bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy of Spinal Anesthesia Drug Concentrations in Mixtures Prepared by Anesthetists
Authors: Heesen Michael , Steuer Christian , Wiedemeier Peter , Schwappach David 
Published: July 2022

Objective
Medication errors include the indirect dosing of drugs. For spinal anesthesia mixtures of local anesthetics, opioids are drawn from ampoules and combined in a syringe, according to clinical practice. We set out to determine the accuracy of the drug mixtures.

Methods
Physicians of our department were invited to prepare the mixture used for spinal anesthesia for cesarean section, consisting of 10-mg hyperbaric bupivacaine (2-mL volume), 20-μg fentanyl (0.4-mL volume), and 100-μg morphine (0.1-mL volume). Concentrations of these drugs were determined by means of high performance liquid chromatography. Interindividual and intraindividual variations were assessed.

Results
We analyzed 96 samples from 31 physicians. Fifty-one percent of the measured bupivacaine concentrations were in ±10% deviation range of the intended concentration; 17% of the fentanyl and 24% of the morphine concentrations were in this range. A total of 2.1% of the samples had a bupivacaine concentration corresponding to a dose of 8 mg or less, and 11.5% of the samples had a morphine concentration corresponding to a dose of 150 μg or greater. Intraindividual variations were 10.9% for bupivacaine, 24.7% for fentanyl, and 38.9% for morphine.

Conclusions
Our results show a high deviation of the obtained from the intended concentrations. Two percent of the samples had bupivacaine concentrations that probably resulted into an insufficient analgesia, and 11% of the samples had morphine concentrations that, according to guidelines, would require a longer monitoring period than with the intended dose.
Brief Report: Financial Burden of Toxoplasmosis Encephalitis Treatment at a Safety Net Hospital
Authors: Bogard Sherri N. , Lee James T. , Patel Manish , Kempker Russell R. 
Published: July 2022

Background:
Although the price increase of pyrimethamine in 2015 received heavy media coverage, there are little data regarding specific implications to hospitals and the total costs of treating inpatients with toxoplasmosis encephalitis (TE).

Methods:
Using average drug wholesale costs, we estimated the inpatient drug costs of TE drugs 3 years prepyrimethamine and postpyrimethamine price increase in August 2015. The drug regimens and total doses were determined through retrospective chart review of patients living with HIV who received treatment for TE while inpatient during this period.

Results:
The 3-year pre-increase TE drug costs for 66 admissions were estimated at $50,310 compared with a total drug cost of $1,026,006 for 61 admissions postincrease. Pyrimethamine made up 98% of the drug costs postincrease, compared with 57% pre-increase. Pyrimethamine-based regimens were the most frequently used throughout the study period.

Conclusions:
The price increase of pyrimethamine in 2015 led to a substantial and unnecessary financial burden to hospitals. This required health care systems to shift valuable resources to continue to provide medications to a vulnerable patient population. There has been more focus on providing high-value care in recent years. Our study highlights the need for further examination of pharmaceutical companies' arbitrary determination of medication costs and how they contribute to patient care.
Saving Money and Reducing Waste With a Tailored Hand Surgery Kit
Authors: Velicki Katherine , Schultz Michelle , Dy Christopher J. 
Published: July 2022

Background and Objectives:
There is growing interest in containing cost and decreasing waste in the operating room. As part of a quality improvement initiative, we redesigned the supply kit used for 2 common surgical procedures (carpal tunnel release and trigger finger release) performed under local anesthesia.

Methods:
A hand surgeon, a medical student, and an operating room nurse examined each item that would be necessary for performing carpal tunnel release and trigger finger release. A new disposable supply kit was formulated on the basis of their recommendations and was implemented over a 7-month period. Cost savings and waste avoidance were calculated.

Results:
The streamlined kit ($43.40) produced a 53% cost savings relative to the standard hand pack ($92.83) per case. The local pack (2.896 kg) was 41% lighter than the standard pack (4.938 kg), translating to significant waste avoidance. The local hand pack was used for 46 cases from September 2020 to April 2021, saving a total of $2246.78 and avoiding 94 kg of waste. There have been no noted interruptions in delivery of surgical care.

