bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time-Variable Training in Medicine: Theoretical Considerations
Authors: ten Cate Olle , Gruppen Larry D. , Kogan Jennifer R. , Lingard Lorelei A. , Teunissen Pim W. 
Published: February 2018

The introduction of competency-based medical education has shifted thinking from a fixed-time model to one stressing attained competencies, independent of the time needed to arrive at those competencies. In this article, the authors explore theoretical and conceptual issues related to time variability in medical training, starting with the Carroll model from the 1960s that put time in the equation of learning. They discuss mastery learning, deliberate practice, and learning curves.
While such behaviorist theories apply well to structured courses and highly structured training settings, learning in the clinical workplace is not well captured in such theories or in the model that Carroll proposed. Important in clinical training are self-regulation and motivation; neurocognitive perspectives of time and learning; professional identity formation; and entrustment as an objective of training—all of which may be viewed from the perspective of the time needed to complete training. The authors conclude that, in approaching time variability, the Carroll equation is too simplistic in its application to the breadth of medical training. The equation may be expanded to include variables that determine effective workplace learning, but future work will need to examine the validity of these additional factors.
Measurement of Teicoplanin Concentration With Liquid Chromatography-Tandem Mass Spectrometry Method Demonstrates the Usefulness of Therapeutic Drug Monitoring in Hematologic Patient Populations
Authors: Chae Hyojin , Lee Jeong Joong , Cha Kyoungho , Her Su Hyun , Kim Hyo-Young , Han Eunhee , Kim Myungshin , Kim Yonggoo , Cho Sung-Yeon , Lee Dong-Gun 
Published: February 2018

Background:Teicoplanin is a glycopeptide antibiotic that has become increasingly popular with the spread of methicillin-resistantStaphylococcus aureus. The aim of the study was to develop and validate an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for teicoplanin, and analyze trough teicoplanin concentrations achieved in patients with hematological diseases.Methods:The UHPLC-MS/MS method for teicoplanin was developed, validated, and applied in a retrospective analysis of trough plasma teicoplanin concentrations from 305 patients receiving standard dose, and 17 patients receiving therapeutic drug monitoring (TDM)-guided individualized dose.Results:The linear range was 3.9–52.9 mg/L. The imprecision was less than 12%, the limits of detection and quantification were less than 0.13 and 0.72 mg/L, respectively. The sample carry-over and ion suppression were insignificant. In the standard dose group, the median teicoplanin concentrations were 7.5 mg/L (days 3–5) and 8.9 mg/L (on days 6–8); and the proportion of trough levels achieving ≥10 mg/L was 20% (days 3–5) and 38% (days 6–8), respectively. In the TDM-guided individualized dose group, median teicoplanin concentration was higher (16.9 mg/L), and the proportion of trough levels ≥10 mg/L was also higher (77%) when compared with the standard dose group.Conclusions:Based on these results, the present UHPLC-MS/MS method can be considered suitable for routine TDM of teicoplanin. Also, based on the insufficient trough teicoplanin concentrations achieved with standard dose regimen, and the higher trough teicoplanin concentrations achieved with TDM-guided individualized dose regimen, this study highlights the importance of TDM of teicoplanin, especially in high-risk patient groups.
Phase II Clinical Trial of Lenalidomide and Dexamethasone Therapy in Japanese Elderly Patients With Newly Diagnosed Multiple Myeloma to Determine Optimal Plasma Concentration of Lenalidomide
Authors: Kobayashi Takahiro , Miura Masatomo , Niioka Takenori , Abumiya Maiko , Ito Fumiko , Kobayashi Isuzu , Ikeda Sho , Yoshioka Tomoko , Kameoka Yoshihiro , Takahashi Naoto 
Published: February 2018

Background:
The authors conducted a phase II clinical trial of lenalidomide and dexamethasone combination therapy in Japanese elderly patients with newly diagnosed multiple myeloma to evaluate its safety and efficacy and to determine whether safety and efficacy correlate with the plasma concentration of lenalidomide.

Methods:
Forty patients received oral lenalidomide on days 1–21 of a 28-day cycle in addition to weekly doses of dexamethasone. Plasma concentrations of lenalidomide were measured, and the area under the concentration–time curve from 0 to 24 hours (AUC0–24) of lenalidomide was predicted using a formula the authors previously reported in this journal.

