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Biomedical subjects

A M Griffiths

Publications and source records attributed to A M Griffiths.

At least 19 recordsLinked to original sources
PubMed2003

Pediatric Crohn Disease Activity Index: responsive to short-term change.

BACKGROUND/AIMS: Despite documented feasibility, reliability, and validity, the Pediatric Crohn's Disease Activity Index (PCDAI) has yet to be demonstrated to be sensitive to change in the time frame of acute treatment trials. We evaluated short-term responsiveness and determined the minimal change in PCDAI score associated with a clinically meaningful improvement in disease activity. METHODS: Standardized effect size (SES) and standardized response mean (SRM) were calculated as measures of responsiveness among pediatric patients being treated for acute exacerbations of Crohn disease 1) in a regular clinical practice setting and 2) as part of a multicenter, randomized controlled trial (RCT). Receiver operating characteristic (ROC) curves were constructed to determine the minimal PCDAI score change associated with significant clinical improvement used as the gold standard in 1) physician global assessment of change and in 2) change in adult Crohn disease activity index (CDAI). RESULTS: Among responders, the SES and SRM of the PCDAI were 1.78 and 1.41 (95% CI: 0.89-1.92) and 2.10 and 1.95 (95% CI: 1.70-2.20) in the clinical practice setting and RCT setting, respectively. The optimal minimal PCDAI change score associated with clinically significant change in physician global assessment was determined to be -12.5 (sensitivity 83.3%, specificity 92.3%). In the RCT setting a change in PCDAI of -10 corresponded to a change in CDAI of not greater-than-or-equal 70 points. CONCLUSIONS: The PCDAI is responsive to improvement in disease activity in Crohn disease patients over a short interval. As such, the PCDAI is an appropriate instrument to use in pediatric acute treatment trials.

Adolescent↗
PubMed2003

A critical assessment of items on the Pediatric Crohn's Disease Activity Index.

OBJECTIVES: Questions have been raised about the discriminative value of the three laboratory items (hematocrit, erythrocyte sedimentation rate, and albumin) and three physical items (height, perirectal disease, and extraintestinal manifestations) included in the Pediatric Crohn's Disease Activity Index (PCDAI). The aim of this study was to analyze the value of these six "criticized" items to the discriminative properties of the PCDAI. METHODS: Data from 71 children with Crohn's disease visiting an outpatient clinic were analyzed. Physician global assessment of disease activity was used as the gold standard. A "basic index" was calculated by subtracting the score of the six criticized items from the score of the PCDAI calculated in the standard fashion. Multivariate logistic regression procedures identified which items significantly contributed to the "basic index". Receiver operating characteristic curves were produced comparing the standard PCDAI score to the "basic index" and a new "clinical index" which included only the criticized items truly contributing to the discriminatory ability of the "basic index". RESULTS: Logistic regression models identified only perirectal disease as contributing to the discriminative abilities of the basic index. The clinical index therefore consists of the three history items (abdominal pain, number of liquid stools, and general well-being), three physical examination items (weight loss, abdominal examination, and perirectal disease) and no laboratory tests. The clinical index had an area under the curve not significantly inferior to that of the original PCDAI (0.93 [95% confidence interval, 0.89-0.99] vs. 0.96 [95% confidence interval, 0.92-0.99]). CONCLUSIONS: A clinical index consisting of three history items and three physical examination items has an accuracy equal to the standard PCDAI in distinguishing children with disease in remission from those with a relapse.

Adolescent↗
PubMed2003

Gastral antral biopsy in the differentiation of pediatric colitides.

