bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequential Monitoring of the Comparative Effectiveness and Safety of Dabigatran in Routine Care
Authors: Schneeweiss Sebastian , Gopalakrishnan Chandrasekar , Bartels Dorothee B. , Franklin Jessica M. , Zint Kristina , Kulldorff Martin , Huybrechts Krista F. 
Published: February 2019

Background:
The increasing availability of electronic healthcare data enables ongoing monitoring of the effectiveness and safety of newly marketed medications. We sought to demonstrate a 5-year prospective monitoring system of dabigatran for stroke prevention that may expedite discovery and allow ongoing evidence development.

Methods and Results:
Between 2011 and 2015, we conducted 9 sequential analyses of dabigatran versus warfarin users in a sequential cohort design in 2 US claims databases. Analyses 4 through 9 were prespecified, and analyses 1 through 3 were added subsequently using the same methodology. New users of anticoagulants with nonvalvular atrial fibrillation were followed until a study outcome of hospitalization for stroke (hemorrhagic and ischemic) or hospitalization for major hemorrhage (intracranial and extracranial). Hazard ratios and 95% CIs were estimated after 1:1 propensity score matching. Sequential analyses 1 through 3 on stroke prevention using data through June 2012 were limited by few events leading to wide CIs. As data accumulated the effect estimate in analysis 4 visually stabilized at a 25% risk reduction with increasingly narrower CIs (−46% to +9% in December 2012 and −42% to −2% in September 2015). Improved data-adaptive confounding adjustment with high-dimensional propensity score reached a stable state already at analysis 3 and was slightly closer to the randomized clinical trial finding (−39%). The risk of major hemorrhage was 28% lower in dabigatran initiators (−35% to −20%) a finding that was stable throughout analyses 2 to 9.

Conclusions:
Prospectively monitoring the effectiveness and safety of dabigatran for stroke prevention allowed for early insights with increasing precision over time.
Maintenance of Gains, Morbidity, and Mortality at 1 Year Following Cardiac Rehabilitation in a Middle‐Income Country: A Wait‐List Control Crossover Trial
Authors: Chaves Gabriela S. S. , Lima de Melo Ghisi Gabriela , Britto Raquel R. , Grace Sherry L. 
Published: February 2019

Background

Despite the epidemic of cardiovascular diseases in middle‐income countries, few trials are testing the benefits of cardiac rehabilitation (
CR
). This trial assessed (1) maintenance of functional capacity, risk factor control, knowledge, and heart‐health behaviors and (2) mortality and morbidity at 6 months following
CR
in a middle‐income country.

Methods and Results

Eligible Brazilian coronary patients were initially randomized (1:1:1 concealed) to 1 of 3 parallel arms (comprehensive
CR
[exercise plus education], exercise‐only
CR
, or wait‐list control). The
CR
programs were 6 months in duration, at which point follow‐up assessments were performed. Mortality and morbidity were ascertained from chart and patient or family report (blinded). Controls were then offered
CR
(crossover). Outcomes were again assessed 6 months later (blinded). ANCOVA was performed for each outcome at 12 months. Overall, 115 (88.5%) patients were randomized, and 62 (53.9%) were retained at 1 year. At 6 months, 23 (58.9%) of those 39 initially randomized to the wait‐list control elected to attend
CR
. Functional capacity, risk factors, knowledge, and heart‐health behaviors were maintained from 6 to 12 months in participants from both
CR
arms (all
P
>0.05). At 1 year, knowledge was significantly greater with comprehensive
CR
at either time point (
P
<0.001). There were 2 deaths. Hospitalizations (
P
=0.03), nonfatal myocardial infarctions (
P
=0.04), and percutaneous coronary interventions (
P
=0.03) were significantly fewer with
CR
than control at 6 months.