Results:
The median age was 75.5 years. Twenty-one patients had renal impairment severe enough to require dose adjustment of lenalidomide. The median initial doses of lenalidomide and dexamethasone were 12.5 and 20 mg, respectively. The overall response rate was 68.6%, and the 2-year overall survival rate was 88.5%. There was no correlation between the response rate and plasma concentration of lenalidomide. Grade 3–4 adverse events (AEs) were observed in 57.5% of patients. The AUC0–24 of lenalidomide was significantly higher in patients with grade 3–4 AEs than in those who did not suffer from AEs (median = 4852.0 versus 2464.9 ng·h−1·mL−1, P = 0.027). Receiver-operating characteristic curve analysis showed that the AUC0–24 of lenalidomide was a good predictor of grade 3–4 AEs, with an area under the receiver-operating characteristic curve of 0.758 (95% confidence interval, 0.572–0.943, P = 0.027). The cutoff value for best prediction of grade 3–4 AEs was 2613.5 ng·h−1·mL−1 (sensitivity 86.7%, specificity 54.5%). Multivariate logistic analysis confirmed the significance of this cutoff value.

Conclusions:
These data suggest that overexposure to lenalidomide could contribute to toxicity. Furthermore, the predicted cutoff value of AUC0–24 can be clinically used to prevent severe AEs.
SILDENAFIL CITRATE INDUCED RETINAL TOXICITY—ELECTRORETINOGRAM, OPTICAL COHERENCE TOMOGRAPHY, AND ADAPTIVE OPTICS FINDINGS
Authors: Yanoga Fatoumata , Gentile Ronald C. , Chui Toco Y. P. , Freund K. Bailey , Fell Millie , Dolz-Marco Rosa , Rosen Richard B. 
Published: February 2018

Background/Purpose:
To report a case of persistent retinal toxicity associated with a high dose of sildenafil citrate intake.

Methods:
Single retrospective case report.

Results:
A 31-year-old white man with no medical history presented with complaints of bilateral multicolored photopsias and erythropsia (red-tinted vision), shortly after taking sildenafil citrate—purchased through the internet. Patient was found to have cone photoreceptor damage, demonstrated using electroretinogram, optical coherence tomography, and adaptive optics imaging. The patient's symptoms and the photoreceptor structural changes persisted for several months.

Conclusion:
Sildenafil citrate is a widely used erectile dysfunction medication that is typically associated with transient visual symptoms in normal dosage. At high dosage, sildenafil citrate can lead to persistent retinal toxicity in certain individuals.
Association of Axial Length Growth and Topographic Change in Orthokeratology
Authors: Lee Eun Jung , Lim Dong Hui , Chung Tae-Young , Hyun Joo , Han Jisang 
Published: February 2018

Objectives:To investigate the topographic factors related to axial length (AL) growth rate in orthokeratology.Methods:Clinical data of myopic children with orthokeratology lenses from 2010 to 2016 were investigated. Corneal topography (Orbscan II) and IOLMaster-measured AL at baseline and every posttreatment visit were analyzed. Optical map topographies from baseline- and posttreatment-stabilized corneas were analyzed to calculate the refractive power difference between the apex and the periphery (apex-periphery refractive power difference [ARPD]), which estimates the change of peripheral refraction. A generalized estimating equation (GEE) was used to assess the associations between AL growth and topographic changes in both eyes.Results:The mean baseline spherical equivalent (SE) was −2.40±1.12 diopters (D) and the mean AL was 24.38±0.77 mm. Over a mean follow-up period of 41.9 months, the mean AL growth rate was 0.22±0.15 mm/year. In a univariable GEE analysis, age at initial lens wear, baseline AL, baseline SE, central corneal thickness (CCT), baseline apex power, and posttreatment ARPD on optical topography maps were all significantly correlated with AL growth rate (P<0.001, 0.009, 0.024, 0.011, 0.010, and 0.006, respectively). In a multivariable GEE, CCT and posttreatment ARPD were identified as significant factors (P=0.014 and 0.016, respectively).Conclusions:The AL growth rate was significantly associated with CCT and posttreatment relative peripheral refractive power, in addition to age at initial lens wear. These associations might possibly demonstrate an effect of treatment-induced peripheral refraction changes on retardation of myopic progression, whereas younger age might significantly influence both AL growth rate and corneal deformation.
Comparison Study of Percutaneous Osseointegrated Bone Conduction Device Complications When Using the 9 mm Abutment Versus 6 mm Abutment at Initial Implantation
Authors: Wise Sean R. , LaRouere Jacqueline S. , Bojrab Dennis I. , LaRouere Michael J. 
Published: February 2018

Objectives:
To assess differences in the incidence, type, and management of complications encountered with implantation of percutaneous osseointegrated bone conduction devices when using a 9 mm abutment versus 6 mm abutment at initial implantation.

