bluuebunny/crossref_metadata_2025_split huggingface dataset:
Costs of shoulder disorders in Denmark: a nationwide cost-of-illness study investigating 617,334 patients and matched controls
Authors: Sørensen Lotte , van Tulder Maurits , Johannsen Hans Viggo , Ovesen Janne , Enemark Ulrika , Blæhr Emely Ek , Oestergaard Lisa Gregersen 
Published: February 2022

Abstract
Shoulder disorders are very common musculoskeletal conditions. Few studies have focused on the costs associated with shoulder disorders, and the economic burden has never been established in a nationwide cost-of-illness study. We aimed to evaluate the healthcare costs and costs of productivity loss (sick leave) and to evaluate if costs were higher for specific subgroups. Using national Danish registers, we identified individuals with shoulder disorders (subacromial pain, stiffness, fracture, or dislocation) diagnosed between 2005 and 2017 and controls matched on age and gender without shoulder disorders. Health care usage, sick leave, and related costs were estimated. During the 13-year inclusion period, 617,334 unique individuals were identified and the incidence rate was 1215 per 100,000 person-years in 2017. The expected additional societal costs were €1.21 billion annually. The mean additional total costs for the 6-year period were €11,334 (11,014-11,654) for individuals aged ≥65 years and €25,771 (25,531-26,012) for individuals aged <65 years. For individuals in the working age, the costs of sick leave accounted for approximately 70% of the total costs. Individuals aged ≥65 years had healthcare costs that were twice as high as individuals aged <65 years. Additionally, the 20% of cases accruing the highest costs accounted for 66% of the total costs. In conclusion, incidence rates of shoulder disorders were high and costs of sick leave accounted for a large proportion of total costs associated with illness in working age people. Furthermore, a minority of patients accounted for a substantial share of the total costs.
Anoctamin 1/TMEM16A in pruritoceptors is essential for Mas-related G protein receptor–dependent itch
Authors: Kim Hyesu , Kim Hyungsup , Cho Hawon , Lee Byeongjun , Lu Huan-Jun , Kim Kyungmin , Chung Sooyoung , Shim Won-Sik , Shin Young Kee , Dong Xinzhong , Wood John N. , Oh Uhtaek 
Published: February 2022

Abstract
Itch is an unpleasant sensation that evokes a desire to scratch. Pathologic conditions such as allergy or atopic dermatitis produce severe itching sensation. Mas-related G protein receptors (Mrgprs) are receptors for many endogenous pruritogens. However, signaling pathways downstream to these receptors in dorsal root ganglion (DRG) neurons are not yet understood. We found that anoctamin 1 (ANO1), a Ca2+-activated chloride channel, is a transduction channel mediating Mrgpr-dependent itch signals. Genetic ablation of Ano1 in DRG neurons displayed a significant reduction in scratching behaviors in response to acute and chronic Mrgpr-dependent itch models and the epidermal hyperplasia induced by dry skin. In vivo Ca2+ imaging and electrophysiological recording revealed that chloroquine and other agonists of Mrgprs excited DRG neurons via ANO1. More importantly, the overexpression of Ano1 in DRG neurons of Ano1-deficient mice rescued the impaired itching observed in Ano1-deficient mice. These results demonstrate that ANO1 mediates the Mrgpr-dependent itch signaling in pruriceptors and provides clues to treating pathologic itch syndromes.
Botulinum Toxin Type A Immunogenicity across Multiple Indications: An Overview Systematic Review
Authors: Rahman Eqram , Banerjee Pooja S. , Asghar Andleeb , Gupta Niraj Kumar , Mosahebi Afsin 
Published: February 2022

Background:
Botulinum toxin type A has been used to treat a wide array of neurologic, medical, and aesthetic indications. Several factors contribute to the formation of neutralizing antibodies, such as shorter intervals of treatment, higher dosage, amounts of antigenic proteins, serotypes, and storage of formulations.

Method:
This overview followed the Cochrane guideline for overview reviews. The AMSTAR-2 (revised version of A Measurement Tool to Assess Systematic Reviews) tool was used for the critical appraisal of the selected systematic reviews.

Results:
Five systematic reviews consisting of 203 studies (17,815 patients) were included, and their AMSTAR-2 scores were low to critically poor. There was high heterogeneity between the studies. Across the clinical indications, neutralizing antibody prevalence was significantly higher in dystonia, spasticity, and urologic conditions, and nil to insignificant in hyperhidrosis and aesthetic indications. The overall rate for the neutralizing antibody formation across three different formulations, abobotulinumtoxinA, incobotulinumtoxinA, and onabotulinumtoxinA, was 1 to 2.1 percent, with no significant difference between them.

