bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homozygous familial hypercholesterolemia: what treatments are on the horizon?
Authors: Bajaj Archna , Cuchel Marina 
Published: April 2020

Purpose of review
Homozygous familial hypercholesterolemia (HoFH) is a rare disorder associated with early atherosclerotic disease due to impairment of the LDL receptor (LDLR) pathway. Because of their molecular defect, current treatment options have limited success in bringing HoFH patient to LDL-C target and morbidity and mortality remain high. We review current and upcoming therapies directed at HoFH, including gene therapy.

Recent findings
Recent real-world studies have confirmed the strength in lomitapide as a treatment adjunct to statins and other lipid-lowering therapies in HoFH patients. The approval of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor monoclonal antibodies has also been a welcome addition to the treatment armamentarium offering an additional average reduction in LDL-C levels of 24% when added to background lipid-lowering therapies in this population. Although achieving adequate LDL-C levels in this population is difficult, there are several therapies on the horizon that may help more patients reach goal. Evinacumab, a monoclonal antibody against ANGPTL3, has been shown to substantially reduce LDL-C of an average of 49%, independently of residual LDLR activity. RNA interference targeting PCSK9 and ANGPTL3 shows promise in clinical trials. Adeno-associated virus-mediated gene transfer and gene editing techniques are in early clinical and preclinical development.

Summary
LDL-C lowering in HoFH patients remains very challenging. However, novel treatment options are emerging. Upcoming therapies directed at PCSK9 and ANPTL3 may offer additional LDL-C reduction, to help patients achieve adequate LDL-C levels. Gene therapy and gene editing techniques, if proven effective, may offer a unique opportunity to treat patients with a one-time treatment.
Telehealth Simulation With Graduate Nurse Practitioner Students
Authors: Emerson Margaret R. , Buchanan Lynne , Golden Amber 
Published: April 2020

Background
Integration of telehealth preparation for nurse practitioner (NP) students varies across programs.

Problem
Nurse practitioner students had gaps in the preparation for using telehealth technology to deliver care and manage specific disorders.

Approach
The purpose of this article is to describe the development and implementation of a telehealth simulation training experience for NP students to prepare them for practice in rural settings.

Outcomes
Nurse practitioner students from various specialties completed the telehealth simulation training experience. The change in presimulation/postsimulation confidence and readiness scores were statistically significant.

Conclusion
This telehealth simulation training experience provided an opportunity for NP students to engage in activities to enhance their knowledge and preparation in providing care via telehealth in a rural setting.
Factors Associated With Neurobehavioral Complications in Pediatric Abdominal Organ Transplant Recipients Identified Using Computable Composite Definitions*
Authors: Alcamo Alicia M. , Clark Robert S. B. , Au Alicia K. , Kantawala Sajel , Yablonsky Eric J. , Sindhi Rakesh , Mazariegos George V. , Aneja Rajesh K. , Horvat Christopher M. 
Published: April 2020

Objectives:
Neurologic complications occur in up to 40% of adult abdominal solid organ transplant recipients and are associated with increased mortality. Comparable pediatric data are sparse. This study describes the occurrence of neurologic and behavioral complications (neurobehavioral complications) in pediatric abdominal solid organ transplant recipients. We examine the association of these complications with length of stay, mortality, and tacrolimus levels.

Design:
The electronic health record was interrogated for inpatient readmissions of pediatric abdominal solid organ transplant recipients from 2009 to 2017. A computable composite definition of neurobehavioral complication, defined using structured electronic data for neurologic and/or behavioral phenotypes, was created.

Setting:
Quaternary children’s hospital with an active transplant program.

Patients:
Pediatric abdominal solid organ transplant recipients.

Interventions:
None.

