bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accelerating Initiation of Adequate Antimicrobial Therapy Using Real-Time Decision Support and Microarray Testing
Authors: Tchou Michael J. , Andersen Heidi , Robinette Eric , Mortensen Joel E. , Powell Eleanor A. , Ankrum Andrea , Washam Matthew C. , Haslam David B. , Courter Joshua D. 
Published: August 2019

Introduction:
Bloodstream infections (BSI) represent a common cause of sepsis and mortality in children. Early and adequate empirical antimicrobial therapy is a critical component of successful treatment of BSI. Rapid PCR-based diagnostic technologies, such as nucleic acid microarrays, can decrease the time needed to identify pathogens and antimicrobial resistance and have the potential to ensure patients are started on adequate antibiotics as early as possible. However, without appropriate processes to support timely and targeted interpretation of these results, these advantages may not be realized in practice.

Methods:
Our Antimicrobial Stewardship Program (ASP) implemented a quality improvement initiative using the Institute for Healthcare Improvement’s Model for Improvement to decrease the time between a nucleic acid microarray result for Gram-positive bacteremia and the time a patient was placed on adequate antimicrobial therapy. The primary effective intervention was a near real-time notification system to the managing physicians of inadequate antimicrobial therapy via a call from the ASP team.

Results:
Following the intervention, the average time to adequate antimicrobial therapy in patients with Gram-positive BSI and inadequate coverage decreased from 38 hours with the nucleic acid microarray result alone to 4.7 hours when results were combined with an ASP clinical decision support intervention, an 87% reduction.

Conclusions:
The positive effects of rapid-detection technologies to improve patient care are enhanced when combined with clinical decision support tools that can target inadequate antimicrobial treatments in near real time.
Impact of Education and Peer Comparison on Antibiotic Prescribing for Pediatric Respiratory Tract Infections
Authors: Clegg Herbert W. , Bean Rebecca A. , Ezzo Stephen J. , Hoth Alycia N. , Sheedy David J. , Anderson William E. 
Published: August 2019

Introduction:
Inappropriate prescribing of broad-spectrum antibiotics is a significant modifiable risk factor for the development of antibiotic resistance. The objective was to improve guideline-concordant care for 3 common acute respiratory tract infections (ARTIs) and to reduce broad-spectrum antibiotic prescribing in ambulatory pediatric patients.

Methods:
Quality measures were developed for 3 ARTIs: viral upper respiratory infection (URI), acute bacterial sinusitis (ABS), and acute otitis media (AOM). Among 22 pediatric clinics, a collaborative of 10 was identified for intervention using baseline data for each ARTI, and 3 plan-do-study-act cycles were planned and completed. Outcomes included guideline-concordant antibiotic utilization and broad-spectrum antibiotic prescribing percentage (BSAP%). Comparison in number of diagnoses for the ARTI measures and total antibiotic prescribing over time served as balancing measures.

Results:
Collaborative clinics had baseline medians for appropriate or first-line treatment of 70% for URI, 53% for ABS, and 36% for AOM. To reach targets for URI, ABS, and AOM required 6, 14, and 18 months, respectively. At 42 months, performance for all 3 ARTIs remained ≥90%. BSAP% decreased from a baseline of 57% to 34% at 24 months. There was a limited effect from financial incentives but a significant decrease was noted in total antibiotic utilization. Diagnosis shifting may have occurred for URI and ABS while the rates for diagnoses for AOM declined over time.

Conclusions:
Through education and peer comparison feedback, guideline-concordant care for 3 ARTIs in collaborative clinics improved and remained beyond above targets and was accompanied by reductions in BSAP% and total antibiotic prescribing.
Neuroimaging-based biomarkers for pain: state of the field and current directions
Authors: van der Miesen Maite M. , Lindquist Martin A. , Wager Tor D. 
Published: August 2019

Abstract
Chronic pain is an endemic problem involving both peripheral and brain pathophysiology. Although biomarkers have revolutionized many areas of medicine, biomarkers for pain have remained controversial and relatively underdeveloped. With the realization that biomarkers can reveal pain-causing mechanisms of disease in brain circuits and in the periphery, this situation is poised to change. In particular, brain pathophysiology may be diagnosable with human brain imaging, particularly when imaging is combined with machine learning techniques designed to identify predictive measures embedded in complex data sets. In this review, we explicate the need for brain-based biomarkers for pain, some of their potential uses, and some of the most popular machine learning approaches that have been brought to bear. Then, we evaluate the current state of pain biomarkers developed with several commonly used methods, including structural magnetic resonance imaging, functional magnetic resonance imaging and electroencephalography. The field is in the early stages of biomarker development, but these complementary methodologies have already produced some encouraging predictive models that must be tested more extensively across laboratories and clinical populations.
Applications of dynamic functional connectivity to pain and its modulation
Authors: Necka Elizabeth A. , Lee In-Seon , Kucyi Aaron , Cheng Joshua C. , Yu Qingbao , Atlas Lauren Y. 
Published: August 2019

