bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addressing New Possibilities and New Challenges: Automated Nondestructive Hematocrit Normalization for Dried Blood Spots
Authors: Luginbühl Marc , Gaugler Stefan 
Published: March 2021

Abstract:
The patient's hematocrit (HCT) level can adversely affect the analysis results when dried blood spots (DBS) are used for sampling. Volumetric DBS sampling has been proposed to nullify the impact of HCT area bias (spreading area) on DBS by normalizing to a known sample volume. However, this strategy ignores DBS-related parameters such as analyte properties (red blood cell–to-plasma ratio) and HCT recovery bias. With the recent release of fully automated HCT measurement systems for DBS analysis, a broad range of end users are now able to measure and correct a sample's HCT level in a nondestructive manner. These systems permit correction for all known HCT-related impacts on DBS, such as analyte properties, HCT recovery bias, HCT area bias, and venous blood–to-DBS ratio, supporting and accelerating future quantitative DBS applications. However, with these novel tools, new questions arise concerning the normalization of analytical results, the choice of technique (single-wavelength reflectance vs near-infrared spectroscopy), and the DBS card-handling process post sampling. Herein, the necessary considerations for end users are addressed and examples are provided.
Unexpected Vancomycin Pharmacokinetic Profile Secondary to Macromolecular Complexing: A Case Series
Authors: Rice Mikhaila L. , Go John Raymond , Rivera Christina G. , Zeuli John D. , Saleh Omar Abu , Baumann Nikola A. , Stevens Ryan W. 
Published: March 2021

Background:
The optimal dosing and monitoring of vancomycin has been largely debated for decades, with key guideline changes for recommended monitoring in 2009 and 2020. Current and past practices for pharmacokinetic dose optimization use serum drug assays to guide dose adjustment to effectively balance efficacy and the risks of toxicity. These assays detect both bound and unbound serum concentrations. Vancomycin is believed to be 50%–55% protein bound in most cases; however, some variability in this parameter has been previously published. The authors report 2 cases of abnormal vancomycin pharmacokinetics discovered based on unexpected serum levels during routine clinical care.

Methods:
Unexpected vancomycin levels, observed during clinical care for 2 separate patients, were further evaluated to determine the source of the abnormal pharmacokinetics. In case 1, serial dilution was performed to assure that assay interference was not associated with the significant elevation (>100 mg/L). In both cases, samples were filtered using a Millipore Centrifree 30 KDa centrifugal filter to separate bound vancomycin, with a Protein G spin kit used to bind IgG and remove IgG complexes from the patient sample. In case 2, a polyethylene glycol precipitation was also performed to precipitate large-molecular-weight complexes.

Results:
In both cases, laboratory analysis revealed abnormal vancomycin protein-binding profiles with macromolecular complex formation. Immunoglobulin G played a role in the macrocomplex in both patients.

Conclusions:
In cases of unusual or unexpected vancomycin pharmacokinetics in the absence of renal dysfunction, an abnormal protein-binding profile should be considered. Bound vancomycin may yield elevated serum levels, leading to poorly informed dose adjustments and risk for treatment failure. Given implications for therapeutic drug monitoring and unknown impacts on efficacy and toxicity, further investigations into population incidence and risk factors for abnormal protein binding of vancomycin are warranted.
Evaluating Functional Outcomes in Reanimation Surgery for Chronic Facial Paralysis: A Systematic Review
Authors: Rodriguez Colon Ricardo , Park Jenn J. , Boczar Daniel , Diep Gustave K. , Berman Zoe P. , Trilles Jorge , Chaya Bachar F. , Rodriguez Eduardo D. 
Published: March 2021

Background:
Chronic facial paralysis can lead to significant functional and psychosocial impairment. Treatment often involves free muscle flap-based facial reanimation surgery. Although surgical techniques have advanced considerably over the years, consensus has yet to be reached for postoperative outcome evaluation. To facilitate outcome comparison between the various techniques for free muscle-flap-based reanimation, a standardized, widely accepted functional outcomes assessment tool must be adopted.

Methods:
In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we performed a systematic review of the PubMed, Cochrane, and Embase databases to identify the reported functional outcome measurement tools used in the free muscle flap-based reanimation literature.

