CARD15/NOD2 risk alleles in the development of Crohn's disease in the Australian population.

We have previously reported strong evidence for linkage between IBD1 and Crohn's disease (CD) in Australian Crohn's disease families. Three risk alleles for Crohn's disease, (Arg702Trp (C/T), Gly908Arg (G/C) and 980fs981 (-/C), were recently identified in the CARD15/NOD2 gene on chromosome 16, implicating this as the IBD1 locus. Using a novel diagnostic PCR-RFLP, we have examined the frequency of these alleles in 205 multiplex IBD families, 107 sporadic Crohn's disease cases and 409 normal individuals. We demonstrate that the three risk alleles are more frequent in Crohn's disease, than in controls, with allelic frequencies of 0.11, 0.02 and 0.07 respectively. Heterozygosity for individual variants conferred a three-fold increase in risk for Crohn's disease while substantially higher risks were associated with being homozygous or compound heterozygous. Despite a significantly lower population allele frequency for the frameshift mutation than reported by other groups, we see a similar contribution by this allele to the risk of developing Crohn's disease. While the three risk alleles influence susceptibility to Crohn's disease in Australia, we show that these alleles do not fully explain the linkage evidence and suggest that there are very likely additional IBD1 susceptibility alleles yet to be described in Australian CD at the NOD2 locus. We also show a second linkage peak in Australian CD that provides some support for a second disease susceptibility locus on chromosome 16.

Does patient knowledge affect the colorectal cancer risk in ulcerative colitis?

OBJECTIVES: Formal efforts to improve patient education are associated with fewer disease complications in a number of conditions. The possible relationship between knowledge about ulcerative colitis and its cancer risk, and the development of colorectal cancer using a previously developed and validated instrument-the Crohn's and colitis knowledge (CCKNOW) score-were investigated. METHODS: The 24 item CCKNOW questionnaire was mailed to patients known to have developed colorectal cancer as a complication of ulcerative colitis (cases) and to colitics from the Leicestershire inflammatory bowel disease patient database who had not developed cancer (controls). RESULTS: The mean (SD) CCKNOW scores for cases was 8.21 (3.02) and for controls was 8.27 (4.3). These scores did not differ significantly between cases and controls (difference 0.06, 95% confidence interval (CI) -1.7 to 1.5, p=0.9). There were four times as many members of the National Association of Crohn's and Colitis (NACC) in the control group compared with the cancer group and patients who are members of NACC achieve statistically significantly higher scores than non-members (11.6 v 7.8, p=0.05, 95% CI -0.1 to 7.6). However, after adjusting for NACC membership, the CCKNOW score did not appear to be associated with having developed cancer (odds ratio 1.04, 95% CI 0.92 to 1.18, p=0.5). CONCLUSIONS: The CCKNOW scores were comparable in cases and controls. Thus, in a retrospective study, no evidence has been demonstrated of an association between patient knowledge and the risk of developing colorectal cancer in patients with ulcerative colitis. However, knowledge may have been increased in cases as a direct result of having had colorectal cancer as a complication of ulcerative colitis.

The risk of colorectal cancer in ulcerative colitis: a meta-analysis.

BACKGROUND AND AIMS: Controversy surrounds the risk of colorectal cancer (CRC) in ulcerative colitis (UC). Many studies have investigated this risk and reported widely varying rates. METHODS: A literature search using Medline with the explosion of references identified 194 studies. Of these, 116 met our inclusion criteria from which the number of patients and cancers detected could be extracted. Overall pooled estimates, with 95% confidence intervals (CI), of cancer prevalence and incidence were obtained using a random effects model on either the log odds or log incidence scale, as appropriate. RESULTS: The overall prevalence of CRC in any UC patient, based on 116 studies, was estimated to be 3.7% (95% CI 3.2-4.2%). Of the 116 studies, 41 reported colitis duration. From these the overall incidence rate was 3/1000 person years duration (pyd), (95% CI 2/1000 to 4/1000). The overall incidence rate for any child was 6/1000 pyd (95% CI 3/1000 to 13/1000). Of the 41 studies, 19 reported results stratified into 10 year intervals of disease duration. For the first 10 years the incidence rate was 2/1000 pyd (95% CI 1/1000 to 2/1000), for the second decade the incidence rate was estimated to be 7/1000 pyd (95% CI 4/1000 to 12/1000), and in the third decade the incidence rate was 12/1000 pyd (95% CI 7/1000 to 19/1000). These incidence rates corresponded to cumulative probabilities of 2% by 10 years, 8% by 20 years, and 18% by 30 years. The worldwide cancer incidence rates varied geographically, being 5/1000 pyd in the USA, 4/1000 pyd in the UK, and 2/1000 pyd in Scandinavia and other countries. Over time the cancer risk has increased since 1955 but this finding was not significant (p=0.8). CONCLUSIONS: Using new meta-analysis techniques we determined the risk of CRC in UC by decade of disease and defined the risk in pancolitics and children. We found a non-significant increase in risk over time and estimated how risk varies with geography.

