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Analogue circuits are an increasingly critical component in embedded system designs. Traditionally, simulation is used for verification, but owing to the infinite state space of analogue components, the 100% correctness of a design cannot be guaranteed. Formal methods, based around applying mathematical expressions and reasoning to prove correctness, have been developed to increase the verification confidence level. This study introduces and demonstrates a methodology for formally verifying safety properties of analogue circuits. In the proposed approach, system equations are automatically extracted from a SPICE netlist by means of energy-conservative bond graph models. Verification based on abstract model checking and constraint solving is then applied on the extracted equation models. The authors methodology avoids an exhaustive and time demanding simulation that is normally encountered during analogue circuit verification. To this end, the authors have used a set of tools to implement the proposed verification flow and applied it on tunnel diode, Chua and Colpitts oscillators as case studies. [ABSTRACT FROM AUTHOR]

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Presents several correspondence on medicine in Great Britain. Increase of death from deliberate inhalation of fuel gases and pressurized aerosols; Function of the end tidal carbon dioxide; Findings on dietary intake and plasma lipid levels.

Background: Amino-acid based medical foods have shown promise in alleviating symptoms of drug induced gastrointestinal side effects; particularly, diarrhea-predominant symptoms. Irritable bowel syndrome (IBS) is a gastrointestinal disorder that affects up to 9% of people globally, with diarrhea predominant IBS (IBS-D) being the most prevalent subtype. Further trials are needed to explore potential added benefits when integrated into standard care for IBS-D., Aim: To assess the effectiveness of an amino acid-based medical food as an adjunct to standard of care for adults with IBS-D., Methods: This is a pragmatic, real world, open label, single arm study comparing a 2-week baseline assessment to a 2-week intervention period. One hundred adults, aged 18 to 65 years, with IBS-D, according to Rome IV criteria, were enrolled after completing a 2-week baseline assessment period and received a 2-week supply of an amino acid based medical food which was consumed at home twice daily on top of their standard of care. The primary outcome was an assessment of tolerability after 2-weeks of consumption, while secondary outcomes included changes in stool consistency (Bristol Stool Form Scale), severity of abdominal pain & discomfort, symptoms of urgency, Global Improvement Survey (GIS), and the IBS severity scoring system (IBS-SSS)., Results: The test product was well-tolerated as each participant successfully completed the full 14-day trial, and there were no instances of dropouts or discontinuation of the study product reported. Forty percent of participants achieved a 50% or more reduction in the number of days with type 6-7 bowel movements (IBS-D stool consistency responders). Fifty-three percent of participants achieved a clinically meaningful reduction of 30% in mean weekly pain scores, and 55% experienced the same for mean weekly discomfort scores (IBS-D pain and discomfort responders). Participants experienced a mean -109.4 (95% confidence interval: -130.1, -88.8) point reduction on the IBS-SSS and 52% experienced a minimally clinically important difference of > 95 points. An IBS-SSS category shift from severe to moderate or mild occurred in 69% of participants. For functional symptoms, 76% of participants reported symptom relief on the GIS., Conclusion: The amino acid-based medical food was well-tolerated, when added to the standard of care, and demonstrated improvements in both overall IBS symptom severity and IBS-D symptoms within just 2 wk., Competing Interests: Conflict-of-interest statement: All authors are employees of Entrinsic Bioscience LLC (EBS) and EBS was the research sponsor. Patent 174821-011205/PCT (PCT/US11/53265) is issued to EBS Holdings, and patent 174821-012001/PCT (PCT/US13/25294) is issued to EBS Holding., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background and Objectives: A single injection lumbar plexus block for acute pain management after hip surgery is usually limited to the immediate postoperative period. We conducted a randomized controlled trial to determine the effect of a continuous lumbar plexus block on perioperative opioid requirements and pain intensity., Methods: Adult patients undergoing elective hip arthroplasty under general anesthesia were randomized to continuous lumbar plexus block combined with patient-controlled analgesia (PCA) or PCA only for postoperative pain. Patients allocated to the lumbar plexus block had the catheter placed before surgery. Patients were followed for 36 hours. Perioperative opioid requirement was the primary outcome; secondary outcomes included assessment of pain intensity, patient and surgeon satisfaction with the analgesic technique, and occurrence of nausea and vomiting., Results: Seventeen patients were randomized to each treatment group. Compared with patients in the PCA group, patients in the continuous lumbar plexus block group required less morphine (12 mg) (95% CI, -12.9 to -3.9), had on average less pain (-2.1 units on a 0 to 10 scale) (95% CI, -3.8 to -1.1), were more satisfied with their analgesic technique, and experienced less nausea and vomiting. One patient in the continuous lumbar plexus block developed a delayed paresis and 1 patient in the PCA group developed respiratory depression., Conclusions: Continuous lumbar plexus block combined with PCA is superior to PCA alone for postoperative pain management following hip replacement. It reduces opioid requirements, opioid related side effects, and enhances patient satisfaction. However, additional research is required to determine its safety in light of the neurologic injury observed.