Results:
The search yielded 219 articles, 43 of which met our inclusion and exclusion criteria. We noted an increase in publications reporting the utilization of objective measures over time, particularly software-based tools, as well as increased utilization of patient reported outcomes measures.

Conclusions:
Based on the trends identified in the literature, we suggest standardization of outcome measures following facial reanimation surgery with free muscle-flap using a combination of the Facial Assessment by Computer Evaluation (FACEgram) software and the Facial Clinimetric Evaluation (FaCE) Scale.
A Novel mRNA Modification Mutation in a Patient With Ligneous Conjunctivitis Coexisting With Heterozygous Familial Mediterranean Fever Mutation
Authors: Koseoglu Neslihan D. , Ceylaner Serdar , Yildirim Nilgun 
Published: March 2021

Purpose:
To describe a novel mRNA mutation associated with ligneous conjunctivitis (LC) in a patient with heterozygous familial Mediterranean fever (FMF) mutation.

Methods:
Case presentation of a patient with LC and heterozygous FMF mutation. The patient was evaluated for various genetically predisposed inflammatory diseases through whole exome sequencing.

Results:
LC is a rare inflammatory ocular pathology presenting with recurrent conjunctivitis episodes with eosinophilic fibrin-rich pseudomembranes. FMF is an autoinflammatory disease presenting with recurrent episodes of fever, arthritis, and other inflammatory conditions. Various plasminogen (PLG) gene mutations have been identified in LC, whereas a variety of mutations in the Mediterranean fever (MEFV) gene have been identified in FMF patients. Based on the inflammatory nature of both pathologies, we aimed to evaluate and identify any potential common genetic pathway. We were not able to identify any mutation in PLG gene through whole gene sequencing; however, the patient was positive for heterozygous M680I FMF mutation, and we observed 22% of NM_000301.3:c.2130T>G (p.T710=) variant in mRNA isolated from affected tissue, which was not present in DNA sequence.

Conclusions:
To the best of our knowledge, this is the first case of LC caused by an mRNA mutation coexisting with another genetically predisposed autoinflammatory disease mutation.
Toric intraocular lens power calculation in cataract patients with keratoconus
Authors: Ton Yokrat , Barrett Graham D. , Kleinmann Guy , Levy Adi , Assia Ehud I. 
Published: March 2021

Purpose:
Intraocular lens (IOL) power calculation in eyes with keratoconus typically results in hyperopic postoperative refractive error. The purpose of this study was to investigate the visual and refractive outcomes in patients with keratoconus having cataract surgery with a toric IOL and compare IOL power calculation accuracy of conventional formulas and keratoconus-specific formulas.

Setting:
Ein-Tal Eye Center, Tel-Aviv, Israel.

Design:
Retrospective case-series study.

Methods:
Postoperative visual acuity and manifest refraction were examined. The error in predicted refraction and IOL power calculation accuracy within a range of 0.50 to 2.00 diopters (D) were compared between different IOL calculating formulas.

Results:
32 eyes with keratoconus were included. Visual acuity improved in all cases, and subjective astigmatism decreased from −2.95 ± 2.10 D to −0.95 ± 0.80 D (P < .001). The mean absolute errors were as follows: Barrett True-K formula for keratoconus with measured or predicted posterior corneal power, 0.34 D; Barrett Universal II formula, 0.64 D; Kane formula, 0.69 D; Kane formula for keratoconus, 0.49 D; SRK/T formula, 0.56 D; Haigis formula, 0.72 D; Holladay 1 formula, 0.71 D, and Hoffer Q formula, 0.87 D. Barrett True-K formula with measured posterior corneal power, SRK/T formula, and Kane formula for keratoconus resulted in a prediction error within ±0.50 D of 87.5%, 59.4%, and 53.1%, respectively.

Conclusions:
Cataract removal with a toric IOL significantly improves visual acuity and decreases astigmatism in keratoconic eyes with a topographic central relatively regular astigmatic component. Keratoconus-specific formulas resulted in lower mean error in predicted refraction compared with conventional calculating formulas. Using the posterior corneal power within the Barrett True-K formula for keratoconus improved IOL power prediction accuracy.
Pharmacokinetic Profile of the Asenapine Transdermal System (HP-3070)
Authors: Suzuki Katsumi , Castelli Mariacristina , Komaroff Marina , Starling Brittney , Terahara Takaaki , Citrome Leslie 
Published: March 2021

Abstract

Purpose/Background
The asenapine transdermal system (HP-3070) is the first antipsychotic patch approved in the United States for treatment of adults with schizophrenia.

