Richard Gearry - Academia.edu (original) (raw)
Papers by Richard Gearry
Nutrition Research, 2015
The worldwide growth in the incidence of gastrointestinal disorders has created an immediate need... more The worldwide growth in the incidence of gastrointestinal disorders has created an immediate need to identify safe and effective interventions. In this randomized, doubleblind, placebo-controlled study, we examined the effects of Actazin and Gold, kiwifruitderived nutritional ingredients, on stool frequency, stool form, and gastrointestinal comfort in healthy and functionally constipated (Rome III criteria for C3 functional constipation) individuals. Using a crossover design, all participants consumed all 4 dietary interventions (Placebo, Actazin low dose [Actazin-L] [600 mg/day], Actazin high dose [Actazin-H] [2400 mg/day], and Gold [2400 mg/day]). Each intervention was taken for 28 days followed by a 14day washout period between interventions. Participants recorded their daily bowel movements and well-being parameters in daily questionnaires. In the healthy cohort (n = 19), the Actazin-H (P = .014) and Gold (P = .009) interventions significantly increased the mean daily bowel movements compared with the washout. No significant differences were observed in stool form as determined by use of the Bristol stool scale. In a subgroup analysis of responders in the healthy cohort, Actazin-L (P = .005), Actazin-H (P < .001), and Gold (P = .001) consumption significantly increased the number of daily bowel movements by greater than 1 bowel movement per week. In the functionally constipated cohort (n = 9), there were no significant differences between interventions for bowel movements and the Bristol stool scale values or in the subsequent subgroup analysis of responders. This study demonstrated that Actazin and Gold produced clinically meaningful increases in bowel movements in healthy individuals.
Arab Journal of Gastroenterology, 2009
The human gut harbors dense and diverse microbial communities which have an impact on host's heal... more The human gut harbors dense and diverse microbial communities which have an impact on host's health. The symbiotic relationship between gut microbial communities and host can be optimized by pharmacological or nutritional intervention on the intestinal ecosystem using probiotics or prebiotics. Worldwide research on the use of prebiotics and probiotics in human and animal health has accelerated in recent years. However, there is lack of information about the practical use of probiotics and prebiotics in Medicine. A major area for medical applications has been the prevention or treatment of gastrointestinal diseases. Recently, a group of international experts appointed by the World Gastroenterology Organization prepared a practical guideline on the current indications of probiotics and prebiotics in Gastroenterology. The full text of the guideline is published in the current issue of our Journal. The document underscores strain-specificity of the clinical effects, and provides precise information on which specific probiotic strains or prebiotic compounds are useful for what particular clinical indications (see ).
Clinical Gastroenterology and Hepatology, 2014
Crohn&amp;amp;amp;#39;s disease (CD) and ulcerative colitis (UC) are chronic immunologica... more Crohn&amp;amp;amp;#39;s disease (CD) and ulcerative colitis (UC) are chronic immunologically mediated diseases that often have a relapsing-remitting course in young persons. Genetic-risk polymorphisms explain less than one third of the heritability of disease. Epidemiologic and laboratory data suggest that environmental factors play a significant role in influencing the risk and natural history of disease. Smoking is the most widely and consistently described risk factor. It, however, increases the risk of CD while conferring protection against UC. The gut microbiome is a key component in the development of inflammatory bowel disease (IBD). Several external factors potentially exert an effect by influencing the composition of the gut microbiome or disrupting the intestinal barrier. These external influences include the use of antibiotics or nonsteroidal anti-inflammatory drugs and the presence of enteric infections. Data on diet have been inconsistent, but high fiber intake, particularly of soluble fiber, appears to protect against CD, whereas protein intake may increase disease risk. Vitamin D may also play an important protective role, particularly in patients with CD. Neurobehavioral factors, such as stress and depression, also influence the risk of IBD. Systematic and rigorous studies of environmental exposures in the management of IBD are needed. In particular, studies of whether environmental factors can be modified to reduce the likelihood of relapse or improve patient outcomes would be valuable.
