Motor control and cognition deficits associated with protein carbamoylation in food (cassava) cyanogenic poisoning: Neurodegeneration and genomic perspectives.

A case-control design determined whether konzo, an upper motoneuron disease linked to food (cassava) toxicity was associated with protein carbamoylation and genetic variations. Exon sequences of thiosulfate sulfurtransferase (TST) or mercaptopyruvate sulfurtransferase (MPST), plasma cyanide detoxification rates, and 2D-LC-MS/MS albumin carbamoylation were assessed in 40 children [21 konzo-affected and 19 putatively healthy controls, mean (SD) age: 9.2 (3.0) years] subjected to cognition and motor testing using the Kaufman Assessment Battery and the Bruininks/Oseretsky Test, respectively. Konzo was significantly associated with higher levels of carbamoylated peptides 206-219 (LDELRDEGKASSAK, pep1) after adjusting for age, gender, albumin concentrations and BUN [regression coefficient: 0.03 (95%CI:0.02-0.05), p = 0.01]. Levels of pep1 negatively correlated with performance scores at all modalities of motor proficiency (r = 0.38 to 0.61; all p < 0.01) or sequential processing (memory)(r = - 0.59, p = 0.00) and overall cognitive performance (r = - 0.48, p = 0.00) but positively with time needed for cyanide detoxification in plasma (r = 0.33, p = 0.04). Rare potentially damaging TST p.Arg206Cys (rs61742280) and MPST p.His317Tyr (rs1038542246) heterozygous variants were identified but with no impact on subject phenotypes. Protein carbamoylation appears to be a reliable marker for cassava related neurodegeneration.

Improving student nurses' aged care understandings through a supported placement.

AIM: The study aimed to identify the potential for aged care placements to deliver benefits for second year nursing students when conducted within a supportive framework with debriefing and critical reflection opportunities. BACKGROUND: Given the ageing population and complex care needs of aged care facility residents, exacerbated by the high prevalence of dementia, the healthcare workforce's ability to meet older people's care needs is paramount. Yet research shows that nursing students are disengaged from aged care. METHODS: Using a quasi-experimental mixed method design within an action research framework, 40 students were allocated a 3-week supported placement in 2011-2012 at one of the two intervention residential aged care facilities in Tasmania, Australia. Staff formed mentor action research groups in each facility and participated in a pre-placement capacity-building programme. Thirty-nine students were placed across 14 control facilities. Data were collected via meetings with students and pre-post placement questionnaires on placement experiences, attitudes and dementia knowledge. RESULTS: The intervention facility placement programme led to mentors and students being well prepared for the placement and to students experiencing enhanced teaching and learning derived from high levels of mentor support and increased autonomy. Students' knowledge, understanding and attitudes around aged care and dementia improved. DISCUSSION: Mentors working together within an action research framework can provide a supported residential aged care placement for nursing students that improves students' aged care attitudes and understandings. CONCLUSION AND IMPLICATIONS FOR NURSING AND HEALTH POLICY: Provision of quality, supported aged care student placements is vital to prepare a new generation of nurses who will have to deal with the complex chronic healthcare needs associated with an ageing population.

Screen-detected colorectal cancers are associated with an improved outcome compared with stage-matched interval cancers.

BACKGROUND: Colorectal cancers (CRCs) detected through the NHS Bowel Cancer Screening Programme (BCSP) have been shown to have a more favourable outcome compared to non-screen-detected cancers. The aim was to identify whether this was solely due to the earlier stage shift of these cancers, or whether other factors were involved. METHODS: A combination of a regional CRC registry (Northern Colorectal Cancer Audit Group) and the BCSP database were used to identify screen-detected and interval cancers (diagnosed after a negative faecal occult blood test, before the next screening round), diagnosed between April 2007 and March 2010, within the North East of England. For each Dukes' stage, patient demographics, tumour characteristics, and survival rates were compared between these two groups. RESULTS: Overall, 322 screen-detected cancers were compared against 192 interval cancers. Screen-detected Dukes' C and D CRCs had a superior survival rate compared with interval cancers (P=0.014 and P=0.04, respectively). Cox proportional hazards regression showed that Dukes' stage, tumour location, and diagnostic group (HR 0.45, 95% CI 0.29-0.69, P<0.001 for screen-detected CRCs) were all found to have a significant impact on the survival of patients. CONCLUSIONS: The improved survival of screen-detected over interval cancers for stages C and D suggest that there may be a biological difference in the cancers in each group. Although lead-time bias may have a role, this may be related to a tumour's propensity to bleed and therefore may reflect detection through current screening tests.