Abstract
Since early work attempting to characterize the brain's role in pain, it has been clear that pain is not generated by a specific brain region, but rather by coordinated activity across a network of brain regions, the “neuromatrix.” The advent of noninvasive whole-brain neuroimaging, including functional magnetic resonance imaging, has provided insight on coordinated activity in the pain neuromatrix and how correlations in activity between regions, referred to as “functional connectivity,” contribute to pain and its modulation. Initial functional connectivity investigations assumed interregion connectivity remained stable over time, and measured variability across individuals. However, new dynamic functional connectivity (dFC) methods allow researchers to measure how connectivity changes over time within individuals, permitting insights on the dynamic reorganization of the pain neuromatrix in humans. We review how dFC methods have been applied to pain, and insights afforded on how brain connectivity varies across time, either spontaneously or as a function of psychological states, cognitive demands, or the external environment. Specifically, we review psychophysiological interaction, dynamic causal modeling, state-based dynamic community structure, and sliding-window analyses and their use in human functional neuroimaging of acute pain, chronic pain, and pain modulation. We also discuss promising uses of dFC analyses for the investigation of chronic pain conditions and predicting pain treatment efficacy and the relationship between state- and trait-based pain measures. Throughout this review, we provide information regarding the advantages and shortcomings of each approach, and highlight potential future applications of these methodologies for better understanding the brain processes associated with pain.
Outcome of Recurrent Surgery in Dupuytren’s Disease: Comparison with Initial Treatment
Authors: Mendelaar Nienke H. A. , Poelstra Ralph , van Nieuwenhoven Christianne A. , Slijper Harm P. , Feitz Reinier , Hovius Steven E. R. , Selles Ruud W. 
Published: August 2019

Background:
There are multiple studies about the effectiveness of primary treatment in Dupuytren’s disease. However, such studies concerning treatment effectiveness of recurrent disease are scarce. Therefore, the primary aim of this study was to compare treatment effectiveness of initial and repeated surgery in patients with Dupuytren’s disease.

Methods:
Patients who underwent both initial and repeated treatment were selected from a prospectively maintained database. Outcome measurements consisted of finger goniometry, the Michigan Hand Outcomes Questionnaire, and complications. Treatment effectiveness was defined as improvement in extension deficit and patient-reported hand function. In addition, measurements at intake of both treatments were compared. Subgroup analyses were performed to evaluate influence of type of surgery of initial treatment on outcomes of repeated treatment.

Results:
One hundred fourteen patients were included in the analyses. Improvement in extension deficit and Michigan Hand Outcomes Questionnaire outcomes was equal for initial and repeated treatments. Extension deficit and Michigan Hand Outcomes Questionnaire scores were worse at intake of repeated treatment compared to these outcomes at intake of initial treatment. In addition, patients who initially underwent needle fasciotomy achieved a better contracture reduction after repeated treatment.

Conclusions:
This study demonstrates that treatment of recurrent Dupuytren’s disease is as effective as initial treatment, despite larger extension deficit and worse self-assessed hand function before undergoing repeated treatment. Complication rates were similar for initial and repeated treatments. Furthermore, needle fasciotomy for initial treatment results in better outcomes of repeated treatment compared to patients who initially underwent limited fasciectomy. These findings can be used for a more evidence-based preoperative counseling with patients with recurrent Dupuytren’s disease.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Soluble Lectin-like Oxidized Low-Density Lipoprotein Receptor 1 Predicts the Changes of Rheumatoid Factor Titers in Rheumatoid Arthritis
Authors: Okahata Akinori , Ito Hiromu , Furu Moritoshi , Ishikawa Masahiro , Fujii Takayuki , Hashimoto Motomu , Tanaka Masao , Morita Yugo , Azukizawa Masayuki , Tomizawa Takuya , Doi Kohei , Nishitani Kohei , Murata Koichi , Yoshitomi Hiroyuki , Mimori Tsuneyo , Matsuda Shuichi 
Published: August 2019

Objective
The aim of this longitudinal study was to examine the clinical significance of soluble lectin-like oxidized low-density lipoprotein receptor 1 (sLOX-1) in patients with rheumatoid arthritis.

