Differences in erythrocyte phospholipid membrane long-chain polyunsaturated fatty acids and the prevalence of fatty acid desaturase genotype among African Americans and European Americans.

Numerous studies have reported an association between genetic variants in fatty acid desaturases (FADS1 and FADS2) and plasma or erythrocyte long chain polyunsaturated fatty acid (PUFA) levels. Increased levels of n-6 PUFAs have been associated with inflammation and several chronic diseases, including diabetes and cancer. We hypothesized that genetic variants of FADS that more efficiently convert precursor n-6 PUFA to arachidonic acid (AA) may explain the higher burden of chronic diseases observed in African Americans. To test this hypothesis, we measured the level of n-6 and n-3 PUFAs in erythrocyte membrane phospholipids and genotyped the rs174537 FADS variants associated with higher AA conversion among African American and European American populations. We included data from 1,733 individuals who participated in the Tennessee Colorectal Polyp Study, a large colonoscopy-based case-control study. Erythrocyte membrane PUFA percentages were measured using gas chromatography. Generalized linear models were used to estimate association of race and genotype on erythrocyte phospholipid membrane PUFA levels while controlling for self-reported dietary intake. We found that African Americans have higher levels of AA and a higher prevalence of GG allele compared to whites, 81% vs 43%, respectively. Homozygous GG genotype was negatively associated with precursor PUFAs (linoleic [LA], di-homo-γ-linolenic [DGLA]), positively associated with both product PUFA (AA, docosahexaenoic acid [DHA]), product to precursor ratio (AA to DGLA), an indirect measure of FADs efficiency and increased urinary isoprostane F2 (F2-IsoP) and isoprostane F3 (F3-IsoP), markers of oxidative stress. Increased consumption of n-6 PUFA and LA resulting in increased AA and subsequent inflammation may be fueling increased prevalence of chronic diseases especially in African descent.

Smoking and red blood cell phospholipid membrane fatty acids.

Smoking is associated with lower n-3 long chain polyunsaturated fatty acids (LCPUFA) concentrations; however, limited studies have accounted for dietary PUFA intake or whether tobacco dose or smoking duration influences this association. We measured red blood cell phospholipid (RBC) membrane concentrations of fatty acids in 126 current smokers, 311 former smokers, and 461 never smokers using gas liquid chromatography and tandem mass spectrometry. Smokers had lower RBC membrane percentages of total n-3 LCPUFAs compared to former smokers or never smokers (median percent: 5.46, [interquartile range (IQR) 4.52, 6.28] versus 6.39; [IQR: 5.18, 7.85] versus 6.59; [IQR 5.34, 8.01]) (p<0.001) and this association remained after adjusting for dietary PUFA intake. Duration of smoking and cigarettes per day were not associated with RBC membrane n-3 LCPUFA differences. Smoking is associated with lower n-3 LCPUFA RBC membrane percentages and this association was not influenced by diet or smoking dose or duration.

Predictors of inadequate bowel preparation for colonoscopy.

OBJECTIVE: Inadequate preparation of the bowel for colonoscopy can result in both missed pathological lesions and cancelled procedures. We looked prospectively at the quality of colonic preparation and evaluated potential associations between specific patient characteristics and inadequate colonic preparation. METHODS: Data were gathered on consecutive patients presenting for colonoscopy who received either a polyethylene glycol lavage or oral sodium phosphate bowel preparation. Patient demographic and medical history information was gathered before scheduled colonoscopy. The endoscopist evaluated the preparation quality during the procedure. Complete data were gathered on 649 of 714 eligible patients (90.8%). Possible predictors of inadequate colonic preparation were analyzed using univariate statistics and multivariate logistic regression models. RESULTS: An inadequate colonic preparation was reported in 21.7% of observed colonoscopies. Only 18% of patients with an inadequate colonic preparation reported a failure to adequately follow preparation instructions. A later colonoscopy starting time, a reported failure to follow preparation instructions, inpatient status, a procedural indication of constipation, taking tricyclic antidepressants, male gender, and a history of cirrhosis, stroke or dementia were all independent predictors of an inadequate colon preparation (all p < 0.05). A procedural indication of previous polypectomy was a negative predictor of inadequate colonic preparation (p < 0.05). CONCLUSION: Several patient characteristics were significantly associated with colonic preparation quality independent of preparation type, compliance with preparation instructions, and procedure starting time. This information may help to identify patients at an increased risk for inadequate colonic preparation for whom alternative preparation protocols would be appropriate.

Cost-utility of one-time colonoscopic screening for colorectal cancer at various ages.

