and 74 to site B. Median length of stay on the clinical decisions unit was 12.6 h at site A and 9.4 h at site B (p = 0.045). Oesophagogastroduodenoscopy was performed on 89/120 (74%) patients at site A compared with only 7/74 (9%) at site B (p<0.001). Six of 120 (5%) patients from site A were admitted to hospital for further observation compared with 6/74 (8%) from site B (p = 0.38). Of the remaining patients, all were discharged within 24 h, and 8/114 (7%) at site A vs 17/68 (25%) at site B were given hospital clinic follow-up (p<0.001). None of the 194 patients had further bleeding or complications within 30 days. CONCLUSIONS: Patients admitted with a low-risk acute upper GI bleeding can be managed safely by a nurse-led process-driven protocol, based on readily available clinical and laboratory variables, with early discharge <24 h. Avoiding in-patient endoscopy appears to be safe but at the price of greater clinic follow-up.

Mycophenolate mofetil therapy for refractory inflammatory bowel disease.

BACKGROUND: Mycophenolate mofetil (MMF) is an immunomodulatory drug, and its use in inflammatory bowel disease has previously been reported. The aim of this study was to review the Leeds Colitis Clinic experience of the safety and efficacy of MMF in treating patients with refractory Crohn's disease (CD) and ulcerative colitis (UC). This is an extension of a previously published study from our center with a longer follow-up period and approximately twice the number of patients. METHODS: A retrospective analysis was performed of the records of all patients treated with MMF for inflammatory bowel disease over a 5-year period. RESULTS: Of 70 patients identified, 67 had previously been treated with azathioprine unsuccessfully. Seventeen of the 70 patients had been successfully maintained in remission with MMF for an average duration of 33 months. Treatment with MMF was discontinued for 53 patients, 17 because of side effects and 36 because they had not responded to the treatment. CONCLUSIONS: In our series, 17 patients (24.3%) had a sustained steroid-free remission with MMF therapy. Nineteen patients (27%) experienced side effects, of which 17 (24.3% of the total group) had to discontinue therapy. An additional 36 (51.4%) required an escalation in medical therapy or surgery because of failure of the MMF therapy. MMF may have a role in the treatment of refractory inflammatory bowel disease, especially in patients who have previously failed standard therapies such as azathioprine.

The outcome of suspected upper gastrointestinal bleeding with 24-hour access to upper gastrointestinal endoscopy: a prospective cohort study.

BACKGROUND AND STUDY AIM: The aim was to evaluate the 30-day mortality after endoscopy for suspected upper gastrointestinal bleed, following the implementation of national audit guidelines at our hospital. PATIENTS AND METHODS: All patients with suspected upper gastrointestinal bleeding, referred for endoscopy to our teaching hospital between October 2001 and December 2003, were included in a prospective cohort study. RESULTS: A total of 716 patients with suspected upper gastrointestinal tract haemorrhage were referred for urgent endoscopy. The median age was 69 years (interquartile range 51 - 80 years). Bleeding from peptic ulcer remained the single most common endoscopic diagnosis (40 %). The overall re-bleeding rate for all patients with a gastrointestinal haemorrhage was 10 %. The overall 30-day mortality rate was 14.6 %. This was not significantly different from the mortality rate in 1995 of 10.5 % ( P = 0.11). Patients who died were significantly older (78 vs. 67 years, 95 %CI of the difference 5 to 12, P < 0.001). However, in only 29 % (30/105) was gastrointestinal haemorrhage stated in the death certificate as a factor which contributed to their death. CONCLUSIONS: Our results show that implementing the good practice guideline has a limited impact on overall mortality because of contributing factors that are beyond the control of clinicians.

Oesophageal haematoma and associated Mallory-Weiss tear.

Intramural oesophageal haematoma is a rare condition that may present as vomiting or haematemesis. Mallory-Weiss tear has been proposed as a possible aetiology but the evidence to support this is circumstantial. A case of oesophageal haematoma associated with evidence of Mallory-Weiss tear on endoscopy that helps to support this hypothesis is presented.

The effect of Helicobacter pylori infection on levels of DNA damage in gastric epithelial cells.

BACKGROUND: Helicobacter pylori infection leads to an increased risk of developing gastric cancer. The mechanism through which this occurs is not known. We aimed to determine the effect of H. pylori and gastritis on levels of DNA damage in gastric epithelial cells. METHODS: Epithelial cells were isolated from antral biopsies from 111 patients. DNA damage was determined using single cell gel electrophoresis and the proportion of cells with damage calculated before and 6 weeks after eradication of H. pylori. Cell suspensions generated by sequential digestions of the same biopsies were assayed to determine the effect of cell position within the gastric pit on DNA damage. RESULTS: DNA damage was significantly higher in normal gastric mucosa than in H. pylori gastritis [median (interquartile range) 65% (58.5-75.8), n = 18 and 21% (11.9-29.8), n = 65, respectively, p <.001]. Intermediate levels were found in reactive gastritis [55.5% (41.3-71.7), n = 13] and H. pylori negative chronic gastritis [50.5% (36.3-60.0), n = 15]. DNA damage rose 6 weeks after successful eradication of H. pylori[to 39.5% (26.3-51.0), p =.007] but was still lower than in normal mucosa. Chronic inflammation was the most important histological factor that determined DNA damage. DNA damage fell with increasing digestion times (r = -.92 and -.88 for normal mucosa and H. pylori gastritis, respectively). CONCLUSIONS: Lower levels of DNA damage in cells isolated from H. pylori infected gastric biopsies may be a reflection of increased cell turnover in H. pylori gastritis. The investigation of mature gastric epithelial cells for DNA damage is unlikely to elucidate the mechanisms underlying gastric carcinogenesis.