OBJECTIVES: Differentiation of Crohn's disease (CD) from ulcerative colitis (UC) is problematic, primarily when inflammation is confined to the colon. In a historical cohort study, we evaluated the usefulness of baseline gastric antral biopsies in the differentiation of pediatric chronic colitides. METHODS: During initial investigation for suspected inflammatory bowel disease, 39 children and adolescents with colitis but normal small bowel radiography underwent pretreatment upper endoscopy concurrently with colonoscopy. Two reviewers assigned a colonoscopic diagnosis (colonic CD, UC, or indeterminate colitis) based on the macroscopic and microscopic appearances of the colonic mucosa. Antral histological findings were compared between groups using Fisher's exact test. RESULTS: Five (14%) of colonoscopic diagnoses (four indeterminate, one UC) were changed to CD by the finding of granulomatous inflammation in antral biopsies. Nonspecific antral gastritis was found in similar proportions of children and adolescents with Crohn's colitis and UC (92% vs 75%). Focal antral gastritis was more common in patients with Crohn's colitis than UC (52% vs 8%). CONCLUSIONS: Nonspecific antral gastritis is common in all forms of chronic colitis. Nevertheless, upper gastrointestinal endoscopy with biopsy is useful in the differentiation of inflammatory bowel disease confined to the colon, particularly when colonoscopic findings are indeterminate.

Adolescent↗
PubMed2001

Enteral nutritional therapy for inducing remission of Crohn's disease.

BACKGROUND: The role of enteral nutrition in Crohn's disease is controversial. Increasing research on the mechanisms by which nutritional therapy improves the clinical well being of patients with Crohn's disease has led to novel formula design and trials comparing two different forms of enteral nutrition. This systematic review aims to provide an update on the existing efficacy data for both corticosteroids versus enteral nutrition and for one form of enteral nutrition versus another for inducing remission of active Crohn's disease. OBJECTIVES: To evaluate the efficacy of exclusive enteral nutrition as primary therapy to induce remission in Crohn's disease and to examine the importance of formula composition on efficacy. SEARCH STRATEGY: Studies were selected using a computer-assisted search of the on-line bibliographic databases MEDLINE (1966-2000) and EMBASE (1984-2000), as well as the Science Citation Index on Web of Science. Additional citations were sought by manual search of references of articles retrieved from the computerized search, abstracts submitted to major gastroenterologic meetings and published in the journals: Gut, Gastroenterology, Journal of Pediatric Gastroenterology and Nutrition, and Journal of Parenteral and Enteral Nutrition, and from the reviewers' personal files or contact with leaders in the field. SELECTION CRITERIA: All randomized and quasi-randomized controlled trials involving patients with active Crohn's disease defined by a clinical disease activity index were considered for review. Studies evaluating the administration of one type of enteral nutrition to one group of patients and another type of enteral nutrition or conventional corticosteroids to the other group were selected for review. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers and any discrepancies were resolved by rereading and discussion. For the dichotomous variable, achievement of remission, individual and pooled trial statistics were calculated as odds ratios (OR) with 95% confidence intervals (CI); both fixed and random effect models were used. The results for each analysis were tested for heterogeneity using the chi square statistic. The studies were separated into two groups: A. one form of enteral nutrition compared with another form of enteral nutrition and B. one form of enteral nutrition compared with corticosteroids. Subgroup analyses were conducted on the basis of clinical or disease criteria and formula composition. Sensitivity analyses were conducted on the basis of the inclusion of abstracts of studies not yet fully published, methodologic quality and by random or fixed effects models. MAIN RESULTS: In part A, of the 11 trials (one abstract) comparing different formulations of enteral nutrition ten compared one [or more (Middleton (a)1995)] elemental formulas to a non-elemental diet. The eleventh study (Akobeng 2000) compared two non-elemental diets differing only by glutamine enrichment in one group. This study was therefore not included in the primary analysis but was part of the subgroup analyses. Meta-analysis of nine studies which included 170 patients treated with an elemental diet and 128 patients treated with a non-elemental diet for active Crohn's disease demonstrated no significant difference among diet formulations [OR 1.15 (95% CI: 0.64, 2.08)]. Significant heterogeneity was not present [chi-square 9.77 (df=8)]. Subgroup and sensitivity analyses had no significant effect on the results. In part B, six trials (two abstracts) comparing enteral nutrition to steroid therapy met the inclusion criteria for review. Meta-analysis of four trials that included 130 patients treated with enteral nutrition and 123 treated with steroids yielded a pooled OR of 0.30 favouring steroid therapy (95% CI: 0.17, 0.52). Heterogeneity was not demonstrated [chi-square 0.43 (df=3)]. The risk difference calculated from this meta-analysis was 0.26, and the NNT (number of patients needed to treat with steroids rather than enteral nutrition to achieve one remission) was four. The same result was found in a sensitivity analysis that included abstracts. The inclusion of abstracts resulted in an increase in the number of participants to 150 in the enteral nutrition group and 142 in the steroid group but the meta-analysis yielded a similar result [OR 0.34 (95% CI: 0.20, 0.56)]. There were inadequate data from full publications to perform further subgroup analyses by age, disease duration and disease location. REVIEWER'S CONCLUSIONS: Corticosteroid therapy is more effective than enteral nutrition for inducing remission of active Crohn's disease as was found in past meta-analyses. There is no significant difference in the efficacy of elemental and non-elemental diets for induction of remission of Crohn's disease.