Study Design:
Retrospective cohort study.

Methods:
One hundred thirty consecutive patients between January 2010 and December 2011 underwent single-stage percutaneous osseointegrated bone conduction device implantation using a 9 or 6 mm abutment. Clinical outcomes assessed for the two groups included the incidence, type, and management of postoperative complications. Abutment size, age, sex, indication for surgery, implant device type, duration of follow-up, and patient comorbidities were evaluated as potential factors affecting outcomes.

Results:
Average duration of follow-up was 16 months (range 6–29 mo). Postoperative complications occurred in 38 (29.2%) patients. Twenty-four (18.4%) patients experienced minor complications requiring simple, local care; eight (6.1%) patients required in-office procedural intervention; and six (4.6%) patients required revision surgery in the operating room. Implant extrusion occurred in three (2.3%) patients. Eleven (8.5%) patients required placement of a longer abutment. Patients receiving the 6 mm abutment at initial surgery were significantly more likely to encounter a complication requiring in-office procedural intervention or revision surgery (p = 0.001).

Conclusion:
Minor complications after implantation of percutaneous osseointegrated bone conduction devices are common. The vast majority of these complications are due to localized skin reactions, most of which are readily addressed through local care. Patients receiving the 9 mm abutment during initial implantation are significantly less likely to require in-office procedural intervention or revision surgery postoperatively as compared with those receiving the shorter, 6 mm abutment.
Autoimmune Encephalitis With Multiple Autoantibodies
Authors: Kim Albert E. , Kang Peter , Bucelli Robert C. , Ferguson Cole J. , Schmidt Robert E. , Varadhachary Arun S. , Day Gregory S. 
Published: February 2018

Introduction:
Indications for autoantibody testing in patients with rapid-onset cognitive impairment have expanded in step with the growing number of disease-associated autoantibodies and clinical syndromes. Although increased access to autoantibody testing has broadened our understanding of the spectrum of autoimmune encephalitis (AE), it has also produced new challenges associated with deciphering the contributions of disease-associated autoantibodies in patients with atypical clinical features and/or multiple autoantibodies. These challenges are illustrated through presentation of a patient with AE associated with autoantibodies against intracellular and cell-surface neuronal antigens. The implications of detection of multiple autoantibodies are considered in the context of relevant literature, and used to frame a diagnostic and therapeutic approach.

Case Report:
A previously well 67-year-old man presented with encephalopathy and psychosis, impaired visual fixation, and ataxia, emerging over 3 months. Hu, CRMP-5, and NMDAR autoantibodies were identified in the cerebrospinal fluid. No malignancy was discovered despite extensive investigations. An aggressive course of immunotherapy temporarily stabilized his course; however, the patient succumbed to his illness 10 months after symptom onset. Lack of sustained response to immunotherapy and neuropathologic findings suggested that AE associated with Hu antibodies was primarily responsible for this patient’s progressive decline.

Conclusions:
Multiple autoantibodies may be detected in patients with AE. When antibodies targeting intracellular and cell-surface antigens are detected together, investigation and treatment of syndromes associated with intracellular antibodies should be prioritized, acknowledging the link between these antibodies and irreversible neuronal injury. In paraneoplastic cases, prognosis may be tied to early detection and treatment of the underlying malignancy.
Reexpansion Pulmonary Edema in Pediatrics
Authors: Hirsch Alexander W. , Nagler Joshua 
Published: February 2018

Abstract
Reexpansion pulmonary edema is a rare complication that may occur after drainage of pneumothorax or pleural effusion. A number of factors have been identified that increase the risk of developing reexpansion pulmonary edema, and pathophysiologic mechanisms have been postulated. Patients may present with radiographic findings alone or may have signs or symptoms that prompt evaluation and diagnosis. Clinical presentations range from mild cough to respiratory failure and hemodynamic compromise. Treatment strategies are supportive, and should be tailored to match the severity of the condition.
The Evolution of Trauma in Los Angeles County Over More Than a Decade
Authors: Chen Sean Shaohua , Bosson Nichole , Gausche-Hill Marianne , Gorospe Deidre D. , Tadeo Richard E. 
Published: February 2018

Objective:
Explore trends in trauma incidence and mortality rates in Los Angeles County.