Measurements and Main Results:
Computable phenotypes demonstrated a specificity 98.7% and sensitivity of 63.0% for identifying neurobehavioral complications. There were 1,542 readmissions among 318 patients, with 65 (20.4%) having at least one admission with a neurobehavioral complication (total 109 admissions). Median time from transplant to admission with neurobehavioral complication was 1.2 years (interquartile range, 0.52–2.28 yr). Compared to encounters without an identified neurobehavioral complication, encounters with a neurobehavioral complication were more likely to experience ICU admission (odds ratio, 3.9; 2.41–6.64; p < 0.001), have longer ICU length of stay (median 10.3 vs 2.2 d; p < 0.001) and hospital length of stay (8.9 vs 4.3 d; p < 0.001), and demonstrate higher maximum tacrolimus level (12.3 vs 9.8 ng/mL; p = 0.001). Patients with a neurobehavioral complication admission were more likely to die (odds ratio, 5.04; 1.49–17.09; p = 0.009). In a multivariable analysis, type of transplant, ICU admission, and tacrolimus levels were independently associated with the presence of a neurobehavioral complication.

Conclusions:
Common electronic health record variables can be used to accurately identify neurobehavioral complications in the pediatric abdominal solid organ transplant population. Late neurobehavioral complications are associated with increased hospital resource utilization, mortality, and tacrolimus exposure. Additional studies are required to delineate the relationship between maximum tacrolimus level and neurobehavioral complications to guide therapeutic drug monitoring and dosing.
How Do Children Die in PICUs Nowadays? A Multicenter Study From Spain*
Authors: Agra-Tuñas Carme , Rodriguez-Ruiz Emilio , Rodríguez Merino Elva ,   on behalf of the MOdos de Morir en UCI Pediátrica-2 (MOMUCIP-2) study group of the Spanish Society of Paediatric Intensive Care (SECIP)
Published: April 2020

Objectives:
To describe how children currently die in Spanish PICUs, their epidemiologic characteristics and clinical diagnoses.

Design:
Prospective multicenter observational study.

Setting:
Eighteen PICUs participating in the MOdos de Morir en UCI Pediátrica-2 (MOMUCI-2) study in Spain.

Patients:
Children 1 to 16 years old who died in PICU during 2017 and 2018.

Interventions:
None.

Measurements and Main Results:
During the 2-year study period, 250 deaths were recorded. Seventy-three children (29.3%) were younger than 1 year, 131 (52.6%) were between 1 and 12 years old, and 45 (18.1%) were older than 12. One-hundred eighty patients (72%) suffered from an underlying chronic disease, 54 (21.6%) had been admitted to PICU in the past 6 months, and 71 (28.4%) were severely disabled upon admission. Deaths occurred more frequently on the afternoon-night shift (62%) after a median PICU length of stay of 3 days (1–12 d). Nearly half of the patients died (48.8%) after life-sustaining treatment limitation, 71 died (28.4%) despite receiving life-sustaining therapies and cardiopulmonary resuscitation, and 57 (22.8%) were declared brain dead. The most frequent type of life-sustaining treatment limitation was the withdrawal of mechanical ventilation (20.8%), followed by noninitiation of cardiopulmonary resuscitation (18%) and withdrawal of vasoactive drugs (13.7%). Life-sustaining treatment limitation was significantly more frequent in patients with an underlying neurologic-neuromuscular disease, respiratory disease as the cause of admission, a previous admission to PICU in the past 6 months, and severe disability. Multivariate analyses indicated that life-sustaining treatment limitation, chronicity, and poor Pediatric Cerebral Performance Category score were closely related.

Conclusions:
Currently, nearly half of the deaths in Spanish PICUs occur after the withdrawal of life-sustaining treatments. These children are more likely to have had previous admissions to the PICU, be severely disabled or to suffer from chronic diseases. Healthcare professionals who treat critically ill children ought to be aware of this situation and should therefore be prepared and trained to provide the best end-of-life care possible.
Generating Subcounty Health Data Products: Methods and Recommendations From a Multistate Pilot Initiative
Authors: Nguyen Trang Q. , Michaels Isaac H. , Bustamante-Zamora Dulce , Waterman Brian , Nagasako Elna , Li Yunshu , Givens Marjory L. , Gennuso Keith 
Published: April 2020

Background:
County Health Rankings & Roadmaps (CHR&R) makes data on health determinants and outcomes available at the county level, but health data at subcounty levels are needed. Three pilot projects in California, Missouri, and New York explored multiple approaches for defining measures and producing data at subcounty geographic and demographic levels based on the CHR&R model. This article summarizes the collective technical and implementation considerations from the projects, challenges inherent in analyzing subcounty health data, and lessons learned to inform future subcounty health data projects.

