Here we assessed associations between null mutations in glutathione-S-transferase (GST)T1 and GSTM1 genes, and the rs1695 polymorphism in GSTP1 (Ile105Val), and risk of breast cancer-specific (n=45) and all-cause (n=99) mortality in a multiethnic, prospective cohort of 533 women diagnosed with stage I-IIIA breast cancer in 1995–1999, enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study.
We measured the presence of the null mutation in GSTT1 and GSTM1, and the rs1695 polymorphism in GSTP1 by polymerase chain reaction. We assessed associations between breast-cancer specific and all-cause mortality using Cox proportional hazards models.
Participants with ER-negative tumors were more likely to be GSTT1 null (χ2=4.52; P=0.03), and African American women were more likely to be GSTM1 null (χ2=34.36; P<0.0001). Neither GSTM1 nor GSTT1 null mutations were associated with breast cancer-specific or all-cause mortality. In a model adjusted for body mass index, race/ethnicity, tumor stage and treatment received at diagnosis, the variant Val allele of rs1695 was associated with increased risk of all-cause (HR=1.81, 95% CI 1.16-2.82, P=0.008), but not breast cancer-specific mortality. The GSTT1 null mutation was associated with significantly higher levels of C-reactive protein.
GSTM1 and GSTT1 null genotypes had no effect on outcome; however the variant allele of rs1695 appears to confer increased risk for all-cause mortality in breast-cancer survivors.
Given the limited sample size of most studies examining associations between GST polymorphisms with breast cancer survival, and the lack of women undergoing more contemporary treatment protocols (treated prior to 1999), it may be helpful to re-examine this issue among larger samples of women diagnosed after the late 1990s, who all received some form of chemotherapy or radiotherapy.
Glutathione-S-transferases; GSTT1; GSTM1; GSTP1; Polymorphisms; Breast cancer survival; Mortality
Lifestyle-based interventions, which typically promote various behavioral modification strategies, can serve as a setting for evaluating specific behaviors and strategies thought to promote or hinder weight loss. The aim of this study was to test the associations of self-monitoring (self-weighing, food journal completion) and eating-related (dietary intake, diet-related weight-control strategies, and meal patterns) behaviors with weight loss in a sample of postmenopausal overweight-to-obese women enrolled in a 12-month dietary weight loss intervention. Changes in body weight and adoption of self-monitoring and eating-related behaviors were assessed in 123 participants. Generalized linear models tested associations of these behaviors with 12-month weight change after adjusting for potential confounders. Mean percent weight loss was 10.7%. In the final model, completing more food journals was associated with a greater % weight loss (interquartile range, 3.7% greater weight loss; p<0.0001) while skipping meals (4.3% lower weight loss; p<0.05) and eating out for lunch (at least once a week, 2.5% lower weight loss; p<0.01) were associated with a lower amount of weight loss. These findings suggest that a greater focus on dietary self-monitoring, home-prepared meals, and consuming meals at regular intervals may improve 12-month weight loss among postmenopausal women enrolled in a dietary weight loss intervention.
Women; behavioral strategies; eating behaviors; weight loss
DNA methylation is an epigenetic modification essential for the regulation of gene expression that has been implicated in many diseases, including cancer. Few studies have investigated the wide range of potential predictors of global DNA methylation, including biomarkers. Here, we investigated associations between DNA methylation and dietary factors, sex-steroid hormones, metabolic, lipid, inflammation, immune and one-carbon biomarkers. Data and baseline biomarker measurements were obtained from 173 overweight/obese postmenopausal women. Global DNA methylation in lymphocyte DNA was measured using the pyrosequencing assay for LINE-1 repeats. We used correlations and linear regression analyses to investigate associations between continuous data and DNA methylation, while t-tests were used for categorical data. Secondary analyses stratified by serum folate levels and multivitamin use were also conducted. There was little variability in LINE-1 methylation (66.3–79.5%). Mean LINE-1 methylation was significantly higher among women with elevated glucose levels. Mean LINE-1 methylation was also higher among women with high CD4+/CD8+ ratio, and lower among women with elevated vitamin B6, but neither reached statistical significance. In analyses stratified by folate status, DNA methylation was negatively associated with sex hormone concentrations (estrone, estradiol, testosterone and sex hormone binding globulin) among women with low serum folate levels (n = 53). Conversely, among women with high serum folate levels (n = 53), DNA methylation was positively associated with several immune markers (CD4/CD8 ratio, NK1656/lymphocytes and IgA). Results from this screening suggest that global DNA methylation is generally stable, with differential associations for sex hormones and immune markers depending on one-carbon status.