Conclusion:
Our redesign of the local hand pack led to substantial cost savings and waste avoidance. We believe there are many opportunities for surgical teams to use similar strategies to decrease cost and environmental waste.
ISO 9001:2015 Internal Audits for Financial and Strategic Decisions in Reducing Blood Culture Contamination
Authors: Sharma Rohit , Szucs Theresa , Reinhartsen Teri Ann 
Published: July 2022

Background and Objectives:
Blood cultures are vital diagnostic tests that detect harmful pathogens in a patient's bloodstream. In this study, we implemented a process-driven quality improvement program to reduce blood culture contamination rates.

Methods:
St Joseph Health (SJH) utilized the ISO 9001:2015 Internal Audit tool, failure mode effect analyses, and the Centers for Disease Control and Prevention's Hierarchy of Controls to identify opportunities for improvement and design effective corrective and preventive action plans. These actions included reeducation and ongoing coaching of staff on the blood culture collection process, reorganizing blood culture supplies on the nursing units, and adding multiple layers of supervision.

Results:
A statistically significant relationship was identified between 2 variables (“contamination rate” and “cumulative cost difference”). The 2 variables had a negative association, demonstrating that as the contamination rate decreased, the cumulative cost difference increased, indicating potential cost savings.

Conclusion:
The estimated value added to the institution through this initiative was approximately $215 743 to $228 543 in potential cost savings. SJH significantly reduced the number of blood culture contaminations in the critical care division, evidenced by a controlled 6-month mean below 1%. Review of the 6-month mean as a reference point demonstrated the sustainability of the implemented corrective and preventive measures.
Variability of Pediatric Cervical Spine Clearance Protocols
Authors: Letica-Kriegel Allison S. , Kaplan Amy , Orlas Claudia , Masiakos Peter T. 
Published: July 2022

Objective:
The objective of this study was to better understand the variability that exists in the contemporary pediatric cervical spine (c-spine) clearance protocols and how this variability affects clinical practice and outcomes.

Background Data:
Pediatric c-spine injury is a rare but potentially devastating event. In the adult population, validated tools, such as the National Emergency X-Radiography Utilization Study (NEXUS) criteria and the Canadian C-spine Rule, are available to aid in safely clearing the c-spine clinically while reducing the utilization of radiography. In the pediatric population, no standardized, validated tool exists, leading to variability in protocols that are put to use.

Methods:
A systematic literature search was conducted in Cochrane, Embase, PubMed/MEDLINE, and Web of Science electronic databases from January 1, 2009 until April 30, 2021. Data were extracted from studies that met inclusion criteria. Quality of the included studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS) criteria.

Results:
There were 19 studies included in this systematic review. From these 19 studies, there were 16 unique protocols, 12 of which (75%) utilized some or all NEXUS criteria. Of the protocols that provided a detailed imaging algorithm (N=14), 12 (85.7%) utilized x-rays as the initial imaging modality. Indications for computed tomography and magnetic resonance imaging varied widely across the protocols. The rate of x-rays, computed tomography, and magnetic resonance imaging utilization ranged from 16.7% to 97.8%, 5.4% to 100%, and 0% to 100%, respectively. Ten studies evaluated the efficacy of protocol implementation, with 9 (90%) of these studies showing an overall reduction of imaging rates in the postprotocol period. No clinically significant missed injuries were reported in the included studies.

Conclusions:
Details of c-spine clearance protocols differed significantly across the included studies, but many applied some or all NEXUS criteria. Overall, while variable, protocols served to safely treat pediatric patients without missing any clinically significant c-spine injuries, while reducing radiation exposure.
The Impact of Psychiatric Diagnoses on Patient-reported Satisfaction and Quality of Life in Postmastectomy Breast Reconstruction
Authors: Shamsunder Meghana G. , Chu Jacqueline J. , Polanco Thais O. , Yin Shen , Muniz Rosario C. , James Monique C. , Mehrara Babak J. , Pusic Andrea L. , Voineskos Sophocles , Nelson Jonas A. 
Published: July 2022

Objective:
The purpose of this study was to determine the prevalence of psychiatric diagnoses among a sample of breast reconstruction patients and measure the association between these diagnoses and reconstruction-related, patient-reported outcomes.

