bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Approach to Developing a Discordance Index for Older Adults With Chronic Kidney Disease
Authors: Hall Rasheeda K , Zhou Hui , Reynolds Kristi , Harrison Teresa N , Bowling C Barrett 
Published: October 2019

Abstract

Background
Older adults with chronic kidney disease (CKD)-discordant conditions (comorbid conditions with treatment recommendations that potentially complicate CKD management) have higher risk of hospitalization and death. Our goal is to develop a CKD-Discordance Index using electronic health records to improve recognition of discordance.

Methods
This retrospective cohort study included Kaiser Permanente Southern California patients aged ≥65 years and older with incident CKD (N = 30,932). To guide inclusion of conditions in the Index and weight each condition, we first developed a prediction model for 1-year hospitalization risk using Cox regression. Points were assigned proportional to regression coefficients derived from the model. Next, the CKD-Discordance Index was calculated as an individual’s total points divided by the maximum possible discordance points. The association between CKD-Discordance Index and hospitalizations, emergency department visits, and mortality was accessed using multivariable-adjusted Cox regression model.

Results
Overall, mean (SD) age was 77.9 (7.6) years, 55% of participants were female, 59.3% were white, and 32% (n = 9,869) had ≥1 hospitalization during 1 year of follow-up. The CKD-Discordance Index included the following variables: heart failure, gastroesophageal reflux disease/peptic ulcer disease, osteoarthritis, dementia, depression, cancer, chronic obstructive pulmonary disease/asthma, and having four or more prescribers. Compared to those with a CKD-Discordance Index of 0, adjusted hazard ratios (95% confidence interval) for hospitalization were 1.39 (1.27–1.51) and 1.81 (1.64–2.01) for those with a CKD-Discordance Index of 0.001–0.24 and ≥0.25, respectively (ptrend &lt; .001). A graded pattern of risk was seen for emergency department visits and all-cause mortality.

Conclusion
A data-driven approach identified CKD-discordant indicators for a CKD-Discordance Index. Higher CKD-Discordance Index was associated with health care utilization and mortality.
Life-Course Circumstances and Frailty in Old Age Within Different European Welfare Regimes: A Longitudinal Study With SHARE
Authors: Van Der Linden Bernadette Wilhelmina Antonia , Sieber Stefan , Cheval Boris , Orsholits Dan , Guessous Idris , Gabriel Rainer , Von Arx Martina , Kelly-Irving Michelle , Aartsen Marja , Blane David , Boisgontier Matthieu P , Courvoisier Delphine , Oris Michel , Kliegel Matthias , Cullati Stéphane 
Published: October 2019

Abstract

Objectives
This study aimed to assess whether cumulative disadvantage in childhood misfortune and adult-life socioeconomic conditions influence the risk of frailty in old age and whether welfare regimes influence these associations.

Method
Data from 23,358 participants aged 50 years and older included in the longitudinal SHARE survey were used. Frailty was operationalized according to Fried’s phenotype as presenting either weakness, shrinking, exhaustion, slowness, or low activity. Confounder-adjusted mixed-effects logistic regression models were used to analyze associations of childhood misfortune and life-course socioeconomic conditions with frailty.

Results
Childhood misfortune and poor adult-life socioeconomic conditions increased the odds of (pre-)frailty at older age. With aging, differences narrowed between categories of adverse childhood experiences (driven by Scandinavian welfare regime) and adverse childhood health experiences (driven by Eastern European welfare regime), but increased between categories of occupational position (driven by Bismarckian welfare regime).

Discussion
These findings suggest that childhood misfortune is linked to frailty in old age. Such a disadvantaged start in life does not seem to be compensated by a person’s life-course socioeconomic trajectory, though certain types of welfare regimes affected this relationship. Apart from main occupational position, our findings do not support the cumulative dis/advantage theory, but rather show narrowing differences.
Correlation of Stool Frequency and Abdominal Pain Measures With Simple Endoscopic Score for Crohn’s Disease
Authors: Lewis James D , Rutgeerts Paul , Feagan Brian G , D’haens Geert , Danese Silvio , Colombel Jean-Frederic , Reinisch Walter , Rubin David T , Selinger Christian , Bewtra Meenakshi , Barcomb Lisa , Lacerda Ana P , Wallace Kori , Butler James W , Wu Meijing , Zhou Qian , Liao Xiaomei , Sandborn William J 
Published: October 2019

Abstract

Background
The Crohn’s Disease Activity Index (CDAI) has been criticized for being weakly correlated with bowel inflammation. We assessed correlation between Simple Endoscopic Score for Crohn’s Disease (SES-CD) and individual CDAI items stratified by disease location to better understand this relationship.

