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1.  Practices and opinions on nitrous oxide/oxygen sedation from dentists licensed to perform relative analgesia in Brazil 
BMC Oral Health  2012;12:21.
Background
Relative analgesia (RA), defined as the use of inhalation sedation with nitrous oxide and oxygen, is one of the most common pharmacological behavior management techniques used to provide sedation and analgesia for dental patients. This study aimed to assess RA licensed Brazilian dentists’ practices and opinions about nitrous oxide/oxygen sedation in the dental setting.
Methods
A cross sectional national survey was conducted with 281 dentists who were certified to perform RA, using an electronically mailed self-administered questionnaire containing closed questions about their practices and opinions regarding RA. Practice and opinion were individually analyzed by descriptive statistics. Non-parametric tests assessed the relationships between RA practice and independent variables. To test the interplay between practices and opinions, a k-means clusters analysis was used to divide the group for statistical comparisons.
Results
The response rate was 45.2%. Women made up 64.6% of the respondents, the mean age was 39.1 years (SD = 9.8), and the mean time since graduation in dentistry was 16 years (SD = 9.7). Seventy-seven percent of respondents reported the use of RA in clinical practice, most of them ‘sometimes’ (53.5%), and focusing more on adult patients. Patients with certain physical or mental deficiencies were indications associated with RA practice. ‘Equipment acquisition’ (p < 0.001) and ‘living in Southeast and South regions’ (p < 0.02) were also associated with RA practice. The scores for dentists’ opinions ranged from 15 to 41 points (mean 29.2, SD = 5.6), based on nine items scored from 1 to 5. Two clusters representing more favorable (n = 65) and less favorable (n = 55) opinions were established. Dentists who were women (p = 0.04), practiced RA in dental settings (p < 0.01) or practiced it frequently (p < 0.001), had more favorable opinions about RA.
Conclusion
Most of the RA licensed Brazilian dentists interviewed currently use RA. Current practice of RA and frequency of use determined the degree of favorable opinion about this inhalation sedation among this group of respondents.
doi:10.1186/1472-6831-12-21
PMCID: PMC3412732  PMID: 22808942
Relative Analgesia; Nitrous Oxide; Dental Clinics; Cross Sectional Survey
2.  Reduced Leaflet Stress in the Stentless Quadrileaflet Mitral Valve: A Finite Element Model 
PLoS ONE  2013;8(7):e67683.
Background
Failure of bioprosthetics is usually caused by calcification of the leaflets as a consequence of high tensile stresses. The stentless valve resembles native mitral valve anatomy, has a flexible leaflet attachment and a suspension at the papillary muscles, and preserves annuloventricular continuity. In this study, the effects of the stentless valve design on leaflet stress were investigated with a finite element model.
Methods
Finite element models of the stentless quadrileaflet mitral valve were created in the close and open configurations. The geometry of the stented trileaflet mitral valve was also analyzed for comparative purposes. Under the designated pressures, the regional stresses were evaluated, and the distributions of stresses were assessed.
Results
Regardless of whether the valve is in the open or close configuration, the maximum first principal stress was significantly lower in the stentless valve than in the stented valve. For the stentless valves, limited stress concentration was discretely distributed in the papillary flaps under both close and open conditions. In contrast, in the stented valve, increased stress concentration was evident at the central belly under the open condition and at the commissural attachment under close condition. In either configuration, the maximum second principal stress was markedly lower in the stentless valve than in the stented valve.
Conclusions
The stentless valve was associated with a significant reduction in leaflet stress and a more homogeneous stress distribution compared to the stented valve. These findings are consistent with recent reports of the clinical effectiveness of the stentless quadrileaflet mitral valve.
doi:10.1371/journal.pone.0067683
PMCID: PMC3699618  PMID: 23844060
3.  Clinical Trials of Different Concentrations of Oxygen and Nitrous Oxide for Obstetric Analgesia: Report to the Medical Research Council of the Committee on Nitrous Oxide and Oxygen Analgesia in Midwifery* 
British Medical Journal  1970;1(5698):709-713.
