Lactoferrin supplementation for taste and smell abnormalities among patients receiving cancer chemotherapy.

PURPOSE: Taste and smell abnormalities (TSA) are common in patients receiving chemotherapy and may lead to altered nutritional intake, treatment withdrawal, and impaired quality of life. Lipid peroxidation in the oral cavity is one cause of TSA. Lactoferrin (LFN), an iron-binding salivary protein, reduces production of lipid oxidation byproducts and has been shown to reduce perception of unpleasant flavors. To assess the feasibility of LFN as a treatment for TSA, we conducted pilot investigations among patients with cancer who self-reported TSA following onset of chemotherapy. The primary objective was to assess change in subjective taste and smell perception from baseline to completion of 30 days of LFN supplementation. METHODS: Patients were treated with 750 mg LFN daily for 30 days and followed for an additional 30 days without LFN. TSA was measured via the taste and smell questionnaire (TSQ) including taste (score 0-10), smell (score 0-6), and composite scores (0-16) (0 = no TSA) at baseline, day 30, and day 60. RESULTS: A total of 26 patients enrolled; 19 remained on study at day 30 and 17 at day 60. Baseline mean TSQ scores were 6.5 (taste), 3.1 (smell), and 9.6 (composite). By day 30, mean composite TSQ score improved by 1.7 (p = 0.018); taste and smell improved by 0.6 (p = 0.062) and 1.1 (p = 0.042), respectively. From baseline to day 60, mean composite TSQ score improved by 3.8 (p < 0.0001); taste and smell improved by 1.9 (p = 0.001) and 1.8 (p = 0.003). CONCLUSIONS: Further evaluation of LFN is warranted to determine its value for improving self-reported TSA among patients receiving chemotherapy.

Physical Function Trajectories in Survivors of Acute Respiratory Failure.

RATIONALE: Survivorship from critical illness has improved; however, factors mediating the functional recovery of persons experiencing a critical illness remain incompletely understood. OBJECTIVES: To identify groups of acute respiratory failure (ARF) survivors with similar patterns of physical function recovery after discharge and to determine the characteristics associated with group membership in each physical function trajectory group. METHODS: We performed a secondary analysis of a randomized controlled trial, using group-based trajectory modeling to identify distinct subgroups of patients with similar physical function recovery patterns after ARF. Chi-square tests and one-way analysis of variance were used to determine which variables were associated with trajectory membership. A multinomial logistic regression analysis was performed to identify variables jointly associated with trajectory group membership. RESULTS: A total of 260 patients enrolled in a trial evaluating standardized rehabilitation therapy in patients with ARF and discharged alive (NCT00976833) were included in this analysis. Physical function was quantified using the Short Physical Performance Battery at hospital discharge and 2, 4, and 6 months after enrollment. Latent class analysis of the Short Physical Performance Battery scores identified four trajectory groups. These groups differ in both the degree and rate of physical function recovery. A multinomial logistic regression analysis was performed using covariates that have been previously identified in the literature as influencing recovery after critical illness. By multinomial logistic regression, age (P < 0.001), female sex (P = 0.001), intensive care unit (ICU) length of stay (LOS) (P = 0.003), and continuous intravenous sedation days (P = 0.004) were the variables that jointly influenced trajectory group membership. Participants in the trajectory demonstrating most rapid and complete functional recovery consisted of younger females with fewer continuous sedation days and a shorter LOS. The participant trajectory that failed to functionally recover consisted of older patients with greater sedation time and the longest LOS. CONCLUSIONS: We identified distinct trajectories of physical function recovery after critical illness. Age, sex, continuous sedation time, and ICU length of stay impact the trajectory of functional recovery after critical illness. Further examination of these groups may assist in clinical trial design to tailor interventions to specific subgroups.

Health literacy and computer-assisted instruction: usability and patient preference.

The authors investigated the feasibility of using computer-assisted instruction in patients of varying literacy levels by examining patients' preferences for learning and their ability to use 2 computer-based educational programs. A total of 263 participants 50-74 years of age with varying health literacy levels interacted with 1 of 2 educational computer programs as part of a randomized trial of a colorectal cancer screening decision aid. A baseline and postprogram evaluation survey were completed. More than half (56%) of the participants had limited health literacy. Regardless of literacy level, doctors were the most commonly used source of medical information-used frequently by 85% of limited and adequate literacy patients. In multivariate logistic regression, only those with health insurance (OR = 2.35, p = .06) and computer use experience (OR = 0.39, p = .03) predicted the ability to complete the programs without assistance compared with those without health insurance or prior computer use, respectively. Although patients with limited health literacy had less computer experience, the majority completed the programs without any assistance and stated that they learned more than they would have from a brochure. Future research should investigate ways that computer-assisted instruction can be incorporated in medical care to enhance patient understanding.

