bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognosis of patients with dementia: results from a prospective nationwide registry linkage study in the Netherlands
Authors: van de Vorst Irene E , Vaartjes Ilonca , Geerlings Mirjam I , Bots Michael L , Koek Huiberdina L 
Published: October 2015

ObjectiveTo report mortality risks of dementia based on national hospital registry data, and to put these risks into perspective by comparing them with those in the general population and following cardiovascular diseases.DesignProspective cohort study from 1 January 2000 through 31 December 2010.SettingHospital-based cohort.ParticipantsA nationwide hospital-based cohort of 59 201 patients with clinical diagnosis of dementia (admitted to a hospital or visiting a day clinic) was constructed (38.7% men, 81.4 years (SD 7.0)).Main outcomes and measures1-year and 5-year age-specific and sex-specific mortality risks were reported for patients with dementia visiting a day clinic compared with the general population; for patients hospitalised with dementia compared with patients hospitalised for acute myocardial infarction (AMI), heart failure or stroke, these were presented as absolute and relative risks (RRs).Results1-year mortality was 38.3% in men and 30.5% in women. 5-year risk was 65.4% and 58.5%, respectively. Mortality risks were significantly higher in patients with dementia admitted to the hospital than in those visiting a day clinic (1-year RR 3.29, 95% CI 3.16 to 3.42; and 5-year RR 1.79, 95% CI 1.76 to 1.83). Compared with the general population, mortality risks were significantly higher among patients visiting a day clinic (1-year RR for women 2.99, 95% CI 2.84 to 3.14; and for men 3.94, 95% CI 3.74 to 4.16). 5-year RRs were somewhat lower, but still significant. Results were more pronounced at younger ages. Mortality risks among admitted patients were comparable or even exceeded those of cardiovascular diseases (1-year RR for women with dementia vs AMI 1.24, 95% CI 1.19 to 1.29; vs heart failure 1.05, 95% CI 1.02 to 1.08; vs stroke 1.07, 95% CI 1.04 to 1.10). 5-year RRs were comparable. For men, RRs were slightly higher.ConclusionsDementia has a poor prognosis as compared with other diseases and the general population. The risks among admitted patients even exceeded those following cardiovascular diseases.
Multimorbidity in primary care: protocol of a national cross-sectional study in Switzerland
Authors: Déruaz-Luyet Anouk , N'Goran A Alexandra , Tandjung Ryan , Frey Peter , Zeller Andreas , Haller Dagmar M , Rosemann Thomas , Burnand Bernard , Bodenmann Patrick , Senn Nicolas , Widmer Daniel , Herzig Lilli 
Published: October 2015

IntroductionWith the ageing of the population and the general improvement of care, an increasing number of people are living with multiple chronic health conditions or ‘multimorbidity’. Multimorbidity often implies multiple medical treatments. As a consequence, the risk of adverse events and the time spent by patients for their treatments increase exponentially. In many cases, treatment guidelines traditionally defined for single conditions are not easily applicable. Primary care for individuals with multimorbidity requires complex patient-centred care and good communication between the patient and the general practitioner (GP). This often includes prioritising among the different chronic conditions.Methods and analysisThe main objectives of this study are to describe the burden related to multimorbidity (disease-related burden and burden of treatment) in primary care and to identify the factors influencing it. Other objectives include evaluating patients’ perception of treatment burden and quality of life, assessing factors influencing that perception, and investigating prioritisation in the management of multimorbidity from the perspectives of GPs and patients. For this cross-sectional study, patient enrolment will take place in GP's private practices across Switzerland. A convenient sample of 100 GPs will participate; overall, 1000 patients with at least three chronic health conditions will be enrolled. Data will be collected as paper-based questionnaires for GPs and delayed telephone interview questionnaires for patients. GPs will provide demographic and practice-related data. In addition, each GP will complete a paper-based questionnaire for each patient that they enrol. Each patient will complete a telephone interview questionnaire.Ethics and disseminationThis study has been approved by the research ethics committee of Canton Vaud, Switzerland (Protocol 315/14). The results of the study will be reported in international peer-reviewed journals.
Vascular expression of annexin A2 in lupus nephritis
Authors: Salle V , Cordonnier C , Schmidt J , Mazière C , Smail A , Attencourt C , Mabille M P , Mazière J C , Makdassi R , Choukroun G , Diouf M , Duhaut P , Ducroix J P 
Published: October 2015