DNA methylation; epigenetics; epidemiology; folate; glucose; metabolic; immune function; inflammation; post-menopausal; sex hormones; women
Using data from a randomized, controlled feeding study, which aimed to recruit 88 participants (including 22 Hispanics and 22 African Americans), we examined strategies for recruiting individuals from underrepresented groups into research trials. Study eligibility criteria included participants who 1) were 18–45 years old; 2) had a body mass index (BMI) >18 < 24.9 or BMI > 28.0 <40.0; 3); had no preexisting health conditions; 4) were non-smoking; 5) had normal fasting blood glucose level (< 100 mg/dL); and 6) spoke English. Participants were recruited using two overarching methods: media-based strategies (flyers and posters, email announcements, announcements in local and campus newspapers, and the Internet) and in-person strategies (presentations in university classes and community events). Participants were enrolled March 2006–March 2009. We present the numbers of individuals requesting study information, completing pre-enrollment screening questionnaires, and enrolling in the study. A total of 1036 individuals requested study information, and 396 completed a pre-enrollment screening questionnaire; 90 enrolled in the study (22 Hispanics and 18 African Americans). Among enrolled participants, in-person recruitment strategies were reported by 39% of African Americans, 73% of Hispanics, and 30% of non-Hispanic Whites (P <0.001). In-person recruitment strategies were successful among Hispanics. Mass media recruitment strategies were successful among non-Hispanic Whites but enlisted relatively few Hispanic participants. Both strategies recruited nearly equal percentages of African Americans. These data suggest that different strategies are needed to effectively recruit racial/ethnic population subgroups into intervention studies.
Patient recruitment; carbohydrate metabolism; Hispanic American; African American
Estrogens and androgens are elevated in obesity and associated with increased postmenopausal breast cancer risk, but the effect of weight loss on these biomarkers is unknown. We evaluated the individual and combined effects of a reduced-calorie weight loss diet and exercise on serum sex hormones in overweight and obese postmenopausal women.
Patients and Methods
We conducted a single-blind, 12-month, randomized controlled trial from 2005 to 2009. Participants (age 50 to 75 years; body mass index > 25.0 kg/m2, exercising < 100 minutes/wk) were randomly assigned using a computer-generated sequence to (1) reduced-calorie weight loss diet (“diet”; n = 118), (2) moderate- to vigorous-intensity aerobic exercise (“exercise”; n = 117), (3) combined reduced-calorie weight loss diet and moderate- to vigorous-intensity aerobic exercise (“diet + exercise”; n = 117), or (4) control (n = 87). Outcomes were estrone concentration (primary) and estradiol, free estradiol, total testosterone, free testosterone, androstenedione, and sex hormone–binding globulin (SHBG) concentrations (secondary).
Mean age and body mass index were 58 years and 30.9 kg/m2, respectively. Compared with controls, estrone decreased 9.6% (P = .001) with diet, 5.5% (P = .01) with exercise, and 11.1% (P < .001) with diet + exercise. Estradiol decreased 16.2% (P < .001) with diet, 4.9% (P = .10) with exercise, and 20.3% (P < .001) with diet + exercise. SHBG increased 22.4% (P < .001) with diet and 25.8% (P < .001) with diet + exercise. Free estradiol decreased 21.4% (P < .001) with diet and 26.0% (P < .001) with diet + exercise. Free testosterone decreased 10.0% (P < .001) with diet and 15.6% (P < .001) with diet + exercise. Greater weight loss produced stronger effects on estrogens and SHBG.
Weight loss significantly lowered serum estrogens and free testosterone, supporting weight loss for risk reduction through lowering exposure to breast cancer biomarkers.
