bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of an Alarm Algorithm, With Nanotechnology Multimodal Sensor, to Predict Impending Infusion Failure and Improve Safety of Peripheral Intravenous Catheters in Neonates
Authors: Bosque Elena M. 
Published: December 2019

Background:Peripheral intravenous catheters connected to an infusion pump are necessary for the delivery of fluids, nutrition, and medications to hospitalized neonates but are not without complications. These adverse events contribute to hospital-acquired patient harm. An artificial intelligence theory called fuzzy logic may allow the use of appropriate variables to predict infusion failure.Purpose:This innovative study aimed to develop an intravenous infusion nanotechnology monitoring system that would alert the nurse to impending peripheral intravenous infusion failure.Methods:An intravenous infusion nanotechnology monitoring system, using predictor variables of pressure, pH, and oxygen saturation used in a fuzzy logic alarm algorithm was developed to alert the nurse to impending peripheral intravenous infusion failure.Findings:The developed intravenous infusion nanotechnology monitoring system is composed of a peripheral intravenous catheter with nanotechnology multimodal sensor, an intravenous pump, a fuzzy logic algorithm, and alarm. For example, using this system, an elevated in-line pressure, a low pH, and a low venous oxygen level would generate an alarm for possible impending infusion failure.Implications for Practice:With further development, this technology may help nurses predict and prevent adverse outcomes from intravenous infusions. This work shows how nurses can be content experts and innovators of technology that they use to make clinical decisions.Implications for Research:After regulatory approval, a randomized controlled trial may be performed to investigate whether interventions at the time of an alarm would result in fewer adverse outcomes and improve safety.
Clinical Frailty Scale Score Before ICU Admission Is Associated With Mobility Disability in Septic Patients Receiving Early Rehabilitation
Authors: Nakajima Hiroki , Nishikimi Mitsuaki , Shimizu Miho , Hayashi Kazuhiro , Inoue Takayuki , Nishida Kazuki , Takahashi Kunihiko , Matsui Shigeyuki , Nishida Yoshihiro , Matsuda Naoyuki 
Published: December 2019

Objectives:
To clarify the relationship between mobility disability at the time of discharge from the ICU and clinical factors evaluated at ICU admission in septic patients.

Design:
A single-center, retrospective, observational study.

Setting:
Ten-bed, the emergency and medical ICU.

Patients:
We analyzed the data of septic patients who were admitted to our ICU between September 2012 and September 2016 and received early rehabilitation.

Interventions:
None.

Measurements and Main Results:
The patients were categorized into two groups based on their scores on the ICU mobility scale at the time of discharge from the ICU: the mobility disability group (ICU mobility scale score < 9) and the no mobility disability group (ICU mobility scale score ≥ 9). Of the 110 eligible patients, 63 met the inclusion criteria; of these, 46 patients (73%) were classified into the mobility disability group, and 17 patients (27%) were classified into the no mobility disability group. The age (median, 72 vs 64 yr; p = 0.024), prevalence of patients with clinical frailty scale scores of greater than or equal to 5 (54% vs 12%; p = 0.003), Sequential Organ Failure Assessment score (median, 9.0 vs 6.0; p = 0.006) and rate of vasopressin use (26% vs 0%; p = 0.026) were significantly higher in the mobility disability group as compared with the no mobility disability group. Among the candidate variables for which values recorded before/at the time of ICU admission were available, the clinical frailty scale score was identified as the only independent, statistically significant predictor of mobility disability at ICU discharge (odds ratio, 7.77; 95% CI, 1.37–44.21; p = 0.021). The positive predictive value and negative predictive value of clinical frailty scale scores greater than or equal to 5 for mobility disability at ICU discharge were 92.6% and 41.7%, respectively.

Conclusions:
The clinical frailty scale score was associated with increased mobility disability at ICU discharge in septic patients receiving early rehabilitation.
GENETIC RISK FACTORS IN SEVERE, NONSEVERE AND ACUTE PHENOTYPES OF CENTRAL SEROUS CHORIORETINOPATHY
Authors: Mohabati Danial , Schellevis Rosa L. , van Dijk Elon H. C. , Fauser Sascha , den Hollander Anneke I. , Hoyng Carel B. , De Jong Eiko K. , Yzer Suzanne , Boon Camiel J. F. 
Published: December 2019

Purpose:
To study genetic predispositions and differences between severe chronic central serous chorioretinopathy (cCSC), nonsevere cCSC, and acute central serous chorioretinopathy (aCSC).