Methods:
The research teams used 12 data sources to produce 40 subcounty measures that replicate or approximate county-level measures from the CHR&R model. Using varying technical methods, the pilot projects followed similar stages: (1) conceptual development of data sources and measures; (2) analysis and presentation of small-area and subpopulation measures for public health, health care, and lay audiences; and (3) positioning the subcounty data initiatives for growth and sustainability. Unique technical considerations, such as degree of data suppression or data stability, arose during the project implementation. A compendium of technical resources, including samples of automated programs for analyzing and reporting subcounty data, was also developed.

Results:
The teams summarized the common themes shared by all projects as well as unique technical considerations arising during the project implementation. Furthermore, technical challenges and implementation challenges involved in subcounty data analyses are discussed. Lessons learned and proposed recommendations for prospective analysts of subcounty data are provided on the basis of project experiences, successes, and challenges.

Conclusions:
This multistate pilot project offers 3 successful approaches for creating and disseminating subcounty data products to communities. Subcounty data often are more difficult to obtain than county-level data and require additional considerations such as estimate stability, validating accuracy, and protecting individual confidentiality. We encourage future projects to further refine techniques for addressing these critical considerations.
Adapting to the Coronavirus Disease 2019 Pandemic in New York City
Authors: Escalon Miguel X. , Herrera Joseph 
Published: April 2020

Abstract
The coronavirus disease 2019 has and continues to overwhelm the medical establishment in New York City. It has moved faster and had rates of mortality higher than what were initially forecast. All departments within large hospital systems have had to learn lessons and adapt in real time to the crisis. We share our experience and what we have learned as it pertains to this pandemic and hope that it aides, guides, and influences other departments of physical medicine and rehabilitation regarding their potential roles and areas of growth during this time.
Prehabilitation May Help Mitigate an Increase in COVID-19 Peripandemic Surgical Morbidity and Mortality
Authors: Silver Julie K. 
Published: April 2020

Abstract
As physicians specializing in rehabilitation medicine consider sequelae from the novel coronavirus pandemic that began in 2019, one issue that should be top of mind is the physiologic effect that large-scale social distancing had on the health of patients in general but, more specifically, on preoperative patients who had their surgeries delayed or will have newly scheduled procedures during the peripandemic period. Predictably, as the virus becomes less prevalent, there will be a tremendous motivation to move forward with scheduling operations from both patient care and institutional perspectives. However, one can anticipate a pandemic-related increase in surgical morbidity and mortality above prepandemic levels, particularly in older or medically frail patients even
if they did not have a novel coronavirus (i.e., COVID-19) infection. Therefore, now is the time to consider for patients awaiting surgery a wider adoption of prehabilitation—physical and psychological assessments that establish a baseline functional level, identify impairments, and provide interventions that promote physical and psychological health to reduce the incidence and/or severity of future impairments.
Practical Considerations for Implementing Virtual Care in Physical Medicine and Rehabilitation
Authors: McIntyre McKyla , Robinson Lawrence R. , Mayo Amanda 
Published: April 2020

Abstract
This article outlines a practical approach to quickly implementing virtual care for physiatrists. This skill is relevant not only during times of a pandemic, when face to face care is impossible, but is also valuable when caring for patients who have physical, financial, logistic, or other challenges to on-site care. Key themes covered in this article include selecting appropriate virtual care platforms, consenting patients for virtual care and conducting successful virtual visits. It also reviews strategies for performing virtual physical examinations and engaging learners in virtual care.
Improving the Compliance of Intraoperative Antibiotic Redosing: A Quality Improvement Initiative
Authors: LeRiger Michelle M. , Phipps Amber R. , Norton Bridget M. , Spitznagel Rachel A. 
Published: April 2020

Introduction:
At Children’s Hospital and Medical Center in Omaha, Nebraska, the intraoperative antibiotic redosing guidelines and the time frame considered compliant for redosing were unclear. This lack of clarity plus an ill-defined process for ensuring intraoperative antibiotic redosing resulted in a compliance rate of 11%. The organization’s surgical site infection (SSI) rate was 3.19%, above the national benchmark of 1.87%. The primary project goal was to increase intraoperative antibiotic redosing compliance. The secondary project goal was to decrease SSIs.