Design:
Data for patients treated at Los Angeles County trauma centers from 2000 to 2011 were analyzed for this study. Age-adjusted incidence and mortality rates were calculated by gender, race, injury type, injury severity, and mechanism of injury. Trends were assessed using linear regression to determine the annual percentage change (APC).

Results:
There were 223 773 patients included. The trauma incidence rate increased by 14.6% driven by an increase in blunt injury of 5.4% annually (P < .05). Penetrating injury decreased at −6.9% APC (P < .01). Mortality rate decreased at −11.5% APC (P < .01), with reduction in both blunt (−6.8% APC [P < .01]) and penetrating injuries (−16.7% APC [P < .01]). The trends in mortality persisted with stratification by age, gender, race, and injury severity score.

Conclusion:
In this mature trauma system, the trauma incidence increased slightly from 2000 to 2011, while the mortality steadily declined. Public health officials in other areas could perform a similar self-evaluation to describe and monitor injury events and trends in their jurisdictions, a reassessment of priority and trauma system resource allocation, which will directly benefit the regional population.
Orbital Interstitial Fluid: Evidence of a Potential Pathway for Extracranial Cerebrospinal Fluid Absorption
Authors: Sachs Jeffrey R. , Zapadka Michael E. , Elster Allen D. 
Published: February 2018

Background and PurposeThe aim of the study was to describe the prevalence and characteristics of orbital interstitial fluid seen on magnetic resonance (MR) images of infants and young children.Materials and MethodsFat-suppressed axial T2-weighted MR images of 100 consecutive infants and young children (<6 years) without orbital pathology were retrospectively reviewed by 2 neuroradiologists. The presence, location, and extent of high-signal orbital interstitial fluid were characterized and tabulated as a function of age.ResultsOrbital interstitial fluid was detected in 90 (90%) of the 100 subjects overall, present in 100% (75/75) of infants and children younger than 3 years, 75% (12/16) of those aged 3 to 5 years, and 33% (3/9) of those aged 5 to 6 years. The fluid was bilateral and symmetric in all cases. Two morphologic patterns were distinguished, which often co-existed: (1) a focal discrete curvilinear band of fluid in the posterior-lateral orbit, more common in younger patients, and (2) an ill-defined, lace-like pattern primarily in the superior orbit seen in subjects of all ages.ConclusionsOrbital interstitial fluid as detected by fat-suppressed T2-weighted MR imaging is a nearly universal finding in infants and young children and should not be considered pathologic. It may have either a focal or lace-like pattern or both. Orbital interstitial fluid decreases in size and prevalence as a function of age but is still present in nearly half of children aged 4 to 6 years. Possible explanations concerning the nature and origin of this fluid are presented, including the fascinating possibility that the fluid represents an extracranial pathway for outflow of cerebrospinal fluid.
Phenotypic Multiorgan Involvement of Subclinical Disease as Quantified by Magnetic Resonance Imaging in Subjects With Prediabetes, Diabetes, and Normal Glucose Tolerance
Authors: Storz Corinna , Rospleszcz Susanne , Lorbeer Roberto , Hetterich Holger , Auweter Sigrid D. , Sommer Wieland , Machann Jürgen , Gatidis Sergios , Rathmann Wolfgang , Heier Margit , Linkohr Birgit , Meisinger Christa , Reiser Maximilian , Hoffmann Udo , Peters Annette , Schlett Christopher L. , Bamberg Fabian 
Published: February 2018

Introduction
Detailed mechanisms in the pathophysiology of diabetes disease are poorly understood, but structural alterations in various organ systems incur an elevated risk for cardiovascular events and adverse outcome. The aim of this study was to compare multiorgan subclinical disease phenotypes by magnetic resonance (MR) imaging to study differences between subjects with prediabetes, diabetes, and normal controls.

Materials and Methods
Subjects without prior cardiovascular disease were enrolled in a prospective case-control study and underwent multiorgan MR for the assessment of metabolic and arteriosclerotic alterations, including age-related white matter changes, hepatic proton density fat fraction, visceral adipose tissue volume, left ventricular remodeling index, carotid plaque, and late gadolinium enhancement. Magnetic resonance features were summarized in a phenotypic-based score (range, 0–6). Univariate, multivariate correlation, and unsupervised clustering were performed.

