Pilot clinical study of the effects of ginger root extract on eicosanoids in colonic mucosa of subjects at increased risk for colorectal cancer.

Colorectal cancer (CRC) remains a significant cause of mortality. Inhibitors of cyclooxygenase (COX) and thus prostaglandin E2, are promising CRC preventives, but have significant toxicities. Ginger has been shown to inhibit COX, to decrease the incidence and multiplicity of adenomas, and decrease PGE2 concentrations in subjects at normal risk for CRC. This study was conducted to determine the effects of 2.0 g/d of ginger given orally on the levels of PGE2, leukotriene B4 (LTB4), 13-hydroxy-octadecadienoic acids, and 5-, 12-, & 15-hydroxyeicosatetraenoic acid, in the colonic mucosa of subjects at increased risk for CRC. We randomized 20 subjects to 2.0 g/d ginger or placebo for 28 d. At baseline and Day 28, a flexible sigmoidoscopy was used to obtain colon biopsies. A liquid chromatography mass spectrometry method was used to determine eicosanoid levels in the biopsies, and levels were expressed per amount of protein or free arachidonic acid (AA). There was a significant decrease in AA between baseline and Day 28 (P = 0.05) and significant increase in LTB4 (P = 0.04) when normalized to protein, in subjects treated with ginger versus placebo. No other changes in eicosanoids were observed. There was no difference between the groups in total adverse events (AE; P = 0.06). Ginger lacks the ability to decrease eicosanoid levels in people at increased risk for CRC. Ginger did appear to be both tolerable and safe; and could have chemopreventive effects through other mechanisms. Further investigation should focus on other markers of CRC risk in those at increased CRC risk.

Preliminary examination of the efficacy and safety of a standardized chamomile extract for chronic primary insomnia: a randomized placebo-controlled pilot study.

BACKGROUND: Despite being the most commonly used herbal for sleep disorders, chamomile's (Matricaria recutita) efficacy and safety for treating chronic primary insomnia is unknown. We examined the preliminary efficacy and safety of chamomile for improving subjective sleep and daytime symptoms in patients with chronic insomnia. METHODS: We performed a randomized, double-blind, placebo-controlled pilot trial in 34 patients aged 18-65 years with DSM-IV primary insomnia for ≥ 6-months. Patients were randomized to 270 mg of chamomile twice daily or placebo for 28-days. The primary outcomes were sleep diary measures. Secondary outcomes included daytime symptoms, safety assessments, and effect size of these measures. RESULTS: There were no significant differences between groups in changes in sleep diary measures, including total sleep time (TST), sleep efficiency, sleep latency, wake after sleep onset (WASO), sleep quality, and number of awakenings. Chamomile did show modest advantage on daytime functioning, although these did not reach statistical significance. Effect sizes were generally small to moderate (Cohen's d ≤ 0.20 to < 0.60) with sleep latency, night time awakenings, and Fatigue Severity Scale (FSS), having moderate effect sizes in favor of chamomile. However, TST demonstrated a moderate effect size in favor of placebo. There were no differences in adverse events reported by the chamomile group compared to placebo. CONCLUSION: Chamomile could provide modest benefits of daytime functioning and mixed benefits on sleep diary measures relative to placebo in adults with chronic primary insomnia. However, further studies in select insomnia patients would be needed to investigate these conclusions.

Expeller-Pressed Canola (Brassica napus) Meal Modulates the Structure and Function of the Cecal Microbiota, and Alters the Metabolome of the Pancreas, Liver, and Breast Muscle of Broiler Chickens.

The inoculation of one-day-old broiler chicks with the cecal contents from a mature broiler breeder resulted in a highly diverse and uniform cecal bacterial community. CM did not affect feed consumption, weight gain, nor the richness, evenness, or diversity of the cecal bacterial community. However, the structure of the bacterial community was altered in birds fed the CM diet. Although the CM diet was formulated to contain equivalent metabolizable energy to the control diet, it contained more dietary fiber. The abundance of bacterial families, including those that are known to contain species able to metabolize fiber was altered (e.g., bacteria within the families, Methanobacteriaceae, Atopobiaceae, Prevotellaceae, Clostridiales Family XIII, Peptostreptococcaceae, and Succinivibrionaceae), and concentrations of SCFAs were higher in the ceca of birds fed the CM diet. Moreover, concentrations of isoleucine, isobutyrate, glutamate, and 2-oxoglutarate were higher, whereas concentrations of phenyllactic acid, indole, glucose, 3-phenylpropionate, and 2-oxobutyrate were lower in the digesta of chickens that were fed CM. The metabolic profiles of pancreas, liver, and breast muscle tissues of birds fed the CM diet differed from control birds. Metabolites that were associated with energy production, protection against oxidative stress, and pathways of amino acid and glycerophospholipid metabolism had altered concentrations in these tissues. Some of the observed changes in metabolite levels may indicate an increased disease risk in birds fed the CM diet (e.g., pancreatitis), and others suggested that birds mounted metabolic response to offset the adverse impacts of CM (e.g., oxidative stress in the liver).