Methods/Procedures
Three phase 1, open-label, randomized studies characterized the pharmacokinetic (PK) profile of HP-3070 by assessing its relative bioavailability compared with sublingual asenapine, its single-/multiple-dose PK and dose proportionality, and the effects of application site, ethnicity, and external heat on bioavailability. Two studies were conducted in healthy subjects, and 1 was conducted in adults with schizophrenia.

Findings/Results
During single HP-3070 administration, asenapine concentrations increased gradually over approximately 12 hours and remained steady until the patch was removed 24 hours after application. Asenapine area under the curve values at HP-3070 3.8 and 7.6 mg/24 hours doses were similar to those for sublingual asenapine 5 and 10 mg twice-daily doses, respectively, whereas peak exposure (maximum observed plasma concentration) was significantly lower. During daily application of HP-3070, steady-state PK was reached within approximately 72 hours after initiating daily dosing and was characterized by peak-to-trough asenapine plasma concentration ratio of approximately 1.5. HP-3070 PK was dose proportional in the dose range studied, not affected by administration site, and similar across the studied ethnic groups. Application of external heat increased the rate of asenapine absorption (time to reach maximum observed plasma concentration) but did not significantly affect peak and total exposure.

Implications/Conclusions
HP-3070 exhibited a dose-dependent PK profile unaffected by site of administration or ethnicity. HP-3070 showed a predictable absorption profile with limited variability, with an area under the curve similar to that of sublingual asenapine. Based on these PK metrics, HP-3070 steadily delivers asenapine with lower peaks and troughs than sublingual administration of asenapine.
Aortic arch calcification: a novel parameter for prediction of masked hypertension
Authors: Akbay Ertan , Çoner Ali , Akinci Sinan , Adar Adem , Çakan Fahri , Müderrisoğlu Haldun 
Published: March 2021

Background
Masked hypertension is directly related to increased cardiovascular morbidity and mortality but remains underdiagnosed in clinical practice. The aim of the study was to search the role of aortic arch calcification (AAC) in the diagnosis of masked hypertension.

Methods and results
Among the patients who underwent ambulatory blood pressure monitoring (ABPM) in our clinic, those with office blood pressure (OBP) <140/90 mmHg were included in the study population. According to OBP, they were divided into two groups as normal (<130/85 mmHg) and high normal (130–139/85–89 mmHg) OBP groups. Subjects were also investigated for the presence of masked hypertension with ABPM and searched in masked hypertension and control groups. Masked hypertension was defined as in the latest 2017 ACC/AHA Hypertension guideline and was diagnosed as the daytime BP ≥ 135/85 mmHg and nighttime BP ≥ 120/70 mmHg. AAC was evaluated on direct X-ray telecardiography. Diagnosis of masked hypertension was searched depending on the presence of AAC and OBP measurements as well. A total of 216 volunteers were involved in the study [mean age 45.2 ± 12.2 years; female gender 120 (55.5%)]. One hundred ten volunteers (50.9%) had masked hypertension according to the ABPM. AAC was significantly more common in the masked hypertension group (44.5% vs. 26.4%) (P = 0.005). AAC had a positive predictive value of 79% in those with high normal OBP in the diagnosis of masked hypertension, and also AAC had a negative predictive value of 74% in those with normal OBP.

Conclusion
AAC can be used as a reliable diagnostic tool to exclude and predict masked hypertension during office examination.
Comparison of Biliary Drainage Techniques for Malignant Biliary Obstruction
Authors: Xie Jesse , Garg Shashank , Perisetti Abhilash , Tharian Benjamin , Murad Mohammad Hassan , Inamdar Sumant 
Published: March 2021

Background and Aims:
Endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic biliary drainage, and endoscopic ultrasound (EUS)-guided biliary drainage are all established techniques for drainage of malignant biliary obstruction. This network meta-analysis (NMA) was aimed at comparing all 3 modalities to each other.

