bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential Selection Bias in Observational Studies Comparing Cervical Disc Arthroplasty to Anterior Cervical Discectomy and Fusion
Authors: Goz Vadim , Martin Brook I. , Donnally Chester J. , Brodke Darrel , Spina Nicholas , Lawrence Brandon , Spiker William Ryan 
Published: February 2020

Study Design.
Retrospective study using a national administrative database.

Objective.
To define the cohort differences in patient characteristics between patients undergoing cervical disc arthroplasty (CDA) and anterior cervical discectomy and fusion (ACDF) in a large national sample, and to describe the impact of those baseline patient characteristics on analyses of costs and complications.

Summary of Background Data.
CDA was initially studied in high quality, randomized trials with strict inclusion criteria. Recently a number of non-randomized, observational studies have been published an attempt to expand CDA indications. These trials are predisposed to falsely attributing differences in outcomes to an intervention due to selection bias.

Methods.
Adults undergoing ACDF or CDA between 2004 and 2014 were identified using International Classification of Diseases, 9th, Clinical Modification (ICD-9-CM) diagnosis and procedure codes. Perioperative demographics, comorbidities, complications, and costs were queried. Patient characteristics were compared via chi-square and t tests. Cost, mortality, and complications were compared between ACDF and CDA cohorts using models that adjusted for demographics and comorbidities, as well as “naïve” models that did not.

Results.
A total of 290,419 procedures, 98.2% ACDF and 1.8% CDA, were included in the sample. Compared with ACDF patients, CDA patients were younger, healthier as evidenced by number of comorbidities, and had an improved socioeconomic status as measured by income and insurance. The naïve logistic regression model showed that hospital costs for CDA were $549 lower than ACDF. In the fully specified model, CDA was $574 more expensive. The naïve model for medical complications suggests a protective advantage for CDA over ACDF, odds ratio of 0.627, P < 0.01. No statistically significant difference was found in the fully specified model in terms of complications.

Conclusion.
Patients undergoing CDA were younger and healthier with higher socioeconomic statuses compared with ACDF patients. Accounting for these baseline differences significantly attenuated the apparent benefit for CDR on costs and medical complications.

Level of Evidence: 3
Neuroanesthesia Guidelines for Optimizing Transcranial Motor Evoked Potential Neuromonitoring During Deformity and Complex Spinal Surgery
Authors: Walker Corey T. , Kim Han Jo , Park Paul , Lenke Lawrence G. , Weller Mark A. , Smith Justin S. , Nemergut Edward C. , Sciubba Daniel M. , Wang Michael Y. , Shaffrey Christopher , Deviren Vedat , Mummaneni Praveen V. , Chang Joyce M. , Mummaneni Valli P. , Than Khoi D. , Berjano Pedro , Eastlack Robert K. , Mundis Gregory M. , Kanter Adam S. , Okonkwo David O. , Shin John H. , Lewis Jason M. , Koski Tyler , Hoh Daniel J. , Glassman Steven D. , Vinci Susan B. , Daniels Alan H. , Clavijo Claudia F. , Turner Jay D. , McLawhorn Marc , Uribe Juan S. 
Published: February 2020

Study Design.
Expert opinion—modified Delphi study.

Objective.
We used a modified Delphi approach to obtain consensus among leading spinal deformity surgeons and their neuroanesthesiology teams regarding optimal practices for obtaining reliable motor evoked potential (MEP) signals.

Summary of Background Data.
Intraoperative neurophysiological monitoring of transcranial MEPs provides the best method for assessing spinal cord integrity during complex spinal surgeries. MEPs are affected by pharmacological and physiological parameters. It is the responsibility of the spine surgeon and neuroanesthesia team to understand how they can best maintain high-quality MEP signals throughout surgery. Nevertheless, varying approaches to neuroanesthesia are seen in clinical practice.

Methods.
We identified 19 international expert spinal deformity treatment teams. A modified Delphi process with two rounds of surveying was performed. Greater than 50% agreement on the final statements was considered “agreement”; >75% agreement was considered “consensus.”

