ONC: Arginine (2006)
- Oral or laryngeal cancer
- Previous weight loss of 5-10%/6 months
- IL-6 level > 5pg/ml
- Severely impaired hepatic function (total bilirubin concentration >3.5mg/dL)
- Severely impaired renal function (serum creatinine > 2.5mg/dL)
- Ongoing infection
- Steroid treatment
- Well-nourished (weight loss <10% body weight)
Recruitment:
Subjects were surgical head and neck cancer patients seen at the School of Medicine, Valladolid University, Valladolid, Simancas, Spain.
Design:
- Prospective concealed randomized trial
- Informed consent was provided by all patients
- Baseline history taking and physical examination was completed prior to surgery
- Patients were randomly allocated at surgery to either an arginine-supplemented enteral formula group or to an isocaloric, isonitrogenous enteral formula
Blinding used:
Study was blinded; randomization was by sealed envelope.
Intervention:
At time of surgery, patients were randomized to one of two groups:
- Enteral formula supplemented with arginine for an average of 20 days (Group 1, n = 14)
- 125 kcal/100 ml, 0.9 g/100 ml dietary fiber, 6.22 g/100 ml protein
- 12.5 g arginine/day
- Isocaloric, isonitrogenous enteral formula without arginine
- 125 kcal/100 ml, 0.9 g/100 ml dietary fiber, 6.22 g/100 ml protein
Statistical Analysis
- Quantitative variables were analyzed using the two-tailed paired or unpaired Student's t-test
- Nonparametric variables were analyzed with the Friedman and Wilcoxen tests
- A study power of 85% and a type I error of 5% required 12 patients in each group
- All data was analyzed on an intent-to-treat basis
- p < 0.05
Timing of Measurements
Study took place from January 2001 to December 2003.
Selected blood parameters were evaluated perioperatively and postoperatively Day 6.
Dependent Variables
Variable One: Prealbumin
- Fasting blood samples were drawn for measurement of prealbumin (18-28 mg/dl)
- Autoanalyzer was used for measurement (Hitachi, ATM, Mannheim, Germany)
Variable Two: Transferrin
- Fasting blood samples were drawn for the measurement of transferrin (250 - 350 mg/dL)
- Autoanalyzer was used for measurement (Hitachi, ATM, Mannheim, Germany)
Variable Three: Lymphocytes
- Lymphocytes (1.2 - 3.5 x 103/µl) were measured with an analyzer (Beckman Coulter, Inc, LA, CA, USA)
Variable Four: Interleukins (IL-6, TNFa)
- Interleukins were measured by immulite analyzer (DPC, Los Angeles, CA, USA)
- 100 µl heparinized plasma was required IL-6 and TNFa
- Analytical sensitivity of IL-6 and TNFa was 5 and 1.7 pg/ml, respectively
Variable Five: CRP
- CRP was measured by immunoturbimetry (Roche Diagnostics GmbH, Mannheim, Germany)
- Analytical sensitivity was 0.5 mg/dL
Samples were duplicated within 1 day by the same investigator to avoid interinvestigator variability
Independent Variables
-
Surgery for head and neck cancer
-
Enteral nutrition
Control Variables
- Isocaloric, isonitrogenous supplement
Initial N:
- Group 1 (arginine supplement): 14 (2 female, 12 male)
- Group 2 (control supplement): 15 (3 female, 12 male)
Attrition (final N):
Data was analyzed for all subjects on an intent-to-treat basis.
Age:
- Group 1: 60.7 + 11.6
- Group 2: 62.96 + 11.6
Ethnicity: Not mentioned
Other relevant demographics:
Characteristics of patients and tumor stage were similar for both groups.
Anthropometrics (e.g., were groups same or different on important measures)
Body mass index:
- Group 1: 24.61 + 3.5
- Group 2: 24.1 + 2.8
Tumor stage:
- Group 1: Stage 1-2 (0); Stage 3 (2); Stage 4 (10)
- Group 2: Stage 1-2 (0); Stage 3 (3); Stage 4 (12)
Cancer diagnosis
- Group 1: 1 oral cavity, 12 larynx (may be error, since n = 14)
- Group 2: 1 oral cavity, 14 larynx
Location:
Vallodolid University, Institute of Endocrinology and Nutrition, Medicine School, Valladolid, Simancas, Spain
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
The authors concluded that both enteral formulas improved inflammatory markers in head and neck cancer patients.
The authors suggest that further studies are needed to determine whether type of formula is the key to improvement, or whether genetic background plays the main role in inflammatory response.
| University/Hospital: | Hospital Rio Hortega, University of Valladolid |
Well designed, carefully implemented study.
The authors state that this study was done to separate out the effects of arginine, following a previous study (De Luis 2003) in which an enteral formula enhanced with arginine and fiber was used.
Unknown whether subject pool was representative of the target patient population.
|
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? | ??? | |
| 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%.) | 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? | 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.) | ??? | |
| 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? | Yes | |
| 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? | Yes | |
| 6.5. | Were co-interventions (e.g., ancillary treatments, other therapies) described? | Yes | |
| 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? | 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? | ??? | |
| 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)? | Yes | |
| 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? | No | |
| 8.7. | If negative findings, was a power calculation reported to address type 2 error? | Yes | |
| 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? | ??? | |
| 10.1. | Were sources of funding and investigators' affiliations described? | No | |
| 10.2. | Was the study free from apparent conflict of interest? | ??? | |