Christian P. Selinger

Gastric Antral Vascular Ectasia (GAVE): An Update on Clinical Presentation, Pathophysiology and Treatment

Gastric antral vascular ectasia (GAVE), though a rare disorder, causes up to 4% of non-variceal upper GI bleeding. This paper gives an overview of studies examining clinical presentation and pathophysiology, and reviews the current evidence for invasive and non-invasive treatments. GAVE is often associated with systemic illnesses, such as cirrhosis of the liver, autoimmune connective tissue disorders, bone marrow transplantation and chronic renal failure. The pathophysiological changes leading to GAVE have not been fully explained and remain controversial. Patient presentation varies from chronic iron-deficiency anaemia to heavy acute gastrointestinal bleeding. It is important to differentiate GAVE from portal hypertensive gastropathy as GAVE does not respond to measures reducing portal pressures. Endoscopic ablation (Nd:YAG-laser or argon plasma coagulation) is the first-line treatment of choice. As evidence for pharmacological therapy with oestrogen (and/or progesterone), tranexamic acid or thalidomide stems from case reports only, these should be used if endoscopic measures have failed to stop chronic blood loss. Surgical antrectomy should be reserved for unresponsive cases as it is associated with a high mortality. Ultimately, treatment of the underlying medical co-morbidities may lead to resolution of GAVE.

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.

Probiotic VSL#3 prevents antibiotic-associated diarrhoea in a double-blind, randomized, placebo- controlled clinical trial

BACKGROUND Antibiotic-associated diarrhoea (AAD) is a frequent complication of systemic antibiotic therapy and Clostridium difficile-associated diarrhoea (CDAD) is its most serious form due to associated morbidity and mortality. AIM This trial aimed to investigate whether the probiotic VSL#3 prevents AAD and CDAD in average-risk hospital patients. METHODS Adult hospital inpatients exposed to systemic antibiotics were recruited to this multicentre, randomized, double-blind, placebo-controlled trial. One sachet of VSL#3 or placebo was given twice daily for the length of the antibiotics course and for seven days thereafter. Primary outcomes were AAD and CDAD. FINDINGS Patients randomized to active (N = 117) and placebo (N = 112) groups were well-matched for baseline demographic patient data. No cases of CDAD were detected. The rate of AAD was significantly lower in the active group on per protocol analysis (0% active vs 11.4% placebo; P = 0.006). On intention-to-treat analysis the difference in AAD incidence (4.3% active vs 8.9% placebo; P = 0.19) was not significant. CONCLUSIONS VSL#3 is associated with a significant reduction in the incidence of AAD in average-risk hospital inpatients exposed to systemic antibiotics. As the incidence of CDAD has fallen sharply, no cases of CDAD were found. Probiotic administration as prophylaxis for CDAD may not be indicated in average-risk hospital patients.

Smoking prevalence and its influence on disease course and surgery in Crohn's disease and ulcerative colitis

Smoking demonstrates divergent effects in Crohns disease (CD) and ulcerative colitis (UC). Smoking frequency is greater in CD and deleterious to its disease course. Conversely, UC is primarily a disease of nonsmokers and ex‐smokers, with reports of disease amelioration in active smoking.

Patients' knowledge of pregnancy‐related issues in inflammatory bowel disease and validation of a novel assessment tool (‘CCPKnow’)

Inflammatory bowel diseases (IBD) require complex therapeutic decisions and life choices concerning pregnancy, but little is known about patients knowledge of IBD and its treatment before and during pregnancy.

Early Use of Thiopurines or Methotrexate Reduces Major Abdominal and Perianal Surgery in Crohnʼs Disease

Background:Earlier introduction of immunomodulators (IM) thiopurine or methotrexate is advocated to improve Crohns 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.

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 Crohns Colitis Association (CCA) membership status. Disease-related knowledge was assessed using the validated Crohns 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.

Cause-specific mortality and 30-year relative survival of Crohn's disease and ulcerative colitis.

Background:Data from the northern hemisphere suggest that patients with ulcerative colitis (UC) have similar survival to the general population, whereas mortality in Crohns disease (CD) is increased by up to 50%. There is a paucity of data from the southern hemisphere, especially in Australia. Methods:A prevalence cohort (1977–1992) of patients with inflammatory bowel disease (IBD) diagnosed after 1970 was studied. Survival status data and causes of death up to December 2010 were extracted from the National Death Index. Relative survival analysis was carried out separately for men and women. Results:Of 816 cases (384 men, 432 women; 373 CD, 401 UC, 42 indeterminate colitis), 211 (25.9%) had died by December 2010. Median follow-up was 22.2 years. Relative survival of all patients with IBD was not significantly different from the general population at 10, 20, and 30 years of follow-up. Separate analyses of survival in CD and UC also showed no differences from the general population. There was no difference in survival between patients diagnosed earlier (1971–1979) or later (1980–1992). At least 17% of the deaths were caused by IBD. Fatal cholangiocarcinomas were more common in IBD (P < 0.001), and fatal colorectal cancers more common in UC (P = 0.047). Conclusions:In Australia, IBD patient survival is similar to the general population. In contrast to data from Europe and North America, survival in CD is not diminished in Australia. IBD caused direct mortality in 17%, especially as biliary and colorectal cancers are significant causes of death.

Mortality from inflammatory bowel diseases

&NA; Ulcerative colitis (UC) and Crohns disease (CD) may directly result in morbidity and rarely mortality from complications such as colorectal cancer or sepsis. Mortality rates compared with the matched general population, measured by standardized mortality ratio, may therefore be increased. This review examines the evidence derived from cohort‐ and population‐based mortality studies. In CD the majority of studies and two meta‐analyses demonstrated increased standardized mortality ratios of ≈1.5‐fold, especially for those diagnosed at younger ages and requiring extensive or multiple resection surgery. In UC mortality rates are similar to those of the general population in most studies and a meta‐analysis. Proctocolectomy removes the inflammatory burden of UC and can manage colorectal dysplasia but may result in perioperative complications. There is no clear temporal trend of improvement in survival for either CD or UC. Few data are available from countries outside Europe and North America, so geographical influences remain largely unknown. (Inflamm Bowel Dis 2012)

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 Crohns 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.