Methods:
With recommendations from the Infectious Disease Society of America, we developed new organizational redosing guidelines, as well as a new antibiotic-specific reminder alert in the electronic medical record. Implementation of the new guidelines and processes occurred after providing education to the anesthesiologists, surgeons, and circulating nurses. Monthly evaluation of data allowed for quick recognition of oversights followed by the initiation of process updates.

Results:
Data showed that the initial compliance rate for the intraoperative redosing of antibiotics was 11%. Following interventions, compliance has reached and sustained an average of 99%. Survey results show that provider knowledge of the guidelines and process has improved. Though not directly related, the National Surgical Quality Improvement Program observed that the SSI rate decreased from 3.19% in 2014 to 2.3% in 2018.

Conclusions:
This project demonstrates that comprehensive education along with antibiotic-specific electronic medical record alerts significantly increased the compliance of intraoperative antibiotic redosing at Children’s Hospital & Medical Center. Continuous education and monthly updates sustained results for over 40 months.
Association Among Glucocorticoid Receptor Sensitivity, Fatigue, and Inflammation in Patients With Head and Neck Cancer
Authors: Xiao Canhua , Eldridge Ronald C. , Beitler Jonathan J. , Higgins Kristin A. , Chico Cynthia E. , Felger Jennifer C. , Wommack Evanthia C. , Knobf Tish , Saba Nabil F. , Shin Dong M. , Bruner Deborah W. , Miller Andrew H. 
Published: April 2020

ABSTRACT

Objective
Fatigued cancer patients often have high peripheral inflammation; however, the biological mechanisms of this association remain unclear. We examined whether decreased sensitivity of immune cells to the anti-inflammatory effects of glucocorticoids may contribute to inflammation and fatigue in head and neck cancer (HNC) patients during treatment.

Methods
HNC patients without distant metastasis and with curative intent (n = 77) were studied 1 week before intensity-modulated radiotherapy (IMRT) and 1 month after IMRT. At each time point, fatigue was measured by the Multidimensional Fatigue Inventory-20 along with plasma inflammation markers and glucocorticoid receptor (GR) sensitivity as determined by in vitro dexamethasone suppression of lipopolysaccharide-induced interleukin 6. Linear regression models were used.

Results
In contrast to our hypothesis, GR sensitivity increased during treatment; however, increased fatigue was associated with a lesser increase in GR sensitivity from baseline to 1 month after IMRT (unstandardized estimate = 4.07, p = .02). This effect was more prominent in human papillomavirus–unrelated HNCs (unstandardized estimate = 8.22, p = .002). Lower increases in GR sensitivity were also associated with increased inflammation at 1 month after IMRT as represented by C-reactive protein, interleukin 6, and tumor necrosis factor α. Addition of inflammation markers to models of GR sensitivity predicting fatigue indicated that these inflammation markers were stronger predictors of fatigue than GR sensitivity.

Conclusions
Lower increases in GR sensitivity during HNC treatment were significantly predictive of increased fatigue and inflammation markers. Inflammation markers in turn predicted fatigue above and beyond levels of GR sensitivity. Our findings indicate that HNC patients with cancer-related fatigue may exhibit a decreased capacity for glucocorticoids to regulate inflammatory processes, as evidenced by a lower increase in GR sensitivity. Larger studies are necessary to verify the findings.
Reinventing Extremity Amputation in the Era of Functional Limb Restoration
Authors: Herr Hugh M. , Clites Tyler R. , Srinivasan Shriya , Talbot Simon G. , Dumanian Gregory A. , Cederna Paul S. , Carty Matthew J. 
Published: April 2020

Background:
Recent progress in biomechatronics and vascularized composite allotransplantation have occurred in the absence of congruent advancements in the surgical approaches generally utilized for limb amputation. Consideration of these advances, as well as of both novel and time-honored reconstructive surgical techniques, argues for a fundamental reframing of the way in which amputation procedures should be performed.