AimsTo evaluate vascular expression of annexin A2 (ANXA2) and its subunit S100A10 in lupus nephritis (LN).MethodsThe present histological study included 14 patients with LN and 11 controls (patients with non-lupus kidney diseases). Kidney biopsies from patients with lupus were scored for lupus glomerulonephritis (according to the International Society of Nephrology/Renal Pathology Society 2003 classification) and vascular lesions (such as microthrombi and antiphospholipid syndrome nephropathy (APSN)). ANXA2 and S100A10 expression in glomerular and peritubular capillaries was evaluated by immunohistochemistry on tissue sections. The staining intensity score ranged from 0 (no expression) to 4 (intense expression).ResultsIn patients with LN, the median age (range) at first kidney biopsy was 36 (18–49). Vascular lesions were observed in six patients (including two with APSN). We observed intense expression of ANXA2 in glomerular and peritubular capillaries while expression of S100A10 was weaker. However, one of the patients with APSN showed strong S100A10 expression. Patients with LN and controls differed significantly in terms of S100A10 expression in peritubular capillaries. We also observed a statistical difference between patients who had LN with renal vascular lesions and those without renal vascular lesions in terms of ANXA2 expression in peritubular capillaries.ConclusionsThe presence of vascular lesions in LN appears to be associated with significant differences in the vascular expression of ANXA2. Vascular expression of ANXA2 was somewhat higher in LN. Vascular expression of S100A10 was somewhat lower in LN (except one of the two patients with APSN). Further studies of ANXA2's putative value as a biomarker of active LN or of vascular lesions in LN are required.
Previous anxiety and depression as risk factors for early labour force exit
Authors: Rudolph Kara E , Eaton William W 
Published: October 2015

BackgroundIndividuals with a history of mental illness have lower earnings than individuals without. A possible reason is that those with prior anxiety or depression may be more likely to exit the labour force prior to retirement age, but evidence has been mixed and limited. Our objective was to compare risk of early labour force exit between employed adults with a history of depression or anxiety versus those without, separately for men and women.MethodsWe used data from the Baltimore Epidemiological Catchment Area Follow-up Cohort, which collected baseline data in 1981 and follow-up data 1993–1996 and 2004–2005. Cox proportional hazards models estimated the relative risk of labour force exit comparing those with versus without prior history of anxiety or depressive disorders.ResultsWomen with prior anxiety or depression are at 37% increased risk of dropping out of the labour force as compared to women without, controlling for age, socioeconomic status, race and marital status (HR: 1.37, 95% CI 1.04 to 1.79). Men with prior anxiety or depression are 18% more likely to subsequently drop out of the labour force as compared to men without, controlling for the above confounders as well as veteran status, but this association is not statistically significant (HR: 1.18, 95% CI 0.72 to 1.27).ConclusionsPrior anxiety or depression increases risk of early labour force exit for women. These findings may help explain previously reported lower earnings among female individuals with a history of mental illness and highlight the importance of considering anxiety and depressive disorders in policies supporting labour force participation.
Modeling Spontaneous Metastasis following Surgery: An In Vivo-In Silico Approach
Authors: Benzekry Sebastien , Tracz Amanda , Mastri Michalis , Corbelli Ryan , Barbolosi Dominique , Ebos John M.L. 
Published: October 2015

