bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of Stroke With Various Types of Menopausal Hormone Therapies
Authors: Løkkegaard Ellen , Nielsen Lars Hougaard , Keiding Niels 
Published: June 2017

Background and Purpose—
Double-blind randomized studies on the effects of oral postmenopausal hormone therapies were stopped mainly because of increased risk of stroke. We aimed to assess the risk of all strokes and various subtypes associated with hormone therapy and explore the influence of regimens and routes of administration.

Methods—
A national historical cohort of women aged 51 to 70 years from 1995 to 2010 was established by linking 5 Danish registries. The National Registry of Medicinal Product Statistics provided information on hormone therapy exposure and the National Patient or Cause of Death Registries supplied data regarding stroke diagnoses (ischemic/hemorrhagic/subarachnoid hemorrhage). Multiply adjusted rate ratios with time-varying covariates were fitted in Poisson regression models.

Results—
Of the 980 003 included women, 20 199 suffered a stroke (78% ischemic, 12% hemorrhagic, and 10% subarachnoid hemorrhage). In total, 36% of women used hormone therapy. Current use conferred a relative rate of 1.16 (95% confidence interval, 1.12–1.22). Compared with never users, the increased rate ratio of all stroke with continuous, cyclic combined estrogen/progestin, and estrogen only oral therapies were 1.29 (95% confidence interval, 1.21–1.37), 1.11 (95% confidence interval, 1.04–1.20), and 1.18 (95% confidence interval, 1.10–1.26), respectively. The increased risk was because of ischemic stroke, but not hemorrhagic stroke. Transdermal application of hormone therapy was not associated with risk of stroke. Vaginal estrogen was associated with a decreased risk of stroke.

Conclusions—
In a national setting, we found an increased risk of stroke, based on ischemic stroke, with oral hormone therapies that was comparable to findings from randomized studies. We found no risk of stroke with transdermal application and a reduced risk with vaginal estrogen.
Abnormal P-Wave Axis and Ischemic Stroke
Authors: Maheshwari Ankit , Norby Faye L. , Soliman Elsayed Z. , Koene Ryan J. , Rooney Mary R. , O’Neal Wesley T. , Alonso Alvaro , Chen Lin Y. 
Published: June 2017

Background and Purpose—
Abnormal P-wave axis (aPWA) has been linked to incident atrial fibrillation and mortality; however, the relationship between aPWA and stroke has not been reported. We hypothesized that aPWA is associated with ischemic stroke independent of atrial fibrillation and other stroke risk factors and tested our hypothesis in the ARIC study (Atherosclerosis Risk In Communities), a community-based prospective cohort study.

Methods—
We included 15 102 participants (aged 54.2±5.7 years; 55.2% women; 26.5% blacks) who attended the baseline examination (1987–1989) and without prevalent stroke. We defined aPWA as any value outside 0 to 75° using 12-lead ECGs obtained during study visits. Each case of incident ischemic stroke was classified in accordance with criteria from the National Survey of Stroke by a computer algorithm and adjudicated by physician review. Multivariable Cox regression was used to estimate hazard ratios and 95% confidence intervals for the association of aPWA with stroke.

Results—
During a mean follow-up of 20.2 years, there were 657 incident ischemic stroke cases. aPWA was independently associated with a 1.50-fold (95% confidence interval, 1.22–1.85) increased risk of ischemic stroke in the multivariable model that included atrial fibrillation. When subtyped, aPWA was associated with a 2.04-fold (95% confidence interval, 1.42–2.95) increased risk of cardioembolic stroke and a 1.32-fold (95% confidence interval, 1.03–1.71) increased risk of thrombotic stroke.

Conclusions—
aPWA is independently associated with ischemic stroke. This association seems to be stronger for cardioembolic strokes. Collectively, our findings suggest that alterations in atrial electric activation may predispose to cardiac thromboembolism independent of atrial fibrillation.
Admission Brain Cortical Volume
Authors: Sagnier Sharmila , Catheline Gwenaëlle , Dilharreguy Bixente , Munsch Fanny , Bigourdan Antoine , Poli Mathilde , Debruxelles Sabrina , Olindo Stéphane , Renou Pauline , Rouanet François , Dousset Vincent , Tourdias Thomas , Sibon Igor 
Published: June 2017

Background and Purpose—
Several markers of poststroke cognitive impairment have been reported. The role of brain cortical volume remains uncertain. The aim of this study was to evaluate the influence of brain cortical volume on cognitive outcomes using a voxel-based morphometry approach in subjects without prestroke dementia.