Materials and Methods:
Multiple databases were searched from inception to October 2019 to identify relevant studies. All the patients were eligible to receive any one of the 3 interventions. Data extraction and risk of bias assessment was performed using standardized tools. Outcomes of interest were technical success, clinical success, adverse events, and reintervention. Direct meta-analyses were performed using the random-effects model. NMA was conducted using a multivariate, consistency model with random-effects meta-regression. The GRADE approach was followed to rate the certainty of evidence.

Results:
The final analysis included 17 studies with 1566 patients. Direct meta-analysis suggested that EUS-guided biliary drainage had a lower reintervention rate than ERCP. NMA did not show statistically significant differences to favor any one intervention with certainty across all the outcomes. The overall certainty of evidence was found to be low to very low for all the outcomes.

Conclusions:
The available evidence did not favor any intervention for drainage of malignant biliary obstruction across all the outcomes assessed. ERCP with or without EUS should be considered first to allow simultaneous tissue acquisition and biliary drainage.
Low Rates of Hepatitis B Virus Treatment Among Treatment-Eligible Patients in Safety-Net Health Systems
Authors: Wong Robert J. , Jain Mamta K. , Therapondos George , Niu Bolin , Kshirsagar Onkar , Thamer Mae 
Published: March 2021

Background:
Timely initiation of antiviral therapy in chronic hepatitis B virus (CHB) reduces risk of disease progression. We evaluate overall treatment rates and predictors of treatment among treatment-eligible safety-net CHB patients.

Methods:
We retrospectively evaluated adults with CHB from 2010 to 2018 across 4 large safety-net health systems in the United States. CHB was identified with ICD-9/10 diagnosis coding and confirmed with laboratory data. Treatment eligibility was determined using American Association for the Study of Liver Diseases (AASLD) guidelines. Comparison of CHB treatment rates among treatment-eligible patients were performed using χ2 testing, Kaplan Meier methods and log-rank testing. Adjusted multivariate Cox proportional hazards models evaluated independent predictors of receiving treatment among eligible patients.

Results:
Among 5157 CHB patients (54.7% male, 34.6% African American, 22.3% Asian), 46.8% were treatment-eligible during the study period. CHB treatment rates were 48.4% overall and 37.3% among CHB patients without human immunodeficiency virus. Significantly lower odds of treatment were observed in females versus males (odds ratio: 0.40, 95% confidence interval: 0.33-0.49, P<0.001) and patients age 65 years or above versus age below 45 years (odds ratio: 0.68, 95% confidence interval: 0.51-0.92, P=0.012). Conversely, significantly greater odds of treatment were observed in African American and Asians versus non-Hispanic whites, CHB patients with indigent care versus commercially insured patients, and non-English speaking versus English speaking patients.

Conclusion:
Among a large multicentered, safety-net cohort of CHB patients, 46.8% of treatment-eligible CHB patients overall and 37.3% of treatment-eligible CHB patients without human immunodeficiency virus received antiviral therapy. Improving CHB treatment rates among treatment-eligible patients represents “low hanging fruit,” given the clear benefits of antiviral therapy in mitigating disease progression.
Proactive therapeutic drug monitoring is more effective than conventional management in inducing fecal calprotectin remission in inflammatory bowel disease
Authors: Fernandes Samuel Raimundo , Serrazina Juliana , Rodrigues Inês Coelho , Bernardo Sónia , Rita Gonçalves Ana , Valente Ana , Baldaia Cilénia , Santos Paula Moura , Correia Luís Araújo , Tato Marinho Rui 
Published: March 2021

Background
Proactive therapeutic drug monitoring (pTDM) may improve treatment outcomes in inflammatory bowel disease.

Aims and methods
We compared 135 patients following a prospective pTDM protocol aiming at an infliximab trough level (IFXTL) between 5 and 10 μg/ml with sequential measurements of Fc, with 108 patients from a retrospective group under conventional management. We evaluated the rates of Fc remission (<250 μg/g) and other clinical outcomes at 2-year of follow-up.

