Early use of thiopurines or methotrexate reduces major abdominal and perianal surgery in Crohn's disease.

BACKGROUND: Earlier introduction of immunomodulators (IM) thiopurine or methotrexate is advocated to improve Crohn's disease (CD) outcomes, but whether abdominal surgery can be prevented remains controversial. METHODS: A specialist-referred cohort of CD was recruited from 1970 to 2009. Early IM use was defined as commencement of azathioprine or methotrexate within 3 years of CD diagnosis and adherence of at least 6 months. Propensity score matching was conducted to correct for confounders influencing early IM introduction. Outcomes of interest were rates of initial and recurrent major abdominal surgery for CD and their predictive factors. RESULTS: A total of 1035 consecutive patients with CD (13,061 patient-years) were recruited. The risk of first and recurrent major abdominal surgery at 1, 5, and 10 years were 17.5%, 28.4%, and 39.5% and 5.9%, 19.0%, and 33.3%, respectively. Early IM use increased over time from 1.3% to 55.3% (P < 0.0001) and was a significant independent predictor of lower rates of initial abdominal surgery (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.35-0.69), recurrent abdominal surgery (HR, 0.44; 95% CI, 0.25-0.79) and perianal surgery (HR, 0.30; 95% CI, 0.16-0.56). Using propensity score matching, early IM significantly reduced surgical rates (HR, 0.54; 95% CI, 0.37-0.79). Number needed to treat to prevent a surgical event at 5 years from diagnosis and after initial surgery was 6.99 (95% CI, 5.34-11.95) and 8.59 (95% CI, 6.26-23.93), respectively. CONCLUSIONS: Early IM use with thiopurines or methotrexate was significantly associated with the reduced need for abdominal and perianal surgery in CD.

Long-term follow-up reveals low incidence of colorectal cancer, but frequent need for resection, among Australian patients with inflammatory bowel disease.

BACKGROUND & AIMS: Inflammatory bowel disease can require surgical resection and also lead to colorectal cancer (CRC). We investigated the cumulative incidence of resection surgeries and CRC among patients with ulcerative colitis (UC) or Crohn's disease (CD). METHODS: We analyzed data from a cohort of patients who participated in an inflammatory bowel disease study (504 with UC and 377 with CD) at 2 academic medical centers in Sydney, Australia from 1977 to 1992 (before the development of biologic therapies). We collected follow-up data on surgeries and development of CRC from hospital and community medical records or via direct contact with patients during a median time period of 14 years. Cumulative incidences of resection surgeries and CRC were calculated by competing risk survival analysis. RESULTS: Among patients with UC, CRC developed in 24, for a cumulative incidence of 1% at 10 years (95% confidence interval [CI], 0%-2%), 3% at 20 years (95% CI, 1%-5%), and 7% at 30 years (95% CI, 4%-10%). Their cumulative incidence of colectomy was 15% at 10 years (95% CI, 11%-19%), 26% at 20 years (95% CI, 21%-30%), and 31% at 30 years (95% CI, 25%-36%). Among patients with CD, 5 of 327 with colon disease developed CRC, with a cumulative incidence of CRC of 1% at 10 years (95% CI, 0%-2%), 1% at 20 years (95% CI, 0%-2%), and 2% at 30 years (95% CI, 0%-4%). Among all patients with CD, the cumulative incidence of resection was 32% at 5 years (95% CI, 27%-37%), 43% at 10 years (95% CI, 37%-49%), and 53% at 15 years (95% CI, 46%-58%). Of these 168 subjects, 42% required a second resection within 15 years of the first surgery (95% CI, 33%-50%). CONCLUSIONS: Patients with UC have a low incidence of CRC during a 30-year period (7% or less); the incidence among patients with CD is even lower. However, almost one-third of patients with UC and about 50% of those with CD will require surgery.

Modifiable factors associated with nonadherence to maintenance medication for inflammatory bowel disease.

BACKGROUND: Poor adherence frequently impaired the efficacy of therapy to maintain remission from inflammatory bowel diseases (IBD). There is a lack of practical and effective interventions to improve adherence. This study aimed to identify modifiable risk factors, which may yield targets for new interventions. METHODS: Participants with IBD were recruited from hospital outpatient clinics and office-based gastroenterologists. Demographic and disease-related data were recorded by means of self-administered questionnaires. Modifiable risk factors were assessed with the validated Belief about Medicine Questionnaire, Hospital Anxiety and Depression Score, and short inflammatory bowel disease questionnaire. Adherence was assessed separately for 5-aminosalicylates, thiopurines, and biological agents using the validated Medicine Adherence Report Scale (good adherence defined as >16). RESULTS: Nonadherence occurred in 102 of 356 participants (28.7%). Adherence increased significantly with more aggressive therapies (median Medicine Adherence Report Scale: 5-aminosalicylates 18, thiopurines 19, biological 20; P < 0.0001). Nonadherence was not associated with anxiety and depression or disease-related patient knowledge. Adherent patients had significantly higher belief of necessity for medication (P < 0.0001) and a trend toward lower concerns about medication (P = 0.08). Membership of an IBD patient organization was associated with better adherence (P < 0.0001). Concerns about medication rose significantly with more aggressive therapies (P = 0.009), but belief of necessity was similar for all medications. CONCLUSIONS: Nonadherence occurs most frequently with 5-aminosalicylates. Belief of necessity may prove the key target for future interventions, although general IBD education is unlikely to yield an adherence benefit. Patient organization membership should be encouraged.