Adrenal Cortex Hormones↗
PubMed2001

Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease.

Linkage disequilibrium (LD) mapping provides a powerful method for fine-structure localization of rare disease genes, but has not yet been widely applied to common disease. We sought to design a systematic approach for LD mapping and apply it to the localization of a gene (IBD5) conferring susceptibility to Crohn disease. The key issues are: (i) to detect a significant LD signal (ii) to rigorously bound the critical region and (iii) to identify the causal genetic variant within this region. We previously mapped the IBD5 locus to a large region spanning 18 cM of chromosome 5q31 (P<10(-4)). Using dense genetic maps of microsatellite markers and single-nucleotide polymorphisms (SNPs) across the entire region, we found strong evidence of LD. We bound the region to a common haplotype spanning 250 kb that shows strong association with the disease (P< 2 x 10(-7)) and contains the cytokine gene cluster. This finding provides overwhelming evidence that a specific common haplotype of the cytokine region in 5q31 confers susceptibility to Crohn disease. However, genetic evidence alone is not sufficient to identify the causal mutation within this region, as strong LD across the region results in multiple SNPs having equivalent genetic evidence-each consistent with the expected properties of the IBD5 locus. These results have important implications for Crohn disease in particular and LD mapping in general.

Chromosome Mapping↗
PubMed2001

Quality of life in inflammatory bowel disease: a cross-cultural comparison of English and Canadian children.

BACKGROUND: Any disease and its treatment has an important impact on health-related quality of life for affected individuals. There have been few previous studies on the quality of life for children with inflammatory bowel disease (IBD). METHODS: A cross-cultural comparison was performed to determine whether the concerns of children with IBD in the United Kingdom are ranked similarly to those of children with IBD in Canada. An item reduction questionnaire, developed from interviews with Canadian children with IBD, was scored by 53 British children with IBD for importance and frequency, as a questionnaire had been scored previously by 117 Canadian children. RESULTS: There was a significant correlation between the mean scores (r = 0.831, P < 0.001) and ranks (r = 0.801, P < 0.001) for the 96 questions, and 43 of the 50 highest-ranking concerns corresponded for both populations. Confidence interval analysis showed a significant difference between the mean values for 21 of the 96 items; 20 of these 21 were ranked higher in the United Kingdom than they had been in Canada, suggesting that the frequency and/or degree of concern was greater for the British children with IBD. CONCLUSIONS: Health-related concerns of British children with Crohn disease and ulcerative colitis correlate closely with those of Canadian children with those diseases. Further studies are needed to determine the sensitivity of individual questions, the most appropriate wording of these questions, and the optimal length for a proposed instrument to assess quality of life in children with IBD.

Adolescent↗
PubMed2001

Controlled ileal release budesonide in pediatric Crohn disease: efficacy and effect on growth.