The SF-36 physical and mental health factors were confirmed in cancer and HIV/AIDS patients.

BACKGROUND AND OBJECTIVE: This study assesses the extent to which the RAND-36/SF-36 items measure physical and mental health (PH and MH), as implied by existing summary scoring systems. METHODS: A total of 1,714 heterogeneous cancer and HIV/AIDS patients were recruited from five institutions. Of these, 56% were women; 81% Caucasians; and about 10% were from each of the major cancer types and HIV/AIDS. RESULTS: Analyses of the SF-36 confirmed the two dimensions of health namely physical and mental. However, item fit statistics and residual factor analysis revealed that some items intended to represent the PH dimension fit better with the MH dimension. CONCLUSION: This paper demonstrated the value of Rasch residual factor analysis for understanding and enhancing interpretation of health.

Defining higher order dimensions of self-reported health: further evidence for a two-dimensional structure.

We illustrate a method for understanding the extent to which a pool of fairly diverse health status questions can be examined for their dimensionality, by first fitting the data to a unidimensional measurement model, then examining item fit and residual factor analysis to determine the pattern of deviations from unidimensionality. We simultaneously administered five questionnaires to 1,714 people with cancer and HIV disease and combined all responses into one analysis. Item responses were cocalibrated onto one presumed underlying construct, often referred to as health-related quality of life (HRQOL). To identify significant, higher order substructures in the data, we then conducted a factor analysis of the data residuals, revealing two definable higher order dimensions: physical well-being and mental well-being. These results agree with other research and provide direction for further studies defining these dimensions within an item response theory (IRT) tradition.

Altered resting brain connectivity in persistent cancer related fatigue.

There is an estimated 3 million women in the US living as breast cancer survivors and persistent cancer related fatigue (PCRF) disrupts the lives of an estimated 30% of these women. PCRF is associated with decreased quality of life, decreased sleep quality, impaired cognition and depression. The mechanisms of cancer related fatigue are not well understood; however, preliminary findings indicate dysfunctional activity in the brain as a potential factor. Here we investigate the relationship between PCRF on intrinsic resting state connectivity in this population. Twenty-three age matched breast cancer survivors (15 fatigued and 8 non-fatigued) who completed all cancer-related treatments at least 12 weeks prior to the study, were recruited to undergo functional connectivity magnetic resonance imaging (fcMRI). Intrinsic resting state networks were examined with both seed based and independent component analysis methods. Comparisons of brain connectivity patterns between groups as well as correlations with self-reported fatigue symptoms were performed. Fatigued patients displayed greater left inferior parietal lobule to superior frontal gyrus connectivity as compared to non-fatigued patients (P < 0.05 FDR corrected). This enhanced connectivity was associated with increased physical fatigue (P = 0.04, r = 0.52) and poor sleep quality (P = 0.04, r = 0.52) in the fatigued group. In contrast greater connectivity in the non-fatigued group was found between the right precuneus to the periaqueductal gray as well as the left IPL to subgenual cortex (P < 0.05 FDR corrected). Mental fatigue scores were associated with greater default mode network (DMN) connectivity to the superior frontal gyrus (P = 0.05 FDR corrected) among fatigued subjects (r = 0.82) and less connectivity in the non-fatigued group (r = -0.88). These findings indicate that there is enhanced intrinsic DMN connectivity to the frontal gyrus in breast cancer survivors with persistent fatigue. As the DMN is a network involved in self-referential thinking we speculate that enhanced connectivity between the DMN and the frontal gyrus may be related to mental fatigue and poor sleep quality. In contrast, enhanced connectivity between the DMN and regions in the subgenual cingulate and brainstem may serve a protective function in the non-fatigued group.

Using a Rasch scale to characterize the clinical features of patients with a clinical diagnosis of uncertain, probable, or possible Alzheimer disease at intake.

