EAL

H/A: Caloric Needs (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine the relationship between the determinants cytokine production and serum testosterone concentration and change in LBM and REE.

Inclusion Criteria:

Not specifically mentioned in this article.

Exclusion Criteria:

Not specifically mentioned in this article.

Description of Study Protocol:

Recruitment

Nutrition for Healthy Living cohort started in 1993 and included 695 subjects as of May 2000.

Design

Longitudinal cohort study.

Statistical Analysis

Absolute changes were modeled using repeated measures regression methods
Restricted cubic spline regression models were used to test significant non-linearity in the independent association between the three dependent variables of interest and the main determinants cytokines and testosterone.

Data Collection Summary:

Timing of Measurements

Subjects are contacted by phone every month and are examined and fill out detailed questionnaires about their health
Every six months, body composition is measured.

Dependent Variables

Body composition through bioelectrical impedance
Resting energy expenditure, measured through indirect calorimetry
Dietary intake, measured from three-day food records
CD4 counts, measured through flow cytometry
Physical activity, estimated using the Physical Activity Recall Scale
Plasma HIV RNA.

Independent Variables

Blood samples for assessment of cytokine production and free testosterone.

Description of Actual Data Sample:

Initial N: 172 men with HIV infection contributed 190 observations
Attrition (final N): 172 men
Mean age: 41 years
Ethnicity: 72% Caucasian
Other relevant demographics: 43% were taking HAART
Location: United States.

Summary of Results:

Other Findings

LBM loss of more than on kg occurred in 35% of the cohort and LBM loss of over 5% occurred in 12.2%, over eight months of observation, but classical wasting (loss of approximately 10%) was rare (2%)
Both TNF-alpha (-150g LBM per ng per ml, P<0.02) and IL-1-beta production (-130g LBM per ng per ml, P<0.01) by peripheral blood mononuclear cells predicted loss of LBM
A rise in REE of over 200kcal per day was found in 17.7% of the subjects, regardless of weight change
IL-1-beta (+9 kcal per day per ng per ml, P<0.002) and TNF-alpha (+10 kcal per day per ng per ml, P<0.02) production predicted change in REE
Serum-free testosterone was inversely associated with TNF-alpha production and was not an independent predictor of either change in LBM or change in REE after adjustment for cytokine production
There was no relationship between change in LBM and free testosterone concentration, age, energy or protein intake, viral load, physical activity, HAART use or race
There were no significant associations between cytokines and viral load or CD4 count.

Author Conclusion:

In conclusion, this study shows for the first time that cachexia, separate from wasting, is a prevalent clinical problem in HIV-infected men, even in the era of HAART
In addition, the results of this study support the notion that cachexia is an immunologically driven process rather than a simple problem of inadequate intake.

Funding Source:

Reviewer Comments:

Only men studied, but investigating effects of testosterone
Sophisticated statistical analysis.

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)	N/A
	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)	N/A

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?	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?	Yes
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?		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?		N/A
	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?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	N/A
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	N/A
	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?	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