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Biomedical subjects

A K Akobeng

Publications and source records attributed to A K Akobeng.

At least 19 recordsLinked to original sources

Tumour necrosis factor alpha blocking agents for induction of remission in ulcerative colitis.

BACKGROUND: Anti-TNF-alpha agents have been shown to be effective for the induction of remission in Crohn's disease. The role of TNF-alpha blocking agents in ulcerative colitis is, however, unclear and recent studies have yielded conflicting results. OBJECTIVES: To evaluate the efficacy of TNF-alpha antibody for induction of remission in ulcerative colitis, and to determine adverse events associated with TNF-alpha antibody treatment. SEARCH STRATEGY: We searched MEDLINE (1966 to 2005), EMBASE (1984 to 2005), the Cochrane Central Register of Controlled Trials (Issue 3, 2004) and the IBD/FBD Review Group Specialized Trials Register. We hand-searched the articles cited in each publication. SELECTION CRITERIA: Only randomised controlled trials in which patients with active ulcerative colitis (defined by a combination of clinical, radiographic, endoscopic and histologic criteria) were randomly allocated to receive a TNF-alpha blocking agent in the treatment arm, and to receive placebo or another treatment in the comparison arm were included. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of methodological quality of each study were independently performed by two reviewers. Any disagreement among reviewers was resolved by consensus. The main outcome measure was the occurrence of remission as defined by the primary studies. Other endpoints were clinical, histological or endoscopic improvement as defined by the primary studies; improvement in quality of life as measured by a validated quality of life tool and the occurrence of adverse events. MAIN RESULTS: Seven randomised controlled trials were identified that satisfied the inclusion criteria. In patients with moderate to severe ulcerative colitis whose disease was refractory to conventional treatment using corticosteroids and/or immunosuppressive agents, infliximab (three intravenous infusions at 0, 2, and 6 weeks) was more effective than placebo in inducing clinical remission (Relative Risk (RR) 3.22, 95% CI 2.18 to 4.76); inducing endoscopic remission (RR 1.88, 95% CI 1.54 to 2.28); and in inducing clinical response (RR 1.99, 95% CI 1.65 to 2.41) at 8 weeks. A single infusion of infliximab was also more effective than placebo in reducing the need for colectomy within 90 days after infusion (RR 0.44, 95% CI 0.22 to 0.87). AUTHORS' CONCLUSIONS: In patients with moderate to severe ulcerative colitis whose disease is refractory to conventional treatment using corticosteroids and/or immunosuppressive agents, infliximab is effective in inducing clinical remission, inducing clinical response, promoting mucosal healing, and reducing the need for colectomy at least in the short term. Serious adverse events attributable to infliximab were not common in the included studies but physicians should be aware of and be prepared to deal with potential adverse events such as anaphylactic reactions and infections.

Anti-Inflammatory Agents↗

Effect of breast feeding on risk of coeliac disease: a systematic review and meta-analysis of observational studies.

BACKGROUND: Coeliac disease (CD) is a disorder that may depend on genetic, immunological, and environmental factors. Recent observational studies suggest that breast feeding may prevent the development of CD. AIM: To evaluate articles that compared effects of breast feeding on risk of CD. METHODS: Systematic review and meta-analysis of observational studies published between 1966 and June 2004 that examined the association between breast feeding and the development of CD. RESULTS: Six case-control studies met the inclusion criteria. With the exception of one small study, all the included studies found an association between increasing duration of breast feeding and decreased risk of developing CD. Meta-analysis showed that the risk of CD was significantly reduced in infants who were breast feeding at the time of gluten introduction (pooled odds ratio 0.48, 95% CI 0.40 to 0.59) compared with infants who were not breast feeding during this period. CONCLUSIONS: Breast feeding may offer protection against the development of CD. Breast feeding during the introduction of dietary gluten, and increasing duration of breast feeding were associated with reduced risk of developing CD. It is, however, not clear from the primary studies whether breast feeding delays the onset of symptoms or provides a permanent protection against the disease. Long term prospective cohort studies are required to investigate further the relation between breast feeding and CD.

Breast Feeding↗

Growth in children with Helicobacter pylori infection and dyspepsia.

