EAL

H/A: Caloric Needs (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The aim of this study was to test for the relations among the degree of weight loss, the level of dietary intake and the severity of diarrhea and malabsorption in individuals with HIV and chronic diarrhea who underwent standardized intestinal and nutritional evaluation.

Inclusion Criteria:

Diarrhea lasting for four weeks or more at the time of the investigations
Mean stool frequency within the 48 hours preceding the hospital stay of more than two per day
Stool weight determined from the two-day stool collection preceding the hospital stay of over 300g per day.

Exclusion Criteria:

None.

Description of Study Protocol:

Recruitment

Ambulatory patients with HIV who complained of chronic diarrhea were referred from Rothschild Hospital Department of Infectious Diseases.

Design

Cross-sectional study.

Blinding Used

Implied for measurements

Statistical Analysis

Pearson's coefficient was used to estimate correlation between two variables
Student's T-tests were performed on the correlation estimates to assess difference from zero
All significant tests were confirmed by nonparametric Spearman's rank correlation coefficient
Multivariate analysis by multiple linear regression was to predict weight loss from the onset of the diarrhea, expressed as percentage of usual weight per day, by using a linear combination of the 10 following variables:
- Caloric intake (kcal per kg usual weight per day),
- Usual weight (kg) defined as the body weight before the onset of diarrhea
- CD4 cell count
- Diarrhea duration (months),
- Stool frequency (movements per day),
- Stool weight (grams per day),
- Serum vitamin B₁₂ level (ug per liter),
- Lipid fecal output (grams per day),
- Nitrogen fecal output (grams per day)
- Type of enteric pathogen.

Data Collection Summary:

Timing of Measurements

June 1992 and March 1996; one time point.

Dependent Variables

Weight loss
Serum albumin.

Independent Variables

Dietary intake: Patients noted food intake during the two days preceding hospitalization; reviewed with a dietitian
Weight and height measured during hospital stay.
Stool collection and analyses

Patients were asked not to take their antidiarrheal symptomatic treatment during the two days preceding hospitalization and during the hospital stay
Stools collected during the 48 hours preceding the hospitalization, stored at 4°C and brought to hospital by patients the morning of their hospital stay
Analyzed for ovum and parasites, stool culture and Clostridium difficile toxin assay
Presence of Cryptosporidia and Microsporida detected using modified acid-fast staining and trichrome staining methods, respectively
Fat and nitrogen concentrations measured on remaining part of homogenized stools
Clinical assessment of diarrhea: Pre-defined standardized questionnaire on diarrhea; permanent diarrhea was defined as more than half of the time in a given month with diarrhea (e.g., more than two bowel movements per day) or antidiarrheal drug intake to lessen this symptom.

Endoscopy: All patients underwent upper GI endoscopy and a left colonoscopy without sedation the morning of their hospital stay.

Control Variables

None, other than variables used in regression.

Description of Actual Data Sample:

Initial N: 109 men; seven women
Attrition (final N): 109; and seven
Age: 32±8 years
Ethnicity: Not given
Other relevant demographics: Not given
Anthropometrics
- Men and women combined; mean±SD; range
  - Body weight (kg): 58.8±9.2; 40.0 to 99.0
  - Body mass index: 18.9±2.3; 14.0 to 27.4
  - Weight loss from the onset of diarrhea (percentage of usual weight): 15.2±8.2; 14.0 to 27.4
- Disease information
  - All subjects tested positive for HIV antibodies by enzyme-linked immunosorbent assay and the Western blot assay
  - HIV infection risks were homosexual contact in 105 patients, heterosexual contact in five patients, intravenous blood transfusion in four patients and blood transfusion in two patients
  - Mean CD4 cell count was 48±101 per mm³ (range one to 800); 12 patients had counts over 100 per mm³
Location: Department of Gastroenterology; Hopital Rothschild, Paris.

Summary of Results:

Variables	Mean±SD	Range
Diarrhea
Stool Frequency^a	8.3±6.8	1.0-40.0
Stool Weight (g/Day)	575.6±469.4	70.0-2810.0
Lipid Fecal Output (g/Day)	15.2±14.5	0.4-94.4
Nitrogen Fecal Output (g/Day)	2.5±1.5	0.3-10.7

Nutrient Intake
Total Caloric Intake (kcal/Usual Weight/Day)	25.2±8.1	9.7-54.7
Protein Intake (g/Day)	61.1±22.1	15.0-165.0
Lipid Intake (g/Day)	62.5±22.6	20.0-160.0
Carbohydrate Intake (g/Day)	224.4±73.3	75.0-440.0

Serum Albumin (g/L)	37.1±5.7	21.0-50.0
Vitamin B₁₂ (ug/L)	506.9±865.7	18.9-7016.0

^a Maximal daily stool frequency within the week preceding the hospital investigations.