Results.
Anesthesia regimens and protocols were obtained from the expert centers. There was a large amount of variability among centers. Two rounds of consensus surveying were performed, and all centers participated in both rounds of surveying. Consensus was obtained for 12 of 15 statements, and majority agreement was obtained for two of the remaining statements. Total intravenous anesthesia was identified as the preferred method of maintenance, with few centers allowing for low mean alveolar concentration of inhaled anesthetic. Most centers advocated for <150 μg/kg/min of propofol with titration to the lowest dose that maintains appropriate anesthesia depth based on awareness monitoring. Use of adjuvant intravenous anesthetics, including ketamine, low-dose dexmedetomidine, and lidocaine, may help to reduce propofol requirements without negatively effecting MEP signals.

Conclusion.
Spine surgeons and neuroanesthesia teams should be familiar with methods for optimizing MEPs during deformity and complex spinal cases. Although variability in practices exists, there is consensus among international spinal deformity treatment centers regarding best practices.

Level of Evidence: 5
Reporting of Outcomes and Outcome Measures in Studies of Interventions to Prevent and/or Treat Delirium in the Critically Ill: A Systematic Review
Authors: Rose Louise , Agar Meera , Burry Lisa , Campbell Noll , Clarke Mike , Lee Jacques , Marshall John , Siddiqi Najma , Page Valerie ,   for the Development of Core Outcome Sets for Effectiveness Trials of Interventions to Prevent and/or Treat Delirium (Del-COrS) Group
Published: February 2020

Objectives:
To inform development of a core outcome set, we evaluated the scope and variability of outcomes, definitions, measures, and measurement time-points in published clinical trials of pharmacologic or nonpharmacologic interventions, including quality improvement projects, to prevent and/or treat delirium in the critically ill.

Data Sources:
We searched electronic databases, systematic review repositories, and trial registries (1980 to March 2019).

Study Selection and Data Extraction:
We included randomized, quasi-randomized, and nonrandomized intervention studies of pharmacologic and nonpharmacologic interventions. We extracted data on study characteristics, verbatim descriptions of study outcomes, and measurement characteristics. We assessed quality of outcome reporting using the Management of Otitis Media with Effusion in Children with Cleft Palate study scoring system; risk of bias and study quality using the Cochrane tool and Scottish Intercollegiate Guidelines Network checklists. We categorized reported outcomes using Core Outcome Measures in Effectiveness Trials taxonomy.

Data Synthesis:
From 195 studies (1/195 pediatric) recruiting 74,632 participants and reporting a mean (sd) of 10 (6.2) outcome domains, we identified 12 delirium-specific outcome domains. Delirium incidence (147, 75% of studies), duration (67, 34%), and antipsychotic use (42, 22%) were most commonly reported. We identified a further 94 non–delirium-specific outcome domains within 19 Core Outcome Measures in Effectiveness Trials taxonomy categories. For both delirium-specific and nonspecific outcome domains, we found multiple outcomes in domains due to differing descriptions and time-points. The Confusion Assessment Method-ICU with Richmond Agitation-Sedation Scale to assess sedation was the most common measure used to ascertain delirium (51, 35%). Measurement generally began at randomization or ICU admission, and lasted from 1 to 30 days, ICU/hospital discharge. Frequency of measurement was highly variable with daily measurement and greater than daily measurement reported for 36% and 37% of studies, respectively.

Conclusions:
We identified substantial heterogeneity and multiplicity of outcome selection and measurement in published studies. These data will inform the consensus building stage of a core outcome set to inform delirium research in the critically ill.
Epigenetics of Sepsis
Authors: Binnie Alexandra , Tsang Jennifer L. Y. , Hu Pingzhao , Carrasqueiro Gabriela , Castelo-Branco Pedro , dos Santos Claudia C. 
Published: February 2020

Objectives:
Recent evidence from the fields of microbiology and immunology, as well as a small number of human sepsis studies, suggest that epigenetic regulation may play a central role in the pathogenesis of sepsis. The term “epigenetics” refers to regulatory mechanisms that control gene expression but are not related to changes in DNA sequence. These include DNA methylation, histone modifications, and regulation of transcription via non-coding RNAs. Epigenetic modifications, occurring in response to external stressors, lead to changes in gene expression, and thus lie at the intersection between genetics and the environment. In this review, we examine data from in vitro studies, animal studies, and the existing human sepsis studies in epigenetics to demonstrate that epigenetic mechanisms are likely central to the pathogenesis of sepsis and that epigenetic therapies may have potential in the treatment of sepsis and its associated organ failures.