Obese and sedentary persons have increased risk for cancer; inflammation is a hypothesized mechanism. We examined the effects of a caloric restriction weight loss diet and exercise on inflammatory biomarkers in 439 women. Overweight and obese postmenopausal women were randomized to 1-year: caloric restriction diet (goal of 10% weight loss, N=118), aerobic exercise (225 minutes/week of moderate-to-vigorous activity, N=117), combined diet+exercise (N=117) or control (N=87). Baseline and 1-year high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA), interleukin-6 (IL-6), leukocyte and neutrophil levels were measured by investigators blind to group. Inflammatory biomarker changes were compared using generalized estimating equations. Models were adjusted for baseline body mass index (BMI), race/ethnicity and age. 438 (N=1 in diet+exercise group was excluded) were analyzed. Relative to controls, hs-CRP decreased by geometric mean (95% confidence interval, p-value) 0.92mg/L (0.53–1.31, P<0.001) in the diet and 0.87mg/L (0.51–1.23, P<0.0001) in the diet+exercise groups. IL-6 decreased by 0.34pg/ml (0.13–0.55, P=0.001) in the diet and 0.32pg/ml (0.15–0.49, P<0.001) in the diet+exercise groups. Neutrophil counts decreased by 0.31×109/L (0.09–0.54, P=0.006) in the diet and 0.30×109/L (0.09–0.50, P=0.005) in the diet+exercise groups. Diet and diet+exercise participants with ≥5% weight loss reduced inflammatory biomarkers (hs-CRP, SAA, and IL-6) compared to controls. The diet and diet+exercise groups reduced hs-CRP in all subgroups of baseline BMI, waist circumference, CRP level, and fasting glucose. Our findings indicate that a caloric restriction weight loss diet with or without exercise reduces biomarkers of inflammation in postmenopausal women, with potential clinical significance for cancer risk reduction.
inflammation; postmenopausal women; obesity; exercise; dietary weight loss
Recent research has identified self-monitoring behaviors as important strategies for both initial weight loss and weight loss maintenance, but relatively little is known about adopters and non-adopters of these behaviors. To test our hypothesis that key characteristics distinguish adopters from non-adopters, we examined the demographic characteristics and eating behaviors (e.g. restrained, uncontrolled, emotional and binge eating) associated with more frequent compared to less frequent use of these behaviors. Baseline demographic characteristics and eating behaviors, as well as, 12-month self-monitoring behaviors (i.e. self-weighing, food journaling, calorie counting) were assessed in 123 postmenopausal women enrolled in a dietary weight-loss intervention. Logistic regression models were used to test associations of self-monitoring use with demographic characteristics and eating behaviors. Non-Whites, compared to non-Hispanic Whites, were less likely to count calories regularly (adjusted OR: 0.36–95% CI: 0.13–0.97, p<0.05), controlling for intervention arm and baseline BMI. Participants with a college degree or higher education were less likely to self-weigh daily (adjusted OR: 0.30, 95% CI: 0.13–0.67, p≤0.01) compared to individuals who attended some college or less. Those with higher baseline binge eating scores were less likely to count calories (adjusted OR: 0.84, 95% CI: 0.73–0.97, p≤0.01) compared to participants with lower binge eating scores. In summary, use of diet-related self-monitoring behaviors varied by race/ethnicity, education, and binge eating score in postmenopausal women who completed a year-long dietary weight loss intervention. Improved recognition of groups less likely to self monitor may be helpful in promoting these behaviors in future interventions.
Weight loss; postmenopausal; women; demographic; psychosocial; behaviors; diet
Many studies have investigated the immediate impact of physical activity on prolactin concentrations; however, it is currently unclear what impact exercise may have on prolactin concentrations in the long-term, particularly among women. Understanding the role of exercise on prolactin is important because epidemiologic studies have reported increased risks of breast cancer in association with high prolactin concentrations. We investigated whether exercise alters serum prolactin concentrations at two time points within a one-year exercise intervention.
