[Show abstract][Hide abstract] ABSTRACT: CCX282-B, also called vercirnon, is a specific, orally-administered chemokine receptor CCR9 antagonist that regulates migration and activation of inflammatory cells in the intestine. This randomized, placebo-controlled trial was conducted to evaluate the safety and efficacy of CCX282-B in 436 patients with Crohn's disease. Crohn's Disease Activity Index (CDAI) scores were 250-450 and C-reactive protein >7.5 mg/L at study entry. In addition to stable concomitant Crohn's medication (85% of subjects), subjects received placebo or CCX282-B (250 mg once daily, 250 mg twice daily, or 500 mg once daily) for 12 weeks. They then received 250 mg CCX282-B twice daily, open-label, through week 16. Subjects who had a clinical response (a ≥70 point drop in CDAI) at week 16 were randomly assigned to groups given placebo or CCX282-B (250 mg, twice daily) for 36 weeks. Primary endpoints were clinical response at Week 8 and sustained clinical response at Week 52. During the 12-week Induction period, the clinical response was highest in the group given 500 mg CCX282-B once daily. Response rates at week 8 were 49% in the placebo group, 52% in the group given CCX282-B 250 mg once daily (odds ratio [OR] = 1.12; p = .667 vs placebo), 48% in the group given CCX282-B 250 mg twice daily (OR = 0.95; p = .833), and 60% in the group given CCX282-B 500 mg once daily (OR = 1.53; p = .111). At week 12, response rates were 47%, 56% (OR = 1.44; p = .168), 49% (OR = 1.07; p = .792), and 61% (OR = 1.74; p = .039), respectively. At the end of the Maintenance period (week 52), 47% of subjects on CCX282-B were in remission, compared to 31% on placebo (OR = 2.01; p = .012); 46% showed sustained clinical responses, compared to 42% on placebo (OR = 1.14; p = .629). CCX282-B was well tolerated. Encouraging results from this clinical trial led to initiation of Phase 3 clinical trials in Crohn's disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT00306215.
[Show abstract][Hide abstract] ABSTRACT: Background and objectives:
The aim of this study is to report the incidence of Clostridium difficile-associated disease (CDAD) in a tertiary-care hospital in South Africa and to identify risk factors, assess patient outcomes and determine the impact of the hypervirulent strain of the organism referred to as North American pulsed-field type 1 (NAP1).
Adults who presented with diarrhoea over a period of 15 months were prospectively evaluated for CDAD using stool toxin enzyme immunoassay (EIA). Positive specimens were evaluated by PCR. Patient demographics, laboratory parameters and outcomes were analysed.
CDAD was diagnosed in 59 (9.2%) of 643 patients (median age 39 years, IQR 30 - 55). Thirty-four (58%) were female. Recent antibiotic exposure was reported in 39 (66%), 27 (46%) had been hospitalised within 3 months, and 14 (24%) had concomitant inflammatory bowel disease (IBD). Nineteen (32%) had community-acquired CDAD (CA-CDAD). The annual incidence of hospital-acquired CDAD (HA-CDAD) was 8.7 cases/10 000 hospitalisations. Two cases of the hypervirulent strain NAP1 were identified. Seven (12%) patients underwent colectomy (OR 6.83; 95% CI 2.41 - 19.3). On logistic regression, only antibiotic exposure independently predicted for CDAD (OR 2.9; 95% CI 1.6 - 5.1). Three (16%) cases of CA-CDAD reported antibiotic exposure (v. 90% of HA-CDAD, p<0.0001). Twelve (86%) patients had concomitant IBD (p<0.0001 v. HA-CDAD). CA-CDAD was significantly associated with antibiotic exposure (OR 0.04, 95% CI 0.01 - 0.24) and IBD (OR 9.6, 95% CI 1.15 - 79.8).
The incidence of HA-CDAD in the South African setting is far lower than that reported in the West. While antibiotic use was a major risk factor for HA-CDAD, CA-CDAD was not associated with antibiotic therapy. Concurrent IBD was a predictor of CA-CDAD.
