Randomized clinical trial of metronidazole ointment versus placebo in perianal Crohn's disease.

BACKGROUND: The potential for metronidazole 10 per cent ointment to exert therapeutic benefit in perianal Crohn's disease, while minimizing the adverse effects found with oral metronidazole, was evaluated in a randomized placebo-controlled study. METHODS: Subjects with perianal Crohn's disease were randomized to metronidazole 10 per cent ointment, 0.7 g applied perianally three times daily, or placebo ointment. The Perianal Crohn's Disease Activity Index (PCDAI) was scored at baseline and after 4 weeks of treatment. Perianal pain was assessed on a visual analogue scale. RESULTS: Seventy-four subjects (33 metronidazole, 41 placebo) were evaluated. The mean(s.e.m.) reduction in PCDAI score at 4 weeks was 2.4(0.5) in the metronidazole group and 2.2(0.4) in the placebo group (P = 0.660). More subjects in the metronidazole group than the placebo group showed a reduction in PCDAI score of at least 5 points (10 of 27 versus 4 of 34; P = 0.031). Perianal discharge was reduced significantly in metronidazole-treated subjects (P = 0.012). A greater reduction in perianal pain was seen in the metronidazole group, which approached statistical significance (P = 0.059). No serious adverse events were reported. CONCLUSION: Metronidazole 10 per cent ointment was not effective in the reduction of PDCAI score, but some secondary outcomes showed improvement suggestive of a treatment effect. It is well tolerated, with minimal adverse effects, and has potential as treatment for pain and discharge associated with perianal Crohn's disease. REGISTRATION NUMBER: NCT00509639 (http://www.clinicaltrials.gov).

Duration of treatment with 5-aminosalicylic acid compounds.

The development of 5-aminosalicylic acid (5-ASA) therapy as a life long treatment for ulcerative colitis is reviewed from its origins in the 1940s to the present day. The drug was designed to treat rheumatoid arthritis, but was found helpful in the management of nine patients with ulcerative colitis. This discovery preceded the emergence of the clinical trial as a tool for assessing a new drug's efficacy; as a result it lacked scientific rigour and was selective in its presentation of results. Nevertheless it identified the future cornerstone of therapy in ulcerative colitis. In 1962, the first double blind controlled trial of sulphasalazine was conducted on 40 patients. Outcome measures were subjective and included symptoms and an assessment of the rectal mucosa. In 1973, the first two papers on the role of sulphasalazine in maintenance of remission were published. Both used placebo controls and had a stratified design. Outcomes were measured using "an intention to treat" approach. The British study of 64 patients used both subjective and objective criteria to assess outcomes. Patients on placebo had a relapse rate four times patients on active treatment and this founded the basis for a life long approach to therapy with 5-ASA compounds in ulcerative colitis. However, in 1985, a small "on demand" study of 32 patients suggested this approach might be as effective as continuous treatment. Some support for this view came from an Italian study which showed no benefit to continued treatment for those in remission for two years or more. The central problem these studies identify is that of adherence to treatment in the long-term. Few studies have considered patients' attitudes to continuous therapy and it is an area that needs further investigation.

Views of specialist registrars on specialty care in the community: employment prospects and the need for additional training.

AIM: To obtain the views of specialist registrars on specialty care in the community. METHOD: Specialist registrars from five Deaneries in England completed an online questionnaire about their views on employment prospects, the role of specialty care in the community, and the need for additional training in this area. RESULTS: One hundred and twenty seven replies were received over a four week period. Thirty (24%) viewed their future employment prospects as consultants as poor or very worrying. Seventy seven (61%) specialist registrars considered that as consultants they will need to work directly in the community. Thirty nine of these (51%) considered the need to work close to patients directly in the community as either a "bad" or "very bad" development. However, 102 (80%) specialist registrars believed that they should receive training on the delivery of specialty care in the community and 96 (76%) wanted this in the form of a university based degree.

It is time to test low level laser therapy in Great Britain.

Low level laser therapy (LLLT) has been used in Eastern Europe and Asia for the treatment of a wide range of conditions for many years. Its continued acceptance in these populations reflects the efficacy with which it is regarded both by clinicians and their patients. Although there have been a substantial number of reports on its clinical benefit and some practitioners have used the technique in North America and Australasia it has yet to be subjected to detailed assessment through randomised clinical trials. The purpose of this review is to stimulate interest in the technique and to encourage rigorous research into its potential value.

Co-prescribing azathiopurine or 6-mercaptopurine and 5-aminosalicylate compounds in ulcerative colitis.

BACKGROUND: A total of 254 senior consultant gastroenterologists with valid e-mail addresses were identified from the membership list of the British Society of Gastroenterology (BSG) 2007. METHODS: They were sent by e-mail a questionnaire which dealt with aspects of clinical practice and addressed cancer prevention in ulcerative colitis (UC). Replies were received from 97 clinicians (38% response rate). RESULTS: Ninety-one (94%) advised patients with established UC to take 5-aminosalicylate (5-ASA) compounds for life. Seventy-two of the 91 (79%) clinicians co-prescribed 5-ASA compounds with immune modulators for patients with UC. Only 3 clinicians advised patients to take folic acid as a daily supplement. A median of 20% (interquartile range 10%-50%) of their patients with UC were co-prescribed a 5-ASA compound and azathioprine or 6-mercaptopurine. Of these, a median of 3.5% (interquartile 1%-5%) developed neutropenia. CONCLUSIONS: Future research needs to be directed at the long-term maintenance treatment and to address questions about which drugs should be used, in what combinations, and with what frequencies.

An investigation of medication adherence to 5-aminosalicylic acid therapy in patients with ulcerative colitis, using self-report and urinary drug excretion measurements.

BACKGROUND: Non-adherence to 5-aminosalicylic acid (5-ASA) medication can limit the established benefits of this therapy in ulcerative colitis (UC). AIM: To determine rates and predictors of non-adherence to 5-ASA therapy in UC patients. METHODS: Medication adherence was assessed using self-report data and urinary drug excretion measurements. Participants completed a study-specific questionnaire and two validated questionnaires: Beliefs about Medicine Questionnaire (BMQ)-Specific and Satisfaction with Information about Medicines Scale. RESULTS: A total of 169 participants provided self-report adherence data; 151 also provided urine samples. Adherence rates were 111/151 (68%) according to self-report and 90/151 (60%) according to urine analysis, but the two measures were not correlated (chi(2) = 0.12, P = 0.725). Logistic regression identified a significant association between self-reported non-adherence and younger age [odds ratio (OR) for increased age 0.954, 95% confidence interval (CI) 0.932-0.976] and also doubts about personal need for medication (OR for BMQ - Specific Necessity scores 0.578, 95% CI 0.366-0.913). For non-adherence based on urine analysis, only South Asian ethnicity was independently associated with non-adherence (OR 2.940, 95% CI 1.303-6.638). CONCLUSIONS: Our observations confirm the difficulty of accurately assessing medication adherence. Nonmodifiable (younger age, South Asian ethnicity) and potentially modifiable (medication beliefs) predictors of non-adherence were identified.