bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and effectiveness of microsurgical clipping, endovascular coiling, and stent assisted coiling for unruptured anterior communicating artery aneurysms: a systematic analysis of observational studies
Authors: O'Neill Anthea H , Chandra Ronil V , Lai Leon T 
Published: September 2016

ObjectiveTreatment outcomes for unruptured anterior communicating artery (ACoA) aneurysms are not well established. We aimed to investigate the safety and effectiveness of microsurgical clipping (MC), endovascular coiling (EC), and stent assisted coiling (SAC) of unruptured ACoA aneurysms to aid pretreatment clinical decisions.MethodsA systematic review of the literature was conducted using the Ovid Medline and EMBASE electronic databases, encompassing all English language studies reporting treatment outcomes for unruptured ACoA aneurysms published between 2005 and 2015. The analyses were directed towards patient focused outcomes: good therapeutic outcome (Glasgow Outcome Score of 5 (GOS 5), modified Rankin Scale (mRS) score of 0–1), poor therapeutic outcome (GOS 1–4, mRS 2–6), 30 day mortality, recurrence/retreatment rates, and post-treatment subarachnoid hemorrhage (SAH).Results14 studies with 862 treated aneurysms were included (EC, n=372; MC, n=401; SAC, n=89). EC resulted in significantly lower treatment related morbidity compared with MC or SAC (EC 0.8%, MC 4.4%, SAC 7.9%; p=0.001); treatment related mortality occurred in 0%, 0.3%, and 1.1%, for EC, MC, and SAC, respectively. MC resulted in significantly lower angiographic recurrence (EC 7.2%, MC 0%, SAC 12.3%; p<0.001) and retreatment (EC 4.9%, MC 0%, SAC 6.8%; p=0.001). SAH from the treated aneurysm was not reported with any treatment modality.ConclusionsWhile there are limitations to the data, EC resulted in a more favorable clinical outcome, and MC resulted in more robust aneurysm repair, for unruptured ACoA aneurysms. SAC had a higher treatment morbidity risk than EC, without reduction in retreatment rate. All treatments were effective in preventing SAH. The current pooled analysis of treatment outcomes provides a useful aid to pretreatment clinical decision making.
The Cost-Effectiveness of Cervical Self-Sampling to Improve Routine Cervical Cancer Screening: The Importance of Respondent Screening History and Compliance
Authors: Burger Emily A. , Sy Stephen , Nygård Mari , Kim Jane J. 
Published: September 2016

Abstract
Background: Human papillomavirus (HPV) testing allows women to self-collect cervico-vaginal cells at home (i.e., self-sampling). Using primary data from a randomized pilot study, we evaluated the long-term consequences and cost-effectiveness of using self-sampling to improve participation to routine cervical cancer screening in Norway.
Methods: We compared a strategy reflecting screening participation (using reminder letters) to strategies that involved mailing self-sampling device kits to women noncompliant to screening within a 5- or 10-year period under two scenarios: (A) self-sampling respondents had moderate under-screening histories, or (B) respondents to self-sampling had moderate and severe under-screening histories. Model outcomes included quality-adjusted life-years (QALY) and lifetime costs. The “most cost-effective” strategy was identified as the strategy just below $100,000 per QALY gained.
Results: Mailing self-sampling device kits to all women noncompliant to screening within a 5- or 10-year period can be more effective and less costly than the current reminder letter policy; however, the optimal self-sampling strategy was dependent on the profile of self-sampling respondents. For example, “10-yearly self-sampling” is preferred ($95,500 per QALY gained) if “5-yearly self-sampling” could only attract moderate under-screeners; however, “5-yearly self-sampling” is preferred if this strategy could additionally attract severe under-screeners.
Conclusions: Targeted self-sampling of noncompliers likely represents good value-for-money; however, the preferred strategy is contingent on the screening histories and compliance of respondents.
Impact: The magnitude of the health benefit and optimal self-sampling strategy is dependent on the profile and behavior of respondents. Health authorities should understand these factors prior to selecting and implementing a self-sampling policy. Cancer Epidemiol Biomarkers Prev; 26(1); 95–103. ©2016 AACR.
Prenatal and Postnatal Medical Conditions and the Risk of Brain Tumors in Children and Adolescents: An International Multicenter Case–Control Study
Authors: Tettamanti Giorgio , Shu Xiaochen , Adel Fahmideh Maral , Schüz Joachim , Röösli Martin , Tynes Tore , Grotzer Michael , Johansen Christoffer , Klaeboe Lars , Kuehni Claudia E. , Lannering Birgitta , Schmidt Lisbeth S. , Vienneau Danielle , Feychting Maria 
Published: September 2016

