Work-Related Psychosocial Factors and Global Cognitive Function: Are Telomere Length and Low-Grade Inflammation Potential Mediators of This Association?

The identification of modifiable factors that could maintain cognitive function is a public health priority. It is thought that some work-related psychosocial factors help developing cognitive reserve through high intellectual complexity. However, they also have well-known adverse health effects and are considered to be chronic psychosocial stressors. Indeed, these stressors could increase low-grade inflammation and promote oxidative stress associated with accelerated telomere shortening. Both low-grade inflammation and shorter telomeres have been associated with a cognitive decline. This study aimed to evaluate the total, direct, and indirect effects of work-related psychosocial factors on global cognitive function overall and by sex, through telomere length and an inflammatory index. A random sample of 2219 participants followed over 17 years was included in this study, with blood samples and data with cognitive function drawn from a longitudinal study of 9188 white-collar workers (51% female). Work-related psychosocial factors were evaluated according to the Demand-Control-Support and the Effort-Reward Imbalance (ERI) models. Global cognitive function was evaluated with the validated Montreal Cognitive Assessment (MoCA). Telomere length and inflammatory biomarkers were measured using standardised protocols. The direct and indirect effects were estimated using a novel mediation analysis method developed for multiple correlated mediators. Associations were observed between passive work or low job control, and shorter telomeres among females, and between low social support at work, ERI or iso-strain, and a higher inflammatory index among males. An association was observed with higher cognitive performance for longer telomeres, but not for the inflammatory index. Passive work overall, and low reward were associated with lower cognitive performance in males; whereas, high psychological demand in both males and females and high job strain in females were associated with a higher cognitive performance. However, none of these associations were mediated by telomere length or the inflammatory index. This study suggests that some work-related psychosocial factors could be associated with shorter telomeres and low-grade inflammation, but these associations do not explain the relationship between work-related psychosocial factors and global cognitive function. A better understanding of the biological pathways, by which these factors affect cognitive function, could guide future preventive strategies to maintain cognitive function and promote healthy aging.

Psychosocial stressors at work and inflammatory biomarkers: PROspective Quebec Study on Work and Health.

BACKGROUND: Chronic low-grade inflammation has been associated with high risk of several chronic diseases such as cardiovascular diseases, diabetes, depression, and dementia. As low-grade inflammation could be present long before the apparition of the disease, identifying modifiable risk factors could allow to act upstream. Psychosocial stressors at work have been suggested as modifiable risk factors of low-grade inflammation, but few longitudinal studies have evaluated the association between these stressors and inflammatory biomarkers, such as C-reactive protein (CRP) and interleukin-6 (IL-6). OBJECTIVE: This longitudinal study evaluate the associations between exposure to psychosocial stressors at work and CRP and IL-6, separately and combined into an inflammatory index. METHODS: Data came from a cohort of 9188 white-collar workers recruited in 1991-1993 (T1) and followed-up after 8 (T2, 1999-2000) and 24 (T3, 2015-2018) years. Participants included in this study were randomly selected at T3 for serum biomarkers studies (n = 2557). CRP and IL-6 were measured using standardized protocols. Psychosocial stressors at work were assessed at T2 according to recognized models: Karasek's Demand-Control-Support model and Siegrist's Effort-Reward Imbalance (ERI) model, using validated questionnaires. High job strain was defined by an exposure to high psychological demand combined with low job control, and iso-strain was defined by an exposure to high job strain combined with low social support at work. ERI was defined by an imbalance between psychological demand and social, economic, and organizational reward. Several covariates were considered including sociodemographic, anthropometric, and lifestyle characteristics, and comorbidities. Prevalence ratios (PRs) and 95% confidence interval (CI) for the highest quartile of CRP, IL-6 and inflammatory index at T3 according to psychosocial stressors at work measured at T2 were calculated using generalized estimating equations. Multiple imputation and inverse probability of censoring weighting were done. RESULTS: In men, an association was observed between exposure to iso-strain and the inflammatory index (PR of 1.42 (95% CI: 1.06;1.90)), mainly among men aged less than 65 years (PR of 2.00 (95% CI: 1.37;2.92)). In this same age group, associations with inflammatory biomarkers were also observed among men with exposure to ERI, and among women with exposure to low reward at work or moderate social support at work. CONCLUSION: These results suggest that psychosocial stressors at work may increase low-grade inflammation. However, further studies are needed to corroborate these results and to clarify the potential differences between men and women. As these stressors are frequent and modifiable, their reduction is important for public health and could play a role in the primary prevention of chronic diseases.