Trials have been organized by a Medical Research Council committee to assess the effectiveness and safety for analgesia in labour of oxygen and nitrous oxide mixtures in different proportions. In a preliminary trial concentrations of 50% and 60% v/v nitrous oxide were compared, but, as the replies of 409 mothers revealed little difference between the two, the results of administering either 50% or 70% nitrous oxide to 778 mothers were then compared. The data relating to normal labour, obtained on 501 of the mothers in this main trial, showed that the relief of pain given was much the same. There was a suggestion, however, that the higher concentration of nitrous oxide might be useful in abnormal labour. The proportion of mothers with normal deliveries who lost consciousness, though very small, was significantly higher with 70% nitrous oxide than with the lower concentration. Ninety-two per cent. of mothers found the gas and oxygen machine helpful, and midwives reported complete or good co-operation by 77% of those using it. It is concluded that the 50% oxygen and 50% nitrous oxide mixture can safely be used by unsupervised midwives.
PMCID: PMC1699836  PMID: 5440545
4.  The effects of idazoxan combined with 30% nitrous oxide on the jaw-opening reflex in the rat. 
Anesthesia Progress  1997;44(3):96-100.
In rats, the jaw-opening reflex is elicited by activation of a nociceptive receptor by the electric stimulation of the tooth pulp. This study was undertaken to assess the effects of 30% nitrous oxide and 30% nitrous oxide with idazoxan, an alpha 2-adrenergic antagonist, on this reflex. Each rat received electric stimulation for the jaw-opening reflex at 3, 5, 7, 10, 15, and 20 min after both the start of inhalation and the withdrawal of 100% oxygen or 30% nitrous oxide in oxygen. Idazoxan, 400 micrograms/ kg, was administered intravenously at the start of the inhalation period. Amplitudes significantly decreased during inhalation of nitrous oxide, but they returned gradually to control levels after cessation of nitrous oxide inhalation. In the cases of 100% oxygen, 100% oxygen with idazoxan, and 30% nitrous oxide in oxygen with idazoxan, amplitudes did not change from controls during and after 30% nitrous oxide inhalation. The latency remained unchanged irrespective of the treatment. Since in rats the degree of inhibition by 30% nitrous oxide in oxygen is partially diminished by administration of idazoxan, we conclude that nitrous oxide affects an alpha 2-adrenergic receptor in the central nervous system.
PMCID: PMC2148931  PMID: 9481969
5.  Nitrous oxide analgesia during intra-articular injection for juvenile idiopathic arthritis 
Archives of Disease in Childhood  2002;86(6):416-418.
Aims: To evaluate the efficacy and safety of nitrous oxide–oxygen for children with juvenile idiopathic arthritis (JIA) undergoing intra-articular corticosteroid injection.
Methods: A total of 55 consecutive patients with JIA undergoing intra-articular corticosteroid injection, using self administered nitrous oxide–oxygen for analgesia were studied. Patient, nurse, and parent pain scores were compared using a 0–10 cm visual analogue scale (VAS) immediately after the procedure.
Results: A total of 70 joints were injected in 55 patients (median age 13.54 years). The median pain score for patient, nurse, and parent was 1 (0–10 cm VAS). The mean rank patient score was 2.12, which was greater than the nurse score (1.97), which was greater than the parent score (1.91). These differences were significant. There were no serious adverse events in any patient.
Conclusions: Nitrous oxide–oxygen provides safe and effective analgesia for intra-articular injection in children. In some cases, nurses and parents underestimated pain related to the procedure compared to the child.
doi:10.1136/adc.86.6.416
PMCID: PMC1762988  PMID: 12023171
6.  An in-vitro assessment of the hydraulic characteristics of the mark II Abrams-Lucas mitral valve prosthesis. 
Thorax  1977;32(3):296-302.
As a result of the durability problems associated with the first Abrams-Lucas mitral valve, a redesigned model has recently been introduced into limited clinical trials. The new valve was subjected to in-vitro pulsatile flow studies, and measurements were made of mean diastolic pressure gradient and volume of reflux on closure. Similar measurements were made on other mitral valve prostheses of comparable size. High-speed cinematography was used to analyse the motion of the occluder during the simulated cardiac cycle, and the flow patterns produced by the valve in the model ventricular cavity were observed and photographed. The pressure gradient of the Abrams-Lucas valve was significantly lower than that of the 29 mm Björk-Shiley valve and all other prostheses tested, but its reflux level was higher at 12 ml per stroke. The valve opened and closed smoothly and the flow visualisation study revealed that the valve produced a large vortex or swirl in the model ventricular cavity.
Images
PMCID: PMC470603  PMID: 882943
7.  A study of central opioid receptor involvement in nitrous oxide analgesia in mice. 
Anesthesia Progress  1990;37(4):181-185.
