External validation of a pharmacokinetic model for target-controlled infusion of cefazolin as a prophylactic antibiotic.

AIMS: This study aimed to evaluate the predictive performance of previously constructed cefazolin pharmacokinetic models and determine whether cefazolin administration via the target-controlled infusion (TCI) method may be possible in clinical practice. METHODS: Twenty-five gastrectomy patients receiving cefazolin as a prophylactic antibiotic were enrolled. Two grams of cefazolin was dissolved in 50 mL of normal saline to give a concentration of 40 mg mL-1 . Before skin incision, cefazolin was administered using a TCI syringe pump, and its administration continued until the end of surgery. The target total plasma concentration was set to 100 µg mL-1 . Total and unbound plasma concentrations of cefazolin were measured in three arterial blood samples collected at 30, 60 and 120 min after the start of cefazolin administration. The predictive performance of the TCI system was evaluated using four measures: inaccuracy, divergence, bias and wobble. RESULTS: Total (n = 75) and unbound (n = 75) plasma concentration measurements from 25 patients were included in the analysis. The pooled median (95% confidence interval) biases and inaccuracies were 6.3 (4.0-8.5) and 10.5 (8.6-12.4) for the total concentration model and -10.3 (-16.8 to -3.7) and 22.4 (18.2-26.7) for the unbound concentration model, respectively. All unbound concentrations were above 10 µg mL-1 . CONCLUSION: Administration of cefazolin by the TCI method showed a clinically acceptable performance. Applying the TCI method by setting the total concentration as the target concentration rather than the unbound concentration is effective in maintaining a constant target concentration of cefazolin.

Association between maternal employment status and presence of children with major congenital anomalies in Denmark.

IMPORTANCE: The burden of caring for children with complex medical problems such as major congenital anomalies falls principally on mothers, who in turn suffer a variety of potentially severe economic consequences. As well, health consequences of caregiving often further impact the social and economic prospects of mothers of children with major congenital anomalies (MCMCAs). Evaluating the long-term economic consequences of extensive in-home caregiving among MCMCAs can inform strategies to mitigate these effects. OBJECTIVE: To assess whether MCMCAs face reduced employment and increased need for disability benefits over a 20-year period. DESIGN: A population-based matched cohort study. SETTING: Denmark. PARTICIPANTS: All women who gave birth to a singleton child with a major congenital anomaly in Denmark between January 1, 1997 and December 31, 2017 (n = 23,637) and a comparison cohort of mothers matched by maternal age, parity, and infant's year of birth (n = 234,586). EXPOSURES: Liveborn infant with a major congenital anomaly. MAIN OUTCOMES AND MEASURES: The primary outcome was mothers' employment status, stratified by their child's age. Employment status was categorized as employed, outside the workforce (on temporary leave, holding a flexible job, or pursuing education), or unemployed; the number of weeks in each category was measured over time. The secondary outcome was time to receipt of a disability pension, which in Denmark implies permanent exit from the labor market. We used a negative binomial regression model to estimate the number of weeks in each employment category, stratified by the child's age (i.e., 0-1 year, > 1-6 years, 7-13 years, 14-18 years). A Cox proportional hazards regression model was used to compute hazard ratios as a measure of the relative risk of receiving a disability pension. Rate ratios and hazard ratios were adjusted for maternal demographics, pregnancy history, health, and infant's year of birth. RESULTS: During 1-6 years after delivery, MCMCAs were outside the workforce for a median of 50 weeks (IQR, 6-107 weeks), while members of the comparison cohort were outside the workforce for a median of 48 weeks (IQR, 4-98 weeks), corresponding to an adjusted rate ratio [ARR] of 1.05 (95% confidence interval [CI], 1.04-1.07). During the first year after delivery, MCMCAs were more likely to be employed than mothers in the comparison cohort (ARR, 1.08; 95% CI, 1.06-1.10). At all timepoints thereafter, MCMCAs had a lower rate of workforce participation. The rate of being outside the workforce was 5% higher than mothers in the comparison cohort during 1-6 years after delivery (ARR, 1.05; 95% CI, 1.04-1.07), 9% higher during 7-13 years after delivery (ARR, 1.09; 95% CI, 1.06-1.12), and 12% higher during 14-18 years after delivery (ARR, 1.12; 95% CI, 1.07-1.18). Overall, MCMCAs had a 20% increased risk of receiving a disability pension during follow-up than mothers in the matched comparison cohort [incidence rates 3.10 per 1000 person-years (95% CI, 2.89-3.32) vs. 2.34 per 1000 person-years (95% CI, 2.29-2.40), adjusted hazard ratio, 1.20; 95% CI, 1.11-1.29]. CONCLUSION AND RELEVANCE: MCMCAs were less likely to participate in the Danish workforce, less likely to be employed, and more likely to receive disability pensions than mothers of unaffected children. The rate of leaving the workforce intensified as their affected children grew older. The high demands of caregiving among MCMCAs may have long-term employment consequences even in nations with comprehensive and heavily tax-supported childcare systems, such as Denmark.