Abstract
Background: Previous studies have evaluated the effect of medical diagnostic radiation on brain tumors. Recent cohort studies have reported an increased risk associated with exposure to head CT scans.
Methods: Information regarding medical conditions, including prenatal and postnatal exposure to medical diagnostic radiation, was obtained from CEFALO, a multicenter case–control study performed in Denmark, Norway, Sweden, and Switzerland through face-to-face interview. Eligible cases of childhood and adolescent brain tumors (CABT) were ages 7 to 19 years, diagnosed between January 1, 2004 and August 31, 2008, and living in the participating countries (n = 352). The cases were matched by age, sex, and region to 646 population-based controls.
Results: Prenatal exposure to medical diagnostic radiation and postnatal exposure to X-rays were not associated with CABTs. A higher risk estimate of CABTs, although not statistically significant, was found for exposure to head CT scan (OR, 1.86; 95% confidence interval, 0.82–4.22). The associations with head injury, febrile seizure, fever in the first 12 weeks, and general anesthesia were close to unity.
Conclusions: Prenatal or postnatal medical conditions, including medical diagnostic radiation, were not associated with CABTs. On the basis of small numbers of exposed children, we observed a nonsignificant increased risk for CT scans of the head.
Impact: We have presented additional evidence, suggesting that exposure to head CT scan may be associated with the occurrence of CABTs. Cancer Epidemiol Biomarkers Prev; 26(1); 110–5. ©2016 AACR.
Inhibition of S-Adenosylmethionine-Dependent Methyltransferase Attenuates TGFβ1-Induced EMT and Metastasis in Pancreatic Cancer: Putative Roles of miR-663a and miR-4787-5p
Authors: Mody Hardik R. , Hung Sau Wai , AlSaggar Mohammad , Griffin Jazmine , Govindarajan Rajgopal 
Published: September 2016

Abstract
The identification of epigenetic reversal agents for use in combination chemotherapies to treat human pancreatic ductal adenocarcinomas (PDAC) remains an unmet clinical need. Pharmacologic inhibitors of Enhancer of Zeste Homolog 2 (EZH2) are emerging as potential histone methylation reversal agents for the treatment of various solid tumors and leukemia; however, the surprisingly small set of mRNA targets identified with EZH2 knockdown suggests novel mechanisms contribute to their antitumorigenic effects. Here, 3-deazaneplanocin-A (DZNep), an inhibitor of S-adenosyl-L-homocysteine hydrolase and EZH2 histone lysine-N-methyltransferase, significantly reprograms noncoding microRNA (miRNA) expression and dampens TGFβ1-induced epithelial-to-mesenchymal (EMT) signals in pancreatic cancer. In particular, miR-663a and miR-4787-5p were identified as PDAC-downregulated miRNAs that were reactivated by DZNep to directly target TGFβ1 for RNA interference. Lentiviral overexpression of miR-663a and miR-4787-5p reduced TGFβ1 synthesis and secretion in PDAC cells and partially phenocopied DZNep's EMT-resisting effects, whereas locked nucleic acid (LNA) antagomiRNAs counteracted them. DZNep, miR-663a, and miR-4787-5p reduced tumor burden in vivo and metastases in an orthotopic mouse pancreatic tumor model. Taken together, these findings suggest the epigenetic reprogramming of miRNAs by synthetic histone methylation reversal agents as a viable approach to attenuate TGFβ1-induced EMT features in human PDAC and uncover putative miRNA targets involved in the process.
Implications: The findings support the potential for synthetic histone methylation reversal agents to be included in future epigenetic–chemotherapeutic combination therapies for pancreatic cancer. Mol Cancer Res; 14(11); 1124–35. ©2016 AACR.
β-Cryptoxanthin Reduced Lung Tumor Multiplicity and Inhibited Lung Cancer Cell Motility by Downregulating Nicotinic Acetylcholine Receptor α7 Signaling
Authors: Iskandar Anita R. , Miao Benchun , Li Xinli , Hu Kang-Quan , Liu Chun , Wang Xiang-Dong 
Published: September 2016