Results
pTDM associated with higher rates of Fc remission (69.6% vs. 50.0%; P = 0.002), and steroid-free clinical remission (78.4% vs. 55.2%, P = 0.028) with a trend for clinical remission (79.3% vs. 68.5%, P = 0.075). There was no difference in treatment discontinuation (P = 0.195), hospitalization (P = 0.156), and surgery (P = 0.110). Higher IFXTL associated with Fc remission at week 14 (6.59 vs. 2.96 μg/ml, P < 0.001), and at the end of follow-up (8.10 vs. 5.03 μg/ml, P = 0.001). In patients reaching Fc remission after week 14, IFXTL increased from week 14 to the end of follow-up (2.71 vs. 8.54 μg/ml, P < 0.001). Fc remission associated with higher rates of clinical (85.8% vs. 56.8% P < 0.001) and steroid-free clinical remission (86.9% vs. 50.0% P < 0.001), lower IFX discontinuation (8.8% vs. 36.8%, P < 0.001), and hospitalization (13.5% vs. 33.7%, P < 0.001), without significance for surgery (6.1% vs. 12.6%, P = 0.101).

Conclusion
pTDM was more effective than conventional management in inducing Fc remission which was associated with improved outcomes.
Natural history and predictors associated with the evolution of portal venous system thrombosis in liver cirrhosis
Authors: Xu Shixue , Guo Xiaozhong , Xu Xiangbo , Wang Le , Tacke Frank , Primignani Massimo , He Yanglan , Yin Yue , Yi Fangfang , Qi Xingshun 
Published: March 2021

Background
Portal venous system thrombosis (PVST) will progress in some cases, indicating worse outcome and the necessity of antithrombotic treatment, but will spontaneously improve in others. It is crucial to understand the natural history of PVST in liver cirrhosis. However, the knowledge regarding how to predict the evolution of PVST in cirrhotic patients is very scant.

Methods
Sixty-nine cirrhotic patients without malignancy, who had undergone repeated contrast-enhanced computed tomography or MRI to evaluate the severity of PVST at the first and last admissions, were included. Logistic regression analysis was performed to identify the risk factors for the evolution of PVST in liver cirrhosis. Odds ratios (ORs) were calculated.

Results
Among 42 patients without PVST at the first admission, 10 (23.8%) developed PVST at the last admission. Serum albumin level (OR = 0.873), prothrombin time (OR = 1.619), activated partial thromboplastin time (OR = 1.169), Child-Pugh score (OR = 1.560) and model for end-stage liver disease (MELD) score (OR = 1.292) at the last admission were significant risk factors associated with the development of PVST. Among 27 patients with PVST at the first admission, 11 (40.7%), 4 (14.8%) and 12 (44.4%) had improvement, stabilization and progression of PVST at the last admission, respectively. ΔMELD score (OR = 0.714) was the only significant risk factor associated with the improvement of PVST; additionally, serum albumin level at the first admission (OR = 1.236) was the only significant risk factor associated with the progression of PVST.

Conclusion
Aggravation and amelioration of liver dysfunction may predict the development and improvement of PVST in liver cirrhosis, respectively.
Standardized Discharge Planning Tool Leads to Earlier Discharges and Fewer Readmissions
Authors: Kucharczuk Colleen , Lightheart Erin , Kodan Allison , Haynes Cassandra , Rabatin Susan , Burke Joy , Senger Jamie , Lee Lindsay , Brinley Sarah , Decena Mary Angela , Cruz Juanita M. , Hirsh Rebecca , McCauley Kathy 
Published: March 2021

Background:
In an inpatient setting, aspects of discharge planning are often left to the provider's memory, leading to errors, inefficiencies, and avoidable costs.

Methods:
A multidisciplinary team of oncology practitioners used process improvement methodologies to redesign the discharge planning process.

Interventions:
The primary intervention was an evidence-based discharge planning tool, called the discharge navigator, used from admission through discharge.

Results:
Thirty-day unplanned readmission rates decreased by 29.0% from preimplementation (March 2017 through August 2017) to postimplementation (September 2017 through March 2020). The percentage of patients discharged before noon increased 76.2%. A comparable service not utilizing the intervention saw lesser or no improvement in these measures.

Conclusion:
The tool provided a systematic approach to discharge planning. Key design elements included a centralized location within the electronic health record and an electronic shortcut to populate the tool. Although developed for a specialized population, most elements are applicable to any hospitalized patient.