bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signatures of Subacute Potentially Catastrophic Illness in the ICU: Model Development and Validation*
Authors: Moss Travis J. , Lake Douglas E. , Calland J. Forrest , Enfield Kyle B. , Delos John B. , Fairchild Karen D. , Moorman J. Randall 
Published: April 2016

Objectives:
Patients in ICUs are susceptible to subacute potentially catastrophic illnesses such as respiratory failure, sepsis, and hemorrhage that present as severe derangements of vital signs. More subtle physiologic signatures may be present before clinical deterioration, when treatment might be more effective. We performed multivariate statistical analyses of bedside physiologic monitoring data to identify such early subclinical signatures of incipient life-threatening illness.

Design:
We report a study of model development and validation of a retrospective observational cohort using resampling (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis type 1b internal validation) and a study of model validation using separate data (type 2b internal/external validation).

Setting:
University of Virginia Health System (Charlottesville), a tertiary-care, academic medical center.

Patients:
Critically ill patients consecutively admitted between January 2009 and June 2015 to either the neonatal, surgical/trauma/burn, or medical ICUs with available physiologic monitoring data.

Interventions:
None.

Measurements and Main Results:
We analyzed 146 patient-years of vital sign and electrocardiography waveform time series from the bedside monitors of 9,232 ICU admissions. Calculations from 30-minute windows of the physiologic monitoring data were made every 15 minutes. Clinicians identified 1,206 episodes of respiratory failure leading to urgent unplanned intubation, sepsis, or hemorrhage leading to multi-unit transfusions from systematic individual chart reviews. Multivariate models to predict events up to 24 hours prior had internally validated C-statistics of 0.61–0.88. In adults, physiologic signatures of respiratory failure and hemorrhage were distinct from each other but externally consistent across ICUs. Sepsis, on the other hand, demonstrated less distinct and inconsistent signatures. Physiologic signatures of all neonatal illnesses were similar.

Conclusions:
Subacute potentially catastrophic illnesses in three diverse ICU populations have physiologic signatures that are detectable in the hours preceding clinical detection and intervention. Detection of such signatures can draw attention to patients at highest risk, potentially enabling earlier intervention and better outcomes.
Inhibition of Intestinal Thiamin Transport in Rat Model of Sepsis
Authors: Sassoon Catherine S. , Zhu Ercheng , Fang Liwei , Subramanian Veedamali S. , Said Hamid M. 
Published: April 2016

Objectives:
Thiamin deficiency is highly prevalent in patients with sepsis, but the mechanism by which sepsis induces thiamin deficiency is unknown. This study aimed to determine the influence of various severity of sepsis on carrier-mediated intestinal thiamin uptake, level of expressions of thiamin transporters (thiamin transporter-1 and thiamin transporter-2), and mitochondrial thiamin pyrophosphate transporter.

Design:
Randomized controlled study.

Setting:
Research laboratory at a Veterans Affairs Medical Center.

Subjects:
Twenty-four Sprague-Dawley rats were randomized into controls, mild, moderate, and severe sepsis with equal number of animals in each group.

Interventions:
Sepsis was induced by cecal ligation and puncture with the cecum ligated below the cecal valve at 25%, 50%, and 75% of cecal length, defined as severe, moderate, and mild sepsis, respectively. Control animals underwent laparotomy only.

Measurements and Main Results:
After 2 days of induced sepsis, carrier-mediated intestinal thiamin uptake was measured using [3H]thiamin. Expressions of thiamin transporter-1, thiamin transporter-2, and mitochondrial thiamin pyrophosphate transporter proteins and messenger RNA were measured. Proinflammatory cytokines (interleukin-1β and interleukin-6) and adenosine triphosphate were also measured. Sepsis inhibited [3H]thiamin uptake, and the inhibition was a function of sepsis severity. Both cell membrane thiamin transporters and mitochondrial thiamin pyrophosphate transporter expression levels were suppressed; also levels of adenosine triphosphate in the intestine of animals with moderate and severe sepsis were significantly lower than that of sham-operated controls.

