bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammatory Markers in Serum and Cerebrospinal Fluid for Early Detection of External Ventricular Drain–associated Ventriculitis in Patients With Subarachnoid Hemorrhage
Authors: Lenski Markus , Huge Volker , Schmutzer Michael , Ueberschaer Moritz , Briegel Josef , Tonn Jörg-Christian , Schichor Christian , Thon Niklas 
Published: February 2018

Background:
External ventricular drain (EVD)-associated ventriculitis is a serious complication. Early diagnosis can be difficult particularly in critically ill patients with aneurysmal subarachnoid hemorrhage (aSAH). We examined the diagnostic potential of standard serum and cerebrospinal fluid (CSF) biomarkers to differentiate between EVD-associated infections and aseptic courses in patients with aSAH.

Materials and Methods:
We retrospectively evaluated the levels of inflammatory markers in serum (white blood cell count, percentage of neutrophils [sN%], and procalcitonin) and CSF (total leukocyte count [CSFTLC], CSFglucose, CSF/serumglucose ratio, CSF total protein [CSFTP]) of 63 consecutive patients with aSAH. Receiver operating characteristic curves and the area-under-the-curve (AUC) were calculated to detect the diagnostic potential, optimized threshold, sensitivity (SE), specificity (SP), + likelihood ratio (LR), and −LR of each biomarker.

Results:
Of all patients, 17 (27%) developed an EVD-associated ventriculitis within a mean of 7.8±2.3 days after implantation. sN% had a very good diagnostic potential (AUC=0.900, SE=70.0%, SP=100%), followed by the CSFTLC with good diagnostic potential (AUC=0.841, SE=75.0%, SP=88.5%), and the CSFTP with moderate diagnostic potential (AUC=0.772, SE=73.3%, SP=76.0%). sN% higher than 70% and a CSFTLC higher than 635/µL were highly associated with the diagnosis of ventriculitis (+LR=∞ and 6.5), sN%<70% or a CSFTLC<635 made a diagnosis of ventriculitis unlikely (−LR=0.3 and 0.28).

Conclusions:
Routine determination of N% and CSFTLC are useful to distinguish ventriculitis from aseptic courses in the acute phase after aSAH and regardless of the bacteriological test result.
The Period 2 Enhancer Nobiletin as Novel Therapy in Murine Models of Circadian Disruption Resembling Delirium*
Authors: Gile Jennifer , Scott Benjamin , Eckle Tobias 
Published: February 2018

Objectives:
Delirium occurs in approximately 30% of critically ill patients, and the risk of dying during admission doubles in those patients. Molecular mechanisms causing delirium are largely unknown. However, critical illness and the ICU environment consistently disrupt circadian rhythms, and circadian disruptions are strongly associated with delirium. Exposure to benzodiazepines and constant light are suspected risk factors for the development of delirium. Thus, we tested the functional role of the circadian rhythm protein Period 2 (PER2) in different mouse models resembling delirium.

Design:
Animal study.

Setting:
University experimental laboratory.

Subjects:
Wildtype, Per2
–/– mice.

Interventions:
Midazolam, lipopolysaccharide (lipopolysaccharide), constant light, nobiletin, or sham-treated animals.

Measurements and Main Results:
Midazolam significantly reduced the expression of PER2 in the suprachiasmatic nucleus and the hippocampus of wild-type mice. Behavioral tests following midazolam exposure revealed a robust phenotype including executive dysfunction and memory impairment suggestive of delirium. These findings indicated a critical role of hippocampal expressed PER2. Similar results were obtained in mice exposed to lipopolysaccharide or constant light. Subsequent studies in Per2
–/– mice confirmed a functional role of PER2 in a midazolam-induced delirium-like phenotype. Using the small molecule nobiletin to enhance PER2 function, the cognitive deficits induced by midazolam or constant light were attenuated in wild-type mice.

Conclusions:
These experiments identify a novel role for PER2 during a midazolam- or constant light–induced delirium-like state, highlight the importance of hippocampal PER2 expression for cognitive function, and suggest the PER2 enhancer nobiletin as potential therapy in delirium-like conditions associated with circadian disruption.
Vancomycin Area Under the Curve Simplified
Authors: Lewis Paul 
Published: February 2018

Background:
Serum trough concentrations as the sole means of monitoring safety and efficacy of vancomycin are insufficient. The daily area under the curve (AUC24) of serum concentration versus time to minimum inhibitory concentration (MIC) ratio of greater than 400 mg × h/L has emerged as a more robust dosing target. A simple and practical method to extrapolate AUC24 from troughs is needed.