Methods:
One hundred seventy-three severe cCSC patients, 272 nonsevere cCSC patients, 135 aCSC patients, and 1,385 control individuals were included. Eight single-nucleotide polymorphisms were genotyped in the ARMS2 (rs10490924), CFH (rs800292, rs1061170, rs1065489, rs1329428, rs2284664, rs3753394), and NR3C2 (rs2070951). Additionally, C4B gene copy numbers were analyzed.

Results:
A significant association in 5 single-nucleotide polymorphisms in the CFH gene could be reproduced among severe cCSC patients, including rs800292 (P = 0.0014; odds ratio [OR] = 1.93; 95% confidence interval [CI] = 1.51–2.47), rs1065489 (P = 2.22 × 10−4; OR = 0.49; 95% CI = 0.34–0.72), rs1329428 (P = 0.001; OR = 1.89; 95% CI = 1.49–2.40), rs2284664 (P = 1.21× 10−4; OR = 1.65; 95% CI = 1.28–2.13), and rs3753394 (P = 6.10× 10−4; OR = 0.61; 95% CI = 0.46–0.81). Carrying three C4B copies was protective for severe cCSC (P = 0.001; OR = 0.29; 95% CI = 0.14–0.61). No significant differences in allele frequencies could be found among the CSC phenotypes.

Conclusion:
Acute CSC, nonsevere cCSC, and severe cCSC all showed a similar association with the CFH and C4B genes, and the three phenotypes could not be distinguished based on the genetics. This shows that despite the differences in clinical presentation and severity, there is an overlap in the genetic predisposition of different CSC phenotypes. Nongenetic factors may play a more important role in determining the clinical course of CSC.
Changing Epidemiology and Predisposing Factors for Invasive Pneumococcal Disease at Two Australian Tertiary Hospitals
Authors: Hernstadt Hayley , Cheung Abigail , Hurem Daniel , Vasilunas Nan , Phuong Linny Kimly , Quinn Patrick , Agrawal Rishi , Daley Andrew J. , Cole Theresa , Gwee Amanda 
Published: December 2019

Background:
Invasive pneumococcal disease (IPD) is associated with significant morbidity and mortality in children. Universal pneumococcal conjugate vaccination has changed the epidemiology of IPD. In vaccinated children, IPD can be a marker of an underlying immunodeficiency.

Methods:
This is a retrospective audit of children younger than 18 years with IPD admitted to 2 tertiary pediatric hospitals in Australia between 2011 and 2017. Data on predisposing conditions, immunologic evaluation, pneumococcal serotype, antibiotic susceptibility and treatment were collected.

Results:
During the 7-year period, there were 131 presentations with IPD in 127 children; 3 children had recurrent IPD. Patients presented with sepsis (41%), empyema (29%), meningitis (18%), mastoiditis (12%), pneumonia (10%) and septic arthritis (4%). In 19 (15%) presentations, risk factors for IPD were present, including malignancy, hematologic disorder, chronic liver disease, chronic kidney disease and cochlear implant. Pneumococcal serotypes were determined in 78/131 (60%) of presentations: the most frequent serotypes were 19A (19%), 3 (13%), 7F (10%) and 19F (8%) and non-vaccine serotypes 22F (8%), 35B (6%), 15A (4%) and 38 (4%). Overall, 11% of isolates were non-susceptible to ceftriaxone. Only 36 patients (32%) had an immunologic evaluation, and 4 patients had proven or probable immunodeficiency.

Conclusion:
Although pneumococcal conjugate vaccine serotypes 19A, 3, 19F and 7F remain frequent causes of IPD, non-vaccine serotypes are emerging. Our data support vancomycin treatment for children with pneumococcal meningitis given 11% of our isolates were not susceptible to ceftriaxone. It is important to consider underlying conditions predisposing to IPD in a population with high rates of pneumococcal vaccination.
Clinical Profile, Liver Dysfunction and Outcome of Dengue Infection in Children
Authors: Prasad Durga , Bhriguvanshi Arpita 
Published: December 2019

Background:
Liver involvement in dengue illness is common and can lead to acute liver failure (ALF). No single method can effectively identify patients at risk for disease progression and bad outcome. We aimed to determine the relationship between liver dysfunction, kinetics of liver function tests (LFTs) and severity of hepatitis on the outcome in pediatric dengue illness.

