Psychological distress and breast cancer : a bidirectional link

Psychological distress is one of the six vital signs among patients with cancer. An increased risk of psychiatric disorders has also been reported among cancer patients, compared with the general population. On the other hand, psychological distress might also influence the initiation and progression of cancer. As breast cancer is the most common cancer, and females are more vulnerable to psychiatric disorders than men, we further investigated the bidirectional link between psychological distress and breast cancer. The potential mechanisms linking together psychological distress and breast cancer include inflammation, neuroendocrine pathways, behavioral factors, and reproductive and hormonal factors. In this thesis, we studied various response processes and consequences of psychological distress in relation to the risk, prognosis, and diagnostic workup of breast cancer, including stress coping ability, anti-inflammatory drug use, and genetic determinants of different stress pathways, to comprehensively investigate such a link. In Study I, we examined whether sense of coherence (SoC), as a measure of resilience to psychological distress, reduced the risk of breast cancer. We included all women who had answered the SoC-13 questionnaire when enrolled in the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA) cohort, and identified incident cases of breast cancer after enrollment of these women through cross-linkages with Swedish national registers. We used the SoC score measured at enrollment as the main exposure because SoC is believed to be stable. We estimated the hazard ratio (HR) and 95% confidence interval (CI) of breast cancer in relation to SoC, based on Cox proportional hazards models, after adjustment for potential confounders. We found no evidence to support an association between SoC and risk of breast cancer (HR: 1.08; 95% CI: 0.90-1.29). In Study II, considering that inflammation is a critical component in both cancer development and stress response (especially chronic stress response), we assessed whether use of non-steroidal anti-inflammatory drugs (NSAIDs) reduced the risk of breast cancer. We used a nested case-control design within the general female population of Sweden as well as within the KARMA cohort. Conditional logistic regression models were used to estimate HRs and 95% CIs, adjusted for potential confounders. We did not find use of aspirin to be associated with the risk of breast cancer. However, use of non-aspirin NSAIDs was associated with a slightly increased risk of early-stage breast cancer (HR: 1.05; 95% CI: 1.02-1.08), a decreased risk of advanced-stage breast cancer (HR: 0.80; 95% CI: 0.73-0.88), and a decreased risk of breast cancer in general among women with dense breasts (HR: 0.72; 95% CI: 0.59-0.89). In study III, we aim to understand the potential genetic determinants of the link between psychological distress and breast cancer prognosis. We assessed whether somatic mutations and gene expression of the neuroendocrine pathways, namely the adrenergic, cholinergic, dopaminergic, glucocorticoid, and serotonergic pathways, which are directly involved in stress response, were associated with breast cancer prognosis. We used a matched extreme case-control design based on two cohorts of breast cancer patients from China, US, and other countries. Somatic mutations and gene expression data were derived from whole exome sequencing (WES) and RNA sequencing on tumor and paired normal breast tissues. Logistic regression was used to estimate the odds ratio of invasive disease-free survival (iDFS). A two-fold increase of somatic mutation burden in genes of the glucocorticoid pathway was associated with a 17% (95% CI: 2%-35%) elevated odds of reaching iDFS endpoints. This association might be regulated through differential gene expression of the glucocorticoid pathway in tumor tissue. In Study IV, we compared the risk of psychiatric disorders potentially related to psychological distress among cancer patients with or without pre-diagnostic use of NSAIDs. We conducted a cohort study including all cancer patients diagnosed during July 2006 to December 2013 in Sweden and followed them for an incident diagnosis of anxiety, depression, or stress-related disorders. Cox proportional hazards models were used to estimate the HR and 95% CI, adjusted for potential confounders. We found a reduced risk of anxiety, depression, and stress-related disorders among cancer patients with pre-diagnostic use of aspirin (HR: 0.88; 95% CI: 0.81-0.97) and contrastingly an increased risk of these psychiatric disorders among patients with pre-diagnostic use of non-aspirin NSAIDs (HR: 1.24; 95% CI: 1.15-1.32). A more prominent risk decreased in relation to aspirin use was found among females and patients with breast cancer. Taken together, the knowledge gained through this thesis work helps to improve our understanding on the role of psychological distress in the risk and prognosis of cancer and supports intervention of severe psychological distress subsequent to a cancer diagnosis. In the long run, such knowledge should also help pave the way for the development of innovative measures for the prevention of cancer and cancer-related morbidity and mortality