Abstract
Despite the consistent association between a higher intake of the provitamin A carotenoid β-cryptoxanthin (BCX) and a lower risk of lung cancer among smokers, potential mechanisms supporting BCX as a chemopreventive agent are needed. We first examined the effects of BCX on 4-[methyl nitrosamino]-1-[3-pyridyl]-1-butanone (NNK)-induced lung tumorigenesis in A/J mice. BCX supplementation was given daily to the mice starting 2 weeks prior to the injection of NNK and continued 16 weeks after NNK injection. BCX supplementation resulted in a dose-dependent increase of BCX concentration in both serum and lungs of the mice without a significant alteration of vitamin A (retinol and retinyl palmitate) concentration. BCX significantly reduced the multiplicity of the NNK-induced lung tumor by 52% to 63% compared with the NNK-treated mice without BCX supplementation. The protective effect of BCX in the lungs was associated with reductions of both mRNA and protein of the homopentameric neuronal nicotinic acetylcholine receptor α7 (α7-nAChR), which has been implicated in lung tumorigenesis. We then conducted an in vitro cell culture study and found that BCX treatment suppressed α7-nAChR expression and inhibited the migration and invasion of α7-nAChR-positive lung cancer cells but not in cells lacking α7-nAChR. The activities of BCX were significantly attenuated by activators of α7-nAChR/PI3K signaling or by overexpression of constitutively active PI3K. Collectively, the results suggest that BCX inhibits lung tumorigenesis and cancer cell motility through the downregulation of α7-nAChR/PI3K signaling, independent of its provitamin A activity. Therefore, BCX can be used as a chemopreventive agent or a chemotherapeutic compound against lung cancer. Cancer Prev Res; 9(11); 875–86. ©2016 AACR.
Opportunities for Preventing Esophageal Adenocarcinoma
Authors: Maret-Ouda John , El-Serag Hashem B , Lagergren Jesper 
Published: September 2016

Abstract
Esophageal adenocarcinoma (EAC) is rapidly increasing in incidence in many Western societies, requires demanding treatment, and is associated with a poor prognosis, therefore preventive measures are highly warranted. To assess the opportunities for prevention, we reviewed the available literature and identified seven main potentially preventive targets. Preventive effects were found on the basis of medium-level observational evidence following treatment of gastroesophageal reflux disease (using both medication and surgery) and tobacco smoking cessation, which should be clinically recommended among exposed patients. Nonsteroidal anti-inflammatory drugs appear to prevent EAC, and the limited existing data also indicate a protective effect of medication with statins or hormone replacement therapy in women, but current evidence is insufficient to guide clinical decision-making regarding these drugs. The evidence is presently insufficient to assess the potentially preventive role of weight loss. Whether avoidance of eradication of Helicobacter pylori prevents EAC is not studied, but there is no evidence that such eradication increases symptoms of gastroesophageal reflux or prevalence of erosive esophagitis. The introduction of preventive actions should be tailored toward high-risk individuals, that is, older men with obesity and gastroesophageal reflux disease and individuals with Barrett esophagus rather than the population at large. Cancer Prev Res; 9(11); 828–34. ©2016 AACR.
Rivaroxaban real-world evidence: Validating safety and effectiveness in clinical practice
Authors: Camm A. , Coleman Craig , Tamayo CAPT , Beyer-Westendorf Jan 
Published: September 2016

SummaryRandomised controlled trials (RCTs) are considered the gold standard of clinical research as they use rigorous methodologies, detailed protocols, pre-specified statistical analyses and well-defined patient cohorts. However, RCTs do not take into account the complexity of real-world clinical decision-making. To tackle this, real-world data are being increasingly used to evaluate the long-term safety and effectiveness of a given therapy in routine clinical practice and in patients who may not be represented in RCTs, addressing key clinical questions that may remain. Real-world evidence plays a substantial role in supporting the use of non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) in clinical practice. By providing data on patient profiles and the use of anticoagulation therapies in routine clinical practice, real-world evidence expands the current awareness of NOACs, helping to ensure that clinicians are well-informed on their use to implement patient-tailored clinical decisions. There are various issues with current anticoagulation strategies, including under- or overtreatment and frequent monitoring with VKAs. Real-world studies have demonstrated that NOAC use is increasing (Dresden NOAC registry and Global Anticoagulant Registry in the FIELD-AF [GARFIELD-AF]), as well as reaffirming the safety and effectiveness of rivaroxaban previously observed in RCTs (XArelto on preveNtion of sTroke and non-central nervoUS system systemic embolism in patients with non-valvular atrial fibrillation [XANTUS] and IMS Disease Analyzer). This article will describe the latest updates in real-world evidence across a variety of methodologies, such as non-interventional studies (NIS), registries and database analyses studies. It is anticipated that these studies will provide valuable clinical insights into the management of thromboembolism, and enhance the current knowledge on anticoagulant use and outcomes for patients.
Spotlight on real-world evidence for the treatment of DVT: XALIA
Authors: Turpie Alexander , Ageno Walter 
Published: September 2016

