Effect of semaglutide 2.4 mg on physical functioning and weight- and health-related quality of life in adults with overweight or obesity: Patient-reported outcomes from the STEP 1-4 trials.

AIMS: To summarize the effects of semaglutide 2.4 mg on weight-related quality of life (WRQOL) and health-related quality of life (HRQOL), focusing on the confirmatory secondary endpoint of physical functioning. MATERIALS AND METHODS: The STEP 1-4 Phase 3a, 68-week, double-blind, randomized controlled trials assessed the efficacy and safety of semaglutide 2.4 mg versus placebo in individuals with overweight/obesity. WRQOL and HRQOL were assessed by change from baseline to Week 68 in two different but complementary measures, the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT; STEP 1 and 2) and the SF-36v2 Health Survey Acute (SF-36v2; STEP 1-4). RESULTS: Superiority for semaglutide 2.4 mg over placebo based on IWQOL-Lite-CT and SF-36v2 physical functioning scores was confirmed in STEP 1 and 2 and in STEP 1, 2 and 4, respectively. At Week 68, a greater proportion of participants treated with semaglutide 2.4 mg than with placebo reached meaningful within-person change (MWPC) thresholds for IWQOL-Lite-CT Physical Function scores in STEP 1 (51.8% vs. 28.3%; p < 0.0001) and STEP 2 (39.6% vs. 29.5%; p = 0.0083) and the MWPC threshold for SF-36v2 Physical Functioning in STEP 1 (39.8% vs. 24.1%; p < 0.0001), STEP 2 (41.0% vs. 27.3%; p = 0.0001) and STEP 4 (18.0% vs. 6.6%; p < 0.0001). All other IWQOL-Lite-CT and SF-36v2 scale scores in STEP 1-4 were numerically improved with semaglutide 2.4 mg versus placebo, except for SF-36v2 Role Emotional in STEP 2. CONCLUSIONS: Semaglutide 2.4 mg significantly improved physical functioning, with greater proportions of participants achieving MWPC compared with placebo, and showed beneficial effects on WRQOL and HRQOL beyond physical functioning.

The improved health utility of once-weekly subcutaneous semaglutide 2.4 mg compared with placebo in the STEP 1-4 obesity trials.

AIM: To assess health utility values in the Semaglutide Treatment Effect in People with obesity (STEP) 1-4 trials. MATERIALS AND METHODS: The STEP 1-4 phase 3a, 68-week, double-blind randomized controlled trials assessed the efficacy and safety of semaglutide 2.4 mg versus placebo in individuals with a body mass index (BMI) of 30 kg/m2 or higher or a BMI of 27 kg/m2 or higher and at least one comorbidity (STEP 1, 3 and 4), or a BMI of 27 kg/m2 or higher and type 2 diabetes (STEP 2). Patients received lifestyle intervention plus intensive behavioural therapy in STEP 3. Health-related quality of life was assessed using the Short Form 36-item Health Survey version 2 (SF-36v2) at baseline and week 68. Scores were converted into Short Form Six-Dimension version 2 (SF-6Dv2) utility scores or mapped onto the European Quality of Life Five-Dimension Three-Level (EQ-5D-3L) utility index using UK health utility weights. RESULTS: At week 68, semaglutide 2.4 mg was associated with minor health utility score improvements from baseline (all trials), while scores for placebo typically decreased. SF-6Dv2 treatment differences by week 68 for semaglutide 2.4 mg versus placebo were significant in STEP 1 and 4 (P ≤ .001), but not STEP 2 or 3. EQ-5D-3L treatment differences by week 68 for semaglutide 2.4 mg versus placebo were significant in STEP 1, 2 and 4 (P < .001 for all), but not STEP 3. CONCLUSIONS: Semaglutide 2.4 mg was associated with improvement in health utility scores compared with placebo, reaching statistical significance in STEP 1, 2 and 4.

Quality of life in thyroid cancer.

To explore the impact of differentiated thyroid cancer (DTC) on quality of life (QoL) a clinical analytical framework was developed. Based on the clinical analytical framework, a systematic literature search was performed to identify studies applying patient-reported outcomes (PRO) instruments among patients with DTC. Subsequently, the scope was narrowed down to studies comparing scores on the Medical Outcomes Study (MOS) Short form 36 (SF-36) to a reference population (clinical interpretability criterion). Further, the currently available thyroid cancer (TC) specific QoL PROs were review in accordance with the standards of the International Society of Quality of Life Research. In the initial search, 213 studies were included. The additional 'clinical interpretability'-criteria, limited the final study sample to 16 studies, 13 cross-sectional and 3 longitudinal. QoL was impacted across all SF-36 scales. The impact was generally modest and the impact was impeded by time since diagnosis and treatment. Four TC specific instruments were identified. Generally, the documentation of their measurement properties, particularly content validity and clinical validity, including substantial quantitative validation, was scarce. As was the cross-cultural applicability of the currently available instruments. This restricted, focused, clinically founded review showed an impact on a broad range of QoL issues. There is a need for large-scale measurement of QoL outcome longitudinally, using well-validated PRO instruments in order to identify with certainty the impact on subgroups.

