Intra- and inter-individual variation of BIS-index? and Entropy? during controlled sedation with midazolam/remifentanil and dexmedetomidine/remifentanil in healthy volunteers: an interventional study

Introduction

We studied intra-individual and inter-individual variability of two online sedation monitors, BIS^® and Entropy^®, in volunteers under sedation.

Methods

Ten healthy volunteers were sedated in a stepwise manner with doses of either midazolam and remifentanil or dexmedetomidine and remifentanil. One week later the procedure was repeated with the remaining drug combination. The doses were adjusted to achieve three different sedation levels (Ramsay Scores 2, 3 and 4) and controlled by a computer-driven drug-delivery system to maintain stable plasma concentrations of the drugs. At each level of sedation, BIS^® and Entropy^® (response entropy and state entropy) values were recorded for 20 minutes. Baseline recordings were obtained before the sedative medications were administered.

Results

Both inter-individual and intra-individual variability increased as the sedation level deepened. Entropy^® values showed greater variability than BIS^® values, and the variability was greater during dexmedetomidine/remifentanil sedation than during midazolam/remifentanil sedation.

Conclusions

The large intra-individual and inter-individual variability of BIS^® and Entropy^® values in sedated volunteers makes the determination of sedation levels by processed electroencephalogram (EEG) variables impossible. Reports in the literature which draw conclusions based on processed EEG variables obtained from sedated intensive care unit (ICU) patients may be inaccurate due to this variability.

Trial registration

clinicaltrials.gov Nr. {"type":"clinical-trial","attrs":{"text":"NCT00641563","term_id":"NCT00641563"}}NCT00641563.     

Long-term stability of procalcitonin in frozen samples and comparison of Kryptor® and VIDAS® automated immunoassays

ObjectivesTo assess long-term stability of PCT in deep-frozen samples and assess whether Kryptor procalcitonin cutoff ranges can be transferred on the bioMérieux VIDAS system.Design and methodsSamples from two intervention studies (ProRESP and ProCAP) were retested on both systems and compared with Passing–Bablok regression, Bland–Altman difference plot, and analysis of concordance over 4 medically relevant cutoff ranges.ResultsProlonged storage resulted in a significant decline of median procalcitonin values of 11.4% and 13.5% in ProRESP and ProCAP cohorts. Regression analysis showed that both methods correlated well (r = 0.982, n = 304) but with a deviation from the line of identity (y = 1.234x ? 0.018). The Bland–Altman plot indicated an average relative bias of 17.1% (2 SD limits: ? 56.4% to 90.5%). Concordance over all 4 categories was 82.6%, without a significant difference in frequency distribution between methods.ConclusionAn only modest decline of measured PCT levels of around 10% after long-term deep-frozen storage was found. The VIDAS procalcitonin assay showed good correlation and concordance with the established Kryptor method. Both techniques can be used with the same nominal procalcitonin cutoff ranges in clinical routine.     

Nurse outcomes in Magnet® and non-magnet hospitals

The important goals of Magnet hospitals are to create supportive professional nursing care environments. A recently published paper found little difference in work environments between Magnet and non-Magnet hospitals. The aim of this study was to determine whether work environments, staffing, and nurse outcomes differ between Magnet and non-Magnet hospitals. A secondary analysis of data from a 4-state survey of 26,276 nurses in 567 acute care hospitals to evaluate differences in work environments and nurse outcomes in Magnet and non-Magnet hospitals was conducted. Magnet hospitals had significantly better work environments (t = -5.29, P < .001) and more highly educated nurses (t = -2.27, P < .001). Magnet hospital nurses were 18% less likely to be dissatisfied with their job (P < .05) and 13% less likely to report high burnout (P < .05). Magnet hospitals have significantly better work environments than non-Magnet hospitals. The better work environments of Magnet hospitals are associated with lower levels of nurse job dissatisfaction and burnout.     

