Randomized Controlled Trial of a Behavior Change Intervention to Increase Physical Activity and Quality of Life in Prostate Cancer Survivors

Background

Physical activity improves health in prostate cancer survivors; however, participation rates are low.

Purpose

This study aims to determine the effects of an implementation intention intervention on physical activity and quality of life in prostate cancer survivors.

Methods

Prostate cancer survivors (N?=?423) were randomly assigned to a standard physical activity recommendation, a self-administered implementation intention, or a telephone-assisted implementation intention. Physical activity and quality of life were assessed at baseline, 1, and 3 months.

Results

Analyses of covariance using multiple imputation showed that physical activity at 1 month increased by 86 min/week in the standard physical activity recommendation group compared with 168 min/week in the self-administered implementation intention group (P?=?0.023) and 105 min/week in the telephone-assisted implementation intention group (P?=?0.35).

Conclusions

A self-administered implementation intention intervention resulted in a meaningful short-term increase in physical activity. Supplementation with additional intervention strategies and more frequent intervention may improve longer-term exercise. (ClinicalTrials.gov number NCT01410656).     

In situ randomised trial investigating abrasive effects of two desensitising toothpastes on dentine with acidic challenge prior to brushing

Objectives

To determine if brushing dentine with 2 moderate RDA desensitising toothpastes, results in a significant dentine wear difference and whether this difference continues to be relevant when preceded with an erosive challenge.

Methods

An in situ, single centre, single blind, randomised, split mouth study, evaluated the difference in abrasion of 2 toothpastes (SFM - Sensodyne Fresh Mint^® RDA 70; CPHM - Crest Pro-Health Clean Mint^® RDA 120) in 28 healthy volunteers. Two toothpaste treatments were administered 3×/day, for each of the two 15 day periods, subjects wearing bi-lateral, lower buccal appliances each with 4 dentine sections. A 2 min extra-oral acidic challenge preceded toothbrushing for 2 study arms. Contact profilometry measured samples at baseline, days 5, 10 and 15.

Results

Brushing with SFM was significantly less abrasive than brushing with CPHM at all time points, with or without a preceding acidic challenge (p < 0.0001). The additional dentine loss arising from the erosive challenge prior to brushing with each paste was linear with time and independent of abrasive effect.

Conclusions

The desensiting toothpastes’ RDA, directly related to dentine loss with toothbrushing. An acidic challenge prior to brushing did not negate the benefits of reduced wear from the lower RDA paste compared to the higher RDA paste. When brushing eroded dentine, the additional wear appeared independent of abrasive effect. Dentine hypersensitivity sufferers should be recommended to use a low-moderate RDA toothpaste, not to brush more than 2×/day and not immediately following an acidic challenge.     

Prospective Longitudinal Substance Use Patterns in Patients Preparing for Hepatitis C Treatment

Objectives: This study prospectively examined the independent courses of alcohol, drugs, and smoking over 18 months in 154 patients preparing for hepatitis C virus (HCV) treatment in relation to functioning, negative coping, and satisfaction with quality of life in data collected from a randomized controlled trial of multiple-family group psychoeducation for patients preparing for HCV treatment. Patients with HCV who had consistent abstinence, consistent use, or achievement of abstinence after study entry were examined for outcomes pertaining to functioning in the context of HCV, negative coping, and satisfaction with quality of life. Methods: Of 309 patients considering treatment for HCV recruited from outpatient clinics at two major university medical centers and a Veterans Affairs medical center for a randomized controlled trial of a psychoeducation intervention, 154 completed baseline, 6-month, and 18-month assessments. The assessments included structured diagnostic interviews; questionnaires examining functioning, coping, and satisfaction with quality of life; medical record review; and urine testing for substances of abuse. For these analyses, substance use patterns were determined as consistent abstinence, consistent use, and achieving abstinence after study entry for alcohol and drug use and smoking. Results: The entire sample generally improved in all of these three outcomes over the course of the study. The course of alcohol, drugs, and smoking predicted HCV-related functioning, negative coping, and satisfaction with quality-of-life outcomes over 18 months. Three specific patterns of use (consistent abstinence, consistent use, and achievement of abstinence after study entry) of these substances diverged in association with outcomes related to functioning, negative coping, and satisfaction with quality of life, not only across trajectories over time within substance types but also among types of substances. Conclusions: This study's finding that different substances were associated with distinct clinical outcomes suggests the need to conceptually unbundle different types of substances in managing HCV. Future research is needed to examine the clinical utility of further unbundling these substances and also to further investigate effects of various amounts of use of these substances.     