Data Sources:
Online search of published scientific literature via Pubmed using the term “epigenetics” in combination with the terms “sepsis”, “infection”, “bacterial infection”, “viral infection”, “critical illness”, “acute respiratory distress syndrome”, and “acute lung injury”.

Study Selection:
Articles were chosen for inclusion based on their relevance to sepsis, acute inflammation, sepsis-related immune suppression, and sepsis-related organ failure. Reference lists were reviewed to identify additional relevant articles.

Data Extraction:
Relevant data was extracted and synthesized for narrative review.

Data Synthesis:
Epigenetic regulation is a key determinant of gene expression in sepsis. At the onset of infection, host-pathogen interactions often result in epigenetic alterations to host cells that favor pathogen survival. In parallel, the host inflammatory response is characterized by epigenetic modifications in key regulatory genes, including tumor necrosis factor and interleukin-1β. In human sepsis patients, multiple epigenetic modifying enzymes show differential expression in early sepsis, suggesting a role for epigenetics in coordinating the response to infection. In the later stages of sepsis, epigenetic modifications accompany endotoxin tolerance and the immune-suppressed state. In animal models, treatment with epigenetic modifiers can mitigate the effects of sepsis and improve survival as well as reverse sepsis-associated organ injury.

Conclusions:
Epigenetic modifications are associated with key phases of sepsis, from the host-pathogen interaction, to acute inflammation, to immune suppression. Epigenetic markers show promise in the diagnosis and prognosis of sepsis and epigenetic modifying agents show promise as therapeutic tools in animal models of sepsis. Human studies in the area of epigenetics are sorely lacking and should be a priority for sepsis researchers.
Initial Assessment of the Percutaneous Electrical Phrenic Nerve Stimulation System in Patients on Mechanical Ventilation
Authors: O’Rourke James , Soták Michal , Curley Gerard F. , Doolan Aoife , Henlín Tomáš , Mullins Gerard , Tyll Tomáš , Omlie William , Ranieri Marco V. 
Published: February 2020

Objectives:
Maintaining diaphragm work using electrical stimulation during mechanical ventilation has been proposed to attenuate ventilator-induced diaphragm dysfunction. This study assessed the safety and feasibility of temporary percutaneous electrical phrenic nerve stimulation on user-specified inspiratory breaths while on mechanical ventilation.

Design:
Two-center, nonblinded, nonrandomized study.

Setting:
Hospital ICU.

Patients:
Twelve patients mechanically ventilated from 48 hours to an expected 7 days.

Interventions:
Leads were inserted to lie close to the phrenic nerve in the neck region using ultrasound guidance. Two initial patients had left-sided placement only with remaining patients undergoing bilateral lead placement. Percutaneous electrical phrenic nerve stimulation was used for six 2-hour sessions at 8-hour intervals over 48 hours.

Measurements and Main Results:
Data collected included lead deployment success, nerve conduction, ventilation variables, work of breathing, electrical stimulation variables, stimulation breath synchrony, and diaphragm thickness measured by ultrasound at baseline, 24, and 48 hours. Primary endpoints included ability to capture the left and/or right phrenic nerves and maintenance of work of breathing within defined limits for 80% of stimulated breaths. Lead insertion was successful in 21 of 22 attempts (95.5%). Analysis of 36,059 stimulated breaths from 10 patients with attempted bilateral lead placement demonstrated a mean inspiratory lag for phrenic nerve stimulation of 23.7 ms (p < 0.001 vs null hypothesis of <88ms). Work of breathing was maintained between 0.2 and 2.0 joules/L 96.8% of the time, exceeding the 80% target. Mean diaphragm thickness increased from baseline by 7.8% at 24 hours (p = 0.022) and 15.0% at 48 hours (p = 0.0001) for patients receiving bilateral stimulation after excluding one patient with pleural effusion. No serious device/procedure-related adverse events were reported.