Methods:
We review sentinel developments in external prosthetic limb technology and limb transplantation, in addition to standard and emerging reconstructive surgical techniques relevant to limb modification, and then propose a new paradigm for limb amputation.

Results:
An approach to limb amputation based on the availability of native tissues is proposed, with the intent of maximizing limb function, limiting neuropathic pain, restoring limb perception/proprioception and mitigating limb atrophy.

Conclusions:
We propose a reinvention of the manner in which limb amputations are performed, framed in the context of time-tested reconstructive techniques, as well as novel, state-of-the-art surgical procedures. Implementation of the proposed techniques in the acute setting has the potential to elevate advanced limb replacement strategies to a clinical solution that perhaps exceeds what is possible through traditional surgical approaches to limb salvage. We therefore argue that amputation, performed with the intent of optimizing the residuum for interaction with either a bionic or a transplanted limb, should be viewed not as a surgical failure, but as an alternative form of limb reconstruction.
New therapeutic strategies for combatting gastrointestinal toxicity
Authors: Sylvester Cyan L. , Anderson Paul H. , Stringer Andrea M. 
Published: April 2020

Purpose of review
An overwhelming majority of chemotherapy agents are known to cause gastrointestinal mucositis, an unwanted side effect of cancer treatment, for which no effective treatment currently exists. The pathological processes underlying the development of gastrointestinal mucositis are many and varied, with multiple pathways thought to be involved in initiation of inflammation and apoptosis. Physiological and or biochemical-based deficiencies, such as vitamin D deficiency and gut microbiome density and population, are also thought to have an impact on mucositis severity.

Recent findings
Recent studies investigating inflammatory pathways, such as cytokines and apoptotic markers, do show that interleukin-blocking proteins alleviate symptoms of gastrointestinal mucositis. However, the effectiveness of these treatments varies depending on the type of anticancer agent administered, meaning blocking compounds may be limited in their application. Targeting the host's gut microbiome in preventing dysbiosis is also thought to be a potential avenue for exploration. The use of probiotic gut bacteria (i.e. Lactobacillus spp.), while beneficial in preventing chemotherapy radiotherapy-induced diarrhoea, does not seem to alleviate the physiological damage caused by gastrointestinal mucositis. Vitamin D has been widely shown to have a host of anti-inflammatory and immunomodulatory effects in the intestine, as well as anticancer properties and therefore, may reduce severity of gastrointestinal mucositis.

Summary
While anti-inflammatory and antiapoptotic agents have shown promise in animal models of gastrointestinal mucositis, there is still no singular mechanism allowing for the development of a therapeutic drug to prevent or cure gastrointestinal injury. A greater insight into the exact mechanistic actions of both probiotics and vitamin D might reveal how to improve their use as therapeutic treatments for gastrointestinal mucositis.
Vaginal Energy-Based Devices
Authors: Alshiek Jonia , Garcia Bobby , Minassian Vatche , Iglesia Cheryl B. , Clark Amanda , Sokol Eric R. , Murphy Miles , Malik Shazia A. , Tran Alexis , Shobeiri S. Abbas 
Published: April 2020

Abstract
This clinical consensus statement on vaginal energy-based devices (EBDs) reflects statements drafted by content experts from the American Urogynecologic Society’s EBD writing group. The American Urogynecologic Society's EBD writing group used a modified Delphi process to assess statements that were evaluated for consensus after a structured literature search. A total of 40 statements were assessed and divided into 5 categories: (1) patient criteria, (2) health care provider criteria, (3) efficacy, (4) safety, and (5) treatment considerations. Of the 40 statements that were assessed, 28 reached consensus and the remaining 12 did not. Lack of evidence was among the main reasons that vulvovaginal EBD treatment statements did not reach consensus.