Association of alcohol use with years lived without major chronic diseases: A multicohort study from the IPD-Work consortium and UK Biobank.

Background: Heavy alcohol consumption increases the risk of several chronic diseases. In this multicohort study, we estimated the number of life-years without major chronic diseases according to different characteristics of alcohol use. Methods: In primary analysis, we pooled individual-level data from up to 129,942 adults across 12 cohort studies with baseline data collection on alcohol consumption, drinking patterns, and history between 1986 and 2005 (the IPD-Work Consortium). Self-reported alcohol consumption was categorised according to UK guidelines - non-drinking (never or former drinkers); moderate consumption (1-14 units); heavy consumption (>14 units per week). We further subdivided moderate and heavy drinkers by binge drinking pattern (alcohol-induced loss of consciousness). In addition, we assessed problem drinking using linked data on hospitalisations due to alcohol abuse or poisoning. Follow-up for chronic diseases for all participants included incident type 2 diabetes, coronary heart disease, stroke, cancer, and respiratory disease (asthma and chronic obstructive pulmonary disease) as ascertained via linkage to national morbidity and mortality registries, repeated medical examinations, and/or self-report. We estimated years lived without any of these diseases between 40 and 75 years of age according to sex and characteristics of alcohol use. We repeated the main analyses using data from 427,621 participants in the UK Biobank cohort study. Findings: During 1·73 million person-years at risk, 22,676 participants in IPD-Work cohorts developed at least one chronic condition. From age 40 to 75 years, never-drinkers [men: 29·3 (95%CI 27·9-30·8) years, women 29·8 (29·2-30·4) years)] and moderate drinkers with no binge drinking habit [men 28·7 (28·4-29·0) years, women 29·6 (29·4-29·7) years] had the longest disease-free life span. A much shorter disease-free life span was apparent in participants who experienced alcohol poisoning [men 23·4 (20·9-26·0) years, women 24·0 (21·4-26·5) years] and those with self-reported heavy overall consumption and binge drinking [men: 26·0 (25·3-26·8), women 27·5 (26·4-28·5) years]. The pattern of results for alcohol poisoning and self-reported alcohol consumption was similar in UK Biobank. In IPD-Work and UK Biobank, differences in disease-free years between self-reported moderate drinkers and heavy drinkers were 1·5 years or less. Interpretation: Individuals with alcohol poisonings or heavy self-reported overall consumption combined with a binge drinking habit have a marked 3- to 6-year loss in healthy longevity. Differences in disease-free life between categories of self-reported weekly alcohol consumption were smaller. Funding: Medical Research Council, National Institute on Aging, NordForsk, Academy of Finland, Finnish Work Environment Fund.

Association of Healthy Lifestyle With Years Lived Without Major Chronic Diseases.

Importance: It is well established that selected lifestyle factors are individually associated with lower risk of chronic diseases, but how combinations of these factors are associated with disease-free life-years is unknown. Objective: To estimate the association between healthy lifestyle and the number of disease-free life-years. Design, Setting, and Participants: A prospective multicohort study, including 12 European studies as part of the Individual-Participant-Data Meta-analysis in Working Populations Consortium, was performed. Participants included 116 043 people free of major noncommunicable disease at baseline from August 7, 1991, to May 31, 2006. Data analysis was conducted from May 22, 2018, to January 21, 2020. Exposures: Four baseline lifestyle factors (smoking, body mass index, physical activity, and alcohol consumption) were each allocated a score based on risk status: optimal (2 points), intermediate (1 point), or poor (0 points) resulting in an aggregated lifestyle score ranging from 0 (worst) to 8 (best). Sixteen lifestyle profiles were constructed from combinations of these risk factors. Main Outcomes and Measures: The number of years between ages 40 and 75 years without chronic disease, including type 2 diabetes, coronary heart disease, stroke, cancer, asthma, and chronic obstructive pulmonary disease. Results: Of the 116 043 people included in the analysis, the mean (SD) age was 43.7 (10.1) years and 70 911 were women (61.1%). During 1.45 million person-years at risk (mean follow-up, 12.5 years; range, 4.9-18.6 years), 17 383 participants developed at least 1 chronic disease. There was a linear association between overall healthy lifestyle score and the number of disease-free years, such that a 1-point improvement in the score was associated with an increase of 0.96 (95% CI, 0.83-1.08) disease-free years in men and 0.89 (95% CI, 0.75-1.02) years in women. Comparing the best lifestyle score with the worst lifestyle score was associated with 9.9 (95% CI 6.7-13.1) additional years without chronic diseases in men and 9.4 (95% CI 5.4-13.3) additional years in women (P < .001 for dose-response). All of the 4 lifestyle profiles that were associated with the highest number of disease-free years included a body-mass index less than 25 (calculated as weight in kilograms divided by height in meters squared) and at least 2 of the following factors: never smoking, physical activity, and moderate alcohol consumption. Participants with 1 of these lifestyle profiles reached age 70.3 (95% CI, 69.9-70.8) to 71.4 (95% CI, 70.9-72.0) years disease free depending on the profile and sex. Conclusions and Relevance: In this multicohort analysis, various healthy lifestyle profiles appeared to be associated with gains in life-years without major chronic diseases.