OBJECTIVE: One-time colonoscopy has been recommended as a possible colorectal cancer (CRC) screening strategy. Because the incidence of colorectal neoplasia increases with age, the effectiveness and cost of this strategy depend on the age at which screening occurs. The purpose of this study was to investigate the age-dependent cost-utility of one-time colonoscopic screening. METHODS: We constructed a computer simulation model of the natural history of colorectal neoplasia. This model was used to compare the cost-utility of no screening and age-based strategies employing one-time colonoscopic screening (age ranges evaluated: 45-49, 50-54, 55-59, and 60-64 yr). RESULTS: We determined that one-time colonoscopic screening in men age <60 yr and in women age <65 yr dominates never screening and screening at older ages. For both sexes, one-time colonoscopic screening between 50 and 54 yr of age is associated with a marginal cost-utility of less than $10,000 per additional quality-adjusted life-year compared to screening between 55 and 60 yr of age. One-time colonoscopic screening between 45 and 49 yr of age is either dominated (women) or associated with a marginal cost-utility of $69,000/per quality-adjusted life-year (men) compared to screening between 50 and 54 yr of age. The marginal cost-utility of one-time colonoscopic screening is relatively insensitive to plausible changes in the cost of colonoscopy, the cost of CRC treatment, the sensitivity of colonoscopy for colorectal neoplasia, the utility values representing the morbidity associated with the CRC-related health states, and the discount rate. CONCLUSIONS: One-time colonoscopic screening between 50 and 54 yr of age is cost-effective compared to no screening and screening at older ages in both men and women. Screening in men between 45 and 49 yr of age may be cost-effective compared to screening between 50 and 54 yr of age depending on societal willingness to pay.

Disease-specific outcomes assessment for diagnosis of colorectal neoplasia: from clinical trials to community practice.

The value of monitoring the performance of diagnostic testing in clinical practice is emphasized through data showing that experts with apparently equal training have substantially different sensitivity for cancer and polyp detection when performing colonic imaging studies. The authors discuss the effects of variation in study population, testing methodology, and expertise of examiners on the outcomes of diagnostic tests for colorectal cancer.

Utility valuations for outcome states of colorectal cancer.

OBJECTIVE: Utilities for the outcome states of colorectal cancer (CRC) must be measured to evaluate the cost-utility of screening and surveillance strategies for this disease. We sought to measure utilities for stage-dependent outcome states of CRC. METHODS: We identified persons who had previously undergone removal of colorectal adenoma. We conducted individual interviews in which these participants were presented with stage-dependent outcome states and were asked to assess utilities for them using the standard gamble technique. RESULTS: A total of 90 participants were interviewed; nine were excluded, leaving 81 for analysis. We obtained the following utility valuations: stage I rectal or stage I/II colon cancer (mean 0.74, median 0.75); stage III colon cancer (mean 0.67, median 0.75); stage II/III rectal cancer without ostomy (mean 0.59, median 0.60), stage II/III rectal cancer with ostomy (mean 0.50, median 0.55), stage IV rectal or colon cancer (mean 0.25, median 0.20). These valuations were statistically different from each other. CONCLUSIONS: We measured utilities for stage-dependent outcome states of CRC in a sample of persons who had previously undergone removal of colorectal adenoma. We found that our participants were able to differentiate between the presented outcome states and assigned lower utility to increasingly morbid states. Our results show that stage-dependent morbidity is an important consideration in CRC and should be incorporated into any decision analysis model evaluating the cost-effectiveness of CRC screening or surveillance.

Translating clinical research to community-based practice: lessons from colorectal cancer screening and diagnosis.

As we have shown using examples from colorectal cancer screening and diagnosis, translation of published studies into community practice is not a simple task. A literature review may not clearly indicate which strategy is best. Even when one strategy has a definite advantage, there may be variation in its actual clinical performance. Prior to initiating a new strategy or when reconsidering an old one, questions should be asked concerning applicability to the community population, the protocols that will be used, and the training, experience, and skill of the clinicians involved in its use. After a clinical strategy is implemented, ongoing information concerning its clinical performance should be continuously collected so that deficiencies can be identified and corrected. This information may be difficult and costly to obtain, but has enormous relevance for guiding healthcare decisions and improving outcomes.

Outcome states of colorectal cancer: identification and description using patient focus groups.

OBJECTIVE: Utilities for the outcome states of colorectal cancer must be measured to evaluate the cost-utility of screening and surveillance strategies for this disease. We sought to identify these outcome states, define their associated areas of morbidity, and construct representative descriptions of them for use in a utilities assessment instrument. METHODS: We identified candidate colorectal cancer outcome states based on a review of the literature and interviews with health care professionals. We organized patient focus groups from each of the candidate outcome states to examine their homogeneity and define their associated areas of morbidity. After analyzing the focus group transcripts, we identified and described outcome states of colorectal cancer for future incorporation into a utilities assessment instrument. RESULTS: Six candidate outcome states of colorectal cancer were identified based on disease stage and location at diagnosis. Thirty-eight patients then participated in six focus groups. Analysis of the focus group transcripts revealed seven areas of morbidity associated with colorectal cancer. These areas included problems with social interaction and cognition, fear of cancer recurrence, pain, fatigue, changes in bowel habits, and sexual dysfunction. Based on differences in the intensity and frequency of the symptoms reported in each of these areas, seven distinct outcome states of colorectal cancer were identified and described. CONCLUSION: Clinically distinct outcome states of colorectal cancer are determined by the stage and location of the cancer at the time of diagnosis. Descriptions of these outcome states were created using data collected from patient focus groups. These descriptions can be incorporated into a utilities assessment instrument.