Cumulative exposure to psychosocial stressors at work and global cognitive function: the PROspective Quebec Study on Work and Health.

OBJECTIVES: Psychosocial stressors at work have been proposed as modifiable risk factors for mild cognitive impairment (MCI). This study aimed to evaluate the effect of cumulative exposure to psychosocial stressors at work on cognitive function. METHODS: This study was conducted among 9188 white-collar workers recruited in 1991-1993 (T1), with follow-ups 8 (T2) and 24 years later (T3). After excluding death, losses to follow-up and retirees at T2, 5728 participants were included. Psychosocial stressors at work were measured according to the Karasek's questionnaire. Global cognitive function was measured with the Montreal Cognitive Assessment. Cumulative exposures to low psychological demand, low job control, passive job and high strain job were evaluated using marginal structural models including multiple imputation and inverse probability of censoring weighting. RESULTS: In men, cumulative exposures (T1 and T2) to low psychological demand, low job control or passive job were associated with higher prevalences of more severe presentation of MCI (MSMCI) at T3 (Prevalence ratios (PRs) and 95% CIs of 1.50 (1.16 to 1.94); 1.38 (1.07 to 1.79) and 1.55 (1.20 to 2.00), respectively), but not with milder presentation of MCI. In women, only exposure to low psychological demand or passive job at T2 was associated with higher prevalences of MSMCI at T3 (PRs and 95% CI of 1.39 (0.97 to 1.99) and 1.29 (0.94 to 1.76), respectively). CONCLUSIONS: These results support the deleterious effect of a low stimulating job on cognitive function and the cognitive reserve theory. Psychosocial stressors at work could be part of the effort for the primary prevention of cognitive decline.

Wage losses among spouses of women with nonmetastatic breast cancer.

BACKGROUND: The aim of this study was to evaluate the wage losses incurred by spouses of women with nonmetastatic breast cancer in the 6 months after the diagnosis. METHODS: A prospective cohort study of spouses of women diagnosed with nonmetastatic breast cancer who were recruited in 8 hospitals in the province of Quebec (Canada) was performed. Information for estimating wage losses was collected by telephone interviews conducted 1 and 6 months after the diagnosis. Log-binomial regressions were used to identify personal, medical, and employment characteristics associated with experiencing wage losses, and generalized linear models were used to identify characteristics associated with the proportion of usual wages lost. RESULTS: Overall, 829 women (86% participation) and 406 spouses (75% participation) consented to participate. Among the 279 employed spouses, 78.5% experienced work absences because of breast cancer. Spouses were compensated for 66.3% of their salary on average during their absence. The median wage loss was $0 (mean, $1820) (2003 Canadian dollars). Spouses were more likely to experience losses if they were self-employed or lived 50 km or farther from the hospital. Among spouses who experienced wage losses, those who were self-employed or whose partners had invasive breast cancer lost a higher proportion of wages. CONCLUSIONS: Although spouses took some time off work, for many, the resulting wage losses were modest because of compensation received. Still, the types of compensation used may hide other forms of burden for families facing breast cancer.

Effects of interdisciplinary teamwork on patient-reported experience of cancer care.

BACKGROUND: Interdisciplinary teamwork (ITW) is deemed necessary for quality cancer care practices. Nevertheless, variation in ITW intensity among cancer teams is understudied, and quantitative evidence of the effect of different ITW intensities among cancer teams on patients' perceived experience of care is limited. This study aims to compare patient-reported experience measures (PREMs) of cancer outpatients followed by teams characterized by high vs. low ITW intensity. METHODS: The study is designed as an ex post facto quasi-experimental study. Participants (n = 1379) were recruited in nine outpatient oncology clinics characterized by different ITW intensities. ITW intensities were evaluated using the characteristics of structure (team composition and size) and process (interactions among team members), as per West's seminal work on team effectiveness. ITW intensity was dichotomized (high vs. low ITW intensity). PREMs were classified and measured using validated scales corresponding to six dimensions: Prompt access to care, Person-centred response, Quality of patient-professional communication, Quality of the care environment, Continuity of care, and Results of care. Dichotomous variables were created for each dimension (positive vs. less positive experience). Multiple logistic regression analyses were performed to assess the association between ITW intensities and the six PREMs dimensions, while controlling for patient and organizational characteristics. PROC GENMOD was used to fit logistic models for categorical variables. RESULTS: Outpatients treated by teams characterized by high ITW intensity reported almost four times more positive perceptions of Prompt access to care compared to patients treated by low ITW intensity teams (OR = 3.99; CI = 1.89-8.41). High ITW intensity also positively affected patients' perceptions of Quality of patient-professional communication (OR = 2.37; CI = 1.25-4.51), Person-centred response (OR = 2.11; CI = 1.05-4.24], and Continuity of care (OR = 2.18; CI = 1.07-4.45). No significant association was found between ITW intensity and perceived Results of care (OR = 1.31; CI = 0.68-2.52) or Quality of the care environment (OR = 0.66; CI = 0.31-1.39). CONCLUSIONS: This study provides empirical evidence, from the patient's perspective, that ITW intensity affects some critical aspects of patient-reported quality of care. Future research will allow explaining how and why ITW structure and processes may contribute to positive cancer care experiences.