Lancet, Jan 23, 2014
Most patients with Crohn's disease need an intestinal resection, but a majority will subseque... more Most patients with Crohn's disease need an intestinal resection, but a majority will subsequently experience disease recurrence and require further surgery. This study aimed to identify the optimal strategy to prevent postoperative disease recurrence. In this randomised trial, consecutive patients from 17 centres in Australia and New Zealand undergoing intestinal resection of all macroscopic Crohn's disease, with an endoscopically accessible anastomosis, received 3 months of metronidazole therapy. Patients at high risk of recurrence also received a thiopurine, or adalimumab if they were intolerant to thiopurines. Patients were randomly assigned to parallel groups: colonoscopy at 6 months (active care) or no colonoscopy (standard care). We used computer-generated block randomisation to allocate patients in each centre to active or standard care in a 2:1 ratio. For endoscopic recurrence (Rutgeerts score ≥i2) at 6 months, patients stepped-up to thiopurine, fortnightly adalimuma...
Journal of Crohn's & colitis, Jan 8, 2015
Patients with Crohn's disease have poorer health related quality of life (HRQoL) than healthy... more Patients with Crohn's disease have poorer health related quality of life (HRQoL) than healthy individuals, even when in remission. Although HRQoL improves in patients who achieve drug induced or surgically induced remission, the effects of surgery overall have not been well characterised. In a randomised trial patients undergoing intestinal resection of all macroscopically diseased bowel were treated with post-operative drug therapy to prevent disease recurrence. All patients were followed prospectively for 18 months. CRP, CDAI and faecal calprotectin (FC) were measured pre-operatively and at 6, 12 and 18 months. HRQoL was assessed with a general (SF36) and disease-specific (IBDQ) questionnaires at the same time points. 174 patients were included. HRQoL was poor pre-operatively but improved significantly (p<0.001) at 6 months post-operatively. This improvement was sustained at 18 months. Females and smokers had a poorer HRQoL when compared to males and non-smokers respectivel...
Hepatology International, 2013
The etiology of autoimmune hepatitis (AIH) likely involves a complex interaction of genetic and e... more The etiology of autoimmune hepatitis (AIH) likely involves a complex interaction of genetic and environmental factors. We aim to investigate the associations between exposure to putative environmental factors and AIH and to quantify AIH risk in a first-degree relative. We conducted a population-based case-control study. Cases were AIH patients who were alive and resided in Canterbury, New Zealand, between 1 July 2011 and 30 June 2012. Controls were randomly selected from the Electoral Roll and were matched 2:1 to each case by age and gender. Self-reporting questionnaires that cover lifestyle factors, childhood factors and family history were used. 72 AIH cases and 144 controls were included. We found that exposure to antibiotics within 12 months prior to AIH diagnosis (OR 12.98, 95 % CI 2.49-67.67, p &amp;lt; 0.01) was an independent risk factor for the development of AIH. Alcohol consumption (OR 0.43, 95 % CI 0.28-0.68, p &amp;lt; 0.01) and childhood home with wood heating (OR 0.30, 95 % CI 0.14-0.63, p &amp;lt; 0.01) were independently associated with reduced risks of later development of AIH. The crude risk of AIH in first-degree relatives of a patient with AIH was 0.2 % (95 % CI &amp;lt;0.1-2.0). We found that antibiotics are an independent risk factor for the development of AIH, whereas alcohol consumption and living in a childhood home with wood heating are independent protective factors against the later development of AIH.
Hepatology International, 2011
Epidemiological data on primary biliary cirrhosis (PBC) in the Southern Hemisphere is scarce. Our... more Epidemiological data on primary biliary cirrhosis (PBC) in the Southern Hemisphere is scarce. Our aim was to perform a population-based epidemiological study of PBC in Canterbury, New Zealand. Multiple case-finding methods were employed. All public and private, adult and pediatric outpatient clinics, hospital discharge summaries, and laboratory and pathology reports were searched to identify all cases in the region. Cases were included if at least two of the following criteria were fulfilled: (1) positive anti-mitochondrial antibodies, (2) elevated alkaline phosphatase for greater than 6 months, and (3) compatible liver histology. A total of 71 cases of PBC were included. The incidence in 2008 was 0.8 (95% confidence interval (CI) 0.1-1.6) per 100,000. The point prevalence on December 31, 2008 was 9.9 (95% CI 7.1-12.7) per 100,000. Male to female ratio was 1:11. At presentation, 45% were asymptomatic. Age at diagnosis peaked at the seventh decade with mean age at diagnosis of 61 (95% CI 58-64). This is the first population-based epidemiological study of PBC conducted in New Zealand and only the second in the Southern Hemisphere. The incidence and prevalence are lower than the Northern Hemisphere, even though the majority of our population has shared genetic background with some of these countries. Our study has provided further support to the hypothesis that there may be a protective effect or lack of a risk factor for PBC in New Zealand.
