bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prophylactic Administration of Uterotonics to Prevent Postpartum Hemorrhage in Women Undergoing Cesarean Delivery for Arrest of Labor
Authors: Balki Mrinalini , Downey Kristi , Walker Andrew , Seaward Gareth , Carvalho Jose C. A. 
Published: February 2021

OBJECTIVE:
To evaluate whether prophylactic administration of oxytocin plus ergonovine or oxytocin plus carboprost is more effective than oxytocin alone in reducing the need for additional uterotonics among women undergoing cesarean delivery for labor arrest.

METHODS:
In this double-blind, three-arm randomized controlled trial, participants were assigned to receive either oxytocin 5 units intravenous alone, or with ergonovine 0.25 mg intravenous or carboprost 0.25 mg intramuscular immediately after delivery, followed with maintenance infusion of oxytocin 40 milliunits/minute in all groups. Uterine tone was assessed at 3, 5, and 10 minutes after delivery, and additional uterotonics were administered if deemed necessary. The primary outcome was intraoperative need for additional uterotonics. Secondary outcomes included uterine tone, calculated blood loss, and side effects. A sample size of 34 per group (n=102), based on the null hypothesis that there is no association between treatment assignment and the need for additional uterotonics, permitted independent post hoc pairwise comparisons between oxytocin plus ergonovine, oxytocin plus carboprost, and oxytocin alone using an adjusted P-value of .025. The association between the need for additional uterotonics and treatment group was assessed using the χ2 test.

RESULTS:
From June 2013 through July 2019, 105 participants were randomized (35 per group) and data from 100 participants were analyzed: oxytocin (n=35), oxytocin plus ergonovine (n=33), and oxytocin plus carboprost (n=32). There was no difference in the requirement of additional intraoperative uterotonics across groups (oxytocin [37%] vs oxytocin plus ergonovine [33%] vs oxytocin plus carboprost [34%], P=.932). Uterine tone and calculated blood loss were similar across groups. Incidence of nausea or vomiting was higher in oxytocin plus ergonovine (85%; odds ratio [OR] 5.3, 95% CI 1.7–16.9, P=.003) and oxytocin plus carboprost (72%; OR 2.4, 95% CI 0.9–6.7, P=.086) compared with the oxytocin (51%) group.

CONCLUSION:
Compared with oxytocin alone, prophylactic use of a combination of uterotonic drugs did not reduce the need for additional uterotonics at cesarean delivery for labor arrest.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT01869556.
Incidental Findings at the Time of Cystoscopy
Authors: Richter Lee A. , Iglesia Cheryl B. 
Published: February 2021

Abstract:
Cystourethroscopy can be performed by obstetrician–gynecologists for diagnostic and occasional operative indications. Intraoperative use of cystourethroscopy to confirm urinary tract (urethral, bladder, and ureteral) integrity is one of the most important indications, because these findings can greatly affect patient care. This monograph provides an overview of appropriate instrumentation and technique for cystourethroscopy in women with normal anatomy. Also, it depicts benign and malignant lesions of the urethra and bladder and shows examples of intraoperative abnormalities, such as incidental bladder or urethral penetration, and nonpatent ureters, foreign body erosion, or fistula-related complications. Clinical vignettes outline differential diagnoses and management of common cystourethroscopic findings.
Methodologies for Validation of Diagnoses in Real-World Data: BONES—A Case Study
Authors: Irwin Debra E. , Kelly Kim , Winer Isabelle , Stürmer Til , Zura Robert 
Published: February 2021

Summary:
The accuracy of any claim-based study is dependent on the quality of real-world coding of the condition of interest. This retrospective, administrative claims analysis presents a method for using a real-world data source to evaluate the accuracy of coding for nonunion of a fifth metatarsal fracture. Patients 21–80 years old with a diagnosis of a fifth metatarsal fracture between January 1, 2016, and October 31, 2016, and a nonunion of the fifth metatarsal fracture within the next 9 months were identified in the MarketScan Databases. Patient health care claims in the 12 months after the nonunion diagnosis were examined for health care encounters and pharmaceutical treatments considered indicative of treatment for nonunion, such as claims for bone growth stimulation or a second claim with a diagnosis of nonunion. Of the 230 patients who had at least one health care encounter attributable to a nonunion of the fifth metatarsal, 95.2% had at least one subsequent health care encounter confirming nonunion diagnosis. The mean number of supporting health care claims was 5.8, and the mean time between nonunion and first confirmatory claim was 33 days. This analysis demonstrated a method for evaluating the quality of coding for a specific condition when a traditional medical chart comparison is not feasible.
Real-World Evidence: A Primer
Authors: Zura Robert , Irwin Debra E. , Mack Christina D. , Aldridge Molly L. , Mackowiak John I. 
Published: February 2021