Factors Associated With Early Discontinuation of Study Treatment in the Mammary Prevention.3 Breast Cancer Chemoprevention Trial.

Purpose Aromatase inhibitors are established breast cancer chemoprevention interventions. However, nonadherence remains a significant challenge. We investigated the association between worsening menopause-specific quality of life, baseline participant characteristics, and early treatment discontinuation within the Mammary Prevention.3 (MAP.3) breast cancer prevention trial. Methods In the MAP.3 randomized, placebo-controlled trial evaluating exemestane, participants completed the Menopause-Specific Quality of Life Questionnaire (MENQOL) at entry and at 6 months. Multivariable log-binomial regression was used to assess the associations of baseline participant characteristics and clinically meaningful worsening in menopause-specific quality of life (QOL) with treatment discontinuation at 1 year. Results Of the 4,501 participants eligible for this analysis, 724 (17%) discontinued assigned treatment within the first year of random assignment of treatment (19% of the exemestane group and 13% of the placebo group). Between 19% and 35% of women experienced a clinically meaningful worsening in the vasomotor, sexual, physical, and psychosocial domains of the MENQOL within 6 months of treatment initiation. Regardless of receiving exemestane or not, experiencing a worsening in any MENQOL domain or, especially, overall menopause-specific QOL, was associated with early treatment discontinuation (relative risk, 1.79; 95% CI, 1.53 to 2.10 for overall worsening). Assignment to exemestane, having a smoking history, and current employment also were significantly associated with early discontinuation. Conclusion Negative changes in menopause-specific QOL influence a woman's decision to stop chemoprevention therapy. Attention to such symptoms may improve QOL and potentially improve chemoprevention adherence.

Telomere Length and Breast Cancer Prognosis: A Systematic Review.

Telomeres ensure genome integrity during replication. Loss of telomeric function leads to cell immortalization and accumulation of genetic alterations. The association of telomere length (TL) with breast cancer prognosis is examined through a systematic review. Electronic databases (MEDLINE, EMBASE, CENTRAL), from inception to December 2015, and relevant reviews were searched. Studies that evaluated TL (blood and/or tumor) in association with breast cancer survival or prognostic factor were included. Thirty-six studies met inclusion criteria. Overall risk of bias was critical. Eight studies reported survival outcomes. Overall, there was a trend toward an association of longer telomeres with better outcomes (tumor, not blood). Of the 33 studies reporting associations with prognostic factors, nine adjusted for potential confounders. Among the latter, shorter telomeres were associated with older age (blood, not tumor), higher local recurrence rates (normal tissue), higher tumor grade (tumor), and lower physical activity (blood), which were reported in one study each. TL was not associated with molecular subtype (blood, one study), family history (tumor, one study), chemotherapy (blood, three of four studies), and stress reduction interventions (blood, two of two studies). Although major methodologic differences preclude from drawing conclusive results, TL could be a valuable breast cancer prognostic marker. Cancer Epidemiol Biomarkers Prev; 26(1); 3-10. ©2016 AACR.

Association of Telomere Length with Breast Cancer Prognostic Factors.