The association between cognitive ability and opioid prescribing in vulnerable older adults with chronic pain in ambulatory care: a secondary data analysis using the Medical Expenditure Panel Survey.

BACKGROUND: Vulnerable older adults living with Alzheimer's disease or Alzheimer's disease and related dementia (AD/ADRD) and chronic pain generally receive fewer pain medications than individuals without AD/ADRD, especially in nursing homes. Little is known about pain management in older adults with AD/ADRD in the community. The aim of the study was to examine opioid prescribing patterns in individuals with chronic pain by levels of cognitive ability in ambulatory care. METHODS: We used the Medical Expenditure Panel Survey (MEPS), years 2002-2017, and identified three levels of cognitive impairment: no cognitive impairment (NCI), individuals reporting cognitive impairment (CI) without an AD/ADRD diagnosis, and individuals with a diagnosis of AD/ADRD. We examined any receipt of an opioid prescription and the number of opioid prescriptions using a logistic and negative binomial regression adjusting for sociodemographic and health characteristics and stratifying by three types of chronic pain (any chronic pain, severe chronic pain, and chronic pain identified through ICD 9/10 chronic pain diagnoses). RESULTS: Among people with any chronic pain, adjusted odds of receiving an opioid for people with CI (OR 1.41, 95% confidence interval 1.31-1.52) and AD/ADRD (OR 1.23, 95% confidence interval 1.04-1.45) were higher compared to NCI. Among people with chronic pain ICD 9/10 conditions, the odds of receiving an opioid were also higher for those with CI (OR 1.43, 95% confidence interval 1.34-1.56) and AD/ADRD (OR 1.48, 95% confidence interval 1.23-1.78) compared to NCI. Among those with severe chronic pain, people with CI were more likely to receive an opioid (OR 1.17, 95% confidence interval 1.07-1.27) relative to NCI (OR 0.89, 95% confidence interval 0.75-1.06). People with AD/ADRD experiencing severe chronic pain were not more likely to receive an opioid compared to the NCI group. Adjusted predicted counts of opioid prescriptions showed more opioids in CI and AD/ADRD in all chronic pain cohorts, with the largest numbers of opioid prescriptions in the severe chronic pain and ICD 9/10 diagnoses groups. CONCLUSIONS: The results suggest increased opioid use in people living with CI and AD/ADRD in the ambulatory care setting and potentially indicate that these individuals either require more analgesics or that opioids may be overprescribed. Further research is needed to examine pain management in this vulnerable population.

Population pharmacokinetic and pharmacodynamic model of propofol externally validated in Korean elderly subjects.

The Eleveld propofol pharmacokinetic (PK) model, which was developed based on a broad range of populations, showed greater bias (- 27%) in elderly subjects in a previous validation study conducted by Vellinga and colleagues. We aimed to develop and externally validate a new PK-pharmacodynamic (PK-PD) model of propofol for elderly subjects. A population PK-PD model was constructed using propofol plasma concentrations and bispectral index (BIS) values that were obtained from 31 subjects aged 65 years older in previously published phase I studies. The predictive performance of the newly-developed PK-PD model (Choi model) was assessed in a separate Korean elderly population and compared with that of the Eleveld model. A three-compartment mammillary model using an allometric expression and a sigmoid Emax model well-described the time courses of propofol concentrations and BIS values. The V1, V2, V3, Cl, Q1, Q2, E0, Emax, Ce50, γ, and ke0 of a 60-kg subject were 8.36, 58.0, 650 L, 1.26, 0.917, 0.669 L/min, 92.1, 18.7, 2.21 µg/mL, 2.89, and 0.138 /min, respectively. In the Choi model and Eleveld model, pooled biases (95% CI) of the propofol concentration were 7.78 ( 3.09-12.49) and 16.70 (9.46-23.93) and pooled inaccuracies were 22.84 (18.87-26.81) and 24.85 (18.07-31.63), respectively. The Choi PK model was less biased than the Eleveld PK model in Korean elderly subjects (age range: 65.0-79.0 yr; weight range: 45.0-75.3 kg). Our results suggest that the Choi PK model, particularly, is applicable to target-controlled infusion in non-obese Korean elderly subjects.

