The routine use of a flumazenil infusion following percutaneous endoscopic gastrostomy placement to reduce early post-procedure mortality.

OBJECTIVES: Percutaneous endoscopic gastrostomy (PEG) insertion offers secure enteral nutrition, but there is a significant mortality associated with the procedure. We reviewed our sedation practice and the effect of yearly protocol changes to establish if the routine reversal of midazolam with a flumazenil infusion improved mortality. METHODS: Since 2003 yearly protocol changes have been introduced, including pre-assessment and sedation reversal. We retrospectively audited one-week and one-month mortality and aspiration rates. RESULTS: The average one-week mortality rate was 9.2%. The pooled death rates within the first week for patients prior to routine sedation reversal (n=522) was 10.7% and for patients who received routine reversal (n=144) was 5.4% (p=0.087). Within the first month, death rates were 26.3% prior to reversal and 21.4% in the sedation reversal group (p=0.30). CONCLUSIONS: The routine use of flumazenil infusion in appropriate patients is safe. Flumazenil infusion may have a role to play in selected patients at highest risk of aspiration. A prospective, randomised study is warranted.

Social networking sites: a novel portal for communication.

BACKGROUND: The internet has transformed many spheres of society. Most notably the advent of social networking websites, such as MySpace, Bebo and Facebook, have attracted many millions of users worldwide. There are over 350 such sites in operation across the internet. There is a paucity of data in the adult literature examining the medical usage of this interesting facet of modern life. AIMS: To ascertain whether Facebook has user groups that are connected with common medical conditions, and to classify the user groups that were identified as well as enumerating the number of individual users contained therein. METHODS: We conducted a search of the entire Facebook website between December 2007 and January 2009. We used medical and lay nomenclature for the most prevalent non-communicable diseases as identified from the World Health Organisation Burden of Disease publication to identify whether they were represented among individual Facebook users and user groups. RESULTS: We identified 290,962 individual users who were part of 757 groups. Patient groups accounted for 47.4%, patient/carer support groups 28.1%, fund raising groups 18.6%, and others 5.8%. Notably, there were other groups containing representations from the scientific research community in addition to educational resources. The groups with the most individual members pertained to malignant neoplasms and cardiovascular disease (141,458 users) consistent with their worldwide prevalence. CONCLUSIONS: Facebook is providing a readily accessible portal for patients, carers and healthcare professionals to share their experiences of investigation, diagnosis and management of disease. Furthermore, this technology is being used for research, education and fundraising. Further research is warranted to explore the further potential of this new technology.

Assessment by a multidisciplinary clinical nutrition team before percutaneous endoscopic gastrostomy placement reduces early postprocedure mortality.

BACKGROUND: The purpose of this study was to determine whether preassessment by a multidisciplinary nutrition team before percutaneous endoscopic gastrostomy (PEG) placement can reduce postprocedure mortality. This was a prospective single-center audit. METHODS: Patients who had been referred to the Gastroenterology Department for consideration of PEG placement between 1995 and 2004 were included. In the index year, 2003-2004, where a formal nutrition team assessment was commenced, 79 patients were enrolled into our study group on a consecutive basis. These patients were subdivided into 3 groups; group A, PEG placed (51 patients); group B, PEG not placed due to severe comorbidity (19 patients); and group C, PEG not placed as deemed unnecessary (9 patients). Comparison was made with previous years where no formal preassessment had occurred. At Staffordshire General Hospital, a comparison of mortality post-PEG placement was made between the index group and previous years. Secondary measures included complication rates and frequency of biochemical monitoring. RESULTS: One week post-PEG mortality fell from 10%-20% in previous years to 0% in the index year (p < .02). This improved survival extended to 3 months postprocedure (p < .016). Three patients (6%) had biochemical evidence of refeeding syndrome postplacement. Biochemical monitoring was inadequate, with only 27/51 (53%) patients being completely monitored. No complications pertaining to the endoscopy were reported. CONCLUSIONS: This study demonstrates that early post-PEG mortality can be reduced by preassessment of patients by a multidisciplinary nutrition team and is evidence supporting the recommendations of the National Confidential Enquiry into Patient Outcome and Death report.