INTRODUCTION: Telomere length, a marker of cell aging, seems to be affected by the same factors thought to be associated with breast cancer prognosis. OBJECTIVE: To examine associations of peripheral blood cell-measured telomere length with traditional and potential prognostic factors in breast cancer patients. METHODS: We conducted a cross-sectional analysis of data collected before surgery from 162 breast cancer patients recruited consecutively between 01/2011 and 05/2012, at a breast cancer reference center. Data on the main lifestyle factors (smoking, alcohol consumption, physical activity) were collected using standardized questionnaires. Anthropometric factors were measured. Tumor biological characteristics were extracted from pathology reports. Telomere length was measured using a highly reproducible quantitative PCR method in peripheral white blood cells. Spearman partial rank-order correlations and multivariate general linear models were used to evaluate relationships between telomere length and prognostic factors. RESULTS: Telomere length was positively associated with total physical activity (rs = 0.17, P = 0.033; Ptrend = 0.069), occupational physical activity (rs = 0.15, P = 0.054; Ptrend = 0.054) and transportation-related physical activity (rs = 0.19, P = 0.019; P = 0.005). Among post-menopausal women, telomere length remained positively associated with total physical activity (rs = 0.27, P = 0.016; Ptrend = 0.054) and occupational physical activity (rs = 0.26, P = 0.021; Ptrend = 0.056) and was only associated with transportation-related physical activity among pre-menopausal women (rs = 0.27, P = 0.015; P = 0.004). No association was observed between telomere length and recreational or household activities, other lifestyle factors or traditional prognostic factors. CONCLUSIONS: Telomeres are longer in more active breast cancer patients. Since white blood cells are involved in anticancer immune responses, these findings suggest that even regular low-intensity physical activity, such as that related to transportation or occupation, could be recommended to breast cancer patients.

Effect of physical activity on sex hormones in women: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Exposure to high levels of endogenous estrogens is a main risk factor for breast cancer in women, and in observational studies was found to be inversely associated with physical activity. The objective of the present study is to determine the effect of physical activity interventions on sex hormone levels in healthy women. METHODS: Electronic databases (MEDLINE, EMBASE, CENTRAL), from inception to December 2014, and reference lists of relevant reviews and clinical trials were searched, with no language restrictions applied. Randomized controlled trials (RCTs) were included if they compared any type of exercise intervention to no intervention or other interventions, and assessed the effects on estrogens, androgens or the sex hormone binding globulin (SHBG) in cancer-free women. Following the method described in the Cochrane Handbook for Systematic Reviews of Interventions, data on populations, interventions, and outcomes were extracted, and combined using the inverse-variance method and a random-effects model. A pre-established protocol was drawn up, in which the primary outcome was the difference in circulating estradiol concentrations between the physical activity (experimental) and the control groups after intervention. Pre-specified subgroup analyses and sensitivity analysis according to the risk of bias were conducted. RESULTS: Data suitable for quantitative synthesis were available from 18 RCTs (1994 participants) for total estradiol and from 5 RCTs (1245 participants) for free estradiol. The overall effect of physical activity was a statistically significant decrease of both total estradiol (standardized mean difference [SMD] -0.12; 95 % confidence interval [CI] -0.20 to -0.03; P = 0.01; I (2) = 0 %) and free estradiol (SMD -0.20; 95 % CI -0.31 to -0.09; P = 0.0005; I (2) = 0 %). Subgroup analyses suggest that this effect is independent of menopausal status and is more noticeable for non-obese women and for high intensity exercise. Meta-analysis for secondary outcomes found that physical activity induces a statistically significant decline of free testosterone, androstenedione, dehydroepiandrosterone-sulfate and adiposity markers, while a significant increase of SHBG was observed. CONCLUSIONS: Although the effect is relatively modest, physical activity induces a decrease in circulating sex hormones and this effect is not entirely explained by weight loss. The findings emphasize the benefits of physical activity for women.

A survivorship care plan for breast cancer survivors: extended results of a randomized clinical trial.

PURPOSE: Prevailing wisdom suggests that implementation of a survivorship care plan (SCP) will address deficits in survivorship care planning and delivery for cancer patients. Here, we present 24-month results of a randomized clinical trial on health service and patient-reported outcomes among breast cancer patients transferred to their primary care physician for follow-up care. The 24-month assessments represent the long-term benefit and sustainability of the implantation of a SCP. METHODS: In all, 408 patients with early-stage breast cancer were randomized to the SCP or control group. Patient self-completed questionnaires, supplemented with telephone interviews, during the 24-month study period assessed health service and patient-reported outcomes. The primary outcome was cancer-specific distress. Secondary outcomes included health-related quality of life, patient satisfaction, continuity and coordination of care, and health service outcomes such as adherence to guidelines. RESULTS: Over the course of 24 months, there were no differences between both groups in health service and patient-reported outcomes. Women from Quebec compared to those from Western Canada (p < 0.001), women within 2 years of completion of primary treatment compared to a longer period (p = 0.013), and those with a higher SF-36 mental component score compared to a lower score (p = 0.044) were positively associated with adherence to guidelines. CONCLUSION: The implementation of a SCP in the transition of survivorship care from cancer center to primary care did not contribute to improved health service or patient-reported outcomes in this study population. Therefore, additional research is needed before widespread implementation of a SCP in clinical practice. IMPLICATIONS OF CANCER SURVIVORS: The transition of survivorship care from cancer center to the primary care setting showed no negative effect on health service and patient-reported outcomes.