BACKGROUND: Although the effectiveness of controlled ileal release (CIR) budesonide in children can be extrapolated from adult studies, there are currently no data available concerning the effects of CIR budesonide therapy on linear growth. In the absence of controlled, prospective pediatric clinical trials, we reviewed the outcomes, particularly linear growth, of children and adolescents given CIR budesonide to treat active intestinal inflammation and to maintain remission. METHODS: Thirty-two children (20 males) aged 14.1 +/- 2.7 years with Crohn disease of the distal ileum with or without right colon involvement were treated for active Crohn disease (baseline Pediatric Crohn Disease Activity Index, 34 +/- 14) with 9 mg daily of CIR budesonide through the Hospital for Sick Children, University of Toronto, Inflammatory Bowel Diseases program. RESULTS: At first follow-up visit 8.7 +/- 6.0 weeks later, 19 of 32 (59%) were judged by the physician to have responded. In the subset of 22 patients who had laboratory tests repeated at the first follow-up visit, their Pediatric Crohn Disease Activity Index fell from 33 +/- 14 to 22 +/- 16 (P = 0.001). The Pediatric Crohn Disease Activity Index score fell to less than 15 (cut-off score remission) in 29%. Six prepubertal responders continued to receive 6 mg CIR budesonide for 6 to 13 months. Five of the 6 experienced only mild or no gastrointestinal symptoms and gained weight. Nevertheless, their mean height velocity was only 2.3 +/- 1.0 cm/year, and none grew at a rate of more than 4cm/year whilst receiving CIR budesonide. CONCLUSIONS: These data provide grade III evidence of modest effectiveness of CIR budesonide in children with active Crohn disease confined to the ileum with or without right colon involvement. The subnormal growth observed with continued therapy is concerning and may reflect either inadequately controlled intestinal inflammation or direct suppression of linear growth, as is observed with conventional corticosteroids. Randomized controlled pediatric trials of CIR budesonide must include parameters of linear growth as an outcome variable.

Adolescent↗
PubMed2001

Repeated doses of porcine secretin in the treatment of autism: a randomized, placebo-controlled trial.

BACKGROUND AND OBJECTIVES: Anecdotal reports on the efficacy of secretin in autism raised great hopes for the treatment of children with this disorder. Initial single-dose, randomized, controlled trials failed to demonstrate any therapeutic effects of secretin. The present study is the first to test the outcome of repeated doses and to examine whether there is a subgroup of children who are more likely to achieve positive effects. METHOD: Sixty-four children with autism (ages 2-7 years; 55 boys and 9 girls) with a range of intelligence quotient and verbal ability were randomly assigned, in a double-blind manner, to secretin or placebo groups. Children received 2 doses of placebo or porcine secretin, 6 weeks apart. Assessments were performed at baseline and 3 weeks after each injection using several outcome measures. RESULTS: There were no group differences on formal measures of language, cognition, or autistic symptomatology. Subgroupings based on cognitive level, the presence or absence of diarrhea, or a history of regression failed to show any significant therapeutic effects of secretin. CONCLUSION: No evidence is provided for the efficacy of repeated doses of porcine secretin in the treatment of children with autism. The possible relationship between relief of biological symptoms and enhanced skill performance is discussed.

Analysis of Variance↗
PubMed2000

Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci.

The chronic inflammatory bowel diseases (IBDs)-Crohn disease (CD) and ulcerative colitis (UC)-are idiopathic, inflammatory disorders of the gastrointestinal tract. These conditions have a peak incidence in early adulthood and a combined prevalence of approximately 100-200/100,000. Although the etiology of IBD is multifactorial, a significant genetic contribution to disease susceptibility is implied by epidemiological data revealing a sibling risk of approximately 35-fold for CD and approximately 15-fold for UC. To elucidate the genetic basis for these disorders, we undertook a genomewide scan in 158 Canadian sib-pair families and identified three regions of suggestive linkage (3p, 5q31-33, and 6p) and one region of significant linkage to 19p13 (LOD score 4.6). Higher-density mapping in the 5q31-q33 region revealed a locus of genomewide significance (LOD score 3.9) that contributes to CD susceptibility in families with early-onset disease. Both of these genomic regions contain numerous genes that are important to the immune and inflammatory systems and that provide good targets for future candidate-gene studies.

Age of Onset↗
PubMed2000

Corticosteroids for maintaining remission of Crohn's disease.

