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PurposeTo examine the effects of a 1-year exercise intervention on sex hormone levels in postmenopausal women and whether any effects are mediated by changes in body fat composition.MethodsWe randomly assigned 189 sedentary postmenopausal women (age 50 to 69 years, body mass index of 22 to 40 kg/m2) to an exercise intervention (n = 96) or a control group (n = 93). The intervention combined aerobic and strength training and comprised supervised group sessions and home-based exercises (a total of 2.5 h/wk). Between-group differences in sex hormone levels (at baseline and 4 and 12 months) were examined with generalized estimating equations.ResultsIn total, 183 women (97%) completed the study. Overall, the exercise intervention did not result in favorable effects on sex hormone levels. Among women who lost more than 2% body fat, declines in all estrogens were not significantly different between exercisers and controls. Androgen levels decreased significantly in the exercise group who lost body fat compared with their peers in the control group. Furthermore, this study confirmed that fat loss was significantly associated with declines in postmenopausal estrogen levels. Although not significant, a similar trend was observed for the androgens.ConclusionThis study confirms that fat loss is associated with changes in postmenopausal sex hormone levels and suggests that exercise may be effective in inducing favorable changes in these hormones.

Objective: To assess the epidemiologic evidence for the association between physical activity and endometrial cancer risk, taking into account the methodologic quality of each study. Design: Systematic review, best evidence synthesis. Data Sources: Studies were identified through a systematic review of literature available on PubMed through December 2006. Review Methods: We included cohort and case-control studies that assessed total and/or leisure time and/or occupational activities in relation to the incidence of endometrial cancer. The methodologic quality of the studies was assessed with a comprehensive scoring system. Results: The included cohort (n = 7) and case-control (n = 13) studies consistently show that physical activity is associated with a decreased risk of endometrial cancer. The best evidence synthesis showed that the majority (80%) of 10 high-quality studies found risk reductions of >20%. Pooling of seven high-quality cohort studies that measured total, leisure time, or occupational activity showed a significantly decreased risk of endometrial cancer (summary estimate: OR, 0.77; 95% CI, 0.70-0.85) for the most active women. Case control studies with relatively unfavorable quality scores reported divergent risk estimates, between 2-fold decreased and 2-fold increased risk. Effect modification by body mass index or menopausal status was not consistently observed. Evidence for an effect of physical activity during childhood or adolescence was limited. Conclusions: Physical activity seems to be associated with a reduction in the risk of endometrial cancer, which is independent of body weight. Further studies, preferably prospective cohort studies, are needed to determine the magnitude of the risk reduction and to assess which aspects of physical activity contribute most strongly to the reduced risk and in which period of life physical activity is most effective. (Cancer Epidemiol Biomarkers Prev 2007;16(4):639–48)

Surgical resection is the treatment of first choice for patients with stage I-II non-small cell lung cancer (NSCLC). However, stereotactic body radiotherapy (SBRT) has been shown to be a good alternative treatment.Overall survival (OS), progression-free survival (PFS) and recurrence rates were compared between patients with stage I-II NSCLC treated with SBRT (n=53) and those treated with surgical resection (n=175). The propensity score method was used to correct for confounding by indication.Before correction, the OS and PFS rates at 1 and 3 years were significantly different between SBRT and surgery, in favor of surgery. After correction, the OS and PFS after SBRT were not significantly different compared to surgery. The recurrence rates for the two treatments were also similar both before and after correction.This retrospective study showed that clinical outcomes after SBRT are equal to those after surgery in patients with stage I-II NSCLC.

Introduction Physical inactivity and overweight are risk factors for postmenopausal breast cancer. The effect of physical activity may be partially mediated by concordant weight loss. We studied the effect on serum sex hormones, which are known to be associated with postmenopausal breast cancer risk, that is attributable to exercise by comparing randomly obtained equivalent weight loss by following a hypocaloric diet only or mainly by exercise. Methods Overweight, insufficiently active women were randomised to a diet (N = 97), mainly exercise (N = 98) or control group (N = 48). The goal of both interventions was to achieve 5–6 kg of weight loss by following a calorie-restricted diet or an intensive exercise programme combined with only a small caloric restriction. Primary outcomes after 16 weeks were serum sex hormones and sex hormone-binding globulin (SHBG). Body fat and lean mass were measured by dual-energy X-ray absorptiometry. Results Both the diet (−4.9 kg) and mainly exercise (−5.5 kg) groups achieved the target weight loss. Loss of body fat was significantly greater with exercise versus diet (difference −1.4 kg, P < 0.001). In the mainly exercise arm, the reduction in free testosterone was statistically significantly greater than that of the diet arm (treatment effect ratio [TER] 0.92, P = 0.043), and the results were suggestive of a difference for androstenedione (TER 0.90, P = 0.064) and SHBG (TER 1.05, P = 0.070). Compared with the control arm, beneficial effects were seen with both interventions, diet and mainly exercise, respectively, on oestradiol (TER 0.86, P = 0.025; TER 0.83, P = 0.007), free oestradiol (TER 0.80, P = 0.002; TER 0.77, P < 0.001), SHBG (TER 1.14; TER 1.21, both P < 0.001) and free testosterone (TER 0.91, P = 0.069; TER = 0.84, P = 0.001). After adjustment for changes in body fat, intervention effects attenuated or disappeared. Conclusions Weight loss with both interventions resulted in favourable effects on serum sex hormones, which have been shown to be associated with a decrease in postmenopausal breast cancer risk. Weight loss induced mainly by exercise additionally resulted in maintenance of lean mass, greater fitness, greater fat loss and a larger effect on (some) sex hormones. The greater fat loss likely explains the observed larger effects on sex hormones. Trial registration ClinicalTrials.gov identifier: NCT01511276. Registered on 12 January 2012. Electronic supplementary material The online version of this article (doi:10.1186/s13058-015-0633-9) contains supplementary material, which is available to authorized users.

Background: Self-management interventions are considered effective in COPD patients, but trials have shown inconsistent results and it is unknown which patients benefit most. Aims: To summarise the evidence on effectiveness of self-management interventions and identify subgroups of COPD patients who benefit most. Methods: Randomised trials on self-management interventions between 1985 and 2013 were identified through a systematic literature search. The original data of selected studies were analysed using generalised mixed effects models. Results: Fourteen trials representing 3282 patients were included. Self-management improved health-related quality of life (standardised mean difference 0.08, 95%CI 0.00-0.16), COPD-related hospitalisation (hazard ratio 0.79, 95%CI 0.66-0.94) and all-cause hospitalisation (hazard ratio 0.80, 95%CI 0.69-0.90), but had no effect on mortality. Pre-specified subgroup analysis showed significant interactions for certain outcomes: interventions were more effective in males (6-month COPD-related hospitalisation: P=0.006), patients with severe lung function (6-month all-cause hospitalisation: P=0.016), moderate self-efficacy (12-month COPD-related hospitalisation: P=0.036), and high body mass index (6-month-COPD-related hospitalisation: P=0.028; and 6-month mortality: P=0.026). Conclusion: Self-management improved health-related quality of life, COPD-related and all-cause hospitalisation in COPD patients. Our findings support implementation of self-management strategies in practice and suggest subgroups with greater benefit. However, the inconsistent subgroup effects across outcomes do not endorse targeting to subgroups at this stage of our understanding.