OBJECTIVE: This study examined the clinical features of patients with clinical diagnoses of probable Alzheimer disease (AD), possible AD, and uncertain. DESIGN: Case study comparing three groups of AD patients diagnosed at their initial visit to an Alzheimer outpatient clinic. SETTING: Southern Illinois University School of Medicine's Center for Alzheimer Disease and Related Disorders (CADRD) assessment sites (20) in rural Illinois. PARTICIPANTS: 300 patients assessed at CADRD between January 1, 1994 and July 1, 2000. MEASUREMENTS: Patients were given an extensive clinical battery consisting of physical and neurologic examination, mental status testing including the Mini-Mental State Exam (MMSE), Short Blessed Dementia (SBD) and Blessed Dementia Scale (ADL), medical history evaluation, and laboratory tests. Other data included age at visit, gender, and medical history variables. RESULTS: Mean MMSE, SBD, and ADL scores differed significantly between groups (p's < 0.01). In all three cognitive tests, the uncertain group was the least impaired while the probable AD group was the most impaired. A Rasch model indicated that only the cognitive measures were useful in discriminating between the three diagnostic groups. CONCLUSION: In general, probable AD patients were distinguished from possible AD patients by the severity of their dementia as measured by the MMSE, ADL and SBD as well as Hachinski-Ischemic Score (HIS) scores. A Rasch model did well at predicting group membership based upon dementia measures only. The uncertain group differed from the AD groups in age and dementia severity as measured by the MMSE, ADL and SBD. Noting differences between this and previous studies, we speculate disparity may be related to differences in population ethnicity.

The Smell Identification Test as a measure of olfactory identification ability in schizophrenia and healthy populations: a Rasch psychometric study.

This study examines University of Pennsylvania Smell Identification Test (UPSIT; R. L. Doty, 1995) performance in 133 controls and 54 chronic, medicated outpatients with schizophrenia (SZ) using item-response theory modeling. Results show that UPSIT items contribute to 1 factor, cover a range of 8 standard errors of measurement, and articulate 3 ability levels. Although it is not difficult enough to discriminate among persons of above-average ability, the test has diagnostic utility in detecting moderate impairment. Independent of item difficulty, 13 items differentiate patients from controls. When 45 patients and 45 controls were matched on gender and age, patient accuracy remained significantly reduced. The findings support the test's utility and demonstrate how traditional data analysis is insensitive to complexities in test performance.

Construction of measures from many-facet data.

An extension to the Rasch model for fundamental measurement is described in which there is parameterization not only for examinee ability and item difficulty but also for judge severity. Variants of this model are discussed and judging plans reviewed. Its use and characteristics are explained by an application of the model to an empirical testing situation. A comparison with Generalizability Theory using a common data set is presented as a contrast in approaches to resolving judge indeterminacy.

Development of a functional movement scale for infants.

The increasing survival rate of infants with a complicated birth and perinatal history generated the need for a test of functional motor performance with the capability of identifying children under four months of age with delayed development which could be addressed with physical therapy. This paper describes a Rasch analysis of the psychometric qualities of the Test of Infant Motor Performance (TIMP) for the purpose of reducing the length of the test while maintaining its precision as a measurement device. Following analysis of fit statistics, item-to-total correlations, redundancy of item difficulty measures, and consideration of clinically-relevant features of test items from analysis of 1732 tests, the TIMP was reduced from 59 to 42 items forming a functional motor scale for prematurely born infants. The resulting person separation index was 4.85 and the item separation index was 23.79.

Comparing traditional and Rasch analyses of the Mississippi PTSD Scale: revealing limitations of reverse-scored items.

This study examined whether Rasch analysis could provide more information than true score theory (TST) in determining the usefulness of reverse-scored items in the Mississippi Scale for Posttraumatic Stress Disorder (M-PTSD). Subjects were 803 individuals in inpatient PTSD units at 10 VA sites. TST indicated that the M-PTSD performed well and could be improved slightly by deleting one item. Factor analysis using raw scores indicated that the reverse-scored items formed the second factor and had poor relationships with normally scored items. However, since item-total correlations supported their usefulness, they were kept. The subsequent Rasch analysis indicated that five of the seven worst fitting items were reverse-scored items. We concluded that using reversed items with disturbed patients can cause confusion that reduces reliability. Deleting them improved validity without loss of reliability. The study supports the use of Rasch analysis over TST in health research since it indicated ways to reduce respondent burden while maintaining reliability and improving validity.

