bluuebunny/crossref_metadata_2025_split huggingface dataset:
Administrative Data Are Unreliable for Ranking Hospital Performance Based on Serious Complications After Spine Fusion
Authors: Greenberg Jacob K. , Olsen Margaret A. , Poe John , Dibble Christopher F. , Yamaguchi Ken , Kelly Michael P. , Hall Bruce L. , Ray Wilson Z. 
Published: April 2021

Study Design.
Retrospective analysis of administrative billing data.

Objective.
To evaluate the extent to which a metric of serious complications determined from administrative data can reliably profile hospital performance in spine fusion surgery.

Summary of Background Data.
While payers are increasingly focused on implementing pay-for-performance measures, quality metrics must reliably reflect true differences in performance among the hospitals profiled.

Methods.
We used State Inpatient Databases from nine states to characterize serious complications after elective cervical and thoracolumbar fusion. Hierarchical logistic regression was used to risk-adjust differences in case mix, along with variability from low case volumes. The reliability of this risk-stratified complication rate (RSCR) was assessed as the variation between hospitals that was not due to chance alone, calculated separately by fusion type and year. Finally, we estimated the proportion of hospitals that had sufficient case volumes to obtain reliable (>0.7) complication estimates.

Results.
From 2010 to 2017 we identified 154,078 cervical and 213,133 thoracolumbar fusion surgeries. 4.2% of cervical fusion patients had a serious complication, and the median RSCR increased from 4.2% in 2010 to 5.5% in 2017. The reliability of the RSCR for cervical fusion was poor and varied substantially by year (range 0.04–0.28). Overall, 7.7% of thoracolumbar fusion patients experienced a serious complication, and the RSCR varied from 6.8% to 8.0% during the study period. Although still modest, the RSCR reliability was higher for thoracolumbar fusion (range 0.16–0.43). Depending on the study year, 0% to 4.5% of hospitals had sufficient cervical fusion case volume to report reliable (>0.7) estimates, whereas 15% to 36% of hospitals reached this threshold for thoracolumbar fusion.

Conclusion.
A metric of serious complications was unreliable for benchmarking cervical fusion outcomes and only modestly reliable for thoracolumbar fusion. When assessed using administrative datasets, these measures appear inappropriate for high-stakes applications, such as public reporting or pay-for-performance.

Level of Evidence: 3
Microinvasive Glaucoma Surgery in US Ophthalmology Residency: Surgical Case Log Cross-sectional Analysis and Proposal for New Glaucoma Procedure Classification
Authors: Qiu Mary , Woreta Fasika A. , Boland Michael V. 
Published: April 2021

Precis:
A cross-sectional sample of the US ophthalmology residency graduating class of 2018 revealed that 18.4% of residents logged <5 traditional glaucoma surgeries, and 63.4% logged at least 1 microinvasive glaucoma surgery (MIGS).

Purpose:
Describe the state of MIGS in US ophthalmology residency training and propose a glaucoma procedure classification system for residents’ surgical case logs.

Methods:
Deidentified case logs from residents graduating in 2018 were requested from US residency program directors.

Results:
Case logs were received for 152/488 (31%) residents from 36/115 (31%) programs. The mean number of traditional glaucoma surgeries per resident was 9.0±5.9 (range: 0 to 31). The mean number of MIGS per resident was 5.2±8.9 cases (range: 0 to 58). There were 28/152 (18.4%) residents from 16/36 (44.4%) programs who logged <5 traditional glaucoma surgeries as primary surgeon, and 3/152 (2.0%) residents from 3/36 (8.3%) programs who logged zero traditional glaucoma surgeries as primary surgeon. There were 98/152 (64.5%) residents from 32/36 (88.8%) programs who logged <5 MIGS as primary surgeon, and 48/152 (31.6%) residents from 25 of 36 (69.4%) programs who logged zero MIGS as primary surgeon. There were 104/152 (63.4%) residents from 33/36 (91.6%) programs who logged at least 1 MIGS as primary surgeon; there were 3/36 (8.3%) residency programs where no resident logged any MIGS as primary surgeon.