Job Strain as a Risk Factor for Peripheral Artery Disease: A Multi-Cohort Study.

Background Job strain is implicated in many atherosclerotic diseases, but its role in peripheral artery disease (PAD) is unclear. We investigated the association of job strain with hospital records of PAD, using individual-level data from 11 prospective cohort studies from Finland, Sweden, Denmark, and the United Kingdom. Methods and Results Job strain (high demands and low control at work) was self-reported at baseline (1985-2008). PAD records were ascertained from national hospitalization data. We used Cox regression to examine the associations of job strain with PAD in each study, and combined the study-specific estimates in random effects meta-analyses. We used τ2, I2, and subgroup analyses to examine heterogeneity. Of the 139 132 participants with no previous hospitalization with PAD, 32 489 (23.4%) reported job strain at baseline. During 1 718 132 person-years at risk (mean follow-up 12.8 years), 667 individuals had a hospital record of PAD (3.88 per 10 000 person-years). Job strain was associated with a 1.41-fold (95% CI, 1.11-1.80) increased average risk of hospitalization with PAD. The study-specific estimates were moderately heterogeneous (τ2=0.0427, I2: 26.9%). Despite variation in their magnitude, the estimates were consistent in both sexes, across the socioeconomic hierarchy and by baseline smoking status. Additional adjustment for baseline diabetes mellitus did not change the direction or magnitude of the observed associations. Conclusions Job strain was associated with small but consistent increase in the risk of hospitalization with PAD, with the relative risks on par with those for coronary heart disease and ischemic stroke.

Health-related quality of life predicted subsequent health care resource utilization in patients with active cancer.

PURPOSE: The objective of this study was to estimate the association between SF-12v2® Health Survey (SF-12v2) scores and subsequent health care resource utilization (HCRU) among patients with cancer. METHODS: We analyzed 18+ year participants in the Medical Expenditure Panel Survey, diagnosed with active cancer or malignancy (n = 647). HCRU was measured by total medical expenditures (MEs) and number of medical events (EVs) in the 6 months following the SF-12v2 assessment. The effect of SF-12v2 scores (physical (PCS) and mental (MCS) component summary scores and the SF-6D health-utility score) on HCRU was estimated using generalized linear models. Estimates were obtained for the entire sample and for the four cancer groups present in the sample: breast, prostate, skin, and lung. RESULTS: For PCS and MCS, a one-point better score was associated with 2% lower MEs (P < 0.001) and 2.5% lower MEs (P = 0.015), respectively. A 0.05-point better SF-6D score was associated with 7% lower MEs (P = 0.003). PCS and SF-6D were more strongly associated with MEs for prostate cancer patients (P = 0.009 and P = 0.003) and PCS was more strongly associated with MEs for skin cancer patients (P = 0.019), compared to other cancer groups. A 1-point better PCS predicted 1% lower EVs, while a 0.05 better SF-6D score predicted 4% lower EVs. CONCLUSIONS: The significant associations between SF-12v2 scores from oncology patients and subsequent HCRU can guide interpretations of SF-12v2 scores in evaluation of therapies and in health policy decisions.

The Work Role Functioning Questionnaire v2.0 Showed Consistent Factor Structure Across Six Working Samples.