Unlabelled: The bispectral index (BIS) has been developed in adults and correlates well with clinical hypnotic effects of anesthetics. We investigated whether BIS reflects clinical markers of hypnosis and demonstrates agent dose-responsiveness in infants and children. In an observational arm of this study, BIS values in children undergoing general anesthesia were observed and compared with similar data collected previously in a study of adults. In a second arm of the study, a range of steady-state end-tidal concentrations of sevoflurane was administered and corresponding BIS documented. Data were examined for differences between infants (0-2 yr) and children (2-12 yr). No difference was seen in BIS values in children before induction, during maintenance, and on emergence compared with adult values. There was no difference in BIS between infants and children at similar clinical levels of anesthesia. In children and infants, BIS was inversely proportional to the end-tidal concentration of sevoflurane. The sevoflurane concentration for a BIS = 50 (95% confidence interval) was significantly different: 1. 55% (1.40-1.70) for infants versus 1.25% (1.12-1.37) for children. Although validation with specific behavioral end points was not possible, BIS correlated with clinical indicators of anesthesia in children as it did in adults: as depth of anesthesia increased, BIS diminished. BIS correlated with sevoflurane concentration in infants and children. The concentration-response difference between infants and children was consistent with data showing that minimum alveolar concentration is higher in children less than 1 yr of age., Implications: The use of bispectral index (BIS) during general anesthesia improves the titration of anesthetics in adults. The data from this study suggest that the same equipment and method of electroencephalogram analysis may be applied to infants and children.

Background: This multicenter, assessor-blinded, randomized study was done to confirm and extend a pilot study showing that intramuscular rocuronium can provide adequate tracheal intubating conditions in infants (2.5 min) and children (3 min) during halothane anesthesia., Methods: Thirty-eight infants (age range, 3-12 months) and 38 children (age range, 1 to 5 yr) classified as American Society of Anesthesiologists physical status 1 and 2 were evaluated at four investigational sites. Anesthesia was maintained with halothane and oxygen (1% end-tidal concentration if <2.5 yr; 0.80% end-tidal concentration if >2.5 yr) for 5 min. One half of the patients received 0.45 mg/kg intravenous rocuronium. The others received 1 mg/kg (infants) or 1.8 mg/kg (children) of intramuscular rocuronium into the deltoid muscle. Intubating conditions and mechanomyographic responses to ulnar nerve stimulation were assessed., Results: The conditions for tracheal intubation at 2.5 and 3 min in infants and children, respectively, were inadequate in a high percentage of patients in the intramuscular group. Nine of 16 infants and 10 of 17 children had adequate or better intubating conditions at 3.5 and 4 min, respectively, after intramuscular rocuronium. Better-than-adequate intubating conditions were achieved in 14 of 15 infants and 16 of 17 children given intravenous rocuronium. Intramuscular rocuronium provided > or =98% blockade in 7.4+/-3.4 min (in infants) and 8+/-6.3 min (in children). Twenty-five percent recovery occurred in 79+/-26 min (in infants) and in 86+/-22 min (in children)., Conclusions: Intramuscular rocuronium, in the doses and conditions tested, does not consistently provide satisfactory tracheal intubating conditions in infants and children and is not an adequate alternative to intramuscular succinylcholine when rapid intubation is necessary.

