EAL

CD: Villous Atrophy (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To establish whether a high daily amount of ingested gluten from wheat starch-based gluten-free products or a low fiber intake has an untoward effect in terms of GI symptoms and general well-being.

Inclusion Criteria:

Diagnosis of CD based on typical villous atrophy and crypt hyperplasia on small-bowel biopsy specimens.

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment

58 consecutive adult CD patients diagnosed in the study hospital nine to 11 years before current evaluation. Controls were close friends or spouses of the patients.

Design

Nonrandomized Clinical Trial, cross-sectional.

Blinding used (if applicable)

No blinding used.

Intervention (if applicable)

Gastrointestinal Symptom Rating Scale was applied to CD patients on a GFD and non-celiac controls.

Statistical Analysis

Data analysis was done using stepwise regression model carried out in forward manner. GSRS was used as a dependent variable and PGWB, estimated dietary gluten, daily fiber consumption and sex were possible predictors. GSRS and PGWB scores were given as mean and 95% confidence limits for CD patients and controls.

Data Collection Summary:

Timing of Measurements

GSRS applied to CD patients and controls. Intake estimates of daily dietary fibre and wheat starch-derived gluten completed. Psychological well-being also evaluated. Some CD patients consented to small-bowel biopsy.

Dependent Variables

GI symptoms evaluated using GSRS
Psychological disturbances evaluated using Psychological General Well-Being inquiry (PGWB)
Small bowel biopsy methodology not described

Independent Variables

Compliance with GFD and analyses of occasional dietary lapses, daily wheat starch consumption and fiber consumption completed by dietitian through interviews and prospective 4 day food records. Gluten content in wheat starch-based gluten-free products was assumed to be the maximum allowed by Codex standard.

Description of Actual Data Sample:

Initial N: 58 consecutive adult CD patients and 110 non-coeliac controls.
Attrition (final N): 53 of the 58 participated (39 women, 16 men) and 100 controls (89 women, 21 men). The 5 that did not participate were not described, no exclusion criteria described.
Age: CD patients, median 42 years (30-76 years); controls, median 48 years (23-87 years)
Ethnicity: Not mentioned
Other relevant demographics: Controls were spouses or close friends of patients.
Location: University of Tampere, Finland.

Summary of Results:

Other Findings

Overall dietary compliance was good. 48 out of 53 consumed wheat starch-based gluten-free products. Average daily intake of gluten estimated from wheat starch was 36 mg (0-180 mg). Average fiber consumption was 13.6 g/day, lower than recommended.
Altogether 23 patients consented to small-bowel biopsy, which was normal in 21 patients, but one had subtotal and one had partial villous atrophy.
The mean GSRS score in CD patients did not differ from controls. The daily amount of wheat starch had no effect on GSRS score.
When GSRS score was used as a dependent variable and PGWB, sex, dietary gluten and fiber as possible predictors, the model showed PGWB as the only significant predictor (R₂=0.49, p<0.001).

Author Conclusion:

Patients with long-term CD did not complain of abdominal symptoms more than their non-celiac counterparts. Moreover, our results do not support earlier findings that GI symptoms may appear on a wheat starch-based GFD; the daily amount of these products did not have any impact on GSRS score. Our results are consistent with earlier observations that wheat starch-based products do not hamper mucosal healing in CD. To conclude, wheat starch-based gluten-free products are well tolerated in most CD patients. Overall dietary compliance is essential in the treatment of the condition.

Funding Source:

University/Hospital:

Tampere University Hospital (Finland)

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

CD patients chose diets independently. Most were consuming a wheat starch-based GFD, but this excludes patients with GI symptoms that might have changed to a naturally GFD. Five non-participants not described. Villous atrophy found in two of 23 patients.

Quality Criteria Checklist: Primary Research
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?	No
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	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?		???
	4.1.	Were follow-up methods described and the same for all groups?	No
	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%.)	No
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	No
	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?		N/A
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	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.)	N/A
	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?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	N/A
	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?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	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)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	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