Objective The Work Role Functioning Questionnaire v2.0 (WRFQ) is an outcome measure linking a persons' health to the ability to meet work demands in the twenty-first century. We aimed to examine the construct validity of the WRFQ in a heterogeneous set of working samples in the Netherlands with mixed clinical conditions and job types to evaluate the comparability of the scale structure. Methods Confirmatory factor and multi-group analyses were conducted in six cross-sectional working samples (total N = 2433) to evaluate and compare a five-factor model structure of the WRFQ (work scheduling demands, output demands, physical demands, mental and social demands, and flexibility demands). Model fit indices were calculated based on RMSEA ≤ 0.08 and CFI ≥ 0.95. After fitting the five-factor model, the multidimensional structure of the instrument was evaluated across samples using a second order factor model. Results The factor structure was robust across samples and a multi-group model had adequate fit (RMSEA = 0.63, CFI = 0.972). In sample specific analyses, minor modifications were necessary in three samples (final RMSEA 0.055-0.080, final CFI between 0.955 and 0.989). Applying the previous first order specifications, a second order factor model had adequate fit in all samples. Conclusion A five-factor model of the WRFQ showed consistent structural validity across samples. A second order factor model showed adequate fit, but the second order factor loadings varied across samples. Therefore subscale scores are recommended to compare across different clinical and working samples.

Job insecurity and risk of diabetes: a meta-analysis of individual participant data.

BACKGROUND: Job insecurity has been associated with certain health outcomes. We examined the role of job insecurity as a risk factor for incident diabetes. METHODS: We used individual participant data from 8 cohort studies identified in 2 open-access data archives and 11 cohort studies participating in the Individual-Participant-Data Meta-analysis in Working Populations Consortium. We calculated study-specific estimates of the association between job insecurity reported at baseline and incident diabetes over the follow-up period. We pooled the estimates in a meta-analysis to produce a summary risk estimate. RESULTS: The 19 studies involved 140 825 participants from Australia, Europe and the United States, with a mean follow-up of 9.4 years and 3954 incident cases of diabetes. In the preliminary analysis adjusted for age and sex, high job insecurity was associated with an increased risk of incident diabetes compared with low job insecurity (adjusted odds ratio [OR] 1.19, 95% confidence interval [CI] 1.09-1.30). In the multivariable-adjusted analysis restricted to 15 studies with baseline data for all covariates (age, sex, socioeconomic status, obesity, physical activity, alcohol and smoking), the association was slightly attenuated (adjusted OR 1.12, 95% CI 1.01-1.24). Heterogeneity between the studies was low to moderate (age- and sex-adjusted model: I2 = 24%, p = 0.2; multivariable-adjusted model: I2 = 27%, p = 0.2). In the multivariable-adjusted analysis restricted to high-quality studies, in which the diabetes diagnosis was ascertained from electronic medical records or clinical examination, the association was similar to that in the main analysis (adjusted OR 1.19, 95% CI 1.04-1.35). INTERPRETATION: Our findings suggest that self-reported job insecurity is associated with a modest increased risk of incident diabetes. Health care personnel should be aware of this association among workers reporting job insecurity.

Prospective assessment of the quality of life before, during and after image guided intensity modulated radiotherapy for prostate cancer.

BACKGROUND: Radiotherapy (RT) in combination with androgen deprivation therapy (ADT) for prostate cancer (PCa) carries a risk of gastrointestinal (GI) and genitourinary toxicity, which might affect the quality of life (QoL). The purpose of this study was to assess the QoL in patients with PCa before, during and after radiotherapy (RT) and to compare the QoL 1 year after RT to a normal population. METHODS: The QoL was evaluated prospectively by the self-administered questionnaire SF-36 in 87 patients with PCa. The SF-36 was completed before RT (baseline), at start of RT, at end of RT and 1 year after RT. A mixed model analysis was used to determine the changes in QoL at each time point compared to baseline. The patients' QoL 1 year after RT was compared to a normal population consisting of 462 reference subjects matched on age and education. RESULTS: One year after RT, patients reported significantly less pain and significantly fewer limitations due to their physical health compared to baseline. Compared to the normal population, patients reported significantly less pain 1 year after RT. However, patients also reported significantly less vitality, worse mental health as well as significantly more limitations due to physical and mental health 1 year after RT compared to the normal population. CONCLUSIONS: In this study, patients with PCa did not experience significant impairment in the QoL 1 year after RT compared to baseline. However, patients reported significantly worse mental health before, during and 1 year after RT compared to the normal population.

Quality-of-Life Impairments Persist Six Months After Treatment of Graves' Hyperthyroidism and Toxic Nodular Goiter: A Prospective Cohort Study.