Inflammatory Bowel Diseases, 2015
In the current management paradigm, mucosal healing is preferred over clinical remission as a the... more In the current management paradigm, mucosal healing is preferred over clinical remission as a therapeutic end point in inflammatory bowel disease (IBD) because of the benefits engendered with respect to durability of remission. Colonoscopy, however, is not suitable for regular disease monitoring, and routine clinical assessment is often inaccurate with respect to endoscopic disease activity. The current investigation set out to characterize the relationship that exists between endoscopically determined IBD activity and clinical and biochemical measures of disease severity and to determine clinically useful thresholds for use in clinical practice. Patients attending for colonoscopy with known or suspected IBD were recruited. Clinical disease activity was recorded as per the Harvey-Bradshaw Index for Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease or the simple clinical colitis activity index for ulcerative colitis. Endoscopic activity was recorded using the simple endoscopic score for Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease or the modified Baron score for ulcerative colitis. Receiver operating characteristic analysis determined the predictive value and optimal predictive thresholds for clinical and biomarker data. The Harvey-Bradshaw Index was not able to distinguish active from inactive Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. The sensitivity, specificity, and positive and negative predictive values of simple clinical colitis activity index to detect endoscopic active disease were 43%, 96%, 94%, and 51%, respectively. Any elevation of C-reactive protein or fecal calprotectin was predictive of active mucosal disease, however, no lower threshold could be identified that predicted disease in remission. C-reactive protein and fecal calprotectin are useful for the identification of endoscopically active IBD, but normal results do not confirm endoscopic remission.
Journal of Gastrointestinal Surgery, 2013
Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp... more Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (CD) is an inflammatory bowel disease (IBD) caused by a combination of genetic, clinical, and environmental factors. Identification of CD patients at high risk of requiring surgery may assist clinicians to decide on a top-down or step-up treatment approach. We conducted a retrospective case-control analysis of a population-based cohort of 503 CD patients. A regression-based data reduction approach was used to systematically analyse 63 genomic, clinical and environmental factors for association with IBD-related surgery as the primary outcome variable. A multi-factor model was identified that yielded the highest predictive accuracy for need for surgery. The factors included in the model were the NOD2 genotype (OR = 1.607, P = 2.3 × 10(-5)), having ever had perianal disease (OR = 2.847, P = 4 × 10(-6)), being post-diagnosis smokers (OR = 6.312, P = 7.4 × 10(-3)), being an ex-smoker at diagnosis (OR = 2.405, P = 1.1 × 10(-3)) and age (OR = 1.012, P = 4.4 × 10(-3)). Diagnostic testing for this multi-factor model produced an area under the curve of 0.681 (P = 1 × 10(-4)) and an odds ratio of 3.169, (95% CI P = 1 × 10(-4)) which was higher than any factor considered independently. The results of this study require validation in other populations but represent a step forward in the development of more accurate prognostic tests for clinicians to prescribe the most optimal treatment approach for complicated CD patients.
Inflammatory Bowel Diseases, 2015
In the current management paradigm, mucosal healing is preferred over clinical remission as a the... more In the current management paradigm, mucosal healing is preferred over clinical remission as a therapeutic end point in inflammatory bowel disease (IBD) because of the benefits engendered with respect to durability of remission. Colonoscopy, however, is not suitable for regular disease monitoring, and routine clinical assessment is often inaccurate with respect to endoscopic disease activity. The current investigation set out to characterize the relationship that exists between endoscopically determined IBD activity and clinical and biochemical measures of disease severity and to determine clinically useful thresholds for use in clinical practice. Patients attending for colonoscopy with known or suspected IBD were recruited. Clinical disease activity was recorded as per the Harvey-Bradshaw Index for Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease or the simple clinical colitis activity index for ulcerative colitis. Endoscopic activity was recorded using the simple endoscopic score for Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease or the modified Baron score for ulcerative colitis. Receiver operating characteristic analysis determined the predictive value and optimal predictive thresholds for clinical and biomarker data. The Harvey-Bradshaw Index was not able to distinguish active from inactive Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. The sensitivity, specificity, and positive and negative predictive values of simple clinical colitis activity index to detect endoscopic active disease were 43%, 96%, 94%, and 51%, respectively. Any elevation of C-reactive protein or fecal calprotectin was predictive of active mucosal disease, however, no lower threshold could be identified that predicted disease in remission. C-reactive protein and fecal calprotectin are useful for the identification of endoscopically active IBD, but normal results do not confirm endoscopic remission.