Out of 96 women aged 40-75 years, 47 were randomized to a 12-month regimen of moderate-intensity physical activity and 49 were randomized to the control group. Participants in the exercise group (exercisers) took part in exercise at gym facilities 3 times per week and 3 times per week on their own. Serum prolactin was collected from participants at baseline, 3 and 12 months. Using generalized linear models, we compared the percent change in prolactin concentrations from baseline to the two follow-up time points in the exercisers versus the control group.
While we observed the suggestion of differences in the change in serum prolactin concentrations in some subgroups, overall there was no difference in the change in prolactin concentrations between exercisers and controls at 3 months (P=0.84) or 12 months (P=0.19).
Our study does not support the hypothesis that long-term exercise influences serum prolactin concentrations.
adherence; biomarker; exercise trial; randomized control trial
Snacking may play a role in weight control. The associations of timing and frequency of snacking with observed weight change and nutrient intake were assessed in an ancillary study to a 12-month randomized controlled trial in Seattle, WA. Overweight-to-obese postmenopausal women (n=123) enrolled in the two dietary weight loss arms from 2007–2008 with complete data at 12-months were included in these analyses. Generalized linear models were used to test the associations between snacking and weight loss (%) and nutrient intake at the 12-month time point. Participants were on average 58 years old and mainly non-Hispanic White (84%). Ninety-seven percent reported ≥ 1 snack/day. Weight loss (%) was significantly lower among mid-morning (10:30am–11:29am) snackers (7.0%, 95% CI 4.3, 9.7) compared to non-mid-morning snackers (11.4%, 95% CI 10.2, 12.6; p value: 0.004). A higher proportion of mid-morning snackers reported more than 1 snack/day (95.7%), compared to afternoon (82.8%) and evening (80.6%) snackers, though differences were not statistically significant. Women who reported ≥2 snacks/day vs. ≤ 1 snack/day had higher fiber intake (p=0.027). Afternoon snackers had higher fruit and vegetable intake compared to non-afternoon-snackers (p=0.035). These results suggest that snack meals can be a source for additional fruits, vegetables, and fiber-rich foods; however, snacking patterns might also reflect unhealthy eating habits and impede weight loss progress. Future dietary weight loss interventions should evaluate the effects of timing, frequency, and quality of snacks on weight loss.
snacking; weight loss; women; nutrient intake
Comprehensive lifestyle interventions are effective in preventing diabetes and restoring glucose regulation; however, the key stimulus for change has not been identified and effects in older individuals are not established. The aim of the study was to investigate the independent and combined effects of dietary weight-loss and exercise on insulin sensitivity and restoration of normal fasting glucose in mid-aged and older women.
Four-arm RCT, conducted between 2005 and 2009 and data analyzed in 2010.
439 inactive, overweight/obese postmenopausal women. Interventions: Women were assigned to: dietary weight loss (n=118), exercise (n=117), exercise+diet (n=117), or control (n=87). The diet intervention was a group-based reduced-calorie program with a 10% weight-loss goal. The exercise intervention was 45 min/day, 5 days/week of moderate-to-vigorous intensity aerobic activity.
Main outcome measures
12-month change in serum insulin, C-peptide, fasting glucose, and whole body insulin resistance (HOMA-IR).
A significant improvement in HOMA-IR was detected in the diet (−24%, p<0.001) and exercise+ diet (−26%, p<0.001) groups, but not in the exercise (−9%, p=0.22) group compared to controls (−2%); these effects were similar in middle-aged (50–60 years) and older women (aged 60–75 years). Among those with impaired fasting glucose (5.6–6.9 mmol/L) at baseline (n=143; 33%), the odds (95% CI) of regressing to normal fasting glucose after adjusting for weight loss and baseline levels were: 2.5 (0.8, 8.4), 2.76 (0.8, 10.0), and 3.1 (1.0, 9.9) in the diet, exercise+diet, and exercise group, respectively, compared to controls.
Dietary weight loss, with or without exercise, significantly improved insulin resistance. Older women derived as much benefit as did the younger postmenopausal women.
Objective. To evaluate the acceptability and validity of an adapted version of the General Level Framework (GLF) as a tool to facilitate and evaluate performance development in general pharmacist practitioners (those with less than 3 years of experience) in a Singapore hospital.