BACKGROUND: The treatment of hyperthyroidism is aimed at improving health-related quality of life (HRQoL) and reducing morbidity and mortality. However, few studies have used validated questionnaires to assess HRQoL prospectively in such patients. The purpose of this study was to assess the impact of hyperthyroidism and its treatment on HRQoL using validated disease-specific and generic questionnaires. METHODS: This prospective cohort study enrolled 88 patients with Graves' hyperthyroidism and 68 with toxic nodular goiter from endocrine outpatient clinics at two Danish university hospitals. The patients were treated with antithyroid drugs, radioactive iodine, or surgery. Disease-specific and generic HRQoL were assessed using the thyroid-related patient-reported outcome (ThyPRO) and the Medical Outcomes Study 36-item Short Form (SF-36), respectively, evaluated at baseline and six-month follow-up. The scores were compared with those from two general population samples who completed ThyPRO (n = 739) and SF-36 (n = 6638). RESULTS: Baseline scores for patients with Graves' hyperthyroidism and toxic nodular goiter were significantly worse than those for the general population scores on all comparable ThyPRO scales and all SF-36 scales and component summaries. ThyPRO scores improved significantly with treatment on all scales in Graves' hyperthyroidism and four scales in toxic nodular goiter, while SF-36 scores improved on five scales and both component summaries in Graves' hyperthyroidism and only one scale in toxic nodular goiter. In Graves' hyperthyroidism, large treatment effects were observed on three ThyPRO scales (Hyperthyroid Symptoms, Tiredness, Overall HRQoL) and moderate effects on three scales (Anxiety, Emotional Susceptibility, Impaired Daily Life), while moderate effects were seen in two ThyPRO scales in toxic nodular goiter (Anxiety, Overall HRQoL). However, significant disease-specific and generic HRQoL deficits persisted on multiple domains across both patient groups. CONCLUSIONS: Graves' hyperthyroidism and toxic nodular goiter cause severe disease-specific and generic HRQoL impairments, and HRQoL deficits persist in both patient groups six months after treatment. These data have the potential to improve communication between physicians and patients by offering realistic estimates of expected HRQoL impairments and treatment effects. Future studies should identify risk factors for persistent HRQoL deficits, compare HRQoL effects of the various therapies, and thereby aid in determining the optimal treatment strategies.

Disease-Specific as Well as Generic Quality of Life Is Widely Impacted in Autoimmune Hypothyroidism and Improves during the First Six Months of Levothyroxine Therapy.

BACKGROUND: Hypothyroidism is often diagnosed, and subsequently treated, due to health-related quality of life (HRQL) issues. However, HRQL following treatment has never previously been assessed in longitudinal descriptive studies using validated instruments. OBJECTIVE: To investigate disease-specific (ThyPRO) and generic (SF-36) HRQL, following levothyroxine therapy in patients with hypothyroidism due to autoimmune thyroiditis. METHODS: This prospective cohort study was set at endocrine outpatient clinics at two Danish university hospitals. Seventy-eight consecutive patients were enrolled and completed HRQL questionnaires before, six weeks, and six months after initiation of levothyroxine therapy. Normative ThyPRO (n = 739) and SF-36 (n = 6,638) data were available for comparison and changes in HRQL following treatment were estimated and quantified. RESULTS: Prior to treatment, all ThyPRO scales were significantly impacted (p<0.0001), compared to the general population sample. The same was observed for seven of eight SF-36 scales, the exception being Bodily Pain. Tiredness (ThyPRO) and Vitality (SF-36) were the most markedly impacted scales. After six weeks of treatment, nine of thirteen ThyPRO scales had significantly improved. ThyPRO improvements were consistent at six months, where five of eight SF-36 scales had also significantly improved, but deficits persisted for a subset of both ThyPRO and SF-36 scales. CONCLUSIONS: In this population of hypothyroid patients, HRQL was widely affected before treatment, with tiredness as the cardinal impairment according to both ThyPRO and SF-36. Many aspects of HRQL improved during the first six months of LT4 therapy, but full recovery was not obtained. Our results may help clinicians inform patients about expected clinical treatment effects.

Workplace social capital and risk of long-term sickness absence. Are associations modified by occupational grade?