Full-text · Article · Mar 2013 · South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde
[Show abstract][Hide abstract] ABSTRACT: Background. Potent immunosuppressive therapy is standard treatment for inflammatory bowel disease (IBD) but carries a risk of reactivating latent tuberculosis (TB). No data exist on the burden of TB in South African patients with IBD. Objective. To evaluate the burden of TB in IBD patients attending a large tertiary IBD clinic. Methods. A retrospective analysis was performed on data pertaining to patients attending the Groote Schuur Hospital IBD clinic. Data were extracted from an existing IBD database, patient notes, the National Health Laboratory Services database and chest X-ray analysis. Results. Of 614 patients, 72 (11.7%) were diagnosed with TB; 40 (55.6%) developed TB prior to the diagnosis of IBD. On regression analysis, coloured IBD patients were at increased risk for TB development (p=0.004, odds ratio (OR) 3.57, 95% confidence interval (CI) 1.49 - 8.56), as were patients with extensive Crohn's disease (CD) compared with those with less extensive disease (p=0.001,OR 2.84, 95% CI 1.27 - 6.33). No other risk factors, including the use of immunosuppressive agents, were identified for the development of TB. Conclusions. Of over 600 patients, 12% had TB either before or after IBD diagnosis. The high rate of previous TB and positive association with ethnicity probably reflects the high burden of TB in a socio-economically disadvantaged community. We recommend that IBD patients should be screened actively and monitored for TB when immunosuppressive medications are used.
No preview · Article · Oct 2012 · South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde
[Show abstract][Hide abstract] ABSTRACT: Intestinal tuberculosis occurs mainly in the terminal ileum and caecum, where the concentration of bile acids is lowest, and rarely in the upper digestive tract.
We examined the effect of physiological concentrations of bile acids on the in vitro growth of Mycobacterium tuberculosis (MTB).
The 4 major bile acids, lithocolic acid, cholic acid, deoxycholic acid and chenodeoxycholic acid, were added to individual Lowenstein-Jensen (LJ) culture media at physiological concentrations. A combined LJ medium was also prepared using all 4 bile acids. These were double-diluted 4 times by the addition of LJ media. Each culture medium was inoculated with the H37Rv strain of MTB and incubated at 37°C for 8 weeks. MTB growth was measured at 2 and 8 weeks in a semiquantitative fashion using cut-offs of >5, >10, >20, >100 colony-forming units.
All lithocolic acid cultures showed uninhibited TB growth at 2 and 8 weeks. Chenodeoxycholic acid, deoxycholic acid and cholic acid alone, and in combination, showed concentration-dependent inhibition of MTB growth at 2 and 8 weeks. Four cultures were lost to contamination.
Certain bile acids alone and in combination, at physiological concentrations, inhibit the growth of MTB in vitro. This might explain why intestinal TB occurs in the ileocaecum in the majority of cases and why gallbladder TB is very rare.
No preview · Article · Jun 2012 · South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde
[Show abstract][Hide abstract] ABSTRACT: Chronic pancreatitis (CP) is defined as a continuing inflammatory disease of the pancreas characterised by irreversible morphological changes, often associated with pain and with the loss of exocrine and/or endocrine function that may be clinically relevant. Alcohol is the predominant cause of CP in the western world and is particularly prevalent in South Africa, especially in the indigent patient. CP ranks high among intractable diseases of the gastrointestinal tract. The tendency for substance abuse in the alcohol-induced group poses major psychological and socio-economic problems.
CP is a disease with significant clinical and pathological heterogeneity. Level 1 evidence to support definitive guidelines for diagnosis, medical management and interventional therapy is lacking. Despite this paucity of robust scientific evidence, it is important to provide some assistance based on the best available evidence as to the current standard of care for CP in the South African context; this will aid all involved in the management of the disease, and includes clinicians, health care managers and funders.
The guidelines were developed as recommendations addressing the diagnosis, medical management and interventions, both endoscopic and surgical, for the management of a very complex and heterogeneous disease of the pancreas. The recommendations are particularly relevant in the South African context where the predominant patho-aetiological agents are alcohol-associated with smoking.