Effectiveness of Combined Health Coaching and Self-Monitoring Apps on Weight-Related Outcomes in People With Overweight and Obesity: Systematic Review and Meta-analysis.

BACKGROUND: Self-monitoring smartphone apps and health coaching have both individually been shown to improve weight-related outcomes, but their combined effects remain unclear. OBJECTIVE: This study aims to examine the effectiveness of combining self-monitoring apps with health coaching on anthropometric, cardiometabolic, and lifestyle outcomes in people with overweight and obesity. METHODS: Relevant articles published from inception till June 9, 2022, were searched through 8 databases (Embase, CINAHL, PubMed, PsycINFO, Scopus, The Cochrane Library, and Web of Science). Effect sizes were pooled using random-effects models. Behavioral strategies used were coded using the behavior change techniques taxonomy V1. RESULTS: A total of 14 articles were included, representing 2478 participants with a mean age of 39.1 years and a BMI of 31.8 kg/m2. Using combined intervention significantly improved weight loss by 2.15 kg (95% CI -3.17 kg to -1.12 kg; P<.001; I2=60.3%), waist circumference by 2.48 cm (95% CI -3.51 cm to -1.44 cm; P<.001; I2=29%), triglyceride by 0.22 mg/dL (95% CI -0.33 mg/dL to 0.11 mg/dL; P=.008; I2=0%), glycated hemoglobin by 0.12% (95% CI -0.21 to -0.02; P=.03; I2=0%), and total calorie consumption per day by 128.30 kcal (95% CI -182.67 kcal to -73.94 kcal; P=.003; I2=0%) kcal, but not BMI, blood pressure, body fat percentage, cholesterol, and physical activity. Combined interventional effectiveness was superior to receiving usual care and apps for waist circumference but only superior to usual care for weight loss. CONCLUSIONS: Combined intervention could improve weight-related outcomes, but more research is needed to examine its added benefits to using an app. TRIAL REGISTRATION: PROSPERO CRD42022345133; https://tinyurl.com/2zxfdpay.

Assessment of explicit and implicit memories during remimazolam anaesthesia using the process dissociation procedure: A prospective cohort study.

BACKGROUND: Memory formation during remimazolam anaesthesia, where a bispectral index (BIS) is sometimes not maintained at less than 60 despite the maximal dose, is worthy of evaluation. OBJECTIVE: Investigate the formation of explicit and implicit memories using the process dissociation procedure during remimazolam anaesthesia at a BIS of 60 to 80. DESIGN: A prospective cohort study. SETTING: A tertiary medical centre in Seoul, South Korea, between March 2022 and July 2022. PATIENTS: One hundred patients undergoing general anaesthesia using remimazolam. INTERVENTIONS: The BIS was maintained at 60 to 80 during anaesthesia induction with remimazolam. Words were spoken to patients via headphones for 15 min. MAIN OUTCOME MEASURE: The primary outcome was the probability of explicit or implicit memory formation as calculated using the original and extended models, within 24 h after word presentation. Conscious recall memory was assessed using a short-structured interview within 1 and 24 h after surgery. Memory formation was inferred to be absent if 0 was included in the 95% confidence interval (CI) of the probability. RESULTS: The main results showed no evidence of explicit or implicit memory. The 95% CI of the probability of explicit memory formation included 0 for both models, -0.01 (-0.04 to 0.02) and -0.04 (-0.10 to 0.01), respectively. The 95% CI of the probability of implicit memory formation did not include 0 when evaluated using the original model, 0.08 (0.06 to 0.10), but included 0 when evaluated using the extended model, 0.00 (-0.03 to 0.03). The modified Brice interview revealed no evidence of awareness. CONCLUSIONS: There was no evidence of explicit or implicit memory formation during remimazolam anaesthesia (BIS 60 to 80). Further research is warranted to establish whether explicit and implicit memories are still absent even in the presence of surgical stimulation. CLINICAL TRIAL REGISTRATION: KCT0006752 ( http://cris.nih.go.kr ).

The expected advantage of administering prophylactic antibiotics using target- concentration controlled infusion: Development of a new pharmacokinetic model of cefazolin.