This study was undertaken to assess the sensitivity of nitrous oxide (N2O) analgesia to antagonism by intrathecally (IT) and intracerebroventricularly (ICV) administered antagonists selective for kappa- and mu-opioid receptors. Male ICR mice were pretreated IT or ICV with the kappa antagonist nor-binaltorphimine (nor-BNI), 1 or 50 nmol, respectively, or distilled water (control), then exposed to N2O (50% or 75% in oxygen). Compared with IT control mice, IT nor-BNI-pretreated mice responded with significantly less analgesia. Compared with ICV control mice, ICV nor-BNI-pretreated mice also showed markedly reduced analgesic response. Other mice were pretreated IT or ICV with either the selective and irreversible mu antagonist beta-funaltrexamine (beta-FNA, 5.0 micrograms) or distilled water (control). When exposed to N2O 24 h later, beta-FNA-pretreated and control mice exhibited comparable analgesic responses. These preliminary results suggest that N2O analagesia in mice may involve spinal and supraspinal kappa-opioid receptors but not mu-opioid receptors.
PMCID: PMC2148669  PMID: 1965769
8.  The Measurement of Opening Angle and Orifice Area of a Bileaflet Mechanical Valve Using Multidetector Computed Tomography 
Korean Circulation Journal  2009;39(4):157-162.
Background and Objectives
The aim of this study was to assess mechanical valve function using 64-slice multidetector computed tomography (MDCT).
Subjects and Methods
In 20 patients (mean age, 50±12 years; male-to-female ratio, 10:10), 30 St. Jude bileaflet mechanical valves (15 aortic and 15 mitral valves) were evaluated using MDCT. We selected images vertical and parallel to the mechanical valve. The valve orifice area (OA) and valve length were determined by manual tracing and the opening and closing angles were measured using a protractor. The OA and length of the mechanical valves were compared with the manufacturer's values.
Results
The geometric orifice areas (GOAs) based on the manufacturer's values and the OAs determined by MDCT were 3.4±0.2 cm2 and 3.4±0.3 cm2 for the mitral valves and 2.1±0.3 cm2 and 2.1±0.4 cm2 for the aortic valves, respectively. The correlation coefficients between the OA measures were 0.433 for the mitral valves and 0.874 for the aortic valves (both p<0.001). The lengths based on the manufacturer's values and determined by MDCT were 29.3±1.99 mm and 29.6±1.65 mm for the mitral valves and 21.5±2.1 mm and 20.7±2.3 mm for the aortic valves, respectively. The correlation coefficients between the measures were 0.651 for the mitral valve and 0.846 for the aortic valve (both p<0.001). The opening and closing angles determined by MDCT were 10.9±0.6° and 131.1±3.2° for the mitral valves and 11.1±0.9° and 120.6±1.7° for the aortic valves, respectively.
Conclusion
MDCT is an accurate modality with which to assess the function and morphology of bileaflet mechanical valves.
doi:10.4070/kcj.2009.39.4.157
PMCID: PMC2771814  PMID: 19949605
Valve; Heart; Computed tomography
9.  Efficacy and Safety of Remifentanil as an Alternative Labor Analgesic 
The objective of this review was to evaluate the clinical efficacy and safety of remifentanil in the management of labor pain. Although neuraxial analgesia is the best option during labor, alternative analgesic options are needed for patients with contraindications. Using a systematic literature search, clinical outcomes of remifentanil for labor pain have been summarized. Also, comparisons of remifentanil to other options including meperidine, epidural analgesia, fentanyl, and nitrous oxide are provided. Based on the literature review, remifentanil is associated with high overall maternal satisfaction and favorable side-effect profile. However, due to the low reporting of adverse events, large, randomized controlled trials are needed to evaluate maternal and neonatal safety adequately and determine the optimal dosing needed to provide effective analgesia. While remifentanil is a feasible alternative for patients who cannot or do not want to receive epidural analgesia, administration should be monitored closely for potential adverse effects.
doi:10.4137/CMWH.S8015
PMCID: PMC3941183  PMID: 24665213
labor analgesia; remifentanil; opioids
10.  Hemodynamics and Mechanobiology of Aortic Valve Inflammation and Calcification 
Cardiac valves function in a mechanically complex environment, opening and closing close to a billion times during the average human lifetime, experiencing transvalvular pressures and pulsatile and oscillatory shear stresses, as well as bending and axial stress. Although valves were originally thought to be passive pieces of tissue, recent evidence points to an intimate interplay between the hemodynamic environment and biological response of the valve. Several decades of study have been devoted to understanding these varied mechanical stimuli and how they might induce valve pathology. Here, we review efforts taken in understanding the valvular response to its mechanical milieu and key insights gained from in vitro and ex vivo whole-tissue studies in the mechanobiology of aortic valve remodeling, inflammation, and calcification.
doi:10.4061/2011/263870
PMCID: PMC3133012  PMID: 21760982
11.  The effects of temperature on nitrous oxide and oxygen mixture homogeneity and stability 
BMC Anesthesiology  2010;10:19.