Methods
We pooled patient-level data from 3 placebo-controlled Crohn’s disease (CD) trials that tested adalimumab, upadacitinib, and risankizumab. Disease location was defined as ileum only, colon only, or ileocolonic based upon colonoscopy at study entry. Pearson correlation coefficients and linear regression assessed correlations between items of the CDAI and SES-CD.

Results
A total of 353 patients were included (20.7% ileal, 30.6% colonic, 48.7% ileocolonic disease). Crohn’s Disease Activity Index and SES-CD scores were moderately correlated (R = 0.33; P < 0.001). Among CDAI items, the strongest correlations with SES-CD were seen with very soft or liquid stool frequency (SF) and patient-reported outcome 2 (PRO2; which includes SF and abdominal pain score; both R = 0.36; P < 0.001); these correlations were numerically stronger in colonic disease (SF: R = 0.46; P < 0.001; PRO2: R = 0.44; P < 0.001) than in ileal disease (SF: R = 0.14; P = 0.23; PRO2: R = 0.21; P = 0.07), although a test for interaction was not significant. In adjusted linear regression models, the proportion of mucosa that was inflamed and the proportion of mucosa with ulceration were positively correlated, whereas the presence of strictures was inversely correlated with SF.

Conclusions
The SF item of the CDAI is moderately correlated with SES-CD and independently correlated with mucosal ulceration, inflammation, and strictures. Understanding why bowel inflammation as measured endoscopically does not correlate more strongly with patients’ symptoms could help develop scales that link CD pathology to patient experience.
Why do marine endotherms eat gelatinous prey?
Authors: Thiebot Jean-Baptiste , McInnes Julie C 
Published: October 2019

AbstractThere is growing evidence that gelatinous zooplanktonic organisms (“gelata”) are regular prey for marine endotherms. Yet the consumption of gelata is intriguing in terms of the energy reward, because endotherms have a high energy demand and the consumption of gelata provides little energy return. In this paper, we take advantage of recent advances in diet analysis methods, notably animal-borne video loggers and DNA analysis in seabirds, to examine our current understanding of this interaction. We suggest that several hypotheses commonly raised to explain predation on gelata (including increased biomass, reduced prey availability, and secondary ingestion) have already been tested and many lack strong support. We emphasize that gelata are widely consumed by endotherms (121 cases reported across 82 species of seabirds, marine mammals, and endothermic fishes) from the Arctic to the Antarctic but noticeably less in the tropics. We propose that in line with research from terrestrial ecosystems atypical food items might be beneficial to the consumers in a non-energetic context, encompassing self-medication, and responding to homeostatic challenges. Changing the “last resort” context for a “functional response” framework may improve our understanding of widespread predation on gelata. Further biochemical analyses are needed to formally examine this perspective.
Perfectly matched absorbing layer for modelling transient wave propagation in heterogeneous poroelastic media
Authors: He Yanbin , Chen Tianning , Gao Jinghuai 
Published: October 2019

AbstractThe perfectly matched layer (PML) has been demonstrated to be an efficient absorbing boundary for near-field wave simulation. For heterogeneous media, the property of the PML needs to be carefully specified to avoid numerical instability and artificial reflection because part of it lies at the discontinuous interface. Coupled acoustic-poroelastic (A-P) media or coupled elastic-poroelastic (E-P) media often arise in the field of geophysics. However, PMLs that appropriately terminate these heterogeneous poroelastic media are still lacking. The main purpose of this paper is to explore the application of unsplit PMLs for transient wave modeling in infinite, heterogeneous, coupled A-P media or coupled E-P media. To this end, a consistent derivation of memory-efficient PML formulations for the second-order Biot's equations, elastic wave equations and acoustic wave equations is performed based on complex coordinate transformation using auxiliary differential equations. Furthermore, the interface boundary conditions inside the absorbing layer are rigorously derived for the considered A-P and E-P cases. Finally, the weak form of PML formulations for coupled poroelastic problems is presented. The finite element method is used to validate the proposed PML based on several two-dimensional benchmarks. The accuracy and stability of weak PML formulations are investigated. In particular, for coupled acoustic-poroelastic PML, two extreme (open-pore and sealed-pore) interface conditions are considered and PML results are compared with known analytical solutions. This study demonstrates the ability of the PML to effectively eliminate outgoing bulk waves and surface waves in coupled poroelastic media.
The Diverse Upper Reference Limits of Serum Thyroid-Stimulating Hormone on the Same Platform for Pregnant Women in China
Authors: Wang Guocheng , Zhang Guojun 
Published: October 2019

Abstract

Objective
To describe the diverse upper reference limits of serum thyroid stimulating hormone on the same platform for pregnant women in China.