Results:
Although there is debate on the prevalence rate across the different botulinum toxin type A formulations in individual systematic reviews, the overall frequency of the development of neutralizing antibodies and the immunogenicity of abobotulinumtoxinA, incobotulinumtoxinA, and onabotulinumtoxinA remain low to insignificant.

Conclusions:
Properly designed comparative trials are required to explore the difference in the prevalence of neutralizing antibodies across the commercially available botulinum toxin type A products. Such studies should also examine the relevance of neutralizing antibody titer to clinical responsiveness and nonresponse.
Size and Perception of Facial Features with Selfie Photographs, and Their Implication in Rhinoplasty and Facial Plastic Surgery
Authors: Pressler Mark P. , Kislevitz Mikaela L. , Davis Justin J. , Amirlak Bardia 
Published: February 2022

Background:
Patients increasingly use photographs taken with a front-facing smartphone camera—“selfies”—to discuss their goals with a plastic surgeon. The purpose of this study was to quantify changes in size and perception of facial features when taking a selfie compared to the gold standard of clinical photography.

Methods:
Thirty volunteers took three series of photographs. A 12-inch and 18-inch series were taken with a front-facing smartphone camera, and the 5-foot clinical photography series was taken with a digital single-lens reflex camera. Afterward, subjects filled out the FACE-Q inventory, once when viewing their 12-inch selfies and once when viewing their clinical photographs. Measurements were taken of the nose, lip, chin, and facial width.

Results:
Nasal length was, on average, 6.4 percent longer in 12-inch selfies compared to clinical photography, and 4.3 percent longer in 18-inch selfies compared to clinical photography. The alar base width did not change significantly in either set of selfies compared to clinical photography. The alar base to facial width ratio represents the size of the nose in relation to the face. This ratio decreased 10.8 percent when comparing 12-inch selfies to clinical photography (p < 0.0001) and decreased 7.8 percent when comparing 18-inch selfies to clinical photography (p < 0.0001).

Conclusions:
This study quantifies the change in facial feature size/perception seen in previous camera-to-subject distance studies. With the increasing popularity of front-facing smartphone photographs, these data allow for a more precise conversation between the surgeon and the patient. In addition, the authors’ findings provide data for manufacturers to improve the societal impact of smartphone cameras.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Diagnostic, III.
Controlling Nasal Tip Projection and Rotation with New Composite Septocolumellar Flap Approaches
Authors: Öztürk Güncel 
Published: February 2022

Background:
Rhinoplasty is one of the most common and challenging surgeries in the field of aesthetic surgery. For obtaining an aesthetically pleasing nose, it is extremely important to control nasal tip projection and rotation as much as possible. Since the last decade, septocolumellar suture techniques have been most frequently used for modifying and controlling nasal tip rotation and projection and for obtaining a better columellar–labial angle during rhinoplasty. In the present study, the author has described 10 different approaches using composite septocolumellar flaps with the aim of obtaining better outcomes, such as the control of nasal tip projection and rotation, in addition to obtaining better tip refinement.

Methods:
The records of 68 patients were included in the present study based on the inclusion and exclusion criteria. Ten composite septocolumellar flap approaches were followed by the same surgeon.

Results:
The initial median Rhinoplasty Outcome Evaluation score was 60.5 points; the score increased to 92.5 points at 12 months after the surgery (p < 0.001). Satisfaction was excellent in 87.5 percent of the patients. The patients were also evaluated in terms of functionality. Their patency scores increased from 6.0 to 9.0 (out of 10) after a 12-month follow-up (p = 0.001).

Conclusions:
The technique has the following advantages: control of nasal tip projection and rotation, fixation of mild deviations, and shortening of the nose with better aesthetic and functional outcomes. Furthermore, because the septocolumellar region is completely protected and remains solid, a dynamic nasal tip is obtained. Surgeons will be able to choose the most suitable approach when a composite septocolumellar flap is needed.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
The Five-Step Rhinoplasty Dead Space Closure Technique
Authors: Savetsky Ira L. , Avashia Yash J. , Rohrich Rod J. 
Published: February 2022