SummaryVenous thromboembolism (VTE), comprising both deep-vein thrombosis (DVT) and pulmonary embolism (PE), is a serious and common cardiovascular disease associated with the risk of chronic complications, recurrent VTE events and even death. The treatment landscape has, in recent years, seen a paradigm shift from the use of traditional anticoagulants (low-molecular-weight heparin [LMWH] overlapping with and followed by a vitamin K antagonist [VKA]) to non-VKA oral anticoagulants (NOACs). This class of agents, encompassing direct factor Xa inhibitors and direct thrombin inhibitors have shown non-inferior efficacy and better safety to standard of care in randomised controlled trials (RCTs). The direct, oral factor Xa inhibitor rivaroxaban was the first to be approved for treatment of acute DVT and PE and secondary prevention of recurrent VTE events based on data from EINSTEIN DVT and EINSTEIN PE, respectively. Real-world evidence now helps to further support data from RCTs, and also bridges the gap for physicians regarding any areas of clinical uncertainty that may not be addressed by RCTs. XA inhibition with rivaroxaban for Long-term and Initial Anticoagulation in venous thromboembolism (XALIA) was the first large, prospective, observational, real-world study that has investigated the safety and effectiveness profile of rivaroxaban in patients with DVT and PE associated with DVT in routine clinical practice. This article will present the key clinical outcomes from this important global non-interventional study, and will discuss remaining questions to be addressed in Phase IV studies.
МЕХАНІЗМИ ЗАБЕЗПЕЧЕННЯ ТА ЗАХИСТУ ПРАВ ПАЦІЄНТІВ В УКРАЇНІ
Authors: Yaremenko N. V. 
Published: September 2016

<p>The questions of research areas for the protection of patients' rights are considered. It is emphasized that despite the recognition by the Constitution and laws of Ukraine human life and health as the highest social value proper mechanisms for patient's fundamental rights enforcement has not been established in Ukraine. The creation of a special law that would determine the mechanisms of implementation and protection of citizens' rights to health and medical care is proposed.</p><p> </p>
Influence of Clinical Trial Site Enrollment on Patient Characteristics, Protocol Completion, and End Points
Authors: Greene Stephen J. , Hernandez Adrian F. , Sun Jie-Lena , Metra Marco , Butler Javed , Ambrosy Andrew P. , Ezekowitz Justin A. , Starling Randall C. , Teerlink John R. , Schulte Phillip J. , Voors Adriaan A. , Armstrong Paul W. , O’Connor Christopher M. , Mentz Robert J. 
Published: September 2016

Background—
Most international acute heart failure trials have failed to show benefit with respect to key end points. The impact of site enrollment and protocol execution on trial performance is unclear.

Methods and Results—

We assessed the impact of varying site enrollment volume among all 7141 acute heart failure patients from the ASCEND-HF trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure). Overall, 398 sites enrolled ≥1 patient, and median enrollment was 12 patients (interquartile range, 5–23). Patients from high enrolling sites (>60 patients/site) tended to have lower ejection fraction, worse New York Heart Association functional class, and lower utilization of guideline-directed medical therapy but fewer comorbidities and lower B-type natriuretic peptide level. Every 10 patient increase (up to 100 patients) in site enrollment correlated with lower likelihood of protocol noncompletion (odds ratio, 0.93; 95% confidence interval [CI], 0.89–0.98). After adjustment, increasing site enrollment predicted higher risk of persistent dyspnea at 6 hours (per 10 patient increase: odds ratio 1.02; 95% CI, 1.01–1.03) but not at 24 hours (odds ratio, 0.99; 95% CI, 0.98–1.00). Higher site enrollment was independently associated with lower risk of 30-day death or rehospitalization (per 10 patient increase: odds ratio, 0.98, 95% CI, 0.96–0.99) but not 180-day mortality (hazard ratio, 0.99; 95% CI, 0.98–1.01). The influence of increasing site enrollment on clinical end points varied across geographic regions with strongest associations in Latin America and Asia-Pacific (all interaction
P
<0.01).