Background
For many long standing practices, the rationale for them is often lost as time passes. This is the situation with respect to the storage and handling of equimolar 50% nitrous oxide and 50% oxygen volume/volume (v/v) mixtures.
Methods
A review was undertaken of existing literature to examine the developmental history of nitrous oxide and oxygen mixtures for anesthesia and analgesia and to ascertain if sufficient bibliographic data was available to support the position that the contents of a cylinder of a 50%/50% volume/volume (v/v) mixture of nitrous oxide and oxygen is in a homogenous single gas phase in a filled cylinder under normal conditions of handling and storage and if justification could be found for the standard instructions given for handling before use.
Results
After ranking and removing duplicates, a total of fifteen articles were identified by the various search strategies and formed the basis of this literature review. Several studies were identified that confirmed that 50%/50% v/v mixture of nitrous oxide and oxygen is in a homogenous single gas phase in a filled cylinder under normal conditions of handling and storage. The effect of temperature on the change of phase of the nitrous oxide in this mixture was further examined by several authors. These studies demonstrated that although it is possible to cause condensation and phase separation by cooling the cylinder, by allowing the cylinder to rewarm to room temperature for at least 48 hours, preferably in a horizontal orientation, and inverting it three times before use, the cylinder consistently delivered the proper proportions of the component gases as a homogenous mixture.
Conclusions
The contents of a cylinder of a 50%/50% volume/volume (v/v) mixture of nitrous oxide and oxygen is in a homogenous single gas phase in a filled cylinder under normal conditions of handling and storage. The standard instructions given for handling before are justified based on previously conducted studies.
doi:10.1186/1471-2253-10-19
PMCID: PMC2967548  PMID: 20950473
12.  Diabetic cardiomyopathy? An echocardiographic study of young diabetics. 
British Medical Journal  1978;1(6110):404-407.
An echocardiographic study was carried out on 23 young diabetics, 19 of whom had retinopathy. Their diastolic function was analysed by comparing the timing and pattern of mitral valve opening with the pattern of left ventricular wall movement. Only six patients had all their values within the normal range. Fourteen patients had abnormalities similar to those seen in patients with cardiomyopathy; the close time relation between mitral valve movement and wall movement was lost and mitral valve opening delayed in eight patients. Three other patients had considerable outward wall movement before mitral valve opening, which is characteristic of ischaemic heart disease. Although these studies provide no definite evidence of a cause, the abnormalities found may reflect a subclinical diabetic cardiomyopathy due to small-vessel disease.
Images
PMCID: PMC1603022  PMID: 624029
13.  Maternal Expectations and Experiences of Labor Analgesia With Nitrous Oxide 
Background
Although there are various methods for painless delivery such as using entonox gas, most of the people are unfamiliar or concerned about it yet.
Objectives
The purpose of this study was to assess maternal expectations and experience of labor analgesia with nitrous oxide.
Patients and Methods
In a clinical trial study, 98 pregnant women in active phase of delivery were studied randomly in two groups (intervention group = 49, control group = 49) after obtaining written consent. Efficacy, experience satisfaction, and also expectation of pregnant women about entonox gas in two groups were compared, likewise in intervention group before and after using entonox gas.
Results
Most of the pregnant women receiving entonox gas had less labor pain (91.8%), and were satisfied with it (98%). The severity of pain in the most of entonox user was moderate level (46.94%), while for the control group it was severe (55.10%) which was significant, 40.82% of the mother in entonox group had a severe pain and 10.20% had a very severe pain, whereas in the control group (55.10%) of the mother had a severe pain and 26.53% of the had very severe pain (P = 0.004). efficacy of labor pain was in moderate level in most cases. 49% of pregnant women receiving gas described their experience as a good and excellent. 80.9% indicated that they will request the mentioned painless method in the future. The amount of suffering from gas side effects was mild in most patients of intervention group (63%). Expectations of the majority of pregnant women in intervention group (before receiving gas) and control group for painless delivery were weak (65.3%, 40.9%). The percentage of positive expectations had increased after receiving entonox gas (P = 0.01). There was a difference between the expectations of intervention group receiving entonox gas and control group (P = 0.001). Positive expectations were more in intervention group than the control group. Most differences of expectations in intervention group before and after receiving the gas were about higher efficacy (P = 0.001), more satisfaction (P = 0.001), fewer complications (P = 0.001), information about gas as painless delivery method (P = 0.02), and also previous experience of intolerable labor pain (P = 0.04).