Summary:
The creation of dead space in rhinoplasty creates a welcoming environment for erratic soft -tissue contraction. If rhinoplasty surgeons can control and reliably predict skin contraction and wound healing, rhinoplasty results will undoubtedly improve. Obliteration of dead space is a key component in rhinoplasty as it minimizes soft-tissue contraction, resulting in a more predictable outcome. In this article, the authors present a systematic five-step dead space closure surgical plan.
Dynamic Liver Magnetic Resonance Imaging During Free Breathing
Authors: Endler Christoph H.-J. , Kukuk Guido M. , Peeters Johannes M. , Beck Gabriele M. , Isaak Alexander , Faron Anton , Mesropyan Narine , Luetkens Julian A. , Attenberger Ulrike I. , Kupczyk Patrick A. 
Published: February 2022

Objective
Robust dynamic contrast-enhanced T1-weighted images are crucial for accurate detection and categorization of focal liver lesions in liver/abdominal magnetic resonance imaging (MRI). As optimal dynamic imaging usually requires multiple breath-holds, its inherent susceptibility to motion artifacts frequently results in degraded image quality in incompliant patients. Because free-breathing imaging may overcome this drawback, the intention of this study was to evaluate a dynamic MRI sequence acquired during free breathing using the variable density, elliptical centric golden angle radial stack-of-stars radial sampling scheme, which so far has not been implemented in 4-dimensional applications.

Materials and Methods
In a prospective pilot study, 27 patients received a routine abdominal MRI protocol including the prototype free-breathing sequence (4DFreeBreathing) for dynamic imaging. This enables more convenient and faster reconstruction through variable density, elliptical centric golden angle radial stack-of-stars without the use of additional reconstruction hardware, and even higher motion robustness through soft-gating. A standard breath-hold sequence performed subsequently served as reference standard. Of the continuous dynamic data sets, each dynamic phase was analyzed regarding image quality, motion artifacts and vessel conspicuity using 5-point Likert scales. Furthermore, correct timing of the late arterial phase was compared with the preexaminations.

Results
4DFreeBreathing delivered motion-free dynamic images with high temporal resolution in each subject. Overall image quality scores were rated good or excellent for 4DFreeBreathing and the gold standard without significant differences (P = 0.34). There were significantly less motion artifacts in the 4DFreeBreathing sequence (P < 0.0001), whereas vessel conspicuity in each dynamic phase was comparable for both groups (P = 0.45, P > 0.99, P = 0.22, respectively). Correct timing of the late arterial phase could be achieved in 27 of 27 (100%) examinations using 4DFreeBreathing versus 35 of 53 (66%) preexaminations using gold standard (P < 0.001).

Conclusion
The benefit of convenient and fast image reconstruction combined with the superiority in motion robustness and timing compared with standard breath hold sequences renders 4DFreeBreathing an attractive alternative to existing free-breathing techniques in dynamic liver MRI.
Obstetric Simulation Training and Teamwork
Authors: Greer Joy A. , Lutgendorf Monica A. , Ennen Christopher S. , Van Petten Lauren , Modzik Adrian , Salas Dominick , Fish Jessica , Middlebrooks Reginald , Spalding Carmen N. , Delorey Donald R. 
Published: February 2022

Introduction
The Obstetric Simulation Training and Teamwork (OB-STaT) curriculum was an in situ interprofessional program to provide standardized postpartum hemorrhage (PPH) simulation training throughout a health system to decrease PPH morbidity. In this study portion, investigators hypothesized that OB-STaT would increase: (a) team member knowledge in diagnosis and management of PPH, (b) teamwork, (c) adherence to established PPH protocols, and (d) patient satisfaction.

Methods
The OB-STaT was implemented at 8 US Navy hospitals between February 2018 and November 2019. Participant PPH treatment and maternal/neonatal resuscitation pretraining/posttraining knowledge was assessed via an 11-item test, whereas teamwork and standardized patient assessment were rated using validated Likert-type scales: the 15-item Clinical Teamwork Scale and 3-item Patient Perception Score, with item ranges of 0 to 10 and 0 to 5, respectively. Local PPH protocol adherence was assessed using role-specific checklists, with a potential maximum of 14 points (anesthesia/nursing) or 22 points (obstetrics).