Better disease specific patient knowledge is associated with greater anxiety in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD)-related knowledge not only empowers patients, but may also engender anxiety. The study aimed to identify predictors of anxiety in IBD and examine the interplay between anxiety and disease-related patient knowledge. The effect of anxiety on quality of life was also explored. METHODS: Ambulatory IBD patients provided data on demographics, their IBD and Crohn's Colitis Association (CCA) membership status. Disease-related knowledge was assessed using the validated Crohn's and Colitis Knowledge score (CCKnow) and disease related QOL using the short IBD questionnaire (SIBDQ). Anxiety and depression were assessed with the Hospital Anxiety and Depression Scores. RESULTS: Of the 258 patients 19.4% had a potential anxiety and a further 22.4% had a probable anxiety disorder. Females (P=0.003), tertiary care patients (P=0.014) and non-Caucasian patients (P=0.037) had significantly higher anxiety levels. CCA members had marginally higher levels of anxiety (P=0.07). Anxiety was associated with significantly better patient knowledge (P=0.016) and increased depression (P<0.001). Disease related quality of life was significantly lower in patients with anxiety (P<0.001). CONCLUSIONS: This is the first study to demonstrate that better patient knowledge is associated with higher anxiety levels. The reason for this is unclear: educating patients about their disease might trigger anxiety, but, equally, anxious patients might seek out information and hence have better knowledge. It is thus noteworthy that an educational intervention may not necessarily reduce anxiety. Further work is needed to evaluate the association between anxiety and knowledge and to develop targeted interventions that will improve knowledge and simultaneously reduce anxiety.

Inflammatory bowel disease and pregnancy: lack of knowledge is associated with negative views.

BACKGROUND: Enabling women with inflammatory bowel diseases (IBD) to have successful pregnancies requires complex decisions. The study aimed to assess patients' views on IBD and pregnancy and to evaluate any association with subject knowledge. METHODS: General attitudes of females with IBD were assessed on fertility, medication use, delivery mode and pregnancy outcomes. Attitudes regarding personal situation were assessed in participants nulliparous since IBD diagnosis. Knowledge of pregnancy-related issues in IBD was assessed by the Crohn's and Colitis Pregnancy Knowledge Score 'CCPKnow'. RESULTS: Of 145 participants 68% of participants agreed with need for medical therapy for flares during pregnancy, but 24% felt it more important to tolerate symptoms. 36% believed that all IBD medication is harmful to unborn children. Of 96 women nulliparous after IBD diagnosis, 46% were worried about infertility, 75% expressed concern about passing IBD to offspring and 30% considered not having children. Nearly all participants worried about the effects of IBD on pregnancy and the effects of pregnancy on IBD. General attitudes that 'medication should be stopped prior to conception' (P<0.001), 'pregnant women should avoid all IBD drugs' (P<0.001), and 'put up with symptoms' (P<0.001) were associated with significantly lower CCPKnow scores. CONCLUSION: Over a third of patients considered IBD medication harmful to unborn children. Fear of infertility and concerns about inheritance may explain high rates of voluntary childlessness. Attitudes contrary to medical evidence were associated with significantly lower knowledge. Young women with IBD, particularly those with poor knowledge, should be offered education and counselling about pregnancy-related issues.

Conveying medication benefits to ulcerative colitis patients and effects on patient attitudes regarding thresholds for adherence.

BACKGROUND AND AIM: Adherence to medication that maintains remission by patients with ulcerative colitis (UC) is poor but little is known regarding patients' perception of medication benefit that may enhance adherence rates. The aims were to study patients' understanding and preference on methods of conveying statistical information and to study indicated thresholds for adherence to medication for UC. METHODS: Four methods of displaying information on benefits of maintenance therapy were explained to patients with UC in remission: relative risk reduction [RR], absolute risk reduction [AR], number needed to treat [NNT] and optical representation via Cates plot [CP]. Patients' understanding and preference for each method were evaluated. Participants were asked to state minimum thresholds relating to relapse prevention and colorectal cancer risk reduction that they would require in order for them to adhere to medication for UC. RESULTS: Of 50 participants, 48% preferred data presentation by RR over CP (28%), AR (20%) and NNT (4%). 94% found RR easy to understand, better than AR (88%), CP (74%), or NNT (48%). For bowel cancer prevention, 94% indicated adherence for benefit levels of 61% RR but only 57% for the corresponding CP (P<0.001). For relapse prevention, 78% of patients indicated adherence for benefit levels of 40% RR but only 43% for the corresponding CP (P<0.001). CONCLUSION: Patients with UC prefer data presented by RR, and apply significantly higher thresholds for adherence when presented with CP compared to RR. Reduction of cancer risk may be a stronger motivator than maintenance of remission.