Conclusions:
For the first time, we demonstrated that sepsis inhibited carrier-mediated intestinal thiamin uptake as a function of sepsis severity, suppressed thiamin transporters and mitochondrial thiamin pyrophosphate transporter, leading to adenosine triphosphate depletion.
Management of Skin Reactions During Cetuximab Treatment in Association With Chemotherapy or Radiotherapy
Authors: Pinto Carmine , Barone Carlo A. , Girolomoni Giampiero , Russi Elvio G. , Merlano Marco C. , Ferrari Daris , Maiello Evaristo 
Published: April 2016

Objectives:
Cetuximab was shown in phase III clinical trials to improve chemotherapy efficacy in patients with advanced colorectal and head-neck cancer. Appropriate management of skin reactions associated with epidermal growth factor receptor inhibitor therapy is necessary to allow adequate drug compliance and to improve patient quality of life and outcomes.

Methods:
The RAND/UCLA Appropriateness Method was used by a group of experts to produce new Italian recommendations on the management of skin reactions in this setting. Statements were generated on the basis of an updated systematic review of the literature and rated twice by a panel of 38 expert physicians. A meeting of the panel was held after the first rating session.

Results:
Skin reactions included acneiformic rash, skin dryness (xerosis), pruritus, paronychia, hair abnormalities, mucositis, and increased growth of eyelashes or facial hair. Updates of the previous recommendations on the prevention and treatment of each type of reaction were proposed.

Conclusions:
This updated Expert Opinion focuses on how to assess and correctly grade skin reactions according to the latest National Cancer Institute Common Terminology Criteria for Adverse Events and on how to manage these adverse events in clinical practice.
Attention-Deficit/Hyperactivity Disorder, Behavior Regulation and Virtual School Support
Authors: Wallace Claire , Ievers-Landis Carolyn E. , Scherer Catherine , Roizen Nancy , Augustyn Marilyn 
Published: April 2016

CASE:
Tony is a 6-year-old multiracial boy diagnosed as having attention-deficit/hyperactivity disorder—combined type who is followed in your primary care practice and has started on a stimulant medication. Tony continues to have difficulty with emotion regulation and impulse control both at home and at school. He was asked to leave his private school soon after beginning first grade because of physical fighting, emotional outbursts, and arguing with teachers.
His mother made the decision to enroll Tony in online virtual schooling for the remainder of the academic year, with the plan to transition back to traditional school for the next academic year. They have enrolled in a program that offers lessons online and sends materials to the home for the child to use to complete certain types of assignments (e.g., science experiments). Virtual schools are different from traditional home schooling because children receive their instruction from teachers online with parental assistance as opposed to parents being responsible for teaching all material. Tony's mother comes to your practice requesting assistance with setting up an appropriate school environment for her son at home, where she can monitor and support his academic progress.
Tony is a bright child, with an Intelligence Quotient in the superior range. He has advanced academic skills, but he becomes dysregulated if he is told he is wrong or that he has answered a question incorrectly. For example, if he answered a question incorrectly in class, he would become verbally abusive toward his teacher and often have temper tantrums. This challenging behavior occurred daily at school and was one of the factors leading to his expulsion. The behavior had predated the introduction of stimulant medication and had remained consistent after he began medication.
Tony's parents are highly educated, and both parents hold professional jobs with steady income. His parents have good command of typical behavior management strategies such as the use of rewards, time out, and behavioral contingencies to target noncompliance and temper tantrums. However, Tony's difficulty identifying and regulating his emotions leads to emotional outbursts and shutdowns that have thus far been unresponsive to standard behavior management techniques. Tony continued to have outbursts even when the behavior was ignored. His mother is concerned not only about his learning during the coming year but also about his social relationships and the family dynamic. Tony's outbursts cause significant disruption in the home and are a source of tension among parents and siblings.
His mother is asking for advice on how to support his behavior better at home now that he will be spending his entire day there. How might you assist this child and his mother by helping to integrate therapeutic goals into the academic environment?
Profiling of plasma metabolites in postmenopausal women with metabolic syndrome
Authors: Iida Miho , Harada Sei , Kurihara Ayako , Fukai Kota , Kuwabara Kazuyo , Sugiyama Daisuke , Takeuchi Ayano , Okamura Tomonori , Akiyama Miki , Nishiwaki Yuji , Suzuki Asako , Hirayama Akiyoshi , Sugimoto Masahiro , Soga Tomoyoshi , Tomita Masaru , Banno Kouji , Aoki Daisuke , Takebayashi Toru 
Published: April 2016