Conclusions:
US ophthalmology residents’ MIGS experience varies widely. Residents can satisfy glaucoma surgery requirements with some MIGS, even in the absence of adequate traditional glaucoma surgeries. We propose a residency case log classification system that better reflects the growing role of MIGS in clinical practice and helps ophthalmic educators more accurately track procedures requiring related skills.
Long-term all-cause mortality among asymptomatic individuals with 80th percentile of coronary calcium score based on age and gender in the St. Francis Heart Study
Authors: Chen Lu Q. , Weber Jonathan , Christian Timothy , Guerci Alan D. , Cao J. Jane 
Published: April 2021

Objectives
High coronary artery calcium score (CAC) is a significant risk factor for cardiovascular morbidity and mortality. We investigated the long-term outcome of subjects with elevated CAC.

Methods
We studied 1005 participants of The St. Francis Heart Study who were asymptomatic and apparently healthy and had CAC scores at 80th percentile or higher for age and gender. They were randomized to receive atorvastatin 20 mg daily or placebo for up to 5 years. We used an as-treated study design accounting for cross-overs at the end of the original trial. All-cause mortality risk was assessed using adjusted hazard ratios.

Results
Mean age was 59 ± 6 years and 26% (N = 263) were female. After 17 ± 3 years follow-up 176 subjects died. High CAC at baseline was associated with increased mortality risk with adjusted hazard ratio for logarithmic transformed CAC at 1.33 and 95% confidence interval 1.06–1.68. The mortality risk associated with CAC was similar between the group with high-sensitivity CRP ≥2 and <2 mg/dL. Those with a family history of premature coronary artery disease exhibited a higher mortality risk in association with high CAC with an adjusted hazard ratio 1.51 (1.09, 2.09).

Conclusion
Elevated CAC is an independent risk for long-term all-cause mortality. The screening of CAC score in addition to identifying conventional risk factors can differentiate asymptomatic individuals with and without increased long-term mortality risk.
Initial optimal medical therapy with or without invasive strategy for stable coronary disease: a meta-analysis and systematic review
Authors: Barbarawi Mahmoud , Alabdouh Ahmad , Barbarawi Owais , Lakshman Harini , Alkasasbeh Mariam , Khallad Muad , Radaideh Qais 
Published: April 2021

Introduction
There is a persistent controversy regarding the benefit and timing of angiography in patients with stable coronary artery disease (CAD). With this meta-analysis of randomized controlled trials (RCTs) the advantages of initial invasive strategy and medical therapy compared with only medical therapy.

Methods
We conducted a literature search of the following databases Pubmed/MEDLINE, Cochrane Library and Embase. Data was collected from all the RCTs that compared early invasive approach with medical therapy alone in treating stable CAD which was conducted by two independent authors. Primary outcomes were all-cause mortality and myocardial infarction (MI), while the secondary outcomes included major adverse cardiovascular events (MACE), cardiovascular mortality, cardiovascular hospitalization, hospitalization due to unstable angina and revascularization events. The Mantel–Haenszel random-effects model was used to estimate risk ratios (RRs) and 95% confidence intervals (CIs).

Results
We included 15 RCTs (13 916 patients, mean age 63.1, 78.9% men). The early invasive strategy, compared with medical therapy alone, did not reveal a significant reduction in the incidence of all-cause mortality (RR, 0.94; 95% CI, 0.84–1.05, P = 0.30) or MI (RR, 0.93; 95% CI, 0.79–1.10, P = 0.42). Furthermore, the early invasive strategy did not reduce the incidence of cardiovascular mortality, cardiovascular hospitalization or the revascularization rate compared with medical therapy alone (P > 0.05). However, the incidence of MACE and hospitalization due to unstable angina were lower in patients treated with early invasive strategy (RR, 0.79; 95% CI, 0.63–0.99, P = 0.04), and (RR, 0.46; 95% CI, 0.32–0.67, P < 0.0001), respectively.