Methods—
Ischemic stroke patients were prospectively recruited 24 to 72 hours post stroke (M0). Cognition was evaluated at M0, 3 months, and 1 year (M12) using the Montreal Cognitive Assessment, the Isaacs set test, and the Zazzo’s cancellation task. A 3-T brain magnetic resonance imaging was performed at M0. Grey matter (GM) was segmented using Statistical Parametric Mapping 12 software. Association between global GM volume and cognitive score slopes between M0 and M12 was evaluated using a linear mixed model. Correlations between focal GM volumes and changes in cognitive performance were evaluated using Statistical Parametric Mapping 12.

Results—

Two-hundred forty-eight patients were included (mean age 65±SD 14 years old, 66% men). Global GM volume was significantly associated with changes in Montreal Cognitive Assessment scores (β=0.01;
P
=0.04) and in the number of errors on the Zazzo’s cancellation task (β=−0.02;
P
=0.04) independently of other clinical/radiological confounders. Subjects with lower GM volumes in the left fronto-temporo-insular cortex were more vulnerable to transient Montreal Cognitive Assessment and Isaacs set test impairment. Subjects with lower GM volumes in right temporo-insular cortex, together with basal ganglia, were more vulnerable to transient cognitive impairment on the Zazzo’s cancellation task.

Conclusions—
Smaller cortical volumes in fronto-temporo-insular areas measured 24 to 72 hours post stroke are associated with cognitive vulnerability in the subacute stroke phase.
Helping patients reduce anxiety and choose new physicians through improved provider biographies
Authors: Perrault Evan K 
Published: June 2017

Objective: Not being able to effectively communicate with a new physician because of high anxiety associated with the interaction could lead to issues not being addressed, or even inaccurate diagnoses. Using uncertainty reduction and media richness theories as guidance, this study sought to find ways health educators within healthcare organisations could help prospective patients reduce their communication apprehension (CA) prior to a consultation. Methods: A total of 90 participants with high Communication Apprehension (CA) with respect to physicians were randomly exposed to two biographies of two different physicians in counterbalanced order that varied in the kind of information provided about the physician (primarily professional or personal), and the media through which the information was presented (text or video). Setting: An online experiment surrounding primary care provider selection. Results: Repeated measures analyses revealed that CA was reduced the greatest when participants viewed video biographies and biographies containing personal information about the physicians. Participants indicated they would want to visit the physician with whom they had the lowest level of CA. Conclusion: This research highlights improvements health educators or service provider managers could make to their physicians’ online biographies to help high-CA patients reduce their apprehension, and make the choice of the next physician much easier. Notably, including personal information about providers, and providing video introductions, reduces CA most significantly.
Microvascular fluid exchange during CPB with deep hypothermia circulatory arrest or low flow
Authors: Elvevoll Bjørg , Husby Paul , Kvalheim Venny L. , Stangeland Lodve , Mongstad Arve , Svendsen Øyvind S. 
Published: June 2017

Objective: Use of deep hypothermic low-flow (DHLF) cardiopulmonary bypass (CPB) has been associated with higher fluid loading than the use of deep hypothermia circulatory arrest (DHCA). We evaluated whether these perfusion strategies influenced fluid extravasation rates and edema generation differently per-operatively. Materials and Methods: Twelve anesthetized pigs, randomly allocated to DHLF (n = 6) or DHCA (n = 6), underwent 2.5 hours CPB with cooling to 20°C for 30 minutes (min), followed by 30 min arrested circulation (DHCA) or 30 min low-flow circulation (DHLF) before 90 min rewarming to normothermia. Perfusion of tissues, fluid requirements, plasma volumes, colloid osmotic pressures and total tissue water contents were recorded and fluid extravasation rates calculated. During the experiments, cerebral microdialysis was performed in both groups. Results: Microvascular fluid homeostasis was similar in both groups, with no between-group differences, reflected by similar fluid extravasation rates, plasma colloid osmotic pressures and total tissue water contents. Although extravasation rates increased dramatically from 0.10 (0.11) ml/kg/min (mean with standard deviation in parentheses) and 0.16 (0.02) ml/kg/min to 1.28 (0.58) ml/kg/min and 1.06 (0.41) ml/kg/min (DHCA and DHLF, respectively) after the initiation of CPB, fluid filtrations during both cardiac arrest and low flow were modest and close to baseline values. Cerebral microdialysis indicated anaerobic metabolism and ischemic brain injury in the DHCA group. Conclusion: No differences in microvascular fluid exchange could be demonstrated as a direct effect of DHCA compared with DHLF. Thirty minutes of DHCA was associated with anaerobic cerebral metabolism and possible brain injury.
Reducing Stigma in Media Professionals: Is there Room for Improvement? Results from a Systematic Review
Authors: Maiorano Alessandra , Lasalvia Antonio , Sampogna Gaia , Pocai Benedetta , Ruggeri Mirella , Henderson Claire 
Published: June 2017