Comparison of screen-detected and interval colorectal cancers in the Bowel Cancer Screening Programme.

BACKGROUND: The NHS Bowel Cancer Screening Programme (BCSP) offers biennial faecal occult blood testing (FOBt) followed by colonoscopy after positive results. Colorectal cancers (CRCs) registered with the Northern Colorectal Cancer Audit Group database were cross-referenced with the BCSP database to analyse their screening history. METHODS: The CRCs in the screening population between April 2007 and March 2010 were identified and classified into four groups: control (diagnosed before first screening invite), screen-detected, interval (diagnosed between screening rounds after a negative FOBt), and non-uptake (declined screening). Patient demographics, tumour characteristics and survival were compared between groups. RESULTS: In all, 511 out of 1336 (38.2%) CRCs were controls; 825 (61.8%) were in individuals invited for screening of which 322 (39.0%) were screen detected, 311 (37.7%) were in the non-uptake group, and 192 (23.3%) were interval cancers. Compared with the control and interval cancer group, the screen-detected group had a higher proportion of men (P=0.002, P=0.003 respectively), left colon tumours (P=0.007, P=0.003), and superior survival (both P<0.001). There was no difference in demographics, tumour location/stage, or survival between control and interval groups. CONCLUSION: The FOBt is better at detecting cancers in the left colon and in men. The significant numbers of interval cancers weren't found to have an improved outcome compared with the non-screened population.

Achieving high quality colonoscopy: using graphical representation to measure performance and reset standards.

AIM: Completeness and thoroughness of colonoscopy are measured by the caecal intubation rate (CIR) and the adenoma detection rate (ADR). National standards are ≥ 90% and ≥ 10% respectively. Variability in CIR and ADR have been demonstrated but comparison between individuals and units is difficult. We aimed to assess the performance of colonoscopy in endoscopy units in the northeast of England. METHOD: Data on colonoscopy performance and sedation use were collected over 3 months from 12 units. Colonoscopies performed by screening colonoscopists were included for the CIR only. Funnel plots with upper and lower 95% confidence limits for CIR and ADR were created. RESULTS: CIR was 92.5% (n = 5720) and ADR 15.9% (n = 4748). All units and 128 (99.2%) colonoscopists were above the lower limit for CIR. All units achieved the ADR standard with 10 above the upper limit. Ninety-nine (76.7%) colonoscopists were above 10%, 16 (12.4%) above the upper limit and 7 (5.4%) below the lower limit. Median medication doses were 2.2 mg midazolam, 29.4 mg pethidine and 83.3 µg fentanyl. In all, 15.1% of colonoscopies were unsedated. Complications were bleeding (0.10%) and perforation (0.02%). There was one death possibly related to bowel preparation. CONCLUSION: Results indicate that colonoscopies are performed safely and to a high standard. Funnel plots can highlight variability and areas for improvement. Analyses of ADR presented graphically around the global mean suggest that the national standard should be reset at 15%.

Multicentre randomized-controlled clinical trial of Ipocol, a new enteric-coated form of mesalazine, in comparison with Asacol in the treatment of ulcerative colitis.

BACKGROUND: 5-Aminosalicylates remain important in the treatment of ulcerative colitis, but it is uncertain if the various preparations currently available are equivalent given the different delivery systems that exist. Generic prescription of mesalazine (mesalamine) is therefore inappropriate. Ipocol has recently become available as an alternative to Asacol-MR. AIM: To compare the two agents in a controlled trial using a non-inferiority design. METHODS: Eighty-eight ulcerative colitis patients with a mild to moderate clinical relapse were randomized to one of the two drugs at a daily dose of 2.4 g for 8 weeks. Safety was the key concern; the primary measured end-point was efficacy as judged from a colitis activity index. RESULTS: There were no unexpected adverse events of clinical consequence. The colitis score improved similarly in both patient groups (by 2.3 with Ipocol and by 1.5 with Asacol: not significant), and a similar proportion was in clinical remission at the end of the study (26.1% for Ipocol and 28.6% for Asacol: not significant). Systemic steroids were needed in 11.9% of the Asacol-treated patients compared with 6.5% with Ipocol (not significant). CONCLUSION: It appears appropriate to conclude that, while not identical to Asacol-MR, Ipocol offers a safe and similarly effective alternative.

The Evolving Role of the Acute Assessment Unit - from inpatient to outpatient care.