Basiliximab for the treatment of steroid-resistant ulcerative colitis: further experience in moderate and severe disease.

BACKGROUND: Preliminary data have suggested that interleukin-2 receptor blockade with basiliximab may increase steroid sensitivity. We have previously reported a small case series demonstrating the potential of basiliximab as a novel agent for the treatment of steroid-resistant ulcerative colitis. AIM: To report further experience of the efficacy and safety of treatment with the interleukin-2 receptor blocking monoclonal antibody basiliximab, in addition to steroids, for the treatment of severe and moderate steroid-resistant ulcerative colitis. METHODS: Twenty patients were enrolled - 13 patients with moderate steroid-resistant ulcerative colitis (Ulcerative Colitis Symptom Score: >or=6) and seven patients with severe steroid-resistant ulcerative colitis. All were given a single dose of 40 mg basiliximab plus standard steroid therapy in an open-label, uncontrolled trial. Primary end point was clinical remission within 8 weeks (Ulcerative Colitis Symptom Score:

Basiliximab (anti-CD25) in combination with steroids may be an effective new treatment for steroid-resistant ulcerative colitis.

BACKGROUND: Steroid resistance represents a major clinical problem in the treatment of ulcerative colitis. In vitro, interleukin-2 renders lymphocytes steroid resistant. AIM: To explore the therapeutic potential of interleukin-2 receptor blockade in steroid-resistant ulcerative colitis with both in vitro measures and a pilot in vivo study. METHODS: Ten patients with steroid-resistant ulcerative colitis received a single bolus of 40 mg of intravenous basiliximab plus steroid treatment in an open-label, uncontrolled, 24-week study. The outcome was assessed using the Ulcerative Colitis Symptom Score, rectal biopsy and Inflammatory Bowel Disease Questionnaire. Lymphocyte steroid sensitivity was measured in vitro in 39 subjects in the presence or absence of basiliximab. RESULTS: Nine of the 10 patients achieved clinical remission within 8 weeks. At 24 weeks, seven patients were in clinical remission. Marked improvement in the Ulcerative Colitis Symptom Score was seen by 1 week (P = 0.004) and on rectal biopsy and Inflammatory Bowel Disease Questionnaire by 2 weeks (both P < 0.05). Improvements persisted to 24 weeks (Ulcerative Colitis Symptom Score, Inflammatory Bowel Disease Questionnaire, both P < 0.005). Eight of the nine responders relapsed (median, 9 weeks), but remission was re-achieved with further corticosteroids and the addition of azathioprine. At 24 weeks, seven patients were in full clinical remission, five off all steroid therapy. In vitro measurement of lymphocyte steroid sensitivity demonstrated steroid resistance in 22% of subjects. All were rendered steroid sensitive in the presence of basiliximab. CONCLUSIONS: Basiliximab appears to be effective at inducing remission in steroid-resistant ulcerative colitis. In vitro, basiliximab also produced a dramatic increase in lymphocyte steroid sensitivity in healthy subjects. Confirmation in randomized controlled studies is required.

Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: a randomised controlled trial.

BACKGROUND: Tumour necrosis factor production is increased in the mucosa of patients with active ulcerative colitis. The benefits of infliximab in Crohn's disease are established. We investigated its efficacy in ulcerative colitis. METHODS: We conducted a randomised placebo controlled trial of infliximab (5 mg/kg) in the treatment of glucocorticoid resistant ulcerative colitis. Infusions were given at weeks 0 and 2. Disease activity and quality of life were recorded over eight weeks of follow up. Remission was defined as an ulcerative colitis symptom score (UCSS) of < or =2 and/or Baron score of 0 at week 6. Patients not in remission were offered open label infliximab 10 mg/kg and reviewed two weeks later. RESULTS: After two weeks, there was no statistically significant difference between the infliximab and placebo groups in the proportion of patients with a Baron score of 0 (13% (3/23) v 5% (1/19) (95% confidence interval (CI) -9% to 24%); p=0.74). After six weeks, remission (UCSS < or =2) rates were 39% (9/23) versus 30% (6/20) (95% CI -19 to 34%; p=0.76). The median improvement in UCSS was 3 for the infliximab group and 2.5 for the placebo group (p=0.82, Mann-Whitney U test). A Baron score of 0 was likely in either group (26% (6/23) v 30% (6/20) (95% CI -30% to 23%); p=0.96). Improvement in the IBDQ and EuroQol was not significantly different between the groups (p=0.22 and 0.3, respectively, Mann-Whitney U test). Twenty eligible patients were given open labelled infusions. Remission was achieved in 3/11 (27%) patients initially treated with infliximab and in 1/9 (11%) patients treated with placebo. CONCLUSION: These data do not support the use of infliximab in the management of moderately active glucocorticoid resistant ulcerative colitis.