Effect of ginger root on cyclooxygenase-1 and 15-hydroxyprostaglandin dehydrogenase expression in colonic mucosa of humans at normal and increased risk for colorectal cancer.

Elevated tissue levels of prostaglandin E2, produced by cyclooxygenase (COX), are an early event in colorectal cancer (CRC). Data suggest the efficacy of nonsteroidal anti-inflammatory drugs, such as cancer preventives, in the inhibition of COX activity; however, side effects of nonsteroidal anti-inflammatory pose unacceptable limitations. Ginger has been reported to have anti-inflammatory activities with significant CRC preventive potential. We investigated whether consumption of 2.0 g ginger daily regulated the level of two key enzymes that control prostaglandin E2 production, COX-1 and NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Thirty participants at normal and 20 participants at increased risk for CRC were randomized and given 2.0 g/day ginger or placebo for 28 days. Flexible sigmoidoscopy was used to obtain colon biopsies at baseline and the end of the study. Tissue levels of COX-1 and 15-PGDH were assessed using western blotting. After ginger consumption, participants at increased risk for CRC had a significantly reduced colonic COX-1 protein level (23.8±41%) compared with the placebo group (18.9±52%; P=0.03). Protein levels of 15-PGDH in the colon were unchanged. In participants who were at normal risk for CRC, neither protein levels of COX-1 nor 15-PGDH in the colon were altered by ginger consumption. Ginger significantly lowered COX-1 protein expression in participants at increased risk for CRC but not in those at normal risk for CRC. Ginger did not alter 15-PGDH protein expression in either increased or normal-risk participants. Further investigation, in larger studies with a longer ginger intervention, is needed to examine the ability of ginger to impact tissue levels of prostaglandin.

Phase II study of the effects of ginger root extract on eicosanoids in colon mucosa in people at normal risk for colorectal cancer.

Inhibitors of COX indicate that upregulation of inflammatory eicosanoids produced by COX, and in particular prostaglandin E(2) (PGE(2)), are early events in the development of colorectal cancer (CRC). Ginger has shown downregulation of COX in vitro and decreased incidence/multiplicity of adenomas in rats. This study was conducted to determine if 2.0 g/d of ginger could decrease the levels of PGE(2), 13-hydroxy-octadecadienoic acids, and 5-, 12-, and 15-hydroxyeicosatetraenoic acid (5-, 12-, and 15-HETE), in the colon mucosa of healthy volunteers. To investigate this aim, we randomized 30 subjects to 2.0 g/d ginger or placebo for 28 days. Flexible sigmoidoscopy at baseline and day 28 was used to obtain colon biopsies. A liquid chromatography mass spectrometry method was used to determine eicosanoid levels in the biopsies, and levels were expressed per protein or per free arachidonic acid. There were no significant differences in mean percent change between baseline and day 28 for any of the eicosanoids, when normalized to protein. There was a significant decrease in mean percent change in PGE(2) (P = 0.05) and 5-HETE (P = 0.04), and a trend toward significant decreases in 12-HETE (P = 0.09) and 15-HETE (P = 0.06) normalized to free arachidonic acid. There was no difference between the groups in terms of total adverse events P = 0.55). On the basis of these results, it seems that ginger has the potential to decrease eicosanoid levels, perhaps by inhibiting their synthesis from arachidonic acid. Ginger also seemed to be tolerable and safe. Further investigation in people at high risk for CRC seems warranted.

Development of an index of physical functional health status in rehabilitation.

OBJECTIVE: To describe (1) the development of an index of physical functional health status (FHS) and (2) its hierarchical structure, unidimensionality, reproducibility of item calibrations, and practical application. DESIGN: Rasch analysis of existing data sets. SETTING: A total of 715 acute, orthopedic outpatient centers and 62 long-term care facilities in 41 states participating with Focus On Therapeutic Outcomes, Inc. PATIENTS: A convenience sample of 92,343 patients (40% male; mean age +/- standard deviation [SD], 48+/-17y; range, 14-99y) seeking rehabilitation between 1993 and 1999. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patients completed self-report health status surveys at admission and discharge. The Medical Outcomes Study 36-Item Short-Form Health Survey's physical functioning scale (PF-10) is the foundation of the physical FHS. The Oswestry Low Back Pain Disability Questionnaire, Neck Disability Index, Lysholm Knee Questionnaire, items pertinent to patients with upper-extremity impairments, and items pertinent to patients with more involved neuromusculoskeletal impairments were cocalibrated into the PF-10. RESULTS: The final FHS item bank contained 36 items (patient separation, 2.3; root mean square measurement error, 5.9; mean square +/- SD infit, 0.9+/-0.5; outfit, 0.9+/-0.9). Analyses supported empirical item hierarchy, unidimensionality, reproducibility of item calibrations, and content and construct validity of the FHS-36. CONCLUSIONS: Results support the reliability and validity of FHS-36 measures in the present sample. Analyses show the potential for a dynamic, computer-controlled, adaptive survey for FHS assessment applicable for group analysis and clinical decision making for individual patients.