The guidelines provide clear recommendations regarding the diagnostic modalities available, both imaging (which includes MRI and endoscopic ultrasound (EUS)) and pancreatic function tests. The section on medical management makes recommendations on the use of analgesics, enzyme replacement and other therapeutic options in the non-interventional management of the majority of patients with CP. The section on interventional procedures identifies the indications and options available for the interventional management of both uncomplicated and complicated CP. The role of endoscopic and surgical modalities is defined, but it is in this context especially that the best available evidence, combined with the experience of the group, influenced the recommendations put forward. Owing to the lack of evidence and the complexity of the disease, it is recommended that, where possible, CP is managed in the context of a multidisciplinary team.
The guidelines are based on best practice principles determined by the available evidence and the opinions of the group, which comprised 7 medical and surgical gastroenterologists with significant experience in dealing with patients with chronic pancreatitis in the South African context. The group convened between May 2009 and August 2010 under the auspices of the Hepato-Pancreatico-Biliary Association of South Africa (HPBASA) and the South African Gastroenterology Society (SAGES), and the guidelines are the result of broad consensus within this group. The draft was presented to other experts in this field of endeavour to ensure broader participation and consensus. PLANS FOR GUIDELINE REVISION: HPBASA and SAGES will publish a revised modification of the recommendations when new levels 1 and 2 evidence data are published.
No preview · Article · Dec 2010 · South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde
[Show abstract][Hide abstract] ABSTRACT: The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability, reimbursement guidelines, and patient preferences guide the choice of first-line biological therapy for luminal Crohn's disease (CD). Infliximab (IFX) has the most extensive clinical trial data, but other biological agents (adalimumab (ADA), certolizumab pegol (CZP), and natalizumab (NAT)) appear to have similar benefits in CD. Steroid-refractory, steroid-dependent, or complex fistulizing CD are indications for starting biological therapy, after surgical drainage of any sepsis. For fistulizing CD, the efficacy of IFX for inducing fistula closure is best documented. Unique risks of NAT account for its labeling as a second-line biological agent in some countries. Patients who respond to induction therapy benefit from systematic re-treatment. The combination of IFX with azathioprine is better than monotherapy for induction of remission and mucosal healing up to 1 year in patients who are naïve to both agents. Whether this applies to other agents remains unknown. IFX is also effective for treatment-refractory, moderate, or severely active ulcerative colitis. Patients who have a diminished or loss of response to anti-tumor necrosis factor (TNF) therapy may respond to dose adjustment of the same agent or switching to another agent. Careful consideration should be given to the reasons for loss of response. There are insufficient data to make recommendations on when to stop anti-TNF therapy. Preliminary evidence suggests that a substantial proportion of patients in clinical remission for >1 year, without signs of active inflammation can remain in remission after stopping treatment.
Full-text · Article · Nov 2010 · The American Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Arthritis and arthralgia are the most common extra-intestinal manifestations of Inflammatory Bowel Disease (IBD), occurring in up to a third of patients. These may affect the peripheral or axial skeletal system and may or may not reflect disease activity. As a result, it is challenging to identify an alternative diagnosis to account for joint manifestations in the setting of IBD.
We describe a case of a 30 year old woman with quiescent Crohn's colitis who presented with 2 weeks of fever, flitting arthralgia, a sore throat and a nocturnal rash on her thighs. She denied any gastrointestinal symptoms to suggest a flare up of IBD. Investigations revealed a neutrophilia and a markedly elevated serum ferritin. The patient met all four major and several minor Yamaguchi criteria for Adult Onset Still's Disease (AOSD). She was treated with corticosteroids and analgesia with resolution of her symptoms and normalisation of her biochemical markers.
While joint manifestations are the most common extra-intestinal symptoms of Inflammatory Bowel Disease, atypical presentations should raise the concern of an additional diagnosis. This case represents a rare presentation of Crohn's disease complicated by AOSD.