Table Two: Correlations Between Nutritional Status and Levels of Nutrient Intake

Variables	Weight Loss (Percentage of Usual Weight)	Serum Albumin (g/L)
Caloric Intake (kcal/kg Usual Weight/Day)	R=-0.39 P<0.0001	R=0.22 P<0.05
Protein Intake (g/Day)	R=-0.40 P<0.0001	R=0.21 P<0.05
Lipid Intake (g/Day)	R=-0.36 P<0.0001	R=0.19 NS
Carbohydrate Intake (g/Day)	R=-0.27 P<0.005	R=0.11 NS

^a From the onset of permanent diarrhea.

Table Three: Correlations Between Nutritional Status and Severity of Diarrhea and Malabsorption

Variables	Weight Loss^a (Percentage of Usual Weight)	Serum Albumin (g/L)
Stool Frequency^b	R=0.29 P<0.01	R=-0.03 NS
Stool Weight (g/Day)	R=0.15 NS	R=-0.07 NS
Lipid Output (g/Day)	R=0.05 NS	R=0.04 NS
Nitrogen Output (g/Day)	R=-0.12 NS	R=0.05 NS

^a From the onset of permanent diarrhea
^b Maximal daily stool frequency within the week preceding the hospital investigations.

Table Four: Correlations Between Levels of Nutrient Intake and Severity of Diarrhea and Malabsorption

Variables	Caloric Intake (kcal/kg Usual Weight/Day)	Protein Intake (g/Day)	Lipid Intake (g/Day)	Carbohydrate Intake (g/Day)
Stool Frequency^a	R=-0.13 NS	R=-0.17 NS	R=-0.19 NS	R=-0.06 NS
Stool Weight (g/Day)	R=-0.01 NS	R=0.01 NS	R=-0.03 NS	R=-0.07 NS
Lipid Output (g/Day)	R=0.01 NS	R=0.14 NS	R=0.14 NS	R=0.14 NS
Nitrogen Output (g/Day)	R=0.15 NS	R0.12 NS	R=0.11 NS	R=0.12 NS

Other Findings

Median interval between onset of pemanent diarrhea and hospitalization was eight months (range, one to 133 months)
Sixty-three patients had one or more pathogens found by either stool examinations or endoscopy
Eighteen patients had a daily fecal weight over 1,000g at the time of evaluation
Albuminemia was significantly positively correlated with both total energy intake and protein intake
Linear regression for explaining weight loss selected the two following variables: Total energy intake (negative correlation, P<0.0005) and stool frequency (positive correlation, P=0.01). These variables accounted for 26% of weight loss variation.
Enteric pathogens

Cryptosporidia: 25 cases
Microsporidia: 23 cases
cytomegaloviru: Eight cases
Isospora belli: Two cases
Mycobacterium avium complex: Two cases
Giardia intestinalis: Two cases
Campylobacter jejuni-coli: Two cases
Clostridium difficle: One case
No pathogen found in remaining 53 patients
One patient had a coinfection with Cryptosporidia and Giardia; another patient had a coinfection with Cryptosporidia and Microsporidia.

Author Conclusion:

Degree of wasting correlates mainly with the reduction of nutrient intake and to a lesser extent, with clinical severity of diarrhea
Level of nutrient malabsorption, reflected by fecal outputs of lipid and nitrogen, does not in itself appear as a significant and independent contributor of weight loss
Results stress the major role of inadequate nutrient intake in the wasting of patients with HIV and chronic diarrhea
Optimizing caloric intake must be regarded as an important goal of the management of patients with HIV and chronic diarrhea
Spontaneous caloric intake should be monitored when antidiarrheal treatments are assessed.

Funding Source:

Reviewer Comments:

Author Limitations

Evaluation of weight loss since onset of chronic diarrhea was not a sequential prospective one and only one assessment of diarrhea and nutritional parameters was performed
Stopping of antidiarrheal treatments may have resulted in an artificial worsening of parameters in some patients and in transient dehydration in the subset of patients with the highest fecal weight
Energy expenditure not assessed.

Limitations from Reviewer

Limited number of women; data combined for men and women
Significant methodological limitations by authors gave this study a neutral rating.

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?	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?	N/A
	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%.)	N/A
	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?	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.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	Yes
	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?	N/A
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	Yes
	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?	N/A
	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?	N/A
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