Methods:
This mathematical model computes the median and range AUC24 using the dose in mg/kg and the observed serum trough concentration. AUC24 is calculated using dose in mg/kg divided by the volume of distribution (Vd) and elimination constant (Ke). Vd is provided using the population median (range) of 0.7 (0.4–1) L/kg. Ke is calculated using the trough and population Vd.

Results:
For doses of 15–20 mg/kg, troughs of at least 11 mg/L will achieve AUC24 of greater than 400 mg × h/L, even with a Vd of 1 L/kg. Using the median Vd and lower, AUC24 greater than 400 mg × h/L can be achieved with troughs as little as 9 mg/L using doses of 15 mg/kg and greater. The AUC24:MIC goal of greater than 400 can still be attained with an MIC of 1.5 mg/L by using doses of at least 15 mg/kg and targeting troughs of at least 16 mg/L for a patient with a Vd of 0.7 L/kg or less.

Conclusions:
Troughs of 15–20 mg/L are rarely needed for organisms with an MIC of 1 mg/L or less. AUC24:MIC goals of greater than 400 can best be achieved with higher doses in mg/kg while targeting lower troughs.
EFFECT OF OPTIC DISK—FOVEA DISTANCE ON MEASUREMENTS OF INDIVIDUAL MACULAR INTRARETINAL LAYERS IN NORMAL SUBJECTS
Authors: Qiu Kunliang , Chen Binyao , Chen Haoyu , Gao Enting , Yang Jianling , Chen Xinjian , Zhang Mingzhi 
Published: February 2018

Purpose:
To investigate the effect of optic disk—fovea distance (DFD) on measurements of macular intraretinal layers using spectral domain optical coherence tomography in normal subjects.

Methods:
One hundred and eighty-two eyes from 182 normal subjects were imaged using spectral domain optical coherence tomography. The average thicknesses of eight macular intraretinal layers were measured using an automatic segmentation algorithm. Partial correlation test and multiple regression analysis were used to determine the effect of DFD on thicknesses of intraretinal layers.

Results:
Disk—fovea distance correlated negatively with the overall average thickness in all the intraretinal layers (r ≤ −0.17, all P ≤ 0.025) except the ganglion cell layer and photoreceptor. In multiple regression analysis, greater DFD was associated with thinner nerve fiber layer (6.78 μm decrease per each millimeter increase in DFD, P < 0.001), thinner ganglion cell—inner plexiform layer (2.16 μm decrease per each millimeter increase in DFD, P = 0.039), thinner ganglion cell complex (8.94 μm decrease per each millimeter increase in DFD, P < 0.001), thinner central macular thickness (18.16 μm decrease per each millimeter increase in DFD, P < 0.001), and thinner total macular thickness (15.94 μm decrease per each millimeter increase in DFD, P < 0.001).

Conclusion:
Thinner measurements of macular intraretinal layers were significantly associated with greater DFD. A clinical assessment of macular intraretinal layers in the evaluation of various macular diseases should always be interpreted in the context of DFD.
“Off-the-Shelf” K2-EDTA for Calcific Band Keratopathy
Authors: Lee Marco E. , Ouano Dean P. , Shapiro Brett , Fong Andrew , Coroneo Minas T. 
Published: February 2018

Purpose:
To explore the effectiveness of “off-the-shelf” dipotassium-ethylenediaminetetraacetic acid (K2-EDTA) as an alternative to sodium EDTA as chelation therapy in removal of calcific band keratopathy (CBK).

Methods:
This study was a retrospective case series involving 4 patients with CBK who underwent superficial keratectomy and subsequent chelation therapy with K2-EDTA in a single center (Coastal Eye Clinic) by the same surgeon. Visual acuity and symptomatic relief were the main outcomes measured in our study.

Results:
All 4 participants in this study were female with an average age of 80.3 years. Three of the patients with reasonable baseline visual acuity experienced improved visual acuity at 1 month. The other patient with multiple ocular comorbidities and severely reduced visual potential reported symptomatic pain relief at 1-month follow-up after the intervention.