Method. Observational evaluations during daily clinical activities were prospectively recorded for 35 pharmacists using the GLF at 2 time points over an average of 9 months. Feedback was provided to the pharmacists and then individualized learning plans were formulated.
Results. Pharmacists’ mean competency cluster scores improved in all 3 clusters, and significant improvement was seen in all but 8 of the 63 behavioral descriptors (p ≤ 0.05). Nonsignificant improvements were attributed to the highest level of performance having been attained upon initial evaluation. Feedback indicated that the GLF process was a positive experience, prompting reflection on practice and culminating in needs-based learning and ultimately improved patient care.
Conclusions. The General Level Framework was an acceptable tool for the facilitation and evaluation of performance development in general pharmacist practitioners in a Singapore hospital.
competency; pharmacist; General Level Framework; Singapore; hospital pharmacy; professional development; assessment
In the US, Hispanic women have a higher incidence of, and mortality from, cervical cancer than non-Hispanic white women. The reason for this disparity may be attributable to both low rates of screening and poor adherence to recommended diagnostic follow-up after an abnormal Pap test. The 'Cervical Cancer Screening and Adherence to Follow-up Among Hispanic Women' study is a collaboration between a research institution and community partners made up of members from community based organizations, the Yakima Valley Farm Workers Clinic and the Breast, Cervical, and Colon Health Program of the Yakima District . The study will assess the efficacy of two culturally-appropriate, tailored educational programs designed to increase cervical cancer screening among Hispanic women, based in the Yakima Valley, Washington, US.
A parallel randomized-controlled trial of 600 Hispanic women aged 21–64, who are non-compliant with Papanicolau (Pap) test screening guidelines. Participants will be randomized using block randomization to (1) a control arm (usual care); (2) a low-intensity information program, consisting of a Spanish-language video that educates women on the importance of cervical cancer screening; or (3) a high-intensity program consisting of the video plus a ‘promotora’ or lay-community health educator-led, home based intervention to encourage cervical cancer screening. Participants who attend cervical cancer screening, and receive a diagnosis of an abnormal Pap test will be assigned to a patient navigator who will provide support and information to promote adherence to follow-up tests, and any necessary surgery or treatment. Primary endpoint: Participants will be tracked via medical record review at community-based clinics, to identify women who have had a Pap test within 7 months of baseline assessment. Medical record reviewers will be blinded to randomization arm. Secondary endpoint: An evaluation of the patient navigator program as a method to improve adherence and reduce time to follow-up among participants who receive an abnormal Pap test result. An additional secondary endpoint is the cost-effectiveness of the two different intensity intervention programs.
This culturally sensitive intervention aims to increase compliance and adherence to cervical screening in a Hispanic population. If effective, such interventions may reduce incidence of cervical cancer.
Hispanic women; Pap test; Cervical cancer screening; Cancer disparities
We investigated exercise effects on health-related quality of life (HRQOL) and exercise self-efficacy, and tested effect modification by baseline body mass index (BMI) and gender.
Middle-aged women (n=100) and men (n=102) were randomly assigned to either exercise (360 minutes/week of moderate-to-vigorous aerobic exercise) or control in Seattle, WA from 2001–2004. Demographics, anthropometrics, exercise self-efficacy (5-item self-efficacy questionnaire) and HRQOL (SF-36) were assessed at baseline and 12 months. Analysis of covariance adjusting for baseline scores was used to compare HRQOL and exercise self-efficacy scores between the exercise and control groups.
At 12 months, exercisers demonstrated higher exercise self-efficacy than controls (percent change from baseline: −6.5% vs. −15.0%, p<0.01), without differences in HRQOL. Baseline BMI category and gender did not modify these effects. In exploratory analyses comparing exercisers and controls within subgroups defined by gender and BMI, 12-month HRQOL scores [(role-physical (+7.0% vs. −13.1%), vitality (+15.6% vs. −4.2%), social functioning (+10.0% vs. −3.5%), and mental health (+6.8% vs. −2.9%)] were higher only among overweight male exercisers (p<0.05, vs. control).