The aim of this study was to explore the utility of target-concentration controlled infusion (TCI) as a prophylactic antibiotic administration method based on the results of a population pharmacokinetic model of cefazolin. In patients undergoing elective gastric surgery, 2 g of cefazolin was dissolved in 50 mL of saline and administered for 10 min prior to skin incision. Arterial blood samples were obtained at preset intervals to measure the total and free plasma concentrations of cefazolin. Population pharmacokinetic analysis was performed using non-linear mixed-effects modelling. To evaluate the effectiveness of the TCI method, stochastic simulation was performed based on the model construction results. In total, 360 total and 360 free plasma concentration measurements from 40 patients were used to characterise the pharmacokinetics of cefazolin. The changes in the total concentration of cefazolin over time were well-explained by the three-compartment mammillary model. Fat-free mass and estimated glomerular filtration rate were significant covariates. The probability of target attainment (PTA) to reach the target 100% fraction of time that the free plasma concentration of cefazolin was maintained above its minimal inhibitory concentration (fT > MIC) at MIC of 4 mg/L was also notably higher in the TCI method (90.7%) than in the standard method (17.0%). When cefazolin is administered by the TCI method, patient-tailored antibiotic dosing may be possible. The potential benefits of administering prophylactic antibiotics by the TCI method were observed. Further research is warranted to confirm the effectiveness of the TCI method.

Predictive performance of pharmacokinetic models for target concentration-controlled infusion of cefoxitin as a prophylactic antibiotic in patients with colorectal surgery.

We aimed to evaluate the predictive performance of previously constructed free (Cfree ) and total (Ctotal ) cefoxitin pharmacokinetic models and the possibility of administering cefoxitin via the target-controlled infusion (TCI) method in clinical practice. Two external validation studies (N = 31 for Cfree model, N = 30 for Ctotal model) were conducted sequentially. Cefoxitin (2 g) was dissolved in 50 mL of normal saline to give a concentration of 40 mg mL-1 . Before skin incision, cefoxitin was infused with a TCI syringe pump. Target concentrations of free concentration and total concentration were set to 25 and 80 µg mL-1 , respectively, which were administered throughout the surgery. Three arterial blood samples were collected to measure the total and free plasma concentrations of cefoxitin at 30, 60 and 120 min, after the start of cefoxitin administration. The predictive performance was evaluated using four parameters: inaccuracy, divergence, bias and wobble. The pooled median (95% confidence interval) biases and inaccuracies were - 45.9 (-47.3 to -44.5) and 45.9 (44.5 to 47.3) for Cfree model (Choi_F model), and - 16.6 (-18.4 to -14.8) and 18.5 (16.7 to 20.2) for Ctotal model (Choi_Told model), respectively. The predictive performance of the newly constructed model (Choi_Tnew model), developed by adding the total concentration data measured in the external validation, was better than that of the Choi_Told model. Models constructed with total concentration data were suitable for clinical use. Administering cefoxitin using the TCI method in patients maintained the free concentration above the minimal inhibitory concentration (MIC) breakpoints of the major pathogens causing surgical site infection throughout the operation period.

Effects of head-elevated position on tracheal intubation using a McGrath MAC videolaryngoscope in patients with a simulated difficult airway: a prospective randomized crossover study.

BACKGROUND: The head-elevated laryngoscopy position has been described to be optimal for intubation, particularly in obese patients and those with anticipated difficult airways. Horizontal alignment of the external auditory meatus and sternal notch (AM-S) can be used as endpoints for optimal positioning. Thus, we aligned the head-elevated position with the AM-S in the horizontal plane and evaluated its effect on laryngeal visualization and ease of intubation using a McGrath MAC videolaryngoscope in patients with a simulated difficult airway. METHODS: Sixty-four patients were included in this prospective, crossover, randomized controlled trial. A cervical collar was used to restrict neck movement and mouth opening. The head-elevated position was achieved by raising the back section of the operation room table and ensuring that the end point was horizontally aligned with the AM-S (table-ramp method). The laryngeal view was randomly assessed in both head-flat and head-elevated positions based on the percentage of glottic opening (POGO) score and modified Cormack-Lehane (MCL) grade. External laryngeal manipulation was not permitted when laryngeal visualization was scored. The trachea was intubated only once (in the second position). The ease of intubation was assessed based on the need for optimization maneuvers, intubation difficulty scale (IDS) scores and time to intubation. RESULTS: The mean table-ramp angle required to achieve the horizontal alignment of AM-S was 17.5 ± 4.1°. The mean POGO score improved significantly in the head-elevated position (59.4 ± 23.8%) when compared with the head-flat position (37.5 ± 24%) (P <  0.0001). MCL grade 1 or 2a was achieved in 56 (85.9%) and 28 (43.7%) of patients in the head-elevated and head-flat positions, respectively (P <  0.0001). Optimization maneuvers for intubation were required in 7 (21.9%) and 17 (53.1%) patients in the head-elevated and head-flat positions, respectively (P <  0.0001). The IDS scores and time to intubation did not differ significantly between the two positions. CONCLUSION: In the head-elevated position, aligning the AM-S in the horizontal plane consistently improved laryngeal visualization without worsening the view when the McGrath MAC videolaryngoscope was used in patients with simulated difficult airways. It also improved the ease of intubation, which reduced the need for optimization maneuvers. TRIAL REGISTRATION: This trial was registered with www. CLINICALTRIALS: gov , NCT04716218 , on 20/01/2021.