Conclusions:
K2-EDTA seems to be an effective alternative to disodium EDTA in its ability to clear calcific plaques and restore visual function. Because of the logistical difficulties associated with acquiring disodium EDTA, and the relative abundance of K2-EDTA in health-care facilities, we believe that our findings warrant further investigation into its use as a more accessible and cost-effective chelating agent in CBK.
Monthly vitamin D supplementation, pain, and pattern of analgesic prescription: secondary analysis from the randomized, double-blind, placebo-controlled Vitamin D Assessment study
Authors: Wu Zhenqiang , Camargo Carlos A. , Malihi Zarintaj , Bartley Jim , Waayer Debbie , Lawes Carlene M.M. , Toop Les , Khaw Kay-Tee , Scragg Robert 
Published: February 2018

Abstract
Observational studies suggest that vitamin D deficiency is associated with higher risk of pain. However, evidence on the effect of vitamin D supplementation on pain is limited and contradictory. The aim of this study was to compare the effect of monthly high-dose vitamin D supplementation on a pain impact questionnaire (PIQ-6) score and prescription of analgesics in the general population. We performed a randomized, double-blind, placebo-controlled trial of 5108 community-dwelling participants, aged 50 to 84 years, who were randomly assigned to receive monthly 100,000-IU capsules of vitamin D3 (n = 2558) or placebo (n = 2550) for a median of 3.3 years. The PIQ-6 was administered at baseline, year 1, and final follow-up. Analgesic prescription data were collected from Ministry of Health. There was no difference in mean PIQ-6 score at the end of follow-up (adjusted mean difference: 0.06; P = 0.82) between the vitamin D (n = 2041) and placebo (n = 2014) participants. The proportion of participants dispensed one or more opioids was similar in the vitamin D group (n = 559, 21.9%) compared with placebo (n = 593, 23.3%); the relative risk (RR) adjusted for age, sex, and ethnicity was 0.94 (P = 0.24). Similar results were observed for dispensing of nonsteroidal anti-inflammatory drugs (RR = 0.94; P = 0.24) and other nonopioids (RR = 0.98; P = 0.34). Focusing on vitamin D deficient participants (<50 nmol/L, 24.9%), there was a lower risk of dispensing nonsteroidal anti-inflammatory drugs in the vitamin D group compared with placebo (RR = 0.87; P = 0.009); all other subgroup analyses were not significant. Long-term monthly high-dose vitamin D supplementation did not improve mean PIQ-6 score or reduce analgesic dispensing in the general population.
Comparison of Video Head Impulse Test in the Posterior Semicircular Canal Plane and Cervical Vestibular Evoked Myogenic Potential in Patients With Vestibular Neuritis
Authors: Park Jin Su , Kim Chang-Hee , Kim Min-Beom 
Published: February 2018

Objective:
The purpose of this study was to evaluate and compare the results of cervical vestibular evoked myogenic potential (cVEMP) and video head impulse test (p-vHIT) of posterior semicircular canal considered tools of inferior vestibular nerve function in vestibular neuritis.

Study Design:
Prospective cohort study.

Setting:
Tertiary otology clinic.

Patients and Interventions:
Seventy-nine patients with vestibular neuritis participated in this study. We analyzed the interaural amplitude difference in cVEMP with a positive rate of p-vHIT according to gain and corrective saccade in the study population.

Main Outcome Measure:
To evaluate the concordance rate of both tests, we analyzed Fleiss’ Kappa value inter-test agreement of cVEMP with p-vHIT. Finally, we performed detailed analysis of the bilaterally absent response on cVEMP according to the p-vHIT results.

Results:
The inter-test agreement between cVEMP and p-vHIT was 69.8% as we also considered the lesion side. This result indicated a statistically fair to good agreement in both tests. In mostly elderly patients with a bilaterally absent response (11 patients) on cVEMP, as a result of vHIT, nine patients with a bilaterally negative response on p-vHIT showed only canal paresis. Two patients showed canal paresis and a unilaterally positive response on p-vHIT.