360 minutes/week of exercise, recommended for weight maintenance, did not have negative effects on exercise self-efficacy or HRQOL. This level of exercise may increase HRQOL among overweight men.
Objectives. To measure Croatian community pharmacists’ progress in competency development using the General Level Framework (GLF) as an educational tool in a longitudinal study.
Methods. Patient care competencies of 100 community pharmacists were evaluated twice, in 2009 and in 2010 in a prospective cohort study. During this 12-month period, tailored educational programs based on the GLF were organized and conducted, new services and standard operating procedures were implemented, and documentation of contributions to patient care in the pharmacist’s portfolio became mandatory.
Results. Pharmacists’ development of all GLF patient care competencies was significant with the greatest improvements seen in the following competencies: patient consultation, monitoring drug therapy, medicine information and patient education, and evaluation of outcomes.
Conclusions. This study, which retested the effectiveness of an evidence-based competency framework, confirmed that GLF is a valid educational tool for pharmacist development.
competency development; pharmacist; general level framework; continuing education; continuing professional development; community pharmacy
Overweight or obese breast cancer patients have a worse prognosis compared with normal-weight patients. This may be attributed to hyperinsulinemia and dysregulation of adipokine levels associated with overweight and obesity. Here, we evaluate whether low levels of adiponectin and a greater level of insulin resistance are associated with breast cancer mortality and all-cause mortality.
Patients and Methods
We measured glucose, insulin, and adiponectin levels in fasting serum samples from 527 women enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer. We evaluated the association between adiponectin and insulin and glucose levels (expressed as the Homeostatic Model Assessment [HOMA] score) represented as continuous measures and median split categories, along with breast cancer mortality and all-cause mortality, using Cox proportional hazards models.
Increasing HOMA scores were associated with reduced breast cancer survival (hazard ratio [HR], 1.12; 95% CI, 1.05 to 1.20) and reduced all-cause survival (HR, 1.09; 95% CI, 1.02 to 1.15) after adjustment for possible confounders. Higher levels of adiponectin (above the median: 15.5 μg/mL) were associated with longer breast cancer survival (HR, 0.39; 95% CI, 0.15 to 0.95) after adjustment for covariates. A continuous measure of adiponectin was not associated with either breast cancer–specific or all-cause mortality.
Elevated HOMA scores and low levels of adiponectin, both associated with obesity, were associated with increased breast cancer mortality. To the best of our knowledge, this is the first demonstration of the association between low levels of adiponectin and increased breast cancer mortality in breast cancer survivors.
To examine the association between serum C-peptide, a marker of insulin secretion, measured 3 years after a breast cancer diagnosis, and death resulting from all causes and breast cancer.
Patients and Methods
This was a prospective, observational study of 604 women enrolled onto the Health, Eating, Activity, and Lifestyle (HEAL) Study who were diagnosed with local or regional breast cancer between 1995 and 1998 and observed until death or December 31, 2006, whichever came first. The hazard ratio (HR) for all deaths and deaths owing to breast cancer and 95% CIs for the HR were estimated using multivariable stratified Cox regression analyses.
Among women without type 2 diabetes, fasting C-peptide levels were associated with an increased risk of death resulting from all causes and from breast cancer. A 1-ng/mL increase in C-peptide was associated with a 31% increased risk of any death (HR = 1.31; 95% CI, 1.06 to 1.63; P = .013) and a 35% increased risk of death as a result of breast cancer (HR = 1.35; 95% CI, 1.02 to 1.87, P = .048). Associations between C-peptide levels and death as a result of breast cancer were stronger in certain subgroups, including women with type 2 diabetes, women with a body mass index less than 25 kg/m2, women diagnosed with a higher stage of disease, and women whose tumors were estrogen receptor positive.
Treatment strategies to reduce C-peptide levels in patients with breast cancer, including dietary-induced weight loss, physical activity, and/or use of insulin-lowering medications, should be explored.
Although lifestyle interventions targeting multiple lifestyle behaviors are more effective in preventing unhealthy weight gain and chronic diseases than intervening on a single behavior, few studies have compared individual and combined effects of diet and/or exercise interventions on health-related quality of life (HRQOL). In addition, the mechanisms of how these lifestyle interventions affect HRQOL are unknown. The primary aim of this study was to examine the individual and combined effects of dietary weight loss and/or exercise interventions on HRQOL and psychosocial factors (depression, anxiety, stress, social support). The secondary aim was to investigate predictors of changes in HRQOL.