Gastroenterology, Jan 22, 2015
Crohn's disease (CD) usually recurs after intestinal resection; post-operative endoscopic mon... more Crohn's disease (CD) usually recurs after intestinal resection; post-operative endoscopic monitoring and tailored treatment can reduce chance of recurrence. We investigated whether monitoring levels of fecal calprotectin (FC) can substitute for endoscopic analysis of the mucosa. We analyzed data collected from 135 participants in a prospective, randomized, controlled trial, performed at 17 hospitals in Australia and 1 in New Zealand, that assessed the ability of endoscopic evaluations and step-up treatment to prevent CD recurrence after surgery. Levels of FC, serum levels of c-reactive protein (CRP), and Crohn's disease activity index (CDAI) scores were measured before surgery and then 6, 12, and 18 months after resection of all macroscopic Crohn's disease. Ileo-colonoscopies were performed at 6 months after surgery in 90 patients and 18 months after surgery in all patients. Levels of FC were measured in 319 samples from 135 patients. The median FC decreased from 1347 μg...
World journal of gastroenterology, Jan 28, 2015
To review the published literature concerning the accuracy of faecal inflammatory markers for ide... more To review the published literature concerning the accuracy of faecal inflammatory markers for identifying mucosal healing. Bibliographical searches were performed in MEDLINE electronic database up to February 2015, using the following terms: "inflammatory bowel disease", "Crohn´s disease", "ulcerative colitis", "faecal markers", "calprotectin", "lactoferrin", "S100A12", "endoscop*", "mucosal healing", "remission". In addition, relevant references from these studies were also included. Data were extracted from the published papers including odds ratios with 95%CI, P values and correlation coefficients. Data were grouped together according to each faecal marker, Crohn's disease or ulcerative colitis, and paediatric compared with adult study populations. Studies included in this review assessed mucosal inflammation by endoscopic and/or histological means and compared these findings t...
Lancet (London, England), Jan 16, 2015
Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease;... more Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34 819 patients (19 713 with Crohn's disease, 14 683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype-phenotype associations across 156 154 genetic variants. We generated genetic risk scores by combining informat...
The New Zealand medical journal, Jan 24, 2003
Free radical biology & medicine, Jan 22, 2015
Calprotectin provides nutritional immunity by sequestering manganese and zinc ions. It is abundan... more Calprotectin provides nutritional immunity by sequestering manganese and zinc ions. It is abundant in the lungs of patients with cystic fibrosis but fails to prevent their recurrent infections. Calprotectin is a major protein of neutrophils and composed of two monomers, S100A8 and S100A9. We show that the ability of calprotectin to limit growth of Staphylococcus aureus and Pseudomonas aeruginosa is exquisitely sensitive to oxidation by hypochlorous acid. The N-terminal cysteine residue on S100A9 was highly susceptible to oxidation which resulted in cross-linking of the protein monomers. The N-terminal methionine of S100A8 was also readily oxidized by hypochlorous acid, forming both methionine sulfoxide and the unique product dehydromethionine. Isolated human neutrophils formed these modifications on calprotectin when their myeloperoxidase generated hypochlorous acid. Up to 90% of the N-terminal amine on S100A8 in bronchoalveolar lavage fluid from young children with cystic fibrosis ...
Journal of Crohn's & colitis, Jan 8, 2015
Patients with Crohn's disease have poorer health related quality of life (HRQoL) than healthy... more Patients with Crohn's disease have poorer health related quality of life (HRQoL) than healthy individuals, even when in remission. Although HRQoL improves in patients who achieve drug induced or surgically induced remission, the effects of surgery overall have not been well characterised. In a randomised trial patients undergoing intestinal resection of all macroscopically diseased bowel were treated with post-operative drug therapy to prevent disease recurrence. All patients were followed prospectively for 18 months. CRP, CDAI and faecal calprotectin (FC) were measured pre-operatively and at 6, 12 and 18 months. HRQoL was assessed with a general (SF36) and disease-specific (IBDQ) questionnaires at the same time points. 174 patients were included. HRQoL was poor pre-operatively but improved significantly (p<0.001) at 6 months post-operatively. This improvement was sustained at 18 months. Females and smokers had a poorer HRQoL when compared to males and non-smokers respectivel...