Abstract
Rapid improvements in the detection and tracking of early-stage tumor progression aim to guide decisions regarding cancer treatments as well as predict metastatic recurrence in patients following surgery. Mathematical models may have the potential to further assist in estimating metastatic risk, particularly when paired with in vivo tumor data that faithfully represent all stages of disease progression. Herein, we describe mathematical analysis that uses data from mouse models of spontaneous metastasis developing after surgical removal of orthotopically implanted primary tumors. Both presurgical (primary tumor) growth and postsurgical (metastatic) growth were quantified using bioluminescence and were then used to generate a mathematical formalism based on general laws of the disease (i.e., dissemination and growth). The model was able to fit and predict pre/postsurgical data at the level of the individual as well as the population. Our approach also enabled retrospective analysis of clinical data describing the probability of metastatic relapse as a function of primary tumor size. In these data-based models, interindividual variability was quantified by a key parameter of intrinsic metastatic potential. Critically, our analysis identified a highly nonlinear relationship between primary tumor size and postsurgical survival, suggesting possible threshold limits for the utility of tumor size as a predictor of metastatic recurrence. These findings represent a novel use of clinically relevant models to assess the impact of surgery on metastatic potential and may guide optimal timing of treatments in neoadjuvant (presurgical) and adjuvant (postsurgical) settings to maximize patient benefit. Cancer Res; 76(3); 535–47. ©2015 AACR.
Clinicopathologic Risk Factor Distributions for MLH1 Promoter Region Methylation in CIMP-Positive Tumors
Authors: Levine A. Joan , Phipps Amanda I. , Baron John A. , Buchanan Daniel D. , Ahnen Dennis J. , Cohen Stacey A. , Lindor Noralane M. , Newcomb Polly A. , Rosty Christophe , Haile Robert W. , Laird Peter W. , Weisenberger Daniel J. 
Published: October 2015

Abstract
Background: The CpG island methylator phenotype (CIMP) is a major molecular pathway in colorectal cancer. Approximately 25% to 60% of CIMP tumors are microsatellite unstable (MSI-H) due to DNA hypermethylation of the MLH1 gene promoter. Our aim was to determine if the distributions of clinicopathologic factors in CIMP-positive tumors with MLH1 DNA methylation differed from those in CIMP-positive tumors without DNA methylation of MLH1.
Methods: We assessed the associations between age, sex, tumor-site, MSI status BRAF and KRAS mutations, and family colorectal cancer history with MLH1 methylation status in a large population-based sample of CIMP-positive colorectal cancers defined by a 5-marker panel using unconditional logistic regression to assess the odds of MLH1 methylation by study variables.
Results: Subjects with CIMP-positive tumors without MLH1 methylation were significantly younger, more likely to be male, and more likely to have distal colon or rectal primaries and the MSI-L phenotype. CIMP-positive MLH1-unmethylated tumors were significantly less likely than CIMP-positive MLH1-methylated tumors to harbor a BRAF V600E mutation and significantly more likely to harbor a KRAS mutation. MLH1 methylation was associated with significantly better overall survival (HR, 0.50; 95% confidence interval, 0.31–0.82).
Conclusions: These data suggest that MLH1 methylation in CIMP-positive tumors is not a completely random event and implies that there are environmental or genetic determinants that modify the probability that MLH1 will become methylated during CIMP pathogenesis.
Impact: MLH1 DNA methylation status should be taken into account in etiologic studies. Cancer Epidemiol Biomarkers Prev; 25(1); 68–75. ©2015 AACR.
Patients with a High Polygenic Risk of Breast Cancer do not have An Increased Risk of Radiotherapy Toxicity
Authors: Dorling Leila , Barnett Gillian C. , Michailidou Kyriaki , Coles Charlotte E. , Burnet Neil G. , Yarnold John , Elliott Rebecca M. , Dunning Alison M. , Pharoah Paul D.P. , West Catharine M. 
Published: October 2015

Abstract
Purpose: It has been hypothesized that increased predisposition to breast cancer may correlate with radiosensitivity, and thus increased risk of toxicity following breast irradiation. This study investigated the relationship between common breast cancer risk variants and radiotherapy toxicity.
Experimental Design: SNP genotypes were determined in female breast cancer patients from the RAPPER (Radiogenomics: Assessment of polymorphisms for predicting the effects of radiotherapy) study using the Illumina CytoSNP12 genome-wide array. A further 15,582,449 genotypes were imputed using the 1000 Genomes Project reference panel. Patient (n = 1,160) polygenic risk scores were generated by summing risk-allele dosages, both unweighted and weighted by published effect sizes for breast cancer risk. Regression models were used to test associations of individual variants and polygenic risk scores with acute and late toxicity phenotypes (telangiectasia, breast edema, photographically assessed shrinkage, induration, pigmentation, breast pain, breast sensitivity, and overall toxicity).
Results: Genotypes of 90 confirmed breast cancer risk variants were accurately determined and polygenic risk scores were approximately normally distributed. Variant rs6964587 was associated with increased breast edema 5 years following radiotherapy (Beta, 0.22; 95% confidence interval, 0.09–0.34; P = 7 × 10−4). No other associations were found between individual variants or the unweighted (P &gt; 0.17) or weighted (P &gt; 0.13) polygenic risk score and radiotherapy toxicity. This study had &gt;87% power to detect an association between the polygenic risk score (relative risk &gt; 1.1) and toxicity.
Conclusions: Cancer patients with a high polygenic predisposition to breast cancer do not have an increased risk of radiotherapy toxicity up to 5 years following radiotherapy but individual variants may increase risk. Clin Cancer Res; 22(6); 1413–20. ©2015 AACR.
Plasma Inflammatory Markers and Risk of Advanced Colorectal Adenoma in Women
Authors: Song Mingyang , Mehta Raaj S. , Wu Kana , Fuchs Charles S. , Ogino Shuji , Giovannucci Edward L. , Chan Andrew T. 
Published: October 2015