Conclusions
This study has shown that using entonox gas caused less labor pain, favorable expectations and experiences and also more maternal satisfaction.
doi:10.5812/ircmj.3470
PMCID: PMC3587869  PMID: 23483128
Labor Pain; Entonox; Pregnancy
14.  A Novel Implantable Glaucoma Valve Using Ferrofluid 
PLoS ONE  2013;8(6):e67404.
Purpose
To present a novel design of an implantable glaucoma valve based on ferrofluidic nanoparticles and to compare it with a well-established FDA approved valve.
Setting
Massachusetts Eye & Ear Infirmary, Boston, USA.
Methods
A glaucoma valve was designed using soft lithography techniques utilizing a water-immiscible magnetic fluid (ferrofluid) as a pressure-sensitive barrier to aqueous flow. Two rare earth micro magnets were used to calibrate the opening and closing pressure. In-vitro flow measurements were performed to characterize the valve and to compare it to Ahmed™ glaucoma valve. The reliability and predictability of the new valve was verified by pressure/flow measurements over a period of three months and X-ray diffraction (XRD) analysis over a period of eight weeks. In vivo assessment was performed in three rabbits.
Results
In the in vitro experiments, the opening and closing pressures of the valve were 10 and 7 mmHg, respectively. The measured flow/pressure response was linearly proportional and reproducible over a period of three months (1.8 µl/min at 12 mmHg; 4.3 µl/min at 16 mmHg; 7.6 µl/min at 21 mmHg). X-ray diffraction analysis did not show oxidization of the ferrofluid when exposed to water or air. Preliminary in vivo results suggest that the valve is biocompatible and can control the intraocular pressure in rabbits.
Conclusions
The proposed valve utilizes ferrofluid as passive, tunable constriction element to provide highly predictable opening and closing pressures while maintaining ocular tone. The ferrofluid maintained its magnetic properties in the aqueous environment and provided linear flow to pressure response. Our in-vitro tests showed reliable and reproducible results over a study period of three months. Preliminary in-vivo results were very promising and currently more thorough investigation of this device is underway.
doi:10.1371/journal.pone.0067404
PMCID: PMC3696055  PMID: 23840691
15.  Modification of nitrous oxide analgesia by benzodiazepine receptors. 
Anesthesia Progress  1989;36(1):5-8.
The interaction with nitrous oxide analgesia of drugs that act at the benzodiazepine receptor was evaluated in the rat tail flick model. Nitrous oxide produced dose-related analgesia, which was potentiated by diazepam, a benzodiazepine agonist, antagonized by noreleagnine, a benzodiazepine inverse agonist. Pretreatment with the benzodiazepine antagonist Ro 15-1788 blocked the effects of both diazepam and noreleagnine on nitrous oxide analgesia. Subanesthetic doses of sodium pentobarbital and chloral hydrate produced nonsignificant trends to reduce the analgesic action of nitrous oxide. These data provide evidence for the presence of specific benzodiazepine receptors capable of modulating the analgesic effect of nitrous oxide.
PMCID: PMC2148651  PMID: 2604055
16.  Mathematical multi-scale model of the cardiovascular system including mitral valve dynamics. Application to ischemic mitral insufficiency 
Background
Valve dysfunction is a common cardiovascular pathology. Despite significant clinical research, there is little formal study of how valve dysfunction affects overall circulatory dynamics. Validated models would offer the ability to better understand these dynamics and thus optimize diagnosis, as well as surgical and other interventions.
Methods
A cardiovascular and circulatory system (CVS) model has already been validated in silico, and in several animal model studies. It accounts for valve dynamics using Heaviside functions to simulate a physiologically accurate "open on pressure, close on flow" law. However, it does not consider real-time valve opening dynamics and therefore does not fully capture valve dysfunction, particularly where the dysfunction involves partial closure. This research describes an updated version of this previous closed-loop CVS model that includes the progressive opening of the mitral valve, and is defined over the full cardiac cycle.