The New Zealand medical journal, Jan 6, 2005
Nutrition Research, 2015
The worldwide growth in the incidence of gastrointestinal disorders has created an immediate need... more The worldwide growth in the incidence of gastrointestinal disorders has created an immediate need to identify safe and effective interventions. In this randomized, doubleblind, placebo-controlled study, we examined the effects of Actazin and Gold, kiwifruitderived nutritional ingredients, on stool frequency, stool form, and gastrointestinal comfort in healthy and functionally constipated (Rome III criteria for C3 functional constipation) individuals. Using a crossover design, all participants consumed all 4 dietary interventions (Placebo, Actazin low dose [Actazin-L] [600 mg/day], Actazin high dose [Actazin-H] [2400 mg/day], and Gold [2400 mg/day]). Each intervention was taken for 28 days followed by a 14day washout period between interventions. Participants recorded their daily bowel movements and well-being parameters in daily questionnaires. In the healthy cohort (n = 19), the Actazin-H (P = .014) and Gold (P = .009) interventions significantly increased the mean daily bowel movements compared with the washout. No significant differences were observed in stool form as determined by use of the Bristol stool scale. In a subgroup analysis of responders in the healthy cohort, Actazin-L (P = .005), Actazin-H (P < .001), and Gold (P = .001) consumption significantly increased the number of daily bowel movements by greater than 1 bowel movement per week. In the functionally constipated cohort (n = 9), there were no significant differences between interventions for bowel movements and the Bristol stool scale values or in the subsequent subgroup analysis of responders. This study demonstrated that Actazin and Gold produced clinically meaningful increases in bowel movements in healthy individuals.
Arab Journal of Gastroenterology, 2009
The human gut harbors dense and diverse microbial communities which have an impact on host's heal... more The human gut harbors dense and diverse microbial communities which have an impact on host's health. The symbiotic relationship between gut microbial communities and host can be optimized by pharmacological or nutritional intervention on the intestinal ecosystem using probiotics or prebiotics. Worldwide research on the use of prebiotics and probiotics in human and animal health has accelerated in recent years. However, there is lack of information about the practical use of probiotics and prebiotics in Medicine. A major area for medical applications has been the prevention or treatment of gastrointestinal diseases. Recently, a group of international experts appointed by the World Gastroenterology Organization prepared a practical guideline on the current indications of probiotics and prebiotics in Gastroenterology. The full text of the guideline is published in the current issue of our Journal. The document underscores strain-specificity of the clinical effects, and provides precise information on which specific probiotic strains or prebiotic compounds are useful for what particular clinical indications (see ).
Clinical Gastroenterology and Hepatology, 2014
Crohn&amp;amp;amp;#39;s disease (CD) and ulcerative colitis (UC) are chronic immunologica... more Crohn&amp;amp;amp;#39;s disease (CD) and ulcerative colitis (UC) are chronic immunologically mediated diseases that often have a relapsing-remitting course in young persons. Genetic-risk polymorphisms explain less than one third of the heritability of disease. Epidemiologic and laboratory data suggest that environmental factors play a significant role in influencing the risk and natural history of disease. Smoking is the most widely and consistently described risk factor. It, however, increases the risk of CD while conferring protection against UC. The gut microbiome is a key component in the development of inflammatory bowel disease (IBD). Several external factors potentially exert an effect by influencing the composition of the gut microbiome or disrupting the intestinal barrier. These external influences include the use of antibiotics or nonsteroidal anti-inflammatory drugs and the presence of enteric infections. Data on diet have been inconsistent, but high fiber intake, particularly of soluble fiber, appears to protect against CD, whereas protein intake may increase disease risk. Vitamin D may also play an important protective role, particularly in patients with CD. Neurobehavioral factors, such as stress and depression, also influence the risk of IBD. Systematic and rigorous studies of environmental exposures in the management of IBD are needed. In particular, studies of whether environmental factors can be modified to reduce the likelihood of relapse or improve patient outcomes would be valuable.