Conclusions:
The present study demonstrated the ability to safely and successfully place percutaneous electrical phrenic nerve stimulation leads in patients on mechanical ventilation and the feasibility of using this approach to synchronize electrical stimulation with inspiration while maintaining work of breathing within defined limits.
Predictors of Statin Intolerance in Patients With a New Diagnosis of Atherosclerotic Cardiovascular Disease Within a Large Integrated Health Care Institution: The IMPRES Study
Authors: Bair Tami L. , May Heidi T. , Knowlton Kirk U. , Anderson Jeffrey L. , Lappe Donald L. , Muhlestein Joseph B. 
Published: February 2020

Abstract:
Statins are among the most prescribed medications because of the well-documented benefits of safely lowering low-density lipoprotein cholesterol. However, many patients are unable or unwilling to continue statin therapy because of real or perceived adverse effects. This study sought to increase understanding about which patients are unlikely to tolerate statin therapy. The Intermountain Healthcare's electronic data repository was queried from January 1, 1999, to December 31, 2013, to identify all adults who survived their first encounter of coronary artery disease (CAD), cerebral vascular disease, or peripheral artery disease and received statin therapy during follow-up. Statin intolerance (SI) was identified by the documentation of clinician-noted intolerance or allergy or by the use of pitavastatin. Patients were followed up for ≥3 years or until death. Of the 48,997 patients evaluated, 3049 (6.2%) were documented with SI. Of those with SI, 9.8% were prescribed a low-intensity, 73.4% a moderate-intensity, and 16.8% a high-intensity statin dose. After adjustment for covariables, significant predictors of SI were female sex [odds ratio (OR) = 1.47, P < 0.0001], age (65–74 vs. <65: OR = 1.15, P = 0.002; ≥75 vs. <65: OR = 0.90, P = 0.03), hypertension (OR = 1.11, P = 0.01), hyperlipidemia (OR = 1.31, P < 0.0001), smoking (OR = 0.88, P = 0.001), renal failure (OR = 1.20, P = 0.009), heart failure (OR = 1.26, P < 0.0001), sleep apnea (OR = 1.22, P < 0.0001), prior malignancy (OR = 1.18, P = 0.007), depression (OR = 1.13, P = 0.04), and index atherosclerotic cardiovascular disease diagnosis (CAD vs. cerebral vascular disease: OR = 1.71, P < 0.0001; CAD vs. peripheral artery disease: OR = 1.23, P = 0.02). In this study, the strongest identified clinical predictor of future SI was female sex. Many standard cardiovascular risk factors were also associated with SI, suggesting that patients with multiple comorbidities are more likely to be vulnerable.
Low-Intensity Ultrasound Modulation May Prevent Myocardial Infarction-induced Sympathetic Neural Activation and Ventricular Arrhythmia
Authors: Wang Songyun , Li Binxun , Li Xuemeng , Wu Lin , Zhu Tongjian , Zhao Dongdong , Jiang Hong 
Published: February 2020

Background:
Low-intensity focused ultrasound (LIFU) has been shown to be a beneficial tool for autonomic nervous system modulation, but its effect on the left stellate ganglion (LSG) remains unknown.

Objective:
To seek the effect of LIFU on myocardial infarction (MI)-induced LSG activation and ventricular arrhythmias (VAs).

Methods:
In this study, 20 dogs were included and randomly divided into the LIFU (LIFU & MI, n = 8), Sham (sham LIFU & MI, n = 8), and Control group (sham LIFU & sham MI, n = 4). For each LIFU intervention (1.0–2.0 W, 10 minutes) of the LSG, the LSG function, ventricular effective refractory period (ERP), and temperature were tested pre-intervention and postintervention. Thereafter, MI was induced by left anterior artery ligation and VAs were recorded for 1 hour. At the end, both the LSG and the heart were extracted for biomedical and histological analysis.

Results:
In the Sham group, no significant change was shown in ventricular ERP or LSG function for any intensity settings of sham LIFU intervention when compared with the group baseline. In the LIFU group, however, both 1.5 and 2.0 W LIFU modulation of LSG resulted in significant prolongation of ERP and attenuation of LSG function. Furthermore, the incidence of VAs was significantly attenuated in the LIFU group compared with the Sham group. Moreover, histological analysis showed that no damage or apoptosis was observed in LSG although a statistically significant increase was shown in temperature (maximal increase <1°C) with 1.5 and 2.0 W LIFU intervention.