Development of a new pharmacokinetic model for target-concentration controlled infusion of cefoxitin as a prophylactic antibiotic in colorectal surgical patients.

AIMS: There are several limitations to the existing method of administering cefoxitin as a prophylactic antibiotic, and the limitations may be overcome by applying the target-concentration controlled infusion (TCI) method. Population pharmacokinetic parameters are required to administer cefoxitin by the TCI method. The aim of this study was to construct a new pharmacokinetic model of cefoxitin for the TCI method in colorectal surgical patients. METHODS: In patients undergoing colorectal surgery, 2 g of cefoxitin was dissolved in 50 mL of saline and administered for 10 minutes prior to skin incision. Arterial blood samples were obtained at preset intervals to measure the total and free plasma concentrations of cefoxitin. Population pharmacokinetic analysis was performed using NONMEM software (ICON Development Solutions, Dublin, Ireland). Additionally, stochastic simulation was used to indirectly evaluate the effectiveness of the two administration methods (standard method vs TCI). RESULTS: In total, 297 plasma concentration measurements from 31 patients were used to characterize the pharmacokinetics of cefoxitin. A three-compartment mammillary model described the pharmacokinetics of cefoxitin. Body weight and creatinine clearance were significant covariates for clearance. The stochastic simulation showed that when compared with the standard method, the TCI method has a significantly higher fraction of time that the free concentration of cefoxitin is maintained above the minimum inhibitory concentration (P < .001). CONCLUSIONS: TCI has the potential to become a new infusion method for patient-tailored dosing in surgical patients. To administer cefoxitin via TCI in clinical practice, the newly constructed pharmacokinetic model should undergo proper external validation.

Do epoch lengths of hypnotic depth indicators affect estimated of blood-brain equilibration rate constants of propofol?

This study aimed to investigate the effect of epoch length of hypnotic depth indicators on the blood-brain equilibration rate constant (ke0) estimates of propofol. Propofol was administered by zero-order infusion (1.5, 3.0, 6, and 12 mg·kg-1·h-1) for one hour in 63 healthy volunteers. The ke0 of propofol was estimated using an effect-compartment model linking pharmacokinetics and pharmacodynamics, in which response variables were electroencephalographic approximate entropy (ApEn) or bispectral index (BIS) (n = 32 each for propofol infusion rates of 6 and 12 mg·kg-1·h-1). Epoch lengths of ApEn were 2, 10, 30, and 60 seconds (s). The correlations between plasma propofol concentrations (Cp) and BIS and ApEn 2, 10, 30, and 60 s were determined, as was the Ce associated with 50% probability of unconsciousness (Ce50,LOC). The pharmacokinetics of propofol were well described by a three-compartment model. The correlation coefficient between Cp and ApEn 2, 10, 30, and 60 s were -0.64, -0.54, -0.39, and -0.26, respectively, whereas correlation coefficient between Cp and BIS was -0.74. The blood-brain equilibration half-life based on the ke0 estimates for ApEn at 2, 10, 30, 60 s and BIS were 4.31, 3.96, 5.78. 6.54, 5.09 min, respectively, whereas the Ce50,LOC for ApEn at 2, 10, 30, 60 s and BIS were 1.55, 1.47, 1.28, 1.04, and 1.55 µg·ml-1, respectively. Since ke0, which determines the onset of drug action, varies according to the epoch length, it is necessary to consider the epoch length together when estimating ke0.

A modified method of measuring plasma volume with indocyanine green: reducing the frequency of blood sampling while maintaining accuracy.