Measurement invariance of English and French Health Education Impact Questionnaire (heiQ) empowerment scales validated for cancer.

PURPOSE: If measurement invariance (MI) is demonstrated for a scale completed by respondents from two different language groups, it means that the scale measures the same construct in the same way in both groups. We assessed MI of the French- and English-language versions of the five Health Education Impact Questionnaire (heiQ) empowerment scales validated for the cancer setting. METHODS: Data came from two cross-sectional studies of Canadian cancer survivors (704 English, 520 French). Single-group confirmatory factor analysis (CFA) was used to test whether the hypothesized factor structure of the French-language heiQ empowerment scales fit the data. Multi-group CFAs were conducted to assess different levels of MI conditions (configural, metric, scalar, strict, as well as MI of factor variances, covariances, and latent means) of the French- and English-language heiQ empowerment scales. RESULTS: The correlated five-factor model showed good fit in both language groups (goodness-of-fit indices: CFI ≥ .97; RMSEA ≤ .07). Goodness-of-fit indices and tests of differences in fit between models supported MI of the five-factor model across the two language groups (∆CFI ≤ -.010 combined with ∆RMSEA ≤ .015). CONCLUSIONS: The French- and English-language heiQ empowerment scales measure the same five dimensions of empowerment in the same way across both language groups. Thus, any observed similarities or differences between French- and English-speaking respondents completing these scales are valid and reflect similarities or differences in empowerment across language groups, not measurement artifact. Consequently, heiQ empowerment data from English- and French-speaking respondents can be directly pooled or contrasted in data analyses.

Indicators for evaluating cancer organizations' support services: performance and associations with empowerment.

BACKGROUND: Community-based cancer organizations provide services to support patients. An anticipated benefit of these services is patient empowerment. However, this outcome has not been evaluated because of the lack of validated health-related empowerment questionnaires in the cancer context. In this validation study, the authors assessed the extent to which 16 indicators used by the Canadian Cancer Society (CCS) and the Cancer Council Victoria, Australia (CCV) to evaluate their services were associated with health-related empowerment. METHODS: Cancer patients/survivors who were diagnosed < 3 years earlier and who used CCS programs completed a questionnaire that included the 16 CCS-CCV indicators and 5 scales from the Health Education Impact Questionnaire (heiQ) measuring key dimensions of empowerment. To determine whether the CCS-CCV indicators captured empowerment, differences in heiQ scores were compared between 2 groups: those with higher levels of agreement (agreeing or agreeing strongly) with an indicator and those with lower levels of agreement (agreeing slightly or disagreeing to any degree). RESULTS: Participation was 72% (207 of 289 eligible CCS users). Compared with participants who had lower levels of agreement on CCS-CCV indicators, those who had higher levels of agreement were more likely to report higher levels of empowerment on the different heiQ scales. For 15 of 16 indicators, these differences were significant (Wilcoxon rank-sum test; P < .10) on ≥ 1 of 5 heiQ scales and for 10 of 16 indicators on ≥ 3 of 5 heiQ scales. Two indicators were associated significantly with all 5 heiQ scales (cope better and feel more in control). CONCLUSIONS: Using CCS-CCV indicators to evaluate community-based cancer organizations' services will help determine whether these services are reaching one of their important goals: namely empowering patients.

Health-related empowerment in cancer: validity of scales from the Health Education Impact Questionnaire.