Methods
We gathered demographic and clinical data for a large rheumatoid arthritis cohort at 3 time points. Blood samples were collected at each time point; the number of samples was 282 cases in 2012, 431 cases in 2013, and 500 cases in 2014. Plasma sLOX-1 was measured by enzyme-linked immunosorbent assay. Correlations between sLOX-1 and clinical data were analyzed. Predictive factors associated with changes in sLOX-1 and rheumatoid factor (RF) were analyzed by multivariate linear regression.

Results
Plasma sLOX-1 level was significantly correlated with RF titer and other clinical parameters. The longitudinal analyses showed that changes in sLOX-1 were significantly correlated with changes in RF titers and with those at baseline. Multivariate linear regression analysis revealed that changes in RF and baseline RF were predictive factors for changes in sLOX-1. Conversely, the changes in RF were significantly correlated with the changes in sLOX-1 in all years. A stepwise regression analysis showed that the change in sLOX-1 was a predictive factor for the change in RF.

Conclusions
The change in sLOX-1 has predictive value for assessing the change in RF, indicating the usefulness of sLOX-1 in clinical practice.
Hematopoietic Stem Cell Transplantation Improves Functional Outcomes of Systemic Sclerosis Patients
Authors: Costa-Pereira Karla R. , Guimarães Ana Luísa , Moraes Daniela Aparecida , Dias Juliana Bernardes Elias , Garcia Juliana Tomé , de Oliveira-Cardoso Erika Arantes , Zombrilli Andréia , Leopoldo Vanessa , Costa Thalita Melo , Simões Belinda Pinto , Oliveira Maria Carolina 
Published: August 2019

Background/Objective
We sought to evaluate if autologous hematopoietic stem cell transplantation (AHSCT) influences the functional status of systemic sclerosis (SSc) patients.

Methods
From 2014 to 2018, a cohort of 27 SSc patients was assessed before, and at 6 and 12 months after AHSCT for modified Rodnan’s skin score (mRSS), mouth opening, hand grip strength, range of motion (ROM), functional ability of upper limbs (DASH questionnaire and Cochin hand function scale—CHFS), 6-minute walk test (6MWT), and quality of life (SF-36 questionnaire). Linear regression models with random effects and Spearman’s test were used for statistical analysis.

Results
At 6 and 12 months after AHSCT, respectively, we observed significant improvement of mRSS (p < 0.01 and p < 0.01), mouth opening (p = 0.02 and p < 0.01), hand function (DASH, p < 0.01 and p < 0.01; CHFS, p < 0.01 and p < 0.01; strength, p < 0.01 and p < 0.01), physical capacity (6MWT, p = 0.02 and p = 0.03) and physical (p < 0.01 and p < 0.01) and mental (ns and p = 0.02) component scores of SF-36. At 12 months after AHSCT, ROM measurements improved (p < 0.05) in five out of six evaluated joints in both hands, compared to baseline. Correlation was significant between physical capacity and quality of life (R = 0.62; p < 0.01), between DASH and quality of life (R = −0.48; p = 0.03), and between skin involvement and wrist ROM measures (dominant hand, R = −0.65, p < 0.01; non-dominant hand, R = −0.59; p < 0.01).

Conclusions
AHSCT enhances the functional status of SSc patients in the first year of follow-up, significantly improving hand function, physical capacity and quality of life. These results are interpreted as positive outcomes of AHSCT for SSc.
Meaningful Patient-centered Outcomes 1 Year Following Cardiac Surgery
Authors: Charles Eric J. , Mehaffey J. Hunter , Hawkins Robert B. , Burks Sandra G. , McMurry Timothy L. , Yarboro Leora T. , Kern John A. , Ailawadi Gorav , Kron Irving L. , Stukenborg George J. , Kozower Benjamin D. 
Published: August 2019

Objective:
To evaluate meaningful, patient-centered outcomes including alive-at-home status and patient-reported quality of life 1 year after cardiac surgery.

Background:
Long-term patient-reported quality of life after cardiac surgery is not well understood. Current operative risk models and quality metrics focus on short-term outcomes.