Among various methods for measuring the plasma volume (PV), the indocyanine green (ICG) dilution technique is a relatively less invasive method. However, the ICG method is rather cumbersome because 10 blood samples need to be obtained within a short time after ICG administration. Thus, reducing the frequency of blood sampling while maintaining the accuracy would facilitate plasma volume measurement in clinical situations. We here developed a modified method to measure plasma volume using 2260 ICG plasma concentration data from 115 surgical patients. The mean relative error (MRE) and the percentage of cases with relative error (RE) greater than 5% in total (PRE) were used to quantify the difference between plasma volumes obtained by the original and modified methods. RE was determined as follows. RE(%) = (PV obtained by original method (PVoriginal)-PV obtained by modified method (PVmodified))/PVoriginal × 100. PVmodified was assumed to be equal to PVoriginal when the RE was < 5%. When the number of samples selected for the plasma volume estimation was 4 or less, the PRE was mostly 10% or more. Five out of the 10 blood samples (order: 1st, 2nd, 3rd, 9th, and 10th) showed similar accuracies with the plasma volume obtained by the original method (original: 2.72 ± 0.64 l, modified: 2.72 ± 0.65 l). This modified method may be able to aptly replace the original method and lead to a wider clinical application of the ICG dilution technique. Further validation is needed to determine if the results of this study may be applied in other populations.

Inhibitory Activities of Dimeric Ellagitannins Isolated from Cornus alba on Benign Prostatic Hypertrophy.

Benign prostatic hypertrophy (BPH) is an intractable chronic inflammatory disease. We studied the efficacy of two ellagitannins, namely camptothin B (1) and cornusiin A (2) that were isolated from Cornus alba (CA) for the treatment of BPH, which is a common health issue in older men. The ellagitannins (1 and 2) were evaluated on its inhibitory activities of the enzyme 5α-reductase and tumor necrosis factor (TNF)-α, its interleukin (IL)-1ß, IL-6, and IL-8 production, and its anti-proliferation and apoptosis induction in prostate cells that show hypertrophy (RWPE-1 cell). In inhibition of 5α-reductase, the ellagitannins (1 and 2) showed potential effects, compared to the positive control, finasteride. In the case of IL-1ß, IL-6, IL-8, and TNF-α, 1 and 2 showed good inhibitory effects as compared to the control group treated with LPS. The ellagitannins (1 and 2) were also shown to inhibit proliferation of, and induce apoptosis in, the RWPE-1 cell. These results suggest that the ellagitannins (1 and 2) may be good candidates for the treatment of BPH.

Phase Lag Entropy as a Surrogate Measurement of Hypnotic Depth during Sevoflurane Anesthesia.

Background and Objectives: Phase lag entropy, an electroencephalographic monitor, evaluates the variety in temporal patterns of phase relationship between frontal and prefrontal brain region. Phase lag entropy can reflect the depth of anesthesia induced by propofol, but the association between sevoflurane and phase lag entropy has not been elucidated. This study examined the effect of sevoflurane on phase lag entropy during induction of general anesthesia. We also explored the pharmacodynamic model between end-tidal anesthetic concentration and electroencephalographic monitor. Materials and Methods: A total of 20 patients were enrolled. General anesthesia was produced by escalating the sevoflurane (1 vol% up to 8 vol%). The relationship between phase lag entropy and end-tidal anesthetic concentration was analyzed. A non-linear mixed-effects model was used to get the relationship of pharmacodynamics between the end-tidal sevoflurane concentration and phase lag entropy. Mean blood pressure, heart rate, and the modified observer's assessment of alertness/sedation scale were also recorded during sevoflurane anesthesia. Results: As level of sedation increased, phase lag entropy decreased. A significant correlation was showed between phase lag entropy and end-tidal sevoflurane concentration (r = -0.759, p < 0.001). The correlation coefficient between the modified observer's assessment of alertness/sedation scale and phase lag entropy was 0.731 (p < 0.001). The pharmacodynamic factors assessed by the sigmoid Emax model were E0 = 84.9, Emax = 42, Ce50 = 1.81, γ = 4.78, and ke0 = 0.692. The prediction probability of phase-lag entropy for measuring the modified observer's assessment of alertness/sedation scale and end-tidal sevoflurane concentration were 0.764 and 0.789, respectively. With the increasing concentration of sevoflurane, mean blood pressure decreased, but heart rate did not change. Conclusions: The continuing escalation in end-tidal sevoflurane concentration caused a decline in phase lag entropy. Phase lag entropy can serve as an indicator of hypnotic depth in patients receiving sevoflurane anesthesia.

Stochastic Particle Approach Electrochemistry (SPAE): Estimating Size, Drift Velocity, and Electric Force of Insulating Particles.

