CD: Villous Atrophy (2006)
Recruitment
Clinical protocol followed from January 1996 to August 1998.
Design
Nonrandomized Clinical Trial.
Blinding used (if applicable)
Duodenal biopsies were assessed without knowledge of initial histological classification or current EmA status.
Intervention (if applicable)
Gluten-free diet for 1 year.
Statistical Analysis
Frequency data reported. Mann-Whitney U test and Fisher's exact test used in other comparisons. Statistical analyses not well defined.
Timing of Measurements
Patients with villous atrophy and EmA had repeat EmA testing at 3, 6 and 12 months after starting gluten-free diet. Follow-up duodenal biopsy at 12 months.
Dependent Variables
- Duodenal biopsies taken from the second part of the duodenum by standard forceps during upper GI endoscopy
- Villous atrophy classified as partial, subtotal and total according to Marsh classification
- EmA was tested by indirect immunofluorescence using primate esophagus as substrate
- Total serum IgA measured to exclude deficiency as a cause of false-positive EmA
Independent Variables
- Gluten-free diet compliance assessed by RD at the 12 months. Food intake was reviewed in detail on a meal-by-meal basis to check for deliberate or inadvertent gluten ingestion.
Control Variables
Initial N: 79 patients confirmed to have villous atrophy on duodenal biopsy. 2 were EmA negative due to IgA deficiency. Of remaining 77, 62 (81%) tested EmA positive. 9 of 62 did not have 12 full months of diet (4 died, 5 were not compliant).
Attrition (final N): 53 completed study protocols: 21 had total villous atrophy, 20 had subtotal villous atrophy, and 12 had partial villous atrophy. 39 (74%) were female.
Age: Mean 51 years (range 16 - 81) at initial biopsy
Ethnicity: Not mentioned.
Other relevant demographics: Not mentioned.
Anthropometrics: Not mentioned.
Location: Ireland
Total/Subtotal VA |
Partial VA |
Total | |
Untreated | 46/57 (81%) | 16/20 (80%) | 62/77 (81%) |
Treated |
3/10 (33%) |
2/22 (9%) |
5/32 (15%) |
P-value |
0.002 |
<0.001 |
<0.001 |
Other Findings
Of 77 patients with newly diagnosed villous atrophy and without IgA deficiency, 62 (81%) had EmA: 46 of 57 (81%) with total or subtotal villous atrophy and 16 of 20 (80%) with partial villous atrophy.
Of 53 initially EmA-positive patients who completed study criteria, EmA was undetectable in 31 patients (58%) after 3 months' diet, in 40 (75%) after 6 months, and in 46 (87%) after 12 months.
Follow-up biopsies at 12 months showed persistent total or subtotal villous atrophy in 10 (24%) of the 41 patients with total or subtotal villous atrophy as the initial lesion. 18 (44%) had partial villous atrophy and the remaining 13 (32%) had complete villous recovery with no excess of intraepithelial lymphocytes.
However, only 21 patients (40%), all seronegative by 12 months, had complete villous recovery. Only 3 (33%) of 10 patients with persisting subtotal or total villous atrophy and 2 (9%) of 22 with partial villous atrophy remained EmA positive.
4 of 5 patients with persisting EmA had poor dietary compliance and no evidence of improvement.
University/Hospital: | Altnageluin Hospital, Royal Victoria Hospital |
Quality Criteria Checklist: Primary Research
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Relevance Questions | |||
1. | Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) | Yes | |
2. | Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? | Yes | |
3. | Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? | Yes | |
4. | Is the intervention or procedure feasible? (NA for some epidemiological studies) | Yes | |
Validity Questions | |||
1. | Was the research question clearly stated? | Yes | |
1.1. | Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? | Yes | |
1.2. | Was (were) the outcome(s) [dependent variable(s)] clearly indicated? | Yes | |
1.3. | Were the target population and setting specified? | Yes | |
2. | Was the selection of study subjects/patients free from bias? | ??? | |
2.1. | Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? | Yes | |
2.2. | Were criteria applied equally to all study groups? | Yes | |
2.3. | Were health, demographics, and other characteristics of subjects described? | ??? | |
2.4. | Were the subjects/patients a representative sample of the relevant population? | ??? | |
3. | Were study groups comparable? | Yes | |
3.1. | Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) | Yes | |
3.2. | Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? | Yes | |
3.3. | Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) | Yes | |
3.4. | If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? | N/A | |
3.5. | If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) | N/A | |
3.6. | If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? | N/A | |
4. | Was method of handling withdrawals described? | Yes | |
4.1. | Were follow-up methods described and the same for all groups? | Yes | |
4.2. | Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) | Yes | |
4.3. | Were all enrolled subjects/patients (in the original sample) accounted for? | Yes | |
4.4. | Were reasons for withdrawals similar across groups? | Yes | |
4.5. | If diagnostic test, was decision to perform reference test not dependent on results of test under study? | N/A | |
5. | Was blinding used to prevent introduction of bias? | Yes | |
5.1. | In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? | Yes | |
5.2. | Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) | Yes | |
5.3. | In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? | N/A | |
5.4. | In case control study, was case definition explicit and case ascertainment not influenced by exposure status? | N/A | |
5.5. | In diagnostic study, were test results blinded to patient history and other test results? | N/A | |
6. | Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? | Yes | |
6.1. | In RCT or other intervention trial, were protocols described for all regimens studied? | Yes | |
6.2. | In observational study, were interventions, study settings, and clinicians/provider described? | N/A | |
6.3. | Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? | Yes | |
6.4. | Was the amount of exposure and, if relevant, subject/patient compliance measured? | Yes | |
6.5. | Were co-interventions (e.g., ancillary treatments, other therapies) described? | Yes | |
6.6. | Were extra or unplanned treatments described? | Yes | |
6.7. | Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? | Yes | |
6.8. | In diagnostic study, were details of test administration and replication sufficient? | N/A | |
7. | Were outcomes clearly defined and the measurements valid and reliable? | Yes | |
7.1. | Were primary and secondary endpoints described and relevant to the question? | Yes | |
7.2. | Were nutrition measures appropriate to question and outcomes of concern? | Yes | |
7.3. | Was the period of follow-up long enough for important outcome(s) to occur? | Yes | |
7.4. | Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? | Yes | |
7.5. | Was the measurement of effect at an appropriate level of precision? | Yes | |
7.6. | Were other factors accounted for (measured) that could affect outcomes? | Yes | |
7.7. | Were the measurements conducted consistently across groups? | Yes | |
8. | Was the statistical analysis appropriate for the study design and type of outcome indicators? | ??? | |
8.1. | Were statistical analyses adequately described and the results reported appropriately? | No | |
8.2. | Were correct statistical tests used and assumptions of test not violated? | ??? | |
8.3. | Were statistics reported with levels of significance and/or confidence intervals? | ??? | |
8.4. | Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? | N/A | |
8.5. | Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? | ??? | |
8.6. | Was clinical significance as well as statistical significance reported? | No | |
8.7. | If negative findings, was a power calculation reported to address type 2 error? | N/A | |
9. | Are conclusions supported by results with biases and limitations taken into consideration? | Yes | |
9.1. | Is there a discussion of findings? | Yes | |
9.2. | Are biases and study limitations identified and discussed? | Yes | |
10. | Is bias due to study's funding or sponsorship unlikely? | Yes | |
10.1. | Were sources of funding and investigators' affiliations described? | Yes | |
10.2. | Was the study free from apparent conflict of interest? | Yes | |