AIMS: To compare the height, weight, and body mass index (BMI) of children presenting with dyspeptic symptoms and Helicobacter pylori infection, to those with dyspepsia but without the infection. METHODS: A retrospective chart review of 257 children was performed. 13C urea breath test was performed to detect H pylori infection; weight and height were recorded and BMI was calculated. Weight, height, and BMI SD scores were determined using the 1990 UK normative data. The Index of Multiple Deprivation 2004 (IMD 2004) scores, which measure deprivation at small area level, were calculated from the patients' postcodes. RESULTS: Ninety seven of the 257 children were H pylori positive. The mean age at diagnosis and presenting symptoms of H pylori positive and negative patients were similar. The mean IMD 2004 scores for children with H pylori infection were significantly higher compared to H pylori negative patients, suggesting that children with the infection came from relatively more deprived areas. The mean weight and height SD score were significantly lower for children with H pylori infection compared to those without. However, this difference was no longer significant after adjusting for socioeconomic deprivation and ethnic differences between the groups. CONCLUSION: Children with dyspepsia and H pylori infection were shorter and lighter than patients with similar symptoms but no infection. The differences in anthropometry may be due to socioeconomic and ethnic factors rather than H pylori infection.

Adolescent↗

Oral 5-aminosalicylic acid for maintenance of medically-induced remission in Crohn's Disease.

BACKGROUND: Prevention of relapses is a major issue in the management of Crohn's disease. Corticosteroids, the mainstay of treatment of acute exacerbations are not effective in the maintenance of remission and its chronic use is limited by numerous adverse events. A number of randomised controlled trials comparing various 5-ASA agents with either placebo or other drugs have had conflicting results. OBJECTIVES: To conduct a systematic review to evaluate the efficacy of oral 5-ASA agents for the maintenance of medically-induced remission in Crohn's disease. SEARCH STRATEGY: We searched MEDLINE (1966 to January 2004), EMBASE (1984-January 2004), the Cochrane Central Register of Controlled Trials from the Cochrane Library (Issue 1, 2004) and the IBD Review Group Specialized Trials Register. We hand-searched the articles cited in each publication. SELECTION CRITERIA: We included randomised controlled trials which compared oral 5-ASA agents with either placebo or sulphasalazine, with treatment durations of at least 6 months. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of methodological quality of each study were independently performed by two reviewers. Any disagreement among reviewers was resolved by consensus. The main outcome measure was the occurrence of relapse as defined by the primary studies. Odds ratios of relapse rates and their 95% confidence intervals were calculated. MAIN RESULTS: 5-ASA VERSUS PLACEBO. In the main analysis, we used as the denominator the total number of patients randomised. We assumed that participants who dropped out of the study, and on whom there was no post withdrawal information, had relapsed during the study period. Using the fixed effects model, the odds ratio for 6 studies where participants were followed up for 12 months was 1.00 (95%CI, 0.80 to 1.24). Using the random effects model in a sensitivity analysis had little effect on the results with an OR of 0.93 (95% CI, 0.65 to 1.33). For the seventh study where follow up was for 24 months, the odds ratio was 0.98; 95% CI, 0.51 to 1.90. In further sensitivity analyses, we analysed only participants who completed the study and ignored the dropouts. The odds ratio (fixed effects model) for the 6 studies where follow up was for 12 months was 0.74 (95% CI, 0.57 to 0.96), but using the random effects model, the OR was 0.68 (95% CI 0.45 to 1.02). The OR for the seventh study where follow up was for 24 months (Gendre 1993a), was 0.86; 95% CI, 0.42 to 1.78. 5-ASA VERSUS SULPHASALAZINE. We did not find any study that satisfied the inclusion criteria. AUTHORS' CONCLUSIONS: We found no evidence in this review to suggest that 5-ASA preparations are superior to placebo for the maintenance of medically-induced remission in patients with Crohn's disease. Therefore it appears that additional randomised trials of this regime are not justified.

Administration, Oral↗

Understanding measures of treatment effect in clinical trials.

Evidence based medicine implies that healthcare professionals are expected to base their practice on the best available evidence. This means that we should acquire the necessary skills for appraising the medical literature, including the ability to understand and interpret the results of published articles. This article discusses in a simple, practical, 'non-statistician' fashion some of the important outcome measures used to report clinical trials comparing different treatments or interventions. Absolute and relative risk measures are explained, and their merits and demerits discussed. The article aims to encourage healthcare professionals to appreciate the use and misuse of these outcome measures and to empower them to calculate these measures themselves when, as is frequently the case, the authors of some original articles fail to present their results in a more clinically friendly format.

Clinical Trials as Topic↗

Understanding randomised controlled trials.