Background: Comparisons of the intubation conditions with mivacurium and rocuronium from previous reports are confounded by the use of varied induction regimens. The authors compared intubation conditions of mivacurium, rocuronium, and a placebo at 90 s and their recovery profiles during anesthesia with nitrous oxide, oxygen, and propofol., Methods: After induction with midazolam, fentanyl, and propofol in a randomized blinded study, 100 patients received one of the following treatments: 0.25 mg/kg mivacurium in divided doses (0.15 mg/kg followed by 0.1 mg/kg 30 s later); 0.45, 0.6, 0.9, or 1.2 mg/kg rocuronium; or placebo. Evoked thumb adduction was measured throughout. Intubation was attempted 90 s after the initial dose of mivacurium and other treatment doses by a "blinded" physician. Intubating conditions were graded as excellent, good, poor, or not possible. Spontaneous recovery was studied until a 25% initial twitch height was reached. Mean arterial blood pressure and heart rate changes between groups were determined before induction through 6 min after administration of the study drugs., Results: There were no important changes or intergroup differences in mean arterial blood pressure and heart rate. Intubation conditions were good or excellent for both mivacurium and rocuronium at the 0.9 mg/kg dose (93%) and at the 1.2 mg/kg dose (100%). Rocuronium at the 0.6 mg/kg dose was excellent in 27% of patients, whereas rocuronium at the 0.45 mg/kg dose had the least number of excellent conditions and the most poor or not possible assessments. Patients given placebo could not be intubated. Times to maximum blockade for 0.9 and 1.2 mg/kg rocuronium were the shortest. The times to 25% recovery for 0.6 mg/kg rocuronium (mean +/- SD = 27 +/- 8.6 min), 0.9 mg/kg (43.1 +/- 10.8), and 1.2 mg/kg (62.3 +/- 17.4 min) were significantly longer than were those for mivacurium (17.4 +/- 6.2 min)., Conclusions: Mivacurium in a 0.25 mg/kg divided dose and rocuronium at 0.9 mg/kg and 1.2 mg/kg provide good or excellent intubation conditions at 90 s in most patients. Rocuronium was faster in onset at the higher doses (0.9 and 1.2 mg/kg) but had more prolonged recovery times to 25% single twitch height.

Background: The bispectral index (BIS) measures changes in the interfrequency coupling of the electroencephalogram (EEG). The purposes of this study were (1) to determine whether BIS correlates with responses to command during sedation and hypnosis induced by propofol or propofol and nitrous oxide, and (2) to compare BIS to targeted and measured concentrations of propofol in predicting participants' responses to commands., Methods: Twenty volunteers (15 men and 5 women, aged 22-50 yr) were given propofol by computer-controlled infusion, and EEG was recorded for off-line analysis of BIS. Responses to randomly ordered verbal commands or voice plus touch were measured with two categorical scales (CS1 and CS2, respectively). All subjects received a propofol infusion targeted to achieve effect site concentrations of 1, 2, 4, 2, 1, and 0 microg/ml. Ten participants had repeated infusion, whereas 10 others breathed 30% nitrous oxide and oxygen and received a propofol infusion targeted for 0.5, 1, 2, 4, 2, 1, 0.5, and 0 microg/ml. Five minutes after each targeted concentration had been reached, CS1, CS2, and arterial propofol concentration were determined. The area under the receiver operating characteristic curve was used to compare the accuracy of (1) BIS, (2) targeted propofol concentration, (3) measured concentration, and (4) treatment history as predictors of response., Results: Bispectral index was a strong predictor of CS1 and CS2 (P < 0.0001) and significantly more accurate than targeted or measured propofol concentrations (P < 0.0003 and P < 0.003, respectively). It also provided additional predictive power when combined with treatment history (P < 0.02). Nitrous oxide slightly decreased the probability of response at a given value of BIS (P < 0.05), but accuracy was unaffected., Conclusions: Bispectral index accurately predicts response to verbal commands during sedation and hypnosis with propofol or propofol plus nitrous oxide. Accuracy is maintained in situations likely to be encountered during clinical use: when propofol concentrations are increasing or decreasing and when repeated measurements are made over time.

Purpose: This study was designed to evaluate pharmacodynamically and pharmacokinetically if the cis-cis isomer of mivacurium contributed to neuromuscular block during prolonged infusions lasting more than four hours in young adult and elderly (> 60 yr) patients., Methods: The mechanomyogramic neuromuscular response of the adductor pollicis was recorded in 32 adults 18-59 yr. and 19 elderly (> 60 yr.) patients during N2O:O2:opioid anaesthesia. The mivacurium infusion rate was adjusted to maintain single twitch depression at 95 +/- 4% of control. Blood samples were taken every 30 min to determine the plasma concentration of cis-cis isomer of mivacurium. At the end of the surgical procedure, patients were allowed to recover spontaneously to at least 25% of control twitch response., Results: The mean mivacurium infusion requirement to maintain 97 +/- 1 (mean +/- SD)% depression of the twitch response was 6.0 +/- 0.4 micrograms.kg-1.min-1 in young adults, and 4.3 +/- 0.3 micrograms.kg-1.min-1 in elderly patients (P < 0.001). The infusion requirement in patients with low plasma cholinesterase activity was the lowest 2.4 +/- 1.2 micrograms.kg-1.min-1. Plasma cis-cis isomer concentrations reached peak levels within one-two hours and remained relatively constant throughout the duration of infusion even in patients with low cholinesterase activity. There was no relationship between duration of infusion, plasma concentrations of cis-cis isomer and the early recovery indices of mivacurium (up to 25%). Neuromuscular transmission recovered adequately with or without antagonism in all patients., Conclusion: When the mivacurium infusion was titrated to maintain 95 +/- 4% twitch depression, the plasma concentration of the cis-cis isomer did not increase during prolonged infusions (four hours) and neuromuscular transmission recovers satisfactorily.