Methods:
We conducted a prospective observational study of hospitalized children (1–12 years) with dengue infection (July 2014–July 2015). Serial monitoring of LFTs was done in confirmed dengue cases. Patients were classified into non-severe (NSD) and severe dengue (SD). Severity of hepatitis was graded: mild, moderate and severe hepatitis. Events were noted during hospitalization.

Results:
One hundred two children (66, boys), median age 72 (48–96) months, were analyzed (NSD, n = 41; SD, n = 61). Elevated transaminases (92%) was the most common abnormality; aspartate transaminase (AST) and alanine transaminase (ALT) in 87% and 82%, respectively. Maximum abnormalities in LFTs peaked at day 5 (AST, ALT) and day 7 (Alkaline Phosphatase [ALP], gamma-glutamyl transferase) of illness. Elevated transaminases was found to be higher in SD than NSD (100% vs. 80%, P = 0.006). Severe hepatitis developed organ dysfunction such as altered sensorium (P < 0.001), ALF (P < 0.001), acute kidney injury (P < 0.001) and shock (P < 0.001), more commonly than those with mild to moderate hepatitis. Fourteen patients died, two-thirds of whom had severe hepatitis (P < 0.001). Using binary logistic regression, presence of severe hepatitis and shock at presentation was an independent predictor for ALF (odds ratio: 77; 95% confidence interval : 13–457, P < 0.001) and mortality (odds ratio: 55; 95% confidence interval: 4.6–66, P < 0.001), respectively.

Conclusions:
Many children with dengue have liver involvement. Severe hepatitis in dengue is associated with significant organ dysfunction and poor outcome.
Low catechol-O-methyltransferase and stress potentiate functional pain and depressive behavior, especially in female mice
Authors: Zhang Xin , Kanter Katie , Chen Jiegen , Kim Seungtae , Wang Yaomin , Adeyemi Clementine , O'Buckley Sandra C. , Nackley Andrea G. 
Published: December 2019

Abstract
Low levels of catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, and stress, which potentiates catecholamine release from sympathetic nerves, are fundamental to chronic functional pain syndromes and comorbid depression, which predominantly affect females. Here, we sought to examine the independent and joint contributions of low COMT and stress to chronic functional pain and depression at the behavioral and molecular level. Male and female C57BL/6 mice received sustained systemic delivery of the COMT inhibitor OR486 over 14 days and underwent a swim stress paradigm on days 8 to 10. Pain and depressive-like behavior were measured over 14 days, and brain-derived neurotrophic factor (BDNF; a factor involved in nociception and depression) and glucocorticoid receptor (GR; a stress-related receptor) expression were measured on day 14. We found that stress potentiates the effect of low COMT on functional pain and low COMT potentiates the effect of stress on depressive-like behavior. The joint effects of low COMT and stress on functional pain and depressive-like behavior were significantly greater in females vs males. Consistent with behavioral data, we found that stress potentiates COMT-dependent increases in spinal BDNF and low COMT potentiates stress-dependent decreases in hippocampal BDNF in females, but not males. Although low COMT increases spinal GR and stress increases hippocampal GR expression, these increases are not potentiated in the OR486 + stress group and are not sex-specific. These results suggest that genetic and environmental factors that enhance catecholamine bioavailability cause abnormalities in BDNF signaling and increase risk of comorbid functional pain and depression, especially among females.
Dexpramipexole blocks Nav1.8 sodium channels and provides analgesia in multiple nociceptive and neuropathic pain models
Authors: Urru Matteo , Muzzi Mirko , Coppi Elisabetta , Ranieri Giuseppe , Buonvicino Daniela , Camaioni Emidio , Coppini Raffaele , Pugliese Anna Maria , Tanaka Brian , Estacion Mark , Waxman Stephen G. , Dib-Hajj Sulayman D. , Chiarugi Alberto 
Published: December 2019