Background Exercise started shortly after breast cancer diagnosis might prevent or diminish fatigue complaints. The Physical Activity during Cancer Treatment (PACT) study was designed to primarily examine the effects of an 18-week exercise intervention, offered in the daily clinical practice setting and starting within 6 weeks after diagnosis, on preventing an increase in fatigue. Methods This multi-centre controlled trial randomly assigned 204 breast cancer patients to usual care (n = 102) or supervised aerobic and resistance exercise (n = 102). By design, all patients received chemotherapy between baseline and 18 weeks. Fatigue (i.e., primary outcome at 18 weeks), quality of life, anxiety, depression, and physical fitness were measured at 18 and 36 weeks. Results Intention-to-treat mixed linear model analyses showed that physical fatigue increased significantly less during cancer treatment in the intervention group compared to control (mean between-group differences at 18 weeks: −1.3; 95 % CI −2.5 to −0.1; effect size −0.30). Results for general fatigue were comparable but did not reach statistical significance (-1.0, 95%CI -2.1; 0.1; effect size -0.23). At 18 weeks, submaximal cardiorespiratory fitness and several muscle strength tests (leg extension and flexion) were significantly higher in the intervention group compared to control, whereas peak oxygen uptake did not differ between groups. At 36 weeks these differences were no longer statistically significant. Quality of life outcomes favoured the exercise group but were not significantly different between groups. Conclusions A supervised 18-week exercise programme offered early in routine care during adjuvant breast cancer treatment showed positive effects on physical fatigue, submaximal cardiorespiratory fitness, and muscle strength. Exercise early during treatment of breast cancer can be recommended. At 36 weeks, these effects were no longer statistically significant. This might have been caused by the control participants’ high physical activity levels during follow-up. Trial registration Current Controlled Trials ISRCTN43801571, Dutch Trial Register NTR2138. Trial registered on December 9th, 2009. Electronic supplementary material The online version of this article (doi:10.1186/s12916-015-0362-z) contains supplementary material, which is available to authorized users.

Introduction: This study investigates the effect of a modest weight loss either by a calorie restricted diet or mainly by increased physical exercise on health related quality of life (HRQoL) in overweight-to-obese and inactive postmenopausal women. We hypothesize that HRQoL improves with weight loss, and that exercise-induced weight loss is more effective for this than diet-induced weight loss. Methods: The SHAPE-2 trial was primarily designed to evaluate any additional effect of weight loss by exercise compared with a comparable amount of weight loss by diet on biomarkers relevant for breast cancer risk. In the present analysis we focus on HRQoL. We randomly assigned 243 eligible women to a diet (n = 97), exercise (n = 98), or control group (n = 48). Both interventions aimed for 5-6 kg weight loss. HRQoL was measured at baseline and after 16 weeks by the SF-36 questionnaire. Results: Data of 214 women were available for analysis. Weight loss was 4.9 kg (6.1%) and 5.5 kg (6.9%) with diet and exercise, respectively. Scores of the SF-36 domain 'health change' increased significantly by 8.8 points (95% CI 1.6;16.1) with diet, and by 20.5 points (95% CI 13.2;27.7) with exercise when compared with control. Direct comparison of diet and exercise showed a statistically significantly stronger improvement with exercise. Both intervention groups showed a tendency towards improvements in most other domains, which were more pronounced in the exercise group, but not statistically different from control or each other. Conclusion: In a randomized trial in overweight-to-obese and inactive postmenopausal women a comparable 6%-7% weight loss was achieved by diet-only or mainly by exercise and showed improvements in physical and mental HRQoL domains, but results were not statistically significant in either the diet or exercise group. However, a modest weight loss does lead to a positive change in self-perceived health status. This effect was significantly larger with exercise-induced weight loss than with comparable diet-induced weight loss. Trial Registration: ClinicalTrials.gov NCT01511276.

Introduction The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention. Methods We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects. Results We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, ORlog2 = 1.35 (95% CI 1.04-1.76), P-trend = 0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (P-het = 0.98) or baseline HT use (P-het = 0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (P-trend = 0.06 vs P-trend = 0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors = 4 years after blood donation (P-trend = 0.01 vs P-trend = 0.63; P-het = 0.04) and among nulliparous women compared to parous women (P-trend = 0.03 vs P-trend = 0.15; P-het = 0.07). Conclusions Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer.The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention.

We aimed to estimate the proportion of Dutch postmenopausal breast cancer cases in 2010 that is attributable to lifestyle-related risk factors. We calculated population attributable fractions (PAFs) of potentially modifiable risk factors for postmenopausal breast cancer in Dutch women aged >50 in 2010. First, age-specific PAFs were calculated for each risk factor, based on their relative risks for postmenopausal breast cancer (from meta-analyses) and age-specific prevalence in the population (from national surveys) around the year 2000, assuming a latency period of 10 years. To obtain the overall PAF, age-specific PAFs were summed in a weighted manner, using the age-specific breast cancer incidence rates (2010) as weights. 95 % confidence intervals for PAF estimates were derived by Monte Carlo simulations. Of Dutch women >40 years, in 2000, 51 % were overweight/obese, 55 % physically inactive (

Purpose Important considerations for exercise trials in cancer patients are contamination and differential drop-out among the control group members that might jeopardize the internal validity. This systematic review provides an overview of different control groups design characteristics of exercise-oncology trials and explores the association with contamination and drop-out rates. Methods Randomized controlled exercise-oncology trials from two Cochrane reviews were included. Additionally, a computer-aided search using Medline (Pubmed), Embase and CINAHL was conducted after completion date of the Cochrane reviews. Eligible studies were classified according to three control group design characteristics: the exercise instruction given to controls before start of the study (exercise allowed or not); and the intervention the control group was offered during (any (e.g., education sessions or telephone contacts) or none) or after (any (e.g., cross-over or exercise instruction) or none) the intervention period. Contamination (yes or no) and excess drop-out rates (i.e., drop-out rate of the control group minus the dropout rate exercise group) were described according to the three design characteristics of the control group and according to the combinations of these three characteristics; so we additionally made subgroups based on combinations of type and timing of instructions received. Results 40 exercise-oncology trials were included based on pre-specified eligibility criteria. The lowest contamination (7.1% of studies) and low drop-out rates (excess drop-out rate -4.7+/-9.2) were found in control groups offered an intervention after the intervention period. When control groups were offered an intervention both during and after the intervention period, contamination (0%) and excess drop-out rates (-10.0+/-12.8%) were even lower. Conclusions Control groups receiving an intervention during and after the study intervention period have lower contamination and drop-out rates. The present findings can be considered when designing future exercise-oncology trials.

Background: Evidence accumulates that physical inactivity is one of the few modifiable risk factors for breast cancer. The mechanism through which physical inactivity affects breast cancer risk is not clear. The study aim was to investigate the association between physical activity and breast density because mammographic density is strongly associated with breast cancer risk. Methods: We did a cross-sectional study in 620 women, of ages 49 to 68 years and participants of the Dutch Prospect-European Prospective Investigation into Cancer and Nutrition cohort. A self-administered questionnaire was used to obtain information on duration and intensity of physical activity (recreational, household, and occupational) during the year preceding study recruitment. A total activity index (inactive, moderately inactive, moderately active, and active) was estimated by combining all activity types. Percent and absolute breast density were determined on screening mammograms using a computer-aided method. Multivariate linear regression was used to examine the association between physical activity and breast density. Results: Mean percent density was 35.3% [95% confidence interval (95% CI), 31.8-38.8] for the inactive category compared with 36.1% (95% CI, 33.0-39.2) for the active category. Mean absolute density values for the inactive and active category were 45.8 cm2 (95% CI, 40.9-50.7) and 42.6 cm2 (95% CI, 38.3-47.0), respectively. Subgroup analysis for postmenopausal women showed similar results, as did separate analyses for recreational and household activity. Conclusions: The result does not support a relation between current physical activity and mammographic density in postmenopausal women. (Cancer Epidemiol Biomarkers Prev 2006;15(3):456–60)

Background: The evidence for the effectiveness and safety of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) is inconclusive. This study determined the cost effectiveness of withdrawing fluticasone propionate (FP) in outpatients with COPD. Methods: The cost effectiveness analysis was based on a randomised, placebo controlled FP withdrawal study. After a 4 month run in period on FP, patients were randomly assigned to continue FP 500 μg twice daily or to receive placebo for 6 months. A decision analytical model evaluated the 6 month incremental cost effectiveness of the ICS versus ICS withdrawal strategy. One way sensitivity analyses and a Monte Carlo simulation were performed to evaluate the robustness of the findings. Results: The average patient with COPD in the FP group generated €511 in direct medical costs, including €238 for FP. The cost of the placebo strategy was €456. The higher direct drug cost of €212 per patient for the FP strategy during the 6 month follow up period compared with the placebo group was partially offset by a lower exacerbation and hospital admission cost of €157. The 6 month incremental cost effectiveness of the FP strategy compared with placebo was €110 per exacerbation prevented and €1286 per hospital admission prevented. Conclusions: Over a 6 month period, withdrawing FP in a pre-selected trial population of COPD patients led to absolute cost savings but with a higher rate of exacerbations and hospital admissions.