Stochastic particle impact electrochemistry (SPIE) is considered one of the most important electro-analytical methods to understand the physicochemical properties of single entities. SPIE of individual insulating particles (IPs) has been particularly crucial for analyses of bioparticles. In this article, we introduce stochastic particle approach electrochemistry (SPAE) for electrochemical analyses of IPs, which is the advanced version of SPIE; SPAE is analogous to SPIE but focuses on deciphering a sudden current drop (SCD) by an IP-approach toward the edge of an ultramicroelectrode (UME). Polystyrene particles (PSPs) with and without different surface functionalities (-COOH and - NH3) as well as fixed human platelets (F-HPs) were used as model IPs. From theory based on finite element analysis, a sudden current drop (SCD) induced by an IP during electro-oxidation (or reduction) of a redox mediator on a UME can represent the rapid approach of an IP toward an edge of a UME, where a strong electric field is generated. It is also found that the amount of current drop, idrop, of an SCD depends strongly on both the size of an IP and the concentration of redox electrolyte. From simulations based on the SPAE model that fit the experimentally obtained SCDs of three types of PSPs or F-HP dispersed in solutions with two redox electrolytes, their size distribution histograms are estimated, from which their average radii determined by SPAE are compared to those from scanning electron microscopic images. In addition, the drift velocity and corresponding electric force of the PSPs and F-HPs during their approach toward an edge of a Pt UME are estimated, which cannot be addressed currently with SPIE. We further learned that the estimated drift velocity and the corresponding electric force could provide a relative order of the number of excess surface charges on the IPs.

Comparison of C-MAC D-blade videolaryngoscope and McCoy laryngoscope efficacy for nasotracheal intubation in simulated cervical spinal injury: a prospective randomized comparative study.

BACKGROUND: Immobilization with cervical spine worsens endotracheal intubation condition. Though various intubation devices have been demonstrated to perform well in oral endotracheal intubation, limited information is available concerning nasotracheal intubation (NTI) in patients with cervical spine immobilization. The present study compared the performance of the C-MAC D-Blade videolaryngoscope with the McCoy laryngoscope for NTI in patients with simulated cervical spine injuries. METHODS: This was a prospective, randomized, controlled, study done in a tertiary hospital. Ninety-five patients requiring NTI were included in data analysis: McCoy group (group M, n = 47) or C-MAC D-Blade videolaryngoscope group (group C, n = 48). A Philadelphia neck collar was applied before anesthetic induction to immobilize the cervical spine. Single experienced anesthesiologist performed NTI. The primary outcome was duration of intubation divided by three steps: nose to oropharynx; oropharynx into glottic inlet; and glottic inlet to trachea. Secondary outcomes included glottic view as percentage of glottis opening (POGO) score and Cormack-Lehance (CL) grade, modified nasal intubation-difficulty scale (NIDS) rating, hemodynamic changes before and after intubation, and complications. RESULTS: Total intubation duration was significantly shorter in group C (39.5 ± 11.4 s) compared to group M (48.1 ± 13.9 s). Group C required significantly less time for glottic visualization and endotracheal tube placement in the trachea. More patients in group C had CL grade I and higher POGO scores (P <  0.001, for both measures). No difficulty in NTI (modified NIDS = 0) was more in group C than group M. Hemodynamic changes and incidence of complications were comparable between groups. CONCLUSION: The C-MAC D-Blade videolaryngoscope is an effective tool for NTI in a simulated difficult airway, which improves glottic visualization and shortens intubation time relative to those with McCoy laryngoscope. TRIAL REGISTRATION: Clinical Research Information Service of the Korea National Institute of Health, Identification number: KCT 0004535, Registered December 10, 2019, Retrospectively registered, http://cris.nih.go.kr.

Target-controlled infusion of dexmedetomidine effect-site concentration for sedation in patients undergoing spinal anaesthesia.

WHAT IS KNOWN AND OBJECTIVE: Dexmedetomidine has been a preferred sedative for patients undergoing regional anaesthesia and is mostly administered via conventional zero-order infusion. Recently, a pharmacokinetic-pharmacodynamic (PKPD) model of dexmedetomidine has been published, but no external validation has been reported in clinical trials. We aimed to administer target-controlled infusion (TCI) of dexmedetomidine at the effect-site concentration (Ce) to patients undergoing spinal anaesthesia and investigate the relationship between dexmedetomidine Ce and the sedative effects. METHODS: Forty-five patients scheduled for orthopaedic surgery received spinal anaesthesia with 0.5% bupivacaine. After confirmation of sensory block level, we initiated effect-site TCI of dexmedetomidine using Colin's model and assessed sedation levels using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale and bispectral index (BIS) with each stepwise increase in the dexmedetomidine Ce. We used a non-linear mixed-effects model to determine the PD relationships between the dexmedetomidine Ce and sedation level. RESULTS: The dexmedetomidine Ce associated with 50% probability (Ce50 ) of the MOAA/S scale ≤4, 3 and 2 was 0.57, 0.89 and 1.19 ng/mL, respectively. Mean dexmedetomidine Ce when BIS decreased ≤70 was 0.99 ± 0.15 ng/mL. As dexmedetomidine Ce increased, the MOAA/S scale decreased significantly (correlation coefficient [r] = -.832, P < .0001). BIS decreased significantly with increasing dexmedetomidine Ce (r = -.811, P < .0001) and decreasing MOAA/S scale (r = .838, P < .0001). The most common side effects were hypertension (26.67%) and bradycardia (20%). WHAT IS NEW AND CONCLUSION: We applied effect-site TCI of dexmedetomidine in patients undergoing spinal anaesthesia for the first time. Dexmedetomidine Ce correlated significantly with MOAA/S scale and BIS, and was 0.89 and 1.19 ng/mL for moderate and deep sedation, respectively.