An interpolation matched interface and boundary method for elliptic interface problems

AbstractAn interpolation matched interface and boundary (IMIB) method with second-order accuracy is developed for elliptic interface problems on Cartesian grids, based on original MIB method proposed by Zhou et al. [Y. Zhou, G. Wei, On the fictious-domain and interpolation formulations of the matched interface and boundary method, J. Comput. Phys. 219 (2006) 228–246]. Explicit and symmetric finite difference formulas at irregular grid points are derived by virtue of the level set function. The difference scheme using IMIB method is shown to satisfy the discrete maximum principle for a certain class of problems. Rigorous error analyses are given for the IMIB method applied to one-dimensional (1D) problems with piecewise constant coefficients and two-dimensional (2D) problems with singular sources. Comparison functions are constructed to obtain a sharp error bound for 1D approximate solutions. Furthermore, we compare the ghost fluid method (GFM), immersed interface method (IIM), MIB and IMIB methods for 1D problems. Finally, numerical examples are provided to show the efficiency and robustness of the proposed method

Effect Modifications of Overhead-View and Eye-Level Urban Greenery on Heat-Mortality Associations: Small-Area Analyses Using Case Time Series Design and Different Greenery Measurements.

BackgroundThe protective effect of urban greenery from adverse heat impacts remains inconclusive. Existing inconsistent findings could be attributed to the different estimation techniques used.ObjectivesWe investigated how effect modifications of urban greenery on heat-mortality associations vary when using different greenery measurements reflecting overhead-view and eye-level urban greenery.MethodsWe collected meteorological and daily mortality data for 286 territory planning units between 2005 and 2018 in Hong Kong. Three greenery measurements were extracted for each unit: a) the normalized difference vegetation index (NDVI) from Landsat remote sensing images, b) the percentage of greenspace based on land use data, and c) eye-level street greenery from street view images via a deep learning technique. Time-series analyses were performed using the case time series design with a linear interaction between the temperature term and each of the three greenery measurements. Effect modifications were also estimated for different age groups, sex categories, and cause-specific diseases.ResultsHigher mortality risks were associated with both moderate and extreme heat, with relative risks (RRs) of 1.022 (95% CI: 1.000, 1.044) and 1.045 (95% CI: 1.013, 1.079) at the 90th and 99th percentiles of temperatures relative to the minimum mortality temperature (MMT). Lower RRs were observed in greener areas whichever of the three greenery measurements was used, but the disparity of RRs between areas with low and high levels of urban greenery was more apparent when using eye-level street greenery as the index at high temperatures (99th percentile relative to MMT), with RRs for low and high levels of greenery, respectively, of 1.096 (95% CI: 1.035, 1.161) and 0.985 (95% CI: 0.920, 1.055) for NDVI (p=0.0193), 1.068 (95% CI: 1.021, 1.117) and 0.990 (95% CI: 0.906, 1.081) for the percentage of greenspace (p=0.1338), and 1.103 (95% CI: 1.034, 1.177) and 0.943 (95% CI: 0.841, 1.057) for eye-level street greenery (p=0.0186). Health discrepancies remained for nonaccidental mortality and cardiorespiratory diseases and were more apparent for older adults (≥65 years of age) and females.DiscussionThis study provides new evidence that eye-level street greenery shows stronger associations with reduced heat-mortality risks compared with overhead-view greenery based on NDVI and percentage of greenspace. The effect modification of urban greenery tends to be amplified as temperatures rise and are more apparent in older adults and females. Heat mitigation strategies and health interventions, in particular with regard to accessible and visible greenery, are needed for helping heat-sensitive subpopulation groups in coping with extreme heat. https://doi.org/10.1289/EHP12589

Aspirin and other non-steroidal anti-inflammatory drugs and depression, anxiety, and stress-related disorders following a cancer diagnosis: a nationwide register-based cohort study