Contains fulltext : 57556.pdf (Publisher’s version ) (Open Access) BACKGROUND: The wide use of antibiotics for treatment of exacerbations of chronic obstructive pulmonary disease (COPD) lacks evidence. The efficacy is debatable, and bacterial involvement in exacerbation is difficult to verify. The aim of this prospective study was to identify factors that can help to estimate the probability that a microorganism is involved in exacerbation of COPD and, therefore, predict the success of antibiotic treatment. METHODS: Clinical data and sputum samples were obtained from 116 patients during exacerbation of COPD. Bacterial infection was defined by the abundant presence of >or=1 potential pathological microorganism in relation to the normal flora in sputum. RESULTS: Of 116 exacerbations, 22 (19%) had bacterial involvement. The combination of a negative result of a sputum Gram stain, a relevant nonclinical decrease in lung function (compared with baseline measurements), and occurrence of

Contains fulltext : 57150.pdf (Publisher’s version ) (Closed access) Chronic obstructive pulmonary disease (COPD) is a systemic disease with major impact worldwide. In the treatment of COPD a holistic approach should be taken. In order to reach this, an individual treatment plan should be made which includes at least elements of smoking cessation, optimisation of pulmonary status by pharmacotherapy and exercise embedded in a new lifestyle. Furthermore, more research on nutritional and metabolic intervention strategies for COPD patients is needed. With the availability of all these treatment options, a nihilistic attitude toward the patient with COPD is no longer justified.

Acute exacerbation is a frequent complication of chronic obstructive pulmonary disease (COPD). Recent studies suggested a role for bacteria such as Streptococcus pneumoniae in the development of acute exacerbation. For this study, we investigated the following in COPD patients: (i) the epidemiology of pneumococcal colonization and infection, (ii) the effect of pneumococcal colonization on the development of exacerbation, and (iii) the immunological response against S. pneumoniae . We cultured sputa of 269 COPD patients during a stable state and during exacerbation of COPD and characterized 115 pneumococcal isolates by use of serotyping. Moreover, we studied serum immunoglobulin G (IgG) antibody titers, antibody avidities, and functional antibody titers against the seven conjugate vaccine serotypes in these patients. Colonization with only pneumococci (monocultures) increased the risk of exacerbation, with a hazard ratio of 2.93 (95% confidence interval, 1.41 to 6.07). The most prevalent pneumococcal serotypes found were serotypes 19F, 3, 14, 9L/N/V, 23A/B, and 11. We calculated the theoretical coverage for the 7- and 11-valent pneumococcal vaccines to be 60 and 73%, respectively. All patients had detectable IgG levels against the seven conjugate vaccine serotypes. These antibody titers were significantly lower than those in vaccinated healthy adults. Finally, on average, a 2.5-fold rise in serotype-specific and functional antibodies in S. pneumoniae -positive sputum cultures was observed during exacerbation. Our data indicate that pneumococcal colonization in COPD patients is frequently caused by vaccine serotype strains. Moreover, pneumococcal colonization is a risk factor for exacerbation of COPD. Finally, our findings demonstrate that COPD patients are able to mount a significant immune response to pneumococcal infection. COPD patients may therefore benefit from pneumococcal vaccination.

BACKGROUND: Self‐management interventions help people with chronic obstructive pulmonary disease (COPD) to acquire and practise the skills they need to carry out disease‐specific medical regimens, guide changes in health behaviour and provide emotional support to enable them to control their disease. Since the 2014 update of this review, several studies have been published. OBJECTIVES: Primary objectives To evaluate the effectiveness of COPD self‐management interventions compared to usual care in terms of health‐related quality of life (HRQoL) and respiratory‐related hospital admissions. To evaluate the safety of COPD self‐management interventions compared to usual care in terms of respiratory‐related mortality and all‐cause mortality. Secondary objectives To evaluate the effectiveness of COPD self‐management interventions compared to usual care in terms of other health outcomes and healthcare utilisation. To evaluate effective characteristics of COPD self‐management interventions. SEARCH METHODS: We searched the Cochrane Airways Trials Register, CENTRAL, MEDLINE, EMBASE, trials registries and the reference lists of included studies up until January 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) and cluster‐randomised trials (CRTs) published since 1995. To be eligible for inclusion, self‐management interventions had to include at least two intervention components and include an iterative process between participant and healthcare provider(s) in which goals were formulated and feedback was given on self‐management actions by the participant. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, assessed trial quality and extracted data. We resolved disagreements by reaching consensus or by involving a third review author. We contacted study authors to obtain additional information and missing outcome data where possible. Primary outcomes were health‐related quality of life (HRQoL), number of respiratory‐related hospital admissions, respiratory‐related mortality, and all‐cause mortality. When appropriate, we pooled study results using random‐effects modelling meta‐analyses. MAIN RESULTS: We included 27 studies involving 6008 participants with COPD. The follow‐up time ranged from two‐and‐a‐half to 24 months and the content of the interventions was diverse. Participants' mean age ranged from 57 to 74 years, and the proportion of male participants ranged from 33% to 98%. The post‐bronchodilator forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) ratio of participants ranged from 33.6% to 57.0%. The FEV1/FVC ratio is a measure used to diagnose COPD and to determine the severity of the disease. Studies were conducted on four different continents (Europe (n = 15), North America (n = 8), Asia (n = 1), and Oceania (n = 4); with one study conducted in both Europe and Oceania). Self‐management interventions likely improve HRQoL, as measured by the St. George’s Respiratory Questionnaire (SGRQ) total score (lower score represents better HRQoL) with a mean difference (MD) from usual care of ‐2.86 points (95% confidence interval (CI) ‐4.87 to ‐0.85; 14 studies, 2778 participants; low‐quality evidence). The pooled MD of ‐2.86 did not reach the SGRQ minimal clinically important difference (MCID) of four points. Self‐management intervention participants were also at a slightly lower risk for at least one respiratory‐related hospital admission (odds ratio (OR) 0.75, 95% CI 0.57 to 0.98; 15 studies, 3263 participants; very low‐quality evidence). The number needed to treat to prevent one respiratory‐related hospital admission over a mean of 9.75 months' follow‐up was 15 (95% CI 8 to 399) for participants with high baseline risk and 26 (95% CI 15 to 677) for participants with low baseline risk. No differences were observed in respiratory‐related mortality (risk difference (RD) 0.01, 95% CI ‐0.02 to 0.04; 8 studies, 1572 participants ; low‐quality evidence) and all‐cause mortality (RD ‐0.01, 95% CI ‐0.03 to 0.01; 24 studies, 5719 participants; low‐quality evidence). We graded the evidence to be of ‘moderate’ to ‘very low’ quality according to GRADE. All studies had a substantial risk of bias, because of lack of blinding of participants and personnel to the interventions, which is inherently impossible in a self‐management intervention. In addition, risk of bias was noticeably increased because of insufficient information regarding a) non‐protocol interventions, and b) analyses to estimate the effect of adhering to interventions. Consequently, the highest GRADE evidence score that could be obtained by studies was ‘moderate’. AUTHORS' CONCLUSIONS: Self‐management interventions for people with COPD are associated with improvements in HRQoL, as measured with the SGRQ, and a lower probability of respiratory‐related hospital admissions. No excess respiratory‐related and all‐cause mortality risks were observed, which strengthens the view that COPD self‐management interventions are unlikely to cause harm. By using stricter inclusion criteria, we decreased heterogeneity in studies, but also reduced the number of included studies and therefore our capacity to conduct subgroup analyses. Data were therefore still insufficient to reach clear conclusions about effective (intervention) characteristics of COPD self‐management interventions. As tailoring of COPD self‐management interventions to individuals is desirable, heterogeneity is and will likely remain present in self‐management interventions. For future studies, we would urge using only COPD self‐management interventions that include iterative interactions between participants and healthcare professionals who are competent using behavioural change techniques (BCTs) to elicit participants' motivation, confidence and competence to positively adapt their health behaviour(s) and develop skills to better manage their disease. In addition, to inform further subgroup and meta‐regression analyses and to provide stronger conclusions regarding effective COPD self‐management interventions, there is a need for more homogeneity in outcome measures. More attention should be paid to behavioural outcome measures and to providing more detailed, uniform and transparently reported data on self‐management intervention components and BCTs. Assessment of outcomes over the long term is also recommended to capture changes in people's behaviour. Finally, information regarding non‐protocol interventions as well as analyses to estimate the effect of adhering to interventions should be included to increase the quality of evidence.