Feldenkrais® Awareness Through Movement and state anxiety

The ability of the Feldenkrais^® Method to reduce state anxiety was investigated. Specifically, both a single Feldenkrais^® Awareness Through Movement lesson and a 10-week Feldenkrais^®Awareness Through Movement programme were studied. Participants volunteered to take part in one 1-hour class each week for 10 weeks. Individuals who declined to participate in the 10-week programme were given the opportunity to participate in a single 1-hour lesson during week 5. Participants were divided into two groups: new and returning students, based on previous experience with Awareness Through Movement lessons. Participants were administered the state scale of the State-Trait Anxiety Inventory (Spielberger et al. 1983) prior to the beginning of the first lesson (week 1 – T1), immediately before and after the fifth lesson (week 5 – T2 and T3), and after the final lesson (week 10 – T4). Findings indicated that state anxiety scores decreased significantly over a single lesson (T2–T3) for both new (n=13) and returning (n=42) students. In addition, state anxiety scores were significantly lower after the 10-week programme (T4) when compared with baseline scores (T1) for new (n=3) and returning (n=42) students, with new students experiencing a significantly greater reduction than returning students. These findings can be interpreted as further support for the efficacy of the Feldenkrais^® Method in reducing state anxiety.     

TEG® and RapidTEG® are unreliable for detecting warfarin-coagulopathy: a prospective cohort study

Background

Thromboelastography^® (TEG) utilizes kaolin, an intrinsic pathway activator, to assess clotting function. Recent published studies suggest that TEG results are commonly normal in patients receiving warfarin, despite an increased International Normalized Ratio (INR). Because RapidTEG? includes tissue factor, an extrinsic pathway activator, as well as kaolin, we hypothesized that RapidTEG would be more sensitive in detecting a warfarin-effect.

Methods

Included in this prospective study were 22 consecutive patients undergoing elective cardioversion and receiving warfarin. Prior to cardioversion, blood was collected to assess INR, Prothrombin Time, TEG, and RapidTEG.

Results

INR Results: 2.8?±?0.5 (1.6 to 4.2). Prothrombin Time Results: 19.1?±?2.2 (13.9. to 24.3). TEG Results (Reference Range): R-Time: 8.3?±?2.7 (2–8); K-Time: 2.1?±?1.4 (1–3); Angle: 62.5?±?10.3 (55–78); MA: 63.2?±?10.3 (51–69); G: 9.4?±?3.5 (4.6-10.9); R-Time within normal range: 10 (45.5%) with INR 2.9?±?0.3; Correlation coefficients for INR and each of the 5 TEG variables were insignificant (P?>?0.05). RapidTEG Results (Reference Range): ACT: 132?±?58 (86–118); K-Time: 1.2?±?0.5 (1–2); Angle: 75.4?±?5.2 (64–80); MA: 63.4?±?5.1 (52–71); G: 8.9?±?2.0 (5.0-11.6); ACT within normal range: 9 (40.9%) with INR 2.7?±?0.5; Correlation coefficients for INR and each of the 5 RapidTEG variables were insignificant (P?>?0.05).

Conclusions

TEG, using kaolin activation, and RapidTEG, with kaolin and tissue factor activation, were normal in a substantial percent of warfarin patients, despite an increased INR. The false-negative rate for detecting warfarin coagulopathy with either test is unacceptable. The lack of correlation between INR and all TEG and RapidTEG components further indicates that these methodologies are insensitive to warfarin effects. Findings suggest that intrinsic pathway activation may mitigate detection of an extrinsic pathway coagulopathy.     

Efficacy and safety of the remOVE System for OTSC® and FTRD® clip removal: data from a PMCF analysis

Introduction: The remOVE System (Ovesco Endoscopy AG, Tuebingen, Germany) is a medical device for the endoscopic removal of OTSC or FTRD clips (Ovesco Endoscopy AG, Tuebingen, Germany). The aim of this paper is to assess the efficacy and safety of this system.

Material and methods: A total of 74 patients underwent clip extraction. The standard removal procedure comprises fragmenting the clip by applying an electrical direct current pulse at two opposing sides of the clip.

Results: Clip fragmentation was successful in 72 of 74 patients (97.3%). In two cases (2.7%) clip fragmentation was not possible. In nine cases (12.2%) a clip fragment could not be removed and was left in place. Complications occurred in three cases (4.1%): two minor bleedings near the clip removal site (2.7%), and one superficial mucosal tear resulting from clip fragment extraction (1.4%).

