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Biomedical subjects

S P L Travis

Publications and source records attributed to S P L Travis.

At least 19 recordsLinked to original sources

Management of acute severe colitis.

The management of acute severe ulcerative colitis depends on early recognition of the unwell patient with colitis, the prompt initiation of treatment and objective assessment of the likelihood of medical failure. This deters 'hopeful expectation' in an attempt to avoid surgery. Intravenous corticosteroids remain first-line therapy but are completely effective in only 40%, partially effective in 30% and around 30% come to colectomy. The decision to use ciclosporin or infliximab for those with a poor response to steroids should be made at an early stage, often 3 or 4 days after starting intensive therapy. Decision-making is becoming more difficult with agents such as visilizumab, tacrolimus and the technique of leucocytapheresis as further options. Nevertheless, intravenous corticosteroids and timely colectomy have reduced mortality from nearly 30% to < 1% in specialist centres. Ciclosporin has delayed the need for urgent colectomy in many patients, but long-term follow-up suggests the majority come to colectomy within 7 years. Long-term outcome with newer agents, including infliximab, is not yet known.

Acute Disease↗

Lack of association of MYO9B genetic variants with coeliac disease in a British cohort.

BACKGROUND AND AIMS: Development of coeliac disease involves an interaction between environmental factors (especially dietary wheat, rye, and barley antigens) and genetic factors (there is strong inherited disease susceptibility). The known human leucocyte antigen (HLA)-DQ2 and -DQ8 association explains only a minority of disease heritability. A recent study in the Dutch population suggested that genetic variation in the 3' region of myosin IXB (MYO9B) predisposes to coeliac disease. MYO9B is a Rho family GTPase activating protein involved in epithelial cell cytoskeletal organisation. MYO9B is hypothesised to influence intestinal permeability and hence intestinal antigen presentation. METHODS: Four single nucleotide polymorphisms were chosen to tag all common haplotypes of the MYO9B 3' haplotype block (exons 15-27). We genotyped 375 coeliac disease cases and 1366 controls (371 healthy and 995 population based). All individuals were of White UK Caucasian ethnicity. RESULTS: UK healthy control and population control allele frequencies were similar for all MYO9B variants. Case control analysis showed no significant association of any variant or haplotype with coeliac disease. CONCLUSIONS: Genetic variation in MYO9B does not have a major effect on coeliac disease susceptibility in the UK population. Differences between populations, a weaker effect size than originally described, or possibly a type I error in the Dutch study might explain these findings.

Adolescent↗

Review article: induction therapy for patients with active ulcerative colitis.

5-aminosalicylic acid (mesalazine) is considered first-line therapy for active mild-moderate, left-sided or extensive ulcerative colitis. With modern delayed-release formulations, conventional doses are very well tolerated, and there is accumulating evidence that increasing the dose, to >4 g/day, leads to higher response rates and earlier symptom relief in patients with ulcerative colitis. There is evidence that combining oral and rectal (enema) formulations of 5-aminosalicylic acid leads to faster and higher remission rates. Despite the fact that clinical trials in ulcerative colitis have often used different endpoints, making it difficult to make objective comparisons, the evidence now strongly suggests that it is appropriate to start patients with mild or moderately active ulcerative colitis on doses of 5-aminosalicylic acid of at least 4 g/day. For those with extensive disease, adding rectal 5-aminosalicylic acid improves remission rates; the same seems likely to be true for limited disease, but robust evidence is lacking. Rectal 5-aminosalicylic acid may in fact be sufficient on its own for patients with active proctitis. Patients with mild-moderate ulcerative colitis who do not improve within 2 weeks of high-dose 5-aminosalicylic acid should have treatment augmented by oral steroids.

Administration, Oral↗

New thinking: theory vs practice. A case study illustrating evidence-based therapeutic decision making.

Evidence-based medicine (EBM) plays a key role for decision making in clinical practice. Clinicians are encouraged to adhere to treatment guidelines based on high quality clinical trials, systematic reviews and meta-analyses, that are the focus of the Cochrane Collaboration. EBM is not, however, a panacea for medical decision making. The results of randomized clinical trials apply to populations of patients, and the challenge is to translate the results to individuals. Individual patients require different thought processes because presentation and response vary, and external factors (e.g. patient preference) influence the choice of treatment. The application of EBM demands clinical judgement. The case of a 28 year old scientist who presented with typical features of moderate ulcerative colitis, illustrates the dilemma. At each stage of his illness the treatment options based on EBM were discussed, including high dose 5-aminosalicyclic acid with or without topical therapy, corticosteroids, infliximab, immunomodulation, complementary therapy and surgery. Ultimately, therapeutic decisions depended on the patient's circumstances, preferences and response. Decisions should avoid circular motion caused by the illusion of progress and always consider the direction of travel.