Methods
The trimester-specific and population-specific TSH reference intervals for pregnant women were established, and then 5 reference intervals on the same platform in China were compared with the reference intervals derived from the present study and the manufacturer.

Results
The most striking difference in the upper reference limits of TSH among 5 reference intervals on the same platform was shown at the first trimester of pregnancy. The calculated regional prevalence rates of subclinical thyroid diseases varied using the data derived from 30,771 pregnant women who visited the largest obstetric center in our district from 2008 to 2018.

Conclusion
We reported differences among 7 reference intervals of TSH on the same platform and showed the changing population factors significantly affected them.
77. Antimicrobial Prescribing Practices for Enteric Bacterial Infections in an Integrated Rural Healthcare System, 2004–2017
Authors: Olson Scott C , Watkins Louise Francois , Watkins Louise Francois , Walter Elaine Scallan , Friedman Cindy R , Friedman Cindy R , McLean Huong 
Published: October 2019

Abstract

Background
Bacterial enteric infections are common in the United States, but few studies have evaluated antibiotic prescribing practices for these illnesses. Unnecessary antibiotics can lead to adverse events and emergence of antimicrobial resistance. We assessed treatment practices among patients with laboratory-confirmed enteric infections in a large regional healthcare system.

Methods
We used electronic health records to identify patients with laboratory-confirmed nontyphoidal Salmonella, Shigella, Shiga toxin-producing E. coli (STEC), and Campylobacter infections from 2004 to 2017. We extracted relevant clinical data, including diagnosis codes for chronic conditions and receipt of immunosuppressive medications in the 60 days before and after the encounter, and antibiotic prescriptions in the 14 days after the encounter. We defined an appropriate treatment based on pathogen, patient characteristics, and IDSA practice guidelines for the study period.

Results
We identified 2,064 patients infected with enteric pathogens: 1,251 (61%) with Campylobacter, 564 (27%) Salmonella, 199 (10%) STEC, and 50 (2%) Shigella. Overall, 425 (20%) patients were immunocompromised, ranging from 17% for Salmonella to 46% for STEC. There were 220 (11%) hospitalizations. The frequency of antibiotic prescribing was highest for Campylobacter (60%), followed by Shigella (50%) and Salmonella (49%). Prescriptions were appropriate for 62% of Campylobacter cases, 92% of Shigella, and 70% of Salmonella. Antibiotics were prescribed for 39% of STEC infections although they are generally not indicated. Appropriate treatment was highest for children with Campylobacter (87%) and lowest for adults ≥50 years with Campylobacter (42%). Among those with Salmonella, appropriate treatment was higher in those with a comorbidity (79% vs. 68% without, P < 0.05). Rates of appropriate use did not improve over time.

Conclusion
Antibiotic prescribing for laboratory-confirmed enteric infections was frequently inappropriate and inconsistent with practice guidelines. Antibiotic stewardship initiatives should address acute bacterial gastrointestinal infections in addition to other common infections.

Disclosures
All Authors: No reported Disclosures.
84. Evaluation of the NHSN Standardized Infection Ratio (SIR) Risk Adjustment for HO-CDI in Oncology and ICU Patients in General Acute Care Hospitals
Authors: Polage Christopher R , Quan Kathleen A , Madey Keith M , Meyers Frank , Krishna Sneha , Grein Jonathan , Gibbs Laurel , Yokoe Deborah S , Mabalot Shannon C , Chinn Raymond , Hallmark Amy , Rubin Zachary A , Fontenot Michael , Cohen Stuart , Wightman Debbra , Birnbaum David , Huang Susan S , Torriani Francesca J 
Published: October 2019

Abstract

Background
The NHSN healthcare-facility onset Clostridioides difficile infection (CDI) standardized infection ratio (SIR) is used to compare hospital quality and set hospital reimbursement but inadequate risk adjustment could penalize hospitals unnecessarily. We hypothesized that general hospitals with large oncology and/or ICU populations were not fully adjusted in the 2015 NHSN acute care hospital CDI Laboratory-Identified (LabID) event prediction model and SIRs would be affected.