Results
Fifty-four interprofessional teams participated. Obstetricians (trainees and attendings) demonstrated significantly improved knowledge test scores (8.33 ± 1.6 vs. 8.66 ± 1.5, P < 0.01). Between the 2 scenarios, overall mean Clinical Teamwork Scale scores improved significantly for all interprofessional teams (5.82 ± 2.0 vs. 7.25 ± 1.9, P < 0.01). Anesthesia, nursing, and obstetric subteams demonstrated significant increases in protocol adherence as measured by critical action scores (12.28 ± 1.7 vs. 13.56 ± 1.0, 12.43 ± 1.6 vs. 13.14 ± 1.3, and 18.14 ± 2.7 vs. 19.56 ± 2.1 respectively, all P < 0.02). Although overall standardized patient satisfaction did not significantly improve, scores for feeling well informed did (3.36 ± 1.0 vs. 3.76 ± 0.8, P < 0.01).

Conclusions
The OB-STaT curriculum modestly improved participants' teamwork, communication, and protocol adherence during simulated PPH scenarios; OB-STaT may decrease PPH morbidity.
Who Can Debriefing Assessment for Simulation in Healthcare? Different Perspectives on Teledebriefing Assessments
Authors: Olvera-Cortés Hugo E. , Hernández-Gutiérrez Laura S. , Scherer-Castanedo Emilio , Ramírez-Arias Jessica D. , Argueta Muñoz Fernando D. , Gutiérrez-Barreto Samuel E. 
Published: February 2022

Introduction
Virtual debriefing is a cardinal element to achieve the effectiveness of telesimulation. There are different instruments to assess face-to-face debriefing to determine the degree of effectiveness of debriefing; Debriefing Assessment for Simulation in Healthcare (DASH) instrument is one of them. This study aims to describe and compare the evaluation of raters, instructors, and students during a virtual debriefing using the DASH.

Methods
A cross-sectional study was performed evaluating the virtual debriefing of 30 instructors after a heart failure telesimulation scenario. The evaluation was conducted by 30 instructors, 338 undergraduate students in the seventh semester, and 7 simulation raters. The 3 versions of the DASH instrument in Spanish were applied, respectively.

Results
Two comparisons were made, student versus instructor and rater versus instructor. Cronbach α was 0.97 for each version. The averages of the results on the DASH instrument were: 6.61 (3.34–7.0), 5.95 (4.65–7.0), and 4.84 (2.68–6.02) for student, rater, and instructor versions, respectively. The size effect between student and debriefer perspectives was 0.42. In contrast, the size effect between instructor and rater was 0.72. All differences were significant.

Conclusions
There are different rates between the persons who use the DASH. In this study, from the perspective of the instructor and rater, the difference was 1 point with a wide range, in contrast with the difference between instructor and student, which is relatively minor. It is necessary to consider the perspectives of experts in the subject to achieve a virtual debriefing of high quality and improve a debriefing by using the DASH.
Intravenous lidocaine for the management of traumatic rib fractures: A double-blind randomized controlled trial (INITIATE program of research)
Authors: Patton Petrease , Vogt Kelly , Priestap Fran , Parry Neil , Ball Ian M. 
Published: February 2022

BACKGROUND
Traumatic rib fractures (TRFs) are common with a 10% incidence in all trauma patients and are associated with significant morbidity and mortality. Adequate analgesia is paramount for preventing pulmonary complications and death. Evidence exists for intravenous (IV) lidocaine's effectiveness and safety in postoperative thoracic and abdominal surgery, and we hypothesized that it would be effective in patients with TRFs.

METHODS
We conducted a single-center, double-blind, randomized control trial comparing IV lidocaine plus usual analgesics to placebo infusion plus usual analgesics for 72 hours to 96 hours. Participants were adult trauma patients diagnosed with two or more TRFs requiring hospital admission. The primary outcome was mean pain score at rest and with movement, as measured on the visual analog scale. Secondary outcomes included patient satisfaction and opioid requirements (standardized total morphine equivalents). The study was powered to detect a 20% reduction in pain scores, which has been deemed clinically meaningful.

RESULTS
Thirty-six patients were enrolled and randomized to IV lidocaine or placebo. Comparison of the mean visual analog scale pain scores demonstrated significant pain reduction with movement in the lidocaine group compared with placebo (7.05 ± 1.72 vs. 8.22 ± 1.28, p = 0.042). Although pain scores at rest were reduced in the lidocaine group, this difference was not statistically significant (3.37 ± 2.00 vs. 3.82 ± 1.97; p = 0.519). Patient satisfaction was higher in the lidocaine group than the placebo group, although this did not reach statistical significance (8.3; interquartile range [IQR], 7.0–9.6 vs. 6.3; IQR, 5.2–7.1; p = 0.105). Total morphine equivalents were lower in the lidocaine group than the placebo group, but this difference did not reach statistical significance (167; IQR, 60–340 vs. 290; IQR 148–390; p = 0.194).