This study was a randomized controlled trial. Overweight/obese postmenopausal women were randomly assigned to 12 months of dietary weight loss (n = 118), moderate-to-vigorous aerobic exercise (225 minutes/week, n = 117), combined diet and exercise (n = 117), or control (n = 87). Demographic, health and anthropometric information, aerobic fitness, HRQOL (SF-36), stress (Perceived Stress Scale), depression [Brief Symptom Inventory (BSI)-18], anxiety (BSI-18) and social support (Medical Outcome Study Social Support Survey) were assessed at baseline and 12 months. The 12-month changes in HRQOL and psychosocial factors were compared using analysis of covariance, adjusting for baseline scores. Multiple regression was used to assess predictors of changes in HRQOL.
Twelve-month changes in HRQOL and psychosocial factors differed by intervention group. The combined diet + exercise group improved 4 aspects of HRQOL (physical functioning, role-physical, vitality, and mental health), and stress (p ≤ 0.01 vs. controls). The diet group increased vitality score (p < 0.01 vs. control), while HRQOL did not change differently in the exercise group compared with controls. However, regardless of intervention group, weight loss predicted increased physical functioning, role-physical, vitality, and mental health, while increased aerobic fitness predicted improved physical functioning. Positive changes in depression, stress, and social support were independently associated with increased HRQOL, after adjusting for changes in weight and aerobic fitness.
A combined diet and exercise intervention has positive effects on HRQOL and psychological health, which may be greater than that from exercise or diet alone. Improvements in weight, aerobic fitness and psychosocial factors may mediate intervention effects on HRQOL.
health-related quality of life; exercise; dietary weight loss; postmenopausal women
Mutations in the p53 tumor suppressor gene and accumulation of its protein in breast tissue are thought to play a role in breast carcinogenesis. However, few studies have prospectively investigated the association of p53 immunopositivity and/or p53 alterations in women with benign breast disease in relation to the subsequent risk of invasive breast cancer. We carried out a case-control study nested within a large cohort of women biopsied for benign breast disease in order to address this question. After exclusions, 491 breast cancer cases and 471 controls were available for analysis. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). Neither p53 immunopositivity nor genetic alterations in p53 (either missense mutations or polymorphisms) was associated with altered risk of subsequent breast cancer. However, the combination of both p53 immunopositivity and any p53 nucleotide change was associated with an approximate 5-fold nonsignificant increase in risk (adjusted OR 4.79, 95% CI 0.28–82.31) but the confidence intervals were extremely wide. Our findings raise the possibility that the combination of p53 protein accumulation and the presence of genetic alterations may identify a group at increased risk of breast cancer.
This study examined the effect of a yearlong exercise intervention on F2-isoprostane, a specific marker of lipid peroxidation and a general marker of oxidative stress.
In a randomized, controlled trial, 173 overweight or obese, postmenopausal, sedentary women were randomized to an aerobic exercise intervention (60–75% observed maximal heart rate) for ≥ 45 min·d−1, 5 d·wk−1 (n = 87), or to a stretching control group (n = 86), on an intent-to-treat basis. Baseline and 12-month measures included: urinary F2-isoprostane, maximal O2 uptake, body weight, body fat percentage, waist circumference, and intra-abdominal fat surface area. Urine samples were available from 172 and 168 women at baseline and 12-months, respectively.
Over the 12-month study, controls minimally changed maximal O2 uptake (+0.2%) and body weight (+0.1 kg), whereas exercisers increased maximal O2 uptake (+13.6%; p-value < 0.0001 versus controls) and decreased body weight (−1.3 kg; p-value = 0.007 versus controls). F2-isoprostane increased slightly among controls (+3.3%) and decreased in exercisers (−6.2%), although the effect was not statistically significant (p-value = 0.26). In planned subgroup analyses, F2-isoprostane decreased linearly with gain in maximal O2 uptake (ptrend = 0.005) relative to controls; exercisers who increased maximal O2 uptake >15% decreased F2-isoprostane 14.1% (p-value = 0.005 versus controls). A borderline statistically significant trend was observed between decreased waist circumference and F2-isoprostane (p-value = 0.06). Similar subgroup analyses by 12-month changes in body fat percentage, weight, and intra-abdominal fat were not statistically significant.