A moderate association exists between body mass index (BMI) and colorectal cancer. Less is known about the effect of weight change.We investigated the relation between BMI and weight change and subsequent colon and rectal cancer risk.This was studied among 328,781 participants in the prospective European Prospective Investigation into Cancer-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating study (mean age: 50 y). Body weight was assessed at recruitment and on average 5 y later. Self-reported weight change (kg/y) was categorized in sex-specific quintiles, with quintiles 2 and 3 combined as the reference category (men: -0.6 to 0.3 kg/y; women: -0.4 to 0.4 kg/y). In the subsequent years, participants were followed for the occurrence of colon and rectal cancer (median period: 6.8 y). Multivariable Cox proportional hazards regression analyses were used to study the association.A total of 1261 incident colon cancer and 747 rectal cancer cases were identified. BMI at recruitment was statistically significantly associated with colon cancer risk in men (HR: 1.04; 95% CI: 1.02, 1.07). Moderate weight gain (quintile 4) in men increased risk further (HR: 1.32; 95% CI: 1.04, 1.68), but this relation did not show a clear trend. In women, BMI or weight gain was not related to subsequent risk of colon cancer. No statistically significant associations for weight loss and colon cancer or for BMI and weight changes and rectal cancer were found.BMI attained at adulthood was associated with colon cancer risk. Subsequent weight gain or loss was not related to colon or rectal cancer risk in men or women.

Purpose: Increased physical activity (PA) is associated with a reduced risk of several cancers. PA may reduce cancer risk by changing endogenous hormones levels, but relatively little research has focused on this topic. The purpose of this study was to elucidate the relation between PA and endogenous hormone concentrations. Methods: A cross-sectional analysis of 798 pre- and 1,360 post-menopausal women included as controls in case-control studies on endogenous hormones (steroids, progesterone, sex-hormone-binding globulin (SHBG), and growth factors) levels, and cancer risk nested within European Prospective Investigation into Cancer and Nutrition cohort was performed. Multivariate regression analyses were performed to compare geometric mean levels of hormones and SHBG by categories of PA. Results: In pre-menopausal women, active women had 19 % significantly lower concentrations of androstenedione, 14 % lower testosterone, and 20 % lower free testosterone than inactive women, while no differences were observed for estrogens, progesterone, SHBG, and growth factors. In post-menopausal women, active women had 18 % significantly lower estradiol and 20 % lower free estradiol concentrations than inactive women, while no differences were observed for the other hormones and SHBG. More vigorous forms of physical activity were associated with higher insulin-like growth factor-I concentrations. Adjustment for body mass index did not alter the associations. Overall, the percentage of variance in hormone concentrations explained by PA levels was

To investigate the relationship between age at menopause, body mass index, and breast cancer risk, we used data from a prospective cohort study (DOM cohort) in the Netherlands. Participants in this breast cancer-screening project included 10,591 women living in Utrecht, aged 49-66 years at enrolment. During a median follow-up period of 19 years, women attended screening rounds at which anthropometric measurements were taken and questions were asked about menopausal status, age at menopause, medication use and other risk factors for breast cancer. Cox regression analysis was used to investigate the relationship between age at menopause and subsequent breast cancer risk. Breast cancer incidence decreased with an earlier age at menopause. Women with a menopausal age of 44 years or younger had a 34% lower risk of breast cancer, than women with a menopausal age over 54 years (hazard ratio is 0.66 (95% confidence interval 0.43-0.91)). The annual hazard of breast cancer incidence decreased by 2.6% per year reduction in age at menopause. The protective effect of an early age at menopause was stronger for women with a low body mass index (or = 27 kg/m2; reduction of 44%) than for women with a high body mass index (27 kg/m2; reduction of 24%), although this difference was not statistically significant (P for interaction = 0.58). This difference was most pronounced in women who had ever smoked. Adjustment for known breast cancer risk factors did not alter the crude risk estimates significantly. In conclusion, this study provides evidence of the protective effect of lower age at menopause on subsequent breast cancer risk. This protective effect may be even stronger in leaner women.

a b s t r a c t Objective: We investigated the association of visceral fat with the metabolic syndrome (MetS) and its separate components; the associations of both physical activity and muscle strength with the MetS and its separate components independent of visceral fat. Furthermore, we studied these associations within participants with low and high amounts of visceral fat. Study design: 400 men (aged 40–80 years) were recruited into a cross-sectional study. Main outcome measures: Logistic regression models were used to study the individual associations in all participants (OR). The associations of physical activity (active vs inactive) and muscle strength (high vs low) within participants with low and high levels of visceral fat (assessed by ultrasonography) were tested using Univariate Analysis of Variance (difference in mean levels of the separate components of MetS) and logistic regression (risk on MetS). Results: High levels of visceral fat were significantly associated with increased risk of MetS (OR 1.7 95%CI 1.5;1.9) and its separate components (p < 0.05). We did not find strong individual associations for physical activity or muscle strength, neither within men with low or high levels of visceral fat. Conclusions: High body fat levels were associated with an unhealthier metabolic risk profile and a higher risk of the MetS. Our cross-sectional data do not indicate associations for physical activity or for muscle strength with the MetS independent of visceral fat. Also no differential associations of physical activity or muscle strength in men with low or high levels of visceral fat were found. © 2013 Elsevier Ireland Ltd. All rights reserved.

The aim of our study was to assess the prognostic value of tumor volume compared to and in addition to T-stage on local control (LC), disease-free survival (DFS), and overall survival (OS) in glottic and supraglottic laryngeal carcinoma patients. In 150 patients, we determined tumor volume on diagnostic CT scans. We applied crude and multivariable Cox regression analysis to relate volume (continuous), T-stage and the combination to 5-year DFS, OS, and LC. Before, we examined the linearity assumption of the association between volume and outcome with restricted cubic spline functions. Prognostic performance of the models was examined by determination of the model’s discrimination. Discriminative ability was determined with the C statistic referring to the ability to discriminate between patients who do and do not develop an event during follow-up. A strong association between tumor volume and DFS and OS was found. The restricted cubic spline plot did not indicate a non-linear relationship between tumor volume and DFS and local control. Tumor volume demonstrated a better discriminative ability to predict DFS and OS compared to T-stage (0.68 and 0.57 vs. 0.59 and 0.54, respectively). For local control, T-stage showed a higher discriminative ability than tumor volume (0.63 vs. 0.61). The combined model increased discriminative power (0.69). Volume seems to be more important than T-stage in prediction of DFS or OS in laryngeal squamous cell carcinoma patients. Perhaps prediction of DFS, OS, and LC could be improved by including tumor volume into the staging process.