Abstract
Evidence remains inconclusive about the association of systemic inflammatory markers with colorectal neoplasia. We investigated whether circulating inflammatory markers were associated with risk of advanced colorectal adenoma. We measured plasma macrophage inhibitory cytokine-1 (MIC-1), C-reactive protein (CRP), interleukin-6 (IL6), and soluble TNF receptor 2 (sTNFR-2) in blood samples drawn from 32,826 women in 1989 to 1990 in the Nurses' Health Study. Through 2008, we documented 757 cases of advanced colorectal adenomas (≥1 cm or any size with advanced histology); each case was matched by age and time of blood draw with one control randomly selected from participants who underwent lower endoscopy and did not have neoplasia. Plasma MIC-1 was associated with higher risk of advanced adenoma (Ptrend = 0.04), with an OR of 1.55 (95% confidence interval, 1.03–2.32) comparing extreme quintiles of MIC-1 after adjusting for colorectal cancer–risk factors and other inflammatory markers. Among cases, MIC-1 level was positively associated with the number of adenomas (P &lt; 0.001) and gradually increased from adenomas located in the rectum, distal colon, and up to the proximal colon. There was a strong positive association between MIC-1 and risk of adenomas with multiplicity, ≥1 cm size and location in the proximal colon (all Ptrend &lt; 0.05). CRP, IL6, or sTNFR-2 was not associated with adenoma risk. In conclusion, plasma MIC-1 was associated with higher risk of colorectal adenoma, especially multiple, large, and proximal adenomas. Our results provide further support for a role for MIC-1 in carcinogenesis and the potential for MIC-1 as an adjunctive biomarker for detection of advanced colorectal adenoma. Cancer Prev Res; 9(1); 27–34. ©2015 AACR.
Does the Volume of Ischemic Stroke Admissions Relate to Clinical Outcomes in the Ontario Stroke System?
Authors: Hall Ruth E. , Fang Jiming , Hodwitz Kathryn , Saposnik Gustavo , Bayley Mark T. 
Published: October 2015

Background—
Better outcomes have been found among hospitals treating higher volumes of patients for specific surgical and medical conditions. We examined hospital ischemic stroke (IS) volume and 30-day mortality to inform regionalization planning.

Methods and Results—

Using a population-based hospital discharge administrative database (2005/2006 to 2011/2012), average annual IS patient volumes were calculated for 162 Ontario acute hospitals. Hospitals were ranked and classified as small (<126), medium (126–202), and large (>202). Hierarchical multivariable logistic regression was used to estimate the odds of death within 7 and 30 days to account for the homogeneity in outcomes for patients treated at the same hospital. Overall, 73 368 patients were hospitalized for IS, and 30-day mortality was 15.3%. The mean (±SD) of annual hospitalizations for IS was 29 (31) for small-volume hospitals, 156 (20) for medium-volume hospitals, and 300 (78) for high-volume hospitals. High-volume hospitals admitted younger patients (mean [±SD] age, 73.0 [13.9] years) compared with medium- and small-volume hospitals (74.0 [13.2] and 75.5 [12.5] years, respectively;
P
<0.0001). Patients at small-volume hospitals were more likely than patients at high-volume hospitals to die at 30 days after an acute IS (adjusted odds ratio, 1.37; 95% confidence interval, 1.14–1.65).