Weight Loss Intervention in Survivors of ER/PR-negative Breast Cancer.

Numerous studies have found that increased body size (weight or body mass index) is a risk factor for breast cancer development, recurrence, and death. The detrimental relationship between body size and breast cancer recurrence may be more pronounced among women with estrogen receptor (ER)/progesterone receptor (PR)-negative breast cancer. Considering the limited availability of treatments, and the association between body size and recurrence, alternative treatments are needed for ER/PR-negative breast cancer survivors, particularly overweight survivors. The objective of this pilot study was to examine the feasibility of a 12-week, multi-component meal-replacement weight loss intervention among overweight or obese ER/PR-negative breast cancer survivors; and to obtain preliminary data on changes in anthropometrics, biomarkers, and health-related quality of life (QOL). The 12-week intervention included a portion-controlled diet (including meal replacements) and a multi-component intervention (including behavioral techniques, diet modification, physical activity, and social support). The goal of the intervention was to help participants lose 5% or more of their initial weight by reducing their caloric intake and increasing their physical activity (to at least 15 minutes each day). Paired t-tests assessed changes in continuous measures. Body weight was measured weekly and mixed-model regression analysis assessed change in weight over time. Nineteen ER/PR-negative breast cancer survivors with a mean age of 59 years participated in the study. All but two of the participants completed the 12-week intervention. Women lost an average of 6.3 ± 4.9 kg (P < 0.001), equivalent to 7.5% of their baseline weight. There were significant reductions in waist circumference (P = 0.001), percent fat mass (P < 0.001), total cholesterol (P = 0.026), and triglycerides (P = 0.002); and improvements in health-related QOL (P = 0.017). Findings suggested that a meal-replacement weight loss approach among ER/PR-negative breast cancer survivors was feasible and was well received.

Explaining age-related differences in depression following breast cancer diagnosis and treatment.

Younger women with breast cancer consistently show greater psychological distress than older women. This study examined a range of factors that might explain these age differences. A total of 653 women within 8 months of a first-time breast cancer diagnosis provided data on patient characteristics, symptoms, and psychosocial variables. Chart reviews provided cancer and treatment-related data. The primary outcome was depressive symptomatology assessed by the Beck Depression Inventory. A succession of models that built hierarchically upon each other was used to determine which variables could account for age group differences in depression. Model 1 contained age group only. Models 2-5 successively added patient characteristics, cancer-related variables, symptoms, and psychosocial variables. As expected, in the unadjusted analysis (Model 1) younger women were significantly more likely to report depressive symptomatology than older women (p < 0.0001). Age remained significantly related to depression until Model 4 which added bodily pain and vasomotor symptoms (p = 0.24; R (2) = 0.27). The addition of psychosocial variables in Model 5 also resulted in a model in which age was nonsignificant (p = 0.49; R (2) = 0.49). Secondary analyses showed that illness intrusiveness (the degree that illness intrudes on specific areas of life such as work, sex life, recreation, etc.) was the only variable which, considered individually with age, made the age group-depression association nonsignificant. Age differences in risk of depression following a breast cancer diagnosis can be explained by the impact of cancer and its treatment on specific areas of a woman's life.

The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans.

BACKGROUND: Arachidonic acid (AA) is a long-chain omega-6 polyunsaturated fatty acid (PUFA) synthesized from the precursor dihomo-gamma-linolenic acid (DGLA) that plays a vital role in immunity and inflammation. Variants in the Fatty Acid Desaturase (FADS) family of genes on chromosome 11q have been shown to play a role in PUFA metabolism in populations of European and Asian ancestry; no work has been done in populations of African ancestry to date. RESULTS: In this study, we report that African Americans have significantly higher circulating levels of plasma AA (p = 1.35 × 10(-48)) and lower DGLA levels (p = 9.80 × 10(-11)) than European Americans. Tests for association in N = 329 individuals across 80 nucleotide polymorphisms (SNPs) in the Fatty Acid Desaturase (FADS) locus revealed significant association with AA, DGLA and the AA/DGLA ratio, a measure of enzymatic efficiency, in both racial groups (peak signal p = 2.85 × 10(-16) in African Americans, 2.68 × 10(-23) in European Americans). Ancestry-related differences were observed at an upstream marker previously associated with AA levels (rs174537), wherein, 79-82% of African Americans carry two copies of the G allele compared to only 42-45% of European Americans. Importantly, the allelic effect of the G allele, which is associated with enhanced conversion of DGLA to AA, on enzymatic efficiency was similar in both groups. CONCLUSIONS: We conclude that the impact of FADS genetic variants on PUFA metabolism, specifically AA levels, is likely more pronounced in African Americans due to the larger proportion of individuals carrying the genotype associated with increased FADS1 enzymatic conversion of DGLA to AA.