Background: Physical inactivity and overweight are two known risk factors for postmenopausal breast cancer. Former exercise intervention studies showed that physical activity influences sex hormone levels, known to be related to postmenopausal breast cancer, mainly when concordant loss of body weight was achieved. The question remains whether there is an additional beneficial effect of physical activity when weight loss is reached. The aim of this study is to investigate the effect attributable to exercise on postmenopausal breast cancer risk biomarkers, when equivalent weight loss is achieved compared with diet-induced weight loss. Design: The SHAPE-2 study is a three-armed, multicentre trial. 243 sedentary, postmenopausal women who are overweight or obese (BMI 25–35 kg/m 2 ) are enrolled. After a 4-6 week run-in period, wherein a baseline diet is prescribed, women are randomly allocated to (1) a diet group, (2) an exercise group or (3) a control group. The aim of both intervention groups is to lose an amount of 5–6 kg body weight in 10–14 weeks. The diet group follows an energy restricted diet and maintains the habitual physical activity level. The exercise group participates in a 16-week endurance and strength training programme of 4 hours per week. Furthermore, they are prescribed a moderate caloric restriction. The control group is asked to maintain body weight and continue the run-in baseline diet. Measurements include blood sampling, questionnaires, anthropometrics (weight, height, waist and hip circumference), maximal cycle exercise test (VO2peak), DEXA-scan (body composition) and abdominal MRI (subcutaneous and visceral fat). Primary outcomes are serum levels of oestradiol, oestrone, testosterone and sex hormone binding globulin (SHBG). Discussion: This study will give insight in the potential attributable effect of physical activity on breast cancer risk biomarkers and whether this effect is mediated by changes in body composition, in postmenopausal women. Eventually this may lead to the design of specific lifestyle guidelines for prevention of breast cancer. Trial registration: The SHAPE-2 study is registered in the register of clinicaltrials.gov, Identifier: NCT01511276.

This special issue of Patient Education and Counseling is long overdue. During most of the last two decades asthma, and notably asthma self-management has been in the spotlight, while COPD has had to endure a nihilistic approach. The first sign that interest was shifting to the treatment of COPD came from a few large randomized trials on the use of inhaled corticosteroids (ICS) in COPD. Although these studies demonstrated a moderate effect of ICS in COPD, it has become clear that true improvements in the management of this chronic disease will have to come from behavioral interventions. This special issue of Patient Education and Counseling is dedicated solely to the non-pharmaceutical management of COPD. It addresses many issues related to behavioral therapy, such as smoking cessation, exercise training, nutritional aspects, and self-management programs, including action plans to self-treat exacerbations. With the availability of all the treatment and management options, described in this special issue, a nihilistic attitude toward the patient with COPD is no longer justified.

Purpose Current literature describes concern for an increase in depression owing to treatment of prostate cancer. Here, depression and coping up to 8 years posttreatment are described for patients treated with 125 I brachytherapy for localized prostate cancer. Methods and Materials Between December 2000 and June 2010, 132 patients received questionnaires at: baseline, 1 month, 6 months, 1 year, and 8 years posttreatment. The measures included the Center for Epidemiologic Studies Depression Scale (CES-D) and the Utrecht Coping List. Also general quality of life measures were used: the Short Form Health Survey (RAND-36), the European Organization for Research and Treatment of Cancer C30 questionnaire (EORTC QLQ-C30 + 3) and a prostate cancer specific questionnaire (EORTC-PR25). Descriptive statistics were performed and correlations among depression, coping, and general quality of life measures were investigated. Results At baseline and all follow-up moments, approximately 10% of the patients had a CES-D score of 16 or more, indicating a clinically significant level of depressive symptoms. Depression did not seem to change in time. Active coping was the most predominant style of coping in problem situations. Coping strategy did not change in time. No relevant correlations were found between coping and depression. No significant associations were found between CES-D mean score and patient characteristics (medical and demographic). Relevant negative correlations were found between depression and HRQOL variables vitality, emotional functioning, and mental health ( ρ > 0.5). Conclusion Prostate brachytherapy does not contribute to an increased risk of depression.

Background: Physical activity has been identified as protective factor for invasive breast cancer risk, whereas comparable studies on in situ carcinoma are rare. Methods: The study included data from 283,827 women of the multinational European Prospective Investigation into C7ancer and Nutrition (EPIC)-cohort study. Detailed information on different types of physical activity conducted during the prior year, such as occupational, recreational, and household activity, as well as on important cofactors, was assessed at baseline. Adjusted HRs for in situ breast cancer were estimated by Cox proportional hazards models. Results: During a median follow-up period of 11.7 years, 1,059 incidents of breast carcinoma in situ were identified. In crude and adjusted multivariable models, no associations were found for occupational, household, and recreational physical activity. Furthermore, total physical activity was not associated with risk of in situ breast cancer. Comparing moderately inactive, moderately active, and active participants with inactive study participants resulted in adjusted HRs of 0.99 [95% confidence interval (CI), 0.83–1.19], 0.99 (95% CI, 0.82–1.20), and 1.07 (95% CI, 0.81–1.40), respectively (P value of trend test: 0.788). No inverse associations were found in any substrata defined by age at diagnosis or body mass index (BMI) status. Conclusions: In this large prospective study, we did not find any evidence of an association between physical activity and in situ breast cancer risk. If not by chance, the contrast between our results for carcinoma in situ and the recognized inverse association for invasive breast cancer suggests that physical activity may have stronger effects on proliferation and late stage carcinogenesis. Cancer Epidemiol Biomarkers Prev; 21(12); 2209–19. ©2012 AACR.

Background and purpose: Evaluation of the variation in tumor growth rate and the influence of tumor growth rate on disease free survival (DFS) and overall survival (OS) in laryngeal squamous cell carcinoma (LSCC). Material and methods: We delineated tumor volume on a diagnostic and planning CT scan in 131 patients with laryngeal squamous cell carcinoma and calculated the tumor growth rate. Primary endpoint was DFS. Follow up data were collected retrospectively. Results: A large variation in tumor growth rate was seen. When dichotomized with a cut-off point of -0.3 In(cc/day), we found a significant association between high growth rate and worse DFS (p = 0.008) and OS (p = 0.013). After stepwise adjustment for potential confounders (age, differentiation and tumor volume) this significant association persisted. However, after adjustment of N-stage association disappeared. Exploratory analyses suggested a strong association between N-stage and tumor growth rate. Conclusions: In laryngeal squamous cell carcinoma, there is a large variation in tumor growth rate. This tumor growth rate seems to be an important factor in disease free survival and OS. This tumor growth rate is independent of age, differentiation and tumor volume associated with DFS, but N-stage seems to be a more important risk factor. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Contains fulltext : 110229.pdf (Publisher’s version ) (Closed access) PURPOSE: To compare patient-reported xerostomia during daytime and during nighttime with objectively measured parotid and submandibular gland function in a cohort of head-and-neck cancer (HNC) patients treated with RT. MATERIALS AND METHODS: A cohort of 138 HNC patients underwent objective measurements of parotid (PF) and submandibular (SMF) gland function and completed a xerostomia questionnaire (XQ) before RT, at 6 weeks, 6 months and 1 year after RT. No attempt was made to spare the submandibular gland(s). The XQ contained specific questions concerning the sensation of dry mouth during day- (XD) and nighttime (XN), scored on a 5-point Likert scale. Patients with no or mild (grade 1-3) xerostomia and patients with more severe (grade 4-5) complaints were grouped together. RESULTS: Before RT, no association existed between dry mouth complaints and PF or SMF. At 6 weeks, 6 months and 1 year after RT; 37%, 51% and 36% had grade 4-5 XD and 65%, 64% and 56% had grade 4-5 XN, respectively. Patients with grade 4-5 XD and XN had significantly worse SMF at all time points after RT compared to patients with grade 1-3 XD and XN, while PF was significantly worse only at 6 weeks after RT. In multivariate analyses, SMF was consistently the most important factor related to XN after treatment. PF significantly influenced XD at 6 weeks and 1 year after RT. CONCLUSIONS: Differentiating between complaints during day- and nighttime in xerostomia research is necessary. Dry mouth at night is a frequent problem after (parotid-sparing) RT for HNC and is explained by submandibular gland dysfunction. Sparing of the contralateral submandibular gland, in addition to parotid gland sparing, may result in improved patient-reported xerostomia.