Conclusions
Early invasive strategy with medical therapy did not reduce the incidence of all-cause mortality and MI when compared with medical therapy alone among patients with stable CAD with significant stenosis. However, there was a significant reduction in the incidence of MACE and hospitalization due to unstable angina in the early invasive group.
Systemic immune-inflammation index predicts the severity of coronary stenosis in patients with coronary heart disease
Authors: Liu Yehong , Ye Ting , Chen Liang , Jin Tianhui , Sheng Ying , Wu Gangyong , Zong Gangjun 
Published: April 2021

Background
Coronary atherosclerosis is a systemic chronic inflammatory disease with variable occurrence and progression. Some laboratory parameters, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and C-reactive protein (CRP) level, are used to evaluate the degree of inflammation and the severity of coronary artery disease (CAD). The neutrophil*platelet/lymphocyte is a novel systemic immune-inflammation index (SII), and its relationship with the development and severity of CAD is unclear.

Objective
To investigate the association between the SII and the severity of CAD.

Methods
Three-hundred and ninety-five patients who underwent coronary angiography were enrolled; among whom, 285 patients were included in the CAD group and 110 patients were included in the non-CAD group according to the WHO guidelines. Patients with CAD were further divided according to the Gensini score into the severe coronary stenosis group and the mild coronary stenosis group. The SII was calculated using the following formula: neutrophil*platelet/lymphocyte.

Results
When the cutoff value of the SII was set at 439.44, the predictive power of CAD was the highest, with a sensitivity and specificity of 64.6 and 68.2%, respectively. When the cutoff value of the SII was set at 652.83, the predictive power of severe coronary stenosis was the highest, with a sensitivity and specificity of 71.0 and 86.0%, respectively. The area under the curve of the SII in predicting severe coronary stenosis was greater than that of the NLR, PLR and CRP level.

Conclusion
The SII is an independent risk factor for the occurrence and severity of CAD.
In (deficit) schizophrenia, a general cognitive decline (G-CoDe) partly mediates the effects of neuro-immune and neuro-oxidative toxicity on the symptomatome and quality of life
Authors: Maes Michael , Kanchanatawan Buranee 
Published: April 2021

ABSTRACTObjectiveSchizophrenia and deficit schizophrenia are accompanied by neurocognitive impairments. The aim of this study was to examine whether a general factor underpins impairments in key Cambridge Neuropsychological Test Automated Battery (CANTAB) probes, verbal fluency (VFT), world list memory (WLM), true recall, and Mini Mental State Examination (MMSE).MethodsWe recruited 80 patients with schizophrenia and 40 healthy controls. All patients were assessed using CANTAB tests, namely paired-association learning (PAL), rapid visual information (RVP), spatial working memory (SWM), one touch stocking (OTS), intra/extradimensional set shifting (IED), and emotional recognition test (ERT).ResultsWe found that a general factor, which is essentially unidimensional, underlies those CANTAB, VFT, WLM, True Recall, and MMSE scores. This common factor shows excellent psychometric properties and fits a reflective model and, therefore, reflects a general cognitive decline (G-CoDe) comprising deficits in semantic and episodic memory, recall, executive functions, strategy use, rule acquisition, visual sustained attention, attention set-shifting, and emotional recognition. Partial least Square analysis showed that 40.5% of the variance in G-Code is explained by CCL11, IgA to tryptophan catabolites, and increased oxidative toxicity; and that G-CoDe explains 44.8% of the variance in a general factor extracted from psychosis, hostility, excitation, mannerism, negative symptoms, formal thought disorders, and psychomotor retardation; and 40.9% in quality of life scores. The G-CoDe is significantly greater in deficit than in nondeficit schizophrenia.ConclusionsA common core shared by a multitude of neurocognitive impairments (G-CoDe) mediates the effects of neurotoxic pathways on the phenome of (deficit) schizophrenia.
Leveraging Health Systems Data to Characterize a Large Effect Variant Conferring Risk for Liver Disease in Puerto Ricans
Authors: Belbin Gillian M. , Rutledge Stephanie , Dodatko Tetyana , Cullina Sinead , Turchin Michael C. , Kohli Sumita , Torre Denis , Yee Muh-Ching , Gignoux Christopher R. , Abul-Husn Noura S. , Houten Sander M. , Kenny Eimear E. 
Published: April 2021