Objective: The mass media may increase stigma against people with mental health problems by reinforcing common stereotypes. Media professionals thus represent a target group for antistigma interventions. This paper aims to review available literature on antistigma interventions for mass media professionals, seeking to clarify what kind of interventions have been found to be effective in reducing mental health stigma among mass media professionals. Method: Six electronic databases (MEDLINE, PsycINFO, Embase, Cochrane Reviews Library and Cochrane Central Register of Controlled Trials, Web of Science, and Applied Social Sciences Index & Abstracts) were systematically searched through March 2017 for studies addressing antistigma interventions on mass media professionals.  Results: A total of 27 studies on antistigma interventions targeted to media professionals were found. Reviewed articles were classified into 3 categories: media-monitoring projects/reporting guidelines ( n = 23), interventions for educating journalists ( n = 2), and interventions for educating journalism students ( n = 2). Overall, antistigma interventions for media professionals seem to have some effect in improving reporting style, thus providing a more balanced portrayal of people with mental health problems: the most promising interventions are contact-based educational approaches and the provision of guidelines by authoritative institutions. Conclusion: It should be useful to promote and disseminate contact-based educational interventions targeted to journalists and to include specific modules on mental health topics in the training curricula of journalism students. However, as research in the field suffers from several limitations, high-quality studies exploring the long-term effect of antistigma interventions for media professionals are needed.
Sol–gel derived lithium-releasing glass for cartilage regeneration
Authors: Li Siwei , Maçon Anthony LB , Jacquemin Manon , Stevens Molly M , Jones Julian R 
Published: June 2017

Wnt-signalling cascade is one of the crucial pathways involved in the development and homeostasis of cartilage. Influencing this pathway can potentially contribute to improved cartilage repair or regeneration. One key molecular regulator of the Wnt pathway is the glycogen synthase kinase-3 enzyme, the inhibition of which allows initiation of the signalling pathway. This study aims to utilise a binary SiO2–Li2O sol–gel derived glass for controlled delivery of lithium, a known glycogen synthase kinase-3 antagonist. The effect of the dissolution products of the glass on chondrogenic differentiation in an in vitro 3D pellet culture model is reported. Dissolution products that contained 5 mM lithium and 3.5 mM silicon were capable of inducing chondrogenic differentiation and hyaline cartilaginous matrix formation without the presence of growth factors such as TGF-β3. The results suggest that sol–gel derived glass has the potential to be used as a delivery vehicle for therapeutic lithium ions in cartilage regeneration applications.
Preparation and in vivo evaluation of a silicate-based composite bone cement
Authors: Ma Bing , Huan Zhiguang , Xu Chen , Ma Nan , Zhu Haibo , Zhong Jipin , Chang Jiang 
Published: June 2017

Silicate-based cements have been developed as a class of bioactive and biodegradable bone cements owing to their good in vitro bioactivity and ability to dissolve in a simulated body fluid. Until recently, however, the in vivo evidence of their ability to support bone regeneration is still scarce. In the present study, a pilot in vivo evaluation of a silicate-based composite bone cement (CSC) was carried out in a rabbit femur defect model. The cement was composed of tricalcium silicate, 45S5 bioglass and calcium sulfate, and the self-setting properties of the material were established. The in vivo bone integration and biodegradability of CSC were investigated and compared with those of bioactive glass particulates, and a calcium phosphate cement. The results showed that CSC underwent a relatively slower in vivo degradation as compared with bioactive glass and calcium phosphate cement. Histological observation demonstrated that bone contact area at the interface between the surrounding bone and CSC gradually increased with time proceeding. CSC kept its structural integrity during implantation in vivo because of its acceptable mechanical strength. These results provide evidence of effectiveness in vivo and suggest potential clinical applications of the silicate-based composite bone cements.
Retrospective analysis of nephritis response and renal outcome in a cohort of 928 Egyptian lupus nephritis patients: a university hospital experience
Authors: Momtaz M , Fayed A , Wadie M , Gamal S M , Ghoniem S A , Sobhy N , Kamal Elden N M , Hamza W M 
Published: June 2017