Adult↗

European evidence based consensus on the diagnosis and management of Crohn's disease: current management.

This second section of the European Crohn's and Colitis Organisation (ECCO) Consensus on the management of Crohn's disease concerns treatment of active disease, maintenance of medically induced remission, and surgery. The first section on definitions and diagnosis includes the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn's disease. The third section on special situations in Crohn's disease includes postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy for Crohn's disease.

Adrenal Cortex Hormones↗

Oral methotrexate in ulcerative colitis.

BACKGROUND: We performed an audit of methotrexate for ulcerative colitis, because efficacy is unclear. Aim : To investigate the role of methotrexate in the management of ulcerative colitis. METHODS: Patients with ulcerative colitis treated with oral methotrexate at the inflammatory bowel disease clinics of Oxford and Wycombe General Hospital, UK, were evaluated. Efficacy was defined by remission (complete steroid withdrawal for >3 months) and response (good, partial or nil, proportionate reduction of steroids). RESULTS: There were 50 patients (42 ulcerative colitis alone; eight had rheumatoid arthritis associated with ulcerative colitis and were analysed separately). Indications for methotrexate in ulcerative colitis alone were azathioprine intolerance (31 of 42) and lack of benefit from azathioprine (11 of 42). The mean dose of methotrexate in ulcerative colitis alone was 19.9 mg/week for a median of 30 weeks (range: 7-395). Remission occurred in 42%. The response was good in 54% and partial in 18%. Side-effects occurred in 23%; 10% stopped treatment because of side-effects. Of those treated with methotrexate because of treatment failure with azathioprine, three of 11 achieved remission, but four came to colectomy within 90 days of starting methotrexate. The colitis remained in remission in seven of eight of those with RA treated with methotrexate and ulcerative colitis (mean dose 15.0 mg/week). CONCLUSION: Oral methotrexate (approximately 20 mg/week) is well-tolerated and moderately effective in steroid-dependent or steroid-refractory patients with ulcerative colitis.

Adolescent↗

Review article: the management of mild to severe acute ulcerative colitis.

The goals for the management of acute ulcerative colitis are the objective evaluation of disease activity, induction of remission, prevention of relapse and treatment of complications. Clinical practice should be guided by simple activity indices, as it is easy to underestimate severity. For the induction of remission, topical treatment with mesalazine (mesalamine) is appropriate initial therapy for distal disease but, if symptoms persist for over a fortnight, decisive treatment is usually appreciated by the patient. For mild to moderate disease, corticosteroids have been the mainstay in Europe, although high-dose aminosalicylates (such as Pentasa, 4 g orally daily and 1 g rectally) are an alternative for symptoms not interfering with daily activity. Novel therapeutic approaches in ulcerative colitis have lagged behind those used for Crohn's disease, but several (epidermal growth factor, RDP 58, basiliximab, leucocytapheresis) are on the horizon. Severe colitis, defined as a bloody stool frequency of more than six per day with any one of tachycardia (pulse > 90 beats/min), temperature (> 37.8 degrees C), anaemia (haemoglobin < 10.5 g/dL) or raised erythrocyte sedimentation rate (> 30 mm/h), is an indication for intensive intravenous treatment. National UK figures indicate that 30% of ulcerative colitis cases progress to colectomy, and objective criteria for predicting the need for colectomy have been validated. The timing of colectomy is the most important decision that a physician is called upon to make, in conjunction with the patient and surgical colleagues. For the maintenance of remission, aminosalicylates continue to be first-line therapy, although the choice of 5-aminosalicylate appears to be influenced as much by geography as by theoretical considerations. Steroids have no place in the maintenance of remission. Indications for azathioprine include patients after a severe relapse of ulcerative colitis, those with early relapse after steroids (dose of < 15 mg/day, or within 6 weeks of stopping) and those needing a second course of steroids within a year. Therapeutic decisions should have a strategy, aimed at navigating the patient around relapses and through to sustained remission. Good management depends on clinical skills, compassion and care of the individual, in addition to pharmaceuticals.

Acute Disease↗