Symptom clusters in patients with newly-diagnosed brain tumors.

A symptom cluster comprises three or more concurrent symptoms. There is a paucity of symptom cluster research in cancer patients. Data from a previously conducted clinical trial were analyzed to search for symptom clusters. This phase III, placebo-controlled, double-blind, prospective, randomized clinical trial of 66 patients assessed the effect of prophylactic d-threo-methylphenidate (d-MPH) on quality of life (QOL) in newly diagnosed brain tumor patients receiving brain radiation therapy. Patients received 5-15 mg of d-MPH or placebo twice daily starting on week 1 of radiation therapy and continuing for 8 weeks post radiotherapy. QOL data were collected at baseline; the end of radiation therapy; and 4, 8, and 12 weeks following radiation therapy using the Functional Assessment of Cancer Therapy (FACT), the FACT-Brain subscale, and the Center for Epidemiologic Studies Depression Scale. Exploratory factor analysis, multidimensional scaling (MDS), and cluster analysis were used to search for symptom clusters. The trial failed to show a treatment effect; patients receiving d-MPH or placebo were analyzed together to search for clusters. Two symptom clusters were identified using exploratory factor analysis--a language cluster including difficulty reading, writing, and finding the right words and a mood cluster including feelings of sadness, anxiety, and depressed mood; these clusters were supported by MDS and cluster analysis. Our results suggest that interventions that target both cognitive function and mood should be considered in this patient population. Further research on symptom clusters in brain tumor patients is needed.

Comparison of the prognostic significance of the electrocardiographic QRS/T angles in predicting incident coronary heart disease and total mortality (from the atherosclerosis risk in communities study).

Spatial QRS/T angle and spatial T-wave axis were shown to be strong independent predictors of incident coronary heart disease (CHD) and total mortality, but they are not routinely available. We evaluated whether frontal plane QRS/T angle, easily obtained as the difference between frontal plane axes of QRS and T, provides a suitable substitute for spatial QRS/T angle as a risk predictor. Our study consisted of 13,973 participants from the ARIC Study. Outcome variables were incident CHD and total mortality during a median follow-up of 14 years. Electrocardiographic variables were categorized as abnormal (>/=95th percentile), borderline (>/=75th and <95th percentile), and normal (<75th percentile) separately for men and women. Cox regression was used to assess the effect of electrocardiographic variables on risk of each outcome. The normal category was considered the reference cell. With adjustment for demographic and clinical characteristics, both QRS/T angles were approximately equally strong predictors of total mortality with >50% increased risk. Spatial QRS/T angle was a stronger predictor of incident CHD in women, with a 114% increased risk, but it was not significantly associated with risk of incident CHD in men. Similarly, frontal plane QRS/T angle was statistically significant for only women with a 74% increased risk of incident CHD. In conclusion, frontal plane QRS/T angle as an easily derived risk measure is a suitable clinical substitute for spatial QRS/T angle for risk prediction.

Efficacy and safety of monoclonal anti-CD20 antibody (rituximab) for the treatment of patients with recurrent low-grade non-Hodgkin's lymphoma after high-dose chemotherapy and autologous hematopoietic cell transplantation.