The hierarchy of evidence in assessing the effectiveness of interventions or treatments is explained, and the gold standard for evaluating the effectiveness of interventions, the randomised controlled trial, is discussed. Issues that need to be considered during the critical appraisal of randomised controlled trials, such as assessing the validity of trial methodology and the magnitude and precision of the treatment effect, and deciding on the applicability of research results, are discussed. Important terminologies such as randomisation, allocation concealment, blinding, intention to treat, p values, and confidence intervals are explained.

Child↗

Understanding systematic reviews and meta-analysis.

This review covers the basic principles of systematic reviews and meta-analyses. The problems associated with traditional narrative reviews are discussed, as is the role of systematic reviews in limiting bias associated with the assembly, critical appraisal, and synthesis of studies addressing specific clinical questions. Important issues that need to be considered when appraising a systematic review or meta-analysis are outlined, and some of the terms used in the reporting of systematic reviews and meta-analyses--such as odds ratio, relative risk, confidence interval, and the forest plot--are introduced.

Child↗

Evidence in practice.

A clinical scenario is used to illustrate how the principles outlined in the previous articles in the series could be applied to help improve patient care. A practical demonstration of the art of formulating answerable clinical questions, finding evidence, critically appraising evidence, and putting evidence into practice is provided. The importance of integrating evidence with patient's preferences, and taking account of issues such as availability of interventions, costs, and so on is discussed. Finally, some of the issues involved in the development of evidence based policies within clinical teams are outlined.

Antibodies, Monoclonal↗

Principles of evidence based medicine.

Health care professionals are increasingly required to base clinical decisions on the best available evidence. Evidence based medicine (EBM) is a systematic approach to clinical problem solving which allows the integration of the best available research evidence with clinical expertise and patient values. This paper explains the concept of EBM and introduces the five step EBM model: formulation of answerable clinical questions; searching for evidence; critical appraisal; applicability of evidence; evaluation of performance. Subsequent articles will focus on the principles and critical appraisal of randomised controlled trials, systematic reviews, and meta-analyses, and provide a practical demonstration of the five step EBM model using a real life clinical scenario.

Child↗

Tumor necrosis factor-alpha antibody for induction of remission in Crohn's disease.

BACKGROUND: Crohn's disease may be refractory to conventional treatments such as corticosteroids, enteral nutrition and immuno-suppressive agents. A number of patients with the disease may also become steroid-dependent leading to increased risk of developing steroid-related adverse effects. Recent studies suggest that TNF-a blocking agents may be effective in inducing remission in Crohn's disease. OBJECTIVES: To conduct a systematic review to evaluate the effectiveness of TNF-a blocking agents in inducing remission in patients with active Crohn's disease. SEARCH STRATEGY: We searched MEDLINE (1966-June 2003), EMBASE (1984-June 2003), the Cochrane Central Register of Controlled Trials from the Cochrane Library (Issue 2, 2003) and the IBD Review Group Specialized Trials Register. We hand-searched the articles cited in each publication obtained. SELECTION CRITERIA: We included only randomised controlled trials in which patients with active Crohn's disease (defined by a validated Crohn's disease activity index) were randomly allocated to receive a TNF-a blocking agent in the treatment arm, or to receive placebo or another treatment in the comparison arm. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of the methodological quality of each trial were independently performed by two reviewers. Any disagreement among reviewers was resolved by consensus. Outcome measures reported in the primary studies included clinical remission, clinical response and changes in disease activity index. MAIN RESULTS: Ten studies were identified of which 4 met the inclusion criteria. The included studies either differed in the type of TNF-a blocking agent used or in the way outcomes were assessed to such an extent that we considered it inappropriate to combine the data statistically. There is evidence from one randomised controlled trial that suggests that a single intravenous infusion of the monoclonal antibody cA2, infliximab, may be effective for induction of remission in Crohn's disease. There was no difference in response rates among infliximab doses of 5, 10 or 20 mg/kg. The results of two other trials suggested that CDP571, the genetically engineered human TNF monoclonal antibody, may also be effective in reducing disease activity index at 2 weeks after an infusion. We did not find any evidence to support the use of etanercept in Crohn's disease. REVIEWER'S CONCLUSIONS: Evidence from one randomized controlled trial suggests that a single infusion of infliximab may be effective for induction of remission in Crohn's disease. Based on this study, we can recommend a dose of 5 mg/kg. There is also some evidence that CDP571 may be effective in inducing remission in Crohn's disease. We did not find any evidence that supports the use of etanercept in Crohn's disease. The period of follow up for the patients in these studies was probably too short to allow adequate assessment of recently reported serious adverse effects such as tuberculosis and lymphoma.

