EAL

CD: Gastrointestinal Outcomes (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To evaluate the causes of persistence of GI symptoms in a series of consecutive celiac patients fully compliant to gluten-free diet.

Inclusion Criteria:

Celiac patients experiencing GI symptoms after at least 6 - 8 months of gluten-free diet. All patients showed a classical form of the disease, showing several GI symptoms. Diagnosis of celiac disease was made according to revised criteria of European Society of Pediatric Gastroenterology and Nutrition.

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment

Recruitment methods not specified.

Design

Nonrandomized Clinical Trial.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Gluten-free diet for 6 - 8 months, followed by additional treatment for specific GI symptoms.

Statistical Analysis

Statistical analysis not described.

Data Collection Summary:

Timing of Measurements

Anti-gliadin antibodies, anti-endomysial antibodies, sorbitol H2-breath tests and histological evaluations completed before and after gluten-free diet. In addition, after gluten-free diet, stool examination, lactose- and lactulose H2-breath tests were also completed.

Dependent Variables

Anti-gliadin antibodies (AGA) tested by ELISA
Anti-endomysial antibodies (EmA) tested by ELISA
Sorbitol H2-breath test tested
Esophagogastroduodenoscopy with histological evaluation completed
Stool examination for presence of parasites or pathogen bacteria
Lactose H2-breath test
Lactulose H2-breath test

Independent Variables

Gluten-free diet for 6 - 8 months - not defined nor monitored
Additional drug and/or diet therapy for specific GI issues

Control Variables

Description of Actual Data Sample:

Initial N: 15 celiac patients, 5 men, 10 women

Attrition (final N): See above

Age: Mean age 36.5 years, range 24 - 59 years

Ethnicity: Not mentioned

Other relevant demographics:

Anthropometrics

Location: Italy

Summary of Results:

Other Findings

Histology improved in all patients after 6 - 8 months of gluten-free diet; therefore, refractory celiac disease could be excluded.

1 patient with Marsh II lesions was fully compliant with diet but had taken an antibiotic containing gluten. 2 patients showed lactose malabsorption, 1 patient had Giardia lamblia and 1 patient had Ascaris lumbricoides infestation. 10 patients (66.6%) showed small intestinal bacterial overgrowth by lactulose H2-BT.

The patient with lactose malabsorption was prescribed a lactose-free diet. The 2 patients with parasites were treated appropriately. The patients with small intestinal bacterial overgrowth were treated with rifaximin 800 mg/day for 1 week.

Patients were re-evaluated in 1 month after new treatments and all patients were symptom-free.

Author Conclusion:

In conclusion, this study showed that small intestinal bacterial overgrowth is the most frequent cause of GI symptom persistence in celiacs after gluten withdrawal. Motility disorders, a predisposing factor in development of small intestinal bacterial overgrowth, may affect celiac disease: therefore, investigation could be performed in all celiac patients before starting a gluten-free diet. Small intestinal bacterial overgrowth should always be carefully checked in cases with persistent GI symptoms after starting gluten-free diet, to obtain resolution of symptoms after adequate antibiotic therapy if small intestinal bacterial overgrowth is confirmed.

Funding Source:

Reviewer Comments:

Inclusion/exclusion criteria and recruitment methods not well defined. Statistical analyis not described. Small sample size. Gluten-free diet not defined nor monitored.

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?	???
	2.2.	Were criteria applied equally to all study groups?	N/A
	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?		N/A
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	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?	N/A
	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?		???
	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?	???
	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?		No
	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?	No
	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?	???
	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