AbstractObjective:The aim of the study was to investigate the associations of amino acids and other polar metabolites with metabolic syndrome (MetS) in postmenopausal women in a lean Asian population.Methods:The participants were 1,422 female residents enrolled in a cohort study from April to August 2012. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III modified for Japanese women. Associations were examined between MetS and 78 metabolites assayed in fasting plasma samples using capillary electrophoresis-mass spectrometry. Replication analysis was performed to confirm the robustness of the results in a separate population created by random allocation.Results:Analysis was performed for 877 naturally postmenopausal women, including 594 in the original population and 283 in the replication population. The average age, body mass index, and levels of high- and low-density lipoprotein cholesterol of the entire population were 64.6 years, 23.0 kg/m2, 72.1 mg/dL, and 126.1 mg/dL, respectively. There was no significant difference in low-density lipoprotein cholesterol levels between women with and without MetS. Thirteen metabolites were significantly related to MetS: multiple plasma amino acids were elevated in women with MetS, including branched-chain amino acids, alanine, glutamate, and proline; and alpha-aminoadipate, which is generated by lysine degradation, was also significantly increased.Conclusions:Our large-scale metabolomic profiling indicates that Japanese postmenopausal women with MetS have abnormal polar metabolites, suggesting altered catabolic pathways. These results may help to understand metabolic disturbance, including in persons with normal body mass index and relatively high levels of high-density lipoprotein cholesterol, and may have clinical utility based on further studies.
Limbal and Conjunctival Epithelial Cell Cultivation on Contact Lenses—Different Affixing Techniques and the Effect of Feeder Cells
Authors: Tóth Enikö , Beyer Dániel , Zsebik Barbara , Vereb György , Takács Lili 
Published: April 2016

Objectives:
Corneal blindness due to limbal stem-cell deficiency can be treated by transplantation of cultivated limbal epithelial stem cells (LESCs). We examined LESC cultivation on a contact lens (CL) carrier. Our goal was to optimize explant affixation and assess the possible benefit of 3T3 feeder cells.

Methods:
Human cadaver limbal and conjunctival explants were allowed to attach to CLs under the airflow of the laminar box (dried group) or affixed on CLs using suturing (sutured group) or tissue adhesives (glued group), then cultivated with or without 3T3 feeder cells. Outgrowth efficiency was statistically analyzed. CEBPδ, p63, CK3/12, and CK13 were detected by immunofluorescence in expanded cells.

Results:
Suturing and gluing provided excellent sample attachment, whereas drying was less effective. Cell expansion was better in sutured than in dried or glued samples. Presence of 3T3 feeder resulted in significantly better cell growth (P=0.048), most importantly in dried samples (P=0.008). Stepwise regression analysis indicated that cell expansion was dependent on the affixing method (P<0.001) and the presence of feeder layer (P=0.003). Expanded cells maintained their CK expression profiles and expressed putative stem-cell markers p63 and CEBPδ. The 3T3 feeder did not influence the expression of putative LESC markers or growth rate.

Conclusions:
Suturing is an effective way to fasten explants to CLs. 3T3 fibroblasts are not necessary in this system, although they may enhance cell outgrowth when samples are exposed to stress. However, once cells begin to expand, neither expression of putative stem-cell markers nor growth rate is influenced by feeder cells.
Assessment of physical function and participation in chronic pain clinical trials: IMMPACT/OMERACT recommendations
Authors: Taylor Ann M. , Phillips Kristine , Patel Kushang V. , Turk Dennis C. , Dworkin Robert H. , Beaton Dorcas , Clauw Daniel J. , Gignac Monique A.M. , Markman John D. , Williams David A. , Bujanover Shay , Burke Laurie B. , Carr Daniel B. , Choy Ernest H. , Conaghan Philip G. , Cowan Penney , Farrar John T. , Freeman Roy , Gewandter Jennifer , Gilron Ian , Goli Veeraindar , Gover Tony D. , Haddox J. David , Kerns Robert D. , Kopecky Ernest A. , Lee David A. , Malamut Richard , Mease Philip , Rappaport Bob A. , Simon Lee S. , Singh Jasvinder A. , Smith Shannon M. , Strand Vibeke , Tugwell Peter , Vanhove Gertrude F. , Veasley Christin , Walco Gary A. , Wasan Ajay D. , Witter James 
Published: April 2016