Refeeding syndrome: effective and safe treatment with Phosphates Polyfusor.

BACKGROUND: Severe hypophosphataemia associated with refeeding syndrome requires treatment with intravenous phosphate to prevent potentially life-threatening complications. However, evidence for replacement regimens is limited and current regimens are complex and replace phosphate inadequately. AIM: To assess the effectiveness and safety of 50 mmol intravenous phosphate infusion, given as a 'Phosphates Polyfusor', for the treatment of severe hypophosphataemia in refeeding syndrome. METHODS: Patients with refeeding syndrome and normal renal function received a Phosphates Polyfusor infusion for the treatment of severe hypophosphataemia (< 0.50 mmol/L). The outcome measures were serial serum phosphate, creatinine and calcium concentrations for 4 days following phosphate infusion and adverse events. RESULTS: Over 2 years, 30 patients were treated. Following treatment, 37% of cases had a normal serum phosphate concentration and 73% had a serum phosphate concentration of > 0.5 mmol/L within 24 h. Ten patients required more than one Phosphates Polyfusor infusion. Within 72 h, 93% of cases had achieved a serum phosphate concentration of > or = 0.50 mmol/L. No patient developed renal failure. Three episodes of transient mild hyperphosphataemia were recorded. Four patients developed mild hypocalcaemia. CONCLUSIONS: This is the largest published series of the use of intravenous phosphate for the treatment of severe hypophosphataemia (< 0.50 mmol/L), and is the most effective regimen described. All patients had refeeding syndrome and were managed on general wards.

Is your patient taking the medicine? A simple assay to measure compliance with 5-aminosalicylic acid-containing compounds.

BACKGROUND: Poor compliance with 5-aminosalicylic acid therapy has been reported amongst patients with inflammatory bowel disease. Currently, there is no easy method to monitor 5-aminosalicylic acid; however, the chemical similarity between 5-aminosalicylic acid and salicylate might provide a solution. AIM: To determine the feasibility of using salicylate levels to monitor compliance with 5-aminosalicylic acid medication. METHODS: Thirty-six patients with inflammatory bowel disease, taking maintenance 5-aminosalicylic acid, provided either a paired serum and urine sample or an intestinal biopsy. Samples were split into two: half were sent to the hospital biochemistry department for salicylate measurement, and half were analysed for 5-aminosalicylic acid and its metabolite, N-acetyl-5-aminosalicylic acid, using high performance liquid chromatography. Correlation between the results was calculated. RESULTS: Serum and urine were available for 25 patients. Serum salicylate was undetectable, but urinary salicylate ranged from 31 to 3254 microg/mL. The correlations between urinary salicylate and 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid were 0.96 (95% confidence interval, 0.91-0.98) and 0.9 (95% confidence interval, 0.77-0.96), respectively. Sixteen biopsies were available from 13 patients. The 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid concentrations were 0.2-657 ng/mg and 1.6-1598 ng/mg, respectively; there was no correlation with bowel salicylate. CONCLUSIONS: The close correlation between 5-aminosalicylic acid and salicylate levels offers a simple method to assess compliance with 5-aminosalicylic acid therapy.

Ingested foreign bodies associated with orthodontic treatment: report of three cases and review of ingestion/aspiration incident management.