Aim We aim to describe the pattern of response to treatment in a cohort of Egyptian lupus nephritis (LN) patients and to define variable prognostic factors. Methods We retrospectively analyzed records of 928 systemic lupus erythematosus (SLE) patients (898 females, 30 males) with biopsy-confirmed LN seen between 2006 and 2012 at Cairo University hospitals. Results Our study involved 928 SLE patients with a mean age of 26.25 ± 6.487 years, mean LN duration at time of renal biopsy 6.48 ± 4.27 months, mean SLEDAI 28.22 ± 11.7, and mean follow-up duration of 44.14 ± 17.34 months. Induction treatment achieved remission in 683 patients. Remission was achieved in all 32 patients with class II LN, compared to 651/896 (72.7%) patients in classes III, IV, and V. Induction by intravenous (IV) cyclophosphamide achieved response in 435/575 (75.7%) patients, while induction by mycophenolate mofetil (MMF) resulted in response in 216/321 (67.3%) patients ( p = 0.0068). Nephritic flares were least observed when MMF was used for maintenance (30/239 (12.6%) patients), compared to 71/365 patients (19.5%) ( p = 0.0266) when azathioprine (AZA) was used, and 22/79 patients (27.8%) ( p = 0.002) with IV cyclophosphamide. Class IV LN, high chronicity index, presence of crescents, and interstitial fibrosis in biopsies were all associated with chronic kidney disease (CKD) development eventually ( p < 0.001, p = 0.005, p = 0.012, and p = 0.031, respectively). By the end of the study duration, 305 (32.7%) patients had CKD. Logistic regression detected that high baseline serum creatinine, failure to achieve remission, hypertension, and nephritic flare were the main risk factors for poor renal outcome ( p < 0.001, p < 0.001, p = 0.004, and p < 0.001, respectively). The 5 years’ mortality was 69 (7.4%) patients with sepsis being the main cause of death. Conclusion IV cyclophosphamide superseded as induction treatment, while MMF was the best maintenance treatment. High serum creatinine, hypertension, and nephritic flare were the main risk factors for poor renal outcome.
Cost-effectiveness of Memory Assessment Services for the diagnosis and early support of patients with dementia in England
Authors: Gomes Manuel , Pennington Mark , Wittenberg Raphael , Knapp Martin , Black Nick , Smith Sarah 
Published: June 2017

Background Policy makers in England advocate referral of patients with suspected dementia to Memory Assessment Services (MAS), but it is unclear how any improvement in patients’ health-related quality of life (HRQL) compares with the associated costs. Aims To evaluate the cost-effectiveness of MAS for the diagnosis and follow-up care of patients with suspected dementia. Method We analysed observational data from 1318 patients referred to 69 MAS, and their lay carers (n = 944), who completed resource use and HRQL questionnaires at baseline, three and six months. We reported mean differences in HRQL (disease-specific DEMQOL and generic EQ-5D-3L), quality-adjusted life years (QALYs) and costs between baseline and six months after referral to MAS. We also assessed the cost-effectiveness of MAS across different patient subgroups and clinic characteristics. Results Referral to MAS was associated with gains in DEMQOL (mean gain: 3.48, 95% confidence interval: 2.84 to 4.12), EQ-5D-3L (0.023, 0.008 to 0.038) and QALYs (0.006, 0.002 to 0.01). Mean total cost over six months, assuming a societal perspective, was £1899 (£1277 to £2539). This yielded a negative incremental net monetary benefit of −£1724 (−£2388 to −£1085), assuming NICE’s recommended willingness-to-pay threshold (£30,000 per QALY). These base case results were relatively robust to alternative assumptions about costs and HRQL. There was some evidence that patients aged 80 or older benefitted more from referral to MAS (p < 0.01 from adjusted mean differences in net benefits) compared to younger patients. MAS with over 75 new patients a month or cost per patient less than £2500 over six months were relatively more cost-effective (p < 0.01) than MAS with fewer new monthly patients or higher cost per patient. Conclusions Diagnosis, treatment and follow-up care provided by MAS to patients with suspected dementia appears to be effective, but not cost-effective, in the six months after diagnosis. Longer term evidence is required before drawing conclusions about the cost-effectiveness of MAS.
Navigating tissue chips from development to dissemination: A pharmaceutical industry perspective
Authors: Ewart Lorna , Fabre Kristin , Chakilam Ananthsrinivas , Dragan Yvonne , Duignan David B , Eswaraka Jeetu , Gan Jinping , Guzzie-Peck Peggy , Otieno Monicah , Jeong Claire G , Keller Douglas A , de Morais Sonia M , Phillips Jonathan A , Proctor William , Sura Radhakrishna , Van Vleet Terry , Watson David , Will Yvonne , Tagle Danilo , Berridge Brian 
Published: June 2017