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

Proliferation and cytogenetic analysis of hairy cell leukemia upon stimulation via the CD40 antigen

Using the CD40 system, in vitro proliferation of hairy cell leukemia (HCL) was examined in 43 patients. In this culture system, cells were stimulated by interleukin-4 (IL-4) and anti-CD40 monoclonal antibodies (MoAbs) that were added in soluble form or were cross-linked via their Fc part using Fc gamma RII-transfected mouse fibroblast cells. Proliferation was induced and confirmed by 3H-thymidine incorporation in 14 cases and by the presence of metaphases in 42 cases. 3H-thymidine incorporation showed a heterogeneous pattern: cross-linking of anti- CD40 gave the highest proliferation in 8 cases; in 11 cases, stimulation with anti-CD40 MoAbs alone, without cross-linking also resulted in proliferation; the addition of IL-4 further enhanced 3H- thymidine incorporation in 5 cases, but suppressed this phenomenon in 5 other cases. The CD40 system proved to be very effective in obtaining cytogenetic data. With a success rate of 42 of 43 patients tested, we found clonal abnormalities in 8 cases (19%) and nonclonal abnormalities with involvement of one or two abnormal metaphases in another 7 cases. The chromosomes most frequently involved in the abnormal karyotypes, both structurally and numerically, were chromosomes 5, 7, and 14. By fluorescence-activated cell-sorting analysis of the cultured cells, and by immunophenotypic analysis of metaphase spreads, T-cell growth could be excluded and the HCL-lineage confirmed. Stimulation via the CD40 antigen is an excellent tool for growing hairy cell leukemia cells.     

Inhibition and complexation of activated protein C by two major inhibitors in plasma

To determine the major physiologic inhibitors of activated protein C (APC), plasma was incubated with APC or with Protac C and subjected to immunoblotting. APC:inhibitor complexes gave two major bands reacting with antiprotein C antibodies when immunoblotted on nondenaturing gels, and additional minor bands that varied between serum and plasma. Formation of one of the two major bands of APC:inhibitor complex, but not the other, was stimulated by heparin and only this band reacted with antibodies to the previously described APC inhibitor that is here designated PCI-1. Plasma immunodepleted of PCI-1 formed complexes with APC as visualized with antiprotein C but not anti-PCI-1 antibodies, and exhibited heparin-independent inhibition of APC activity, providing evidence for the existence of a second major physiologic APC inhibitor, PCI-2. Formation of APC:PCI-2 complexes in PCI-1-depleted plasma paralleled inhibition of APC amidolytic activity. PCI-2 was separated from PCI-1 and partially purified using column chromatography. PCI-2 formed inactive complexes of approximately 110,000 molecular weight (mol wt) with APC suggesting PCI-2 has an approximate mol wt of 50,000. Thus, inhibition of APC in plasma involves two major distinct 50,000 mol wt inhibitors, the heparin-dependent PCI-1 and the heparin- independent PCI-2.     

Factor relationships of metabolic syndrome and echocardiographic phenotypes in the HyperGEN study

BACKGROUND: Metabolic syndrome and its risk factors are predictors of cardiovascular events. Metabolic syndrome is also directly associated with echocardiographic phenotypes. METHODS: The current study is the first to investigate the factors associated with both metabolic syndrome risk factors and echocardiographic phenotypes and assess their heritability. Multivariate factor analysis was performed on 15 traits in 1393 African-Americans and 1133 whites, as well as stratified by type 2 diabetes mellitus status. RESULTS: Factor analysis with varimax rotation established four to five latent factors across ethnicities and diabetes mellitus stratifications. Among metabolic syndrome risk factors, blood pressure was the most highly correlated with cardiac traits. The factor domains, in the order of the proportion of variance explained, were 'left ventricle wall thickness', 'left ventricle geometry', 'blood pressure', 'BMI-insulin', and 'lipid-insulin'. Factor analysis without any rotation identified special (cross domain) metabolic syndrome-echocardiographic factors, 'blood pressure-left ventricle geometry' and 'blood pressure-left ventricle dimension-wall thickness' in whites. Fifty to 57% of the total original risk factor variance was explained by the latent factors. Heritability was highest for BMI-insulin (37-53%), lowest for 'blood pressure' factors (15-27%), and intermediate for metabolic syndrome-echocardiographic factors. CONCLUSION: These latent factors identified can be utilized as summary phenotypes in epidemiological, linkage, and association studies.     

Properties of sulfatides in factor-XII-dependent contact activation

Incubation of normal human plasma with low amounts of sulfatides resulted in the initiation of intrinsic coagulation and the appearance of kallikrein activity. The optimal initiation of procoagulant and kallikrein amidolytic activity was dependent on the presence of factor XII, high molecular weight kininogen, and prekallikrein. Since the activated partial thromboplastin clotting times in prekallikrein- deficient plasma approach normal values upon prolonged incubation with kaolin, this phenomenon of autocorrection was studied and found to be even more pronounced in the presence of sulfatides. Autocorrection was essentially completed in 5 min in the presence of sulfatides, whereas a preincubation of 15-20 min was required in the presence of kaolin. The limited proteolysis of 125I-factor XII in plasma during incubation with activating material or during clotting was determined. Cleavage of factor XII was more rapid and more extensive in the presence of sulfatides than in the presence of kaolin. In prekallikrein-deficient plasma, factor XII cleavage was completed within 5 min in the presence of sulfatides and within 15 min in the presence of kaolin. Thus, the appearance of factor-XII-dependent coagulant activity correlates with the limited proteolysis of factor XII when normal or prekallikrein- deficient plasma is activated by sulfatides or kaolin.