How gastroenterologists screen for colonic cancer in ulcerative colitis: an analysis of performance.

BACKGROUND: The aim of this study was to assess the colorectal cancer surveillance practices of British gastroenterologists for patients with ulcerative colitis. METHODS: A questionnaire that investigated aspects of surveillance in patients with ulcerative colitis was mailed to all consultant gastroenterologists in the U.K. (n = 413). RESULTS: Three hundred forty-one questionnaires were returned (response rate 83%). Ninety-four percent of consultants practice cancer surveillance in ulcerative colitis, with 35% maintaining a registry of patients in surveillance programs. All gastroenterologists perform surveillance in patients with pancolitis, 24% in those with left-sided colitis and 2% in patients with proctitis. The mean duration of disease before surveillance is commenced is 9.2 years for pancolitis and 12.4 years for left-sided colitis (p < 0.0001). Only 4% of gastroenterologists routinely offer patients with disease of more than 10 years' duration a prophylactic colectomy. Colonoscopies are conducted by an accredited gastroenterologist in 65% of cases and biopsies are reviewed by specialists in gastrointestinal pathology in 45%. When histology reveals low-grade dysplasia only 4% advise colectomy and when high-grade dysplasia is found 53% recommend colectomy. Sixteen percent of gastroenterologists were unaware of the significance of a dysplasia associated lesion or mass. CONCLUSION: The majority of gastroenterologists practice surveillance on a disorganized basis. There is inconsistency in the management of patients with dysplasia and education of gastroenterologists is needed.

The Crohn's and Colitis Knowledge Score: a test for measuring patient knowledge in inflammatory bowel disease.

OBJECTIVE: The aim of this study was to develop a valid and reliable questionnaire assessing patient knowledge of inflammatory bowel disease (IBD) and its treatment--the Crohn's and Colitis Knowledge (CCKNOW) Score. METHODS: A total of 30 multiple choice questions were constructed into a draft questionnaire. This was piloted on a random selection of participants with differing IBD knowledge levels; junior doctors, nurses, and ward clerks. Factor analysis eliminated questions with poor discriminant ability. The resulting 24-item questionnaire (CCKNOW score) was retested on the three groups, and a Kruskal-Wallis test determined the questionnaire's ability to discriminate between the groups. Reliability and readability were tested using Cronbach's a and the Flesch Kincaid reading score. The validated CCKNOW was then tested on patients from the Leicestershire IBD database. RESULTS: CCKNOW scores differed significantly across the groups of doctors, nurses, and ward clerks (median 22, 16, and five, respectively) T = 40.35, p < 0.0001. The reliability was very good with a Cronbach's alpha of 0.95 and the readability was also high. The median score on the CCKNOW for IBD patients was 10, with no significant difference between ulcerative colitis and Crohn's disease. Patients who are members of NACC (National Association of Crohn's and Colitis) achieve statistically significantly higher scores than do nonmembers (difference in medians 4, 95% confidence interval 4-6, p < 0.0001). CONCLUSIONS: The CCKNOW score provides a valuable index of overall knowledge. It is self-administered and psychometric tests show it to be valid, reliable, and readable. It may be used in the future as a tool to evaluate patient education programs.

Social implications of childhood Crohn's disease.

BACKGROUND: Children with Crohn's disease may have an impaired quality of life. METHODS: A validated questionnaire was mailed to the parents of all child members of Crohn's in Childhood Research Association (CICRA) (age range, 5-17 years). It investigated aspects of the quality of life of children with Crohn's disease. Sixty-four questionnaires were returned together with another 35 from those outside the defined age range. Patients in the latter group were not included in the analysis. RESULTS: Of the children investigated, 60% had significant absences from school, with a mean of 3+/-2.8 months' absence in the previous year. Most (53%) thought that their teachers knew nothing about Crohn's disease, and 50% thought that teachers were unsympathetic. Of the 24 who had taken examinations 80% thought they had underachieved because of ill health. Sixty-seven percent of children were unable to participate in sports on a regular basis, 60% felt unable to leave the house, and 50% were unable to play with their friends. Information about Crohn's disease had predominantly come from doctors (89%), information booklets (83%), and nursing staff (42%). The commonest questions asked by the children were: what is Crohn's disease (50%), why me (64%), will it affect my schooling (52%), and will it affect my chances of getting a job (67%). CONCLUSION: Children with Crohn's disease have a significantly impaired quality of life. They fear everyday childhood activities and fear for their future. These children need sympathetic management, and effort should be concentrated on improving their day-to-day existence to enable them to lead as normal a life as possible.