No preview · Article · Oct 2010 · Journal of Crohn s and Colitis
[Show abstract][Hide abstract] ABSTRACT: The watery diarrhoea, hypokalaemia and achlorhydria syndrome is a rare cause of secretory diarrhoea. In this case report, we highlight a young female with watery diarrhoea, hypokalaemia and achlorhydria syndrome as a consequence of a vasoactive intestinal peptide producing composite adrenal phaeochromocytoma-ganglioneuroma. She made a complete recovery after curative surgical resection.
No preview · Article · Mar 2010 · European journal of gastroenterology & hepatology
[Show abstract][Hide abstract] ABSTRACT: While disorders such as gastro-oesophageal reflux disease, gastrointestinal (GI) cancers and inflammatory bowel disease are prevalent among all racial groups in the Western Cape, there is little knowledge of local GI service provision. The state of equipment, facilities and staffing is largely unrecorded and to date unknown. The aim of this study was to audit the availability of GI facilities in the provincial sector, which provides care for the majority of people in the Western Cape.
All hospitals in the Western Cape providing endoscopy were evaluated by means of a hands-on audit, to identify available organisational infrastructure. Data including staffing, details and utilisation of existing equipment, maintenance and disinfection techniques and delays in service provision were collected.
Over a period of 12 months, 17 Western Cape hospitals were visited: 3 tertiary, 5 regional and 9 district-level institutions. There are currently 89 GI endoscopes in state service, with an average age of 6.1 years (range 1-23 years). While most institutions utilise video endoscopy, in many instances equipment is near the end of its economic life. A total of 26,434 endoscopic procedures were performed over a 12-month period. Overall at least 60% of all adult endoscopy was undertaken at tertiary institutions. The mean delay from consultation until gastroscopy or colonoscopy was 9.25 weeks (range 0.5-28 weeks) and 8 weeks (range 1-20 weeks), respectively. Only 1 tertiary and 1 regional hospital employed fully trained, registered nurses, and the majority of institutions did not conform to internationally accepted standards for the maintenance and disinfection of endoscopic equipment.
While endoscopy equipment is widely distributed throughout the province, it is evident from this study that services in the Western Cape fall short of international standards, with delays in endoscopic provision, lack of adequate equipment, inadequate scope maintenance and disinfection and a shortage of trained staff. As such, much of the population reliant on state facilities has poor access to GI health care. These deficiencies need to be addressed.
Preview · Article · Sep 2008 · South African journal of surgery. Suid-Afrikaanse tydskrif vir chirurgie
[Show abstract][Hide abstract] ABSTRACT: The rapid urease test (RUT) is used at Groote Schuur Hospital for diagnosing Helicobacter pylori infection. This is an in-house method, which has not been validated.
To validate our practice of reading the RUT immediately after endoscopy (RUT(0)), by comparing this with a reading at 24 hours (RUT(24)) and with histological analysis.
Ninety consecutive patients undergoing upper endoscopy over a 6-week period from October 2005 to November 2005, and in whom rapid urease testing was indicated, were included in the study. Patients with recent exposure (within 2 weeks of endoscopy) to proton pump inhibitors (PPIs), histamine receptor antagonists (H2RAs) and antibiotics (confounders) were noted and included in the cohort. Two antral and two body biopsies were taken for histological examination and a third antral biopsy was placed in the RUT bottle. Both haematoxylin and eosin and modified Giemsa staining methods were used to identify H. pylori. The RUT was read immediately (within 5 minutes of upper endoscopy) (RUT(0)), as per our current practice, and each specimen was re-read at 24 hours (RUT(24)). Sensitivity, specificity, positive and negative predictive values and the impact of confounders were calculated.
Of the 90 patients undergoing rapid urease testing, 39% were male and 61% were female, with a mean age of 55 years (range 22-79 years). Histological examination revealed H. pylori in 67.8% (N=61) of the biopsy specimens. In the 65 patients without confounders, the sensitivity and specificity of the RUT(0) were 65.9% and 100% respectively, and 90.9% and 100% for RUT(24). After including the 25 patients with confounders, the sensitivity and specificity were 68.8% and 100% for RUT(0), and 90.1% and 100% for RUT(24) respectively. Thirteen RUT(0) specimens (30.9%) that were initially negative became positive at the RUT(24) reading. There were 6 (9.8%) RUT(0)- and RUT(24)-negative but histology-positive specimens. Four of these 6 false-negative RUT(24) results could be accounted for by a low H. pylori density on histological analysis (2 patients were taking PPIs). Confounders did not alter the sensitivity and specificity outcomes or impact on the number of false-negative RUTs.