Antibodies, Monoclonal↗

Measuring the nutritional status of children with juvenile idiopathic arthritis using the bioelectrical impedance method.

OBJECTIVE: To assess the nutritional status of children with juvenile idiopathic arthritis (JIA) using anthropometric measurements and bioelectrical impedance. METHODS: Twenty-two consecutive JIA patients (seven pauciarticular, 15 polyarticular) attending the rheumatology clinic at Booth Hall Children's Hospital were compared with 22 age- and sex-matched controls attending the accident and emergency department of the same hospital. There were no patients with systemic-onset JIA in the cohort. Height, weight, head circumference and skinfold thickness at four sites (biceps, triceps, subscapular and suprailiac) were measured. Regression equations were used to calculate body fat as a percentage of weight, and arm muscle circumference. In addition, bioelectrical impedance measurements were made using a Holtain body composition analyser. These measurements were then used to calculate the total body water, which could be used as an indirect estimate of the lean body mass. RESULTS: Of the JIA patients, 22.7% were below the third centile for height, 18.1% had a weight less than the third centile. Mid-arm circumference was below the fifth centile in 36.4% of the patients. Patients with polyarticular disease showed significantly more signs of malnutrition than patients with pauciarticular disease. In the polyarticular group, comparison with controls revealed significant P values for reduction in height (0.047), weight (0.045), mid-arm circumference (0.002), arm muscle circumference (0.012), percentage body fat (0.008) and total body water (0.031). CONCLUSIONS: In view of the findings of lower total body water, indicating lower lean mass, in more nutritionally deprived JIA patients (as deduced by the other physical parameters measured), we conclude that bioelectrical impedance is a useful adjunct to anthropometric measures in assessing nutritional status in JIA.

Adolescent↗

Double-blind randomized controlled trial of glutamine-enriched polymeric diet in the treatment of active Crohn's disease.

BACKGROUND: Glutamine is traditionally considered a nonessential amino acid but may be conditionally essential in patients with catabolic conditions. Glutamine-supplemented foods in these patients have been shown to prevent deterioration of gut permeability, protect against the development of intestinal mucosal atrophy, and improve nitrogen balance. Animal models of inflammatory bowel disease suggest that glutamine-enriched enteral diets may lead to less severe intestinal damage, less weight loss, improved nitrogen balance, and reduced disease activity. The purpose of the current study was to compare the efficacy of a glutamine-enriched polymeric diet with a standard low-glutamine polymeric diet in the treatment of active Crohn's disease. METHODS: Eighteen children with active Crohn's disease were randomly assigned to receive a 4-week course of either a standard polymeric diet with a low glutamine content (4% of amino acid composition; group S) or a glutamine-enriched polymeric diet (42% of amino acid composition; Group G). The two diets were isocaloric and isonitrogenous with an identical essential amino acid profile. Remission rates were analysed on an intent-to-treat basis. Changes in clinical and laboratory parameters of disease activity were also compared after 4 weeks of nutritional treatment. RESULTS: Two of the children, both in group G, were withdrawn from the trial because of nontolerance of the diet. There was no difference between the two groups in proportion of patients achieving remission (intent-to-treat basis): 5 (55.5%) of 9 in group S versus 4 (44.4%) of 9 in group G (p = 0.5). Improvement in mean paediatric Crohn's disease activity index (PCDAI) was significantly more in group S (p = 0.002) but changes in orosomucoid level, platelet count, and weight were not different between the groups. CONCLUSIONS: The findings suggest that a glutamine-enriched polymeric diet offers no advantage over a standard low-glutamine polymeric diet in the treatment of active Crohn's disease. Rather, it appears to be less effective in improving PCDAI. The reported beneficial effects of glutamine seen in many catabolic states must be viewed with caution when extrapolating to the management of Crohn's disease.

Acute-Phase Proteins↗

Technical aspects of feeding the disabled child.

Children with neurological impairment frequently have difficulties in consuming sufficient energy and other nutrients to maintain adequate nutritional status. Under-nutrition is a significant contributory factor to growth failure. Eating may be distressing and time-consuming for the child and carer. Aspiration of feeds is common and may predispose to chronic chest infections. Gastro-oesophageal reflux is also common and may contribute to significant morbidity. This paper discusses some of the issues involved in the nutritional management of neurologically impaired children.

Child↗