BACKGROUND: Empowerment refers to an individual's feelings of being able to manage the challenges of the cancer experience and of having a sense of control over one's life. However, empowerment questionnaires that have been validated for the cancer setting are lacking. The objective of this study was to validate scales from the Health Education Impact Questionnaire (heiQ), which assesses the effects of health education programs among individuals with chronic conditions. The heiQ scales Social integration and support, Health service navigation, Constructive attitudes and approaches, Skill and technique acquisition, and Emotional distress were identified as key dimensions of empowerment for the cancer context. METHODS: Adults who were diagnosed with cancer < 3 years earlier were recruited from a population-based cancer registry and from the Canadian Cancer Society's information and peer-support programs. The 731 participants completed a mailed questionnaire, which included the heiQ scales, related constructs, and demographics. Reliability was assessed using Cronbach α values, and validity was determined using confirmatory factor analysis and scale correlations with related constructs (self-efficacy, intrusive thoughts about cancer, and mental and physical health). RESULTS: The hypothesized 5-factor model fit the data adequately (chi-square statistic, 528.17; degrees of freedom, 265; root mean square error of approximation, .04; non-normed fit index, .99; comparative fit index, 1.00; standardized root mean residual, .05). Factor loadings were high (23 of 25 were ≥ .70), and the factor correlations indicated separate but related constructs. Cronbach α values ranged from .75 to .90. A priori hypotheses about the correlations between heiQ scales and related constructs all were supported. CONCLUSIONS: The current results support the validity of these 5 heiQ scales as generic measures of health-related empowerment in the cancer setting. These scales could fill an important gap in the measures currently available to evaluate proximal effects of support interventions.

Smoking at time of diagnosis and breast cancer-specific survival: new findings and systematic review with meta-analysis.

INTRODUCTION: In women with breast cancer who smoke, it is unclear whether smoking could impair their survival from the disease. METHODS: We examined the relation of smoking at diagnosis to breast cancer-specific and overall survival among 5,892 women with invasive breast cancer treated in one Canadian center (1987 to 2008). Women were classified as never, former or current smokers. Current smokers were further classified according to total, intensity and duration of smoking. Deaths were identified through linkage to population mortality data. Cox proportional-hazards multivariate models were used. A systematic review with meta-analysis combines new findings with published results. RESULTS: Compared with never smokers, current smokers at diagnosis had a slightly, but not statistically significant, higher breast cancer-specific mortality (hazard ratio = 1.15, 95% confidence interval (CI): 0.97 to 1.37). Among current smokers, breast cancer-specific mortality increased with total exposure to, intensity and duration of smoking (all Ptrend <0.05). Compared to never smokers, breast cancer-specific mortality was 32 to 56% higher among heavy smokers (more than 30 pack years of smoking, more than 20 cigarettes per day or more than 30 years of smoking). Smoking at diagnosis was associated with an increased all-cause mortality rate. A meta-analysis of all studies showed a statistically significant, 33% increased mortality from breast cancer in women with breast cancer who are smokers at diagnosis compared to never smokers (hazard ratio = 1.33, 95% CI: 1.12 to 1.58). CONCLUSIONS: Available evidence to date indicates that smoking at diagnosis is associated with a reduction of both overall and breast cancer-specific survival. Studies of the effect of smoking cessation after diagnosis on breast cancer-specific outcomes are needed.

Quality of life in MAP.3 (Mammary Prevention 3): a randomized, placebo-controlled trial evaluating exemestane for prevention of breast cancer.

PURPOSE: Exemestane, a steroidal aromatase inhibitor, reduced invasive breast cancer incidence by 65% among 4,560 postmenopausal women randomly assigned to exemestane (25 mg per day) compared with placebo in the National Cancer Institute of Canada (NCIC) Clinical Trials Group MAP.3 (Mammary Prevention 3) trial, but effects on quality of life (QOL) were not fully described. PATIENTS AND METHODS: Menopause-specific and health-related QOL were assessed by using the four Menopause-Specific Quality of Life Questionnaire (MENQOL) domains and the eight Medical Outcomes Study Short Form Health Survey (SF-36) scales at baseline, 6 months, and yearly thereafter. MENQOL questionnaire completion was high (88% to 98%) in both groups at each follow-up visit. Change scores for each MENQOL and SF-36 scale, calculated at each assessment time relative to baseline, were compared by using the Wilcoxon rank-sum test. Clinically important worsened QOL was defined as a MENQOL change score increase of more than 0.5 (of 8) points and an SF-36 change score decrease of more than 5 (of 100) points from baseline. RESULTS: Exemestane had small negative effects on women's self-reported vasomotor symptoms, sexual symptoms, and pain, which occurred mainly in the first 6 months to 2 years after random assignment. However, these changes represented only a small excess number of women being given exemestane with clinically important worsening of QOL at one time or another; specifically, 8% more in the vasomotor domain and 4% more each in the sexual domain and for pain. No other between-group differences were observed. Overall, slightly more women in the exemestane arm (32%) than in the placebo arm (28%) discontinued assigned treatment. CONCLUSION: Exemestane given for prevention has limited negative impact on menopause-specific and health-related QOL in healthy postmenopausal women at risk for breast cancer.