Validity of the Test of Infant Motor Performance for prediction of 6-, 9- and 12-month scores on the Alberta Infant Motor Scale.

The Test of Infant Motor Performance (TIMP) is a test of functional movement in infants from 32 weeks' post-conceptional age to 4 months postterm. The purpose of this study was to assess in 96 infants (44 females, 52 males) with varying risk, the relation between measures on the TIMP at 7, 30, 60, and 90 days after term age and percentile ranks (PR) on the Alberta Infant Motor Scale (AIMS). Correlation between scores on the TIMP and the AIMS was highest for TIMP tests at 90 days and AIMS testing at 6 months (r=0.67, p=0.0001), but all comparisons were statistically significant except those between the TIMP at 7 days and AIMS PR at 9 months. In a multiple regression analysis combining a perinatal risk score and 7-day TIMP measures to predict 12-month AIMS PR, risk, but not TIMP, predicted outcome (21% of variance explained). At older ages TIMP measures made increasing contributions to prediction of 12-month AIMS PR (30% of variance explained by 90-day TIMP). The best TIMP score to maximize specificity and correctly identify 84% of the infants above versus below the 10th PR at 6 months was a cut-off point of 1 SD below the mean. The same cut-off point correctly identified 88% of the infants at 12 months. A cut-off of -0.5 SD, however, maximized sensitivity at 92%. A negative test result, i.e. score above -0.5 SD at 3 months, carried only a 2% probability of a poor 12-month outcome. We conclude that TIMP scores significantly predict AIMS PR 6 to 12 months later, but the TIMP at 3 months of age has the greatest degree of validity for predicting motor performance on the AIMS at 12 months and can be used clinically to identify infants likely to benefit from intervention.

Measurement characteristics of the Functional Independence Measure.

Clinicians and researchers recognize the need for measures offunctional status that possess linear properties and are reliable and valid. Rasch rating scale analysis provides the means for converting raw scores from functional assessment tools to linear measures for which measurement error can be quantified. The extent to which clinicians perceive patients who are undergoing rehabilitation after stroke as similarto other patient groups was investigated using the Functional Independence Measure (FIM). Earlier work demonstrated that the first 13 items of the FIM represent a measure of motor function and that the last 5 items represent a measu re of cognitive function. The FIM was used for patients with stroke in a manner similar to that for most other impairment groups on the motor items. Patients with stroke were, however, unlike many impairment groups in their ratings on the cognitive items. Tables showing raw score to scaled measure conversions are provided for two sets of impairment groups on the motor items and three sets of impairment groups on the cognitive items. Clinicians can be confident that the measures derived from the FIM are linear across the range of the instrument and are attuned to the uniqueness of patients with stroke and other specific impairments.

The talking touchscreen: a new approach to outcomes assessment in low literacy.

PURPOSE: Cancer patients who are deficient in literacy skills are particularly vulnerable to experiencing different outcomes due to disparities in care or barriers to care. Outcomes measurement in low literacy patients may provide new insight into problems previously undetected due to the challenges of completing paper-and-pencil forms. DESCRIPTION OF STUDY: A multimedia program was developed to provide a quality of life assessment platform that would be acceptable to patients with varying literacy skills and computer experience. One item at a time is presented on the computer touchscreen, accompanied by a recorded reading of the question. Various colors, fonts and graphic images are used to enhance visibility, and a small picture icon appears near each text element allowing patients to replay the sound as many times as they wish. Evaluation questions are presented to assess patient burden and preferences. RESULTS: An ethnically diverse group of 126 cancer patients with a range of literacy skills and computer experience reported that the 'talking touchscreen' (TT) was easy to use, and commented on the usefulness of the multimedia approach. CLINICAL IMPLICATIONS: The TT is a practical, user-friendly data acquisition method that provides greater opportunities to measure self-reported outcomes in patients with a range of literacy skills.