Conclusions:
Inter-test agreement between cVEMP and p-vHIT assessed in vestibular neuritis was relatively lower than we had predicted. Probably, p-vHIT can provide additional information on the differential diagnosis of dysfunction of the inferior vestibular nerve which is composed of the saccular nerve and the posterior ampullary nerve.
Changes in liver stiffness and steatosis among patients with hepatitis C virus infection who received direct-acting antiviral therapy and achieved sustained virological response
Authors: Kobayashi Natsuko , Iijima Hiroko , Tada Toshifumi , Kumada Takashi , Yoshida Masahiro , Aoki Tomoko , Nishimura Takashi , Nakano Chikage , Takata Ryo , Yoh Kazunori , Ishii Akio , Takashima Tomoyuki , Sakai Yoshiyuki , Aizawa Nobuhiro , Nishikawa Hiroki , Ikeda Naoto , Iwata Yoshinori , Enomoto Hirayuki , Hirota Seiichi , Fujimoto Jiro , Nishiguchi Shuhei 
Published: February 2018

Aim
Whether direct-acting antiviral (DAA) therapy can reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus (HCV) infection remains unclear. We evaluated sequential changes in liver stiffness and steatosis using transient elastography (TE) and the TE-based controlled attenuation parameter (CAP) in patients with HCV who received DAA therapy.

Patients and methods
A total of 57 patients with HCV who received DAA therapy and achieved sustained virological response (SVR) were analyzed. Liver stiffness as evaluated with TE, steatosis as evaluated with CAP, and laboratory data were assessed before treatment (baseline), at end of treatment (EOT), 24 weeks after EOT (SVR24), and 48 weeks after EOT (SVR48).

Results
Alanine aminotransferase levels, corresponding to the presence of necroinflammatory activity, significantly decreased overall, with significant differences between baseline and EOT, EOT, and SVR24, and baseline and SVR48. However, alanine aminotransferase levels showed no significant changes between SVR24 and SVR48. Median (interquartile range) liver stiffness values at baseline, EOT, SVR24, and SVR48 were 8.3 (5.0–14.8), 7.4 (4.6–14.7), 5.3 (4.1–11.8), and 5.4 (4.0–13.4) kPa, respectively (baseline vs. EOT, P=0.044; EOT vs. SVR24, P=0.011; and SVR24 vs. SVR48, P=0.054). In patients with fatty liver (CAP≥236 dB/m, n=14), CAP values at baseline and SVR48 were 253 (245–278) and 229 (209–249) dB/m, respectively (P=0.020).

Conclusion
Liver stiffness at SVR24 might reflect liver fibrosis in the patients who received DAA therapy and achieved SVR. In addition, liver steatosis reduces in the same cohort with fatty liver.
Understanding Functional Communication in Head and Neck Cancer Survivors Using a Mixed Methods Design
Authors: Fletcher Barbara Swore , Schumacher Karen , Cohen Marlene Z. , Kupzyk Kevin , Lydiatt William 
Published: February 2018

Background
Functional communication, defined as everyday communication with family and friends, at work, and in the community, is an important but understudied concept in the head and neck cancer (HNC) survivor population.

Objective
The aim of this study was to better understand functional communication by using a mixed methods approach.

Methods
Head and neck cancer survivors participated in semistructured interviews and completed self-report questionnaires assessing multiple aspects of well-being and health-related quality of life (HRQOL). These qualitative and quantitative data were collected concurrently, analyzed separately, and then integrated.

Results
Survivors' perceptions of functional communication ranged from “Communication is good” to “Communication has changed” to “Communication is difficult.” Using these qualitative results, survivors were categorized into 3 mutually exclusive groups. Clinically meaningful cut points were exceeded on measures of depressive symptoms (18%), state (40%) and trait (54%) anxiety, and pain (18%). Health-related quality of life scores were moderate to high for the sample as a whole. Statistically significant group differences were found only on the HNC-specific measure of HRQOL. A surprising finding was that the lowest mean score on social function was in the “Communication has changed” group. This group perceived changes in speech and voice that bothered them when communicating in social situations, although their speech was clear to a listener.

Conclusion
An underrecognized subpopulation of HNC survivors may exist, whose day-to-day functional communication has changed in ways that impact their relationships and sense of self.