Background:
The impact of psychiatric disorders in conjunction with breast cancer diagnosis, treatment, and reconstruction have the potential to cause significant patient distress but remains not well understood.

Methods:
A retrospective review of postmastectomy breast reconstruction patients from 2007 to 2018 at Memorial Sloan Kettering Cancer Center was conducted. Patient demographics, comorbidities, cancer characteristics, psychiatric diagnoses, and BREAST-Q Reconstruction Module scores (measuring satisfaction with breast, well-being of the chest, psychosocial, and sexual well-being) at postoperative years 1 to 3 were examined. Mixed-effects models and cross-sectional linear regressions were conducted to measure the effect of psychiatric diagnostic class type and number on scores.

Results:
Of 7414 total patients, 50.1% had at least 1 psychiatric diagnosis. Patients with any psychiatric diagnoses before reconstruction had significantly lower BREAST-Q scores for all domains at all time points. Anxiety (50%) and depression (27.6%) disorders were the most prevalent and had the greatest impact on BREAST-Q scores. Patients with a greater number of psychiatric diagnostic classes had significantly worse patient-reported outcomes compared with patients with no psychiatric diagnosis. Psychosocial (β: −7.29; 95% confidence interval: −8.67, −5.91), and sexual well-being (β: −7.99; 95% confidence interval: −9.57, −6.40) were most sensitive to the impact of psychiatric diagnoses.

Conclusions:
Mental health status is associated with psychosocial and sexual well-being after breast reconstruction surgery as measured with the BREAST-Q. Future research will need to determine what interventions (eg, screening, early referral) can help improve outcomes for breast cancer patients with psychiatric disorders undergoing breast reconstruction.
Separating the effects of early and later life adiposity on colorectal cancer risk: a Mendelian randomization study
Authors: Papadimitriou Nikos , Bull Caroline J , Jenab Mazda , Hughes David J. , Bell Joshua A , Sanderson Eleanor , Timpson Nicholas J , Smith George Davey , Albanes Demetrius , Campbell Peter T , Küry Sébastien , Marchand Loic Le , Ulrich Cornelia M , Visvanathan Kala , Figueiredo Jane C , Newcomb Polly A , Pai Rish K , Peters Ulrike , Tsilidis Kostas K , Boer Jolanda M.A. , Vincent Emma E , Mariosa Daniela , Gunter Marc J , Richardson Tom G , Murphy Neil 
Published: July 2022

AbstractBackgroundObservational studies have linked childhood obesity with elevated risk of colorectal cancer, however, it is unclear if this association is causal or independent from the effects of obesity in adulthood on colorectal cancer risk.MethodsWe conducted Mendelian randomization (MR) analyses to investigate potential causal relationships between self-perceived body size in early life (age 10) and measured body mass index in adulthood (mean age 56.5) with risk of colorectal cancer. The total and independent effects of body size exposures were estimated using univariable and multivariable MR, respectively. Summary data were obtained from a genome-wide association study of 453,169 participants in UK Biobank for body size and from a genome-wide association study meta-analysis of three colorectal cancer consortia of 125,478 participants.ResultsGenetically predicted early life body size was estimated to increase odds of colorectal cancer (odds ratio [OR] per category change: 1.12, 95% confidence interval [CI]: 0.98-1.27), with stronger results for colon cancer (OR: 1.16, 95% CI: 1.00-1.35), and distal colon cancer (OR: 1.25, 95% CI: 1.04-1.51). After accounting for adult body size using multivariable MR, effect estimates for early life body size were attenuated towards the null for colorectal cancer (OR: 0.97, 95% CI: 0.77-1.22) and colon cancer (OR: 0.97, 95% CI: 0.76-1.25), while the estimate for distal colon cancer was of similar magnitude but more imprecise (OR: 1.27, 95% CI: 0.90-1.77).ConclusionsOur findings suggest that the positive association between early life body size and colorectal cancer risk is likely due to large body size retainment into adulthood.
A personalized antibody score for predicting individual COVID-19 vaccine-elicited antibody levels from basic demographic and health information
Authors: Nakamura Naotoshi , Park Hyeongki , Kim Kwang Su , Sato Yoshitaka , Jeong Yong Dam , Iwanami Shoya , Fujita Yasuhisa , Zhao Tianchen , Tani Yuta , Nishikawa Yoshitaka , Yamamoto Chika , Kobashi Yurie , Kawamura Takeshi , Sugiyama Akira , Nakayama Aya , Kaneko Yudai , Aihara Kazuyuki , Iwami Shingo , Tsubokura Masaharu 
Published: July 2022