Methods:
In this combined retrospective/prospective study, cardiac surgery patients at an academic institution (2014–2015) were followed to obtain vital status, living location, and patient-reported outcomes (PROs) at 1 year using the NIH Patient-Reported Outcomes Measurement Information System (PROMIS). We assessed the impact of cardiac surgery, discharge location, and Society of Thoracic Surgeons perioperative predicted risk of morbidity or mortality on 1-year outcomes.

Results:
A total of 782 patients were enrolled; 84.1% (658/782) were alive-at-home at 1 year. One-year PROMIS scores were global physical health (GPH) = 48.8 ± 10.2, global mental health (GMH) = 51.2 ± 9.6, and physical functioning (PF) = 45.5 ± 10.2 (general population reference = 50 ± 10). All 3 PROMIS domains at 1 year were significantly higher compared with preoperative scores (GPH: 41.7 ± 8.5, GMH: 46.9 ± 7.9, PF: 39.6 ± 9.0; all P < 0.001). Eighty-two percent of patients discharged to a facility were alive-at-home at 1 year. These patients, however, had significantly lower 1-year scores (difference: GPH = −5.1, GMH = −5.1, PF = −7.9; all P < 0.001). Higher Society of Thoracic Surgeons perioperative predicted risk was associated with significantly lower PRO at 1 year (P < 0.001).

Conclusions:
Cardiac surgery results in improved PROMIS scores at 1 year, whereas discharge to a facility and increasing perioperative risk correlate with worse long-term PRO. One-year alive-at-home status and 1-year PRO are meaningful, patient-centered metrics that help define long-term quality and the benefit of cardiac surgery.
Intraoperative Hypertension and Thrombocytopenia Associated With Intracranial Hemorrhage After Liver Transplantation
Authors: Gao Wei , Li Jun , Nguyen-Buckley Christine , Nguyen-Lee Jennifer , Wray Christopher , Agopian Vatche , Busuttil Ronald W. , Steadman Randolph H. , Xia Victor W. 
Published: August 2019

Background.
Intracranial hemorrhage (ICH) is a devastating complication. Although hypertension and thrombocytopenia are well-known risk factors for ICH in the general population, their roles in ICH after liver transplantation (LT) have not been well established.

Methods.
We performed a retrospective study and hypothesized that intraoperative hypertension and thrombocytopenia were associated with posttransplant ICH. New onset of spontaneous hemorrhage in the central nervous system within 30 days after LT were identified by reviewing radiologic reports and medical records. Risk factors were identified by multivariate logistic regression. Receiver operating characteristic analysis and Youden index were used to find the cutoff value with optimal sensitivity and specificity.

Results.
Of 1836 adult patients undergoing LT at University of California, Los Angeles, 36 (2.0%) developed ICH within 30 days after LT. Multivariate logistic regression demonstrated that intraoperative mean arterial pressure ≥105 mm Hg (≥10 min) (odds ratio, 6.5; 95% confidence interval, 2.7-7.7; P < 0.001) and platelet counts ≤30 × 109/L (odds ratio, 3.3; 95% confidence interval, 14-7.7; P = 0.006) were associated with increased risk of postoperative ICH. Preoperative total bilirubin ≥7 mg/dL was also a risk factor. Thirty-day mortality in ICH patients was 48.3%, significantly higher compared with the non-ICH group (3.0%; P < 0.001). Patients with all 3 risk factors had a 16% chance of developing ICH.

Conclusions.
In the current study, postoperative ICH was uncommon but associated with high mortality. Prolonged intraoperative hypertension and severe thrombocytopenia were associated with postoperative ICH. More studies are warranted to confirm our findings and develop a strategy to prevent this devastating posttransplant complication.
Donor-specific B Cell Memory in Alloimmunized Kidney Transplant Recipients: First Clinical Application of a Novel Method
Authors: Wehmeier Caroline , Karahan Gonca E. , Krop Juliette , de Vaal Yvonne , Langerak-Langerak Janneke , Binet Isabelle , Schaub Stefan , Roelen Dave L. , Claas Frans H.J. , Heidt Sebastiaan ,   the Swiss Transplant Cohort Study
Published: August 2019

Background.
HLA-specific memory B cells may contribute to the serum HLA antibody pool upon antigen reexposure. The aim of this pilot study was to investigate the presence of concurrent donor-specific memory B cell–derived HLA antibodies (DSA-M) in renal allograft recipients with pretransplant donor-specific HLA antibodies (DSA) and its association with occurrence of antibody-mediated rejection (AMR) using a recently developed method.