Lancet, Jan 23, 2014
Most patients with Crohn's disease need an intestinal resection, but a majority will subseque... more Most patients with Crohn's disease need an intestinal resection, but a majority will subsequently experience disease recurrence and require further surgery. This study aimed to identify the optimal strategy to prevent postoperative disease recurrence. In this randomised trial, consecutive patients from 17 centres in Australia and New Zealand undergoing intestinal resection of all macroscopic Crohn's disease, with an endoscopically accessible anastomosis, received 3 months of metronidazole therapy. Patients at high risk of recurrence also received a thiopurine, or adalimumab if they were intolerant to thiopurines. Patients were randomly assigned to parallel groups: colonoscopy at 6 months (active care) or no colonoscopy (standard care). We used computer-generated block randomisation to allocate patients in each centre to active or standard care in a 2:1 ratio. For endoscopic recurrence (Rutgeerts score ≥i2) at 6 months, patients stepped-up to thiopurine, fortnightly adalimuma...
Journal of Crohn's & colitis, Jan 8, 2015
Patients with Crohn's disease have poorer health related quality of life (HRQoL) than healthy... more Patients with Crohn's disease have poorer health related quality of life (HRQoL) than healthy individuals, even when in remission. Although HRQoL improves in patients who achieve drug induced or surgically induced remission, the effects of surgery overall have not been well characterised. In a randomised trial patients undergoing intestinal resection of all macroscopically diseased bowel were treated with post-operative drug therapy to prevent disease recurrence. All patients were followed prospectively for 18 months. CRP, CDAI and faecal calprotectin (FC) were measured pre-operatively and at 6, 12 and 18 months. HRQoL was assessed with a general (SF36) and disease-specific (IBDQ) questionnaires at the same time points. 174 patients were included. HRQoL was poor pre-operatively but improved significantly (p<0.001) at 6 months post-operatively. This improvement was sustained at 18 months. Females and smokers had a poorer HRQoL when compared to males and non-smokers respectivel...
Hepatology International, 2013
The etiology of autoimmune hepatitis (AIH) likely involves a complex interaction of genetic and e... more The etiology of autoimmune hepatitis (AIH) likely involves a complex interaction of genetic and environmental factors. We aim to investigate the associations between exposure to putative environmental factors and AIH and to quantify AIH risk in a first-degree relative. We conducted a population-based case-control study. Cases were AIH patients who were alive and resided in Canterbury, New Zealand, between 1 July 2011 and 30 June 2012. Controls were randomly selected from the Electoral Roll and were matched 2:1 to each case by age and gender. Self-reporting questionnaires that cover lifestyle factors, childhood factors and family history were used. 72 AIH cases and 144 controls were included. We found that exposure to antibiotics within 12 months prior to AIH diagnosis (OR 12.98, 95 % CI 2.49-67.67, p &amp;lt; 0.01) was an independent risk factor for the development of AIH. Alcohol consumption (OR 0.43, 95 % CI 0.28-0.68, p &amp;lt; 0.01) and childhood home with wood heating (OR 0.30, 95 % CI 0.14-0.63, p &amp;lt; 0.01) were independently associated with reduced risks of later development of AIH. The crude risk of AIH in first-degree relatives of a patient with AIH was 0.2 % (95 % CI &amp;lt;0.1-2.0). We found that antibiotics are an independent risk factor for the development of AIH, whereas alcohol consumption and living in a childhood home with wood heating are independent protective factors against the later development of AIH.
Hepatology International, 2011
Epidemiological data on primary biliary cirrhosis (PBC) in the Southern Hemisphere is scarce. Our... more Epidemiological data on primary biliary cirrhosis (PBC) in the Southern Hemisphere is scarce. Our aim was to perform a population-based epidemiological study of PBC in Canterbury, New Zealand. Multiple case-finding methods were employed. All public and private, adult and pediatric outpatient clinics, hospital discharge summaries, and laboratory and pathology reports were searched to identify all cases in the region. Cases were included if at least two of the following criteria were fulfilled: (1) positive anti-mitochondrial antibodies, (2) elevated alkaline phosphatase for greater than 6 months, and (3) compatible liver histology. A total of 71 cases of PBC were included. The incidence in 2008 was 0.8 (95% confidence interval (CI) 0.1-1.6) per 100,000. The point prevalence on December 31, 2008 was 9.9 (95% CI 7.1-12.7) per 100,000. Male to female ratio was 1:11. At presentation, 45% were asymptomatic. Age at diagnosis peaked at the seventh decade with mean age at diagnosis of 61 (95% CI 58-64). This is the first population-based epidemiological study of PBC conducted in New Zealand and only the second in the Southern Hemisphere. The incidence and prevalence are lower than the Northern Hemisphere, even though the majority of our population has shared genetic background with some of these countries. Our study has provided further support to the hypothesis that there may be a protective effect or lack of a risk factor for PBC in New Zealand.