Discussion: Based on this study, the use of the remOVE System for OTSC or FTRD clip removal can be considered safe and effective.     

Is the combination of remifentanil and propopfol suitable for transsphenoid resection of the hypophysis?

In a multi-center trial, the feasibility of combining remifentanil (RF) and target-controlled infusion of propofol (P) for patients undergoing transsphenoidal resection of the pituitary gland was tested. After IRB approval, 74 patients (29 male/45 female) were included in the study. The concentration of RF and the target concentration of P were recorded as were heart rate (HR) and mean arterial blood pressure (MAP). For intubation the RF dosage was 0.26 +/- 0.06 microgram.kg-1.min-1 and the target concentration of P was 3.16 +/- 0.63 micrograms.ml-1. After induction, HR and MAP decreased significantly. The painful events of the operation were preparation of the nasal mucous membrane and penetration of the sella turcica. By adjusting the RF dose to 0.31 +/- 0.09 microgram.kg-1. min-1 and the target concentration of P to 3.48 +/- 1.49 micrograms.ml-1, an increase of HR and MAP above initial values was avoided at this time. Hypotension and bardycardia were treated in eight patients (10.8%) with a vasopressor, in four patients (5.4%) with atropine and in four more patients (5.4%) with a combination of these drugs. Two patients (2.7%) needed antihypertensive therapy. The average time interval between the end of P-TCI and spontaneous breathing was 6 +/- 3 min (median 6 min) and till patients opened their eyes 9 +/- 4 min (median 9 min). After 13 +/- 4 min (median 13 min) the patients became orientated. The average doses of analgetics were 19.5 +/- 19.9 mg piritramide and 1.8 +/- 1.0 g metamizol during the first 12 hours postoperatively. Eight patients (10.8%) did not need any analgetics. We suggest that the combination of RF and P as a "fast track concept" can supplement the repertoire of anaesthetic managements used for transsphenoidal resection of the pituitary gland.     

The interaction of Geliperm® and cells in culture

The polyacrylamide agarose wound dressing Geliperm® may exert an effect upon cells and may have potential as a tissue culture support material. These two aspects were examined: (a) the ability of the Geliperm to support growth of attachment-dependent and attachment-independent cells; (b) the effect upon cell growth and division in vitro. HeLa and Hep 2, peripheral blood mononuclear and gingival epithelial cells were innoculated onto hydrated Geliperm previously placed into tissue culture trays. Millipore® filters were seeded with HeLa and Hep 2 cells, overlaid with hydrated Geliperm, placed on rings and immersed in tissue culture medium in petri dishes. The cultures were examined at 24-hour intervals for up to five days by light and scanning electron microscopy; cell counts and viability were also determined. None of the cell types seeded on to the Geliperm remained at 24 hours and growth, continuing beneath the Geliperm was significantly impaired in terms of viability and total count for cells examined. Cells cultured on Millipore filter, beneath gel, were of improved appearance compared to cells not covered by Geliperm; cell counts and viabilities at each time were higher in the presence of the Geliperm. It would appear that Geliperm favourably affected the growth of the cells examined when grown in vitro beneath the Geliperm and on a Millipore filter.     

Relationship Between Performance on the NBME® Comprehensive Clinical Science Self-Assessment and USMLE® Step 2 Clinical Knowledge for USMGs and IMGs

Background: The Comprehensive Clinical Science Self-Assessment (CCSSA) is a web-administered multiple-choice examination that includes content that is typically covered during the core clinical clerkships in medical school. Because the content of CCSSA items resembles the content of the items on Step 2 Clinical Knowledge (CK), CCSSA is intended to be a tool for students to help assess whether they are prepared for Step 2 CK and to become familiar with its content, format, and pacing. Purposes: This study examined the relationship between performance on the National Board of Medical Examiners® CCSSA and performance on the United States Medical Licensing Examination® Step 2 CK for U.S./Canadian (USMGs) and international medical school students/graduates (IMGs). Methods: The study included 9,789 participants who took CCSSA prior to their first Step 2 CK attempt. Linear and logistic regression analyses investigated the relationship between CCSSA performance and performance on Step 2 CK for both USMGs and IMGs. Results: CCSSA scores explained 58% of the variation in first Step 2 CK scores for USMGs and 60% of the variation for IMGs; the relationship was somewhat different for the two groups as indicated by statistically different intercepts and slopes for the regression lines based on each group. Logistic regression results showed that examinees in both groups with low scores on CCSSA were at a higher risk of failing their first Step 2 CK attempt. Conclusions: Results suggest that CCSSA can provide students with a valuable practice tool and a realistic self-assessment of their readiness to take Step 2 CK.     