Female university students' menstrual-hygiene management and factors associated with genitourinary-tract infections in Korea.

This study examined female university students' menstrual-hygiene management and identified factors associated with genitourinary tract infections in this sample. This study was conducted as a descriptive survey. Participants were 383 female students from six universities in South Korea. Data were collected between April and June, 2017. Multiple logistic regression analysis was used to access the factors associated with genitourinary-tract infections. Multiple logistic regression revealed that genitourinary tract infections were significantly associated with low socioeconomic level, history of sexual intercourse, and vaginal douching during menstruation. We evaluated menstrual hygiene practices and their relation to genitourinary tract infections. Korean college students were relatively good at managing menstrual hygiene. However, some menstrual hygiene behaviors were improper. Therefore, school and community health agencies should provide education to maintain adequate menstrual hygiene and correct erroneous hygiene practices to prevent genitourinary tract infections.

Time Transient Electrochemical Monitoring of Tetraalkylammonium Polybromide Solid Particle Formation: Observation of Ionic Liquid-to-Solid Transitions.

Energy storage systems (ESSs) using a Br-/Br2 redox reaction such as a Zn/Br redox flow battery (RFB) or a redox-enhanced electrochemical capacitor (Redox-EC) suffer from self-discharge reactions resulting in significant Coulombic loss. To inhibit the self-discharge, quaternary ammonium (Q+) and tetraalkylammonium (T+) bromide are added to form ionic liquid (QBr2 n+1) and solid (TBr3) polybromides during the ESS charging process. The electrochemical formation of liquid QBr2 n+1 and its electrochemical properties have been examined. The detailed mechanisms of ionic solid TBr3 formation, however, have not yet been explored. In this article, we analyzed the ionic liquid-to-solid phase transition of TBr3 particles using a time transient electrochemical method. We suggest the formation of ionic solid TBr3 particles via hydrated TBr3 droplets as an intermediate phase, which are generated by electro-oxidation of Br- in an aqueous TBr solution. We found the phase transition time of TBr3 particles is strongly dependent on the chemical structure of T+ and the concentration of TBr in an aqueous solution.

Comparison of Pentax Airway Scope and Macintosh laryngoscope for orotracheal intubation in children: A randomised non-inferiority trial.

BACKGROUND: Pentax Airway Scope (AWS) is a recently developed videolaryngoscope for use in both normal and difficult airways, yet its use in paediatric patients has not been established. The purpose of this study was to evaluate the efficacy of the Pentax AWS regarding intubation time, laryngeal view and ease of intubation in paediatric patients with normal airway, compared to Macintosh laryngoscope. METHOD: A total of 136 paediatric patients aged 1-10 with American Society of Anaesthesiologists physical status I or II undergoing general anaesthesia were randomly allocated into two groups: Macintosh laryngoscope (n = 68) and Pentax Airway Scope (n = 68). Primary outcome was intubation time. Cormack-Lehane laryngeal view grade, application of optimal laryngeal external manipulation, intubation difficulty scale, intubation failure rate and adverse events were also measured. RESULT: No significant difference was observed between the two groups regarding intubation time (P = 0.713). As for the laryngeal view grade, the Pentax group resulted in lower graded cases compared to the Macintosh group (P = 0.000). No optimal laryngeal external manipulation application was required in the Pentax group. Intubation difficulty scale resulted in lower values for Pentax group (P = 0.001). Failure rate was not different between the two groups (P = 0.619). There were significantly more teeth injury cases in the Pentax group than Macintosh group (P = 0.042). CONCLUSION: Pentax Airway Scope provided similar intubation time and success rate, while improving laryngeal view, compared to Macintosh laryngoscopy in children with normal airway. When using Pentax AWS in children, however, the risk of teeth injury may increase.