Results
Simulations of the cardiovascular system with healthy mitral valve are performed, and, the global hemodynamic behaviour is studied compared with previously validated results. The error between resulting pressure-volume (PV) loops of already validated CVS model and the new CVS model that includes the progressive opening of the mitral valve is assessed and remains within typical measurement error and variability. Simulations of ischemic mitral insufficiency are also performed. Pressure-Volume loops, transmitral flow evolution and mitral valve aperture area evolution follow reported measurements in shape, amplitude and trends.
Conclusions
The resulting cardiovascular system model including mitral valve dynamics provides a foundation for clinical validation and the study of valvular dysfunction in vivo. The overall models and results could readily be generalised to other cardiac valves.
doi:10.1186/1475-925X-10-86
PMCID: PMC3271239  PMID: 21942971
17.  Study of Mitral Valve in Human Cadaveric Hearts 
Objectives:
The mitral valve is a complex structure that is altered by disease states. The classical image of the mitral valve is a bicuspid valve with two leaflets and two papillary muscles. The reason for the present study is to study the morphology and morphometry of the mitral valve.
Materials and Methods:
This study was carried out on 116 human cadaveric hearts. Hearts were opened along the left border through the atrioventricular valve. The diameter and circumference of the annulus was measured and the number of valve leaflets was observed.
Results:
The mean annular diameter was 2.22 cm. The mean circumference of mitral valve annulus was 9.12 cm. The standard description of the mitral valve is bicuspid. In the present study, we found the number of cusps to be variable, from monocuspid to hexacuspid and classified them accordingly.
Conclusions:
The mitral valve is not always a bicuspid valve. The number of cusps varies greatly. An increase in the number of the cusp and their improper approximation most likely causes various valvular disorders.
doi:10.4103/1995-705X.105729
PMCID: PMC3573357  PMID: 23439693
Atrioventricular valve; leaflets/cusps; variation
18.  Strain improvement of Aspergillus niger for the enhanced production of asperenone 
Indian Journal of Microbiology  2008;48(2):274-278.
The enhancement of production of asperenone (Fig. 1), an inhibitor of lipoxygenase and human platelet aggregation from Aspergillus niger CFTRI 1105, was achieved by UV and nitrous acid mutagenesis. Nitrous acid mutants exhibited increased inhibitor production when compared with UV irradiated mutants. I N 41 a first-generation nitrous acid mutant produced 5.1 fold increased asperenone over parent strain. Mutant II N 31 obtained by second-generation nitrous acid treatment produced 60.3 mg asperenone/g biomass, which was 131 fold increase when compared to first generated mutant I N 41 and 670 fold increase over the parent strain. This mutant was stable for several generations on production medium.
doi:10.1007/s12088-008-0026-1
PMCID: PMC3450179  PMID: 23100720
Asperenone; Aspergillus niger; Mutagenesis; Nitrous acid; UV irradiation
19.  Kidney Function after Methoxyflurane Analgesia during Labour 
British Medical Journal  1972;1(5792):81-83.
In a study of the effects of methoxyflurane on renal function, the urinary and blood urea concentrations, the urinary and plasma osmolalities, and the packed cell volume were studied in each of 50 mothers before and after delivery. Methoxyflurane 0·35% was used as an analgesic in 25 patients and the other 25 had 50% nitrous oxide and 50% oxygen (Entonox). There was no evidence of renal dysfunction in either group, nor were there any significant differences between the groups. In a further 200 mothers, of whom 100 had methoxyflurane and 100 had nitrous oxide analgesia, the urinary and blood urea concentrations were measured on the morning of discharge from hospital. There were no significant differences between the groups. These results suggest that methoxyflurane is not nephrotoxic when used as a self-administered analgesic.
PMCID: PMC1789263  PMID: 5007074
20.  PAin SoluTions In the Emergency Setting (PASTIES); a protocol for two open-label randomised trials of patient-controlled analgesia (PCA) versus routine care in the emergency department 
BMJ Open  2013;3(2):e002577.
Introduction
Pain is the commonest reason that patients present to an emergency department (ED), but it is often not treated effectively. Patient controlled analgesia (PCA) is used in other hospital settings but there is little evidence to support its use in emergency patients. We describe two randomised trials aiming to compare PCA to nurse titrated analgesia (routine care) in adult patients who present to the ED requiring intravenous opioid analgesia for the treatment of moderate to severe pain and are subsequently admitted to hospital.