Tissue chips are poised to deliver a paradigm shift in drug discovery. By emulating human physiology, these chips have the potential to increase the predictive power of preclinical modeling, which in turn will move the pharmaceutical industry closer to its aspiration of clinically relevant and ultimately animal-free drug discovery. Despite the tremendous science and innovation invested in these tissue chips, significant challenges remain to be addressed to enable their routine adoption into the industrial laboratory. This article describes the main steps that need to be taken and highlights key considerations in order to transform tissue chip technology from the hands of the innovators into those of the industrial scientists. Written by scientists from 13 pharmaceutical companies and partners at the National Institutes of Health, this article uniquely captures a consensus view on the progression strategy to facilitate and accelerate the adoption of this valuable technology. It concludes that success will be delivered by a partnership approach as well as a deep understanding of the context within which these chips will actually be used. Impact statement The rapid pace of scientific innovation in the tissue chip (TC) field requires a cohesive partnership between innovators and end users. Near term uptake of these human-relevant platforms will fill gaps in current capabilities for assessing important properties of disposition, efficacy and safety liabilities. Similarly, these platforms could support mechanistic studies which aim to resolve challenges later in development (e.g. assessing the human relevance of a liability identified in animal studies). Building confidence that novel capabilities of TCs can address real world challenges while they themselves are being developed will accelerate their application in the discovery and development of innovative medicines. This article outlines a strategic roadmap to unite innovators and end users thus making implementation smooth and rapid. With the collective contributions from multiple international pharmaceutical companies and partners at National Institutes of Health, this article should serve as an invaluable resource to the multi-disciplinary field of TC development.
Severe periodontitis and higher cirrhosis mortality
Authors: Ladegaard Grønkjær Lea , Holmstrup Palle , Schou Søren , Jepsen Peter , Vilstrup Hendrik 
Published: June 2017

Background Periodontitis and edentulism are prevalent in patients with cirrhosis, but their clinical significance is largely unknown. Objective The objective of this article is to determine the association of severe periodontitis and edentulism with mortality in patients with cirrhosis. Methods A total of 184 cirrhosis patients underwent an oral examination. All-cause and cirrhosis-related mortality was recorded. The associations of periodontitis and edentulism with mortality were explored by Kaplan–Meier survival plots and Cox proportional hazards regression adjusted for age, gender, cirrhosis etiology, Child–Pugh score, Model for End-Stage Liver Disease score, smoker status, present alcohol use, comorbidity, and nutritional risk score. Results The total follow-up time was 74,197 days (203.14 years). At entry, 44% of the patients had severe periodontitis and 18% were edentulous. Forty-four percent of the patients died during follow-up. Severe periodontitis was associated with higher all-cause mortality in the crude analysis (HR 1.56, 95% CI 1.06–2.54), but not in the adjusted analysis (HR 1.45, 95% CI 0.79–2.45). Severe periodontitis was even more strongly associated with higher cirrhosis-related mortality (crude HR 2.19, 95% CI 1.07–4.50 and adjusted HR 2.29, 95% CI 1.04–4.99). No association was found between edentulism and mortality. Conclusion The presence of severe periodontitis predicted a more than double one-year cirrhosis mortality. These findings may motivate intervention trials on the effect of periodontitis treatment in patients with cirrhosis.