Summary:
The insights that real-world data (RWD) can provide, beyond what can be learned within the traditional clinical trial setting, have gained enormous traction in recent years. RWD, which are increasingly available and accessible, can further our understanding of disease, disease progression, and safety and effectiveness of treatments with the speed and accuracy required by the health care environment and patients today. Over the decades since RWD were first recognized, innovation has evolved to take real-world research beyond finding ways to identify, store, and analyze large volumes of data. The research community has developed strong methods to address challenges of using RWD and as a result has increased the acceptance of RWD in research, practice, and policy. Historic concerns about RWD relate to data quality, privacy, and transparency; however, new tools, methods, and approaches mitigate these challenges and expand the utility of RWD to new applications. Specific guidelines for RWD use have been developed and published by numerous groups, including regulatory authorities. These and other efforts have shown that the more RWD are used and understood and the more the tools for handling it are refined, the more useful it will be.
Real-World Evidence: A Review of Real-World Data Sources Used in Orthopaedic Research
Authors: Hak David J. , Mackowiak John I. , Irwin Debra E. , Aldridge Molly L. , Mack Christina D. 
Published: February 2021

Summary:Real-world data (RWD) play an increasingly important role in orthopaedics as demonstrated by the rapidly growing number of publications using registry, administrative, and other databases. Each type of RWD source has its strengths and weaknesses, as does each specific database. Linkages between real-world data sets provide even greater utility and value for research than single data sources. The unique qualities of an RWD data source and all data linkages should be considered before use. Close attention to data quality and use of appropriate analysis methods can help alleviate concerns about validity of orthopaedic studies using RWD. This article describes the main types of RWD used in orthopaedics and provides brief descriptions and a sample listing of publications from selected, key data sources.
Effects of Preoperative Motor Status on Intraoperative Motor-evoked Potential Monitoring for High-risk Spinal Surgery
Authors: Kobayashi Kazuyoshi , Imagama Shiro , Yoshida Go , Ando Muneharu , Kawabata Shigenori , Yamada Kei , Kanchiku Tsukasa , Fujiwara Yasushi , Taniguchi Shinichirou , Iwasaki Hiroshi , Tadokoro Nobuaki , Takahashi Masahito , Wada Kanichiro , Yamamoto Naoya , Shigematsu Hideki , Funaba Masahiro , Yasuda Akimasa , Kobayashi Sho , Ushirozako Hiroki , Tani Toshikazu , Matsuyama Yukihiro 
Published: February 2021

Study Design.
Prospective multicenter observational study.

Objective.
To evaluate transcranial motor-evoked potentials (Tc-MEPs) baseline characteristics of lower limb muscles and to determine the accuracy of Tc-MEPs monitoring based on preoperative motor status in surgery for high-risk spinal disease.

Summary of Background Data.
Neurological complications are potentially serious side effects in surgery for high-risk spine disease. Intraoperative spinal neuromonitoring (IONM) using Tc-MEPs waveforms can be used to identify neurologic deterioration, but cases with preoperative motor deficit tend to have poor waveform derivation.

Methods.
IONM was performed using Tc-MEPs for 949 patients in high-risk spinal surgery. A total of 4454 muscles in the lower extremities were chosen for monitoring. The baseline Tc-MEPs was recorded immediately after exposure of the spine. The derivation rate was defined as muscles detected/muscles prepared for monitoring. A preoperative neurological grade was assigned using the manual muscle test (MMT) score.

Results.
The 949 patients (mean age 52.5 ± 23.3 yrs, 409 males [43%]) had cervical, thoracic, thoracolumbar, and lumbar lesions at rates of 32%, 40%, 26%, and 13%, respectively. Preoperative severe motor deficit (MMT ≤3) was present in 105 patients (11%), and thoracic ossification of the posterior longitudinal ligament (OPLL) was the most common disease in these patients. There were 32 patients (3%) with no detectable waveform in any muscles, and these cases had mostly thoracic lesions. Baseline Tc-MEPs responses were obtained from 3653/4454 muscles (82%). Specificity was significantly lower in the severe motor deficit group. Distal muscles had a higher waveform derivation rate, and the abductor hallucis (AH) muscle had the highest derivation rate, including in cases with preoperative severe motor deficit.