Validating the content of a brief informational intervention to empower patients and spouses facing breast cancer: perspectives of both couple members.

PURPOSE: The study objectives were to identify key information components that would be the basic content of a brief informational intervention, developed from a population perspective, to empower individual couple members facing breast cancer and to validate the relevance and acceptability of these components. METHODS: A review of information relevant to couples facing cancer presented in internet sites and documents of national cancer organizations was made to identify information components to include in a brief informational intervention. These information components were framed as messages, that is, very brief sentences or tips. To validate the relevance and acceptability of these messages, six focus groups were conducted in Quebec City and Montreal among women who had had breast cancer and their spouses. Reactions to the messages were synthesized by analyzing the verbatim transcripts. RESULTS: A total of 70 individuals (35 women with an average of 14 months since diagnosis and 35 spouses) participated in the groups. The content of almost all messages was seen as relevant, although nuances and improvements were discussed. However, the message format provoked irritation and will need improvement. CONCLUSIONS: Findings provide validation of the relevance, from the viewpoint of women and their spouses, of the message content to be part of a brief informational intervention intended to empower couples as they cope with breast cancer. IMPLICATIONS FOR CANCER SURVIVORS: Couples approved of the idea of being guided in their adjustment to breast cancer. However, the message format requires adaptation and further testing.

Acupuncture for menopausal hot flushes.

BACKGROUND: Hot flushes are the most common menopausal vasomotor symptom. Hormone therapy (HT) has frequently been recommended for relief of hot flushes, but concerns about the health risks of HT have encouraged women to seek alternative treatments. It has been suggested that acupuncture may reduce hot flush frequency and severity. OBJECTIVES: To determine whether acupuncture is effective and safe for reducing hot flushes and improving the quality of life of menopausal women with vasomotor symptoms. SEARCH METHODS: We searched the following databases in January 2013: the Cochrane Menstrual Disorders and Subfertility Group Specialised Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, CINAHL, PsycINFO, Chinese Biomedical Literature Database (CBM), Chinese Medical Current Content (CMCC), China National Knowledge Infrastructure (CNKI), VIP database, Dissertation Abstracts International, Current Controlled Trials, Clinicaltrials.gov, National Center for Complementary and Alternative Medicine (NCCAM), BIOSIS, AMED, Acubriefs, and Acubase. SELECTION CRITERIA: Randomized controlled trials comparing any type of acupuncture to no treatment/control or other treatments for reducing menopausal hot flushes and improving the quality of life of symptomatic perimenopausal/postmenopausal women were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Sixteen studies, with 1155 women, were eligible for inclusion. Three review authors independently assessed trial eligibility and quality, and extracted data. We pooled data where appropriate and calculated mean differences (MDs) and standardized mean differences (SMDs) with 95% confidence intervals (CI). We evaluated the overall quality of the evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. MAIN RESULTS: Eight studies compared acupuncture versus sham acupuncture. No significant difference was found between the groups for hot flush frequency (MD -1.13 flushes per day, 95% CI -2.55 to 0.29, 8 RCTs, 414 women, I(2) = 70%, low-quality evidence) but flushes were significantly less severe in the acupuncture group, with a small effect size (SMD -0.45, 95% CI -0.84 to -0.05, 6 RCTs, 297 women, I(2) = 62%, very-low-quality evidence). There was substantial heterogeneity for both these outcomes. In a post hoc sensitivity analysis excluding studies of women with breast cancer, heterogeneity was reduced to 0% for hot flush frequency and 34% for hot flush severity and there was no significant difference between the groups for either outcome.Three studies compared acupuncture versus HT. Acupuncture was associated with significantly more frequent hot flushes than HT (MD 3.18 flushes per day, 95% CI 2.06 to 4.29, 3 RCTs, 114 women, I(2) = 0%, low-quality evidence). There was no significant difference between the groups for hot flush severity (SMD 0.53, 95% CI -0.14 to 1.20, 2 RCTs, 84 women, I(2) = 57%, low-quality evidence).One study compared electroacupuncture versus relaxation. There was no significant difference between the groups for either hot flush frequency (MD -0.40 flushes per day, 95% CI -2.18 to 1.38, 1 RCT, 38 women, very-low-quality evidence) or hot flush severity (MD 0.20, 95% CI -0.85 to 1.25, 1 RCT, 38 women, very-low-quality evidence).Four studies compared acupuncture versus waiting list or no intervention. Traditional acupuncture was significantly more effective in reducing hot flush frequency from baseline (SMD -0.50, 95% CI -0.69 to -0.31, 3 RCTs, 463 women, I(2) = 0%, low-quality evidence), and was also significantly more effective in reducing hot flush severity (SMD -0.54, 95% CI -0.73 to -0.35, 3 RCTs, 463 women, I(2) = 0%, low-quality evidence). The effect size was moderate in both cases.For quality of life measures, acupuncture was significantly less effective than HT, but traditional acupuncture was significantly more effective than no intervention. There was no significant difference between acupuncture and other comparators for quality of life. Data on adverse effects were lacking. AUTHORS' CONCLUSIONS: We found insufficient evidence to determine whether acupuncture is effective for controlling menopausal vasomotor symptoms. When we compared acupuncture with sham acupuncture, there was no evidence of a significant difference in their effect on menopausal vasomotor symptoms. When we compared acupuncture with no treatment there appeared to be a benefit from acupuncture, but acupuncture appeared to be less effective than HT. These findings should be treated with great caution as the evidence was low or very low quality and the studies comparing acupuncture versus no treatment or HT were not controlled with sham acupuncture or placebo HT. Data on adverse effects were lacking.