BACKGROUND: Workplace social capital (WSC) is an emerging topic among both work environment professionals and researchers. We examined (i) whether high WSC protected against risk of long-term sickness absence (LTSA) in a random sample of the Danish workforce during a 1-year follow-up and (ii) whether the association of WSC with sickness absence was modified by occupational grade. METHODS: We measured WSC by self-report in a cohort of 3075 employees and linked responses to a national register of sickness absence. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) of onset of LTSA (≥21 days), adjusted for covariates. We stratified analyses by occupational grade and examined if there was an interaction effect of WSC and occupational grade. RESULTS: A one standard deviation higher WSC score predicted a reduced risk of sickness absence after adjustment for sociodemographic variables, prevalent health problems and health behaviours (HR = 0.85, 95% CI = 0.74-0.99). The HR was attenuated and lost statistical significance after further adjustment for occupational grade (HR = 0.90, 95% CI = 0.78-1.04). When stratified by occupational grade, high WSC predicted a decreased risk of sickness absence among higher grade workers (HR = 0.61, 95% CI = 0.44-0.84) but not among lower grade workers (HR = 0.98, 95% CI = 0.83-1.15). The interaction effect of WSC and occupational grade was statistically significant (HR = 0.97, 95% CI = 0.95-0.99). CONCLUSION: High WSC might reduce risk of LTSA. However, the protective effect appears to be limited to workers of higher occupational grade.

Quality of life in patients with benign nontoxic goiter: impact of disease and treatment response, and comparison with the general population.

BACKGROUND: While health-related quality of life (HRQoL) issues often prompt treatment of benign nontoxic goiter (NTG), few clinical studies have systematically assessed HRQoL in patients with this condition. The purpose of the present study was to evaluate thyroid-related and generic HRQoL in patients with benign NTG, as compared to the general population, before and six months after treatment. METHODS: Thyroid-related and generic HRQoL were assessed with Thyroid Patient-Reported Outcome (ThyPRO) and Medical Outcomes Study 36-item Short Form (SF-36), respectively. Baseline and six-month post-treatment HRQoL assessments were obtained from 111 patients with NTG who underwent radioiodine therapy (32%), hemithyroidectomy (53%), total thyroidectomy (12%), or cyst aspiration with ethanol sclerotherapy (4%). Euthyroid patients were enrolled at baseline, 80% of whom remained euthyroid six months post-treatment, with 20% experiencing subclinical thyroid dysfunction. Normative ThyPRO (n=739) and SF-36 (n=6638) data were collected from representative general population samples. Score differences between patients and the general population were analyzed with multivariate linear regression analysis, adjusting for age, sex, comorbidity, and educational status. Changes in scores between baseline and follow-up were analyzed with the paired t-test, and magnitudes of score changes were evaluated as effect sizes (mean difference/SDbaseline; 0.2-0.5 indicating small, 0.5-0.8 moderate, and >0.8 large effects). RESULTS: Patients' baseline scores were significantly worse than those in the general population on 9 of the 13 ThyPRO scales. Six months after treatment, the patients' ThyPRO scores had improved on six scales, with large/moderate effects on the Goiter Symptoms and Anxiety scales. However, on eight scales, the post-treatment patient scores were still significantly worse than the general population scores. At baseline, patients had worse scores than the general population on four of the eight SF-36 scales and the SF-36 Mental Component Summary, none of which improved after treatment. CONCLUSIONS: Compared with the general population, patients with NTG had greatest HRQoL impairment at baseline on the Goiter Symptoms and Anxiety scales, which also demonstrated the largest post-treatment improvements. However, both disease-specific and generic HRQoL deficits persisted six months after treatment. In order to improve individualized care, future studies should focus on identifying risk factors for persistent HRQoL deficits and compare HRQoL effects of the various goiter treatment modalities in relation to thyroid phenotype.

Influence of lifestyle factors on long-term sickness absence among female healthcare workers: a prospective cohort study.

BACKGROUND: While previous research has indicated that unhealthy lifestyle is associated with sickness absence, this association may be confounded by occupational class. To avoid this potential confounding, we examined the association between lifestyle factors (smoking, leisure-time physical activity and body mass index) and the occurrence of long-term sickness absence (LTSA; more than three consecutive weeks of registered sickness absence) within a cohort of female health care workers. METHODS: A total of 7401 employees filled out a questionnaire about their health behaviour and work environment. Subsequently, they were followed for 12 months in a national register on social transfer payments (DREAM register). Cox's regression analyses, applied to grouped survival data, were used to estimate the prospective association between these lifestyle factors and LTSA. RESULTS: We found significant associations between all three lifestyle factors and risk of LTSA. The strongest lifestyle factor was current smoking, which increased the risk of LTSA by 35% (95% CI: 1.17-1.54) compared to non- smokers. For body mass index, the risk of LTSA increased with the distance away from 18.5 kg/m2 in either direction (below 18.5 kg/m2: HR: 1.32 per kg/m2; 95% CI. 1.06-1.66; above 18.5 kg/m2: HR: 1.04 per kg/m2; 95% CI: 1.03-1.05). In other words, the more underweight or overweight the women were, the higher the risk of LTSA. A dose-response relationship was found between LTSA and leisure-time physical activity (trend test p-value = 0.01), so that increasing physical activity results in decreasing risk of LTSA. CONCLUSION: In female healthcare workers, an unhealthy lifestyle (too high/ too low body mass index, smoking, and low physical activity) is associated with higher risk of LTSA.