Conclusions—
Hospital IS volume is associated with 30-day mortality in Ontario. Patients admitted to hospitals with annual IS volumes <126 annually are more likely to die within 30 days than patients admitted to hospitals that see on average 300 patients annually. This finding supports centralizing care in stroke-specialized hospitals.
Academic-Community Hospital Comparison of Vulnerabilities in Door-to-Needle Process for Acute Ischemic Stroke
Authors: Prabhakaran Shyam , Khorzad Rebeca , Brown Alexandra , Nannicelli Anna P. , Khare Rahul , Holl Jane L. 
Published: October 2015

Background—
Although best practices have been developed for achieving door-to-needle (DTN) times ≤60 minutes for stroke thrombolysis, critical DTN process failures persist. We sought to compare these failures in the Emergency Department at an academic medical center and a community hospital.

Methods and Results—
Failure modes effects and criticality analysis was used to identify system and process failures. Multidisciplinary teams involved in DTN care participated in moderated sessions at each site. As a result, DTN process maps were created and potential failures and their causes, frequency, severity, and existing safeguards were identified. For each failure, a risk priority number and criticality score were calculated; failures were then ranked, with the highest scores representing the most critical failures and targets for intervention. We detected a total of 70 failures in 50 process steps and 76 failures in 42 process steps at the community hospital and academic medical center, respectively. At the community hospital, critical failures included (1) delay in registration because of Emergency Department overcrowding, (2) incorrect triage diagnosis among walk-in patients, and (3) delay in obtaining consent for thrombolytic treatment. At the academic medical center, critical failures included (1) incorrect triage diagnosis among walk-in patients, (2) delay in stroke team activation, and (3) delay in obtaining computed tomographic imaging.

Conclusions—
Although the identification of common critical failures suggests opportunities for a generalizable process redesign, differences in the criticality and nature of failures must be addressed at the individual hospital level, to develop robust and sustainable solutions to reduce DTN time.
International Arctic Systems for Observing the Atmosphere: An International Polar Year Legacy Consortium
Authors: Uttal Taneil , Starkweather Sandra , Drummond James R. , Vihma Timo , Makshtas Alexander P. , Darby Lisa S. , Burkhart John F. , Cox Christopher J. , Schmeisser Lauren N. , Haiden Thomas , Maturilli Marion , Shupe Matthew D. , De Boer Gijs , Saha Auromeet , Grachev Andrey A. , Crepinsek Sara M. , Bruhwiler Lori , Goodison Barry , McArthur Bruce , Walden Von P. , Dlugokencky Edward J. , Persson P. Ola G. , Lesins Glen , Laurila Tuomas , Ogren John A. , Stone Robert , Long Charles N. , Sharma Sangeeta , Massling Andreas , Turner David D. , Stanitski Diane M. , Asmi Eija , Aurela Mika , Skov Henrik , Eleftheriadis Konstantinos , Virkkula Aki , Platt Andrew , Førland Eirik J. , Iijima Yoshihiro , Nielsen Ingeborg E. , Bergin Michael H. , Candlish Lauren , Zimov Nikita S. , Zimov Sergey A. , O’Neill Norman T. , Fogal Pierre F. , Kivi Rigel , Konopleva-Akish Elena A. , Verlinde Johannes , Kustov Vasily Y. , Vasel Brian , Ivakhov Viktor M. , Viisanen Yrjö , Intrieri Janet M. 
Published: October 2015

Abstract
International Arctic Systems for Observing the Atmosphere (IASOA) activities and partnerships were initiated as a part of the 2007–09 International Polar Year (IPY) and are expected to continue for many decades as a legacy program. The IASOA focus is on coordinating intensive measurements of the Arctic atmosphere collected in the United States, Canada, Russia, Norway, Finland, and Greenland to create synthesis science that leads to an understanding of why and not just how the Arctic atmosphere is evolving. The IASOA premise is that there are limitations with Arctic modeling and satellite observations that can only be addressed with boots-on-the-ground, in situ observations and that the potential of combining individual station and network measurements into an integrated observing system is tremendous. The IASOA vision is that by further integrating with other network observing programs focusing on hydrology, glaciology, oceanography, terrestrial, and biological systems it will be possible to understand the mechanisms of the entire Arctic system, perhaps well enough for humans to mitigate undesirable variations and adapt to inevitable change.