AbstractBroad-scale adoption of genomic data in health systems offers opportunities for extending methods for the discovery of variation linked to underlying genomic disease risk. We applied a population-scale linkage mapping approach in a large multi-ethnic biobank to a spectrum of disease outcomes derived from Electronic Health Records (EHRs) and uncovered a risk locus for liver disease. We used genome sequencing and in silico approaches to fine-map the signal to a non-coding variant (c.2784-12T>C) in the gene ABCB4. In vitro analysis confirmed the variant disrupted splicing of the ABCB4 pre-mRNA. Four of five homozygotes had evidence of advanced liver disease, and there was a significant association with liver disease among heterozygotes, suggesting the variant is linked to increased risk of liver disease in an allele dose-dependent manner. Population-level screening revealed the variant to be at a carrier rate of 1.95% in Puerto Rican individuals, likely as the result of a Puerto Rican founder effect. This work demonstrates that integrating EHR and genomic data at a population-scale can facilitate novel strategies for understanding the continuum of genomic risk for common diseases, particularly in populations underrepresented in genomic medicine.
Novel prognostic determinants of COVID-19-related mortality: a pilot study on severely-ill patients in Russia
Authors: Rubina K. , Shmakova A. , Shabanov A. , Andreev Yu. , Borovkova N. , Kulabukhov V. , Evseev A. , Popugaev K. , Petrikov S. , Semina E. 
Published: April 2021

AbstractCOVID-19 pandemic has posed a severe healthcare challenge calling for an integrated approach in determining the clues for early non-invasive diagnostics of the potentially severe cases and efficient patient stratification.Here we analyze the clinical, laboratory and CT scan characteristics associated with high risk of COVID-19-related death outcome in the cohort of severely-ill patients in Russia. The data obtained reveal that elevated dead lymphocyte counts, decreased early apoptotic lymphocytes, decreased CD14+/HLA-Dr+ monocytes, increased expression of JNK in PBMCs, elevated IL-17 and decreased PAI-1 serum levels are associated with a high risk of COVID-19-related mortality thus suggesting them to be new prognostic factors. This set of determinants could be used as early predictors of potentially severe course of COVID-19 for trials of prevention or timely treatment.FundingThe reported study was funded by RFBR according to the research project № 20-24-60029.
Neutrophil-mediated Oxidative Stress and Albumin Structural Damage Predict COVID-19-associated Mortality
Authors: Badawy Mohamed A. , Yasseen Basma A. , El-Messiery Riem M. , Abdel-Rahman Engy A. , Elkhodiry Aya A. , Kamel Azza G. , Shedra Asmaa M. , Hamdy Rehab , Zidan Mona , Al-Raawi Diaa , Hammad Mahmoud , Elsharkawy Nahla , Ansary Mohamed El , Al-Halfawy Ahmed , Elhadad Alaa , Hatem Ashraf , Abouelnaga Sherif , Dugan Laura L. , Ali Sameh S. 
Published: April 2021