Methods and analysis
Two prospective multi-centre open-label randomised trials of PCA versus routine care in emergency department patients who require intravenous opioid analgesia followed by admission to hospital; one trial involving patients with traumatic musculoskeletal injuries and the second involving patients with non-traumatic abdominal pain. In each trial, 200 participants will be randomised to receive either routine care or PCA, and followed for the first 12 h of their hospital stay. The primary outcome measure is hourly pain score recorded by the participant using a visual analogue scale (VAS) over the 12 h study period, with the primary statistical analyses based on the area under the curve of these pain scores. Secondary outcomes include total opioid use, side effects, time spent asleep, patient satisfaction, length of hospital stay and incremental cost effectiveness ratio.
Ethics and dissemination
The study is approved by the South Central—Southampton A Research Ethics Committee (REC reference 11/SC/0151). Data collection will be completed by August 2013, with statistical analyses starting after all final data queries are resolved. Dissemination plans include presentations at local, national and international scientific meetings held by relevant Colleges and societies. Publications should be ready for submission during 2014. A lay summary of the results will be available to study participants on request, and disseminated via a publically accessible website.
Registration details
The study is registered with the European Clinical Trials Database (EudraCT Number: 2011-000194-31) and is on the ISCRTN register (ISRCTN25343280).
doi:10.1136/bmjopen-2013-002577
PMCID: PMC3586149  PMID: 23418302
Accident & Emergency Medicine; Health Economics; Pain Management; Trauma Management
21.  An extended paIn relief trial utilizing the infiltration of a long-acting Multivesicular liPosome foRmulation Of bupiVacaine, EXPAREL (IMPROVE): a Phase IV health economic trial in adult patients undergoing ileostomy reversal 
Journal of Pain Research  2013;6:549-555.
Background
Opioid analgesics are effective for postsurgical pain but are associated with opioid-related adverse events, creating a significant clinical and economic burden. Gastrointestinal surgery patients are at high risk for opioid-related adverse events. We conducted a study to assess the impact of an opioid-sparing multimodal analgesia regimen with liposome bupivacaine, compared with the standard of care (intravenous [IV] opioid-based, patient-controlled analgesia [PCA]) on postsurgical opioid use and health economic outcomes in patients undergoing ileostomy reversal.
Methods
In this open-label, multicenter study, sequential cohorts of patients undergoing ileostomy reversal received IV opioid PCA (first cohort); or multimodal analgesia including a single intraoperative administration of liposome bupivacaine (second cohort). Rescue analgesia was available to all patients. Primary outcome measures were postsurgical opioid use, hospital length of stay, and hospitalization costs. Incidence of opioid-related adverse events was also assessed.
Results
Twenty-seven patients were enrolled, underwent the planned surgery, and did not meet any intraoperative exclusion criteria; 16 received liposome bupivacaine-based multimodal analgesia and eleven received the standard IV opioid PCA regimen. The multimodal regimen was associated with significant reductions in opioid use compared with the IV opioid PCA regimen (mean, 20 mg versus 112 mg; median, 6 mg versus 48 mg, respectively; P < 0.01), postsurgical length of stay (median, 3.0 days versus 5.1 days, respectively; P < 0.001), and hospitalization costs (geometric mean, $6482 versus $9282, respectively; P = 0.01).
Conclusion
A liposome bupivacaine-based multimodal analgesic regimen resulted in statistically significant and clinically meaningful reductions in opioid consumption, shorter length of stay, and lower inpatient costs than an IV opioid-based analgesic regimen.
doi:10.2147/JPR.S46467
PMCID: PMC3720574  PMID: 23901290
surgery; ileostomy; multimodal analgesia; opioid-related adverse events; hospitalization cost; length of stay
22.  Biomechanical characterization of aortic valve tissue in humans and common animal models 
Journal of biomedical materials research. Part A  2012;100(6):10.1002/jbm.a.34099.
Aortic valve disease develops in an escalating fashion in elderly patients. Current treatments including total valve replacement and valve repair techniques are still suboptimal. A thorough understanding of the animal and human valve tissue properties, particularly their differences, is crucial for the establishment of preclinical animal models and strategies for evaluating new valve treatment techniques, such as transcatheter valve intervention and tissue engineered valves. The goal of this study was to characterize and compare the biomechanical properties and histological structure of healthy ovine, porcine, and human aortic valve leaflets. The biaxial mechanical properties of the aortic valve leaflets of 10 ovine (~1 year), 10 porcine (6–9 months), and 10 aged human (80.6 ± 8.34) hearts were quantified. Tissue microstructure was analyzed via histological techniques. Aged human aortic valve leaflets were significantly less compliant than both ovine and porcine leaflets, with the ovine leaflets being the most compliant. Histological analysis revealed structural differences between the species: the human and porcine leaflets contained more collagen and elastin than the ovine leaflets. Significant mechanical and structural differences in the aortic valve tissues of 6- to 9-month-old porcine models and 1-year-old ovine models with respect to those of aged humans, suggest that these animal models may not be representative of the typical patient undergoing aortic valve replacement.