Dietary antioxidants and DNA damage in patients on long-term acid-suppression therapy: a randomized controlled study.

Free radicals and reactive species produced in vivo can trigger cell damage and DNA modifications resulting in carcinogenesis. Dietary antioxidants trap these species limiting their damage. The present study evaluated the role of vitamins C and E in the prevention of potentially premalignant modifications to DNA in the human stomach by supplementing patients who, because of hypochlorhydria and possible depletion of gastric antioxidants, could be at increased risk of gastric cancer. Patients undergoing surveillance for Barrett's oesophagus (n 100), on long-term proton pump inhibitors were randomized into two groups: vitamin C (500 mg twice/d) and vitamin E (100 mg twice/d) for 12 weeks (the supplemented group) or placebo. Those attending for subsequent endoscopy had gastric juice, plasma and mucosal measurements of vitamin levels and markers of DNA damage. Seventy-two patients completed the study. Plasma ascorbic acid, total vitamin C and vitamin E were elevated in the supplemented group consistent with compliance. Gastric juice ascorbic acid and total vitamin C levels were raised significantly in the supplemented group (P=0.01) but supplementation had no effect on the mucosal level of this vitamin. However, gastric juice ascorbic acid and total vitamin C were within normal ranges in the unsupplemented group. Mucosal malondialdehyde, chemiluminescence and DNA damage levels in the comet assay were unaffected by vitamin supplementation. In conclusion, supplementation does not affect DNA damage in this group of patients. This is probably because long-term inhibition of the gastric proton pump alone does not affect gastric juice ascorbate and therefore does not increase the theoretical risk of gastric cancer because of antioxidant depletion.

Levels of malondialdehyde-deoxyguanosine in the gastric mucosa: relationship with lipid peroxidation, ascorbic acid, and Helicobacter pylori.

Helicobacter pylori infection is associated with elevated gastric mucosal concentrations of the lipid peroxidation product malondialdehyde and reduced gastric juice vitamin C concentrations. Malondialdehyde can react with DNA bases to form the mutagenic adduct malondialdehyde-deoxyguanosine (M(1)-dG). We aimed to determine gastric mucosal levels of M(1)-dG in relation to H. pylori infection and malondialdehyde and vitamin C concentrations. Patients (n = 124) attending for endoscopy were studied. Levels of antral mucosal M(1)-dG were determined using a sensitive immunoslot-blot technique; antral mucosal malondialdehyde was determined by thiobarbituric acid extraction, and gastric juice and antral mucosal ascorbic acid and total vitamin C were determined by high-performance liquid chromatography. Sixty-four H. pylori-positive patients received eradication therapy, and endoscopy was repeated at 6 and 12 months. Levels of M(1)-dG did not differ between subjects with H. pylori gastritis (n = 85) and those with normal mucosa without H. pylori infection (n = 39; 56.6 versus 60.1 adducts/10(8) bases) and were unaffected by age or smoking habits. Malondialdehyde levels were higher (123.7 versus 82.5 pmol/g; P < 0.001), gastric juice ascorbic acid was lower (5.7 versus 15.0 micromol/ml; P < 0.001), and antral mucosal ascorbic acid was unchanged (48.0 versus 42.7 micromol/g) in H. pylori gastritis compared with normal mucosa. Multiple regression analysis revealed that M(1)-dG increased significantly with increasing levels of malondialdehyde, antral ascorbic acid, and total antral vitamin C. M(1)-dG levels were unchanged 6 months (63.3 versus 87.0 adducts/10(8) bases; P = 0.24; n = 38) and 12 months (66.7 versus 77.5 adducts/10(8) bases; P = 0.8; n = 13) after successful eradication of H. pylori. M(1)-dG thus is detectable in gastric mucosa, but is not affected directly by H. pylori.

Influence of smoking and alcohol on gastric chemokine mRNA expression in patients with Helicobacter pylori infection.

AIM: Chemokines that play a primary role in active inflammation are increased in gastric mucosa infected with Helicobacter pylori. Cigarette smoking increases the risk of peptic ulcer disease and gastric cancer, whereas alcohol might exert an antibacterial role. The aim of this study was to examine the association between smoking or alcohol consumption and mucosal chemokine mRNA expression in H pylori associated gastritis. METHODS: Gastric biopsy specimens were obtained from 46 patients with dyspepsia who were infected with H pylori, and total RNA was extracted. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed to quantify the mRNA expression of three C-X-C chemokines (interleukin 8 (IL-8), growth related oncogene alpha (GRO alpha), epithelial neutrophil activating protein 78 (ENA-78)) and two C-C chemokines (regulated on activation normal T cell expressed and secreted (RANTES) and monocyte chemotactic protein 1 (MCP-1)). RESULTS: GRO alpha and ENA-78 mRNA expression was significantly increased (p < 0.05) in 22 smokers compared with 24 non-smokers; however, no difference was seen in the expression of IL-8, RANTES, and MCP-1 mRNA. No differences were observed in chemokine mRNA expression in relation to alcohol consumption. CONCLUSIONS: The increased C-X-C chemokine mRNA expression seen in smokers might play a role in inducing enhanced inflammatory activity in gastritis and the consequent severe diseases associated with H pylori infection.