Acute Assessment Units (AAUs) have been developed to meet the demand for emergency care. Traditionally, AAUs have been an admission route to secondary care but the role is now evolving to assessment. AAUs are complex and have many interactions both in hospitals and the community. The effective functioning of an AAU requires excellent clinical leadership, appropriate facilities, timely access to diagnostics and input from the multi-disciplinary team. Increasingly, AAUs will have to develop services which are not dependent on using hospital beds. A variety of emergency medical presentations can, with the appropriate resources, be delivered in an out-patient setting.

Empirical use of antisecretory drug therapy delays diagnosis of upper gastrointestinal adenocarcinoma but does not effect outcome.

BACKGROUND: Upper gastrointestinal cancer carries a poor prognosis. Although the incidence of gastric adenocarcinoma is falling, oesophageal adenocarcinoma is increasing. This has been attributed to an increasing prevalence of gastro-oesophageal reflux disease, commonly treated empirically in primary care with antisecretory drugs. Treatment has been associated with delayed diagnosis but it is unclear if this influences prognosis. AIMS: To ascertain the effect of antisecretory drugs on time to diagnosis, symptoms, tumour stage and outcome. METHODS: A retrospective cohort study of primary care records for 747 patients diagnosed with upper gastrointestinal adenocarcinoma at South Tees NHS Trust between 1991 and 2001. RESULTS: Mean time from the onset of symptoms to diagnosis was 30 weeks. Mean and median times at the primary care stage were longer than at the hospital stage for both oesophageal and gastric cancer (P < 0.0001). Patients with benign symptoms prescribed antisecretory drugs were referred later than those not on antisecretory drugs (P < 0.0001), as were patients with alarm symptoms (P = 0.0008). Prior use of antisecretory drugs delayed diagnosis by 17.6 weeks (mean) but had no effect on tumour stage at diagnosis or survival. CONCLUSION: Prior antisecretory drug therapy was associated with delayed diagnosis of upper gastrointestinal adenocarcinoma irrespective of presenting symptoms. Concerns that delays might adversely affect tumour stage or long-term survival were not substantiated.

Oesophageal stricturing secondary to adult Stevens-Johnson syndrome: similarities in presentation and management to corrosive injury.

Clinical decisions often have to be made in the absence of evidence. In some cases, it is appropriate to use evidence from similar but more common conditions for which studies have resulted in evidence-based practice. This report describes a case of oesophageal stricture following Stevens-Johnson syndrome illustrating this concept, although it is likely that there are many other conditions in which the same principle will stand the clinician in good stead. Dilatation led to long-standing relief of dysphagia in our case.

Oral antioxidant supplementation for fatigue associated with primary biliary cirrhosis: results of a multicentre, randomized, placebo-controlled, cross-over trial.

BACKGROUND: We have previously reported, in an uncontrolled trial, an improvement in fatigue scores in patients with primary biliary cirrhosis given oral antioxidant supplementation. We now present data from a controlled trial. PATIENTS AND METHODS: Sixty-one patients with primary biliary cirrhosis-associated fatigue were randomized into a double-blind, placebo-controlled, cross-over trial. Participants received 12 weeks each of placebo and antioxidant supplementation (vitamins A, C and E, selenium, methionine and ubiquinone) in random order, separated by a 4-week washout period. The primary trial outcome (fatigue) was assessed using the Fisk scale. Other symptoms of primary biliary cirrhosis were measured using Likert and visual analogue scales. RESULTS: Forty-four patients completed both arms of the trial. No significant changes in fatigue were recorded in the active phase of treatment (median improvement in Fisk score, 1; P = 0.61). Small improvements in Fisk scores were recorded during placebo therapy (median improvement, 4; P = 0.03). Neither medication was associated with improvement in any other symptoms related to primary biliary cirrhosis. Adverse effects were more common during active therapy and were mild and self-limiting. One patient died from unrelated causes during active treatment. CONCLUSIONS: Although oral antioxidant supplementation appears to be safe, we could not find any evidence for a beneficial effect on fatigue or other liver-related symptoms.

Creutzfeldt-Jakob disease: implications for gastroenterology.

The current clinical views regarding variant Creutzfeldt-Jakob disease, and in particular transmission via endoscopy, of those representing both gastroenterology and the Spongiform Encephalopathy Advisory Committee are presented in an attempt to guide clinicians as to "best practice" given the current state of our knowledge.

Variant Creutzfeldt-Jakob disease (vCJD) and gastrointestinal endoscopy.