AbstractHuman serum albumin (HSA) is the frontline antioxidant protein in blood with established anti-inflammatory and anticoagulation functions. Here we report that COVID-19-induced oxidative stress inflicts structural damages to HSA and is linked with mortality outcome in critically ill patients. We recruited 25 patients who were followed up for a median of 12.5 days (1-35 days), among them 14 had died. Analyzing blood samples from patients and healthy individuals (n=10), we provide evidence that neutrophils are major sources of oxidative stress in blood and that hydrogen peroxide is highly accumulated in plasmas of non-survivors. We then analyzed electron paramagnetic resonance (EPR) spectra of spin labelled fatty acids (SLFA) bound with HSA in whole blood of control, survivor, and non-survivor subjects (n=10-11). Non-survivors’ HSA showed dramatically reduced protein packing order parameter, faster SLFA correlational rotational time, and smaller S/W ratio (strong-binding/weak-binding sites within HSA), all reflecting remarkably fluid protein microenvironments. Stratified at the means, Kaplan–Meier survival analysis indicated that lower values of S/W ratio and accumulated H2O2 in plasma significantly predicted in-hospital mortality (S/W<0.16, 80% (9/12) vs. S/W>0.16, 20% (2/10), p=0.008; plasma [H2O2]>7.1 μM, 83.3% (5/6) vs. 16.7% (1/6), p=0.049). When we combined these two parameters as the ratio ((S/W)/[H2O2]) to derive a risk score, the resultant risk score lower than the mean (< 0.0253) predicted mortality with 100% accuracy (100% (6/6) vs. 0% (0/6), logrank χ2 = 12.01, p = 5×10−4). The derived parameters may provide a surrogate marker to assess new candidates for COVID-19 treatments targeting HSA replacements.
Trust boosts recovery of countries from COVID-19
Authors: Lenton Timothy M. , Boulton Chris A. , Scheffer Marten 
Published: April 2021

AbstractWhy have some countries suppressed waves of the COVID-19 pandemic much more effectively than others? We find that the decay rate of daily cases or deaths from peak levels varies by a factor of ∼40 between countries. This measure of country-level resilience to COVID-19 is positively correlated with trust within society, and with the adaptive increase in stringency of government interventions when epidemic waves occur. All countries where >40% agree “most people can be trusted” achieve a near complete reduction of new cases and deaths. In contrast, countries where governments maintain greater background stringency tend to be less trusting and less resilient. Building trust is therefore critical to resilience, both to epidemics and other unexpected disruptions, of which COVID-19 is unlikely to be the last.
Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19
Authors: Klaric Lucija , Gisby Jack S. , Papadaki Artemis , Muckian Marisa D. , Macdonald-Dunlop Erin , Zhao Jing Hua , Tokolyi Alex , Persyn Elodie , Pairo-Castineira Erola , Morris Andrew P , Kalnapenkis Anette , Richmond Anne , Landini Arianna , Hedman Åsa K. , Prins Bram , Zanetti Daniela , Wheeler Eleanor , Kooperberg Charles , Yao Chen , Petrie John R. , Fu Jingyuan , Folkersen Lasse , Walker Mark , Magnusson Martin , Eriksson Niclas , Mattsson-Carlgren Niklas , Timmers Paul R.H.J. , Hwang Shih-Jen , Enroth Stefan , Gustafsson Stefan , Vosa Urmo , Chen Yan , Siegbahn Agneta , Reiner Alexander , Johansson Åsa , Thorand Barbara , Gigante Bruna , Hayward Caroline , Herder Christian , Gieger Christian , Langenberg Claudia , Levy Daniel , Zhernakova Daria V. , Smith J. Gustav , Campbell Harry , Sundstrom Johan , Danesh John , Michaëlsson Karl , Suhre Karsten , Lind Lars , Wallentin Lars , Padyukov Leonid , Landén Mikael , Wareham Nicholas J. , Göteson Andreas , Hansson Oskar , Eriksson Per , Strawbridge Rona J. , Assimes Themistocles L. , Esko Tonu , Gyllensten Ulf , Baillie J. Kenneth , Paul Dirk S. , Joshi Peter K. , Butterworth Adam S. , Mälarstig Anders , Pirastu Nicola , Wilson James F. , Peters James E. 
Published: April 2021

AbstractSevere COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at theFASlocus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.