CONCLUSION
These results demonstrate that lidocaine has a beneficial analgesic effect in patients with TRFs. Future work is needed to evaluate lidocaine's ability to reduce patient important consequences of inadequate analgesia.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level II.
The brain state of motor imagery is reflected in the causal information of functional near-infrared spectroscopy
Authors: Du Qiang , Luo Jingjing , Chu Chenxi , Wang Youhao , Cheng Qiying , Guo Shijie 
Published: February 2022

Background
Brain–computer interface (BCI) is a promising neurorehabilitation strategy for ameliorating post-stroke function disorders. Physiological changes in the brain, such as functional near-infrared spectroscopy (fNIRS) dedicated to exploring cerebral circulatory responses during neurological rehabilitation tasks, are essential for gaining insights into neurorehabilitation mechanisms. However, the relationship between the neurovascular responses in different brain regions under rehabilitation tasks remains unknown.

Objective
The present study explores the fNIRS interactions between brain regions under different motor imagery (MI) tasks, emphasizing functional characteristics of brain network patterns and BCI motor task classification.

Methods
Granger causality analysis (GCA) is carried out for oxyhemoglobin data from 29 study participants in left- and right-hand MI tasks.

Results
According to research findings, homozygous and heterozygous states in the two brain connectivity modes reveal one and nine channel pairs, respectively, with significantly different (P < 0.05) GC values under the left- and right-hand MI tasks in the population. With reference to the total 10 channel pairs of causality differences between the two brain working states, a support vector machine is used to classify the two tasks with an overall accuracy of 83% for five-fold cross-validation.

Conclusion
As demonstrated in the present study, fNIRS offers causality patterns in different brain states of MIBCI motor tasks. The research findings show that fNIRS causality can be used to assess different states of the brain, providing theoretical support for its application to neurorehabilitation assessment protocols to ultimately improve patients’ quality of life.
Video Abstract: http://links.lww.com/WNR/A653.
Neutralization Of SARS-CoV-2 Variants By A Human Polyclonal Antibody Therapeutic (COVID-HIG, NP-028) With High Neutralizing Titers To SARS-CoV-2
Authors: Toth Derek 
Published: February 2022

AbstractSince the start of the COVID-19 outbreak the World Health Organization (WHO) has classified multiple SARS-CoV-2 Variants-of-Concern and Variants-of-Interest (VOC/VOI) with mutations in their Spike protein that increase transmissibility and/or reduce the effectiveness of vaccines and monoclonal antibody therapeutics. The emergence of these variants represents a significant health risk and highlights the need for additional COVID-19 therapeutics that maintain the ability to neutralize current, as well as future variants.COVID-HIG (NP-028) is a polyclonal Anti-SARS-CoV-2 human Immunoglobulin purified from source human plasma screened for high antibody titers to SARS-CoV-2 antigens. COVID-HIG was previously evaluated in INSIGHT 013 clinical trial [NCT04546581] which was an international, multi-center, adaptive, randomized, double-blind, placebo-controlled trial of the safety, tolerability and efficacy of a single dose infusion (up to 400 mL) of Anti-Coronavirus Hyperimmune Intravenous Immunoglobulin (hIVIG) for the treatment of adult recently hospitalized COVID-19 patients (N=593). COVID-HIG is currently being evaluated for clinical efficacy in a Phase 3 placebo-controlled study INSIGHT 012 (NCT04910269) to compare the safety and efficacy of a single infusion of anti-COVID-19 hyperimmune immunoglobulin (hIVIG) versus placebo among adults with recently diagnosed SARS-CoV-2 infection who do not require hospitalization.In the present study, in-vitro pseudovirus and live virus neutralization assays were used to assess the impact of SARS-CoV-2 variant spike mutations on neutralizing potency of COVID-HIG. These assays are valuable tools for monitoring the potential impact of variant mutations on efficacy of antibody therapeutics as well as vaccines/natural immunity.To date, COVID-HIG (NP-028) has been shown to retain neutralizing potency against 20 full spike protein sequence SARS-CoV-2 pseudovirus variants including all currently classified VOC/VOI (Alpha, Beta, Gamma, Delta/Delta+, Eta, Iota, Kappa, Lambda, Mu as of Sept 2021) as well as 4 live virus variants (Alpha, Beta, Gamma, and Iota).