Foreign body ingestion/aspiration episodes are potential complications in all branches of dentistry. The handling of small orthodontic components requires particular care, especially where the patient is supine or semi-recumbent. Three cases of foreign body ingestion are presented, involving patients undergoing orthodontic treatment. Once the foreign bodies had been located, all instances were treated using a combination of serial radiography and 'watchful waiting'. All patients remained asymptomatic during this period, although none of the foreign bodies were retrieved. No active intervention was deemed necessary, and the patients were able to resume their orthodontic treatment. The potential complications of ingestion/aspiration episodes are discussed and a management regime suggested.

Audit of cyclosporin use in inflammatory bowel disease: limited benefits, numerous side-effects.

BACKGROUND: The failure of standard treatments for inflammatory bowel disease (IBD) has led to the use of immuno-modulatory therapy. Most reports of the use of cyclosporin are from single specialist centres. AIM: To survey the use of cyclosporin in IBD in Bristol's three teaching hospitals. PATIENTS AND METHODS: Over a 4-year period, all patients receiving cyclosporin for IBD were identified and the following data recorded: diagnosis, duration of disease, initial treatment, date initiated, dose of cyclosporin, side-effects, initial clinical response, and current patient status. RESULTS: Thirty-three patients were identified, of whom 26 had ulcerative colitis (UC), six had Crohn's disease and one had indeterminant colitis. The most frequent indication was as 'rescue' therapy in acute severe UC. The overall initial response rate was 63%, but this was only maintained in 30% long-term patients, with over half of them reporting side-effects. Four patients had life threatening side-effects. CONCLUSION: Although the initial response rates are encouraging, the long-term results are poor and at the expense of a high incidence of side-effects. We feel that the use of cyclosporin in IBD should be reconsidered until more information from randomized controlled studies becomes available.

Effect of cholecystectomy on bowel function: a prospective, controlled study.

BACKGROUND: Published estimates of the prevalence of postcholecystectomy diarrhoea derive from retrospective or uncontrolled data. They ignore functional bowel syndromes and possible changes in diet and drug use. AIMS: To determine prospectively whether and how often cholecystectomy leads to changes in bowel function and bowel symptoms, especially to liquid stools, over and above any non-specific effect of laparoscopic surgery. PATIENTS: 106 adults undergoing laparoscopic cholecystectomy (85 women, 21 men). CONTROLS: 37 women undergoing laparoscopic sterilisation. METHODS: Before and 2-6 months after surgery patients were administered questionnaires about bowel frequency, bowel symptoms, diet, and drugs, and kept records of five consecutive defecations with assessment of stool form or appearance on a seven point scale. RESULTS: In cholecystectomised women, stated bowel frequency increased, on average by one movement a week, and fewer subjects felt that they became constipated. However, records showed no consistent change in bowel frequency, stool form, or defecatory symptoms. Six women reported diarrhoea after the operation but in only one was it clearly new and in her it was mild. Change in dietary fibre intake did not associate with change in bowel function but stopping constipating drugs did in a minority. In women being sterilised there was no consistent change in bowel function. In men having cholecystectomy no consistent changes were observed. CONCLUSIONS: In women, cholecystectomy leads to the perception of less constipation and slightly more frequent defecations but short term recordings show no consistent change in bowel function. Clinical diarrhoea develops rarely and is not severe.

Wide variation in lymphocyte steroid sensitivity among healthy human volunteers.

Steroids are frequently used to treat inflammatory conditions in which lymphocytes play a role. We have recently shown that in severe ulcerative colitis, treatment outcome correlates better with in vitro estimates of lymphocyte steroid sensitivity (LSS) than with disease severity. This lead us to examine the range and variability of LSS in the healthy population. Dexamethasone inhibition of lymphocyte proliferation was measured on 54 occasions in 18 volunteers (mean age, 46 yr; range, 23-60 yr) over an 8-month period. Inter- and intra-assay variation in LSS was low when expressed as maximum inhibition achieved, Imax (2.9% and 3.4%, respectively), allowing us to demonstrate a very wide variation in Imax between healthy individuals (-6.7% to 99.7%). In contrast, within-individual variation of Imax was significantly less than between-individual variation (F test, P < 0.0001), consistent with stability of this parameter over time. No correlation was seen between LSS and glucocorticoid receptor density or affinity, suggesting a postreceptor mechanism. Serum cortisol at the time of sampling and skin sensitivity to glucocorticoids also failed to correlate with LSS. This study suggests Imax is a sufficiently stable parameter to categorize healthy individuals according to LSS. The wide range of LSS demonstrated is striking and suggests that up to 30% of the healthy population would fail to respond to steroid therapy for severe inflammatory conditions.

