EAL

CD: Gastrointestinal Outcomes (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To study the prevalence and/or cause of chronic diarrhea in patients with celiac sprue after treatment with a gluten-free diet.

Inclusion Criteria:

Patients with celiac sprue, diagnosed on the basis of typical symptoms, signs, and small intestinal histopathology a minimum of 12 months before the start of the study, and to have experienced improved health since intitiating a gluten-free diet, over 18 years of age.

Exclusion Criteria:

3 patients who had never undergone a small intestinal biopsy procedure and 4 patients who had received their diagnosis <12 months before the start of the study were excluded.

Description of Study Protocol:

Recruitment

Adult members of a support group for patients with celiac sprue in Dallas-Fort Worth.

Design

Cross-Sectional Study.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Survey and extensive diagnostic evaluation to determine cause of chronic diarrhea.

Statistical Analysis

Methods not described. Frequency data.

Data Collection Summary:

Timing of Measurements

Patients were surveyed about bowel habits from previous 6 months; those with chronic diarrhea (loose stools >3 days/week) underwent thorough diagnostic evaluation.

Dependent Variables

Survey assessing average frequency of loose or watery stools over past 6 months, validity tested by giving 2 control groups same survey
Diagnostic evaluation: blood samples analyzed for CBC, automated chemistry profile, prothrombin time, quantitative Igs, TSH, thyroxine, reverse triiodothyronine uptake, and calculated free thyroid index by routine clinical methods.
Titres of antigliadin IgA and IgG antibodies measured by ELISA
Antireticulin IgG and antiendomysial IgA antibodies measured by indirect immunofluorescence
HLA-DR and HLA-DQ loci typed serologically using microcytotoxicity method
Lactose breath hydrogen test
48-hour quantitative stool collection
Esophagogastroduodenoscopy
Anorectal manometry
CT of abdomen and pelvis

Independent Variables

Gluten-free diet for at least 12 months, not defined nor monitored

Control Variables

Description of Actual Data Sample:

Initial N: 78 patients with celiac sprue (59 women, 19 men)

Attrition (final N): 78 patients

Age: Mean and median age 52 years (range 19 - 77 years)

Ethnicity: Not mentioned

Other relevant demographics: Not mentioned

Anthropometrics:

Location: Texas

Summary of Results:

GI Symptoms in Patients Before and After Treatment with Gluten-Free Diet

	Before GFD	After GFD
Weight Loss	64 (82%)	0 (0%)
Chronic Diarrhea	62 (79%)	13 (17%)
Excessive Flatulence	58 (74%)	0 (0%)
Abdominal Bloating/Distention	53 (68%)	0 (0%)
Nausea	28 (36%)	0 (0%)
Vomiting	15 (19%)	0 (0%)
Constipation	5 (6%)	1 (1%)
No Symptoms (Iron Deficiency Anemia)	4 (5%)	0 (0%)

Other Findings

62/78 patients (79%) experienced diarrhea before treatment, and 13 (17%) had chronic diarrhea (of lesser severity) after treatment.

The frequency of diarrhea in groups of treated sprue patients was statistically significantly greater than that in the general population (by chi-square analysis, P < 0.02) but not significantly different from each other.

Of 13 with chronic diarrhea, 11 consented to diagnostic evaluation and the causes were microscopic colitis, steatorrhea secondary to exocrine pancreatic insufficiency, dietary lactose or fructose malabsorption, anal sphincter dysfunction causing fecal incontinence, and the irritable bowel syndrome. Only 1 patient had antigliadin antibodies detected in serum or small intestinal villous atrophy.

Author Conclusion:

In summary, treatment of celiac sprue with a gluten-free diet will improve patient health and well-being, but approximately 20% of treated patients will still have chronic diarrhea. The results of this study indicate that such diarrhea should not be passed off as "normal for a celiac", considered certain evidence of gluten ingestion, or viewed necessarily as a sign of a poor response of the small intestinal pathology to treatment. If the patient seems compliant with his or her dietary treatment, and there is no objective evidence of gluten ingestion, the diarrhea should be investigated as it would be in any patient presenting with chronic diarrhea.

Funding Source:

Government:	Veterans Affairs Medical Center
University/Hospital:	Baylor University Medical Center; University of Texas

Reviewer Comments:

Survey tested for validity of self-reporting. Diet not defined nor monitored. Recruited from local support group, limited generalizability.

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?	Yes
	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?		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?		???
	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?	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)?	N/A
	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