Out-of-pocket costs in the year after early breast cancer among Canadian women and spouses.

BACKGROUND: We lack comprehensive information about the extent of out-of-pocket costs after diagnosis of early breast cancer and their effects on the family's financial situation. METHODS: This longitudinal study assessed out-of-pocket costs and wage losses during the first year after diagnosis of early breast cancer among Canadian women and spouses. Out-of-pocket costs for treatments and follow-up, consultations with other practitioners, home help, clothing, and natural health products were estimated, with information collected from telephone interviews. Generalized linear models were used to identify women at risk of having higher costs and the effects of out-of-pocket costs on perceptions of the family's financial situation. RESULTS: Overall, 829 women (participation, 86.2%) and 391 spouses participated. Women's median net out-of-pocket costs during the year after diagnosis were $1002 (2003 Canadian dollars; mean = $1365; SD = $1238), and 74.4% of these costs resulted from treatments and follow-up. Spouses' median costs were $111 (mean = $234; SD = $320), or 9% of couples' total expenses. In multivariable analyses, the percentage of women with out-of-pocket costs of $1773 or more (upper quartile) was statistically significantly associated with higher education, working at diagnosis, living more than 50 km from the hospital where surgery was performed, and having two and three different types of adjuvant treatment (all 2-sided P values ≤ .01). However, when considered simultaneously with wage losses, out-of-pocket costs were not associated with perceived deterioration in the family's financial situation; rather, wage losses were the driving factor. CONCLUSIONS: Overall, out-of-pocket costs from breast cancer for the year after diagnosis are probably not unmanageable for most women. However, some women were at higher risk of experiencing financial burden resulting from these costs.

Iron and cardiac ischemia: a natural, quasi-random experiment comparing eligible with disqualified blood donors.

BACKGROUND: The theory that elevated iron stores can induce vascular injury and ischemia remains controversial. We conducted a cohort study of the effect of blood donation on the risk of coronary heart disease (CHD) by taking advantage of the quasi-random exclusion of donors who obtained a falsely reactive test for a transmissible disease (TD) marker. STUDY DESIGN AND METHODS: Whole blood donors who were permanently disqualified because of a false-reactive test between 1990 and 2007 in the province of Quebec were compared to donors who remained eligible, matched for baseline characteristics. The incidence of CHD after entry into the study was determined through hospitalization and death records. We compared eligible and disqualified donors using an "intention-to-treat" framework. RESULTS: Overall, 12,357 donors who were permanently disqualified were followed for 124,123 person-years of observation, plus 50,889 donors who remained eligible (516,823 person-years). On average, donors who remained eligible made 0.36 donation/year during follow-up and had an incidence of hospitalizations or deaths attributable to CHD of 3.60/1000 person-years, compared to 3.52 among permanently disqualified donors (rate ratio, 1.02; 95% confidence interval, 0.92-1.13). CONCLUSION: Donors who remained eligible did not have a lower risk of CHD, compared to donors who were permanently disqualified due to a false-reactive TD marker. Because of the quasi-random nature of false-reactive screening tests, this natural experiment has a level of validity approaching that of a randomized trial evaluating the effect of regular blood donation on CHD risk. These results do not support the iron hypothesis.