Conclusions—
In this large, acute heart failure trial, site enrollment correlated with protocol completion and was independently associated with trial end points. Individual and regional site performance present challenges to be considered in design of future acute heart failure trials.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00475852.
Ultrasonic Assessment of Myocardial Microstructure in Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers With and Without Left Ventricular Hypertrophy
Authors: Hiremath Pranoti , Lawler Patrick R. , Ho Jennifer E. , Correia Andrew W. , Abbasi Siddique A. , Kwong Raymond Y. , Jerosch-Herold Michael , Ho Carolyn Y. , Cheng Susan 
Published: September 2016

Background—
The noninvasive assessment of altered myocardium in patients with genetic mutations that are associated with hypertrophic cardiomyopathy (HCM) remains challenging. In this pilot study, we evaluated whether a novel echocardiography-based assessment of myocardial microstructure, the signal intensity coefficient (SIC), could detect tissue-level alterations in HCM sarcomere mutation carriers with and without left ventricular hypertrophy.

Methods and Results—

We studied 3 groups of genotyped individuals: sarcomere mutation carriers with left ventricular hypertrophy (clinical HCM; n=36), mutation carriers with normal left ventricular wall thickness (subclinical HCM; n=28), and healthy controls (n=10). We compared measurements of echocardiographic SIC with validated assessments of cardiac microstructural alteration, including cardiac magnetic resonance measures of interstitial fibrosis (extracellular volume fraction), as well as serum biomarkers (NTproBNP, hs-cTnI, and PICP). In age-, sex-, and familial relation–adjusted analyses, the SIC was quantitatively different across subjects with overt HCM, subclinical HCM, and healthy controls (
P
<0.001). Compared with controls, the SIC was 61% higher in overt HCM and 47% higher in subclinical HCM (
P
<0.001 for both). The SIC was significantly correlated with extracellular volume (
r
=0.72;
P
<0.01), with left ventricular mass and E′ velocity (
r
=0.45, -0.60, respectively;
P
<0.01 for both), and with serum NTproBNP levels (
r
=0.36;
P
<0.001).

Conclusions—
Our findings suggest that the SIC could serve as a noninvasive quantitative tool for assessing altered myocardial tissue characteristics in patients with genetic mutations associated with HCM. Further studies are needed to determine whether the SIC could be used to identify subclinical changes in patients at risk for HCM and to evaluate the effects of interventions.
Smoking and Cardiac Structure and Function in the Elderly
Authors: Nadruz Wilson , Claggett Brian , Gonçalves Alexandra , Querejeta-Roca Gabriela , Fernandes-Silva Miguel M. , Shah Amil M. , Cheng Susan , Tanaka Hirofumi , Heiss Gerardo , Kitzman Dalane W. , Solomon Scott D. 
Published: September 2016

Background—
Cigarette smoking has been associated with higher risk of incident heart failure independent of coronary artery disease, but the impact of tobacco use on cardiac structure and function in the general population is uncertain. This study evaluated the relationship between smoking and echocardiographic measures in a large elderly cohort.

Methods and Results—

We studied 4580 participants free of overt coronary artery disease, heart failure, and significant valvular disease from the fifth visit of the ARIC study (Atherosclerosis Risk in Communities) who underwent transthoracic echocardiography. Participants were classified into 3 categories based on self-reported smoking habits: never (43.2%), former (50.5%), and current smokers (6.3%). Pack-years and years of smoking were also estimated. Compared with never smokers, current smokers had greater left ventricular (LV) mass index (80.4±1.1 versus 76.7±0.4 g/m
2
;
P
<0.001), LV mass/volume ratio (1.93±0.03 versus 1.83±0.03 g/mL;
P
<0.001), higher prevalence of LV hypertrophy (15% versus 9%;
P
=0.008), and worse diastolic function, as reflected by higher E/E′ ratio (11.7±0.2 versus 10.9±0.1;
P
<0.001), after adjusting for potential confounding factors. In contrast, former smokers showed similar echocardiographic features when compared with never smokers. Furthermore, estimated pack-years and years of smoking, measures of cumulative cigarette exposure, were associated with greater LV mass index, LV mass/volume ratio, and worse diastolic function (higher E/E′ ratio) in current smokers after multivariable analysis (all
P
<0.01).

Conclusions—
Active smoking and cumulative cigarette exposure were associated with subtle alterations in LV structure and function in an elderly, community-based population free of overt coronary artery disease and heart failure.