OBJECTIVES: To evaluate the effectiveness and safety of conventional systemic corticosteroid therapy in maintaining clinical remission in Crohn's disease. SEARCH STRATEGY: A computer-assisted search of the on-line bibliographic database MEDLINE of studies published in English, French, Spanish, Italian and German between 1966 and May, 1998. Manual searches of the reference lists from the potentially relevant studies were performed in order to identify additional studies that may have been missed using the computer-assisted search strategy. Proceedings from major gastrointestinal meetings were also manually searched from 1985 to 1997 in order to identify unpublished studies. The Cochrane Controlled Trials Register and the Inflammatory Bowel Disease Review Group Trials Register were also searched. SELECTION CRITERIA: Randomized double-blind placebo-controlled trials involving patients of any age with Crohn's disease in clinical remission as defined by a CDAI < 150 or by the presence of no symptoms or only mild symptoms at the time of entry into the trial. The experimental treatment consisted of oral conventional corticosteroid therapy (excluding budesonide, fluticasone, etc). Clinical disease relapse was used as the outcome measure of interest. DATA COLLECTION AND ANALYSIS: Eligible studies were selected by 4 reviewers and data were extracted onto standardized data extraction forms. Disagreements in eligibility or data extraction were resolved by consensus. Data were converted into individual 2x2 tables for each study. The presence of significant heterogeneity among studies was tested using the chi-square test. The 2x2 tables were synthesized into a summary test statistic using the pooled odds ratio and 95% confidence intervals as described by Cochran and Mantel and Haenszel (the 'odds ratio' in MetaView). A fixed effects model was used for the pooling of data. MAIN RESULTS: Four studies were initially judged as being eligible for inclusion. After obtaining additional information on one of the studies it was excluded because it was not double-blind. The total number of subjects included in the analysis at the time points of 6, 12 and 24 months were 142, 131 and 95 for the corticosteroid group and 161, 138 and 87 for the control group. The odds ratios for relapse on active treatment and the corresponding 95% confidence intervals were 0.71 (0.39, 1.31), 0.82 (0.47, 1.43) and 0.72 (0.38, 1.35) at 6, 12 and 24 months. The numbers needed to treat with corticosteroids to prevent one additional relapse were 24, 35, 15 respectively. REVIEWER'S CONCLUSIONS: The use of conventional systemic corticosteroids in patients with clinically quiescent Crohn's disease does not appear to reduce the risk of relapse over a 24 month period of follow-up.

Adrenal Cortex Hormones↗
PubMed2000

Analysis of the effects of increasing delivered dialysis treatment to malnourished peritoneal dialysis patients.

BACKGROUND: Poor nutrition is associated with a loss of residual renal function and inferior clinical outcome in peritoneal dialysis (PD) patients. The value of increasing the PD dose in these individuals is unclear. METHODS: An open, prospective, longitudinal, "intention to treat" study was performed on a whole PD population. All patients treated during an 18-month recruitment period underwent nutritional assessment and were defined as malnourished if they had a subjective global assessment (SGA) of B or C and were 5% or more below their desirable body weight. These patients received an intended dialysis dose increase of 25% and were reassessed after six months. Dialysis was not increased in the remaining patients, unless dictated by uremic symptoms. RESULTS: Forty-eight of 153 patients were malnourished by the previously mentioned criteria. When compared with well-nourished PD patients, they had evidence of declining nutrition over the previous 12 months, as judged by a loss in body weight and mid-arm circumference (MAC), a reduced creatinine appearance, a reduced appetite for protein and calories, and low plasma albumin. They had been on treatment longer and had less residual renal function, resulting in significantly poorer solute clearances. Their peritoneal membrane function, plasma bicarbonate, comorbid, Karnofsky, Hospital Anxiety and Depression (HAD) scores were not different. Following intervention, their peritoneal Kt/Vurea was increased by 22.5%, and their total Kt/Vurea by 18%, because of a continued loss of residual function. There was also an increase in dialysis-derived calories. Weight and MAC stabilized after an initial deterioration, and creatinine appearance increased. There was no increase in protein intake, as judged by dietetic interview or protein nitrogen appearance. Oral calorie intake improved, as did plasma albumin after an initial decline. Both of these improvements were correlated with the achieved increase in Kt/Vurea. Objective measures of improvement (plasma albumin and protein nitrogen appearance) were significant in those patients without comorbid disease. CONCLUSIONS: These results support the existing evidence that malnutrition is acquired on PD in those patients who lose residual renal function. It is feasible to increase the dialysis dose in these individuals without a detrimental effect, and there is evidence of a modest benefit in patients without comorbidity.