Abstract
Although pain reduction is commonly the primary outcome in chronic pain clinical trials, physical functioning is also important. A challenge in designing chronic pain trials to determine efficacy and effectiveness of therapies is obtaining appropriate information about the impact of an intervention on physical function. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) and Outcome Measures in Rheumatology (OMERACT) convened a meeting to consider assessment of physical functioning and participation in research on chronic pain. The primary purpose of this article is to synthesize evidence on the scope of physical functioning to inform work on refining physical function outcome measurement. We address issues in assessing this broad construct and provide examples of frequently used measures of relevant concepts. Investigators can assess physical functioning using patient-reported outcome (PRO), performance-based, and objective measures of activity. This article aims to provide support for the use of these measures, covering broad aspects of functioning, including work participation, social participation, and caregiver burden, which researchers should consider when designing chronic pain clinical trials. Investigators should consider the inclusion of both PROs and performance-based measures as they provide different but also important complementary information. The development and use of reliable and valid PROs and performance-based measures of physical functioning may expedite development of treatments, and standardization of these measures has the potential to facilitate comparison across studies. We provide recommendations regarding important domains to stimulate research to develop tools that are more robust, address consistency and standardization, and engage patients early in tool development.
Predicting pain outcomes after traumatic musculoskeletal injury
Authors: Rosenbloom Brittany N. , Katz Joel , Chin Kelly Y.W. , Haslam Lynn , Canzian Sonya , Kreder Hans J. , McCartney Colin J.L. 
Published: April 2016

Abstract
Traumatic musculoskeletal injury results in a high incidence of chronic pain; however, there is little evidence about the nature, quality, and severity of the pain. This study uses a prospective, observational, longitudinal design to (1) examine neuropathic pain symptoms, pain severity, pain interference, and pain management at hospital admission and 4 months after traumatic musculoskeletal injury (n = 205), and (2) to identify predictors of group membership for patients with differing moderate-to-severe putative neuropathic pain trajectories. Data were collected on mechanism of injury, injury severity, pain (intensity, interference, neuropathic quality), anxiety (anxiety sensitivity, general anxiety, pain catastrophizing, pain anxiety), depression, and posttraumatic stress while patients were in-hospital and 4 months after injury. A third of patients had chronic moderate-to-severe neuropathic pain 4 months after injury. Specifically, 11% of patients developed moderate-to-severe pain by 4 months and 21% had symptoms immediately after injury that persisted over time. Significant predictors of the development and maintenance of moderate-to-severe neuropathic pain included high levels of general anxiety while in-hospital immediately after injury (P < 0.001) and symptoms of posttraumatic stress 4 months after injury (P < 0.001). Few patients had adequate pharmacological, physical, or psychological pain management in-hospital and at 4 months. Future research is needed among trauma patients to better understand the development of chronic pain and to determine the best treatment approaches.
Gi-protein–coupled 5-HT1B/D receptor agonist sumatriptan induces type I hyperalgesic priming
Authors: Araldi Dioneia , Ferrari Luiz F. , Levine Jon D. 
Published: April 2016