Inflammatory Bowel Diseases, 2015
In the current management paradigm, mucosal healing is preferred over clinical remission as a the... more In the current management paradigm, mucosal healing is preferred over clinical remission as a therapeutic end point in inflammatory bowel disease (IBD) because of the benefits engendered with respect to durability of remission. Colonoscopy, however, is not suitable for regular disease monitoring, and routine clinical assessment is often inaccurate with respect to endoscopic disease activity. The current investigation set out to characterize the relationship that exists between endoscopically determined IBD activity and clinical and biochemical measures of disease severity and to determine clinically useful thresholds for use in clinical practice. Patients attending for colonoscopy with known or suspected IBD were recruited. Clinical disease activity was recorded as per the Harvey-Bradshaw Index for Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease or the simple clinical colitis activity index for ulcerative colitis. Endoscopic activity was recorded using the simple endoscopic score for Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease or the modified Baron score for ulcerative colitis. Receiver operating characteristic analysis determined the predictive value and optimal predictive thresholds for clinical and biomarker data. The Harvey-Bradshaw Index was not able to distinguish active from inactive Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. The sensitivity, specificity, and positive and negative predictive values of simple clinical colitis activity index to detect endoscopic active disease were 43%, 96%, 94%, and 51%, respectively. Any elevation of C-reactive protein or fecal calprotectin was predictive of active mucosal disease, however, no lower threshold could be identified that predicted disease in remission. C-reactive protein and fecal calprotectin are useful for the identification of endoscopically active IBD, but normal results do not confirm endoscopic remission.
Journal of Gastrointestinal Surgery, 2013
Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp... more Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (CD) is an inflammatory bowel disease (IBD) caused by a combination of genetic, clinical, and environmental factors. Identification of CD patients at high risk of requiring surgery may assist clinicians to decide on a top-down or step-up treatment approach. We conducted a retrospective case-control analysis of a population-based cohort of 503 CD patients. A regression-based data reduction approach was used to systematically analyse 63 genomic, clinical and environmental factors for association with IBD-related surgery as the primary outcome variable. A multi-factor model was identified that yielded the highest predictive accuracy for need for surgery. The factors included in the model were the NOD2 genotype (OR = 1.607, P = 2.3 × 10(-5)), having ever had perianal disease (OR = 2.847, P = 4 × 10(-6)), being post-diagnosis smokers (OR = 6.312, P = 7.4 × 10(-3)), being an ex-smoker at diagnosis (OR = 2.405, P = 1.1 × 10(-3)) and age (OR = 1.012, P = 4.4 × 10(-3)). Diagnostic testing for this multi-factor model produced an area under the curve of 0.681 (P = 1 × 10(-4)) and an odds ratio of 3.169, (95% CI P = 1 × 10(-4)) which was higher than any factor considered independently. The results of this study require validation in other populations but represent a step forward in the development of more accurate prognostic tests for clinicians to prescribe the most optimal treatment approach for complicated CD patients.
Inflammatory Bowel Diseases, 2015
In the current management paradigm, mucosal healing is preferred over clinical remission as a the... more In the current management paradigm, mucosal healing is preferred over clinical remission as a therapeutic end point in inflammatory bowel disease (IBD) because of the benefits engendered with respect to durability of remission. Colonoscopy, however, is not suitable for regular disease monitoring, and routine clinical assessment is often inaccurate with respect to endoscopic disease activity. The current investigation set out to characterize the relationship that exists between endoscopically determined IBD activity and clinical and biochemical measures of disease severity and to determine clinically useful thresholds for use in clinical practice. Patients attending for colonoscopy with known or suspected IBD were recruited. Clinical disease activity was recorded as per the Harvey-Bradshaw Index for Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease or the simple clinical colitis activity index for ulcerative colitis. Endoscopic activity was recorded using the simple endoscopic score for Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease or the modified Baron score for ulcerative colitis. Receiver operating characteristic analysis determined the predictive value and optimal predictive thresholds for clinical and biomarker data. The Harvey-Bradshaw Index was not able to distinguish active from inactive Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. The sensitivity, specificity, and positive and negative predictive values of simple clinical colitis activity index to detect endoscopic active disease were 43%, 96%, 94%, and 51%, respectively. Any elevation of C-reactive protein or fecal calprotectin was predictive of active mucosal disease, however, no lower threshold could be identified that predicted disease in remission. C-reactive protein and fecal calprotectin are useful for the identification of endoscopically active IBD, but normal results do not confirm endoscopic remission.