Conclusions

CR
participation is associated with lower morbidity, long‐term maintenance of functional capacity, risk factors, and heart‐health behaviors, as well as with greater cardiovascular knowledge compared with no
CR
.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
02575976.
Guiding Neuroevolution with Structural Objectives
Authors: Ellefsen Kai Olav , Huizinga Joost , Torresen Jim 
Published: February 2019

Abstract
The structure and performance of neural networks are intimately connected, and by use of evolutionary algorithms, neural network structures optimally adapted to a given task can be explored. Guiding such neuroevolution with additional objectives related to network structure has been shown to improve performance in some cases, especially when modular neural networks are beneficial. However, apart from objectives aiming to make networks more modular, such structural objectives have not been widely explored. We propose two new structural objectives and test their ability to guide evolving neural networks on two problems which can benefit from decomposition into subtasks. The first structural objective guides evolution to align neural networks with a user-recommended decomposition pattern. Intuitively, this should be a powerful guiding target for problems where human users can easily identify a structure. The second structural objective guides evolution towards a population with a high diversity in decomposition patterns. This results in exploration of many different ways to decompose a problem, allowing evolution to find good decompositions faster. Tests on our target problems reveal that both methods perform well on a problem with a very clear and decomposable structure. However, on a problem where the optimal decomposition is less obvious, the structural diversity objective is found to outcompete other structural objectives—and this technique can even increase performance on problems without any decomposable structure at all.
An Opaque Pun
Authors: Chen Ruixuan 
Published: February 2019

Abstract
Various interpretations of Kāśyapaparivarta § 68 have been attempted in the Yogācāra-Vijñānavāda tradition. This passage, which consists in a simile likening a magician devoured by his own creation to a monk involved in meditation practice, appears prima facie absurd, insofar as the similarity between the tenor and the vehicle is not readily apparent. This article mainly consists of two parts: The first part examines the received interpretations of the simile and reconstructs their interrelationship from a historical perspective. The second part explores the literary dimension of the simile and argues that its ostensible absurdity is rooted in a pun which is visible only in Middle Indo-Aryan and seems to serve no purpose. Coming to terms with the opaque and pointless pun, this essay is aimed at a new interpretation of Kāśyapaparivarta § 68 and, it is hoped, a deeper understanding of the literary playfulness inherent in the making of the Kāśyapaparivarta as a so-called early Mahāyāna sūtra against the backdrop of the Sanskritization of Buddhist sūtra literature.
Bias Correction of Zero-Inflated RCM Precipitation Fields: A Copula-Based Scheme for Both Mean and Extreme Conditions
Authors: Maity Rajib , Suman Mayank , Laux Patrick , Kunstmann Harald 
Published: February 2019

Abstract
Changes in extreme precipitation due to climate change often require the application of methods to bias correct simulated atmospheric fields, including extremes. Most existing bias correction techniques (i) only focus on the bias in the mean value or on the extreme values separately, and (ii) exclude zero values from analysis, even though their presence is significant in daily precipitation. We developed a copula-based bias correction scheme that is suitable for zero-inflated daily precipitation data to correct the bias in mean as well as in extreme precipitation at any specific statistical quantile. In considering the whole of Germany as a test bed, the proposed scheme is found to work well across the entire study area, including the German Alpine regions. The joint distribution between observed and regional climate model (RCM)-derived precipitation is developed through copulas. In particular, the joint distribution is modified to make it discrete at zero in order to account for zero values. The benefit of considering zero precipitation values is revealed through the improved performance of bias correction both in the mean and extreme values. Second, the quantile that best captures the bias (whether in the mean or any extreme value) is determined for a specific location and varies spatially and seasonally. This relaxation in selecting the location-specific optimal quantile renders the proposed methodology spatially transferable. By acknowledging possible changes in extreme precipitation due to climate change, the proposed scheme is expected to be suitable for climate change impact assessments for extreme events worldwide.
A Quantitative Self-Assessment of Seminarians’ Response to a Curriculum Addition on Marriage, Sexuality, FertilityCare, and Naprotechnology: The Kenrick–Glennon Experience (2006–2015)
Authors: Daly K. Diane , Richárd Edward , Hilgers Thomas W. 
Published: February 2019