Evidence-based architectural and space design supports Magnet® empirical outcomes

This department expands nursing leaders' knowledge and competencies in health facility design. The editor of this department, Dr Jaynelle Stichler, asked guest authors, Drs Ecoff and Brown, to describe the process of using the conceptual models of a nursing evidence-based practice model and the Magnet Recognition Program? as a structured process to lead decision making in the planning and design processes and to achieve desired outcomes in hospital design.     

A comparative of Magnet® organizations and accountable care organizations

While Magnet? is a commitment to excellence and thus recognition, the accountable care organization (ACO) focus is to quality and reimbursement. Each can be built on a model of shared characteristics that in the end will prove a source of success for the creation of an organization that is both an ACO and Magnet. In an effort to align strategic initiatives as synergistic processes, not competing priorities, 10 shared characteristics of Magnet organizations and ACOs are presented.     

The COBAS ® TaqMan ® hepatitis C virus assays: automated systems for accurate and sensitive viral load quantification

In recent years, the real time-based TaqMan(?) technology has allowed the development of highly sensitive hepatitis viral load tests with broad dynamic ranges. The increasing applications of these tests in clinical diagnostics have shown the utility of viral load as a predictive marker of treatment response and proven its key role in invidualized antiviral therapies. Future refinement in viral load assays, including higher sensitivity, genotype inclusivity, standardization and automation, will further foster the concept of personalized healthcare in the clinical management of chronic hepatitis C.     

Safety and tolerance of Ester-C® compared with regular ascorbic acid

The goal of this randomized, double-blind crossover clinical trial in 50 healthy volunteers sensitive to acidic foods was to evaluate whether Ester-C calcium ascorbate causes fewer epigastric adverse effects than are produced by regular ascorbic acid (AA). Volunteers were randomly separated into 2 groups of 25. The study comprised an observation period of 9 days (phase 1 medication for 3 consecutive days, washout phase for 3 consecutive days, phase 2 medication for 3 consecutive days). Participants took 1000 mg vitamin C as Ester-C during phase 1 of the study followed by 1000 mg of vitamin C as AA during phase 2, or vice versa. During the course of the study, 3 examinations for the evaluation of epigastric adverse effects were performed (on days 0, 3, and 9). Participants used a diary to record epigastric adverse effects on a daily basis. In total, 28 (56%) of 50 participants reported 88 epigastric adverse effects of mild to moderate intensity. Of these 88 adverse effects, 33 (37.5%) occurred after intake of Ester-C and 55 (62.5%) were noted after intake of AA. The tolerability of Ester-C was rated "very good" by 72% of participants, whereas AA was rated "very good" by only 54%. This difference is statistically significant (P<.05). Investigators concluded that Ester-C compared with AA caused significantly fewer epigastric adverse effects in participants sensitive to acidic foods and that Ester-C is much better tolerated.     

Comparison of the Glidescope® and Pentax AWS® laryngoscopes to the Macintosh laryngoscope for use by Advanced Paramedics in easy and simulated difficult intubation

Background

Accurate forecasting of emergency department (ED) attendances can be a valuable tool for micro and macro level planning.

Methods

Data for analysis was the counts of daily patient attendances at the ED of an acute care regional general hospital from July 2005 to Mar 2008. Patients were stratified into three acuity categories; i.e. P1, P2 and P3, with P1 being the most acute and P3 being the least acute. The autoregressive integrated moving average (ARIMA) method was separately applied to each of the three acuity categories and total patient attendances. Independent variables included in the model were public holiday (yes or no), ambient air quality measured by pollution standard index (PSI), daily ambient average temperature and daily relative humidity. The seasonal components of weekly and yearly periodicities in the time series of daily attendances were also studied. Univariate analysis by t-tests and multivariate time series analysis were carried out in SPSS version 15.