Gastroenterology, Jan 22, 2015
Crohn's disease (CD) usually recurs after intestinal resection; post-operative endoscopic mon... more Crohn's disease (CD) usually recurs after intestinal resection; post-operative endoscopic monitoring and tailored treatment can reduce chance of recurrence. We investigated whether monitoring levels of fecal calprotectin (FC) can substitute for endoscopic analysis of the mucosa. We analyzed data collected from 135 participants in a prospective, randomized, controlled trial, performed at 17 hospitals in Australia and 1 in New Zealand, that assessed the ability of endoscopic evaluations and step-up treatment to prevent CD recurrence after surgery. Levels of FC, serum levels of c-reactive protein (CRP), and Crohn's disease activity index (CDAI) scores were measured before surgery and then 6, 12, and 18 months after resection of all macroscopic Crohn's disease. Ileo-colonoscopies were performed at 6 months after surgery in 90 patients and 18 months after surgery in all patients. Levels of FC were measured in 319 samples from 135 patients. The median FC decreased from 1347 μg...
World journal of gastroenterology, Jan 28, 2015
To review the published literature concerning the accuracy of faecal inflammatory markers for ide... more To review the published literature concerning the accuracy of faecal inflammatory markers for identifying mucosal healing. Bibliographical searches were performed in MEDLINE electronic database up to February 2015, using the following terms: "inflammatory bowel disease", "Crohn´s disease", "ulcerative colitis", "faecal markers", "calprotectin", "lactoferrin", "S100A12", "endoscop*", "mucosal healing", "remission". In addition, relevant references from these studies were also included. Data were extracted from the published papers including odds ratios with 95%CI, P values and correlation coefficients. Data were grouped together according to each faecal marker, Crohn's disease or ulcerative colitis, and paediatric compared with adult study populations. Studies included in this review assessed mucosal inflammation by endoscopic and/or histological means and compared these findings t...
Lancet (London, England), Jan 16, 2015
Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease;... more Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34 819 patients (19 713 with Crohn's disease, 14 683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype-phenotype associations across 156 154 genetic variants. We generated genetic risk scores by combining informat...
The New Zealand medical journal, Jan 24, 2003
Free radical biology & medicine, Jan 22, 2015
Calprotectin provides nutritional immunity by sequestering manganese and zinc ions. It is abundan... more Calprotectin provides nutritional immunity by sequestering manganese and zinc ions. It is abundant in the lungs of patients with cystic fibrosis but fails to prevent their recurrent infections. Calprotectin is a major protein of neutrophils and composed of two monomers, S100A8 and S100A9. We show that the ability of calprotectin to limit growth of Staphylococcus aureus and Pseudomonas aeruginosa is exquisitely sensitive to oxidation by hypochlorous acid. The N-terminal cysteine residue on S100A9 was highly susceptible to oxidation which resulted in cross-linking of the protein monomers. The N-terminal methionine of S100A8 was also readily oxidized by hypochlorous acid, forming both methionine sulfoxide and the unique product dehydromethionine. Isolated human neutrophils formed these modifications on calprotectin when their myeloperoxidase generated hypochlorous acid. Up to 90% of the N-terminal amine on S100A8 in bronchoalveolar lavage fluid from young children with cystic fibrosis ...
Journal of Crohn's & colitis, Jan 8, 2015
Patients with Crohn's disease have poorer health related quality of life (HRQoL) than healthy... more Patients with Crohn's disease have poorer health related quality of life (HRQoL) than healthy individuals, even when in remission. Although HRQoL improves in patients who achieve drug induced or surgically induced remission, the effects of surgery overall have not been well characterised. In a randomised trial patients undergoing intestinal resection of all macroscopically diseased bowel were treated with post-operative drug therapy to prevent disease recurrence. All patients were followed prospectively for 18 months. CRP, CDAI and faecal calprotectin (FC) were measured pre-operatively and at 6, 12 and 18 months. HRQoL was assessed with a general (SF36) and disease-specific (IBDQ) questionnaires at the same time points. 174 patients were included. HRQoL was poor pre-operatively but improved significantly (p<0.001) at 6 months post-operatively. This improvement was sustained at 18 months. Females and smokers had a poorer HRQoL when compared to males and non-smokers respectivel...
The New Zealand medical journal, Jan 6, 2005