Methods
We validated a negative binomial regression HO-CDI event prediction model identical to the 2015 published model and used FY2016 data from eight general hospitals in California to test our hypothesis. We compared HO-CDI events and SIR values, with and without oncology/hematopoietic stem cell transplant or ICU unit events, patient-days, admissions, bed counts, and adjustment parameters included.

Results
Seven major teaching and one nonteaching general acute care hospitals were included (see Table). Eight had oncology/hematopoietic stem cell transplant units; seven had ≥43 ICU beds (median: 134; interquartile range [IQR]: 84–161). The median facility unmodified FacWideIn SIR was 1.23 [IQR: 1.15, 1.29]. Removal of oncology unit data resulted in a 15% median facility decrease in HO-CDI events (IQR: 14%, 21%) and −8% median facility decrease in SIR (IQR: −2%, −14%). Removal of ICU unit data resulted in a 22% median facility decrease in HO-CDI events (IQR: 16%, 26%) and 97% median facility increase in SIR at each facility (IQR: 78%, 105%).

Conclusion
The ICU bed adjustment in the 2015 NHSN SIR is a powerful correction that fully adjusted for ICU HO-CDI events at all hospitals in the study. However, the lack of risk adjustment for oncology/hematopoietic stem cell transplant unit HO-CDI events suggests that the current model unfairly penalizes general acute facilities, many of which also provide specialized oncologic care. Thus, the model needs to be re-adjusted to account for this important specialty care population in general acute care facilities.

Disclosures
All Authors: No reported Disclosures.
841. Implications of C. difficile Treatment on Environmental Contamination: A Randomized Controlled Trial with Microbiologic, Environmental, and Molecular Outcomes
Authors: Turner Nicholas A , Gergen Maria , Rutala William , Sexton Daniel J , Fowler, Jr. Vance G , Addison Rachel , Anderson Deverick J 
Published: October 2019

Abstract

Background
Clostridioides difficile is a leading cause of healthcare-associated infection. Despite multimodal prevention efforts, in-hospital transmission continues to occur. In this study, we tested whether the choice of treatment can reduce C. difficile shedding and contamination of the inpatient environment.

Methods
We conducted a prospective, unblinded, randomized controlled trial of adult inpatients with C. difficile at Duke University Hospital. Thirty subjects were randomized 1:1:1 to receive metronidazole, vancomycin, or fidaxomicin. Stool specimens and environmental samples from five high-touch surfaces were serially collected throughout each subject’s hospital stay. Each specimen was assessed by quantitative culture and PCR ribotyping. Primary outcomes included the change over time in C. difficile stool burden and environmental contamination relative to treatment choice. As a secondary outcome, we examined the correlation between infecting strains and contaminating strains present in the care environment.

Results
Relative to metronidazole (Figure 1), C. difficile stool shedding decreased more rapidly for patients receiving vancomycin (P = 0.05) and most rapidly with fidaxomicin (P = 0.002). Treatment choice had no significant effect on total C. difficile colony counts across sites sampled over time (Figure 2). However, both vancomycin (P = 0.001) and fidaxomicin (P = 0.01) were associated with lower proportions of positive environmental cultures than metronidazole (Figure 3). Ribotyping of subjects’ stool isolates matched surrounding environmental isolates >90% of the time (Figure 4).

Conclusion
Fidaxomicin and vancomycin reduced C. difficile stool burden more rapidly than metronidazole. Environmental results were mixed: fidaxomicin and vancomycin were associated with fewer positive surface cultures, but no difference in total colony counts. High concordance between stool and environmental ribotypes confirms that most room contamination originated from study subjects, without a significant contribution from any additional sources. Treatment choice may have a role in reducing C. difficile contamination of the hospital environment. Further study is needed to assess for effect on disease incidence.

Disclosures
All Authors: No reported Disclosures.
843. The PALM Consortium: A Multicenter, Multioutbreak Randomized Controlled Trial of Ebola Virus Disease Therapeutics
Authors: Mulangu Sabue 
Published: October 2019

Abstract

Background
Recent outbreaks of Ebola virus disease in the Democratic Republic of the Congo (DRC) reinforce the desperate need to establish definitively the comparative safety and efficacy of different medical countermeasures (MCM).