These findings suggest that aerobic exercise, when accompanied by relatively marked gains in aerobic fitness, decreases oxidative stress among previously sedentary older women, and that these effects occur with minimal change in mass or body composition.
intervention; women; aerobic; maximal oxygen uptake; F2-isoprostane; overweight/obese
We used a nested case–control design within a large, multi-center cohort of women who underwent a biopsy for benign breast disease (BBD) to assess the association of broad histologic groupings and specific histologic entities with risk of breast cancer.
Cases were all women who had a biopsy for BBD and who subsequently developed breast cancer; controls were individually matched to cases and were women with a biopsy for BBD who did not develop breast cancer in the same follow-up interval as that for the cases. After exclusions, 1,239 records (615 cases and 624 controls) were available for analysis. We used conditional logistic regression to estimate odds ratios and 95% confidence intervals (CIs).
Relative to non-proliferative BBD/normal pathology, the multivariable-adjusted odds ratio for proliferative lesions without atypia was 1.45 (95% CI 1.10–1.90), and that for atypical hyperplasia was 5.27 (95% CI 2.29–12.15). The presence of multiple foci of columnar cell hyperplasia and of complex fibroadenoma without atypia was associated with a non-significantly increased risk of breast cancer, whereas sclerosing adenosis, radial scar, and papilloma showed no association with risk.
Our results indicate that, compared to women with normal pathology/non-proliferative disease, women with proliferative disease without atypia have a modestly increased risk of breast cancer, whereas women with atypical hyperplasia have a substantially increased risk.
Benign breast disease; Proliferative disease; Atypical hyperplasia; Breast cancer
To assess Croatian community pharmacists' patient care competencies using the General Level Framework (GLF).
The competencies of 100 community pharmacists working in 38 community pharmacies were evaluated using an adapted version of the GLF.
Pharmacists demonstrated the best performance in the competency areas drug specific issues and provision of drug products; the poorest performance was in the competency areas evaluation of outcomes and monitoring drug therapy. Pharmacists' behavior varied the most in the following areas: ensuring that the prescription is legal, prioritization of medication management problems, and identification of drug-drug interactions.
Competencies were identified that need to be developed to improve pharmacist interventions in community settings. This study provides the first data on pharmacists' performance in Croatia and serves as a starting point for future studies and actions.
competency; pharmacist; General Level Framework; Croatia; community pharmacy
Cancer drugs are high risk drugs and medication errors in their prescribing, preparation and administration have serious consequences, including death. The importance of a multidisciplinary approach and the benefits of pharmacists’ contribution to cancer treatment to minimise risk have been established. However, the impact of services provided by pharmacists to cancer patient care is poorly studied. This study explored the clinical interventions made by pharmacists in dispensing of chemotherapy doses, and evaluated pharmacists’ contribution to patient care.
Pharmacists at the Chemotherapy Preparation Unit at a tertiary cancer centre in London were shadowed by two research pharmacists during the clinical screening of chemotherapy prescriptions and release of prepared drugs. An expert panel of pharmacy staff rated the clinical significance of the recorded interventions.
Twenty-one pharmacists’ interventions were recorded during the screening or releasing of 130 prescriptions or drugs. “Drug and therapy” (38%), “clerical” (22%) and “dose, frequency and duration” (19%) related problems most often required an intervention, identifying areas in chemotherapy prescribing that need improvement. The proposed recommendations were implemented in 86% of the cases. Many recorded interventions (48%) were ranked to have had a “very significant” influence on patient care.
Clinical interventions made by pharmacists had a significant impact on patient care. The integration of pharmacists’ technical and clinical roles into dispensing of chemotherapy doses is required for providing high-quality cancer services.
pharmacy; cancer; chemotherapy; drug compounding; medication errors