Our locally prepared RUT is a specific test for the detection of H. pylori infection. The sensitivity is greatly enhanced by reading the test at 24 hours. The use of PPIs, H(2)RAs and antibiotics preceding endoscopy did not impact significantly on the results.
Preview · Article · Jan 2008 · South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde
[Show abstract][Hide abstract] ABSTRACT: The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastroenterological disorders seen most often in patients. Published with practicing clinicians in mind, the journal aims to be easily accessible, organizing its content by topic, both online and in print. www.amjgastro.com, *2007 Journal Citation Report (Thomson Reuters, 2008)
Full-text · Article · Aug 2007 · The American Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Distinguishing Crohn's disease from intestinal tuberculosis in endemic areas is challenging as both conditions have overlapping clinical, radiological, endoscopic and histological characteristics. Furthermore, high rates of latent tuberculosis confer a considerable risk of reactivation once therapy for established Crohn's disease is started.
To review current strategies in differentiating these two conditions, and in managing Crohn's disease, in populations with high rates of tuberculosis.
Literature review and clinical experience.
While various clinical, radiological, endoscopic and histological parameters may aid in differentiating Crohn's disease from intestinal tuberculosis, these remain imperfect and as treatment options differ misdiagnosis has grave consequences. We propose a diagnostic algorithm, based on currently available evidence and experience, to aid in this dilemma. We also discuss approaches to the management of Crohn's disease, including agents targeting tumour necrosis factor-alpha, in patients at risk of developing tuberculosis.
A diagnosis of Crohn's disease in individuals at risk for tuberculosis should only be made after careful interpretation of clinical signs, abdominal imaging and systematic endoscopic and histological assessment. Newer techniques for the diagnosis of latent tuberculosis still need to be validated in this environment, and guidelines on the treatment of latent tuberculosis in this setting require clarification.
[Show abstract][Hide abstract] ABSTRACT: The histological differential diagnosis of Crohn's disease and intestinal tuberculosis can be very challenging, as both are chronic granulomatous disorders with overlapping histological features.
To evaluate selected clinical and histological parameters in colonic biopsy specimens for their ability to discriminate between Crohn's disease and intestinal tuberculosis.
25 patients with Crohn's disease and 18 patients with intestinal tuberculosis were selected for this study on the basis of established clinical, radiological and histological criteria. Clinical data and selected histological parameters in colonoscopic biopsy specimens were assessed retrospectively. A total of 103 and 41 biopsy sites were evaluated in patients with Crohn's disease and intestinal tuberculosis, respectively.
Clinical parameters helpful in differentiating intestinal tuberculosis from Crohn's disease included chest radiographic features of tuberculosis (56% v 0%), perianal fistulae (0% v 40%) and extraintestinal manifestations of Crohn's disease (0% v 40%). Histopathological features that seemed to reliably differentiate between intestinal tuberculosis and Crohn's disease included confluent granulomas, > or =10 granulomas per biopsy site and caseous necrosis (in biopsy samples of 50%, 33% and 22% of patients with intestinal tuberculosis, respectively, v 0% of patients with Crohn's disease). Features that were observed more often in patients with intestinal tuberculosis than in those with Crohn's disease included granulomas exceeding 0.05 mm(2) (67% v 8%), ulcers lined by conglomerate epithelioid histiocytes (61% v 8%) and disproportionate submucosal inflammation (67% v 10%).
Clinical features and selected histological parameters in colonoscopic biopsy specimens can help in differentiating between Crohn's disease and intestinal tuberculosis.
Full-text · Article · Aug 2006 · Journal of Clinical Pathology