AbstractAntibody titers wane after two-dose COVID-19 vaccinations, but individual variation in vaccine-elicited antibody dynamics remains to be explored. Here, we created a personalized antibody score that enables individuals to infer their antibody status by use of a simple calculation. We recently developed a mathematical model of B cell differentiation to accurately interpolate the longitudinal data from a community-based cohort in Fukushima, Japan, which consists of 2,159 individuals who underwent serum sampling two or three times after a two-dose vaccination with either BNT162b2 or mRNA-1273. Using the individually reconstructed time course of the vaccine-elicited antibody response, we first elucidated individual background factors that contributed to the main features of antibody dynamics, i.e., the peak, the duration, and the area under the curve. We found that increasing age was a negative factor and a longer interval between the two doses was a positive factor for individual antibody level. We also found that the presence of underlying disease and the use of medication affected antibody levels negatively, whereas the presence of adverse reactions upon vaccination affected antibody levels positively. We then applied to these factors a recently proposed computational method to optimally fit clinical scores, which resulted in an integer-based score that can be used to evaluate the antibody status of individuals from their basic demographic and health information. This score can be easily calculated by individuals themselves or by medical practitioners. There is a potential usefulness of this score for identifying vulnerable populations and encouraging them to get booster vaccinations.Significance statementDifferent individuals show different antibody titers even after the same COVID-19 vaccinations, making some individuals more prone to breakthrough infections than others. Such variability remains to be clarified. Here we used mathematical modeling to reconstruct individual post-vaccination antibody dynamics from a cohort of 2,159 individuals in Fukushima, Japan. Machine learning identified several positive and negative factors affecting individual antibody titers. Positive factors included adverse reactions after vaccinations and a longer interval between two vaccinations. Negative factors included age, underlying medical conditions, and medications. We combined these factors and developed an “antibody score” to estimate individual antibody dynamics from basic demographic and health information. This score can help to guide individual decision-making about taking further precautions against COVID-19.
First-in-patient dose prediction for adeno-associated virus-mediated hemophilia gene therapy using allometric scaling
Authors: Zou Peng 
Published: July 2022

AbstractRational first-in-patient (FIP) dose selection is critical for successful clinical development of gene therapy. In this study, the author compared the performance of two allometric scaling approaches and body weight-based dose conversion approach for FIP dose prediction for adeno-associated virus (AAV)-mediated hemophilia gene therapy. The performance of the three approaches was examined using preclinical and clinical efficacy data of nine AAV vectors. In general, body weight-based direct conversion of effective doses in monkeys or dogs was more likely to underestimate FIP dose but worked better for one bioengineered vector with a high transduction efficiency specifically in humans. In contrast, allometric scaling between gene efficiency factor (logGEF) and body weight (logW) was likely to overestimate FIP dose but worked better than the other two approaches when vector capsid-specific T-cell responses were detected in patients. The third approach, allometric scaling between logGEF and W-0.25 was appropriate for FIP dose prediction in the absence of T-cell responses to AAV vectors or a dramatic difference in vector transduction efficiency between animals and humans. A decision tree was tentatively proposed to facilitate approach selection for FIP dose prediction in AAV-mediated hemophilia gene therapy.
Peri-saccadic orientation identification performance and visual neural sensitivity are higher in the upper visual field
Authors: Fracasso Alessio , Buonocore Antimo , Hafed Ziad M. 
Published: July 2022