Results
Among 243 subjects with complete multiorgan MR data sets included in the analysis (55.6 ± 8.9 years, 62% males), 48 were classified as subjects with prediabetes and 38 as subjects with diabetes. The MR phenotypic score was significantly higher in subjects with prediabetes and diabetes as compared with controls (mean score, 3.00 ± 1.04 and 2.69 ± 0.98 vs 1.22 ± 0.98, P < 0.001 respectively), also after adjustment for potential confounders. We identified 2 clusters of MR phenotype patterns associated with glycemic status (P < 0.001), independent of the MR score (cluster II–metabolic specific: odds ratio, 2.49; 95% CI, 1.00–6.17; P = 0.049).

Discussion
Subjects with prediabetes and diabetes have a significantly higher phenotypic-based score with a distinctive multiorgan phenotypic pattern, which may enable improved disease characterization.
Continuous Hepatic Arterial Multiphase Magnetic Resonance Imaging During Free-Breathing
Authors: Weiss Jakob , Notohamiprodjo Mike , Taron Jana , Martirosian Petros , Nickel Dominik , Bamberg Fabian , Nikolaou Konstantin , Othman Ahmed E. 
Published: February 2018

Purpose
The aim of this study was to evaluate the feasibility of a prototype volume-interpolated breath-hold examination (VIBE) sequence using compressed sensing (VIBECS) for rapid multiphase arterial magnetic resonance imaging (MRI) at different temporal resolution during free-breathing in comparison with a conventional breath-hold approach (VIBESTD).

Material and Methods
A total of 40 patients with liver malignancies were prospectively included in this study and underwent contrast-enhanced liver MRI at 1.5 T to evaluate the performance of VIBECS for rapid arterial multiphase imaging. An additional 40 patients examined with a VIBESTD were included serving as standard of reference. The VIBECS study cohort was subdivided into 2 groups (each n = 20). In both groups, VIBECS was continuously acquired for 60 seconds starting with the contrast agent administration (group A, temporal resolution 4 seconds; group B, temporal resolution 8 seconds). Subsequently, the time point with the subjectively best image quality was selected and defined as hepatic arterial dominant (HAD) phase. Overall image quality, lesion conspicuity, vessel contrast, and artifacts of HAD phase were assessed by 2 radiologists independently on a 5-point Likert scale (5 = excellent) and compared with arterial phase images of VIBESTD. In addition, signal attenuation/time curves of VIBECS were plotted for each patient to quantify the hepatic arterial enhancement.

Results
No patients were excluded and all HAD phases were reliably recorded in the investigated VIBECS cohort. Most commonly, HAD was observed at the ninth time point (36 seconds after intravenous contrast injection) in group A and at the fifth time point (40 seconds after intravenous contrast injection) in group B. Timing with VIBESTD was only adequate in 65% (26/40). Image quality, lesion conspicuity, and vessel contrast were good to excellent without significant differences between both VIBECS groups (P ≥ 0.2) and with significantly higher reading scores as compared with VIBESTD with respect to lesion conspicuity (P ≤ 0.006) and image quality (group B; P < 0.001). VIBECS showed reconstruction artifacts, which were significantly higher in group A (P = 0.001). Mean peak arterial enhancement was observed at the ninth time point (36 seconds) in group A and at the sixth (48 seconds) in group B.

Conclusion
VIBECS allows for robust multiphase arterial imaging during free-breathing at high spatial and temporal resolution (preferably 8 seconds) with improved image quality and lesion conspicuity as compared with VIBESTD.
Simple Technique for Reducing the Buccal Fat Pad During Mandibular Orthognathic Surgery
Authors: Kawase-Koga Yoko , Shibata Kaoru , Kimoto Akira , Watanabe Masato , Chikazu Daichi 
Published: February 2018

Abstract
Sagittal split ramus osteotomy and intraoral vertical ramus osteotomy are commonly performed for the correction of jaw deformities. However, during mandibular orthognathic surgeries such as sagittal split ramus osteotomy and intraoral vertical ramus osteotomy , the authors sometimes encounter exposure of the buccal fat pad (BFP), which decreases the surgical field. The exposed BFP makes it difficult to perform these operations, may result in unexpected complications, and may increase the operation time. Therefore, the authors herein describe a simple, safe, and convenient technique for reducing the volume of the exposed BFP during mandibular orthognathic surgery using an electric knife in the coagulation mode.