Methods
Through a multipartner governance framework under WHO coordination, the Institut National de Recherche Biomédicale and NIAID collaborated with clinical partners (the MOH, ALIMA, MSF) to launch a randomized controlled trial in 2018 in the North Kivu/Ituri provinces of DRC. PCR+ participants receiving enhanced supportive care are being randomized 1:1:1:1 to receive either ZMapp™ (control arm), remdesivir, mAb114, or REG-EB3 according to standard treatment regimens. Stratification is by site, country, and baseline nucleoprotein (NP) PCR cycle threshold (CT) ≤ 22 or > 22. The primary objective is a comparison of 28-day mortality relative to the control arm. The planned accrual is for 125 patients per arm. Secondary objectives include an evaluation of the comparative safety and tolerability of the 4 investigational MCMs, relative changes in viral load over time, comparisons of treatment efficacy according to baseline risk categories, 58-day mortality, RNA clearance from semen, and an assessment of the validity of drug-class comparisons, including efficacy. The study is monitored by an independent data and safety monitoring committee (DSMB).

Results
Enrollment commenced in the Ebola Treatment Unit in Beni in November, 2018, with sites in Butembo and Katwa added in early 2019. Time from study concept initiation to study start was only 3.5 months. Ongoing hurdles encountered to date include maintenance of cold chain requirements for the MCMs and marked volatility in the security situation surrounding sites affecting staff and patient safety. Despite these challenges, data quality and completed follow-up have been remarkably high and by mid-April, 2019, accrual to date (see table) had already surpassed the predefined threshold triggering an interim DSMB review.

Conclusion
Scientifically rigorous and ethically sound clinical research can take place during disease outbreaks even within a conflict zone. Results about the relative efficacy of the evaluated investigational MCMs are pending the completion of the trial.

Disclosures
All Authors: No reported Disclosures.
845. Children with Clinical Plasmodium falciparum Infection Have Increased Sharing of Haplotypes with Household Members as well as Temporally Proximal, Symptomatic Peers
Authors: Nelson Cody S , Sumner Kelsey , Freedman Betsy , Obala Andrew , Mangeni Jane , Taylor Steve , O’Meara Wendy 
Published: October 2019

Abstract

Background
Falciparum malaria transmission has failed to decline in proportion to control efforts in certain regions such as Bungoma county, western Kenya. One proposed strategy to eradicate malaria is ring testing and treatment; however, it remains unknown whether infections spread locally or if asymptomatically infected household members are a risk factor for clinical disease.

Methods
From April 2013 to June 2014, we enrolled 442 cases (RDT+ children hospitalized with malaria) and 442 matched controls; all household members of cases and controls were also enrolled and tested, of which 13.6% (n = 608/4449) were RDT+. From each RDT+ participant, parasite gDNA was PCR-amplified at both Pf circumsporozoite protein (csp) and apical membrane antigen 1 (ama1) loci, amplicons sequenced on an Illumina Miseq, and haplotypes inferred using dada2.

Results
We identified 120 csp and 180 ama1 unique haplotypes (Figure 1). We evaluated the genetic distance between infected individuals using three novel indices: sharing of parasite haplotypes on binary and proportional scales and the L1 norm. Case children median [IQR] binary/proportional sharing of both csp and ama1 haplotypes was significantly increased with members of their origin household (e.g., csp binary sharing: origin = 50.3 [0–87.5] vs. similar household = 0 [0–50.3]; P = 0.01; Wilcoxon sign-rank test), indicating that cases are more likely to share haplotype-identical parasites with members of their own household (Figure 2). We also computed population-level haplotype sharing indices for all pairs of case children and observed no association between genetic relatedness and geographic distance. In contrast, we identified a strong inverse relationship between haplotype sharing and temporal distance, which we exploited to identify the molecular signature of an outbreak (Figure 3).

Conclusion
Overall, these findings suggest that, although haplotype sharing is more common within households, temporal rather than geographic proximity predicts parasite genetic similarity. The observation that identical haplotype combinations are found nearly simultaneously across the study area implies that ring testing approaches may not effectively reduce transmission.

Disclosures
All Authors: No reported Disclosures.