Methods.
Twenty patients with Luminex single antigen bead (SAB) assay-defined DSA but negative complement-dependent cytotoxicity crossmatches were enrolled. Plasma samples and peripheral blood mononuclear cells were collected at 3 timepoints (pretransplant, mo 6, mo 12). We analyzed IgG-purified and concentrated culture supernatants from polyclonally activated peripheral blood mononuclear cells using SAB assays and compared HLA antibody profiles with same day plasma results.

Results.
Plasma SAB analysis revealed 35 DSA in 20 patients pretransplant. DSA-M were detected in 9 of 20 (45%) patients and for 10 of 35 specificities (29%). While median mean fluorescence intensity values of DSA with concurrent DSA-M (5877) were higher than those of DSA without DSA-M (1476), 3 of 6 patients with AMR and low mean fluorescence intensity DSA (<3000) had DSA-M. Overall, pretransplant DSA/DSA-Mpos allograft recipients showed a higher incidence of biopsy-proven (sub)clinical AMR (P = 0.032) and a higher extent (g≥1 + ptc≥1) of microvascular inflammation (67% vs 9%, P = 0.02). In 17 patients (28 DSA) with posttransplant analyses, persisting DSA posttransplant had more often DSA-M (6/12; 50%) than nonpersisting DSA (2/16; 13%).

Conclusions.
Assessment of DSA-M might be a novel tool to supplement serum HLA antibody analysis for pretransplant risk stratification in patients with DSA.
Equity–Efficiency Trade-offs Associated With Alternative Approaches to Deceased Donor Kidney Allocation: A Patient-level Simulation
Authors: Li Bernadette , Cairns John A. , Johnson Rachel J. , Watson Christopher J.E. , Roderick Paul , Oniscu Gabriel C. , Metcalfe Wendy , Bradley J. Andrew , Tomson Charles R. , Draper Heather , Forsythe John L. , Dudley Christopher , Ravanan Rommel 
Published: August 2019

Background.
The number of patients waiting to receive a kidney transplant outstrips the supply of donor organs. We sought to quantify trade-offs associated with different approaches to deceased donor kidney allocation in terms of quality-adjusted life years (QALYs), costs, and access to transplantation.

Methods.
An individual patient simulation model was developed to compare 5 different approaches to kidney allocation, including the 2006 UK National Kidney Allocation Scheme (NKAS) and a QALY maximization approach designed to maximize health gains from a limited supply of donor organs. We used various sources of patient-level data to develop multivariable regression models to predict survival, health state utilities, and costs. We simulated the allocation of kidneys from 2200 deceased donors to a waiting list of 5500 patients and produced estimates of total lifetime costs and QALYs for each allocation scheme.

Results.
Among patients who received a transplant, the QALY maximization approach generated 48 045 QALYs and cost £681 million, while the 2006 NKAS generated 44 040 QALYs and cost £625 million. When also taking into consideration outcomes for patients who were not prioritized to receive a transplant, the 2006 NKAS produced higher total QALYs and costs and an incremental cost-effectiveness ratio of £110 741/QALY compared with the QALY maximization approach.

Conclusions.
Compared with the 2006 NKAS, a QALY maximization approach makes more efficient use of deceased donor kidneys but reduces access to transplantation for older patients and results in greater inequity in the distribution of health gains between patients who receive a transplant and patients who remain on the waiting list.
Enlarged and Enhancing Optic Nerves in Advanced Glial Fibrillary Acidic Protein Meningoencephalomyelitis
Authors: White Daniel , Mollan Susan P. , Ramalingam Satheesh , Nagaraju Santhoosh , Hayton Tom , Jacob Saiju 
Published: August 2019

Abstract:
A 36-year-old woman presented with intermittent fever, nausea and vomiting, generalized polyarthralgias, and bilateral optic disc swelling. She had a history of difficult-to-control myasthenia gravis since the age of 18 years. Lumbar puncture demonstrated a normal opening pressure; cerebrospinal fluid (CSF) was remarkable for high protein, low glucose, and a mononuclear pleocytosis. Although initial MRI of the brain was normal, a repeat study 8 weeks later revealed enlarged and enhancing bilateral intraorbital and intracranial optic nerves. After a nondiagnostic brain biopsy, a CSF sample tested positive for antibodies to glial fibrillary acidic protein (GFAP). Findings in this case indicate that optic nerve swelling encountered in GFAP meningoencephalomyelitis is more likely due to optic nerve inflammation rather than elevated intracranial pressure.