The major cause of treatment failure following high-dose therapy with autologous hematopoietic cell transplantation (AHCT) for low-grade lymphomas (non-Hodgkin's lymphoma [NHL]) is persistent disease or recurrence. Most patients whose disease progresses following AHCT have resistant disease and limited bone marrow reserve. In this setting, treatment options are limited and responses to conventional chemotherapy are generally poor. Rituximab is a chimeric immunoglobulin G1 kappa monoclonal antibody that recognizes the CD20 antigen on B-cells. Published data on the use of rituximab for the treatment of recurrent NHL after autologous transplantation are limited. We present a detailed report of anti-CD20 antibody treatment for 8 patients with recurrent follicular low-grade NHL after high-dose therapy and autologous transplantation. Rituximab was administered at 375 mg/m2 intravenously once weekly for a total of 4 infusions. Median follow-up for this study was 23.4 months. Six (75%) of 8 patients responded to rituximab (2 complete response, 4 partial response). The Kaplan-Meier estimated median time to progression was 17.8 months. Rituximab was generally well tolerated. One patient developed delayed neutropenia. Other side effects were infusion related and transient. Two patients were re-treated with rituximab for progressive disease and achieved partial response. In summary, this retrospective study suggests that anti-CD20 antibody treatment is feasible in the treatment of patients who relapse or progress with low-grade NHL after autologous transplantation. There appears to be a high proportion of patients who benefit and have durable responses. Anti-CD20 antibody should be considered as a first-line salvage treatment for patients with CD20+ recurrent low-grade NBL in whom high-dose therapy has failed.

In vivo ultrasonic debridement forces in bicuspids: a pilot study.

BACKGROUND: Hand instruments lead to application of excessive forces, resulting in extensive root substance removal. Ultrasonic debridement primarily removes accretions from root surfaces. However, there is a lack of information on procedural aspects of ultrasonic debridement. The purpose of the present study was to assess the forces applied by different therapists during ultrasonic root surface debridement of bicuspids in periodontal patients in vivo. METHODS: Ten dentists and 10 dental hygienists each debrided 1 aspect of a bicuspid with moderate chronic periodontitis using an ultrasonic curet. The forces applied were recorded using a piezo-electric receiver built into the handle of the ultrasonic curet, an electronic transducer, and an analogous writer. The force recordings were converted from millivolts into Newtons (N). Mean positive and negative forces were calculated for each therapist, and t tests were used to assess differences in these forces between dentists and dental hygienists. RESULTS: The results showed that the mean positive force applied by dentists was 1.00 N (range 0.53 to 1.34 N). The corresponding mean value for dental hygienists was 0.77 N (range 0.20 to 1.22 N). The mean root debridement time was 110.2 seconds (range 38 to 165 seconds) for dentists and 90.8 seconds (range 38 to 244 seconds) for dental hygienists. The mean percentage of total debridement time used for positive force application by dentists was 76.1%, and for dental hygienists 63.9%. Negative forces impacting on the periodontal soft tissues were also recorded. These negative forces reached a mean of 0.16 N for dentists and 0.31 N for dental hygienists. CONCLUSIONS: From these observations, it may be concluded that application of ultrasonic debridement therapy is highly subjective, and that dentists and dental hygienists may not be adequately trained to use these instruments optimally.

Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer--a phase II study.

BACKGROUND: 5-fluorouracil remains the standard therapy for patients with advanced/metastatic colorectal cancer. Pre-clinical studies have demonstrated the biological modulation of 5-fluorouracil by methotrexate and leucovorin. This phase II study was initiated to determine the activity and toxicity of sequential methotrexate--leucovorin and 5-fluorouracil chemotherapy in patients with advanced colorectal cancer. METHODS: Ninety-seven patients with metastatic colorectal cancer were enrolled onto the study. Methotrexate--30 mg/m2 was administered every 6 hours for 6 doses followed by a 2 hour infusion of LV--500 mg/m2. Midway through the leucovorin infusion, patients received 5-fluorouracil--600 mg/m2. This constituted a cycle of therapy and was repeated every 2 weeks until progression. RESULTS: The median age was 64 yrs (34-84) and the Eastern Cooperative Group Oncology performance score was 0 in 37%, 1 in 55% and 2 in 8% of patients. Partial and complete responses were seen in 31% of patients with a median duration of response of 6.4 months. The overall median survival was 13.0 months. The estimated 1-year survival was 53.7%. Grade III and IV toxic effects were modest and included mucositis, nausea and vomiting. CONCLUSIONS: This phase II study supports previously reported data demonstrating the modest clinical benefit of 5-FU modulation utilizing methotrexate and leucovorin in patients with metastatic colorectal cancer. Ongoing studies evaluating 5-fluorouracil modulation with more novel agents (Irinotecan and/or oxaliplatin) are in progress and may prove encouraging.