Publisher's version (útgefin grein)Background: Cancer patients have a highly increased risk of psychiatric disorders following diagnosis, compared with cancer-free individuals. Inflammation is involved in the development of both cancer and psychiatric disorders. The role of non-steroidal anti-inflammatory drugs (NSAIDs) in the subsequent risk of psychiatric disorders after cancer diagnosis is however unknown. Methods: We performed a cohort study of all patients diagnosed with a first primary malignancy between July 2006 and December 2013 in Sweden. Cox proportional hazards models were used to assess the association of NSAID use during the year before cancer diagnosis with the risk of depression, anxiety, and stress-related disorders during the first year after cancer diagnosis. Results: Among 316,904 patients identified, 5613 patients received a diagnosis of depression, anxiety, or stress-related disorders during the year after cancer diagnosis. Compared with no use of NSAIDs, the use of aspirin alone was associated with a lower rate of depression, anxiety, and stress-related disorders (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.81 to 0.97), whereas the use of non-aspirin NSAIDs alone was associated with a higher rate (HR, 1.24; 95% CI, 1.15 to 1.32), after adjustment for sociodemographic factors, comorbidity, indications for NSAID use, and cancer characteristics. The association of aspirin with reduced rate of depression, anxiety, and stress-related disorders was strongest for current use (HR, 0.84; 95% CI, 0.75 to 0.93), low-dose use (HR, 0.88; 95% CI, 0.80 to 0.98), long-term use (HR, 0.84; 95% CI, 0.76 to 0.94), and among patients with cardiovascular disease (HR, 0.81; 95% CI, 0.68 to 0.95) or breast cancer (HR, 0.74; 95% CI, 0.56 to 0.98). Conclusion: Pre-diagnostic use of aspirin was associated with a decreased risk of depression, anxiety, and stress-related disorders during the first year following cancer diagnosis.This study was supported by grants awarded to FF by Swedish Cancer Society (No. CAN 2017/322) and the Swedish Research Council for Health, Working Life and Welfare (No. 2017-00531), to KH by China Scholarship Council (No. 201806240005), to ES by National Health and Medical Research Council (GNT1147498) and National Breast Cancer Foundation (IIRS-20 to 025), and to AW by the National Breast Cancer Foundation (PF-15 to 014). The researchers were independent of the funding agencies. The funding bodies have no role in the design of the study or collection, analysis, and interpretation of data or in writing the manuscript. Open access funding provided by Karolinska Institute.Peer Reviewe

Spine surgeon specialty differences in single-level percutaneous kyphoplasty

Background Percutaneous kyphoplasty (PKP) is a procedure performed by a spine surgeon who undergoes either orthopedic or neurosurgical training. The relationship between short-term adverse outcomes and spine specialty is presently unknown. To compare short-term adverse outcomes of single-level PKP when performed by neurosurgeons and orthopedic surgeons in order to develop more concretely preventive strategies for patients under consideration for single-level PKP. Methods We evaluated patients who underwent single-level PKP from 2012 to 2014 through the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). We used univariate analysis and multivariate logistic regression to assess the association between spine surgeon specialty and short-term adverse events, including postoperative complication and unplanned readmission, and to identify different independent risk predictors between two specialties. Results Of 2248 patients who underwent single-level PKP procedure, 1229 patients (54.7%) had their operations completed by a neurosurgeon. There were no significant differences in the development of the majority of postoperative complications and the occurrence of unplanned readmission between the neurosurgical cohort (NC) and the orthopedic cohort (OC). A difference in the postoperative blood transfusion rate (0.7% NS vs. 1.7% OC, P = 0.039) was noted and may due to the differences in comorbidities between patients. Multivariate regression analysis revealed different independent predictors of postoperative adverse events for the two spine specialties. Conclusions By comparing a large range of demographic feature, preoperative comorbidities, and intraoperative factors, we find that short-term adverse events in single-level PKP patients does not affect by spine surgeon specialty, except that the OC had higher postoperative blood transfusion rate. In addition, the different perioperative predictors of postoperative complications and unplanned readmissions were identified between the two specialties. These findings can lead to better evidence-based patient counseling and provide valuable information for medical evaluation and potentially devise methods to reduce patients’ risk