Purpose To assess the risk of second primary cancer (SPC) after [125I]iodine prostate cancer brachytherapy compared with prostatectomy and the general population. Patients and Methods In a cohort consisting of 1,888 patients with prostate cancer who received monotherapy with brachytherapy (n = 1,187; 63%) or prostatectomy (n = 701; 37%), SPC incidences were retrieved by linkage with the Dutch Cancer Registry. Standardized incidence rates (SIRs) and absolute excess risks (AERs) were calculated for comparison. Results A total of 223 patients were diagnosed with SPC, 136 (11%) after brachytherapy and 87 (12%) after prostatectomy, with a median follow-up of 7.5 years. The SIR for all malignancies, bladder cancer, and rectal cancer were 0.94 (95% CI, 0.78 to 1.12), 1.69 (95% CI, 0.98 to 2.70), and 0.90 (95% CI, 0.41 to 1.72) for brachytherapy and 1.04 (95% CI, 0.83 to 2.28), 1.82 (95% CI, 0.87 to 3.35), and 1.50 (95% CI, 0.68 to 2.85) for prostatectomy, respectively. Bladder SPC risk was significantly increased after brachytherapy for patients age 60 years or younger (SIR, 5.84; 95% CI, 2.14 to 12.71; AER, 24.03) and in the first 4 years of follow-up (SIR, 2.14; 95% CI, 1.03 to 3.94; AER, 12.24). Adjusted for age, the hazard ratio (brachytherapy v prostatectomy) for all SPCs combined was 0.87 (95% CI, 0.64 to 1.18). Conclusion Overall, we found no difference in SPC incidence between patients with prostate cancer treated with prostatectomy or brachytherapy. Furthermore, no increased tumor incidence was found compared with the general population. We observed a higher than expected incidence of bladder SPC after brachytherapy in the first 4 years of follow-up, probably resulting from lead time or screening bias. Because of power limitations, a small increased SPC risk cannot be formally excluded.

Objective Assessing effects of lifestyle interventions in cancer patients has some specific challenges. Although randomization is urgently needed for evidence-based knowledge, sometimes it is difficult to apply conventional randomization (i.e., consent preceding randomization and intervention) in daily settings. Randomization before seeking consent was proposed by Zelen, and additional modifications were proposed since. We discuss four alternatives for conventional randomization: single and double randomized consent design, two-stage randomized consent design, and the design with consent to postponed information. Study Design and Setting We considered these designs when designing a study to assess the impact of physical activity on cancer-related fatigue and quality of life. We tested the modified Zelen design with consent to postponed information in a pilot. The design was chosen to prevent drop out of participants in the control group because of disappointment about the allocation. Results The result was a low overall participation rate most likely because of perceived lack of information by eligible patients and a relatively high dropout in the intervention group. Conclusion We conclude that the alternatives were not better than conventional randomization.

A major scientific challenge for the next few decades is to understand the interaction between genetic susceptibility and environmental factors in the aetiology of chronic diseases. The most promising approach to discover these interactions requires a combined effort of epidemiology and molecular genetics and large sample sizes for sufficient power. Already in the early 90s, the European Prospective Investigation Into Cancer and Nutrition (EPIC) was initiated in 10 European countries to create a large cohort to study the aetiology of chronic diseases. The Netherlands has contributed two cohort studies to EPIC: the Prospect cohort of 17 357 women of the Julius Center in Utrecht, and the Monitoring Project on Risk Factors for Chronic Diseases (MORGEN) cohort of 22 654 men and women of the National Institute for Public Health and the Environment (RIVM) in Bilthoven. In the design phase, both cohorts collaborated closely to obtain maximal synergy in the design of the questionnaires and to follow identical protocols in the collection of biological samples. Because of the efficiency gain in maintaining the cohort infrastructure and in conducting scientific analyses, the Julius Center and the RIVM decided to combine efforts to maintain and expand the cohorts and biobanks by merging them into one EPICNetherlands (EPIC-NL) study.

Background Fatigue is a major problem of cancer patients. Thirty percent of cancer survivors report serious fatigue three years after finishing treatment. There is evidence that physical exercise during cancer treatment reduces fatigue. This may also lead to an improvement of quality of life. Such findings may result in a decrease of healthcare related expenditures and societal costs due to sick leave. However, no studies are known that investigated these hypotheses. Therefore, the primary aim of our study is to assess the effect of exercise during cancer treatment on reducing complaints of fatigue and on reducing health service utilisation and sick leave. Methods/Design The Physical Activity during Cancer Treatment study is a multicentre randomised controlled trial in 150 breast and 150 colon cancer patients undergoing cancer treatment. Participants will be randomised to an exercise or a control group. In addition to the usual care, the exercise group will participate in an 18-week supervised group exercise programme. The control group will be asked to maintain their habitual physical activity pattern. Study endpoints will be assessed after 18 weeks (short term) and after 9 months (long term). Validated questionnaires will be used. Primary outcome: fatigue (Multidimensional Fatigue Inventory and Fatigue Quality List) and cost-effectiveness, health service utilisation and sick leave. Secondary outcome: health related quality of life (European Organisation Research and Treatment of Cancer-Quality of Life questionnaire-C30, Short Form 36 healthy survey), impact on functioning and autonomy (Impact on functioning and autonomy questionnaire), anxiety and depression (Hospital Anxiety and Depression Scale), physical fitness (aerobic peak capacity, muscle strength), body composition and cognitive-behavioural aspects. To register health service utilisation and sick leave, participants will keep diaries including the EuroQuol-5D. Physical activity level will be measured using the Short Questionnaire to Assess Health-Enhancing Physical Activity and will be monitored with an exercise log and a pedometer. Discussion This study investigates the (cost)-effectiveness of exercise during adjuvant treatment of patients with breast or colon cancer. If early physical exercise proves to be (cost) effective, establishing standardised physical exercise programmes during cancer treatment will be planned. Trial registration Current Controlled trials ISRCTN43801571, Dutch Trial Register NTR2138

Background Early treatment of COPD exacerbations has shown to be important. Despite a non-negligible negative impact on health related quality of life, a large proportion of these episodes is not reported (no change in treatment). Little is known whether (low burden) strategies are able to capture these unreported exacerbations. Methods The Clinical COPD Questionnaire (CCQ) is a short questionnaire with great evaluative properties in measuring health status. The current explorative study evaluates the discriminative properties of weekly CCQ assessment in detecting exacerbations. Results In a multicentre prospective cohort study, 121 patients, age 67.4 ± 10.5 years, FEV1 47.7 ± 18.5% pred were followed for 6 weeks by daily diary card recording and weekly CCQ assessment. Weeks were retrospectively labeled as stable or exacerbation (onset) weeks using the Anthonisen symptom diary-card algorithm. Change in CCQ total scores are significantly higher in exacerbation-onset weeks, 0.35 ± 0.69 compared to -0.04 ± 0.37 in stable weeks (p < 0.001). Performance of the Δ CCQ total score discriminating between stable and exacerbation onset weeks was sufficient (area under the ROC curve 0.75). At a cut off point of 0.2, sensitivity was 62.5 (50.3-73.4), specificity 82.0 (79.3-84.4), and a positive and negative predictive value of 43.5 (35.0-51.0) and 90.8 (87.8-93.5), respectively. Using this cut off point, 22 (out of 38) unreported exacerbations were detected while 39 stable patients would have been false positively 'contacted'. Conclusions Weekly CCQ assessment is a promising, low burden method to detect unreported exacerbations. Further research is needed to validate discriminative performance and practical implications of the CCQ in detecting exacerbations in daily care.