Conclusion.
In high-risk spinal surgery, Tc-MEPs collected with multi-channel monitoring had significantly lower specificity in cases with preoperative severe motor deficit. Distal muscles had a higher waveform derivation rate and the AH muscle had the highest rate, regardless of the severity of motor deficit preoperatively.

Level of Evidence: 3
Does Achieving Global Spinal Alignment Lead to Higher Patient Satisfaction and Lower Disability in Adult Spinal Deformity?
Authors: Sheikh Alshabab Basel , Gupta Munish C. , Lafage Renaud , Bess Shay , Shaffrey Christopher , Kim Han Jo , Ames Christopher P. , Burton Douglas C. , Smith Justin S. , Eastlack Robert K. , Klineberg Eric O. , Mundis Gregory M. , Schwab Frank J. , Lafage Virginie 
Published: February 2021

Study Design.
Multicenter retrospective review of prospective database.

Objective.
The aim of this study was to investigate potential associations between postoperative alignment and satisfaction.

Summary of Background Data.
Achieving high satisfaction is the main goal of any treatment, including adult spinal deformity (ASD) surgery. Despite being one of the key elements, literature is sparse regarding postoperative factors influencing patient satisfaction.

Methods.
ASD patients with 2-year follow-up were retrospectively reviewed. Patients without revision after the index procedure were stratified according to deformity type: sagittal (T1 pelvic angle >22°), coronal (C7 plumb line [C7PL] >5 cm or MaxCobb >50°), or mixed. Bivariate correlation between satisfaction and postoperative data was conducted on the entire cohort as well as by type of preoperative deformity. Multivariate regression controlling for pre-op alignment and demographic information was used to identify independent predictors of 2Y satisfaction.

Results.
A total of 509 patients were included in the analysis (58.7 ± 14.8, 80% females). The quality of life significantly improved between pre- and 2-year (ΔOswestry Disability Index [ODI]: 17.6, p < 0.001). At 2 years, SRS22 satisfaction was 4.27 ± 0.89 (median 4.5). Significant associations were found between satisfaction and disability (ODI, r = −0.50) and global coronal (C7PL r = −0.15) and sagittal (sagittal vertical axis [SVA], r = −0.10) alignment (all p < 0.01) but not with the coronal clavicle angle. Stratification by preoperative deformity revealed significant associations between satisfaction and SVA for sagittal deformity only, C7PL and MaxCobb for coronal only, and C7PL for combined deformity. In the multivariate analysis controlling for demographic and pre-op deformity, 2-year ODI and 2-year C7PL were independent predictors of satisfaction. Multilinear regression demonstrated 2-year SVA, pre-op ODI and patient's age were the independent predictors 2-year ODI.

Conclusion.
The ability to restore global alignment depends on the severity of the preoperative deformity as well as the correction of the main aspect of the deformity. Achieving global coronal and sagittal alignment is an independent predictor of both satisfaction and disability at 2 years post-op. Patients who continue to be disabled are also not satisfied.

Level of Evidence: 3
Collagen VI-Related Myopathy Caused by Compound Heterozygous Mutations of COL6A3 in a Consanguineous Kurdish Family
Authors: Mihaylova Violeta , Chablais Fabian , Bremer Juliane , Guggenberger Roman , Rushing Elisabeth J. , Bethge Tobias , Spiegel Roland , Jung Hans-Heinrich 
Published: February 2021

Abstract
Collagen VI-related myopathies are caused by mutations of COL6A1, COL6A2, and COL6A3 and present with a wide phenotypic spectrum ranging from severe Ulrich congenital muscular dystrophy to mild Bethlem myopathy. Here, we report a consanguineous Kurdish family with 3 siblings affected by autosomal-recessive Bethlem myopathy caused by compound heterozygous mutations of COL6A3. We found the previously described missense mutation c.7447A > G/p.(Lys2483Glu) and a novel large deletion encompassing the exon 1–39 of the COL6A3 gene. Apart from the classical clinical symptoms, all patients had keratoconus, which expands the phenotype of the collagen VI-related myopathies.
Autoimmune Small Fiber Neuropathy Associated With Ehlers–Danlos Syndrome Treated With Intravenous Immunoglobulins
Authors: Cook Melissa K. , Jordan Morgan 
Published: February 2021