A special course on Marriage, the Family and Human Sexuality was established at Kenrick-Glennon Seminary in St. Louis so as to assist the seminarians in their better understanding of the Church’s teaching relative to natural methods of family planning and women’s health care. This article compares the response at the beginning of this three-credit semester course to the same seven-item questionnaire given at the conclusion of the course. The pre- and postcourse scores were calculated for each of the questions. The scores obtained after the course were all significantly higher than they were before the course with p values ranging from 0.01 to <0.0001. Four of the items showed marked improvement including an understanding of the church’s teaching related to natural methods, current methods of natural family planning, the impact of a natural method on a couple’s marriage, and also the impact of a natural method on family life. Statistically significant improvement was also seen in their understanding of the topic of natural family planning and the Creighton Model System and its relevance toward the seminarian’s vocation, the use of the methods to either achieve or avoid pregnancy, and how contraception and abortion are linked. In these last three items, the level of statistical significance was quite high, although not as high as the other four items. There were 104 seminarians over an eight-year period of time, who provided answers to these questions, both before and after the course. This course was modeled after a course that was initiated at the Pope Paul VI Institute for the Study of Human Reproduction, which was for priests, seminarians, and Catholic leaders, titled Love & Life Unlimited. Nontechnical Summary: This is an evaluation of a ten-point, seven-question questionnaire that was utilized at the beginning of a course at Kenrick Seminary in Marriage, Sexuality, Creighton Model and NaProTECHNOLOGY. The same questionnaire was given to the students at the beginning of the course and then two to three months later at the conclusion of the three-credit course. The results show that there is a significant improvement in the seminarians’ knowledge and general attitude about natural methods of family planning and suggests that such courses would be beneficial to establish in seminaries throughout the country.
Is interferential current effective in the management of pain, range of motion, and edema following total knee arthroplasty surgery? A randomized double-blind controlled trial
Authors: Kadı Mehmet Resul , Hepgüler Simin , Atamaz Funda Calıs , Dede Emine , Aydoğdu Semih , Aktuglu Kemal , Ozkayın Nadir , Ozturk Cihat 
Published: February 2019

Objective: To investigate the effectiveness of interferential current implementation following total knee arthroplasty surgery. Design: Double-blind randomized controlled study. Setting: Orthopedics and traumatology in-patient clinic. Participants: From an initial enrollment of 132 patients, 113 who met the study inclusion criteria were randomly separated into two groups: the interferential current group ( n = 57) and the sham current group ( n = 56). A total of 98 patients completed the study: 49 in the interferential current group and 49 in the sham group. Intervention: Patients in the interferential current group received interferential current treatment for 30 minutes, twice a day for five days postoperatively. For the patients in the sham interferential current treatment group, the same pads were applied to the patients for the same time periods but no electrical stimulation was applied. Main outcome measures: Patients were assessed in respect of pain, range of motion (ROM), edema, and the amount of paracetamol used at baseline and on the 5th and 30th days after surgery. Results: No significant difference was determined between the groups in respect of pain, ROM, and edema at days 0, 5, and 30. At the end of the 5th day, the amount of paracetamol used was significantly lower in the interferential current group ( P < 0.05). Conclusion: In this study, both groups showed significant improvements in pain, ROM, and edema with no significant difference between the groups. Although there was a significant difference in paracetamol intake of the two groups, this cannot be argued as showing the effectiveness of interferential current.
Predicting outcomes following holistic breathlessness services: A pooled analysis of individual patient data
Authors: Brighton Lisa Jane , Gao Wei , Farquhar Morag , Booth Sara , Bajwah Sabrina , Man William D-C , Reilly Charles C , Yi Deokhee , Higginson Irene J , Maddocks Matthew 
Published: February 2019