Background: The rationale for choosing certain anesthetic options in children when they are being treated with pulsed lasers is unclear., Objective: Our purpose was to assess the safety and side effects of general anesthesia in the treatment of vascular lesions and to compare this to treatment outcome in the office setting., Methods: We carried out a retrospective chart review of 179 patients, with an age range of 5 weeks to 18 years, who received laser treatment and underwent different anesthetic modalities. The age of the patient and the size, location, and severity of the vascular lesion were also noted., Results: The factors determining the type of anesthesia to use included (1) the age of the patient, (2) the number of treatments, and (3) the size and location of the lesion. Our data showed minimal risk and sequelae of general anesthesia in the treatment of vascular lesions in children., Conclusion: Proper selection of anesthesia is a key factor in dealing with children. Office surgery can be performed safely when small lesions are treated. The use of general anesthesia in the treatment of port-wine stains in children does not appear to be accompanied by increased risk.

Study Objectives: To determine the neuromuscular, cardiovascular, and histamine releasing properties of doxacurium and pipecuronium at three times effective ED95 doses (3XFD95)., Design: Prospective, randomized clinical trial of adult patients., Setting: University teaching hospital., Patients: 20 ASA status I and II adult patients., Interventions: Subjects were anesthetized with thiopental sodium, fentanyl, and nitrous oxide and oxygen (N2O:O2). Plasma samples were taken preoperatively, after thiopental, and 2 and 5 minutes after doxacurium 75 micrograms/kg or pipecuronium 123 micrograms/kg were given for the determination of histamine levels. The ulnar nerve was stimulated via surface electrodes using train-of-four stimulation at 0.1 Hz. The force of contraction of adductor pollicis was recorded using a mechanomyograph. Recovery of the twitch response was followed and, if necessary, neuromuscular block was antagonized with neostigmine and glycopyrrolate., Measurements and Main Results: Three patients in the doxacurrium group and one patient in the pipecuronium group exhibited a marked increase in plasma histamine levels. In both groups statistically significant changes were seen in heart rate (HR) measurements (p < 0.02). Doxacurium had a slower onset than pipecuronium [3.1 +/- 0.2 min vs. 1.8 +/- 0.1 min (p < 0.0003)] and a more rapid recovery [72 +/- 8 min vs. 123 +/- 9 min (p < 0.01)]., Conclusion: Neither drug caused a clinically significant change in HR or histamine release. In the doses chosen for this study, the rate of onset of block is slower with doxacurium while recovery is more rapid. Histamine release in three patients was caused by thiopental, while in a fourth patient it may have been due to doxacurium.

The effect of mivacurium after atracurium was evaluated in 36 children anesthetized with halothane-nitrous oxide-oxygen by measuring the force of contraction of the adductor pollicis during train-of-four stimulation at 0.1 Hz. The children were evaluated in two main groups. In Group 1 the effect of bolus doses of mivacurium after equipotent repeat doses of atracurium were evaluated. When the first twitch of the train-of-four response (T1) had recovered to 25% of control after a tracheally intubating dose of atracurium, a repeat dose of atracurium was given, on subsequent recovery to 25%, an equipotent dose of mivacurium was administered. In Group 2 when T1 had recovered to > 10% from 0.5 mg/kg atracurium, a mivacurium infusion was started; the initial infusion rate was 4 micrograms.kg-1.min-1 with adjustments made to maintain 90%-99% depression of T1. Patients were allowed to recover spontaneously from the effect of the relaxants. In Group 1 prolongation of the effect of mivacurium was noted after atracurium; the recovery indices (25%-75% and 5%-95%) of mivacurium were longer than those seen when mivacurium is the sole relaxant but shorter than atracurium. In Group 2, 15 min after the start of the mivacurium infusion, the dose requirement was 3.7 +/- 0.3 micrograms.kg-1.min-1 (approximately about one-third that required after a tracheally intubating dose of mivacurium). The infusion requirement increased gradually (P < 0.0001) until, at 90 min of infusion, it was 7.4 +/- 0.8 micrograms.kg-1.min-1. In Group 2 the recovery indices were similar to those seen when mivacurium is the sole relaxant given. When mivacurium is given after atracurium, evidence of the residual neuromuscular effects of the atracurium are detected beyond the usual recovery range.