Abstract
Patients with Ehlers–Danlos syndrome (EDS) have many associated symptoms of unclear cause, most recently suggested to be due to small fiber neuropathy (SFN). Small fiber neuropathies are sorely underestimated and with minimal treatment options. We report 2 cases of patients with EDS with presumed immune-mediated SFN, successfully treated with IV immunoglobulins. There is a stark need for further investigational studies into immunosuppressant treatments for immune-mediated SFN as well as the link between EDS and immune-mediated SFN.
What Is in the Neuromuscular Junction Literature?
Authors: Lacomis David , Wolfe Gil I. 
Published: February 2021

Abstract
This update covers recommendations for myasthenia gravis (MG) in patients with coronavirus 2019 disease as well as reports of the clinical features of patients with MG and coronavirus 2019. Updated advisory committee recommendations for the use of thymectomy in generalized MG are also provided. Other MG topics include lipoprotein receptor-4 and agrin antibody associations, factors influencing conversion of ocular to generalized MG, the use of rituximab for more recent onset disease, immunoglobulins for maintenance therapy, and fatigue and depression.
Deep Learning-based Propensity Scores for Confounding Control in Comparative Effectiveness Research
Authors: Weberpals Janick , Becker Tim , Davies Jessica , Schmich Fabian , Rüttinger Dominik , Theis Fabian J. , Bauer-Mehren Anna 
Published: February 2021

Background:
Due to the non-randomized nature of real-world data, prognostic factors need to be balanced, which is often done by propensity scores (PSs). This study aimed to investigate whether autoencoders, which are unsupervised deep learning architectures, might be leveraged to compute PS.

Methods:
We selected patient-level data of 128,368 first-line treated cancer patients from the Flatiron Health EHR-derived de-identified database. We trained an autoencoder architecture to learn a lower-dimensional patient representation, which we used to compute PS. To compare the performance of an autoencoder-based PS with established methods, we performed a simulation study. We assessed the balancing and adjustment performance using standardized mean differences, root mean square errors (RMSE), percent bias, and confidence interval coverage. To illustrate the application of the autoencoder-based PS, we emulated the PRONOUNCE trial by applying the trial’s protocol elements within an observational database setting, comparing two chemotherapy regimens.

Results:
All methods but the manual variable selection approach led to well-balanced cohorts with average standardized mean differences <0.1. LASSO yielded on average the lowest deviation of resulting estimates (RMSE 0.0205) followed by the autoencoder approach (RMSE 0.0248). Altering the hyperparameter setup in sensitivity analysis, the autoencoder approach led to similar results as LASSO (RMSE 0.0203 and 0.0205, respectively). In the case study, all methods provided a similar conclusion with point estimates clustered around the null (e.g., HRautoencoder 1.01 [95% confidence interval = 0.80, 1.27] vs. HRPRONOUNCE 1.07 [0.83, 1.36]).

Conclusions:
Autoencoder-based PS computation was a feasible approach to control for confounding but did not perform better than some established approaches like LASSO.
Opioid Use following Open versus Endoscopic Carpal Tunnel Release: A Population Study
Authors: Withers Jacquelyn A. , Lalchandani Gopal R. , Halvorson Ryan T. , Immerman Igor , Rahgozar Paymon 
Published: February 2021

Background:
Open (OCTR) and endoscopic carpal tunnel release (ECTR) are both effective treatments for carpal tunnel syndrome, with similar outcomes and complication rates. Given the opioid epidemic, it is important to consider how surgical modality impacts narcotic use. We compared narcotic use after OCTR and ECTR to identify trends and risk factors for prolonged postoperative use.

Methods:
We utilized the PearlDiver database to identify patients who underwent OCTR and ECTR between 2008 and 2015. Patients with opioid use were analyzed for trends. Early refills, prolonged postoperative opioid use, and new persistent opioid use were defined by time periods relating to the date of surgery. Age, gender, Charlson comorbidity index (CCI), and surgery type (open versus endoscopic) were analyzed as predictors for opioid use.

Results:
A total of 29,583 patients were included: 4125 (14%) ECTR and 25,458 (86%) OCTR. Significantly more OCTR patients filled perioperative prescriptions (62% versus 60%), and the OCTR group filled higher quantities of perioperative opioids (411 OME versus 379 OME). Patients in the OCTR group were also significantly more likely to obtain early refills and to have prolonged postoperative use. There was no difference in the rate of new persistent use.