Optimal sedation for gastrointestinal endoscopy: review and recommendations.

Sedation practices for endoscopy vary widely. The present review focuses on the commonly used regimens in endoscopic sedation and the associated risks and benefits together with the appropriate safety measures and monitoring practices. In addition, alternatives and additions to intravenous sedation are discussed. Personnel requirements for endoscopic sedation are reviewed; there is evidence presented to indicate that non-anesthetists can administer sedative drugs, including propofol, safely and efficaciously in selected cases. The development of endoscopic sedation as a multi-disciplinary field is highlighted with the formation of the Australian Tripartite Endoscopy Sedation Committee. This comprises representatives of the Australian and New Zealand College of Anaesthetists, the Gastroenterological Society of Australia and the Royal Australasian College of Surgeons. Possible future directions in this area are also briefly summarized.

Subepithelial mass lesions in the upper gastrointestinal tract.

The finding of a mass lesion in the upper gastrointestinal tract at endoscopy with apparent normal overlying mucosa is common. The differential diagnosis of such lesions is broad and includes those of intramural or extramural origin. Endoscopic ultrasound provides accurate imaging of subepithelial mass lesions and characterizes them according to size, echogenicity, and origin including the histologic layer if the lesion is intramural which narrows the differential diagnosis. Endoscopic ultrasound allows a guided tissue sample to be obtained for histologic confirmation which is especially important for hypoechoic lesions arising from the 3rd or 4th echogenic layers. The purpose of this article is to review the diagnosis of the more common subepithelial mass lesions with an emphasis on endoscopic ultrasound and the subsequent management or monitoring.

Role of endoscopic ultrasound in staging upper gastrointestinal cancers.

The key clinical management points in this article are that (i) endoscopic ultrasound is the most accurate imaging method for local staging of oesophageal, gastric and pancreatic neoplasms; (ii) addition of fine-needle aspiration biopsy to the technique is safe and well tolerated and increases diagnostic accuracy for nodal staging purposes; and (iii) endoscopic ultrasound +/- fine-needle aspiration has the capacity to influence significantly, the management of patients with malignancies of the upper gastrointestinal tract, particularly with respect to selection for surgery. The learning objectives were that at the end of this paper the reader should be able to (i) understand the usefulness and limitations of various imaging methods in the staging of upper gastrointestinal cancers; and (ii) incorporate the various imaging methods, particularly endoscopic ultrasound, into management algorithms for oesophageal cancer, gastric cancer, mucosa-associated lymphoid tissue lymphomas, gastrointestinal stromal tumours, pancreatic cystic lesions and pancreatic cancer.

Validity of the 13C-caffeine breath test as a noninvasive, quantitative test of liver function.

The properties of caffeine render it an ideal substrate for a quantitative test of liver function. The aim of this study was to determine whether the caffeine breath test (CBT) using orally administered 13C-caffeine correlates reliably with plasma caffeine clearance and reflects varying degrees of liver dysfunction. The CBT was performed in 25 healthy controls; 20 subjects with noncirrhotic, chronic hepatitis B or C; and 20 subjects with cirrhosis. Plasma caffeine clearance was assayed simultaneously with the CBT in a cohort of these subjects. Over a broad range of caffeine clearances, the CBT exhibited a highly significant correlation with plasma clearance (r = 0.85, P <.001). Cirrhotic patients were characterized by significantly reduced CBT values (1.15 +/- 0.75 delta per thousand mg(-1)) compared with controls (2.23 +/- 0.76; P =.001) and hepatitic patients (1.83 +/- 1.05; P =.04). There was a significant inverse relationship between the CBT and Child-Pugh score (r = -.74, P =.002). The intraclass correlation coefficient between repeated CBTs in 20 subjects with normal and cirrhotic livers was 0.89. Although smoking was associated with an 86% to 141% increase in CBT in all groups, the CBT was able to distinguish control, hepatitic, and cirrhotic smokers (5.36 +/- 0.82, 3.63 +/- 1.21, and 2.14 +/- 1.14, respectively, P =.001). Multivariate analysis revealed that only smoking (P <.001) and disease state (P =.001) were significant predictors of the CBT. In conclusion, the 13C-CBT represents a valid indicator of plasma caffeine clearance and correlates reproducibly with hepatic dysfunction.