Background: The newly developed neuromuscular blocking agent, mivacurium, has been evaluated in adults and children, but there are no data on its effects in infants. This study was designed to evaluate the neuromuscular effects of mivacurium by dose-response analysis, and its cardiovascular effects in 90 infants 2-11 months of age anesthetized with 1% halothane and nitrous oxide:oxygen., Methods: The neuromuscular response was measured by recording the force of contraction of the adductor pollicis during train-of-four stimulation at 0.1 Hz. The infants were divided according to age into two equal groups of 45; group A infants were 2-6 months of age, and group B infants were 7-11 months of age. Each group was further subdivided into five subgroups of nine. Infants in group A received mivacurium at sequential doses of 40, 50, 55, 75, and 150 micrograms/kg, while those in group B received mivacurium at doses 40, 50, 60, 75, and 150 micrograms/kg. The first four doses in each group were used to determine dose-response relationships. The last two doses of 75 and 150 micrograms/kg were based on the observed preceding dose-response data to approximate the ED95 and 2XED95. Heart rate and blood pressure were determined every minute for a minimum of 3 min after mivacurium., Results: The effective doses for 50% depression of the first twitch response of the train-of-four (ED50) were 44-50 micrograms/kg (confidence limits 29-74 micrograms/kg), without any significant difference between groups A and B. In both groups, a larger dose of mivacurium, 150 micrograms/kg, caused complete ablation of the twitch response in 1.3 +/- 0.2 min (mean +/- SE) with recovery to 5, 25, and 95% of control in 7.6 +/- 0.5, 9.4 +/- 0.6, and 16.2 +/- 0.9 min, respectively. In infants, the 25-75% recovery index was 3.8 +/- 0.4 min, and the 5-95% recovery index was 8.5 +/- 0.8 min. In 28 infants, in whom surgical relaxation was required for more than 20 min, the infusion requirements to maintain 90-99% neuromuscular block in infants 2-6 and 7-11 months of age were 12.1 +/- 1 and 9.9 +/- 1 micrograms.kg-1.min-1, respectively (NS). No significant changes of heart rate of blood pressure occurred in infants, except in the subgroup of infants 7-11 months of age who received 150 micrograms/kg mivacurium. In this group, a 13-mmHg increase in mean systolic blood pressure was seen without any significant change in diastolic pressure or heart rate. In addition, in 7 of 36 patients receiving 75-150 micrograms/kg mivacurium, a greater than 29% change in systolic or diastolic pressure occurred. One infant with cholinesterase deficiency had a prolonged neuromuscular block from mivacurium., Conclusions: The ED50 duration of action and infusion requirements of mivacurium in infants 2-6 months of age are comparable with those of infants 7-11 months of age.

The aim of this study was to assess the effects of diamorphine on breathlessness and exercise tolerance in patients with severe chronic airflow obstruction and normal arterial carbon dioxide tension (PCO2) levels ("pink puffer" syndrome). In this double-blind, cross-over, randomized study we examined both acute and chronic effects of single and multiple doses of oral diamorphine in 14 "pink puffer" patients. Their mean resting forced expiratory volume in one second (FEV1) was 36% predicted normal, mean arterial oxygen tension (PaO2) was 9.2 kPa and mean PaCO2 was 5.2 kPa. Ten patients took either diamorphine 2.5 or 5 mg or placebo elixir 6 hourly for 2 weeks, recording on a diary card dyspnoea, sleepiness and well-being on a visual analogue scale (VAS). The final treatment was given 30 min before measuring spirometry, arterial blood gases, plasma morphine levels, 6 min walking distances, time walked on treadmill and self-assessment of dyspnoea on a VAS scale after exercise. On two further days, eight patients took two doses, 4 h apart, of either diamorphine 7.5 mg or placebo elixir. Spirometry, 6 min walking distance with a VAS score for dyspnoea were measured before and at 1 h after each dose. Morphine levels and blood gases were also measured. Whether given in single or repeated doses, oral diamorphine had no significant effect on exercise tolerance and breathlessness when compared with placebo. Diamorphine 2.5-7.5 mg produced neither sleepiness nor a deterioration in blood gases. However, plasma levels associated with analgesic efficacy were not achieved with these doses. Thus, as given in this study, oral diamorphine is unlikely to have therapeutic potential in the treatment of dyspnoea in the "pink puffer" syndrome.

A new oesophageal intubation detector device, the Fenem CO2 detector, was used in 100 patients intubated during anaesthesia for elective surgery. This new device was 100% accurate in the differentiation between tracheal and oesophageal placement of a tube.