Abstract
Selective targeting of sodium channel subtypes Nav1.7, Nav1.8, and Nav1.9, preferentially expressed by peripheral nociceptors, represents a unique opportunity to develop analgesics devoid of central side effects. Several compounds that target Nav1.7 and Nav1.8 with different degrees of selectivity have been developed and are currently being tested in clinical trials for multiple pain indications. Among these chemicals, benzothiazole-like compounds emerged as potent sodium channel blockers. We evaluated the effects of dexpramipexole, a benzothiazole-bearing drug with pleiotypic neuroactive properties and a good safety profile in humans, on sodium conductances of dorsal root ganglia neurons, as well as in multiple nociceptive and neuropathic pain models. Dexpramipexole blocks TTX-resistant sodium conductances in cultured rat dorsal root ganglion neurons with an IC50 of 294.4 nM, suggesting selectivity towards Nav1.8. In keeping with this, dexpramipexole does not affect sodium currents in dorsal root ganglion neurons from Nav1.8 null mice and acquires binding pose predicted to overlap that of the Nav1.8 channel-selective blocker A-8034637. The drug provides analgesia when parenterally, orally, or topically applied in inflammatory and visceral mouse pain models, as well as in mice affected by neuropathic pain induced by oxaliplatin, nerve constriction, or diabetes. Pain reduction in mice occurs at doses consistent with those adopted in clinical trials. The present findings confirm the relevance of selective targeting of peripheral Nav1.8 channels to pain therapy. In light of the excellent tolerability of dexpramipexole in humans, our results support its translational potential for treatment of pain.
Correlates and motivations of prescription opioid use among adolescents 12 to 17 years of age in the United States
Authors: Groenewald Cornelius B. , Patel Kushang V. , Rabbitts Jennifer A. , Palermo Tonya M. 
Published: December 2019

Abstract:
Despite significant efforts, the opioid crisis remains a pressing health concern affecting adolescents. The primary aim of this study was to describe recent sociodemographic shifts in the opioid epidemic. We examined whether rates of opioid use, including opioid misuse and opioid use disorder among 12 to 17 year olds in the United States, differ according to sociodemographic factors, physical and mental health, and substance use characteristics using data from the 2015 and 2016 National Survey on Drug Use and Health. We also examined motivations for opioid misuse. The study included 27,857 participants. Black, non-Hispanic adolescents were more likely to both use and misuse opioids as compared to white, non-Hispanic adolescents, a clear difference from previous studies. The main motivation for misuse by adolescents was relief of physical pain (50%, 95% confidence interval 46%-54%). Adolescents who reported pain relief as the major reason for misuse had increased odds of substance use as compared to adolescents who did not report any opioid misuse. However, odds for substance use was greatest among adolescents who reported reasons other than pain relief for opioid misuse. National Survey on Drug Use and Health self-report data suggest recent shifts in opioid misuse with minority adolescents appearing to be at increased risk of opioid misuse compared with white adolescents. Relief of physical pain is the most common motivation for opioid misuse.
Patient self-inflicted lung injury and positive end-expiratory pressure for safe spontaneous breathing
Authors: Yoshida Takeshi , Grieco Domenico L. , Brochard Laurent , Fujino Yuji 
Published: December 2019

Purpose of review
The potential risks of spontaneous effort and their prevention during mechanical ventilation is an important concept for clinicians and patients. The effort-dependent lung injury has been termed ‘patient self-inflicted lung injury (P-SILI)’ in 2017. As one of the potential strategies to render spontaneous effort less injurious in severe acute respiratory distress syndrome (ARDS), the role of positive end-expiratory pressure (PEEP) is now discussed.

Recent findings
Experimental and clinical data indicate that vigorous spontaneous effort may worsen lung injury, whereas, at the same time, the intensity of spontaneous effort seems difficult to control when lung injury is severe. Experimental studies found that higher PEEP strategy can be effective to reduce lung injury from spontaneous effort while maintaining some muscle activity. The recent clinical trial to reevaluate systemic early neuromuscular blockade in moderate–severe ARDS (i.e., reevaluation of systemic early neuromuscular blockade (ROSE) trial) support that a higher PEEP strategy can facilitate ‘safe’ spontaneous breathing under the light sedation targets (i.e., no increase in barotrauma nor 90 days mortality versus early muscle paralysis).