AbstractVisual neural processing is distributed among a multitude of sensory and sensory-motor brain areas exhibiting varying degrees of functional specializations and spatial representational anisotropies. Such diversity raises the question of how perceptual performance is determined, at any one moment in time, during natural active visual behavior. Here, exploiting a known dichotomy between the primary visual cortex and superior colliculus in representing either the upper or lower visual fields, we asked whether peri-saccadic orientation identification performance is dominated by one or the other spatial anisotropy. Humans (48 participants, 29 females) reported the orientation of peri-saccadic upper visual field stimuli significantly better than lower visual field stimuli, unlike their performance during steady-state gaze fixation, and contrary to expected perceptual superiority in the lower visual field in the absence of saccades. Consistent with this, peri-saccadic superior colliculus visual neural responses in two male rhesus macaque monkeys were also significantly stronger in the upper visual field than in the lower visual field. Thus, peri-saccadic orientation identification performance is more in line with oculomotor, rather than visual, map spatial anisotropies.Significance statementDifferent brain areas respond to visual stimulation, but they differ in the degrees of functional specializations and spatial anisotropies that they exhibit. For example, the superior colliculus both responds to visual stimulation, like the primary visual cortex, and controls oculomotor behavior. Compared to the primary visual cortex, the superior colliculus exhibits an opposite pattern of upper/lower visual field anisotropy, being more sensitive to the upper visual field. Here, we show that human peri-saccadic orientation identification performance is better in the upper compared to the lower visual field. Consistent with this, monkey superior colliculus visual neural responses to peri-saccadic stimuli follow a similar pattern. Our results indicate that peri-saccadic perceptual performance reflects oculomotor, rather than visual, map spatial anisotropies.
Single Cell RNA-Sequence Analyses Reveal Uniquely Expressed Genes and Heterogeneous Immune Cell Involvement in the Rat Model of Intervertebral Disc Degeneration
Authors: Rohanifar Milad , Clayton Sade W. , Easson Garrett , Patil Deepanjali S. , Lee Frank , Jing Liufang , Barcellona Marcos N. , Speer Julie E. , Stivers Jordan J. , Tang Simon Y. , Setton Lori A. 
Published: July 2022

ABSTRACTIntervertebral disc (IVD) degeneration is characterized by a loss of cellularity, and changes in cell-mediated activity that drives anatomic changes to IVD structure. In this study, we use single cell RNA-sequencing analysis of cells extracted from the degenerating tissues of the rat IVD following lumbar disc puncture. Two control, uninjured IVDs (L2-3, L3-4) and two degenerated, injured IVDs (L4-5, L5-6) from each animal were examined either at two- and eight-week post-operative time points. The cells from these IVDs were extracted and transcriptionally profiled at a single-cell resolution. Unsupervised cluster analysis revealed the presence of 4 known cell types in both non-degenerative and degenerated IVDs based on previously established gene markers: IVD cells, endothelial cells, myeloid cells, and lymphoid cells. As a majority of cells were associated with the IVD cell cluster, sub-clustering was used to further identify the cell populations of the nucleus pulposus, inner and outer annulus fibrosus. The most notable difference between control and degenerated IVDs was the increase of myeloid and lymphoid cells in degenerated samples at 2- and 8- weeks post-surgery. Differential gene expression analysis revealed multiple distinct cell types from the myeloid and lymphoid lineages, most notably macrophages and B lymphocytes and demonstrated a high degree of immune specificity during degeneration. In addition to the heterogenous infiltrating immune cell populations in the degenerating IVD, the increased number of cells in the AF sub-cluster expressingNgfandNgfr, encoding for p75NTR, suggest that NGF signaling may be one of the key mediators of the IVD crosstalk between immune and neuronal cell populations. These findings provide the basis for future work to understand the involvement of select subsets of non-resident cells in IVD degeneration.