Background: Holistic breathlessness services have been developed for people with advanced disease and chronic breathlessness, leading to improved psychological aspects of breathlessness and health. The extent to which patient characteristics influence outcomes is unclear. Aim: To identify patient characteristics predicting outcomes of mastery and distress due to breathlessness following holistic breathlessness services. Design: Secondary analysis of pooled individual patient data from three clinical trials. Our primary analysis assessed predictors of clinically important improvements in Chronic Respiratory Questionnaire mastery scores (+0.5 point), and our secondary analysis predictors of improvements in Numerical Rating Scale distress due to breathlessness (−1 point). Variables significantly related to improvement in univariate models were considered in separate backwards stepwise logistic regression models. Participants: The dataset comprised 259 participants (118 female; mean (standard deviation) age 69.2 (10.6) years) with primary diagnoses of chronic obstructive pulmonary disease (49.8%), cancer (34.7%) and interstitial lung disease (10.4%). Results: Controlling for age, sex and trial, baseline mastery remained the only significant independent predictor of improvement in mastery (odds ratio 0.57, 95% confidence intervals 0.43–0.74; p < 0.001), and baseline distress remained the only significant predictor of improvement in distress (odds ratio 1.64; 95% confidence intervals 1.35–2.03; p < 0.001). Baseline lung function, breathlessness severity, health status, mild anxiety and depression, and diagnosis did not predict outcomes. Conclusions: Outcomes of mastery and distress following holistic breathlessness services are influenced by baseline scores for these variables, and not by diagnosis, lung function or health status. Stratifying patients by levels of mastery and/or distress due to breathlessness appears appropriate for clinical trials and services.
Predictive factors for patients receiving intravitreal anti-vascular endothelial growth factor for the treatment of diabetic macular edema
Authors: Carroll Robert M , Yu Yinxi , VanderBeek Brian L 
Published: February 2019

Purpose: To determine whether anemia and other demographic or laboratory “risk factors” impact anti-vascular endothelial growth factor treatment in diabetic macular edema patients. Methods: This is a retrospective, time-varying cohort study using a medical claims database to identify new diabetic macular edema patients who had received at least one intravitreal injection of anti-vascular endothelial growth factor. Exclusion occurred for having <2 years in the plan prior to diabetic macular edema diagnosis, any history of proliferative retinopathy or any treatment that is used for diabetic macular edema. Covariates of interest were demographic characteristics, laboratory values, and clinical factors such as previous anti-vascular endothelial growth factor used, number of involved eyes, year of treatment, and time since last injection. Those variables that changed with time were assessed and updated at each visit. The main outcome measure was the odds of receiving treatment at any visit. Results: In total, 189 new diabetic macular edema patients with follow-up were analyzed, covering 729 visits with 543 (74.5%) receiving treatment. Univariate analysis showed that male gender (odds ratio: 0.54, 95% confidence interval: 0.32–0.91, p = 0.03), every week since last injection (odds ratio: 0.94, 95% confidence interval: 0.91–0.97, p = 0.001), and having two eyes affected (odds ratio: 2.09, 95% confidence interval: 1.10–3.97, p = 0.02) were associated with getting an injection. After multivariate analysis, only time since previous injection with every week that passed reduced the odds on having an injection at the next visit (odds ratio: 0.95, 95% confidence interval: 0.92–0.97, p < 0.001). Anemia was not associated with receiving an injection (odds ratio: 1.05, 95% confidence interval: 0.61–1.80, p = 0.86). Conclusion: This study used time-varying methodology to better identify which patients will likely need an injection at any one visit. While anemia was not found to impact injections, our results can aid future endeavors that may incorporate clinical visit information in developing a full prediction model to help make diabetic macular edema care more efficient.
Multimodal imaging evaluation of combined hamartoma of the retina and retinal pigment epithelium
Authors: Scupola Andrea , Grimaldi Gabriela , Sammarco Maria G , Sasso Paola , Marullo Michele , Blasi Maria A 
Published: February 2019