Summary
To prevent P-SILI in ARDS, it seems feasible to facilitate ‘safe’ spontaneous breathing in patients using a higher PEEP strategy in severe ARDS.
Prader Willi syndrome: endocrine updates and new medical therapies
Authors: Harris Rebecca M. , Stafford Diane E.J. 
Published: December 2019

Purpose of review
Prader Willi syndrome is characterized not only by hyperphagia frequently resulting in obesity, but also by endocrine dysfunction across a variety of axes. This article reviews the most recent literature regarding possible causes of hyperphagia and the nature of endocrinopathies seen in Prader Willi syndrome, as well as current research into possible therapies.

Recent findings
Investigation into neurologic, metabolic and hormonal drivers of hyperphagia and obesity has revealed new insights and clarified underlying pathophysiology. Additional studies continue to elucidate the hormonal deficiencies seen in the syndrome, allowing for improvements in clinical care.

Summary
The underlying causes of the hyperphagia and progressive obesity frequently seen in Prader Willi Syndrome are largely unknown and likely multifactorial. Understanding the hormonal and metabolic drivers at work in PWS, as well as the nature of other hormonal dysfunction seen in the syndrome is necessary to guide current management and future research directions.
Novel insights into the pathobiology of humoral alloimmune memory in kidney transplantation
Authors: Torija Alba , Favà Alex , Meneghini Maria , Crespo Elena , Bestard Oriol 
Published: December 2019

Purpose of review
Humoral alloimmunity against human leukocyte antigen (HLA) antigens is the main barrier for successful transplantation. Recent researches have shown that this complex effector immune mechanism is driven by a number of B-cell subsets, which can orchestrate in a perfect and synergistic multistep manner the rejection of the organ transplant. Herein, our purpose is to review the immunobiology of humoral response and discuss novel therapeutic strategies derived from this evidence.

Recent findings
Among the distinct cellular components of the humoral alloimmune system, memory B cells (mBC) have been shown to play a key role initiating and maintaining the antidonor humoral alloimmune response, thus its assessment apart from monitoring donor (HLA)-specific antibodies (DSA) in the sera may improve the understanding of the alloimmune status of transplant patients at different time points. Furthermore, targeting alloreactive mBC as well as other B and T-cell counterparts have highlighted for the first time, that novel therapeutic strategies with a more mechanistic rationale are highly warranted for achieving an effective anti-HLA humoral alloimmune control, also in human kidney transplantation.

Summary
The complex mechanisms of humoral allorecognitition in transplantation seem to be progressively better understood with the implementation of novel immune technologies. This new insight should serve for the development of novel immunosuppressive strategies to achieve an optimal humoral alloimmune regulation.
Genetic background and transplantation outcomes: insights from genome-wide association studies
Authors: Zanoni Francesca , Kiryluk Krzysztof 
Published: December 2019

Purpose of review
The current review summarizes recent advances in the genetic studies of transplantation outcomes, including new genome-wide association studies for acute rejection, allograft survival, pharmacogenomics, and common transplant comorbidities.

Recent findings
Genetic studies of kidney transplantation outcomes have begun to address the question of genetic compatibility beyond human leukocyte antigens, including the role of genome-wide mismatches in missense variants, and the ‘genomic collision’ hypothesis under which the risk of rejection may be increased in recipients homozygous for loss-of-function variants with grafts from nonhomozygous donors. In recent pilot studies, missense mismatch scores for transmembrane and secreted proteins were associated with antibodies against the mismatched peptides and reduced allograft survival. A ‘genomic collision’ at the LIMS1 locus involving a common deletion near LIMS1 gene was associated with anti-LIMS1 antibody response and increased risk of rejection. Additional genetic factors under active investigation include genome-wide polygenic risk scores for renal function and apolipoprotein L1 risk genotypes in African-American kidney donors. Due to the heterogeneity and complexity of clinical outcomes, new genome-wide association studies for rejection, allograft survival, and specific transplant comorbidities will require larger multicenter meta-analyses.

Summary
Genetic compatibilities between donor and recipient represent an important determinant of rejection and long-term allograft survival. Genetic background of transplant donors may be additionally predictive of allograft function, while recipient's genomes are likely determinant of a wide range of transplantation outcomes, from rejection susceptibility to pharmacogenetics and various comorbidities related to prolonged immunosuppression.