Conclusion:
LIFU stimulation may be a safe and beneficial tool for LSG attenuation and VA prevention in the MI canine model.
Leadership in Disruptive Times: The Key to Changing Healthcare
Authors: Agee Nancy Howell 
Published: February 2020

Summary
Quality and safety are the top priorities of every hospital and health system. Patients put their trust in us as healthcare leaders, often in the most vulnerable moments of their lives, and we must respond with high-quality, highly reliable, and compassionate care.
Patients have the right to expect the best return for their healthcare dollars. Recognizing that expectation, progressive hospitals and health systems are embracing the move to value-based care and are enhancing affordability. The goal is to provide greater value to patients by improving quality, lowering costs, and enhancing the patient experience.
Ever-changing market forces affect how hospitals and health systems deliver care and may also affect how much they are reimbursed for services. We must stretch to transform, improve, and even redefine care delivery for all of our patients as well as our teams of caregivers and staff.
Carilion Clinic demonstrates this commitment in our continuing evolution as an integrated delivery system, along with our participation in new national collaborations to improve affordability and advance innovation. We are catalysts for change in a sector that is ripe for it.
Patient Perspectives on Declining to Participate in Home-Based Cardiac Rehabilitation
Authors: Schopfer David W. , Nicosia Francesca M. , Ottoboni Linda , Whooley Mary A. 
Published: February 2020

Purpose:
A minority of eligible patients participate in cardiac rehabilitation (CR) programs. Availability of home-based CR programs improves participation in CR, yet many continue to decline to enroll. We sought to explore among patients the rationale for declining to participate in CR even when a home-based CR program is available.

Methods:
We conducted a mixed-methods evaluation of reasons for declining to participate in CR. Between August 2015 and August 2017, a total of 630 patients were referred for CR evaluation during index hospitalization (San Francisco VA Medical Center). Three hundred three patients (48%) declined to participate in CR. Of these, 171 completed a 14-item survey and 10 patients also provided qualitative data through semistructured phone interviews.

Results:
The most common reason, identified by 61% of patients on the survey, was “I already know what to do for my heart.” Interviews helped clarify reasons for nonparticipation and identified system barriers and personal barriers. These interviews further highlighted that declining to participate in CR was often due to competing life priorities, no memory of the initial CR consultation, and inadequate understanding of CR despite referral.

Conclusion:
We identified that most patients declining to participate in a home-based CR program did not understand the benefits and rationale for CR. This could be related to the timing of the consultation or presentation method. Many patients also indicated that competing life priorities prevented their participation. Modifications in the consultation process and efforts to accommodate personal barriers may improve participation.
Pediatric HIV Care Cascade in Southern Mozambique: Missed Opportunities for Early ART and Re-engagement in Care
Authors: Fernández-Luis Sheila , Nhampossa Tacilta , Fuente-Soro Laura , Augusto Orvalho , Casellas Aina , Bernardo Edson , Ruperez Maria , Gonzalez Raquel , Maculuve Sonia , Saura-Lázaro Anna , Menendez Clara , Naniche Denise , Lopez-Varela Elisa 
Published: February 2020

Background:
There are 170,000 children living with HIV in 2017 in Mozambique. Scaling-up HIV care requires effective retention along the cascade. We sought to evaluate the pediatric cascade in HIV care at the Manhiça District Hospital.

Methods:
A prospective cohort of children <15 years was followed from enrollment in HIV care (January 2013 to December 2015) until December 2016. Loss to follow-up (LTFU) was defined as not attending the HIV hospital visits for ≥90 days following last visit attended.

Results:
From the 438 children included {median age at enrollment in care of 3,6 [interquartile range (IQR): 1.1–8.6] years}, 335 (76%) were antiretroviral therapy (ART) eligible and among those, 263 (78%) started ART at enrollment in HIV care. A total of 362 children initiated ART during the study period and the incidence rate of LTFU at 12, 24, and 36 months post-ART initiation was 41 [95% confidence interval (CI): 34–50], 34 (95% CI: 29–41), and 31 (95% CI: 27–37) per 100 children-years, respectively. Median time to LTFU was 5.8 (IQR: 1.4–12.7) months. Children 5–9 years of age had a lower risk of LTFU compared with children <1 year [adjusted subhazard ratio 0.36 (95% CI: 0.20–0.61)]. Re-engagement in care (RIC) was observed in 25% of the LTFU children.

Conclusions:
The high LTFU found in this study highlights the special attention that should be given to younger children during the first 6 months post-ART initiation to prevent LTFU. Once LTFU, only a quarter of those children return to the health unit. Elucidating factors associated with RIC could help to fine tune interventions which promote RIC.