doi:10.1002/jbm.a.34099
PMCID: PMC3882754  PMID: 22447518
aortic valve; mechanical properties; animal trials; transcatheter aortic valve
23.  Comparison of outcome of low-risk labour in an isolated general practice maternity unit and specialist maternity hospital 
The outcome of labour of 185 low-risk pregnancies at an isolated general practitioner maternity unit was compared with that for 185 comparable low-risk pregnancies at a specialist maternity hospital. No difference was found in mode of delivery or in the proportion of women requiring no analgesia, although significantly more women in the general practice group received analgesia beyond nitrous oxide. There was a significantly higher level of intervention in labour in the maternity hospital group in the form of fetal monitoring and augmentation of labour. The duration of first stage of labour was longer and meconium staining less frequent in the general practice group. Fourteen (7.6%) of the general practice group were transferred in labour to the specialist unit.
The results suggest that where considerations for selection of low-risk pregnancy permit, the general practice maternity unit can provide a distinctive style of intrapartum care with minimum intervention.
PMCID: PMC1711124  PMID: 3505637
24.  Echocardiographic abnormalities of tricuspid valve motion in pulmonary embolism. 
British Heart Journal  1982;47(5):454-460.
Echocardiographic findings in five patients with pulmonary embolism were studied. Tricuspid echocardiograms showed abnormalities in valve motion, that is a monophasic triangular wave during diastole in all the patients as well as an increased dimension of the right ventricle. An "a' dip of the pulmonary valve echocardiogram was also recognised in all five. Later tricuspid echocardiograms regained the normal M-shaped configuration. The monophasic triangular pattern of the tricuspid valve during diastole may be related to the shorter duration of tricuspid valve opening compared with that of the mitral valve. Tachycardia cannot explain this difference between tricuspid and mitral valve motion, which seems to be caused by a prolonged isovolumic relaxation time of the right ventricle resulting in a delayed opening of the tricuspid valve. These results were obtained by comparing these data with those of control subjects and patients with chronic right ventricular overloading resulting from atrial septal defect.
Images
PMCID: PMC481162  PMID: 7073906
25.  Remifentanil patient controlled analgesia versus epidural analgesia in labour. A multicentre randomized controlled trial 
Background
Pain relief during labour is a topic of major interest in the Netherlands. Epidural analgesia is considered to be the most effective method of pain relief and recommended as first choice. However its uptake by pregnant women is limited compared to other western countries, partly as a result of non-availability due to logistic problems. Remifentanil, a synthetic opioid, is very suitable for patient controlled analgesia. Recent studies show that epidural analgesia is superior to remifentanil patient controlled analgesia in terms of pain intensity score; however there was no difference in satisfaction with pain relief between both treatments.
Methods/design
The proposed study is a multicentre randomized controlled study that assesses the cost-effectiveness of remifentanil patient controlled analgesia compared to epidural analgesia. We hypothesize that remifentanil patient controlled analgesia is as effective in improving pain appreciation scores as epidural analgesia, with lower costs and easier achievement of 24 hours availability of pain relief for women in labour and efficient pain relief for those with a contraindication for epidural analgesia.
Eligible women will be informed about the study and randomized before active labour has started. Women will be randomly allocated to a strategy based on epidural analgesia or on remifentanil patient controlled analgesia when they request pain relief during labour. Primary outcome is the pain appreciation score, i.e. satisfaction with pain relief.
Secondary outcome parameters are costs, patient satisfaction, pain scores (pain-intensity), mode of delivery and maternal and neonatal side effects.
The economic analysis will be performed from a short-term healthcare perspective. For both strategies the cost of perinatal care for mother and child, starting at the onset of labour and ending ten days after delivery, will be registered and compared.
Discussion
This study, considering cost effectiveness of remifentanil as first choice analgesia versus epidural analgesia, could strongly improve the care for 180.000 women, giving birth in the Netherlands yearly by giving them access to pain relief during labour, 24 hours a day.
Trial registration number
Dutch Trial Register NTR2551, http://www.trialregister.nl
doi:10.1186/1471-2393-12-63
PMCID: PMC3464937  PMID: 22748068
Analgesia; Labour; Remifentanil; Patient controlled analgesia; Epidural

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