HERTOGH, E. M., Y. VERGOUWE, A. J. SCHUIT, P. H. M. PEETERS, and E. M. MONNINKHOF. Behavioral Changes after a 1-yr Exercise Program and Predictors of Maintenance. Med. Sci. Sports Exerc., Vol. 42, No. 5, pp. 886–892, 2010. Purpose: Public health strategies attempt to stimulate participation in physical activity, aiming at permanent behavior change. We assessed the sustained effect of participating in an exercise program on physical activity behavior 1 yr after completion of the program. Furthermore, we aimed to identify factors that predict sustained exercise participation. Methods: Previously low-active, postmenopausal women originally participating in an exercise intervention study (the Sex Hormones and Physical Exercise study) were recontacted 1 yr after finishing the study. Their current level of physical activity was assessed by the Modified Baecke Questionnaire. MET-hours per week spent on at least moderate-intensity activities were calculated and used to assess compliance to the international physical activity recommendation. Multivariable linear regression analysis was applied to investigate which factors predict a higher level of physical activity in the intervention group 1 yr after the study. Results: Participation in the Sex Hormones and Physical Exercise study resulted in an increased level of physical activity in both the intervention (median at baseline and at 12 months = 4.9 and 19.8 METIhIwk j1 , respectively) and the control groups (median at baseline and at 12 months = 4.3 and 5.8 METIhIwk j1 , respectively). Although the intervention group did not maintain the high physical activity level achieved during the study, 1 yr later they remained more active than the control group (median = 12.1 and 7.9 METIhIwk j1 , respectively, P = 0.04). Age, baseline activity, and employment were the strongest predictors of the physical activity level in the intervention group 1 yr after finishing the study. Conclusion: Sustained changes in

Background Early detection of exacerbations by COPD patients initiating prompt interventions has shown to be clinically relevant. Until now, research failed to identify the effectiveness of a written individualized Action Plan (AP) to achieve this. Methods/Design The current multicenter, single-blind RCT with a follow-up period of 6 months, evaluates the hypothesis that individualized AP's reduce exacerbation recovery time. Patients are included from regular respiratory nurse clinics and allocated to either usual care or the AP intervention. The AP provides individualized treatment prescriptions (pharmaceutical and non-pharmaceutical) related to a color coded symptom status (reinforcement at 1 and 4 months). Although usually not possible in self-management trials, we ensured blinding of patients, using a modified informed consent procedure in which patients give consent to postponed information. Exacerbations in both study arms are defined using the Anthonisen symptom diary-card algorithm. The Clinical COPD Questionnaire (CCQ) is assessed every 3-days. CCQ-recovery time of an exacerbation is the primary study outcome. Additionally, healthcare utilization, anxiety, depression, treatment delay, and self-efficacy are assessed at baseline and 6 months. We aim at including 245 COPD patients from 7 hospitals and 5 general practices to capture the a-priori sample size of at least 73 exacerbations per study arm. Discussion This RCT identifies if an AP is an effective component of self-management in patients with COPD and clearly differentiates from existing studies in its design, outcome measures and generalizability of the results considering that the study is carried out in multiple sites including general practices. Trial Registration NCT00879281

OBJECTIVE: To analyse the association between types of physical activity (occupational, recreational and household, vigorous and overall) and risk of primary oesophageal (OAC) or gastric adenocarcinoma (GAC). METHODS: From nine European countries, 420,449 participants were recruited between 1991 and 2000 and followed-up for a mean of 8.8 years to register incident GAC and OAC. Information on physical activity (PA), diet, lifestyle and health-related variables was obtained at baseline. Helicobacter pylori infection status was considered in a subset of 1,211 participants. Analyses were repeated by tumour site (cardia/non-cardia) and histological type (intestinal/diffuse). RESULTS: During the follow-up, 410 GAC and 80 OAC occurred. A lower risk of overall and non-cardia GAC was found for increasing levels of a PA index which combined occupational PA with weekly time spent in sports and cycling. The hazard ratio (HR) of GAC was 0.69, 95% CI: 0.50-0.94, for the comparison between active and inactive participants according to the PA index (HR = 0.44, 95% CI:0.26-0.74, for non-cardia GAC). No effect was found for cardia tumours or histological subtypes of GAC. PA of any kind was not associated with OAC. CONCLUSIONS: Overall and distal (non-cardia) gastric tumours were inversely associated with time spent on cycling and sports and a total PA index. No association was found for any type of PA and risk of cardia cancers of the stomach. Some authors are partners of ECNIS, a network of excellence of the EC (6FP contract 513943).

Many definitions of COPD exacerbations are reported. The choice for a definition determines the number of exacerbations observed. However, the effect of different definitions on the effect sizes of randomized controlled trials is unclear. This article provides an overview of the large variation of definitions of COPD exacerbations from the literature. Furthermore, the effect of using different definitions on effect sizes (relative risk and hazard ratio) was investigated in a randomized controlled discontinuation trial of inhaled corticosteroids. The following definitions were applied: (1) unscheduled medical attention, (2) a course of oral corticosteroids/antibiotics, (3) deterioration in two major or one major and one minor symptom according to Anthonisen (referenced later), (4) a change in one or more symptoms, (5) a change in two or more symptoms, and (6) a combination of numbers 2 and 4. Relative risks for the exacerbation rate ranged from 1.19 to 1.49, and hazard ratios for time to first exacerbation ranged from 1.36 to 1.84 for the various definitions, varying from nonsignificant to significant. Because the definition of a COPD exacerbation has an impact on the effect size of interventions, there is an urgent need for concerted attempts to reach agreement on a definition of an exacerbation. Also, the exact definition to be used in a study should be specified in the protocol.

Purpose: To assess the influence of dose on the risk of acute urinary retention (AUR) after iodine-125 prostate brachytherapy. Methods and Materials: Between January 2005 and December 2008, 714 consecutive patients with localized prostate cancer were treated with iodine-125 prostate brachytherapy at our department. All patients completed four imaging studies: magnetic resonance imaging before and 4 weeks after treatment and intraoperative three-dimensional transrectal ultrasonography before and after implantation. The development of AUR was prospectively recorded. The evaluated treatment and dosimetric parameters included prostate volume, number of needles and seeds used, intra- and postoperative prostate edema, percentage of prostate volume receiving 100%, 150%, and 200% of the prescribed dose to the prostate, minimal dose received by 90% of the prostate volume, and percentage of the urethra receiving 100%, 150%, and 200% of the prescribed dose. Logistic regression analysis was used to examine which factors were associated with AUR. Results: Of the 714 patients, 57 (8.0%) developed AUR. On univariate analysis, the following treatment and dosimetric factors were significantly associated with AUR: International Prostate Symptom Score (odds ratio [OR], 2.07, per 10-point increase), preimplant prostate volume (OR, 1.06), postimplant prostate volume (OR, 1.04), number of needles used (OR, 1.09), and number ofmore » seeds used (OR, 1.03). On multivariate analysis, the only independent predictive factors for AUR were pretreatment prostate volume (OR, 1.05) and International Prostate Symptom Score (OR, 1.76, per 10-point increase). Patients with a pretreatment prostate volume >35 cm{sup 3} had a 10.4% risk of developing AUR compared with 5.4% for those with a prostate volume of {

OBJECTIVE: The aim of this study was to investigate the effect of a 12-month moderate-to-vigorous exercise program combining aerobic and muscle strength training on body composition among sedentary, postmenopausal women. METHODS: A randomized controlled trial was conducted. A total of 189 sedentary postmenopausal women (age 50-69 y, body mass index 22-40 kg/m) were randomly assigned to an exercise (n = 96) or a control group (n = 93). Study parameters measured at baseline, 4 months, and 12 months were as follows: body weight and body height (body mass index), waist and hip circumference (body fat distribution), and dual-energy x-ray absorptiometry (total body fat and lean mass). Differences in changes in study parameters between exercise and control group were examined with generalized estimating equations analysis. RESULTS: The exercise program did not result in significant effects on weight, body mass index, and hip circumference. The exercise group experienced a statistically significant greater loss in total body fat, both absolute (-0.33 kg) (borderline) as in a percentage (-0.43%) compared with the control group. In addition, lean mass increased significantly (+0.31 kg), whereas waist circumference (-0.57 cm) decreased significantly compared with the control group. CONCLUSIONS: We conclude that a 12-month exercise program combining aerobic and muscle strength training did not affect weight but positively influenced body composition of postmenopausal women. Affecting body fat distribution and waist circumference may have important health implications because it is an independent risk factor in obese but also in nonobese people. Therefore, this study gives further credence to efforts of public health and general practitioners aiming to increase physical activity levels of postmenopausal women. © 2009 The North American Menopause Society.