Predicting therapeutic outcome in severe ulcerative colitis by measuring in vitro steroid sensitivity of proliferating peripheral blood lymphocytes.

BACKGROUND: Up to 29% of patients with severe ulcerative colitis (UC) fail to respond to steroid treatment and require surgery. Previous studies have failed to show a clear correlation between failure of steroid treatment in severe UC and measures of disease severity. The reasons for treatment failure therefore remain unknown. AIM: To investigate the hypothesis that patients with severe UC who fail to respond to steroid treatment have steroid resistant T lymphocytes. METHODS: Eighteen patients with severe UC were studied. After seven days' treatment with high dose intravenous steroids they were classified as complete responders (CR), incomplete responders (IR), or treatment failures (TF). Within 48 hours of admission blood was taken and the antiproliferative effect of dexamethasone on phytohaemagglutinin stimulated peripheral blood T lymphocytes was measured. Maximum dexamethasone induced inhibition of proliferation (I(max)) was measured. RESULTS: In vitro T lymphocyte steroid sensitivity of TF and IR patients was significantly less than that of CR patients. Both TF and 3/5 IR patients had an I(max) of less than 60%; all CR patients had an I(max) of greater than 60%. No significant correlation was seen between response to treatment and disease severity on admission. When in vitro T lymphocyte steroid sensitivity was remeasured three months later, there was no difference between the groups. CONCLUSIONS: Results suggest that T lymphocyte steroid resistance is an important factor in determining response to steroid treatment in patients with severe UC and may be more predictive of outcome than disease severity.

In vitro measurement of lymphocyte steroid sensitivity: lack of agreement between whole blood culture and separated lymphocyte culture.

The use of a whole blood culture to measure steroid sensitivity has previously been compared to the use of a separated lymphocyte assay. Good correlation between the two methods was reported. However the number of subjects studied appears to have been small and no patients with steroid resistance were studied. We have studied a large number of subjects and compared steroid sensitivity measured by a whole blood culture with an established separated lymphocyte assay. Proliferation was stimulated with phytohaemagglutinin and inhibited by dexamethasone. A wide range of steroid sensitivity was found between individuals. In steroid sensitive subjects, good agreement was seen between the two assays. However in individuals identified as steroid resistant by the separated lymphocyte assay, steroid resistance was not seen using the whole blood assay. This is important because in vitro lymphocyte steroid resistance, as measured by the separated lymphocyte assay has been shown to predict a poor in vivo response to steroid therapy. Using the whole blood culture this steroid resistance would not be demonstrated. Hence the use of a whole blood assay can not be recommended.

Two ECGs and a history: a guide to early hospital discharge of patients with 'chest pain? cause'.

OBJECTIVES: To shorten the stay in hospital of patients admitted with chest pain of uncertain origin, using clinical history and an unchanging ECG as a basis to inform patients on the post-take ward round of imminent discharge that same day (pending normal cardiac enzyme results), thereby facilitating actual discharge on the same day. DESIGN: A prospective observational study over a two-month period of consecutive patients admitted with chest pain of uncertain origin. SETTING: District general hospital in North-West England with a regional cardiothoracic centre on site. RESULTS: Of the 115 patients enrolled in the study (15% of acute medical admissions), 43 (37%) were identified by the investigators as likely to have normal cardiac enzymes and only one of them had evidence of important cardiac ischaemia (median actual length of stay, 3 days). The specificity of the protocol was 98%, with a sensitivity of 89%. CONCLUSIONS: A careful clinical history taken by experienced junior staff together with two sequential ECGs, can identify patients who may be discharged within 24 hours of admission with chest pain of uncertain origin. Significant bed savings would result from the instigation of this practice, with minimal requirement for extra resources.