The thyroid-related quality of life measure ThyPRO has good responsiveness and ability to detect relevant treatment effects.

BACKGROUND AND PURPOSE: Patient-reported outcomes have become important endpoints in comparative effectiveness research and in patient-centered health care. Valid patient-reported outcome measures detect and respond to clinically relevant changes. The purpose of this study was to evaluate responsiveness of the thyroid-related quality of life (QoL) instrument ThyPRO in patients undergoing relevant clinical treatments for benign thyroid diseases and to compare it with responsiveness of the generic SF-36 Health Survey. METHODS: A sample of 435 patients undergoing treatment completed the ThyPRO and SF-36 Health Survey (Version 2) at baseline and 6 months after treatment initiation. Responsiveness was evaluated in three thyroid patient groups: patients with hyperthyroidism (n = 66) and hypothyroidism (n = 84) rendered euthyroid after medical therapy, and patients with a clinically detectable nontoxic goiter treated with surgery or radioactive iodine and remaining euthyroid (n = 62). Changes in QoL were evaluated in terms of effect size and compared to the changes predicted by clinical experts. The responsiveness of equivalent scales from ThyPRO and SF-36 Health Survey were compared with the relative validity index. RESULTS: The ThyPRO demonstrated good responsiveness across the whole range of QoL aspects in patients with hyper- and hypothyroidism. Responsiveness to treatment of nontoxic goiter was also demonstrated for physical and mental symptoms and overall QoL, but not for impact on social life or cosmetic complaints, in contrast to clinicians' predictions. For all comparable scales except one, the ThyPRO was more responsive to treatment than the SF-36 Health Survey. CONCLUSIONS: The ThyPRO was responsive to treatment across the range of benign thyroid diseases. We suggest implementing this measurement instrument as a patient-reported outcome in clinical studies and in clinical management.

Do colleagues influence our lifestyle: the matter of smoking, body mass index and leisure-time physical activity?

OBJECTIVE: Previous research has indicated that health behaviours tend to cluster in social networks, but few have studied the cluster effect in workgroups. We examined the effect of workgroups on current state and change in three indicators of health behaviours (smoking, body mass index (BMI) and physical activity). Further, we examined whether health behaviours of the respondents at group level predicted lifestyle changes. METHODS: In a prospective cohort (n=4730), employees from 250 workgroups in the Danish eldercare sector answered questionnaires at baseline (2005) and follow-up (2006). Multilevel regression models were used to examine the effect of workgroups. RESULTS: Workgroups accounted for 6.49% of the variation in smoking status, 6.56% of amount smoked and 2.62% of the variation in current BMI. We found no significant workgroup clustering in physical activity or lifestyle changes. Furthermore, changes in smoking status (cessation) and weight gain were seen in workgroups with high percentage of smokers and high levels of BMI. CONCLUSION: We found modest evidence for clustering of some health behaviours within workgroups, which could be due to social learning or selection into and out of workgroups. Future health promotion programmes at worksites should recognize the potential clustering of lifestyle behaviours within workgroups.

The chronic autoimmune thyroiditis quality of life selenium trial (CATALYST): study protocol for a randomized controlled trial.

BACKGROUND: Patients with chronic autoimmune thyroiditis have impaired health-related quality of life. The thyroid gland has a high selenium concentration, and specific selenoprotein enzyme families are crucial to immune function, and catalyze thyroid hormone metabolism and redox processes in thyroid cells. Previous randomized controlled trials have found that selenium supplementation decreases thyroid-disease-specific antibody levels. We hypothesize that selenium might be beneficial in the treatment of chronic autoimmune thyroiditis. METHODS/DESIGN: The CATALYST trial is an investigator-initiated randomized, blinded, multicentre clinical trial of selenium supplementation versus placebo in patients with chronic autoimmune thyroiditis. INCLUSION CRITERIA: age ≥18 years; serum thyroid peroxidase antibody level ≥100 IU/ml within the previous 12 months; treatment with levothyroxine and written informed consent. EXCLUSION CRITERIA: previous diagnosis of toxic nodular goitre, Graves' hyperthyroidism, postpartum thyroiditis, Graves' orbitopathy; previous antithyroid drug treatment, radioiodine therapy or thyroid surgery; immune-modulatory or other medication affecting thyroid function; pregnancy, planned pregnancy or breastfeeding; allergy towards any intervention or placebo component; intake of selenium supplementation >55 µg/day; inability to read or understand Danish or lack of informed consent. The trial will include 2 × 236 participants. The experimental intervention and control groups will receive 200 µg selenium-enriched yeast or matching placebo tablets daily for 12 months. The experimental supplement will be SelenoPrecise®. The primary outcome is thyroid-related quality of life assessed by the Thyroid Patient-Reported Outcome (ThyPRO) questionnaire. Secondary outcomes include serum thyroid peroxidase antibody concentration; serum triiodothyronine/thyroxine ratio; levothyroxine dosage; adverse reactions and serious adverse reactions and events. DISCUSSION: In this pragmatic trial, participating patients follow their usual treatment at their usual hospitals. In order to collect high-quality data on the clinical course and quality of life, and to minimize missing data, an elaborate trial management system has been designed. 12 months intervention duration was selected in consideration of the primary outcome, thyroid-related quality of life. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02013479.

