EAL

H/A: Diarrhea/Malabsorption (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine whether a medium-chain triglyceride-based diet compared to a long-chain triglyceride based diet, conveys a beneficial effect on diarrhea and fat malabsorption in HIV-infected individuals with chronic diarrhea and weight loss, and to evaluate the pathogens associated with the diarrhea and to evaluate whether the etiologic agent was a determinant of response to the nutritional intervention.

Inclusion Criteria:

HIV
Diarrhea of greater than four weeks of duration
Fat malabsorption by stool fecal fat determination
Loss of 10% to 20% IBW
Karnofsky status of more than 50%
Life expectancy of more than four weeks.

Exclusion Criteria:

Excluded if not included above.

Description of Study Protocol:

Recruitment

Patients recruited from outpatient infectious disease clinic.

Design

Randomized clinical trial.

Blinding Used

Double blind.

Intervention

Randomly assigned to one to two complete nutritional products with either medium- or long-chain triglyceride fat (both 35% of energy as fat) exclusively for 12 days followed by treatment of infectious pathogens.

Statistical Analysis

Patient demographics and baseline characteristics compared among two groups using two sample T-tests, Wilcoxon rank sum tests and Fisher's exact test. Stool and urine assessments were compared between groups at baseline using two sample T-tests. Change from baseline to endpoint was compared using ANCOVA. Changes in laboratory parameters from baseline to endpoint were assessed using Wilcoxon signed rank and Stuart Maxwell tests.

Data Collection Summary:

Timing of Measurements

Weights, symptom scores, numbers and consistency of stools and amount of product consumed were monitored daily.

Dependent Variables

Evaluation of diarrheal pathogens made by stool examination, upper and lower endoscopy with quantitative culture and biopsy
Body composition calculated according to method of Durnin and Womersley
Total body mass estimated from corrected arm muscle area, which was calculated by the mid-arm circumference
Measurements of fat, carbohydrate and vitamin absorption
Routine laboratories including CBC, liver function assessment, determination of creatinine, creatine kinase, cholesterol and triglyceride.

Independent Variables

Randomly assigned to one of two complete nutritional products with either medium- or long-chain triglyceride fat (both 35% of energy as fat) exclusively for 12 days followed by treatment of infectious pathogens.

Description of Actual Data Sample:

Initial N: 24 patients, all male
Attrition (final N): 24
Age: Mean age 35±9.5 years for MCT group, 32.9±4.4 years for LCT group
Anthropometrics: There were no significant differences between groups at baseline
Location: United States.

Summary of Results:

	Pre-MCT	Post-MCT	Pre-LCT	Post-LCT
Number Stools per day	4.1±0.5	2.5±0.3, P<0.05	5.7±0.7	2.7±0.7, P<0.05
Fecal fat (g per day)	14±2.3	5.4±0.6, P<0.05	14.8±1.7	12±2.6
Fecal weight (g per day)	428±74	262±50, P<0.05	480±57	356±80
Fecal Nitrogen (g per day)	2.5±0.3	1.6±0.2	1.7±0.3	1.6±0.5
Urine Nitrogen (g per day)	9.7±0.7	12.3±1, P<0.05	7.7±0.8	11±1.1, P<0.05

Other Findings

10 patients had Microsporidium and nine patients had no identifiable pathogen.

All patients responded to intervention with both nutritional products overall with 45% fewer stools, decreased stool fat and weight and a significant increase in urine nitrogen.

The group that received the MCT product demonstrated significantly decreased stool number (mean four to 2.5), stool fat (mean 14 to 5.4g) and stool weight (mean 428 to 262g) compared with baseline (P<0.01 for all).

Patients with both species of microsporidia and with pathogen negative diarrhea had good response.

Author Conclusion:

We found that patients with diarrhea, regardless of etiology and documented fat malabsorption, may benefit symptomatically from a diet composed of an MCT-based liquid supplement.

Funding Source:

Reviewer Comments:

Authors note that the duration of the study was not long enough to document any long-term benefit other than maintenance of body weight and body composition.

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?		Yes
	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?	Yes
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?	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?		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?		???
	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?	???
	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?		???
	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?	???
	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