Variant Creutzfeldt-Jakob disease (vCJD) is a transmissible form of spongiform encephalopathy believed to be contracted from the consumption of bovine spongiform encephalopathy (BSE) infected beef products. To date over 100 individuals have developed this incurable disease. There have been no documented cases of iatrogenic infection, but there is a theoretical risk that surgical procedures could transmit the disease. This review describes the background of the disease and assesses the possible risks of transmission through endoscopic procedures. The risk of transmission by endoscopy is small and probably negligible if suitable procedures are followed. The greatest potential danger arises from healthy individuals who are incubating the disease. Pathological prions (PrP(sc)) may be found in lymphatic tissue of these individuals (particularly tonsils), but smaller amounts have been identified in the appendix and Peyer's patches. These prions are resistant to all forms of conventional sterilization. There is a theoretical risk that biopsy forceps and the operating channel of endoscopes could become contaminated. This review gives recommendations as to how these small risks can be minimized. They include the employment of single-use forceps for biopsies taken from the terminal ileum, greater attention to the maintenance of endoscopic equipment and accessories, more rigorous manual cleaning of endoscopic equipment and the use of well designed, disposable cleaning brushes for the operating channel of the endoscope.

Necrotizing fasciitis in Crohn's disease.

We report a case of a 34-year-old woman, presenting initially with anaemia followed by sacro-iliac pain, and subsequently found to have necrotizing fasciitis complicating Crohn's disease where the organisms were introduced via a fistulous tract. It is perhaps surprising that this is not a more common complication of fistulating Crohn's disease, but we believe this is the first case report of this particular complication.

Detection of upper gastrointestinal cancer in patients taking antisecretory therapy prior to gastroscopy.

BACKGROUND: The incidence of early gastric cancer has not increased despite better access to endoscopic facilities for general practitioners. Many patients receive a course of symptomatic treatment while waiting for gastroscopy. AIMS: To ascertain the effect of antisecretory therapy on the diagnostic process and findings for patients with upper gastrointestinal cancer. METHODS: A consecutive case study survey of the primary care records of 133 patients who had died of upper gastrointestinal cancer during 1995-97 in the South Tees health district in the north-east of England (population 300 000). RESULTS: From the 133 patients identified, 116 had died from adenocarcinoma of the oesophagus (31) or stomach (85). Failure to reach the diagnosis of cancer at the index gastroscopy was associated with prior acid suppression therapy. Only one of 54 patients on no treatment or antacids alone was erroneously diagnosed as suffering from benign disease, whereas 22 of 62 patients treated with acid suppression were diagnosed as suffering from benign disease but at varying times later turned out to have adenocarcinoma. Twenty of 45 patients taking a proton pump inhibitor had a delayed diagnosis compared with two of 17 taking an H(2) receptor antagonist. The commonest lesion seen at index gastroscopy in those in whom the diagnosis was initially missed was gastric ulcer. Healing occurred in six patients taking a proton pump inhibitor, despite their later diagnosis of malignancy. CONCLUSIONS: The treatment of dyspeptic symptoms with acid suppression prior to gastroscopy masks and delays the detection of gastric and oesophageal adenocarcinoma on endoscopy in one third of patients.

Case report: oral antioxidant therapy for the treatment of primary biliary cirrhosis: a pilot study.

BACKGROUND: The symptoms of the chronic cholestatic liver disease primary biliary cirrhosis (PBC), in particular fatigue and chronic pruritus, adversely affect quality of life and respond only poorly to treatment. Recent studies have suggested that oxidative stress may play a role in tissue damage in cholestatic liver disease and may contribute to symptoms, such as fatigue. We have, therefore, examined, in an open-label pilot study, the therapeutic effects of antioxidant medication on the biochemistry and symptomatology of PBC. METHODS: Patients were randomized to 3 months treatment with a compound antioxidant vitamin preparation (Bio-Antox), four tablets daily (n = 11, group 1), or the combination of Bio-Quinone Q10 (100 mg) with Bio-Antox (n = 13, group 2). Biochemical and symptomatic responses were assessed at 3 months. RESULTS: Significant improvement in both pruritus and fatigue was seen in the patients in group 2. Mean itch visual analogue score improved from 2.4 +/- 3.0 to 0.4 +/- 0.7 post therapy (P < 0.05) while mean night itch severity score improved from 2.6 +/- 1.9 to 1.3 +/- 0.7 (P < 0.05). Nine of 13 of these patients reported less fatigue, while 10/13 showed an improvement in at least one domain of their Fisk Fatigue Severity Score. No significant improvement in itch and only limited improvement in fatigue were seen in the patients in group 1. No change in biochemical parameters was seen in either group. CONCLUSIONS: Antioxidant therapy, as a combination of Bio-Antox and Bio-Quinone Q10, may improve the pruritus and fatigue of PBC. This combination of therapy should be investigated further in a double-blind, placebo-controlled trial.