Distress, circadian rhythms, immunity, and survival in presurgical breast cancer patients.

Women with breast cancer experience significant stress related to diagnosis and treatment, which may negatively affect physiology (e.g., circadian, endocrine, and immune) and contribute to cancer progression. Demographic (e.g., ethnic minority) and neighborhood factors can contribute to cancer-related stress. African American women with breast cancer experience more adverse disease pathology and earlier mortality; however, factors that explain these disparities rarely have been explored. It is hypothesized that psychosocial stressors (i.e., ethnicity, neighborhood stress, and cancerrelated stress) will be related to one another. Associations of psychosocial stress with physiological disruption are posited with regard to circadian, endocrine, and immune function. It is also hypothesized that psychosocial stress and physiological disruption will predict earlier cancer recurrence/mortality. Presurgical breast cancer patients (N=57) reported on demographics and cancerrelated stress and provided three-day home-based collection of rest/activity rhythms and salivary cortisol. Neighborhood stress data were obtained via the 2010 Census. Immune parameters were assessed in serum samples. Progression-free survival status was obtained at a median of seven years post-enrollment. Bivariate correlations examined relationships between psychosocial stressors. Hierarchical linear regressions adjusted for age, cancer stage, and income in tests of associations between psychosocial stress and physiological disruption. Cox proportional hazards analyses tested the prognostic value of psychosocial stress and physiological disruption on progression-free survival from initial diagnosis and study entry. African Americans had higher neighborhood stress compared to non-Hispanic White patients. Patients with greater neighborhood stress had greater overall cortisol secretion (ΔR2 = .246, p = .001). Patients reporting greater cancer-related stress had accentuated diurnal cortisol rhythms (ΔR2 = .084, p = .047). Exploratory post hoc analyses revealed this finding was likely driven by avoidance of cancer-related thoughts. Psychosocial stress was not significantly related to circadian or immune disruption, nor was psychosocial stress or physiological disruption predictive of progression-free survival. Improved resources within disadvantaged neighborhoods may help counter the effects of neighborhood stress on cortisol disruption by reducing stress and improving health outcomes. Interestingly, during the acutely stressful presurgical period, avoidance appears to serve as an adaptive coping strategy. Therefore, the presurgical period may be the opportune time to introduce psychosocial interventions to combat challenges throughout one’s cancer journey

Work disability, economic situation, and societal costs of multiple sclerosis in Sweden

Background: Multiple sclerosis (MS) affects many aspects of life and often leads to a reduction in an individual’s work capacity. This reduction, referred to as work disability, may lead to the use of social protections to replace lost earnings upon being absent and societal costs from the lost production. This thesis aimed to investigate the working life and economic situation of individuals in the early stages of their MS as well as the societal costs of MS. Methods: Four cohort studies using Swedish register data of working-aged individuals were conducted. Work disability was operationalised as net days with sickness absence (SA) and/or disability pension (DP). In Study I, the heterogeneity of disposable income (DI) trajectories from 7 years before to 4 years after the diagnosis year (2008-9) of 1528 people with MS (PwMS) was explored with group-based trajectory modelling. The trajectory members were characterised through use of chi2-tests and multinomial logistic regressions. In Study II, common patterns of working life among 2652 PwMS diagnosed in 2008-11 were identified with sequence analysis. Sequences from 1 year before and 5 years after the diagnosis year were constructed and the members of the sequence types were characterised with multinomial logistic regressions and dependent t-tests. In Study III and IV, productivity losses were calculated with the human capital approach from the days with work disability. Healthcare costs included the costs of specialised out- and inpatient healthcare as well as dispensed drugs. Excess costs of MS were estimated by comparing the all-cause costs of PwMS with the costs of matched references with independent t-tests. Study III quantified the annual excess costs of 1988 PwMS and 7981 matched references without MS from 4 years before to 4 years after the diagnosis year (2010-12). Generalised estimation equation (GEE) models tested the interaction of MS and time. In Study IV, the excess costs from resource use in 2018 with bootstrapped 95% CIs were estimated for 2806 PwMS in Stockholm and 28,060 matched references without MS. Primary healthcare and disease modifying therapies were also costed, with analyses stratified by time since diagnosis. Results: Seven DI trajectories were identified in Study I: Four increasing with different gradients (39.0% of individuals), two constantly low (50.7%), and one decreasing (10.3%). Older age profiles and higher proportions of men were observed in the increasing trajectories and higher proportions with work disability and without university education in the decreasing and constantly low trajectories. In Study II, six types of working life sequences were identified: Stable High Activity (48.4% of the sequences), three types with mixed activity and varying SA/DP regarding the number of days per year and timing (32.6%), Stable High SA/DP (14.5%), and Other (4.5%). Stable High Activity had the highest odds for university education. All sequence types, except Stable High SA/DP, had higher DI in the final study year than the first. In Study III, excess costs of MS were observed already before MS diagnosis. Mean annual excess costs of MS of 2285 SEK (95% CI: 613-3956) per person for healthcare costs and 16,310 SEK (95% CI: 8980-23,640) for productivity losses were observed four years before diagnosis. The excess costs of MS increased thereafter and were reflected in the MS and time interaction estimates. In Study IV, the mean annual excess healthcare costs of MS were 77,383 SEK (95% CI: 73,299-81,950) per person with MS. Primary healthcare accounted for 9% and disease modifying therapies for 48% of the excess healthcare costs. The mean annual excess productivity losses of MS were 138,121 SEK (95% CI: 149,224-146,985) per person with MS, mostly due to DP (79%). The resource use behind the excess costs of MS differed by time since diagnosis. Conclusions: The findings describe the economic situation of PwMS and quantify the excess societal costs of early MS. Most PwMS were in work and had increasing or stable DI in the study periods close to MS diagnosis. However, work disability was often and increasingly a part of PwMS’ working life and was associated with decreasing DI trajectories or relatively low levels of DI as well as unstable working life sequences. Excess costs of MS for lost production and healthcare use were incurred already before MS diagnosis and increased thereafter. The progression of the excess costs of MS reflected different patterns of resource use with time from MS diagnosis. The increasing excess costs of MS from productivity losses began in the early stages of MS and may reflect unmet needs of PwMS regarding morbidity and work capacity which early intervention may ameliorate