Background As neoadjuvant chemotherapy (NAC) is increasingly used to downstage patients with breast cancer, the timing of the sentinel node (SN) biopsy has become an important issue. This review was conducted to determine the accuracy of SN biopsy following NAC. Methods We searched Medline, Embase and Cochrane databases from 1993 to February 2009 for studies on patients with invasive breast cancer who underwent SN biopsy after NAC followed by an axillary lymph node dissection (ALND). Results Of 574 eligible studies, 27 were included in this review with a total study population of 2148 patients. The pooled SN identification rate was 90.9% (95% confidence interval (CI) = 88.0–93.1%) and the false-negative rate was 10.5% (95% CI = 8.1–13.6%). Negative predictive value and accuracy after NAC were 89.0% (95% CI = 85.1–92.1%) and 94.4% (95% CI = 92.6–95.8%), respectively. The reported SN success rates were heterogeneous and several variables were reported to be associated with decreased SN accuracy, i.e. initially positive clinical nodal status. Conclusions There is a potential role for SN biopsy following NAC which could be considered on an individual basis. However, there is insufficient evidence to recommend this as a standard procedure. Further research with subgroup analysis using variables reported to be associated with decreased SN accuracy is required in order to clearly define its value in the subgroups of breast cancer patients.

To assess clinical outcome in terms of biochemical No evidence of disease (bNED) for patients with stranded seed implants versus loose seed implants in prostate brachytherapy.From December 2000 until October 2006, we treated 896 Tor =2C Nx/0 Mx/0, prostate cancer patients with either stranded seed (n=538) or loose seed (n=358) I-125 implants. A total of 211 patients received a 6 months course of anti-androgen therapy, before treatment, for prostate volume reduction to50 cc. Patients with very small and large gland volumes or a history of transurethral prostate resection, were preferably treated with stranded seeds, otherwise selection was arbitrary.The 5-year bNED rates (95% Confidence Interval) for stranded seed patients and loose seed patients were respectively 86% (82-90) and 90% (85-95), the total 5-year bNED rate was 87% (85-90). When adjusted for possible confounding factors in a Cox-regression analysis, type of seed was significantly associated with biochemical failure with a 43% risk reduction (hazard ratio: 0.57; 95% CI: 0.34-0.97) for loose seeds versus stranded seeds.These results suggest that seed-type affects clinical outcome in prostate brachytherapy, with better bNED for patients with loose seed implants.

Purpose: To evaluate the impact of acute urinary retention (AUR) in patients treated with {sup 125}I prostate brachytherapy on short- and long-term health-related quality of life (HRQOL); and to assess whether pretreatment HRQOL has additional value in the prediction of AUR. Methods and Materials: For 127 patients treated with {sup 125}I brachytherapy for localized prostate cancer between December 2000 and June 2003, toxicity and HRQOL data were prospectively collected. Patients received a HRQOL questionnaire at five time points: before and 1 month, 6 months, 1 year, and 6 years after treatment. The questionnaire included the RAND-36 generic health survey, the cancer-specific European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30), the tumor-specific EORTC prostate cancer module (EORTC QLQ-PR25), and the American Urological Association (AUA) symptom index. Results: Of 127 patients, 13 (10.2%) developed AUR. Patients with AUR had a significantly worse urinary QOL at all time points compared with patients without AUR. The mean difference over time (6 years) between both groups for the EORTC QLQ-PR25 urinary symptom score was 13.0 points (p < 0.001) and for the AUA urinary symptom score was 15.7 points (p = 0.001). Global QOL scores (EORTC QLQ-C30) over time for patientsmore » who developed AUR were significantly worse compared with patients without AUR (mean difference 6.7 points; p = 0.043). In multivariate logistic regression analysis, pretreatment International Prostate Symptom Score (p = 0.004) and neoadjuvant hormonal treatment (p = 0.034) were predictors of AUR. Quality of life did not have added predictive value. Conclusion: Acute urinary retention after prostate brachytherapy has a significant negative impact on patient's HRQOL up to 6 years after treatment, in terms of both global QOL measures and urinary symptom scores. Furthermore, our results suggest limited value of pretreatment HRQOL measures for the prediction of AUR.« less

Contains fulltext : 71169.pdf (Publisher’s version ) (Open Access) There are many reports on the frequency of non-sentinel lymph node involvement when isolated tumor cells are found in the sentinel node, but results and recommendations for the use of an axillary lymph node dissection differ among studies. This systematic review was conducted to give an overview of this issue and to provide recommendations for the use of an axillary lymph node dissection in these patients. We searched Medline, Embase, and Cochrane databases from January 1, 2002, through November 27, 2007, for articles on patients with invasive breast cancer who had isolated tumor cells in the sentinel lymph node (according to the sixth edition of the Cancer Staging Manual of the American Joint Committee on Cancer) and who also underwent axillary lymph node dissection. Of 411 selected articles, 29 (including 836 patients) were included in this review. These 29 studies were heterogeneous, reporting a wide range of non-sentinel lymph node involvement (defined as the presence of isolated tumor cells or micro- or macrometastases) associated with isolated tumor cells in the sentinel lymph node, with an overall pooled risk for such involvement of 12.3% (95% confidence interval = 9.5% to 15.7%). This pooled risk estimate was marginally higher than the risk of a false-negative sentinel lymph node biopsy examination (ie, 7%-8%) but marginally lower than the risk of non-sentinel lymph node metastases in patients with micrometastases (ie, approximately 20%) who are currently eligible for an axillary lymph node dissection. Because 36 (64%) of the 56 patients with isolated tumor cells in their sentinel lymph node also had non-sentinel lymph node macrometastases, those patients with isolated tumor cells in the sentinel lymph node without other indications for adjuvant systemic therapy might be candidates for axillary lymph node dissection.

The multicenter cross-sectional study was designed to develop a simple rule to predict the risk of osteoporosis in the patients with a low-energy fracture (LEF). Furthermore, we aimed to investigate the incidence of fall-related risk factors. We included 206 patients with age over 50 and an LEF at the emergency room. All patients underwent osteoporosis and fall risk assessment and dual-energy X-ray absorptiometry (DEXA) of both hips and the lumbar spine. The incidence of osteoporosis in our study population was 41% (84 cases of 206). Fifty-four percent of the patients reported at least one fall-related risk factor. Mobility problems occurred in 31% and osteoarthritis in 19%. The final osteoporosis prediction rule included age, positive family history, immobility, and low-body weight. The discrimination of the rule after correction for over-optimism was good (receiver operating curve (ROC)=ROC area=0.79). This simple rule may be helpful to select patients who need further osteoporosis assessment.

Background In epidemiological research, physical activity is usually assessed by questionnaires. Questionnaires are suitable for large study populations since they are relatively inexpensive and not very time consuming. However, questionnaire information is by definition subjective and prone to recall bias, especially among elderly subjects. The Modified Baecke Questionnaire, developed by Voorrips and coworkers, measures habitual physical activity in the elderly. The questionnaire includes questions on household activities, sports, and leisure time activities, over a time period of one year. The Modified Baecke Questionnaire results in a score to classify people as high, moderate, or low in daily physical activity, based on tertiles. Methods The validity of the Modified Baecke Questionnaire score was assessed among 21 elderly men and women using the doubly labeled water method as the reference criterion. This method is considered to be the gold standard for measuring energy expenditure in free-living individuals. Energy expenditure on physical activity is estimated by the ratio of total energy expenditure measured by the doubly labeled water method and resting metabolic rate measured by indirect calorimetry. This ratio is called the physical activity ratio. Results The Spearman correlation coefficient between the questionnaire score and the physical activity ratio (PAR) was 0.54 (95% CI 0.22–0.66). Correct classification by the questionnaire occurred in 71% of participants who were in the lowest tertile of PAR, in 14% of participants in the middle tertile, and in 43% of participants in the highest tertile. Subjects were not wrongly classified in an opposite tertile. Conclusion The validity of the Modified Baecke Questionnaire is fair-to-moderate. This study shows that the questionnaire can correctly classify individuals as low or high active, but does a poor job for moderately active individuals.