Purpose: Combined hamartoma of the retina and retinal pigment epithelium is a rare benign tumor characterized by a variable combination of glial, vascular, and pigmented components. The purpose of our study was to analyze the features of combined hamartoma of the retina and retinal pigment epithelium on optical coherence tomography angiography. Methods: Small case series of two cases of combined hamartoma of the retina and retinal pigment epithelium with macular and optic nerve involvement, evaluated with multimodal imaging including optical coherence tomography, fluorescein angiography, and optical coherence tomography angiography. Results: On optical coherence tomography, combined hamartoma of the retina and retinal pigment epithelium is characterized by disruption of the inner neurosensory retina and a variable degree of involvement of the external retina. Optical coherence tomography angiography showed diffuse alterations of the retinal vessels of the superficial and deeper layers, extended to the peripapillary area. Vessel abnormalities included increased tortuosity and caliber of vessels, vascular traction, and vessel stretching within the lesion. Conclusion: Optical coherence tomography angiography allows in-depth multilayer analysis of tumor vascular network, highlighting the fine abnormalities of retinal vasculature characteristic of combined hamartoma of the retina and retinal pigment epithelium.
Predictors of Clinical Outcomes After Proximal Hamstring Repair
Authors: Bowman Eric N. , Marshall Nathan E. , Gerhardt Michael B. , Banffy Michael B. 
Published: February 2019

Background: Proximal hamstring avulsions cause considerable morbidity. Operative repair results in improved pain, function, and patient satisfaction; however, outcomes remain variable. Purpose: To evaluate the predictors of clinical outcomes after proximal hamstring repair. Study Design: Case series; Level of evidence, 4. Methods: We retrospectively reviewed proximal hamstring avulsions repaired between January 2014 and June 2017 with at least 1-year follow-up. Independent variables included patient demographics, medical comorbidities, tear characteristics, and repair technique. Primary outcome measures were the Single Assessment Numerical Evaluation (SANE), International Hip Outcome Tool–12 (iHOT-12), and Kerlan-Jobe Orthopaedic Clinic (KJOC) Athletic Hip score. Secondary outcome measures included satisfaction, visual analog scale for pain, Tegner score, and timing of return to sports. Results: Of 102 proximal hamstring repairs, 86 were eligible, 58 were enrolled and analyzed (67%), and patient-reported outcomes were available for 45 (52%), with a mean 29-month follow-up. The mean patient age was 51 years, and 57% were female. Acute tears accounted for 66%; 78% were complete avulsions. Open repair was performed on 90%. Overall satisfaction was 94%, although runners were less satisfied compared with other athletes ( P = .029). A majority of patients (88%) returned to sports by 7.6 months, on average, with 72% returning at the same level. Runners returned at 6.3 months, on average, but to the same level 50% of the time and at a decreased number of miles per week compared to nonrunners (15.7 vs 7.8, respectively; P < .001). Postoperatively, 78% had good/excellent SANE Activity scores, but the mean Tegner score decreased (from 5.5 to 5.1). Acute tears had higher SANE Activity scores. The mean iHOT-12 and KJOC scores were 99 and 77, respectively. Endoscopic repairs had equivalent outcome scores to open repairs, although conclusions were limited given the small number of patients in the endoscopic group. Greater satisfaction was noted in patients older than 50 years ( P = .024), although they were less likely to return to running ( P = .010). Conclusion: Overall, patient satisfaction and functionality were high. With the numbers available, we were unable to detect any significant differences in functional outcome scores based on patient age, sex, body mass index, smoking status, medical comorbidities, tear grade, activity level, or open versus endoscopic technique. Acute tears had better SANE Activity scores. Runners should be cautioned that they may be unable to return to the same preinjury activity level after proximal hamstring repair. Clinical Relevance: When counseling patients with proximal hamstring tears, runners and those with chronic tears should set appropriate expectations.