Results

By time series analyses, P1 attendances did not show any weekly or yearly periodicity and was only predicted by ambient air quality of PSI > 50. P2 and total attendances showed weekly periodicities, and were also significantly predicted by public holiday. P3 attendances were significantly correlated with day of the week, month of the year, public holiday, and ambient air quality of PSI > 50. After applying the developed models to validate the forecast, the MAPE of prediction by the models were 16.8%, 6.7%, 8.6% and 4.8% for P1, P2, P3 and total attendances, respectively. The models were able to account for most of the significant autocorrelations present in the data.

Conclusion

Time series analysis has been shown to provide a useful, readily available tool for predicting emergency department workload that can be used to plan staff roster and resource planning.     

Type-specific detection of herpes simplex virus type 1 and type 2 using the cobas® HSV 1 and 2 test on the cobas® 4800 platform

Introduction: HSV-1 and HSV-2 are among the most common causes of sexually transmitted infections (stis) globally. these infections are strongly associated with increased risk of hiv acquisition and rare, but devastating, neonatal disease. available treatment options can reduce HSV transmission and improve quality of life. accurate diagnosis early in disease can improve patient management.

Areas covered: This paper describes the clinical manifestations of HSV infection often used for clinical diagnostic purposes. The paper then describes the evolution of laboratory diagnostic assays. Serology, culture and molecular diagnostics are described since all are currently in use. The features and performance characteristics of the cobas 4800 HSV1 and HSV2 Test (cobas HSV) on the cobas 4800® system (cobas 4800) are described in detail.

Expert commentary: Diagnosis of HSV has historically been unreliable or technically difficult, but the availability of molecular assays such as the cobas HSV test for detection and typing of herpes can improve our ability to correctly manage this disease. Utilization of tools such as the cobas HSV assay may help shorten the time to accurate diagnosis and treatment thus potentially reducing the risk of transmission and the global burden of HSV.     

Ocular distribution, bactericidal activity and settling characteristics of TobraDex® ST ophthalmic suspension compared with TobraDex® ophthalmic suspension

Introduction

TobraDex® ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.1%; Alcon Laboratories Inc, Fort Worth, Tex) is frequently used for inflammatory ocular conditions where a risk of bacterial ocular infection exists. A new formulation, TobraDex® ST ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.05%, Alcon), utilises a novel suspension technology to reduce viscosity and help prevent settling in the container.

Methods

A rabbit model that closely mimics the human eye and a clinical study with cataract patients was used to compare the pharmacokinetics and tissue permeability of TobraDex ST and TobraDex. An in-vitro model was used to assess the bactericidal activity using the rabbit tear concentrations of tobramycin 10 minutes after a single topical dose.

Results

Concentrations of both tobramycin and dexamethasone were greater in the tear film and ocular tissues of rabbits treated with TobraDex ST. There was an 8.3-fold increase in tobramycin concentration in the rabbit tear film 10 minutes after dosing with TobraDex ST compared with TobraDex. Concentrations of tobramycin and dexamethasone in ocular tissues from rabbits exposed to TobraDex ST were up to 12.5-fold greater relative to TobraDex. The in-vitro bactericidal activity (>99.9% kill, 3-log reduction) of TobraDex ST toward tobramycin-resistant and methicillin-resistant Staphylococcus aureus occurred in 90 minutes. TobraDex ST killed Streptococcus pneumoniae 3-log in 5 minutes. TobraDex had no activity toward tobramycin-resistant, methicillin-resistant S. aureus and required approximately 120 minutes for 3-log reduction of S. pneumoniae. In humans, the mean ratio of dexamethasone levels in the aqueous humour at 1 hour was 1.17 in favour of TobraDex ST.

Conclusion

TobraDex ST demonstrated improved suspension formulation characteristics, enhanced pharmacokinetic distribution and improved bactericidal characteristics, and may provide a useful alternative as compared to TobraDex.