Work stress and risk of cancer: meta-analysis of 5700 incident cancer events in 116,000 European men and women.

OBJECTIVE: To investigate whether work related stress, measured and defined as job strain, is associated with the overall risk of cancer and the risk of colorectal, lung, breast, or prostate cancers. DESIGN: Meta-analysis of pooled prospective individual participant data from 12 European cohort studies including 116,056 men and women aged 17-70 who were free from cancer at study baseline and were followed-up for a median of 12 years. Work stress was measured and defined as job strain, which was self reported at baseline. Incident cancers (all n=5765, colorectal cancer n=522, lung cancer n=374, breast cancer n=1010, prostate cancer n=865) were ascertained from cancer, hospital admission, and death registers. Data were analysed in each study with Cox regression and the study specific estimates pooled in meta-analyses. Models were adjusted for age, sex, socioeconomic position, body mass index (BMI), smoking, and alcohol intake RESULTS: A harmonised measure of work stress, high job strain, was not associated with overall risk of cancer (hazard ratio 0.97, 95% confidence interval 0.90 to 1.04) in the multivariable adjusted analyses. Similarly, no association was observed between job strain and the risk of colorectal (1.16, 0.90 to 1.48), lung (1.17, 0.88 to 1.54), breast (0.97, 0.82 to 1.14), or prostate (0.86, 0.68 to 1.09) cancers. There was no clear evidence for an association between the categories of job strain and the risk of cancer. CONCLUSIONS: These findings suggest that work related stress, measured and defined as job strain, at baseline is unlikely to be an important risk factor for colorectal, lung, breast, or prostate cancers.

Job strain as a risk factor for coronary heart disease: a collaborative meta-analysis of individual participant data.

BACKGROUND: Published work assessing psychosocial stress (job strain) as a risk factor for coronary heart disease is inconsistent and subject to publication bias and reverse causation bias. We analysed the relation between job strain and coronary heart disease with a meta-analysis of published and unpublished studies. METHODS: We used individual records from 13 European cohort studies (1985-2006) of men and women without coronary heart disease who were employed at time of baseline assessment. We measured job strain with questions from validated job-content and demand-control questionnaires. We extracted data in two stages such that acquisition and harmonisation of job strain measure and covariables occurred before linkage to records for coronary heart disease. We defined incident coronary heart disease as the first non-fatal myocardial infarction or coronary death. FINDINGS: 30,214 (15%) of 197,473 participants reported job strain. In 1·49 million person-years at risk (mean follow-up 7·5 years [SD 1·7]), we recorded 2358 events of incident coronary heart disease. After adjustment for sex and age, the hazard ratio for job strain versus no job strain was 1·23 (95% CI 1·10-1·37). This effect estimate was higher in published (1·43, 1·15-1·77) than unpublished (1·16, 1·02-1·32) studies. Hazard ratios were likewise raised in analyses addressing reverse causality by exclusion of events of coronary heart disease that occurred in the first 3 years (1·31, 1·15-1·48) and 5 years (1·30, 1·13-1·50) of follow-up. We noted an association between job strain and coronary heart disease for sex, age groups, socioeconomic strata, and region, and after adjustments for socioeconomic status, and lifestyle and conventional risk factors. The population attributable risk for job strain was 3·4%. INTERPRETATION: Our findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking. FUNDING: Finnish Work Environment Fund, the Academy of Finland, the Swedish Research Council for Working Life and Social Research, the German Social Accident Insurance, the Danish National Research Centre for the Working Environment, the BUPA Foundation, the Ministry of Social Affairs and Employment, the Medical Research Council, the Wellcome Trust, and the US National Institutes of Health.