AbstractWe have recently described a novel form of hyperalgesic priming (type II) induced by agonists at two clinically important Gi-protein–coupled receptors (Gi-GPCRs), mu-opioid and A1-adenosine. Like mu-opioids, the antimigraine triptans, which act at 5-HT1B/DGi-GPCRs, have been implicated in pain chronification. We determined whether sumatriptan, a prototypical 5-HT1B/Dagonist, produces type II priming. Characteristic of hyperalgesic priming, intradermal injection of sumatriptan (10 ng) induced a change in nociceptor function such that a subsequent injection of prostaglandin-E2(PGE2) induces prolonged mechanical hyperalgesia. However, onset to priming was delayed 3 days, characteristic of type I priming. Also characteristic of type I priming, a protein kinase Cε, but not a protein kinase A inhibitor attenuated the prolongation phase of PGE2hyperalgesia. The prolongation of PGE2hyperalgesia was also permanently reversed by intradermal injection of cordycepin, a protein translation inhibitor. Also, hyperalgesic priming did not occur in animals pretreated with pertussis toxin or isolectin B4–positive nociceptor toxin, IB4–saporin. Finally, as observed for other agonists that induce type I priming, sumatriptan did not induce priming in female rats. The prolongation of PGE2hyperalgesia induced by sumatriptan was partially prevented by coinjection of antagonists for the 5-HT1Band 5-HT1D, but not 5-HT7, serotonin receptors and completely prevented by coadministration of a combination of the 5-HT1Band 5-HT1Dantagonists. Moreover, the injection of selective agonists, for 5-HT1Band 5-HT1Dreceptors, also induced hyperalgesic priming. Our results suggest that sumatriptan, which signals through Gi-GPCRs, induces type I hyperalgesic priming, unlike agonists at other Gi-GPCRs, which induce type II priming.
Inpatient Unit Heart Failure Discharge Volume Predicts All-cause 30-Day Hospital Readmission
Authors: Dordunoo Dzifa , Thomas Sue A. , Friedmann Erika , Russell Stuart D. , Newhouse Robin P. , Akintade Bim 
Published: April 2016

Background:
All-cause 30-day hospital readmission is a heart failure (HF) quality of care metric. Readmission costs the healthcare system $30.7 million annually. Specific structure, process, or patient factors that predispose patients to readmission are unclear.

Objective:
The aim of this study is to determine whether the addition of unit-level structural factors (attending medical service, patient-to-nurse ratio, and unit HF volume) predicts readmission beyond patient factors.

Methods:
A retrospective chart review of 425 patients who resided in Maryland and were discharged home in 2011 with the primary diagnosis of HF from a large, urban academic center was conducted.

Results:
The patients were predominately (66.6%) black/African American, with mean (SD) age of 62.2 (14.8) years. Men represented 48.2% of the sample; 32% had nonischemic HF, 31.3% had preserved ejection fractions, 25.4% had implantable cardioverter defibrillators, and 15.3% had permanent pacemakers. Average length of stay was 6.0 days. All-cause 30-day hospital readmission rate was 20.2%. Inpatient unit HF discharge volume significantly predicted readmission after controlling for patient factors.

Conclusions:
The study found that discharge from inpatient units with higher HF discharge volume was associated with increased risk of readmission. The findings suggest that in caring for patients with severe HF, inpatient unit HF discharge volume may negatively impact care processes, increasing the odds of hospital readmission. It is unclear what specific care processes are responsible. The discharge period is a vulnerable point in care transition that warrants further investigation.
Unmet Nursing Care Linked to Rehospitalizations Among Older Black AMI Patients
Authors: Brooks-Carthon J. Margo , Lasater Karen B. , Rearden Jessica , Holland Sara , Sloane Douglas M. 
Published: April 2016

Background:
Recent studies suggest that nurses may be unable to complete all aspects of necessary care due to a lack of time. Research is needed to determine whether unmet nursing care contributes to disparities in readmissions for vulnerable populations.

Objectives:
To examine differences in the relationship between nursing care left undone and acute myocardial infarction readmissions among older black patients compared with older white patients.

Research Design:
Cross-sectional analysis of multiple datasets, including: 2006 to 2007 administrative discharge data, a survey of registered nurses, and the American Hospital Association Annual Survey. Risk-adjusted logistic regression models were used to estimate the association between care left undone and 30-day readmission. Interactions were used to examine the moderating effect of care left undone on readmission by race.

Results:
The sample included 69,065 patients in 253 hospitals in California, New Jersey, and Pennsylvania. Older black patients were 18% more likely to experience a readmission after adjusting for patient and hospital characteristics and more likely to be in hospitals where nursing care was often left undone. Black patients were more likely to be readmitted when nurses were unable to talk/comfort patients [odds ratio (OR), 1.09; 95% confidence interval (CI), 1.01–1.19], complete documentation (OR, 1.16; 95% CI, 1.01–1.32), or administer medications in a timely manner (OR, 1.26; 95% CI, 1.09–1.46).

Conclusions:
Unmet nursing care is associated with readmissions for older black patients following acute myocardial infarction. Investment in nursing resources to improve the delivery of nursing care may decrease disparities in readmission.