Implications for Practice
Clinical identification of this subpopulation and provision of appropriate interventions are essential to facilitate optimal HRQOL after HNC treatment.
Facial Behavior During an Attachment Interview in Patients With Complicated Grief
Authors: Gander Manuela , Schiestl Cathrin , Dahlbender Rainer , Ronel Joram , Buchheim Anna 
Published: February 2018

Abstract
The present study investigated differences in various aspects of facial behavior among female patients with complicated grief (CG; n = 18) and healthy controls (n = 18) during the assessment of their attachment representation using the Adult Attachment Projective Picture System. All patients were classified with an unresolved attachment status. On a behavioral level, they demonstrated longer gazing behavior away from the interviewer and the picture stimuli, more speech pauses, less smiling toward the interviewer, and more crying, especially in response to stimuli portraying the theme of loss. Focusing on the in-depth analysis of death-related stimuli using the Facial Action Coding System, patients demonstrated less facial affective behavior, less disgust, and less smiling in response to these stimuli compared with the healthy controls. The impaired capacity of patients with CG responding in an affective appropriate manner regarding bereavement might be interpreted as a specific emotion dysregulation when their attachment and mourning system is activated.
Preventive Antibiotics for Poststroke Infection in Patients With Acute Stroke
Authors: Han Xiaonian , Huang Jing , Jia Xiaotao , Peng Lirong , Yan Kangkang , Zan Xin , Ma Li 
Published: February 2018

Aims:
To determine if preventive antibiotics is effective in poststroke infection in patients with acute stroke in comparison with no prophylaxis.

Materials and Methods:
MEDLINE (1950 to January 2017), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2017) and EMBASE (1974 to January 2017) databases were used to search for randomized controlled trials with intervening measures related to the preventive antibiotics in patients with acute stroke. Besides, the reference lists of the retrieved publications were manually searched to explore other relevant studies.

Results:
We included 6 randomized controlled trials involving 4110 stroke patients. The study population, study design, intervening measures, and definition of infection were different. Preventive antibiotics significantly reduced the incidence of algorithm-defined infection in patients with acute stroke from 11.14% (220/1975) to 7.43% (149/2006); odds ratio (OR)=0.41; 95% confidence interval (CI), 0.20-0.87; P=0.02. There was no difference in mortality between 2 groups, the mortality in preventive antibiotics group was 17.03% (347/2037) and control group was 16.10% (328/2037); OR=1.07; 95% CI, 0.90-1.27; P=0.44. And preventive antibiotics did not improve the proportion of good outcome, the proportion of good outcome in preventive antibiotics group was 45.47% (909/1999) and control group was 45.76% (913/1995); OR=0.89; 95% CI, 0.62-1.28; P=0.53. None of the studies reported severe adverse relevant to the study antibiotics.

Conclusions:
Preventive antibiotics significantly reduced the incidence of algorithm-defined infection in patients with acute stroke, but did not decrease the mortality or improve the proportion of good outcome. Future research should aim to identify the group of stroke patients who will benefit most from antibiotic prophylaxis.
Acute Basilar Artery Occlusion
Authors: Chiang Chia-Chun , Dumitrascu Oana M. , Wingerchuk Dean M. , O’Carroll Cumara B. 
Published: February 2018

Background:
Acute basilar artery occlusion (BAO) is a devastating, life-threatening condition that accounts for approximately 1% of all strokes. Currently, there is no consensus on the best treatment strategy for patients with BAO. Whereas endovascular reperfusion therapy is proven to improve outcomes in anterior circulation stroke, its benefit in acute BAO has not been confirmed in randomized controlled trials.

Objective:
To critically assess the current evidence regarding recanalization in acute BAO, and to discuss the outcomes of different treatment strategies in the management of acute BAO.

Materials and Methods:
The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, and content experts in the field of vascular and hospital neurology.

Results:
A recent meta-analysis was selected for critical appraisal to assess the recanalization hypothesis in acute BAO. The authors performed a systematic literature search through August 2013 and pooled in the analysis of 45 studies and 2056 patients. The overall recanalization rate was 75% in this meta-analysis. The authors concluded that recanalization was associated with a 1.5-fold reduction in the risk of death or dependency, and a 2-fold reduction in the risk of mortality. Subgroup analysis comparing different modes of intervention revealed data that favor endovascular intervention over intravenous thrombolysis (IVT). However, the authors were not able to obtain a statistically valid direct comparison of the 2 therapies as their meta-analysis included observational studies. Subgroup analysis on the treatment window revealed that onset-to-treatment time of <12 hours was associated with a higher recanalization rate (81%) and a lower intracranial hemorrhage rate (10%) compared with onset-to-treatment time >12 hours.

Conclusions:
IVT is the standard of care for BAO patients presenting within 4.5 hours of symptom onset, whereas recanalization is associated with better outcomes regardless of how recanalization is achieved. Randomized controlled trials comparing IVT plus endovascular treatment versus IVT in the treatment of acute BAO are needed to provide evidence-based management guidance.