Conclusions:
Compared with ECTR, patients who underwent OCTR filled higher quantities of opioids in the perioperative period, were more likely to obtain early refills, and were more likely to have prolonged postoperative use. These findings suggest either a lower opioid requirement after ECTR or a lower perceived requirement reflected in the difference in prescribing habits between techniques.
LEBER CONGENITAL AMAUROSIS DUE TO CEP290 MUTATIONS—SEVERE VISION IMPAIRMENT WITH A HIGH UNMET MEDICAL NEED
Authors: Leroy Bart P. , Birch David G. , Duncan Jacque L. , Lam Byron L. , Koenekoop Robert K. , Porto Fernanda B. O. , Russell Stephen R. , Girach Aniz 
Published: February 2021

Purpose:
Leber congenital amaurosis due to CEP290 mutations (LCA10) is an inherited retinal disease that often results in severe visual impairment or blindness in early childhood. Currently, there are no approved treatments, highlighting the considerable unmet medical need associated with LCA10. We aimed to review the clinical characteristics of LCA10, its impact on patients and society, and the investigational treatment strategies currently in development.

Methods:
Review of the current literature.

Results:
LCA10 is an autosomal recessive ciliopathy, for which the CEP290 intronic variant c.2991+1655A>G (p.Cys998X) is the most common mutation. Usually diagnosed in early childhood, most patients with LCA10 have severe visual impairment during their first decade of life, which significantly affects the quality of life and development. LCA10 also has a significant societal burden (direct and indirect costs). RNA editing using antisense oligonucleotides or Staphylococcus aureus CRISPR-associated protein-9 nuclease is currently under investigation for treatment of p.Cys998X LCA10. Specifically, the antisense oligonucleotide therapy QR-110 (sepofarsen) has demonstrated encouraging safety and efficacy data in a first-in-human trial; a phase 3 clinical trial is ongoing.

Conclusion:
Interventions that can preserve or improve vision in patients with LCA10 have considerable potential to improve the patient quality of life and reduce burden of disease.
Radial Endothelial Striae Over 360 Degrees in Fuchs Corneal Endothelial Dystrophy: New Pathophysiological Findings
Authors: Thuret Gilles , Ain Anthony , Koizumi Noriko , Okumura Naoki , Gain Philippe , He Zhiguo 
Published: February 2021

Purpose:
To report evidences that the abnormal endothelium of some Fuchs endothelial corneal dystrophy (FECD) present centripetal radial lines over 360 degrees

Methods:
A case report of retroilluminated pictures of 2 patients with FECD and flat mounts of isolated Descemet membranes of 1 patient with FECD and of 1 healthy donor. Interpretation and development of a new pathophysiological theory.

Results:
The 3 FECD images unequivocally demonstrate the existence of very numerous radial centripetal lines over 360 degrees, in the central 8 to 9 mm of the cornea and ending in the area of maximum guttae concentration. These lines resemble, in a much longer length, the physiological striae that we described in 2012 at the periphery of the endothelium of normal corneas.

Conclusions:
We suppose that these lines reflect an accelerated migration of a population of pathological endothelial cells that deposit collagen on their path before being slowed down and then blocked in the center, explaining the progressive accumulation of guttae in this area. This new migration theory assumes that FECD behaves as a corneal endothelial stem-cell disease.
Surgical Treatment of a Corneal Epithelial Cyst
Authors: Wasilewski Daniel 
Published: February 2021

Purpose:
To describe a case of intracorneal epithelial cyst and present a surgical technique successfully used to treat this patient.

Methods:
This interventional case report presents a 4-year-old boy with a progressive intrastromal corneal opacity and decreased vision in his right eye. The patient had no previous history of trauma or ocular surgery. After clinical examination and corneal optical coherence tomography, a presumptive diagnosis of a developmental epithelial cyst was made, and surgery was indicated. Four years later, when the patient was 8 year old, he returned after having performed drainage of the cyst in another service but still complaining of low vision. The biomicroscopy showed an intrastromal recurrent cyst. At this time, we recommended the surgical retreatment. The cyst was drained, a lamellar keratosclerectomy was performed at the site of the limbus where the epithelial nest was placed, and distilled water was used to wash the corneal cyst - to eliminate the epithelial cells. A donor cornea button was cut manually and was transplanted to cover the area where the corneoscleral tissue was removed.

Results:
The surgical technique described resulted in nearly complete clearing of the opacity and improved vision, and no recurrence was documented up to 19 months of follow-up. The best-corrected visual acuity improved from 20/100 before surgery to 20/30 after surgery.

Conclusions:
This surgical technique may be a good alternative to other previously described treatments for intracorneal epithelial cysts aiming to avoid recurrence and without the need for central corneal transplantation.