Aged↗
PubMed2000

Oral tacrolimus treatment of severe colitis in children.

OBJECTIVE: To evaluate the efficacy of oral tacrolimus as an induction agent in steroid-refractory severe colitis. STUDY DESIGN: Open-label, multicenter trial of oral tacrolimus in patients with severe colitis. Patients not responding to conventional therapy received tacrolimus, 0.1 mg/kg/dose given twice a day, and the dosage was adjusted to achieve blood levels between 10 and 15 ng/mL. Response was defined as improvement in a number of clinical parameters (including abdominal pain, diarrhea, rectal bleeding, and cessation of transfusions). Patients who responded by 14 days continued to receive tacrolimus, and 6-mercaptopurine or azathioprine was added as a steroid-sparing agent 4 to 6 weeks after the tacrolimus was instituted. RESULTS: Fourteen patients were enrolled in the study. One patient elected to withdraw after 48 hours. Of the 13 remaining, 9 (69%) responded and were discharged. Tacrolimus was continued for 2 to 3 months in the responders, except for 1 patient who was given tacrolimus for 11 months. After 1 year of follow-up, only 5 (38%) patients were receiving maintenance therapy; the other 4 responders had undergone colectomy. CONCLUSION: Although tacrolimus is effective induction therapy for severe ulcerative or Crohn's colitis, fewer than 50% of patients treated will successfully achieve a long-term remission.

Adolescent↗
PubMed2000

Magnetic resonance imaging to distinguish the type and severity of pediatric inflammatory bowel diseases.

BACKGROUND: The distinction between ulcerative colitis and Crohn's disease is important, because treatment options and clinical course may vary. Magnetic resonance imaging (MRI) allows noninvasive transmural assessment of the intestine and may facilitate differentiation of ulcerative colitis from Crohn's disease. The objective of this prospective study was to determine whether MRI differentiates Crohn's disease from ulcerative colitis in children as effectively as colonoscopy with mucosal biopsies. METHODS: Fifteen patients underwent colonoscopy with biopsies followed by abdominal MRI. The MRI diagnosis, determined by two radiologists independently completing a standardized form was compared with the gastroenterologic diagnosis. RESULTS: After colonoscopy and review of histology, Crohn's disease was diagnosed in nine patients, ulcerative colitis in five, and indeterminate colitis in one, who was excluded from study. Agreement of the MRI diagnosis with the gastroenterologic diagnosis was 4 of 4 (100%) for ulcerative colitis, 4 of 10 (40%) for Crohn's disease considering both radiologists, and 5 of 10 (50%) for Crohn's disease for each radiologist individually. Percentage of enhancement by MRI did not correlate with the severity of inflammation determined at endoscopy among the patients with Crohn's disease (r = -0.3, P = 0.366). There was agreement on severity of inflammation in three of four patients with ulcerative colitis. CONCLUSIONS: Current MRI interpretation of inflammatory bowel disease did not adequately recognize Crohn's disease in children. Therefore, colonoscopy with biopsy remains the most accurate tool for determining the type and severity of inflammatory bowel disease in children and adolescents.

Adolescent↗
PubMed2000

Nutrition in inflammatory bowel disease.

Recent developments concerning nutritional complications of inflammatory bowel disease include a better understanding of disease-associated anorexia and increasing recognition of the interaction of nutrition and cytokines in the pathogenesis of growth impairment of children. Decreased bone mineral density is a multifactorial complication and an increased focus of research. Enteral nutrition continues to play an important role in the therapy of Crohn's disease. The mechanisms whereby specific nutrients, such as n-3 fatty acids, antioxidants, and butyrate, ameliorate inflammation are being elucidated in in-vitro studies, but beneficial effects have yet to be translated into the clinical sphere.

Anorexia↗