The role of complementary medicine in European and Asian patients with inflammatory bowel disease.

Three hundred and eighty-two patients with known inflammatory bowel disease (IBD) (190 European and 192 Asians) and 190 with coeliac disease were sent a previously validated questionnaire to investigate patients' use of alternative medicine and their views on its effectiveness. Details sought included whether they have ever consulted an alternative practitioner, whether they had followed a course of treatment and its clinical effects. Information about where patients had heard about such alternative practitioners and whether they were told to discontinue their current allopathic medication was sought. Results were analysed after three consecutive mailings, including one in Gujurati to Asian patients. A randomly selected group was re-interviewed four months later. To validate the study alternative medicine practitioners were also interviewed to investigate what percentage of their attendees have IBD and how many of those clients were Asians. One hundred and fifty-eight questionnaires were returned from European patients with IBD (response rate = 83%), 145 from patients with coeliac disease (response rate = 76%) but only 81 Asian patients with IBD (response rate = 42%). Forty-seven European and Asian patients with inflammatory bowel disease sought advice or treatment from an alternative practitioner, compared with only 11 with coeliac disease (chi(2) = 11.64, df = 12, P < 0.003). There was no significant difference in consultation rates between Asian and European patients with IBD (Yates corrected chi(2) = 0.78, ns). The most common practitioners consulted by all groups were homeopaths (n = 23) and herbalists (n = 27) but 20 patients consulted more than one practitioner at a time. Patients with coeliac disease and European patients with IBD had consulted osteopaths (n = 6) and reflexologists (n = 7). Ten patients with IBD had also attended a spiritualist and five Asian patients a hakim. Common sources of information about alternative remedies included friends and relatives (n = 13), the media (n = 11), word of mouth (n = 11) and family practitioners (n = 6). Most patients were advised to continue their current medications, although two had been told to stop and 10 advised to reduce the dose of their allopathic medications. Twenty alternative medicine practitioners stated that overall between 2-5% of their attendees have IBD with 10% of those clients being Asian. Asians preferred to consult Asian practitioners rather than European practitioners. There was no clear consensus as to whether complementary therapies were felt beneficial, although many patients with IBD believed them to be helpful.

Are we telling patients enough? A pilot study to assess patient information needs in a gastroenterology outpatient department.

OBJECTIVE: To define whether gastroenterology patients wish to receive more information concerning many aspects of their illness and to elicit their attitude after receiving written communication from their hospital practitioner. METHODS: In stage 1, 73 gastroenterology patients were interviewed and completed a structured questionnaire after their hospital outpatient visit, to assess whether they would like to receive more information about their condition. Stage 2 involved posting a copy of the general practitioner's letter, dictated in the clinic, to the patient and assessing their opinion of its value, by using a second questionnaire. In stage 3 a group of outpatients received a letter specifically prepared for them which summarized the outcome of their clinic visit (with avoidance of medical terms) and they again completed a questionnaire. RESULTS: More than 75% of patients wished to receive written communication from their hospital practitioner. Ninety percent wanted to know more about diagnostic tests and 92% requested more information about their medication. Ninety percent of patients who received a copy of their GP's letter claimed to understand its contents and felt it was beneficial. Ninety four percent wanted the service to continue. However, there was no advantage in preparing a special letter for patients compared with a simple copy of that sent to their GP. CONCLUSION: There is considerable interest amongst gastroenterology patients concerning their diagnosis and the management of their disease. The provision of simplified letters about their outpatient management does not seem to have any advantage over simply providing copies of all relevant correspondence sent to GPs.

Patients with inflammatory bowel disease: their response to information leaflets about medical therapy in particular azathioprine.

Thirty-eight patients with inflammatory bowel disease who had been treated with azathioprine were asked to complete an anonymous questionnaire about information they had received on the drug. Twenty responded of which 16 recalled having had information on azathioprine. Recall of the content on an information leaflet was poor with up to 25% of patients failing to recall warnings about side effects. Documentation of this advice on the clinical notes was also poor with this happening in only one case. This failure to both recall and record information must increase the chances of successful litigation.